{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T13:37:30Z","timestamp":1783777050838,"version":"3.55.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Youth Science Fund Project of Fujian Provincial Maternity and Children\u2019s Hospital Maternity","award":["YCXQ 18-14"],"award-info":[{"award-number":["YCXQ 18-14"]}]},{"DOI":"10.13039\/501100003392","name":"Fujian Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2018J01235"],"award-info":[{"award-number":["2018J01235"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003392","name":"Fujian Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["2017J01238"],"award-info":[{"award-number":["2017J01238"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Etiopathogenesis of fetal ventriculomegaly is poorly understood. Associations between fetal isolated ventriculomegaly and copy number variations (CNVs) have been previously described. We investigated the correlations between fetal ventriculomegaly\u2014with or without other ultrasound anomalies\u2014and chromosome abnormalities. 222 fetuses were divided into four groups: (I) 103 (46.4%) cases with isolated ventriculomegaly, (II) 41 (18.5%) cases accompanied by soft markers, (III) 33 (14.9%) cases complicated with central nervous system (CNS) anomalies, and (IV) 45 (20.3%) cases with accompanying anomalies. Karyotyping and single nucleotide polymorphism (SNP) array were used in parallel. Karyotype abnormalities were identified in 15\/222 (6.8%) cases. Karyotype abnormalities in group I, II, III, and IV were 4\/103 (3.9%), 2\/41 (4.9%), 4\/33 (12.1%), and 5\/45 (11.1%), respectively. Concerning the SNP array analysis results, 31\/222 (14.0%) were CNVs, CNVs in groups I, II, III, and IV were 11\/103 (10.7%), 6\/41 (14.6%), 9\/33 (27.3%), and 5\/45 fetuses (11.1%), respectively. Detections of clinical significant CNVs were higher in non-isolated ventriculomegaly than in isolated ventriculomegaly (16.81% vs 10.7%, P\u2009=\u20090.19). SNP arrays can effectively identify CNVs in fetuses with ventriculomegaly and increase the abnormal chromosomal detection rate by approximately 7.2%, especially ventriculomegaly accompanied by CNS anomalies.<\/jats:p>","DOI":"10.1038\/s41598-021-83147-7","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:03:22Z","timestamp":1614942202000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Detection of copy number variation associated with ventriculomegaly in fetuses using single nucleotide polymorphism arrays"],"prefix":"10.1038","volume":"11","author":[{"given":"Huili","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aili","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangpu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"issue":"1","key":"83147_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jpeds.2012.12.084","volume":"163","author":"TZ Movsas","year":"2013","unstructured":"Movsas, T. Z. et al. Autism spectrum disorder is associated with ventricular enlargement in a low birth weight population. J. Pediatr. 163(1), 73\u201378 (2013).","journal-title":"J. Pediatr."},{"issue":"8","key":"83147_CR2","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1093\/cercor\/bht062","volume":"24","author":"V Kyriakopoulou","year":"2014","unstructured":"Kyriakopoulou, V. et al. Cortical overgrowth in fetuses with isolated ventriculomegaly. Cerebr. Cortex. 24(8), 2141\u20132150 (2014).","journal-title":"Cerebr. Cortex."},{"issue":"1","key":"83147_CR3","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3174\/ajnr.A1767","volume":"31","author":"PD Griffiths","year":"2010","unstructured":"Griffiths, P. D. et al. A prospective study of fetuses with isolated ventriculomegaly investigated by antenatal sonography and in utero MR imaging. AJNR Am. J. Neuroradiol. 31(1), 106\u2013111 (2010).","journal-title":"AJNR Am. J. Neuroradiol."},{"issue":"6","key":"83147_CR4","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1097\/AOG.0b013e3182732b53","volume":"120","author":"T Hannon","year":"2012","unstructured":"Hannon, T., Tennant, P. W., Rankin, J. & Robson, S. C. Epidemiology, natural history, progression, and postnatal outcome of severe fetal ventriculomegaly. Obstetr. Gynecol. 120(6), 1345\u20131353 (2012).","journal-title":"Obstetr. Gynecol."},{"issue":"10","key":"83147_CR5","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/pd.3945","volume":"32","author":"LG Shaffer","year":"2012","unstructured":"Shaffer, L. G. et al. Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies. Prenat. Diagn. 32(10), 976\u2013985 (2012).","journal-title":"Prenat. Diagn."},{"issue":"7","key":"83147_CR6","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1038\/ejhg.2012.253","volume":"21","author":"F Fiorentino","year":"2013","unstructured":"Fiorentino, F. et al. Chromosomal microarray analysis as a first-line test in pregnancies with a priori low risk for the detection of submicroscopic chromosomal abnormalities. Eur. J. Hum. Genet. EJHG. 21(7), 725\u2013730 (2013).","journal-title":"Eur. J. Hum. Genet. EJHG."},{"issue":"7339","key":"83147_CR7","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nature09884","volume":"471","author":"V Vacic","year":"2011","unstructured":"Vacic, V. et al. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature 471(7339), 499\u2013503 (2011).","journal-title":"Nature"},{"issue":"11","key":"83147_CR8","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1097\/GIM.0b013e3181f8baad","volume":"12","author":"M Manning","year":"2010","unstructured":"Manning, M. & Hudgins, L. Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet. Med. 12(11), 742\u2013745 (2010).","journal-title":"Genet. Med."},{"issue":"1","key":"83147_CR9","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/ng.1013","volume":"44","author":"J Elia","year":"2011","unstructured":"Elia, J. et al. Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Nat. Genet. 44(1), 78\u201384 (2011).","journal-title":"Nat. Genet."},{"issue":"6","key":"83147_CR10","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1002\/mgg3.477","volume":"6","author":"D Zhao","year":"2018","unstructured":"Zhao, D., Cai, A., Wang, B., Lu, X. & Meng, L. Presence of chromosomal abnormalities in fetuses with isolated ventriculomegaly on prenatal ultrasound in China. Mol. Genet. Genom. Med. 6(6), 1015\u20131020 (2018).","journal-title":"Mol. Genet. Genom. Med."},{"issue":"5","key":"83147_CR11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.3109\/01443615.2014.896885","volume":"34","author":"C Gezer","year":"2014","unstructured":"Gezer, C. et al. Chromosome abnormality incidence in fetuses with cerebral ventriculomegaly. J. Obstetr. Gynaecol. 34(5), 387\u2013391 (2014).","journal-title":"J. Obstetr. Gynaecol."},{"issue":"2","key":"83147_CR12","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2174\/1566524017666170303125529","volume":"17","author":"P Hu","year":"2017","unstructured":"Hu, P. et al. Copy number variations with isolated fetal ventriculomegaly. Curr. Mol. Med. 17(2), 133\u2013139 (2017).","journal-title":"Curr. Mol. Med."},{"key":"83147_CR13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13039-019-0425-5","volume":"12","author":"H Xue","year":"2019","unstructured":"Xue, H. et al. Molecular cytogenetic identification of small supernumerary marker chromosomes using chromosome microarray analysis. Mol. Cytogenet. 12, 13 (2019).","journal-title":"Mol. Cytogenet."},{"issue":"3","key":"83147_CR14","doi-asserted-by":"publisher","first-page":"103736","DOI":"10.1016\/j.ejmg.2019.103736","volume":"63","author":"SQ Zhang","year":"2020","unstructured":"Zhang, S. Q. et al. Intragenic CNTN4 copy number variants associated with a spectrum of neurobehavioral phenotypes. Eur. J. Med. Genet. 63(3), 103736 (2020).","journal-title":"Eur. J. Med. Genet."},{"key":"83147_CR15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s11689-016-9140-2","volume":"8","author":"RT Molenhuis","year":"2016","unstructured":"Molenhuis, R. T. et al. Limited impact of Cntn4 mutation on autism-related traits in developing and adult C57BL\/6J mice. J. Neurodev. Disord. 8, 6 (2016).","journal-title":"J. Neurodev. Disord."},{"issue":"2","key":"83147_CR16","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1002\/uog.7307","volume":"34","author":"K Melchiorre","year":"2009","unstructured":"Melchiorre, K., Bhide, A., Gika, A. D., Pilu, G. & Papageorghiou, A. T. Counseling in isolated mild fetal ventriculomegaly. Ultrasound Obstetr. Gynecol. 34(2), 212\u2013224 (2009).","journal-title":"Ultrasound Obstetr. Gynecol."},{"issue":"6","key":"83147_CR17","first-page":"789","volume":"32","author":"Z Zhang","year":"2015","unstructured":"Zhang, Z. et al. Chromosomal microarray analysis for lateral ventriculomegaly in fetus. Chin. J. Med. Genet. 32(6), 789\u2013792 (2015).","journal-title":"Chin. J. Med. Genet."},{"issue":"5","key":"83147_CR18","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1046\/j.1469-0705.1999.14050320.x","volume":"14","author":"G Pilu","year":"1999","unstructured":"Pilu, G. et al. The clinical significance of fetal isolated cerebral borderline ventriculomegaly: Report of 31 cases and review of the literature. Ultrasound Obstetr .Gynecol. 14(5), 320\u2013326 (1999).","journal-title":"Ultrasound Obstetr .Gynecol."},{"issue":"2","key":"83147_CR19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1002\/uog.12575","volume":"43","author":"MC de Wit","year":"2014","unstructured":"de Wit, M. C. et al. Additional value of prenatal genomic array testing in fetuses with isolated structural ultrasound abnormalities and a normal karyotype: A systematic review of the literature. Ultrasound Obstetr. Gynecol. 43(2), 139\u2013146 (2014).","journal-title":"Ultrasound Obstetr. Gynecol."},{"issue":"7","key":"83147_CR20","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/pd.88","volume":"21","author":"A Mercier","year":"2001","unstructured":"Mercier, A. et al. Isolated mild fetal cerebral ventriculomegaly: A retrospective analysis of 26 cases. Prenat. Diagn. 21(7), 589\u2013595 (2001).","journal-title":"Prenat. Diagn."},{"issue":"3","key":"83147_CR21","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1007\/s10048-019-00581-6","volume":"20","author":"MT Bonati","year":"2019","unstructured":"Bonati, M. T. et al. 9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression. Neurogenetics. 20(3), 145\u2013154 (2019).","journal-title":"Neurogenetics."},{"issue":"2","key":"83147_CR22","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1136\/jmedgenet-2014-102757","volume":"52","author":"W Hofmeister","year":"2015","unstructured":"Hofmeister, W. et al. CTNND2-a candidate gene for reading problems and mild intellectual disability. J. Med. Genet. 52(2), 111\u2013122 (2015).","journal-title":"J. Med. Genet."},{"issue":"2","key":"83147_CR23","doi-asserted-by":"publisher","first-page":"e0149189","DOI":"10.1371\/journal.pone.0149189","volume":"11","author":"C Lane","year":"2016","unstructured":"Lane, C., Milne, E. & Freeth, M. Cognition and behaviour in sotos syndrome: A systematic review. PLoS ONE 11(2), e0149189 (2016).","journal-title":"PLoS ONE"},{"issue":"1","key":"83147_CR24","first-page":"2","volume":"12","author":"JF Sotos","year":"2014","unstructured":"Sotos, J. F. Sotos syndrome 1 and 2. Pediatr. Endocrinol. Rev. PER. 12(1), 2\u201316 (2014).","journal-title":"Pediatr. Endocrinol. Rev. PER."},{"issue":"4","key":"83147_CR25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1136\/jmg.2004.027755","volume":"42","author":"K Tatton-Brown","year":"2005","unstructured":"Tatton-Brown, K. et al. Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome. J. Med. Genet. 42(4), 307\u2013313 (2005).","journal-title":"J. Med. Genet."},{"issue":"1","key":"83147_CR26","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/ajmg.a.33715","volume":"155A","author":"MH Willemsen","year":"2011","unstructured":"Willemsen, M. H. et al. Further molecular and clinical delineation of the Wisconsin syndrome phenotype associated with interstitial 3q24q25 deletions. Am. J. Med. Genet. 155A(1), 106\u2013112 (2011).","journal-title":"Am. J. Med. Genet."},{"issue":"1","key":"83147_CR27","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/ajmg.a.38002","volume":"173","author":"V Bertini","year":"2017","unstructured":"Bertini, V. et al. A 6.5 mb deletion at 3q24q25.2 narrows Wisconsin syndrome critical region to a 750 kb interval: A potential role for MBNLI. Am. J. Med. Genet. 173(1), 280\u2013284 (2017).","journal-title":"Am. J. Med. Genet."},{"issue":"7","key":"83147_CR28","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1111\/aogs.12146","volume":"92","author":"EM Vestergaard","year":"2013","unstructured":"Vestergaard, E. M., Christensen, R., Petersen, O. B. & Vogel, I. Prenatal diagnosis: array comparative genomic hybridization in fetuses with abnormal sonographic findings. Acta Obstetr. et Gynecol. Scand. 92(7), 762\u2013768 (2013).","journal-title":"Acta Obstetr. et Gynecol. Scand."},{"issue":"4","key":"83147_CR29","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1097\/AOG.0b013e3182117471","volume":"117","author":"F Sethna","year":"2011","unstructured":"Sethna, F., Tennant, P. W. & Rankin, J. Prevalence, natural history, and clinical outcome of mild to moderate ventriculomegaly. Obstetr. Gynecol. 117(4), 867\u2013876 (2011).","journal-title":"Obstetr. Gynecol."},{"issue":"2","key":"83147_CR30","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/uog.20111","volume":"54","author":"E Thorup","year":"2019","unstructured":"Thorup, E. et al. Neurodevelopmental disorder in children believed to have isolated mild ventriculomegaly prenatally. Ultrasound Obstetr. Gynecol. 54(2), 182\u2013189 (2019).","journal-title":"Ultrasound Obstetr. Gynecol."},{"issue":"3","key":"83147_CR31","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/humu.22742","volume":"36","author":"D Van Opstal","year":"2015","unstructured":"Van Opstal, D. et al. Benefits and burdens of using a SNP array in pregnancies at increased risk for the common aneuploidies. Hum. Mutat. 36(3), 319\u2013326 (2015).","journal-title":"Hum. Mutat."},{"issue":"23","key":"83147_CR32","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1056\/NEJMoa1203382","volume":"367","author":"RJ Wapner","year":"2012","unstructured":"Wapner, R. J. et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N. Engl. J. Med. 367(23), 2175\u20132184 (2012).","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"83147_CR33","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/gim.2012.164","volume":"15","author":"JA Rosenfeld","year":"2013","unstructured":"Rosenfeld, J. A., Coe, B. P., Eichler, E. E., Cuckle, H. & Shaffer, L. G. Estimates of penetrance for recurrent pathogenic copy-number variations. Genet. Med. 15(6), 478\u2013481 (2013).","journal-title":"Genet. Med."},{"issue":"1","key":"83147_CR34","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/ejhg.2012.109","volume":"21","author":"V Guida","year":"2013","unstructured":"Guida, V. et al. A variant in the carboxyl-terminus of connexin 40 alters GAP junctions and increases risk for tetralogy of Fallot. Eur. J. Hum. Genet. EJHG. 21(1), 69\u201375 (2013).","journal-title":"Eur. J. Hum. Genet. EJHG."},{"issue":"16","key":"83147_CR35","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1056\/NEJMoa0805384","volume":"359","author":"HC Mefford","year":"2008","unstructured":"Mefford, H. C. et al. Recurrent rearrangements of chromosome 1q21.1 and variable pediatric phenotypes. N. Engl. J. Med. 359(16), 1685\u20131699 (2008).","journal-title":"N. Engl. J. Med."},{"issue":"5","key":"83147_CR36","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1016\/j.tjog.2018.08.022","volume":"57","author":"CP Chen","year":"2018","unstructured":"Chen, C. P. et al. Prenatal diagnosis of a familial 15q11.2 (BP1-BP2) microdeletion encompassing TUBGCP5, CYFIP1, NIPA2 and NIPA1 in a fetus with ventriculomegaly, microcephaly and intrauterine growth restriction on prenatal ultrasound. Taiwan J. Obstet. Gynecol. 57(5), 730\u2013733 (2018).","journal-title":"Taiwan J. Obstet. Gynecol."},{"issue":"14","key":"83147_CR37","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1056\/NEJMoa1200395","volume":"367","author":"S Girirajan","year":"2012","unstructured":"Girirajan, S. et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N. Engl. J. Med. 367(14), 1321\u20131331 (2012).","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"83147_CR38","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1111\/jir.12382","volume":"61","author":"MG Butler","year":"2017","unstructured":"Butler, M. G. Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder. J. Intellect. Disabil. Res. 61(6), 568\u2013579 (2017).","journal-title":"J. Intellect. Disabil. Res."},{"issue":"7483","key":"83147_CR39","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/nature12818","volume":"505","author":"H Stefansson","year":"2014","unstructured":"Stefansson, H. et al. CNVs conferring risk of autism or schizophrenia affect cognition in controls. Nature 505(7483), 361\u2013366 (2014).","journal-title":"Nature"},{"issue":"6","key":"83147_CR40","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1002\/pd.4342","volume":"34","author":"B Oneda","year":"2014","unstructured":"Oneda, B. et al. High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power. Prenat. Diagn. 34(6), 525\u2013533 (2014).","journal-title":"Prenat. Diagn."},{"issue":"6","key":"83147_CR41","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1002\/uog.12464","volume":"41","author":"SC Hillman","year":"2013","unstructured":"Hillman, S. C. et al. Use of prenatal chromosomal microarray: Prospective cohort study and systematic review and meta-analysis. Ultrasound Obstetr. Gynecol. 41(6), 610\u2013620 (2013).","journal-title":"Ultrasound Obstetr. Gynecol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83147-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83147-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83147-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T04:42:19Z","timestamp":1670042539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-83147-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["83147"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-83147-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]},"assertion":[{"value":"22 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5291"}}