{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:09:11Z","timestamp":1787004551866,"version":"build-2736575974"},"reference-count":56,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T00:00:00Z","timestamp":1615766400000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The endothelial-to-mesenchymal transition (EndMT) is a critical process that occurs during the development of the outflow tract (OFT). Malformations of the OFT can lead to the occurrence of conotruncal defect (CTD). SOX7 duplication has been reported in patients with congenital CTD, but its specific role in OFT development remains poorly understood. To decipher this, histological analysis showed that SRY-related HMG-box 7 (SOX7) was regionally expressed in the endocardial endothelial cells and in the mesenchymal cells of the OFT, where EndMT occurs. Experiments, using in vitro collagen gel culture system, revealed that SOX7 was a negative regulator of EndMT that inhibited endocardial cell (EC) migration and resulted in decreased number of mesenchymal cells. Forced expression of SOX7 in endothelial cells blocked further migration and improved the expression of the adhesion protein vascular endothelial (VE)-cadherin (VE-cadherin). Moreover, a VE-cadherin knockdown could partly reverse the SOX7-mediated repression of cell migration. Luciferase and electrophoretic mobility shift assay (EMSA) demonstrated that SOX7 up-regulated VE-cadherin by directly binding to the gene\u2019s promoter in endothelial cells. The coding exons and splicing regions of the SOX7 gene were also scanned in the 536 sporadic CTD patients and in 300 unaffected controls, which revealed four heterozygous SOX7 mutations. Luciferase assays revealed that two SOX7 variants weakened the transactivation of the VE-cadherin promoter. In conclusion, SOX7 inhibited EndMT during OFT development by directly up-regulating the endothelial-specific adhesion molecule VE-cadherin. SOX7 mutations can lead to impaired EndMT by regulating VE-cadherin, which may give rise to the molecular mechanisms associated with SOX7 in CTD pathogenesis.<\/jats:p>","DOI":"10.1042\/cs20201496","type":"journal-article","created":{"date-parts":[[2021,3,15]],"date-time":"2021-03-15T08:26:17Z","timestamp":1615796777000},"page":"829-846","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["SOX7 suppresses endothelial-to-mesenchymal transitions by enhancing VE-cadherin expression during outflow tract development"],"prefix":"10.1042","volume":"135","author":[{"given":"Xuechao","family":"Jiang","sequence":"first","affiliation":[{"name":"Scientific Research Center, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Shanghai Children\u2019s Medical Center, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4841-1912","authenticated-orcid":false,"given":"Rang","family":"Xu","sequence":"additional","affiliation":[{"name":"Scientific Research Center, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,3,26]]},"reference":[{"key":"2021113011201654900_B1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.5830\/CVJA-2013-028","article-title":"The global burden of congenital heart disease","volume":"24","author":"Hoffman","year":"2013","journal-title":"Cardiovasc. J. Africa"},{"key":"2021113011201654900_B2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/j.1749-6632.2009.05099.x","article-title":"Notch and cardiac outflow tract development","volume":"1188","author":"Jain","year":"2010","journal-title":"Ann. N.Y. Acad. Sci."},{"key":"2021113011201654900_B3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/wdev.98","article-title":"Cardiac outflow tract anomalies","volume":"2","author":"Neeb","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"2021113011201654900_B4","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1161\/01.RES.0000141429.13560.cb","article-title":"Lineage and morphogenetic analysis of the cardiac valves","volume":"95","author":"de Lange","year":"2004","journal-title":"Circ. Res."},{"key":"2021113011201654900_B5","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1161\/CIRCRESAHA.111.245035","article-title":"Nfatc1 coordinates valve endocardial cell lineage development required for heart valve formation","volume":"109","author":"Wu","year":"2011","journal-title":"Circ. Res."},{"key":"2021113011201654900_B6","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/BF00315651","article-title":"Development of mouse semilunar valves","volume":"160","author":"Hurle","year":"1980","journal-title":"Anat. Embryol. (Berl.)"},{"key":"2021113011201654900_B7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1471-213X-12-22","article-title":"Loss of muscleblind-like 1 promotes invasive mesenchyme formation in endocardial cushions by stimulating autocrine tgfbeta3","volume":"12","author":"LeMasters","year":"2012","journal-title":"BMC Dev. Biol."},{"key":"2021113011201654900_B8","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1073\/pnas.88.4.1516","article-title":"Epithelial-mesenchymal transformation of embryonic cardiac endothelial cells is inhibited by a modified antisense oligodeoxynucleotide to transforming growth factor beta 3","volume":"88","author":"Potts","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011201654900_B9","doi-asserted-by":"publisher","first-page":"e72515","DOI":"10.1371\/journal.pone.0072515","article-title":"A potential relationship among beta-defensins haplotype, sox7 duplication and cardiac defects","volume":"8","author":"Long","year":"2013","journal-title":"PLoS ONE"},{"key":"2021113011201654900_B10","doi-asserted-by":"publisher","first-page":"2657","DOI":"10.1182\/blood-2007-07-100412","article-title":"Sox18 and sox7 play redundant roles in vascular development","volume":"111","author":"Cermenati","year":"2008","journal-title":"Blood"},{"key":"2021113011201654900_B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1387\/ijdb.130323mw","article-title":"Sox7 in vascular development: review, insights and potential mechanisms","volume":"58","author":"Wat","year":"2014","journal-title":"Int. J. Dev. Biol."},{"key":"2021113011201654900_B12","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1084\/jem.20170123","article-title":"Sox7 promotes high-grade glioma by increasing vegfr2-mediated vascular abnormality","volume":"215","author":"Kim","year":"2018","journal-title":"J. Exp. Med."},{"key":"2021113011201654900_B13","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1242\/dev.071282","article-title":"Sox7 regulates the expression of ve-cadherin in the haemogenic endothelium at the onset of haematopoietic development","volume":"139","author":"Costa","year":"2012","journal-title":"Development"},{"key":"2021113011201654900_B14","doi-asserted-by":"publisher","first-page":"4813","DOI":"10.1182\/blood-2009-06-226290","article-title":"Sox7-sustained expression alters the balance between proliferation and differentiation of hematopoietic progenitors at the onset of blood specification","volume":"114","author":"Gandillet","year":"2009","journal-title":"Blood"},{"key":"2021113011201654900_B15","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.1242\/dev.140970","article-title":"Interplay between sox7 and runx1 regulates hemogenic endothelial fate in the yolk sac","volume":"143","author":"Lilly","year":"2016","journal-title":"Development"},{"key":"2021113011201654900_B16","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.3390\/ijms19051451","article-title":"Sox7 target genes and their contribution to its tumor suppressive function","volume":"19","author":"Zhang","year":"2018","journal-title":"Int. J. Mol. Sci."},{"key":"2021113011201654900_B17","doi-asserted-by":"publisher","first-page":"6196","DOI":"10.1038\/s41388-019-0865-8","article-title":"Sox7 regulates mapk\/erk-bim mediated apoptosis in cancer cells","volume":"38","author":"Sun","year":"2019","journal-title":"Oncogene"},{"key":"2021113011201654900_B18","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1182\/blood-2014-06-580993","article-title":"Suppression of sox7 by DNA methylation and its tumor suppressor function in acute myeloid leukemia","volume":"125","author":"Man","year":"2015","journal-title":"Blood"},{"key":"2021113011201654900_B19","doi-asserted-by":"publisher","first-page":"4274","DOI":"10.1093\/nar\/29.21.4274","article-title":"Sox7 transcription factor: sequence, chromosomal localisation, expression, transactivation and interference with wnt signalling","volume":"29","author":"Takash","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2021113011201654900_B20","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/S0167-4781(99)00047-0","article-title":"Isolation and characterization of a mouse sry-related cdna, msox7","volume":"1445","author":"Taniguchi","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"2021113011201654900_B21","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1002\/dvdy.20565","article-title":"Sox7 and sox18 are essential for cardiogenesis in xenopus","volume":"234","author":"Zhang","year":"2005","journal-title":"Dev. Dyn."},{"key":"2021113011201654900_B22","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1161\/CIRCRESAHA.107.166066","article-title":"Redundant roles for sox7 and sox18 in arteriovenous specification in zebrafish","volume":"102","author":"Herpers","year":"2008","journal-title":"Circ. Res."},{"key":"2021113011201654900_B23","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.ydbio.2008.01.028","article-title":"Zebrafish sox7 and sox18 function together to control arterial-venous identity","volume":"317","author":"Pendeville","year":"2008","journal-title":"Dev. Biol."},{"key":"2021113011201654900_B24","doi-asserted-by":"publisher","first-page":"4115","DOI":"10.1093\/hmg\/dds241","article-title":"Mouse model reveals the role of sox7 in the development of congenital diaphragmatic hernia associated with recurrent deletions of 8p23.1","volume":"21","author":"Wat","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"2021113011201654900_B25","doi-asserted-by":"publisher","first-page":"36133","DOI":"10.1038\/srep36133","article-title":"Identification of candidate genes for congenital heart defects on proximal chromosome 8p","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"2021113011201654900_B26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ydbio.2019.10.022","article-title":"Frs2alpha-dependent cell fate transition during endocardial cushion morphogenesis","volume":"458","author":"Chen","year":"2019","journal-title":"Dev. Biol."},{"key":"2021113011201654900_B27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1002\/dvdy.24216","article-title":"Impairment of endothelial-mesenchymal transformation during atrioventricular cushion formation in tmem100 null embryos","volume":"244","author":"Mizuta","year":"2015","journal-title":"Dev. Dyn."},{"key":"2021113011201654900_B28","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1172\/JCI42666","article-title":"Integration of a notch-dependent mesenchymal gene program and bmp2-driven cell invasiveness regulates murine cardiac valve formation","volume":"120","author":"Luna-Zurita","year":"2010","journal-title":"J. Clin. Invest."},{"key":"2021113011201654900_B29","doi-asserted-by":"publisher","first-page":"11893","DOI":"10.1073\/pnas.1300805110","article-title":"Analysis of dll4 regulation reveals a combinatorial role for sox and notch in arterial development","volume":"110","author":"Sacilotto","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011201654900_B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1161\/01.RES.77.1.1","article-title":"Molecular regulation of atrioventricular valvuloseptal morphogenesis","volume":"77","author":"Eisenberg","year":"1995","journal-title":"Circ. Res."},{"key":"2021113011201654900_B31","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1101\/gad.276304","article-title":"Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation","volume":"18","author":"Timmerman","year":"2004","journal-title":"Genes Dev."},{"key":"2021113011201654900_B32","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1006\/dbio.2000.9883","article-title":"Phylogeny of the sox family of developmental transcription factors based on sequence and structural indicators","volume":"227","author":"Bowles","year":"2000","journal-title":"Dev. Biol."},{"key":"2021113011201654900_B33","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.bbrc.2007.06.093","article-title":"Redundant roles of sox17 and sox18 in early cardiovascular development of mouse embryos","volume":"360","author":"Sakamoto","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021113011201654900_B34","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.semcancer.2019.08.032","article-title":"Novel role of sex-determining region y-box 7 (sox7) in tumor biology and cardiovascular developmental biology","volume":"67","author":"Hu","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"2021113011201654900_B35","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1016\/j.ajpath.2013.07.025","article-title":"The regulation of sox7 and its tumor suppressive role in breast cancer","volume":"183","author":"Stovall","year":"2013","journal-title":"Am. J. Pathol."},{"key":"2021113011201654900_B36","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s10238-015-0398-6","article-title":"Overexpression of mir-664 is associated with enhanced osteosarcoma cell migration and invasion ability via targeting sox7","volume":"17","author":"Bao","year":"2017","journal-title":"Clin. Exp. Med."},{"key":"2021113011201654900_B37","first-page":"439","article-title":"Sox7: from a developmental regulator to an emerging tumor suppressor","volume":"29","author":"Stovall","year":"2014","journal-title":"Histol. Histopathol."},{"key":"2021113011201654900_B38","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1096\/fj.201701453RR","article-title":"Classic sry-box protein sox7 functions as a tumor suppressor regulating wnt signaling and is methylated in renal cell carcinoma","volume":"33","author":"Wang","year":"2019","journal-title":"FASEB J."},{"key":"2021113011201654900_B39","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/0012-1606(87)90206-5","article-title":"Myocardial specificity for initiating endothelial-mesenchymal cell transition in embryonic chick heart correlates with a particulate distribution of fibronectin","volume":"119","author":"Mjaatvedt","year":"1987","journal-title":"Dev. Biol."},{"key":"2021113011201654900_B40","doi-asserted-by":"publisher","first-page":"11953","DOI":"10.1038\/s41598-019-48321-y","article-title":"Endocardium differentiation through sox17 expression in endocardium precursor cells regulates heart development in mice","volume":"9","author":"Saba","year":"2019","journal-title":"Sci. Rep."},{"key":"2021113011201654900_B41","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/380711a0","article-title":"Defects in cardiac outflow tract formation and pro-b-lymphocyte expansion in mice lacking sox-4","volume":"380","author":"Schilham","year":"1996","journal-title":"Nature"},{"key":"2021113011201654900_B42","doi-asserted-by":"publisher","first-page":"6502","DOI":"10.1073\/pnas.0401711101","article-title":"Essential role of sox9 in the pathway that controls formation of cardiac valves and septa","volume":"101","author":"Akiyama","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011201654900_B43","doi-asserted-by":"publisher","first-page":"6635","DOI":"10.1128\/MCB.24.15.6635-6644.2004","article-title":"Gene targeting reveals a widespread role for the high-mobility-group transcription factor sox11 in tissue remodeling","volume":"24","author":"Sock","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"2021113011201654900_B44","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s12565-009-0027-0","article-title":"Roles of tgfbeta and bmp during valvulo-septal endocardial cushion formation","volume":"84","author":"Yamagishi","year":"2009","journal-title":"Anat. Sci. Int."},{"key":"2021113011201654900_B45","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1242\/jcs.028282","article-title":"Snail is required for tgfbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells","volume":"121","author":"Kokudo","year":"2008","journal-title":"J. Cell Sci."},{"key":"2021113011201654900_B46","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.ydbio.2010.08.030","article-title":"Vegf signaling has distinct spatiotemporal roles during heart valve development","volume":"347","author":"Stankunas","year":"2010","journal-title":"Dev. Biol."},{"key":"2021113011201654900_B47","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1242\/dev.097360","article-title":"Bmp signaling represses vegfa to promote outflow tract cushion development","volume":"140","author":"Bai","year":"2013","journal-title":"Development"},{"key":"2021113011201654900_B48","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1083\/jcb.200710067","article-title":"Slug is a direct notch target required for initiation of cardiac cushion cellularization","volume":"182","author":"Niessen","year":"2008","journal-title":"J. Cell Biol."},{"key":"2021113011201654900_B49","doi-asserted-by":"publisher","first-page":"4489","DOI":"10.1073\/pnas.0308466101","article-title":"Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling","volume":"101","author":"Liu","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113011201654900_B50","doi-asserted-by":"publisher","first-page":"5601","DOI":"10.1242\/dev.02156","article-title":"Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning","volume":"132","author":"Ma","year":"2005","journal-title":"Development"},{"key":"2021113011201654900_B51","doi-asserted-by":"publisher","first-page":"3200","DOI":"10.1002\/dvdy.21743","article-title":"Bmp4 is required in the anterior heart field and its derivatives for endocardial cushion remodeling, outflow tract septation, and semilunar valve development","volume":"237","author":"McCulley","year":"2008","journal-title":"Dev. Dyn."},{"key":"2021113011201654900_B52","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1083\/jcb.118.6.1511","article-title":"A novel endothelial-specific membrane protein is a marker of cell-cell contacts","volume":"118","author":"Lampugnani","year":"1992","journal-title":"J. Cell Biol."},{"key":"2021113011201654900_B53","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1161\/CIRCRESAHA.116.305629","article-title":"Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition","volume":"116","author":"Xu","year":"2015","journal-title":"Circ. Res."},{"key":"2021113011201654900_B54","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/S0092-8674(00)81010-7","article-title":"Targeted deficiency or cytosolic truncation of the ve-cadherin gene in mice impairs vegf-mediated endothelial survival and angiogenesis","volume":"98","author":"Carmeliet","year":"1999","journal-title":"Cell"},{"key":"2021113011201654900_B55","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1002\/ajmg.a.32896","article-title":"Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia","volume":"149A","author":"Wat","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"2021113011201654900_B56","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/ajmg.a.35767","article-title":"8p23.1 duplication syndrome; common, confirmed, and novel features in six further patients","volume":"161A","author":"Barber","year":"2013","journal-title":"Am. J. Med. Genet. A"}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/6\/829\/906402\/cs-2020-1496.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/6\/829\/906402\/cs-2020-1496.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T07:17:38Z","timestamp":1638256658000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/135\/6\/829\/228080\/SOX7-suppresses-endothelial-to-mesenchymal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":56,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,3,26]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20201496","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,3]]},"published":{"date-parts":[[2021,3]]}}}