{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:02:11Z","timestamp":1790550131297,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"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>Neonatal hypotonia is extremely challenging to diagnose because numerous disorders present similar clinical manifestations. Two panels for diagnosing neonatal hypotonia were developed, which enriches 35 genes corresponding to 61 neonatal hypotonia-related disorders. A cohort of 214 neonates with hypotonia was recruited from 2012 to 2014 in China for this study. Of these subjects, twenty-eight neonates with hypotonia were eliminated according to exclusion criteria and 97 were confirmed using traditional detection methods. The clinical diagnoses of the remaining 89 neonates with hypotonia were approached by targeted next-generation sequencing (NGS). Among the 89 tested neonates, 25 potentially pathogenic variants in nine genes (<jats:italic>RYR1, MECP2, MUT, CDKL5, MPZ, PMM2, MTM1, LAMA2<\/jats:italic> and <jats:italic>DMPK<\/jats:italic>) were identified in 22 patients. Six of these pathogenic variants were novel. Of the 186 neonates with hypotonia, we identified the genetic causes for 117 neonates by the traditional detection methods and targeted NGS, achieving a high solving rate of 62.9%. In addition, we found seven neonates with RETT syndrome carrying five mutations, thus expanding the mutation profiles in Chinese neonates with hypotonia. Our study highlights the utility of comprehensive molecular genetic testing, which provides the advantage of speed and diagnostic specificity without invasive procedures.<\/jats:p>","DOI":"10.1038\/srep29088","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T11:23:40Z","timestamp":1467199420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Next-generation sequencing-based molecular diagnosis of neonatal hypotonia in Chinese Population"],"prefix":"10.1038","volume":"6","author":[{"given":"Yan","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jing","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Qiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Nan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Min","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-li","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Chun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,29]]},"reference":[{"key":"BFsrep29088_CR1","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1177\/08830738050200100401","volume":"20","author":"K Birdi","year":"2005","unstructured":"Birdi, K., Prasad, A. N., Prasad, C., Chodirker, B. & Chudley, A. E. The floppy infant: retrospective analysis of clinical experience (1990\u20132000) in a tertiary care facility. J Child Neurol 20, 803\u2013808 (2005).","journal-title":"J Child Neurol"},{"key":"BFsrep29088_CR2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/S0887-8994(01)00277-6","volume":"25","author":"LP Richer","year":"2001","unstructured":"Richer, L. P., Shevell, M. I. & Miller, S. P. Diagnostic profile of neonatal hypotonia: an 11-year study. Pediatr Neurol 25, 32\u201337, doi: S0887-8994(01)00277-6 [pii] (2001).","journal-title":"Pediatr Neurol"},{"key":"BFsrep29088_CR3","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jpeds.2004.08.047","volume":"146","author":"I Vasta","year":"2005","unstructured":"Vasta, I. et al. Can clinical signs identify newborns with neuromuscular disorders? J Pediatr 146, 73\u201379 (2005).","journal-title":"J Pediatr"},{"key":"BFsrep29088_CR4","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00431-007-0539-3","volume":"167","author":"V Laugel","year":"2008","unstructured":"Laugel, V. et al. Diagnostic approach to neonatal hypotonia: retrospective study on 144 neonates. Eur J Pediatr 167, 517\u2013523 (2008).","journal-title":"Eur J Pediatr"},{"key":"BFsrep29088_CR5","doi-asserted-by":"publisher","first-page":"e66","DOI":"10.1542\/pir.30-9-e66","volume":"30","author":"DE Peredo","year":"2009","unstructured":"Peredo, D. E. & Hannibal, M. C. The floppy infant: evaluation of hypotonia. Pediatr Rev 30, e66\u2013e76 (2009).","journal-title":"Pediatr Rev"},{"key":"BFsrep29088_CR6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.siny.2010.11.002","volume":"16","author":"AN Prasad","year":"2011","unstructured":"Prasad, A. N. & Prasad, C. Genetic evaluation of the floppy infant. Semin Fetal Neonatal Med 16, 99\u2013108 (2011).","journal-title":"Semin Fetal Neonatal Med"},{"key":"BFsrep29088_CR7","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/(SICI)1096-8628(19981116)80:3<263::AID-AJMG16>3.0.CO;2-G","volume":"80","author":"B Muralidhar","year":"1998","unstructured":"Muralidhar, B. & Butler, M. G. Methylation PCR analysis of Prader-Willi syndrome, Angelman syndrome, and control subjects. Am J Med Genet 80, 263\u2013265 (1998).","journal-title":"Am J Med Genet"},{"key":"BFsrep29088_CR8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1089\/109065703322783626","volume":"7","author":"R Xu","year":"2003","unstructured":"Xu, R., Ogino, S., Lip, V., Fang, H. & Wu, B. L. Comparison of PCR-RFLP with allele-specific PCR in genetic testing for spinal muscular atrophy. Genet Test 7, 277\u2013281 (2003).","journal-title":"Genet Test"},{"key":"BFsrep29088_CR9","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1007\/s12031-012-9944-9","volume":"50","author":"K Hamzi","year":"2013","unstructured":"Hamzi, K., Bellayou, H., Itri, M. & Nadifi, S. PCR-RFLP, sequencing, and quantification in molecular diagnosis of spinal muscular atrophy: limits and advantages. J Mol Neurosci 50, 270\u2013274 (2013).","journal-title":"J Mol Neurosci"},{"key":"BFsrep29088_CR10","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1089\/gte.2007.0105","volume":"12","author":"T Munce","year":"2008","unstructured":"Munce, T., Simpson, R. & Bowling, F. Molecular characterization of Prader-Willi syndrome by real-time PCR. Genet Test 12, 319\u2013324 (2008).","journal-title":"Genet Test"},{"key":"BFsrep29088_CR11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1089\/gte.2004.8.387","volume":"8","author":"G Raca","year":"2004","unstructured":"Raca, G., Buiting, K. & Das, S. Deletion analysis of the imprinting center region in patients with Angelman syndrome and Prader-Willi syndrome by real-time quantitative PCR. Genet Test 8, 387\u2013394 (2004).","journal-title":"Genet Test"},{"key":"BFsrep29088_CR12","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1586\/14737159.2015.976555","volume":"15","author":"TJ de Koning","year":"2015","unstructured":"de Koning, T. J., Jongbloed, J. D., Sikkema-Raddatz, B. & Sinke, R. J. Targeted next-generation sequencing panels for monogenetic disorders in clinical diagnostics: the opportunities and challenges. Expert Rev Mol Diagn 15, 61\u201370 (2015).","journal-title":"Expert Rev Mol Diagn"},{"key":"BFsrep29088_CR13","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1007\/s00125-013-2962-5","volume":"56","author":"S Ellard","year":"2013","unstructured":"Ellard, S. et al. Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 56, 1958\u20131963 (2013).","journal-title":"Diabetologia"},{"key":"BFsrep29088_CR14","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1007\/s00438-014-0847-z","volume":"289","author":"Y Wang","year":"2014","unstructured":"Wang, Y. et al. Whole dystrophin gene analysis by next-generation sequencing: a comprehensive genetic diagnosis of Duchenne and Becker muscular dystrophy. Mol Genet Genomics 289, 1013\u20131021 (2014).","journal-title":"Mol Genet Genomics"},{"key":"BFsrep29088_CR15","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ygeno.2013.06.001","volume":"102","author":"Y Yang","year":"2013","unstructured":"Yang, Y. et al. Two homozygous nonsense mutations of GNPTAB gene in two Chinese families with mucolipidosis II alpha\/beta using targeted next-generation sequencing. Genomics 102, 169\u2013173 (2013).","journal-title":"Genomics"},{"key":"BFsrep29088_CR16","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1471-2350-15-14","volume":"15","author":"FR Lepri","year":"2014","unstructured":"Lepri, F. R. et al. Diagnosis of Noonan syndrome and related disorders using target next generation sequencing. BMC Med Genet 15, 14 (2014).","journal-title":"BMC Med Genet"},{"key":"BFsrep29088_CR17","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1007\/s00415-013-7008-x","volume":"260","author":"KR Kumar","year":"2013","unstructured":"Kumar, K. R. et al. Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia. J Neurol 260, 2516\u20132522 (2013).","journal-title":"J Neurol"},{"key":"BFsrep29088_CR18","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1002\/humu.22332","volume":"34","author":"B Sikkema-Raddatz","year":"2013","unstructured":"Sikkema-Raddatz, B. et al. Targeted next-generation sequencing can replace Sanger sequencing in clinical diagnostics. Hum Mutat 34, 1035\u20131042 (2013).","journal-title":"Hum Mutat"},{"key":"BFsrep29088_CR19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/S0387-7604(02)00168-7","volume":"25","author":"HM Johnston","year":"2003","unstructured":"Johnston, H. M. The floppy weak infant revisited. Brain Dev 25, 155\u2013158 (2003).","journal-title":"Brain Dev"},{"key":"BFsrep29088_CR20","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/S0387-7604(03)00066-4","volume":"25","author":"AN Prasad","year":"2003","unstructured":"Prasad, A. N. & Prasad, C. The floppy infant: contribution of genetic and metabolic disorders. Brain Dev 25, 457\u2013476 (2003).","journal-title":"Brain Dev"},{"key":"BFsrep29088_CR21","doi-asserted-by":"publisher","first-page":"e53","DOI":"10.1093\/nar\/gkr1257","volume":"40","author":"MX Li","year":"2012","unstructured":"Li, M. X., Gui, H. S., Kwan, J. S., Bao, S. Y. & Sham, P. C. A comprehensive framework for prioritizing variants in exome sequencing studies of Mendelian diseases. Nucleic Acids Res 40, e53 (2012).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep29088_CR22","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s00439-002-0869-1","volume":"112","author":"V Biancalana","year":"2003","unstructured":"Biancalana, V. et al. Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype. Human genetics 112, 135\u2013142 (2003).","journal-title":"Human genetics"},{"key":"BFsrep29088_CR23","first-page":"1236","volume":"38","author":"T Dua","year":"2001","unstructured":"Dua, T. et al. Spectrum of floppy children in Indian scenario. Indian Pediatr 38, 1236\u20131243 (2001).","journal-title":"Indian Pediatr"},{"key":"BFsrep29088_CR24","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1002\/ajmg.10633","volume":"111","author":"HA Heilstedt","year":"2002","unstructured":"Heilstedt, H. A., Shahbazian, M. D. & Lee, B. Infantile hypotonia as a presentation of Rett syndrome. Am J Med Genet 111, 238\u2013242 (2002).","journal-title":"Am J Med Genet"},{"key":"BFsrep29088_CR25","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/501261a","volume":"501","author":"V Marx","year":"2013","unstructured":"Marx, V. Next-generation sequencing: The genome jigsaw. Nature 501, 263\u2013268 (2013).","journal-title":"Nature"},{"key":"BFsrep29088_CR26","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","volume":"43","author":"MA DePristo","year":"2011","unstructured":"DePristo, M. A. et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet 43, 491\u2013498 (2011).","journal-title":"Nat Genet"},{"key":"BFsrep29088_CR27","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1038\/ng.437","volume":"41","author":"C Alkan","year":"2009","unstructured":"Alkan, C. et al. Personalized copy number and segmental duplication maps using next-generation sequencing. Nat Genet 41, 1061\u20131067 (2009).","journal-title":"Nat Genet"},{"key":"BFsrep29088_CR28","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.cell.2011.09.008","volume":"147","author":"JR Lupski","year":"2011","unstructured":"Lupski, J. R., Belmont, J. W., Boerwinkle, E. & Gibbs, R. A. Clan genomics and the complex architecture of human disease. Cell 147, 32\u201343 (2011).","journal-title":"Cell"},{"key":"BFsrep29088_CR29","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/ng.3300","volume":"47","author":"I Surakka","year":"2015","unstructured":"Surakka, I. et al. The impact of low-frequency and rare variants on lipid levels. Nat Genet 47, 589\u2013597 (2015).","journal-title":"Nat Genet"},{"key":"BFsrep29088_CR30","doi-asserted-by":"publisher","first-page":"e31039","DOI":"10.1371\/journal.pone.0031039","volume":"7","author":"C Cruchaga","year":"2012","unstructured":"Cruchaga, C. et al. Rare variants in APP, PSEN1 and PSEN2 increase risk for AD in late-onset Alzheimer\u2019s disease families. PLoS One 7, e31039 (2012).","journal-title":"PLoS One"},{"key":"BFsrep29088_CR31","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/gb-2012-13-12-182","volume":"13","author":"A Platt","year":"2012","unstructured":"Platt, A. & Novembre, J. A new era of human population genetics. Genome Biol 13, 182 (2012).","journal-title":"Genome Biol"},{"key":"BFsrep29088_CR32","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nature11632","volume":"491","author":"GR Abecasis","year":"2012","unstructured":"Abecasis, G. R. et al. An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56\u201365 (2012).","journal-title":"Nature"},{"key":"BFsrep29088_CR33","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1177\/088307380401900608","volume":"19","author":"D Paro-Panjan","year":"2004","unstructured":"Paro-Panjan, D. & Neubauer, D. Congenital hypotonia: is there an algorithm? J Child Neurol 19, 439\u2013442 (2004).","journal-title":"J Child Neurol"},{"key":"BFsrep29088_CR34","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1073\/pnas.90.6.2509","volume":"90","author":"P Rasch","year":"1993","unstructured":"Rasch, P., Wiedemann, U., Wienberg, J. & Heckl, W. M. Analysis of banded human chromosomes and in situ hybridization patterns by scanning force microscopy. Proc Natl Acad Sci USA 90, 2509\u20132511 (1993).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep29088_CR35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.ymgme.2006.05.001","volume":"89","author":"WC Hubbard","year":"2006","unstructured":"Hubbard, W. C. et al. Combined liquid chromatography-tandem mass spectrometry as an analytical method for high throughput screening for X-linked adrenoleukodystrophy and other peroxisomal disorders: preliminary findings. Mol Genet Metab 89, 185\u2013187 (2006).","journal-title":"Mol Genet Metab"},{"key":"BFsrep29088_CR36","doi-asserted-by":"publisher","first-page":"446","DOI":"10.2353\/jmoldx.2009.090015","volume":"11","author":"W Wang","year":"2009","unstructured":"Wang, W., Law, H. Y. & Chong, S. S. Detection and discrimination between deletional and non-deletional Prader-Willi and Angelman syndromes by methylation-specific PCR and quantitative melting curve analysis. J Mol Diagn 11, 446\u2013449 (2009).","journal-title":"J Mol Diagn"},{"key":"BFsrep29088_CR37","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s10048-006-0051-3","volume":"7","author":"O Scarciolla","year":"2006","unstructured":"Scarciolla, O. et al. Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification. Neurogenetics 7, 269\u2013276 (2006).","journal-title":"Neurogenetics"},{"key":"BFsrep29088_CR38","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/jhg.2015.65","volume":"60","author":"T Shimokaze","year":"2015","unstructured":"Shimokaze, T. et al. Genotype-phenotype relationship in Japanese patients with congenital central hypoventilation syndrome. J Hum Genet 60, 473\u2013477 (2015).","journal-title":"J Hum Genet"},{"key":"BFsrep29088_CR39","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","volume":"26","author":"H Li","year":"2010","unstructured":"Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589\u2013595 (2010).","journal-title":"Bioinformatics"},{"key":"BFsrep29088_CR40","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1093\/nar\/29.1.308","volume":"29","author":"ST Sherry","year":"2001","unstructured":"Sherry, S. T. et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29, 308\u2013311 (2001).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep29088_CR41","doi-asserted-by":"publisher","first-page":"D980","DOI":"10.1093\/nar\/gkt1113","volume":"42","author":"MJ Landrum","year":"2014","unstructured":"Landrum, M. J. et al. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res 42, D980\u2013D985 (2014).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep29088_CR42","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/bioinformatics\/btq330","volume":"26","author":"W McLaren","year":"2010","unstructured":"McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26, 2069\u20132070 (2010).","journal-title":"Bioinformatics"},{"key":"BFsrep29088_CR43","doi-asserted-by":"publisher","first-page":"2725","DOI":"10.1093\/molbev\/mst197","volume":"30","author":"K Tamura","year":"2013","unstructured":"Tamura, K., Stecher, G., Peterson, D., Filipski, A. & Kumar, S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Molecular biology and evolution 30, 2725\u20132729 (2013).","journal-title":"Molecular biology and evolution"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep29088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29088","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep29088.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T04:45:55Z","timestamp":1672893955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep29088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,29]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,27]]}},"alternative-id":["BFsrep29088"],"URL":"https:\/\/doi.org\/10.1038\/srep29088","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,29]]},"assertion":[{"value":"5 March 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 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":"29088"}}