{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:32:02Z","timestamp":1787596322086,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteosarcoma is an aggressive malignant bone tumor that often requires chemotherapy with agents such as doxorubicin (Dox), which is known for its potent cytotoxic and genotoxic effects. To manage cancer-related pain, morphine is widely used due to its strong analgesic properties. The concurrent administration of these drugs in clinical practice might affect cancer therapy, since Dox is a well-established inducer of genomic instability, whereas the potential contribution of morphine to this process remains poorly understood. This study evaluated the cytotoxicity, genotoxicity, and chromosomal damage induced by morphine, both alone and in combination with Dox. Cytotoxicity was assessed in MG63 osteosarcoma cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genotoxicity and chromosomal damage were evaluated in MG63 and non-tumor V79 fibroblast cells using the comet assay and the cytokinesis-block micronucleus (CBMN) assay. Morphine alone induced DNA damage in both MG63 and V79 cells in the comet assay and increased micronucleus frequency only in MG63 cells. In co-treatment, morphine significantly reduced Dox-induced DNA damage and chromosomal instability parameters in the CBMN assay in MG63 cells. Conversely, micronucleus frequency increased in co-treatment in V79 cells. Overall, morphine alone increased chromosomal damage in MG63 tumor cells but not in V79 non-tumor cells. However, in combination with Dox, morphine attenuated Dox-induced genomic instability in osteosarcoma cells while enhancing chromosomal damage in non-tumor fibroblasts. These findings suggest that morphine may differentially modulate the genomic effects of Dox, potentially impacting both antitumor efficacy and genomic stability in normal cells.<\/jats:p>","DOI":"10.1093\/mutage\/geag028","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:37:58Z","timestamp":1785843478000},"source":"Crossref","is-referenced-by-count":0,"title":["Morphine modulates doxorubicin-induced genomic instability with distinct effects in osteosarcoma and fibroblast cells"],"prefix":"10.1093","author":[{"given":"Jayne Torres","family":"de Sousa","sequence":"first","affiliation":[{"name":"Laboratory of Genetic Toxicology, Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]},{"name":"Laboratory Toxigen, Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Rodrigues","family":"Dihl","sequence":"additional","affiliation":[{"name":"Laboratory Toxigen, Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Brauwers","family":"Kubiaki","sequence":"additional","affiliation":[{"name":"Laboratory Toxigen, Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]},{"name":"Laboratory of Cancer Biology. Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5896-3171","authenticated-orcid":false,"given":"Gumercindo","family":"Pimentel-Peralta","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Toxicology, Universidade La Salle , Avenida Victor Barreto 2288, 92010-000 Canoas, Rio Grande do Sul ,","place":["Brazil"]},{"name":"Post-Graduate Program in Genetics and Molecular Biology (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS) , Avenida Bento Gon\u00e7alves 9500, 91501-970 Porto Alegre, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Toxicology, Universidade La Salle , Avenida Victor Barreto 2288, 92010-000 Canoas, Rio Grande do Sul ,","place":["Brazil"]},{"name":"Post-Graduate Program in Genetics and Molecular Biology (PPGBM), Universidade Federal do Rio Grande do Sul (UFRGS) , Avenida Bento Gon\u00e7alves 9500, 91501-970 Porto Alegre, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Grivicich","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology. Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaqueline Nascimento","family":"Picada","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Toxicology, Universidade Luterana do Brasil (ULBRA) , Avenida Farroupilha 8001, 92425-900 Canoas, Rio Grande do Sul ,","place":["Brazil"]},{"name":"Post-Graduate Program in Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul (UFRGS) , Rua Ramiro Barcelos 2600, 90050-170 Porto Alegre, Rio Grande do Sul ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026082414061977000_ref1","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1002\/cncr.34163","article-title":"Osteosarcoma: a surveillance, epidemiology, and end results program-based analysis from 1975 to 2017","volume":"128","author":"Cole","year":"2022","journal-title":"Cancer."},{"key":"2026082414061977000_ref2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J Clin"},{"key":"2026082414061977000_ref3","doi-asserted-by":"publisher","first-page":"vii320","DOI":"10.1093\/annonc\/mdq276","article-title":"Osteosarcoma","volume":"Suppl 7","author":"Ritter","year":"2010","journal-title":"Ann Oncol"},{"key":"2026082414061977000_ref4","doi-asserted-by":"publisher","first-page":"e501","DOI":"10.1097\/BPO.0000000000002109","article-title":"Outpatient opioid prescribing habits in pediatric patients with bone sarcomas after undergoing primary tumor resection","volume":"42","author":"Ramos","year":"2022","journal-title":"J Pediatr Orthop"},{"key":"2026082414061977000_ref5","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.janh.2017.02.001","article-title":"The chemical history of morphine: an 8000-year journey, from resin to de-novo synthesis","volume":"3","author":"Brook","year":"2017","journal-title":"J Anesth Hist"},{"key":"2026082414061977000_ref6","doi-asserted-by":"publisher","first-page":"976","DOI":"10.3390\/cells9040976","article-title":"The osteosarcoma microenvironment: a complex but targetable ecosystem","volume":"9","author":"Corre","year":"2020","journal-title":"Cells."},{"key":"2026082414061977000_ref7","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000054586","article-title":"Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells","volume":"72","author":"P\u00e9rez-Castrill\u00f3n","year":"2000","journal-title":"Neuroendocrinology."},{"key":"2026082414061977000_ref8","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.pain.2006.01.032","article-title":"Cancer-related bone pain is attenuated by a systemically available delta-opioid receptor agonist","volume":"122","author":"Brainin-Mattos","year":"2006","journal-title":"Pain."},{"key":"2026082414061977000_ref9","doi-asserted-by":"publisher","first-page":"6885","DOI":"10.3390\/ijms21186885","article-title":"Targeting molecular mechanisms underlying treatment efficacy and resistance in osteosarcoma: a review of current and future strategies","volume":"21","author":"Lilienthal","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026082414061977000_ref10","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s12032-025-02629-0","article-title":"From conventional to cutting edge: an exploration of osteosarcoma treatments","volume":"42","author":"Sellers","year":"2025","journal-title":"Med Oncol"},{"key":"2026082414061977000_ref11","doi-asserted-by":"publisher","first-page":"520","DOI":"10.3390\/ph18040520","article-title":"Advancements in osteosarcoma therapy: overcoming chemotherapy resistance and exploring novel pharmacological strategies","volume":"18","author":"Zhra","year":"2025","journal-title":"Pharmaceuticals (Basel)"},{"key":"2026082414061977000_ref12","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s40709-018-0089-z","article-title":"Combined study on clastogenic, aneugenic and apoptotic properties of doxorubicin in human cells in vitro","volume":"25","author":"Chondrou","year":"2018","journal-title":"J Biol Res (Thessalon)"},{"key":"2026082414061977000_ref13","doi-asserted-by":"publisher","first-page":"7582730","DOI":"10.1155\/2018\/7582730","article-title":"Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib","volume":"2018","author":"Gorini","year":"2018","journal-title":"Oxidative Med Cell Longev"},{"key":"2026082414061977000_ref14","doi-asserted-by":"publisher","first-page":"104864","DOI":"10.1016\/j.tiv.2020.104864","article-title":"An engineered non-erythropoietic erythropoietin-derived peptide, ARA290, attenuates doxorubicin induced genotoxicity and oxidative stress","volume":"66","author":"Shokrzadeh","year":"2020","journal-title":"Toxicol in Vitro"},{"key":"2026082414061977000_ref15","doi-asserted-by":"publisher","first-page":"101115","DOI":"10.1016\/j.jbior.2025.101115","article-title":"DNA intercalating drugs: mechanisms of action in cancer treatment","volume":"98","author":"Oyeyode","year":"2025","journal-title":"Adv Biol Regul"},{"key":"2026082414061977000_ref16","doi-asserted-by":"publisher","first-page":"110652","DOI":"10.1016\/j.cbi.2023.110652","article-title":"Morphine decreases cytotoxicity and mutagenicity of doxorubicin in vitro: implications for cancer chemotherapy","volume":"382","author":"Sousa","year":"2023","journal-title":"Chem Biol Interact"},{"key":"2026082414061977000_ref17","doi-asserted-by":"publisher","DOI":"10.1787\/9789264264861-en","volume-title":"In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4","author":"OECD 487","year":"2023"},{"key":"2026082414061977000_ref18","doi-asserted-by":"publisher","first-page":"503520","DOI":"10.1016\/j.mrgentox.2022.503520","article-title":"Do cytotoxicity and cell death cause false positive results in the in vitro comet assay?","volume":"881","author":"Azqueta","year":"2022","journal-title":"Mutat Res Genet Toxicol Environ Mutagen"},{"key":"2026082414061977000_ref19","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.3390\/genes11101203","article-title":"Cytokinesis-block micronucleus Cytome assay evolution into a more comprehensive method to measure chromosomal instability","volume":"11","author":"Fenech","year":"2020","journal-title":"Genes (Basel)"},{"key":"2026082414061977000_ref20","first-page":"10993","article-title":"International standard ISO 10993\u20135, biological evaluation of medical devices - part 5: tests for cytotoxicity","author":"ISO\/EN","year":"2009","journal-title":"In Vitro Methods"},{"key":"2026082414061977000_ref21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"2026082414061977000_ref22","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/(sici)1098-2280(2000)35:3&lt;206::aid-em8&gt;3.0.co;2-j","article-title":"Single cell gel\/comet assay: guidelines for in vitro and in vivo genetic toxicology testing","volume":"35","author":"Tice","year":"2000","journal-title":"Environ Mol Mutagen"},{"key":"2026082414061977000_ref23","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/s41596-022-00754-y","article-title":"Measuring DNA modifications with the comet assay: a compendium of protocols","volume":"18","author":"Collins","year":"2023","journal-title":"Nat Protoc"},{"key":"2026082414061977000_ref24","doi-asserted-by":"publisher","first-page":"460","DOI":"10.2174\/0115665240314564241129044548","article-title":"Morphine-induced elevation of reactive oxygen species attenuates chemotherapy efficacy in diverse cancer cell types","volume":"25","author":"Chen","year":"2025","journal-title":"Curr Mol Med"},{"key":"2026082414061977000_ref25","first-page":"639","article-title":"Lithium chloride protects PC12 pheochromocytoma cell line from morphine-induced apoptosis","volume":"11","author":"Sahebgharani","year":"2008","journal-title":"Arch Iran Med"},{"key":"2026082414061977000_ref26","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.7314\/apjcp.2012.13.4.1377","article-title":"Exogenous morphine inhibits human gastric cancer MGC-803 cell growth by cell cycle arrest and apoptosis induction","volume":"13","author":"Qin","year":"2012","journal-title":"Asian Pac J Cancer Prev"},{"key":"2026082414061977000_ref27","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s00540-019-02645-1","article-title":"Morphine inhibits cell viability and growth via suppression of vascular endothelial growth factor in human oral cancer HSC-3 cells","volume":"33","author":"Nishiwada","year":"2019","journal-title":"J Anesth"},{"key":"2026082414061977000_ref28","doi-asserted-by":"publisher","first-page":"70","DOI":"10.4103\/ijmr.IJMR_2443_19","article-title":"Morphine counteracts the effects of paclitaxel in triple-negative breast cancer cells","volume":"156","author":"Sezer","year":"2022","journal-title":"Indian J Med Res"},{"key":"2026082414061977000_ref29","first-page":"2413","article-title":"Induction of early apoptosis marker by morphine in human lung and breast carcinoma cell lines","volume":"23","author":"Hatsukari","year":"2003","journal-title":"Anticancer Res"},{"key":"2026082414061977000_ref30","first-page":"857","article-title":"Induction of apoptosis by morphine in human tumor cell lines in vitro","volume":"27","author":"Hatsukari","year":"2007","journal-title":"Anticancer Res"},{"key":"2026082414061977000_ref31","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.yrtph.2007.11.002","article-title":"An evaluation of the genotoxicity of the antitussive drug dextromethorphan","volume":"50","author":"Aardema","year":"2008","journal-title":"Regul Toxicol Pharmacol"},{"key":"2026082414061977000_ref32","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0165-1218(80)90031-2","article-title":"Cytogenetic assay of potential mutagenicity in vivo of two narcotic analgesics","volume":"78","author":"Swain","year":"1980","journal-title":"Mutat Res"},{"key":"2026082414061977000_ref33","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1002\/em.2850250403","article-title":"Induction of micronuclei in murine lymphocytes by morphine","volume":"25","author":"Sawant","year":"1995","journal-title":"Environ Mol Mutagen"},{"key":"2026082414061977000_ref34","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s1383-5718(01)00274-1","article-title":"The role of adrenal corticosteroids in induction of micronuclei by morphine","volume":"498","author":"Sawant","year":"2001","journal-title":"Mutat Res"},{"key":"2026082414061977000_ref35","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.3390\/cancers12082130","article-title":"Molecular biology of osteosarcoma","volume":"12","author":"Czarnecka","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2026082414061977000_ref36","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41420-021-00658-y","article-title":"Severe cellular stress activates apoptosis independently of p53 in osteosarcoma","volume":"7","author":"Ho","year":"2021","journal-title":"Cell Death Discov"},{"key":"2026082414061977000_ref37","doi-asserted-by":"publisher","first-page":"4284","DOI":"10.3390\/cancers13174284","article-title":"TP53 in biology and treatment of osteosarcoma","volume":"13","author":"Synoradzki","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026082414061977000_ref38","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41420-022-01078-2","article-title":"Severe cellular stress drives apoptosis through a dual control mechanism independently of p53","volume":"8","author":"Wang","year":"2022","journal-title":"Cell Death Discov"},{"key":"2026082414061977000_ref39","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00210-011-0672-4","article-title":"The role of morphine in regulation of cancer cell growth","volume":"384","author":"Gach","year":"2011","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"key":"2026082414061977000_ref40","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1007\/s00210-018-1565-6","article-title":"Morphine as a treatment of cancer-induced pain-is it safe? A review of in vivo studies and mechanisms","volume":"391","author":"Brinkman","year":"2018","journal-title":"Naunyn Schmiedeberg's Arch Pharmacol"},{"key":"2026082414061977000_ref41","doi-asserted-by":"publisher","first-page":"3068","DOI":"10.1016\/S0021-9258(17)35747-2","article-title":"Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical","volume":"261","author":"Doroshow","year":"1986","journal-title":"J Biol Chem"},{"key":"2026082414061977000_ref42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.phrs.2003.07.012","article-title":"In vitro antioxidant properties of morphine","volume":"49","author":"G\u00fcl\u00e7in","year":"2004","journal-title":"Pharmacol Res"},{"key":"2026082414061977000_ref43","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1042\/BJ20070186","article-title":"Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells","volume":"406","author":"Lin","year":"2007","journal-title":"Biochem J"},{"key":"2026082414061977000_ref44","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.taap.2010.05.011","article-title":"Involvement of DNA polymerase beta in repairing oxidative damages induced by antitumor drug adriamycin","volume":"246","author":"Liu","year":"2010","journal-title":"Toxicol Appl Pharmacol"},{"key":"2026082414061977000_ref45","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1093\/mutage\/geg024","article-title":"Aneugenic and clastogenic effects of doxorubicin in human lymphocytes","volume":"18","author":"Dhawan","year":"2003","journal-title":"Mutagenesis."},{"key":"2026082414061977000_ref46","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1080\/10934529.2011.551744","article-title":"The effect of apigenin on cyclophosphamide and doxorubicin genotoxicity in vitro and in vivo","volume":"46","author":"Bokuli\u0107","year":"2011","journal-title":"J Environ Sci Health A Tox Hazard Subst Environ Eng"},{"key":"2026082414061977000_ref47","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1046\/j.1523-1755.1998.00758.x","article-title":"Morphine modulates proliferation of kidney fibroblasts","volume":"53","author":"Singhal","year":"1998","journal-title":"Kidney Int"},{"key":"2026082414061977000_ref48","doi-asserted-by":"publisher","first-page":"559","DOI":"10.3892\/etm.2016.3346","article-title":"Comparison of oxycodone and morphine on the proliferation, apoptosis and expression of related molecules in the A549 human lung adenocarcinoma cell line","volume":"12","author":"Tian","year":"2016","journal-title":"Exp Ther Med"},{"key":"2026082414061977000_ref49","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1101\/gad.353408.125","article-title":"Mutant p53: evolving perspectives","volume":"40","author":"Efe","year":"2026","journal-title":"Genes Dev"},{"key":"2026082414061977000_ref50","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/clpt.1990.145","article-title":"Oral morphine in cancer pain: influences on morphine and metabolite concentration","volume":"48","author":"McQuay","year":"1990","journal-title":"Clin Pharmacol Ther"},{"key":"2026082414061977000_ref51","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/0885-3924(95)00148-4","article-title":"Morphine and morphine-6-glucuronide plasma concentrations and effect in cancer pain","volume":"11","author":"Faura","year":"1996","journal-title":"J Pain Symptom Manag"},{"key":"2026082414061977000_ref52","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1007\/s40262-016-0471-7","article-title":"A prospective population pharmacokinetic study on morphine metabolism in cancer patients","volume":"56","author":"Oosten","year":"2017","journal-title":"Clin Pharmacokinet"}],"container-title":["Mutagenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mutage\/advance-article-pdf\/doi\/10.1093\/mutage\/geag028\/70528744\/geag028.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mutage\/advance-article-pdf\/doi\/10.1093\/mutage\/geag028\/70528744\/geag028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:06:27Z","timestamp":1787594787000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mutage\/advance-article\/doi\/10.1093\/mutage\/geag028\/8753926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":52,"URL":"https:\/\/doi.org\/10.1093\/mutage\/geag028","relation":{},"ISSN":["0267-8357","1464-3804"],"issn-type":[{"value":"0267-8357","type":"print"},{"value":"1464-3804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"geag028"}}