{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:06:45Z","timestamp":1790770005206,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"U.S. Department of Health & Human Services | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA202104"],"award-info":[{"award-number":["R21 CA202104"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1038\/s41388-018-0550-3","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T13:04:46Z","timestamp":1540472686000},"page":"1802-1814","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dual inhibition of PI3K signaling and histone deacetylation halts proliferation and induces lethality in mantle cell lymphoma"],"prefix":"10.1038","volume":"38","author":[{"given":"Hui","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongfeng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjian","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie J.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Lorence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3778-4438","authenticated-orcid":false,"given":"Changying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makhdum","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle J.","family":"Nomie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-5486","authenticated-orcid":false,"given":"Michael","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"key":"550_CR1","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1200\/JCO.2015.63.5904","volume":"34","author":"CY Cheah","year":"2016","unstructured":"Cheah CY, Seymour JF, Wang ML. Mantle cell lymphoma. J Clin Oncol. 2016;34:1256\u201369.","journal-title":"J Clin Oncol"},{"key":"550_CR2","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/S0140-6736(15)00667-4","volume":"387","author":"M Dreyling","year":"2016","unstructured":"Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387:770\u20138.","journal-title":"Lancet"},{"key":"550_CR3","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.hoc.2016.07.014","volume":"30","author":"A Goy","year":"2016","unstructured":"Goy A. Mantle cell lymphoma: is it time for a new treatment paradigm? Hematol Oncol Clin North Am. 2016;30:1345\u201370.","journal-title":"Hematol Oncol Clin North Am"},{"key":"550_CR4","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0140-6736(16)30451-2","volume":"388","author":"P Martin","year":"2016","unstructured":"Martin P. Mantle cell lymphoma treatment: plus ca change. Lancet. 2016;388:535\u20136.","journal-title":"Lancet"},{"key":"550_CR5","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/S0140-6736(15)01040-5","volume":"387","author":"P Martin","year":"2016","unstructured":"Martin P. Ibrutinib--a new standard treatment for relapsed mantle cell lymphoma? Lancet. 2016;387:728\u20139.","journal-title":"Lancet"},{"key":"550_CR6","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1182\/blood-2016-06-719294","volume":"129","author":"IE Ahn","year":"2017","unstructured":"Ahn IE, Underbayev C, Albitar A, Herman SE, Tian X, Maric I, et al. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood. 2017;129:1469\u201379.","journal-title":"Blood"},{"key":"550_CR7","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/leu.2014.263","volume":"29","author":"S Cheng","year":"2015","unstructured":"Cheng S, Guo A, Lu P, Ma J, Coleman M, Wang YL. Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors. Leukemia. 2015;29:895\u2013900.","journal-title":"Leukemia"},{"key":"550_CR8","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1158\/2159-8290.CD-14-0098","volume":"4","author":"D Chiron","year":"2014","unstructured":"Chiron D, Di Liberto M, Martin P, Huang X, Sharman J, Blecua P, et al. Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discov. 2014;4:1022\u201335.","journal-title":"Cancer Discov"},{"key":"550_CR9","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1200\/JCO.2016.70.2282","volume":"35","author":"JA Woyach","year":"2017","unstructured":"Woyach JA, Ruppert AS, Guinn D, Lehman A, Blachly JS, Lozanski A, et al. BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia. J Clin Oncol. 2017;35:1437\u201343.","journal-title":"J Clin Oncol"},{"key":"550_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14920","volume":"8","author":"X Zhao","year":"2017","unstructured":"Zhao X, Lwin T, Silva A, Shah B, Tao J, Fang B, et al. Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma. Nat Commun. 2017;8:14920.","journal-title":"Nat Commun"},{"key":"550_CR11","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/nm.3435","volume":"20","author":"R Rahal","year":"2014","unstructured":"Rahal R, Frick M, Romero R, Korn JM, Kridel R, Chan FC, et al. Pharmacological and genomic profiling identifies NF-kappaB-targeted treatment strategies for mantle cell lymphoma. Nat Med. 2014;20:87\u201392.","journal-title":"Nat Med"},{"key":"550_CR12","doi-asserted-by":"publisher","first-page":"3357","DOI":"10.1182\/blood-2015-03-633156","volume":"125","author":"CY Cheah","year":"2015","unstructured":"Cheah CY, Nastoupil LJ, Neelapu SS, Forbes SG, Oki Y, Fowler NH. Lenalidomide, idelalisib, and rituximab are unacceptably toxic in patients with relapsed\/refractory indolent lymphoma. Blood. 2015;125:3357\u20139.","journal-title":"Blood"},{"key":"550_CR13","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1056\/NEJMoa1314583","volume":"370","author":"AK Gopal","year":"2014","unstructured":"Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008\u201318.","journal-title":"N Engl J Med"},{"key":"550_CR14","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1182\/blood-2016-12-757740","volume":"129","author":"AK Gopal","year":"2017","unstructured":"Gopal AK, Kahl BS, Flowers CR, Martin P, Ansell SM, Abella-Dominicis E, et al. Idelalisib is effective in patients with high-risk follicular lymphoma and early relapse after initial chemoimmunotherapy. Blood. 2017;129:3037\u20139.","journal-title":"Blood"},{"key":"550_CR15","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1517\/14656566.2016.1135130","volume":"17","author":"SA Graf","year":"2016","unstructured":"Graf SA, Gopal AK. Idelalisib for the treatment of non-Hodgkin lymphoma. Expert Opin Pharmacother. 2016;17:265\u201374.","journal-title":"Expert Opin Pharmacother"},{"key":"550_CR16","doi-asserted-by":"publisher","first-page":"e156","DOI":"10.3324\/haematol.2016.151738","volume":"102","author":"G Salles","year":"2017","unstructured":"Salles G, Schuster SJ, de Vos S, Wagner-Johnston ND, Viardot A, Blum KA, et al. Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study. Haematologica. 2017;102:e156\u20139.","journal-title":"Haematologica"},{"key":"550_CR17","doi-asserted-by":"crossref","unstructured":"Ali D, Alshammari H, Vishnubalaji R, Chalisserry EP, Hamam R, Alfayez M, et al. CUDC-907 promotes bone marrow adipocytic differentiation through inhibition of histone deacetylase and regulation of cell cycle. Stem Cells Dev. 2017;26:353\u201362.","DOI":"10.1089\/scd.2016.0183"},{"key":"550_CR18","doi-asserted-by":"crossref","unstructured":"Sun K, Atoyan R, Borek MA, DellaRocca S, Samson ME, Ma AW, et al. Dual HDAC and PI3K inhibitor CUDC-907 downregulates MYC and suppresses growth of MYC-dependent cancers. Mol Cancer Ther. 2017;16:285\u201399.","DOI":"10.1158\/1535-7163.MCT-16-0390"},{"key":"550_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.9","volume":"4","author":"JE Bolden","year":"2013","unstructured":"Bolden JE, Shi W, Jankowski K, Kan CY, Cluse L, Martin BP, et al. HDAC inhibitors induce tumor-cell-selective pro-apoptotic transcriptional responses. Cell Death Dis. 2013;4:e519.","journal-title":"Cell Death Dis"},{"key":"550_CR20","doi-asserted-by":"publisher","first-page":"28783","DOI":"10.1074\/jbc.M113.489732","volume":"288","author":"A Dudakovic","year":"2013","unstructured":"Dudakovic A, Evans JM, Li Y, Middha S, McGee-Lawrence ME, van Wijnen AJ, et al. Histone deacetylase inhibition promotes osteoblast maturation by altering the histone H4 epigenome and reduces Akt phosphorylation. J Biol Chem. 2013;288:28783\u201391.","journal-title":"J Biol Chem"},{"key":"550_CR21","doi-asserted-by":"publisher","first-page":"4628","DOI":"10.1158\/1078-0432.CCR-06-0511","volume":"12","author":"F Giles","year":"2006","unstructured":"Giles F, Fischer T, Cortes J, Garcia-Manero G, Beck J, Ravandi F, et al. A phase I study of intravenous LBH589, a novel cinnamic hydroxamic acid analogue histone deacetylase inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res. 2006;12:4628\u201335.","journal-title":"Clin Cancer Res"},{"key":"550_CR22","doi-asserted-by":"publisher","first-page":"14639","DOI":"10.1073\/pnas.1008522107","volume":"107","author":"JH Lee","year":"2010","unstructured":"Lee JH, Choy ML, Ngo L, Foster SS, Marks PA. Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proc Natl Acad Sci USA. 2010;107:14639\u201344.","journal-title":"Proc Natl Acad Sci USA"},{"key":"550_CR23","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1158\/1078-0432.CCR-05-1132","volume":"12","author":"DZ Qian","year":"2006","unstructured":"Qian DZ, Kato Y, Shabbeer S, Wei Y, Verheul HM, Salumbides B, et al. Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res. 2006;12:634\u201342.","journal-title":"Clin Cancer Res"},{"key":"550_CR24","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.jdermsci.2017.12.006","volume":"89","author":"K Ghosh","year":"2018","unstructured":"Ghosh K, O\u2019Neil K, Capell BC. Histone modifiers: dynamic regulators of the cutaneous transcriptome. J Dermatol Sci. 2018;89:226\u201332.","journal-title":"J Dermatol Sci"},{"key":"550_CR25","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.3324\/haematol.2011.040659","volume":"97","author":"DJ Medina","year":"2012","unstructured":"Medina DJ, Goodell L, Glod J, Gelinas C, Rabson AB, Strair RK. Mesenchymal stromal cells protect mantle cell lymphoma cells from spontaneous and drug-induced apoptosis through secretion of B-cell activating factor and activation of the canonical and non-canonical nuclear factor kappaB pathways. Haematologica. 2012;97:1255\u201363.","journal-title":"Haematologica"},{"key":"550_CR26","doi-asserted-by":"publisher","first-page":"4507","DOI":"10.1182\/blood-2008-09-177881","volume":"114","author":"M Rahmani","year":"2009","unstructured":"Rahmani M, Anderson A, Habibi JR, Crabtree TR, Mayo M, Harada H, et al. The BH3-only protein Bim plays a critical role in leukemia cell death triggered by concomitant inhibition of the PI3K\/Akt and MEK\/ERK1\/2 pathways. Blood. 2009;114:4507\u201316.","journal-title":"Blood"},{"key":"550_CR27","doi-asserted-by":"publisher","first-page":"5093","DOI":"10.1182\/blood-2007-10-117762","volume":"111","author":"A Scuto","year":"2008","unstructured":"Scuto A, Kirschbaum M, Kowolik C, Kretzner L, Juhasz A, Atadja P, et al. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells. Blood. 2008;111:5093\u2013100.","journal-title":"Blood"},{"key":"550_CR28","doi-asserted-by":"publisher","first-page":"4654","DOI":"10.1016\/j.febslet.2014.10.037","volume":"588","author":"C Wang","year":"2014","unstructured":"Wang C, Chen Z, Ge Q, Hu J, Li F, Hu J, et al. Up-regulation ofp21(WAF1\/CIP1) by miRNAs and its implications in bladder cancer cells. FEBS Lett. 2014;588:4654\u201364.","journal-title":"FEBS Lett"},{"key":"550_CR29","first-page":"462","volume":"10","author":"M Lemoine","year":"2010","unstructured":"Lemoine M, Younes A. Histone deacetylase inhibitors in the treatment of lymphoma. Discov Med. 2010;10:462\u201370.","journal-title":"Discov Med"},{"key":"550_CR30","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ygyno.2013.02.008","volume":"129","author":"T Yoshioka","year":"2013","unstructured":"Yoshioka T, Yogosawa S, Yamada T, Kitawaki J, Sakai T. Combination of a novel HDAC inhibitor OBP-801\/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS. Gynecol Oncol. 2013;129:425\u201332.","journal-title":"Gynecol Oncol"},{"key":"550_CR31","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/S1470-2045(15)00584-7","volume":"17","author":"A Younes","year":"2016","unstructured":"Younes A, Berdeja JG, Patel MR, Flinn I, Gerecitano JF, Neelapu SS, et al. Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial. Lancet Oncol. 2016;17:622\u201331.","journal-title":"Lancet Oncol"},{"key":"550_CR32","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/icb.2011.100","volume":"90","author":"O Khan","year":"2012","unstructured":"Khan O, La Thangue NB. HDAC inhibitors in cancer biology: emerging mechanisms and clinical applications. Immunol Cell Biol. 2012;90:85\u201394.","journal-title":"Immunol Cell Biol"},{"key":"550_CR33","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.bbrc.2011.09.083","volume":"414","author":"EJ Lee","year":"2011","unstructured":"Lee EJ, Kim N, Kang KH, Kim JW. Phosphorylation\/inactivation of PTEN by Akt-independent PI3K signaling in retinal pigment epithelium. Biochem Biophys Res Commun. 2011;414:384\u20139.","journal-title":"Biochem Biophys Res Commun"},{"key":"550_CR34","doi-asserted-by":"publisher","first-page":"5765","DOI":"10.21873\/anticanres.11160","volume":"36","author":"HJ Lim","year":"2016","unstructured":"Lim HJ, Wang X, Crowe P, Goldstein D, Yang JL. Targeting the PI3K\/PTEN\/AKT\/mTOR Pathway in Treatment of Sarcoma Cell Lines. Anticancer Res. 2016;36:5765\u201371.","journal-title":"Anticancer Res"},{"key":"550_CR35","doi-asserted-by":"publisher","first-page":"4640","DOI":"10.1073\/pnas.051042298","volume":"98","author":"ON Ozes","year":"2001","unstructured":"Ozes ON, Akca H, Mayo LD, Gustin JA, Maehama T, Dixon JE, et al. A phosphatidylinositol 3-kinase\/Akt\/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1. Proc Natl Acad Sci USA. 2001;98:4640\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"550_CR36","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nrc839","volume":"2","author":"I Vivanco","year":"2002","unstructured":"Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer. 2002;2:489\u2013501.","journal-title":"Nat Rev Cancer"},{"key":"550_CR37","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-168","volume":"11","author":"XC Zhang","year":"2013","unstructured":"Zhang XC, Zhang J, Li M, Huang XS, Yang XN, Zhong WZ, et al. Establishment of patient-derived non-small cell lung cancer xenograft models with genetic aberrations within EGFR, KRAS and FGFR1: useful tools for preclinical studies of targeted therapies. J Transl Med. 2013;11:168.","journal-title":"J Transl Med"},{"key":"550_CR38","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.3324\/haematol.2017.172882","volume":"102","author":"Y Oki","year":"2017","unstructured":"Oki Y, Kelly KR, Flinn I, Patel MR, Gharavi R, Ma A, et al. CUDC-907 in relapsed\/refractory diffuse large B-cell lymphoma, including patients with MYC-alterations: results from an expanded phase I trial. Haematologica. 2017;102:1923\u201330.","journal-title":"Haematologica"},{"key":"550_CR39","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1158\/1078-0432.CCR-16-2703","volume":"23","author":"L Zhang","year":"2017","unstructured":"Zhang L, Nomie K, Zhang H, Bell T, Pham L, Kadri S, et al. B-cell lymphoma patient-derived xenograft models enable drug discovery and are a platform for personalized therapy. Clin Cancer Res. 2017;23:4212\u201323.","journal-title":"Clin Cancer Res"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41388-018-0550-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41388-018-0550-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41388-018-0550-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:14:22Z","timestamp":1684617262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41388-018-0550-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,25]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["550"],"URL":"https:\/\/doi.org\/10.1038\/s41388-018-0550-3","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,25]]},"assertion":[{"value":"20 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 October 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}