{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T08:14:42Z","timestamp":1789200882362,"version":"build-2803163510"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T00:00:00Z","timestamp":1485993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T00:00:00Z","timestamp":1485993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hypertens Res"],"published-print":{"date-parts":[[2017,6]]},"DOI":"10.1038\/hr.2017.2","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T07:00:57Z","timestamp":1486018857000},"page":"552-561","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["MiR-126a-5p is involved in the hypoxia-induced endothelial-to-mesenchymal transition of neonatal pulmonary hypertension"],"prefix":"10.1038","volume":"40","author":[{"given":"Yan-ping","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-li","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-ping","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-zhong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,2]]},"reference":[{"key":"BFhr20172_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1542\/peds.105.1.14","volume":"105","author":"MC Walsh-Sukys","year":"2000","unstructured":"Walsh-Sukys MC, Tyson JE, Wright LL, Bauer CR, Korones SB, Stevenson DK, Verter J, Stoll BJ, Lemons JA, Papile LA, Shankaran S, Donovan EF, Oh W, Ehrenkranz RA, Fanaroff AA . Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics 2000; 105: 14\u201320.","journal-title":"Pediatrics"},{"key":"BFhr20172_CR2","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1146\/annurev.physiol.67.040403.102229","volume":"67","author":"KR Stenmark","year":"2005","unstructured":"Stenmark KR, Abman SH . Lung vascular development: implications for the pathogenesis of bronchopulmonary dysplasia. Annu Rev Physiol 2005; 67: 623\u2013661.","journal-title":"Annu Rev Physiol"},{"key":"BFhr20172_CR3","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1161\/01.RES.0000243584.45145.3f","volume":"99","author":"KR Stenmark","year":"2006","unstructured":"Stenmark KR, Fagan KA, Frid MG . Hypoxia-induced pulmonary vascular remodeling: cellular and molecular mechanisms. Circ Res 2006; 99: 675\u2013691.","journal-title":"Circ Res"},{"key":"BFhr20172_CR4","doi-asserted-by":"publisher","first-page":"L1013","DOI":"10.1152\/ajplung.00217.2009","volume":"297","author":"KR Stenmark","year":"2009","unstructured":"Stenmark KR, Meyrick B, Galie N, Mooi WJ, McMurtry IF . Animal models of pulmonary arterial hypertension: the hope for etiological discovery and pharmacological cure. Am J Physiol Lung Cell Mol Physiol 2009; 297: L1013\u2013L1032.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFhr20172_CR5","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1056\/NEJM200203143461117","volume":"346","author":"RJ Vosatka","year":"2002","unstructured":"Vosatka RJ . Persistent pulmonary hypertension of the newborn. N Engl J Med 2002; 346: 864.","journal-title":"N Engl J Med"},{"key":"BFhr20172_CR6","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1038\/hr.2015.80","volume":"38","author":"X Yun","year":"2015","unstructured":"Yun X, Chen Y, Yang K, Wang S, Lu W, Wang J . Upregulation of canonical transient receptor potential channel in the pulmonary arterial smooth muscle of a chronic thromboembolic pulmonary hypertension rat model. Hypertens Res 2015; 38: 821\u2013828.","journal-title":"Hypertens Res"},{"key":"BFhr20172_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1084-2756(02)00195-1","volume":"8","author":"SG Haworth","year":"2003","unstructured":"Haworth SG, Hislop AA . Lung development-the effects of chronic hypoxia. Semin Neonatol 2003; 8: 1\u20138.","journal-title":"Semin Neonatol"},{"key":"BFhr20172_CR8","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1161\/CIRCRESAHA.109.197533","volume":"104","author":"KC Young","year":"2009","unstructured":"Young KC, Torres E, Hatzistergos KE, Hehre D, Suguihara C, Hare JM . Inhibition of the SDF-1\/CXCR4 axis attenuates neonatal hypoxia-induced pulmonary hypertension. Circ Res 2009; 104: 1293\u20131301.","journal-title":"Circ Res"},{"key":"BFhr20172_CR9","doi-asserted-by":"publisher","first-page":"227ra34","DOI":"10.1126\/scitranslmed.3006927","volume":"6","author":"BC Cooley","year":"2014","unstructured":"Cooley BC, Nevado J, Mellad J, Yang D, St HC, Negro A, Fang F, Chen G, San H, Walts AD, Schwartzbeck RL, Taylor B, Lanzer JD, Wragg A, Elagha A, Beltran LE, Berry C, Feil R, Virmani R, Ladich E, Kovacic JC, Boehm M . TGF-\u03b2 signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling. Sci Transl Med 2014; 6: 227ra34.","journal-title":"Sci Transl Med"},{"key":"BFhr20172_CR10","doi-asserted-by":"publisher","first-page":"315","DOI":"10.4103\/2045-8932.114758","volume":"3","author":"R Sessa","year":"2013","unstructured":"Sessa R, Hata A . Role of microRNAs in lung development and pulmonary diseases. Pulm Circ 2013; 3: 315\u2013328.","journal-title":"Pulm Circ"},{"key":"BFhr20172_CR11","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1161\/ATVBAHA.109.202028","volume":"30","author":"P Caruso","year":"2010","unstructured":"Caruso P, MacLean MR, Khanin R, McClure J, Soon E, Southgate M, MacDonald RA, Greig JA, Robertson KE, Masson R, Denby L, Dempsie Y, Long L, Morrell NW, Baker AH . Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline. Arterioscler Thromb Vasc Biol 2010; 30: 716\u2013723.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"BFhr20172_CR12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1530\/JME-10-0143","volume":"47","author":"YP Xu","year":"2011","unstructured":"Xu YP, Zhu JJ, Cheng F, Jiang KW, Gu WZ, Shen Z, Wu YD, Liang L, Du LZ . Ghrelin ameliorates hypoxia-induced pulmonary hypertension via phospho-GSK3 \u03b2\/\u03b2-catenin signaling in neonatal rats. J Mol Endocrinol 2011; 47: 33\u201343.","journal-title":"J Mol Endocrinol"},{"key":"BFhr20172_CR13","doi-asserted-by":"publisher","first-page":"L1079","DOI":"10.1152\/ajplung.00526.2005","volume":"291","author":"TA John","year":"2006","unstructured":"John TA, Ibe BO, Usha RJ . Oxygen alters caveolin-1 and nitric oxide synthase-3 functions in ovine fetal and neonatal lung microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 2006; 291: L1079\u2013L1093.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"BFhr20172_CR14","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jpeds.2011.06.038","volume":"160","author":"DC Vijlbrief","year":"2012","unstructured":"Vijlbrief DC, Benders MJ, Kemperman H, van Bel F, de Vries WB . B-type natriuretic peptide and rebound during treatment for persistent pulmonary hypertension. J Pediatr 2012; 160: 111\u2013115.e1.","journal-title":"J Pediatr"},{"key":"BFhr20172_CR15","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1159\/000063609","volume":"82","author":"TG Krediet","year":"2002","unstructured":"Krediet TG, Valk L, Hempenius I, Egberts J, van Bel F . Nitric oxide production and plasma cyclic guanosine monophosphate in premature infants with respiratory distress syndrome. Biol Neonate 2002; 82: 150\u2013154.","journal-title":"Biol Neonate"},{"key":"BFhr20172_CR16","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.chest.2016.09.001","volume":"151","author":"KJ Dunham-Snary","year":"2016","unstructured":"Dunham-Snary KJ, Wu D, Sykes EA, Thakrar A, Parlow LR, Mewburn JD, Parlow JL, Archer SL . Hypoxic pulmonary vasoconstriction: from molecular mechanisms to medicine. Chest 2016; 151: 181\u2013192.","journal-title":"Chest"},{"key":"BFhr20172_CR17","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/iub.1059","volume":"64","author":"F Lin","year":"2012","unstructured":"Lin F, Wang N, Zhang TC . The role of endothelial-mesenchymal transition in development and pathological process. IUBMB Life 2012; 64: 717\u2013723.","journal-title":"IUBMB Life"},{"key":"BFhr20172_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1089\/cell.2012.0054","volume":"15","author":"A Schindeler","year":"2013","unstructured":"Schindeler A, Kolind M, Little DG . Cellular transitions and tissue engineering. Cell Reprogram 2013; 15: 101\u2013106.","journal-title":"Cell Reprogram"},{"key":"BFhr20172_CR19","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/jb\/mvr121","volume":"151","author":"H Mihira","year":"2012","unstructured":"Mihira H, Suzuki HI, Akatsu Y, Yoshimatsu Y, Igarashi T, Miyazono K, Watabe T . TGF-\u03b2-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A. J Biochem 2012; 151: 145\u2013156.","journal-title":"J Biochem"},{"key":"BFhr20172_CR20","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1093\/jb\/mvt032","volume":"153","author":"A Saito","year":"2013","unstructured":"Saito A . EMT and EndMT: regulated in similar ways. J Biochem 2013; 153: 493\u2013495.","journal-title":"J Biochem"},{"issue":"4","key":"BFhr20172_CR21","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1080\/19336918.2016.1225633","volume":"11","author":"Dangjai Souvannakitti","year":"2016","unstructured":"Souvannakitti D, Peerapen P, Thongboonkerd V . Hypobaric hypoxia down-regulated junctional protein complex: implications to vascular leakage. Cell Adh Migr (e-pub ahead of print 14 September 2016; doi:10.1080\/19336918.2016.1225633).","journal-title":"Cell Adhesion & Migration"},{"key":"BFhr20172_CR22","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.cellsig.2011.12.024","volume":"24","author":"AK Ghosh","year":"2012","unstructured":"Ghosh AK, Nagpal V, Covington JW, Michaels MA, Vaughan DE . Molecular basis of cardiac endothelial-to-mesenchymal transition (EndMT): differential expression of microRNAs during EndMT. Cell Signal 2012; 24: 1031\u20131036.","journal-title":"Cell Signal"},{"key":"BFhr20172_CR23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1086\/675980","volume":"4","author":"F Potus","year":"2014","unstructured":"Potus F, Graydon C, Provencher S, Bonnet S . Vascular remodeling process in pulmonary arterial hypertension, with focus on miR-204 and miR-126 (2013 Grover Conference series). Pulm Circ 2014; 4: 175\u2013184.","journal-title":"Pulm Circ"},{"key":"BFhr20172_CR24","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1083\/jcb.200403050","volume":"166","author":"S Liebner","year":"2004","unstructured":"Liebner S, Cattelino A, Gallini R, Rudini N, Iurlaro M, Piccolo S, Dejana E . Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. J Cell Biol 2004; 166: 359\u2013367.","journal-title":"J Cell Biol"},{"key":"BFhr20172_CR25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1161\/CIRCRESAHA.110.225045","volume":"108","author":"J Zou","year":"2011","unstructured":"Zou J, Li WQ, Li Q, Li XQ, Zhang JT, Liu GQ, Chen J, Qiu XX, Tian FJ, Wang ZZ, Zhu N, Qin YW, Shen B, Liu TX, Jing Q . Two functional microRNA-126s repress a novel target gene p21-activated kinase 1 to regulate vascular integrity in zebrafish. Circ Res 2011; 108: 201\u2013209.","journal-title":"Circ Res"},{"key":"BFhr20172_CR26","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","volume":"15","author":"JE Fish","year":"2008","unstructured":"Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D . miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 2008; 15: 272\u2013284.","journal-title":"Dev Cell"},{"key":"BFhr20172_CR27","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1042\/BJ20101500","volume":"437","author":"D Medici","year":"2011","unstructured":"Medici D, Potenta S, Kalluri R . Transforming growth factor-\u03b22 promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling. Biochem J 2011; 437: 515\u2013520.","journal-title":"Biochem J"},{"key":"BFhr20172_CR28","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1242\/jcs.028282","volume":"121","author":"T Kokudo","year":"2008","unstructured":"Kokudo T, Suzuki Y, Yoshimatsu Y, Yamazaki T, Watabe T, Miyazono K . Snail is required for TGFbeta-induced endothelial-mesenchymal transition of embryonic stem cell-derived endothelial cells. J Cell Sci 2008; 121: 3317\u20133324.","journal-title":"J Cell Sci"},{"key":"BFhr20172_CR29","first-page":"577","volume":"18","author":"H Deissler","year":"2006","unstructured":"Deissler H, Deissler H, Lang GK, Lang GE . TGFbeta induces transdifferentiation of iBREC to alphaSMA-expressing cells. Int J Mol Med 2006; 18: 577\u2013582.","journal-title":"Int J Mol Med"},{"key":"BFhr20172_CR30","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1002\/dvdy.20771","volume":"235","author":"AL Tavares","year":"2006","unstructured":"Tavares AL, Mercado-Pimentel ME, Runyan RB, Kitten GT . TGF beta-mediated RhoA expression is necessary for epithelial-mesenchymal transition in the embryonic chick heart. Dev Dyn 2006; 235: 1589\u20131598.","journal-title":"Dev Dyn"},{"key":"BFhr20172_CR31","doi-asserted-by":"publisher","first-page":"31853","DOI":"10.1074\/jbc.M113.463745","volume":"288","author":"L Zeng","year":"2013","unstructured":"Zeng L, Wang G, Ummarino D, Margariti A, Xu Q, Xiao Q, Wang W, Zhang Z, Yin X, Mayr M, Cockerill G, Li JY, Chien S, Hu Y, Xu Q . Histone deacetylase 3 unconventional splicing mediates endothelial-to-mesenchymal transition through transforming growth factor \u03b22. J Biol Chem 2013; 288: 31853\u201331866.","journal-title":"J Biol Chem"},{"key":"BFhr20172_CR32","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/dvdy.21854","volume":"238","author":"M Azhar","year":"2009","unstructured":"Azhar M, Runyan RB, Gard C, Sanford LP, Miller ML, Andringa A, Pawlowski S, Rajan S, Doetschman T . Ligand-specific function of transforming growth factor beta in epithelial-mesenchymal transition in heart development. Dev Dyn 2009; 238: 431\u2013442.","journal-title":"Dev Dyn"},{"key":"BFhr20172_CR33","doi-asserted-by":"publisher","first-page":"48453","DOI":"10.1074\/jbc.M305602200","volume":"278","author":"K Ueki","year":"2003","unstructured":"Ueki K, Fruman DA, Yballe CM, Fasshauer M, Klein J, Asano T, Cantley LC, Kahn CR . Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling. J Biol Chem 2003; 278: 48453\u201348466.","journal-title":"J Biol Chem"},{"key":"BFhr20172_CR34","doi-asserted-by":"publisher","first-page":"5181","DOI":"10.2147\/OTT.S112358","volume":"9","author":"J Xiao","year":"2016","unstructured":"Xiao J, Lin HY, Zhu YY, Zhu YP, Chen LW . MiR-126 regulates proliferation and invasion in the bladder cancer BLS cell line by targeting the PIK3R2-mediated PI3K\/Akt signaling pathway. Onco Targets Ther 2016; 9: 5181\u20135193.","journal-title":"Onco Targets Ther"},{"key":"BFhr20172_CR35","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1515\/hsz-2013-0107","volume":"394","author":"F Huang","year":"2013","unstructured":"Huang F, Fang ZF, Hu XQ, Tang L, Zhou SH, Huang JP . Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K\/Akt and MAPK\/ERK pathways and release of paracrine factors. Biol Chem 2013; 394: 1223\u20131233.","journal-title":"Biol Chem"},{"key":"BFhr20172_CR36","doi-asserted-by":"publisher","first-page":"e83294","DOI":"10.1371\/journal.pone.0083294","volume":"8","author":"J Zhang","year":"2013","unstructured":"Zhang J, Zhang Z, Zhang DY, Zhu J, Zhang T, Wang C . microRNA 126 inhibits the transition of endothelial progenitor cells to mesenchymal cells via the PIK3R2-PI3K\/Akt signalling pathway. PLoS ONE 2013; 8: e83294.","journal-title":"PLoS ONE"},{"key":"BFhr20172_CR37","doi-asserted-by":"publisher","first-page":"675","DOI":"10.5603\/CJ.2011.0032","volume":"18","author":"JJ Chen","year":"2011","unstructured":"Chen JJ, Zhou SH . Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT\/ERK-related pathway. Cardiol J 2011; 18: 675\u2013681.","journal-title":"Cardiol J"},{"key":"BFhr20172_CR38","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1159\/000448713","volume":"53","author":"Y Li","year":"2016","unstructured":"Li Y, Zhou Q, Pei C, Liu B, Li M, Fang L, Sun Y, Li Y, Meng S . Hyperglycemia and advanced glycation end products regulate miR-126 expression in endothelial progenitor cells. J Vasc Res 2016; 53: 94\u2013104.","journal-title":"J Vasc Res"},{"key":"BFhr20172_CR39","doi-asserted-by":"publisher","first-page":"108","DOI":"10.5551\/jat.19257","volume":"21","author":"XQ Sui","year":"2014","unstructured":"Sui XQ, Xu ZM, Xie MB, Pei DA . Resveratrol inhibits hydrogen peroxide-induced apoptosis in endothelial cells via the activation of PI3K\/Akt by miR-126. J Atheroscler Thromb 2014; 21: 108\u2013118.","journal-title":"J Atheroscler Thromb"},{"key":"BFhr20172_CR40","doi-asserted-by":"publisher","first-page":"7223","DOI":"10.1093\/nar\/gkr254","volume":"39","author":"A Turchinovich","year":"2011","unstructured":"Turchinovich A, Weiz L, Langheinz A, Burwinkel B . Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011; 39: 7223\u20137233.","journal-title":"Nucleic Acids Res"}],"container-title":["Hypertension Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/hr20172","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/hr20172.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/hr.2017.2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/hr20172.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T02:20:41Z","timestamp":1641003641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/hr20172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,2]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2017,6]]}},"alternative-id":["BFhr20172"],"URL":"https:\/\/doi.org\/10.1038\/hr.2017.2","relation":{},"ISSN":["0916-9636","1348-4214"],"issn-type":[{"value":"0916-9636","type":"print"},{"value":"1348-4214","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,2]]},"assertion":[{"value":"15 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2016","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 December 2016","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}