{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T05:37:25Z","timestamp":1772689045699,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Interstitial cystitis (IC) is a chronic urinary tract disease that is characterized by unpleasant sensations, such as persistent pelvic pain, in the absence of infection or other identifiable causes. We previously performed comprehensive metabolomics profiling of urine samples from IC patients using nuclear magnetic resonance and gas-chromatography\/mass spectrometry and found that urinary \u03b1-oxoglutarate (\u03b1-OG), was significantly elevated. \u03b1-OG, a tricarboxylic acid (TCA) cycle intermediate, reportedly functions to suppress the proliferation of immortalized normal human bladder epithelial cells. Here, we identified AT-rich interactive domain 1\u2009A (ARID1A), a key chromatin remodeler, as being hypomethylated and upregulated by \u03b1-OG treatment. This was done through EPIC DNA methylation profiling and subsequent biochemical approaches, including quantitative RT-PCR and western blot analyses. Furthermore, we found that \u03b1-OG almost completely suppresses ten-eleven translocation (TET) activity, but does not affect DNA methyltransferase (DNMT) activity. Altogether, our studies reveal the potential role of \u03b1-OG in epigenetic remodeling through its effects on ARID1A and TET expression in the bladder. This may provide a new possible therapeutic strategy in treating IC.<\/jats:p>","DOI":"10.1038\/s41598-018-22771-2","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T11:32:19Z","timestamp":1520508739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alpha-oxoglutarate inhibits the proliferation of immortalized normal bladder epithelial cells via an epigenetic switch involving ARID1A"],"prefix":"10.1038","volume":"8","author":[{"given":"Muhammad","family":"Shahid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-5648","authenticated-orcid":false,"given":"Nicole","family":"Gull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Austin","family":"Yeon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eunho","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jooeun","family":"Bae","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun Seok","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3513-1783","authenticated-orcid":false,"given":"Sungyong","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minjung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2099-9005","authenticated-orcid":false,"given":"Benjamin P.","family":"Berman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"key":"22771_CR1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nm0211-143","volume":"17","author":"M Pflumm","year":"2011","unstructured":"Pflumm, M. Animal instinct helps doctors ferret out disease. Nature medicine 17, 143, https:\/\/doi.org\/10.1038\/nm0211-143 (2011).","journal-title":"Nature medicine"},{"issue":"Suppl 1","key":"22771_CR2","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1007\/s00192-005-1301-x","volume":"16","author":"P Hanno","year":"2005","unstructured":"Hanno, P., Keay, S., Moldwin, R. & Van Ophoven, A. International Consultation on IC - Rome, September 2004\/Forging an International Consensus: progress in painful bladder syndrome\/interstitial cystitis. Report and abstracts. International urogynecology journal and pelvic floor dysfunction 16(Suppl 1), S2\u2013S34, https:\/\/doi.org\/10.1007\/s00192-005-1301-x (2005).","journal-title":"International urogynecology journal and pelvic floor dysfunction"},{"key":"22771_CR3","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/S0022-5347(17)39933-0","volume":"143","author":"P Hanno","year":"1990","unstructured":"Hanno, P. et al. Diagnosis of interstitial cystitis. The Journal of urology 143, 278\u2013281 (1990).","journal-title":"The Journal of urology"},{"key":"22771_CR4","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1097\/01.ju.0000158452.15915.e2","volume":"173","author":"TJ Ness","year":"2005","unstructured":"Ness, T. J., Powell-Boone, T., Cannon, R., Lloyd, L. K. & Fillingim, R. B. Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis. The Journal of urology 173, 1983\u20131987, https:\/\/doi.org\/10.1097\/01.ju.0000158452.15915.e2 (2005).","journal-title":"The Journal of urology"},{"key":"22771_CR5","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.eururo.2003.11.021","volume":"45","author":"J Nordling","year":"2004","unstructured":"Nordling, J. et al. Primary evaluation of patients suspected of having interstitial cystitis (IC). European urology 45, 662\u2013669, https:\/\/doi.org\/10.1016\/j.eururo.2003.11.021 (2004).","journal-title":"European urology"},{"key":"22771_CR6","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/00042307-200201000-00013","volume":"12","author":"JW Warren","year":"2002","unstructured":"Warren, J. W. & Keay, S. K. Interstitial cystitis. Current opinion in urology 12, 69\u201374 (2002).","journal-title":"Current opinion in urology"},{"key":"22771_CR7","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00192-010-1252-8","volume":"22","author":"JT Anger","year":"2011","unstructured":"Anger, J. T. et al. Treatment choice, duration, and cost in patients with interstitial cystitis and painful bladder syndrome. International urogynecology journal 22, 395\u2013400, https:\/\/doi.org\/10.1007\/s00192-010-1252-8 (2011).","journal-title":"International urogynecology journal"},{"key":"22771_CR8","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.juro.2011.03.132","volume":"186","author":"SH Berry","year":"2011","unstructured":"Berry, S. H. et al. Prevalence of symptoms of bladder pain syndrome\/interstitial cystitis among adult females in the United States. The Journal of urology 186, 540\u2013544, https:\/\/doi.org\/10.1016\/j.juro.2011.03.132 (2011).","journal-title":"The Journal of urology"},{"key":"22771_CR9","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.juro.2012.08.088","volume":"189","author":"AM Suskind","year":"2013","unstructured":"Suskind, A. M. et al. The prevalence and overlap of interstitial cystitis\/bladder pain syndrome and chronic prostatitis\/chronic pelvic pain syndrome in men: results of the RAND Interstitial Cystitis Epidemiology male study. The Journal of urology 189, 141\u2013145, https:\/\/doi.org\/10.1016\/j.juro.2012.08.088 (2013).","journal-title":"The Journal of urology"},{"key":"22771_CR10","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1016\/j.juro.2009.12.103","volume":"183","author":"SH Berry","year":"2010","unstructured":"Berry, S. H. et al. Development, validation and testing of an epidemiological case definition of interstitial cystitis\/painful bladder syndrome. The Journal of urology 183, 1848\u20131852, https:\/\/doi.org\/10.1016\/j.juro.2009.12.103 (2010).","journal-title":"The Journal of urology"},{"key":"22771_CR11","doi-asserted-by":"publisher","unstructured":"Clemens, J. Q. et al. Validation of a modified National Institutes of Health chronic prostatitis symptom index to assess genitourinary pain in both men and women. Urology 74, 983\u2013987, quiz 987 e981-983, https:\/\/doi.org\/10.1016\/j.urology.2009.06.078 (2009).","DOI":"10.1016\/j.urology.2009.06.078"},{"key":"22771_CR12","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.juro.2006.09.032","volume":"177","author":"LM Bogart","year":"2007","unstructured":"Bogart, L. M., Berry, S. H. & Clemens, J. Q. Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases in women: a systematic review. The Journal of urology 177, 450\u2013456, https:\/\/doi.org\/10.1016\/j.juro.2006.09.032 (2007).","journal-title":"The Journal of urology"},{"key":"22771_CR13","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1007\/s00216-012-6117-1","volume":"404","author":"A Zhang","year":"2012","unstructured":"Zhang, A., Sun, H. & Wang, X. Serum metabolomics as a novel diagnostic approach for disease: a systematic review. Analytical and bioanalytical chemistry 404, 1239\u20131245, https:\/\/doi.org\/10.1007\/s00216-012-6117-1 (2012).","journal-title":"Analytical and bioanalytical chemistry"},{"key":"22771_CR14","doi-asserted-by":"publisher","first-page":"595","DOI":"10.2174\/138620712802650522","volume":"15","author":"T Gebregiworgis","year":"2012","unstructured":"Gebregiworgis, T. & Powers, R. Application of NMR metabolomics to search for human disease biomarkers. Combinatorial chemistry & high throughput screening 15, 595\u2013610 (2012).","journal-title":"Combinatorial chemistry & high throughput screening"},{"key":"22771_CR15","doi-asserted-by":"publisher","first-page":"321","DOI":"10.4155\/bio.11.320","volume":"4","author":"NJ Serkova","year":"2012","unstructured":"Serkova, N. J. & Brown, M. S. Quantitative analysis in magnetic resonance spectroscopy: from metabolic profiling to in vivo biomarkers. Bioanalysis 4, 321\u2013341, https:\/\/doi.org\/10.4155\/bio.11.320 (2012).","journal-title":"Bioanalysis"},{"key":"22771_CR16","doi-asserted-by":"publisher","DOI":"10.1021\/pr5007729","author":"H Wen","year":"2014","unstructured":"Wen, H. et al. Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers. Journal of proteome research. https:\/\/doi.org\/10.1021\/pr5007729 (2014).","journal-title":"Journal of proteome research"},{"key":"22771_CR17","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40170-017-0165-0","volume":"5","author":"R Vatrinet","year":"2017","unstructured":"Vatrinet, R. et al. The alpha-ketoglutarate dehydrogenase complex in cancer metabolic plasticity. Cancer & metabolism 5, 3, https:\/\/doi.org\/10.1186\/s40170-017-0165-0 (2017).","journal-title":"Cancer & metabolism"},{"key":"22771_CR18","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nature23475","volume":"548","author":"T Xu","year":"2017","unstructured":"Xu, T. et al. Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism. Nature 548, 228\u2013233, https:\/\/doi.org\/10.1038\/nature23475 (2017).","journal-title":"Nature"},{"key":"22771_CR19","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s11626-010-9350-y","volume":"47","author":"J Kim","year":"2011","unstructured":"Kim, J. et al. An hTERT-immortalized human urothelial cell line that responds to anti-proliferative factor. In vitro cellular & developmental biology. Animal 47, 2\u20139, https:\/\/doi.org\/10.1007\/s11626-010-9350-y (2011).","journal-title":"In vitro cellular & developmental biology. Animal"},{"key":"22771_CR20","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1093\/nar\/gkw967","volume":"45","author":"W Zhou","year":"2017","unstructured":"Zhou, W., Laird, P. W. & Shen, H. Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes. Nucleic acids research 45, e22, https:\/\/doi.org\/10.1093\/nar\/gkw967 (2017).","journal-title":"Nucleic acids research"},{"key":"22771_CR21","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/bioinformatics\/btw691","volume":"33","author":"JP Fortin","year":"2017","unstructured":"Fortin, J. P., Triche, T. J. Jr. & Hansen, K. D. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics 33, 558\u2013560, https:\/\/doi.org\/10.1093\/bioinformatics\/btw691 (2017).","journal-title":"Bioinformatics"},{"key":"22771_CR22","doi-asserted-by":"publisher","first-page":"e90","DOI":"10.1093\/nar\/gkt090","volume":"41","author":"TJ Triche Jr.","year":"2013","unstructured":"Triche, T. J. Jr., Weisenberger, D. J., Van Den Berg, D., Laird, P. W. & Siegmund, K. D. Low-level processing of Illumina Infinium DNA Methylation BeadArrays. Nucleic acids research 41, e90, https:\/\/doi.org\/10.1093\/nar\/gkt090 (2013).","journal-title":"Nucleic acids research"},{"key":"22771_CR23","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1093\/nar\/gkv1507","volume":"44","author":"A Colaprico","year":"2016","unstructured":"Colaprico, A. et al. TCGAbiolinks: an R\/Bioconductor package for integrative analysis of TCGA data. Nucleic acids research 44, e71, https:\/\/doi.org\/10.1093\/nar\/gkv1507 (2016).","journal-title":"Nucleic acids research"},{"key":"22771_CR24","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847\u20132849, https:\/\/doi.org\/10.1093\/bioinformatics\/btw313 (2016).","journal-title":"Bioinformatics"},{"key":"22771_CR25","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nprot.2008.211","volume":"4","author":"W Huang da","year":"2009","unstructured":"Huang da, W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature protocols 4, 44\u201357, https:\/\/doi.org\/10.1038\/nprot.2008.211 (2009).","journal-title":"Nature protocols"},{"key":"22771_CR26","doi-asserted-by":"publisher","first-page":"D362","DOI":"10.1093\/nar\/gkw937","volume":"45","author":"D Szklarczyk","year":"2017","unstructured":"Szklarczyk, D. et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic acids research 45, D362\u2013D368, https:\/\/doi.org\/10.1093\/nar\/gkw937 (2017).","journal-title":"Nucleic acids research"},{"key":"22771_CR27","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research 13, 2498\u20132504, https:\/\/doi.org\/10.1101\/gr.1239303 (2003).","journal-title":"Genome research"},{"key":"22771_CR28","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/j.juro.2011.03.064","volume":"185","author":"PM Hanno","year":"2011","unstructured":"Hanno, P. M. et al. AUA guideline for the diagnosis and treatment of interstitial cystitis\/bladder pain syndrome. The Journal of urology 185, 2162\u20132170, https:\/\/doi.org\/10.1016\/j.juro.2011.03.064 (2011).","journal-title":"The Journal of urology"},{"key":"22771_CR29","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/j.juro.2015.01.086","volume":"193","author":"PM Hanno","year":"2015","unstructured":"Hanno, P. M., Erickson, D., Moldwin, R., Faraday, M. M. & American Urological, A. Diagnosis and treatment of interstitial cystitis\/bladder pain syndrome: AUA guideline amendment. The Journal of urology 193, 1545\u20131553, https:\/\/doi.org\/10.1016\/j.juro.2015.01.086 (2015).","journal-title":"The Journal of urology"},{"key":"22771_CR30","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1080\/15384101.2017.1295184","volume":"16","author":"BH Choi","year":"2017","unstructured":"Choi, B. H. et al. Differential perturbation of the interstitial cystitis-associated genes of bladder and urethra in rat model. Cell cycle 16, 749\u2013758, https:\/\/doi.org\/10.1080\/15384101.2017.1295184 (2017).","journal-title":"Cell cycle"},{"key":"22771_CR31","doi-asserted-by":"publisher","first-page":"3795","DOI":"10.1016\/j.febslet.2007.06.058","volume":"581","author":"J Kim","year":"2007","unstructured":"Kim, J., Keay, S. K., Dimitrakov, J. D. & Freeman, M. R. p53 mediates interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human urothelial cells. FEBS letters 581, 3795\u20133799, https:\/\/doi.org\/10.1016\/j.febslet.2007.06.058 (2007).","journal-title":"FEBS letters"},{"key":"22771_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0090-4295(01)01166-9","volume":"57","author":"JE Tomaszewski","year":"2001","unstructured":"Tomaszewski, J. E. et al. Biopsy features are associated with primary symptoms in interstitial cystitis: results from the interstitial cystitis database study. Urology 57, 67\u201381 (2001).","journal-title":"Urology"},{"key":"22771_CR33","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1016\/S0090-4295(03)00005-0","volume":"61","author":"S Keay","year":"2003","unstructured":"Keay, S., Zhang, C. O., Shoenfelt, J. L. & Chai, T. C. Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis. Urology 61, 1278\u20131284 (2003).","journal-title":"Urology"},{"key":"22771_CR34","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1152\/physiolgenomics.00055.2003","volume":"14","author":"S Keay","year":"2003","unstructured":"Keay, S., Seillier-Moiseiwitsch, F., Zhang, C. O., Chai, T. C. & Zhang, J. Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment. Physiological genomics 14, 107\u2013115, https:\/\/doi.org\/10.1152\/physiolgenomics.00055.2003 (2003).","journal-title":"Physiological genomics"},{"key":"22771_CR35","doi-asserted-by":"publisher","unstructured":"Hodges, C., Kirkland, J. G. & Crabtree, G. R. The Many Roles of BAF (mSWI\/SNF) and PBAF Complexes in Cancer. Cold Spring Harbor perspectives in medicine 6, https:\/\/doi.org\/10.1101\/cshperspect.a026930 (2016).","DOI":"10.1101\/cshperspect.a026930"},{"key":"22771_CR36","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nrc3068","volume":"11","author":"BG Wilson","year":"2011","unstructured":"Wilson, B. G. & Roberts, C. W. SWI\/SNF nucleosome remodellers and cancer. Nature reviews. Cancer 11, 481\u2013492, https:\/\/doi.org\/10.1038\/nrc3068 (2011).","journal-title":"Nature reviews. Cancer"},{"key":"22771_CR37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1158\/2159-8290.CD-12-0361","volume":"3","author":"JN Wu","year":"2013","unstructured":"Wu, J. N. & Roberts, C. W. ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer discovery 3, 35\u201343, https:\/\/doi.org\/10.1158\/2159-8290.CD-12-0361 (2013).","journal-title":"Cancer discovery"},{"key":"22771_CR38","doi-asserted-by":"publisher","first-page":"E252","DOI":"10.1073\/pnas.1114817109","volume":"109","author":"AH Shain","year":"2012","unstructured":"Shain, A. H. et al. Convergent structural alterations define SWItch\/Sucrose NonFermentable (SWI\/SNF) chromatin remodeler as a central tumor suppressive complex in pancreatic cancer. Proceedings of the National Academy of Sciences of the United States of America 109, E252\u2013259, https:\/\/doi.org\/10.1073\/pnas.1114817109 (2012).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"22771_CR39","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1038\/ng.982","volume":"43","author":"K Wang","year":"2011","unstructured":"Wang, K. et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nature genetics 43, 1219\u20131223, https:\/\/doi.org\/10.1038\/ng.982 (2011).","journal-title":"Nature genetics"},{"key":"22771_CR40","doi-asserted-by":"publisher","first-page":"2233","DOI":"10.1016\/j.humpath.2014.07.003","volume":"45","author":"SF Faraj","year":"2014","unstructured":"Faraj, S. F. et al. ARID1A immunohistochemistry improves outcome prediction in invasive urothelial carcinoma of urinary bladder. Human pathology 45, 2233\u20132239, https:\/\/doi.org\/10.1016\/j.humpath.2014.07.003 (2014).","journal-title":"Human pathology"},{"key":"22771_CR41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.humpath.2016.04.006","volume":"55","author":"J Li","year":"2016","unstructured":"Li, J., Lu, S., Lombardo, K., Monahan, R. & Amin, A. ARID1A alteration in aggressive urothelial carcinoma and variants of urothelial carcinoma. Human pathology 55, 17\u201323, https:\/\/doi.org\/10.1016\/j.humpath.2016.04.006 (2016).","journal-title":"Human pathology"}],"updated-by":[{"DOI":"10.1038\/s41598-018-24827-9","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-22771-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-22771-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-22771-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T03:28:11Z","timestamp":1671593291000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-22771-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,14]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["22771"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-22771-2","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s41598-018-24827-9","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,14]]},"assertion":[{"value":"28 November 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2018","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"4505"}}