{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:43:53Z","timestamp":1764873833145,"version":"3.40.5"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T00:00:00Z","timestamp":1612396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>A review of Uganda\u2019s HIV Early Infant Diagnosis (EID) program in 2010 revealed poor retention outcomes for HIV-exposed infants (HEI) after testing. The review informed development of the \u2018EID Systems Strengthening\u2019 model: a set of integrated initiatives at health facilities to improve testing, retention, and clinical care of HIV-exposed and infected infants. The program model was piloted at several facilities and later scaled countrywide. This mixed-methods study evaluates the program\u2019s impact and assesses its implementation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a retrospective cohort study at 12 health facilities in Uganda, comprising all HEI tested by DNA PCR from June 2011 to May 2014 (n = 707). Cohort data were collected manually at the health facilities and analyzed. To assess impact, retention outcomes were statistically compared to the baseline study\u2019s cohort outcomes. We conducted a cross-sectional qualitative assessment of program implementation through 1) structured clinic observation and 2) key informant interviews with health workers, district officials, NGO technical managers, and EID trainers (n = 51).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The evaluation cohort comprised 707 HEI (67 HIV+). The baseline study cohort contained 1268 HEI (244 HIV+). Among infants testing HIV+, retention in care at an ART clinic increased from 23% (57\/244) to 66% (44\/67) (p &lt; .0001). Initiation of HIV+ infants on ART increased from 36% (27\/75) to 92% (46\/50) (p &lt; .0001). HEI receiving 1st PCR results increased from 57% (718\/1268) to 73% (518\/707) (p &lt; .0001). Among breastfeeding HEI with negative 1st PCR, 55% (192\/352) received a confirmatory PCR test, a substantial increase from baseline period. Testing coverage improved significantly: HIV+ pregnant women who brought their infants for testing after birth increased from 18% (67\/367) to 52% (175\/334) (p &lt; .0001). HEI were tested younger: mean age at DBS test decreased from 6.96 to 4.21 months (p &lt; .0001). Clinical care for HEI was provided more consistently. Implementation fidelity was strong for most program components. The strongest contributory interventions were establishment of \u2018EID Care Points\u2019, integration of clinical care, longitudinal patient tracking, and regular health worker mentorship. Gaps included limited follow up of lost infants, inconsistent buy-in\/ownership of health facility management, and challenges sustaining health worker motivation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\" sec-type=\"conclusions\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>Uganda\u2019s \u2018EID Systems Strengthening\u2019 model has produced significant gains in testing and retention of HEI and HIV+ infants, yet the country still faces major challenges. The 3 core concepts of Uganda\u2019s model are applicable to any country: establish a central service point for HEI, equip it to provide high-quality care and tracking, and develop systems to link HEI to the service point. Uganda\u2019s experience has shown the importance of intensively targeting systemic bottlenecks to HEI retention at facility level, a necessary complement to deploying rapidly scalable technologies and other higher-level initiatives.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0246546","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T22:31:32Z","timestamp":1612564292000},"page":"e0246546","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Uganda\u2019s \u201cEID Systems Strengthening\u201d model produces significant gains in testing, linkage, and retention of HIV-exposed and infected infants: An impact evaluation"],"prefix":"10.1371","volume":"16","author":[{"given":"Charles","family":"Kiyaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-7321","authenticated-orcid":true,"given":"Vijay","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"McConnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Elyanu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda Nabitaka","family":"Kisaakye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeodata","family":"Kekitiinwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Grosz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,2,4]]},"reference":[{"key":"pone.0246546.ref001","unstructured":"UNAIDS. Fact Sheet: Latest global and regional statistics of the status of the AIDS epidemic. 2020 [Cited 25 July 2020]. Available from: https:\/\/www.unaids.org\/en\/resources\/documents\/2020\/UNAIDS_FactSheet."},{"key":"pone.0246546.ref002","unstructured":"Uganda Ministry of Health. HIV Program Data. 2019. Kampala, Uganda."},{"issue":"1","key":"pone.0246546.ref003","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/QAD.0b013e32831c54bd","article-title":"Emergence of a peak in early infant mortality due to HIV\/AIDS in South Africa","volume":"23","author":"DE Bourne","year":"2009","journal-title":"AIDS"},{"issue":"21","key":"pone.0246546.ref004","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1056\/NEJMoa0800971","article-title":"Early antiretroviral therapy and mortality among HIV-infected infants","volume":"359","author":"A Violari","year":"2008","journal-title":"New England Journal of Medicine"},{"issue":"9441","key":"pone.0246546.ref005","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/S0140-6736(04)17140-7","article-title":"Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis","volume":"364","author":"ML Newell","year":"2004","journal-title":"Lancet"},{"issue":"9396","key":"pone.0246546.ref006","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/S0140-6736(03)14793-9","article-title":"Short-term risk of disease progression in HIV-1-infected children receiving no antiretroviral therapy or zidovudine monotherapy: a meta-analysis","volume":"362","author":"D Dunn","year":"2003","journal-title":"Lancet"},{"issue":"6","key":"pone.0246546.ref007","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1097\/00002030-200304110-00012","article-title":"Maternal health factors and early pediatric antiretroviral therapy influence the rate of perinatal HIV-1 disease progression in children","volume":"17","author":"EJ Abrams","year":"2003","journal-title":"AIDS"},{"issue":"1","key":"pone.0246546.ref008","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/INF.0b013e3181469050","article-title":"Early diagnosis of human immunodeficiency virus in infants using polymerase chain reaction on dried blood spots in Botswana\u2019s national program for prevention of mother-to-child transmission","volume":"27","author":"T Creek","year":"2008","journal-title":"Pediatr Infect Dis J"},{"volume-title":"Antiretroviral therapy for HIV infection in infants and children: recommendations for a public health approach. 2010 revision","year":"2010","author":"World Health Organization","key":"pone.0246546.ref009"},{"issue":"1","key":"pone.0246546.ref010","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1186\/s12879-018-3275-6","article-title":"Retention outcomes and drivers of loss among HIV-exposed and infected infants in Uganda: a retrospective cohort study","volume":"18","author":"C Kiyaga","year":"2018","journal-title":"BMC Infectious Diseases"},{"issue":"2","key":"pone.0246546.ref011","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5588\/pha.16.0119","article-title":"Early infant diagnosis and outcomes in HIV-exposed infants at a central and a district hospital, Northern Malawi","volume":"7","author":"N Phiri","year":"2017","journal-title":"Public Health Action"},{"issue":"1","key":"pone.0246546.ref012","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12913-017-1998-5","article-title":"Rate and associated factors of non-retention of mother-baby pairs in HIV care in the elimination of mother-to-child transmission programme, Gulu-Uganda: a cohort study.","volume":"17","author":"G Obai","year":"2017","journal-title":"BMC Health Services Research"},{"issue":"2","key":"pone.0246546.ref013","doi-asserted-by":"crossref","first-page":"e55308","DOI":"10.1371\/journal.pone.0055308","article-title":"Linkage of HIV-infected infants from diagnosis to antiretroviral therapy services across the Western Cape, South Africa","volume":"8","author":"NY Hsiao","year":"2013","journal-title":"PloS One"},{"issue":"12","key":"pone.0246546.ref014","doi-asserted-by":"crossref","first-page":"e115171","DOI":"10.1371\/journal.pone.0115171","article-title":"Intra-facility linkage of HIV-positive mothers and HIV-exposed babies into HIV chronic care: rural and urban experience in a resource limited setting","volume":"9","author":"C Mugasha","year":"2014","journal-title":"PLoS One"},{"issue":"1","key":"pone.0246546.ref015","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1186\/1471-2458-11-553","article-title":"Implementing services for Early Infant Diagnosis (EID) of HIV: a comparative descriptive analysis of national programs in four countries","volume":"11","author":"A Chatterjee","year":"2011","journal-title":"BMC Public Health"},{"issue":"46","key":"pone.0246546.ref016","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.15585\/mmwr.mm6546a2","article-title":"Early Diagnosis of HIV Infection in Infants\u2014One Caribbean and Six Sub-Saharan African Countries, 2011\u20132015","volume":"65","author":"K Diallo","year":"2016","journal-title":"MMWR Morbidity Mortal Weekly Report"},{"issue":"1","key":"pone.0246546.ref017","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/QAI.0000000000002366","article-title":"Challenges in the Early Infant HIV Diagnosis and Treatment Cascade","volume":"84","author":"L Mofenson","year":"2020","journal-title":"JAIDS Journal of Acquired Immune Deficiency Syndromes"},{"issue":"11","key":"pone.0246546.ref018","doi-asserted-by":"crossref","first-page":"e25209","DOI":"10.1002\/jia2.25209","article-title":"Attrition of HIV-exposed infants from early infant diagnosis services in low- and middle-income countries: a systematic review and meta-analysis","volume":"21","author":"J Carlucci","year":"2018","journal-title":"Journal of the International AIDS Society"},{"key":"pone.0246546.ref019","doi-asserted-by":"crossref","first-page":"S197","DOI":"10.1097\/QAD.0000000000000104","article-title":"Improved access to early infant diagnosis is a critical part of a child-centric prevention of mother-to-child transmission agenda","volume":"27","author":"A Ghadrshenas","year":"2013","journal-title":"AIDS"},{"key":"pone.0246546.ref020","doi-asserted-by":"crossref","first-page":"S207","DOI":"10.1097\/QAD.0000000000000095","article-title":"Linkage, initiation and retention of children in the antiretroviral therapy cascade","volume":"27","author":"B Phelps","year":"2013","journal-title":"AIDS"},{"issue":"1","key":"pone.0246546.ref021","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1741-7015-9-59","article-title":"Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions","volume":"9","author":"AL Ciaranello","year":"2011","journal-title":"BMC Medicine"},{"issue":"7","key":"pone.0246546.ref022","doi-asserted-by":"crossref","first-page":"e024907","DOI":"10.1136\/bmjopen-2018-024907","article-title":"What interventions are effective in improving uptake and retention of HIV-positive pregnant and breastfeeding women and their infants in prevention of mother to child transmission care programmes in low-income and middle-income countries? A systematic review and meta-analysis","volume":"9","author":"LM Ritchie","year":"2019","journal-title":"BMJ Open"},{"key":"pone.0246546.ref023","unstructured":"Uganda Ministry of Health. HIV Program Data. 2010. AIDS Control Programme, Kampala, Uganda"},{"issue":"9383","key":"pone.0246546.ref024","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1016\/S0140-6736(03)14154-2","article-title":"HIV-positive mothers in Uganda resort to breastfeeding","volume":"362","author":"C Wendo","year":"2003","journal-title":"Lancet"},{"issue":"4","key":"pone.0246546.ref025","doi-asserted-by":"crossref","first-page":"602","DOI":"10.2307\/2392366","article-title":"Mixing qualitative and quantitative methods: Triangulation in action","volume":"24","author":"TD Jick","year":"1979","journal-title":"Administrative science quarterly"},{"issue":"3","key":"pone.0246546.ref026","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1097\/QAI.0000000000001023","article-title":"Impact of a systems engineering intervention on PMTCT service delivery in Cote d\u2019Ivoire, Kenya, Mozambique: a cluster randomized trial","volume":"72","author":"AS Rustagi","year":"2016","journal-title":"Journal of acquired immune deficiency syndromes (1999)"},{"key":"pone.0246546.ref027","doi-asserted-by":"crossref","first-page":"2325958219857724","DOI":"10.1177\/2325958219857724","article-title":"Increasing HIV-free survival of infants: reorganizing care using quality improvement for the optimal health and nutrition of HIV-positive women and their exposed infants in Uganda","volume":"18","author":"T Nsubuga-Nyombi","year":"2019","journal-title":"Journal of the International Association of Providers of AIDS Care (JIAPAC)"},{"issue":"11","key":"pone.0246546.ref028","doi-asserted-by":"crossref","first-page":"e13891","DOI":"10.1371\/journal.pone.0013891","article-title":"Improving a mother to child HIV transmission programme through health system redesign: quality improvement, protocol adjustment and resource addition","volume":"5","author":"MS Youngleson","year":"2010","journal-title":"PloS One"},{"issue":"6","key":"pone.0246546.ref029","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1093\/intqhc\/mzu085","article-title":"Improving rates of cotrimoxazole prophylaxis in resource-limited settings: implementation of a quality improvement approach","volume":"26","author":"J Bardfield","year":"2014","journal-title":"International Journal for Quality in Health Care"},{"issue":"3","key":"pone.0246546.ref030","doi-asserted-by":"crossref","first-page":"239","DOI":"10.7196\/SAMJ.7605","article-title":"Elimination of mother-to-child transmission of HIV in South Africa: rapid scale-up using quality improvement","volume":"104","author":"S Bhardwaj","year":"2014","journal-title":"South African Medical Journal"},{"key":"pone.0246546.ref031","unstructured":"MEASURE Evaluation. Evaluation of the partnership for hiv-free survival country assessment: Uganda. 2018. Available from: https:\/\/www.measureevaluation.org\/resources\/publications\/fs-18-255."},{"issue":"12","key":"pone.0246546.ref032","doi-asserted-by":"crossref","first-page":"e0187605","DOI":"10.1371\/journal.pone.0187605","article-title":"Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study","volume":"12","author":"S Muhumuza","year":"2017","journal-title":"PloS One"},{"key":"pone.0246546.ref033","unstructured":"Esiru G, Narayan V, Grosz J, Nabitaka L. Uganda\u2019s innovative interventions in PMTCT produce dramatic gains in linkage and retention of HIV+ pregnant women and their HIV-exposed children. Presented at the 20th Conference on Retroviruses and opportunistic infections (CROI). March 2013. Atlanta, Georgia."},{"volume-title":"Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach","year":"2016","author":"World Health Organization","key":"pone.0246546.ref034"},{"issue":"7","key":"pone.0246546.ref035","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/JCM.00431-12","article-title":"Early diagnosis of in utero and intrapartum HIV infection in infants prior to 6 weeks of age","volume":"50","author":"RR Lilian","year":"2012","journal-title":"Journal of Clinical Microbiology"},{"issue":"3","key":"pone.0246546.ref036","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/QAI.0000000000001387","article-title":"Performance of virological testing for early infant diagnosis: a systematic review","volume":"75","author":"D Mallampati","year":"2017","journal-title":"JAIDS Journal of Acquired Immune Deficiency Syndromes"},{"issue":"11","key":"pone.0246546.ref037","doi-asserted-by":"crossref","first-page":"e78609","DOI":"10.1371\/journal.pone.0078609","article-title":"Uganda\u2019s new national laboratory sample transport system: a successful model for improving access to diagnostic services for early infant HIV diagnosis and other programs","volume":"8","author":"C Kiyaga","year":"2013","journal-title":"PLoS One"},{"issue":"2","key":"pone.0246546.ref038","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1057\/jphp.2015.7","article-title":"Consolidating HIV testing in a public health laboratory for efficient and sustainable early infant diagnosis (EID) in Uganda","volume":"36","author":"C Kiyaga","year":"2015","journal-title":"Journal of Public Health Policy"},{"issue":"5","key":"pone.0246546.ref039","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/QAI.0000000000001526","article-title":"Impact of SMS\/GPRS Printers in Reducing Time to Early Infant Diagnosis Compared With Routine Result Reporting: A Systematic Review and Meta-Analysis","volume":"76","author":"L Vojnov","year":"2017","journal-title":"Journal of Acquired Immune Deficiency Syndromes (1999)"},{"issue":"7","key":"pone.0246546.ref040","doi-asserted-by":"crossref","first-page":"20299","DOI":"10.7448\/IAS.18.7.20299","article-title":"Reducing mortality in HIV-infected infants and achieving the 90\u201390\u201390 target through innovative diagnosis approaches","volume":"18","author":"S Essajee","year":"2015","journal-title":"Journal of International AIDS Society"},{"volume-title":"Novel Point-of-Care Tools for Early Infant Diagnosis of HIV","year":"2017","author":"World Health Organization","key":"pone.0246546.ref041"},{"issue":"12","key":"pone.0246546.ref042","doi-asserted-by":"crossref","first-page":"e0189226","DOI":"10.1371\/journal.pone.0189226","article-title":"Field evaluation of HIV point-of-care testing for early infant diagnosis in Cape Town, South Africa","volume":"12","author":"L Dunning","year":"2017","journal-title":"PloS one"},{"key":"pone.0246546.ref043","unstructured":"Technau K, Sherman G, Bhowan K, Murnane P, Coovadia AH, Kuhn L. Comparing Point of Care to Laboratory HIV PCR testing at birth in a hospital setting in Johannesburg, South Africa. Presented at the 8th International Workshop on HIV Pediatrics (Abstract O_14). July 2016. Durban, South Africa."},{"key":"pone.0246546.ref044","doi-asserted-by":"crossref","first-page":"e373","DOI":"10.1016\/S2352-3018(19)30033-5","article-title":"Evaluation of a routine point-of-care intervention for early infant diagnosis of HIV: an observational study in eight African countries","volume":"6","author":"F Bianchi","year":"2019","journal-title":"Lancet HIV"},{"issue":"5","key":"pone.0246546.ref045","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/cid\/ciy169","article-title":"Significant patient impact observed upon implementation of point-of-care early infant diagnosis technologies in an observational study in Malawi","volume":"67","author":"R Mwenda","year":"2018","journal-title":"Clinical Infectious Diseases"},{"issue":"11","key":"pone.0246546.ref046","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1097\/QAD.0000000000001846","article-title":"Effect of point-of-care early infant diagnosis on antiretroviral therapy initiation and retention of patients","volume":"32","author":"IV Jani","year":"2018","journal-title":"AIDS"},{"issue":"1","key":"pone.0246546.ref047","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1097\/QAI.0000000000002384","article-title":"Strengthening Existing Laboratory-Based Systems vs. Investing in Point-of-Care Assays for Early Infant Diagnosis of HIV: A Model-Based Cost-Effectiveness Analysis","volume":"84","author":"NC McCann","year":"2020","journal-title":"Journal of Acquired Immune Deficiency Syndromes (1999)"},{"issue":"1","key":"pone.0246546.ref048","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1186\/s12879-019-4393-5","article-title":"What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV?.","volume":"19","author":"AE Goga","year":"2019","journal-title":"BMC Infectious Diseases"},{"key":"pone.0246546.ref049","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1097\/QAI.0000000000001319","article-title":"Scale-up of early infant HIV diagnosis and improving access to pediatric HIV care in global plan countries: past and future perspectives","volume":"75","author":"S Essajee","year":"2017","journal-title":"Journal of Acquired Immune Deficiency Syndromes"},{"issue":"1","key":"pone.0246546.ref050","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1758-2652-13-3","article-title":"Integration of HIV\/AIDS services into African primary health care: lessons learned for health system strengthening in Mozambique-a case study","volume":"13","author":"J Pfeiffer","year":"2010","journal-title":"J Int AIDS Soc"},{"issue":"4","key":"pone.0246546.ref051","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/heapol\/czt035","article-title":"When do vertical programmes strengthen health systems? A comparative assessment of disease-specific interventions in India","volume":"29","author":"KD Rao","year":"2014","journal-title":"Health Policy and Planning"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246546","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T22:32:30Z","timestamp":1612564350000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0246546"}},"subtitle":[],"editor":[{"given":"Julie AE","family":"Nelson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,2,4]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0246546","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2021,2,4]]}}}