{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:14:58Z","timestamp":1791947698007,"version":"4.3.4"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,6,1]],"date-time":"2018-06-01T00:00:00Z","timestamp":1527811200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Congenital hypothyroidism (CH), the most common neonatal metabolic disorder, is characterized by impaired neurodevelopment. Although several candidate genes have been associated with CH, comprehensive screening of causative genes has been limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design and methods<\/jats:title><jats:p>One hundred ten patients with primary CH were recruited in this study. All exons and exon\u2013intron boundaries of 21 candidate genes for CH were analyzed by next-generation sequencing. And the inheritance pattern of causative genes was analyzed by the study of family pedigrees.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that 57 patients (51.82%) carried biallelic mutations (containing compound heterozygous mutations and homozygous mutations) in six genes (<jats:italic>DUOX2<\/jats:italic>,<jats:italic>DUOXA2<\/jats:italic>,<jats:italic>DUOXA1<\/jats:italic>,<jats:italic>TG<\/jats:italic>,<jats:italic>TPO<\/jats:italic>and<jats:italic>TSHR<\/jats:italic>) involved in thyroid hormone synthesis. Autosomal recessive inheritance of CH caused by mutations in<jats:italic>DUOX2<\/jats:italic>,<jats:italic>DUOXA2<\/jats:italic>,<jats:italic>TG<\/jats:italic>and<jats:italic>TPO<\/jats:italic>was confirmed by analysis of 22 family pedigrees. Notably, eight mutations in four genes (<jats:italic>FOXE1<\/jats:italic>,<jats:italic>NKX2-1<\/jats:italic>,<jats:italic>PAX8<\/jats:italic>and<jats:italic>HHEX<\/jats:italic>) that lead to thyroid dysgenesis were identified in eight probands. These mutations were heterozygous in all cases and hypothyroidism was not observed in parents of these probands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Most cases of congenital hypothyroidism in China were caused by thyroid dyshormonogenesis rather than thyroid dysgenesis. This study identified previously reported causative genes for 57\/110 Chinese patients and revealed<jats:italic>DUOX2<\/jats:italic>was the most frequently mutated gene in these patients. Our study expanded the mutation spectrum of CH in Chinese patients, which was significantly different from Western countries.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-17-1017","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T16:25:24Z","timestamp":1523550324000},"page":"623-633","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":100,"title":["The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes"],"prefix":"10.1093","volume":"178","author":[{"given":"Feng","family":"Sun","sequence":"first","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Xiu","family":"Zhang","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, Maternal and Child Health Institute of Bozhou, Bozhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, Fujian Province Maternity & Children Hospital of Fujian Medical University, Fuzhou, Fujian Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Qi","family":"Gao","sequence":"additional","affiliation":[{"name":"4Department of Endocrinology, The Linyi People\u2019s Hospital, Linyi, Shandong Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Bin","family":"Zhu","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, Fujian Province Maternity & Children Hospital of Fujian Medical University, Fuzhou, Fujian Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Le","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Yue","family":"Wan","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Ye","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ru","family":"Ma","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Man","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui-Cui","family":"Guo","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"5Department of Endocrinology, Fujian Province Hospital, Fuzhou, Fujian Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yi","family":"Song","sequence":"additional","affiliation":[{"name":"6Department of Endocrinology, The People\u2019s Hospital of Bozhou, Bozhou, Anhui Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Dong","family":"Song","sequence":"additional","affiliation":[{"name":"1The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"ref41","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/jmg.2004.024158","article-title":"Genetics of congenital hypothyroidism","volume":"42","year":"2005","journal-title":"Journal of Medical Genetics"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1210\/jc.2011-1073","article-title":"Is the incidence of congenital hypothyroidism really increasing? A 20-year retrospective population-based study in Quebec","volume":"96","year":"2011","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1210\/en.2014-1628","article-title":"Functional zebrafish studies based on human genotyping point to netrin-1 as a link between aberrant cardiovascular development and thyroid dysgenesis","volume":"156","year":"2015","journal-title":"Endocrinology"},{"key":"ref301","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.mce.2010.02.008","article-title":"Genetics and phenomics of hypothyroidism and goiter due to TPO mutations","volume":"322","year":"2010","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/cen.12622","article-title":"Pseudodominant inheritance in a family with nonautoimmune hypothyroidism due to biallelic DUOX2 mutations","volume":"83","year":"2015","journal-title":"Clinical Endocrinology"},{"key":"ref401","first-page":"413","article-title":"Thyroid developmental anomalies among first-degree relatives of children with thyroid dysgenesis and congenital hypothyroidism","volume":"25","year":"2012","journal-title":"Journal of Pediatric Endocrinology and Metabolism"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.lpm.2015.07.022","article-title":"TRalpha receptor mutations extend the spectrum of syndromes of reduced sensitivity to thyroid hormone","volume":"44","year":"2015","journal-title":"Presse Medicale"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.beem.2013.08.005","article-title":"Genetics of normal and abnormal thyroid development in humans","volume":"28","year":"2014","journal-title":"Best Practice and Research Clinical Endocrinology and Metabolism"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s40618-015-0382-8","article-title":"Mutation screening of DUOX2 in Chinese patients with congenital hypothyroidism","volume":"38","year":"2015","journal-title":"Journal of Endocrinological Investigation"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/j.1365-2826.2008.01733.x","article-title":"Neurodevelopmental and neurophysiological actions of thyroid hormone","volume":"20","year":"2008","journal-title":"Journal of Neuroendocrinology"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ijc.30437","article-title":"Multiregion sequencing reveals the intratumor heterogeneity of driver mutations in TP53-driven non-small cell lung cancer","volume":"140","year":"2017","journal-title":"International Journal of Cancer"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","year":"2015","journal-title":"Genetics in Medicine"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.1210\/jc.2017-01251","article-title":"Prenatal diagnosis of resistance to thyroid hormone and its clinical implications","volume":"102","year":"2017","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref311","doi-asserted-by":"publisher","first-page":"201196","DOI":"10.1210\/jc.2010-2467","article-title":"De MarcoGAgrettiPMontanelliLDi CosmoCBagattiniBDe ServiMFerrariniEDimidaAFreitas FerreiraACet Identification and functional analysis of novel dual oxidase mutations in children with congenital or subclinical hypothyroidism of and https org","author":"DUOX","journal-title":"Journal Clinical Endocrinology Metabolism"},{"key":"ref331","doi-asserted-by":"publisher","first-page":"201031","DOI":"10.1002\/humu.21227","article-title":"HosteCRiguttoSVan Compound heterozygosity for a novel hemizygous missense mutation and a partial deletion affecting the catalytic core of the - generating enzyme associated with transient congenital hypothyroidism https org","author":"VlietGMiotFDe DekenX","journal-title":"Human Mutation"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1210\/jc.2016-1879","article-title":"Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ","volume":"101","year":"2016","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1530\/EC-17-0289","article-title":"The incidence of congenital hypothyroidism (CH) in Guangxi, China and the predictors of permanent and transient CH","volume":"6","year":"2017","journal-title":"Endocrine Connections"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/ng.788","article-title":"Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia","volume":"43","year":"2011","journal-title":"Nature Genetics"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1038\/jhg.2016.62","article-title":"Mutations in the genes for thyroglobulin and thyroid peroxidase cause thyroid dyshormonogenesis and autosomal-recessive intellectual disability","volume":"61","year":"2016","journal-title":"Journal of Human Genetics"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ajhg.2017.04.015","article-title":"Evaluating the clinical validity of gene-disease associations: an evidence-based framework developed by the clinical genome resource","volume":"100","year":"2017","journal-title":"American Journal of Human Genetics"},{"key":"ref421","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1210\/jcem.86.5.7501","article-title":"Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors","volume":"86","year":"2001","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.1210\/jc.2009-0646","article-title":"Six new mutations of the thyroglobulin gene discovered in Taiwanese children presenting with thyroid dyshormonogenesis","volume":"94","year":"2009","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1210\/jc.2017-00529","article-title":"Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism","volume":"102","year":"2017","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"8977","DOI":"10.1073\/pnas.86.22.8977","article-title":"Generalized resistance to thyroid hormone associated with a mutation in the ligand-binding domain of the human thyroid receptor B","volume":"86","year":"1989","journal-title":"PNAS"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1530\/eje.1.01826","article-title":"Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism","volume":"152","year":"2005","journal-title":"European Journal of Endocrinology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1055\/s-0042-112224","article-title":"The prevalence, clinical, and molecular characteristics of congenital hypothyroidism caused by DUOX2 mutations: a population-based cohort study in Guangzhou","volume":"48","year":"2016","journal-title":"Hormone and Metabolic Research"},{"key":"ref371","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000363156","article-title":"Clinical genetics of congenital hypothyroidism","volume":"26","year":"2014","journal-title":"Endocrine Development"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","year":"2010","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cca.2017.02.009","article-title":"Next-generation sequencing analysis of twelve known causative genes in congenital hypothyroidism","volume":"468","year":"2017","journal-title":"Clinica Chimica Acta"},{"key":"ref351","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.mce.2016.01.007","article-title":"Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism","volume":"423","year":"2016","journal-title":"Molecular and Cellular Endocrinology"},{"key":"ref411","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1056\/NEJM200008103430614","article-title":"Familial forms of thyroid dysgenesis among infants with congenital hypothyroidism","volume":"343","year":"2000","journal-title":"New England Journal of Medicine"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.cca.2015.10.030","article-title":"Newborn screening for congenital hypothyroidism in Henan province, China","volume":"452","year":"2016","journal-title":"Clinica Chimica Acta"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"194","DOI":"10.14310\/horm.2002.1733","article-title":"Severe neurological abnormalities in a young boy with impaired thyroid hormone sensitivity due to a novel mutation in the MCT8 gene","volume":"16","year":"2017","journal-title":"Hormones"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/jcem.87.2.8268","article-title":"Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism","volume":"87","year":"2002","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000362235","article-title":"High frequency of DUOX2 mutations in transient or permanent congenital hypothyroidism with eutopic thyroid glands","volume":"82","year":"2014","journal-title":"Hormone Research in Paediatrics"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1365-2265.2011.04249.x","article-title":"Congenital goitrous hypothyroidism: mutation analysis in the thyroid peroxidase gene","volume":"76","year":"2012","journal-title":"Clinical Endocrinology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ecl.2016.01.007","article-title":"Update of thyroid developmental genes","volume":"45","year":"2016","journal-title":"Endocrinology and Metabolism Clinics of North America"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1097\/MOP.0b013e32834726a4","article-title":"Genetic causes of congenital hypothyroidism due to dyshormonogenesis","volume":"23","year":"2011","journal-title":"Current Opinion in Pediatrics"},{"key":"ref391","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.ejmg.2016.07.004","article-title":"High prevalence of DUOX2 gene mutations among children with congenital hypothyroidism in central China","volume":"59","year":"2016","journal-title":"European Journal of Medical Genetics"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4274\/jcrpe.2456","article-title":"Screening of HHEX mutations in Chinese children with thyroid dysgenesis","volume":"8","year":"2016","journal-title":"Journal of Clinical Research in Pediatric Endocrinology"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1530\/EJE-07-0037","article-title":"High prevalence of thyroid peroxidase gene mutations in patients with thyroid dyshormonogenesis","volume":"156","year":"2007","journal-title":"European Journal of Endocrinology"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1210\/er.2014-1081","article-title":"Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand?","volume":"36","year":"2015","journal-title":"Endocrine Reviews"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1089\/10507250360731550","article-title":"Thyroperoxidase gene mutations in congenital goitrous hypothyroidism with total and partial iodide organification defect","volume":"13","year":"2003","journal-title":"Thyroid"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/jc.2013-1891","article-title":"European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism.","volume":"99","year":"2014","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"5505","DOI":"10.1093\/hmg\/ddu250","article-title":"Genome-wide association study identifies a novel susceptibility gene for serum TSH levels in Chinese populations","volume":"23","year":"2014","journal-title":"Human Molecular Genetics"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/178\/6\/EJE-17-1017.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1530\/EJE-17-1017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T16:34:35Z","timestamp":1751560475000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/178\/6\/623\/6655358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6]]},"references-count":45,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-17-1017","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6]]}}}