{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:44:20Z","timestamp":1759970660838,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["GR-2018-12365278"],"award-info":[{"award-number":["GR-2018-12365278"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Monosomy 7 and deletion 7q are common chromosomal abnormalities in myeloid malignancies, and they are associated with a poor prognosis. The mechanism underlying their acquisition remains elusive. We identified a cohort of 24 patients exhibiting clones with different chromosome 7 abnormalities, such as deletion 7q, unstable derivatives (ring chromosomes or \u2018naked\u2019 centromeres), and monosomy 7. We designated this group as having cytogenetic clonal evolution of chromosome 7 abnormalities (CCE7). In some cases, CCE7 correlated with disease progression, suggesting that deletions or other derivatives involving the q-arm of chromosome 7 may arise early in the disease course. These abnormalities may be transient but can potentially evolve into monosomy 7. Within the CCE7 group, telomere loss or shortening may contribute to chromosomal instability and the emergence of unstable derivatives, as the chromosome 7 derivatives displayed loss or rearrangement of subtelomeric regions. Moreover, we identified variants in genes implicated in telomere biology disorders and observed specific genetic mutation profiles associated with different chromosome 7 abnormalities. These findings shed light on a potential mechanism leading to monosomy 7 through the evolution of chromosome 7q abnormalities. Identifying patients at risk of developing monosomy 7, based on the presence of unstable derivatives with telomere loss or a specific mutation profile, could potentially enhance patient management and guide the development of novel therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms26031162","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T07:45:12Z","timestamp":1738136712000},"page":"1162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emergence and Cytogenetic Clonal Evolution of Chromosome 7 Abnormalities in Myeloid Malignancies: Investigating the Role of Telomere Dysfunction"],"prefix":"10.3390","volume":"26","author":[{"given":"Carmen","family":"Baldazzi","sequence":"first","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenza","family":"Bandini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-4888","authenticated-orcid":false,"given":"Valentina","family":"Robustelli","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2135-0209","authenticated-orcid":false,"given":"Agnese","family":"Patuelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Venturi","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Grassi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Marzocchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Ielpo","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4828-6955","authenticated-orcid":false,"given":"Vincenza","family":"Solli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Teresa","family":"Bochicchio","sequence":"additional","affiliation":[{"name":"Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) \u201cDino Amadori\u201d, 47014 Meldola, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Paolini","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2356-5691","authenticated-orcid":false,"given":"Chiara","family":"Sartor","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Zingarelli","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Curti","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Ottaviani","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Testoni","sequence":"additional","affiliation":[{"name":"IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, 40138 Bologna, Italy"},{"name":"Dipartimento di Scienze Mediche e Chirurgiche, Universit\u00e0 di Bologna, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1182\/blood-2009-11-254441","article-title":"National Cancer Research Institute Adult Leukaemia Working Group. Refinement of cytogenetic classification in acute myeloid leukemia: Determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials","volume":"116","author":"Grimwade","year":"2010","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00277-008-0483-y","article-title":"Cytogenetic features in myelodysplastic syndromes","volume":"87","author":"Haase","year":"2008","journal-title":"Ann. Hematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/leu.2008.17","article-title":"Genetics of therapy-related myelodysplasia and acute myeloid leukemia","volume":"22","author":"Andersen","year":"2008","journal-title":"Leukemia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1200\/JCO.2011.35.6394","article-title":"New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge","volume":"30","author":"Schanz","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/cncr.26279","article-title":"Better prognosis for patients with del (7q) than for patients with monosomy 7 in myelodysplastic syndrome","volume":"118","author":"Cordoba","year":"2012","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/ajh.23230","article-title":"Sole abnormalities of chromosome 7 in myeloid malignancies: Spectrum, histopathologic correlates, and prognostic implications","volume":"87","author":"Hussain","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1038\/s41375-020-0728-x","article-title":"Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7","volume":"34","author":"Kulasekararaj","year":"2020","journal-title":"Leukemia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/s41375-023-02003-x","article-title":"Genomics of deletion 7 and 7q in myeloid neoplasm: From pathogenic culprits to potential synthetic lethal therapeutic targets","volume":"37","author":"Mori","year":"2023","journal-title":"Leukemia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/s13045-024-01590-1","article-title":"Genomic characterization of AML with aberrations of chromosome 7: A multinational cohort of 519 patients","volume":"17","author":"Halik","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1200\/JCO.2010.29.2771","article-title":"Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)\/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia","volume":"28","author":"Lugthart","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/gcc.22341","article-title":"Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities","volume":"55","author":"Baldazzi","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1158\/0008-5472.CAN-16-1386","article-title":"Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality","volume":"77","author":"Eisfeld","year":"2017","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1182\/blood-2017-12-822262","article-title":"The enigma of monosomy 7","volume":"131","author":"Inaba","year":"2018","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1038\/onc.2014.196","article-title":"-7\/7q-syndrome in myeloid-lineage hematopoietic malignancies: Attempts to understand this complex disease entity","volume":"34","author":"Honda","year":"2015","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1182\/blood-2014-10-607572","article-title":"Telomere attrition and candidate gene mutations preceding monosomy 7 in aplastic anemia","volume":"125","author":"Dumitriu","year":"2015","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e26714","DOI":"10.1002\/pbc.26714","article-title":"Monosomy 7\/del (7q) in inherited bone marrow failure syndromes: A systematic review","volume":"64","author":"Pezeshki","year":"2017","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1182\/blood.2019003264","article-title":"Cancer spectrum and outcomes in the Mendelian short telomere syndromes","volume":"135","author":"Schratz","year":"2020","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1182\/blood-2017-09-806489","article-title":"A landscape of germ line mutations in a cohort of inherited bone marrow failure patients","volume":"131","author":"Bluteau","year":"2018","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1182\/blood-2014-05-526285","article-title":"Bone marrow failure and the telomeropathies","volume":"124","author":"Townsley","year":"2014","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1111\/ejh.13153","article-title":"Aplastic anemia: Etiology, molecular pathogenesis, and emerging concepts","volume":"101","author":"Shallis","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1080\/17474086.2019.1662720","article-title":"An update on the biology and management of dyskeratosis congenita and related telomere biology disorders","volume":"12","author":"Niewisch","year":"2019","journal-title":"Expert Rev. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/nrg3123","article-title":"Causes and consequences of aneuploidy in cancer","volume":"13","author":"Gordon","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.ceb.2010.08.007","article-title":"Mechanisms of aneuploidy","volume":"23","author":"Compton","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000138881","article-title":"Ring chromosomes in human neoplasias","volume":"121","author":"Gebhart","year":"2008","journal-title":"Cytogenet. Genome Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s004390050960","article-title":"The structure and dynamics of ring chromosomes in human neoplastic and non-neoplastic cells","volume":"104","author":"Gisselsson","year":"1999","journal-title":"Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/gcc.20749","article-title":"Whole chromosome loss is promoted by telomere dysfunction in primary cells","volume":"49","author":"Pampalona","year":"2010","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4238\/vol9-1gmr707","article-title":"Ring chromosome instability evaluation in six patients with autosomal rings","volume":"9","author":"Guilherme","year":"2010","journal-title":"Genet. Mol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Shorokhova, M., Nikolsky, N., and Grinchuk, T. (2021). Chromothripsis-Explosion in Genetic Science. Cells, 10.","DOI":"10.3390\/cells10051102"},{"key":"ref_30","first-page":"307","article-title":"Telomere length and hTERT expression in patients with acute myeloid leukemia correlates with chromosomal abnormalities","volume":"90","author":"Hartmann","year":"2005","journal-title":"Haematologica"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1002\/gcc.20286","article-title":"Critically short telomeres in acute myeloid leukemia with loss or gain of parts of chromosomes","volume":"45","author":"Swiggers","year":"2006","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gaspar, T.B., S\u00e1, A., Lopes, J.M., Sobrinho-Sim\u00f5es, M., Soares, P., and Vinagre, J. (2018). Telomere Maintenance Mechanisms in Cancer. Genes, 9.","DOI":"10.3390\/genes9050241"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0092-8674(01)00504-9","article-title":"The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability","volume":"107","author":"Hemann","year":"2001","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4873","DOI":"10.1182\/bloodadvances.2020001721","article-title":"Telomere biology disorder prevalence and phenotypes in adults with familial hematologic and\/or pulmonary presentations","volume":"4","author":"Feurstein","year":"2020","journal-title":"Blood Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/leu.2011.272","article-title":"Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia","volume":"26","author":"Calado","year":"2012","journal-title":"Leukemia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1182\/bloodadvances.2017008110","article-title":"Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms","volume":"2","author":"Marsh","year":"2018","journal-title":"Blood Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/jmcb\/mjz007","article-title":"The long and the short of it: The MDM4 tail so far","volume":"11","author":"Haupt","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eaay3511","DOI":"10.1126\/sciadv.aay3511","article-title":"Germline mutation of MDM4, a major p53 regulator, in a familial syndrome of defective telomere maintenance","volume":"6","author":"Toufektchan","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/j.celrep.2013.05.028","article-title":"Mutant mice lacking the p53 C-terminal domain model telomere syndromes","volume":"3","author":"Simeonova","year":"2013","journal-title":"Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rakotopare, J., and Toledo, F. (2023). p53 in the Molecular Circuitry of Bone Marrow Failure Syndromes. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914940"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1182\/blood-2022-168631","article-title":"Germline Variants in MDM4 Cause a Disorder of P53 Dysregulation and Insufficient Telomere Maintenance","volume":"140","author":"Meyer","year":"2022","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1182\/blood-2022-162614","article-title":"Germline Loss-of-Function Mutations in MDM4 Cause P53-Dependent Hematopoietic Cell Death in Patients with Variable Bone Marrow Failure Phenotypes","volume":"140","author":"Sharma","year":"2022","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1182\/bloodadvances.2021006239","article-title":"TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS\/AML","volume":"6","author":"Weinberg","year":"2022","journal-title":"Blood Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"719","DOI":"10.7150\/ijms.12612","article-title":"Genomic Copy Number Variations in the Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients with del(5q) and\/or -7\/del(7q)","volume":"12","author":"Zhang","year":"2015","journal-title":"Int. J. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/ajh.25714","article-title":"The impact of concomitant cytogenetic abnormalities on acute myeloid leukemia with monosomy 7 or deletion 7q after HLA-matched allogeneic stem cell transplantation","volume":"95","author":"Labopin","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000516655","article-title":"Re: International System for Human Cytogenetic or Cytogenomic Nomenclature (ISCN): Some Thoughts, by T. Liehr","volume":"161","author":"Hastings","year":"2021","journal-title":"Cytogenet. Genome Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mayrhofer, M., Viklund, B., and Isaksson, A. (2016). Rawcopy: Improved copy number analysis with Affymetrix arrays. Sci. Rep., 6.","DOI":"10.1038\/srep36158"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1016\/j.csbj.2022.06.062","article-title":"BoBafit: A copy number clustering tool designed to refit and recalibrate the baseline region of tumors\u2019 profiles","volume":"20","author":"Mazzocchetti","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:38:18Z","timestamp":1759919898000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":48,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031162"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031162","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,1,29]]}}}