{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:58:25Z","timestamp":1790996305651,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,30]],"date-time":"2018-12-30T00:00:00Z","timestamp":1546128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Epigenetic changes, including altered small non-coding RNAs, appear to be implicated in the pathogenesis of sporadic parathyroid adenomas (PAs). In this study, we investigated the circular RNAs (circRNAs) expression profile in sporadic PAs. Sixteen tissue samples of sporadic PAs, and four samples of normal parathyroid tissue (NPT) were investigated. Sample preparation and microarray hybridization were performed based on the Arraystar\u2019s standard protocols, and circRNAs sequences were predicted by bioinformatics tools. We identified 35 circRNAs that were differentially expressed in sporadic PAs compared to NPT; 22 were upregulated, and 13 were downregulated, according to the pre-defined thresholds of fold-change &gt; 2.0 and p &lt; 0.05. In the subgroup analysis of PAs from male patients (n = 7) compared to PAs from female patients (n = 9), we also find a different expression profile. In particular, 19 circRNAs were significantly upregulated, and four circRNAs were significantly downregulated in male patients, compared to female counterparts. We show here for the first time a differential circRNA expression pattern in sporadic PAs compared to NPT, and a different expression profile in PA samples from male compared to female patients, suggesting an epigenetic role in the PA pathogenesis, and also an effect of gender in the epigenetic regulation of PAs.<\/jats:p>","DOI":"10.3390\/cells8010015","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T07:22:30Z","timestamp":1546240950000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Role for Circular Non-Coding RNAs in the Pathogenesis of Sporadic Parathyroid Adenomas and the Impact of Gender-Specific Epigenetic Regulation"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6501-3692","authenticated-orcid":false,"given":"Maria P.","family":"Yavropoulou","sequence":"first","affiliation":[{"name":"1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, School of Medicine, Laikon General Hospital, Athens 11527, Greece"},{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Poulios","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickos","family":"Michalopoulos","sequence":"additional","affiliation":[{"name":"3rd Department of Surgery, AHEPA Univ. Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadni","family":"Gatzou","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Chrisafi","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stylianos","family":"Mantalovas","sequence":"additional","affiliation":[{"name":"3rd Department of Surgery, AHEPA Univ. Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-9889","authenticated-orcid":false,"given":"Theodosis","family":"Papavramidis","sequence":"additional","affiliation":[{"name":"1st Department of Surgery, AHEPA Univ. Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Daskalaki","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Electra","family":"Sofou","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-740X","authenticated-orcid":false,"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaak","family":"Kesisoglou","sequence":"additional","affiliation":[{"name":"3rd Department of Surgery, AHEPA Univ. Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Zebekakis","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Yovos","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,30]]},"reference":[{"key":"ref_1","first-page":"N18","article-title":"Epidemiology of primary hyperparathyroidism in Europe","volume":"17","author":"Adami","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00268-002-6621-0","article-title":"Primary hyperparathyroidism revisited in menopausal women with serum calcium in the upper normal range at population-based screening 8 years ago","volume":"26","author":"Lundgren","year":"2002","journal-title":"World J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/cncr.22790","article-title":"Parathyroid carcinoma, atypical parathyroid adenoma, or parathyromatosis?","volume":"110","author":"Khanafshar","year":"2007","journal-title":"Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.11138\/ccmbm\/2017.14.1.060","article-title":"Molecular genetics in primary hyperparathyroidism: the role of genetic tests in differential diagnosis, disease prevention strategy, and therapeutic planning. A 2017 update","volume":"14","author":"Marini","year":"2017","journal-title":"Clin. Cases Miner. Bone Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nrd4140","article-title":"MicroRNAs and other non-coding RNAs as targets for anticancer drug development","volume":"12","author":"Ling","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s12020-015-0555-4","article-title":"Epigenetic alterations in human parathyroid tumors","volume":"49","author":"Verdelli","year":"2015","journal-title":"Endocrine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1136\/jmedgenet-2016-103758","article-title":"Circular RNAs: A new frontier in the study of human diseases","volume":"53","author":"Chen","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/1097-0142(197303)31:3<600::AID-CNCR2820310316>3.0.CO;2-0","article-title":"Parathyroid carcinoma. A study of 70 cases","volume":"31","author":"Schantz","year":"1973","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s12022-010-9121-z","article-title":"Parafibromin and APC as screening markers for malignant potential in atypical parathyroid adenomas","volume":"21","author":"Juhlin","year":"2010","journal-title":"Endocr. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1245\/s10434-013-3288-8","article-title":"Negative parafibromin staining predicts malignant behavior in atypical parathyroid adenomas","volume":"21","author":"Kruijff","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1097\/PAI.0000000000000378","article-title":"Parafibromin, APC, and MIB-1 Are Useful Markers for Distinguishing Parathyroid Carcinomas from Adenomas","volume":"25","author":"Siddiqui","year":"2017","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Salzman, J., Gawad, C., Wang, P.L., Lacayo, N., and Brown, P.O. (2012). Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030733"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jdermsci.2016.05.012","article-title":"Circular RNA expression in cutaneous squamous cell carcinoma","volume":"83","author":"Sand","year":"2016","journal-title":"J. Dermatol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1080\/15476286.2015.1128065","article-title":"CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs","volume":"13","author":"Dudekula","year":"2016","journal-title":"RNA Biol."},{"key":"ref_15","first-page":"412","article-title":"Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: A paraffin immunohistochemical study","volume":"12","author":"Vasef","year":"1999","journal-title":"Mod. Pathol."},{"key":"ref_16","first-page":"1736","article-title":"Cyclin D1\/PRAD1 expression in parathyroid adenomas: An immunohistochemical study","volume":"81","author":"Hsi","year":"1996","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s12672-013-0147-9","article-title":"Germline and somatic mutations in cyclin-dependent kinase inhibitor genes CDKN1A, CDKN2B, and CDKN2C in sporadic parathyroid adenomas","volume":"4","author":"Soong","year":"2013","journal-title":"Horm. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1038\/s41598-017-03143-8","article-title":"Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas","volume":"7","author":"Arya","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mce.2013.09.005","article-title":"Genetic and epigenetic changes in sporadic endocrine tumors: Parathyroid tumors","volume":"386","author":"Arnold","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4631","DOI":"10.1210\/jc.2012-2484","article-title":"Evidence of a functional estrogen receptor in parathyroid adenomas","volume":"97","author":"Haglund","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrg3722","article-title":"The rise of regulatory RNA","volume":"15","author":"Morris","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1242\/dev.128074","article-title":"Circular RNAs: Analysis, expression and potential functions","volume":"143","author":"Barrett","year":"2016","journal-title":"Development"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Peng, N., Shi, L., Zhang, Q., Hu, Y., Wang, N., and Ye, H. (2017). Microarray profiling of circular RNAs in human papillary thyroid carcinoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0170287"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cca.2015.02.018","article-title":"Using circular RNA as a novel type of biomarker in the screening of gastric cancer","volume":"444","author":"Li","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3233\/CBM-150552","article-title":"Hsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma","volume":"16","author":"Qin","year":"2016","journal-title":"Cancer Biomark."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e3811","DOI":"10.1097\/MD.0000000000003811","article-title":"Comprehensive circular RNA profiling reveals that hsa_circ_0005075, a new circular RNA biomarker, is involved in hepatocellular crcinoma development","volume":"95","author":"Shang","year":"2016","journal-title":"Medicine"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yu, L., Gong, X., Sun, L., Zhou, Q., Lu, B., and Zhu, L. (2016). The Circular RNA Cdr1as act as an oncogene in hepatocellular carcinoma through targeting miR-7 Expression. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158347"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37982","DOI":"10.1038\/srep37982","article-title":"Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes","volume":"6","author":"Dou","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Huang, G., Zhu, H., Shi, Y., Wu, W., Cai, H., and Chen, X. (2015). cir-ITCH plays an inhibitory role in colorectal cancer by regulating the Wnt\/beta-catenin pathway. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131225"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s13277-014-2771-6","article-title":"MicroRNA-93 suppress colorectal cancer development via Wnt\/beta-catenin pathway downregulating","volume":"36","author":"Tang","year":"2015","journal-title":"Tumour. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"30919","DOI":"10.1038\/srep30919","article-title":"Screening differential circular RNA expression profiles reveals the regulatory role of circTCF25-miR-103a-3p\/miR-107-CDK6 pathway in bladder carcinoma","volume":"6","author":"Zhong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1579490","DOI":"10.1155\/2016\/1579490","article-title":"Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt\/beta-catenin pathway","volume":"2016","author":"Wan","year":"2016","journal-title":"Biomed. Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39918","DOI":"10.1038\/srep39918","article-title":"Peripheral blood circular RNA hsa_circ_0124644 can be used as a diagnostic biomarker of coronary artery disease","volume":"7","author":"Zhao","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3389\/fgene.2013.00307","article-title":"Circular RNA (circRNA) in Alzheimer\u2019s disease (AD)","volume":"4","author":"Lukiw","year":"2013","journal-title":"Front. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s00592-016-0943-0","article-title":"Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus","volume":"54","author":"Zhao","year":"2017","journal-title":"Acta Diabetol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12453","DOI":"10.1038\/srep12453","article-title":"The circular RNA Cdr1as, via miR-7 and its targets, regulates insulin transcription and secretion in islet cells","volume":"5","author":"Xu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3389\/fmolb.2017.00038","article-title":"Circular RNAs: Biogenesis, Function and Role in Human Diseases","volume":"4","author":"Greene","year":"2017","journal-title":"Front. Mol. Biosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.molcel.2014.08.019","article-title":"circRNA biogenesis competes with pre-mRNA splicing","volume":"56","author":"Meyer","year":"2014","journal-title":"Mol. Cell."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4414","DOI":"10.1038\/emboj.2011.359","article-title":"miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA","volume":"30","author":"Hansen","year":"2011","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nrm2104","article-title":"The highways and byways of mRNA decay","volume":"8","author":"Garneau","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1101\/gr.134312.111","article-title":"Global analysis reveals multiple pathways for unique regulation of mRNA decay in induced pluripotent stem cells","volume":"22","author":"Neff","year":"2012","journal-title":"Genome Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1245\/s10434-010-1359-7","article-title":"Identification of differentially expressed microRNA in parathyroid tumors","volume":"18","author":"Rahbari","year":"2011","journal-title":"Ann. Surg. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1530\/JME-11-0189","article-title":"The microRNA cluster C19MC is deregulated in parathyroid tumours","volume":"49","author":"Vaira","year":"2012","journal-title":"J. Mol. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Luzi, E., Marini, F., Giusti, F., Galli, G., Cavalli, L., and Brandi, M.L. (2012). The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the \u201cKnudson\u2019s second hit\u201d. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039767"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/ijc.29021","article-title":"MicroRNA expression signatures for the prediction of BRCA1\/2 mutation-associated hereditary breast cancer in paraffin-embedded formalin-fixed breast tumors","volume":"136","author":"Tanic","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.lungcan.2014.06.010","article-title":"MicroRNA-binding site SNPs in deregulated genes are associated with clinical outcome of non-small cell lung cancer","volume":"85","author":"Xu","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/s12974-017-1003-6","article-title":"MicroRNA expression changes in association with changes in interleukin-1ss\/interleukin10 ratios produced by monocytes in autism spectrum disorders: Their association with neuropsychiatric symptoms and comorbid conditions (observational study)","volume":"14","author":"Jyonouchi","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_48","first-page":"154","article-title":"Differential microRNA epression in asthma and the role of miR-1248 in regulation of IL-5","volume":"1","author":"Panganiban","year":"2012","journal-title":"Am. J. Clin. Exp. Immunol."},{"key":"ref_49","first-page":"725","article-title":"Age-related changes in microRNA levels in serum","volume":"5","author":"Fitzpatrick","year":"2013","journal-title":"Aging (Albany NY)"},{"key":"ref_50","first-page":"481","article-title":"Loss of expression for the Wnt pathway components adenomatous polyposis coli and glycogen synthase kinase 3-beta in parathyroid carcinomas","volume":"34","author":"Juhlin","year":"2009","journal-title":"Int. J. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/1476-4598-9-294","article-title":"Aberrant WNT\/beta-catenin signaling in parathyroid carcinoma","volume":"9","author":"Svedlund","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Juhlin, C.C., Kiss, N.B., Villablanca, A., Haglund, F., Nordenstrom, J., Hoog, A., and Larsson, C. (2010). Frequent promoter hypermethylation of the APC and RASSF1A tumour suppressors in parathyroid tumours. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009472"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E1307","DOI":"10.1210\/jc.2011-3136","article-title":"Hypermethylated in cancer 1 (HIC1), a tumor suppressor gene epigenetically deregulated in hyperparathyroid tumors by histone H3 lysine modification","volume":"97","author":"Svedlund","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:36:47Z","timestamp":1760197007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,30]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["cells8010015"],"URL":"https:\/\/doi.org\/10.3390\/cells8010015","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,30]]}}}