{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T06:41:32Z","timestamp":1793428892143,"version":"4.5.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health, USA","doi-asserted-by":"crossref","award":["R01-AI50237"],"award-info":[{"award-number":["R01-AI50237"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013500","name":"Diabetestutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["personal grant for JEL"],"award-info":[{"award-number":["personal grant for JEL"]}],"id":[{"id":"10.13039\/501100013500","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010114","name":"Yrj\u00f6 Jahnssonin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["personal grants for JEL"],"award-info":[{"award-number":["personal grants for JEL"]}],"id":[{"id":"10.13039\/100010114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010114","name":"Yrj\u00f6 Jahnssonin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["MO"],"award-info":[{"award-number":["MO"]}],"id":[{"id":"10.13039\/100010114","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["Grant#2018PG-T1D053"],"award-info":[{"award-number":["Grant#2018PG-T1D053"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","award":["G-2108-04793"],"award-info":[{"award-number":["G-2108-04793"]}],"id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001648","name":"European Foundation for the Study of Diabetes","doi-asserted-by":"publisher","award":["97013"],"award-info":[{"award-number":["97013"]}],"id":[{"id":"10.13039\/501100001648","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Global Virus Network (GVN), University of Maryland, Baltimore"},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["25-2012-770"],"award-info":[{"award-number":["25-2012-770"]}],"id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["JDRF 25-2012-516"],"award-info":[{"award-number":["JDRF 25-2012-516"]}],"id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022690","name":"JDRF","doi-asserted-by":"publisher","award":["nPOD: 5-SRA-2018-557-Q-R"],"award-info":[{"award-number":["nPOD: 5-SRA-2018-557-Q-R"]}],"id":[{"id":"10.13039\/100022690","id-type":"DOI","asserted-by":"publisher"}]},{"name":"network for Pancreatic Organ donors with Diabetes, nPOD","award":["RRID:SCR_014641"],"award-info":[{"award-number":["RRID:SCR_014641"]}]},{"DOI":"10.13039\/501100005431","name":"Pirkanmaan Rahasto","doi-asserted-by":"publisher","award":["personal grant for JEL"],"award-info":[{"award-number":["personal grant for JEL"]}],"id":[{"id":"10.13039\/501100005431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"Seventh Framework Programme","doi-asserted-by":"publisher","award":["Persistent Virus Infection in Diabetes Network [PE"],"award-info":[{"award-number":["Persistent Virus Infection in Diabetes Network [PE"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["for HH"],"award-info":[{"award-number":["for HH"]}],"id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002341","name":"Research Council of Finland","doi-asserted-by":"publisher","award":["288671"],"award-info":[{"award-number":["288671"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["personal grants for JEL"],"award-info":[{"award-number":["personal grants for JEL"]}],"id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","award":["MO"],"award-info":[{"award-number":["MO"]}],"id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tampere University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>The nPOD-Virus group collaboratively applied innovative technologies to detect and sequence viral RNA in pancreas and other tissues from organ donors with type 1 diabetes. These analyses involved the largest number of pancreas samples collected to date. The aim of the current work was to examine the presence of enterovirus RNA in pancreas and lymphoid tissues of organ donors with and without type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed pancreas, spleen, pancreatic lymph nodes and duodenum samples from the following groups: (1) donors with type 1 diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      =71) with (\n                      <jats:italic>n<\/jats:italic>\n                      =35) or without (\n                      <jats:italic>n<\/jats:italic>\n                      =36) insulin-containing islets; (2) donors with single or double islet autoantibody positivity without diabetes (\n                      <jats:italic>n<\/jats:italic>\n                      =22); and (3) autoantibody-negative donors without diabetes (control donors) (\n                      <jats:italic>n<\/jats:italic>\n                      =74). Five research laboratories participated in this collaborative effort using approaches for unbiased discovery of RNA viruses (two RNA-Seq platforms), targeted detection of\n                      <jats:italic>Enterovirus A\u2013D<\/jats:italic>\n                      species using RT-PCR, and tests for virus growth in cell culture.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Direct RNA-Seq did not detect virus signal in pancreas samples, whereas RT-PCR detected enterovirus RNA confirmed by sequencing in low amounts in pancreas samples in three of the five donor groups: donors with type 1 diabetes with insulin-containing islets, 16% (5\/32) being positive; donors with single islet autoantibody positivity, 53% (8\/15) being positive; and non-diabetic donors, 8% (4\/49) being positive. Detection of enterovirus RNA was significantly more frequent in single islet autoantibody-positive donors compared with donors with type 1 diabetes with insulin-deficient islets (\n                      <jats:italic>p<\/jats:italic>\n                      &lt;0.001) and control (non-diabetic) donors (\n                      <jats:italic>p<\/jats:italic>\n                      =0.004). In some donors, pancreatic lymph nodes were also positive. RT-PCR detected enterovirus RNA also in the spleen of a small number of donors and virus enrichment in susceptible cell lines before RT-PCR resulted in much higher rate in spleen positivity, particularly in donors with type 1 diabetes. Interestingly, the enterovirus strains detected did not cause a typical lytic infection, possibly reflecting their persistence-prone nature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>This was the largest coordinated effort to examine the presence of enterovirus RNA in the pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that donors with type 1 diabetes and donors with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06359-w","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T05:25:13Z","timestamp":1742189113000},"page":"1211-1225","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes"],"prefix":"10.1007","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-4651","authenticated-orcid":false,"given":"Jutta E.","family":"Laiho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-6774","authenticated-orcid":false,"given":"Sami","family":"Oikarinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-4548","authenticated-orcid":false,"given":"Sofia","family":"Morfopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1329-1508","authenticated-orcid":false,"given":"Maarit","family":"Oikarinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashlie","family":"Renner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4292-0599","authenticated-orcid":false,"given":"Daniel","family":"Depledge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-8829","authenticated-orcid":false,"given":"Matthew C.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5097-6050","authenticated-orcid":false,"given":"Ivan C.","family":"Gerling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-0534","authenticated-orcid":false,"given":"Judith","family":"Breuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4046-6898","authenticated-orcid":false,"given":"Joseph F.","family":"Petrosino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-9215","authenticated-orcid":false,"given":"Vincent","family":"Plagnol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7211-0319","authenticated-orcid":false,"given":"Alberto","family":"Pugliese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3008-2126","authenticated-orcid":false,"given":"Antonio","family":"Toniolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6550-3237","authenticated-orcid":false,"given":"Richard E.","family":"Lloyd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-4145","authenticated-orcid":false,"given":"Heikki","family":"Hy\u00f6ty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the nPOD-Virus Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"issue":"6","key":"6359_CR1","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1007\/s00125-009-1276-0","volume":"52","author":"SJ Richardson","year":"2009","unstructured":"Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG (2009) The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia 52(6):1143\u20131151. https:\/\/doi.org\/10.1007\/s00125-009-1276-0","journal-title":"Diabetologia"},{"issue":"12","key":"6359_CR2","doi-asserted-by":"publisher","first-page":"5115","DOI":"10.1073\/pnas.0700442104","volume":"104","author":"F Dotta","year":"2007","unstructured":"Dotta F, Censini S, van Halteren AGS et al (2007) Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A 104(12):5115\u20135120. https:\/\/doi.org\/10.1073\/pnas.0700442104","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"6359_CR3","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.2337\/db14-1370","volume":"64","author":"L Krogvold","year":"2015","unstructured":"Krogvold L, Edwin B, Buanes T et al (2015) Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes 64(5):1682\u20131687. https:\/\/doi.org\/10.2337\/db14-1370","journal-title":"Diabetes"},{"issue":"2","key":"6359_CR4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00125-003-1297-z","volume":"47","author":"P Ylipaasto","year":"2004","unstructured":"Ylipaasto P, Klingel K, Lindberg AM et al (2004) Enterovirus infection in human pancreatic islet cells, islet tropism in vivo and receptor involvement in cultured islet beta cells. Diabetologia 47(2):225\u2013239. https:\/\/doi.org\/10.1007\/s00125-003-1297-z","journal-title":"Diabetologia"},{"issue":"3","key":"6359_CR5","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1507\/endocrj.K09E-291","volume":"57","author":"S Shibasaki","year":"2010","unstructured":"Shibasaki S, Imagawa A, Tauriainen S et al (2010) Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes. Endocr J 57(3):211\u2013219. https:\/\/doi.org\/10.1507\/endocrj.K09E-291","journal-title":"Endocr J"},{"issue":"11","key":"6359_CR6","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1007\/s00125-021-05525-0","volume":"64","author":"S Oikarinen","year":"2021","unstructured":"Oikarinen S, Krogvold L, Edwin B et al (2021) Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study. Diabetologia 64(11):2491\u20132501. https:\/\/doi.org\/10.1007\/s00125-021-05525-0","journal-title":"Diabetologia"},{"issue":"8190","key":"6359_CR7","first-page":"354","volume":"2","author":"AB Jenson","year":"1980","unstructured":"Jenson AB, Rosenberg HS, Notkins AL (1980) Pancreatic islet-cell damage in children with fatal viral infections. Lancet 2(8190):354\u2013358","journal-title":"Lancet"},{"issue":"5","key":"6359_CR8","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1111\/neup.12121","volume":"34","author":"SJ Bissel","year":"2014","unstructured":"Bissel SJ, Winkler CC, DelTondo J, Wang G, Williams K, Wiley CA (2014) Coxsackievirus B4 myocarditis and meningoencephalitis in newborn twins. Neuropathology 34(5):429\u2013437. https:\/\/doi.org\/10.1111\/neup.12121","journal-title":"Neuropathology"},{"issue":"12","key":"6359_CR9","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1007\/s00125-022-05779-2","volume":"65","author":"L Krogvold","year":"2022","unstructured":"Krogvold L, Genoni A, Puggioni A et al (2022) Live enteroviruses, but not other viruses, detected in human pancreas at the onset of type 1 diabetes in the DiViD study. Diabetologia 65(12):2108\u20132120. https:\/\/doi.org\/10.1007\/s00125-022-05779-2","journal-title":"Diabetologia"},{"issue":"1\u20132","key":"6359_CR10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.virusres.2006.11.004","volume":"124","author":"A Elshebani","year":"2007","unstructured":"Elshebani A, Olsson A, Westman J, Tuvemo T, Korsgren O, Frisk G (2007) Effects on isolated human pancreatic islet cells after infection with strains of enterovirus isolated at clinical presentation of type 1 diabetes. Virus Res 124(1\u20132):193\u2013203. https:\/\/doi.org\/10.1016\/j.virusres.2006.11.004","journal-title":"Virus Res"},{"issue":"11","key":"6359_CR11","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1007\/s00125-018-4704-1","volume":"61","author":"E Ifie","year":"2018","unstructured":"Ifie E, Russell MA, Dhayal S et al (2018) Unexpected subcellular distribution of a specific isoform of the Coxsackie and adenovirus receptor, CAR-SIV, in human pancreatic beta cells. Diabetologia 61(11):2344\u20132355. https:\/\/doi.org\/10.1007\/s00125-018-4704-1","journal-title":"Diabetologia"},{"issue":"12","key":"6359_CR12","doi-asserted-by":"publisher","first-page":"1865","DOI":"10.1038\/s41591-019-0667-0","volume":"25","author":"K Vehik","year":"2019","unstructured":"Vehik K, Lynch KF, Wong MC et al (2019) Prospective virome analyses in young children at increased genetic risk for type 1 diabetes. Nat Med 25(12):1865\u20131872. https:\/\/doi.org\/10.1038\/s41591-019-0667-0","journal-title":"Nat Med"},{"issue":"5","key":"6359_CR13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nrendo.2016.30","volume":"12","author":"A Op de Beeck","year":"2016","unstructured":"Op de Beeck A, Eizirik DL (2016) Viral infections in type 1 diabetes mellitus\u2013why the \u03b2 cells? Nat Rev Endocrinol 12(5):263\u2013273. https:\/\/doi.org\/10.1038\/nrendo.2016.30","journal-title":"Nat Rev Endocrinol"},{"issue":"2","key":"6359_CR14","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1002\/jmv.24039","volume":"87","author":"S Tracy","year":"2015","unstructured":"Tracy S, Smithee S, Alhazmi A, Chapman N (2015) Coxsackievirus can persist in murine pancreas by deletion of 5 \u2019 terminal genomic sequences. J Med Virol 87(2):240\u2013247. https:\/\/doi.org\/10.1002\/jmv.24039","journal-title":"J Med Virol"},{"key":"6359_CR15","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/978-3-540-75546-3_13","volume":"323","author":"NM Chapman","year":"2008","unstructured":"Chapman NM, Kim KS (2008) Persistent coxsackievirus infection: enterovirus persistence in chronic myocarditis and dilated cardiomyopathy. Curr Top Microbiol Immunol 323:275\u2013292. https:\/\/doi.org\/10.1007\/978-3-540-75546-3_13","journal-title":"Curr Top Microbiol Immunol"},{"issue":"3","key":"6359_CR16","doi-asserted-by":"publisher","first-page":"687","DOI":"10.2337\/db11-1157","volume":"61","author":"M Oikarinen","year":"2012","unstructured":"Oikarinen M, Tauriainen S, Oikarinen S et al (2012) Type 1 diabetes is associated with enterovirus infection in gut mucosa. Diabetes 61(3):687\u2013691. https:\/\/doi.org\/10.2337\/db11-1157","journal-title":"Diabetes"},{"issue":"1","key":"6359_CR17","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1111\/j.1365-2249.2007.03529.x","volume":"151","author":"M Oikarinen","year":"2008","unstructured":"Oikarinen M, Tauriainen S, Honkanen T et al (2008) Detection of enteroviruses in the intestine of type 1 diabetic patients. Clin Exp Immunol 151(1):71\u201375. https:\/\/doi.org\/10.1111\/j.1365-2249.2007.03529.x","journal-title":"Clin Exp Immunol"},{"issue":"9","key":"6359_CR18","doi-asserted-by":"publisher","first-page":"2479","DOI":"10.1007\/s00125-012-2591-4","volume":"55","author":"A Mercalli","year":"2012","unstructured":"Mercalli A, Lampasona V, Klingel K et al (2012) No evidence of enteroviruses in the intestine of patients with type 1 diabetes. Diabetologia 55(9):2479\u20132488. https:\/\/doi.org\/10.1007\/s00125-012-2591-4","journal-title":"Diabetologia"},{"key":"6359_CR19","doi-asserted-by":"publisher","first-page":"e4039","DOI":"10.3791\/4039-v","volume":"63","author":"ML Campbell-Thompson","year":"2012","unstructured":"Campbell-Thompson ML, Montgomery EL, Foss RM et al (2012) Collection protocol for human pancreas. J Vis Exp 63:e4039. https:\/\/doi.org\/10.3791\/4039-v","journal-title":"J Vis Exp"},{"issue":"11","key":"6359_CR20","doi-asserted-by":"publisher","first-page":"e27805","DOI":"10.1371\/journal.pone.0027805","volume":"6","author":"DP Depledge","year":"2011","unstructured":"Depledge DP, Palser AL, Watson SJ et al (2011) Specific capture and whole-genome sequencing of viruses from clinical samples. PloS One 6(11):e27805. https:\/\/doi.org\/10.1371\/journal.pone.0027805","journal-title":"PloS One"},{"issue":"1","key":"6359_CR21","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00125-012-2745-4","volume":"56","author":"SJ Richardson","year":"2013","unstructured":"Richardson SJ, Leete P, Bone AJ, Foulis AK, Morgan NG (2013) Expression of the enteroviral capsid protein VP1 in the islet cells of patients with type 1 diabetes is associated with induction of protein kinase R and downregulation of Mcl-1. Diabetologia 56(1):185\u2013193. https:\/\/doi.org\/10.1007\/s00125-012-2745-4","journal-title":"Diabetologia"},{"key":"6359_CR22","doi-asserted-by":"publisher","unstructured":"Rodriguez-Calvo T, Laiho JE, Oikarinen M et al (2025) Enterovirus VP1 protein and HLA class I hyperexpression in pancreatic islet cells of organ donors with type 1 diabetes. Diabetologia.\u00a0https:\/\/doi.org\/10.1007\/s00125-025-06384-9","DOI":"10.1007\/s00125-025-06384-9"},{"issue":"11","key":"6359_CR23","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1007\/s00125-016-4067-4","volume":"59","author":"SJ Richardson","year":"2016","unstructured":"Richardson SJ, Rodriguez-Calvo T, Gerling IC et al (2016) Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes. Diabetologia 59(11):2448\u20132458. https:\/\/doi.org\/10.1007\/s00125-016-4067-4","journal-title":"Diabetologia"},{"issue":"10","key":"6359_CR24","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1128\/JCM.01052-16","volume":"54","author":"JR Brown","year":"2016","unstructured":"Brown JR, Roy S, Ruis C, Yara Romero E et al (2016) Norovirus whole-genome sequencing by SureSelect target enrichment: a robust and sensitive method. J Clin Microbiol 54(10):2530\u20132537. https:\/\/doi.org\/10.1128\/JCM.01052-16","journal-title":"J Clin Microbiol"},{"issue":"6","key":"6359_CR25","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","volume":"27","author":"R Schmieder","year":"2011","unstructured":"Schmieder R, Edwards R (2011) Quality control and preprocessing of metagenomic datasets. Bioinforma Oxf Engl 27(6):863\u2013864. https:\/\/doi.org\/10.1093\/bioinformatics\/btr026","journal-title":"Bioinforma Oxf Engl"},{"issue":"3","key":"6359_CR26","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","volume":"215","author":"SF Altschul","year":"1990","unstructured":"Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403\u2013410. https:\/\/doi.org\/10.1016\/S0022-2836(05)80360-2","journal-title":"J Mol Biol"},{"issue":"5","key":"6359_CR27","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1101\/gr.074492.107","volume":"18","author":"DR Zerbino","year":"2008","unstructured":"Zerbino DR, Birney E (2008) Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18(5):821\u2013829. https:\/\/doi.org\/10.1101\/gr.074492.107","journal-title":"Genome Res"},{"issue":"4","key":"6359_CR28","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9(4):357\u2013359. https:\/\/doi.org\/10.1038\/nmeth.1923","journal-title":"Nat Methods"},{"issue":"18","key":"6359_CR29","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1093\/bioinformatics\/btv317","volume":"31","author":"S Morfopoulou","year":"2015","unstructured":"Morfopoulou S, Plagnol V (2015) Bayesian mixture analysis for metagenomic community profiling. Bioinforma Oxf Engl 31(18):2930\u20132938. https:\/\/doi.org\/10.1093\/bioinformatics\/btv317","journal-title":"Bioinforma Oxf Engl"},{"key":"6359_CR30","doi-asserted-by":"publisher","first-page":"104908","DOI":"10.1016\/j.jcv.2021.104908","volume":"141","author":"JJC de Vries","year":"2021","unstructured":"de Vries JJC, Brown JR, Fischer N et al (2021) Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples. J Clin Virol 141:104908. https:\/\/doi.org\/10.1016\/j.jcv.2021.104908","journal-title":"J Clin Virol"},{"issue":"307","key":"6359_CR31","doi-asserted-by":"publisher","first-page":"307ra154","DOI":"10.1126\/scitranslmed.aac4227","volume":"7","author":"CJA Duncan","year":"2015","unstructured":"Duncan CJA, Mohamad SMB, Young DF et al (2015) Human IFNAR2 deficiency: lessons for antiviral immunity. Sci Transl Med 7(307):307ra154. https:\/\/doi.org\/10.1126\/scitranslmed.aac4227","journal-title":"Sci Transl Med"},{"issue":"5","key":"6359_CR32","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1056\/NEJMc1509458","volume":"375","author":"S Morfopoulou","year":"2016","unstructured":"Morfopoulou S, Brown JR, Davies EG et al (2016) Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med 375(5):497\u2013498. https:\/\/doi.org\/10.1056\/NEJMc1509458","journal-title":"N Engl J Med"},{"issue":"1","key":"6359_CR33","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s00401-016-1629-y","volume":"133","author":"S Morfopoulou","year":"2017","unstructured":"Morfopoulou S, Mee ET, Connaughton SM et al (2017) Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis. Acta Neuropathol (Berl) 133(1):139\u2013147. https:\/\/doi.org\/10.1007\/s00401-016-1629-y","journal-title":"Acta Neuropathol (Berl)"},{"issue":"6","key":"6359_CR34","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1111\/tid.12607","volume":"18","author":"SH Lum","year":"2016","unstructured":"Lum SH, Turner A, Guiver M et al (2016) An emerging opportunistic infection: fatal astrovirus (VA1\/HMO-C) encephalitis in a pediatric stem cell transplant recipient. Transpl Infect Dis 18(6):960\u2013964. https:\/\/doi.org\/10.1111\/tid.12607","journal-title":"Transpl Infect Dis"},{"issue":"6","key":"6359_CR35","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/cid\/ciu940","volume":"60","author":"JR Brown","year":"2015","unstructured":"Brown JR, Morfopoulou S, Hubb J et al (2015) Astrovirus VA1\/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients. Clin Infect Dis 60(6):881\u2013888. https:\/\/doi.org\/10.1093\/cid\/ciu940","journal-title":"Clin Infect Dis"},{"issue":"4","key":"6359_CR36","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.jcv.2012.11.018","volume":"56","author":"H Honkanen","year":"2013","unstructured":"Honkanen H, Oikarinen S, Pakkanen O et al (2013) Human enterovirus 71 strains in the background population and in hospital patients in Finland. J Clin Virol 56(4):348\u2013353. https:\/\/doi.org\/10.1016\/j.jcv.2012.11.018","journal-title":"J Clin Virol"},{"issue":"1","key":"6359_CR37","doi-asserted-by":"publisher","first-page":"5013","DOI":"10.1038\/s41598-017-04993-y","volume":"7","author":"A Genoni","year":"2017","unstructured":"Genoni A, Canducci F, Rossi A et al (2017) Revealing enterovirus infection in chronic human disorders: an integrated diagnostic approach. Sci Rep 7(1):5013. https:\/\/doi.org\/10.1038\/s41598-017-04993-y","journal-title":"Sci Rep"},{"key":"6359_CR38","doi-asserted-by":"publisher","first-page":"24757","DOI":"10.1038\/srep24757","volume":"6","author":"G Maccari","year":"2016","unstructured":"Maccari G, Genoni A, Sansonno S, Toniolo A (2016) Properties of two enterovirus antibodies that are utilized in diabetes research. Sci Rep 6:24757. https:\/\/doi.org\/10.1038\/srep24757","journal-title":"Sci Rep"},{"issue":"2","key":"6359_CR39","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1007\/s00125-013-3094-7","volume":"57","author":"SJ Richardson","year":"2014","unstructured":"Richardson SJ, Leete P, Dhayal S et al (2014) Evaluation of the fidelity of immunolabelling obtained with clone 5D8\/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia 57(2):392\u2013401. https:\/\/doi.org\/10.1007\/s00125-013-3094-7","journal-title":"Diabetologia"},{"key":"6359_CR40","doi-asserted-by":"crossref","unstructured":"Burch TC, Hitefield NL, Morris MA et al (2024) Proteomic and mass spectrometry-based identification of viral proteins in human tissue samples from the Network for Pancreatic Organ Donors with Diabetes. medRxiv. Available from: https:\/\/www.medrxiv.org\/content\/10.1101\/2024.10.24.24315944v1 (Preprint) (accessed 11 Dec 2024)","DOI":"10.1101\/2024.10.24.24315944"},{"key":"6359_CR41","doi-asserted-by":"publisher","unstructured":"Richardson SJ, Rodriguez-Calvo T, Laiho JE et al (2025) Joint analysis of the nPOD-virus group data: the association of enterovirus with type 1 diabetes is supported by multiple markers of infection in pancreas tissue. Diabetologia.\u00a0https:\/\/doi.org\/10.1007\/s00125-025-06401-x","DOI":"10.1007\/s00125-025-06401-x"},{"issue":"10","key":"6359_CR42","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.2337\/db24-0076","volume":"73","author":"E Manduchi","year":"2024","unstructured":"Manduchi E, Descamps HC, Schug J et al (2024) No evidence for persistent enteroviral B infection of pancreatic islets in patients with type 1 diabetes and prediabetes from RNA sequencing data. Diabetes 73(10):1697\u20131704. https:\/\/doi.org\/10.2337\/db24-0076","journal-title":"Diabetes"},{"issue":"2","key":"6359_CR43","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.virol.2008.02.030","volume":"375","author":"NM Chapman","year":"2008","unstructured":"Chapman NM, Kim KS, Drescher KM, Oka K, Tracy S (2008) 5\u2019 terminal deletions in the genome of a coxsackievirus B2 strain occurred naturally in human heart. Virology 375(2):480\u2013491. https:\/\/doi.org\/10.1016\/j.virol.2008.02.030","journal-title":"Virology"},{"issue":"11","key":"6359_CR44","doi-asserted-by":"publisher","first-page":"7024","DOI":"10.1128\/JVI.79.11.7024-7041.2005","volume":"79","author":"KS Kim","year":"2005","unstructured":"Kim KS, Tracy S, Tapprich W et al (2005) 5\u2019-Terminal deletions occur in coxsackievirus B3 during replication in murine hearts and cardiac myocyte cultures and correlate with encapsidation of negative-strand viral RNA. J Virol 79(11):7024\u20137041. https:\/\/doi.org\/10.1128\/JVI.79.11.7024-7041.2005","journal-title":"J Virol"},{"issue":"7","key":"6359_CR45","doi-asserted-by":"publisher","first-page":"747","DOI":"10.3390\/v12070747","volume":"12","author":"M Oikarinen","year":"2020","unstructured":"Oikarinen M, Bertolet L, Toniolo A et al (2020) Differential detection of encapsidated versus unencapsidated enterovirus RNA in samples containing pancreatic enzymes\u2014relevance for diabetes studies. Viruses 12(7):747. https:\/\/doi.org\/10.3390\/v12070747","journal-title":"Viruses"},{"issue":"5","key":"6359_CR46","doi-asserted-by":"publisher","first-page":"770","DOI":"10.3390\/vaccines10050770","volume":"10","author":"NM Chapman","year":"2022","unstructured":"Chapman NM (2022) Persistent enterovirus infection: little deletions, long infections. Vaccines 10(5):770. https:\/\/doi.org\/10.3390\/vaccines10050770","journal-title":"Vaccines"},{"issue":"44","key":"6359_CR47","doi-asserted-by":"publisher","first-page":"6017","DOI":"10.1016\/j.vaccine.2015.05.108","volume":"33","author":"PY Lim","year":"2015","unstructured":"Lim PY, Hickey AC, Jamiluddin MF et al (2015) Immunogenicity and performance of an enterovirus 71 virus-like-particle vaccine in nonhuman primates. Vaccine 33(44):6017\u20136024. https:\/\/doi.org\/10.1016\/j.vaccine.2015.05.108","journal-title":"Vaccine"},{"issue":"Suppl O","key":"6359_CR48","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/eurheartj\/16.suppl_O.42","volume":"16","author":"K Klingel","year":"1995","unstructured":"Klingel K, McManus BM, Kandolf R (1995) Enterovirus-infected immune cells of spleen and lymph nodes in the murine model of chronic myocarditis: a role in pathogenesis? Eur Heart J 16(Suppl O):42\u201345. https:\/\/doi.org\/10.1093\/eurheartj\/16.suppl_O.42","journal-title":"Eur Heart J"},{"issue":"4","key":"6359_CR49","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3109\/00365548909167452","volume":"21","author":"DO Ho-Yen","year":"1989","unstructured":"Ho-Yen DO, Hardie R, McClure J, Cunningham NE, Bell EJ (1989) Fatal outcome of echovirus 7 infection. Scand J Infect Dis 21(4):459\u2013461. https:\/\/doi.org\/10.3109\/00365548909167452","journal-title":"Scand J Infect Dis"},{"issue":"2\u20133","key":"6359_CR50","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0928-0197(96)00217-6","volume":"5","author":"K Klingel","year":"1996","unstructured":"Klingel K, Kandolf R (1996) Molecular in situ localization techniques in diagnosis and pathogenicity studies of enteroviral heart disease. Clin Diagn Virol 5(2\u20133):157\u2013166. https:\/\/doi.org\/10.1016\/0928-0197(96)00217-6","journal-title":"Clin Diagn Virol"},{"issue":"8","key":"6359_CR51","doi-asserted-by":"publisher","first-page":"100371","DOI":"10.1016\/j.xcrm.2021.100371","volume":"2","author":"S Geravandi","year":"2021","unstructured":"Geravandi S, Richardson S, Pugliese A, Maedler K (2021) Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies. Cell Rep Med 2(8):100371. https:\/\/doi.org\/10.1016\/j.xcrm.2021.100371","journal-title":"Cell Rep Med"},{"key":"6359_CR52","doi-asserted-by":"publisher","first-page":"104334","DOI":"10.1016\/j.jcv.2020.104334","volume":"128","author":"A Honkimaa","year":"2020","unstructured":"Honkimaa A, Sioofy-Khojine AB, Oikarinen S, Bertin A, Hober D, Hy\u00f6ty H (2020) Eradication of persistent coxsackievirus B infection from a pancreatic cell line with clinically used antiviral drugs. J Clin Virol 128:104334. https:\/\/doi.org\/10.1016\/j.jcv.2020.104334","journal-title":"J Clin Virol"},{"issue":"3","key":"6359_CR53","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1182\/blood.V84.3.823.823","volume":"84","author":"T Vuorinen","year":"1994","unstructured":"Vuorinen T, Vainionp\u00e4\u00e4 R, Kettinen H, Hyypi\u00e4 T (1994) Coxsackievirus B3 infection in human leukocytes and lymphoid cell lines. Blood 84(3):823\u2013829. https:\/\/doi.org\/10.1182\/blood.V84.3.823.823","journal-title":"Blood"},{"issue":"4","key":"6359_CR54","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/S0002-9440(10)65223-6","volume":"155","author":"I Mena","year":"1999","unstructured":"Mena I, Perry CM, Harkins S, Rodriguez F, Gebhard J, Whitton JL (1999) The role of B lymphocytes in coxsackievirus B3 infection. Am J Pathol 155(4):1205\u20131215. https:\/\/doi.org\/10.1016\/S0002-9440(10)65223-6","journal-title":"Am J Pathol"},{"issue":"12","key":"6359_CR55","doi-asserted-by":"publisher","first-page":"9018","DOI":"10.1128\/jvi.70.12.9018-9023.1996","volume":"70","author":"T Vuorinen","year":"1996","unstructured":"Vuorinen T, Vainionp\u00e4\u00e4 R, Vanharanta R, Hyypi\u00e4 T (1996) Susceptibility of human bone marrow cells and hematopoietic cell lines to coxsackievirus B3 infection. J Virol 70(12):9018\u20139023. https:\/\/doi.org\/10.1128\/jvi.70.12.9018-9023.1996","journal-title":"J Virol"},{"issue":"10","key":"6359_CR56","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1007\/s00125-022-05753-y","volume":"65","author":"AB Sioofy-Khojine","year":"2022","unstructured":"Sioofy-Khojine AB, Richardson SJ, Locke JM et al (2022) Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage. Diabetologia 65(10):1701\u20131709. https:\/\/doi.org\/10.1007\/s00125-022-05753-y","journal-title":"Diabetologia"},{"issue":"1","key":"6359_CR57","doi-asserted-by":"publisher","first-page":"6466","DOI":"10.1038\/s41467-024-50936-3","volume":"15","author":"RE Baker","year":"2024","unstructured":"Baker RE, Yang W, Vecchi GA, Takahashi S (2024) Increasing intensity of enterovirus outbreaks projected with climate change. Nat Commun 15(1):6466. https:\/\/doi.org\/10.1038\/s41467-024-50936-3","journal-title":"Nat Commun"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06359-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-025-06359-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06359-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T15:05:35Z","timestamp":1747062335000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-025-06359-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":57,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["6359"],"URL":"https:\/\/doi.org\/10.1007\/s00125-025-06359-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.09.11.24313112","asserted-by":"object"}]},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]},"assertion":[{"value":"25 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors wish to thank all families associated with organ donation for research purposes for their gift that made efforts like those in this programme possible. In addition, appreciation is given to the organ procurement organisations who make the nPOD programme possible. Part of the data has been included in the PhD thesis (2019) of J.E. Laiho (ISBN:978-952-03-1031-8).The authors would like to thank J. Ilom\u00e4ki, T. Kuusela and M. Ovaskainen (Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland) for technical assistance. The authors thank all the members of the nPOD-Virus group. A list is included as electronic supplementary material (\n                      \n                      ).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Data generated and analysed during this study are available through the corresponding author upon request.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This study was supported by Breakthrough T1D (formerly known as JDRF) grants for the nPOD-Virus Group, JDRF 25-2012-516 and JDRF 25-2012-770, as well as the European Commission (Persistent Virus Infection in Diabetes Network [PEVNET], Frame Programme 7, contract no. 261441). JEL and MO were supported by grants from Sakari and P\u00e4ivikki Sohlberg\u2019s Foundation, Finland and Yrj\u00f6 Jahnsson\u2019s Foundation, Finland. JEL was also supported by the grants from The Diabetes Research Foundation in Finland and Finnish Cultural foundation. HH has additionally received funding from the Sigrid Juselius Foundation, European Foundation for the Study of Diabetes (grant no. 97013) and the Academy of Finland (grant no. 288671), which contributed to this work. REL also was funded by NIH grant R01-AI50237. The support of the Global Virus Network (GVN; University of Maryland, Baltimore, USA) is gratefully acknowledged. This research was performed with support from the Network for Pancreatic Organ donors with Diabetes (nPOD; RRID:SCR_014641), a collaborative type 1 diabetes research project supported by Breakthrough T1D (formerly known as JDRF) (nPOD: 5-SRA-2018-557-Q-R) and The Leona M. & Harry B. Helmsley Charitable Trust (grant no. 2018PG-T1D053, G-2108-04793). The content and views expressed are the responsibility of the authors and do not necessarily reflect the official view of nPOD. Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at\n                      \n                      .","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"HH is a board member and stock owner of Vactech Oy, a Finnish biotech company that has contributed to the development of a coxsackie B virus vaccine. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"AP, SO, JEL, HH, VP, JFP and AT were responsible for the overall design of the study. SO was responsible for the virus PCR and sequencing analyses at Tampere laboratory, and AR and REL were responsible for the virus PCR and sequencing analyses at BCM. SM, DD, ICG, JB and VP contributed to the RNA-Seq analyses at UCL. MCR and JFP were responsible for the WGS sequencing at BCM. AT was responsible for the virus propagation studies at the Varese laboratory. MO and JEL performed the overall data analyses. JEL, SO, SM and MO were the primary contributors in the preparation of the manuscript. All authors contributed to data interpretation and discussion, reviewed the manuscript and approved the final version. JEL is the guarantor of this work and, as such, has full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}