{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:07:48Z","timestamp":1791587268702,"version":"4.3.4"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"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":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chromosome 15 (C15) imprinting disorders including Prader\u2013Willi (PWS), Angelman (AS) and chromosome 15 duplication (Dup15q) syndromes are severe neurodevelopmental disorders caused by abnormal expression of genes from the 15q11\u2013q13 region, associated with abnormal DNA methylation and\/or copy number changes. This study compared changes in mRNA levels of <jats:italic>UBE3A<\/jats:italic> and <jats:italic>SNORD116<\/jats:italic> located within the 15q11\u2013q13 region between these disorders and their subtypes and related these to the clinical phenotypes. The study cohort included 58 participants affected with a C15 imprinting disorder (PWS\u2009=\u200927, AS\u2009=\u200921, Dup15q\u2009=\u200910) and 20 typically developing controls. Semi-quantitative analysis of mRNA from peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription droplet digital polymerase chain reaction (PCR) for <jats:italic>UBE3A<\/jats:italic> and <jats:italic>SNORD116<\/jats:italic> normalised to a panel of internal control genes determined using the geNorm approach. Participants completed an intellectual\/developmental functioning assessment and the Autism Diagnostic Observation Schedule-2nd Edition. The Dup15q group was the only condition with significantly increased <jats:italic>UBE3A<\/jats:italic> mRNA levels when compared to the control group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Both the AS and Dup15q groups also had significantly elevated <jats:italic>SNORD116<\/jats:italic> mRNA levels compared to controls (AS: <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001; Dup15q: <jats:italic>p<\/jats:italic>\u2009=\u20090.002). Both <jats:italic>UBE3A<\/jats:italic> and <jats:italic>SNORD116<\/jats:italic> mRNA levels were positively correlated with all developmental functioning scores in the deletion AS group (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and autism features (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) in the non-deletion PWS group. The findings suggest presence of novel interactions between expression of <jats:italic>UBE3A<\/jats:italic> and <jats:italic>SNORD116<\/jats:italic> in PBMCs and brain specific processes underlying motor and language impairments and autism features in these disorders.<\/jats:p>","DOI":"10.1038\/s41398-020-01034-7","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T02:02:40Z","timestamp":1603936960000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders"],"prefix":"10.1038","volume":"10","author":[{"given":"Emma K.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merlin G.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha N.","family":"Hartin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh","family":"Bui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-934X","authenticated-orcid":false,"given":"Michael J.","family":"Field","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie","family":"Slee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinusha","family":"Gamage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-8511","authenticated-orcid":false,"given":"David J.","family":"Amor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6405-269X","authenticated-orcid":false,"given":"David E.","family":"Godler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"1034_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s11689-018-9242-0","volume":"10","author":"EK Baker","year":"2018","unstructured":"Baker, E. K. et al. Exploring autism symptoms in an Australian cohort of patients with Prader-Willi and Angelman syndromes. J. Neurodev. Disord. 10, 24 (2018).","journal-title":"J. Neurodev. Disord."},{"key":"1034_CR2","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.nbd.2008.08.011","volume":"38","author":"A Hogart","year":"2010","unstructured":"Hogart, A., Wu, D., LaSalle, J. M. & Schanen, N. C. The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13. Neurobiol. Dis. 38, 181\u2013191 (2010).","journal-title":"Neurobiol. Dis."},{"key":"1034_CR3","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.pcl.2015.03.004","volume":"62","author":"L Kalsner","year":"2015","unstructured":"Kalsner, L. & Chamberlain, S. J. Prader-Willi, Angelman, and 15q11-q13 duplication syndromes. Pediatr. Clin. North. Am. 62, 587\u2013606 (2015).","journal-title":"Pediatr. Clin. North. Am."},{"key":"1034_CR4","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/342281a0","volume":"342","author":"RD Nicholls","year":"1989","unstructured":"Nicholls, R. D., Knoll, J. H. M., Butler, M. G., Karam, S. & Lalande, M. Genetic imprinting suggested by maternal heterodisomy in non-deletion Prader-Willi syndrome. Nature 342, 281\u2013285 (1989).","journal-title":"Nature"},{"key":"1034_CR5","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/ajmg.1320350306","volume":"35","author":"MG Butler","year":"1990","unstructured":"Butler, M. G. Prader-Willi syndrome: current understanding of cause and diagnosis. Am. J. Med. Genet. 35, 319\u2013332 (1990).","journal-title":"Am. J. Med. Genet."},{"key":"1034_CR6","unstructured":"Dagli A. I., Mueller J., Williams C. A. Angelman Syndrome. GeneReviews\u00ae. (University of Washington, WA, Seattle, 1998) [Updated 21 Dec 2017]."},{"key":"1034_CR7","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1007\/s40618-015-0312-9","volume":"38","author":"MA Angulo","year":"2015","unstructured":"Angulo, M. A., Butler, M. G. & Cataletto, M. E. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J. Endocrinol. Investig. 38, 1249\u20131263 (2015).","journal-title":"J. Endocrinol. Investig."},{"key":"1034_CR8","unstructured":"Driscoll D. J., Miller J. L., Schwartz S., Cassidy S. B. Prader-Willi syndrome. in (eds Adam M. P., Ardinger H. H., Pagon R. A., Wallace S. E., Bean LJH, Stephens K., et al.). GeneReviews\u00ae. (University of Washington, Seattle, WA, 1993)."},{"key":"1034_CR9","first-page":"488","volume":"101","author":"YN Teng","year":"2002","unstructured":"Teng, Y. N. et al. Referral diagnosis of Prader-Willi syndrome and Angelman syndrome based on methylation-specific polymerase chain reaction. J. Formos. Med. Assoc. 101, 488\u2013494 (2002).","journal-title":"J. Formos. Med. Assoc."},{"key":"1034_CR10","first-page":"928","volume":"60","author":"EH Cook","year":"1997","unstructured":"Cook, E. H. et al. Autism or atypical autism in maternally but not paternally derived proximal 15q duplication. Am. J. Hum. Genet. 60, 928\u2013934 (1997).","journal-title":"Am. J. Hum. Genet."},{"key":"1034_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005993","volume":"12","author":"AR Isles","year":"2016","unstructured":"Isles, A. R. et al. Parental origin of interstitial duplications at 15q11.2-q13.3 in schizophrenia and neurodevelopmental disorders. PLoS Genet. 12, e1005993 (2016).","journal-title":"PLoS Genet."},{"key":"1034_CR12","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1111\/cge.13142","volume":"93","author":"AM Manzardo","year":"2018","unstructured":"Manzardo, A. M., Weisensel, N., Ayala, S., Hossain, W. & Butler, M. G. Prader-Willi syndrome genetic subtypes and clinical neuropsychiatric diagnoses in residential care adults. Clin. Genet. 93, 622\u2013631 (2018).","journal-title":"Clin. Genet."},{"issue":"Pt 1","key":"1034_CR13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1046\/j.1365-2788.2000.00250.x","volume":"44","author":"E Roof","year":"2000","unstructured":"Roof, E. et al. Intellectual characteristics of Prader-Willi syndrome: comparison of genetic subtypes. J. Intellect. Disabil. Res. 44(Pt 1), 25\u201330 (2000).","journal-title":"J. Intellect. Disabil. Res."},{"key":"1034_CR14","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1542\/peds.113.3.565","volume":"113","author":"MG Butler","year":"2004","unstructured":"Butler, M. G., Bittel, D. C., Kibiryeva, N., Talebizadeh, Z. & Thompson, T. Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy. Pediatrics 113, 565\u2013573 (2004).","journal-title":"Pediatrics"},{"key":"1034_CR15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13072-017-0134-4","volume":"10","author":"PR Hillman","year":"2017","unstructured":"Hillman, P. R. et al. Genomic imprinting does not reduce the dosage of UBE3A in neurons. Epigenetics Chromatin 10, 27 (2017).","journal-title":"Epigenetics Chromatin"},{"key":"1034_CR16","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/s00439-004-1104-z","volume":"114","author":"M Runte","year":"2004","unstructured":"Runte, M. et al. SNURF-SNRPN and UBE3A transcript levels in patients with Angelman syndrome. Hum. Genet. 114, 553\u2013561 (2004).","journal-title":"Hum. Genet."},{"key":"1034_CR17","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/ng.158","volume":"40","author":"T Sahoo","year":"2008","unstructured":"Sahoo, T. et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C\/D box small nucleolar RNA cluster. Nat. Genet. 40, 719\u2013721 (2008).","journal-title":"Nat. Genet."},{"key":"1034_CR18","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/hmg\/ddg106","volume":"12","author":"K Yamasaki","year":"2003","unstructured":"Yamasaki, K. et al. Neurons but not glial cells show reciprocal imprinting of sense and antisense transcripts of Ube3a. Hum. Mol. Genet. 12, 837\u2013847 (2003).","journal-title":"Hum. Mol. Genet."},{"key":"1034_CR19","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1006\/geno.2001.6543","volume":"73","author":"SJ Chamberlain","year":"2001","unstructured":"Chamberlain, S. J. & Brannan, C. I. The Prader-Willi syndrome imprinting center activates the paternally expressed murine Ube3a antisense transcript but represses paternal Ube3a. Genomics 73, 316\u2013322 (2001).","journal-title":"Genomics"},{"key":"1034_CR20","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1126\/science.aav8130","volume":"364","author":"D Velmeshev","year":"2019","unstructured":"Velmeshev, D. et al. Single-cell genomics identifies cell type\u2013specific molecular changes in autism. Science 364, 685\u2013689 (2019).","journal-title":"Science"},{"key":"1034_CR21","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/genes7090068","volume":"7","author":"YT Hwang","year":"2016","unstructured":"Hwang, Y. T. et al. Molecular inconsistencies in a fragile X male with early onset ataxia. Genes 7, 68 (2016).","journal-title":"Genes"},{"key":"1034_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-21990-x","volume":"8","author":"M Arpone","year":"2018","unstructured":"Arpone, M. et al. Intragenic DNA methylation in buccal epithelial cells and intellectual functioning in a paediatric cohort of males with fragile X. Sci. Rep. 8, 3644 (2018).","journal-title":"Sci. Rep."},{"key":"1034_CR23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1136\/jmedgenet-2018-105301","volume":"56","author":"MG Butler","year":"2019","unstructured":"Butler, M. G. et al. Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study. J. Med. Genet. 56, 149\u2013153 (2019).","journal-title":"J. Med. Genet."},{"key":"1034_CR24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1097\/GIM.0b013e3182064362","volume":"13","author":"DZ Loesch","year":"2011","unstructured":"Loesch, D. Z. et al. Evidence for the toxicity of bidirectional transcripts and mitochondrial dysfunction in blood associated with small CGG expansions in the FMR1 gene in patients with parkinsonism. Genet. Med. 13, 392 (2011).","journal-title":"Genet. Med."},{"key":"1034_CR25","volume-title":"Mullen Scales of Early Learning","author":"EM Mullen","year":"1995","unstructured":"Mullen, E. M. Mullen Scales of Early Learning. (American Guidance Service, MN, 1995)."},{"key":"1034_CR26","volume-title":"Wechsler Preschool and Primary Scale of Intelligence\u2014Third Edition Australian Standardised Edition","author":"D Wechsler","year":"2004","unstructured":"Wechsler, D. Wechsler Preschool and Primary Scale of Intelligence\u2014Third Edition Australian Standardised Edition. (NCS Pearson Inc., NSW, 2004)."},{"key":"1034_CR27","volume-title":"Wechsler Intelligence Scale for Children\u2013Fourth Edition Australian Standardised Edition","author":"D Wechsler","year":"2003","unstructured":"Wechsler, D. Wechsler Intelligence Scale for Children\u2013Fourth Edition Australian Standardised Edition. (NCS Pearson Inc., NSW, 2003)."},{"key":"1034_CR28","volume-title":"Wechsler Adult Intelligence Scale\u2014Fourth Edition Australian and New Zealand Language Adaptation","author":"D Wechsler","year":"2008","unstructured":"Wechsler, D. Wechsler Adult Intelligence Scale\u2014Fourth Edition Australian and New Zealand Language Adaptation. (NCS Pearson Inc., NSW, 2008)."},{"key":"1034_CR29","unstructured":"Lord C., et al. Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2). (Western Psychological Services, Los Angeles, CA, 2012)."},{"key":"1034_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034","volume":"3","author":"J Vandesompele","year":"2002","unstructured":"Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, 0034.1 (2002).","journal-title":"Genome Biol."},{"key":"1034_CR31","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","volume":"55","author":"SA Bustin","year":"2009","unstructured":"Bustin, S. A. et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin. Chem. 55, 611\u2013622 (2009).","journal-title":"Clin. Chem."},{"key":"1034_CR32","doi-asserted-by":"publisher","first-page":"3995","DOI":"10.1093\/hmg\/ddx289","volume":"26","author":"NA Copping","year":"2017","unstructured":"Copping, N. A. et al. Neuronal overexpression of Ube3a isoform 2 causes behavioral impairments and neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome. Hum. Mol. Genet. 26, 3995\u20134010 (2017).","journal-title":"Hum. Mol. Genet."},{"key":"1034_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02217-x","volume":"7","author":"SC Taylor","year":"2017","unstructured":"Taylor, S. C., Laperriere, G. & Germain, H. Droplet digital PCR versus qPCR for gene expression analysis with low abundant targets: from variable nonsense to publication quality data. Sci. Rep. 7, 2409 (2017).","journal-title":"Sci. Rep."},{"key":"1034_CR34","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-2-19","volume":"2","author":"HA Scoles","year":"2011","unstructured":"Scoles, H. A., Urraca, N., Chadwick, S. W., Reiter, L. T. & Lasalle, J. M. Increased copy number for methylated maternal 15q duplications leads to changes in gene and protein expression in human cortical samples. Mol. Autism 2, 19 (2011).","journal-title":"Mol. Autism"},{"key":"1034_CR35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1097\/00041444-200512000-00006","volume":"15","author":"MW Veltman","year":"2005","unstructured":"Veltman, M. W., Craig, E. E. & Bolton, P. F. Autism spectrum disorders in Prader-Willi and Angelman syndromes: a systematic review. Psychiatr. Genet. 15, 243\u2013254 (2005).","journal-title":"Psychiatr. Genet."},{"key":"1034_CR36","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1002\/humu.22800","volume":"36","author":"A Noor","year":"2015","unstructured":"Noor, A. et al. 15q11.2 duplication encompassing only the UBE3A gene is associated with developmental delay and neuropsychiatric phenotypes. Hum. Mutat. 36, 689\u2013693 (2015).","journal-title":"Hum. Mutat."},{"key":"1034_CR37","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.cell.2015.06.045","volume":"162","author":"JJ Yi","year":"2015","unstructured":"Yi, J. J. et al. An Autism-linked mutation disables phosphorylation control of UBE3A. Cell 162, 795\u2013807 (2015).","journal-title":"Cell"},{"key":"1034_CR38","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.psychres.2019.03.019","volume":"275","author":"I Salminen","year":"2019","unstructured":"Salminen, I., Read, S., Hurd, P. & Crespi, B. Genetic variation of UBE3A is associated with schizotypy in a population of typical individuals. Psychiatry Res. 275, 94\u201399 (2019).","journal-title":"Psychiatry Res."},{"key":"1034_CR39","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.neubiorev.2019.04.007","volume":"103","author":"S Tordjman","year":"2019","unstructured":"Tordjman, S., Celume, M. P., Denis, L., Motillon, T. & Keromnes, G. Reframing schizophrenia and autism as bodily self-consciousness disorders leading to a deficit of theory of mind and empathy with social communication impairments. Neurosci. Biobehav. Rev. 103, 401\u2013413 (2019).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"1034_CR40","doi-asserted-by":"publisher","first-page":"3401","DOI":"10.1016\/j.celrep.2018.03.018","volume":"22","author":"EG Bochukova","year":"2018","unstructured":"Bochukova, E. G. et al. A transcriptomic signature of the hypothalamic response to fasting and BDNF deficiency in Prader-Willi syndrome. Cell Rep. 22, 3401\u20133408 (2018).","journal-title":"Cell Rep."},{"key":"1034_CR41","doi-asserted-by":"publisher","first-page":"359","DOI":"10.2174\/1566523220666200107151025","volume":"19","author":"C Tsagkaris","year":"2020","unstructured":"Tsagkaris, C. et al. Gene therapy for Angelman Syndrome: contemporary approaches and future endeavors. Curr. Gene Ther. 19, 359\u2013366 (2020).","journal-title":"Curr. Gene Ther."},{"key":"1034_CR42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118226","volume":"10","author":"A Zmienko","year":"2015","unstructured":"Zmienko, A. et al. Selection of reference genes for qPCR- and ddPCR-based analyses of gene expression in Senescing Barley leaves. PLoS ONE 10, e0118226 (2015).","journal-title":"PLoS ONE"},{"key":"1034_CR43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107320","volume":"9","author":"A Lukoshe","year":"2014","unstructured":"Lukoshe, A., Hokken-Koelega, A. C., van der Lugt, A. & White, T. Reduced cortical complexity in children with Prader-Willi Syndrome and its association with cognitive impairment and developmental delay. PLoS ONE 9, e107320 (2014).","journal-title":"PLoS ONE"},{"key":"1034_CR44","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-019-0271-7","volume":"10","author":"EK Baker","year":"2019","unstructured":"Baker, E. K. et al. Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features. Mol. Autism 10, 21 (2019).","journal-title":"Mol. Autism"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-01034-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-01034-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-01034-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T14:57:11Z","timestamp":1670252231000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-020-01034-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,29]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["1034"],"URL":"https:\/\/doi.org\/10.1038\/s41398-020-01034-7","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,29]]},"assertion":[{"value":"18 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 September 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 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":"362"}}