{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:50:42Z","timestamp":1788353442333,"version":"build-2803163510"},"reference-count":49,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n               <jats:title>Purpose<\/jats:title>\n               <jats:p>Glaucoma is the second commonest cause of blindness. We assessed the gene expression profile of astrocytes in the optic nerve head to identify possible prognostic biomarkers for glaucoma.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Method<\/jats:title>\n               <jats:p>A total of 20 patient and nine normal control subject samples were derived from the <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE9944\">GSE9944<\/jats:uri> (six normal samples and 13 patient samples) and <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE2378\">GSE2378<\/jats:uri> (three normal samples and seven patient samples) datasets, screened by microarray-tested optic nerve head tissues, were obtained from the Gene Expression Omnibus (GEO) database. We used a weighted gene coexpression network analysis (WGCNA) to identify coexpressed gene modules. We also performed a functional enrichment analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Genes expression was represented by boxplots, functional geneset enrichment analyses (GSEA) were used to profile the expression patterns of all the key genes. Then the key genes were validated by the external dataset.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Results<\/jats:title>\n               <jats:p>A total 8,606 genes and 19 human optic nerve head samples taken from glaucoma patients in the <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE9944\">GSE9944<\/jats:uri> were compared with normal control samples to construct the co-expression gene modules. After selecting the most common clinical traits of glaucoma, their association with gene expression was established, which sorted two modules showing greatest correlations. One with the correlation coefficient is 0.56 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01) and the other with the correlation coefficient is \u22120.56 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01). Hub genes of these modules were identified using scatterplots of gene significance versus module membership. A functional enrichment analysis showed that the former module was mainly enriched in genes involved in cellular inflammation and injury, whereas the latter was mainly enriched in genes involved in tissue homeostasis and physiological processes. This suggests that genes in the green\u2013yellow module may play critical roles in the onset and development of glaucoma. A LASSO regression analysis identified three hub genes: Recombinant Bone Morphogenetic Protein 1 gene (<jats:italic>BMP1<\/jats:italic>), Duchenne muscular dystrophy gene (<jats:italic>DMD<\/jats:italic>) and mitogens induced GTP-binding protein gene (<jats:italic>GEM<\/jats:italic>). The expression levels of the three genes in the glaucoma group were significantly lower than those in the normal group. GSEA further illuminated that <jats:italic>BMP1<\/jats:italic>,<jats:italic> DMD<\/jats:italic> and<jats:italic> GEM<\/jats:italic> participated in the occurrence and development of some important metabolic progresses. Using the <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE2378\">GSE2378<\/jats:uri> dataset, we confirmed the high validity of the model, with an area under the receiver operator characteristic curve of 85%.<\/jats:p>\n            <\/jats:sec>\n            <jats:sec>\n               <jats:title>Conclusion<\/jats:title>\n               <jats:p>We identified several key genes, including <jats:italic>BMP1<\/jats:italic>, <jats:italic>DMD<\/jats:italic> and <jats:italic>GEM,<\/jats:italic> that may be involved in the pathogenesis of glaucoma. Our results may help to determine the prognosis of glaucoma and\/or to design gene- or molecule-targeted drugs.<\/jats:p>\n            <\/jats:sec>","DOI":"10.7717\/peerj.9462","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T09:40:10Z","timestamp":1599126010000},"page":"e9462","source":"Crossref","is-referenced-by-count":9,"title":["Expression profile analysis to predict potential biomarkers for glaucoma: BMP1, DMD and GEM"],"prefix":"10.7717","volume":"8","author":[{"given":"Dao\u00a0wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"},{"name":"State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"},{"name":"State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"10.7717\/peerj.9462\/ref-1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/ng0493-283","article-title":"The structural and functional diversity of dystrophin","volume":"3","author":"Ahn","year":"1993","journal-title":"Nature Genetics"},{"key":"10.7717\/peerj.9462\/ref-2","doi-asserted-by":"publisher","first-page":"22728","DOI":"10.1074\/jbc.M002345200","article-title":"Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain","volume":"275","author":"Amano","year":"2000","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.9462\/ref-3","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/brain\/awf012","article-title":"Brain function in Duchenne muscular dystrophy","volume":"125","author":"Anderson","year":"2002","journal-title":"Brain"},{"key":"10.7717\/peerj.9462\/ref-4","doi-asserted-by":"publisher","first-page":"F1430","DOI":"10.1152\/ajprenal.00230.2019","article-title":"BMP1 inhibitor UK-383, 367 attenuates renal fibrosis and inflammation in CKD","volume":"317","author":"Bai","year":"2019","journal-title":"American Journal of Physiology: Renal Physiology"},{"key":"10.7717\/peerj.9462\/ref-5","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/349117a0","article-title":"The GTPase superfamily: conserved structure and molecular mechanism","volume":"349","author":"Bourne","year":"1991","journal-title":"Nature"},{"key":"10.7717\/peerj.9462\/ref-6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1126\/science.3513311","article-title":"A receptor-mediated pathway for cholesterol homeostasis","volume":"232","author":"Brown","year":"1986","journal-title":"Science"},{"key":"10.7717\/peerj.9462\/ref-7","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/1471-2164-15-300","article-title":"Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer","volume":"15","author":"Chou","year":"2014","journal-title":"BMC Genomics"},{"key":"10.7717\/peerj.9462\/ref-8","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.survophthal.2015.01.004","article-title":"The interactions of genes, age, and environment in glaucoma pathogenesis","volume":"60","author":"Doucette","year":"2015","journal-title":"Survey of Ophthalmology"},{"key":"10.7717\/peerj.9462\/ref-9","doi-asserted-by":"publisher","first-page":"e0210431","DOI":"10.1371\/journal.pone.0210431","article-title":"Assessment of complementarity of WGCNA and NERI results for identification of modules associated to schizophrenia spectrum disorders","volume":"14","author":"Feltrin","year":"2019","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.9462\/ref-10","doi-asserted-by":"publisher","first-page":"100801","DOI":"10.1016\/j.preteyeres.2019.100801","article-title":"Beyond intraocular pressure: optimizing patient-reported outcomes in glaucoma","volume":"76","author":"Fenwick","year":"2019","journal-title":"Progress in Retina and Eye Research"},{"key":"10.7717\/peerj.9462\/ref-11","doi-asserted-by":"publisher","first-page":"5319","DOI":"10.1167\/iovs.17-23045","article-title":"Another piece of the puzzle: MYOC and Myocilin glaucoma","volume":"58","author":"Fini","year":"2017","journal-title":"Investigative Ophthalmology and Visual Science"},{"issue":"6348","key":"10.7717\/peerj.9462\/ref-12","doi-asserted-by":"publisher","first-page":"eaal2380","DOI":"10.1126\/science.aal2380","article-title":"Epigenetic plasticity and the hallmarks of cancer","volume":"357","author":"Flavahan","year":"2017","journal-title":"Science"},{"key":"10.7717\/peerj.9462\/ref-13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"Journal of Statistical Software"},{"key":"10.7717\/peerj.9462\/ref-14","doi-asserted-by":"publisher","first-page":"6237","DOI":"10.18632\/aging.102185","article-title":"Prognostic value of long non-coding RNA signatures in bladder cancer","volume":"11","author":"He","year":"2019","journal-title":"Aging"},{"issue":"12","key":"10.7717\/peerj.9462\/ref-15","doi-asserted-by":"publisher","first-page":"a008391","DOI":"10.1101\/cshperspect.a008391","article-title":"Eye development and retinogenesis","volume":"4","author":"Heavner","year":"2012","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"10.7717\/peerj.9462\/ref-16","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/glia.10051","article-title":"Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray","volume":"38","author":"Hernandez","year":"2002","journal-title":"Glia"},{"key":"10.7717\/peerj.9462\/ref-17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S0925-4773(01)00310-0","article-title":"Dystrophin and Dp71, two products of the DMD gene, show a different pattern of expression during embryonic development in zebrafish","volume":"102","author":"Bola\u00f1os-Jim\u00e9nez","year":"2001","journal-title":"Mechanisms of Development"},{"key":"10.7717\/peerj.9462\/ref-18","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/s0140-6736(17)31469-1","article-title":"Glaucoma","volume":"390","author":"Jonas","year":"2017","journal-title":"Lancet"},{"key":"10.7717\/peerj.9462\/ref-19","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: the protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"10.7717\/peerj.9462\/ref-20","doi-asserted-by":"publisher","first-page":"2808","DOI":"10.4161\/cc.20946","article-title":"Toward an integrative view of Optineurin functions","volume":"11","author":"Kachaner","year":"2012","journal-title":"Cell Cycle"},{"key":"10.7717\/peerj.9462\/ref-21","doi-asserted-by":"publisher","first-page":"103380","DOI":"10.1016\/j.compbiomed.2019.103380","article-title":"Comparison of methods for differential co-expression analysis for disease biomarker prediction","volume":"113","author":"Kakati","year":"2019","journal-title":"Computers in Biology and Medicine"},{"key":"10.7717\/peerj.9462\/ref-22","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"10.7717\/peerj.9462\/ref-23","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.exer.2017.05.002","article-title":"Major review: molecular genetics of primary open-angle glaucoma","volume":"160","author":"Liu","year":"2017","journal-title":"Experimental Eye Research"},{"key":"10.7717\/peerj.9462\/ref-24","doi-asserted-by":"publisher","first-page":"R111","DOI":"10.1186\/gb-2008-9-7-r111","article-title":"Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors","volume":"9","author":"Lukas","year":"2008","journal-title":"Genome Biology"},{"key":"10.7717\/peerj.9462\/ref-25","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1517\/14728214.2016.1151001","article-title":"Emerging drugs to treat glaucoma: targeting prostaglandin F and E receptors","volume":"21","author":"Lusthaus","year":"2016","journal-title":"Expert Opinion on Emerging Drugs"},{"key":"10.7717\/peerj.9462\/ref-26","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1038\/s41588-018-0176-y","article-title":"Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma","volume":"50","author":"MacGregor","year":"2018","journal-title":"Nature Genetics"},{"key":"10.7717\/peerj.9462\/ref-27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1126\/science.7912851","article-title":"Gem: an induced, immediate early protein belonging to the Ras family","volume":"265","author":"Maguire","year":"1994","journal-title":"Science"},{"key":"10.7717\/peerj.9462\/ref-28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.optom.2016.02.003","article-title":"Glaucoma history and risk factors","volume":"10","author":"McMonnies","year":"2017","journal-title":"Journal of Optometry"},{"key":"10.7717\/peerj.9462\/ref-29","first-page":"426","article-title":"Orthograde and retrograde axoplasmic transport during acute ocular hypertension in the monkey","volume":"16","author":"Minckler","year":"1977","journal-title":"Investigative Ophthalmology and Visual Science"},{"key":"10.7717\/peerj.9462\/ref-30","doi-asserted-by":"publisher","first-page":"137","DOI":"10.3389\/fgene.2016.00137","article-title":"Gene coexpression analyses differentiate networks associated with diverse cancers harboring TP53 missense or null mutations","volume":"7","author":"Oros Klein","year":"2016","journal-title":"Frontiers in Genetics"},{"key":"10.7717\/peerj.9462\/ref-31","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1006\/mgme.1998.2784","article-title":"Effects of dystrophin isoforms on signal transduction through neural retina: genotype-phenotype analysis of duchenne muscular dystrophy mouse mutants","volume":"66","author":"Pillers","year":"1999","journal-title":"Molecular Genetics and Metabolism"},{"key":"10.7717\/peerj.9462\/ref-32","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1007\/s12325-016-0333-6","article-title":"Quality of life in glaucoma: a review of the literature","volume":"33","author":"Quaranta","year":"2016","journal-title":"Advances in Therapy"},{"key":"10.7717\/peerj.9462\/ref-33","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/ejhg.2015.135","article-title":"Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system","volume":"24","author":"Ricotti","year":"2016","journal-title":"European Journal of Human Genetics"},{"key":"10.7717\/peerj.9462\/ref-34","doi-asserted-by":"publisher","first-page":"39","DOI":"10.14797\/mdcj-15-1-39","article-title":"HDL and reverse cholesterol transport biomarkers","volume":"15","author":"Riggs","year":"2019","journal-title":"Methodist DeBakey Cardiovascular Journal"},{"key":"10.7717\/peerj.9462\/ref-35","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"10.7717\/peerj.9462\/ref-36","doi-asserted-by":"publisher","first-page":"30504","DOI":"10.1074\/jbc.M004846200","article-title":"Bone morphogenetic protein-1 processes probiglycan","volume":"275","author":"Scott","year":"2000","journal-title":"Journal of Biological Chemistry"},{"key":"10.7717\/peerj.9462\/ref-37","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: biology and pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathologica"},{"key":"10.7717\/peerj.9462\/ref-38","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.ejpb.2014.12.022","article-title":"Treatment of ocular disorders by gene therapy","volume":"95","author":"Solinis","year":"2015","journal-title":"European Journal of Pharmaceutics and Biopharmaceutics"},{"key":"10.7717\/peerj.9462\/ref-39","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1126\/science.275.5300.668","article-title":"Identification of a gene that causes primary open angle glaucoma","volume":"275","author":"Stone","year":"1997","journal-title":"Science"},{"key":"10.7717\/peerj.9462\/ref-40","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"10.7717\/peerj.9462\/ref-41","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1002\/jbmr.2473","article-title":"Defective proteolytic processing of fibrillar procollagens and prodecorin due to biallelic BMP1 mutations results in a severe, progressive form of osteogenesis imperfecta","volume":"30","author":"Syx","year":"2015","journal-title":"Journal of Bone and Mineral Research"},{"key":"10.7717\/peerj.9462\/ref-42","doi-asserted-by":"publisher","first-page":"a017244","DOI":"10.1101\/cshperspect.a017244","article-title":"Common and rare genetic risk factors for glaucoma","volume":"4","author":"Wang","year":"2014","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"10.7717\/peerj.9462\/ref-43","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1128\/mcb.24.2.651-661.2004","article-title":"Phosphorylation of critical serine residues in Gem separates cytoskeletal reorganization from down-regulation of calcium channel activity","volume":"24","author":"Ward","year":"2004","journal-title":"Molecular and Cellular Biology"},{"key":"10.7717\/peerj.9462\/ref-44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10495398.2018.1523796","article-title":"Molecular characterization of GTP binding protein overexpressed in skeletal muscle (GEM) and its role in promoting adipogenesis in goat intramuscular preadipocytes","volume":"31","author":"Xu","year":"2018","journal-title":"Animal Biotechnology"},{"key":"10.7717\/peerj.9462\/ref-45","doi-asserted-by":"publisher","first-page":"5536","DOI":"10.7150\/jca.30614","article-title":"Combined therapy sensitivity index based on a 13-gene signature predicts prognosis for IDH wild-type and MGMT promoter unmethylated glioblastoma patients","volume":"10","author":"Ye","year":"2019","journal-title":"Journal of Cancer"},{"key":"10.7717\/peerj.9462\/ref-46","doi-asserted-by":"publisher","first-page":"4849","DOI":"10.1002\/cam4.1782","article-title":"Circulating microRNA biomarkers for lung cancer detection in Western populations","volume":"7","author":"Yu","year":"2018","journal-title":"Cancer Medicine"},{"key":"10.7717\/peerj.9462\/ref-47","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/s12032-017-0963-9","article-title":"The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data","volume":"34","author":"Zhang","year":"2017","journal-title":"Medical Oncology"},{"key":"10.7717\/peerj.9462\/ref-48","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1093\/bib\/bbu003","article-title":"Combining multidimensional genomic measurements for predicting cancer prognosis: observations from TCGA","volume":"16","author":"Zhao","year":"2015","journal-title":"Briefings in Bioinformatics"},{"key":"10.7717\/peerj.9462\/ref-49","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","article-title":"Metascape provides a biologist-oriented resource for the analysis of systems-level datasets","volume":"10","author":"Zhou","year":"2019","journal-title":"Nature Communications"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/9462.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/9462.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/9462.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/9462.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T09:40:15Z","timestamp":1599126015000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/9462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":49,"alternative-id":["10.7717\/peerj.9462"],"URL":"https:\/\/doi.org\/10.7717\/peerj.9462","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]},"article-number":"e9462"}}