{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:11:32Z","timestamp":1792606292128,"version":"4.5.0"},"reference-count":53,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1016\/j.ejphar.2021.174176","type":"journal-article","created":{"date-parts":[[2021,5,15]],"date-time":"2021-05-15T19:51:13Z","timestamp":1621108273000},"page":"174176","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Inhibition of osteoclastogenesis by histone deacetylase inhibitor Quisinostat protects mice against titanium particle-induced bone loss"],"prefix":"10.1016","volume":"904","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0515-9841","authenticated-orcid":false,"given":"Liwei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongji","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxuan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-6287","authenticated-orcid":false,"given":"Jianquan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2021.174176_bib1","doi-asserted-by":"crossref","first-page":"6841","DOI":"10.1158\/1078-0432.CCR-09-0547","article-title":"JNJ-26481585, a novel \"second-generation\" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity","volume":"15","author":"Arts","year":"2009","journal-title":"Clin. Canc. Res."},{"key":"10.1016\/j.ejphar.2021.174176_bib2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2106\/JBJS.D.01772","article-title":"Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis","volume":"87","author":"Bhandari","year":"2005","journal-title":"J Bone Joint Surg Am"},{"key":"10.1016\/j.ejphar.2021.174176_bib3","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/physrev.00004.2015","article-title":"Histone deacetylases in bone development and skeletal disorders","volume":"95","author":"Bradley","year":"2015","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.ejphar.2021.174176_bib4","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1093\/rheumatology\/kev022","article-title":"Inhibiting histone deacetylase 1 suppresses both inflammation and bone loss in arthritis","volume":"54","author":"Cantley","year":"2015","journal-title":"Rheumatology"},{"key":"10.1016\/j.ejphar.2021.174176_bib5","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1002\/jcp.22684","article-title":"Inhibitors of histone deacetylases in class I and class II suppress human osteoclasts in vitro","volume":"226","author":"Cantley","year":"2011","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.ejphar.2021.174176_bib6","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bone.2016.11.028","article-title":"Histone deacetylases (HDAC) in physiological and pathological bone remodelling","volume":"95","author":"Cantley","year":"2017","journal-title":"Bone"},{"key":"10.1016\/j.ejphar.2021.174176_bib7","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.3892\/ijmm.2012.1145","article-title":"MMP-9 inhibition suppresses wear debris-induced inflammatory osteolysis through downregulation of RANK\/RANKL in a murine osteolysis model","volume":"30","author":"Chen","year":"2012","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.ejphar.2021.174176_bib8","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1186\/s13287-020-02004-y","article-title":"Moderate SMFs attenuate bone loss in mice by promoting directional osteogenic differentiation of BMSCs","volume":"11","author":"Chen","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.ejphar.2021.174176_bib9","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/jbmr.2348","article-title":"mTORC2 signaling promotes skeletal growth and bone formation in mice","volume":"30","author":"Chen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.ejphar.2021.174176_bib10","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1002\/jbmr.1834","article-title":"\u03b2-catenin promotes bone formation and suppresses bone resorption in postnatal growing mice","volume":"28","author":"Chen","year":"2013","journal-title":"J. Bone Miner. Res."},{"key":"10.1016\/j.ejphar.2021.174176_bib11","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1093\/rheumatology\/keq108","article-title":"Histone deacetylase inhibitors MS-275 and SAHA induced growth arrest and suppressed lipopolysaccharide-stimulated NF-kappaB p65 nuclear accumulation in human rheumatoid arthritis synovial fibroblastic E11 cells","volume":"49","author":"Choo","year":"2010","journal-title":"Rheumatology"},{"key":"10.1016\/j.ejphar.2021.174176_bib12","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1007\/s00223-010-9458-9","article-title":"Parathyroid hormone treatment increases fixation of orthopedic implants with gap healing: a biomechanical and histomorphometric canine study of porous coated titanium alloy implants in cancellous bone","volume":"88","author":"Daugaard","year":"2011","journal-title":"Calcif. Tissue Res."},{"key":"10.1016\/j.ejphar.2021.174176_bib13","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1038\/leu.2009.121","article-title":"The effects of JNJ-26481585, a novel hydroxamate-based histone deacetylase inhibitor, on the development of multiple myeloma in the 5T2MM and 5T33MM murine models","volume":"23","author":"Deleu","year":"2009","journal-title":"Leukemia"},{"key":"10.1016\/j.ejphar.2021.174176_bib14","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.3389\/fimmu.2018.02963","article-title":"Mechanism and prevention of titanium particle-induced inflammation and osteolysis","volume":"9","author":"Eger","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejphar.2021.174176_bib15","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3390\/molecules24071355","article-title":"Regulation of osteoclast differentiation and skeletal maintenance by histone deacetylases","volume":"24","author":"Faulkner","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejphar.2021.174176_bib16","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/38664","article-title":"Histone acetylation in chromatin structure and transcription","volume":"389","author":"Grunstein","year":"1997","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2021.174176_bib17","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.arth.2015.09.026","article-title":"Contemporary surgical indications and referral trends in revision total hip arthroplasty: a 10-year review","volume":"31","author":"Haynes","year":"2016","journal-title":"J. Arthroplasty"},{"key":"10.1016\/j.ejphar.2021.174176_bib18","doi-asserted-by":"crossref","first-page":"e393","DOI":"10.1371\/journal.pbio.0030393","article-title":"Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun","volume":"3","author":"Hazzalin","year":"2005","journal-title":"PLoS Biol."},{"key":"10.1016\/j.ejphar.2021.174176_bib19","doi-asserted-by":"crossref","first-page":"e1166","DOI":"10.1038\/cddis.2014.133","article-title":"Preclinical anti-arthritic study and pharmacokinetic properties of a potent histone deacetylase inhibitor MPT0G009","volume":"5","author":"Hsieh","year":"2014","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejphar.2021.174176_bib20","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2021.174176_bib21","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.85061","article-title":"Histone deacetylase inhibitor panobinostat induces calcineurin degradation in multiple myeloma","volume":"1","author":"Imai","year":"2016","journal-title":"JCI Insight"},{"key":"10.1016\/j.ejphar.2021.174176_bib22","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.biomaterials.2004.04.035","article-title":"The role of macrophages in osteolysis of total joint replacement","volume":"26","author":"Ingham","year":"2005","journal-title":"Biomaterials"},{"key":"10.1016\/j.ejphar.2021.174176_bib23","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1063127","article-title":"Translating the histone code","volume":"293","author":"Jenuwein","year":"2001","journal-title":"Science"},{"key":"10.1016\/j.ejphar.2021.174176_bib24","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1038\/boneres.2016.14","article-title":"A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response","volume":"4","author":"Kandahari","year":"2016","journal-title":"Bone Res"},{"key":"10.1016\/j.ejphar.2021.174176_bib25","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ejphar.2009.09.025","article-title":"Trichostatin A inhibits osteoclastogenesis and bone resorption by suppressing the induction of c-Fos by RANKL","volume":"623","author":"Kim","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174176_bib26","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ejphar.2012.07.034","article-title":"MS-275, a benzamide histone deacetylase inhibitor, prevents osteoclastogenesis by down-regulating c-Fos expression and suppresses bone loss in mice","volume":"691","author":"Kim","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174176_bib27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1080\/17453674.2017.1300746","article-title":"Denosumab reduces early migration in total knee replacement","volume":"88","author":"Ledin","year":"2017","journal-title":"Acta Orthop."},{"key":"10.1016\/j.ejphar.2021.174176_bib28","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1210\/me.2006-0061","article-title":"Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation","volume":"20","author":"Lee","year":"2006","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ejphar.2021.174176_bib29","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/sj.bjp.0707165","article-title":"Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents","volume":"150","author":"Lin","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174176_bib30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"10.1016\/j.ejphar.2021.174176_bib31","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nrrheum.2013.27","article-title":"Determining who should be referred for total hip and knee replacements","volume":"9","author":"Mandl","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"10.1016\/j.ejphar.2021.174176_bib32","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.bone.2011.01.007","article-title":"Suberoylanilide hydroxamic acid (SAHA; vorinostat) causes bone loss by inhibiting immature osteoblasts","volume":"48","author":"McGee-Lawrence","year":"2011","journal-title":"Bone"},{"key":"10.1016\/j.ejphar.2021.174176_bib33","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1242\/jcs.189068","article-title":"Actin visualization at a glance","volume":"130","author":"Melak","year":"2017","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.ejphar.2021.174176_bib34","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.4049\/jimmunol.175.9.5809","article-title":"Inhibition of histone deacetylase suppresses osteoclastogenesis and bone destruction by inducing IFN-beta production","volume":"175","author":"Nakamura","year":"2005","journal-title":"J. Immunol."},{"key":"10.1016\/j.ejphar.2021.174176_bib35","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1302\/0301-620X.95B8.31229","article-title":"The role of osteoblasts in peri-prosthetic osteolysis","volume":"95-b","author":"O'Neill","year":"2013","journal-title":"Bone Joint Lett. J"},{"key":"10.1016\/j.ejphar.2021.174176_bib36","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s00418-018-1636-2","article-title":"Recent advances in osteoclast biology","volume":"149","author":"Ono","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"10.1016\/j.ejphar.2021.174176_bib37","doi-asserted-by":"crossref","first-page":"706","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of RANK signaling in osteoclast differentiation and maturation","volume":"40","author":"Park","year":"2017","journal-title":"Mol. Cell."},{"key":"10.1016\/j.ejphar.2021.174176_bib38","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.1016\/S0140-6736(18)32344-4","article-title":"Knee replacement","volume":"392","author":"Price","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2021.174176_bib39","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1182\/blood-2002-08-2622","article-title":"Two histone deacetylase inhibitors, trichostatin A and sodium butyrate, suppress differentiation into osteoclasts but not into macrophages","volume":"101","author":"Rahman","year":"2003","journal-title":"Blood"},{"key":"10.1016\/j.ejphar.2021.174176_bib40","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.arth.2013.01.012","article-title":"Revision surgery after total joint arthroplasty: a complication-based analysis using worldwide arthroplasty registers","volume":"28","author":"Sadoghi","year":"2013","journal-title":"J. Arthroplasty"},{"key":"10.1016\/j.ejphar.2021.174176_bib41","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1111\/j.1528-1167.2009.02516.x","article-title":"Adverse effects of valproate on bone: defining a model to investigate the pathophysiology","volume":"51","author":"Senn","year":"2010","journal-title":"Epilepsia"},{"key":"10.1016\/j.ejphar.2021.174176_bib42","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s00198-018-4488-7","article-title":"Bisphosphonates for the preservation of periprosthetic bone mineral density after total joint arthroplasty: a meta-analysis of 25 randomized controlled trials","volume":"29","author":"Shi","year":"2018","journal-title":"Osteoporos. Int."},{"key":"10.1016\/j.ejphar.2021.174176_bib43","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJMoa1505467","article-title":"A randomized, controlled trial of total knee replacement","volume":"373","author":"Skou","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejphar.2021.174176_bib44","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1007\/s11999-014-3765-9","article-title":"Are biologic treatments a potential approach to wear- and corrosion-related problems?","volume":"472","author":"Smith","year":"2014","journal-title":"Clin. Orthop. Relat. Res."},{"key":"10.1016\/j.ejphar.2021.174176_bib45","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nprot.2008.221","article-title":"A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow","volume":"4","author":"Soleimani","year":"2009","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.ejphar.2021.174176_bib46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/47412","article-title":"The language of covalent histone modifications","volume":"403","author":"Strahl","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.ejphar.2021.174176_bib47","doi-asserted-by":"crossref","first-page":"715","DOI":"10.2106\/JBJS.M.01534","article-title":"Current failure mechanisms after knee arthroplasty have changed: polyethylene wear is less common in revision surgery","volume":"97","author":"Thiele","year":"2015","journal-title":"J. Bone Joint Surg. Am."},{"key":"10.1016\/j.ejphar.2021.174176_bib48","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jbspin.2010.03.009","article-title":"Histone deacetylase inhibitors: new treatment options for inflammatory joint disease?","volume":"77","author":"Toussirot","year":"2010","journal-title":"Joint Bone Spine"},{"key":"10.1016\/j.ejphar.2021.174176_bib49","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.2217\/epi-2017-0027","article-title":"Targeting transcription factor lysine acetylation in inflammatory airway diseases","volume":"9","author":"van den Bosch","year":"2017","journal-title":"Epigenomics"},{"key":"10.1016\/j.ejphar.2021.174176_bib50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/aps.2012.182","article-title":"Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo","volume":"34","author":"Xu","year":"2013","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.ejphar.2021.174176_bib51","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jot.2020.03.001","article-title":"A modified tape transfer approach for rapidly preparing high-quality cryosections of undecalcified adult rodent bones","volume":"26","author":"Yang","year":"2021","journal-title":"J Orthop Translat"},{"key":"10.1016\/j.ejphar.2021.174176_bib52","doi-asserted-by":"crossref","first-page":"172550","DOI":"10.1016\/j.ejphar.2019.172550","article-title":"Glycyrrhizic acid suppresses osteoclast differentiation and postmenopausal osteoporosis by modulating the NF-\u03baB, ERK, and JNK signaling pathways","volume":"859","author":"Yin","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2021.174176_bib53","doi-asserted-by":"crossref","first-page":"6638","DOI":"10.7150\/thno.44793","article-title":"Genetic and pharmacological activation of Hedgehog signaling inhibits osteoclastogenesis and attenuates titanium particle-induced osteolysis partly through suppressing the JNK\/c-Fos-NFATc1 cascade","volume":"10","author":"Zhang","year":"2020","journal-title":"Theranostics"}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921003290?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921003290?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T22:51:39Z","timestamp":1757976699000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921003290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":53,"alternative-id":["S0014299921003290"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174176","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhibition of osteoclastogenesis by histone deacetylase inhibitor Quisinostat protects mice against titanium particle-induced bone loss","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174176","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"174176"}}