{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:37:09Z","timestamp":1788784629311,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> A 25-base pair (25bp) intronic deletion in the <jats:italic>MYBPC3<\/jats:italic> gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> As a pilot study, 10 asymptomatic SA carriers of the <jats:italic>MYBPC3<\/jats:italic><jats:sup>\u039425bp<\/jats:sup> variant (52.9 \u00b1 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 \u00b1 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of \u039425bp had significantly higher LV ejection fraction (%) (CI: 4.57 \u00b1 1.93; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), LV outflow tract peak velocity (m\/s) (CI: 0.19 \u00b1 0.07; <jats:italic>p<\/jats:italic> &amp;lt; 0.0001), and higher aortic valve (AV) peak velocity (m\/s) (CI: 0.103 \u00b1 0.08; <jats:italic>p<\/jats:italic> = 0.01) in comparison to NCs, and E\/A ratio, a marker of diastolic compliance, was significantly lower in \u039425bp carriers (CI: 0.107 \u00b1 0.102; <jats:italic>p<\/jats:italic> = 0.038). Interestingly, LV end-diastolic diameter (LVID<jats:sub>dia<\/jats:sub>) was augmented in NCs in response to stress, while it did not increase in \u039425bp carriers (CI: 0.239 \u00b1 0.125; <jats:italic>p<\/jats:italic> = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m\/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; <jats:italic>p<\/jats:italic> = 0.0001), suggesting right ventricle functional differences between the two groups.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> These data support that <jats:italic>MYBPC3<\/jats:italic><jats:sup>\u039425bp<\/jats:sup> is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.<\/jats:p>","DOI":"10.3389\/fcvm.2021.766339","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T08:39:03Z","timestamp":1640248743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["South Asian-Specific MYBPC3\u039425bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress"],"prefix":"10.3389","volume":"8","author":[{"given":"Sholeh","family":"Bazrafshan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Sibilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saavia","family":"Girgla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Kumar","family":"Viswanathan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan J.","family":"Puckelwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiranpal S.","family":"Sangha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit R.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashhood","family":"Kakroo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Jandarov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Rubinstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"McNally","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakthivel","family":"Sadayappan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1161\/01.CIR.92.4.785","article-title":"Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study Coronary Artery Risk Development in (Young) Adults","volume":"92","author":"Maron","year":"1995","journal-title":"Circulation."},{"key":"B2","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/0002-9149(94)90337-9","article-title":"Prevalence of hypertrophic cardiomyopathy in an outpatient population referred for echocardiographic study","volume":"73","author":"Maron","year":"1994","journal-title":"Am J Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1016\/j.jacc.2015.01.019","article-title":"New perspectives on the prevalence of hypertrophic cardiomyopathy","volume":"65","author":"Semsarian","year":"2015","journal-title":"J Am Coll Cardiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e533","DOI":"10.1161\/CIR.0000000000000938","article-title":"2020 AHA\/ACC Guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: a report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"142","author":"Ommen","year":"2020","journal-title":"Circulation."},{"key":"B5","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/ng0493-333","article-title":"A disease locus for familial hypertrophic cardiomyopathy maps to chromosome 1q3","volume":"3","author":"Watkins","year":"1993","journal-title":"Nat Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/ng1295-434","article-title":"Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy","volume":"11","author":"Watkins","year":"1995","journal-title":"Nat Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1038\/ng1295-438","article-title":"Cardiac myosin binding protein-C gene splice acceptor site mutation is associated with familial hypertrophic cardiomyopathy","volume":"11","author":"Bonne","year":"1995","journal-title":"Nat Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1050-1738(97)00144-8","article-title":"Cardiac Myosin-binding protein C and hypertrophic cardiomyopathy","volume":"8","author":"Carrier","year":"1998","journal-title":"Trends Cardiovasc Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1056\/NEJM199703133361107","article-title":"The management of hypertrophic cardiomyopathy","volume":"336","author":"Spirito","year":"1997","journal-title":"N Engl J Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1161\/CIRCRESAHA.110.231670","article-title":"In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament","volume":"108","author":"Harris","year":"2011","journal-title":"Circ Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1161\/CIR.0b013e318223e230","article-title":"2011 ACCF\/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: executive summary: a report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines","volume":"124","author":"Gersh","year":"2011","journal-title":"Circulation."},{"key":"B12","doi-asserted-by":"publisher","first-page":"H807","DOI":"10.1152\/ajpheart.00913.2013","article-title":"Contractile dysfunction in a mouse model expressing a heterozygous MYBPC3 mutation associated with hypertrophic cardiomyopathy","volume":"306","author":"Barefield","year":"2014","journal-title":"Am J Physiol Heart Circ Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00424-013-1417-7","article-title":"MYBPC3's alternate ending: consequences and therapeutic implications of a highly prevalent 25 bp deletion mutation","volume":"466","author":"Kuster","year":"2014","journal-title":"Pflugers Arch."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1126\/science.1223602","article-title":"Molecular mechanics of cardiac myosin-binding protein C in native thick filaments","volume":"337","author":"Previs","year":"2012","journal-title":"Science."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1056\/NEJMoa075463","article-title":"Shared genetic causes of cardiac hypertrophy in children and adults","volume":"358","author":"Morita","year":"2008","journal-title":"N Engl J Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1056\/NEJM199804303381802","article-title":"Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy","volume":"338","author":"Niimura","year":"1998","journal-title":"N Engl J Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1161\/01.CIR.101.12.1396","article-title":"A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance","volume":"101","author":"Moolman","year":"2000","journal-title":"Circulation."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1161\/CIRCULATIONAHA.114.011207","article-title":"Nationwide study on hypertrophic cardiomyopathy in Iceland: evidence of a MYBPC3 founder mutation","volume":"130","author":"Adalsteinsdottir","year":"2014","journal-title":"Circulation."},{"key":"B19","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1161\/CIRCGENETICS.113.000448","article-title":"Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy","volume":"7","author":"Helms","year":"2014","journal-title":"Circ Cardiovasc Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2593","DOI":"10.1093\/eurheartj\/ehp306","article-title":"Disease penetrance and risk stratification for sudden cardiac death in asymptomatic hypertrophic cardiomyopathy mutation carriers","volume":"30","author":"Michels","year":"2009","journal-title":"Eur Heart J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1161\/CIRCGENETICS.111.960831","article-title":"Cardiac myosin binding protein-C mutations in families with hypertrophic cardiomyopathy: disease expression in relation to age, gender, and long term outcome","volume":"5","author":"Page","year":"2012","journal-title":"Circ Cardiovasc Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1161\/hc0402.102990","article-title":"Sarcomere protein gene mutations in hypertrophic cardiomyopathy of the elderly","volume":"105","author":"Niimura","year":"2002","journal-title":"Circulation."},{"key":"B23","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1001\/jama.1996.03540030033028","article-title":"Sudden death in young competitive athletes. Clinical, demographic, and pathological profiles","volume":"276","author":"Maron","year":"1996","journal-title":"JAMA."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/0735-1097(95)00390-8","article-title":"Phenotypic spectrum and patterns of left ventricular hypertrophy in hypertrophic cardiomyopathy: morphologic observations and significance as assessed by two-dimensional echocardiography in 600 patients","volume":"26","author":"Klues","year":"1995","journal-title":"J Am Coll Cardiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.amjmed.2003.10.012","article-title":"Hypertrophic cardiomyopathy: an important global disease","volume":"116","author":"Maron","year":"2004","journal-title":"Am J Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/ng.309","article-title":"A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia","volume":"41","author":"Dhandapany","year":"2009","journal-title":"Nat Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1001\/jamacardio.2018.0618","article-title":"Association of cardiomyopathy with MYBPC3 D389V and MYBPC3Delta25bpIntronic deletion in South Asian Descendants","volume":"3","author":"Viswanathan","year":"2018","journal-title":"JAMA Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/s12551-020-00725-1","article-title":"Genetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3(Delta25bp) variant","volume":"12","author":"Arif","year":"2020","journal-title":"Biophys Rev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/S0022-2828(03)00050-6","article-title":"Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy","volume":"35","author":"Waldmuller","year":"2003","journal-title":"J Mol Cell Cardiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e002986","DOI":"10.1161\/CIRCGEN.120.002986","article-title":"South Asian-specific MYBPC3(Delta25bp) intronic deletion and its role in cardiomyopathies and heart failure","volume":"13","author":"Sadayappan","year":"2020","journal-title":"Circ Genom Precis Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"e002783","DOI":"10.1161\/CIRCGEN.119.002783","article-title":"Reevaluation of the South Asian MYBPC3(Delta25bp) intronic deletion in hypertrophic cardiomyopathy","volume":"13","author":"Harper","year":"2020","journal-title":"Circ Genom Precis Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1093\/bioinformatics\/btu071","article-title":"Supercomputing for the parallelization of whole genome analysis","volume":"30","author":"Puckelwartz","year":"2014","journal-title":"Bioinformatics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG laboratory quality assurance committee. standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"5","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B34","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1161\/CIRCGENETICS.109.862128","article-title":"Echocardiographic strain imaging to assess early and late consequences of sarcomere mutations in hypertrophic cardiomyopathy","volume":"2","author":"Ho","year":"2009","journal-title":"Circ Cardiovasc Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jcmg.2008.08.003","article-title":"Diastolic abnormalities as the first feature of hypertrophic cardiomyopathy in Dutch myosin-binding protein C founder mutations","volume":"2","author":"Michels","year":"2009","journal-title":"JACC Cardiovasc Imaging."},{"key":"B36","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1161\/CIRCHEARTFAILURE.112.967026","article-title":"Patterns of disease progression in hypertrophic cardiomyopathy: an individualized approach to clinical staging","volume":"5","author":"Olivotto","year":"2012","journal-title":"Circ Heart Fail."},{"key":"B37","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/s11010-011-1077-x","article-title":"A low prevalence of MYH7\/MYBPC3 mutations among familial hypertrophic cardiomyopathy patients in India","volume":"360","author":"Bashyam","year":"2012","journal-title":"Mol Cell Biochem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/j.1469-1809.2010.00561.x","article-title":"Limited distribution of a cardiomyopathy-associated variant in India","volume":"74","author":"Simonson","year":"2010","journal-title":"Ann Hum Genet."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e24123","DOI":"10.1371\/journal.pone.0024123","article-title":"Association of 25 bp deletion in MYBPC3 gene with left ventricle dysfunction in coronary artery disease patients","volume":"6","author":"Srivastava","year":"2011","journal-title":"PLoS ONE."},{"key":"B40","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ahj.2016.10.010","article-title":"Safety profile and utility of treadmill exercise in patients with high-gradient hypertrophic cardiomyopathy","volume":"184","author":"Sorensen","year":"2017","journal-title":"Am Heart J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jcmg.2013.08.010","article-title":"Exercise echocardiography in asymptomatic HCM: exercise capacity, and not LV outflow tract gradient predicts long-term outcomes","volume":"7","author":"Desai","year":"2014","journal-title":"JACC Cardiovasc Imaging."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1001\/jama.290.12.1600","article-title":"Ability of exercise testing to predict cardiovascular and all-cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study","volume":"290","author":"Mora","year":"2003","journal-title":"JAMA."},{"key":"B43","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1056\/NEJMoa011858","article-title":"Exercise capacity and mortality among men referred for exercise testing","volume":"346","author":"Myers","year":"2002","journal-title":"N Engl J Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s12041-016-0623-4","article-title":"Role of common sarcomeric gene polymorphisms in genetic susceptibility to left ventricular dysfunction","volume":"95","author":"Kumar","year":"2016","journal-title":"J Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.3390\/cells10061326","article-title":"The C0-C1f region of cardiac myosin binding protein-C induces pro-inflammatory responses in fibroblasts via TLR4 signaling","volume":"10","author":"Yogeswaran","year":"2021","journal-title":"Cells."},{"key":"B46","doi-asserted-by":"publisher","first-page":"5855","DOI":"10.1074\/jbc.M114.607911","article-title":"A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction","volume":"290","author":"Kuster","year":"2015","journal-title":"J Biol Chem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/j.athoracsur.2019.03.072","article-title":"Cardiac myosin-binding protein c release profile after cardiac surgery in intensive care unit","volume":"108","author":"Chen","year":"2019","journal-title":"Ann Thorac Surg."},{"key":"B48","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s00424-018-2226-9","article-title":"Allelic imbalance and haploinsufficiency in MYBPC3-linked hypertrophic cardiomyopathy","volume":"471","author":"Glazier","year":"2019","journal-title":"Pflugers Arch."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1986","DOI":"10.1093\/cvr\/cvz111","article-title":"Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy","volume":"115","author":"Kuster","year":"2019","journal-title":"Cardiovasc Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1161\/01.RES.0000036750.81083.83","article-title":"Identification of novel interactions between domains of Myosin binding protein-C that are modulated by hypertrophic cardiomyopathy missense mutations","volume":"91","author":"Moolman-Smook","year":"2002","journal-title":"Circ Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1172\/JCI7377","article-title":"Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice","volume":"104","author":"McConnell","year":"1999","journal-title":"J Clin Invest."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1093\/cvr\/cvz167","article-title":"Myosin binding protein-C and hypertrophic cardiomyopathy: role of altered C10 domain","volume":"115","author":"Hossain","year":"2019","journal-title":"Cardiovasc Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e0180064","DOI":"10.1371\/journal.pone.0180064","article-title":"MYBPC3 mutations are associated with a reduced super-relaxed state in patients with hypertrophic cardiomyopathy","volume":"12","author":"McNamara","year":"2017","journal-title":"PLoS ONE."},{"key":"B54","doi-asserted-by":"publisher","first-page":"eaat1199","DOI":"10.1126\/scitranslmed.aat1199","article-title":"Hypertrophic cardiomyopathy mutations in MYBPC3 dysregulate myosin","volume":"11","author":"Toepfer","year":"2019","journal-title":"Sci. Transl. Med"},{"key":"B55","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1161\/res.125.suppl_1.772","article-title":"The highly prevalent 25bp intronic deletion of MYBPC3 is benign under baseline conditions","volume":"125","author":"McNamara","year":"2019","journal-title":"Circ Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.jacc.2005.04.043","article-title":"Gender-related differences in the clinical presentation and outcome of hypertrophic cardiomyopathy","volume":"46","author":"Olivotto","year":"2005","journal-title":"J Am Coll Cardiol."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.766339\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T08:39:09Z","timestamp":1640248749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.766339\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":56,"alternative-id":["10.3389\/fcvm.2021.766339"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.766339","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]},"article-number":"766339"}}