{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:36:02Z","timestamp":1789673762010,"version":"4.0.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Syst Biol"],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The COVID\u201019 pandemic caused by SARS\u2010CoV\u20102 has been a global health challenge. Angiotensin\u2010converting enzyme 2 (\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    ) is the host receptor for SARS\u2010CoV\u20102 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers have a higher risk of COVID\u201019 infection as these drugs could upregulate\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    , motivating the study of\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    expression. We find that ACEIs are enriched for\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    \u2010upregulating drugs, while antineoplastic agents are enriched for\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    \u2010downregulating drugs. Vorinostat and isotretinoin are the top\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    up\/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID\u201019, significantly upregulates\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    both\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    . Further top\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    regulators\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    or in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. Our study provides leads for future work studying\n                    <jats:italic>ACE<\/jats:italic>\n                    <jats:italic>2<\/jats:italic>\n                    expression modulators.\n                  <\/jats:p>","DOI":"10.15252\/msb.20209628","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T02:15:06Z","timestamp":1596075306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["In vitro and in\u00a0vivo identification of clinically approved drugs that modify ACE2 expression"],"prefix":"10.1038","volume":"16","author":[{"given":"Sanju","family":"Sinha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8118-5243","authenticated-orcid":false,"given":"Kuoyuan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2147-8033","authenticated-orcid":false,"given":"Alejandro A","family":"Sch\u00e4ffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Aldape","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Schiff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-3940","authenticated-orcid":false,"given":"Eytan","family":"Ruppin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,29]]},"reference":[{"key":"BFMSB209628_CR1","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1172\/JCI89857","volume":"127","author":"E Bekerman","year":"2017","unstructured":"Bekerman E, Neveu G, Shulla A, Brannan J, Pu S\u2010Y, Wang S, Xiao F, Barouch\u2010Bentov R, Bakken RR, Mateo R et\u00a0al (2017) Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad\u2010spectrum antiviral effects. J Clin Invest 127: 1338\u20131352","journal-title":"J Clin Invest"},{"key":"BFMSB209628_CR2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3390\/v12050497","volume":"12","author":"ES Brielle","year":"2020","unstructured":"Brielle ES, Schneidman\u2010Duhovny D, Linial M (2020) The SARS\u2010CoV\u20102 exerts a distinctive strategy for interacting with the ACE2 human receptor. Viruses 12: 497","journal-title":"Viruses"},{"key":"BFMSB209628_CR4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nm.4306","volume":"23","author":"SM Corsello","year":"2017","unstructured":"Corsello SM, Bittker JA, Liu Z, Gould J, McCarren P, Hirschman JE, Johnston SE, Vrcic A, Wong B, Khan M et\u00a0al (2017) The Drug Repurposing Hub: a next\u2010generation drug library and information resource. Nat Med 23: 405\u2013408","journal-title":"Nat Med"},{"key":"BFMSB209628_CR5","doi-asserted-by":"crossref","first-page":"taaa041","DOI":"10.1093\/jtm\/taaa041","volume":"27","author":"JH Diaz","year":"2020","unstructured":"Diaz JH (2020) Hypothesis: angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID\u201019. J Travel Med 27: taaa041","journal-title":"J Travel Med"},{"key":"BFMSB209628_CR6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/s41371-018-0138-y","volume":"33","author":"C Dimou","year":"2019","unstructured":"Dimou C, Antza C, Akrivos E, Doundoulakis I, Stabouli S, Haidich AB, Kotsis V (2019) A systematic review and network meta\u2010analysis of the comparative efficacy of angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers in hypertension. J Hum Hypertens 33: 188\u2013201","journal-title":"J Hum Hypertens"},{"key":"BFMSB209628_CR7","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1128\/AAC.03036-14","volume":"58","author":"J Dyall","year":"2014","unstructured":"Dyall J, Coleman CM, Hart BJ, Venkataraman T, Holbrook MR, Kindrachuk J, Johnson RF, Olinger GG Jr, Jahrling PB, Laidlaw M et\u00a0al (2014) Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother 58: 4885\u20134893","journal-title":"Antimicrob Agents Chemother"},{"key":"BFMSB209628_CR8","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1097\/HJH.0000000000002450","volume":"38","author":"M Esler","year":"2020","unstructured":"Esler M, Esler D (2020) Can angiotensin receptor\u2010blocking drugs perhaps be harmful in the COVID\u201019 pandemic? J Hypertens 38: 781\u2013782","journal-title":"J Hypertens"},{"key":"BFMSB209628_CR9","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1016\/S2213-2600(20)30116-8","volume":"8","author":"L Fang","year":"2020","unstructured":"Fang L, Karakiulakis G, Roth M (2020) Are patients with hypertension and diabetes mellitus at increased risk for COVID\u201019 infection? Lancet Respir Med 8: e21","journal-title":"Lancet Respir Med"},{"key":"BFMSB209628_CR10","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1161\/CIRCULATIONAHA.104.510461","volume":"111","author":"CM Ferrario","year":"2005","unstructured":"Ferrario CM, Jessup J, Chappell MC, Averill DB, Brosnihan KB, Tallant EA, Diz DI, Gallagher PE (2005) Effect of angiotensin\u2010converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin\u2010converting enzyme 2. Circulation 111: 2605\u20132610","journal-title":"Circulation"},{"key":"BFMSB209628_CR11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/ajh\/hpu086","volume":"28","author":"M Furuhashi","year":"2015","unstructured":"Furuhashi M, Moniwa N, Mita T, Fuseya T, Ishimura S, Ohno K, Shibata S, Tanaka M, Watanabe Y, Akasaka H et\u00a0al (2015) Urinary angiotensin\u2010converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker. Am J Hypertens 28: 15\u201321","journal-title":"Am J Hypertens"},{"key":"BFMSB209628_CR12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/j.1365-4632.2009.04232.x","volume":"49","author":"C Gorpelioglu","year":"2010","unstructured":"Gorpelioglu C, Ozol D, Sarifakioglu E (2010) Influence of isotretinoin on nasal mucociliary clearance and lung function in patients with acne vulgaris. Int J Dermatol 49: 87\u201390","journal-title":"Int J Dermatol"},{"key":"BFMSB209628_CR13","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21656","author":"D Gurwitz","year":"2020","unstructured":"Gurwitz D (2020) Angiotensin receptor blockers as tentative SARS\u2010CoV\u20102 therapeutics. Drug Dev Res https:\/\/doi.org\/10.1002\/ddr.21656","journal-title":"Drug Dev Res"},{"key":"BFMSB209628_CR14","doi-asserted-by":"publisher","DOI":"10.1101\/2020.06.22.20137273","author":"P Horby","year":"2020","unstructured":"Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E et\u00a0al (2020) Effect of dexamethasone in hospitalized patients with COVID\u201019: preliminary report. medRxiv https:\/\/doi.org\/10.1101\/2020.06.22.20137273 [PREPRINT]","journal-title":"medRxiv"},{"key":"BFMSB209628_CR15","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nrcardio.2014.59","volume":"11","author":"F Jiang","year":"2014","unstructured":"Jiang F, Yang J, Zhang Y, Dong M, Wang S, Zhang Q, Liu FF, Zhang K, Zhang C (2014) Angiotensin\u2010converting enzyme 2 and angiotensin 1\u20107: novel therapeutic targets. Nat Rev Cardiol 11: 413\u2013426","journal-title":"Nat Rev Cardiol"},{"key":"BFMSB209628_CR250","doi-asserted-by":"crossref","unstructured":"Korotkevich G, Sukhov V, Sergushichev A (2019) bioRxivhttps:\/\/doi.org\/10.1101\/060012 [PREPRINT]","DOI":"10.1101\/060012"},{"key":"BFMSB209628_CR16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.phrs.2017.06.005","volume":"125","author":"XC Li","year":"2017","unstructured":"Li XC, Zhang J, Zhuo JL (2017) The vasoprotective axes of the renin\u2010angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res 125: 21\u201338","journal-title":"Pharmacol Res"},{"key":"BFMSB209628_CR17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000368486","volume":"40","author":"Y Liang","year":"2015","unstructured":"Liang Y, Deng H, Bi S, Cui ZAL, Zheng D, Wang Y (2015) Urinary angiotensin converting enzyme 2 increases in patients with type 2 diabetic mellitus. Kidney Blood Press Res 40: 101\u2013110","journal-title":"Kidney Blood Press Res"},{"key":"BFMSB209628_CR251","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","volume":"45","author":"J Lonsdale","year":"2013","unstructured":"Lonsdale J, Thomas J, Salvatore M, Phillips R, Lo E, Shad S, Hasz R, Walters G, Garcia F, Young N et al (2013) The genotype\u2010tissue expression (GTEx) project. Nat Genet 45: 580\u2010585","journal-title":"Nat Genet"},{"key":"BFMSB209628_CR18","doi-asserted-by":"publisher","unstructured":"Lyu X, Hu M, Peng J, Zhang X, Sanders YY (2019) HDAC inhibitors as antifibrotic drugs in cardiac and pulmonary fibrosis. Ther Adv Chronic Dis 10: https:\/\/doi.org\/10.1177\/2040622319862697","DOI":"10.1177\/2040622319862697"},{"key":"BFMSB209628_CR19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12931-019-1161-4","volume":"20","author":"TM Maher","year":"2019","unstructured":"Maher TM, Strek ME (2019) Antifibrotic therapy for idiopathic pulmonary fibrosis: time to treat. Respir Res 20: 205","journal-title":"Respir Res"},{"key":"BFMSB209628_CR20","doi-asserted-by":"crossref","first-page":"2000607","DOI":"10.1183\/13993003.00607-2020","volume":"55","author":"RJ Mason","year":"2020","unstructured":"Mason RJ (2020) Pathogenesis of COVID\u201019 from a cell biology perspective. Eur Respir J 55: 2000607","journal-title":"Eur Respir J"},{"key":"BFMSB209628_CR21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41569-019-0244-8","volume":"17","author":"M Paz Ocaranza","year":"2020","unstructured":"Paz Ocaranza M, Riquelme JA, Garc\u00eda L, Jalil JE, Chiong M, Santos RAS, Lavandero S (2020) Counter\u2010regulatory renin\u2010angiotensin system in cardiovascular disease. Nat Rev Cardiol 17: 116\u2013129","journal-title":"Nat Rev Cardiol"},{"key":"BFMSB209628_CR22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1128\/AAC.01532-12","volume":"57","author":"O Perwitasari","year":"2013","unstructured":"Perwitasari O, Yan X, Johnson S, White C, Brooks P, Tompkins SM, Tripp RA (2013) Targeting organic anion transporter 3 with probenecid as a novel anti\u2010influenza a virus strategy. Antimicrob Agents Chemother 57: 475\u2013483","journal-title":"Antimicrob Agents Chemother"},{"key":"BFMSB209628_CR23","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) limma powers differential expression analyses for RNA\u2010sequencing and microarray studies. Nucleic Acids Res 43: e47","journal-title":"Nucleic Acids Res"},{"key":"BFMSB209628_CR26","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.cell.2017.10.049","volume":"171","author":"A Subramanian","year":"2017","unstructured":"Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK et\u00a0al (2017) A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell 171: 1437\u20131452.e17","journal-title":"Cell"},{"key":"BFMSB209628_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1164\/ajrccm-conference.2010.181.1_meetingabstracts.a1979","volume-title":"Alveolar Epithelial Cells through a Posttranscriptional Mechanism Inhibitable by Angiotensin","author":"B Uhal","year":"2010","unstructured":"Uhal B, Abdul\u2010Hafez A (2010) Bleomycin downregulates ACE\u20102. In Alveolar Epithelial Cells through a Posttranscriptional Mechanism Inhibitable by Angiotensin, pp. 1\u20137. A58. ANIMAL MODELS OF PULMONARY FIBROSIS Available at: https:\/\/doi.org\/10.1164\/ajrccm-conference.2010.181.1_meetingabstracts.a1979"},{"key":"BFMSB209628_CR28","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","volume":"25","author":"FA Vieira Braga","year":"2019","unstructured":"Vieira Braga FA, Kar G, Berg M, Carpaij OA, Polanski K, Simon LM, Brouwer S, Gomes T, Hesse L, Jiang J et\u00a0al (2019) A cellular census of human lungs identifies novel cell states in health and in asthma. Nat Med 25: 1153\u20131163","journal-title":"Nat Med"},{"key":"BFMSB209628_CR29","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s00726-014-1889-6","volume":"47","author":"RN Vuille\u2010dit-Bille","year":"2015","unstructured":"Vuille\u2010dit-Bille RN, Camargo SM, Emmenegger L, Sasse T, Kummer E, Jando J, Hamie QM, Meier CF, Hunziker S, Forras\u2010Kaufmann Z et\u00a0al (2015) Human intestine luminal ACE2 and amino acid transporter expression increased by ACE\u2010inhibitors. Amino Acids 47: 693\u2013705","journal-title":"Amino Acids"},{"key":"BFMSB209628_CR30","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","volume":"46","author":"DS Wishart","year":"2018","unstructured":"Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z et\u00a0al (2018) DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res 46: D1074\u2013D1082","journal-title":"Nucleic Acids Res"},{"key":"BFMSB209628_CR31","volume-title":"WHO collaborating centre for drug statistics methodology: ATC classification index with DDDs and guidelines for ATC classification and DDD assignment","author":"World Health Organization","year":"2006","unstructured":"World Health Organization (2006) WHO collaborating centre for drug statistics methodology: ATC classification index with DDDs and guidelines for ATC classification and DDD assignment. Oslo, Norway: Norwegian Institute of Public Health"},{"key":"BFMSB209628_CR32","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.cpcardiol.2020.100618","volume":"45","author":"S Zaim","year":"2020","unstructured":"Zaim S, Chong JH, Sankaranarayanan V, Harky A (2020) COVID\u201019 and multiorgan response. Curr Probl Cardiol 45: 100618","journal-title":"Curr Probl Cardiol"},{"key":"BFMSB209628_CR33","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1161\/CIRCRESAHA.120.317134","volume":"126","author":"P Zhang","year":"2020","unstructured":"Zhang P, Zhu L, Cai J, Lei F, Qin J\u2010J, Xie J, Liu Y\u2010M, Zhao Y\u2010C, Huang X, Lin L et\u00a0al (2020) Association of inpatient use of angiotensin\u2010converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID\u201019. Circ Res 126: 1671\u20131681","journal-title":"Circ Res"},{"key":"BFMSB209628_CR34","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41569-020-0360-5","volume":"17","author":"Y\u2010Y Zheng","year":"2020","unstructured":"Zheng Y\u2010Y, Ma Y\u2010T, Zhang J\u2010Y, Xie X (2020) COVID\u201019 and the cardiovascular system. Nat Rev Cardiol 17: 259\u2013260","journal-title":"Nat Rev Cardiol"},{"key":"BFMSB209628_CR35","doi-asserted-by":"crossref","first-page":"9218","DOI":"10.1074\/jbc.M116.716100","volume":"291","author":"N Zhou","year":"2016","unstructured":"Zhou N, Pan T, Zhang J, Li Q, Zhang X, Bai C, Huang F, Peng T, Zhang J, Liu C et\u00a0al (2016) Glycopeptide antibiotics potently inhibit cathepsin L in the late endosome\/lysosome and block the entry of ebola virus, middle east respiratory syndrome coronavirus (MERS\u2010CoV), and severe acute respiratory syndrome coronavirus (SARS\u2010CoV). J Biol Chem 291: 9218\u20139232","journal-title":"J Biol Chem"},{"key":"BFMSB209628_CR36","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1093\/bioinformatics\/btn520","volume":"24","author":"Y Zhu","year":"2008","unstructured":"Zhu Y, Davis S, Stephens R, Meltzer PS, Chen Y (2008) GEOmetadb: powerful alternative search engine for the Gene Expression Omnibus. Bioinformatics 24: 2798\u20132800","journal-title":"Bioinformatics"}],"container-title":["Molecular Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.15252%2Fmsb.20209628","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/msb.20209628.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.15252\/msb.20209628","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.15252\/msb.20209628\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.embopress.org\/doi\/pdf\/10.15252\/msb.20209628","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.15252\/msb.20209628.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T02:50:19Z","timestamp":1779072619000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.15252\/msb.20209628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,1]]},"references-count":35,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7,1]]}},"alternative-id":["BFMSB209628"],"URL":"https:\/\/doi.org\/10.15252\/msb.20209628","relation":{},"ISSN":["1744-4292"],"issn-type":[{"value":"1744-4292","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,1]]},"assertion":[{"value":"10 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 July 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"MSB209628"}}