{"status":"ok","message-type":"work-list","message-version":"1.0.0","message":{"facets":{},"total-results":101669,"items":[{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:56:34Z","timestamp":1783511794318,"version":"3.55.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220540\/Z\/20\/A"],"award-info":[{"award-number":["220540\/Z\/20\/A"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Educ"],"abstract":"Abstract<\/jats:title>\n Background<\/jats:title>\n The clinical utility of whole genome sequencing (WGS) in paediatric cancer has been demonstrated in recent years. WGS has been routinely available in the National Health Service (NHS) England for all children with cancer in England since 2021, but its uptake has been variable geographically. To explore the underlying barriers to routine use of WGS in this population across England and more widely in the United Kingdom (UK) and the Republic of Ireland (ROI), a one-day workshop was held in Cambridge, United Kingdom in October 2022.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n Following a series of talks, delegates participated in open, round-table discussions to outline local and broader challenges limiting routine WGS for diagnostic work-up for children with cancer in their Principal Treatment Centres (PTCs) and Genomic Laboratory Hubs (GLHs). Within smaller groups, delegates answered structured questions regarding clinical capability, education and training needs, and workforce competence and requirements. Data was recorded, centrally collated, and analysed following the event using thematic analysis.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n Sixty participants attended the workshop with broad representation from the 20 PTCs across the UK and ROI and the seven GLHs in England. All healthcare professionals involved in the WGS pathway were represented, including paediatric oncologists, clinical geneticists, clinical scientists, and histopathologists. The main themes highlighted by the group in ensuring equitable access to WGS identified were: lack of knowledge equity between NHS trusts, with a perception of WGS being for research only; and perception of lack of financial support for the clinical process surrounding WGS, including lack of time to take informed consent from patients. The latter also included limited trained staff available for data interpretation, affecting the turnaround time for reporting. Finally, the need for an integrated digital pathway to order, track, and return data to clinicians was highlighted.<\/jats:p>\n <\/jats:sec>\n Conclusion<\/jats:title>\n At the workshop, the general motivation for including WGS in the diagnostic work up for children with cancer was high throughout the UK, however a perceived lack of resources and education opportunities limit the widespread use of this commissioned assay. This workshop has led to some recommendations to increase access to WGS in this population in England and more widely in the devolved national of the UK and the ROI.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12909-024-06219-y","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T19:01:46Z","timestamp":1730919706000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identifying barriers and opportunities to facilitate the uptake of whole genome sequencing in paediatric haematology and oncology practice"],"prefix":"10.1186","volume":"24","author":[{"given":"Michelle","family":"Bishop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Vedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Bowdin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Bartram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Bentley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Elizabeth","family":"Hook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian Hon","family":"Yin Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parker","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Rowitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Tarpey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Behjati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Murray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"6219_CR1","doi-asserted-by":"crossref","unstructured":"Wise J. Genome sequencing of children promises a new era in oncology. BMJ. 2019;l105.","DOI":"10.1136\/bmj.l105"},{"issue":"2","key":"6219_CR2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s43018-022-00474-y","volume":"4","author":"A Villani","year":"2022","unstructured":"Villani A, Davidson S, Kanwar N, Lo WW, Li Y, Cohen-Gogo S, et al. The clinical utility of integrative genomics in childhood cancer extends beyond targetable mutations. Nat Cancer. 2022;4(2):203\u201321.","journal-title":"Nat Cancer"},{"key":"6219_CR3","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ejca.2016.06.009","volume":"65","author":"BC Worst","year":"2016","unstructured":"Worst BC, van Tilburg CM, Balasubramanian GP, Fiesel P, Witt R, Freitag A, et al. Next-generation personalised medicine for high-risk paediatric cancer patients \u2013 the INFORM pilot study. Eur J Cancer. 2016;65:91\u2013101.","journal-title":"Eur J Cancer"},{"issue":"12","key":"6219_CR4","doi-asserted-by":"publisher","first-page":"3008","DOI":"10.1158\/2159-8290.CD-20-1631","volume":"11","author":"S Newman","year":"2021","unstructured":"Newman S, Nakitandwe J, Kesserwan CA, Azzato EM, Wheeler DA, Rusch M, et al. Genomes for kids: the scope of pathogenic mutations in Pediatric Cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discov. 2021;11(12):3008\u201327.","journal-title":"Cancer Discov"},{"issue":"8","key":"6219_CR5","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1038\/s41591-022-01856-6","volume":"28","author":"AJ Church","year":"2022","unstructured":"Church AJ, Corson LB, Kao PC, Imamovic-Tuco A, Reidy D, Doan D, et al. Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer. Nat Med. 2022;28(8):1581\u20139.","journal-title":"Nat Med"},{"issue":"1","key":"6219_CR6","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1038\/s41467-022-30233-7","volume":"13","author":"N Shukla","year":"2022","unstructured":"Shukla N, Levine MF, Gundem G, Domenico D, Spitzer B, Bouvier N, et al. Feasibility of whole genome and transcriptome profiling in pediatric and young adult cancers. Nat Commun. 2022;13(1):2485.","journal-title":"Nat Commun"},{"issue":"11","key":"6219_CR7","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1038\/s41591-020-1072-4","volume":"26","author":"M Wong","year":"2020","unstructured":"Wong M, Mayoh C, Lau LMS, Khuong-Quang DA, Pinese M, Kumar A, et al. Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer. Nat Med. 2020;26(11):1742\u201353.","journal-title":"Nat Med"},{"key":"6219_CR8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.ejca.2022.09.001","volume":"175","author":"KPS Langenberg","year":"2022","unstructured":"Langenberg KPS, Meister MT, Bakhuizen JJ, Boer JM, van Eijkelenburg NKA, Hulleman E, et al. Implementation of paediatric precision oncology into clinical practice: the Individualized therapies for children with cancer program \u2018iTHER\u2019. Eur J Cancer. 2022;175:311\u201325.","journal-title":"Eur J Cancer"},{"key":"6219_CR9","doi-asserted-by":"publisher","unstructured":"Wadensten E, Wessman S, Abel F, Diaz De St\u00e5hl T, Tesi B, Orsmark Pietras C et al. Diagnostic Yield From a Nationwide Implementation of Precision Medicine for all Children With Cancer. JCO Precis Oncol [Internet]. 2023;(7). https:\/\/doi.org\/10.1200\/PO.23.00039.","DOI":"10.1200\/PO.23.00039"},{"key":"6219_CR10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.semcancer.2021.06.018","volume":"84","author":"R Rosenquist","year":"2022","unstructured":"Rosenquist R, Cuppen E, Buettner R, Caldas C, Dreau H, Elemento O, et al. Clinical utility of whole-genome sequencing in precision oncology. Semin Cancer Biol. 2022;84:32\u20139.","journal-title":"Semin Cancer Biol"},{"key":"6219_CR11","doi-asserted-by":"crossref","unstructured":"Melton C, Reuter JA, Spacek DV, Snyder M. Recurrent somatic mutations in regulatory regions of human cancer genomes. Nature Genetics 2015 47:7 [Internet]. 2015 Jun 8 [cited 2023 Sep 13];47(7):710\u20136. https:\/\/www.nature.com\/articles\/ng.3332.","DOI":"10.1038\/ng.3332"},{"issue":"7793","key":"6219_CR12","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/s41586-020-1969-6","volume":"578","author":"LA Aaltonen","year":"2020","unstructured":"Aaltonen LA, Abascal F, Abeshouse A, Aburatani H, Adams DJ, Agrawal N, et al. Pan-cancer analysis of whole genomes. Nature. 2020;578(7793):82\u201393.","journal-title":"Nature"},{"key":"6219_CR13","doi-asserted-by":"crossref","unstructured":"Fredriksson NJ, Ny L, Nilsson JA, Larsson E. Systematic analysis of noncoding somatic mutations and gene expression alterations across 14 tumor types. Nature Genetics. 2014 46:12 [Internet]. 2014 Nov 10 [cited 2023 Sep 13];46(12):1258\u201363. https:\/\/www.nature.com\/articles\/ng.3141.","DOI":"10.1038\/ng.3141"},{"key":"6219_CR14","unstructured":"https:\/\/www.chathamhouse.org\/about-us\/chatham-house-rule. Accessed 21 Dec. 2023."},{"issue":"1","key":"6219_CR15","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1748-5908-6-42","volume":"6","author":"S Michie","year":"2011","unstructured":"Michie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011;6(1):42.","journal-title":"Implement Sci"},{"issue":"2","key":"6219_CR16","doi-asserted-by":"publisher","first-page":"317","DOI":"10.3390\/genes12020317","volume":"12","author":"S Best","year":"2021","unstructured":"Best S, Long JC, Gaff C, Braithwaite J, Taylor N. Investigating the adoption of Clinical Genomics in Australia. An implementation Science Case Study. Genes (Basel). 2021;12(2):317.","journal-title":"Genes (Basel)"},{"issue":"2","key":"6219_CR17","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/opo.12782","volume":"41","author":"D Spillane","year":"2021","unstructured":"Spillane D, Courtenay M, Chater A, Family H, Whitaker A, Acton JH. Factors influencing the prescribing behaviour of independent prescriber optometrists: a qualitative study using the theoretical domains Framework. Ophthalmic Physiol Opt. 2021;41(2):301\u201315.","journal-title":"Ophthalmic Physiol Opt"},{"issue":"3","key":"6219_CR18","doi-asserted-by":"publisher","first-page":"e044114","DOI":"10.1136\/bmjopen-2020-044114","volume":"11","author":"A Chater","year":"2021","unstructured":"Chater A, Milton S, Green J, Gilworth G, Roposch A. Understanding physician behaviour in the 6\u20138 weeks hip check in primary care: a qualitative study using the COM-B. BMJ Open. 2021;11(3):e044114.","journal-title":"BMJ Open"},{"key":"6219_CR19","doi-asserted-by":"crossref","unstructured":"Bingham AJ, Witkowsky P. Deductive and inductive approaches to qualitative data analysis. In: Vanover C, Mihas P, Saldana J, editors. Analyzing and interpreting qualitative data: after the interview. SAGE; 2022. pp. 133\u201346.","DOI":"10.3102\/1682697"},{"key":"6219_CR20","unstructured":"https:\/\/www.england.nhs.uk\/publication\/national-genomic-test-directories\/. Accessed 21 Dec. 2023."},{"issue":"1","key":"6219_CR21","doi-asserted-by":"publisher","first-page":"64","DOI":"10.34197\/ats-scholar.2021-0074OC","volume":"3","author":"J Chiarchiaro","year":"2022","unstructured":"Chiarchiaro J, Arnold RM, Ernecoff NC, Claxton R, Childers JW, Schell JO. Serious illness communication skills training during a global pandemic. ATS Sch. 2022;3(1):64\u201375.","journal-title":"ATS Sch"},{"issue":"8","key":"6219_CR22","doi-asserted-by":"publisher","first-page":"E717","DOI":"10.1001\/amajethics.2018.717","volume":"20","author":"Four Communication Skills from Psychiatry Useful in","year":"2018","unstructured":"Four Communication Skills from Psychiatry Useful in. Palliative Care and how to teach them. AMA J Ethics. 2018;20(8):E717\u2013723.","journal-title":"AMA J Ethics"},{"key":"6219_CR23","doi-asserted-by":"crossref","unstructured":"Bylund CL, Brown R, di Ciccone BL, Konopasek L. Facilitating skills practice in communication role-play sessions: essential elements and training facilitators. Handbook of communication in Oncology and Palliative Care. Oxford University Press; 2010. pp. 597\u2013606.","DOI":"10.1093\/acprof:oso\/9780199238361.003.0051"},{"key":"6219_CR24","unstructured":"https:\/\/www.genomicseducation.hee.nhs.uk. Accessed 21 Dec. 2023."},{"issue":"1","key":"6219_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1748-5908-4-11","volume":"4","author":"LC Li","year":"2009","unstructured":"Li LC, Grimshaw JM, Nielsen C, Judd M, Coyte PC, Graham ID. Evolution of Wenger\u2019s concept of community of practice. Implement Sci. 2009;4(1):11.","journal-title":"Implement Sci"}],"container-title":["BMC Medical Education"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12909-024-06219-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12909-024-06219-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12909-024-06219-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T19:01:49Z","timestamp":1730919709000},"score":10.244609,"resource":{"primary":{"URL":"https:\/\/bmcmededuc.biomedcentral.com\/articles\/10.1186\/s12909-024-06219-y"}},"issued":{"date-parts":[[2024,11,6]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["6219"],"URL":"https:\/\/doi.org\/10.1186\/s12909-024-06219-y","ISSN":["1472-6920"],"issn-type":[{"value":"1472-6920","type":"electronic"}],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"21 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Genome Research Limited Research Governance team, which oversees all work conducted by Wellcome Connecting Science, has undertaken an ethical assessment for this workshop and the collection and analysis of the data from this workshop. This Research Governance team have confirmed that this study does not constitute research and as such no further review was required from the organisation. Participants were informed in the original email invitation and in pre-workshop papers that de-identified data would be collected during the workshop and that this data would be analysed and published. This information stated that agreeing to attend and attendance on the day would be taken as consent for the data to be collected, analysed and reported. This information was also repeated in person at the beginning of the workshop. MB was present at the workshop to answer any questions and address any concerns including removal of any data from participants who preferred their de-identified information not be included in any reports.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1273"},{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T10:48:12Z","timestamp":1774522092580,"version":"3.50.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]},{"name":"Wellcome","award":["226699\/Z\/22\/Z"],"award-info":[{"award-number":["226699\/Z\/22\/Z"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Public Health"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Schools are called upon to use data-informed practice to support student health and well-being. However, they face implementation challenges including data accessibility and literacy. Data dashboards offer a method to address these challenges, thereby promoting data-informed practice. This paper reports on a pilot of The School Health Research Network Data Dashboard with secondary schools.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The Dashboard was piloted by three secondary schools (recruited by size; free school meal entitlement) in Wales, UK. Interviews with school staff (\n N<\/jats:italic>\n \u2009=\u20097) and public health practitioners (\n N<\/jats:italic>\n \u2009=\u20096) were conducted. Data were analysed thematically. Research design, including interview questions, analytical interpretation and code, and theme development utilised Complex Adaptive Systems as the conceptual framework.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n School staff had access to multiple data sets for health promotion but often lacked the time and capacity to utilise them. The Dashboard was perceived to be a user-friendly method of enhancing data accessibility and usability in secondary schools, providing appropriate training and guidance for school staff was available to avoid data misinterpretation. National roll-out of the Dashboard was supported if it aligned with the needs of schools and the wider education system.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The Dashboard presents an opportunity for data-informed health and well-being practice and could also support schools to meet education system requirements, providing school staff receive appropriate training. This paper offers novel practical, policy-relevant insights on the interaction of digital dashboards with school systems, capacity constraints, and professional learning needs and valuable insights for public health systems seeking to support data-informed practice in educational settings.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12889-026-26647-3","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:25:10Z","timestamp":1771399510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piloting a data dashboard to support data-informed health promotion in secondary schools: qualitative analysis of stakeholder interviews"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5288-6614","authenticated-orcid":false,"given":"J.","family":"Van Godwin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1284-9645","authenticated-orcid":false,"given":"S.","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Bowen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3388-8902","authenticated-orcid":false,"given":"H.","family":"Reed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4671-2797","authenticated-orcid":false,"given":"N.","family":"Page","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-4039","authenticated-orcid":false,"given":"M.","family":"Svobodova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3380-4966","authenticated-orcid":false,"given":"M.","family":"Boffey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9484-1729","authenticated-orcid":false,"given":"F.","family":"Rice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0254-3397","authenticated-orcid":false,"given":"Y.","family":"Shenderovich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-9825","authenticated-orcid":false,"given":"R.","family":"Bevan-Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3589-3681","authenticated-orcid":false,"given":"S.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6215-0870","authenticated-orcid":false,"given":"J.","family":"Segrott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"issue":"9801","key":"26647_CR1","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/S0140-6736(11)60827-1","volume":"378","author":"C Kieling","year":"2011","unstructured":"Kieling C, Baker-Henningham H, Belfer M, Conti G, Ertem I, Omigbodun O, et al. Child and adolescent mental health worldwide: evidence for action. Lancet. 2011;378(9801):1515\u201325.","journal-title":"Lancet"},{"key":"26647_CR2","doi-asserted-by":"publisher","first-page":"h4300","DOI":"10.1136\/bmj.h4300","volume":"351","author":"WM Were","year":"2015","unstructured":"Were WM, Daelmans B, Bhutta Z, Duke T, Bahl R, Boschi-Pinto C, et al. Children\u2019s health priorities and interventions. BMJ. 2015;351:h4300.","journal-title":"BMJ"},{"key":"26647_CR3","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.healthplace.2012.12.001","volume":"21","author":"C Bonell","year":"2013","unstructured":"Bonell C, Parry W, Wells H, Jamal F, Fletcher A, Harden A, et al. The effects of the school environment on student health: A systematic review of multi-level studies. Health Place. 2013;21:180\u201391.","journal-title":"Health Place"},{"key":"26647_CR4","doi-asserted-by":"publisher","first-page":"g3078","DOI":"10.1136\/bmj.g3078","volume":"348","author":"C Bonell","year":"2014","unstructured":"Bonell C, Humphrey N, Fletcher A, Moore L, Anderson R, Campbell R. Why schools should promote students\u2019 health and wellbeing. BMJ. 2014;348:g3078.","journal-title":"BMJ"},{"issue":"10","key":"26647_CR5","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1111\/j.1746-1561.2011.00632.x","volume":"81","author":"CE Basch","year":"2011","unstructured":"Basch CE. Healthier students are better learners: a missing link in school reforms to close the achievement gap. J Sch Health. 2011;81(10):593\u20138.","journal-title":"J Sch Health"},{"key":"26647_CR6","unstructured":"WHO. Promoting health through schools: report of a WHO expert committee on comprehensive school health education and promotion. World Health Organization Technical Report Series no. 870. Geneva; 1997. https:\/\/www.who.int\/publications\/i\/item\/WHO-TRS-870."},{"key":"26647_CR7","unstructured":"WHO. Making every school a health-promoting school: implementation guidance. World Health Organization. Geneva; 2021. https:\/\/www.who.int\/publications\/i\/item\/9789240025073."},{"key":"26647_CR8","doi-asserted-by":"publisher","DOI":"10.4324\/9780429280696","volume-title":"The educators\u2019 guide to whole-school wellbeing: A practical guide to getting started, best-practice process and effective implementation","author":"DM Quinlan","year":"2020","unstructured":"Quinlan DM, Hone LC. The educators\u2019 guide to whole-school wellbeing: A practical guide to getting started, best-practice process and effective implementation. London: Routledge; 2020."},{"issue":"1","key":"26647_CR9","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1186\/s12889-019-7510-x","volume":"19","author":"PE Jessiman","year":"2019","unstructured":"Jessiman PE, Campbell R, Jago R, Van Sluijs EMF, Newbury-Birch D. A qualitative study of health promotion in academy schools in England. BMC Public Health. 2019;19(1):1186.","journal-title":"BMC Public Health"},{"issue":"4","key":"26647_CR10","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1002\/berj.3861","volume":"49","author":"SJ Long","year":"2023","unstructured":"Long SJ, Hawkins J, Murphy S, Moore G. School health and wellbeing and National education system reform: A qualitative study. Br Educ Res J. 2023;49(4):674\u201392.","journal-title":"Br Educ Res J"},{"key":"26647_CR11","doi-asserted-by":"publisher","unstructured":"Chambers S, Haughton D, Mabelis J, Brown J, Inchley J. Feasibility of using health and wellbeing data for school planning: the SHINE pilot in Scotland. Health Promot Int. 2022;37(6):daac149. https:\/\/doi.org\/10.1093\/heapro\/daac149.","DOI":"10.1093\/heapro\/daac149"},{"issue":"3","key":"26647_CR12","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1093\/her\/cyad002","volume":"38","author":"R Brown","year":"2023","unstructured":"Brown R, Van Godwin J, Edwards A, Burdon M, Moore G. A qualitative exploration of stakeholder perspectives on the implementation of a whole school approach to mental health and emotional well-being in Wales. Health Educ Res. 2023;38(3):241\u201353.","journal-title":"Health Educ Res"},{"issue":"3","key":"26647_CR13","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1080\/00131881.2019.1625716","volume":"61","author":"K Schildkamp","year":"2019","unstructured":"Schildkamp K. Data-based decision-making for school improvement: research insights and gaps. Educ Res. 2019;61(3):257\u201373.","journal-title":"Educ Res"},{"key":"26647_CR14","doi-asserted-by":"publisher","first-page":"482","DOI":"10.5334\/ijic.ICIC24229","volume":"25","author":"B Clarke","year":"2025","unstructured":"Clarke B, Anderson D, Rallapalli G, McCluney J, McWilliams P, Corrigan D, et al. Delivering a population health profile for pilot area integrated partnership board (AIPB) in Northern Ireland through development of a dashboard. Int J Integr Care. 2025;25:482.","journal-title":"Int J Integr Care"},{"issue":"1","key":"26647_CR15","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1177\/23998083241245759","volume":"52","author":"Y Nidam","year":"2025","unstructured":"Nidam Y, Gibson R, Houston-Read R, Picard M, Gavin V. Practicing data inclusion: Co-creation of an urban data dashboard. Environ Plan B Urban Anal City Sci. 2025;52(1):7\u201325.","journal-title":"Environ Plan B Urban Anal City Sci"},{"issue":"2","key":"26647_CR16","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1080\/10550887.2017.1291051","volume":"36","author":"AT Ramsey","year":"2017","unstructured":"Ramsey AT, Baumann A, Patterson DSW, Yan Y, Cooper B, Proctor E. The need for data-informed clinical supervision in substance use disorder treatment. J Addict Dis. 2017;36(2):117\u201326.","journal-title":"J Addict Dis"},{"issue":"1","key":"26647_CR17","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s41239-021-00313-7","volume":"19","author":"T Susnjak","year":"2022","unstructured":"Susnjak T, Ramaswami GS, Mathrani A. Learning analytics dashboard: a tool for providing actionable insights to learners. Int J Educ Technol High Educ. 2022;19(1):12.","journal-title":"Int J Educ Technol High Educ"},{"issue":"4","key":"26647_CR18","first-page":"61","volume":"21","author":"S Michaeli","year":"2020","unstructured":"Michaeli S, Kroparo D, Hershkovitz A. Teachers\u2019 use of education dashboards and professional growth. Int Rev Res Open Distrib Learn. 2020;21(4):61\u201378.","journal-title":"Int Rev Res Open Distrib Learn"},{"issue":"4","key":"26647_CR19","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1097\/PHH.0000000000001746","volume":"29","author":"NW Anderson","year":"2023","unstructured":"Anderson NW, Russ SA, Eisenberg D, Halfon N. Dashboards as mechanisms for community empowerment: developing a prototype for child and adolescent Well-being in California. J Public Health Manag Pract. 2023;29(4):529\u201338.","journal-title":"J Public Health Manag Pract"},{"issue":"10","key":"26647_CR20","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1016\/j.socscimed.2010.01.034","volume":"70","author":"N Keshavarz","year":"2010","unstructured":"Keshavarz N, Nutbeam D, Rowling L, Khavarpour F. Schools as social complex adaptive systems: a new way to understand the challenges of introducing the health promoting schools concept. Soc Sci Med. 2010;70(10):1467\u201374.","journal-title":"Soc Sci Med"},{"issue":"1","key":"26647_CR21","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s11121-018-0969-3","volume":"22","author":"S Murphy","year":"2021","unstructured":"Murphy S, Littlecott H, Hewitt G, MacDonald S, Roberts J, Bishop J, et al. A transdisciplinary complex adaptive systems (T-CAS) approach to developing a National school-Based culture of prevention for health improvement: the school health research network (SHRN) in Wales. Prev Sci. 2021;22(1):50\u201361.","journal-title":"Prev Sci"},{"key":"26647_CR22","doi-asserted-by":"publisher","unstructured":"Page N, Liu S, Morgan K, Angel L, Ogada E, Roberts C et al. Data resource profile: the school health research network (SHRN) student health and Well-being (SHW) survey of 11\u201316-year-olds (2017\u20132023). Int J Epidemiol.\u00a02024;53(6). https:\/\/doi.org\/10.1093\/ije\/dyae161.","DOI":"10.1093\/ije\/dyae161"},{"key":"26647_CR23","unstructured":"Welsh Government. https:\/\/mylocalschool.gov.wales\/."},{"key":"26647_CR24","unstructured":"Public Health Wales. Welsh Network of Healthy School Schemes https:\/\/ https:\/\/phw.nhs.wales\/services-and-teams\/welsh-network-of-healthy-school-schemes\/ : Public Health Wales."},{"issue":"4","key":"26647_CR25","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1080\/2159676X.2019.1628806","volume":"11","author":"V Braun","year":"2019","unstructured":"Braun V, Clarke V. Reflecting on reflexive thematic analysis. QQual Res Sport Exerc Health. 2019;11(4):589\u201397.","journal-title":"QQual Res Sport Exerc Health"},{"issue":"2","key":"26647_CR26","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1191\/1478088706qp063oa","volume":"3","author":"V Braun","year":"2006","unstructured":"Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77\u2013101.","journal-title":"Qual Res Psychol"},{"issue":"3\u20134","key":"26647_CR27","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s10464-009-9229-9","volume":"43","author":"P Hawe","year":"2009","unstructured":"Hawe P, Shiell A, Riley T. Theorising interventions as events in systems. Am J Community Psychol. 2009;43(3\u20134):267\u201376.","journal-title":"Am J Community Psychol"},{"issue":"1","key":"26647_CR28","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1186\/s12889-023-15713-9","volume":"23","author":"E Widnall","year":"2023","unstructured":"Widnall E, Hatch L, Albers PN, Hopkins G, Kidger J, de Vocht F, et al. Implementing a regional school health research network in England to improve adolescent health and well-being, a qualitative process evaluation. BMC Public Health. 2023;23(1):745.","journal-title":"BMC Public Health"},{"key":"26647_CR29","unstructured":"Welsh Government. Curriculum for Wales Available from: https:\/\/hwb.gov.wales\/curriculum-for-wales. \/ [Accessed 20th June 2024]2020 [Available from: https:\/\/hwb.gov.wales\/curriculum-for-wales\/."},{"key":"26647_CR30","unstructured":"Welsh Government. Framework on embedding a whole-school approach to emotional and mental well-being. [Available from: https:\/\/www.gov.wales\/framework-embedding-whole-school-approach-emotional-and-mental-wellbeing. [Accessed 20th June 2024].2021 [Available from: https:\/\/www.gov.wales\/framework-embedding-whole-school-approach-emotional-and-mental-wellbeing."},{"issue":"1","key":"26647_CR31","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/rev3.3246","volume":"9","author":"GA Koh","year":"2021","unstructured":"Koh GA, Askell-Williams H. Sustainable school\u2010improvement in complex adaptive systems: a scoping review. Rev Educ. 2021;9(1):281\u2013314.","journal-title":"Rev Educ"},{"issue":"3","key":"26647_CR32","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1093\/pubmed\/fdt103","volume":"36","author":"S Dewhirst","year":"2013","unstructured":"Dewhirst S, Pickett K, Speller V, Shepherd J, Byrne J, Almond P, et al. Are trainee teachers being adequately prepared to promote the health and well-being of school children? A survey of current practice. J Public Health (Oxf). 2013;36(3):467\u201375.","journal-title":"J Public Health (Oxf)"},{"issue":"1","key":"26647_CR33","doi-asserted-by":"publisher","first-page":"1946928","DOI":"10.1080\/17482631.2021.1946928","volume":"16","author":"D Byrne","year":"2021","unstructured":"Byrne D, Carthy DA. A qualitative exploration of post-primary educators\u2019 attitudes regarding the promotion of student wellbeing. Int J Qual Stud Health Well-being. 2021;16(1):1946928.","journal-title":"Int J Qual Stud Health Well-being"},{"key":"26647_CR34","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.tate.2017.10.020","volume":"69","author":"J Byrne","year":"2018","unstructured":"Byrne J, Rietdijk W, Pickett K. Teachers as health promoters: factors that influence early career teachers to engage with health and wellbeing education. Teach Teach Educ. 2018;69:289\u201399.","journal-title":"Teach Teach Educ"},{"key":"26647_CR35","doi-asserted-by":"publisher","unstructured":"Sivkovych H, Slyvka L, Hamerska I. Pre-service teachers training for efficient health promoting school activities performance. Adv Educ. 7(16):88\u201397. https:\/\/doi.org\/10.20535\/2410-8286.216792.","DOI":"10.20535\/2410-8286.216792"},{"issue":"3","key":"26647_CR36","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1177\/2373379916644449","volume":"2","author":"J Byrne","year":"2016","unstructured":"Byrne J, Pickett K, Rietdijk W, Shepherd J, Grace M, Roderick P. A longitudinal study to explore the impact of preservice teacher health training on early career teachers\u2019 roles as health promoters. Pedagogy Health Promot. 2016;2(3):170\u201383.","journal-title":"Pedagogy Health Promot"},{"issue":"1","key":"26647_CR37","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1177\/1356389018803219","volume":"25","author":"GF Moore","year":"2019","unstructured":"Moore GF, Evans RE, Hawkins J, Littlecott H, Melendez-Torres GJ, Bonell C, et al. From complex social interventions to interventions in complex social systems: future directions and unresolved questions for intervention development and evaluation. Evaluation (Lond). 2019;25(1):23\u201345.","journal-title":"Evaluation (Lond)"},{"issue":"4","key":"26647_CR38","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1108\/HE-07-2013-0031","volume":"114","author":"R Preiser","year":"2014","unstructured":"Preiser R, Struthers P, Mohamed S, Cameron N, Lawrence E. External stakeholders and health promoting schools: complexity and practice in South Africa. Health Educ. 2014;114(4):260\u201370.","journal-title":"Health Educ"},{"key":"26647_CR39","unstructured":"Page N, Angel L, Ogada E, Young H, Murphy S. Student health and wellbeing in wales: report of the 2021\/22 health behaviour in school-aged children survey and school health research network student health and wellbeing survey. Cardiff, UK: Cardiff University; 2023."}],"container-title":["BMC Public Health"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12889-026-26647-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-026-26647-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-026-26647-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T09:47:13Z","timestamp":1774518433000},"score":10.130024,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12889-026-26647-3"}},"issued":{"date-parts":[[2026,2,18]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["26647"],"URL":"https:\/\/doi.org\/10.1186\/s12889-026-26647-3","ISSN":["1471-2458"],"issn-type":[{"value":"1471-2458","type":"electronic"}],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"31 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Jeremy Segrott, Hayley Reed, and Nicholas Page led the early design and development of the SHRN data dashboard, with Martina Svobodova and Maria Boffey also contributing at this stage. Fran Rice, Yulia Shenderovich, Rhys Bevan Jones, and Simon Murphy served on the steering group, providing support and guidance throughout development. Nicholas Page and Maria Boffey are funded by SHRN, and Simon Murphy was its director during the research. The pilot study itself was conducted by Jordan Van Godwin, Brianna Bowen, and Sara Long, who were not involved in the dashboard\u2019s design or employed by SHRN.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"987"},{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:47:54Z","timestamp":1787870874526,"version":"build-2784847793"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["221616"],"award-info":[{"award-number":["221616"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Antimicrob Resist Infect Control"],"abstract":"Abstract<\/jats:title>\n The use of antimicrobials in Thailand has been reported as one of the highest in the world in human and animal sectors. Our engagement project aimed to improve our understanding of the issue of antimicrobial use and antimicrobial resistance (AMR) among adult Thai communities, and co-create locally relevant solutions to AMR, especially those focusing on raising awareness to improve related policies in Thailand.<\/jats:p>\n We conducted a series of online and in-person \u2018conversations\u2019 according to Wellcome\u2019s \u2018Responsive Dialogues\u2019 engagement approach, designed to bring together different voices to understand complex AMR problems and find potential solutions. This approach enabled key AMR stakeholders and policy makers to hear directly from communities and members of the public, and vice versa. Conversations events took place between 25 November 2020 and 8 July 2022, and we engaged 179 AMR key stakeholders and members of the public across Thailand.<\/jats:p>\n The issues found were: there were quite a lot of misunderstandings around antimicrobials and AMR; participants felt that communications and engagement around antimicrobial resistance had limited reach and impact; asking for and taking antibiotics for self-limiting ailments is a social norm in Thailand; and there appeared to be a wide availability of cheap antimicrobials. To mitigate the spread of AMR, participants suggested that the messages around AMR should be tailored to the target audience, there should be more initiatives to increase general health literacy, there should be increased availability of AMR related information at the local level and there should be increased local leadership of AMR mitigation efforts.<\/jats:p>\n \n Trial registration\u00a0<\/jats:bold>\n Thaiclinicaltrials.org registration: TCTR20210528003 (28\/05\/2021).\n <\/jats:p>","DOI":"10.1186\/s13756-024-01416-2","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T08:01:37Z","timestamp":1720080097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Embedding community and public voices in co-created solutions to mitigate antimicrobial resistance (AMR) in Thailand using the \u2018Responsive Dialogues\u2019 public engagement framework"],"prefix":"10.1186","volume":"13","author":[{"given":"Tassawan","family":"Poomchaichote","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niyada","family":"Kiatying-Angsulee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanpong","family":"Boonthaworn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhensri","family":"Naemiratch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supanat","family":"Ruangkajorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravikanya","family":"Prapharsavat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaiwat","family":"Thirapantu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karnjariya","family":"Sukrung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Osterrieder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaik Yeong","family":"Cheah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"issue":"7","key":"1416_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1179\/2047773215y.0000000030[publishedOnlineFirst:20150907]","volume":"109","author":"F Prestinaci","year":"2015","unstructured":"Prestinaci F, Pezzotti P, Pantosti A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog Glob Health. 2015;109(7):309\u201318. https:\/\/doi.org\/10.1179\/2047773215y.0000000030[publishedOnlineFirst:20150907].","journal-title":"Pathog Glob Health"},{"issue":"3","key":"1416_CR2","doi-asserted-by":"publisher","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482[publishedOnlineFirst:20180626]","volume":"4","author":"WC Reygaert","year":"2018","unstructured":"Reygaert WC. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol. 2018;4(3):482\u2013501. https:\/\/doi.org\/10.3934\/microbiol.2018.3.482[publishedOnlineFirst:20180626].","journal-title":"AIMS Microbiol"},{"key":"1416_CR3","doi-asserted-by":"publisher","first-page":"106103","DOI":"10.1016\/j.ejps.2021.106103","volume":"170","author":"T Pulingam","year":"2022","unstructured":"Pulingam T, Parumasivam T, Gazzali AM, et al. Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome. Eur J Pharm Sci. 2022;170:106103. https:\/\/doi.org\/10.1016\/j.ejps.2021.106103.","journal-title":"Eur J Pharm Sci"},{"issue":"10325","key":"1416_CR4","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","volume":"399","author":"CJL Murray","year":"2022","unstructured":"Murray CJL, Ikuta KS, Sharara F, et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022;399(10325):629\u201355. https:\/\/doi.org\/10.1016\/S0140-6736(21)02724-0.","journal-title":"Lancet"},{"issue":"1","key":"1416_CR5","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s12992-023-00930-z","volume":"19","author":"YA Adebisi","year":"2023","unstructured":"Adebisi YA. Balancing the risks and benefits of antibiotic use in a globalized world: the ethics of antimicrobial resistance. Glob Health. 2023;19(1):27. https:\/\/doi.org\/10.1186\/s12992-023-00930-z.","journal-title":"Glob Health"},{"key":"1416_CR6","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/978-3-030-27874-8_262020","volume-title":"Ethics and Drug Resistance: Collective Responsibility for Global Public Health","author":"J Littmann","year":"2020","unstructured":"Littmann J, Viens AM, Silva DS. The super-wicked problem of antimicrobial resistance. In: Jamrozik E, Selgelid M, editors. Ethics and Drug Resistance: Collective Responsibility for Global Public Health. Cham: Springer International Publishing; 2020. p. 421\u201343. https:\/\/doi.org\/10.1007\/978-3-030-27874-8_262020."},{"key":"1416_CR7","doi-asserted-by":"publisher","unstructured":"Varadan SR, Chandler CIR, Weed K, et al. A just transition for antimicrobial resistance: planning for an equitable and sustainable future with antimicrobial resistance. Lancet. 2023. https:\/\/doi.org\/10.1016\/S0140-6736(23)01687-2.","DOI":"10.1016\/S0140-6736(23)01687-2"},{"issue":"4","key":"1416_CR8","doi-asserted-by":"publisher","first-page":"e012874","DOI":"10.1136\/bmjgh-2023-012874","volume":"9","author":"P Sunil","year":"2024","unstructured":"Sunil P, Bipin A, Tess J, et al. Interventions to address antimicrobial resistance: an ethical analysis of key tensions and how they apply in low- income and middle-income countries. BMJ Glob Health. 2024;9(4):e012874. https:\/\/doi.org\/10.1136\/bmjgh-2023-012874.","journal-title":"BMJ Glob Health"},{"key":"1416_CR9","unstructured":"The World Bank. The World Bank in Thailand 2023. [Available from: https:\/\/www.worldbank.org\/en\/country\/thailand Accessed 22 Apr 2024]."},{"key":"1416_CR10","unstructured":"Worldometer. Thailand Population 2023 [Available from: https:\/\/www.worldometers.info\/world-population\/thailand-population\/. Accessed 22 April 2024]."},{"key":"1416_CR11","doi-asserted-by":"publisher","unstructured":"Lim C, Takahashi E, Hongsuwan M, et al. Epidemiology and burden of multidrug-resistant bacterial infection in a developing country. Elife 2016;5 https:\/\/doi.org\/10.7554\/eLife.18082 [published Online First: 2016\/09\/07]","DOI":"10.7554\/eLife.18082"},{"issue":"9","key":"1416_CR12","doi-asserted-by":"publisher","first-page":"ofac305","DOI":"10.1093\/ofid\/ofac305","volume":"9","author":"C Lim","year":"2022","unstructured":"Lim C, Teparrukkul P, Nuntalohit S, et al. Excess mortality attributable to hospital-acquired antimicrobial-resistant infections: a 2-year prospective surveillance study in Northeast Thailand. Open Forum Infect Dis. 2022;9(9):ofac305. https:\/\/doi.org\/10.1093\/ofid\/ofac305. published Online First: 20220620.","journal-title":"Open Forum Infect Dis"},{"issue":"8","key":"1416_CR13","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1093\/jac\/dkz185","volume":"74","author":"D Limmathurotsakul","year":"2019","unstructured":"Limmathurotsakul D, Sandoe JAT, Barrett DC, et al. \u201cAntibiotic footprint\u201d as a communication tool to aid reduction of antibiotic consumption. J Antimicrob Chemother. 2019;74(8):2122\u20137. https:\/\/doi.org\/10.1093\/jac\/dkz185. published Online First: 2019\/05\/11.","journal-title":"J Antimicrob Chemother"},{"issue":"2","key":"1416_CR14","doi-asserted-by":"publisher","first-page":"94","DOI":"10.2471\/BLT.17.195834[publishedOnlineFirst:2018\/02\/07]","volume":"96","author":"G Wongsuvan","year":"2018","unstructured":"Wongsuvan G, Wuthiekanun V, Hinjoy S, et al. Antibiotic use in poultry: a survey of eight farms in Thailand. Bull World Health Organ. 2018;96(2):94\u2013100. https:\/\/doi.org\/10.2471\/BLT.17.195834[publishedOnlineFirst:2018\/02\/07].","journal-title":"Bull World Health Organ"},{"key":"1416_CR15","unstructured":"World Health Organization. WHO report on surveillance of antibiotic consumption: 2016\u20132018 early implementation. 2018."},{"key":"1416_CR16","unstructured":"Nundy M, Bhatt P (2022). The Health System in the Kingdom of Thailand: Reforms, achievements, and challenges. (CSEP Working Paper 45). Centre for Social and Economic Progress. Available from: https:\/\/csep.org\/working-paper\/health-system-in-the-kingdom-of-thailand-reforms-acheivements-and-challenges\/2022."},{"key":"1416_CR17","unstructured":"World Health Organization. Primary health care systems (PRIMASYS): case study from Thailand, abridged version. 2017. Available from: https:\/\/ahpsr.who.int\/publications\/i\/item\/primasys-abridged-case-study-from-thailand2017."},{"key":"1416_CR18","doi-asserted-by":"publisher","unstructured":"Siltrakool B, Berrou I, Griffiths D, et al. Antibiotics' use in Thailand: community pharmacists' knowledge, attitudes and practices. Antibiotics (Basel) 2021;10(2). https:\/\/doi.org\/10.3390\/antibiotics10020137 [published Online First: 20210131]","DOI":"10.3390\/antibiotics10020137"},{"key":"1416_CR19","first-page":"S72","volume":"29","author":"S Pumtong","year":"2020","unstructured":"Pumtong S, Suwannaprom P, Suttajit S, et al. Irrational antibiotic use and distribution in the Thai community: a complex situation in need of integrative solution - \u0e2a\u0e16\u0e32\u0e19\u0e01\u0e32\u0e23\u0e13\u0e4c\u0e01\u0e32\u0e23\u0e43\u0e0a\u0e49\u0e41\u0e25\u0e30\u0e01\u0e23\u0e30\u0e08\u0e32\u0e22\u0e22\u0e32\u0e1b\u0e0f\u0e34\u0e0a\u0e35\u0e27\u0e19\u0e30\u0e43\u0e19\u0e0a\u0e38\u0e21\u0e0a\u0e19\u0e02\u0e2d\u0e07\u0e44\u0e17\u0e22: \u0e1b\u0e31\u0e0d\u0e2b\u0e32\u0e0b\u0e31\u0e1a\u0e0b\u0e49\u0e2d\u0e19\u0e17\u0e35\u0e48\u0e15\u0e49\u0e2d\u0e07\u0e08\u0e31\u0e14\u0e01\u0e32\u0e23\u0e41\u0e1a\u0e1a\u0e1a\u0e39\u0e23\u0e13\u0e32\u0e01\u0e32\u0e23. J Health Sci Thailand. 2020;29:S72\u201381.","journal-title":"J Health Sci Thailand"},{"issue":"4","key":"1416_CR20","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ajic.2017.09.022","volume":"46","author":"N Sutthiruk","year":"2018","unstructured":"Sutthiruk N, Considine J, Hutchinson A, et al. Thai clinicians\u2019 attitudes toward antimicrobial stewardship programs. Am J Infect Control. 2018;46(4):425\u201330. https:\/\/doi.org\/10.1016\/j.ajic.2017.09.022.","journal-title":"Am J Infect Control"},{"issue":"4","key":"1416_CR21","doi-asserted-by":"publisher","first-page":"e0298972","DOI":"10.1371\/journal.pone.0298972","volume":"19","author":"M Sunpuwan","year":"2024","unstructured":"Sunpuwan M, Punpuing S, Jaruruengpaisan W, et al. Understanding antibiotic use in the community setting in Thailand: Does communication matter? PLoS ONE. 2024;19(4):e0298972. https:\/\/doi.org\/10.1371\/journal.pone.0298972.","journal-title":"PLoS ONE"},{"issue":"1","key":"1416_CR22","doi-asserted-by":"publisher","first-page":"2298940","DOI":"10.1080\/17441692.2023.2298940","volume":"19","author":"N Alhusein","year":"2024","unstructured":"Alhusein N, Charoenboon N, Wichuwaranan K, et al. The unseen use of antimicrobials: Drivers of human antibiotic use in a community in Thailand and implications for surveillance. Glob Public Health. 2024;19(1):2298940. https:\/\/doi.org\/10.1080\/17441692.2023.2298940.","journal-title":"Glob Public Health"},{"key":"1416_CR23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2147\/dhps.S339808","volume":"14","author":"TZ Lin","year":"2022","unstructured":"Lin TZ, Jayasvasti I, Tiraphat S, et al. The predictors influencing the rational use of antibiotics among public sector: a community-based survey in Thailand. Drug Healthc Patient Saf. 2022;14:27\u201336. https:\/\/doi.org\/10.2147\/dhps.S339808.","journal-title":"Drug Healthc Patient Saf"},{"issue":"8","key":"1416_CR24","doi-asserted-by":"publisher","first-page":"e0220990","DOI":"10.1371\/journal.pone.0220990","volume":"14","author":"S Chanvatik","year":"2019","unstructured":"Chanvatik S, Kosiyaporn H, Lekagul A, et al. Knowledge and use of antibiotics in Thailand: A 2017 national household survey. PLoS ONE. 2019;14(8):e0220990. https:\/\/doi.org\/10.1371\/journal.pone.0220990. published Online First: 2019\/08\/10.","journal-title":"PLoS ONE"},{"issue":"1","key":"1416_CR25","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1186\/s12889-021-12237-y","volume":"21","author":"V Tangcharoensathien","year":"2021","unstructured":"Tangcharoensathien V, Chanvatik S, Kosiyaporn H, et al. Population knowledge and awareness of antibiotic use and antimicrobial resistance: results from national household survey 2019 and changes from 2017. BMC Pub Health. 2021;21(1):2188. https:\/\/doi.org\/10.1186\/s12889-021-12237-y.","journal-title":"BMC Pub Health"},{"key":"1416_CR26","doi-asserted-by":"publisher","unstructured":"Niyomyart A, Chow SK, Bualoy W, et al. Antibiotic knowledge, antibiotic resistance knowledge, and antibiotic use: A cross-sectional study among community members of Bangkok in Thailand. Antibiotics. 2023;12(8):1312. https:\/\/doi.org\/10.3390\/antibiotics12081312.","DOI":"10.3390\/antibiotics12081312"},{"issue":"4","key":"1416_CR27","doi-asserted-by":"publisher","first-page":"e001590","DOI":"10.1136\/bmjgh-2019-001590","volume":"4","author":"L Denyer Willis","year":"2019","unstructured":"Denyer Willis L, Chandler C. Quick fix for care, productivity, hygiene and inequality: reframing the entrenched problem of antibiotic overuse. BMJ Glob Health. 2019;4(4):e001590. https:\/\/doi.org\/10.1136\/bmjgh-2019-001590. published Online First: 2019\/09\/10.","journal-title":"BMJ Glob Health"},{"key":"1416_CR28","doi-asserted-by":"publisher","unstructured":"Lambraki IA, Chadag MV, Cousins M, et al. Factors impacting antimicrobial resistance in the South East Asian food system and potential places to intervene: A participatory, one health study. Front Microbiol 2023;13 https:\/\/doi.org\/10.3389\/fmicb.2022.992507","DOI":"10.3389\/fmicb.2022.992507"},{"key":"1416_CR29","unstructured":"Wellcome Trust (2021). Responsive Dialogues on drug resistant infections Version 2 2021. Available from: https:\/\/cms.wellcome.org\/sites\/default\/files\/2021-02\/responsive-dialogues-drug-resistant-infections-tollkit.pdf2021."},{"key":"1416_CR30","doi-asserted-by":"publisher","first-page":"188","DOI":"10.12688\/wellcomeopenres.17066.2","volume":"6","author":"T Poomchaichote","year":"2021","unstructured":"Poomchaichote T, Osterrieder A, Prapharsavat R, et al. \u201cAMR Dialogues\u201d: a public engagement initiative to shape policies and solutions on antimicrobial resistance (AMR) in Thailand. Wellcome Open Res. 2021;6:188. https:\/\/doi.org\/10.12688\/wellcomeopenres.17066.2. published Online First: 20220407.","journal-title":"Wellcome Open Res"},{"key":"1416_CR31","unstructured":"The Coordination and Integration Committee on Antimicrobial Resistance 2016 Thailand National Strategic Plan on Antimicrobial Resistance 2017\u20132021. Available from: https:\/\/rr-asia.woah.org\/wp-content\/uploads\/2020\/03\/thailand_thailands-national-strategic-plan-on-amr-2017-2021.pdf."},{"issue":"9","key":"1416_CR32","doi-asserted-by":"publisher","first-page":"661","DOI":"10.2471\/blt.20.280644","volume":"99","author":"N Sumpradit","year":"2021","unstructured":"Sumpradit N, Wongkongkathep S, Malathum K, et al. Thailand\u2019s national strategic plan on antimicrobial resistance: progress and challenges. Bull World Health Organ. 2021;99(9):661\u201373. https:\/\/doi.org\/10.2471\/blt.20.280644. published Online First: 20210701.","journal-title":"Bull World Health Organ"},{"key":"1416_CR33","unstructured":"Poomchaichote T, Praphasavat R. Embedding public and community voices in shaping Thailand\u2019s National Strategic Plan on Antimicrobial Resistance. 2022. Available from: https:\/\/youtu.be\/DPc9oCqwJCo2022."},{"key":"1416_CR34","unstructured":"Poomchaichote T, Boonthaworn K, Naemiratch B, et al. Summary of key findings of Antimicrobial Resistance Dialogues in Thailand (\u0e2a\u0e23\u0e38\u0e1b\u0e2a\u0e32\u0e23\u0e30\u0e2a\u0e33\u0e04\u0e31\u0e0d\u0e08\u0e32\u0e01\u0e42\u0e04\u0e23\u0e07\u0e01\u0e32\u0e23\u0e40\u0e2a\u0e27\u0e19\u0e32\u0e40\u0e23\u0e37\u0e48\u0e2d\u0e07\u0e40\u0e0a\u0e37\u0e49\u0e2d\u0e14\u0e37\u0e49\u0e2d\u0e22\u0e32\u0e43\u0e19\u0e1b\u0e23\u0e30\u0e40\u0e17\u0e28\u0e44\u0e17\u0e22) (1.0 date 20230611). 2023. 10.5281\/zenodo.8024656. Available from: https:\/\/zenodo.org\/records\/8024656."},{"key":"1416_CR35","unstructured":"Sumpradit N., Krobanan K., Youngkong S., et al. (2019). Mapping and prioritization of research on antimicrobial resistance in Thailand. Food and Drug Administration, Ministry of Public Health. Available from: https:\/\/amrthailand.net\/Report2019."},{"key":"1416_CR36","doi-asserted-by":"publisher","unstructured":"Osterrieder A, Ruangkajorn S, Cheah PY. Terms of reference for the Bangkok Health Research and Ethics Interest Group (HREIG). 2020. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.4312633.","DOI":"10.5281\/zenodo.4312633"},{"key":"1416_CR37","unstructured":"Thirapantu C, Sukrung K, Poomchaichote T, et al. Agenda of Antimicrobial Resistance (AMR) Dialogues in the North-eastern region of Thailand (1.0). 2023. 10.5281\/zenodo.8314771. Available from: https:\/\/doi.org\/10.5281\/zenodo.8314771."},{"issue":"4","key":"1416_CR38","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1080\/2159676X.2019.1628806","volume":"11","author":"V Braun","year":"2019","unstructured":"Braun V, Clarke V. Reflecting on reflexive thematic analysis. Qual Res Sport Exerc Health. 2019;11(4):589\u201397. https:\/\/doi.org\/10.1080\/2159676X.2019.1628806.","journal-title":"Qual Res Sport Exerc Health"},{"key":"1416_CR39","doi-asserted-by":"publisher","first-page":"j3415","DOI":"10.1136\/bmj.j2423","volume":"358","author":"N Sumpradit","year":"2017","unstructured":"Sumpradit N, Wongkongkathep S, Poonpolsup S, et al. New chapter in tackling antimicrobial resistance in Thailand. BMJ. 2017;358:j3415. https:\/\/doi.org\/10.1136\/bmj.j2423. published Online First: 2017\/09\/07.","journal-title":"BMJ"},{"issue":"sp1","key":"1416_CR40","first-page":"47","volume":"6","author":"Y Jeena","year":"2018","unstructured":"Jeena Y, Jeena R. \u201cBa Worn Santisook Project\u201d\u202f: A participatory model of Home, Temple, School for promote morality of 12 values, Chiang Mai. J MCU Peace Stud. 2018;6(sp1):47\u201360.","journal-title":"J MCU Peace Stud"},{"issue":"2","key":"1416_CR41","doi-asserted-by":"publisher","first-page":"502","DOI":"10.14456\/psruhss.2021.38","volume":"15","author":"Y Phongrod","year":"2021","unstructured":"Phongrod Y, Limsiriwong S, Tana S, et al. Model development of participatory process in moving forward B.W.R. principle (Home, Temple, School) in order to build strong and sustainable communities: case Study of Ban Khlong Toei Community, Bueng Kok Sub-district, Bangrakam District, Phitsanulok Province. Human Soc Sci J Pibulsongkram Rajabhat University. 2021;15(2):502\u201316. https:\/\/doi.org\/10.14456\/psruhss.2021.38.","journal-title":"Human Soc Sci J Pibulsongkram Rajabhat University"},{"issue":"7","key":"1416_CR42","doi-asserted-by":"publisher","first-page":"472","DOI":"10.2471\/BLT.14.030714","volume":"92","author":"S Wibulpolprasert","year":"2014","unstructured":"Wibulpolprasert S, Fleck F. Thailand\u2019s health ambitions pay off. Bull World Health Organ. 2014;92(7):472\u20133. https:\/\/doi.org\/10.2471\/BLT.14.030714.","journal-title":"Bull World Health Organ"},{"issue":"1","key":"1416_CR43","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1186\/s12889-019-7300-5","volume":"19","author":"M Sunpuwan","year":"2019","unstructured":"Sunpuwan M, Punpuing S, Jaruruengpaisan W, et al. What is in the drug packet?: access and use of non-prescribed poly-pharmaceutical packs (Yaa Chud) in the community in Thailand. BMC Pub Health. 2019;19(1):971. https:\/\/doi.org\/10.1186\/s12889-019-7300-5.","journal-title":"BMC Pub Health"},{"issue":"2","key":"1416_CR44","doi-asserted-by":"publisher","first-page":"NP2480","DOI":"10.1177\/1010539513479968","volume":"27","author":"S Arparsrithongsagul","year":"2015","unstructured":"Arparsrithongsagul S, Kulsomboon V, Zuckerman IH. Multidisciplinary perspective intervention with community involvement to decrease antibiotic sales in village groceries in Thailand. Asia Pac J Public Health. 2015;27(2):NP2480\u20138. https:\/\/doi.org\/10.1177\/1010539513479968.","journal-title":"Asia Pac J Public Health"},{"issue":"3","key":"1416_CR45","first-page":"270","volume":"99","author":"S Khamsarn","year":"2016","unstructured":"Khamsarn S, Nampoonsak Y, Busamaro S, et al. Epidemiology of antibiotic use and antimicrobial resistance in selected communities in Thailand. J Med Assoc Thai. 2016;99(3):270\u20135.","journal-title":"J Med Assoc Thai"},{"issue":"11","key":"1416_CR46","doi-asserted-by":"publisher","first-page":"2647","DOI":"10.1080\/17441692.2021.2003839","volume":"17","author":"J Mitchell","year":"2022","unstructured":"Mitchell J, Cooke P, Ahorlu C, et al. Community engagement: The key to tackling antimicrobial resistance (AMR) across a One Health context? Glob Public Health. 2022;17(11):2647\u201364. https:\/\/doi.org\/10.1080\/17441692.2021.2003839.","journal-title":"Glob Public Health"},{"issue":"11","key":"1416_CR47","doi-asserted-by":"publisher","first-page":"e0225172","DOI":"10.1371\/journal.pone.0225172","volume":"14","author":"S Chanvatik","year":"2019","unstructured":"Chanvatik S, Donnua S, Lekagul A, et al. Antibiotic use in mandarin production (Citrus reticulata Blanco) in major mandarin-producing areas in Thailand: A survey assessment. PLoS ONE. 2019;14(11):e0225172. https:\/\/doi.org\/10.1371\/journal.pone.0225172. published Online First: 20191113.","journal-title":"PLoS ONE"},{"key":"1416_CR48","unstructured":"Thamlikitkul V, Rattanaumpawan P, Boonyasiri A, et al. Operational actions of the Thailand antimicrobial resistance (AMR) containment and prevention program in response to the World Health Organization (WHO) Global Action Plan on AMR. J Health Syst Res. 2017;11(4):453\u201370."},{"issue":"8","key":"1416_CR49","doi-asserted-by":"publisher","first-page":"e028224","DOI":"10.1136\/bmjopen-2018-028224","volume":"9","author":"MJ Haenssgen","year":"2019","unstructured":"Haenssgen MJ, Charoenboon N, Zanello G, et al. Antibiotic knowledge, attitudes and practices: new insights from cross-sectional rural health behaviour surveys in low-income and middle-income South-East Asia. BMJ Open. 2019;9(8):e028224. https:\/\/doi.org\/10.1136\/bmjopen-2018-028224. published Online First: 20190820.","journal-title":"BMJ Open"},{"key":"1416_CR50","doi-asserted-by":"publisher","unstructured":"Prapharsavat R, Lim C, Sunthornsut P, et al. The utility of an AMR dictionary as an educational tool to improve public understanding of antimicrobial resistance [version 1; peer review: 1 approved]. Wellcome Open Res 2021;6(113) https:\/\/doi.org\/10.12688\/wellcomeopenres.16488.1","DOI":"10.12688\/wellcomeopenres.16488.1"},{"issue":"3","key":"1416_CR51","doi-asserted-by":"publisher","first-page":"e001239","DOI":"10.1136\/bmjgh-2018-001239","volume":"4","author":"B Huttner","year":"2019","unstructured":"Huttner B, Saam M, Moja L, et al. How to improve antibiotic awareness campaigns: findings of a WHO global survey. BMJ Glob Health. 2019;4(3):e001239. https:\/\/doi.org\/10.1136\/bmjgh-2018-001239.","journal-title":"BMJ Glob Health"},{"issue":"4","key":"1416_CR52","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/jppr.1801","volume":"52","author":"P Phueanpinit","year":"2022","unstructured":"Phueanpinit P, Siriwattanasakul N, Tichakorn P, et al. Knowledge and perceptions of outpatients regarding upper respiratory tract infections and awareness of an Antibiotics Smart Use campaign in Thailand. J Pharm Pract Res. 2022;52(4):294\u2013302. https:\/\/doi.org\/10.1002\/jppr.1801.","journal-title":"J Pharm Pract Res"},{"issue":"4","key":"1416_CR53","doi-asserted-by":"publisher","first-page":"216","DOI":"10.5281\/zenodo.8314771","volume":"35","author":"S Arnstein","year":"1969","unstructured":"Arnstein S. A ladder of citizen participation. J Am Plann Assoc. 1969;35(4):216\u201324. https:\/\/doi.org\/10.5281\/zenodo.8314771.","journal-title":"J Am Plann Assoc"},{"key":"1416_CR54","unstructured":"Health Policy and Systems Research on Antimicrobial Resistance Network (2021). Thailand\u2019s One Health Report on antimicrobial consumption and antimicrobial resistance in 2019. Available from: https:\/\/ihppthaigov.net\/publication\/thailands-one-health-report-on-antimicrobial-consumption-and-antimicrobial-resistance-in-20212021."},{"key":"1416_CR55","doi-asserted-by":"publisher","unstructured":"Tompson AC, Chandler CI (2021). Addressing antibiotic use: insights from social science around the world. Project report. London School of Hygiene & Tropical Medicine. Available from: https:\/\/doi.org\/10.17037\/PUBS.04659562 2021.","DOI":"10.17037\/PUBS.04659562"},{"issue":"1","key":"1416_CR56","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1186\/s12889-020-09033-5","volume":"20","author":"R King","year":"2020","unstructured":"King R, Hicks J, Rassi C, et al. A process for developing a sustainable and scalable approach to community engagement: community dialogue approach for addressing the drivers of antibiotic resistance in Bangladesh. BMC Public Health. 2020;20(1):950. https:\/\/doi.org\/10.1186\/s12889-020-09033-5.","journal-title":"BMC Public Health"},{"key":"1416_CR57","doi-asserted-by":"publisher","unstructured":"Mpundu M, Mathew P, Chanda R, et al. What would it take to move the global AMR agenda forward in the global South? 2023. https:\/\/doi.org\/10.1093\/oso\/9780192899477.003.0007 . Accessed 16 Apr 2024. Access 2023.","DOI":"10.1093\/oso\/9780192899477.003.0007"},{"issue":"12","key":"1416_CR58","doi-asserted-by":"publisher","first-page":"905","DOI":"10.2471\/blt.12.105445","volume":"90","author":"N Sumpradit","year":"2012","unstructured":"Sumpradit N, Chongtrakul P, Anuwong K, et al. Antibiotics Smart Use: a workable model for promoting the rational use of medicines in Thailand. Bull World Health Organ. 2012;90(12):905\u201313. https:\/\/doi.org\/10.2471\/blt.12.105445.","journal-title":"Bull World Health Organ"},{"issue":"4","key":"1416_CR59","doi-asserted-by":"publisher","DOI":"10.1016\/j.infpip.2023.100315","volume":"5","author":"N Shamas","year":"2023","unstructured":"Shamas N, Stokle E, Ashiru-Oredope D, et al. Challenges of implementing antimicrobial stewardship tools in Low to Middle Income Countries (LMICs). Infect Prev Pract. 2023;5(4): 100315. https:\/\/doi.org\/10.1016\/j.infpip.2023.100315.","journal-title":"Infect Prev Pract"},{"issue":"4","key":"1416_CR60","doi-asserted-by":"publisher","first-page":"100314","DOI":"10.1016\/j.infpip.2023.100314","volume":"5","author":"H Rickard","year":"2023","unstructured":"Rickard H, Watkin S, Baldwin N, et al. Antimicrobial resistance as a super wicked problem: how do we engage the public to be part of the solution. Infect Prev Pract. 2023;5(4):100314. https:\/\/doi.org\/10.1016\/j.infpip.2023.100314.","journal-title":"Infect Prev Pract"},{"key":"1416_CR61","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.jiph.2023.11.008","volume":"16","author":"AS Mukherjee","year":"2023","unstructured":"Mukherjee AS, Sahay S. Systems thinking based approaches to engage with health inequities shaping Antimicrobial Resistance in low and lower-middle-income countries. J Infect Pub Heal. 2023;16:129\u201333. https:\/\/doi.org\/10.1016\/j.jiph.2023.11.008.","journal-title":"J Infect Pub Heal"}],"container-title":["Antimicrobial Resistance & Infection Control"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13756-024-01416-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13756-024-01416-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13756-024-01416-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T08:03:13Z","timestamp":1720080193000},"score":10.094261,"resource":{"primary":{"URL":"https:\/\/aricjournal.biomedcentral.com\/articles\/10.1186\/s13756-024-01416-2"}},"issued":{"date-parts":[[2024,7,4]]},"references-count":61,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1416"],"URL":"https:\/\/doi.org\/10.1186\/s13756-024-01416-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.10.06.23296658","asserted-by":"object"}]},"ISSN":["2047-2994"],"issn-type":[{"value":"2047-2994","type":"electronic"}],"published":{"date-parts":[[2024,7,4]]},"assertion":[{"value":"14 November 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"},{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:33:41Z","timestamp":1789659221219,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,13]]},"group-title":"Cell Biology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome","award":["222810"],"award-info":[{"award-number":["222810"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome","award":["220780"],"award-info":[{"award-number":["220780"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome","award":["319314"],"award-info":[{"award-number":["319314"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome","award":["203149"],"award-info":[{"award-number":["203149"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome","award":["226791"],"award-info":[{"award-number":["226791"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Wellcome","award":["206211"],"award-info":[{"award-number":["206211"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"award":["BB\/X00705\/1"],"award-info":[{"award-number":["BB\/X00705\/1"]}],"id":[{"id":"https:\/\/ror.org\/00cwqg982","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"accepted":{"date-parts":[[2026,9,13]]},"abstract":"Summary<\/jats:title>\n \n Kinetochores are complex protein assemblies at centromeres that direct and regulate chromosome segregation\n 1<\/jats:sup>\n . During gamete formation by meiosis, kinetochore specialisations drive two sequential and distinct segregation events to partition half the genome to the offspring\n 2,3<\/jats:sup>\n . Age-dependent segregation errors in human oocytes are a major cause of reproductive failure and are linked to kinetochore dysfunction\n 4\u20136<\/jats:sup>\n , however the molecular composition and function of mammalian meiotic centromeric chromatin and kinetochores remains poorly defined. Here, we reconstitute vertebrate meiosis I and II centromeric chromatin using meiosis I and II endogenous proteins to uncover conserved regulators of chromosome segregation in mammalian meiosis. We find that, in addition to canonical kinetochore proteins, a specific subset of chromatin regulators is enriched on meiotic centromeric chromatin. We discover previously unrecognized kinetochore proteins conserved from frogs to mouse and humans and demonstrate their localisation at mammalian oocyte centromeres. Among these, we show that the newly identified centromeric protein HSPBAP1, is required to maintain chromosome integrity and ensure faithful segregation in both mouse and human oocytes. These findings define the composition of vertebrate meiotic kinetochores and uncover conserved factors that safeguard mammalian meiotic chromosome segregation, a highly error-prone process and major cause of aneuploidy and reproductive failure in humans\n 7<\/jats:sup>\n .\n <\/jats:p>","DOI":"10.64898\/2026.09.11.750869","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T13:10:11Z","timestamp":1789305011000},"source":"Crossref","is-referenced-by-count":0,"title":["Meiotic kinetochore reconstitution identifies chromosome segregation factors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-7441","authenticated-orcid":false,"given":"Gerard H.","family":"Pieper","sequence":"first","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh","family":"O\u2019Loughlin","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3806-6748","authenticated-orcid":false,"given":"Mansour","family":"Aboelenain","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"},{"name":"Theriogenology department, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8185-7280","authenticated-orcid":false,"given":"Lucy","family":"Munro","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1375-5491","authenticated-orcid":false,"given":"Kousik","family":"Sundararajan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-1158","authenticated-orcid":false,"given":"Elizabeth","family":"Torres-Arce","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina","family":"Lisichkina","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4376-8242","authenticated-orcid":false,"given":"Christos","family":"Spanos","sequence":"additional","affiliation":[{"name":"Discovery Research Platform for Hidden Cell Biology, School of Biological Sciences, University of Edinburgh, EH9 3BF"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-5215","authenticated-orcid":false,"given":"Tony","family":"Ly","sequence":"additional","affiliation":[{"name":"Molecular Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regenerative and Repair, University of Edinburgh, Edinburgh EH16 4TJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5885-7881","authenticated-orcid":false,"given":"Aaron F.","family":"Straight","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-9407","authenticated-orcid":false,"given":"Adele L.","family":"Marston","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"},{"name":"Discovery Research Platform for Hidden Cell Biology, School of Biological Sciences, University of Edinburgh, EH9 3BF"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091610403750000_2026.09.11.750869v1.1","first-page":"13.1","article-title":"The Four Causes: The Functional Architecture of Centromeres and Kinetochores","volume":"56","year":"2022","journal-title":"Annu. Rev. Genet"},{"key":"2026091610403750000_2026.09.11.750869v1.2","doi-asserted-by":"crossref","first-page":"102486","DOI":"10.1016\/j.ceb.2025.102486","article-title":"The functional organisation of the centromere and kinetochore during meiosis","volume":"94","year":"2025","journal-title":"Curr. Opin. Cell Biol"},{"key":"2026091610403750000_2026.09.11.750869v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature14097"},{"key":"2026091610403750000_2026.09.11.750869v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.09.006"},{"key":"2026091610403750000_2026.09.11.750869v1.5","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06633"},{"key":"2026091610403750000_2026.09.11.750869v1.6","doi-asserted-by":"publisher","DOI":"10.1242\/bio.016394"},{"key":"2026091610403750000_2026.09.11.750869v1.7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-072820-033609"},{"key":"2026091610403750000_2026.09.11.750869v1.8","doi-asserted-by":"publisher","DOI":"10.1101\/gad.255554.114"},{"key":"2026091610403750000_2026.09.11.750869v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/srep41926"},{"key":"2026091610403750000_2026.09.11.750869v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7321"},{"key":"2026091610403750000_2026.09.11.750869v1.11","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20190043"},{"key":"2026091610403750000_2026.09.11.750869v1.12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-083118-015143"},{"key":"2026091610403750000_2026.09.11.750869v1.13","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.devcel.2025.08.017","article-title":"Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation","volume":"61","year":"2026","journal-title":"Dev. Cell"},{"key":"2026091610403750000_2026.09.11.750869v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/nature10379"},{"key":"2026091610403750000_2026.09.11.750869v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.112"},{"key":"2026091610403750000_2026.09.11.750869v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1717509115"},{"key":"2026091610403750000_2026.09.11.750869v1.17","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.1494"},{"key":"2026091610403750000_2026.09.11.750869v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.09.011"},{"key":"2026091610403750000_2026.09.11.750869v1.19","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E09-05-0378"},{"key":"2026091610403750000_2026.09.11.750869v1.20","doi-asserted-by":"crossref","first-page":"e202412042","DOI":"10.1083\/jcb.202412042","article-title":"Interactions with multiple inner kinetochore proteins determine mitotic localization of FACT","volume":"224","year":"2025","journal-title":"J. Cell Biol"},{"key":"2026091610403750000_2026.09.11.750869v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00724-4"},{"key":"2026091610403750000_2026.09.11.750869v1.22","doi-asserted-by":"crossref","first-page":"e2000018","DOI":"10.1002\/bies.202000018","article-title":"Meiosis I Kinase Regulators: Conserved Orchestrators of Reductional Chromosome Segregation","volume":"42","year":"2020","journal-title":"BioEssays News Rev. Mol. Cell. Dev. Biol"},{"key":"2026091610403750000_2026.09.11.750869v1.23","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00418-024-02316-7","article-title":"MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase \u2013 anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte","volume":"162","year":"2024","journal-title":"Histochem. Cell Biol"},{"key":"2026091610403750000_2026.09.11.750869v1.24","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.17.4513"},{"key":"2026091610403750000_2026.09.11.750869v1.25","doi-asserted-by":"publisher","DOI":"10.1101\/gad.320705"},{"key":"2026091610403750000_2026.09.11.750869v1.26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707537104"},{"key":"2026091610403750000_2026.09.11.750869v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2006.12.045"},{"key":"2026091610403750000_2026.09.11.750869v1.28","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1242\/jcs.107.11.3005","article-title":"Meiosis-specific cell cycle regulation in maturing Xenopus oocytes","volume":"107","year":"1994","journal-title":"J. Cell Sci"},{"key":"2026091610403750000_2026.09.11.750869v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.09.005"},{"key":"2026091610403750000_2026.09.11.750869v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg330"},{"key":"2026091610403750000_2026.09.11.750869v1.31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1235"},{"key":"2026091610403750000_2026.09.11.750869v1.32","doi-asserted-by":"crossref","first-page":"9154","DOI":"10.1093\/nar\/gkab217","article-title":"RbAp46\/48LIN-53 and HAT-1 are required for initial CENP-AHCP-3 deposition and de novo holocentromere formation on artificial chromosomes in Caenorhabditis elegans embryos","volume":"49","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"2026091610403750000_2026.09.11.750869v1.33","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.162305"},{"key":"2026091610403750000_2026.09.11.750869v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01247-07"},{"key":"2026091610403750000_2026.09.11.750869v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/pcp\/pcae030"},{"key":"2026091610403750000_2026.09.11.750869v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.adv9309"},{"key":"2026091610403750000_2026.09.11.750869v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1945"},{"key":"2026091610403750000_2026.09.11.750869v1.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0072-4"},{"key":"2026091610403750000_2026.09.11.750869v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.025"},{"key":"2026091610403750000_2026.09.11.750869v1.40","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6407"},{"key":"2026091610403750000_2026.09.11.750869v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00593-z"},{"key":"2026091610403750000_2026.09.11.750869v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.033"},{"key":"2026091610403750000_2026.09.11.750869v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0028-3"},{"key":"2026091610403750000_2026.09.11.750869v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELREP.2014.05.050"},{"key":"2026091610403750000_2026.09.11.750869v1.45","first-page":"9","article-title":"Histone demethylases in chromatin biology and beyond","volume":"16","year":"2015","journal-title":"EMBO Rep"},{"key":"2026091610403750000_2026.09.11.750869v1.46","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03460-8"},{"key":"2026091610403750000_2026.09.11.750869v1.47","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/978-1-59745-000-3_32","article-title":"Oocyte Extracts for the Study of Meiotic M-M Transition","volume":"322","year":"2006","journal-title":"Xenopus Protocols, Methods in Molecular Biology"},{"key":"2026091610403750000_2026.09.11.750869v1.48","first-page":"719","article-title":"Centromere and kinetochore assembly in xenopus laevis egg extract","volume":"2018","year":"2018","journal-title":"Cold Spring Harb. Protoc"},{"key":"2026091610403750000_2026.09.11.750869v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1322"},{"key":"2026091610403750000_2026.09.11.750869v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.261"},{"key":"2026091610403750000_2026.09.11.750869v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth1060"},{"key":"2026091610403750000_2026.09.11.750869v1.52","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0638-x"},{"key":"2026091610403750000_2026.09.11.750869v1.53","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx936"},{"key":"2026091610403750000_2026.09.11.750869v1.54","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae979"},{"key":"2026091610403750000_2026.09.11.750869v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.147"},{"key":"2026091610403750000_2026.09.11.750869v1.56","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"2026091610403750000_2026.09.11.750869v1.57","first-page":"1.30.1","article-title":"The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses","volume":"54","year":"2016","journal-title":"Curr. Protoc. Bioinforma"},{"key":"2026091610403750000_2026.09.11.750869v1.58","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAC1000"},{"key":"2026091610403750000_2026.09.11.750869v1.59","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAD347"}],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.11.750869","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T17:40:45Z","timestamp":1789580445000},"score":10.020029,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.11.750869"}},"issued":{"date-parts":[[2026,9,13]]},"references-count":59,"URL":"https:\/\/doi.org\/10.64898\/2026.09.11.750869","published":{"date-parts":[[2026,9,13]]},"subtype":"preprint"},{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:21:56Z","timestamp":1790716916611,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["106185\/Z\/14\/Z"],"award-info":[{"award-number":["106185\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["103986\/Z\/14\/Z"],"award-info":[{"award-number":["103986\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["215189\/Z\/19\/Z"],"award-info":[{"award-number":["215189\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220001\/Z\/19\/Z"],"award-info":[{"award-number":["220001\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["204057\/Z\/16\/Z"],"award-info":[{"award-number":["204057\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220001\/Z\/19\/Z"],"award-info":[{"award-number":["220001\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Syst Biol"],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"Abstract<\/jats:title>\n \n Ultradian oscillations of HES Transcription Factors (TFs) at the single\u2010cell level enable cell state transitions. However, the tissue\u2010level organisation of HES5 dynamics in neurogenesis is unknown. Here, we analyse the expression of HES5\n ex vivo<\/jats:italic>\n in the developing mouse ventral spinal cord and identify microclusters of 4\u20136 cells with positively correlated HES5 level and ultradian dynamics. These microclusters are spatially periodic along the dorsoventral axis and temporally dynamic, alternating between high and low expression with a supra\u2010ultradian persistence time. We show that Notch signalling is required for temporal dynamics but not the spatial periodicity of HES5. Few Neurogenin 2 cells are observed per cluster, irrespective of high or low state, suggesting that the microcluster organisation of HES5 enables the stable selection of differentiating cells. Computational modelling predicts that different cell coupling strengths underlie the HES5 spatial patterns and rate of differentiation, which is consistent with comparison between the motoneuron and interneuron progenitor domains. Our work shows a previously unrecognised spatiotemporal organisation of neurogenesis, emergent at the tissue level from the synthesis of single\u2010cell dynamics.\n <\/jats:p>","DOI":"10.15252\/msb.20209902","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T03:12:59Z","timestamp":1621912379000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A dynamic, spatially periodic, micro\u2010pattern of HES5 underlies neurogenesis in the mouse spinal cord"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-385X","authenticated-orcid":false,"given":"Veronica","family":"Biga","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2122-7530","authenticated-orcid":false,"given":"Joshua","family":"Hawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-1837","authenticated-orcid":false,"given":"Ximena","family":"Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6383-055X","authenticated-orcid":false,"given":"Emma","family":"Johns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9088-1651","authenticated-orcid":false,"given":"Daniel","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5408-0013","authenticated-orcid":false,"given":"Antony D","family":"Adamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0314-9623","authenticated-orcid":false,"given":"Jochen","family":"Kursawe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Glendinning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-5878","authenticated-orcid":false,"given":"Cerys S","family":"Manning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6992-6870","authenticated-orcid":false,"given":"Nancy","family":"Papalopulu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"BFMSB20209902_CR1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2004162","volume":"16","author":"C Baek","year":"2018","unstructured":"Baek C, Freem L, Goiame R, Sang H, Morin X, Tozer S (2018) Mib1 prevents Notch Cis\u2010inhibition to defer differentiation and preserve neuroepithelial integrity during neural delamination. PLoS Biol 16: e2004162","journal-title":"PLoS Biol"},{"key":"BFMSB20209902_CR2","doi-asserted-by":"crossref","first-page":"3156","DOI":"10.1242\/dev.147256","volume":"144","author":"S Bansod","year":"2017","unstructured":"Bansod S, Kageyama R, Ohtsuka T (2017) Hes5 regulates the transition timing of neurogenesis and gliogenesis in mammalian neocortical development. Development 144: 3156\u20133167","journal-title":"Development"},{"key":"BFMSB20209902_CR3","doi-asserted-by":"crossref","DOI":"10.1098\/rsif.2019.0436","volume":"16","author":"JW Baron","year":"2019","unstructured":"Baron JW, Galla T (2019) Intrinsic noise, Delta\u2010Notch signalling and delayed reactions promote sustained, coherent, synchronized oscillations in the presomitic mesoderm. J R Soc Interface 16: 20190436","journal-title":"J R Soc Interface"},{"key":"BFMSB20209902_CR4","volume-title":"Harmonic analysis and applications","author":"JJ Benedetto","year":"1996","unstructured":"Benedetto JJ (1996) Harmonic analysis and applications. Boca Raton, FL: CRC Press"},{"key":"BFMSB20209902_CR5","first-page":"E402","volume":"112","author":"M Boareto","year":"2015","unstructured":"Boareto M, Jolly MK, Lu M, Onuchic JN, Clementi C, Ben\u2010Jacob E (2015) Jagged\u2010delta asymmetry in Notch signaling can give rise to a sender\/receiver hybrid phenotype. Proc Natl Acad Sci USA 112: E402\u2013E409","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFMSB20209902_CR6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.celrep.2012.05.017","volume":"2","author":"B Bonev","year":"2012","unstructured":"Bonev B, Stanley P, Papalopulu N (2012) MicroRNA\u20109 Modulates Hes1 ultradian oscillations by forming a double\u2010negative feedback loop. Cell Rep 2: 10\u201318","journal-title":"Cell Rep"},{"key":"BFMSB20209902_CR7","doi-asserted-by":"crossref","first-page":"3996","DOI":"10.1242\/dev.129452","volume":"142","author":"J Briscoe","year":"2015","unstructured":"Briscoe J, Small S (2015) Morphogen rules: design principles of gradient\u2010mediated embryo patterning. Development 142: 3996\u20134009","journal-title":"Development"},{"key":"BFMSB20209902_CR8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1103\/PhysRevE.61.371","volume":"61","author":"MY Choi","year":"2000","unstructured":"Choi MY, Kim HJ, Kim D, Hong H (2000) Synchronization in a system of globally coupled oscillators with time delay. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 61: 371\u2013381","journal-title":"Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics"},{"key":"BFMSB20209902_CR9","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.devcel.2010.06.006","volume":"19","author":"M Cohen","year":"2010","unstructured":"Cohen M, Georgiou M, Stevenson NL, Miodownik M, Baum B (2010) Dynamic filopodia transmit intermittent Delta\u2010Notch signaling to drive pattern refinement during lateral inhibition. Dev Cell 19: 78\u201389","journal-title":"Dev Cell"},{"key":"BFMSB20209902_CR10","doi-asserted-by":"crossref","DOI":"10.1126\/science.aai7407","volume":"356","author":"F Corson","year":"2017","unstructured":"Corson F, Couturier L, Rouault H, Mazouni K, Schweisguth F (2017) Self\u2010organized Notch dynamics generate stereotyped sensory organ patterns in Drosophila. Science 356: eaai7407","journal-title":"Science"},{"key":"BFMSB20209902_CR11","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/embor.2012.42","volume":"13","author":"RM Das","year":"2012","unstructured":"Das RM, Storey KG (2012) Mitotic spindle orientation can direct cell fate and bias Notch activity in chick neural tube. EMBO Rep 13: 448\u2013454","journal-title":"EMBO Rep"},{"key":"BFMSB20209902_CR12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1126\/science.1247521","volume":"343","author":"RM Das","year":"2014","unstructured":"Das RM, Storey KG (2014) Apical abscission alters cell polarity and dismantles the primary cilium during neurogenesis. Science 343: 200\u2013204","journal-title":"Science"},{"key":"BFMSB20209902_CR13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/nature02157","volume":"426","author":"C De Joussineau","year":"2003","unstructured":"De Joussineau C, Soul\u00e9 J, Martin M, Anguille C, Montcourrier P, Alexandre D (2003) Delta\u2010promoted filopodia mediate long\u2010range lateral inhibition in Drosophila. Nature 426: 555\u2013559","journal-title":"Nature"},{"key":"BFMSB20209902_CR14","doi-asserted-by":"crossref","DOI":"10.1242\/dev.173807","volume":"146","author":"J Delile","year":"2019","unstructured":"Delile J, Rayon T, Melchionda M, Edwards A, Briscoe J, Sagner A (2019) Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord. Development 146: dev.173807","journal-title":"Development"},{"key":"BFMSB20209902_CR15","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/bioinformatics\/btg454","volume":"20","author":"PH Eilers","year":"2004","unstructured":"Eilers PH, Goeman JJ (2004) Enhancing scatterplots with smoothed densities. Bioinformatics 20: 623\u2013628","journal-title":"Bioinformatics"},{"key":"BFMSB20209902_CR16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/dgd.12644","volume":"62","author":"J Falo\u2010Sanjuan","year":"2020","unstructured":"Falo\u2010Sanjuan J, Bray SJ (2020) Decoding the Notch signal. Dev Growth Differ 62: 4\u201314","journal-title":"Dev Growth Differ"},{"key":"BFMSB20209902_CR17","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevE.80.021909","volume":"80","author":"T Galla","year":"2009","unstructured":"Galla T (2009) Intrinsic fluctuations in stochastic delay systems: theoretical description and application to a simple model of gene regulation. Phys Rev E 80: 021909","journal-title":"Phys Rev E"},{"key":"BFMSB20209902_CR18","doi-asserted-by":"crossref","first-page":"3399","DOI":"10.1038\/ncomms4399","volume":"5","author":"M Goodfellow","year":"2014","unstructured":"Goodfellow M, Phillips NE, Manning C, Galla T, Papalopulu N (2014) microRNA input into a neural ultradian oscillator controls emergence and timing of alternative cell states. Nat Commun 5: 3399","journal-title":"Nat Commun"},{"key":"BFMSB20209902_CR19","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.devcel.2019.05.035","volume":"49","author":"Z Hadjivasiliou","year":"2019","unstructured":"Hadjivasiliou Z, Moore RE, McIntosh R, Galea GL, Clarke JDW, Alexandre P (2019) Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation. Dev Cell 49: 907\u2013919","journal-title":"Dev Cell"},{"key":"BFMSB20209902_CR20","doi-asserted-by":"crossref","DOI":"10.1242\/dev.172148","volume":"146","author":"D Henrique","year":"2019","unstructured":"Henrique D, Schweisguth F (2019) Mechanisms of Notch signaling: a simple logic deployed in time and space. Development 146: dev172148","journal-title":"Development"},{"key":"BFMSB20209902_CR21","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.cub.2010.06.034","volume":"20","author":"L Herrgen","year":"2010","unstructured":"Herrgen L, Ares S, Morelli LG, Schr\u00f6ter C, J\u00fclicher F, Oates AC (2010) Intercellular coupling regulates the period of the segmentation clock. Curr Biol 20: 1244\u20131253","journal-title":"Curr Biol"},{"key":"BFMSB20209902_CR22","first-page":"2305","volume":"143","author":"GL Hunter","year":"2016","unstructured":"Hunter GL, Hadjivasiliou Z, Bonin H, He L, Perrimon N, Charras G, Baum B (2016) Coordinated control of Notch\/Delta signalling and cell cycle progression drives lateral inhibition\u2010mediated tissue patterning. Development 143: 2305\u20132310","journal-title":"Development"},{"key":"BFMSB20209902_CR23","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1126\/science.1242366","volume":"342","author":"I Imayoshi","year":"2013","unstructured":"Imayoshi I, Isomura A, Harima Y, Kawaguchi K, Kori H, Miyachi H, Fujiwara T, Ishidate F, Kageyama R (2013) Oscillatory control of factors determining multipotency and fate in mouse neural progenitors. Science 342: 1203\u20131208","journal-title":"Science"},{"key":"BFMSB20209902_CR24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.neuron.2014.03.018","volume":"82","author":"I Imayoshi","year":"2014","unstructured":"Imayoshi I, Kageyama R (2014) bHLH factors in self\u2010renewal, multipotency, and fate choice of neural progenitor cells. Neuron 82: 9\u201323","journal-title":"Neuron"},{"key":"BFMSB20209902_CR25","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1101\/gad.294546.116","volume":"31","author":"A Isomura","year":"2017","unstructured":"Isomura A, Ogushi F, Kori H, Kageyama R (2017) Optogenetic perturbation and bioluminescence imaging to analyze cell\u2010to\u2010cell transfer of oscillatory information. Genes Dev 31: 524\u2013535","journal-title":"Genes Dev"},{"key":"BFMSB20209902_CR26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0014-5793(03)00279-5","volume":"541","author":"MH Jensen","year":"2003","unstructured":"Jensen MH, Sneppen K, Tiana G (2003) Sustained oscillations and time delays in gene expression of protein Hes1. FEBS Lett 541: 176\u2013177","journal-title":"FEBS Lett"},{"key":"BFMSB20209902_CR27","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1038\/nn.2208","volume":"11","author":"R Kageyama","year":"2008","unstructured":"Kageyama R, Ohtsuka T, Shimojo H, Imayoshi I (2008) Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition. Nat Neurosci 11: 1247\u20131251","journal-title":"Nat Neurosci"},{"key":"BFMSB20209902_CR28","doi-asserted-by":"crossref","DOI":"10.1126\/science.1254927","volume":"345","author":"A Kicheva","year":"2014","unstructured":"Kicheva A, Bollenbach T, Ribeiro A, Valle HP, Lovell\u2010Badge R, Episkopou V, Briscoe J (2014) Coordination of progenitor specification and growth in mouse and chick spinal cord. Science 345: 1254927","journal-title":"Science"},{"key":"BFMSB20209902_CR29","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1101\/gad.1823109","volume":"23","author":"T Kobayashi","year":"2009","unstructured":"Kobayashi T, Mizuno H, Imayoshi I, Furusawa C, Shirahige K, Kageyama R (2009) The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells. Genes Dev 23: 1870\u20131875","journal-title":"Genes Dev"},{"key":"BFMSB20209902_CR30","volume":"10","author":"K Kuzmicz\u2010Kowalska","year":"2020","unstructured":"Kuzmicz\u2010Kowalska K, Kicheva A (2020) Regulation of size and scale in vertebrate spinal cord development. Wiley Interdiscip Rev Dev Biol 10: e383","journal-title":"Wiley Interdiscip Rev Dev Biol"},{"key":"BFMSB20209902_CR31","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/S0960-9822(03)00534-7","volume":"13","author":"J Lewis","year":"2003","unstructured":"Lewis J (2003) Autoinhibition with transcriptional delay. Curr Biol 13: 1398\u20131408","journal-title":"Curr Biol"},{"key":"BFMSB20209902_CR32","doi-asserted-by":"publisher","DOI":"10.1101\/335869","author":"KH de Lichtenberg","year":"2018","unstructured":"de Lichtenberg KH, Funa N, Nakic N, Ferrer J, Zhu Z, Huangfu D, Serup P (2018) Genome\u2010wide identification of HES1 target genes uncover novel roles for HES1 in pancreatic development. bioRxiv https:\/\/doi.org\/10.1101\/335869 [PREPRINT]","journal-title":"bioRxiv"},{"key":"BFMSB20209902_CR33","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1016\/j.neuron.2018.09.031","volume":"100","author":"V Lopes\u2010Dos\u2010Santos","year":"2018","unstructured":"Lopes\u2010Dos\u2010Santos V, van de Ven GM, Morley A, Trouche S, Campo\u2010Urriza N, Dupret D (2018) Parsing hippocampal theta oscillations by nested spectral components during spatial exploration and memory\u2010guided behavior. Neuron 100: 940\u2013952","journal-title":"Neuron"},{"key":"BFMSB20209902_CR34","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1038\/nprot.2013.109","volume":"8","author":"A Lyubimova","year":"2013","unstructured":"Lyubimova A, Itzkovitz S, Junker JP, Fan ZP, Wu X, van Oudenaarden A (2013) Single\u2010molecule mRNA detection and counting in mammalian tissue. Nat Protoc 8: 1743\u20131758","journal-title":"Nat Protoc"},{"key":"BFMSB20209902_CR35","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0896-6273(00)80988-5","volume":"20","author":"Q Ma","year":"1998","unstructured":"Ma Q, Chen Z, del Barco BI, de la Pompa JL, Anderson DJ (1998) neurogenin1 is essential for the determination of neuronal precursors for proximal cranial sensory ganglia. Neuron 20: 469\u2013482","journal-title":"Neuron"},{"key":"BFMSB20209902_CR36","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1038\/s41467-019-10734-8","volume":"10","author":"CS Manning","year":"2019","unstructured":"Manning CS, Biga V, Boyd J, Kursawe J, Ymisson B, Spiller DG, Sanderson CM, Galla T, Rattray M, Papalopulu N (2019) Quantitative single\u2010cell live imaging links HES5 dynamics with cell\u2010state and fate in murine neurogenesis. Nat Commun 10: 2835","journal-title":"Nat Commun"},{"key":"BFMSB20209902_CR37","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1242\/dev.036806","volume":"137","author":"U Marklund","year":"2010","unstructured":"Marklund U, Hansson EM, Sundstr\u00f6m E, de Angelis MH, Przemeck GK, Lendahl U, Muhr J, Ericson J (2010) Domain\u2010specific control of neurogenesis achieved through patterned regulation of Notch ligand expression. Development 137: 437\u2013445","journal-title":"Development"},{"key":"BFMSB20209902_CR38","doi-asserted-by":"crossref","first-page":"8409","DOI":"10.1073\/pnas.1813492116","volume":"116","author":"AN Marra","year":"2019","unstructured":"Marra AN, Adeeb BD, Chambers BE, Drummond BE, Ulrich M, Addiego A, Springer M, Poureetezadi SJ, Chambers JM, Ronshaugen M et al (2019) Prostaglandin signaling regulates renal multiciliated cell specification and maturation. Proc Natl Acad Sci USA 116: 8409\u20138418","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFMSB20209902_CR39","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.jtbi.2008.07.013","volume":"254","author":"H Momiji","year":"2008","unstructured":"Momiji H, Monk NAM (2008) Dissecting the dynamics of the Hes1 genetic oscillator. J Theor Biol 254: 784\u2013798","journal-title":"J Theor Biol"},{"key":"BFMSB20209902_CR40","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S0960-9822(03)00494-9","volume":"13","author":"NAM Monk","year":"2003","unstructured":"Monk NAM (2003) Oscillatory expression of Hes1, p53, and NF\u2010\u03baB driven by transcriptional time delays. Curr Biol 13: 1409\u20131413","journal-title":"Curr Biol"},{"key":"BFMSB20209902_CR41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2976\/1.3027088","volume":"3","author":"LG Morelli","year":"2009","unstructured":"Morelli LG, Ares S, Herrgen L, Schr\u00f6ter C, J\u00fclicher F, Oates AC (2009) Delayed coupling theory of vertebrate segmentation. HFSP J 3: 55\u201366","journal-title":"HFSP J"},{"key":"BFMSB20209902_CR42","volume":"9","author":"BR Nelson","year":"2020","unstructured":"Nelson BR, Hodge RD, Daza RA, Tripathi PP, Arnold SJ, Millen KJ, Hevner RF (2020) Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches. eLife 9: e53777","journal-title":"eLife"},{"key":"BFMSB20209902_CR43","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.gde.2020.04.008","volume":"63","author":"AC Oates","year":"2020","unstructured":"Oates AC (2020) Waiting on the Fringe: cell autonomy and signaling delays in segmentation clocks. Curr Opin Genet Dev 63: 61\u201370","journal-title":"Curr Opin Genet Dev"},{"key":"BFMSB20209902_CR44","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1093\/emboj\/18.8.2196","volume":"18","author":"T Ohtsuka","year":"1999","unstructured":"Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F, Kageyama R (1999) Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J 18: 2196\u20132207","journal-title":"EMBO J"},{"key":"BFMSB20209902_CR45","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.0040015","volume":"4","author":"EM \u00d6zbudak","year":"2008","unstructured":"\u00d6zbudak EM, Lewis J (2008) Notch signalling synchronizes the zebrafish segmentation clock but is not needed to create somite boundaries. PLoS Genet 4: e15","journal-title":"PLoS Genet"},{"key":"BFMSB20209902_CR46","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/embr.201438447","volume":"15","author":"JT Paridaen","year":"2014","unstructured":"Paridaen JT, Huttner WB (2014) Neurogenesis during development of the vertebrate central nervous system. EMBO Rep 15: 351\u2013364","journal-title":"EMBO Rep"},{"key":"BFMSB20209902_CR47","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1242\/dev.108100","volume":"141","author":"J Petrovic","year":"2014","unstructured":"Petrovic J, Formosa\u2010Jordan P, Luna\u2010Escalante JC, Abello G, Iban M, Es NJ, Giraldez F, Abell\u00f3 G, Iba\u00f1es M et al (2014) Ligand\u2010dependent Notch signaling strength orchestrates lateral induction and lateral inhibition in the developing inner ear. Development 141: 2313\u20132324","journal-title":"Development"},{"key":"BFMSB20209902_CR48","volume":"5","author":"NE Phillips","year":"2016","unstructured":"Phillips NE, Manning CS, Pettini T, Biga V, Marinopoulou E, Stanley P, Boyd J, Bagnall J, Paszek P, Spiller DG et al (2016) Stochasticity in the miR\u20109\/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation. eLife 5: e16118","journal-title":"eLife"},{"key":"BFMSB20209902_CR49","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0015515","volume":"5","author":"C Ramos","year":"2010","unstructured":"Ramos C, Rocha S, Gaspar C, Henrique D (2010) Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord. PLoS One 5: e15515","journal-title":"PLoS One"},{"key":"BFMSB20209902_CR50","doi-asserted-by":"crossref","DOI":"10.1242\/dev.182154","volume":"146","author":"A Sagner","year":"2019","unstructured":"Sagner A, Briscoe J (2019) Establishing neuronal diversity in the spinal cord: a time and a place. Development 146: dev182154","journal-title":"Development"},{"key":"BFMSB20209902_CR51","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.2003127","volume":"16","author":"A Sagner","year":"2018","unstructured":"Sagner A, Gaber ZB, Delile J, Kong JH, Rousso DL, Pearson CA, Weicksel SE, Melchionda M, Mousavy Gharavy SN, Briscoe J et al (2018) Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics. PLoS Biol 16: e2003127","journal-title":"PLoS Biol"},{"key":"BFMSB20209902_CR52","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.gde.2011.07.007","volume":"21","author":"O Shaya","year":"2011","unstructured":"Shaya O, Sprinzak D (2011) From Notch signaling to fine\u2010grained patterning: modeling meets experiments. Curr Opin Genet Dev 21: 732\u2013739","journal-title":"Curr Opin Genet Dev"},{"key":"BFMSB20209902_CR53","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1101\/gad.270785.115","volume":"30","author":"H Shimojo","year":"2016","unstructured":"Shimojo H, Isomura A, Ohtsuka T, Kori H, Miyachi H, Kageyama R (2016) Oscillatory control of Delta\u2010like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis. Genes Dev 30: 102\u2013116","journal-title":"Genes Dev"},{"key":"BFMSB20209902_CR54","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.semcdb.2016.01.017","volume":"49","author":"H Shimojo","year":"2016","unstructured":"Shimojo H, Kageyama R (2016) Oscillatory control of Delta\u2010like1 in somitogenesis and neurogenesis: a unified model for different oscillatory dynamics. Semin Cell Dev Biol 49: 76\u201382","journal-title":"Semin Cell Dev Biol"},{"key":"BFMSB20209902_CR55","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.cell.2018.01.026","volume":"172","author":"KF Sonnen","year":"2018","unstructured":"Sonnen KF, Lauschke VM, Uraji J, Falk HJ, Petersen Y, Funk MC, Beaupeux M, Fran\u00e7ois P, Merten CA, Aulehla A (2018) Modulation of phase shift between Wnt and Notch signaling oscillations controls mesoderm segmentation. Cell 172: 1079\u20131090","journal-title":"Cell"},{"key":"BFMSB20209902_CR56","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019103558","volume":"39","author":"X Soto","year":"2020","unstructured":"Soto X, Biga V, Kursawe J, Lea R, Doostdar P, Thomas R, Papalopulu N (2020) Dynamic properties of noise and Her6 levels are optimized by miR\u20109, allowing the decoding of the Her6 oscillator. EMBO J 39: e103558","journal-title":"EMBO J"},{"key":"BFMSB20209902_CR57","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/nature08959","volume":"465","author":"D Sprinzak","year":"2010","unstructured":"Sprinzak D, Lakhanpal A, Lebon L, Santat LA, Fontes ME, Anderson GA, Garcia\u2010Ojalvo J, Elowitz MB (2010) Cis\u2010interactions between Notch and Delta generate mutually exclusive signalling states. Nature 465: 86\u201390","journal-title":"Nature"},{"key":"BFMSB20209902_CR58","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jtbi.2017.06.006","volume":"430","author":"HB Tiedemann","year":"2017","unstructured":"Tiedemann HB, Schneltzer E, Beckers J, Przemeck GKH, Hrab\u011b de Angelis M (2017) Modeling coexistence of oscillation and Delta\/Notch\u2010mediated lateral inhibition in pancreas development and neurogenesis. J Theor Biol 430: 32\u201344","journal-title":"J Theor Biol"},{"key":"BFMSB20209902_CR59","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.cell.2016.01.028","volume":"164","author":"CD Tsiairis","year":"2016","unstructured":"Tsiairis CD, Aulehla A (2016) Self\u2010organization of embryonic genetic oscillators into spatiotemporal wave patterns. Cell 164: 656\u2013667","journal-title":"Cell"},{"key":"BFMSB20209902_CR60","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1741-7007-9-58","volume":"9","author":"F Vilas\u2010Boas","year":"2011","unstructured":"Vilas\u2010Boas F, Fior R, Swedlow JR, Storey KG, Henrique D (2011) A novel reporter of notch signalling indicates regulated and random Notch activation during vertebrate neurogenesis. BMC Biol 9: 58","journal-title":"BMC Biol"},{"key":"BFMSB20209902_CR61","volume":"5","author":"AB Webb","year":"2016","unstructured":"Webb AB, Lengyel IM, J\u00f6rg DJ, Valentin G, J\u00fclicher F, Morelli LG, Oates AC (2016) Persistence, period and precision of autonomous cellular oscillators from the zebrafish segmentation clock. eLife 5: e08438","journal-title":"eLife"},{"key":"BFMSB20209902_CR62","first-page":"E9469","volume":"115","author":"YE Wu","year":"2018","unstructured":"Wu YE, Enoki R, Oda Y, Huang ZL, Honma KI, Honma S (2018) Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus. Proc Natl Acad Sci USA 115: E9469\u2013E9478","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Molecular Systems Biology"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/msb.20209902.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/msb.20209902","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/msb.20209902\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/msb.20209902","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/msb.20209902.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T02:58:38Z","timestamp":1779073118000},"score":9.872314,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/msb.20209902"}},"issued":{"date-parts":[[2021,5,1]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5,1]]}},"alternative-id":["BFMSB20209902"],"URL":"https:\/\/doi.org\/10.15252\/msb.20209902","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.08.03.234369","asserted-by":"object"}]},"ISSN":["1744-4292"],"issn-type":[{"value":"1744-4292","type":"electronic"}],"published":{"date-parts":[[2021,5,1]]},"assertion":[{"value":"3 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 April 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"MSB20209902"},{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:56:09Z","timestamp":1789264569215,"version":"build-2803163510"},"reference-count":69,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T00:00:00Z","timestamp":1507852800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["109916"],"award-info":[{"award-number":["109916"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["104648"],"award-info":[{"award-number":["104648"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["108504"],"award-info":[{"award-number":["108504"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["093853"],"award-info":[{"award-number":["093853"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["097383"],"award-info":[{"award-number":["097383"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["092076"],"award-info":[{"award-number":["092076"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["200885"],"award-info":[{"award-number":["200885"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"abstract":"Numerous links exist between co-transcriptional RNA processing and the transcribing RNAPII. In particular, pre-mRNA splicing was reported to be associated with slowed RNAPII elongation. Here, we identify a site of ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry path. Ubiquitination was increased in the absence of the Bre5-Ubp3 ubiquitin protease complex. Bre5 binds RNA in vivo, with a preference for exon 2 regions of intron-containing pre-mRNAs and poly(A) proximal sites. Ubiquitinated RNAPII showed similar enrichment. The absence of Bre5 led to impaired splicing and defects in RNAPII elongation in vivo on a splicing reporter construct. Strains expressing RNAPII with a K1246R mutation showed reduced co-transcriptional splicing. We propose that ubiquinitation of RNAPII is induced by RNA processing events and linked to transcriptional pausing, which is released by Bre5-Ubp3 associated with the nascent transcript.<\/jats:p>","DOI":"10.7554\/elife.27082","type":"journal-article","created":{"date-parts":[[2017,10,13]],"date-time":"2017-10-13T08:00:24Z","timestamp":1507881624000},"source":"Crossref","is-referenced-by-count":22,"title":["RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit"],"prefix":"10.7554","volume":"6","author":[{"given":"Laura","family":"Milligan","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8226-7272","authenticated-orcid":true,"given":"Camille","family":"Sayou","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Tuck","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsiana","family":"Auchynnikava","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane EA","family":"Reid","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Alexander","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia de Lima","family":"Alves","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Allshire","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Spanos","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juri","family":"Rappsilber","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"},{"name":"Institute of Biotechnology, Technische Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean D","family":"Beggs","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Kudla","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2894-2772","authenticated-orcid":true,"given":"David","family":"Tollervey","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2017,10,13]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1261\/rna.2119903","article-title":"Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors","volume":"9","author":"Albers","year":"2003","journal-title":"RNA"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1261\/rna.2162610","article-title":"RiboSys, a high-resolution, quantitative approach to measure the in vivo kinetics of pre-mRNA splicing and 3'-end processing in Saccharomyces cerevisiae","volume":"16","author":"Alexander","year":"2010","journal-title":"RNA"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.molcel.2010.11.005","article-title":"Splicing-dependent RNA polymerase pausing in yeast","volume":"40","author":"Alexander","year":"2010","journal-title":"Molecular Cell"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"W39","DOI":"10.1093\/nar\/gkv416","article-title":"The MEME Suite","volume":"43","author":"Bailey","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"39067","DOI":"10.1074\/jbc.M508064200","article-title":"Atg19p ubiquitination and the cytoplasm to vacuole trafficking pathway in yeast","volume":"280","author":"Baxter","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1002\/(SICI)1097-0061(19980915)14:12<1127::AID-YEA300>3.0.CO;2-#","article-title":"Functional analysis of yeast essential genes using a promoter-substitution cassette and the tetracycline-regulatable dual expression system","volume":"14","author":"Bell\u00ed","year":"1998","journal-title":"Yeast"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1016\/j.dnarep.2007.04.010","article-title":"The Bre5\/Ubp3 ubiquitin protease complex from budding yeast contributes to the cellular response to DNA damage","volume":"6","author":"Bilsland","year":"2007","journal-title":"DNA Repair"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2013.07.033","article-title":"From structure to systems: high-resolution, quantitative genetic analysis of RNA polymerase II","volume":"154","author":"Braberg","year":"2013","journal-title":"Cell"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1016\/j.molcel.2017.01.005","article-title":"Nuclear RNA Decay Pathways Aid Rapid Remodeling of Gene Expression in Yeast","volume":"65","author":"Bresson","year":"2017","journal-title":"Molecular Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1016\/j.molcel.2010.11.004","article-title":"Global analysis of nascent RNA reveals transcriptional pausing in terminal exons","volume":"40","author":"Carrillo Oesterreich","year":"2010","journal-title":"Molecular Cell"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.molcel.2014.01.017","article-title":"A splicing-dependent transcriptional checkpoint associated with prespliceosome formation","volume":"53","author":"Chathoth","year":"2014","journal-title":"Molecular Cell"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1042\/BJ20101152","article-title":"Transcriptional activation requires protection of the TATA-binding protein Tbp1 by the ubiquitin-specific protease Ubp3","volume":"431","author":"Chew","year":"2010","journal-title":"Biochemical Journal"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nature09652","article-title":"Nascent transcript sequencing visualizes transcription at nucleotide resolution","volume":"469","author":"Churchman","year":"2011","journal-title":"Nature"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/ncb1003","article-title":"Ubp3 requires a cofactor, Bre5, to specifically de-ubiquitinate the COPII protein, Sec23","volume":"5","author":"Cohen","year":"2003","journal-title":"Nature Cell Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1038\/nature05649","article-title":"Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map","volume":"446","author":"Collins","year":"2007","journal-title":"Nature"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/nrm3956","article-title":"Orchestrating transcription with the Pol II CTD","volume":"16","author":"Conaway","year":"2015","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1126\/science.1180823","article-title":"The genetic landscape of a cell","volume":"327","author":"Costanzo","year":"2010","journal-title":"Science"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"5821","DOI":"10.1073\/pnas.0710533105","article-title":"Linking functionally related genes by sensitive and quantitative characterization of genetic interaction profiles","volume":"105","author":"Decourty","year":"2008","journal-title":"PNAS"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"895","DOI":"10.3390\/biology1030895","article-title":"FLEXBAR-Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms","volume":"1","author":"Dodt","year":"2012","journal-title":"Biology"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1006\/abio.1993.1170","article-title":"Solubilization and purification of enzymatically active glutathione S-transferase (pGEX) fusion proteins","volume":"210","author":"Frangioni","year":"1993","journal-title":"Analytical Biochemistry"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nmeth.3170","article-title":"A robust pipeline for rapid production of versatile nanobody repertoires","volume":"11","author":"Fridy","year":"2014","journal-title":"Nature Methods"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jprot.2013.10.029","article-title":"Technical considerations for large-scale parallel reaction monitoring analysis","volume":"100","author":"Gallien","year":"2014","journal-title":"Journal of Proteomics"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"9613","DOI":"10.1073\/pnas.0901997106","article-title":"Identification of protein binding sites on U3 snoRNA and pre-rRNA by UV cross-linking and high-throughput analysis of cDNAs","volume":"106","author":"Granneman","year":"2009","journal-title":"PNAS"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.1038\/emboj.2011.256","article-title":"A cluster of ribosome synthesis factors regulate pre-rRNA folding and 5.8S rRNA maturation by the Rat1 exonuclease","volume":"30","author":"Granneman","year":"2011","journal-title":"The EMBO Journal"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"20705","DOI":"10.1073\/pnas.0907052106","article-title":"Distinct ubiquitin ligases act sequentially for RNA polymerase II polyubiquitylation","volume":"106","author":"Harreman","year":"2009","journal-title":"PNAS"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/S1097-2765(03)00488-X","article-title":"Cytoplasmic degradation of splice-defective pre-mRNAs and intermediates","volume":"12","author":"Hilleren","year":"2003","journal-title":"Molecular Cell"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"e1005735","DOI":"10.1371\/journal.pgen.1005735","article-title":"Loss of the Yeast SR Protein Npl3 Alters Gene Expression Due to Transcription Readthrough","volume":"11","author":"Holmes","year":"2015","journal-title":"PLOS Genetics"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1038\/sj.embor.7400612","article-title":"Yeast Trf5p is a nuclear poly(A) polymerase","volume":"7","author":"Houseley","year":"2006","journal-title":"EMBO reports"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"2119","DOI":"10.1101\/gad.200303.112","article-title":"The RNA polymerase II CTD coordinates transcription and RNA processing","volume":"26","author":"Hsin","year":"2012","journal-title":"Genes & Development"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S0021-9673(02)01402-4","article-title":"Microcolumns with self-assembled particle frits for proteomics","volume":"979","author":"Ishihama","year":"2002","journal-title":"Journal of Chromatography A"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"e1002627","DOI":"10.1371\/journal.pgen.1002627","article-title":"Dissection of Pol II trigger loop function and Pol II activity-dependent control of start site selection in vivo","volume":"8","author":"Kaplan","year":"2012","journal-title":"PLoS Genetics"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/ncb1723","article-title":"Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p\/Bre5p ubiquitin protease","volume":"10","author":"Kraft","year":"2008","journal-title":"Nature Cell Biology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.molcel.2008.04.018","article-title":"Reversal of RNA polymerase II ubiquitylation by the ubiquitin protease Ubp3","volume":"30","author":"Kvint","year":"2008","journal-title":"Molecular Cell"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nsmb.3000","article-title":"CDK9 inhibitors define elongation checkpoints at both ends of RNA polymerase II-transcribed genes","volume":"22","author":"Laitem","year":"2015","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"29176","DOI":"10.1074\/jbc.M502975200","article-title":"Structural basis for interaction between the Ubp3 deubiquitinating enzyme and its Bre5 cofactor","volume":"280","author":"Li","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1093\/nar\/gkv005","article-title":"Interaction between the RNA-dependent ATPase and poly(A) polymerase subunits of the TRAMP complex is mediated by short peptides and important for snoRNA processing","volume":"43","author":"Losh","year":"2015","journal-title":"Nucleic Acids Research"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/bioinformatics\/btq054","article-title":"Skyline: an open source document editor for creating and analyzing targeted proteomics experiments","volume":"26","author":"MacLean","year":"2010","journal-title":"Bioinformatics"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.cell.2015.03.010","article-title":"Native elongating transcript sequencing reveals human transcriptional activity at nucleotide resolution","volume":"161","author":"Mayer","year":"2015","journal-title":"Cell"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1128\/MCB.00463-08","article-title":"A yeast exosome cofactor, Mpp6, functions in RNA surveillance and in the degradation of noncoding RNA transcripts","volume":"28","author":"Milligan","year":"2008","journal-title":"Molecular and Cellular Biology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"874","DOI":"10.15252\/msb.20166869","article-title":"Strand-specific, high-resolution mapping of modified RNA polymerase II","volume":"12","author":"Milligan","year":"2016","journal-title":"Molecular Systems Biology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1038\/nsmb.2468","article-title":"Global analysis of yeast mRNPs","volume":"20","author":"Mitchell","year":"2013","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/S0092-8674(00)80139-7","article-title":"A deubiquitinating enzyme interacts with SIR4 and regulates silencing in S. cerevisiae","volume":"86","author":"Moazed","year":"1996","journal-title":"Cell"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1146\/annurev-biochem-060614-034242","article-title":"Regulation of alternative splicing through coupling with transcription and chromatin structure","volume":"84","author":"Naftelberg","year":"2015","journal-title":"Annual Review of Biochemistry"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/sj.embor.7400026","article-title":"Formation and nuclear export of tRNA, rRNA and mRNA is regulated by the ubiquitin ligase Rsp5p","volume":"4","author":"Neumann","year":"2003","journal-title":"EMBO Reports"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.cell.2015.03.027","article-title":"Mammalian NET-Seq Reveals Genome-wide Nascent Transcription Coupled to RNA Processing","volume":"161","author":"Nojima","year":"2015","journal-title":"Cell"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1101\/gad.285604","article-title":"A pre-ribosome-associated HEAT-repeat protein is required for export of both ribosomal subunits","volume":"18","author":"Oeffinger","year":"2004","journal-title":"Genes & Development"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"3351","DOI":"10.1016\/j.yexcr.2010.09.005","article-title":"The Rsp5 ubiquitin ligase and the AAA-ATPase Cdc48 control the ubiquitin-mediated degradation of the COPII component Sec23","volume":"316","author":"Ossareh-Nazari","year":"2010","journal-title":"Experimental Cell Research"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/nrm3943","article-title":"Transcription termination and the control of the transcriptome: why, where and how to stop","volume":"16","author":"Porrua","year":"2015","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1021\/ac026117i","article-title":"Stop and go extraction tips for matrix-assisted laser desorption\/ionization, nanoelectrospray, and LC\/MS sample pretreatment in proteomics","volume":"75","author":"Rappsilber","year":"2003","journal-title":"Analytical Chemistry"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1038\/13732","article-title":"A generic protein purification method for protein complex characterization and proteome exploration","volume":"17","author":"Rigaut","year":"1999","journal-title":"Nature Biotechnology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1038\/nature11715","article-title":"Structure and function of the initially transcribing RNA polymerase II-TFIIB complex","volume":"493","author":"Sainsbury","year":"2013","journal-title":"Nature"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1016\/j.jmb.2016.04.017","article-title":"Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing","volume":"428","author":"Saldi","year":"2016","journal-title":"Journal of Molecular Biology"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"e00165-17","DOI":"10.1128\/MCB.00165-17","article-title":"RNA binding by histone methyltransferases Set1 and Set2","volume":"37","author":"Sayou","year":"2017","journal-title":"Molecular and Cellular Biology"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/yea.2898","article-title":"Genetic interactions of yeast NEP1 (EMG1), encoding an essential factor in ribosome biogenesis","volume":"29","author":"Schilling","year":"2012","journal-title":"Yeast"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.molcel.2012.08.013","article-title":"Transcriptome-wide analysis of exosome targets","volume":"48","author":"Schneider","year":"2012","journal-title":"Molecular Cell"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.15252\/embj.201488757","article-title":"The exosome-binding factors Rrp6 and Rrp47 form a composite surface for recruiting the Mtr4 helicase","volume":"33","author":"Schuch","year":"2014","journal-title":"The EMBO Journal"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1021\/ac950914h","article-title":"Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels","volume":"68","author":"Shevchenko","year":"1996","journal-title":"Analytical Chemistry"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.cell.2007.01.046","article-title":"Communication between distant sites in RNA polymerase II through ubiquitylation factors and the polymerase CTD","volume":"129","author":"Somesh","year":"2007","journal-title":"Cell"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1101\/gad.1925010","article-title":"The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome","volume":"24","author":"Song","year":"2010","journal-title":"Genes & Development"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"31816","DOI":"10.1074\/jbc.M113.491290","article-title":"Cotranscriptional recruitment of RNA exosome cofactors Rrp47p and Mpp6p and two distinct Trf-Air-Mtr4 polyadenylation (TRAMP) complexes assists the exonuclease Rrp6p in the targeting and degradation of an aberrant messenger ribonucleoprotein particle (mRNP) in yeast","volume":"288","author":"Stuparevic","year":"2013","journal-title":"Journal of Biological Chemistry"},{"key":"bib64","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1002\/j.1460-2075.1987.tb02763.x","article-title":"A yeast small nuclear RNA is required for normal processing of pre-ribosomal RNA","volume":"6","author":"Tollervey","year":"1987","journal-title":"The EMBO Journal"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.cell.2013.07.047","article-title":"A transcriptome-wide atlas of RNP composition reveals diverse classes of mRNAs and lncRNAs","volume":"154","author":"Tuck","year":"2013","journal-title":"Cell"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"R8","DOI":"10.1186\/gb-2014-15-1-r8","article-title":"PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast","volume":"15","author":"Webb","year":"2014","journal-title":"Genome Biology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"e46398","DOI":"10.1371\/journal.pone.0046398","article-title":"MultiDsk: a ubiquitin-specific affinity resin","volume":"7","author":"Wilson","year":"2012","journal-title":"PLoS One"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nmeth.1322","article-title":"Universal sample preparation method for proteome analysis","volume":"6","author":"Wi\u015bniewski","year":"2009","journal-title":"Nature Methods"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1038\/nature07728","article-title":"Bidirectional promoters generate pervasive transcription in yeast","volume":"457","author":"Xu","year":"2009","journal-title":"Nature"}],"container-title":["eLife"],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/27082\/elife-27082-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/27082\/elife-27082-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/27082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:55:55Z","timestamp":1697057755000},"score":9.826745,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/27082"}},"issued":{"date-parts":[[2017,10,13]]},"references-count":69,"aliases":["10.7554\/elife.27082.034","10.7554\/elife.27082.031"],"alternative-id":["10.7554\/eLife.27082"],"URL":"https:\/\/doi.org\/10.7554\/elife.27082","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"uri","id":"https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE94944","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.27082.033","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.27082.032","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"published":{"date-parts":[[2017,10,13]]},"article-number":"e27082"},{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:44:29Z","timestamp":1785415469275,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,21]]},"group-title":"Cell Biology","reference-count":66,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome","award":["220780"],"award-info":[{"award-number":["220780"]}]},{"name":"Wellcome","award":["319314"],"award-info":[{"award-number":["319314"]}]},{"name":"Wellcome","award":["218470"],"award-info":[{"award-number":["218470"]}]},{"name":"Wellcome","award":["203149"],"award-info":[{"award-number":["203149"]}]},{"name":"Wellcome","award":["226791"],"award-info":[{"award-number":["226791"]}]},{"id":[{"id":"https:\/\/ror.org\/00fzhcx31","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"accepted":{"date-parts":[[2026,4,21]]},"abstract":"Abstract<\/jats:title>\n \n Meiosis generates haploid gametes from a diploid progenitor. In meiosis I, homologous chromosomes segregate while sister chromatids co-orient toward the same spindle pole. The mechanisms underlying this specialized segregation pattern remain incompletely understood. Here we identify pathways required for meiosis I chromosome segregation through a forward genetic screen in\n Saccharomyces cerevisiae<\/jats:italic>\n . We find that meiosis I is highly sensitive to perturbations in diverse components of the segregation machinery and define key functional interfaces within complexes important for this division. These include meiosis I\u2013specific regulators that establish the specialized chromosome pattern, namely the monopolin complex that directs sister kinetochore co-orientation and the Spo13\n MOKIR<\/jats:sup>\n \u2013Cdc5\n Polo<\/jats:sup>\n module that promotes meiosis I chromosome segregation. In addition, we identify mutations affecting the core segregation machinery, including the spindle pole body, spindle midzone, and outer kinetochore, which can disrupt coupling between the chromosome segregation program and the meiotic spindle cycle. Together, our findings reveal that multiple pathways coordinate chromosome segregation with the meiotic divisions and highlight the unique demands of meiosis I.\n <\/jats:p>","DOI":"10.64898\/2026.04.17.719180","type":"posted-content","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:05:16Z","timestamp":1776816316000},"source":"Crossref","is-referenced-by-count":0,"title":["Multiple pathways couple kinetochore orientation to the meiotic spindle cycle"],"prefix":"10.64898","author":[{"given":"Aparna","family":"Vinod","sequence":"first","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Turner","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-3766","authenticated-orcid":false,"given":"Shaun","family":"Webb","sequence":"additional","affiliation":[{"name":"Discovery Research Platform for Hidden Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3596-9407","authenticated-orcid":false,"given":"Adele L.","family":"Marston","sequence":"additional","affiliation":[{"name":"Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, Michael Swann Building, Max Born Crescent, Edinburgh, EH9 3BF UK"},{"name":"Discovery Research Platform for Hidden Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3BF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026042509452281000_2026.04.17.719180v1.1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-10-0918"},{"key":"2026042509452281000_2026.04.17.719180v1.2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004666"},{"key":"2026042509452281000_2026.04.17.719180v1.3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74447"},{"key":"2026042509452281000_2026.04.17.719180v1.4","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201103076"},{"key":"2026042509452281000_2026.04.17.719180v1.5","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.117.300527"},{"key":"2026042509452281000_2026.04.17.719180v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.10.025"},{"key":"2026042509452281000_2026.04.17.719180v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/yea.843"},{"key":"2026042509452281000_2026.04.17.719180v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00129-1"},{"key":"2026042509452281000_2026.04.17.719180v1.9","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E23-01-0014"},{"key":"2026042509452281000_2026.04.17.719180v1.10","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02583"},{"key":"2026042509452281000_2026.04.17.719180v1.11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.155242"},{"key":"2026042509452281000_2026.04.17.719180v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/ncb977"},{"key":"2026042509452281000_2026.04.17.719180v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.070"},{"key":"2026042509452281000_2026.04.17.719180v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.07.017"},{"key":"2026042509452281000_2026.04.17.719180v1.15","doi-asserted-by":"publisher","DOI":"10.1101\/gad.255554.114"},{"key":"2026042509452281000_2026.04.17.719180v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.05.032"},{"key":"2026042509452281000_2026.04.17.719180v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/163.1.47"},{"key":"2026042509452281000_2026.04.17.719180v1.18","doi-asserted-by":"publisher","DOI":"10.1128\/jb.104.1.202-210.1970"},{"key":"2026042509452281000_2026.04.17.719180v1.19","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.10507.1"},{"key":"2026042509452281000_2026.04.17.719180v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.04.003"},{"key":"2026042509452281000_2026.04.17.719180v1.21","doi-asserted-by":"publisher","DOI":"10.1002\/cpmb.103"},{"key":"2026042509452281000_2026.04.17.719180v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.08.054"},{"key":"2026042509452281000_2026.04.17.719180v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.12.020"},{"key":"2026042509452281000_2026.04.17.719180v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81876-0"},{"key":"2026042509452281000_2026.04.17.719180v1.25","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201103019"},{"key":"2026042509452281000_2026.04.17.719180v1.26","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E07-06-0584"},{"key":"2026042509452281000_2026.04.17.719180v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nature14097"},{"key":"2026042509452281000_2026.04.17.719180v1.28","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1093\/genetics\/96.3.567","article-title":"Isolation of SPO12-1 and SPO13-1 from a natural variant of yeast that undergoes a single meiotic division","volume":"96","year":"1980","journal-title":"Genetics"},{"key":"2026042509452281000_2026.04.17.719180v1.29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.110117"},{"key":"2026042509452281000_2026.04.17.719180v1.30","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1126\/science.1081846","article-title":"Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation","volume":"300","year":"2003","journal-title":"Science (New York, N.Y.)"},{"key":"2026042509452281000_2026.04.17.719180v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.12.033"},{"key":"2026042509452281000_2026.04.17.719180v1.32","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0061(199807)14:10<953::AID-YEA293>3.0.CO;2-U"},{"key":"2026042509452281000_2026.04.17.719180v1.33","doi-asserted-by":"publisher","DOI":"10.1093\/g3journal\/jkaf121"},{"key":"2026042509452281000_2026.04.17.719180v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/128.1.79"},{"key":"2026042509452281000_2026.04.17.719180v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00130-8"},{"key":"2026042509452281000_2026.04.17.719180v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094220"},{"key":"2026042509452281000_2026.04.17.719180v1.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.026"},{"key":"2026042509452281000_2026.04.17.719180v1.38","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12527"},{"key":"2026042509452281000_2026.04.17.719180v1.39","doi-asserted-by":"publisher","DOI":"10.15252\/EMBJ.2020106812"},{"key":"2026042509452281000_2026.04.17.719180v1.40","doi-asserted-by":"publisher","DOI":"10.1002\/yea.2967"},{"key":"2026042509452281000_2026.04.17.719180v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2024.07.025"},{"key":"2026042509452281000_2026.04.17.719180v1.42","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.17.2272"},{"key":"2026042509452281000_2026.04.17.719180v1.43","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201809138"},{"key":"2026042509452281000_2026.04.17.719180v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1401"},{"key":"2026042509452281000_2026.04.17.719180v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/J.DEVCEL.2021.10.017"},{"key":"2026042509452281000_2026.04.17.719180v1.46","doi-asserted-by":"publisher","DOI":"10.1007\/BF00264206"},{"key":"2026042509452281000_2026.04.17.719180v1.47","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.150.6.1223"},{"key":"2026042509452281000_2026.04.17.719180v1.48","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00947"},{"key":"2026042509452281000_2026.04.17.719180v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.07.029"},{"key":"2026042509452281000_2026.04.17.719180v1.50","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-019-00700-0"},{"key":"2026042509452281000_2026.04.17.719180v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.03.038"},{"key":"2026042509452281000_2026.04.17.719180v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00086-8"},{"key":"2026042509452281000_2026.04.17.719180v1.53","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00048-16"},{"key":"2026042509452281000_2026.04.17.719180v1.54","doi-asserted-by":"publisher","DOI":"10.1038\/nature07876"},{"key":"2026042509452281000_2026.04.17.719180v1.55","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256729"},{"key":"2026042509452281000_2026.04.17.719180v1.56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003610"},{"key":"2026042509452281000_2026.04.17.719180v1.57","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1808809"},{"key":"2026042509452281000_2026.04.17.719180v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.02.023"},{"key":"2026042509452281000_2026.04.17.719180v1.59","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1126\/science.289.5477.300","article-title":"Requirement of the spindle checkpoint for proper chromosome segregation in budding yeast meiosis","volume":"289","year":"2000","journal-title":"Science (New York, N.Y.)"},{"key":"2026042509452281000_2026.04.17.719180v1.60","doi-asserted-by":"publisher","DOI":"10.1101\/2025.08.19.671082"},{"key":"2026042509452281000_2026.04.17.719180v1.61","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00217-8"},{"key":"2026042509452281000_2026.04.17.719180v1.62","doi-asserted-by":"publisher","DOI":"10.1007\/BF00330883"},{"key":"2026042509452281000_2026.04.17.719180v1.63","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200308"},{"key":"2026042509452281000_2026.04.17.719180v1.64","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694082"},{"key":"2026042509452281000_2026.04.17.719180v1.65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.09.013"},{"key":"2026042509452281000_2026.04.17.719180v1.66","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012905"}],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.17.719180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T16:45:38Z","timestamp":1777135538000},"score":9.819632,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.17.719180"}},"issued":{"date-parts":[[2026,4,21]]},"references-count":66,"URL":"https:\/\/doi.org\/10.64898\/2026.04.17.719180","published":{"date-parts":[[2026,4,21]]},"subtype":"preprint"},{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:37:34Z","timestamp":1777426654923,"version":"3.51.4"},"reference-count":67,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["203077"],"award-info":[{"award-number":["203077"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["084538"],"award-info":[{"award-number":["084538"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["101910\/Z\/13\/Z"],"award-info":[{"award-number":["101910\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G19\/9"],"award-info":[{"award-number":["G19\/9"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["091758"],"award-info":[{"award-number":["091758"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["202800"],"award-info":[{"award-number":["202800"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["084226"],"award-info":[{"award-number":["084226"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["067431"],"award-info":[{"award-number":["067431"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"abstract":"Malaria has been a major driving force in the evolution of the human genome. In sub-Saharan African populations, two neighbouring polymorphisms in the Complement Receptor One (CR1) gene, named Sl2 and McCb, occur at high frequencies, consistent with selection by malaria. Previous studies have been inconclusive. Using a large case-control study of severe malaria in Kenyan children and statistical models adjusted for confounders, we estimate the relationship between Sl2 and McCb and malaria phenotypes, and find they have opposing associations. The Sl2 polymorphism is associated with markedly reduced odds of cerebral malaria and death, while the McCb polymorphism is associated with increased odds of cerebral malaria. We also identify an apparent interaction between Sl2 and \u03b1+thalassaemia, with the protective association of Sl2 greatest in children with normal \u03b1-globin. The complex relationship between these three mutations may explain previous conflicting findings, highlighting the importance of considering genetic interactions in disease-association studies.<\/jats:p>","DOI":"10.7554\/elife.31579","type":"journal-article","created":{"date-parts":[[2018,4,24]],"date-time":"2018-04-24T20:00:11Z","timestamp":1524600011000},"source":"Crossref","is-referenced-by-count":29,"title":["Two complement receptor one alleles have opposing associations with cerebral malaria and interact with \u03b1+thalassaemia"],"prefix":"10.7554","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-4365","authenticated-orcid":true,"given":"D Herbert","family":"Opi","sequence":"first","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7386-2849","authenticated-orcid":true,"given":"Olivia","family":"Swann","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Macharia","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Uyoga","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Band","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyne M","family":"Ndila","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewen M","family":"Harrison","sequence":"additional","affiliation":[{"name":"Centre for Medical Infomatics, Usher Insitute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2679-035X","authenticated-orcid":true,"given":"Mahamadou A","family":"Thera","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdoulaye K","family":"Kone","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dapa A","family":"Diallo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ogobara K","family":"Doumbo","sequence":"additional","affiliation":[{"name":"Malaria Research and Training Centre, Faculty of Medicine, Pharmacy, and Dentistry, University of Bamako, Bamako, Mali"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirsten E","family":"Lyke","sequence":"additional","affiliation":[{"name":"Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher V","family":"Plowe","sequence":"additional","affiliation":[{"name":"Division of Malaria Research, Institute for Global Health, University of Maryland School of Medicine, Baltimore, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joann M","family":"Moulds","sequence":"additional","affiliation":[{"name":"Lifeshare Blood Centers, Shreveport, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Shebbe","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neema","family":"Mturi","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Peshu","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Maitland","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Department of Medicine, Imperial College, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed","family":"Raza","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic P","family":"Kwiatkowski","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"},{"name":"Wellcome Trust Sanger Institute, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-9299","authenticated-orcid":true,"given":"Kirk A","family":"Rockett","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4456-2382","authenticated-orcid":true,"given":"Thomas N","family":"Williams","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute-Wellcome Trust Research Programme, Kilifi, Kenya"},{"name":"Department of Medicine, Imperial College, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-1892","authenticated-orcid":true,"given":"J Alexandra","family":"Rowe","sequence":"additional","affiliation":[{"name":"Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4374","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1182\/blood-2013-10-533489","article-title":"Epistasis between the haptoglobin common variant and \u03b1+thalassemia influences risk of severe malaria in Kenyan children","volume":"123","author":"Atkinson","year":"2014","journal-title":"Blood"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"e1003509","DOI":"10.1371\/journal.pgen.1003509","article-title":"Imputation-based meta-analysis of severe malaria in three African populations","volume":"9","author":"Band","year":"2013","journal-title":"PLoS Genetics"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"Journal of Statistical Software"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"e15266","DOI":"10.7554\/eLife.15266","article-title":"Admixture into and within sub-Saharan Africa","volume":"5","author":"Busby","year":"2016","journal-title":"eLife"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.1182\/blood.V84.11.3909.bloodjournal84113909","article-title":"Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation","volume":"84","author":"Carlson","year":"1994","journal-title":"Blood"},{"key":"bib6","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1182\/blood.V95.1.360","article-title":"Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia","volume":"95","author":"Chong","year":"2000","journal-title":"Blood"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"e15085","DOI":"10.7554\/eLife.15085","article-title":"Characterisation of the opposing effects of G6PD deficiency on cerebral malaria and severe malarial anaemia","volume":"6","author":"Clarke","year":"2017","journal-title":"eLife"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1073\/pnas.0305306101","article-title":"A human complement receptor 1 polymorphism that reduces Plasmodium falciparum rosetting confers protection against severe malaria","volume":"101","author":"Cockburn","year":"2004","journal-title":"PNAS"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1537-2995.2007.01077.x","article-title":"Knops blood group haplotypes among distinct Brazilian populations","volume":"47","author":"Covas","year":"2007","journal-title":"Transfusion"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"987","DOI":"10.4269\/ajtmh.2009.09-0406","article-title":"High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children","volume":"81","author":"Doumbo","year":"2009","journal-title":"American Journal of Tropical Medicine and Hygiene"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/1475-2875-9-119","article-title":"Candidate malaria susceptibility\/protective SNPs in hospital and population-based studies: the effect of sub-structuring","volume":"9","author":"Eid","year":"2010","journal-title":"Malaria Journal"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/nature03631","article-title":"Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria","volume":"435","author":"Fairhurst","year":"2005","journal-title":"Nature"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1177\/1745691612462587","article-title":"The Long Way From \u03b1-Error Control to Validity Proper: Problems With a Short-Sighted False-Positive Debate","volume":"7","author":"Fiedler","year":"2012","journal-title":"Perspectives on Psychological Science : A Journal of the Association for Psychological Science"},{"key":"bib14","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4269\/ajtmh.2004.71.330","article-title":"Large-scale candidate gene study of leprosy susceptibility in the Karonga district of northern Malawi","volume":"71","author":"Fitness","year":"2004","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1371\/journal.pmed.0050056","article-title":"Increased microerythrocyte count in homozygous alpha(+)-thalassaemia contributes to protection against severe malarial anaemia","volume":"5","author":"Fowkes","year":"2008","journal-title":"PLoS Medicine"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1093\/hmg\/ddm331","article-title":"Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria","volume":"17","author":"Fry","year":"2008","journal-title":"Human Molecular Genetics"},{"key":"bib17","first-page":"288","article-title":"Role of CR1 Knops polymorphism in the pathophysiology of malaria: Indian scenario","volume":"46","author":"Gandhi","year":"2009","journal-title":"Journal of Vector Borne Diseases"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1084\/jem.192.12.1797","article-title":"Complement receptor 1\/CD35 is a receptor for mannan-binding lectin","volume":"192","author":"Ghiran","year":"2000","journal-title":"The Journal of Experimental Medicine"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1159\/000108939","article-title":"Graphical tests for Hardy-Weinberg equilibrium based on the ternary plot","volume":"65","author":"Graffelman","year":"2008","journal-title":"Human Heredity"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1186\/1475-2875-12-400","article-title":"Human genetic polymorphisms in the Knops blood group are not associated with a protective advantage against Plasmodium falciparum malaria in Southern Ghana","volume":"12","author":"Hansson","year":"2013","journal-title":"Malaria Journal"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/ng.388","article-title":"Genome-wide and fine-resolution association analysis of malaria in West Africa","volume":"41","author":"Jallow","year":"2009","journal-title":"Nature Genetics"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/epi.12173","article-title":"The genetic risk of acute seizures in African children with falciparum malaria","volume":"54","author":"Kariuki","year":"2013","journal-title":"Epilepsia"},{"key":"bib23","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1182\/blood.V78.3.812.812","article-title":"Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions","volume":"78","author":"Kaul","year":"1991","journal-title":"Blood"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"e37214","DOI":"10.1371\/journal.pone.0037214","article-title":"\u03b1-Thalassemia impairs the cytoadherence of Plasmodium falciparum-infected erythrocytes","volume":"7","author":"Krause","year":"2012","journal-title":"PLoS ONE"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1034\/j.1600-065X.2001.1800110.x","article-title":"Structure-function relationships of complement receptor type 1","volume":"180","author":"Krych-Goldberg","year":"2001","journal-title":"Immunological Reviews"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S1471-4914(02)02419-X","article-title":"Human complement receptor type 1 (CR1) binds to a major malarial adhesin","volume":"8","author":"Krych-Goldberg","year":"2002","journal-title":"Trends in Molecular Medicine"},{"key":"bib27","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4269\/ajtmh.2003.69.253","article-title":"Association of intraleukocytic Plasmodium falciparum malaria pigment with disease severity, clinical manifestations, and prognosis in severe malaria","volume":"69","author":"Lyke","year":"2003","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nature15390","article-title":"A novel locus of resistance to severe malaria in a region of ancient balancing selection","volume":"526","author":"Malaria Genomic Epidemiology Network","year":"2015","journal-title":"Nature"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"e47463","DOI":"10.1371\/journal.pone.0047463","article-title":"Candidate human genetic polymorphisms and severe malaria in a Tanzanian population","volume":"7","author":"Manjurano","year":"2012","journal-title":"PLoS ONE"},{"key":"bib30","doi-asserted-by":"crossref","first-page":"734","DOI":"10.4269\/ajtmh.2003.68.734","article-title":"Spatial and temporal heterogeneity of Anopheles mosquitoes and Plasmodium falciparum transmission along the Kenyan coast","volume":"68","author":"Mbogo","year":"2003","journal-title":"The American Journal of Tropical Medicine and Hygiene"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1111\/j.1537-2995.2004.00615.x","article-title":"Identification of the Kna\/Knb polymorphism and a method for Knops genotyping","volume":"44","author":"Moulds","year":"2004","journal-title":"Transfusion"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"2879","DOI":"10.1182\/blood.V97.9.2879","article-title":"Molecular identification of Knops blood group polymorphisms found in long homologous region D of complement receptor 1","volume":"97","author":"Moulds","year":"2001","journal-title":"Blood"},{"key":"bib33","doi-asserted-by":"crossref","first-page":"2","DOI":"10.21307\/immunohematology-2019-193","article-title":"The Knops blood-group system: a review","volume":"26","author":"Moulds","year":"2010","journal-title":"Immunohematology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1093\/beheco\/arh107","article-title":"A farewell to Bonferroni: the problems of low statistical power and publication bias","volume":"15","author":"Nakagawa","year":"2004","journal-title":"Behavioral Ecology"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.1111\/j.1537-2995.2011.03161.x","article-title":"Knops blood group polymorphism and susceptibility to Mycobacterium tuberculosis infection","volume":"51","author":"Noumsi","year":"2011","journal-title":"Transfusion"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1093\/ajcn\/80.6.1604","article-title":"Malaria and nutritional status in children living on the coast of Kenya","volume":"80","author":"Nyakeriga","year":"2004","journal-title":"The American Journal of Clinical Nutrition"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1555","DOI":"10.1016\/S0140-6736(08)61655-4","article-title":"Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya","volume":"372","author":"O'Meara","year":"2008","journal-title":"The Lancet"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ebiom.2014.10.006","article-title":"Mechanistic studies of the negative epistatic malaria-protective interaction between sickle cell trait and alphathalassemia","volume":"1","author":"Opi","year":"2014","journal-title":"EBioMedicine"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/gene.2016.2","article-title":"Red blood cell complement receptor one level varies with Knops blood group, \u03b1(+)thalassaemia and age among Kenyan children","volume":"17","author":"Opi","year":"2016","journal-title":"Genes & Immunity"},{"key":"bib40","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.4049\/jimmunol.141.11.3889","article-title":"Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane","volume":"141","author":"Paccaud","year":"1988","journal-title":"Journal of Immunology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"21242","DOI":"10.1073\/pnas.0910840106","article-title":"Epistatic interactions between genetic disorders of hemoglobin can explain why the sickle-cell gene is uncommon in the Mediterranean","volume":"106","author":"Penman","year":"2009","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1136\/bmj.316.7139.1236","article-title":"What's wrong with Bonferroni adjustments","volume":"316","author":"Perneger","year":"1998","journal-title":"BMJ"},{"key":"bib43","article-title":"R: A language and environment for statistical computing","author":"R Development Core Team","year":"2010","unstructured":"R Development Core Team. 2010. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. 2.11.1."},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1038\/ng.3107","article-title":"Reappraisal of known malaria resistance loci in a large multicenter study","volume":"46","author":"Rockett","year":"2014","journal-title":"Nature Genetics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1097\/00001648-199001000-00010","article-title":"No adjustments are needed for multiple comparisons","volume":"1","author":"Rothman","year":"1990","journal-title":"Epidemiology"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1007\/s11606-013-2755-z","article-title":"Six persistent research misconceptions","volume":"29","author":"Rothman","year":"2014","journal-title":"Journal of General Internal Medicine"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"e16","DOI":"10.1017\/S1462399409001082","article-title":"Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications","volume":"11","author":"Rowe","year":"2009","journal-title":"Expert Reviews in Molecular Medicine"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"17471","DOI":"10.1073\/pnas.0705390104","article-title":"Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting","volume":"104","author":"Rowe","year":"2007","journal-title":"PNAS"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/40888","article-title":"P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1","volume":"388","author":"Rowe","year":"1997","journal-title":"Nature"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"6341","DOI":"10.4049\/jimmunol.165.11.6341","article-title":"Mapping of the region of complement receptor (CR) 1 required for Plasmodium falciparum rosetting and demonstration of the importance of CR1 in rosetting in field isolates","volume":"165","author":"Rowe","year":"2000","journal-title":"The Journal of Immunology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.molimm.2015.03.006","article-title":"More than just immune evasion: Hijacking complement by Plasmodium falciparum","volume":"67","author":"Schmidt","year":"2015","journal-title":"Molecular Immunology"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1093\/ije\/dys062","article-title":"Profile: The kilifi health and demographic surveillance system (KHDSS)","volume":"41","author":"Scott","year":"2012","journal-title":"International Journal of Epidemiology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"e1000968","DOI":"10.1371\/journal.ppat.1000968","article-title":"Complement receptor 1 is a sialic acid-independent erythrocyte receptor of Plasmodium falciparum","volume":"6","author":"Spadafora","year":"2010","journal-title":"PLoS Pathogens"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"17825","DOI":"10.1038\/s41598-017-17664-9","article-title":"No evidence that knops blood group polymorphisms affect complement receptor 1 clustering on erythrocytes","volume":"7","author":"Swann","year":"2017","journal-title":"Scientific Reports"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"e34820","DOI":"10.1371\/journal.pone.0034820","article-title":"Lack of evidence from studies of soluble protein fragments that Knops blood group polymorphisms in complement receptor-type 1 are driven by malaria","volume":"7","author":"Tetteh-Quarcoo","year":"2012","journal-title":"PLoS ONE"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1179\/2047773215Y.0000000011","article-title":"Severity of malaria in relation to a complement receptor 1 polymorphism: a case-control study","volume":"109","author":"Tettey","year":"2015","journal-title":"Pathogens and Global Health"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"17327","DOI":"10.1073\/pnas.1008151107","article-title":"Complement receptor 1 is the host erythrocyte receptor for Plasmodium falciparum PfRh4 invasion ligand","volume":"107","author":"Tham","year":"2010","journal-title":"PNAS"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1475-2875-4-54","article-title":"Complement receptor 1 polymorphisms associated with resistance to severe malaria in Kenya","volume":"4","author":"Thathy","year":"2005","journal-title":"Malaria Journal"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"e43987","DOI":"10.1371\/journal.pone.0043987","article-title":"Candidate polymorphisms and severe malaria in a Malian population","volume":"7","author":"Toure","year":"2012","journal-title":"PLoS ONE"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"e119","DOI":"10.1093\/nar\/29.23.e119","article-title":"Single tube genotyping of sickle cell anaemia using PCR-based SNP analysis","volume":"29","author":"Waterfall","year":"2001","journal-title":"Nucleic Acids Research"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3","volume-title":"Ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2009"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1086\/430744","article-title":"Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases","volume":"192","author":"Williams","year":"2005","journal-title":"The Journal of Infectious Diseases"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/ng1660","article-title":"Negative epistasis between the malaria-protective effects of alpha+-thalassemia and the sickle cell trait","volume":"37","author":"Williams","year":"2005","journal-title":"Nature Genetics"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1016\/S0140-6736(09)61374-X","article-title":"Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case-control study","volume":"374","author":"Williams","year":"2009","journal-title":"The Lancet"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1182\/blood-2005-01-0313","article-title":"Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya","volume":"106","author":"Williams","year":"2005","journal-title":"Blood"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.humimm.2012.10.024","article-title":"The polymorphism of Knops blood group system in Korean population and their relationship with HLA system","volume":"74","author":"Yoon","year":"2013","journal-title":"Human Immunology"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/sj.gene.6363980","article-title":"CR1 Knops blood group alleles are not associated with severe malaria in the Gambia","volume":"4","author":"Zimmerman","year":"2003","journal-title":"Genes & Immunity"}],"container-title":["eLife"],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31579\/elife-31579-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/31579\/elife-31579-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/31579","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:48:46Z","timestamp":1697057326000},"score":9.809329,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/31579"}},"issued":{"date-parts":[[2018,4,25]]},"references-count":67,"alternative-id":["10.7554\/eLife.31579"],"URL":"https:\/\/doi.org\/10.7554\/elife.31579","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"uri","id":"https:\/\/www.malariagen.net\/projects\/consortial-project-1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.31579.025","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.31579.024","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"published":{"date-parts":[[2018,4,25]]},"article-number":"e31579"},{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:00:30Z","timestamp":1790805630002,"version":"4.1.0"},"reference-count":77,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"56","funder":[{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["213555\/Z\/18\/Z"],"award-info":[{"award-number":["213555\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["208961\/Z\/17\/Z"],"award-info":[{"award-number":["208961\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["206194"],"award-info":[{"award-number":["206194"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","award":["110020\/Z\/15\/Z"],"award-info":[{"award-number":["110020\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2021,2,12]]},"abstract":"Integrated single-cell transcriptomic and BCR analyses reveal how antibody class switching influences human B cell fate and function.<\/jats:p>","DOI":"10.1126\/sciimmunol.abe6291","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T23:56:34Z","timestamp":1613260594000},"source":"Crossref","is-referenced-by-count":287,"title":["Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics"],"prefix":"10.1126","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5972-8926","authenticated-orcid":true,"given":"Hamish W.","family":"King","sequence":"first","affiliation":[{"name":"Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK."},{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nara","family":"Orban","sequence":"additional","affiliation":[{"name":"Barts Health Ear, Nose and Throat Service, Royal London Hospital, London E1 1BB, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3425-7686","authenticated-orcid":true,"given":"John C.","family":"Riches","sequence":"additional","affiliation":[{"name":"Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK."},{"name":"Francis Crick Institute, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-5642","authenticated-orcid":true,"given":"Andrew J.","family":"Clear","sequence":"additional","affiliation":[{"name":"Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7614-6266","authenticated-orcid":true,"given":"Gary","family":"Warnes","sequence":"additional","affiliation":[{"name":"Flow Cytometry Core Facility, Blizard Institute, Queen Mary University of London, London E1 2AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6294-6366","authenticated-orcid":true,"given":"Sarah A.","family":"Teichmann","sequence":"additional","affiliation":[{"name":"Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK."},{"name":"Theory of Condensed Matter, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0EH, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2252-4636","authenticated-orcid":true,"given":"Louisa K.","family":"James","sequence":"additional","affiliation":[{"name":"Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.016"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.09.001"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.03.006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401849"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16578"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0427-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12744"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni752"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6456"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.65"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3460"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.11.022"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1213230"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001155"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"V. Kleshchevnikov A. Shmatko E. Dann A. Aivazidis H. W. King T. Li A. Lomakin V. Kedlian M. S. Jain J. S. Park L. Ramona E. Tuck A. Arutyunyan R. Vento-Tormo M. Gerstung L. James O. Stegle O. A. Bayraktar Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics. bioRxiv 2020.11.15.378125 [ Preprint ]. 17 November 2020. https:\/\/doi.org\/10.1101\/2020.11.15.378125.","DOI":"10.1101\/2020.11.15.378125"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200483"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0591-3"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250020"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2303"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20012065"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.07.001"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.27.17025"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.8.3605"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601678113"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101321"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx380"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13290"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.10.009"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201747360"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303216"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0181-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-504597"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.235275"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13765"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.644"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090738"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20152003"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-518605"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12651"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050879"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aai8153"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12795"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501027"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1814"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9575"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1416276112"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-008-9264-6"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021686"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02820"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12311"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901982"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-626176"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00108"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3942"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4630"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061254"},{"key":"e_1_3_2_59_2","doi-asserted-by":"crossref","unstructured":"N. R. Mathew J. K. Jayanthan I. Smirnov J. L. Robinson H. Axelsson S. S. Nakka A. Emmanouilidi P. Czarnewski W. T. Yewdell C. Lebrero-Fern\u00e1ndez V. Bernasconi A. M. Harandi N. Lycke N. Borcherding J. W. Yewdell V. Greiff M. Bemark D. Angeletti Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses. bioRxiv 2020.08.24.264069 [ Preprint ]. 24 August 2020. https:\/\/doi.org\/10.1101\/2020.08.24.264069.","DOI":"10.1101\/2020.08.24.264069"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu138"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt382"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417683112"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0602-z"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay3224"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4197"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7563.1"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.97"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1193"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1449-6"}],"container-title":["Science Immunology"],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1126\/sciimmunol.abe6291","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciimmunol.abe6291","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T05:53:09Z","timestamp":1705384389000},"score":9.798704,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abe6291"}},"issued":{"date-parts":[[2021,2,12]]},"references-count":77,"journal-issue":{"issue":"56","published-print":{"date-parts":[[2021,2,12]]}},"alternative-id":["10.1126\/sciimmunol.abe6291"],"URL":"https:\/\/doi.org\/10.1126\/sciimmunol.abe6291","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.28.054775","asserted-by":"object"}]},"ISSN":["2470-9468"],"issn-type":[{"value":"2470-9468","type":"electronic"}],"published":{"date-parts":[[2021,2,12]]},"article-number":"eabe6291"},{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:21:06Z","timestamp":1790688066083,"version":"4.1.0"},"reference-count":102,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["098387\/Z\/12\/Z"],"award-info":[{"award-number":["098387\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["212284\/Z\/18\/Z"],"award-info":[{"award-number":["212284\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["109109\/Z\/15\/Z"],"award-info":[{"award-number":["109109\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["095552\/Z\/11\/Z"],"award-info":[{"award-number":["095552\/Z\/11\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"abstract":"\n During meiosis, homologous chromosomes pair and recombine, enabling balanced segregation and generating genetic diversity. In many vertebrates, double-strand breaks (DSBs) initiate recombination within hotspots where PRDM9 binds, and deposits H3K4me3 and H3K36me3. However, no protein(s) recognising this unique combination of histone marks have been identified. We identified\n Zcwpw1<\/jats:italic>\n , containing H3K4me3 and H3K36me3 recognition domains, as having highly correlated expression with\n Prdm9<\/jats:italic>\n . Here, we show that ZCWPW1 has co-evolved with PRDM9 and, in human cells, is strongly and specifically recruited to PRDM9 binding sites, with higher affinity than sites possessing H3K4me3 alone. Surprisingly, ZCWPW1 also recognises CpG dinucleotides. Male\n Zcwpw1<\/jats:italic>\n knockout mice show completely normal DSB positioning, but persistent DMC1 foci, severe DSB repair and synapsis defects, and downstream sterility. Our findings suggest ZCWPW1 recognition of PRDM9-bound sites at DSB hotspots is critical for synapsis, and hence fertility.\n <\/jats:p>","DOI":"10.7554\/elife.53392","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T08:00:39Z","timestamp":1596441639000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.53392","source":"Crossref","is-referenced-by-count":64,"title":["ZCWPW1 is recruited to recombination hotspots by PRDM9 and is essential for meiotic double strand break repair"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2007-8978","authenticated-orcid":true,"given":"Daniel","family":"Wells","sequence":"first","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Statistics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3439-2113","authenticated-orcid":true,"given":"Emmanuelle","family":"Bitoun","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Statistics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Moralli","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Hinch","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Jankowska","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Donnelly","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Statistics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Green","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-9626","authenticated-orcid":true,"given":"Simon R","family":"Myers","sequence":"additional","affiliation":[{"name":"The Wellcome Centre for Human Genetics, Roosevelt Drive, University of Oxford, Oxford, United Kingdom"},{"name":"Department of Statistics, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/BF00292841","article-title":"In vivo BrdU-33258 hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cells","volume":"58","author":"Allen","year":"1976","journal-title":"Chromosoma"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28383","article-title":"A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis","volume":"6","author":"Altemose","year":"2017","journal-title":"eLife"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Research"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"5101","DOI":"10.1111\/j.1742-4658.2005.04945.x","article-title":"Protein database searches using compositionally adjusted substitution matrices","volume":"272","author":"Altschul","year":"2005","journal-title":"FEBS Journal"},{"key":"bib5","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1242\/jcs.114.4.685","article-title":"Localization of two mammalian cyclin dependent kinases during mammalian meiosis","volume":"114","author":"Ashley","year":"2001","journal-title":"Journal of Cell Science"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/nsmb.2796","article-title":"Transcriptionally active chromatin recruits homologous recombination at DNA double-strand breaks","volume":"21","author":"Aymard","year":"2014","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.24133","article-title":"Repeated losses of PRDM9-directed recombination despite the conservation of PRDM9 across vertebrates","volume":"6","author":"Baker","year":"2017","journal-title":"eLife"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.ccell.2018.07.006","article-title":"The SS18-SSX oncoprotein hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma","volume":"34","author":"Banito","year":"2018","journal-title":"Cancer Cell"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000076","article-title":"ATM promotes the obligate XY crossover and both crossover control and chromosome Axis integrity on autosomes","volume":"4","author":"Barchi","year":"2008","journal-title":"PLOS Genetics"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cell.2007.05.009","article-title":"High-resolution profiling of histone methylations in the human genome","volume":"129","author":"Barski","year":"2007","journal-title":"Cell"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1126\/science.1183439","article-title":"PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice","volume":"327","author":"Baudat","year":"2010","journal-title":"Science"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.14541.1","article-title":"drawProteins: a bioconductor\/R package for reproducible and programmatic generation of protein schematics","volume":"7","author":"Brennan","year":"2018","journal-title":"F1000Research"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/nature11089","article-title":"Genetic recombination is directed away from functional genomic elements in mice","volume":"485","author":"Brick","year":"2012","journal-title":"Nature"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005653","article-title":"Small Rad51 and Dmc1 complexes often Co-occupy both ends of a meiotic DNA double strand break","volume":"11","author":"Brown","year":"2015","journal-title":"PLOS Genetics"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/s00412-019-00692-x","article-title":"Leagues of their own: sexually dimorphic features of meiotic prophase I","volume":"128","author":"Cahoon","year":"2019","journal-title":"Chromosoma"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006529","article-title":"A versatile viral system for expression and depletion of proteins in mammalian cells","volume":"4","author":"Campeau","year":"2009","journal-title":"PLOS ONE"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1093\/bioinformatics\/btm270","article-title":"Predicting functionally important residues from sequence conservation","volume":"23","author":"Capra","year":"2007","journal-title":"Bioinformatics"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1089\/bio.2015.0032","article-title":"A novel approach to High-Quality postmortem tissue procurement: the GTEx project","volume":"13","author":"Carithers","year":"2015","journal-title":"Biopreservation and Biobanking"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02482","article-title":"SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint","volume":"3","author":"Carvalho","year":"2014","journal-title":"eLife"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/7506976","article-title":"Noncoding centromeric RNA expression impairs chromosome stability in human and murine stem cells","volume":"2017","author":"Chan","year":"2017","journal-title":"Disease Markers"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1038\/nature16931","article-title":"Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice","volume":"530","author":"Davies","year":"2016","journal-title":"Nature"},{"key":"bib22","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-12-236","article-title":"Alu elements: know the SINEs","volume":"12","author":"Deininger","year":"2011","journal-title":"Genome Biology"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.molcel.2018.01.033","article-title":"PRDM9 methyltransferase activity is essential for meiotic DNA Double-Strand break formation at its binding sites","volume":"69","author":"Diagouraga","year":"2018","journal-title":"Molecular Cell"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.devcel.2007.03.018","article-title":"SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice","volume":"12","author":"Ding","year":"2007","journal-title":"Developmental Cell"},{"key":"bib25","volume-title":"data.table: Extension of `data.frame`","author":"Dowle","year":"2019","unstructured":"Dowle M, Srinivasan A. 2019. data.table: Extension of `data.frame`."},{"key":"bib26","volume-title":"viridis: Default Color Maps from \u201cmatplotlib","author":"Garnier","year":"2018","unstructured":"Garnier S. 2018. viridis: Default Color Maps from \u201cmatplotlib."},{"key":"bib27","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1002\/cyto.a.22463","article-title":"Optimized flow cytometry isolation of murine spermatocytes","volume":"85","author":"Gaysinskaya","year":"2014","journal-title":"Cytometry Part A"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1186\/s13072-018-0186-0","article-title":"Transient reduction of DNA methylation at the onset of meiosis in male mice","volume":"11","author":"Gaysinskaya","year":"2018","journal-title":"Epigenetics & Chromatin"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"2595","DOI":"10.1093\/bioinformatics\/btv153","article-title":"PRROC: computing and visualizing precision-recall and receiver operating characteristic curves in R","volume":"31","author":"Grau","year":"2015","journal-title":"Bioinformatics"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34282","article-title":"Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice","volume":"7","author":"Gregorova","year":"2018","journal-title":"eLife"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/nature04112","article-title":"A histone H3 methyltransferase controls epigenetic events required for meiotic prophase","volume":"438","author":"Hayashi","year":"2005","journal-title":"Nature"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.2210\/pdb2rr4\/pdb","article-title":"Complex structure of the zf-CW domain and the H3K4me3 peptide","volume":"18","author":"He","year":"2010","journal-title":"Structure"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/j.str.2010.06.012","article-title":"Structural insight into the zinc finger CW domain as a histone modification reader","volume":"18","author":"He","year":"2010","journal-title":"Structure"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1002\/dvdy.24183","article-title":"Poly peak parser: method and software for identification of unknown indels using Sanger sequencing of polymerase chain reaction products","volume":"243","author":"Hill","year":"2014","journal-title":"Developmental Dynamics"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau8861","article-title":"Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm","volume":"363","author":"Hinch","year":"2019","journal-title":"Science"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"41906","DOI":"10.1074\/jbc.M105563200","article-title":"Saccharomyces cerevisiae Dmc1 protein promotes renaturation of single-strand DNA (ssDNA) and assimilation of ssDNA into homologous super-coiled duplex DNA","volume":"276","author":"Hong","year":"2001","journal-title":"Journal of Biological Chemistry"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1083\/jcb.201304004","article-title":"A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton","volume":"202","author":"Horn","year":"2013","journal-title":"The Journal of Cell Biology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"7811","DOI":"10.1074\/jbc.RA118.002839","article-title":"H3K36me3-mediated mismatch repair preferentially protects actively transcribed genes from mutation","volume":"293","author":"Huang","year":"2018","journal-title":"Journal of Biological Chemistry"},{"key":"bib40","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53459","article-title":"The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair","volume":"9","author":"Huang","year":"2020","journal-title":"eLife"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11282-x","article-title":"The histone methyltransferase Setd2 is indispensable for V(D)J recombination","volume":"10","author":"Ji","year":"2019","journal-title":"Nature Communications"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-388","article-title":"A comparative study of conservation and variation scores","volume":"11","author":"Johansson","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43966","article-title":"Unified single-cell analysis of testis gene regulation and pathology in five mouse strains","volume":"8","author":"Jung","year":"2019","journal-title":"eLife"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1093\/bioinformatics\/btq351","article-title":"BigWig and BigBed: enabling browsing of large distributed datasets","volume":"26","author":"Kent","year":"2010","journal-title":"Bioinformatics"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1101\/gr.130583.111","article-title":"Sensitive mapping of recombination hotspots using sequencing-based detection of ssDNA","volume":"22","author":"Khil","year":"2012","journal-title":"Genome Research"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"2520","DOI":"10.1093\/bioinformatics\/bts480","article-title":"Snakemake--a scalable bioinformatics workflow engine","volume":"28","author":"K\u00f6ster","year":"2012","journal-title":"Bioinformatics"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1038\/s41580-019-0126-2","article-title":"Quality and quantity control of gene expression by nonsense-mediated mRNA decay","volume":"20","author":"Kurosaki","year":"2019","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.cell.2016.09.035","article-title":"The landscape of mouse meiotic Double-Strand break formation, processing, and repair","volume":"167","author":"Lange","year":"2016","journal-title":"Cell"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"41725","DOI":"10.1074\/jbc.M508312200","article-title":"CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1\/COMPASS complex","volume":"280","author":"Lee","year":"2005","journal-title":"Journal of Biological Chemistry"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1128\/MCB.01356-07","article-title":"Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A histone H3-Lys4 methyltransferase complex to transcription start sites of transcribed human genes","volume":"28","author":"Lee","year":"2008","journal-title":"Molecular and Cellular Biology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.cell.2013.03.025","article-title":"The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutS\u03b1","volume":"153","author":"Li","year":"2013","journal-title":"Cell"},{"key":"bib52","article-title":"Aligning sequence reads\u00a0clone sequences and assembly contigs with BWA-MEM","volume-title":"\u00a0arXiv","author":"Li","year":"2013","unstructured":"Li H. 2013. Aligning sequence reads\u00a0clone sequences and assembly contigs with BWA-MEM. \u00a0arXiv. https:\/\/arxiv.org\/abs\/1303.3997."},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax1101","article-title":"The histone modification reader ZCWPW1 is required for meiosis prophase I in male but not in female mice","volume":"5","author":"Li","year":"2019","journal-title":"Science Advances"},{"key":"bib54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11675-y","article-title":"A high-resolution map of non-crossover events reveals impacts of genetic diversity on mammalian meiotic recombination","volume":"10","author":"Li","year":"2019","journal-title":"Nature Communications"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00339","article-title":"Overexpression of the heterochromatinization factor BAHD1 in HEK293 cells differentially reshapes the DNA methylome on autosomes and X chromosome","volume":"6","author":"Libertini","year":"2015","journal-title":"Frontiers in Genetics"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"9000","DOI":"10.1074\/jbc.M116.718973","article-title":"Family-wide characterization of histone binding abilities of human CW Domain-containing proteins","volume":"291","author":"Liu","year":"2016","journal-title":"Journal of Biological Chemistry"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1093\/bioinformatics\/btp302","article-title":"pGenTHREADER and pDomTHREADER: new methods for improved protein fold recognition and superfamily discrimination","volume":"25","author":"Lobley","year":"2009","journal-title":"Bioinformatics"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1080\/15384101.2014.998070","article-title":"Double-strand break repair on sex chromosomes: challenges during male meiotic prophase","volume":"14","author":"Lu","year":"2015","journal-title":"Cell Cycle"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1101\/gr.111120.110","article-title":"Stampy: a statistical algorithm for sensitive and fast mapping of illumina sequence reads","volume":"21","author":"Lunter","year":"2011","journal-title":"Genome Research"},{"key":"bib60","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/784706","article-title":"Dynamic alu methylation during normal development, aging, and tumorigenesis","volume":"2014","author":"Luo","year":"2014","journal-title":"BioMed Research International"},{"key":"bib61","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53360","article-title":"Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice","volume":"9","author":"Mahgoub","year":"2020","journal-title":"eLife"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"W327","DOI":"10.1093\/nar\/gkh454","article-title":"CD-Search: protein domain annotations on the fly","volume":"32","author":"Marchler-Bauer","year":"2004","journal-title":"Nucleic Acids Research"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1007\/s00018-017-2517-x","article-title":"Shaping the cellular landscape with Set2\/SETD2 methylation","volume":"74","author":"McDaniel","year":"2017","journal-title":"Cellular and Molecular Life Sciences"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1101\/gr.244426.118","article-title":"Histone methyltransferase PRDM9 is not essential for meiosis in male mice","volume":"29","author":"Mihola","year":"2019","journal-title":"Genome Research"},{"key":"bib65","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1242\/jcs.115.8.1611","article-title":"The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination","volume":"115","author":"Moens","year":"2002","journal-title":"Journal of Cell Science"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1530\/rep.1.00865","article-title":"Not all germ cells are created equal: aspects of sexual dimorphism in mammalian meiosis","volume":"130","author":"Morelli","year":"2005","journal-title":"Reproduction"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.molcel.2008.10.025","article-title":"CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation","volume":"32","author":"Mulligan","year":"2008","journal-title":"Molecular Cell"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1126\/science.1182363","article-title":"Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination","volume":"327","author":"Myers","year":"2010","journal-title":"Science"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/nature04885","article-title":"Clarifying the mechanics of DNA strand exchange in meiotic recombination","volume":"442","author":"Neale","year":"2006","journal-title":"Nature"},{"key":"bib70","volume-title":"RColorBrewer: ColorBrewer Palettes","author":"Neuwirth","year":"2014","unstructured":"Neuwirth E. 2014. RColorBrewer: ColorBrewer Palettes."},{"key":"bib71","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181495","article-title":"Prdm9 controls activation of mammalian recombination hotspots","volume":"327","author":"Parvanov","year":"2010","journal-title":"Science"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1091\/mbc.e16-09-0686","article-title":"PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal Axis in meiosis","volume":"28","author":"Parvanov","year":"2017","journal-title":"Molecular Biology of the Cell"},{"key":"bib73","volume-title":"ggforce: Accelerating \u201cggplot2","author":"Pedersen","year":"2016","unstructured":"Pedersen TL. 2016. ggforce: Accelerating \u201cggplot2."},{"key":"bib74","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1023\/a:1018445520117","article-title":"A drying-down technique for the spreading of mammalian meiocytes from the male and female germline","volume":"5","author":"Peters","year":"1997","journal-title":"Chromosome Research : An International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/S1534-5807(03)00369-1","article-title":"The Hop2 protein has a direct role in promoting interhomolog interactions during mouse meiosis","volume":"5","author":"Petukhova","year":"2003","journal-title":"Developmental Cell"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.celrep.2014.05.026","article-title":"SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability","volume":"7","author":"Pfister","year":"2014","journal-title":"Cell Reports"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1093\/bioinformatics\/btu056","article-title":"Bwtool: a tool for bigWig files","volume":"30","author":"Pohl","year":"2014","journal-title":"Bioinformatics"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006146","article-title":"The meiotic recombination activator PRDM9 trimethylates both H3K36 and H3K4 at recombination hotspots in vivo","volume":"12","author":"Powers","year":"2016","journal-title":"PLOS Genetics"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256442","article-title":"DNA recombination recombination initiation maps of individual human genomes","volume":"346","author":"Pratto","year":"2014","journal-title":"Science"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.tibs.2014.09.001","article-title":"Structure and function of the nucleosome-binding PWWP domain","volume":"39","author":"Qin","year":"2014","journal-title":"Trends in Biochemical Sciences"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"bib82","article-title":"R: A Language and Environment for Statistical Computing","author":"R Development Core Team","year":"2018","unstructured":"R Development Core Team. 2018. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. http:\/\/www.r-project.org."},{"key":"bib83","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s12551-015-0190-6","article-title":"PWWP domains and their modes of sensing DNA and histone methylated lysines","volume":"8","author":"Rona","year":"2016","journal-title":"Biophysical Reviews"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1101\/gad.973302","article-title":"SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins","volume":"16","author":"Schultz","year":"2002","journal-title":"Genes & Development"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/nature02563","article-title":"Human meiotic recombinase Dmc1 promotes ATP-dependent homologous DNA strand exchange","volume":"429","author":"Sehorn","year":"2004","journal-title":"Nature"},{"key":"bib86","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2011.0330","article-title":"Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers","volume":"368","author":"Seisenberger","year":"2013","journal-title":"Philosophical Transactions of the Royal Society B: Biological Sciences"},{"key":"bib87","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962","article-title":"SeqKit: a Cross-Platform and ultrafast toolkit for FASTA\/Q file manipulation","volume":"11","author":"Shen","year":"2016","journal-title":"PLOS ONE"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1038\/ncb2896","article-title":"The TRF1-binding protein TERB1 promotes chromosome movement and telomere rigidity in meiosis","volume":"16","author":"Shibuya","year":"2014","journal-title":"Nature Cell Biology"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/nature09869","article-title":"Genome-wide analysis reveals novel molecular features of mouse recombination hotspots","volume":"472","author":"Smagulova","year":"2011","journal-title":"Nature"},{"key":"bib90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005531","article-title":"A gene regulatory program for meiotic prophase in the fetal ovary","volume":"11","author":"Soh","year":"2015","journal-title":"PLOS Genetics"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1101\/gad.333542.119","article-title":"HELLS and PRDM9 form a pioneer complex to open chromatin at meiotic recombination hot spots","volume":"34","author":"Spruce","year":"2020","journal-title":"Genes & Development"},{"key":"bib92","volume-title":"GNU Parallel","author":"Tange","year":"2018","unstructured":"Tange O. 2018. GNU Parallel. http:\/\/Lulu.com."},{"key":"bib93","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1083\/jcb.147.2.207","article-title":"RAD51 and DMC1 form mixed complexes associated with mouse meiotic chromosome cores and synaptonemal complexes","volume":"147","author":"Tarsounas","year":"1999","journal-title":"Journal of Cell Biology"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration","volume":"14","author":"Thorvaldsd\u00f3ttir","year":"2013","journal-title":"Briefings in Bioinformatics"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1073\/pnas.1618465114","article-title":"Speedy A-Cdk2 binding mediates initial telomere-nuclear envelope attachment during meiotic prophase I independent of Cdk2 activation","volume":"114","author":"Tu","year":"2017","journal-title":"PNAS"},{"key":"bib96","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419","article-title":"Proteomics Tissue-based map of the human proteome","volume":"347","author":"Uhl\u00e9n","year":"2015","journal-title":"Science"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/nrm3274","article-title":"Understanding the language of Lys36 methylation at histone H3","volume":"13","author":"Wagner","year":"2012","journal-title":"Nature Reviews Molecular Cell Biology"},{"key":"bib98","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"Ggplot2: Elegant Graphics for Data Analysis","author":"Wickham","year":"2016"},{"key":"bib99","volume-title":"cowplot: Streamlined Plot Theme and Plot Annotations for \u201cggplot2.","author":"Wilke","year":"2018","unstructured":"Wilke CO. 2018. cowplot: Streamlined Plot Theme and Plot Annotations for \u201cggplot2."},{"key":"bib100","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1467-9868.2010.00749.x","article-title":"Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models","volume":"73","author":"Wood","year":"2011","journal-title":"Journal of the Royal Statistical Society: Series B"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"4099","DOI":"10.1093\/nar\/gkr017","article-title":"Genome-wide quantitative assessment of variation in DNA methylation patterns","volume":"39","author":"Xie","year":"2011","journal-title":"Nucleic Acids Research"},{"key":"bib102","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08676-2","article-title":"A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination","volume":"10","author":"Zhang","year":"2019","journal-title":"Nature Communications"}],"container-title":["eLife"],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/53392\/elife-53392-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/53392\/elife-53392-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/53392","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:00:47Z","timestamp":1697058047000},"score":9.798704,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/53392"}},"issued":{"date-parts":[[2020,8,3]]},"references-count":102,"alternative-id":["10.7554\/eLife.53392"],"URL":"https:\/\/doi.org\/10.7554\/elife.53392","archive":["CLOCKSS"],"relation":{"references":[{"id-type":"accession","id":"GSE59836","asserted-by":"subject"},{"id-type":"accession","id":"GSE73833","asserted-by":"subject"},{"id-type":"accession","id":"GSE84689","asserted-by":"subject"},{"id-type":"accession","id":"GSE35498","asserted-by":"subject"},{"id-type":"accession","id":"GSE99407","asserted-by":"subject"},{"id-type":"accession","id":"GSE51867","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"GSE141516","asserted-by":"subject"}],"has-preprint":[{"id-type":"doi","id":"10.1101\/821678","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.53392.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.53392.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"published":{"date-parts":[[2020,8,3]]},"article-number":"e53392"},{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:31:44Z","timestamp":1779366704532,"version":"3.53.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["217650\/Z\/19\/Z"],"award-info":[{"award-number":["217650\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"Abstract<\/jats:title>\n \n Muscle ultrasound has been shown to be a valid and safe imaging modality to assess muscle wasting in critically ill patients in the intensive care unit (ICU). This typically involves manual delineation to measure the rectus femoris cross-sectional area (RFCSA), which is a subjective, time-consuming, and laborious task that requires significant expertise. We aimed to develop and evaluate an AI tool that performs automated recognition and measurement of RFCSA to support non-expert operators in measurement of the RFCSA using muscle ultrasound. Twenty patients were recruited between Feb 2023 and July 2023 and were randomized sequentially to operators using AI (n\u2009=\u200910) or non-AI (n\u2009=\u200910). Muscle loss during ICU stay was similar for both methods: 26\u2009\u00b1\u200915% for AI and 23\u2009\u00b1\u200911% for the non-AI, respectively (\n p<\/jats:italic>\n \u2009=\u20090.13). In total 59 ultrasound examinations were carried out (30 without AI and 29 with AI). When assisted by our AI tool, the operators showed less variability between measurements with higher intraclass correlation coefficients (ICCs 0.999 95% CI 0.998\u20130.999 vs. 0.982 95% CI 0.962\u20130.993) and lower Bland Altman limits of agreement (\u00b1\u20091.9% vs. \u00b1\u20096.6%) compared to not using the AI tool. The time spent on scans reduced significantly from a median of 19.6 min (IQR 16.9\u201321.7) to 9.4 min (IQR 7.2\u201311.7) compared to when using the AI tool (\n p<\/jats:italic>\n \u2009<\u20090.001). AI-assisted muscle ultrasound removes the need for manual tracing, increases reproducibility and saves time. This system may aid monitoring muscle size in ICU patients assisting rehabilitation programmes.\n <\/jats:p>","DOI":"10.1038\/s41598-024-64564-w","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T15:21:54Z","timestamp":1719415314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical evaluation of AI-assisted muscle ultrasound for monitoring muscle wasting in ICU patients"],"prefix":"10.1038","volume":"14","author":[{"given":"Phung Tran Huy","family":"Nhat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen","family":"Van Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lam Minh","family":"Yen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Hoang","family":"Anh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Phu","family":"Khiem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamideh","family":"Kerdegari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thanh","family":"Phuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vo Tan","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thanh","family":"Ngoc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Ngoc Minh","family":"Thu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truong Ngoc","family":"Trung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Pisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"VITAL Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liane","family":"Canas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamideh","family":"Kerdegari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Modat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Razavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Xochicale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang Phuong","family":"Thao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang Trung","family":"Kien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doan Bui Xuan","family":"Thy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Huu Khanh","family":"Trinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du Hong","family":"Duc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Geskus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Bich","family":"Hai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Quang","family":"Chanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho","family":"Van Hien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huynh Trung","family":"Trieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyne","family":"Kestelyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Dinh","family":"Van Khoa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thuy Thuy","family":"Khanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luu Hoai Bao","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luu Phuoc","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Mcbride","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Lam","family":"Vuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Quang","family":"Huy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Than Ha","family":"Quyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi","family":"Giang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Diem","family":"Trinh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi","family":"Le Thanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Phuong","family":"Dung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Phuong","family":"Thao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninh Thi Thanh","family":"Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham Tieu","family":"Kieu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan Nguyen Quoc","family":"Khanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phung Khanh","family":"Lam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tran Minh","family":"Duc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinh Manh","family":"Hung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer Ilo","family":"Van Nuil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Ngo Thanh","family":"Huyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao Thi","family":"Tam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duong Bich","family":"Thuy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Thi Hai","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Dang Trung","family":"Nghia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Buu","family":"Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Mau","family":"Toan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Ngoc Minh","family":"Thu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le Thi Mai","family":"Thao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luong Thi Hue","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Hoan","family":"Phu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Quoc","family":"Viet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thanh","family":"Dung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thanh","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thanh","family":"Phong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Kim","family":"Anh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen","family":"Van Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen","family":"Van Thanh Duoc","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham Kieu Nguyet","family":"Oanh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan Thi Hong","family":"Van","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan Tu","family":"Qui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phan Vinh","family":"Tho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Truong Thi Phuong","family":"Thao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Pisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Schultz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Clifton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"English","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannis","family":"Hagenah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"McKnight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Denehy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rollinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Georgiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard Hernandez","family":"Perez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerri","family":"Hill-Cawthorne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Karolcik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Ming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Moser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus Rodriguez","family":"Manzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Karlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Razavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Yacoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen","family":"Van Vinh Chau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Denehy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gomez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"64564_CR1","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1097\/CCM.0b013e318232da75","volume":"40","author":"DM Needham","year":"2012","unstructured":"Needham, D. M. et al. Improving long-term outcomes after discharge from intensive care unit: Report from a stakeholders\u2019 conference. Crit Care Med 40, 502\u2013509 (2012).","journal-title":"Crit Care Med"},{"key":"64564_CR2","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1001\/jama.2013.278481","volume":"310","author":"ZA Puthucheary","year":"2013","unstructured":"Puthucheary, Z. A. et al. Acute skeletal muscle wasting in critical illness. JAMA 310, 1591\u20131600 (2013).","journal-title":"JAMA"},{"key":"64564_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13054-020-03282-x","volume":"24","author":"Z Turan","year":"2020","unstructured":"Turan, Z., Topaloglu, M. & Ozyemisci Taskiran, O. Medical research council-sumscore: A tool for evaluating muscle weakness in patients with post-intensive care syndrome. Crit Care 24, 1\u20132 (2020).","journal-title":"Crit Care"},{"key":"64564_CR4","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.jcrc.2015.05.024","volume":"30","author":"SM Parry","year":"2015","unstructured":"Parry, S. M. et al. Ultrasonography in the intensive care setting can be used to detect changes in the quality and quantity of muscle and is related to muscle strength and function. J Crit Care 30, 1151-e9 (2015).","journal-title":"J Crit Care"},{"key":"64564_CR5","doi-asserted-by":"crossref","unstructured":"Van Hao, N. et al. The management of tetanus in adults in an intensive care unit in Southern Vietnam. Wellcome Open Res. 6 (2021).","DOI":"10.12688\/wellcomeopenres.16731.2"},{"key":"64564_CR6","doi-asserted-by":"crossref","unstructured":"Trung, T. N. et al. Functional outcome and muscle wasting in adults with tetanus. Trans. R. Soc. Trop. Med. Hyg. 113 (2019).","DOI":"10.1093\/trstmh\/trz055"},{"key":"64564_CR7","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1097\/CCM.0000000000001016","volume":"43","author":"ZA Puthucheary","year":"2015","unstructured":"Puthucheary, Z. A. et al. Qualitative ultrasound in acute critical illness muscle wasting. Crit Care Med 43, 1603\u20131611 (2015).","journal-title":"Crit Care Med"},{"key":"64564_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13054-022-04253-0","volume":"27","author":"B Fazzini","year":"2023","unstructured":"Fazzini, B. et al. The rate and assessment of muscle wasting during critical illness: A systematic review and meta-analysis. Crit Care 27, 1\u201326 (2023).","journal-title":"Crit Care"},{"key":"64564_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13047-021-00446-y","volume":"14","author":"JK Sponbeck","year":"2021","unstructured":"Sponbeck, J. K. et al. Leg muscle cross-sectional area measured by ultrasound is highly correlated with MRI. J Foot Ankle Res 14, 1\u20137 (2021).","journal-title":"J Foot Ankle Res"},{"key":"64564_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12871-018-0647-9","volume":"18","author":"E Pardo","year":"2018","unstructured":"Pardo, E. et al. Reliability of ultrasound measurements of quadriceps muscle thickness in critically ill patients. BMC Anesthesiol 18, 1\u20138 (2018).","journal-title":"BMC Anesthesiol"},{"key":"64564_CR11","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1164\/rccm.201604-0875LE","volume":"195","author":"ZA Puthucheary","year":"2017","unstructured":"Puthucheary, Z. A. et al. Rectus femoris cross-sectional area and muscle layer thickness: Comparative markers of muscle wasting and weakness. Am J Respir Crit Care Med 195, 136\u2013138 (2017).","journal-title":"Am J Respir Crit Care Med"},{"key":"64564_CR12","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/CPT.0000000000000102","volume":"30","author":"SM Parry","year":"2019","unstructured":"Parry, S. M., Burtin, C., Denehy, L., Puthucheary, Z. A. & Bear, D. Ultrasound evaluation of quadriceps muscle dysfunction in respiratory disease. Cardiopulm Phys Ther J 30, 15\u201323 (2019).","journal-title":"Cardiopulm Phys Ther J"},{"key":"64564_CR13","doi-asserted-by":"publisher","first-page":"18280","DOI":"10.1038\/s41598-021-97680-y","volume":"11","author":"W Zhang","year":"2021","unstructured":"Zhang, W. et al. Changes in muscle ultrasound for the diagnosis of intensive care unit acquired weakness in critically ill patients. Sci Rep 11, 18280 (2021).","journal-title":"Sci Rep"},{"key":"64564_CR14","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1111\/j.1475-097X.2011.01115.x","volume":"32","author":"KMM e Lima","year":"2012","unstructured":"e Lima, K. M. M., da Matta, T. T. & de Oliveira, L. F. Reliability of the rectus femoris muscle cross-sectional area measurements by ultrasonography. Clin Physiol Funct Imaging 32, 221\u2013226 (2012).","journal-title":"Clin Physiol Funct Imaging"},{"key":"64564_CR15","doi-asserted-by":"crossref","unstructured":"Chen, X., Xie, C., Chen, Z. & Li, Q. Automatic tracking of muscle cross\u2010sectional area using convolutional neural networks with ultrasound. J. Ultrasound Med. 38 (2019).","DOI":"10.1002\/jum.14995"},{"key":"64564_CR16","doi-asserted-by":"crossref","unstructured":"Ritsche, P. et al. DeepACSA: Automatic segmentation of cross-sectional area in ultrasound images of lower limb muscles using deep learning. Med. Sci. Sports Exerc. (2022).","DOI":"10.1101\/2021.12.27.21268258"},{"key":"64564_CR17","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3390\/diagnostics13020217","volume":"13","author":"S Katakis","year":"2023","unstructured":"Katakis, S. et al. Muscle cross-sectional area segmentation in transverse ultrasound images using vision transformers. Diagnostics 13, 217 (2023).","journal-title":"Diagnostics"},{"key":"64564_CR18","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1513\/AnnalsATS.201612-967PS","volume":"14","author":"M Mourtzakis","year":"2017","unstructured":"Mourtzakis, M., Parry, S., Connolly, B. & Puthucheary, Z. Skeletal muscle ultrasound in critical care: A tool in need of translation. Ann Am Thorac Soc 14, 1495\u20131503 (2017).","journal-title":"Ann Am Thorac Soc"},{"key":"64564_CR19","doi-asserted-by":"crossref","unstructured":"Gomez, A. et al. PRETUS: A plug-in based platform for real-time ultrasound imaging research. SoftwareX 17 (2022).","DOI":"10.1016\/j.softx.2021.100959"},{"key":"64564_CR20","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/(SICI)1097-0258(19980115)17:1<101::AID-SIM727>3.0.CO;2-E","volume":"17","author":"SD Walter","year":"1998","unstructured":"Walter, S. D., Eliasziw, M. & Donner, A. Sample size and optimal designs for reliability studies. Stat Med 17, 101\u2013110 (1998).","journal-title":"Stat Med"},{"key":"64564_CR21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jcm.2016.02.012","volume":"15","author":"TK Koo","year":"2016","unstructured":"Koo, T. K. & Li, M. Y. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med 15, 155\u2013163 (2016).","journal-title":"J Chiropr Med"},{"key":"64564_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12874-020-01182-w","volume":"20","author":"HS Christensen","year":"2020","unstructured":"Christensen, H. S., Borgbjerg, J., B\u00f8rty, L. & B\u00f8gsted, M. On Jones et al.\u2019s method for extending Bland\u2013Altman plots to limits of agreement with the mean for multiple observers. BMC Med. Res. Methodol. 20, 1\u20138 (2020).","journal-title":"BMC Med. Res. Methodol."}],"container-title":["Scientific Reports"],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-64564-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-64564-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-64564-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T15:24:19Z","timestamp":1719415459000},"score":9.785701,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-64564-w"}},"issued":{"date-parts":[[2024,6,26]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["64564"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-64564-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3456993\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"20 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14798"},{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:42:12Z","timestamp":1770039732398,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222574\/Z\/21\/Z"],"award-info":[{"award-number":["222574\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["106680\/Z\/14\/Z"],"award-info":[{"award-number":["106680\/Z\/14\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["2\/226120\/Z\/22\/Z"],"award-info":[{"award-number":["2\/226120\/Z\/22\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"Abstract<\/jats:title>\n Background<\/jats:title>\n Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n We evaluated anti-spike IgG (Abbott) and neutralising (cPASS\/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180\u00a0days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline\/day) and Omicron B.1.1.529\/BA.2 nAbs declined between day 28\u201390, and IgG titers plateaued between day 90\u2013360. During the BA.1\/BA.2 wave (February\u2013March 2022), 34.6% (27\/78) of individuals experienced a VBI (median 181\u00a0days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529\/BA.2 nAbs, which were restored post-VBI.<\/jats:p>\n <\/jats:sec>\n Conclusions<\/jats:title>\n mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1\/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12879-024-09644-y","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T09:03:13Z","timestamp":1722502993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-SARS-CoV-2 antibody dynamics after primary vaccination with two-dose inactivated whole-virus vaccine, heterologous mRNA-1273 vaccine booster, and Omicron breakthrough infection in Indonesian health care workers"],"prefix":"10.1186","volume":"24","author":[{"given":"Suwarti","family":"Suwarti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Lazarus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabighoh","family":"Zanjabila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Sinto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fransiska","family":"Fransiska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresia","family":"Deborah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwi","family":"Oktavia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junaidah","family":"Junaidah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santayana","family":"Santayana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Surendra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeng","family":"Yuliana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herlina","family":"Pardosi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nunung","family":"Nuraeni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saraswati","family":"Soebianto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Novi Dwi","family":"Susilowati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Decy","family":"Subekti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariel","family":"Pradipta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Kevin","family":"Baird","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Van","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Dunachie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuraj H.","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erni J.","family":"Nelwan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raph L.","family":"Hamers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"SEACOVARIANTS Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen To","family":"Anh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thi Thu","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Truong Hoang Chau","family":"Truc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thi Han","family":"Ny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Duong Kim","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Kim","family":"Thanh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lam Anh","family":"Nguyet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cao Thu","family":"Thuy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Nguyen Truc","family":"Nhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tran Tan","family":"Thanh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lam Minh","family":"Yen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Thi\u00a0Ty","family":"Hang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pham Tieu","family":"Kieu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vo Tan","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thi","family":"Thao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Chambers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vu Duy","family":"Thanh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tran Chieu","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Louise","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Thwaites","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Rogier","family":"van Doorn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trinh Son","family":"Tung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juthathip","family":"Mongkolsapaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin","family":"Screaton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiete","family":"Dijokaite-Guraliuc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raksha","family":"Das","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piyada","family":"Supasa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneeswaran","family":"Selvaraj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna J.","family":"Dunachie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Yvonne","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David I.","family":"Stuart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Kronsteiner-Dobramysl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Zewdie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyanka","family":"Abraham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Hill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanie","family":"Tayipto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isana","family":"Paramita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Lin-Fa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tan Chee","family":"Wah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yap Wee","family":"Chee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lim Beng","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"family":"Suwarti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Simarmata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragil","family":"Dien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanwisa","family":"Dejnirattisai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Warangkana","family":"Chantima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narisara","family":"Chantratita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prapassorn","family":"Poolchanuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vichapon","family":"Tiacharoen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adul","family":"Dulsuk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophon","family":"Iamsirithaworn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nick","family":"Day","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phaik Yeong","family":"Cheah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tassawan","family":"Poomchaichote","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanpong","family":"Boonthaworn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nghiem My","family":"Ngoc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Grifoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"9644_CR1","doi-asserted-by":"publisher","first-page":"e0000893","DOI":"10.1371\/journal.pgph.0000893","volume":"2","author":"LL Ekawati","year":"2022","unstructured":"Ekawati LL, Arif A, Hidayana I, Nurhasim A, Munziri MZ, Lestari KD, et al. Mortality among healthcare workers in Indonesia during 18 months of COVID-19. PLOS Glob Public Heal. 2022;2:e0000893. https:\/\/doi.org\/10.1371\/journal.pgph.0000893.","journal-title":"PLOS Glob Public Heal"},{"key":"9644_CR2","doi-asserted-by":"publisher","unstructured":"Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning immune humoral response to BNT162b2 Covid-19 Vaccine over 6 Months. N Engl J Med. 2021;385:e84. https:\/\/doi.org\/10.1056\/NEJMoa2114583.","DOI":"10.1056\/NEJMoa2114583"},{"key":"9644_CR3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2114114","author":"H Chemaitelly","year":"2021","unstructured":"Chemaitelly H, Tang P, Hasan MR, AlMukdad S, Yassine HM, Benslimane FM, et al. Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar. N Engl J Med. 2021. https:\/\/doi.org\/10.1056\/NEJMoa2114114.","journal-title":"N Engl J Med"},{"key":"9644_CR4","doi-asserted-by":"publisher","unstructured":"Andrews N, Stowe J, Kirsebom F, Toffa S, Rickeard T, Gallagher E, et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N Engl J Med. 2022;386:1532\u201346. https:\/\/doi.org\/10.1056\/NEJMoa2119451.","DOI":"10.1056\/NEJMoa2119451"},{"key":"9644_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/S0140-6736(22)00094-0","volume":"399","author":"SA Costa Clemens","year":"2022","unstructured":"Costa Clemens SA, Weckx L, Clemens R, Almeida Mendes AV, Ramos Souza A, Silveira MBV, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study. Lancet. 2022;399:521\u20139. https:\/\/doi.org\/10.1016\/S0140-6736(22)00094-0.","journal-title":"Lancet"},{"key":"9644_CR6","doi-asserted-by":"publisher","unstructured":"Jara A, Undurraga EA, Gonz\u00e1lez C, Paredes F, Fontecilla T, Jara G, et al. Effectiveness of an Inactivated SARS-CoV-2 vaccine in Chile. N Engl J Med. 2021;385:875\u201384. https:\/\/doi.org\/10.1056\/NEJMoa2107715.","DOI":"10.1056\/NEJMoa2107715"},{"key":"9644_CR7","doi-asserted-by":"publisher","first-page":"e423","DOI":"10.1016\/S2666-5247(21)00177-4","volume":"2","author":"WW Lim","year":"2021","unstructured":"Lim WW, Mak L, Leung GM, Cowling BJ, Peiris M. Comparative immunogenicity of mRNA and inactivated vaccines against COVID-19. Lancet Microbe. 2021;2:e423. https:\/\/doi.org\/10.1016\/S2666-5247(21)00177-4.","journal-title":"Lancet Microbe"},{"key":"9644_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/S1473-3099(21)00479-5","volume":"22","author":"D Saur\u00e9","year":"2022","unstructured":"Saur\u00e9 D, O\u2019Ryan M, Torres JP, Zuniga M, Santelices E, Basso LJ. Dynamic IgG seropositivity after rollout of CoronaVac and BNT162b2 COVID-19 vaccines in Chile: a sentinel surveillance study. Lancet Infect Dis. 2022;22:56\u201363. https:\/\/doi.org\/10.1016\/S1473-3099(21)00479-5.","journal-title":"Lancet Infect Dis"},{"key":"9644_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fimmu.2023.1255676","volume":"14","author":"J Sembera","year":"2023","unstructured":"Sembera J, Baine C, Ankunda V, Katende JS, Oluka GK, Akoli CH, et al. Sustained spike-specific IgG antibodies following CoronaVac (Sinovac) vaccination in sub-Saharan Africa, but increased breakthrough infections in baseline spike-naive individuals. Front Immunol. 2023;14:1\u201312. https:\/\/doi.org\/10.3389\/fimmu.2023.1255676.","journal-title":"Front Immunol."},{"key":"9644_CR10","doi-asserted-by":"publisher","first-page":"e149","DOI":"10.1016\/S2666-5247(22)00290-7","volume":"4","author":"D Saur\u00e9","year":"2023","unstructured":"Saur\u00e9 D, O\u2019Ryan M, Torres JP, Zu\u00f1iga M, Soto-Rifo R, Valiente-Echeverr\u00eda F, et al. COVID-19 lateral flow IgG seropositivity and serum neutralising antibody responses after primary and booster vaccinations in Chile: a cross-sectional study. Lancet Microbe. 2023;4:e149\u201358. https:\/\/doi.org\/10.1016\/S2666-5247(22)00290-7.","journal-title":"Lancet Microbe"},{"key":"9644_CR11","doi-asserted-by":"publisher","unstructured":"Reynolds CJ, Pade C, Gibbons JM, Otter AD, Lin KM, Sandoval DM, et al. Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure. Science (80- ). 2022;377. https:\/\/doi.org\/10.1126\/science.abq1841.","DOI":"10.1126\/science.abq1841"},{"key":"9644_CR12","doi-asserted-by":"publisher","unstructured":"Sinto R, Utomo D, Suwarti, Nelwan EJ, Surendra H, Natasha C, et al. Antibody responses and reactogenicity of a heterologous, full-dose messenger RNA-1273 booster in heavily SARS-CoV-2\u2013exposed Coronavac-vaccinated health-care workers in Indonesia: A real-world observational study. Am J Trop Med Hyg. 2023;108:115\u201323. https:\/\/doi.org\/10.4269\/ajtmh.22-0256.","DOI":"10.4269\/ajtmh.22-0256"},{"key":"9644_CR13","doi-asserted-by":"publisher","first-page":"100603","DOI":"10.1016\/j.xcrm.2022.100603","volume":"3","author":"G Mantus","year":"2022","unstructured":"Mantus G, Nyhoff LE, Edara V-V, Zarnitsyna VI, Ciric CR, Flowers MW, et al. Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination. Cell Reports Med. 2022;3:100603. https:\/\/doi.org\/10.1016\/j.xcrm.2022.100603.","journal-title":"Cell Reports Med"},{"key":"9644_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v15040917","volume":"15","author":"J Wang","year":"2023","unstructured":"Wang J, Huang L, Guo N, Yao YP, Zhang C, Xu R, et al. Dynamics of SARS-CoV-2 antibody responses up to 9 months post-vaccination in individuals with previous SARS-CoV-2 infection receiving inactivated vaccines. Viruses. 2023;15:1\u201316. https:\/\/doi.org\/10.3390\/v15040917.","journal-title":"Viruses"},{"key":"9644_CR15","doi-asserted-by":"publisher","first-page":"e0266701","DOI":"10.1371\/journal.pone.0266701","volume":"17","author":"JR Richardson","year":"2022","unstructured":"Richardson JR, G\u00f6tz R, Mayr V, Lohse MJ, Holthoff H-P, Ungerer M. SARS-CoV2 wild type and mutant specific humoral and T cell immunity is superior after vaccination than after natural infection. PLoS ONE. 2022;17:e0266701. https:\/\/doi.org\/10.1371\/journal.pone.0266701.","journal-title":"PLoS ONE"},{"key":"9644_CR16","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.cell.2022.01.018","volume":"185","author":"K R\u00f6ltgen","year":"2022","unstructured":"R\u00f6ltgen K, Nielsen SCA, Silva O, Younes SF, Zaslavsky M, Costales C, et al. Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell. 2022;185:1025-1040.e14. https:\/\/doi.org\/10.1016\/j.cell.2022.01.018.","journal-title":"Cell"},{"key":"9644_CR17","doi-asserted-by":"publisher","unstructured":"Kaku CI, Champney ER, Normark J, Garcia M, Johnson CE, Ahlm C, et al. Broad anti\u2013SARS-CoV-2 antibody immunity induced by heterologous ChAdOx1\/mRNA-1273 vaccination. Science (80- ). 2022;375:1041\u20137. https:\/\/doi.org\/10.1126\/science.abn2688.","DOI":"10.1126\/science.abn2688"},{"key":"9644_CR18","doi-asserted-by":"crossref","unstructured":"Gilboa M, Regev-Yochay G, Mandelboim M, Indenbaum V, Asraf K, Fluss R, et al. Durability of immune response after COVID-19 booster vaccination and association with COVID-19 omicron infection. JAMA Netw open. 2022;5:e2231778. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.31778.","DOI":"10.1001\/jamanetworkopen.2022.31778"},{"key":"9644_CR19","doi-asserted-by":"publisher","unstructured":"Gilboa M, Gonen T, Barda N, Cohn S, Indenbaum V, Weiss-Ottolenghi Y, et al. Factors associated with protection from SARS-CoV-2 omicron variant infection and disease among vaccinated health care workers in Israel. JAMA Netw open. 2023;6:e2314757. https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.14757.","DOI":"10.1001\/jamanetworkopen.2023.14757"},{"key":"9644_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01705-6","author":"E P\u00e9rez-Then","year":"2022","unstructured":"P\u00e9rez-Then E, Lucas C, Monteiro VS, Miric M, Brache V, Cochon L, et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat Med. 2022. https:\/\/doi.org\/10.1038\/s41591-022-01705-6.","journal-title":"Nat Med"},{"key":"9644_CR21","doi-asserted-by":"publisher","first-page":"E2228900","DOI":"10.1001\/jamanetworkopen.2022.28900","volume":"5","author":"OT Ng","year":"2022","unstructured":"Ng OT, Marimuthu K, Lim N, Lim ZQ, Thevasagayam NM, Koh V, et al. Analysis of COVID-19 Incidence and Severity among Adults Vaccinated with 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines with and Without Boosters in Singapore. JAMA Netw Open. 2022;5:E2228900. https:\/\/doi.org\/10.1001\/jamanetworkopen.2022.28900.","journal-title":"JAMA Netw Open"},{"key":"9644_CR22","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1016\/S1473-3099(22)00345-0","volume":"22","author":"ME McMenamin","year":"2022","unstructured":"McMenamin ME, Nealon J, Lin Y, Wong JY, Cheung JK, Lau EHY, et al. Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study. Lancet Infect Dis. 2022;22:1435\u201343. https:\/\/doi.org\/10.1016\/S1473-3099(22)00345-0.","journal-title":"Lancet Infect Dis"},{"key":"9644_CR23","doi-asserted-by":"publisher","first-page":"100348","DOI":"10.1016\/j.lansea.2023.100348","volume":"22","author":"A Karuniawati","year":"2024","unstructured":"Karuniawati A, Pasaribu AP, Lazarus G, Irawany V, Nusantara DU, Sinto R, et al. Characteristics and clinical outcomes of patients with pre-delta, delta and omicron SARS-CoV-2 infection in Indonesia (2020\u20132023): a multicentre prospective cohort study. Lancet Reg Heal - Southeast Asia. 2024;22:100348. https:\/\/doi.org\/10.1016\/j.lansea.2023.100348.","journal-title":"Lancet Reg Heal - Southeast Asia"},{"key":"9644_CR24","doi-asserted-by":"publisher","unstructured":"Chen Y, Zhao T, Chen L, Jiang G, Geng Y, Li W, et al. SARS-CoV-2 Omicron infection augments the magnitude and durability of systemic and mucosal immunity in triple-dose CoronaVac recipients. MBio. 2024:e0240723. https:\/\/doi.org\/10.1128\/mbio.02407-23b.","DOI":"10.1128\/mbio.02407-23b"},{"key":"9644_CR25","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.1038\/s41591-023-02503-4","volume":"29","author":"AR Branche","year":"2023","unstructured":"Branche AR, Rouphael NG, Diemert DJ, Falsey AR, Losada C, Baden LR, et al. Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial. Nat Med. 2023;29:2334\u201346. https:\/\/doi.org\/10.1038\/s41591-023-02503-4.","journal-title":"Nat Med"},{"key":"9644_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-023-38892-w","volume":"14","author":"S Chalkias","year":"2023","unstructured":"Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, et al. Three-month antibody persistence of a bivalent Omicron-containing booster vaccine against COVID-19. Nat Commun. 2023;14:1\u20137. https:\/\/doi.org\/10.1038\/s41467-023-38892-w.","journal-title":"Nat Commun"},{"key":"9644_CR27","doi-asserted-by":"publisher","unstructured":"Ho-Yan Fong C, Zhang X, Chen LL, Wing-Shan Poon R, Pui-Chun Chan B, Zhao Y, et al. Effect of vaccine booster, vaccine type, and hybrid immunity on humoral and cellular immunity against SARS-CoV-2 ancestral strain and Omicron variant sublineages BA.2 and BA.5 among older adults with comorbidities: a cross sectional study. eBioMedicine. 2023;88:104446. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104446.","DOI":"10.1016\/j.ebiom.2023.104446"},{"key":"9644_CR28","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1038\/s41590-022-01313-z","volume":"23","author":"N Brasu","year":"2022","unstructured":"Brasu N, Elia I, Russo V, Montacchiesi G, Stabile SA, De Intinis C, et al. Memory CD8+ T cell diversity and B cell responses correlate with protection against SARS-CoV-2 following mRNA vaccination. Nat Immunol. 2022;23:1445\u201356. https:\/\/doi.org\/10.1038\/s41590-022-01313-z.","journal-title":"Nat Immunol"},{"key":"9644_CR29","doi-asserted-by":"publisher","unstructured":"M\u00e9ndez C, Pe\u00f1aloza HF, Schultz BM, Pi\u00f1a-Iturbe A, R\u00edos M, Moreno-Tapia D, et al. Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults. eBioMedicine. 2023;91:1\u201314. https:\/\/doi.org\/10.1016\/j.ebiom.2023.104563.","DOI":"10.1016\/j.ebiom.2023.104563"},{"key":"9644_CR30","doi-asserted-by":"publisher","unstructured":"Lasrado N, Collier A ris Y, Hachmann NP, Miller J, Rowe M, Schonberg ED, et al. Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86. Vaccine. 2023;41:6904\u20139. https:\/\/doi.org\/10.1016\/j.vaccine.2023.10.051.","DOI":"10.1016\/j.vaccine.2023.10.051"}],"container-title":["BMC Infectious Diseases"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09644-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-024-09644-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09644-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T09:04:49Z","timestamp":1722503089000},"score":9.78072,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-024-09644-y"}},"issued":{"date-parts":[[2024,8,1]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9644"],"URL":"https:\/\/doi.org\/10.1186\/s12879-024-09644-y","ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"published":{"date-parts":[[2024,8,1]]},"assertion":[{"value":"8 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The INVITE study was approved by the research ethics committee of the Faculty of Medicine Universitas Indonesia (841\/UN2.F1.ETIK\/PPM.00.02\/2021) and the Oxford Tropical Research Ethics Committee (22\u201321). All participants provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"768"},{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:31Z","timestamp":1785416491830,"version":"3.56.0"},"reference-count":87,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["100229\/Z\/12\/Z"],"award-info":[{"award-number":["100229\/Z\/12\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220291\/Z\/20\/Z"],"award-info":[{"award-number":["220291\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["203147\/Z\/16\/Z"],"award-info":[{"award-number":["203147\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["205103\/Z\/16\/Z"],"award-info":[{"award-number":["205103\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["224562\/Z\/21\/Z"],"award-info":[{"award-number":["224562\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"Reading is central to academic and vocational success. Some deaf children face reading challenges due to limited access to spoken or signed language. Robust phonological representations are key to reading development in hearing children. Spoken language phonology may be one of many contributors to reading development in deaf children. Indeed, speechreading ability correlates with reading skill in both deaf and hearing individuals, suggesting it is linked to reading development regardless of hearing status. Further support for this hypothesis would be provided by evidence that similar neural representations of speech phonology are evoked by visual speech and other language forms (auditory speech and text) and that these neural representations are related to reading proficiency. We used fMRI and representational similarity analysis (RSA) to identify shared neural representations of spoken language phonological structure. A group of deaf adult participants (N = 22), with a mixture of sign language and spoken language backgrounds and reading abilities, were presented with single lexical items as visual speech and dynamic text (cursive text, revealed letter-by-letter to promote a phonological reading strategy). Adult hearing participants (N = 25) were presented with the same words, but as visual speech and auditory speech. Shared neural representations of phonological structure of English words were found in each group in the superior and middle temporal cortex (STC\/MTC) and these abstract representations were more similar across different language forms in better readers. Our data provide neurobiological evidence of the contribution of visual speech to abstract phonological representations of spoken language, that relate to reading proficiency, in both deaf and hearing adults.<\/jats:p>","DOI":"10.1073\/pnas.2535704123","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:11:09Z","timestamp":1779819069000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Reading ability in both deaf and hearing adults is linked to neural representations of abstract phonology derived from visual speech"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9667-0671","authenticated-orcid":false,"given":"Samuel","family":"Evans","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Cognitive Neuroscience, University College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Deafness Cognition and Language Research Centre, Division of Psychology and Language Sciences, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy J.","family":"Price","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Imaging Neuroscience, Queen Square Institute of Neurology, University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0264-8532","authenticated-orcid":false,"given":"J\u00f6rn","family":"Diedrichsen","sequence":"additional","affiliation":[{"name":"Western Institute for Neuroscience, Western University","place":["London, Canada"]},{"name":"Department of Computer Science, Western University","place":["London, Canada"]},{"name":"Department of Statistical and Actuarial Sciences, Western University","place":["London, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-5895","authenticated-orcid":false,"given":"Tae","family":"Twomey","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Cognitive Neuroscience, University College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Deafness Cognition and Language Research Centre, Division of Psychology and Language Sciences, University College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Imaging Neuroscience, Queen Square Institute of Neurology, University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indie","family":"Beedie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Cognitive Neuroscience, University College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Deafness Cognition and Language Research Centre, Division of Psychology and Language Sciences, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Fraser","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Cognitive Neuroscience, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2315-3507","authenticated-orcid":false,"given":"Mair\u00e9ad","family":"MacSweeney","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Cognitive Neuroscience, University College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Deafness Cognition and Language Research Centre, Division of Psychology and Language Sciences, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1353\/aad.2012.1611"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10882-011-9246-0"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enr028"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11145-004-5894-0"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0963-7214.2005.00376.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1177\/1529100618772271"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2006.01700.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/eng012"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.deafed.a014351"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enj037"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1353\/aad.2014.0032"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2015.01153"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enq049"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enac018"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1044\/2020_JSLHR-20-00159"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enj021"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jecp.2010.04.011"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1044\/2024_LSHSS-23-00129"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/02699200500266745"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1992.0009"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1044\/2019_JSLHR-H-19-0073"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2015.07.013"},{"key":"e_1_3_4_23_2","first-page":"1","article-title":"Hierarchical organization of auditory and motor representations in speech perception: Evidence from searchlight similarity analysis","author":"Evans S.","year":"2015","unstructured":"S. Evans, M. H. Davis, Hierarchical organization of auditory and motor representations in speech perception: Evidence from searchlight similarity analysis, Cerebral cortex (New York, N.Y.: 1991), (2015), pp. 1\u201317, 10.1093\/cercor\/bhv136.","journal-title":"Cerebral cortex (New York, N.Y.: 1991)"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164318"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.07.023"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.01.060"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0114-21.2021"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-8119(03)00343-4"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0093-934X(03)00403-6"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1037\/a0030266"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","unstructured":"M. S. Beauchamp K. E. Lee B. D. Argall A. Martin Integration of auditory and visual information about objects in superior temporal sulcus. Neuron 41 809\u2013823 (2004).","DOI":"10.1016\/S0896-6273(04)00070-4"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26713"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4572-10.2011"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2009.10.004"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2015.00151"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.08.075"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","unstructured":"I. Simanova P. Hagoort R. Oostenveld M. A. J. van Gerven \u201cModality-independent decoding of semantic information from the human brain\u201d in Cerebral Cortex (New York N.Y.: 1991) (2014) vol. 24 pp. 426\u2013434.","DOI":"10.1093\/cercor\/bhs324"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.56972"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1415-24.2025"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_00161"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1057\/9780230625396_6"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/264746a0"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/dev.20032"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.02.061"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2023.105304"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10548-023-00959-8"},{"key":"e_1_3_4_47_2","unstructured":"J. Alegria J. Leybaert C. Hage \u201cThe origin of phonological representations in the deaf\u201d in Language Processing in Spanish M. Carreiras J. E. Garcia-Albea N. Sebastian-Galles Eds. (1992) pp. 107\u2013132."},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1044\/2025_JSLHR-24-00872"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/desc.13124"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/desc.13431"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1044\/2015_JSLHR-S-14-0269"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-7610.00648"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","unstructured":"V. L. Hanson C. A. Fowler Phonological coding in word reading: Evidence from hearing and deaf readers. Mem. Cogn. 15 199\u2013207 (1987).","DOI":"10.3758\/BF03197717"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0327142"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0963-7214.2005.00372.x"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/wcs.1404"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2013.05.001"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bandl.2016.06.007"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2018.07.010"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1162\/NOL.a.13"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1111\/lnc3.12407"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2006.12.046"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.12.047"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.04.003"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2007.11.026"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054696"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.01.025"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/jdsade\/enag004"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2022.716554"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/deafed\/enw065"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.deafed.a014308"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1353\/sls.2015.0006"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139610"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.3390\/languages8010059"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ridd.2015.10.004"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2113"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2331"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.04.062"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2020.03.019"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00206"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00524"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.04.001"},{"key":"e_1_3_4_83_2","first-page":"11","article-title":"Reading comprehension test","volume":"7","author":"Warden V.","year":"1996","unstructured":"V. Warden, Reading comprehension test. Dyslexia Review 7, 11\u201316 (1996).","journal-title":"Dyslexia Review"},{"key":"e_1_3_4_84_2","unstructured":"T. Ellis M. MacSweeney B. Dodd R. Campbell \u201cTAS: A new test of adult speechreading. Deaf people really can be better speechreaders\u201d in International Conference on Auditory-Visual Speech Processing (2001) pp. 1\u20135."},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003553"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.12.012"},{"key":"e_1_3_4_87_2","doi-asserted-by":"crossref","unstructured":"S. Evans Reading ability in both deaf and hearing adults is linked to neural representations of abstract phonology derived from visual speech. OSF. https:\/\/osf.io\/cba8z\/overview. Deposited 1 May 2026.","DOI":"10.1101\/2025.11.09.684749"}],"container-title":["Proceedings of the National Academy of Sciences"],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2535704123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T18:13:09Z","timestamp":1779819189000},"score":9.770207,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2535704123"}},"issued":{"date-parts":[[2026,5,26]]},"references-count":87,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2026,6,2]]}},"alternative-id":["10.1073\/pnas.2535704123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2535704123","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.11.09.684749","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"2025-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2535704123"},{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:17:41Z","timestamp":1772165861419,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["220866\/Z\/20\/Z"],"award-info":[{"award-number":["220866\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Public Health"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization\u2019s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection\/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12\u00a0months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~\u20094,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12\u00a0months later to estimate the rate of re-infection.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan.<\/jats:p>\n <\/jats:sec>\n \n Study registration<\/jats:title>\n This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12889-023-17290-3","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:02:47Z","timestamp":1702875767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol"],"prefix":"10.1186","volume":"23","author":[{"given":"Ambreen","family":"Arif","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aliya","family":"Hasnain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Auj","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Asim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad Nabeel","family":"Shafqat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abeer","family":"Altaf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noor","family":"Saba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polychronis","family":"Kemos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Azim","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Metcalfe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vickerman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huma","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saeed","family":"Hamid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asad Ali","family":"Choudhry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saad Khalid","family":"Niaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham R.","family":"Foster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naheed","family":"Choudhry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"key":"17290_CR1","unstructured":"Seth Nelson M, Yusuf AM. Hepatitis C is on the rise: centracare \u2013 family health clinic; 2022 . Available from: https:\/\/www.centracare.com\/blog\/2022\/august\/hepatitis-c-is-on-therise\/#:~:text=There%20are%20more%20than%2058,hepatitis%20B%20and%20hepatitis%20C. (Accessed 18 Apr 2023)."},{"issue":"4","key":"17290_CR2","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1111\/jvh.13802","volume":"30","author":"E Mooneyhan","year":"2023","unstructured":"Mooneyhan E, Qureshi H, Mahmood H, Tariq M, Maqbool NA, Anwar M, et al. Hepatitis C prevalence and elimination planning in Pakistan, a bottom-up approach accounting for provincial variation. J Viral Hepat. 2023;30(4):345\u201354.","journal-title":"J Viral Hepat"},{"key":"17290_CR3","unstructured":"APEX Consulting. Final report \u2013 population based prevalence survey of hepatitis B&C Punjab, 2018. Bureau of Statistics Planning and Development Board, Government of Pakistan; 2019. 2018 Available from: https:\/\/www.globalhep.org\/sites\/default\/files\/content\/news\/files\/202206\/Pakistan%20National%20Hepatitis%20Elimination%20Profile-FINAL.pdf.(Accessed 04 May 2023)."},{"key":"17290_CR4","unstructured":"World Health Organization. Global health sector strategy on viral hepatitis 2016\u20132021. Towards ending viral hepatitis 2016. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/246177.(Accessed 18 Apr 2023)."},{"key":"17290_CR5","unstructured":"National Hepatitis Elimination Profile for Pakistan: Key Takeaways: Coalition for Global Hepatitis Elimination. Available from: https:\/\/www.globalhep.org\/news\/national-hepatitis-elimination-profile-pakistan-key-takeaways. (Accessed 1 Aug 2023)."},{"issue":"8","key":"17290_CR6","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1097\/MEG.0000000000001376","volume":"31","author":"S Sarwar","year":"2019","unstructured":"Sarwar S, Tarique S, Aleem A, Khan AA. Effect of adding daclatasvir in sofosbuvir-based therapy in genotype 3 hepatitis C: real-world experience in Pakistan. Eur J Gastroenterol Hepatol. 2019;31(8):1035\u20139.","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"1","key":"17290_CR7","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1186\/s12882-019-1631-4","volume":"20","author":"SUR Cheema","year":"2019","unstructured":"Cheema SUR, Rehman MS, Hussain G, Cheema SS, Gilani N. Efficacy and tolerability of sofosbuvir and daclatasvir for treatment of hepatitis C genotype 1 & 3 in patients undergoing hemodialysis- a prospective interventional clinical trial. BMC Nephrol. 2019;20(1):438.","journal-title":"BMC Nephrol"},{"issue":"7","key":"17290_CR8","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.12669\/pjms.37.7.4627","volume":"37","author":"N Butt","year":"2021","unstructured":"Butt N, Anoshia, Khan MA, Akbar A. Effectiveness of Sofosbuvir and Daclatasvir in treatment of Hepatitis-C: An experience of tertiary care hospital in Karachi. Pak J Med Sci. 2021;37(7):2014\u20139.","journal-title":"Pak J Med Sci."},{"issue":"5","key":"17290_CR9","first-page":"e38833","volume":"15","author":"AS Rahman","year":"2023","unstructured":"Rahman AS, Amir M, Jamal Q, Riaz M, Fareed K, Siddiqui M. End treatment response and sustained viral response in patients with hepatitis C virus receiving sofosbuvir and daclatasvir. Cureus. 2023;15(5):e38833.","journal-title":"Cureus"},{"issue":"1","key":"17290_CR10","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jceh.2017.06.003","volume":"8","author":"V Mehta","year":"2018","unstructured":"Mehta V, Mahajan R, Midha V, Narang V, Kaur K, Singh A, et al. Impact of direct acting antiviral therapy for treatment of hepatitis C genotypes 1, 3 and 4: a real life experience from India. J Clin Exp Hepatol. 2018;8(1):7\u201314.","journal-title":"J Clin Exp Hepatol"},{"issue":"4","key":"17290_CR11","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1002\/hep.27726","volume":"61","author":"DR Nelson","year":"2015","unstructured":"Nelson DR, Cooper JN, Lalezari JP, Lawitz E, Pockros PJ, Gitlin N, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology. 2015;61(4):1127\u201335.","journal-title":"Hepatology"},{"issue":"1","key":"17290_CR12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.12669\/pjms.331.12163","volume":"33","author":"S Sarwar","year":"2017","unstructured":"Sarwar S, Khan AA. Sofosbuvir based therapy in hepatitis C patients with and without cirrhosis: is there difference? Pak J Med Sci. 2017;33(1):37\u201341.","journal-title":"Pak J Med Sci"},{"key":"17290_CR13","doi-asserted-by":"publisher","first-page":"550205","DOI":"10.3389\/fphar.2020.550205","volume":"11","author":"S Mushtaq","year":"2020","unstructured":"Mushtaq S, Akhter TS, Khan A, Sohail A, Khan A, Manzoor S. Efficacy and safety of generic sofosbuvir plus daclatasvir and sofosbuvir\/velpatasvir in HCV genotype 3-infected patients: real-world outcomes from Pakistan. Front Pharmacol. 2020;11:550205.","journal-title":"Front Pharmacol"},{"issue":"4","key":"17290_CR14","doi-asserted-by":"publisher","first-page":"e0175562","DOI":"10.1371\/journal.pone.0175562","volume":"12","author":"YA Capileno","year":"2017","unstructured":"Capileno YA, Van den Bergh R, Donchunk D, Hinderaker SG, Hamid S, Auat R, et al. Management of chronic hepatitis C at a primary health clinic in the high-burden context of Karachi, Pakistan. PLoS ONE. 2017;12(4):e0175562.","journal-title":"PLoS ONE"},{"issue":"4","key":"17290_CR15","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1053\/j.gastro.2018.06.042","volume":"155","author":"R Esteban","year":"2018","unstructured":"Esteban R, Pineda JA, Calleja JL, Casado M, Rodriguez M, Turnes J, et al. Efficacy of Sofosbuvir and Velpatasvir, with and without ribavirin, in patients with hepatitis C virus genotype 3 infection and cirrhosis. Gastroenterology. 2018;155(4):1120\u20137 e4.","journal-title":"Gastroenterology."},{"issue":"3","key":"17290_CR16","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1053\/j.gastro.2019.05.007","volume":"157","author":"PAC Wing","year":"2019","unstructured":"Wing PAC, Jones M, Cheung M, DaSilva S, Bamford C, Jason Lee WY, et al. Amino acid substitutions in genotype 3a hepatitis C virus polymerase protein affect responses to Sofosbuvir. Gastroenterology. 2019;157(3):692\u2013704 e9.","journal-title":"Gastroenterology."},{"issue":"2","key":"17290_CR17","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)\u2013a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377\u201381.","journal-title":"J Biomed Inform"},{"key":"17290_CR18","doi-asserted-by":"publisher","first-page":"103208","DOI":"10.1016\/j.jbi.2019.103208","volume":"95","author":"PA Harris","year":"2019","unstructured":"Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O\u2019Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.","journal-title":"J Biomed Inform"},{"issue":"3","key":"17290_CR19","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"G EuroQol","year":"1990","unstructured":"EuroQol G. EuroQol\u2013a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199\u2013208.","journal-title":"Health Policy"},{"issue":"3","key":"17290_CR20","first-page":"282","volume":"29","author":"S Manolakopoulos","year":"2016","unstructured":"Manolakopoulos S, Zacharakis G, Zissis M, Giannakopoulos V. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C. Ann Gastroenterol. 2016;29(3):282\u201396.","journal-title":"Ann Gastroenterol"},{"issue":"4","key":"17290_CR21","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/S2468-1253(22)00386-7","volume":"8","author":"F Cui","year":"2023","unstructured":"Cui F, Blach S, Manzengo Mingiedi C, Gonzalez MA, Sabry Alaama A, Mozalevskis A, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol. 2023;8(4):332\u201342.","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"17290_CR22","unstructured":"World Health Organization. Combating hepatitis B and C to reach elimination by 2030: advocacy brief: World Health Organization.; 2016. Available from: https:\/\/apps.who.int\/iris\/handle\/10665\/206453. (Accessed 2 Sep 2023)."}],"container-title":["BMC Public Health"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-023-17290-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12889-023-17290-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12889-023-17290-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,19]],"date-time":"2023-12-19T21:03:13Z","timestamp":1703019793000},"score":9.766291,"resource":{"primary":{"URL":"https:\/\/bmcpublichealth.biomedcentral.com\/articles\/10.1186\/s12889-023-17290-3"}},"issued":{"date-parts":[[2023,12,18]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["17290"],"URL":"https:\/\/doi.org\/10.1186\/s12889-023-17290-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3324435\/v1","asserted-by":"object"}]},"ISSN":["1471-2458"],"issn-type":[{"value":"1471-2458","type":"electronic"}],"published":{"date-parts":[[2023,12,18]]},"assertion":[{"value":"4 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study is being conducted in accordance with the UK Policy Framework for Health and Social Care Research.This study was reviewed and approved by the Queen Mary Ethics Review Committee (Reference number QMERC20.306) on 27th May 2021, the Institutional Review Board of Aga Khan University (Reference number: 2021\u20136341-18329) on 29th June 2021 and Dow University of Health Sciences (Approval number: 2139\/DUHS\/Approval\/2021\/463) on June 12th 2021. The study was approved by the National Bioethics Committee (NBC) Pakistan (Ref: No.4\u201387\/NBC-677\/21\/439) on 9th Sep 2021.This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.At enrollment, written informed consent will be obtained from all eligible participants after explaining details of the study and available treatment options and this will be confirmed by an independent witness.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MAA, is supported by Sir Henry Dale Fellowship jointly funded by the Royal Society and Wellcome Trust (220171\/Z\/20\/Z). EB, has received consultancy fees from Roche, AstraZeneca and Vaccitech. PV, has received unrestricted research funding from Gilead that is unrelated to this study. GRF, has received consultancy and speaker fees from Abbvie, Biomarin, CSL Behring, GSK, Gilead and Pfizer. None of the other authors have any competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2529"},{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:22:38Z","timestamp":1790904158275,"version":"4.1.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215471\/Z\/19\/Z"],"award-info":[{"award-number":["215471\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2024,12]]},"abstract":"Abstract<\/jats:title>\n \n Distressing voices are a core symptom of psychosis, for which existing treatments are currently suboptimal; as such, new effective treatments for distressing voices are needed. AVATAR therapy involves voice-hearers engaging in a series of facilitated dialogues with a digital embodiment of the distressing voice. This randomized phase 2\/3 trial assesses the efficacy of two forms of AVATAR therapy, AVATAR-Brief (AV-BRF) and AVATAR-Extended (AV-EXT), both combined with treatment as usual (TAU) compared to TAU alone, and conducted an intention-to-treat analysis. We recruited 345 participants with psychosis; data were available for 300 participants (86.9%) at 16 weeks and 298 (86.4%) at 28 weeks. The primary outcome was voice-related distress at both time points, while voice severity and voice frequency were key secondary outcomes. Voice-related distress improved, compared with TAU, in both forms at 16 weeks but not at 28 weeks. Distress at 16 weeks was as follows: AV-BRF, effect \u22121.05 points, 96.5% confidence interval (CI)\u2009=\u2009\u22122.110 to 0,\n P<\/jats:italic>\n \u2009=\u20090.035, Cohen\u2019s\n d<\/jats:italic>\n \u2009=\u20090.38 (CI\u2009=\u20090 to 0.767); AV-EXT \u22121.60 points, 96.5% CI\u2009=\u2009\u22123.133 to \u22120.058,\n P<\/jats:italic>\n \u2009=\u20090.029, Cohen\u2019s\n d<\/jats:italic>\n \u2009=\u20090.58 (CI\u2009=\u20090.021 to 1.139). Distress at 28 weeks was: AV-BRF, \u22120.62 points, 96.5% CI\u2009=\u2009\u22121.912 to 0.679,\n P<\/jats:italic>\n \u2009=\u20090.316, Cohen\u2019s\n d<\/jats:italic>\n \u2009=\u20090.22 (CI\u2009=\u2009\u22120.247 to 0.695); AV-EXT \u22121.06 points, 96.5% CI\u2009=\u2009\u22122.700 to 0.586,\n P<\/jats:italic>\n \u2009=\u20090.175, Cohen\u2019s\n d<\/jats:italic>\n \u2009=\u20090.38 (CI\u2009=\u2009\u22120.213 to 0.981). Voice severity improved in both forms, compared with TAU, at 16 weeks but not at 28 weeks whereas frequency was reduced in AV-EXT but not in AV-BRF at both time points. There were no related serious adverse events. These findings provide partial support for our primary hypotheses. AV-EXT met our threshold for a clinically significant change, suggesting that future work should be primarily guided by this protocol. ISRCTN registration:\n ISRCTN55682735<\/jats:ext-link>\n .\n <\/jats:p>","DOI":"10.1038\/s41591-024-03252-8","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T13:02:27Z","timestamp":1730120547000},"page":"3658-3668","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Digital AVATAR therapy for distressing voices in psychosis: the phase 2\/3 AVATAR2 trial"],"prefix":"10.1038","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5637-1340","authenticated-orcid":false,"given":"Philippa A.","family":"Garety","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clementine J.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4541-6419","authenticated-orcid":false,"given":"Hassan","family":"Jafari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Emsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-5552","authenticated-orcid":false,"given":"Mark","family":"Huckvale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-3875","authenticated-orcid":false,"given":"Mar","family":"Rus-Calafell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Fornells-Ambrojo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gumley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-5774","authenticated-orcid":false,"given":"Gillian","family":"Haddock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-1815","authenticated-orcid":false,"given":"Hamish J.","family":"McLeod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moya","family":"Clancy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fitzsimmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1178-5080","authenticated-orcid":false,"given":"Hannah","family":"Ball","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Montague","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikos","family":"Xanidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-6093","authenticated-orcid":false,"given":"Amy","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas K. J.","family":"Craig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-5755","authenticated-orcid":false,"given":"Thomas","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"3252_CR1","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/S2215-0366(18)30296-7","volume":"5","author":"C Hollis","year":"2018","unstructured":"Hollis, C. et al. Identifying research priorities for digital technology in mental health care: results of the James Lind Alliance Priority Setting Partnership. Lancet Psychiatry 5, 845\u2013854 (2018).","journal-title":"Lancet Psychiatry"},{"key":"3252_CR2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/papt.12222","volume":"92","author":"S Bucci","year":"2019","unstructured":"Bucci, S., Schwannauer, M. & Berry, N. The digital revolution and its impact on mental health care. Psychol. Psychother. 92, 277\u2013297 (2019).","journal-title":"Psychol. Psychother."},{"key":"3252_CR3","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1176\/appi.ajp.2017.16121358","volume":"174","author":"S Leucht","year":"2017","unstructured":"Leucht, S. et al. Sixty years of placebo-controlled antipsychotic drug trials in acute schizophrenia: systematic review, Bayesian meta-analysis, and meta-regression of efficacy predictors. Am. J. Psychiatry 174, 927\u2013942 (2017).","journal-title":"Am. J. Psychiatry"},{"key":"3252_CR4","doi-asserted-by":"publisher","first-page":"402","DOI":"10.3389\/fpsyt.2020.00402","volume":"11","author":"DT Turner","year":"2020","unstructured":"Turner, D. T. et al. Efficacy and moderators of cognitive behavioural therapy for psychosis versus other psychological interventions: an individual-participant data meta-analysis. Front. Psychiatry 11, 402 (2020).","journal-title":"Front. Psychiatry"},{"key":"3252_CR5","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1080\/17522439.2013.773457","volume":"6","author":"J Leff","year":"2014","unstructured":"Leff, J., Williams, G., Huckvale, M., Arbuthnot, M. & Leff, A. P. Avatar therapy for persecutory auditory hallucinations: what is it and how does it work? Psychosis 6, 166\u2013176 (2014).","journal-title":"Psychosis"},{"key":"3252_CR6","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.schres.2016.11.019","volume":"183","author":"M Hayward","year":"2017","unstructured":"Hayward, M., Jones, A.-M., Bogen-Johnston, L., Thomas, N. & Strauss, C. Relating therapy for distressing auditory hallucinations: a pilot randomized controlled trial. Schizophr. Res. 183, 137\u2013142 (2017).","journal-title":"Schizophr. Res."},{"key":"3252_CR7","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.schres.2022.11.007","volume":"250","author":"E Longden","year":"2022","unstructured":"Longden, E. et al. A psychological intervention for engaging dialogically with auditory hallucinations (Talking With Voices): a single-site, randomised controlled feasibility trial. Schizophr. Res. 250, 172\u2013179 (2022).","journal-title":"Schizophr. Res."},{"key":"3252_CR8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S2215-0366(17)30427-3","volume":"5","author":"TK Craig","year":"2018","unstructured":"Craig, T. K. et al. AVATAR therapy for auditory verbal hallucinations in people with psychosis: a single-blind, randomised controlled trial. Lancet Psychiatry 5, 31\u201340 (2018).","journal-title":"Lancet Psychiatry"},{"key":"3252_CR9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.schres.2018.02.031","volume":"197","author":"OP du Sert","year":"2018","unstructured":"du Sert, O. P. et al. Virtual reality therapy for refractory auditory verbal hallucinations in schizophrenia: a pilot clinical trial. Schizophr. Res. 197, 176\u2013181 (2018).","journal-title":"Schizophr. Res."},{"key":"3252_CR10","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1093\/schbul\/sbaa061","volume":"46","author":"T Ward","year":"2020","unstructured":"Ward, T. et al. AVATAR therapy for distressing voices: a comprehensive account of therapeutic targets. Schizophr. Bull. 46, 1038\u20131044 (2020).","journal-title":"Schizophr. Bull."},{"key":"3252_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-021-05301-w","volume":"22","author":"P Garety","year":"2021","unstructured":"Garety, P. et al. Optimising AVATAR therapy for people who hear distressing voices: study protocol for the AVATAR2 multi-centre randomised controlled trial. Trials 22, 366 (2021).","journal-title":"Trials"},{"key":"3252_CR12","doi-asserted-by":"publisher","first-page":"2748","DOI":"10.3390\/jcm9092748","volume":"9","author":"M Rus-Calafell","year":"2020","unstructured":"Rus-Calafell, M. et al. The role of sense of voice presence and anxiety reduction in AVATAR therapy. J. Clin. Med. 9, 2748 (2020).","journal-title":"J. Clin. Med."},{"key":"3252_CR13","doi-asserted-by":"publisher","first-page":"S265","DOI":"10.1093\/schbul\/sbu014","volume":"40","author":"TS Woodward","year":"2014","unstructured":"Woodward, T. S. et al. Symptom dimensions of the psychotic symptom rating scales in psychosis: a multisite study. Schizophr. Bull. 40, S265\u2013S274 (2014).","journal-title":"Schizophr. Bull."},{"key":"3252_CR14","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/17522439.2023.2215298","volume":"16","author":"E Longden","year":"2024","unstructured":"Longden, E., Branitsky, A., Sheaves, B., Chauhan, N. & Morrison, A. P. Preferred treatment outcomes in psychological therapy for voices: a comparison of staff and service-user perspectives. Psychosis 16, 107\u2013117 (2024).","journal-title":"Psychosis"},{"key":"3252_CR15","doi-asserted-by":"publisher","first-page":"sgaa023","DOI":"10.1093\/schizbullopen\/sgaa023","volume":"1","author":"K Sitko","year":"2020","unstructured":"Sitko, K., Bewick, B. M., Owens, D. & Masterson, C. Meta-analysis and meta-regression of cognitive behavioral therapy for psychosis (CBTp) across time: the effectiveness of CBTp has improved for delusions. Schizophr. Bull. Open 1, sgaa023 (2020).","journal-title":"Schizophr. Bull. Open"},{"key":"3252_CR16","unstructured":"National Institute for Health and Care Excellence (NICE). Psychosis and Schizophrenia in Adults: Prevention and Management. Clinical Guideline [CG178] https:\/\/www.nice.org.uk\/guidance\/cg178 (2014)."},{"key":"3252_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-022-06683-1","volume":"23","author":"LC Smith","year":"2022","unstructured":"Smith, L. C. et al. The CHALLENGE trial: the effects of a virtual reality-assisted exposure therapy for persistent auditory hallucinations versus supportive counselling in people with psychosis: study protocol for a randomised clinical trial. Trials 23, 773 (2022).","journal-title":"Trials"},{"key":"3252_CR18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41537-021-00139-2","volume":"7","author":"L Dellazizzo","year":"2021","unstructured":"Dellazizzo, L., Potvin, S., Phraxayavong, K. & Dumais, A. One-year randomized trial comparing virtual reality-assisted therapy to cognitive\u2013behavioral therapy for patients with treatment-resistant schizophrenia. NPJ Schizophr. 7, 9 (2021).","journal-title":"NPJ Schizophr."},{"key":"3252_CR19","first-page":"1","volume":"52","author":"T Ward","year":"2021","unstructured":"Ward, T. et al. The role of characterisation in everyday voice engagement and AVATAR therapy dialogue. Psychol. Med. 52, 1\u20138 (2021).","journal-title":"Psychol. Med."},{"key":"3252_CR20","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1016\/S2215-0366(17)30153-0","volume":"4","author":"SM Gold","year":"2017","unstructured":"Gold, S. M. et al. Control conditions for randomised trials of behavioural interventions in psychiatry: a decision framework. Lancet Psychiatry 4, 725\u2013732 (2017).","journal-title":"Lancet Psychiatry"},{"key":"3252_CR21","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1002\/wps.20883","volume":"20","author":"J Torous","year":"2021","unstructured":"Torous, J. et al. The growing field of digital psychiatry: current evidence and the future of apps, social media, chatbots, and virtual reality. World Psychiatry 20, 318\u2013335 (2021).","journal-title":"World Psychiatry"},{"key":"3252_CR22","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1001\/jamapsychiatry.2021.0326","volume":"78","author":"P Garety","year":"2021","unstructured":"Garety, P. et al. Effects of SlowMo, a blended digital therapy targeting reasoning, on paranoia among people with psychosis: a randomized clinical trial. JAMA Psychiatry 78, 714\u2013725 (2021).","journal-title":"JAMA Psychiatry"},{"key":"3252_CR23","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/S2215-0366(22)00103-1","volume":"9","author":"AI Gumley","year":"2022","unstructured":"Gumley, A. I. et al. The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia. Lancet Psychiatry 9, 477\u2013486 (2022).","journal-title":"Lancet Psychiatry"},{"key":"3252_CR24","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.schres.2022.07.013","volume":"248","author":"M Cella","year":"2022","unstructured":"Cella, M. et al. Virtual reality therapy for the negative symptoms of schizophrenia (V-NeST): a pilot randomised feasibility trial. Schizophr. Res. 248, 50\u201357 (2022).","journal-title":"Schizophr. Res."},{"key":"3252_CR25","unstructured":"National Institute for Health and Care Excellence (NICE). Digital Health Technologies to Help Manage Symptoms of Psychosis and Prevent Relapse in Adults and Young People: Early Value Assessment https:\/\/www.nice.org.uk\/guidance\/hte17 (2024)."},{"key":"3252_CR26","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1017\/S0033291799008661","volume":"29","author":"G Haddock","year":"1999","unstructured":"Haddock, G., McCarron, J., Tarrier, N. & Faragher, E. B. Scales to measure dimensions of hallucinations and delusions: the psychotic symptom rating scales (PSYRATS). Psychol. Med. 29, 879\u2013889 (1999).","journal-title":"Psychol. Med."},{"key":"3252_CR27","doi-asserted-by":"publisher","first-page":"1192655","DOI":"10.3389\/fpsyt.2023.1192655","volume":"14","author":"CJ Edwards","year":"2023","unstructured":"Edwards, C. J. et al. The Voice Characterisation Checklist: psychometric properties of a brief clinical assessment of voices as social agents. Front. Psychiatry 14, 1192655 (2023).","journal-title":"Front. Psychiatry"},{"key":"3252_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/1477-7525-5-63","volume":"5","author":"R Tennant","year":"2007","unstructured":"Tennant, R. et al. The Warwick-Edinburgh Mental Well-being Scale (WEMWBS): development and UK validation. Health Qual. Life Outcomes 5, 63 (2007).","journal-title":"Health Qual. Life Outcomes"},{"key":"3252_CR29","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1093\/schbul\/sbp117","volume":"36","author":"KE Greenwood","year":"2010","unstructured":"Greenwood, K. E. et al. CHoice of Outcome In Cbt for psychosEs (CHOICE): the development of a new service user-led outcome measure of CBT for psychosis. Schizophr. Bull. 36, 126\u2013135 (2010).","journal-title":"Schizophr. Bull."},{"key":"3252_CR30","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1037\/0022-3514.61.2.226","volume":"61","author":"K Bartholomew","year":"1991","unstructured":"Bartholomew, K. & Horowitz, L. M. Attachment styles among young adults: a test of a four-category model. J. Pers. Soc. Psychol. 61, 226\u2013244 (1991).","journal-title":"J. Pers. Soc. Psychol."},{"key":"3252_CR31","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/jclp.20366","volume":"63","author":"F Shawyer","year":"2007","unstructured":"Shawyer, F. et al. The voices acceptance and action scale (VAAS): pilot data. J. Clin. Psychol. 63, 593\u2013606 (2007).","journal-title":"J. Clin. Psychol."},{"key":"3252_CR32","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1348\/014466505X29657","volume":"44","author":"JD Henry","year":"2005","unstructured":"Henry, J. D. & Crawford, J. R. The short\u2010form version of the Depression Anxiety Stress Scales (DASS\u201021): construct validity and normative data in a large non\u2010clinical sample. Br. J. Clin. Psychol. 44, 227\u2013239 (2005).","journal-title":"Br. J. Clin. Psychol."},{"key":"3252_CR33","doi-asserted-by":"crossref","unstructured":"Beck, A. T., Steer, R. A. & Brown, G. K. BDI-II: Beck Depression Inventory (Pearson, 1996).","DOI":"10.1037\/t00742-000"},{"key":"3252_CR34","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1017\/S0033291799001828","volume":"30","author":"M Birchwood","year":"2000","unstructured":"Birchwood, M., Meaden, A., Trower, P., Gilbert, P. & Plaistow, J. The power and omnipotence of voices: subordination and entrapment by voices and significant others. Psychol. Med. 30, 337\u2013344 (2000).","journal-title":"Psychol. Med."},{"key":"3252_CR35","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1192\/bjp.177.3.229","volume":"177","author":"P Chadwick","year":"2000","unstructured":"Chadwick, P., Lees, S. & Birchwood, M. The revised Beliefs About Voices Questionnaire (BAVQ\u2013R). Br. J. Psychiatry 177, 229\u2013232 (2000).","journal-title":"Br. J. Psychiatry"},{"key":"3252_CR36","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1111\/acps.12956","volume":"138","author":"M Cloitre","year":"2018","unstructured":"Cloitre, M. et al. The International Trauma Questionnaire: development of a self-report measure of ICD-11 PTSD and complex PTSD. Acta Psychiatr. Scand. 138, 536\u2013546 (2018).","journal-title":"Acta Psychiatr. Scand."},{"key":"3252_CR37","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1176\/appi.ajp.2012.12010109","volume":"170","author":"AM Kring","year":"2013","unstructured":"Kring, A. M., Gur, R. E., Blanchard, J. J., Horan, W. P. & Reise, S. P. The Clinical Assessment Interview for Negative Symptoms (CAINS): final development and validation. Am. J. Psychiatry 170, 165\u2013172 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"3252_CR38","volume-title":"Scale for the Assessment of Positive Symptoms (SAPS)","author":"NC Andreasen","year":"1985","unstructured":"Andreasen, N. C Scale for the Assessment of Positive Symptoms (SAPS) (Univ. of Iowa, 1985)."},{"key":"3252_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-018-2735-z","volume":"19","author":"S Grant","year":"2018","unstructured":"Grant, S. et al. CONSORT-SPI 2018 Explanation and Elaboration: guidance for reporting social and psychological intervention trials. Trials 19, 406 (2018).","journal-title":"Trials"},{"key":"3252_CR40","unstructured":"Stata Statistical Software: Release 18 (StataCorp LLC, 2023)."},{"key":"3252_CR41","unstructured":"R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2024)."},{"key":"3252_CR42","doi-asserted-by":"crossref","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2016).","DOI":"10.1007\/978-3-319-24277-4_9"}],"updated-by":[{"DOI":"10.1038\/s41591-026-04540-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000}}],"container-title":["Nature Medicine"],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03252-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03252-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03252-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:52:10Z","timestamp":1782906730000},"score":9.76457,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-03252-8"}},"issued":{"date-parts":[[2024,10,28]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["3252"],"URL":"https:\/\/doi.org\/10.1038\/s41591-024-03252-8","ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"published":{"date-parts":[[2024,10,28]]},"assertion":[{"value":"10 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41591-026-04540-1","URL":"https:\/\/doi.org\/10.1038\/s41591-026-04540-1","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.H. is a shareholder of Avatar Therapy Ltd. T.K.J.C. and P.A.G. are unpaid scientific advisers to Avatar Therapy Ltd. S.B. is Director and shareholder of CareLoop Health Ltd, which develops and markets digital therapeutics for schizophrenia and a digital screening app for postnatal depression. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]},{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T19:06:26Z","timestamp":1777662386859,"version":"3.51.4"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["205177\/Z\/16\/Z"],"award-info":[{"award-number":["205177\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"Abstract<\/jats:title>\n Urbanization results in increased numbers of people living in cities and poses challenges and opportunities to public health policies. Studies of urban scaling have unveiled how cities\u2019 socio-economic and infrastructural attributes vary systematically with city size. Previous studies have explored the scaling properties of health outcomes across metropolitan areas in different countries, but chronic diseases have been infrequently examined. This paper examines scaling behaviors of 4 cardiovascular risk factors: hypertension, diabetes, tobacco smoking, and obesity across 230 cities in six countries of Latin America. In analyses pooled across countries, diabetes and hypertension showed weakly superlinear scaling (higher prevalence in larger cities). In comparison, obesity showed linear scaling, and tobacco showed weakly sublinear scaling (lower prevalence in larger cities), although most coefficients did not differ significantly from the null. In country-specific analyses, hypertension and diabetes tended to show a superlinear pattern across most countries, obesity tended to show a sublinear pattern in most countries, and tobacco tended to be superlinear (in contrast to the analysis pooled across countries where it was sublinear). Results suggest the need to examine further the drivers of this varying scaling of risk factors.<\/jats:p>","DOI":"10.1038\/s41598-025-92087-5","type":"journal-article","created":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T08:45:51Z","timestamp":1740818751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Scaling of cardiovascular risk factors in 230 Latin American cities"],"prefix":"10.1038","volume":"15","author":[{"given":"Aureliano S. S.","family":"Paiva","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Usama","family":"Bilal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto F. S.","family":"Andrade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudiano C. Cruz","family":"Neto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Firmino","family":"de Sousa Filho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerv\u00e1sio F.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maur\u00edcio L.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel A.","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pricila","family":"Mullachery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brisa","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana V.","family":"Diez-Roux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Montes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9s","family":"Trotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"Alfaro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Jaime","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tonatiuh","family":"Barrientos-Gutierrez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"92087_CR1","unstructured":"UN-Habitat. Urbanization and Development: Emerging Futures. World Cities Report 2016 264 (United Nations, 2016)."},{"key":"92087_CR2","unstructured":"United Nations. World Urbanization Prospects: The 2018 Revision (United Nations, 2019)."},{"key":"92087_CR3","doi-asserted-by":"publisher","first-page":"e111015","DOI":"10.1371\/journal.pone.0111015","volume":"9","author":"FJ Antonio","year":"2014","unstructured":"Antonio, F. J., De Piccoli, S., Teixeira, J. J. V. & Mendes, R. D. S. Growth patterns and scaling laws governing AIDS epidemic in Brazilian cities. PLoS ONE 9, e111015 (2014).","journal-title":"PLoS ONE"},{"key":"92087_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15517\/es.2023.55397","volume":"1","author":"O Patterson-Lomba","year":"2023","unstructured":"Patterson-Lomba, O. & Gomez-Lievano, A. On the scaling patterns of infectious disease incidence in cities. Epi. Sci. 1, 1 (2023).","journal-title":"Epi. Sci."},{"key":"92087_CR5","doi-asserted-by":"publisher","first-page":"e0293518","DOI":"10.1371\/journal.pone.0293518","volume":"18","author":"ASS Paiva","year":"2023","unstructured":"Paiva, A. S. S. et al. A scaling investigation of urban form features in Latin America cities. PLoS ONE 18, e0293518 (2023).","journal-title":"PLoS ONE"},{"key":"92087_CR6","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1126\/science.1235823","volume":"340","author":"LM Bettencourt","year":"2013","unstructured":"Bettencourt, L. M. A. The origins of scaling in cities. Science 340, 1438\u20131441 (2013).","journal-title":"Science"},{"key":"92087_CR7","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1080\/15389588.2016.1162904","volume":"17","author":"YS Chang","year":"2016","unstructured":"Chang, Y. S., Lee, W. J. & Lee, J. H. Are there higher pedestrian fatalities in larger cities? A scaling analysis of 115 to 161 largest cities in the united States. Traffic Inj. Prev. 17, 720\u2013728 (2016).","journal-title":"Traffic Inj. Prev."},{"key":"92087_CR8","doi-asserted-by":"publisher","first-page":"e0183110","DOI":"10.1371\/journal.pone.0183110","volume":"12","author":"M Oliveira","year":"2017","unstructured":"Oliveira, M., Bastos-Filho, C. & Menezes, R. The scaling of crime concentration in cities. PLoS ONE 12, e0183110 (2017).","journal-title":"PLoS ONE"},{"key":"92087_CR9","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s11524-021-00577-4","volume":"99","author":"EM McCulley","year":"2022","unstructured":"McCulley, E. M. et al. Urban scaling of health outcomes: a scoping review. J. Urban Health 99, 409\u2013426 (2022).","journal-title":"J. Urban Health"},{"key":"92087_CR10","unstructured":"Choi, S. B., Lee, Y. J. & Chang, Y. S. Population Size and Urban Health Advantage: Scaling Analyses of Four Major Diseases for 417 US Counties."},{"key":"92087_CR11","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1016\/S0140-6736(15)60901-1","volume":"386","author":"S Whitmee","year":"2015","unstructured":"Whitmee, S. et al. Safeguarding human health in the anthropocene epoch: report of the rockefeller Foundation\u2013Lancet commission on planetary health. Lancet 386, 1973\u20132028 (2015).","journal-title":"Lancet"},{"key":"92087_CR12","unstructured":"West, G. B. Scale: the Universal Laws of Growth, Innovation, Sustainability, and the Pace of Life in Organisms, Cities, Economies, and Companies (Penguin, 2017)."},{"key":"92087_CR13","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/35001159","volume":"403","author":"V Smil","year":"2000","unstructured":"Smil, V. Laying down the low: every living thing obeys the rules of scaling discovered by max Kleiber. Nature 403, 597\u2013598 (2000).","journal-title":"Nature"},{"key":"92087_CR14","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/421713a","volume":"421","author":"GB West","year":"2003","unstructured":"West, G. B. et al. Why does metabolic rate scale with body size? Physiology (communication arising). Nature 421, 713\u2013713 (2003).","journal-title":"Nature"},{"key":"92087_CR15","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1136\/sextrans-2014-051932","volume":"91","author":"O Patterson-Lomba","year":"2015","unstructured":"Patterson-Lomba, O., Goldstein, E., G\u00f3mez-Li\u00e9vano, A., Castillo-Chavez, C. & Towers, S. Per capita incidence of sexually transmitted infections increases systematically with urban population size: a cross-sectional study. Sex. Transm. Infect. 91, 610\u2013614 (2015).","journal-title":"Sex. Transm Infect."},{"key":"92087_CR16","doi-asserted-by":"publisher","first-page":"eabl6325","DOI":"10.1126\/sciadv.abl6325","volume":"7","author":"U Bilal","year":"2021","unstructured":"Bilal, U. et al. Scaling of mortality in 742 metropolitan areas of the Americas. Sci. Adv. 7, eabl6325 (2021).","journal-title":"Sci. Adv."},{"key":"92087_CR17","unstructured":"United Nations. The World\u2019s Cities in 2016\u2014Data Booklet (eds P.D. Department of Economic and Social Affairs) (United Nations, 2016)."},{"key":"92087_CR18","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1038\/s41591-020-01214-4","volume":"27","author":"U Bilal","year":"2021","unstructured":"Bilal, U. et al. Life expectancy and mortality in 363 cities of Latin America. Nat. Med. 27, 463\u2013470 (2021).","journal-title":"Nat. Med."},{"key":"92087_CR19","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1136\/tc.11.4.305","volume":"11","author":"J Barnoya","year":"2002","unstructured":"Barnoya, J. Tobacco industry success in preventing regulation of secondhand smoke in Latin America: the \u2018Latin project\u2019. Tob. Control 11, 305\u2013314 (2002).","journal-title":"Tob. Control"},{"key":"92087_CR20","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1080\/17441692.2017.1316414","volume":"13","author":"A Arredondo","year":"2018","unstructured":"Arredondo, A., Azar, A. & Recam\u00e1n, A. L. Diabetes, a global public health challenge with a high epidemiological and economic burden on health systems in Latin America. Glob. Public Health 13, 780\u2013787 (2018).","journal-title":"Glob. Public Health"},{"key":"92087_CR21","doi-asserted-by":"publisher","first-page":"5142","DOI":"10.1017\/S1368980021001403","volume":"24","author":"C Palacios","year":"2021","unstructured":"Palacios, C. et al. Obesity in Latin America, a scoping review of public health prevention strategies and an overview of their impact on obesity prevention. Public Health Nutr. 24, 5142\u20135155 (2021).","journal-title":"Public Health Nutr."},{"key":"92087_CR22","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1007\/s11524-015-9976-x","volume":"92","author":"LEC Rocha","year":"2015","unstructured":"Rocha, L. E. C., Thorson, A. E. & Lambiotte, R. The non-linear health consequences of living in larger cities. J. Urban Health 92, 785\u2013799 (2015).","journal-title":"J. Urban Health"},{"key":"92087_CR23","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1161\/CIRCULATIONAHA.104.521708","volume":"112","author":"M Ezzati","year":"2005","unstructured":"Ezzati, M., Henley, S. J., Thun, M. J. & Lopez, A. D. Role of smoking in global and regional cardiovascular mortality. Circulation 112, 489\u2013497 (2005).","journal-title":"Circulation"},{"key":"92087_CR24","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.healthplace.2006.11.001","volume":"13","author":"B Idris","year":"2007","unstructured":"Idris, B. et al. Higher smoking prevalence in urban compared to non-urban areas: time trends in six European countries. Health Place 13, 702\u2013712 (2007).","journal-title":"Health Place"},{"key":"92087_CR25","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12942-017-0092-x","volume":"16","author":"T Yang","year":"2017","unstructured":"Yang, T. et al. Contextual influences affecting patterns of overweight and obesity among university students: a 50 universities population-based study in China. Int. J. Health Geogr. 16, 18 (2017).","journal-title":"Int. J. Health Geogr."},{"key":"92087_CR26","doi-asserted-by":"publisher","unstructured":"Balandr\u00e1n, A. et al. Health Systems in Transition: Mexico. https:\/\/doi.org\/10.3138\/9781487538422 (University of Toronto, 2021).","DOI":"10.3138\/9781487538422"},{"key":"92087_CR27","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1590\/S0104-12902013000200013","volume":"22","author":"MA Separavich","year":"2013","unstructured":"Separavich, M. A. & Canesqui, A. M. Sa\u00fade do homem e masculinidades Na pol\u00edtica Nacional de Aten\u00e7\u00e3o integral \u00e0 Sa\u00fade do Homem: uma Revis\u00e3o bibliogr\u00e1fica. Saude Soc. 22, 415\u2013428 (2013).","journal-title":"Saude Soc."},{"key":"92087_CR28","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1590\/S0102-311X2007000300015","volume":"23","author":"R Gomes","year":"2007","unstructured":"Gomes, R., Nascimento, E. F. D. & Ara\u00fajo, F. C. D. Por Que Os homens Buscam Menos Os servi\u00e7os de Sa\u00fade do Que as mulheres? As explica\u00e7\u00f5es de homens com Baixa escolaridade e homens com Ensino superior. Cad Saude Publica. 23, 565\u2013574 (2007).","journal-title":"Cad Saude Publica"},{"key":"92087_CR29","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1177\/0898264314527477","volume":"26","author":"LS Rohlfsen","year":"2014","unstructured":"Rohlfsen, L. S. & Jacobs Kronenfeld, J. Gender differences in trajectories of self-rated health in middle and old age: an examination of differential exposure and differential vulnerability. J. Aging Health. 26, 637\u2013662 (2014).","journal-title":"J. Aging Health"},{"key":"92087_CR30","unstructured":"UN Women. Progress of the World\u2019s Women 2015\u20132016: Transforming Economies, Realizing Rights 342 (2015)."},{"key":"92087_CR31","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1186\/s12889-022-13752-2","volume":"22","author":"M Castillo-Riquelme","year":"2022","unstructured":"Castillo-Riquelme, M. et al. Aging and self-reported health in 114 Latin American cities: gender and socio-economic inequalities. BMC Public Health. 22, 1499 (2022).","journal-title":"BMC Public Health"},{"key":"92087_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/409083","volume":"2013","author":"V Mohan","year":"2013","unstructured":"Mohan, V., Seedat, Y. K. & Pradeepa, R. The rising burden of diabetes and hypertension in Southeast Asian and African regions: need for effective strategies for prevention and control in primary health care settings. Int. J. Hypertens. 2013, 1\u201314 (2013).","journal-title":"Int. J. Hypertens."},{"key":"92087_CR33","doi-asserted-by":"publisher","first-page":"e55149","DOI":"10.1590\/1980-0037.2019v21e55149","volume":"21","author":"EZ Martinez","year":"2019","unstructured":"Martinez, E. Z. et al. Association between diabetes, hypertension, activities of daily living and physical activity among elderly users of primary healthcare facilities. Rev. Bras. Cineantropom Desempenho Hum. 21, e55149 (2019).","journal-title":"Rev. Bras. Cineantropom Desempenho Hum."},{"key":"92087_CR34","doi-asserted-by":"publisher","first-page":"264","DOI":"10.17843\/rpmesp.2023.403.13284","volume":"1","author":"A Alcaraz","year":"2023","unstructured":"Alcaraz, A. & Pichon-Riviere, A. El control Del Tabaco En Am\u00e9rica Latina: Logros, pendientes y Nuevos desaf\u00edos. Rev. Peru Med. Exp. Salud Publica 1, 264\u2013266. https:\/\/doi.org\/10.17843\/rpmesp.2023.403.13284 (2023).","journal-title":"Rev. Peru Med. Exp. Salud Publica"},{"key":"92087_CR35","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S0140-6736(19)31243-7","volume":"394","author":"MC Castro","year":"2019","unstructured":"Castro, M. C. et al. Brazil\u2019s unified health system: the first 30 years and prospects for the future. Lancet 394, 345\u2013356 (2019).","journal-title":"Lancet"},{"key":"92087_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/0102-311x00113016","volume":"33","author":"MJ Marro","year":"2017","unstructured":"Marro, M. J., Cardoso, A. M. & Leite, I. D. C. Desigualdades regionales En La Mortalidad Por diabetes mellitus y En El acceso a La Salud En Argentina. Cad Sa\u00fade P\u00fabl. 33, 1 (2017).","journal-title":"Cad Sa\u00fade P\u00fabl."},{"key":"92087_CR37","doi-asserted-by":"publisher","first-page":"57","DOI":"10.37757\/MR2017.V19.N2-3.10","volume":"19","author":"A Castillo-Laborde","year":"2017","unstructured":"Castillo-Laborde, A. et al. Health insurance scheme performance and effects on health and health inequalities in Chile. MEDICC Rev. 19, 57\u201364 (2017).","journal-title":"MEDICC Rev."},{"key":"92087_CR38","first-page":"100148","volume":"7","author":"RM Carrillo-Larco","year":"2022","unstructured":"Carrillo-Larco, R. M. et al. Peru\u2014Progress in health and sciences in 200 years of independence. Lancet Reg. Health Am. 7, 100148 (2022).","journal-title":"Lancet Reg. Health Am."},{"key":"92087_CR39","doi-asserted-by":"publisher","first-page":"737","DOI":"10.7705\/biomedica.4453","volume":"39","author":"L Hilari\u00f3n-Gait\u00e1n","year":"2019","unstructured":"Hilari\u00f3n-Gait\u00e1n, L., D\u00edaz-Jim\u00e9nez, D. & Cotes-Cantillo, K. Casta\u00f1eda-Orjuela, C. Desigualdades En Salud Seg\u00fan r\u00e9gimen de afiliaci\u00f3n y eventos notificados al sistema de vigilancia (Sivigila) En Colombia, 2015. Biomedica 39, 737\u2013747 (2019).","journal-title":"Biomedica"},{"key":"92087_CR40","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1111\/j.1468-0009.2005.00398.x","volume":"83","author":"AR Omran","year":"2005","unstructured":"Omran, A. R. The epidemiologic transition: A theory of the epidemiology of population change. Milbank Q. 83, 731\u2013757 (2005).","journal-title":"Milbank Q."},{"key":"92087_CR41","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.compenvurbsys.2016.04.006","volume":"63","author":"C Cottineau","year":"2017","unstructured":"Cottineau, C., Hatna, E., Arcaute, E. & Batty, M. Diverse cities or the systematic paradox of urban scaling laws. Comput. Environ. Urban Syst. 63, 80\u201394 (2017).","journal-title":"Comput. Environ. Urban Syst."},{"key":"92087_CR42","doi-asserted-by":"crossref","unstructured":"Portugali, J. et al. Complexity Theories of Cities Have Come of Age: An Overview with Implications to Urban Planning and Design 449 (Springer, 2012).","DOI":"10.1007\/978-3-642-24544-2"},{"key":"92087_CR43","doi-asserted-by":"publisher","first-page":"13759","DOI":"10.1073\/pnas.1906258116","volume":"116","author":"M Keuschnigg","year":"2019","unstructured":"Keuschnigg, M. Scaling trajectories of cities. Proc. Natl. Acad. Sci. U.S.A. 116, 13759\u201313761 (2019).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"92087_CR44","doi-asserted-by":"publisher","first-page":"20150937","DOI":"10.1098\/rsif.2015.0937","volume":"13","author":"H Youn","year":"2016","unstructured":"Youn, H. et al. Scaling and universality in urban economic diversification. J. R. Soc. Interface 13, 20150937 (2016).","journal-title":"J. R. Soc. Interface"},{"key":"92087_CR45","doi-asserted-by":"publisher","first-page":"20190846","DOI":"10.1098\/rsif.2019.0846","volume":"17","author":"LMA Bettencourt","year":"2020","unstructured":"Bettencourt, L. M. A. et al. The interpretation of urban scaling analysis in time. J. R. Soc. Interface 17, 20190846 (2020).","journal-title":"J. R. Soc. Interface"},{"key":"92087_CR46","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/467912a","volume":"467","author":"L Bettencourt","year":"2010","unstructured":"Bettencourt, L. & West, G. A unified theory of urban living. Nature 467, 912\u2013913 (2010).","journal-title":"Nature"},{"key":"92087_CR47","doi-asserted-by":"crossref","unstructured":"Bettencourt, L. M. A., Lobo, J., Helbing, D., K\u00fchnert, C. & West, G. B. Growth, innovation, scaling, and the pace of life in cities. Proc. Natl. Acad. Sci. U.S.A. 104, 7301\u20137306 (2007).","DOI":"10.1073\/pnas.0610172104"},{"key":"92087_CR48","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s11524-018-00326-0","volume":"96","author":"DA Quistberg","year":"2019","unstructured":"Quistberg, D. A. et al. Building a data platform for cross-country urban health studies: the SALURBAL study. J. Urban Health 96, 311\u2013337 (2019).","journal-title":"J. Urban Health"},{"key":"92087_CR49","doi-asserted-by":"publisher","first-page":"1800013","DOI":"10.1002\/gch2.201800013","volume":"3","author":"AV Diez Roux","year":"2019","unstructured":"Diez Roux, A. V. et al. A novel international partnership for actionable evidence on urban health in Latin America: LAC-urban health and SALURBAL. Global Challenges 3, 1800013 (2019).","journal-title":"Global Challenges"},{"key":"92087_CR50","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1136\/jech-2020-216116","volume":"75","author":"A Braverman-Bronstein","year":"2021","unstructured":"Braverman-Bronstein, A. et al. Association of education level with diabetes prevalence in Latin American cities and its modification by City social environment. J. Epidemiol. Community Health 75, 874\u2013880 (2021).","journal-title":"J. Epidemiol. Community Health"},{"key":"92087_CR51","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1017\/S1368980021002457","volume":"25","author":"M Mazariegos","year":"2022","unstructured":"Mazariegos, M. et al. Educational inequalities in obesity: a multilevel analysis of survey data from cities in Latin America. Public Health Nutr. 25, 1790\u20131798 (2022).","journal-title":"Public Health Nutr."},{"key":"92087_CR52","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1097\/EDE.0000000000001118","volume":"31","author":"H Quick","year":"2020","unstructured":"Quick, H., Terloyeva, D., Wu, Y., Moore, K. & Diez Roux, A. V. Trends in tract-level prevalence of obesity in Philadelphia by race-ethnicity, space, and time. Epidemiology 31, 15\u201321 (2020).","journal-title":"Epidemiology"}],"container-title":["Scientific Reports"],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92087-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92087-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92087-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T09:19:13Z","timestamp":1740820753000},"score":9.7533045,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-92087-5"}},"issued":{"date-parts":[[2025,3,1]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["92087"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-92087-5","ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"published":{"date-parts":[[2025,3,1]]},"assertion":[{"value":"3 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The SALURBAL study protocol was approved by the Drexel University Institutional Review Board with ID #1612005035 and by appropriate site-specific IRBs.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"7279"},{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:00:02Z","timestamp":1790838002945,"version":"4.1.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"15","license":[{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:00:00Z","timestamp":1625184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wellcome","award":["108183"],"award-info":[{"award-number":["108183"]}]},{"name":"Wellcome","award":["220863"],"award-info":[{"award-number":["220863"]}]},{"name":"Wellcome","award":["108079"],"award-info":[{"award-number":["108079"]}]},{"name":"Wellcome","award":["207511"],"award-info":[{"award-number":["207511"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO J"],"published-print":{"date-parts":[[2021,8,2]]},"DOI":"10.15252\/embj.2021107826","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T18:08:46Z","timestamp":1623175726000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":213,"title":["SARS\u2010CoV\u20102 sensing by RIG\u2010I and MDA5 links epithelial infection to macrophage inflammation"],"prefix":"10.1038","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7358-6047","authenticated-orcid":false,"given":"Lucy G","family":"Thorne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-3519","authenticated-orcid":false,"given":"Ann\u2010Kathrin","family":"Reuschl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4682-4043","authenticated-orcid":false,"given":"Lorena","family":"Zuliani\u2010Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0441-3358","authenticated-orcid":false,"given":"Matthew V X","family":"Whelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9358-6001","authenticated-orcid":false,"given":"Jane","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4774-0853","authenticated-orcid":false,"given":"Mahdad","family":"Noursadeghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-2281","authenticated-orcid":false,"given":"Clare","family":"Jolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7707-0264","authenticated-orcid":false,"given":"Greg J","family":"Towers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,2]]},"reference":[{"key":"BFEMBJ2021107826_CR1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1038\/s41562-020-00944-2","volume":"4","author":"WE Allen","year":"2020","unstructured":"Allen WE, Altae\u2010Tran H, Briggs J, Jin X, McGee G, Shi A, Raghavan R, Kamariza M, Nova N, Pereta A et\u00a0al (2020) Population\u2010scale longitudinal mapping of COVID\u201019 symptoms, behaviour and testing. Nat Hum Behav 4: 972\u2013982","journal-title":"Nat Hum Behav"},{"key":"BFEMBJ2021107826_CR2","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMoa1401505","volume":"370","author":"EI Azhar","year":"2014","unstructured":"Azhar EI, El\u2010Kafrawy SA, Farraj SA, Hassan AM, Al\u2010Saeed MS, Hashem AM, Madani TA (2014) Evidence for camel\u2010to\u2010human transmission of MERS coronavirus. N Engl J Med 370: 2499\u20132505","journal-title":"N Engl J Med"},{"key":"BFEMBJ2021107826_CR3","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.cell.2020.10.004","volume":"183","author":"AK Banerjee","year":"2020","unstructured":"Banerjee AK, Blanco MR, Bruce EA, Honson DD, Chen LM, Chow A, Bhat P, Ollikainen N, Quinodoz SA, Loney C et\u00a0al (2020) SARS\u2010CoV\u20102 disrupts splicing, translation, and protein trafficking to suppress host defenses. Cell 183: 1325\u20131339.e1321","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR4","doi-asserted-by":"crossref","first-page":"eabd4585","DOI":"10.1126\/science.abd4585","volume":"370","author":"P Bastard","year":"2020","unstructured":"Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, B\u00e9ziat V, et\u00a0al (2020) Autoantibodies against type I IFNs in patients with life\u2010threatening COVID\u201019. Science 370: eabd4585","journal-title":"Science"},{"key":"BFEMBJ2021107826_CR5","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1056\/NEJMoa2007764","volume":"383","author":"JH Beigel","year":"2020","unstructured":"Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S et\u00a0al (2020) Remdesivir for the Treatment of Covid\u201019 \u2014 final report. N Engl J Med 383: 1813\u20131826","journal-title":"N Engl J Med"},{"key":"BFEMBJ2021107826_CR6","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","volume":"181","author":"D Blanco\u2010Melo","year":"2020","unstructured":"Blanco\u2010Melo D, Nilsson\u2010Payant BE, Liu W\u2010C, Uhl S, Hoagland D, M\u00f8ller R, Jordan TX, Oishi K, Panis M, Sachs D et\u00a0al (2020) Imbalanced host response to SARS\u2010CoV\u20102 drives development of COVID\u201019. Cell 181: 1036\u20131045.e1039","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR7","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41564-020-0771-4","volume":"5","author":"MF Boni","year":"2020","unstructured":"Boni MF, Lemey P, Jiang X, Lam TT, Perry BW, Castoe TA, Rambaut A, Robertson DL (2020) Evolutionary origins of the SARS\u2010CoV\u20102 sarbecovirus lineage responsible for the COVID\u201019 pandemic. Nat Microbiol 5: 1408\u20131417","journal-title":"Nat Microbiol"},{"key":"BFEMBJ2021107826_CR8","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/j.cell.2020.05.006","volume":"181","author":"P Bost","year":"2020","unstructured":"Bost P, Giladi A, Liu Y, Bendjelal Y, Xu G, David E, Blecher\u2010Gonen R, Cohen M, Medaglia C, Li H et\u00a0al (2020) Host\u2010viral infection maps reveal signatures of severe COVID\u201019 patients. Cell 181: 1475\u20131488.e1412","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR9","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.3389\/fimmu.2019.01586","volume":"10","author":"M Brisse","year":"2019","unstructured":"Brisse M, Ly H (2019) Comparative structure and function analysis of the RIG\u2010I\u2010Like receptors: RIG\u2010I and MDA5. Front Immunol 10: 1586","journal-title":"Front Immunol"},{"key":"BFEMBJ2021107826_CR10","doi-asserted-by":"crossref","first-page":"6409","DOI":"10.1172\/JCI141772","volume":"130","author":"V Bronte","year":"2020","unstructured":"Bronte V, Ugel S, Tinazzi E, Vella A, De Sanctis F, Can\u00e8 S, Batani V, Trovato R, Fiore A, Petrova V et\u00a0al (2020) Baricitinib restrains the immune dysregulation in patients with severe COVID\u201019. J Clin Invest 130: 6409\u20136416","journal-title":"J Clin Invest"},{"key":"BFEMBJ2021107826_CR11","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41587-020-0602-4","volume":"38","author":"RL Chua","year":"2020","unstructured":"Chua RL, Lukassen S, Trump S, Hennig BP, Wendisch D, Pott F, Debnath O, Th\u00fcrmann L, Kurth F, V\u00f6lker MT et\u00a0al (2020) COVID\u201019 severity correlates with airway epithelium\u2010immune cell interactions identified by single\u2010cell analysis. Nat Biotechnol 38: 970\u2013979","journal-title":"Nat Biotechnol"},{"key":"BFEMBJ2021107826_CR12","first-page":"2000045","volume":"25","author":"VM Corman","year":"2020","unstructured":"Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DKW, Bleicker T, Br\u00fcnink S, Schneider J, Schmidt ML et\u00a0al (2020) Detection of 2019 novel coronavirus (2019\u2010nCoV) by real\u2010time RT\u2010PCR. Euro Surveill 25: 2000045","journal-title":"Euro Surveill"},{"key":"BFEMBJ2021107826_CR13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13073-020-00763-0","volume":"12","author":"AD Davidson","year":"2020","unstructured":"Davidson AD, Williamson MK, Lewis S, Shoemark D, Carroll MW, Heesom KJ, Zambon M, Ellis J, Lewis PA, Hiscox JA et\u00a0al (2020) Characterisation of the transcriptome and proteome of SARS\u2010CoV\u20102 reveals a cell passage induced in\u2010frame deletion of the furin\u2010like cleavage site from the spike glycoprotein. Genome Med 12: 68","journal-title":"Genome Med"},{"key":"BFEMBJ2021107826_CR14","doi-asserted-by":"crossref","first-page":"m1985","DOI":"10.1136\/bmj.m1985","volume":"369","author":"AB Docherty","year":"2020","unstructured":"Docherty AB, Harrison EM, Green CA, Hardwick HE, Pius R, Norman L, Holden KA, Read JM, Dondelinger F, Carson G et\u00a0al (2020) Features of 20 133 UK patients in hospital with covid\u201019 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ 369: m1985","journal-title":"BMJ"},{"key":"BFEMBJ2021107826_CR15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1021\/acscentsci.0c00489","volume":"6","author":"RT Eastman","year":"2020","unstructured":"Eastman RT, Roth JS, Brimacombe KR, Simeonov A, Shen M, Patnaik S, Hall MD (2020) Remdesivir: A review of its discovery and development leading to emergency use authorization for treatment of COVID\u201019. ACS Central Sci 6: 672\u2013683","journal-title":"ACS Central Sci"},{"key":"BFEMBJ2021107826_CR16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009292","volume":"17","author":"JK Fiege","year":"2021","unstructured":"Fiege JK, Thiede JM, Nanda HA, Matchett WE, Moore PJ, Montanari NR, Thielen BK, Daniel J, Stanley E, Hunter RC et\u00a0al (2021) Single cell resolution of SARS\u2010CoV\u20102 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium. PLoS Pathog 17: e1009292","journal-title":"PLoS Pathog"},{"key":"BFEMBJ2021107826_CR17","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.chom.2020.04.009","volume":"27","author":"EJ Giamarellos\u2010Bourboulis","year":"2020","unstructured":"Giamarellos\u2010Bourboulis EJ, Netea MG, Rovina N, Akinosoglou K, Antoniadou A, Antonakos N, Damoraki G, Gkavogianni T, Adami ME, Katsaounou P et\u00a0al (2020) Complex immune dysregulation in COVID\u201019 patients with severe respiratory failure. Cell Host Microbe 27: 992\u20131000.e1003","journal-title":"Cell Host Microbe"},{"key":"BFEMBJ2021107826_CR18","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.cell.2020.11.007","volume":"184","author":"TN Hoang","year":"2020","unstructured":"Hoang TN, Pino M, Boddapati AK, Viox EG, Starke CE, Upadhyay AA, Gumber S, Nekorchuk M, Busman\u2010Sahay K, Strongin Z et\u00a0al (2020) Baricitinib treatment resolves lower\u2010airway macrophage inflammation and neutrophil recruitment in SARS\u2010CoV\u20102\u2010infected rhesus macaques. Cell 184: 460\u2013475.e21","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR19","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine\u2010Weber H, Schroeder S, Kr\u00fcger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu N\u2010H, Nitsche A et\u00a0al (2020) SARS\u2010CoV\u20102 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor. Cell 181: 271\u2013280.e278","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR20","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.1132505","volume":"314","author":"V Hornung","year":"2006","unstructured":"Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann K\u2010k, Schlee M et\u00a0al (2006) 5'\u2010Triphosphate RNA is the ligand for RIG\u2010I. Science 314: 994\u2013997","journal-title":"Science"},{"key":"BFEMBJ2021107826_CR21","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature04734","volume":"441","author":"H Kato","year":"2006","unstructured":"Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ et\u00a0al (2006) Differential roles of MDA5 and RIG\u2010I helicases in the recognition of RNA viruses. Nature 441: 101\u2013105","journal-title":"Nature"},{"key":"BFEMBJ2021107826_CR22","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1038\/s41564-019-0592-5","volume":"4","author":"K Kim","year":"2019","unstructured":"Kim K, Dauphin A, Komurlu S, McCauley SM, Yurkovetskiy L, Carbone C, Diehl WE, Strambio\u2010De\u2010Castillia C, Campbell EM, Luban J (2019) Cyclophilin A protects HIV\u20101 from restriction by human TRIM5\u03b1. Nat Microbiol 4: 2044\u20132051","journal-title":"Nat Microbiol"},{"key":"BFEMBJ2021107826_CR23","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S1473-3099(20)30912-9","volume":"21","author":"M Koopmans","year":"2020","unstructured":"Koopmans M (2020) SARS\u2010CoV\u20102 and the human\u2010animal interface: outbreaks on mink farms. Lancet Infect Dis 21: 18\u201319","journal-title":"Lancet Infect Dis"},{"key":"BFEMBJ2021107826_CR24","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1038\/s41591-020-1038-6","volume":"26","author":"AG Laing","year":"2020","unstructured":"Laing AG, Lorenc A, del Molino del Barrio I, Das A, Fish M, Monin L, Mu\u00f1oz\u2010Ruiz M, McKenzie DR, Hayday TS, Francos\u2010Quijorna I et\u00a0al (2020) A dynamic COVID\u201019 immune signature includes associations with poor prognosis. Nat Med 26: 1623\u20131635","journal-title":"Nat Med"},{"key":"BFEMBJ2021107826_CR25","doi-asserted-by":"crossref","first-page":"6472","DOI":"10.1128\/JVI.00016-10","volume":"84","author":"J Li","year":"2010","unstructured":"Li J, Liu Y, Zhang X (2010) Murine coronavirus induces type I interferon in oligodendrocytes through recognition by RIG\u2010I and MDA5. J Virol 84: 6472\u20136482","journal-title":"J Virol"},{"key":"BFEMBJ2021107826_CR26","volume":"118","author":"Y Li","year":"2021","unstructured":"Li Y, Renner DM, Comar CE, Whelan JN, Reyes HM, Cardenas\u2010Diaz FL, Truitt R, Tan LH, Dong B, Alysandratos KD et\u00a0al (2021) SARS\u2010CoV\u20102 induces double\u2010stranded RNA\u2010mediated innate immune responses in respiratory epithelial\u2010derived cells and cardiomyocytes. PNAS 118: e2022643118","journal-title":"PNAS"},{"key":"BFEMBJ2021107826_CR27","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41591-020-0901-9","volume":"26","author":"M Liao","year":"2020","unstructured":"Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, Cheng L, Li J, Wang X, Wang F et\u00a0al (2020) Single\u2010cell landscape of bronchoalveolar immune cells in patients with COVID\u201019. Nat Med 26: 842\u2013844","journal-title":"Nat Med"},{"key":"BFEMBJ2021107826_CR28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/978-1-59745-394-3_24","volume":"510","author":"BD Lindenbach","year":"2009","unstructured":"Lindenbach BD (2009) Measuring HCV infectivity produced in cell culture and in\u00a0vivo. Methods Mol Biol 510: 329\u2013336","journal-title":"Methods Mol Biol"},{"key":"BFEMBJ2021107826_CR29","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41564-021-00884-1","volume":"6","author":"G Liu","year":"2021","unstructured":"Liu G, Lee JH, Parker ZM, Acharya D, Chiang JJ, van Gent M, Riedl W, Davis\u2010Gardner ME, Wies E, Chiang C et\u00a0al (2021) ISG15\u2010dependent activation of the sensor MDA5 is antagonized by the SARS\u2010CoV\u20102 papain\u2010like protease to evade host innate immunity. Nat Microbiol 6: 467\u2013478","journal-title":"Nat Microbiol"},{"key":"BFEMBJ2021107826_CR31","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","volume":"584","author":"C Lucas","year":"2020","unstructured":"Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B et\u00a0al (2020) Longitudinal analyses reveal immunological misfiring in severe COVID\u201019. Nature 584: 463\u2013469","journal-title":"Nature"},{"key":"BFEMBJ2021107826_CR32","doi-asserted-by":"crossref","first-page":"m3847","DOI":"10.1136\/bmj.m3847","volume":"371","author":"E Mahase","year":"2020","unstructured":"Mahase E (2020) Covid\u201019: Anti\u2010TNF drug adalimumab to be trialled for patients in the community. BMJ 371: m3847","journal-title":"BMJ"},{"key":"BFEMBJ2021107826_CR33","first-page":"e102","volume":"382","author":"MR Mehra","year":"2020","unstructured":"Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN (2020) Cardiovascular disease, drug therapy, and mortality in Covid\u201019. N Engl J Med 382: e102","journal-title":"N Engl J Med"},{"key":"BFEMBJ2021107826_CR34","doi-asserted-by":"crossref","first-page":"28344","DOI":"10.1073\/pnas.2016650117","volume":"117","author":"L Miorin","year":"2020","unstructured":"Miorin L, Kehrer T, Sanchez\u2010Aparicio MT, Zhang Ke, Cohen P, Patel RS, Cupic A, Makio T, Mei M, Moreno E et\u00a0al (2020) SARS\u2010CoV\u20102 Orf6 hijacks Nup98 to block STAT nuclear import and antagonize interferon signaling. Proc Natl Acad Sci USA 117: 28344\u201328354","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFEMBJ2021107826_CR35","doi-asserted-by":"publisher","DOI":"10.1101\/2020.07.21.212639","author":"CJ Neufeldt","year":"2020","unstructured":"Neufeldt CJ, Cerikan B, Cortese M, Frankish J, Lee J\u2010Y, Plociennikowska A, Heigwer F, Joecks S, Burkart SS, Zander DY et\u00a0al (2020) SARS\u2010CoV\u20102 infection induces a pro\u2010inflammatory cytokine response through cGAS\u2010STING and NF\u2010\u03baB. bioRxiv https:\/\/doi.org\/10.1101\/2020.07.21.212639 [PREPRINT]","journal-title":"bioRxiv"},{"key":"BFEMBJ2021107826_CR36","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(03)13413-7","volume":"361","author":"JM Nicholls","year":"2003","unstructured":"Nicholls JM, Poon LLM, Lee KC, Ng WF, Lai ST, Leung CY, Chu CM, Hui PK, Mak KL, Lim W et\u00a0al (2003) Lung pathology of fatal severe acute respiratory syndrome. Lancet 361: 1773\u20131778","journal-title":"Lancet"},{"key":"BFEMBJ2021107826_CR37","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1099\/jgv.0.001453","volume":"101","author":"NS Ogando","year":"2020","unstructured":"Ogando NS, Dalebout TJ, Zevenhoven\u2010Dobbe JC, Limpens RWAL, van der Meer Y, Caly L, Druce J, de Vries JJC, Kikkert M, B\u00e1rcena M et\u00a0al (2020) SARS\u2010coronavirus\u20102 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. J Gen Virol 101: 925\u2013940","journal-title":"J Gen Virol"},{"key":"BFEMBJ2021107826_CR38","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-020-03065-y","volume":"591","author":"E Pairo\u2010Castineira","year":"2020","unstructured":"Pairo\u2010Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, Walker S, Parkinson N, Fourman MH, Russell CD et\u00a0al (2020) Genetic mechanisms of critical illness in Covid\u201019. Nature 591: 92\u201398","journal-title":"Nature"},{"key":"BFEMBJ2021107826_CR39","volume":"10","author":"I Paranjpe","year":"2020","unstructured":"Paranjpe I, Russak AJ, De Freitas JK, Lala A, Miotto R, Vaid A, Johnson KW, Danieletto M, Golden E, Meyer D et\u00a0al (2020) Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID\u201019 in New York City. BMJ Open 10: e040736","journal-title":"BMJ Open"},{"key":"BFEMBJ2021107826_CR40","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.chom.2020.05.008","volume":"27","author":"A Park","year":"2020","unstructured":"Park A, Iwasaki A (2020) Type I and Type III interferons \u2010 induction, signaling, evasion, and application to combat COVID\u201019. Cell Host Microbe 27: 870\u2013878","journal-title":"Cell Host Microbe"},{"key":"BFEMBJ2021107826_CR41","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nature12769","volume":"503","author":"J Rasaiyaah","year":"2013","unstructured":"Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL, James LC, Noursadeghi M et\u00a0al (2013) HIV\u20101 evades innate immune recognition through specific cofactor recruitment. Nature 503: 402\u2013405","journal-title":"Nature"},{"key":"BFEMBJ2021107826_CR42","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02415-20","volume":"95","author":"A Rebendenne","year":"2021","unstructured":"Rebendenne A, Chaves Valad\u00e3o AL, Tauziet M, Maarifi G, Bonaventure B, McKellar J, Plan\u00e8s R, Nisole S, Arnaud\u2010Arnould M, Moncorg\u00e9 O et\u00a0al (2021) SARS\u2010CoV\u20102 triggers an MDA\u20105\u2010dependent interferon response which is unable to control replication in lung epithelial cells. J Virol 95: e02415\u201020","journal-title":"J Virol"},{"key":"BFEMBJ2021107826_CR43","first-page":"493","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed LJ, Muench H (1938) A simple method of estimating fifty percent end points. Am J Hyg 27: 493\u2013497","journal-title":"Am J Hyg"},{"key":"BFEMBJ2021107826_CR44","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2010.01.020","volume":"140","author":"J Rehwinkel","year":"2010","unstructured":"Rehwinkel J, Tan CP, Goubau D, Schulz O, Pichlmair A, Bier K, Robb N, Vreede F, Barclay W, Fodor E et\u00a0al (2010) RIG\u2010I detects viral genomic RNA during negative\u2010strand RNA virus infection. Cell 140: 397\u2013408","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR45","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20201707","volume":"218","author":"TS Rodrigues","year":"2021","unstructured":"Rodrigues TS, de S\u00e1 KSG, Ishimoto AY, Becerra A, Oliveira S, Almeida L, Gon\u00e7alves AV, Perucello DB, Andrade WA, Castro R et\u00a0al (2021) Inflammasomes are activated in response to SARS\u2010CoV\u20102 infection and are associated with COVID\u201019 severity in patients. J Exp Med 218: e20201707","journal-title":"J Exp Med"},{"key":"BFEMBJ2021107826_CR46","doi-asserted-by":"crossref","first-page":"9829","DOI":"10.1128\/JVI.01199-08","volume":"82","author":"JK Roth\u2010Cross","year":"2008","unstructured":"Roth\u2010Cross JK, Bender SJ, Weiss SR (2008) Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brain macrophages\/microglia. J Virol 82: 9829\u20139838","journal-title":"J Virol"},{"key":"BFEMBJ2021107826_CR47","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","volume":"9","author":"J Schindelin","year":"2012","unstructured":"Schindelin J, Arganda\u2010Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B et\u00a0al (2012) Fiji: an open\u2010source platform for biological\u2010image analysis. Nat Methods 9: 676\u2013682","journal-title":"Nat Methods"},{"key":"BFEMBJ2021107826_CR48","doi-asserted-by":"crossref","first-page":"107863","DOI":"10.1016\/j.celrep.2020.107863","volume":"32","author":"ML Stanifer","year":"2020","unstructured":"Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S, Mukenhirn M, Kraeusslich HG, Alexandrov T, Bartenschlager R, Boulant S (2020) Critical role of Type III interferon in controlling SARS\u2010CoV\u20102 infection in human intestinal epithelial cells. Cell Rep 32: 107863","journal-title":"Cell Rep"},{"key":"BFEMBJ2021107826_CR49","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2019103958","volume":"39","author":"RP Sumner","year":"2020","unstructured":"Sumner RP, Harrison L, Touizer E, Peacock TP, Spencer M, Zuliani\u2010Alvarez L, Towers GJ (2020) Disrupting HIV\u20101 capsid formation causes cGAS sensing of viral DNA. EMBO J 39: e103958","journal-title":"EMBO J"},{"key":"BFEMBJ2021107826_CR50","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.3389\/fimmu.2017.01246","volume":"8","author":"RP Sumner","year":"2017","unstructured":"Sumner RP, Thorne LG, Fink DL, Khan H, Milne RS, Towers GJ (2017) Are evolution and the intracellular innate immune system key determinants in HIV transmission? Front Immunol 8: 1246","journal-title":"Front Immunol"},{"key":"BFEMBJ2021107826_CR51","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.15.20208041","author":"PA Szabo","year":"2020","unstructured":"Szabo PA, Dogra P, Gray JI, Wells SB, Connors TJ, Weisberg SP, Krupska I, Matsumoto R, Poon MML, Idzikowski E, et\u00a0al (2020) Analysis of respiratory and systemic immune responses in COVID\u201019 reveals mechanisms of disease pathogenesis. medRxiv https:\/\/doi.org\/10.1101\/2020.10.15.20208041 [PREPRINT]","journal-title":"medRxiv"},{"key":"BFEMBJ2021107826_CR52","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.coviro.2012.04.004","volume":"2","author":"AL Totura","year":"2012","unstructured":"Totura AL, Baric RS (2012) SARS coronavirus pathogenesis: host innate immune responses and viral antagonism of interferon. Curr Opin Virol 2: 264\u2013275","journal-title":"Curr Opin Virol"},{"key":"BFEMBJ2021107826_CR53","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/S0140-6736(20)31100-4","volume":"395","author":"TA Treibel","year":"2020","unstructured":"Treibel TA, Manisty C, Burton M, McKnight \u00c1, Lambourne J, Augusto JB, Couto\u2010Parada X, Cutino\u2010Moguel T, Noursadeghi M, Moon JC (2020) COVID\u201019: PCR screening of asymptomatic health\u2010care workers at London hospital. Lancet 395: 1608\u20131610","journal-title":"Lancet"},{"key":"BFEMBJ2021107826_CR54","first-page":"325","volume":"315","author":"LF Wang","year":"2007","unstructured":"Wang LF, Eaton BT (2007) Bats, civets and the emergence of SARS. Curr Top Microbiol Immunol 315: 325\u2013344","journal-title":"Curr Top Microbiol Immunol"},{"key":"BFEMBJ2021107826_CR55","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41586-020-2521-4","volume":"584","author":"EJ Williamson","year":"2020","unstructured":"Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, Curtis HJ, Mehrkar A, Evans D, Inglesby P et\u00a0al (2020) Factors associated with COVID\u201019\u2010related death using OpenSAFELY. Nature 584: 430\u2013436","journal-title":"Nature"},{"key":"BFEMBJ2021107826_CR56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s15010-020-01509-1","volume":"49","author":"D Wolff","year":"2020","unstructured":"Wolff D, Nee S, Hickey NS, Marschollek M (2020) Risk factors for Covid\u201019 severity and fatality: a structured literature review. Infection 49: 15\u201328","journal-title":"Infection"},{"key":"BFEMBJ2021107826_CR57","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.cell.2012.11.048","volume":"152","author":"B Wu","year":"2013","unstructured":"Wu B, Peisley A, Richards C, Yao H, Zeng X, Lin C, Chu F, Walz T, Hur S (2013) Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell 152: 276\u2013289","journal-title":"Cell"},{"key":"BFEMBJ2021107826_CR58","doi-asserted-by":"crossref","first-page":"108234","DOI":"10.1016\/j.celrep.2020.108234","volume":"33","author":"H Xia","year":"2020","unstructured":"Xia H, Cao Z, Xie X, Zhang X, Chen JY, Wang H, Menachery VD, Rajsbaum R, Shi PY (2020) Evasion of Type I Interferon by SARS\u2010CoV\u20102. Cell Rep 33: 108234","journal-title":"Cell Rep"},{"key":"BFEMBJ2021107826_CR59","doi-asserted-by":"crossref","first-page":"108628","DOI":"10.1016\/j.celrep.2020.108628","volume":"34","author":"X Yin","year":"2021","unstructured":"Yin X, Riva L, Pu Y, Martin\u2010Sancho L, Kanamune J, Yamamoto Y, Sakai K, Gotoh S, Miorin L, De Jesus PD et\u00a0al (2021) MDA5 governs the innate immune response to SARS\u2010CoV\u20102 in lung epithelial cells. Cell Rep 34: 108628","journal-title":"Cell Rep"},{"key":"BFEMBJ2021107826_CR60","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1080\/22221751.2020.1780953","volume":"9","author":"C\u2010K Yuen","year":"2020","unstructured":"Yuen C\u2010K, Lam J\u2010Y, Wong W\u2010M, Mak L\u2010F, Wang X, Chu H, Cai J\u2010P, Jin D\u2010Y, To K\u2010W, Chan J\u2010W et\u00a0al (2020) SARS\u2010CoV\u20102 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg Microbes Infect 9: 1418\u20131428","journal-title":"Emerg Microbes Infect"},{"key":"BFEMBJ2021107826_CR61","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abc3582","volume":"5","author":"R Zang","year":"2020","unstructured":"Zang R, Gomez Castro MF, McCune BT, Zeng Q, Rothlauf PW, Sonnek NM, Liu Z, Brulois KF, Wang X, Greenberg HB et\u00a0al (2020) TMPRSS2 and TMPRSS4 promote SARS\u2010CoV\u20102 infection of human small intestinal enterocytes. Sci Immunol 5: eabc3582","journal-title":"Sci Immunol"},{"key":"BFEMBJ2021107826_CR62","volume":"370","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada\u2010Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, et\u00a0al (2020) Inborn errors of type I IFN immunity in patients with life\u2010threatening COVID\u201019. Science 370: eabd4570","journal-title":"Science"},{"key":"BFEMBJ2021107826_CR63","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1093\/infdis\/jiaa753","volume":"223","author":"J Zheng","year":"2021","unstructured":"Zheng J, Wang Y, Li K, Meyerholz DK, Allamargot C, Perlman S (2021) Severe acute respiratory syndrome coronavirus 2\u2010induced immune activation and death of monocyte\u2010derived human macrophages and dendritic cells. J Infect Dis 223: 785\u2013795","journal-title":"J Infect Dis"},{"key":"BFEMBJ2021107826_CR64","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","volume":"395","author":"F Zhou","year":"2020","unstructured":"Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X et\u00a0al (2020) Clinical course and risk factors for mortality of adult inpatients with COVID\u201019 in Wuhan, China: a retrospective cohort study. Lancet 395: 1054\u20131062","journal-title":"Lancet"}],"container-title":["The EMBO Journal"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021107826.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/embj.2021107826","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/embj.2021107826\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/embj.2021107826","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/embj.2021107826.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T20:28:57Z","timestamp":1779308937000},"score":9.75173,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/embj.2021107826"}},"issued":{"date-parts":[[2021,7,2]]},"references-count":63,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2021,8,2]]}},"alternative-id":["BFEMBJ2021107826"],"URL":"https:\/\/doi.org\/10.15252\/embj.2021107826","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.12.23.424169","asserted-by":"object"}]},"ISSN":["0261-4189","1460-2075"],"issn-type":[{"value":"0261-4189","type":"print"},{"value":"1460-2075","type":"electronic"}],"published":{"date-parts":[[2021,7,2]]},"assertion":[{"value":"26 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 May 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"EMBJ2021107826"},{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T22:27:49Z","timestamp":1772749669919,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T00:00:00Z","timestamp":1724025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 220818\/Z\/20\/Z"],"award-info":[{"award-number":["WT 220818\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"Abstract<\/jats:title>\n Background<\/jats:title>\n Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated.<\/jats:p>\n <\/jats:sec>\n Methods<\/jats:title>\n During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs).<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma<\/jats:italic> ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium<\/jats:italic> and S. mattheei<\/jats:italic> ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni<\/jats:italic> and possible S. haematobium<\/jats:italic>-S. mattheei<\/jats:italic> hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis<\/jats:italic> and other STIs.<\/jats:p>\n <\/jats:sec>\n Conclusion<\/jats:title>\n Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12879-024-09732-z","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T09:02:22Z","timestamp":1724058142000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Detection of male genital schistosomiasis (MGS) associated with human, zoonotic and hybrid schistosomes in Southern Malawi"],"prefix":"10.1186","volume":"24","author":[{"given":"Sekeleghe","family":"Kayuni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucas","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bright","family":"Mainga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingase","family":"Kumwenda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Lally","family":"Jnr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla","family":"Chammudzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donales","family":"Kapira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gladys","family":"Namacha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Chisale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tereza","family":"Nchembe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Kinley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ephraim","family":"Chibwana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bessie","family":"Ntaba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Chapweteka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleke","family":"Khumalo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Chibowa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Kumfunda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Juhasz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Archer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus M.","family":"O\u2019Ferrall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Rollason","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Chiphwanya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Makaula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. James","family":"LaCourse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janelisa","family":"Musaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Russell","family":"Stothard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,8,19]]},"reference":[{"issue":"1","key":"9732_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","volume":"4","author":"DP McManus","year":"2018","unstructured":"McManus DP, Dunne DW, Sacko M, Utzinger J, Vennervald BJ, Zhou XN, Schistosomiasis. Nat Rev Dis Primers. 2018;4(1):13.","journal-title":"Nat Rev Dis Primers"},{"key":"9732_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.apar.2021.12.003","volume":"115","author":"AL Bustinduy","year":"2022","unstructured":"Bustinduy AL, Randriansolo B, Sturt AS, Kayuni SA, Leutscher PD, Webster BL, et al. An update on female and male genital schistosomiasis and a call to integrate efforts to escalate diagnosis, treatment and awareness in endemic and non-endemic settings: the time is now. Adv Parasitol. 2022;115:1\u201344.","journal-title":"Adv Parasitol"},{"issue":"4593","key":"9732_CR3","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/S0140-6736(00)51898-4","volume":"178","author":"F Madden","year":"1911","unstructured":"Madden F, TWO, RARE MANIFESTATIONS OF BILHARZIOSIS. Lancet. 1911;178(4593):754\u20135.","journal-title":"Lancet"},{"key":"9732_CR4","doi-asserted-by":"crossref","unstructured":"Mabey D, Gill GG, Parry E, Weber MW, Whitty CJ, Louis J et al. Principles of medicine in Africa. 2014.","DOI":"10.1017\/CBO9780511751660"},{"key":"9732_CR5","unstructured":"Farrar J, Hotez PJ, Junghanss T, Kang G, Lalloo D, White NJ et al. Manson\u2019s Tropical Diseases E-Book: Elsevier health sciences; 2023."},{"issue":"9198","key":"9732_CR6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0140-6736(99)04856-4","volume":"355","author":"P Leutscher","year":"2000","unstructured":"Leutscher P, Ramarokoto C-E, Reimert C, Feldmeier H, Esterre P, Vennervald BJ. Community-based study of genital schistosomiasis in men from Madagascar. Lancet. 2000;355(9198):117\u20138.","journal-title":"Lancet"},{"key":"9732_CR7","doi-asserted-by":"publisher","first-page":"e00077","DOI":"10.1016\/j.parepi.2018.e00077","volume":"4","author":"S Kayuni","year":"2019","unstructured":"Kayuni S, Lampiao F, Makaula P, Juziwelo L, Lacourse EJ, Reinhard-Rupp J, et al. A systematic review with epidemiological update of male genital schistosomiasis (MGS): a call for integrated case management across the health system in sub-saharan Africa. Parasite Epidemiol Control. 2019;4:e00077.","journal-title":"Parasite Epidemiol Control"},{"issue":"9541","key":"9732_CR8","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","volume":"368","author":"B Gryseels","year":"2006","unstructured":"Gryseels B, Polman K, Clerinx J, Kestens L. Human schistosomiasis. Lancet. 2006;368(9541):1106\u201318.","journal-title":"Lancet"},{"issue":"8","key":"9732_CR9","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S1473-3099(16)00175-4","volume":"16","author":"J Boissier","year":"2016","unstructured":"Boissier J, Grech-Angelini S, Webster BL, Allienne J-F, Huyse T, Mas-Coma S, et al. Outbreak of urogenital schistosomiasis in Corsica (France): an epidemiological case study. Lancet Infect Dis. 2016;16(8):971\u20139.","journal-title":"Lancet Infect Dis"},{"issue":"7","key":"9732_CR10","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/S1473-3099(15)00084-5","volume":"15","author":"J Boissier","year":"2015","unstructured":"Boissier J, Mon\u00e9 H, Mitta G, Bargues MD, Molyneux D, Mas-Coma S. Schistosomiasis reaches Europe. Lancet Infect Dis. 2015;15(7):757\u20138.","journal-title":"Lancet Infect Dis"},{"issue":"7","key":"9732_CR11","doi-asserted-by":"publisher","first-page":"e0008201","DOI":"10.1371\/journal.pntd.0008201","volume":"14","author":"JR Stothard","year":"2020","unstructured":"Stothard JR, Kayuni SA, Al-Harbi MH, Musaya J, Webster BL. Future schistosome hybridizations: will all Schistosoma haematobium hybrids please stand-up! PLoS Negl Trop Dis. 2020;14(7):e0008201.","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"9732_CR12","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3201\/eid2506.190020","volume":"25","author":"BL Webster","year":"2019","unstructured":"Webster BL, Alharbi MH, Kayuni S, Makaula P, Halstead F, Christiansen R, et al. Schistosome interactions within the Schistosoma Haematobium Group, Malawi. Emerg Infect Dis. 2019;25(6):1245\u20137.","journal-title":"Emerg Infect Dis"},{"issue":"4","key":"9732_CR13","doi-asserted-by":"publisher","first-page":"e2110","DOI":"10.1371\/journal.pntd.0002110","volume":"7","author":"BL Webster","year":"2013","unstructured":"Webster BL, Diaw OT, Seye MM, Webster JP, Rollinson D. Introgressive hybridization of Schistosoma haematobium group species in Senegal: species barrier break down between ruminant and human schistosomes. PLoS Negl Trop Dis. 2013;7(4):e2110.","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"9732_CR14","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1097\/LGT.0000000000000756","volume":"27","author":"JD Shukla","year":"2023","unstructured":"Shukla JD, Kleppa E, Holmen S, Ndhlovu PD, Mtshali A, Sebitloane M, et al. The Association between Female Genital Schistosomiasis and other infections of the Lower Genital Tract in adolescent girls and Young women: a cross-sectional study in South Africa. J Lower Genit Tract Dis. 2023;27(3):291\u20136.","journal-title":"J Lower Genit Tract Dis"},{"key":"9732_CR15","doi-asserted-by":"crossref","unstructured":"Midzi N, Mduluza T, Mudenge B, Foldager L, Leutscher PD, editors. Decrease in seminal HIV-1 RNA load after praziquantel treatment of urogenital schistosomiasis coinfection in HIV-positive men\u2014an observational study. Open Forum Infectious Diseases; 2017: Oxford University Press US.","DOI":"10.1093\/ofid\/ofx199"},{"issue":"1","key":"9732_CR16","doi-asserted-by":"publisher","first-page":"14154","DOI":"10.1038\/s41598-023-40756-8","volume":"13","author":"SA Kayuni","year":"2023","unstructured":"Kayuni SA, Abdullahi A, Alharbi MH, Makaula P, Lampiao F, Juziwelo L, et al. Prospective pilot study on the relationship between seminal HIV-1 shedding and genital schistosomiasis in men receiving antiretroviral therapy along Lake Malawi. Sci Rep. 2023;13(1):14154.","journal-title":"Sci Rep"},{"key":"9732_CR17","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s00038-015-0714-7","volume":"60","author":"CW Stecher","year":"2015","unstructured":"Stecher CW, Kallestrup P, Kjetland EF, Vennervald B, Petersen E. Considering treatment of male genital schistosomiasis as a tool for future HIV prevention: a systematic review. Int J Public Health. 2015;60:839\u201348.","journal-title":"Int J Public Health"},{"issue":"10","key":"9732_CR18","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1111\/tmi.12165","volume":"18","author":"ML Ndeffo Mbah","year":"2013","unstructured":"Ndeffo Mbah ML, Poolman EM, Drain PK, Coffee MP, van der Werf MJ, Galvani AP. HIV and Schistosoma haematobium prevalences correlate in sub-saharan Africa. Tropical Med Int Health. 2013;18(10):1174\u20139.","journal-title":"Tropical Med Int Health"},{"key":"9732_CR19","doi-asserted-by":"crossref","unstructured":"Cheesbrough M. District laboratory practice in tropical countries, part 2. Cambridge University Press; 2005.","DOI":"10.1017\/CBO9780511581304"},{"key":"9732_CR20","doi-asserted-by":"crossref","unstructured":"Kayuni SA, Alharbi MH, Makaula P, Lampiao F, Juziwelo L, LaCourse EJ et al. Male genital Schistosomiasis along the shoreline of Lake Malawi: Baseline Prevalence and Associated Knowledge, attitudes and practices among local fishermen in Mangochi District, Malawi. Front Public Health. 2021;9.","DOI":"10.3389\/fpubh.2021.590695"},{"key":"9732_CR21","doi-asserted-by":"crossref","unstructured":"Kayuni SA, Alharbi MH, Shaw A, Fawcett J, Makaula P, Lampiao F, et al. Detection of male genital schistosomiasis (MGS) by real-time TaqMan\u00ae PCR analysis of semen from fishermen along the southern shoreline of Lake Malawi. Heliyon. 2023;9(7).","DOI":"10.1016\/j.heliyon.2023.e17338"},{"issue":"12","key":"9732_CR22","doi-asserted-by":"publisher","first-page":"e1396","DOI":"10.1371\/journal.pntd.0001396","volume":"5","author":"PS Mbabazi","year":"2011","unstructured":"Mbabazi PS, Andan O, Fitzgerald DW, Chitsulo L, Engels D, Downs JA. Examining the relationship between urogenital schistosomiasis and HIV infection. PLoS Negl Trop Dis. 2011;5(12):e1396.","journal-title":"PLoS Negl Trop Dis"}],"container-title":["BMC Infectious Diseases"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09732-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-024-09732-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-024-09732-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T09:02:44Z","timestamp":1724058164000},"score":9.751521,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-024-09732-z"}},"issued":{"date-parts":[[2024,8,19]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["9732"],"URL":"https:\/\/doi.org\/10.1186\/s12879-024-09732-z","ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"published":{"date-parts":[[2024,8,19]]},"assertion":[{"value":"21 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was conducted in accordance with the Declaration of Helsinki and approved by the College of Medicine Research Ethics Committee (COMREC) of Kamuzu University of Health Sciences (KUHeS) in Malawi, (approval number: P.08\/21\/3381) and LSTM Research Ethics Committee (LSTM REC) in the United Kingdom (approval number: 22\u2013028). Informed consent to participate in the study was obtained from all of the participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not Applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"839"},{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:53:43Z","timestamp":1790351623694,"version":"4.1.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T00:00:00Z","timestamp":1705276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223195\/Z\/21\/Z"],"award-info":[{"award-number":["223195\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223195\/Z\/21\/Z"],"award-info":[{"award-number":["223195\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Other"],"award-info":[{"award-number":["Other"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"abstract":"Abstract<\/jats:title>\n \n Brief summary<\/jats:title>\n In early symptomatic COVID-19 treatment, high dose oral favipiravir did not accelerate viral clearance.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Favipiravir, an anti-influenza drug, has in vitro antiviral activity against SARS-CoV-2. Clinical trial evidence to date is inconclusive. Favipiravir has been recommended for the treatment of COVID-19 in some countries.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In a multicentre open-label, randomised, controlled, adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomised to one of ten treatment arms including high dose oral favipiravir (3.6g on day 0 followed by 1.6g daily to complete 7 days treatment) or no study drug. The primary outcome was the rate of viral clearance (derived under a linear mixed-effects model from the daily log\n 10<\/jats:sub>\n viral densities in standardised duplicate oropharyngeal swab eluates taken daily over 8 days [18 swabs per patient]), assessed in a modified intention-to-treat population (mITT). The safety population included all patients who received at least one dose of the allocated intervention. This ongoing adaptive platform trial was registered at ClinicalTrials.gov (NCT05041907) on 13\/09\/2021.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In the final analysis, the mITT population contained data from 114 patients randomised to favipiravir and 126 patients randomised concurrently to no study drug. Under the linear mixed-effects model fitted to all oropharyngeal viral density estimates in the first 8 days from randomisation (4,318 swabs), there was no difference in the rate of viral clearance between patients given favipiravir and patients receiving no study drug; a -1% (95% credible interval: -14 to 14%) difference. High dose favipiravir was well-tolerated.<\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n Favipiravir does not accelerate viral clearance in early symptomatic COVID-19. The viral clearance rate estimated\u00a0from quantitative measurements of oropharyngeal eluate viral densities assesses the antiviral efficacy of drugs in vivo with comparatively few studied\u00a0patients.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12879-023-08835-3","type":"journal-article","created":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T06:02:18Z","timestamp":1705298538000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial"],"prefix":"10.1186","volume":"24","author":[{"given":"Viravarn","family":"Luvira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H. K.","family":"Schilling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Podjanee","family":"Jittamala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaya","family":"Siripoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thundon","family":"Ngamprasertchai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro J.","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maneerat","family":"Ekkapongpisit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cintia","family":"Cruz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Callery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runch","family":"Tuntipaiboontana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varaporn","family":"Kruabkontho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatsanun","family":"Ngernseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaruwan","family":"Tubprasert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Yazid","family":"Abdad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srisuda","family":"Keayarsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanassanan","family":"Madmanee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato S.","family":"Aguiar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciele M.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pongtorn","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borimas","family":"Hanboonkunupakarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittiyod","family":"Poovorawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallika","family":"Imwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter R. J.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasin","family":"Chotivanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesinee","family":"Chotivanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasithon","family":"Pukrittayakamee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjen M.","family":"Dondorp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P. J.","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M.","family":"Teixeira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Watcharapong","family":"Piyaphanee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weerapong","family":"Phumratanaprapin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the PLATCOV Collaborative Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,15]]},"reference":[{"key":"8835_CR1","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1128\/AAC.46.4.977-981.2002","volume":"46","author":"Y Furuta","year":"2002","unstructured":"Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, et al. In vitro and in vivo activities of anti-influenza virus compound T-705. Antimicrob Agents Chemother. 2002;46:977\u201381.","journal-title":"Antimicrob Agents Chemother"},{"key":"8835_CR2","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.antiviral.2013.09.015","volume":"100","author":"Y Furuta","year":"2013","unstructured":"Furuta Y, Gowen BB, Takahashi K, Shiraki K, Smee DF, Barnard DL. Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res. 2013;100:446\u201354.","journal-title":"Antiviral Res"},{"key":"8835_CR3","doi-asserted-by":"publisher","first-page":"e1001967","DOI":"10.1371\/journal.pmed.1001967","volume":"13","author":"D Sissoko","year":"2016","unstructured":"Sissoko D, Laouenan C, Folkesson E, M\u2019Lebing AB, Beavogui AH, Baize S, et al. Experimental treatment with favipiravir for ebola virus disease (the JIKI Trial): a historically controlled, single-arm proof-of-concept trial in Guinea. PLoS Med. 2016;13:e1001967.","journal-title":"PLoS Med"},{"key":"8835_CR4","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41422-020-0282-0","volume":"30","author":"M Wang","year":"2020","unstructured":"Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30:269\u201371.","journal-title":"Cell Res"},{"key":"8835_CR5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cell.2020.05.034","volume":"182","author":"Q Wang","year":"2020","unstructured":"Wang Q, Wu J, Wang H, Gao Y, Liu Q, Mu A, et al. Structural basis for RNA replication by the SARS-CoV-2 polymerase. Cell. 2020;182:417\u201328.","journal-title":"Cell"},{"key":"8835_CR6","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1093\/jac\/dkaa171","volume":"75","author":"EA Coomes","year":"2020","unstructured":"Coomes EA, Haghbayan H. Favipiravir, an antiviral for COVID-19? J Antimicrob Chemother. 2020;75:2013\u20134.","journal-title":"J Antimicrob Chemother"},{"key":"8835_CR7","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1128\/AAC.01739-09","volume":"54","author":"K Sleeman","year":"2010","unstructured":"Sleeman K, Mishin VP, Deyde VM, Furuta Y, Klimov AI, Gubareva LV. In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses. Antimicrob Agents Chemother. 2010;54:2517\u201324.","journal-title":"Antimicrob Agents Chemother"},{"key":"8835_CR8","doi-asserted-by":"publisher","first-page":"26955","DOI":"10.1073\/pnas.2014441117","volume":"117","author":"SJF Kaptein","year":"2020","unstructured":"Kaptein SJF, Jacobs S, Langendries L, Seldeslachts L, Ter Horst S, Liesenborghs L, et al. Favipiravir at high doses has potent antiviral activity in SARS-CoV-2-infected hamsters, whereas hydroxychloroquine lacks activity. Proc Natl Acad Sci USA. 2020;117:26955\u201365.","journal-title":"Proc Natl Acad Sci USA"},{"key":"8835_CR9","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1038\/s41467-021-21992-w","volume":"12","author":"JS Driouich","year":"2021","unstructured":"Driouich JS, Cochin M, Lingas G, Moureau G, Touret F, Petit PR, et al. Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model. Nat Commun. 2021;12:1735.","journal-title":"Nat Commun"},{"key":"8835_CR10","doi-asserted-by":"publisher","first-page":"4551","DOI":"10.2147\/IJGM.S349241","volume":"15","author":"PK Reddy","year":"2022","unstructured":"Reddy PK, Patil S, Khobragade A, Balki A, Raj A, Kalikar M, et al. Evaluation of the safety and efficacy of favipiravir in adult Indian patients with mild-to-moderate COVID-19 in a real-world setting. Int J Gen Med. 2022;15:4551\u201363.","journal-title":"Int J Gen Med"},{"key":"8835_CR11","doi-asserted-by":"publisher","first-page":"e31681","DOI":"10.1097\/MD.0000000000031681","volume":"101","author":"T Sitasuwan","year":"2022","unstructured":"Sitasuwan T, Phisalprapa P, Srivanichakorn W, Washirasaksiri C, Auesomwang C, Tinmanee R, et al. Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients. Medicine (Baltimore). 2022;101:e31681.","journal-title":"Medicine (Baltimore)"},{"issue":"10","key":"8835_CR12","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/j.eng.2020.03.007","volume":"6","author":"Q Cai","year":"2020","unstructured":"Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering. 2020;6(10):1192\u20138.","journal-title":"Engineering"},{"key":"8835_CR13","unstructured":"Doi Y, Ishihara T, Banno S, Ando M, Kondo M. Favipiravir Observational Study. Favipiravir for symptomatic COVID-19: a nationwide observational cohort study. J Infect Chemother. 2022:S1341\u2013321X(22)00291\u20134."},{"issue":"3","key":"8835_CR14","doi-asserted-by":"publisher","first-page":"397","DOI":"10.55519\/JAMC-03-10305","volume":"34","author":"B Abdulrahman","year":"2022","unstructured":"Abdulrahman B, Mady A, Odat MA, Tayar AA, Rana MA, Alharthy A, et al. Favipiravir efficacy and safety for the treatment of severe coronavirus disease 2019: a retrospective study. J Ayub Med Coll Abbottabad. 2022;34(3):397\u2013402.","journal-title":"J Ayub Med Coll Abbottabad"},{"key":"8835_CR15","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1080\/22221751.2022.2117092","volume":"11","author":"R Sirijatuphat","year":"2022","unstructured":"Sirijatuphat R, Manosuthi W, Niyomnaitham S, Owen A, Copeland KK, Charoenpong L, et al. Early treatment of Favipiravir in COVID-19 patients without pneumonia: a multicentre, open-labelled, randomized control study. Emerg Microbes Infect. 2022;11:2197\u2013206.","journal-title":"Emerg Microbes Infect"},{"key":"8835_CR16","doi-asserted-by":"publisher","first-page":"e01897","DOI":"10.1128\/AAC.01897-20","volume":"64","author":"Y Doi","year":"2020","unstructured":"Doi Y, Hibino M, Hase R, Yamamoto M, Kasamatsu Y, Hirose M, et al. Prospective, randomized, open-label trial of early versus late favipiravir therapy in hospitalized patients with COVID-19. Antimicrob Agents Chemother. 2020;64:e01897\u201320.","journal-title":"Antimicrob Agents Chemother."},{"key":"8835_CR17","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.ijid.2020.11.008","volume":"102","author":"F Khamis","year":"2021","unstructured":"Khamis F, Al Naabi H, Al Lawati A, Ambusaidi Z, Al Sharji M, Al Barwani U, et al. Randomized controlled open label trial on the use of favipiravir combined with inhaled interferon beta-1b in hospitalized patients with moderate to severe COVID-19 pneumonia. Int J Infect Dis. 2021;102:538\u201343.","journal-title":"Int J Infect Dis"},{"key":"8835_CR18","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1093\/cid\/ciaa1176","volume":"73","author":"AA Ivashchenko","year":"2021","unstructured":"Ivashchenko AA, Dmitriev KA, Vostokova NV, Azarova VN, Blinow AA, Egorova AN, et al. AVIFAVIR for treatment of patients with moderate coronavirus disease 2019 (COVID-19): interim results of a phase ii\/iii multicenter randomized clinical trial. Clin Infect Dis. 2021;73:531\u20134.","journal-title":"Clin Infect Dis"},{"key":"8835_CR19","doi-asserted-by":"crossref","unstructured":"Zhao H, Zhang C, Zhu Q, Chen X, Chen G, Sun W, et al. Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial. Int Immunopharmacol. 2021;97:107702.","DOI":"10.1016\/j.intimp.2021.107702"},{"key":"8835_CR20","doi-asserted-by":"publisher","first-page":"107522","DOI":"10.1016\/j.intimp.2021.107522","volume":"95","author":"M Solaymani-Dodaran","year":"2021","unstructured":"Solaymani-Dodaran M, Ghanei M, Bagheri M, Qazvini A, Vahedi E, Hassan Saadat S, et al. Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia. Int Immunopharmacol. 2021;95:107522.","journal-title":"Int Immunopharmacol"},{"key":"8835_CR21","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ijid.2020.11.142","volume":"103","author":"ZF Udwadia","year":"2021","unstructured":"Udwadia ZF, Singh P, Barkate H, Patil S, Rangwala S, Pendse A, et al. Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: a randomized, comparative, open-label, multicenter, phase 3 clinical trial. Int J Infect Dis. 2021;103:62\u201371.","journal-title":"Int J Infect Dis"},{"issue":"1","key":"8835_CR22","doi-asserted-by":"publisher","first-page":"4925","DOI":"10.1038\/s41598-022-08794-w","volume":"12","author":"M Al Qahtani","year":"2022","unstructured":"Al Qahtani M, Kumar N, Aljawder D, Abdulrahman A, Mohamed MW, Alnashaba F, et al. Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild\/moderate COVID-19 disease. Sci Rep. 2022;12(1):4925.","journal-title":"Sci Rep"},{"key":"8835_CR23","doi-asserted-by":"publisher","first-page":"3184","DOI":"10.1002\/jmv.27724","volume":"94","author":"M Hassaniazad","year":"2022","unstructured":"Hassaniazad M, Farshidi H, Gharibzadeh A, Bazram A, Khalili E, Noormandi A, Fathalipour M. Efficacy and safety of favipiravir plus interferon-beta versus lopinavir\/ritonavir plus interferon-beta in moderately ill patients with COVID-19: a randomized clinical trial. J Med Virol. 2022;94:3184\u201391.","journal-title":"J Med Virol"},{"key":"8835_CR24","doi-asserted-by":"publisher","first-page":"101703","DOI":"10.1016\/j.eclinm.2022.101703","volume":"54","author":"JH McMahon","year":"2022","unstructured":"McMahon JH, Lau JSY, Coldham A, Roney J, Hagenauer M, Price S, et al. Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial. EClinicalMedicine. 2022;54:101703.","journal-title":"EClinicalMedicine"},{"key":"8835_CR25","doi-asserted-by":"publisher","first-page":"e1004120","DOI":"10.1371\/journal.pmed.1004120","volume":"19","author":"DM Lowe","year":"2022","unstructured":"Lowe DM, Brown LK, Chowdhury K, Davey S, Yee P, Ikeji F, et al. Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): a randomised, double-blind, 2 \u00d7 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19. PLoS Med. 2022;19:e1004120.","journal-title":"PLoS Med"},{"key":"8835_CR26","first-page":"ciac712","volume":"6","author":"Y Golan","year":"2022","unstructured":"Golan Y, Campos JAS, Woolson R, Cilla D, Hanabergh R, Gonzales-Rojas Y, et al. Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial. Clin Infect Dis. 2022;6:ciac712.","journal-title":"Clin Infect Dis."},{"key":"8835_CR27","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.cmi.2021.12.026","volume":"28","author":"M Bosaeed","year":"2022","unstructured":"Bosaeed M, Alharbi A, Mahmoud E, Alrehily S, Bahlaq M, Gaifer Z, et al. Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicentre, placebo-controlled clinical trial. Clin Microbiol Infect. 2022;28:602\u20138.","journal-title":"Clin Microbiol Infect"},{"key":"8835_CR28","doi-asserted-by":"publisher","first-page":"e432","DOI":"10.1093\/cid\/ciab962","volume":"75","author":"CH Chuah","year":"2022","unstructured":"Chuah CH, Chow TS, Hor CP, Cheng JT, Ker HB, Lee HG, et al. Efficacy of early treatment with favipiravir on disease progression among high-risk patients with coronavirus disease 2019 (COVID-19): a randomized open-label clinical trial. Clin Infect Dis. 2022;75:e432\u20139.","journal-title":"Clin Infect Dis"},{"key":"8835_CR29","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1093\/cid\/ciac312","volume":"75","author":"M Holubar","year":"2022","unstructured":"Holubar M, Subramanian A, Purington N, Hedlin H, Bunning B, Walter KS, et al. Favipiravir for treatment of outpatients with asymptomatic or uncomplicated coronavirus disease 2019: a double-blind, randomized, placebo-controlled, phase 2 trial. Clin Infect Dis. 2022;75:1883\u201392.","journal-title":"Clin Infect Dis"},{"key":"8835_CR30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1002\/em.22471","volume":"63","author":"MD Waters","year":"2022","unstructured":"Waters MD, Warren S, Hughes C, Lewis P, Zhang F. Human genetic risk of treatment with antiviral nucleoside analog drugs that induce lethal mutagenesis: the special case of molnupiravir. Environ Mol Mutagen. 2022;63:37\u201363.","journal-title":"Environ Mol Mutagen"},{"key":"8835_CR31","doi-asserted-by":"publisher","unstructured":"Schilling WHK, Jittamala P, Watson JA, Boyd S, Luvira V, Siripoon T, et al. Antiviral efficacy of molnupiravir versus ritonavir-boosted nirmatrelvir in patients with early symptomatic COVID-19 (PLATCOV): an open-label, phase 2, randomised, controlled, adaptive trial. Lancet Infect Dis. 2023:S1473-3099(23)00493-0. https:\/\/doi.org\/10.1016\/S1473-3099(23)00493-0. Epub ahead of print. Erratum in: Lancet Infect Dis. 2023;23(12):e511.","DOI":"10.1016\/S1473-3099(23)00493-0"},{"key":"8835_CR32","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1002\/cpt.1844","volume":"108","author":"YX Du","year":"2020","unstructured":"Du YX, Chen XP. Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection. Clin Pharmacol Ther. 2020;108:242\u20137.","journal-title":"Clin Pharmacol Ther"},{"key":"8835_CR33","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1056\/NEJMoa2116044","volume":"386","author":"A Jayk Bernal","year":"2022","unstructured":"Jayk Bernal A, Gomes da Silva MM, Musungaie DB, Kovalchuk E, Gonzalez A, Delos Reyes V, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2022;386:509\u201320.","journal-title":"N Engl J Med"},{"key":"8835_CR34","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1056\/NEJMoa2118542","volume":"386","author":"J Hammond","year":"2022","unstructured":"Hammond J, Leister-Tebbe H, Gardner A, Abreu P, Bao W, Wisemandle W, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022;386:1397\u2013408.","journal-title":"N Engl J Med"},{"key":"8835_CR35","doi-asserted-by":"publisher","first-page":"e0005389","DOI":"10.1371\/journal.pntd.0005389","volume":"11","author":"TH Nguyen","year":"2017","unstructured":"Nguyen TH, Guedj J, Anglaret X, Laou\u00e9nan C, Madelain V, Taburet AM, et al. Favipiravir pharmacokinetics in Ebola-Infected patients of the JIKI trial reveals concentrations lower than targeted. PLoS Negl Trop Dis. 2017;11:e0005389.","journal-title":"PLoS Negl Trop Dis"},{"key":"8835_CR36","doi-asserted-by":"publisher","unstructured":"Schilling WHK, Jittamala P, Watson JA, Ekkapongpisit M, Siripoon T, Ngamprasertchai T, et al. Pharmacometrics of high-dose ivermectin in early COVID-19 from an open label, randomized, controlled adaptive platform trial (PLATCOV). Elife. 2023;12:e83201. https:\/\/doi.org\/10.7554\/eLife.83201.","DOI":"10.7554\/eLife.83201"},{"key":"8835_CR37","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1056\/NEJMoa2115869","volume":"386","author":"G Reis","year":"2022","unstructured":"Reis G, Silva EASM, Silva DCM, Thabane L, Milagres AC, Ferreira TS, et al. Effect of early treatment with ivermectin among patients with Covid-19. N Engl J Med. 2022;386:1721\u201331.","journal-title":"N Engl J Med"},{"issue":"10","key":"8835_CR38","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1093\/infdis\/jiad275","volume":"228","author":"P Jittamala","year":"2023","unstructured":"Jittamala P, Schilling WHK, Watson JA, Luvira V, Siripoon T, Ngamprasertchai T, et al. Clinical antiviral efficacy of remdesivir in COVID-19: an open label, randomized, controlled adaptive platform trial (PLATCOV). J Infect Dis. 2023;228(10):1318\u201325. https:\/\/doi.org\/10.1093\/infdis\/jiad275.","journal-title":"J Infect Dis"},{"key":"8835_CR39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1056\/NEJMoa2116846","volume":"386","author":"RL Gottlieb","year":"2022","unstructured":"Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2022;386:305\u201315.","journal-title":"N Engl J Med"},{"key":"8835_CR40","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1056\/NEJMoa2035002","volume":"384","author":"DM Weinreich","year":"2021","unstructured":"Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with COVID-19. N Engl J Med. 2021;384:238\u201351.","journal-title":"N Engl J Med"},{"key":"8835_CR41","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.1056\/NEJMoa2109682","volume":"385","author":"MP O'Brien","year":"2021","unstructured":"O\u2019Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, et al. Covid-19 phase 3 prevention trial team. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184\u201395.","journal-title":"N Engl J Med."},{"key":"8835_CR42","doi-asserted-by":"publisher","first-page":"eabl7430","DOI":"10.1126\/scitranslmed.abl7430","volume":"14","author":"WA Fischer 2nd","year":"2022","unstructured":"Fischer WA 2nd, Eron JJ Jr, Holman W, Cohen MS, Fang L, Szewczyk LJ, et al. A phase 2a clinical trial of molnupiravir in patients with COVID-19 shows accelerated SARS-CoV-2 RNA clearance and elimination of infectious virus. Sci Transl Med. 2022;14:eabl7430.","journal-title":"Sci Transl Med"},{"key":"8835_CR43","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/S0140-6736(22)02597-1","volume":"401","author":"CC Butler","year":"2023","unstructured":"Butler CC, Hobbs DR, Gbinigie OA, Rahman NM, Hayward G, Richards DB, et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet. 2023;401:281\u201393.","journal-title":"Lancet"},{"key":"8835_CR44","doi-asserted-by":"publisher","first-page":"e0019222","DOI":"10.1128\/aac.00192-22","volume":"66","author":"JA Watson","year":"2022","unstructured":"Watson JA, Kissler SM, Day NPJ, Grad YH, White NJ. Characterizing SARS-CoV-2 viral clearance kinetics to improve the design of antiviral pharmacometric studies. Antimicrob Agents Chemother. 2022;66:e0019222.","journal-title":"Antimicrob Agents Chemother"}],"container-title":["BMC Infectious Diseases"],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-023-08835-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12879-023-08835-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-023-08835-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,15]],"date-time":"2024-01-15T18:01:47Z","timestamp":1705341707000},"score":9.747235,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-023-08835-3"}},"issued":{"date-parts":[[2024,1,15]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["8835"],"URL":"https:\/\/doi.org\/10.1186\/s12879-023-08835-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2675703\/v1","asserted-by":"object"}]},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"published":{"date-parts":[[2024,1,15]]},"assertion":[{"value":"10 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients provided fully informed written consent. The trial was approved by local and national research ethics boards in Thailand (Faculty of Tropical Medicine Ethics Committee, Mahidol University, FTMEC Ref: TMEC 21\u2013058) and the Central Research Ethics Committee (CREC, Bangkok, Thailand, CREC Ref: CREC048\/64BP-MED34), in Brazil by the Research Ethics Committee of the Universidade Federal de Minas Gerais (COEP-UFMG, Minas Gerais, Brazil, COEP-UFMG) and National Research Ethics Commission- (CONEP, Brazil, COEP-UFMG and CONEP Ref: CAAE:51593421.1.0000.5149), and by the Oxford University Tropical Research Ethics Committee (OxTREC, Oxford, UK, OxTREC Ref: 24\u201321). All methods were performed in accordance with the relevant guidelines and regulations (e.g. Declaration of Helsinki).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"89"},{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:06:15Z","timestamp":1790445975703,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210572\/Z\/18\/Z"],"award-info":[{"award-number":["210572\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eye"],"published-print":{"date-parts":[[2023,4]]},"abstract":"Abstract<\/jats:title>\n \n Aims<\/jats:title>\n Age-related macular degeneration (AMD) is characterised by a progressive loss of central vision. Intermediate AMD is a risk factor for progression to advanced stages categorised as geographic atrophy (GA) and neovascular AMD. However, rates of progression to advanced stages vary between individuals. Recent advances in imaging and computing technologies have enabled deep phenotyping of intermediate AMD. The aim of this project is to utilise machine learning (ML) and advanced statistical modelling as an innovative approach to discover novel features and accurately quantify markers of pathological retinal ageing that can individualise progression to advanced AMD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n The PINNACLE study consists of both retrospective and prospective parts. In the retrospective part, more than 400,000 optical coherent tomography (OCT) images collected from four University Teaching Hospitals and the UK Biobank Population Study are being pooled, centrally stored and pre-processed. With this large dataset featuring eyes with AMD at various stages and healthy controls, we aim to identify imaging biomarkers for disease progression for intermediate AMD via supervised and unsupervised ML. The prospective study part will firstly characterise the progression of intermediate AMD in patients followed between one and three years; secondly, it will validate the utility of biomarkers identified in the retrospective cohort as predictors of progression towards late AMD. Patients aged 55\u201390 years old with intermediate AMD in at least one eye will be recruited across multiple sites in UK, Austria and Switzerland for visual function tests, multimodal retinal imaging and genotyping. Imaging will be repeated every four months to identify early focal signs of deterioration on spectral-domain optical coherence tomography (OCT) by human graders. A focal event triggers more frequent follow-up with visual function and imaging tests. The primary outcome is the sensitivity and specificity of the OCT imaging biomarkers. Secondary outcomes include sensitivity and specificity of novel multimodal imaging characteristics at predicting disease progression, ROC curves, time from development of imaging change to development of these endpoints, structure-function correlations, structure-genotype correlation and predictive risk models.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This is one of the first studies in intermediate AMD to combine both ML, retrospective and prospective AMD patient data with the goal of identifying biomarkers of progression and to report the natural history of progression of intermediate AMD with multimodal retinal imaging.<\/jats:p>\n <\/jats:sec>","DOI":"10.1038\/s41433-022-02097-0","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T06:04:07Z","timestamp":1653458647000},"page":"1275-1283","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Developing and validating a multivariable prediction model which predicts progression of intermediate to late age-related macular degeneration\u2014the PINNACLE trial protocol"],"prefix":"10.1038","volume":"37","author":[{"given":"Janice","family":"Sutton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Menten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Riedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-0894","authenticated-orcid":false,"given":"Hrvoje","family":"Bogunovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Leingang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1690-9043","authenticated-orcid":false,"given":"Philipp","family":"Anders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3372-7885","authenticated-orcid":false,"given":"Ahmed M.","family":"Hagag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-6279","authenticated-orcid":false,"given":"Sebastian","family":"Waldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1987-8900","authenticated-orcid":false,"given":"Angela J.","family":"Cree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislaine","family":"Traber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2110-1690","authenticated-orcid":false,"given":"Lars G.","family":"Fritsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Scholl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rueckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-7311","authenticated-orcid":false,"given":"Ursula","family":"Schmidt-Erfurth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobha","family":"Sivaprasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby","family":"Prevost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-4305","authenticated-orcid":false,"given":"Andrew","family":"Lotery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"2097_CR1","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong WL, Su X, Li X, Cheung CMG, Klein R, Cheng C-Y, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:e106\u2013e116.","journal-title":"Lancet Glob Health"},{"key":"2097_CR2","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.ophtha.2015.09.036","volume":"123","author":"S Schmitz-Valckenberg","year":"2016","unstructured":"Schmitz-Valckenberg S, Sahel JA, Danis R, Fleckenstein M, Jaffe GJ, Wolf S, et al. Natural history of geographic atrophy progression secondary to age-related macular degeneration (Geographic Atrophy Progression Study). Ophthalmology. 2016;123:361\u20138.","journal-title":"Ophthalmology"},{"key":"2097_CR3","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.ophtha.2006.09.016","volume":"114","author":"JS Sunness","year":"2007","unstructured":"Sunness JS, Margalit E, Srikumaran D, Applegate CA, Tian Y, Perry D, et al. The long-term natural history of geographic atrophy from age-related macular degeneration: enlargement of atrophy and implications for interventional clinical trials. Ophthalmology. 2007;114:271\u20137.","journal-title":"Ophthalmology"},{"key":"2097_CR4","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1016\/j.ophtha.2011.05.008","volume":"118","author":"Z Yehoshua","year":"2011","unstructured":"Yehoshua Z, Wang F, Rosenfeld PJ, Penha FM, Feuer WJ, Gregori G. Natural history of drusen morphology in age-related macular degeneration using spectral domain optical coherence tomography. Ophthalmology. 2011;118:2434\u201341.","journal-title":"Ophthalmology"},{"key":"2097_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.survophthal.2016.02.005","volume":"61","author":"S Sivaprasad","year":"2016","unstructured":"Sivaprasad S, Bird A, Nitiahpapand R, Nicholson L, Hykin P, Chatziralli I. Perspectives on reticular pseudodrusen in age-related macular degeneration. Surv Ophthalmol. 2016;61:521\u201337.","journal-title":"Surv Ophthalmol"},{"key":"2097_CR6","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1016\/j.ophtha.2008.04.041","volume":"115","author":"AA Khanifar","year":"2008","unstructured":"Khanifar AA, Koreishi AF, Izatt JA, Toth CA. Drusen ultrastructure imaging with spectral domain optical coherence tomography in age-related macular degeneration. Ophthalmology. 2008;115:1883\u201390.","journal-title":"Ophthalmology"},{"key":"2097_CR7","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1167\/iovs.18-24106","volume":"59","author":"U Schmidt-Erfurth","year":"2018","unstructured":"Schmidt-Erfurth U, Waldstein SM, Klimscha S, Sadeghipour A, Hu X, Gerendas BS, et al. Prediction of Individual Disease Conversion in Early AMD Using Artificial Intelligence. Investig Ophthalmol Vis Sci. 2018;59:3199\u2013208.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"2097_CR8","doi-asserted-by":"publisher","first-page":"1798","DOI":"10.1109\/TPAMI.2013.50","volume":"35","author":"Y Bengio","year":"2013","unstructured":"Bengio Y, Courville A, Vincent P. Representation learning: a review and new perspectives. IEEE Trans Pattern Anal Mach Intell. 2013;35:1798\u2013828.","journal-title":"IEEE Trans Pattern Anal Mach Intell"},{"key":"2097_CR9","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature14539","volume":"521","author":"Y LeCun","year":"2015","unstructured":"LeCun Y, Bengio Y, Hinton G. Deep learning. Nature. 2015;521:436\u201344.","journal-title":"Nature"},{"key":"2097_CR10","doi-asserted-by":"publisher","first-page":"20120072","DOI":"10.1098\/rsfs.2012.0072","volume":"3","author":"K Antila","year":"2013","unstructured":"Antila K, Lotjonen J, Thurfjell L, Laine J, Massimini M, Rueckert D, et al. The PredictAD project: development of novel biomarkers and analysis software for early diagnosis of the Alzheimer\u2019s disease. Interface Focus. 2013;3:20120072.","journal-title":"Interface Focus"},{"key":"2097_CR11","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1159\/000332600","volume":"10","author":"H Soininen","year":"2012","unstructured":"Soininen H, Mattila J, Koikkalainen J, van Gils M, Hviid Simonsen A, Waldemar G, et al. Software tool for improved prediction of Alzheimer\u2019s disease. Neuro-degenerative Dis. 2012;10:149\u201352.","journal-title":"Neuro-degenerative Dis"},{"key":"2097_CR12","first-page":"437","volume":"24","author":"T Schlegl","year":"2015","unstructured":"Schlegl T, Waldstein SM, Vogl WD, Schmidt-Erfurth U, Langs G. Predicting semantic descriptions from medical images with convolutional neural networks. Inf Process Med Imaging. 2015;24:437\u201348.","journal-title":"Inf Process Med Imaging"},{"key":"2097_CR13","first-page":"56","volume":"58","author":"P Seeb\u00f6ck","year":"2017","unstructured":"Seeb\u00f6ck P, Waldstein SM, Donner R, Gerendas BS, Sadeghipour A, Osborne A, et al. Defining disease endophenotypes in neovascular AMD by unsupervised machine learning of large-scale OCT data. Investig Ophthalmol Vis Sci. 2017;58:56\u201356.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"2097_CR14","unstructured":"Schlegl T, Seebock P, Waldstein SM, Schmidt-Erfurth U, Langs G. Unsupervised anomaly detection with generative adversarial networks to guide marker discovery. https:\/\/arxiv.org\/abs\/1703.05921."},{"key":"2097_CR15","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1167\/tvst.9.2.25","volume":"9","author":"A Bhuiyan","year":"2020","unstructured":"Bhuiyan A, Wong TY, Ting DSW, Govindaiah A, Souied EH, Smith RT. Artificial intelligence to stratify severity of age-related macular degeneration (AMD) and predict risk of progression to late AMD. Transl Vis Sci Technol. 2020;9:25.","journal-title":"Transl Vis Sci Technol"},{"key":"2097_CR16","doi-asserted-by":"crossref","unstructured":"Schmidt-Erfurth U, Waldstein SM, Klimscha S, Sadeghipour A, Hu X, Gerendas BS, et al. Prediction of Individual Disease Conversion in Early AMD Using Artificial Intelligence. Investig Ophthalmol Vis Sci. 2018;59:3199\u2013208.","DOI":"10.1167\/iovs.18-24106"},{"key":"2097_CR17","doi-asserted-by":"publisher","first-page":"3240","DOI":"10.1167\/iovs.16-21053","volume":"58","author":"H Bogunovic","year":"2017","unstructured":"Bogunovic H, Waldstein SM, Schlegl T, Langs G, Sadeghipour A, Liu X, et al. Prediction of Anti-VEGF treatment requirements in neovascular AMD using a machine learning approach. Invest Ophthalmol Vis Sci. 2017;58:3240\u20138.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2097_CR18","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.1016\/j.neuroimage.2010.10.019","volume":"54","author":"M Kuklisova-Murgasova","year":"2011","unstructured":"Kuklisova-Murgasova M, Aljabar P, Srinivasan L, Counsell SJ, Doria V, Serag A, et al. A dynamic 4D probabilistic atlas of the developing brain. Neuroimage. 2011;54:2750\u201363.","journal-title":"Neuroimage"},{"key":"2097_CR19","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s42256-020-0154-9","volume":"2","author":"Q Yan","year":"2020","unstructured":"Yan Q, Weeks DE, Xin H, Swaroop A, Chew EY, Huang H, et al. Deep-learning-based prediction of late age-related macular degeneration progression. Nat Mach Intell. 2020;2:141\u201350.","journal-title":"Nat Mach Intell"},{"key":"2097_CR20","first-page":"3398","volume":"58","author":"U Schmidt-Erfurth","year":"2017","unstructured":"Schmidt-Erfurth U, Bogunovic H, Klimscha S, Hu X, Schlegl T, Sadeghipour A, et al. Machine learning to predict the individual progression of AMD from imaging biomarkers. Investig Ophthalmol Vis Sci. 2017;58:3398\u20133398.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"2097_CR21","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.oret.2017.03.015","volume":"2","author":"U Schmidt-Erfurth","year":"2018","unstructured":"Schmidt-Erfurth U, Bogunovic H, Sadeghipour A, Schlegl T, Langs G, Gerendas BS, et al. Machine learning to analyze the prognostic value of current imaging biomarkers in neovascular age-related macular degeneration. Ophthalmol Retin. 2018;2:24\u201330.","journal-title":"Ophthalmol Retin"},{"key":"2097_CR22","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.ophtha.2017.09.028","volume":"125","author":"SR Sadda","year":"2018","unstructured":"Sadda SR, Guymer R, Holz FG, Schmitz-Valckenberg S, Curcio CA, Bird AC, et al. Consensus definition for atrophy associated with age-related macular degeneration on OCT: classification of atrophy report 3. Ophthalmology. 2018;125:537\u201348.","journal-title":"Ophthalmology"},{"key":"2097_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-69814-1","volume":"10","author":"SM Waldstein","year":"2020","unstructured":"Waldstein SM, Seeb\u00f6ck P, Donner R, Sadeghipour A, Bogunovi\u0107 H, Osborne A, et al. Unbiased identification of novel subclinical imaging biomarkers using unsupervised deep learning. Sci Rep. 2020;10:12954.","journal-title":"Sci Rep"},{"key":"2097_CR24","doi-asserted-by":"crossref","unstructured":"Azizi S. Big self-supervised models advance medical image classification. Proceedings of the IEEE\/CVF International Conference on Computer Vision. Computer Vision Foundation New York, USA, 2021. p. 347\u201388.","DOI":"10.1109\/ICCV48922.2021.00346"},{"key":"2097_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-85110-y","volume":"11","author":"W-D Vogl","year":"2021","unstructured":"Vogl W-D, Bogunovi\u0107 H, Waldstein SM, Riedl S, Schmidt-Erfurth U. Spatio-temporal alterations in retinal and choroidal layers in the progression of age-related macular degeneration (AMD) in optical coherence tomography. Sci Rep. 2021;11:5743.","journal-title":"Sci Rep"},{"key":"2097_CR26","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1001\/jamaophthalmol.2020.1376","volume":"138","author":"SM Waldstein","year":"2020","unstructured":"Waldstein SM, Vogl WD, Bogunovic H, Sadeghipour A, Riedl S, Schmidt-Erfurth U. Characterization of drusen and hyperreflective foci as biomarkers for disease progression in age-related macular degeneration using artificial intelligence in optical coherence tomography. JAMA Ophthalmol. 2020;138:740\u20137.","journal-title":"JAMA Ophthalmol"},{"key":"2097_CR27","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","volume":"120","author":"FL Ferris 3rd","year":"2013","unstructured":"Ferris FL 3rd, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844\u201351.","journal-title":"Ophthalmology"},{"key":"2097_CR28","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1016\/j.ophtha.2014.06.034","volume":"121","author":"Z Wu","year":"2014","unstructured":"Wu Z, Luu CD, Ayton LN, Goh JK, Lucci LM, Hubbard WC, et al. Optical coherence tomography-defined changes preceding the development of drusen-associated atrophy in age-related macular degeneration. Ophthalmology. 2014;121:2415\u201322.","journal-title":"Ophthalmology"},{"key":"2097_CR29","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1126\/science.1153717","volume":"319","author":"JZ Li","year":"2008","unstructured":"Li JZ, Absher DM, Tang H, Southwick AM, Casto AM, Ramachandran S, et al. Worldwide human relationships inferred from genome-wide patterns of variation. Science. 2008;319:1100\u20134.","journal-title":"Science"},{"key":"2097_CR30","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen WM. Robust relationship inference in genome-wide association studies. Bioinformatics. 2010;26:2867\u201373.","journal-title":"Bioinformatics"},{"key":"2097_CR31","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-021-03205-y","volume":"590","author":"D Taliun","year":"2021","unstructured":"Taliun D, Harris DN, Kessler MD, Carlson J, Szpiech ZA, Torres R, et al. Sequencing of 53,831 diverse genomes from the NHLBI TOPMed program. Nature. 2021;590:290\u20139.","journal-title":"Nature"},{"key":"2097_CR32","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/ng.3643","volume":"48","author":"S McCarthy","year":"2016","unstructured":"McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016;48:1279\u201383.","journal-title":"Nat Genet"},{"key":"2097_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2288-13-33","volume":"13","author":"P Royston","year":"2013","unstructured":"Royston P, Altman DG. External validation of a Cox prognostic model: principles and methods. BMC Med Res Methodol. 2013;13:33.","journal-title":"BMC Med Res Methodol"},{"key":"2097_CR34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/sj.bjc.6601907","volume":"91","author":"A Burton","year":"2004","unstructured":"Burton A, Altman DG. Missing covariate data within cancer prognostic studies: a review of current reporting and proposed guidelines. Br J Cancer. 2004;91:4\u20138.","journal-title":"Br J Cancer"},{"key":"2097_CR35","doi-asserted-by":"publisher","first-page":"Bio141","DOI":"10.1167\/iovs.17-21789","volume":"58","author":"H Bogunovic","year":"2017","unstructured":"Bogunovic H, Montuoro A, Baratsits M, Karantonis MG, Waldstein SM, Schlanitz F, et al. Machine learning of the progression of intermediate age-related macular degeneration based on OCT imaging. Investivg Ophthalmol Vis Sci. 2017;58:Bio141\u2013bio150.","journal-title":"Investivg Ophthalmol Vis Sci"},{"key":"2097_CR36","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1001\/archopht.123.11.1570","volume":"123","author":"FL Ferris","year":"2005","unstructured":"Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570\u20134.","journal-title":"Arch Ophthalmol"},{"key":"2097_CR37","doi-asserted-by":"publisher","first-page":"b604","DOI":"10.1136\/bmj.b604","volume":"338","author":"P Royston","year":"2009","unstructured":"Royston P, Moons KGM, Altman DG, Vergouwe Y. Prognosis and prognostic research: developing a prognostic model. BMJ. 2009;338:b604.","journal-title":"BMJ"},{"key":"2097_CR38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/1467-985X.00122","volume":"162","author":"W Sauerbrei","year":"1999","unstructured":"Sauerbrei W, Royston P. Building multivariable prognostic and diagnostic models: transformation of the predictors by using fractional polynomials. J R Stat Soc: Ser A (Stat Soc). 1999;162:71\u201394.","journal-title":"J R Stat Soc: Ser A (Stat Soc)"},{"key":"2097_CR39","doi-asserted-by":"publisher","first-page":"b605","DOI":"10.1136\/bmj.b605","volume":"338","author":"DG Altman","year":"2009","unstructured":"Altman DG, Vergouwe Y, Royston P, Moons KGM. Prognosis and prognostic research: validating a prognostic model. BMJ. 2009;338:b605.","journal-title":"BMJ"}],"updated-by":[{"DOI":"10.1038\/s41433-022-02131-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000}}],"container-title":["Eye"],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41433-022-02097-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41433-022-02097-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41433-022-02097-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T12:09:06Z","timestamp":1681387746000},"score":9.743244,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41433-022-02097-0"}},"issued":{"date-parts":[[2022,5,25]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["2097"],"URL":"https:\/\/doi.org\/10.1038\/s41433-022-02097-0","ISSN":["0950-222X","1476-5454"],"issn-type":[{"value":"0950-222X","type":"print"},{"value":"1476-5454","type":"electronic"}],"published":{"date-parts":[[2022,5,25]]},"assertion":[{"value":"4 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 May 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2022","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41433-022-02131-1","URL":"https:\/\/doi.org\/10.1038\/s41433-022-02131-1","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AL is a consultant for Gyroscope Therapeutics Ltd, Eyebio, Complement Therapeutics, Novartis, Allergan, Apellis and Tarsus Pharmaceuticals. DR is a co-founder and shareholder of IXICO Plc. SS has attended advisory board meetings and received research grants and is a consultant for Genentech Inc.\/F. Hoffmann-La Roche Ltd, Allergen, Bayer and Novartis, Oxurion, Ophtea, Optos, Oculis, Apellis, Eyebio, Gyroscope. SW is a consultant to Bayer, Roche, Santen, B\u00f6hringer Ingelheim and Novartis. USE receives grant support from Genentech, Kodiak, Novartis, RetInSight and Roche and is a consultant for Apellis. HB has received research grants from Heidelberg Engineering and Apellis, and speaker fees from Bayer, Roche, and Apellis. HS is a member of the Scientific Advisory Board of: Astellas Pharma Global Development, Inc.\/Astellas Institute for Regenerative Medicine; Boehringer Ingelheim Pharma GmbH & Co; Gyroscope Therapeutics Ltd.; Janssen Research & Development, LLC (Johnson & Johnson); Novartis Pharma AG (CORE); Okuvision GmbH; and Third Rock Ventures, LLC. He is a consultant of Gerson Lehrman Group; Guidepoint Global, LLC; and Tenpoint Therapeutics Limited. HS is a member of the Data Monitoring and Safety Board\/Committee of Belite Bio (CT2019-CTN-04690-1), ReNeuron Group Plc\/Ora Inc. (NCT02464436), F. Hoffmann-La Roche Ltd (VELODROME trial, NCT04657289; DIAGRID trial, NCT05126966) and member of the Steering Committee of Novo Nordisk (FOCUS trial; NCT03811561). He is a co-director of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) which receives funding from the University of Basel, the University Hospital Basel, Novartis, and the government of Basel-Stadt.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}],"items-per-page":20,"query":{"start-index":0,"search-terms":null}}}