{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:31:52Z","timestamp":1779881512870,"version":"3.53.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T00:00:00Z","timestamp":1540252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A6A3A11931738"],"award-info":[{"award-number":["2016R1A6A3A11931738"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A2B4014593"],"award-info":[{"award-number":["2016R1A2B4014593"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2015R1A5A2009656"],"award-info":[{"award-number":["2015R1A5A2009656"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Centrosome-associated proteins are recognized as prognostic factors in many cancers because centrosomes are critical structures for the cell cycle progression and genomic stability. SAC3D1, however, is associated with centrosome abnormality, although its prognostic potential has not been evaluated in hepatocellular carcinoma (HCC). In this study, 3 independent cohorts (GSE10186, n\u2009=\u200980; TCGA, n\u2009=\u2009330 and ICGC, n\u2009=\u2009237) were used to assess SAC3D1 as a biomarker, which demonstrated SAC3D1 overexpression in HCC tissues when compared to the matched normal tissues. Kaplan-Meier survival analysis also showed that its overexpression was associated with poor prognosis of HCC with good discriminative ability in 3 independent cohorts (GSE10186, <jats:italic>P<\/jats:italic>\u2009=\u20090.00469; TCGA, <jats:italic>P<\/jats:italic>\u2009=\u20090.0000413 and ICGC, <jats:italic>P<\/jats:italic>\u2009=\u20090.0000114). Analysis of the C-indices and AUC values further supported its discriminative ability. Finally, multivariate analysis confirmed its prognostic significance (GSE10186, <jats:italic>P<\/jats:italic>\u2009=\u20090.00695; TCGA, <jats:italic>P<\/jats:italic>\u2009=\u20090.0000289 and ICGC, <jats:italic>P<\/jats:italic>\u2009=\u20090.0000651). These results suggest a potential of SAC3D1 as a biomarker for HCC.<\/jats:p>","DOI":"10.1038\/s41598-018-34129-9","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T09:16:57Z","timestamp":1539767817000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["SAC3D1: a novel prognostic marker in hepatocellular carcinoma"],"prefix":"10.1038","volume":"8","author":[{"given":"Myoung-Eun","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Hak","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae-Ock","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,23]]},"reference":[{"key":"34129_CR1","doi-asserted-by":"publisher","first-page":"153","DOI":"10.3389\/fonc.2014.00153","volume":"4","author":"AL Parker","year":"2014","unstructured":"Parker, A. L., Kavallaris, M. & McCarroll, J. A. Microtubules and their role in cellular stress in cancer. Front Oncol 4, 153, https:\/\/doi.org\/10.3389\/fonc.2014.00153 (2014).","journal-title":"Front Oncol"},{"key":"34129_CR2","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nrd3253","volume":"9","author":"C Dumontet","year":"2010","unstructured":"Dumontet, C. & Jordan, M. A. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 9, 790\u2013803, https:\/\/doi.org\/10.1038\/nrd3253 (2010).","journal-title":"Nat Rev Drug Discov"},{"key":"34129_CR3","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.4161\/cbt.3.11.1216","volume":"3","author":"S Don","year":"2004","unstructured":"Don, S. et al. Neuronal-associated microtubule proteins class III beta-tubulin and MAP2c in neuroblastoma: role in resistance to microtubule-targeted drugs. Mol Cancer Ther 3, 1137\u20131146 (2004).","journal-title":"Mol Cancer Ther"},{"key":"34129_CR4","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1111\/j.1600-0625.2009.01020.x","volume":"19","author":"Z Song","year":"2010","unstructured":"Song, Z. et al. Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo. Exp Dermatol 19, 958\u2013964, https:\/\/doi.org\/10.1111\/j.1600-0625.2009.01020.x (2010).","journal-title":"Exp Dermatol"},{"key":"34129_CR5","first-page":"5803","volume":"61","author":"M Kavallaris","year":"2001","unstructured":"Kavallaris, M. et al. Multiple microtubule alterations are associated with Vinca alkaloid resistance in human leukemia cells. Cancer Res 61, 5803\u20135809 (2001).","journal-title":"Cancer Res"},{"key":"34129_CR6","first-page":"1207","volume":"63","author":"LA Martello","year":"2003","unstructured":"Martello, L. A. et al. Elevated levels of microtubule destabilizing factors in a Taxol-resistant\/dependent A549 cell line with an alpha-tubulin mutation. Cancer Res 63, 1207\u20131213 (2003).","journal-title":"Cancer Res"},{"key":"34129_CR7","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/sj.bjc.6605537","volume":"102","author":"TY Jeon","year":"2010","unstructured":"Jeon, T. Y. et al. Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer 102, 710\u2013718, https:\/\/doi.org\/10.1038\/sj.bjc.6605537 (2010).","journal-title":"Br J Cancer"},{"key":"34129_CR8","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/genetics\/121.4.659","volume":"121","author":"P Novick","year":"1989","unstructured":"Novick, P., Osmond, B. C. & Botstein, D. Suppressors of yeast actin mutations. Genetics 121, 659\u2013674 (1989).","journal-title":"Genetics"},{"key":"34129_CR9","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1182\/blood-2008-01-133405","volume":"113","author":"H Nakajima","year":"2009","unstructured":"Nakajima, H. et al. SHD1 is a novel cytokine-inducible, negative feedback regulator of STAT5-dependent transcription. Blood 113, 1027\u20131036, https:\/\/doi.org\/10.1182\/blood-2008-01-133405 (2009).","journal-title":"Blood"},{"key":"34129_CR10","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0378-1119(00)00336-X","volume":"255","author":"E Abe","year":"2000","unstructured":"Abe, E. et al. Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication. Gene 255, 219\u2013227 (2000).","journal-title":"Gene"},{"key":"34129_CR11","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1182\/blood.V95.7.2321","volume":"95","author":"K Kuwahara","year":"2000","unstructured":"Kuwahara, K. et al. A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication. Blood 95, 2321\u20132328 (2000).","journal-title":"Blood"},{"issue":"Pt 6","key":"34129_CR12","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1242\/jcs.109.6.1575","volume":"109","author":"A Bauer","year":"1996","unstructured":"Bauer, A. & Kolling, R. The SAC3 gene encodes a nuclear protein required for normal progression of mitosis. J Cell Sci 109(Pt 6), 1575\u20131583 (1996).","journal-title":"J Cell Sci"},{"key":"34129_CR13","doi-asserted-by":"publisher","first-page":"46182","DOI":"10.1074\/jbc.M405347200","volume":"279","author":"SE Khuda","year":"2004","unstructured":"Khuda, S. E. et al. The Sac3 homologue shd1 is involved in mitotic progression in mammalian cells. J Biol Chem 279, 46182\u201346190, https:\/\/doi.org\/10.1074\/jbc.M405347200 (2004).","journal-title":"J Biol Chem"},{"key":"34129_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-28280-6","volume":"8","author":"H Huang","year":"2018","unstructured":"Huang, H. et al. Identification of pathways and genes associated with synovitis in osteoarthritis using bioinformatics analyses. Sci Rep 8, 10050, https:\/\/doi.org\/10.1038\/s41598-018-28280-6 (2018).","journal-title":"Sci Rep"},{"key":"34129_CR15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.ctrv.2016.02.008","volume":"45","author":"SL Chan","year":"2016","unstructured":"Chan, S. L., Wong, A. M., Lee, K., Wong, N. & Chan, A. K. Personalized therapy for hepatocellular carcinoma: Where are we now? Cancer Treat Rev 45, 77\u201386, https:\/\/doi.org\/10.1016\/j.ctrv.2016.02.008 (2016).","journal-title":"Cancer Treat Rev"},{"key":"34129_CR16","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1053\/j.gastro.2016.11.048","volume":"152","author":"D Sia","year":"2017","unstructured":"Sia, D., Villanueva, A., Friedman, S. L. & Llovet, J. M. Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis. Gastroenterology 152, 745\u2013761, https:\/\/doi.org\/10.1053\/j.gastro.2016.11.048 (2017).","journal-title":"Gastroenterology"},{"key":"34129_CR17","doi-asserted-by":"publisher","first-page":"68381","DOI":"10.18632\/oncotarget.20266","volume":"8","author":"YH Kim","year":"2017","unstructured":"Kim, Y. H. et al. SLC2A2 (GLUT2) as a novel prognostic factor for hepatocellular carcinoma. Oncotarget 8, 68381\u201368392, https:\/\/doi.org\/10.18632\/oncotarget.20266 (2017).","journal-title":"Oncotarget"},{"key":"34129_CR18","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.3748\/wjg.v20.i12.3135","volume":"20","author":"SL Chan","year":"2014","unstructured":"Chan, S. L. & Yeo, W. Development of systemic therapy for hepatocellular carcinoma at 2013: updates and insights. World J Gastroenterol 20, 3135\u20133145, https:\/\/doi.org\/10.3748\/wjg.v20.i12.3135 (2014).","journal-title":"World J Gastroenterol"},{"key":"34129_CR19","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/S1470-2045(15)00050-9","volume":"16","author":"AX Zhu","year":"2015","unstructured":"Zhu, A. X. et al. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 16, 859\u2013870, https:\/\/doi.org\/10.1016\/S1470-2045(15)00050-9 (2015).","journal-title":"Lancet Oncol"},{"key":"34129_CR20","doi-asserted-by":"publisher","first-page":"889","DOI":"10.2217\/fon.09.64","volume":"5","author":"SL Chan","year":"2009","unstructured":"Chan, S. L., Chan, A. T. & Yeo, W. Role of alpha-fetoprotein in hepatocellular carcinoma: prognostication, treatment monitoring or both? Future Oncol 5, 889\u2013899, https:\/\/doi.org\/10.2217\/fon.09.64 (2009).","journal-title":"Future Oncol"},{"key":"34129_CR21","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1001\/jama.2014.7189","volume":"312","author":"AX Zhu","year":"2014","unstructured":"Zhu, A. X. et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 312, 57\u201367, https:\/\/doi.org\/10.1001\/jama.2014.7189 (2014).","journal-title":"JAMA"},{"key":"34129_CR22","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1158\/1535-7163.MCT-14-0768","volume":"14","author":"H Huynh","year":"2015","unstructured":"Huynh, H. et al. Loss of Tuberous Sclerosis Complex 2 (TSC2) Is Frequent in Hepatocellular Carcinoma and Predicts Response to mTORC1 Inhibitor Everolimus. Mol Cancer Ther 14, 1224\u20131235, https:\/\/doi.org\/10.1158\/1535-7163.MCT-14-0768 (2015).","journal-title":"Mol Cancer Ther"},{"key":"34129_CR23","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"Cancer Genome Atlas Research, N","year":"2013","unstructured":"Cancer Genome Atlas Research, N. et al. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45, 1113\u20131120, https:\/\/doi.org\/10.1038\/ng.2764 (2013).","journal-title":"Nat Genet"},{"key":"34129_CR24","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","volume":"2","author":"E Cerami","year":"2012","unstructured":"Cerami, E. et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2, 401\u2013404, https:\/\/doi.org\/10.1158\/2159-8290.CD-12-0095 (2012).","journal-title":"Cancer Discov"},{"key":"34129_CR25","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nature08987","volume":"464","author":"International Cancer Genome, C","year":"2010","unstructured":"International Cancer Genome, C. et al. International network of cancer genome projects. Nature 464, 993\u2013998, https:\/\/doi.org\/10.1038\/nature08987 (2010).","journal-title":"Nature"},{"key":"34129_CR26","doi-asserted-by":"publisher","first-page":"7385","DOI":"10.1158\/0008-5472.CAN-09-1089","volume":"69","author":"Y Hoshida","year":"2009","unstructured":"Hoshida, Y. et al. Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma. Cancer Res 69, 7385\u20137392, https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-1089 (2009).","journal-title":"Cancer Res"},{"key":"34129_CR27","doi-asserted-by":"publisher","unstructured":"Shtraizent, N. et al. MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect. Elife 6, https:\/\/doi.org\/10.7554\/eLife.22477 (2017).","DOI":"10.7554\/eLife.22477"},{"key":"34129_CR28","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1515\/hsz-2013-0184","volume":"394","author":"HC Thakur","year":"2013","unstructured":"Thakur, H. C. et al. Role of centrosomal adaptor proteins of the TACC family in the regulation of microtubule dynamics during mitotic cell division. Biol Chem 394, 1411\u20131423, https:\/\/doi.org\/10.1515\/hsz-2013-0184 (2013).","journal-title":"Biol Chem"},{"key":"34129_CR29","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1074\/jbc.M113.532333","volume":"289","author":"HC Thakur","year":"2014","unstructured":"Thakur, H. C. et al. The centrosomal adaptor TACC3 and the microtubule polymerase chTOG interact via defined C-terminal subdomains in an Aurora-A kinase-independent manner. J Biol Chem 289, 74\u201388, https:\/\/doi.org\/10.1074\/jbc.M113.532333 (2014).","journal-title":"J Biol Chem"},{"key":"34129_CR30","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1158\/1078-0432.CCR-1057-03","volume":"10","author":"YM Jeng","year":"2004","unstructured":"Jeng, Y. M., Peng, S. Y., Lin, C. Y. & Hsu, H. C. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Res 10, 2065\u20132071 (2004).","journal-title":"Clin Cancer Res"},{"key":"34129_CR31","doi-asserted-by":"publisher","first-page":"3027","DOI":"10.1007\/s00018-014-1582-7","volume":"71","author":"G Neumayer","year":"2014","unstructured":"Neumayer, G., Belzil, C., Gruss, O. J. & Nguyen, M. D. TPX2: of spindle assembly, DNA damage response, and cancer. Cell Mol Life Sci 71, 3027\u20133047, https:\/\/doi.org\/10.1007\/s00018-014-1582-7 (2014).","journal-title":"Cell Mol Life Sci"},{"key":"34129_CR32","doi-asserted-by":"publisher","first-page":"e244","DOI":"10.1371\/journal.pone.0000244","volume":"2","author":"T Clausen","year":"2007","unstructured":"Clausen, T. & Ribbeck, K. Self-organization of anastral spindles by synergy of dynamic instability, autocatalytic microtubule production, and a spatial signaling gradient. PLoS One 2, e244, https:\/\/doi.org\/10.1371\/journal.pone.0000244 (2007).","journal-title":"PLoS One"},{"key":"34129_CR33","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1038\/ncb870","volume":"4","author":"OJ Gruss","year":"2002","unstructured":"Gruss, O. J. et al. Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Nat Cell Biol 4, 871\u2013879, https:\/\/doi.org\/10.1038\/ncb870 (2002).","journal-title":"Nat Cell Biol"},{"key":"34129_CR34","doi-asserted-by":"publisher","first-page":"18148","DOI":"10.3390\/ijms151018148","volume":"15","author":"Y Huang","year":"2014","unstructured":"Huang, Y., Guo, W. & Kan, H. TPX2 is a prognostic marker and contributes to growth and metastasis of human hepatocellular carcinoma. Int J Mol Sci 15, 18148\u201318161, https:\/\/doi.org\/10.3390\/ijms151018148 (2014).","journal-title":"Int J Mol Sci"},{"key":"34129_CR35","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.bbcan.2008.07.003","volume":"1786","author":"G Vader","year":"2008","unstructured":"Vader, G. & Lens, S. M. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta 1786, 60\u201372, https:\/\/doi.org\/10.1016\/j.bbcan.2008.07.003 (2008).","journal-title":"Biochim Biophys Acta"},{"key":"34129_CR36","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1007\/s00268-010-0928-z","volume":"35","author":"WY Kao","year":"2011","unstructured":"Kao, W. Y. et al. A comparison of prognosis between patients with hepatitis B and C virus-related hepatocellular carcinoma undergoing resection surgery. World J Surg 35, 858\u2013867, https:\/\/doi.org\/10.1007\/s00268-010-0928-z (2011).","journal-title":"World J Surg"},{"key":"34129_CR37","doi-asserted-by":"publisher","first-page":"7563","DOI":"10.7314\/APJCP.2014.15.18.7563","volume":"15","author":"A Munaf","year":"2014","unstructured":"Munaf, A., Memon, M. S., Kumar, P., Ahmed, S. & Kumar, M. B. Comparison of viral hepatitis-associated hepatocellular carcinoma due to HBV and HCV - cohort from liver clinics in Pakistan. Asian Pac J Cancer Prev 15, 7563\u20137567 (2014).","journal-title":"Asian Pac J Cancer Prev"},{"key":"34129_CR38","doi-asserted-by":"publisher","first-page":"77515","DOI":"10.18632\/oncotarget.20548","volume":"8","author":"YH Kim","year":"2017","unstructured":"Kim, Y. H. et al. Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients. Oncotarget 8, 77515\u201377526, https:\/\/doi.org\/10.18632\/oncotarget.20548 (2017).","journal-title":"Oncotarget"},{"key":"34129_CR39","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1053\/j.gastro.2013.03.051","volume":"145","author":"JC Nault","year":"2013","unstructured":"Nault, J. C. et al. A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology 145, 176\u2013187, https:\/\/doi.org\/10.1053\/j.gastro.2013.03.051 (2013).","journal-title":"Gastroenterology"},{"key":"34129_CR40","doi-asserted-by":"publisher","first-page":"2817","DOI":"10.1056\/NEJMoa041588","volume":"351","author":"S Paik","year":"2004","unstructured":"Paik, S. et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351, 2817\u20132826, https:\/\/doi.org\/10.1056\/NEJMoa041588 (2004).","journal-title":"N Engl J Med"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34129-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34129-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34129-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:42:44Z","timestamp":1671619364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-34129-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,23]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["34129"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-34129-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,23]]},"assertion":[{"value":"27 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2018","order":3,"name":"first_online","label":"First Online","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":"15608"}}