{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:16:31Z","timestamp":1792131391680,"version":"4.4.0"},"reference-count":50,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP 1111169"],"award-info":[{"award-number":["APP 1111169"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL096384"],"award-info":[{"award-number":["R01 HL096384"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1107643"],"award-info":[{"award-number":["APP1107643"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Propranolol is an approved non-selective \u03b2-adrenergic blocker that is first line therapy for infantile hemangioma. Despite the clinical benefit of propranolol therapy in hemangioma, the mechanistic understanding of what drives this outcome is limited. Here, we report successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18. Using a mouse pre-clinical model of HLTRS, we show that propranolol treatment rescues its corneal neo-vascularisation phenotype. Dissection of the molecular mechanism identified the R(+)-propranolol enantiomer as a small molecule inhibitor of the SOX18 transcription factor, independent of any anti-adrenergic effect. Lastly, in a patient-derived in vitro model of infantile hemangioma and pre-clinical model of HLTRS we demonstrate the therapeutic potential of the R(+) enantiomer. Our work emphasizes the importance of SOX18 etiological role in vascular neoplasms, and suggests R(+)-propranolol repurposing to numerous indications ranging from vascular diseases to metastatic cancer.<\/jats:p>","DOI":"10.7554\/elife.43026","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T20:00:19Z","timestamp":1564430419000},"source":"Crossref","is-referenced-by-count":68,"title":["R-propranolol is a small molecule inhibitor of the SOX18 transcription factor in a rare vascular syndrome and hemangioma"],"prefix":"10.7554","volume":"8","author":[{"given":"Jeroen","family":"Overman","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Wylie-Sears","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Moustaqil","sequence":"additional","affiliation":[{"name":"Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Huang","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Meurer","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM Marseille Cancer Research Centre), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University UM105, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivy Kim","family":"Chiang","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Lesieur","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatin","family":"Patel","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Diamantina Institute, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Zuegg","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy","family":"Pasquier","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille (CRCM Marseille Cancer Research Centre), Inserm UMR1068, CNRS UMR7258, Aix-Marseille University UM105, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Sierecki","sequence":"additional","affiliation":[{"name":"Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7378-8976","authenticated-orcid":true,"given":"Yann","family":"Gambin","sequence":"additional","affiliation":[{"name":"Single Molecule Science, Lowy Cancer Research Centre, The University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Dubai Healthcare City, Dubai, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiarash","family":"Khosrotehrani","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Diamantina Institute, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Andelfinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Montreal, Ste-Justine University Hospital Centre, Montr\u00e9al, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6367-1974","authenticated-orcid":true,"given":"Joyce","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9846-6882","authenticated-orcid":true,"given":"Mathias","family":"Francois","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1111\/j.1525-1470.2011.01644.x","article-title":"Recurrence of infantile hemangiomas treated with propranolol","volume":"28","author":"Bagazgoitia","year":"2011","journal-title":"Pediatric Dermatology"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.mcp.2015.11.005","article-title":"A novel SOX18 mutation uncovered in jordanian patient with hypotrichosis-lymphedema-telangiectasia syndrome by whole exome sequencing","volume":"30","author":"Bastaki","year":"2016","journal-title":"Molecular and Cellular Probes"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1016\/j.ajpath.2011.07.040","article-title":"VEGFR-1 mediates endothelial differentiation and formation of blood vessels in a murine model of infantile hemangioma","volume":"179","author":"Boscolo","year":"2011","journal-title":"The American Journal of Pathology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1111\/j.1349-7006.2010.01582.x","article-title":"Role of beta1-adrenoceptor in increased lipolysis in cancer cachexia","volume":"101","author":"Cao","year":"2010","journal-title":"Cancer Science"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001097","article-title":"Propranolol reduces cancer risk: a Population-Based cohort study","volume":"94","author":"Chang","year":"2015","journal-title":"Medicine"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1111\/pde.12192","article-title":"Serum-level changes of vascular endothelial growth factor in children with infantile hemangioma after oral propranolol therapy","volume":"30","author":"Chen","year":"2013","journal-title":"Pediatric Dermatology"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"2629","DOI":"10.1242\/dev.146241","article-title":"SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development","volume":"144","author":"Chiang","year":"2017","journal-title":"Development"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Advances in Enzyme Regulation"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1093\/hmg\/ddp219","article-title":"Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation","volume":"18","author":"Downes","year":"2009","journal-title":"Human Molecular Genetics"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.chembiol.2017.01.003","article-title":"Small-Molecule inhibitors of the SOX18 transcription factor","volume":"24","author":"Fontaine","year":"2017","journal-title":"Cell Chemical Biology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/nature07391","article-title":"Sox18 induces development of the lymphatic vasculature in mice","volume":"456","author":"Fran\u00e7ois","year":"2008","journal-title":"Nature"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.1073\/pnas.1119291109","article-title":"Studies on Axenfeld-Rieger syndrome patients and mice reveal Foxc1's role in corneal neovascularization","volume":"109","author":"Fran\u00e7ois","year":"2012","journal-title":"PNAS"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jbiotec.2014.12.006","article-title":"Gateway-compatible vectors for high-throughput protein expression in pro- and eukaryotic cell-free systems","volume":"195","author":"Gagoski","year":"2015","journal-title":"Journal of Biotechnology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"5314","DOI":"10.1074\/jbc.M308512200","article-title":"The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18","volume":"279","author":"Hosking","year":"2004","journal-title":"Journal of Biological Chemistry"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1242\/dev.034827","article-title":"Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice","volume":"136","author":"Hosking","year":"2009","journal-title":"Development"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1086\/375614","article-title":"Mutations in the transcription factor gene SOX18 underlie recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia","volume":"72","author":"Irrthum","year":"2003","journal-title":"The American Journal of Human Genetics"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"2592","DOI":"10.1172\/JCI33493","article-title":"Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice","volume":"118","author":"Khan","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.ymeth.2011.06.006","article-title":"Leishmania cell-free protein expression system","volume":"55","author":"Kovtun","year":"2011","journal-title":"Methods"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.vph.2010.08.002","article-title":"Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells","volume":"53","author":"Lamy","year":"2010","journal-title":"Vascular Pharmacology"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1001\/jamaophthalmol.2013.1476","article-title":"Attenuation of choroidal neovascularization by \u03b2(2)-adrenoreceptor antagonism","volume":"131","author":"Lavine","year":"2013","journal-title":"JAMA Ophthalmology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1056\/NEJMc0708819","article-title":"Propranolol for severe hemangiomas of infancy","volume":"358","author":"L\u00e9aut\u00e9-Labr\u00e8ze","year":"2008","journal-title":"New England Journal of Medicine"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1056\/NEJMoa1404710","article-title":"A randomized, controlled trial of oral propranolol in infantile hemangioma","volume":"372","author":"L\u00e9aut\u00e9-Labr\u00e8ze","year":"2015","journal-title":"New England Journal of Medicine"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1056\/NEJMc1503811","article-title":"Oral propranolol for infantile hemangioma","volume":"373","author":"L\u00e9aut\u00e9-Labr\u00e8ze","year":"2015","journal-title":"The New England Journal of Medicine"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1111\/bjd.13048","article-title":"Propranolol targets the contractility of infantile haemangioma-derived pericytes","volume":"171","author":"Lee","year":"2014","journal-title":"British Journal of Dermatology"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nchembio790","article-title":"Identifying off-target effects and hidden phenotypes of drugs in human cells","volume":"2","author":"MacDonald","year":"2006","journal-title":"Nature Chemical Biology"},{"key":"bib26","first-page":"185","article-title":"Stereospecific pharmacokinetics and pharmacodynamics of beta-adrenergic blockers in humans","volume":"4","author":"Mehvar","year":"2001","journal-title":"Journal of Pharmacy & Pharmaceutical Sciences : A Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1111\/cge.12388","article-title":"Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene","volume":"87","author":"Moalem","year":"2015","journal-title":"Clinical Genetics"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nbt.1556","article-title":"Species-independent translational leaders facilitate cell-free expression","volume":"27","author":"Mureev","year":"2009","journal-title":"Nature Biotechnology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.bbrc.2015.06.087","article-title":"Infantile hemangioma-derived stem cells and endothelial cells are inhibited by class 3 semaphorins","volume":"464","author":"Nakayama","year":"2015","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.3892\/ol.2018.8819","article-title":"Role of the SOX18 protein in neoplastic processes","volume":"16","author":"Olbromski","year":"2018","journal-title":"Oncology Letters"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21221","article-title":"Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice","volume":"6","author":"Overman","year":"2017","journal-title":"eLife"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1620\/tjem.229.61","article-title":"Propranolol as an alternative treatment option for pediatric lymphatic malformation","volume":"229","author":"Ozeki","year":"2013","journal-title":"The Tohoku Journal of Experimental Medicine"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.1038\/bjc.2013.205","article-title":"\u03b2-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma","volume":"108","author":"Pasquier","year":"2013","journal-title":"British Journal of Cancer"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/74301","article-title":"Mutations in Sox18 underlie cardiovascular and hair follicle defects in ragged mice","volume":"24","author":"Pennisi","year":"2000","journal-title":"Nature Genetics"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"628","DOI":"10.18632\/oncotarget.101009","article-title":"Beta-blocker drug therapy reduces secondary cancer formation in breast cancer and improves cancer specific survival","volume":"1","author":"Powe","year":"2010","journal-title":"Oncotarget"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1098\/rsfs.2013.0018","article-title":"A cell-free approach to accelerate the study of protein-protein interactions in vitro","volume":"3","author":"Sierecki","year":"2013","journal-title":"Interface Focus"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1074\/mcp.M113.037275","article-title":"Rapid mapping of interactions between human SNX-BAR proteins measured in vitro by AlphaScreen and single-molecule spectroscopy","volume":"13","author":"Sierecki","year":"2014","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1007\/BF02984073","article-title":"The morphology and development of ragged\u2014 a mutant affecting the skin and hair of the house mouse II. Genetics, Embryology and Gross Juvenile Morphology","volume":"55","author":"Slee","year":"1957","journal-title":"Journal of Genetics"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1111\/j.1600-0404.1976.tb04342.x","article-title":"Short-term clinical trial of phopranolol in racemic form (Inderal), D-propranolol and placebo in migraine","volume":"53","author":"Stensrud","year":"1976","journal-title":"Acta Neurologica Scandinavica"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/clpt.1992.45","article-title":"Racemic (R,S)-propranolol versus half-dosed optically pure (S)-propranolol in humans at steady state: hemodynamic effects, plasma concentrations, and influence on thyroid hormone levels","volume":"51","author":"Stoschitzky","year":"1992","journal-title":"Clinical Pharmacology and Therapeutics"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1097\/00005344-199502000-00012","article-title":"Stereoselective vascular effects of the (R)- and (S)-enantiomers of propranolol and atenolol","volume":"25","author":"Stoschitzky","year":"1995","journal-title":"Journal of Cardiovascular Pharmacology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3892\/etm.2013.1159","article-title":"Induction of apoptosis in infantile hemangioma endothelial cells by propranolol","volume":"6","author":"Tu","year":"2013","journal-title":"Experimental and Therapeutic Medicine"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.ejmg.2018.01.001","article-title":"Further delineation of the SOX18-related hypotrichosis, lymphedema, telangiectasia syndrome (HTLS)","volume":"61","author":"Valenzuela","year":"2018","journal-title":"European Journal of Medical Genetics"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1242\/dev.143917","article-title":"Dominant-negative Sox18 function inhibits dermal papilla maturation and differentiation in all murine hair types","volume":"144","author":"Villani","year":"2017","journal-title":"Development"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ab.2008.04.036","article-title":"Standardization of real-time PCR gene expression data from independent biological replicates","volume":"379","author":"Willems","year":"2008","journal-title":"Analytical Biochemistry"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.18632\/oncotarget.1083","article-title":"Anti-tumor activity of the beta-adrenergic receptor antagonist propranolol in neuroblastoma","volume":"5","author":"Wolter","year":"2014","journal-title":"Oncotarget"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1097\/PRS.0b013e318267d3db","article-title":"Propranolol accelerates adipogenesis in hemangioma stem cells and causes apoptosis of hemangioma endothelial cells","volume":"130","author":"Wong","year":"2012","journal-title":"Plastic and Reconstructive Surgery"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10456-009-9161-5","article-title":"A switch in notch gene expression parallels stem cell to endothelial transition in infantile hemangioma","volume":"13","author":"Wu","year":"2010","journal-title":"Angiogenesis"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"135.e1","DOI":"10.1016\/j.cjca.2015.04.004","article-title":"Aortic dilatation associated with a de novo mutation in\u00a0the\u00a0SOX18 Gene: Expanding the Clinical Spectrum of\u00a0Hypotrichosis-Lymphedema-Telangiectasia Syndrome","volume":"32","author":"W\u00fcnnemann","year":"2016","journal-title":"Canadian Journal of Cardiology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1007\/s00383-013-3283-y","article-title":"Propranolol therapy of infantile hemangiomas: efficacy, adverse effects, and recurrence","volume":"29","author":"Xiao","year":"2013","journal-title":"Pediatric Surgery International"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/43026\/elife-43026-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/43026\/elife-43026-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/43026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:53:25Z","timestamp":1697057605000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/43026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,30]]},"references-count":50,"alternative-id":["10.7554\/eLife.43026"],"URL":"https:\/\/doi.org\/10.7554\/elife.43026","archive":["CLOCKSS"],"relation":{"has-review":[{"id-type":"doi","id":"10.7554\/eLife.43026.017","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.43026.016","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,30]]},"article-number":"e43026"}}