{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:18:12Z","timestamp":1778642292094,"version":"3.51.4"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T00:00:00Z","timestamp":1479772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T00:00:00Z","timestamp":1479772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To investigate whether single nucleotide polymorphisms (SNPs) of the Tumor Necrosis Factor Superfamily 4 (TNFSF4) gene are associated with Vogt\u2013Koyanagi\u2013Harada (VKH) and Behcet\u2019s disease (BD) in a Chinese Han population. A two-stage case control study was carried out in 1331 VKH, 938 BD and 1752 healthy controls. Ten TNFSF4 SNPs, including rs1234314, rs1234315, rs2205960, rs704840, rs2795288, rs844654, rs12039904, rs10912580, rs844665, and rs844644, were genotyped using the PCR-restriction fragment length polymorphism method. Genotype and allele frequencies were analyzed between cases and healthy controls using the X<jats:sup>2<\/jats:sup> or Fisher\u2019s exact test and p values were corrected for multiple comparisons. We observed a significantly increased frequency of the TT genotype of rs1234315 in BD patients (Pc\u2009=\u20091.44\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>, OR\u2009=\u20091.734, 95% CI\u2009=\u20091.398\u20132.151). The frequency of the TT genotype of rs12039904 was significantly higher in patients with VKH disease as compared to controls (Pc\u2009=\u20094.62\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>, OR\u2009=\u20091.959, 95% CI\u2009=\u20091.483\u20132.588). Analysis of clinical manifestations in VKH disease and BD did not show an association with the TNFSF4 gene polymorphisms. The study suggests that the TNFSF4 gene may be involved in the susceptibility to VKH disease and BD in Han Chinese.<\/jats:p>","DOI":"10.1038\/srep37257","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T09:59:51Z","timestamp":1479808791000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Association of TNFSF4 Polymorphisms with Vogt-Koyanagi-Harada and Behcet\u2019s Disease in Han Chinese"],"prefix":"10.1038","volume":"6","author":[{"given":"Sha","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengfang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengping","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peizeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,22]]},"reference":[{"key":"BFsrep37257_CR1","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.ophtha.2007.04.056","volume":"115","author":"P Yang","year":"2008","unstructured":"Yang, P. et al. Clinical features of Chinese patients with Behcet\u2019s disease. Ophthalmology 115, 312\u2013318 e314 (2008).","journal-title":"Ophthalmology"},{"key":"BFsrep37257_CR2","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.ophtha.2006.07.040","volume":"114","author":"P Yang","year":"2007","unstructured":"Yang, P. et al. Clinical characteristics of Vogt\u2013Koyanagi\u2013Harada syndrome in Chinese patients. Ophthalmology 114, 606\u2013614 (2007).","journal-title":"Ophthalmology"},{"key":"BFsrep37257_CR3","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1080\/02713680500263606","volume":"30","author":"P Yang","year":"2005","unstructured":"Yang, P. et al. Clinical patterns and characteristics of uveitis in a tertiary center for uveitis in China. Curr Eye Res 30, 943\u2013948 (2005).","journal-title":"Curr Eye Res"},{"key":"BFsrep37257_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1067\/mlc.2003.1","volume":"141","author":"I Bank","year":"2003","unstructured":"Bank, I., Duvdevani, M. & Livneh, A. Expansion of gammadelta T-cells in Behcet\u2019s disease: role of disease activity and microbial flora in oral ulcers. J Lab Clin Med 141, 33\u201340 (2003).","journal-title":"J Lab Clin Med"},{"key":"BFsrep37257_CR5","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/j.jaci.2007.01.010","volume":"119","author":"W Chi","year":"2007","unstructured":"Chi, W. et al. IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease. J Allergy Clin Immunol 119, 1218\u20131224 (2007).","journal-title":"J Allergy Clin Immunol"},{"key":"BFsrep37257_CR6","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1097\/01.wco.0000169753.31321.4e","volume":"18","author":"SJ Sheu","year":"2005","unstructured":"Sheu, S. J. Update on uveomeningoencephalitides. Curr Opin Neurol 18, 323\u2013329 (2005).","journal-title":"Curr Opin Neurol"},{"key":"BFsrep37257_CR7","doi-asserted-by":"publisher","first-page":"4104","DOI":"10.1002\/art.37708","volume":"64","author":"S Hou","year":"2012","unstructured":"Hou, S. et al. Identification of a susceptibility locus in STAT4 for Behcet\u2019s disease in Han Chinese in a genome-wide association study. Arthritis Rheum 64, 4104\u20134113 (2012).","journal-title":"Arthritis Rheum"},{"key":"BFsrep37257_CR8","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/ng.3061","volume":"46","author":"S Hou","year":"2014","unstructured":"Hou, S. et al. Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3. Nat Genet 46, 1007\u20131011 (2014).","journal-title":"Nat Genet"},{"key":"BFsrep37257_CR9","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1034\/j.1399-0039.1999.540301.x","volume":"54","author":"DH Verity","year":"1999","unstructured":"Verity, D. H., Marr, J. E., Ohno, S., Wallace, G. R. & Stanford, M. R. Beh\u00e7et\u2019s disease, the Silk Road and HLA-B51:historical and geographical perspectives. Tissue Antigens 54, 213\u2013220 (1999).","journal-title":"Tissue Antigens"},{"key":"BFsrep37257_CR10","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/ng.625","volume":"42","author":"EF Remmers","year":"2010","unstructured":"Remmers, E. F. et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Beh\u00e7et\u2019s disease. Nat Genet 42, 698\u2013702 (2010).","journal-title":"Nat Genet"},{"key":"BFsrep37257_CR11","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/ng.624","volume":"42","author":"N Mizuki","year":"2010","unstructured":"Mizuki, N. et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Beh\u00e7et\u2019s disease susceptibility loci. Nat Genet 42, 703\u2013706 (2010).","journal-title":"Nat Genet"},{"key":"BFsrep37257_CR12","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1001\/archopht.1991.01080030070041","volume":"109","author":"M Zhao","year":"1991","unstructured":"Zhao, M., Jiang, Y. & Abrahams, I. W. Association of HLA antigens with Vogt-Koyanagi-Harada syndrome in a Han Chinese population. Arch Ophthalmol 109, 368\u2013370 (1991).","journal-title":"Arch Ophthalmol"},{"key":"BFsrep37257_CR13","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.humimm.2010.06.020","volume":"71","author":"Q Shu","year":"2010","unstructured":"Shu, Q. et al. Interleukin-17 gene polymorphism is associated with Vogt-Koyanagi-Harada syndrome but not with Beh\u00e7et\u2019s disease in a Chinese Han population. Hum Immunol 71, 988\u2013991 (2010).","journal-title":"Hum Immunol"},{"key":"BFsrep37257_CR14","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1136\/ard.2010.141838","volume":"70","author":"L Bossini-Castillo","year":"2011","unstructured":"Bossini-Castillo, L. et al. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort. Ann Rheum Dis 70(4), 638\u2013641 (2011).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep37257_CR15","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/gene.2008.95","volume":"10","author":"A Delgado-Vega","year":"2009","unstructured":"Delgado-Vega, A. et al. Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus. Genes & Immunity 10(3), 248\u2013253 (2009).","journal-title":"Genes & Immunity"},{"key":"BFsrep37257_CR16","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/gene.2009.16","volume":"10","author":"YK Chang","year":"2009","unstructured":"Chang, Y. K. et al. Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese. Genes Immun 10(5), 414\u2013420 (2009).","journal-title":"Genes Immun"},{"key":"BFsrep37257_CR17","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1002\/art.33318","volume":"64","author":"XJ Zhou","year":"2012","unstructured":"Zhou, X. J. et al. Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus. Arthritis Rheum 64(1), 222\u2013231 (2012).","journal-title":"Arthritis Rheum"},{"key":"BFsrep37257_CR18","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00296-009-1247-2","volume":"31","author":"SQ Zhang","year":"2011","unstructured":"Zhang, S. Q. et al. A single-nucleotide polymorphism of the TNFSF4 gene is associated with systemic lupus erythematosus in Chinese Han population. Rheumatol Int 31(2), 227\u2013231 (2011).","journal-title":"Rheumatol Int"},{"key":"BFsrep37257_CR19","doi-asserted-by":"publisher","first-page":"686","DOI":"10.3109\/s10165-012-0708-8","volume":"23","author":"MM Lu","year":"2013","unstructured":"Lu, M. M. et al. Association of TNFSF4 polymorphisms with systemic lupus erythematosus: a meta-analysis. Mod Rheumatol 23(4), 686\u2013693 (2013).","journal-title":"Mod Rheumatol"},{"key":"BFsrep37257_CR20","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.humimm.2012.07.044","volume":"73","author":"YH Lee","year":"2012","unstructured":"Lee, Y. H. & Song, G. G. Associations between TNFSF4 and TRAF1-C5 gene polymorphisms and systemic lupus erythematosus: a meta-analysis. Hum Immunol 73(10), 1050\u20131054 (2012).","journal-title":"Hum Immunol"},{"key":"BFsrep37257_CR21","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1136\/ard.2009.116434","volume":"69","author":"P Gourh","year":"2010","unstructured":"Gourh, P. et al. Association of TNFSF4 (OX40L) polymorphisms with susceptibility to systemic sclerosis. Ann Rheum Dis 69(3), 550\u2013555 (2010).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep37257_CR22","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/gene.2010.44","volume":"12","author":"G Nordmark","year":"2010","unstructured":"Nordmark, G. et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sj\u00f6gren\u2019s syndrome. Genes Immun 12(2), 100\u2013109 (2010).","journal-title":"Genes Immun"},{"key":"BFsrep37257_CR23","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1038\/nri2526","volume":"9","author":"M Croft","year":"2009","unstructured":"Croft, M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9, 271\u2013285 (2009).","journal-title":"Nat Rev Immunol"},{"key":"BFsrep37257_CR24","first-page":"3992","volume":"13","author":"PR Baum","year":"1994","unstructured":"Baum, P. R. et al. Molecular characterization of murine and human OX40\/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34. E MBO J 13, 3992\u20134001 (1994).","journal-title":"E MBO J"},{"key":"BFsrep37257_CR25","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/eji.1830240329","volume":"24","author":"U Latza","year":"1994","unstructured":"Latza, U. et al. The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen. Eur J Immunol 24, 677\u2013683 (1994).","journal-title":"Eur J Immunol"},{"key":"BFsrep37257_CR26","doi-asserted-by":"publisher","first-page":"13138","DOI":"10.1073\/pnas.0603107103","volume":"03","author":"T Ito","year":"2006","unstructured":"Ito, T. et al. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci USA 03, 13138\u201313143 (2006).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep37257_CR27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.cellimm.2008.04.010","volume":"253","author":"J Li","year":"2008","unstructured":"Li, J. et al. Negative regulation of IL-17 production by OX40\/OX40L interaction. Cell Immunol 253, 31\u201337 (2008).","journal-title":"Cell Immunol"},{"key":"BFsrep37257_CR28","doi-asserted-by":"crossref","first-page":"6510","DOI":"10.4049\/jimmunol.161.12.6510","volume":"161","author":"I Gramaglia","year":"1998","unstructured":"Gramaglia, I., Weinberg, A. D., Lemon, M. & Croft, M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol 161, 6510\u20136517 (1998).","journal-title":"J Immunol"},{"key":"BFsrep37257_CR29","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.4049\/jimmunol.181.5.3193","volume":"181","author":"X Xiao","year":"2008","unstructured":"Xiao, X. et al. OX40\/OX40L costimulation affects induction of Foxp3+ regulatory T-cells in part by expanding memory T-cells in vivo. J Immunol 181, 3193\u20133201 (2008).","journal-title":"J Immunol"},{"key":"BFsrep37257_CR30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/s00296-008-0697-2","volume":"29","author":"YB Zhou","year":"2009","unstructured":"Zhou, Y. B., Ye, R. G., Li, Y. J. & Xie, C. M. Targeting the CD134-CD134L interaction using anti-CD134 and\/or rhCD134 fusion protein as a possible strategy to prevent lupus nephritis. Rheumatology International 29(4), 417\u2013425 (2009).","journal-title":"Rheumatology International"},{"key":"BFsrep37257_CR31","doi-asserted-by":"publisher","first-page":"29","DOI":"10.4103\/0256-4947.75775","volume":"31","author":"MN Farres","year":"2011","unstructured":"Farres, M. N., Al-Zifzaf, D. S., Aly, A. A. & Abd Raboh, N. M. OX40\/OX40L in systemic lupus erythematosus: association with disease activity and lupus nephritis. Annals of Saudi Medicine 31(1), 29\u201334 (2011).","journal-title":"Annals of Saudi Medicine"},{"key":"BFsrep37257_CR32","doi-asserted-by":"publisher","first-page":"8520","DOI":"10.1167\/iovs.11-7664","volume":"52","author":"X Wu","year":"2011","unstructured":"Wu, X. et al. Activation of OX40 Prolongs and Exacerbates Autoimmune Experimental Uveitis. Investigative Ophthalmology & Visual Science 52(11), 8520\u20138526 (2011).","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"BFsrep37257_CR33","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00109-008-0431-2","volume":"87","author":"H Manku","year":"2009","unstructured":"Manku, H., Graham, D. S. & Vyse, T. J. Association of the co-stimulator OX40L with systemic lupus erythematosus. J Mol Med 87(3), 229\u2013234 (2009).","journal-title":"J Mol Med"},{"key":"BFsrep37257_CR34","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1136\/ard.57.1.45","volume":"57","author":"I Fresko","year":"1998","unstructured":"Fresko, I. et al. Genetic anticipation in Behcet\u2019s syndrome. Ann Rheum Dis 57, 45\u201348 (1998).","journal-title":"Ann Rheum Dis"},{"key":"BFsrep37257_CR35","first-page":"335","volume":"10","author":"S Ohno","year":"1981","unstructured":"Ohno, S. Immunological aspects of Behcet\u2019s and Vogt\u2013Koyanagi-Harada\u2019s diseases. Trans Ophthalmol Soc K 10, 335\u2013341 (1981).","journal-title":"Trans Ophthalmol Soc K"},{"key":"BFsrep37257_CR36","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1097\/00004397-200201000-00004","volume":"42","author":"K Yamaki","year":"2002","unstructured":"Yamaki, K., Gocho, K. & Sakuragi, S. Pathogenesis of Vogt-Koyanagi-Harada disease. Int Ophthalmol Clin 42, 13\u201323 (2002).","journal-title":"Int Ophthalmol Clin"},{"key":"BFsrep37257_CR37","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1097\/00006982-199414050-00008","volume":"14","author":"A Ishikawa","year":"1994","unstructured":"Ishikawa, A., Shiono, T. & Uchida, S. Vogt\u2013Koyanagi\u2013Harada disease in identical twins. Retina 14, 435\u2013437 (1994).","journal-title":"Retina"},{"key":"BFsrep37257_CR38","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1093\/rheumatology\/ker345","volume":"51","author":"F Chen","year":"2012","unstructured":"Chen, F. et al. CD40 gene polymorphisms confer risk of Behcet\u2019s disease but not of Vogt-Koyanagi-Harada syndrome in a Han Chinese population. Rheumatology (Oxford) 51, 47\u201351 (2012).","journal-title":"Rheumatology (Oxford)"},{"key":"BFsrep37257_CR39","doi-asserted-by":"publisher","first-page":"4104","DOI":"10.1002\/art.37708","volume":"64","author":"S Hou","year":"2012","unstructured":"Hou, S. et al. Genome-wide association study identifies susceptible locus in STAT4 for Behcet\u2019s disease in Han Chinese. Arthritis Rheum 64(12), 4104\u20134013 (2012).","journal-title":"Arthritis Rheum"},{"key":"BFsrep37257_CR40","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1167\/iovs.11-8440","volume":"53","author":"K Hu","year":"2012","unstructured":"Hu, K., Hou, S., Jiang, Z., Kijlstra, A. & Yang, P. JAK2 and STAT3 polymorphisms in a Han Chinese population with Behcet\u2019s disease. Invest Ophthalmol Vis Sci 53, 538\u2013541 (2012).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFsrep37257_CR41","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.humimm.2010.04.007","volume":"71","author":"K Hu","year":"2010","unstructured":"Hu, K. et al. STAT4 polymorphism in a Chinese Han population with Vogt\u2013Koyanagi\u2013Harada syndrome and Behcet\u2019sdisease. Human Immunology 71, 723\u2013726 (2010).","journal-title":"Human Immunology"},{"key":"BFsrep37257_CR42","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1167\/iovs.05-1547","volume":"47","author":"S Sugita","year":"2006","unstructured":"Sugita, S. et al. Ocular infiltrating CD4+ T cells from patients with Vogt-Koyanagi-Harada disease recognize human melanocyte antigens. Invest Ophthalmol Vis Sci 47, 2547\u20132554 (2006).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"BFsrep37257_CR43","first-page":"335","volume":"101","author":"S Ohno","year":"1981","unstructured":"Ohno, S. Immunological aspects of Behcet\u2019s and Vogt-Koyanagi-Harada\u2019s diseases. Trans Ophthalmol Soc UK 101, 335\u2013341 (1981).","journal-title":"Trans Ophthalmol Soc UK"},{"key":"BFsrep37257_CR44","doi-asserted-by":"crossref","unstructured":"Criteria for diagnosis of Behcet\u2019s disease. International Study Group for Behcet\u2019s disease. Lancet 335, 1078\u20131080 (1990).","DOI":"10.1016\/0140-6736(90)92643-V"},{"key":"BFsrep37257_CR45","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/S0002-9394(01)00925-4","volume":"131","author":"RW Read","year":"2001","unstructured":"Read, R. W. et al. Revised diagnostic criteria for Vogt\u2013Koyanagi\u2013Harada disease: Report of an international committee on nomenclature. Am J Ophthalmol 131, 647\u2013652 (2001).","journal-title":"Am J Ophthalmol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep37257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37257","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep37257.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T02:22:59Z","timestamp":1672885379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep37257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,22]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep37257"],"URL":"https:\/\/doi.org\/10.1038\/srep37257","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,22]]},"assertion":[{"value":"31 August 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"37257"}}