{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:45:56Z","timestamp":1783521956582,"version":"3.55.0"},"reference-count":47,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing","doi-asserted-by":"crossref","award":["CSTB2024NSCQ-MSX0514"],"award-info":[{"award-number":["CSTB2024NSCQ-MSX0514"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Institutions Performance Incentive Guidance Special Fund of Chongqing","award":["cstc2022jxjl0234"],"award-info":[{"award-number":["cstc2022jxjl0234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>To evaluate the safety profiles of EZH2-targeted inhibitors in cancer treatment, focusing on treatment-related adverse events (TRAEs) across various clinical trials.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a systematic review and meta-analysis using data from clinical trials involving EZH2 inhibitors reported up to May 31, 2024. Databases searched included PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and <jats:uri xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:uri>. Studies included were those involving patients treated with EZH2 inhibitors as monotherapy or in combination, specifically detailing the incidence of TRAEs. Data on all-grade TRAEs, grade 3 or higher TRAEs, and severe TRAEs were extracted and analyzed using random-effects models.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Our systematic review and meta-analysis included 22 studies encompassing 1,002 patients who met the inclusion criteria. TRAEs were commonly observed during EZH2 inhibitor therapy, affecting 86% of patients (95% CI [79\u201394%]%; I<jats:sup>2<\/jats:sup> = 89.5%). The incidence of grade 3 or higher TRAEs was 33% (95% CI [21\u201344%]; I<jats:sup>2<\/jats:sup> = 93.5%), while severe TRAEs occurred in 15% of the cases (95% CI [9\u201322%]; I<jats:sup>2<\/jats:sup> = 87.5%). The most frequently reported grade 3 or higher TRAEs in the pooled analysis were neutropenia (8%), thrombocytopenia (8%), and anemia (6%). Specifically, for tazemetostat, the most common grade 3 or higher TRAE was neutropenia (5%). For SHR2554, the most prevalent grade 3 or higher TRAEs were thrombocytopenia (17%), neutropenia (8%), and anemia (7%). Notably, treatment-related fatalities were rare, with only 0.9% of patients experiencing potentially fatal outcomes due to therapy.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>EZH2 inhibitors demonstrate a manageable safety profile with a low incidence of severe TRAEs, emphasizing their potential as safe therapeutic options in cancer treatment. The low rate of severe TRAEs and the rare occurrences of treatment-related deaths support the continued clinical use and further investigation of EZH2 inhibitors.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.18871","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T08:47:01Z","timestamp":1737967621000},"page":"e18871","source":"Crossref","is-referenced-by-count":8,"title":["Safety profile of EZH2 inhibitors for cancer: a systematic review and meta-analysis"],"prefix":"10.7717","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7349-7159","authenticated-orcid":true,"given":"Zhou","family":"Zhao","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China"},{"name":"Department of General Surgery, Center for Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayang","family":"Pang","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Center for Minimally Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Sun","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Center, Chongqing University Cancer Hospital, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"10.7717\/peerj.18871\/ref-1","doi-asserted-by":"publisher","first-page":"S636","DOI":"10.1016\/j.annonc.2021.08.1099","article-title":"586P Safety of tazemetostat (TAZ) in combination with abiraterone\/prednisone (A\/P) or enzalutamide (E) in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC)","volume":"32","author":"Abida","year":"2021","journal-title":"Annals of Oncology"},{"issue":"2","key":"10.7717\/peerj.18871\/ref-2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/s41417-022-00555-1","article-title":"EZH1\/2 as targets for cancer therapy","volume":"30","author":"An","year":"2023","journal-title":"Cancer Gene Therapy"},{"key":"10.7717\/peerj.18871\/ref-3","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2021.39.15_suppl.11563","volume-title":"Results of the phase 1b soft-tissue sarcoma (STS) portion of the global randomized, double-blind, placebo-controlled study of tazemetostat (TAZ) plus doxorubicin (DOX) as frontline therapy for advanced epithelioid sarcoma (ES)","author":"Chawla","year":"2021"},{"key":"10.7717\/peerj.18871\/ref-4","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2022.40.16_suppl.10040","volume-title":"Update on phase 1 study of tazemetostat, an enhancer of zeste homolog 2 inhibitor, in pediatric patients with relapsed or refractory integrase interactor 1-negative tumors","author":"Chi","year":"2022"},{"issue":"11","key":"10.7717\/peerj.18871\/ref-5","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1093\/jnci\/djad085","article-title":"Tazemetostat for tumors harboring SMARCB1\/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C","volume":"115","author":"Chi","year":"2023","journal-title":"JNCI: Journal of the National Cancer Institute"},{"key":"10.7717\/peerj.18871\/ref-6","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.1158\/1078-0432.Ccr-23-3383","article-title":"A phase I\/II study of valemetostat (DS-3201b), an EZH1\/2 inhibitor, in combination with irinotecan in patients with recurrent small-cell lung cancer","volume":"30","author":"Choudhury","year":"2024","journal-title":"Clinical Cancer Research"},{"issue":"6","key":"10.7717\/peerj.18871\/ref-7","doi-asserted-by":"publisher","first-page":"297","DOI":"10.5582\/ddt.2022.01085","article-title":"Valemetostat: first approval as a dual inhibitor of EZH1\/2 to treat adult T-cell leukemia\/lymphoma","volume":"16","author":"Dou","year":"2022","journal-title":"Drug Discoveries & Therapeutics"},{"key":"10.7717\/peerj.18871\/ref-8","article-title":"Study of tazemetostat in participants with relapsed or refractory B-cell non-hodgkin\u2019s lymphoma With EZH2 gene mutation","author":"Eisai","year":"2022"},{"key":"10.7717\/peerj.18871\/ref-9","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2023.41.16_suppl.2507","volume-title":"Phase I study of the bifunctional anti-PD-L1\/TGF-\u03b2RII agent SHR-1701 combined with SHR2554, an EZH2 inhibitor, in patients with previously treated advanced lymphoma and solid tumors","author":"Feng","year":"2023"},{"issue":"20","key":"10.7717\/peerj.18871\/ref-10","doi-asserted-by":"publisher","first-page":"e183391","DOI":"10.1172\/JCI183391","article-title":"Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges","volume":"134","author":"Gold","year":"2024","journal-title":"Journal of Clinical Investigation"},{"issue":"11","key":"10.7717\/peerj.18871\/ref-11","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/S1470-2045(20)30451-4","article-title":"Tazemetostat in advanced epithelioid sarcoma with loss of INI1\/SMARCB1: an international, open-label, phase 2 basket study","volume":"21","author":"Gounder","year":"2020","journal-title":"The Lancet Oncology"},{"issue":"6","key":"10.7717\/peerj.18871\/ref-12","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1158\/1078-0432.CCR-23-2174","article-title":"Translational aspects of Epithelioid Sarcoma: current consensus","volume":"30","author":"Gr\u00fcnewald","year":"2024","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.18871\/ref-13","doi-asserted-by":"publisher","first-page":"iii7","DOI":"10.1093\/annonc\/mdy048.001","article-title":"A phase 1 study of CPI-1205, a small molecule inhibitor of EZH2, preliminary safety in patients with B-cell lymphomas","volume":"29","author":"Harb","year":"2018","journal-title":"Annals of Oncology"},{"issue":"5","key":"10.7717\/peerj.18871\/ref-14","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s40265-020-01288-x","article-title":"Tazemetostat: first approval","volume":"80","author":"Hoy","year":"2020","journal-title":"Drugs"},{"issue":"4","key":"10.7717\/peerj.18871\/ref-15","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1021\/acs.jmedchem.2c01607","article-title":"Design, synthesis, and biological evaluation of a potent dual EZH2-BRD4 inhibitor for the treatment of some solid tumors","volume":"66","author":"Huang","year":"2023","journal-title":"Journal of Medicinal Chemistry"},{"key":"10.7717\/peerj.18871\/ref-16","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2024.42.16_suppl.4574","volume-title":"A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183)","author":"Hussain","year":"2024"},{"issue":"5","key":"10.7717\/peerj.18871\/ref-17","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S1470-2045(18)30145-1","article-title":"Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study","volume":"19","author":"Italiano","year":"2018","journal-title":"The Lancet Oncology"},{"issue":"10","key":"10.7717\/peerj.18871\/ref-18","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1182\/blood.2022016862","article-title":"An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia\/lymphoma","volume":"141","author":"Izutsu","year":"2023","journal-title":"Blood"},{"key":"10.7717\/peerj.18871\/ref-19","doi-asserted-by":"publisher","first-page":"216706","DOI":"10.1016\/j.canlet.2024.216706","article-title":"EZH2-mediated development of therapeutic resistance in cancer","volume":"586","author":"Kaur","year":"2024","journal-title":"Cancer Letters"},{"issue":"16","key":"10.7717\/peerj.18871\/ref-20","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1007\/s40265-022-01800-5","article-title":"Valemetostat tosilate: first approval","volume":"82","author":"Keam","year":"2022","journal-title":"Drugs"},{"issue":"6","key":"10.7717\/peerj.18871\/ref-21","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.7150\/thno.83353","article-title":"Histone H3K27 methyltransferase EZH2 regulates apoptotic and inflammatory responses in sepsis-induced AKI","volume":"13","author":"Li","year":"2023","journal-title":"Theranostics"},{"issue":"33","key":"10.7717\/peerj.18871\/ref-22","doi-asserted-by":"publisher","first-page":"e2303010120","DOI":"10.1073\/pnas.2303010120","article-title":"Ezh2 promotes mammary tumor initiation through epigenetic regulation of the Wnt and mTORC1 signaling pathways","volume":"120","author":"Liu","year":"2023","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"6","key":"10.7717\/peerj.18871\/ref-23","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s12032-023-02025-6","article-title":"The roles of EZH2 in cancer and its inhibitors","volume":"40","author":"Liu","year":"2023","journal-title":"Medical Oncology"},{"issue":"14","key":"10.7717\/peerj.18871\/ref-24","doi-asserted-by":"publisher","first-page":"175590","DOI":"10.1016\/j.ejphar.2023.175590","article-title":"Use of histone methyltransferase inhibitors in cancer treatment: a systematic review","volume":"944","author":"Marzochi","year":"2023","journal-title":"European Journal of Pharmacology"},{"key":"10.7717\/peerj.18871\/ref-25","volume-title":"Introductory guide for standardised MeDRa queries (SMQs) Version 21.0","author":"MedDRA","year":"2018"},{"issue":"11","key":"10.7717\/peerj.18871\/ref-26","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/S1470-2045(20)30441-1","article-title":"Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial","volume":"21","author":"Morschhauser","year":"2020","journal-title":"The Lancet Oncology"},{"issue":"5","key":"10.7717\/peerj.18871\/ref-27","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1007\/s00280-024-04658-4","article-title":"Pharmacology and pharmacokinetics of tazemetostat","volume":"93","author":"Orleni","year":"2024","journal-title":"Cancer Chemotherapy and Pharmacology"},{"issue":"1","key":"10.7717\/peerj.18871\/ref-28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA, 2020 statement: an updated guideline for reporting systematic reviews","volume":"10","author":"Page","year":"2021","journal-title":"Systematic Reviews"},{"key":"10.7717\/peerj.18871\/ref-29","volume-title":"Targeting EZH2 to overcome the resistance to immunotherapy in microsatellite stable colorectal cancer: results from the CAIRE study","author":"Palmieri","year":"2023"},{"issue":"7","key":"10.7717\/peerj.18871\/ref-30","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.clml.2021.12.014","article-title":"Combination of atezolizumab and tazemetostat in patients with relapsed\/refractory diffuse large B-cell lymphoma: results from a phase Ib study","volume":"22","author":"Palomba","year":"2022","journal-title":"Clinical Lymphoma Myeloma and Leukemia"},{"key":"10.7717\/peerj.18871\/ref-31","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2023.41.16_suppl.6022","volume-title":"Tazemetostat, a selective EZH2 inhibitor, with pembrolizumab as treatment of anti-PD-1 resistant head and neck squamous-cell carcinoma (HNSCC): a phase 1-2 trial","author":"Puram","year":"2023"},{"key":"10.7717\/peerj.18871\/ref-32","doi-asserted-by":"publisher","first-page":"3452","DOI":"10.1038\/s41467-024-47701-x","article-title":"EZH2 mutations in follicular lymphoma distort H3K27me3 profiles and alter transcriptional responses to PRC2 inhibition","volume":"15","author":"Romero","year":"2024","journal-title":"Nature Communications"},{"issue":"1","key":"10.7717\/peerj.18871\/ref-33","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13148-023-01452-6","article-title":"Clinical advances in epigenetic therapies for lymphoma","volume":"15","author":"Rosenthal","year":"2023","journal-title":"Clinical Epigenetics"},{"issue":"4","key":"10.7717\/peerj.18871\/ref-34","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/cge.14576","article-title":"EZH2-associated tumor malignancy: a prominent target for cancer treatment","volume":"106","author":"Sabour-Takanlou","year":"2024","journal-title":"Clinical Genetics"},{"key":"10.7717\/peerj.18871\/ref-35","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.1182\/blood-2023-179910","article-title":"Tazemetostat in combination with lenalidomide and rituximab in patients with relapsed\/refractory follicular lymphoma: updated phase 1b results of symphony-1 with 22.5 months follow-up","volume":"142","author":"Salles","year":"2023","journal-title":"Blood"},{"issue":"13","key":"10.7717\/peerj.18871\/ref-36","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1158\/1078-0432.CCR-19-3741","article-title":"A LYSA phase Ib study of tazemetostat (EPZ-6438) plus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) with poor prognosis features","volume":"26","author":"Sarkozy","year":"2020","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.18871\/ref-37","doi-asserted-by":"publisher","first-page":"S763","DOI":"10.1016\/j.annonc.2022.07.616","article-title":"488P Phase I trial of PF-06821497, a potent and selective inhibitor of enhancer of zeste homolog 2 (EZH2), in follicular lymphoma (FL), small cell lung cancer (SCLC) and castration-resistant prostate cancer (CRPC)","volume":"33","author":"Schweizer","year":"2022","journal-title":"Annals of Oncology"},{"key":"10.7717\/peerj.18871\/ref-38","volume-title":"Common terminology criteria for adverse events","author":"Shah","year":"2022"},{"issue":"9","key":"10.7717\/peerj.18871\/ref-39","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","article-title":"Methodological index for non-randomized studies (minors): development and validation of a new instrument","volume":"73","author":"Slim","year":"2003","journal-title":"ANZ Journal of Surgery"},{"issue":"7","key":"10.7717\/peerj.18871\/ref-40","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1158\/1078-0432.CCR-23-2582","article-title":"Enhancer of zeste homolog 2 inhibitor SHR2554 in relapsed or refractory peripheral T-cell lymphoma: data from the first-in-human phase I study","volume":"30","author":"Song","year":"2024","journal-title":"Clinical Cancer Research"},{"issue":"7","key":"10.7717\/peerj.18871\/ref-41","doi-asserted-by":"publisher","first-page":"e493","DOI":"10.1016\/S2352-3026(22)00134-X","article-title":"SHR2554, an EZH2 inhibitor, in relapsed or refractory mature lymphoid neoplasms: a first-in-human, dose-escalation, dose-expansion, and clinical expansion phase 1 trial","volume":"9","author":"Song","year":"2022","journal-title":"The Lancet Haematology"},{"issue":"2","key":"10.7717\/peerj.18871\/ref-42","doi-asserted-by":"publisher","first-page":"158","DOI":"10.6004\/jadpro.2022.13.2.7","article-title":"Tazemetostat: EZH2 inhibitor","volume":"13","author":"Straining","year":"2022","journal-title":"Journal of the Advanced Practitioner in Oncology"},{"issue":"1","key":"10.7717\/peerj.18871\/ref-43","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1002\/cpdd.1315","article-title":"Safety, tolerability, and pharmacokinetics of valemetostat tablets and the effect of food on valemetostat pharmacokinetics in healthy subjects: two phase 1 studies","volume":"13","author":"Tachibana","year":"2024","journal-title":"Clinical Pharmacology in Drug Development"},{"issue":"4","key":"10.7717\/peerj.18871\/ref-44","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/13543776.2023.2206018","article-title":"A patent review of EZH2 inhibitors from 2017 and beyond","volume":"33","author":"Wan","year":"2023","journal-title":"Expert Opinion on Therapeutic Patents"},{"issue":"24","key":"10.7717\/peerj.18871\/ref-45","doi-asserted-by":"publisher","first-page":"7331","DOI":"10.1158\/1078-0432.CCR-18-4121","article-title":"Phase I study of the novel enhancer of Zeste homolog 2 (EZH2) inhibitor GSK2816126 in patients with advanced hematologic and solid tumors","volume":"25","author":"Yap","year":"2019","journal-title":"Clinical Cancer Research"},{"issue":"6","key":"10.7717\/peerj.18871\/ref-46","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/S1470-2045(22)00277-7","article-title":"EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study","volume":"23","author":"Zauderer","year":"2022","journal-title":"The Lancet Oncology"},{"issue":"12","key":"10.7717\/peerj.18871\/ref-47","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1016\/S1470-2045(24)00503-5","article-title":"Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study","volume":"25","author":"Zinzani","year":"2024","journal-title":"The Lancet Oncology"}],"container-title":["PeerJ"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/peerj.com\/articles\/18871.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18871.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18871.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/peerj.com\/articles\/18871.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T08:47:19Z","timestamp":1737967639000},"score":1,"resource":{"primary":{"URL":"https:\/\/peerj.com\/articles\/18871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":47,"alternative-id":["10.7717\/peerj.18871"],"URL":"https:\/\/doi.org\/10.7717\/peerj.18871","archive":["CLOCKSS","LOCKSS","Portico"],"relation":{},"ISSN":["2167-8359"],"issn-type":[{"value":"2167-8359","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"article-number":"e18871"}}