{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T19:32:21Z","timestamp":1787340741867,"version":"build-2736575974"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":232,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"REGIONE PUGLIA\u2014MALATTIE RARE\u2014Petruzzella","award":["246.10.09.2019"],"award-info":[{"award-number":["246.10.09.2019"]}]},{"name":"CollaGe and Fondazione Opera Pia Monte di Piet\u00e0 e Confidenze"},{"name":"Italian Ministry of Health\u2014Ricerca Corrente","award":["2021\u20145X1000"],"award-info":[{"award-number":["2021\u20145X1000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Charcot\u2013Marie\u2013Tooth disease type 4B3 (CMT4B3) is an ultra-rare autosomal recessive neuropathy caused by mutations in the MTMR5\/SBF1 gene. In this study, we characterized dermal fibroblasts derived from a patient carrying compound-heterozygous MTMR5\/SBF1 variants (R763H\/G1064E) and identified alterations affecting mitochondrial metabolism and cellular stress pathways. Patient fibroblasts exhibited fragmented mitochondrial networks with a shift toward fission, together with reduced ATP production, while mitochondrial mass, respiratory chain assembly, and markers of mitochondrial biogenesis were preserved. In line with our previous evidence of enhanced mitophagy, these findings support the presence of altered mitochondrial quality control. The reduction in cellular energy production was not accompanied by increased glycolytic activity, indicating a metabolically quiescent phenotype. Transcriptomic profiling revealed dysregulation of the PI3K\/AKT signalling pathway. AKT phosphorylation at Ser473 was increased in the absence of complete canonical AKT activation. These signalling changes were associated with increased expression of p53 and p21 and with features consistent with premature cellular senescence. Overall, our findings identify metabolic quiescence and premature senescence as previously unrecognized aspects of CMT4B3 cellular pathology and suggest that altered coordination between mitochondrial metabolism and intracellular signalling may contribute to disease pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddag080","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T11:51:51Z","timestamp":1786017111000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial dysfunction, metabolic quiescence and premature senescence in CMT4B3 fibroblasts"],"prefix":"10.1093","volume":"35","author":[{"given":"Paola","family":"Zanfardino","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience - DiBraiN, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 , Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Amati","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience - DiBraiN, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 , Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro , Via Orabona, 70124 Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Agrimi","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro , Via Orabona, 70124 Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"U.O.C. Medicina Molecolare, Neurogenetica e Malattie Neuromuscolari IRCCS Fondazione Stella Maris, Viale del Tirreno, 156018 CALAMBRONE , Pisa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio","family":"Fern\u00e1ndez-Silva","sequence":"additional","affiliation":[{"name":"Department Biochemistry and Molecular and Cell Biology, Faculty of Sciences, Campus San Francisco Square, Biocomputation and Complex Systems Physics Institute (BIFI), University of Zaragoza, E-50009 Zaragoza, Spain , Zaragoza ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apollonia","family":"Tullo","sequence":"additional","affiliation":[{"name":"Institute of Biomembrane, Bioenergetics and Molecular Biotechnology (IBIOM) \u2013Bari - CNR, -Via Amendola 122\/D 70126 , Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Rosati","sequence":"additional","affiliation":[{"name":"Cellular Reprogramming Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 , San Giovanni Rotondo ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M","family":"Santorelli","sequence":"additional","affiliation":[{"name":"U.O.C. Medicina Molecolare, Neurogenetica e Malattie Neuromuscolari IRCCS Fondazione Stella Maris, Viale del Tirreno, 156018 CALAMBRONE , Pisa ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-6033","authenticated-orcid":false,"given":"Vittoria","family":"Petruzzella","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience - DiBraiN, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 , Bari ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026082114460181500_ref1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1385\/NMM:8:1-2:3","article-title":"Clinical and electrophysiological aspects of Charcot-Marie-tooth disease","volume":"8","author":"Pareyson","year":"2006","journal-title":"NeuroMolecular Med"},{"key":"2026082114460181500_ref2","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/ana.25500","article-title":"A multicenter retrospective study of charcot-marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins (MTMRs)","volume":"86","author":"Pareyson","year":"2019","journal-title":"Ann Neurol"},{"key":"2026082114460181500_ref3","doi-asserted-by":"publisher","first-page":"e70084","DOI":"10.1111\/ene.70084","article-title":"Disease progression in Charcot-Marie-tooth disease type 4B (CMT4B) associated with mutations in myotubularin-related proteins 2 and 13","volume":"32","author":"Bertini","year":"2025","journal-title":"Eur J Neurol"},{"key":"2026082114460181500_ref4","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1016\/j.febslet.2010.02.054","article-title":"The role of PI3P phosphatases in the regulation of autophagy","volume":"584","author":"Vergne","year":"2010","journal-title":"FEBS Lett"},{"key":"2026082114460181500_ref5","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1093\/oxfordjournals.hmg.a018913","article-title":"Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway","volume":"9","author":"Blondeau","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2026082114460181500_ref6","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.tcb.2006.06.001","article-title":"Myotubularin phosphatases: policing 3-phosphoinositides","volume":"16","author":"Robinson","year":"2006","journal-title":"Trends Cell Biol"},{"key":"2026082114460181500_ref7","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1111\/j.1600-0854.2005.00338.x","article-title":"The myotubularin family of lipid phosphatases","volume":"6","author":"Clague","year":"2005","journal-title":"Traffic"},{"key":"2026082114460181500_ref8","doi-asserted-by":"publisher","first-page":"1364604","DOI":"10.3389\/fcvm.2024.1364604","article-title":"Recent advances of myotubularin-related (MTMR) protein family in cardiovascular diseases","volume":"11","author":"Wang","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"2026082114460181500_ref9","doi-asserted-by":"publisher","first-page":"100693","DOI":"10.1016\/j.jbior.2020.100693","article-title":"Phosphoinositides in cell proliferation and metabolism","volume":"75","author":"Hirsch","year":"2020","journal-title":"Adv Biol Regul"},{"key":"2026082114460181500_ref10","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/s41580-022-00490-x","article-title":"Phosphoinositides as membrane organizers","volume":"23","author":"Posor","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026082114460181500_ref11","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/febs.15127","article-title":"Phosphoinositides in autophagy: current roles and future insights","volume":"287","author":"Palamiuc","year":"2020","journal-title":"FEBS J"},{"key":"2026082114460181500_ref12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1038\/s41419-025-07616-x","article-title":"Phosphoinositide signaling at the cytoskeleton in the regulation of cell dynamics","volume":"16","author":"Hou","year":"2025","journal-title":"Cell Death Dis"},{"key":"2026082114460181500_ref13","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1007\/s00018-002-8465-z","article-title":"Phosphoinositides and signal transduction","volume":"59","author":"Toker","year":"2002","journal-title":"Cell Mol Life Sci"},{"key":"2026082114460181500_ref14","doi-asserted-by":"publisher","first-page":"8660","DOI":"10.1073\/pnas.1033097100","article-title":"Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP","volume":"100","author":"Nandurkar","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"2026082114460181500_ref15","doi-asserted-by":"publisher","first-page":"4492","DOI":"10.1073\/pnas.0431052100","article-title":"Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase","volume":"100","author":"Kim","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"2026082114460181500_ref16","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1093\/hmg\/ddab311","article-title":"Distinct roles for the Charcot\u2013Marie\u2013tooth disease-causing endosomal regulators Mtmr5 and Mtmr13 in axon radial sorting and Schwann cell myelination","volume":"31","author":"Mammel","year":"2022","journal-title":"Hum Mol Genet"},{"key":"2026082114460181500_ref17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1212\/WNL.0b013e31829a3421","article-title":"SET binding factor 1 (SBF1) mutation causes Charcot-Marie-tooth disease type 4B3","volume":"81","author":"Nakhro","year":"2013","journal-title":"Neurology"},{"key":"2026082114460181500_ref18","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1002\/ajmg.a.33417","article-title":"Multiple cranial nerve neuropathies, microcephaly, neurological degeneration, and \u201cfork and bracket sign\u201d in the MRI: a distinct syndrome","volume":"152A","author":"M\u00e9garban\u00e9","year":"2010","journal-title":"Am J Med Genet A"},{"key":"2026082114460181500_ref19","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/j.1399-0004.2010.01524.x","article-title":"A novel syndromic form of sensory-motor polyneuropathy is linked to chromosome 22q13.31-q13.33","volume":"79","author":"Bohlega","year":"2011","journal-title":"Clin Genet"},{"key":"2026082114460181500_ref20","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.1212\/WNL.0000000000000331","article-title":"SET binding factor 1 (SBF1) mutation causes Charcot-Marie-tooth disease type 4B3","volume":"82","author":"Alazami","year":"2014","journal-title":"Neurology"},{"key":"2026082114460181500_ref21","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s10048-016-0505-1","article-title":"SBF1 mutations associated with autosomal recessive axonal neuropathy with cranial nerve involvement","volume":"18","author":"Manole","year":"2017","journal-title":"neurogenetics"},{"key":"2026082114460181500_ref22","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1111\/cge.13419","article-title":"Novel SBF1 splice-site null mutation broadens the clinical spectrum of Charcot-Marie-tooth type 4B3 disease","volume":"94","author":"Flusser","year":"2018","journal-title":"Clin Genet"},{"key":"2026082114460181500_ref23","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s12920-021-01001-1","article-title":"Bi-allelic variants in MTMR5\/SBF1 cause Charcot-Marie-tooth type 4B3 featuring mitochondrial dysfunction","volume":"14","author":"Berti","year":"2021","journal-title":"BMC Med Genet"},{"key":"2026082114460181500_ref24","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s40142-026-00236-7","article-title":"Charcot-Marie-tooth 4B3 phenotype expansion and confounding factors","volume":"14","author":"Silva","year":"2026","journal-title":"Curr Genet Med Rep"},{"key":"2026082114460181500_ref25","doi-asserted-by":"crossref","DOI":"10.1093\/hmg\/ddac201","article-title":"Mitofusin 2 mutation drives cell proliferation in Charcot-Marie-tooth 2A fibroblasts","volume":"32","author":"Zanfardino","year":"2023","journal-title":"Hum Mol Genet"},{"key":"2026082114460181500_ref26","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1093\/hmg\/ddae008","article-title":"OPA 1 mutation affects autophagy and triggers senescence in autosomal dominant optic atrophy plus fibroblasts","volume":"33","author":"Zanfardino","year":"2024","journal-title":"Hum Mol Genet"},{"key":"2026082114460181500_ref27","doi-asserted-by":"publisher","first-page":"123995","DOI":"10.1016\/j.lfs.2025.123995","article-title":"Selective mitophagy activation and protein aggregate accumulation in MTMR5\/SBF1-deficient fibroblasts","volume":"381","author":"Zanfardino","year":"2025","journal-title":"Life Sci"},{"key":"2026082114460181500_ref28","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s00018-025-05612-0","article-title":"Charcot Marie tooth disease pathology is associated with mitochondrial dysfunction and lower glutathione production","volume":"82","author":"Komilova","year":"2025","journal-title":"Cell Mol Life Sci"},{"key":"2026082114460181500_ref29","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.devcel.2017.02.020","article-title":"The putative Drp1 inhibitor mdivi-1 is a reversible mitochondrial complex I inhibitor that modulates reactive oxygen species","volume":"40","author":"Bordt","year":"2017","journal-title":"Dev Cell"},{"key":"2026082114460181500_ref30","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.molcel.2008.10.021","article-title":"Respiratory active mitochondrial Supercomplexes","volume":"32","author":"Ac\u00edn-P\u00e9rez","year":"2008","journal-title":"Mol Cell"},{"key":"2026082114460181500_ref31","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.ymeth.2008.09.023","article-title":"Electrophoresis techniques to investigate defects in oxidative phosphorylation","volume":"46","author":"Calvaruso","year":"2008","journal-title":"Methods"},{"key":"2026082114460181500_ref32","doi-asserted-by":"publisher","first-page":"2471","DOI":"10.1093\/brain\/awab226","article-title":"Induced pluripotent stem cell-derived motor neurons of CMT type 2 patients reveal progressive mitochondrial dysfunction","volume":"144","author":"Van Lent","year":"2021","journal-title":"Brain"},{"key":"2026082114460181500_ref33","doi-asserted-by":"publisher","first-page":"eaav3249","DOI":"10.1126\/scisignal.aav3249","article-title":"AMPK directly activates mTORC2 to promote cell survival during acute energetic stress","volume":"12","author":"Kazyken","year":"2019","journal-title":"Sci Signal"},{"key":"2026082114460181500_ref34","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/376599a0","article-title":"Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction","volume":"376","author":"Burgering","year":"1995","journal-title":"Nature"},{"key":"2026082114460181500_ref35","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1126\/science.1106148","article-title":"Phosphorylation and regulation of Akt\/PKB by the Rictor-mTOR complex","volume":"307","author":"Sarbassov","year":"2005","journal-title":"Science"},{"key":"2026082114460181500_ref36","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.molcel.2006.03.029","article-title":"Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt\/PKB","volume":"22","author":"Sarbassov","year":"2006","journal-title":"Mol Cell"},{"key":"2026082114460181500_ref37","doi-asserted-by":"publisher","first-page":"40406","DOI":"10.1074\/jbc.M508361200","article-title":"mTOR\u00b7RICTOR is the Ser473 kinase for Akt\/protein kinase B in 3T3-L1 adipocytes","volume":"280","author":"Hresko","year":"2005","journal-title":"J Biol Chem"},{"key":"2026082114460181500_ref38","doi-asserted-by":"publisher","first-page":"101001","DOI":"10.1016\/j.jbior.2023.101001","article-title":"A new role for phosphoinositides in regulating mitochondrial dynamics","volume":"91","author":"Lourdes","year":"2024","journal-title":"Adv Biol Regul"},{"key":"2026082114460181500_ref39","doi-asserted-by":"publisher","first-page":"eabq5209","DOI":"10.1126\/science.abq5209","article-title":"Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function","volume":"378","author":"Jang","year":"2022","journal-title":"Science"},{"key":"2026082114460181500_ref40","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.1093\/hmg\/ddx216","article-title":"Mitochondrial deficits and abnormal mitochondrial retrograde axonal transport play a role in the pathogenesis of mutant Hsp27-induced Charcot Marie tooth disease","volume":"26","author":"Kalmar","year":"2017","journal-title":"Hum Mol Genet"},{"key":"2026082114460181500_ref41","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1136\/jnnp-2013-306387","article-title":"Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy","volume":"85","author":"Tucci","year":"2014","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2026082114460181500_ref42","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1177\/0271678X211069266","article-title":"Aging related impairment of brain microvascular bioenergetics involves oxidative phosphorylation and glycolytic pathways","volume":"42","author":"Sakamuri","year":"2022","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026082114460181500_ref43","doi-asserted-by":"publisher","first-page":"3430","DOI":"10.7150\/jca.21125","article-title":"The glycolytic switch in tumors: how many players are involved?","volume":"8","author":"Yu","year":"2017","journal-title":"J Cancer"},{"key":"2026082114460181500_ref44","doi-asserted-by":"publisher","first-page":"168090","DOI":"10.1016\/j.jmb.2023.168090","article-title":"Structural mechanisms of mitochondrial quality control mediated by PINK1 and parkin","volume":"435","author":"Trempe","year":"2023","journal-title":"J Mol Biol"},{"key":"2026082114460181500_ref45","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.3390\/ijms21051772","article-title":"PINK1\/parkin mediated mitophagy, Ca2+ signalling, and ER\u2013mitochondria contacts in Parkinson\u2019s disease","volume":"21","author":"Barazzuol","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026082114460181500_ref46","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1038\/s41419-021-03913-3","article-title":"Mitochondrial Ca2+ oscillation induces mitophagy initiation through the PINK1-parkin pathway","volume":"12","author":"Yu","year":"2021","journal-title":"Cell Death Dis"},{"key":"2026082114460181500_ref47","doi-asserted-by":"publisher","first-page":"433","DOI":"10.3390\/biom15030433","article-title":"The balance of MFN2 and OPA1 in mitochondrial dynamics, cellular homeostasis, and disease","volume":"15","author":"Zanfardino","year":"2025","journal-title":"Biomolecules"},{"key":"2026082114460181500_ref48","doi-asserted-by":"publisher","first-page":"102946","DOI":"10.1016\/j.scr.2022.102946","article-title":"Generation and characterization of CSSi016-a (9938) human pluripotent stem cell line carrying two biallelic variants in MTMR5\/SBF1 gene resulting in a case of severe CMT4B3","volume":"65","author":"Maria Turco","year":"2022","journal-title":"Stem Cell Res"},{"key":"2026082114460181500_ref49","doi-asserted-by":"publisher","first-page":"403","DOI":"10.2217\/nnm-2016-0342","article-title":"Cerium oxide nanoparticles: the regenerative redox machine in bioenergetic imbalance","volume":"12","author":"Pezzini","year":"2017","journal-title":"Nanomed."},{"key":"2026082114460181500_ref50","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"2026082114460181500_ref51","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2026082114460181500_ref52","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/gerona\/glq161","article-title":"Protective effects of resveratrol against senescence-associated changes in cultured human fibroblasts","volume":"66A","author":"Giovannelli","year":"2011","journal-title":"J Gerontol Ser A"}],"container-title":["Human Molecular Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/17\/ddag080\/70759515\/ddag080.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/hmg\/article-pdf\/35\/17\/ddag080\/70759515\/ddag080.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T18:46:07Z","timestamp":1787337967000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/hmg\/article\/doi\/10.1093\/hmg\/ddag080\/8767923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":52,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2026,8,10]]}},"URL":"https:\/\/doi.org\/10.1093\/hmg\/ddag080","relation":{},"ISSN":["0964-6906","1460-2083"],"issn-type":[{"value":"0964-6906","type":"print"},{"value":"1460-2083","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"ddag080"}}