{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:46:37Z","timestamp":1787460397843,"version":"build-2736575974"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T00:00:00Z","timestamp":1539216000000},"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>Vascular endothelial growth factor A (<jats:italic>VEGFA<\/jats:italic>) dysfunction may contribute to a number of pathological processes that characterize psychotic disorders. However, the influence of <jats:italic>VEGFA<\/jats:italic> gene variants on clinical and neuroimaging phenotypes in psychotic disorders has yet to be shown. In the present study, we examined whether different <jats:italic>VEGFA<\/jats:italic> gene variants influence psychosis risk, symptom severity, cognition, and brain volume. The study group included 480 probands (Bipolar I disorder with psychosis, <jats:italic>n<\/jats:italic>\u2009=\u2009205; Schizoaffective disorder, <jats:italic>n<\/jats:italic>\u2009=\u2009112; Schizophrenia, <jats:italic>n<\/jats:italic>\u2009=\u2009163) and 126 healthy controls that were recruited across six sites in the B-SNIP consortium. <jats:italic>VEGFA<\/jats:italic> variants identified for analysis (rs699947, rs833070, and rs2146323) were quantified via SNP chip array. We assessed symptoms and cognition using standardized clinical and neuropsychological batteries. The dorsolateral prefrontal cortex (DLPFC), medial temporal lobe, and hippocampal volumes were quantified using FreeSurfer. In our sample, <jats:italic>VEGFA<\/jats:italic> rs2146323 A- carriers showed reduced odds of being a proband (<jats:italic>p<\/jats:italic>\u2009=\u20090.037, OR\u2009=\u20090.65, 95% CI\u2009=\u20090.43\u20130.98) compared to noncarriers, but not for rs699947 or rs833070. In probands, rs2146323 A- carriers demonstrated fewer hallucinations (<jats:italic>p<\/jats:italic>\u2009=\u20090.035, Cohen\u2019s <jats:italic>d<\/jats:italic>\u2009=\u20090.194), as well as significantly greater DLPFC (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05, Cohen\u2019s <jats:italic>d<\/jats:italic>\u2009=\u2009\u22120.21) and parahippocampal volumes (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, Cohen\u2019s <jats:italic>d<\/jats:italic>\u2009=\u2009\u22120.27). No clinical or neuroimaging associations were identified for rs699947 or rs833070. In general, we found that the three SNPs exhibited several significant negative relationships between psychosis symptoms and brain structure. In the probands and control groups, positive relationships were identified between several cognitive and brain volume measures. The findings suggest <jats:italic>VEGFA<\/jats:italic> effects in the DLPFC and hippocampus found in animals may also extend to humans. <jats:italic>VEGFA<\/jats:italic> variations may have important implications in identifying dimensional moderators of function that could be targeted through <jats:italic>VEGFA-<\/jats:italic>mediated interventions.<\/jats:p>","DOI":"10.1038\/s41398-018-0271-y","type":"journal-article","created":{"date-parts":[[2018,10,11]],"date-time":"2018-10-11T12:04:39Z","timestamp":1539259479000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["VEGFA GENE variation influences hallucinations and frontotemporal morphology in psychotic disorders: a B-SNIP study"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-6697","authenticated-orcid":false,"given":"Paulo","family":"Lizano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-2991","authenticated-orcid":false,"given":"Olivia","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-1771","authenticated-orcid":false,"given":"George","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3958-5424","authenticated-orcid":false,"given":"Jaya","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Tandon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Tamminga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godfrey","family":"Pearlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gualberto","family":"Ruan\u0303o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Kocherla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Windemuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Clementz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-8631","authenticated-orcid":false,"given":"Elliot","family":"Gershon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matcheri","family":"Keshavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,11]]},"reference":[{"key":"271_CR1","doi-asserted-by":"publisher","first-page":"11946","DOI":"10.1073\/pnas.182296499","volume":"99","author":"K Jin","year":"2002","unstructured":"Jin, K. et al. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc. Natl Acad. Sci. USA 99, 11946\u201311950 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"271_CR2","doi-asserted-by":"publisher","first-page":"2803","DOI":"10.1111\/j.1460-9568.2003.03041.x","volume":"18","author":"K Fabel","year":"2003","unstructured":"Fabel, K. et al. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur. J. Neurosci. 18, 2803\u20132812 (2003).","journal-title":"Eur. J. Neurosci."},{"key":"271_CR3","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/ng1395","volume":"36","author":"L Cao","year":"2004","unstructured":"Cao, L. et al. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat. Genet. 36, 827\u2013835 (2004).","journal-title":"Nat. Genet."},{"key":"271_CR4","doi-asserted-by":"publisher","first-page":"29","DOI":"10.2174\/156720506775697133","volume":"3","author":"MJ During","year":"2006","unstructured":"During, M. J. & Cao, L. VEGF, a mediator of the effect of experience on hippocampal neurogenesis. Curr. Alzheimer Res. 3, 29\u201333 (2006).","journal-title":"Curr. Alzheimer Res."},{"key":"271_CR5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020198","volume":"6","author":"KR Howell","year":"2011","unstructured":"Howell, K. R., Kutiyanawalla, A. & Pillai, A. Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex. PLoS ONE 6, e20198 (2011).","journal-title":"PLoS ONE"},{"key":"271_CR6","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.neuroscience.2012.01.023","volume":"207","author":"T Kiuchi","year":"2012","unstructured":"Kiuchi, T., Lee, H. & Mikami, T. Regular exercise cures depression-like behavior via VEGF-Flk-1 signaling in chronically stressed mice. Neuroscience 207, 208\u2013217 (2012).","journal-title":"Neuroscience"},{"key":"271_CR7","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.schres.2009.06.005","volume":"115","author":"S Fulzele","year":"2009","unstructured":"Fulzele, S. & Pillai, A. Decreased VEGF mRNA expression in the dorsolateral prefrontal cortex of schizophrenia subjects. Schizophr. Res. 115, 372\u2013373 (2009).","journal-title":"Schizophr. Res."},{"key":"271_CR8","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/mp.2009.18","volume":"14","author":"PR Maycox","year":"2009","unstructured":"Maycox, P. R. et al. Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Mol. Psychiatry 14, 1083\u20131094 (2009).","journal-title":"Mol. Psychiatry"},{"key":"271_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046368","volume":"7","author":"LW Harris","year":"2012","unstructured":"Harris, L. W. et al. Comparison of peripheral and central schizophrenia biomarker profiles. PLoS ONE 7, e46368 (2012).","journal-title":"PLoS ONE"},{"key":"271_CR10","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jpsychires.2016.07.018","volume":"82","author":"M Hino","year":"2016","unstructured":"Hino, M. et al. Decreased VEGFR2 expression and increased phosphorylated Akt1 in the prefrontal cortex of individuals with schizophrenia. J. Psychiatr. Res. 82, 100\u2013108 (2016).","journal-title":"J. Psychiatr. Res."},{"issue":"Suppl 3","key":"271_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-016-0229-y","volume":"9","author":"SA Lee","year":"2016","unstructured":"Lee, S. A. & Huang, K. C. Epigenetic profiling of human brain differential DNA methylation networks in schizophrenia. Bmc Med. Genom. 9(Suppl 3), 68 (2016).","journal-title":"Bmc Med. Genom."},{"key":"271_CR12","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/j.biopsych.2008.07.003","volume":"64","author":"HP Blumberg","year":"2008","unstructured":"Blumberg, H. P. et al. Influence of vascular endothelial growth factor variation on human hippocampus morphology. Biol. Psychiatry 64, 901\u2013903 (2008).","journal-title":"Biol. Psychiatry"},{"key":"271_CR13","doi-asserted-by":"publisher","first-page":"3516","DOI":"10.1002\/hbm.23369","volume":"38","author":"H Takeuchi","year":"2017","unstructured":"Takeuchi, H. et al. The VEGF gene polymorphism impacts brain volume and arterial blood volume. Hum Brain Mapp 38, 3516\u20133526 (2017).","journal-title":"Hum Brain Mapp"},{"key":"271_CR14","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/nature13595","volume":"511","author":"Schizophrenia Working Group of the Psychiatric Genomics C.","year":"2014","unstructured":"Schizophrenia Working Group of the Psychiatric Genomics C. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421\u2013427 (2014).","journal-title":"Nature"},{"key":"271_CR15","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1176\/appi.ajp.2013.12101298","volume":"170","author":"SK Hill","year":"2013","unstructured":"Hill, S. K. et al. Neuropsychological impairments in schizophrenia and psychotic bipolar disorder: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Am. J. Psychiatry 170, 1275\u20131284 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"271_CR16","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1001\/jamapsychiatry.2014.453","volume":"71","author":"I Mathew","year":"2014","unstructured":"Mathew, I. et al. Medial temporal lobe structures and hippocampal subfields in psychotic disorders: findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. JAMA Psychiatry 71, 769\u2013777 (2014).","journal-title":"JAMA Psychiatry"},{"key":"271_CR17","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1093\/schbul\/sbu075","volume":"41","author":"JL Padmanabhan","year":"2015","unstructured":"Padmanabhan, J. L. et al. Correlations between brain structure and symptom dimensions of psychosis in schizophrenia, schizoaffective, and psychotic bipolar I disorders. Schizophr. Bull. 41, 154\u2013162 (2015).","journal-title":"Schizophr. Bull."},{"key":"271_CR18","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1176\/appi.ajp.2013.12101339","volume":"170","author":"CA Tamminga","year":"2013","unstructured":"Tamminga, C. A. et al. Clinical phenotypes of psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am. J. Psychiatry 170, 1263\u20131274 (2013).","journal-title":"Am. J. Psychiatry"},{"key":"271_CR19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.clgc.2011.03.001","volume":"9","author":"V Kunene","year":"2011","unstructured":"Kunene, V. & Porfiri, E. Sunitinib-induced acute psychosis: case report. Clin. Genitourin. Cancer 9, 70\u201372 (2011).","journal-title":"Clin. Genitourin. Cancer"},{"key":"271_CR20","doi-asserted-by":"publisher","first-page":"450 e5","DOI":"10.1016\/j.genhosppsych.2012.03.001","volume":"36","author":"YL Kuo","year":"2014","unstructured":"Kuo, Y. L., Yang, Y. K., Cheng, H. C., Yen, C. J. & Chen, P. S. Psychotic disorder induced by a combination of sorafenib and BAY86-9766. Gen. Hosp. Psychiatry 36, 450 e5\u2013e7 (2014).","journal-title":"Gen. Hosp. Psychiatry"},{"key":"271_CR21","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","volume":"31","author":"RS Desikan","year":"2006","unstructured":"Desikan, R. S. et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31, 968\u2013980 (2006).","journal-title":"Neuroimage"},{"key":"271_CR22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neulet.2015.01.069","volume":"590","author":"K Gao","year":"2015","unstructured":"Gao, K. et al. Association study of VEGFA polymorphisms with schizophrenia in Han Chinese population. Neurosci. Lett. 590, 121\u2013125 (2015).","journal-title":"Neurosci. Lett."},{"key":"271_CR23","doi-asserted-by":"publisher","first-page":"E2066","DOI":"10.1073\/pnas.1313093111","volume":"111","author":"SA Meda","year":"2014","unstructured":"Meda, S. A. et al. Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia. Proc. Natl Acad. Sci. USA 111, E2066\u2013E2075 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"271_CR24","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nprot.2009.38","volume":"4","author":"FH Pettersson","year":"2009","unstructured":"Pettersson, F. H. et al. Marker selection for genetic case-control association studies. Nat. Protoc. 4, 743\u2013752 (2009).","journal-title":"Nat. Protoc."},{"key":"271_CR25","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1176\/appi.ajp.2015.14091200","volume":"173","author":"BA Clementz","year":"2016","unstructured":"Clementz, B. A. et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am. J. Psychiatry 173, 373\u2013384 (2016).","journal-title":"Am. J. Psychiatry"},{"key":"271_CR26","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/ng.943","volume":"43","author":"Psychiatric GCBDWG.","year":"2011","unstructured":"Psychiatric GCBDWG. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat. Genet. 43, 977\u2013983 (2011).","journal-title":"Nat. Genet."},{"key":"271_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096021","volume":"9","author":"SV Kalmady","year":"2014","unstructured":"Kalmady, S. V. et al. Relationship between Interleukin-6 gene polymorphism and hippocampal volume in antipsychotic-naive schizophrenia: evidence for differential susceptibility? PLoS ONE 9, e96021 (2014).","journal-title":"PLoS ONE"},{"key":"271_CR28","doi-asserted-by":"publisher","first-page":"3611","DOI":"10.1167\/iovs.07-1383","volume":"49","author":"AJ Churchill","year":"2008","unstructured":"Churchill, A. J. et al. VEGF polymorphisms are associated with severity of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 49, 3611\u20133616 (2008).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"271_CR29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016982","volume":"6","author":"D Ruggiero","year":"2011","unstructured":"Ruggiero, D. et al. Genetics of VEGF serum variation in human isolated populations of cilento: importance of VEGF polymorphisms. PLoS ONE 6, e16982 (2011).","journal-title":"PLoS ONE"},{"key":"271_CR30","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1183\/09031936.00113008","volume":"33","author":"S Sharma","year":"2009","unstructured":"Sharma, S. et al. Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness. Eur. Respir. J. 33, 1287\u20131294 (2009).","journal-title":"Eur. Respir. J."},{"key":"271_CR31","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ophtha.2009.06.037","volume":"117","author":"I Immonen","year":"2010","unstructured":"Immonen, I. et al. Vascular endothelial growth factor gene variation and the response to photodynamic therapy in age-related macular degeneration. Ophthalmology 117, 103\u2013108 (2010).","journal-title":"Ophthalmology"},{"key":"271_CR32","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1001\/jamaophthalmol.2014.109","volume":"132","author":"SA Hagstrom","year":"2014","unstructured":"Hagstrom, S. A. et al. VEGFA and VEGFR2 gene polymorphisms and response to anti-vascular endothelial growth factor therapy: comparison of age-related macular degeneration treatments trials (CATT). JAMA Ophthalmol. 132, 521\u2013527 (2014).","journal-title":"JAMA Ophthalmol."},{"key":"271_CR33","doi-asserted-by":"publisher","first-page":"5081","DOI":"10.1073\/pnas.1007640108","volume":"108","author":"T Licht","year":"2011","unstructured":"Licht, T. et al. Reversible modulations of neuronal plasticity by VEGF. Proc. Natl Acad. Sci. USA 108, 5081\u20135086 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"271_CR34","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1038\/mp.2015.96","volume":"21","author":"A Pillai","year":"2016","unstructured":"Pillai, A. et al. Association of serum VEGF levels with prefrontal cortex volume in schizophrenia. Mol. Psychiatry 21, 686\u2013692 (2016).","journal-title":"Mol. Psychiatry"},{"key":"271_CR35","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.schres.2015.12.001","volume":"170","author":"PL Lizano","year":"2016","unstructured":"Lizano, P. L. et al. Angiogenic and immune signatures in plasma of young relatives at familial high-risk for psychosis and first-episode patients: a preliminary study. Schizophr. Res. 170, 115\u2013122 (2016).","journal-title":"Schizophr. Res."},{"key":"271_CR36","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.schres.2016.11.015","volume":"183","author":"P Lizano","year":"2016","unstructured":"Lizano, P. et al. Association of sFlt-1 and worsening psychopathology in relatives at high risk for psychosis: a longitudinal study. Schizophrenia Res 183, 75\u201381 (2016).","journal-title":"Schizophrenia Res"},{"key":"271_CR37","doi-asserted-by":"publisher","first-page":"961","DOI":"10.4103\/0973-1482.160919","volume":"11","author":"NS Demirci","year":"2015","unstructured":"Demirci, N. S., Erdem, G. U., Dogan, M., Ozdemir, N. Y. & Zengin, N. A rare case: hallucination associated with pazopanib. J. Cancer Res. Ther. 11, 961\u2013962 (2015).","journal-title":"J. Cancer Res. Ther."},{"key":"271_CR38","first-page":"232","volume":"14","author":"TH Kim","year":"2007","unstructured":"Kim, T. H., Kdh, Lee, S. K., Son, B. K. & Jung, J. S. The effect of antipsychotic drug treatment on serum VEGF, sVEGFR-1, and sVEGFR-2 level in schizophrenia\u2014a preliminary study. Korean J. Biol. Psychiatry 14, 232\u2013240 (2007).","journal-title":"Korean J. Biol. Psychiatry"},{"key":"271_CR39","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.schres.2015.08.027","volume":"169","author":"L Haring","year":"2015","unstructured":"Haring, L. et al. Antipsychotic treatment reduces psychotic symptoms and markers of low-grade inflammation in first episode psychosis patients, but increases their body mass index. Schizophr. Res. 169, 22\u201329 (2015).","journal-title":"Schizophr. Res."},{"key":"271_CR40","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1007\/s11481-016-9672-y","volume":"11","author":"F Benedetti","year":"2016","unstructured":"Benedetti, F. et al. Stem Cell Factor (SCF) is a putative biomarker of antidepressant response. J. Neuroimmune Pharmacol. 11, 248\u2013258 (2016).","journal-title":"J. Neuroimmune Pharmacol."},{"key":"271_CR41","doi-asserted-by":"publisher","first-page":"4647","DOI":"10.1073\/pnas.0610282104","volume":"104","author":"JL Warner-Schmidt","year":"2007","unstructured":"Warner-Schmidt, J. L. & Duman, R. S. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc. Natl Acad. Sci. USA 104, 4647\u20134652 (2007).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0271-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0271-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0271-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T11:31:44Z","timestamp":1671535904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-018-0271-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,11]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["271"],"URL":"https:\/\/doi.org\/10.1038\/s41398-018-0271-y","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,11]]},"assertion":[{"value":"27 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2018","order":3,"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":"215"}}