{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:42:16Z","timestamp":1784612536307,"version":"3.55.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1-2","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/05586-2"],"award-info":[{"award-number":["2022\/05586-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/00945-1"],"award-info":[{"award-number":["2019\/00945-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Ministry of Science, Technology and Innovation | Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["308609\/2018-2"],"award-info":[{"award-number":["308609\/2018-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pharmacogenomics J"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1038\/s41397-025-00363-4","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T18:29:46Z","timestamp":1740421786000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CYP3A5 and POR gene polymorphisms as predictors of infection and graft rejection in post-liver transplant patients treated with tacrolimus - a cohort study"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9440-8255","authenticated-orcid":false,"given":"Graziella D\u2019 Agostino Ribeiro","family":"Naldi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane Boccoli","family":"Minari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thales D. M.","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Fossaluza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2549-1311","authenticated-orcid":false,"given":"Nicholas Wagner","family":"Eugenio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Alves","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8379-0452","authenticated-orcid":false,"given":"Guilherme H.","family":"Greg\u00f3rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Nacif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Augusto Carneiro","family":"D Albuquerque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"di Lazzaro Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo Luiz Rachid","family":"Can\u00e7ado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzane Kioko","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"363_CR1","unstructured":"Centers for Disease Control and Prevention: Chronic liver disease cirrhosis. 2020. https:\/\/www.cdc.gov\/nchs\/fastats\/liver-disease.htm 2020."},{"key":"363_CR2","first-page":"100731","volume":"33","author":"J Guimaraes","year":"2023","unstructured":"Guimaraes J, Mesquita J, Kimura T, Oliveira A, Leite M, Oliveria A. Burden of liver diseases in Brazil, 1996-2022: epidemiology and impact to public healthcare. Lancet Reg Health Am. 2023;33:100731.","journal-title":"Lancet Reg Health Am"},{"key":"363_CR3","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1111\/tri.13358","volume":"31","author":"R Adam","year":"2018","unstructured":"Adam R, Karam V, Cailliez V, O Grady JG, Mirza D, Cherqui D, et al. 2018 annual report of the european liver transplant registry (ELTR) \u2013 50-year evolution of liver transplantation. Transpl Int. 2018;31:1293\u2013317.","journal-title":"Transpl Int"},{"key":"363_CR4","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1111\/aor.13551","volume":"44","author":"Y Bentata","year":"2019","unstructured":"Bentata Y. Tacrolimus: 20 years of use in adult kidney transplantation. What we should know about its nephrotoxicity. Artif Organs. 2019;44:140\u201352.","journal-title":"Artif Organs"},{"key":"363_CR5","doi-asserted-by":"publisher","first-page":"101681","DOI":"10.1016\/j.bpg.2020.101681","volume":"46","author":"T Di Maira","year":"2020","unstructured":"Di Maira T, Little EC, Berenguer M. Immunosuppression in liver transplant. Best Pract Res Clin Gastroenterol. 2020;46:101681.","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"363_CR6","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.jhep.2015.10.006","volume":"64","author":"European Association for the Study of the Liver","year":"2016","unstructured":"European Association for the Study of the Liver. EASL clinical practice guidelines: liver transplantation. J Hepatol. 2016;64:433\u201385.","journal-title":"J Hepatol"},{"key":"363_CR7","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1111\/ajt.14623","volume":"18","author":"LB Jeng","year":"2018","unstructured":"Jeng LB, Lee SG, Soin AS, Lee WC, Suh KS, Joo DJ, et al. Am J Transplant. 2018;18:1435\u201346.","journal-title":"Am J Transplant"},{"key":"363_CR8","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1002\/lt.23522","volume":"18","author":"ML Weber","year":"2012","unstructured":"Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl. 2012;18:1290\u2013301.","journal-title":"Liver Transpl"},{"key":"363_CR9","doi-asserted-by":"publisher","first-page":"101762","DOI":"10.1016\/j.bpg.2021.101762","volume":"54-55","author":"J Noble","year":"2021","unstructured":"Noble J, Terrec F, Malvezzi P, Rostaing L. Adverse effects of immunosuppression after liver transplantation. Best Pract Res Clin Gastroenterol. 2021;54-55:101762.","journal-title":"Best Pract Res Clin Gastroenterol"},{"key":"363_CR10","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1111\/tri.12118","volume":"26","author":"A Rub\u00edn","year":"2013","unstructured":"Rub\u00edn A, S\u00e1nchez-Montes C, Aguilera V, Juan FS, Ferrer I, Moya A, et al. Long-term outcome of \u201clong-term liver transplant survivors\u201d. Transpl Int. 2013;26:740\u201350.","journal-title":"Transpl Int"},{"key":"363_CR11","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.3390\/pharmaceutics14091755","volume":"14","author":"M Brunet","year":"2022","unstructured":"Brunet M, Pastor-Anglada M. Insights into the pharmacogenetics of tacrolimus pharmacokinetics and pharmacodynamics. Pharmaceutics. 2022;14:1755.","journal-title":"Pharmaceutics"},{"key":"363_CR12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.5500\/wjt.v10.i5.90","volume":"10","author":"M Salvadori","year":"2020","unstructured":"Salvadori M, Tsalouchos A. Pharmacogenetics of immunosuppressant drugs: A new aspect for individualized therapy. World J Transplant. 2020;10:90\u2013103.","journal-title":"World J Transplant"},{"key":"363_CR13","doi-asserted-by":"publisher","first-page":"4454","DOI":"10.3390\/jcm12134454","volume":"12","author":"S Turolo","year":"2023","unstructured":"Turolo S, Edefonti A, Syren ML, Montini G. Pharmacogenomics of old and new immunosuppressive drugs for precision medicine in kidney transplantation. J Clin Med. 2023;12:4454.","journal-title":"J Clin Med"},{"key":"363_CR14","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1002\/cpt.2563","volume":"112","author":"C Rodriguez-Antona","year":"2022","unstructured":"Rodriguez-Antona C, Savieo JL, Lauschke VM, Sangkuhl K, Dr\u00f6gem\u00f6ller BI, Wang D, et al. PharmVar GeneFocus: CYP3A5. Clin Pharmacol Ther. 2022;112:1159\u201371.","journal-title":"Clin Pharmacol Ther"},{"key":"363_CR15","doi-asserted-by":"publisher","first-page":"342","DOI":"10.2174\/1389200219666180101104159","volume":"19","author":"K Schutte-Nutgen","year":"2018","unstructured":"Schutte-Nutgen K, Tholking G, Suwelack B, Reuter S. Tacrolimus \u2013 pharmacokinetic considerations for clinicians. Curr Drug Metab. 2018;19:342\u201350.","journal-title":"Curr Drug Metab"},{"key":"363_CR16","doi-asserted-by":"publisher","first-page":"141","DOI":"10.2165\/11317350-000000000-00000","volume":"49","author":"CE Staatz","year":"2010","unstructured":"Staatz CE, Goodman LK, Tett SE. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clin Pharmacokinet. 2010;49:141\u201375.","journal-title":"Clin Pharmacokinet"},{"key":"363_CR17","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/cpt.113","volume":"98","author":"KA Birdwell","year":"2015","unstructured":"Birdwell KA, Decker B, Barbarino JM, Peterson JF, Stein CM, Sadee W, et al. Clinical pharmacogenetics implementation consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clin Pharmacol Ther. 2015;98:19\u201324.","journal-title":"Clin Pharmacol Ther"},{"key":"363_CR18","doi-asserted-by":"publisher","first-page":"e13306","DOI":"10.1111\/ctr.13306","volume":"32","author":"F Hendijani","year":"2018","unstructured":"Hendijani F, Azarpira N, Kaviani M. Effect of CYP3A5*1 expression on tacrolimus required dose after liver transplantation: a systematic review and meta-analysis. Clin Transplant. 2018;32:e13306.","journal-title":"Clin Transplant"},{"key":"363_CR19","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/FPC.0000000000000060","volume":"24","author":"M Uesugi","year":"2014","unstructured":"Uesugi M, Kikuchi M, Shinke H, Omura T, Yonezawa A, Matsubara K, et al. Impact of cytochrome P450 3A5 polymorphism in graft livers on the frequency of acute cellular rejection in living-donor liver transplantation. Pharmacogenet Genomics. 2014;24:356\u201366.","journal-title":"Pharmacogenet Genomics"},{"key":"363_CR20","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1098\/rstb.2005.1693","volume":"360","author":"RR Shah","year":"2005","unstructured":"Shah RR. Pharmacogenetics in drug regulation: promise, potential and pitfalls. Philos Trans R Soc Lond B Biol Sci. 2005;360:1617\u201338.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"363_CR21","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1097\/TP.0000000000001651","volume":"101","author":"JM Neuberger","year":"2017","unstructured":"Neuberger JM, Bechstein WO, Kuypers DRJ, Burra P, Citterio F, De Geest S, et al. Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the consensus on managing modifiable risk in transplantation (COMMIT) group. Transplantation. 2017;101:S1\u201356.","journal-title":"Transplantation"},{"key":"363_CR22","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.3748\/wjg.v26.i12.1273","volume":"26","author":"T Kelava","year":"2020","unstructured":"Kelava T, Turcic P, Markotic A, Ostojic A, Sisl D, Mrzljak A. Importance of genetic polymorphisms in liver transplantation outcomes. World J Gastroenterol. 2020;26:1273\u201385.","journal-title":"World J Gastroenterol"},{"key":"363_CR23","doi-asserted-by":"publisher","unstructured":"Langman L, Van Gelder T, Van Schaik RHN Pharmacogenomics aspect of immunosuppressant therapy. Personalized Immunosuppression in Transplantation. 2016:109-24. https:\/\/doi.org\/10.1016\/B978-0-12-800885-0.00005-9.","DOI":"10.1016\/B978-0-12-800885-0.00005-9"},{"key":"363_CR24","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3390\/pharmaceutics14020261","volume":"14","author":"DH Lee","year":"2022","unstructured":"Lee DH, Lee H, Yoon HY, Yee J, Gwak HS. Association of P450 oxidoreductase gene polymorphism with tacrolimus pharmacokinetics in renal transplant recipients: a systematic review and meta-analysis. Pharmaceutics. 2022;14:261.","journal-title":"Pharmaceutics"},{"key":"363_CR25","first-page":"1004","volume":"13","author":"M Naslavsky","year":"2022","unstructured":"Naslavsky M, Scliar M, Yamamoto G, Wang J, Zverinova S, Karp T, et al. Whole-genome sequencing of 1171 elderly admixed individuals from Brazil. Nature. 2022;13:1004.","journal-title":"Nature"},{"key":"363_CR26","doi-asserted-by":"crossref","unstructured":"Elens L, Hesselink DA, Bouamar R, Budde K, De Fijter JW, De Meyer M, et al. Impact of POR*28 on the pharmacokinetics of tacrolimus and cyclosporine a in renal transplant patients. 2014. http:\/\/www.drug-monitoring.com. Accessed 15 jun 2022.","DOI":"10.1097\/FTD.0b013e31829da6dd"},{"key":"363_CR27","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3390\/jpm12050823","volume":"12","author":"K Sridharan","year":"2022","unstructured":"Sridharan K, Shah S, Jassim A, Hammad M, Al Gadhban JE, Al Segai O. Evaluation of pharmacogenetics of drug-metabolizing enzymes and drug efflux transporter in renal transplants receiving immunosuppressants. J Pers Med. 2022;12:823.","journal-title":"J Pers Med"},{"key":"363_CR28","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.3390\/ijms21072287","volume":"21","author":"T Nakamura","year":"2020","unstructured":"Nakamura T, Fukuda M, Matsukane R, Suetsugu K, Harada N, Yoshizumi T, et al. Influence of POR*28 polymorphisms on 5*3-associated variations in tacrolimus blood levels at an early stage after liver transplantation. Int J Mol Sci. 2020;21:2287.","journal-title":"Int J Mol Sci"},{"key":"363_CR29","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1002\/jcph.154","volume":"53","author":"MA G\u00f3mez-Bravo","year":"2013","unstructured":"G\u00f3mez-Bravo MA, Salcedo M, Fondevila C, Suarez F, Castellote J, Rufian S, et al. Impact of donor and recipient CYP3A5 and ABCB1 genetic polymorphisms on tacrolimus dosage requirements and rejection in caucasian spanish liver transplant patients. J Clin Pharmacol. 2013;53:1146\u201354.","journal-title":"J Clin Pharmacol"},{"key":"363_CR30","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.therap.2016.09.016","volume":"72","author":"JB Woillard","year":"2017","unstructured":"Woillard JB, Chouchana L, Picard N, Loriot MA. Pharmacogenetics of immunosuppressants: state of the art and clinical implementation \u2013 recommendations from the french national network of pharmacogenetics (RNPGx). Therapie. 2017;72:285\u201399.","journal-title":"Therapie"},{"key":"363_CR31","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1097\/FTD.0000000000000640","volume":"41","author":"M Brunet","year":"2019","unstructured":"Brunet M, Van Gelder T, \u00c5sberg A, Haufroid V, Hesselink DA, Langman L, et al. Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report. Ther Drug Monit. 2019;41:261\u2013307.","journal-title":"Ther Drug Monit"},{"key":"363_CR32","unstructured":"U.S Food & Drug Administration. https:\/\/www.fda.gov\/medical-devices\/precision-medicine\/table-pharmacogenetic-associations. 2022."},{"key":"363_CR33","doi-asserted-by":"publisher","first-page":"146007","DOI":"10.1016\/j.gene.2021.146007","volume":"809","author":"Y Dong","year":"2022","unstructured":"Dong Y, Xu Q, Li R, Tao Y, Zhang Q, Li J, et al. CYP3A7, CYP3A4, and CYP3A5 genetic polymorphisms in recipients rather than donors influence tacrolimus concentrations in the early stages after liver transplantation. Gene. 2022;809:146007.","journal-title":"Gene"},{"key":"363_CR34","doi-asserted-by":"publisher","first-page":"207","DOI":"10.2217\/pgs-2022-0180","volume":"24","author":"N Maseko","year":"2023","unstructured":"Maseko N, Yang S, Li C, Zhang S, Wang R, Zhang Y, et al. Impact of genetic polymorphisms on tacrolimus trough blood concentration in Chinese liver transplant recipients. Pharmacogenomics. 2023;24:207\u201317.","journal-title":"Pharmacogenomics"},{"key":"363_CR35","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.1111\/bcp.13980","volume":"85","author":"S Anutrakulchai","year":"2019","unstructured":"Anutrakulchai S, Pongskul C, Kritmetapak K, Limwattananon C, Vannaprasaht S. Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 genotype-guided doses in renal transplantation patients. Br J Clin Pharmacol. 2019;85:1964\u201373.","journal-title":"Br J Clin Pharmacol"},{"key":"363_CR36","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1399-0012.1997.tb00812.x","volume":"11","author":"SR Katari","year":"1997","unstructured":"Katari SR, Magnone M, Shapiro R, Jordan M, Scantlebury V, Vivas C, et al. Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. Clin Transplant. 1997;11:237\u201342.","journal-title":"Clin Transplant"},{"key":"363_CR37","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1097\/TP.0000000000001394","volume":"100","author":"M Debette-Gratien","year":"2016","unstructured":"Debette-Gratien M, Woillard JB, Picard N, Sebagh M, Loustaud-Ratti V, Sautereau D, et al. Influence of donor and recipient CYP3A4, CYP3A5, and ABCB1 genotypes on clinical outcomes and nephrotoxicity in liver transplant recipients. Transplantation. 2016;100:2129\u201337.","journal-title":"Transplantation"},{"key":"363_CR38","doi-asserted-by":"publisher","first-page":"575","DOI":"10.2217\/pgs-2020-0013","volume":"21","author":"V Kim","year":"2020","unstructured":"Kim V, Wal TV, Nishi MY, Montenegro LR, Carrilho FJ, Hoshida Y, et al. Brazilian cohort and genes encoding for drug-metabolizing enzymes and drug transporters. Pharmacogenomics. 2020;21:575\u201386.","journal-title":"Pharmacogenomics"}],"container-title":["The Pharmacogenomics Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41397-025-00363-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41397-025-00363-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41397-025-00363-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T02:41:38Z","timestamp":1745376098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41397-025-00363-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":38,"journal-issue":{"issue":"1-2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["363"],"URL":"https:\/\/doi.org\/10.1038\/s41397-025-00363-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3399704\/v1","asserted-by":"object"}]},"ISSN":["1470-269X","1473-1150"],"issn-type":[{"value":"1470-269X","type":"print"},{"value":"1473-1150","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"assertion":[{"value":"29 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 January 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 February 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2025","order":4,"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"}},{"value":"FAPESP: 2019\/00945-1; CNPq: 308609\/2018-2; GDARN: CAPES Scholarship. The opinions, hypotheses, conclusions, or recommendations expressed in this material are the sole responsibility of the authors and do not necessarily reflect FAPESP\u2019s, CNPq\u2019s or CAPES\u2019s view.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Financial support statement"}}],"article-number":"4"}}