{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:36:10Z","timestamp":1790660170026,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e9 Paris-Saclay"},{"name":"Hopitaux Universitaires Paris-Saclay"},{"name":"Agence Nationale de Biom\u00e9decine"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diminished ovarian reserve (DOR) and primary ovarian insufficiency (POI) are major causes of female infertility. We recently found a monogenic etiology in 29.3% of POI, leading to personalized medicine. The genetic landscape of DOR is unknown. A prospective study (2018\u20132023) of an international cohort of 120 patients with unexplained DOR was performed using a large custom targeted next-generation sequencing panel including all known POI-causing genes. The diagnostic yield, based on the American College of Medical Genetics, was 24, 2%. Genes belong to different pathways: metabolism and mitochondria (29.7%), follicular growth (24.3%), DNA repair\/meiosis (18.9%), aging (16.2%), ovarian development (8.1%), and autophagy (2.7%). Five genes were recurrently found: LMNA, ERCC6, SOX8, POLG, and BMPR1B. Six genes identified in single families with POI were involved in DOR, GNAS, TGFBR3, XPNPEP2, EXO1, BNC1, ATG, highlighting their role in maintaining ovarian reserve. In our cohort, 26 pregnancies were recorded, but no pregnancy was observed when meiosis\/DNA repair genes were involved, suggesting severely impaired oocyte quality. Additional studies should confirm these preliminary results. This study with a large NGS panel defines the genetic landscape of a large cohort of DOR. It supports routine genetic diagnosis. Genetics could be a biomarker predicting infertility and progression to POI.<\/jats:p>","DOI":"10.3390\/ijms252211915","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:03:24Z","timestamp":1730865804000},"page":"11915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic Landscape of a Cohort of 120 Patients with Diminished Ovarian Reserve: Correlation with Infertility"],"prefix":"10.3390","volume":"25","author":[{"given":"Im\u00e8ne","family":"Lafraoui","sequence":"first","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire des Maladies M\u00e9taboliques et de la Reproduction, H\u00f4pital Bic\u00eatre, Facult\u00e9 de M\u00e9decine Paris Saclay, INSERM U1193, 94275 Le Kremlin-Bic\u00eatre, France"},{"name":"Laboratoire de Biologie Mol\u00e9culaire National de R\u00e9f\u00e9rence-LBMR Pour les Infertilit\u00e9s G\u00e9n\u00e9tiques Chez la Femme et l\u2019Homme, H\u00f4pitaux Universitaires Paris Saclay, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1966-5462","authenticated-orcid":false,"given":"Abdelkader","family":"Heddar","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Mol\u00e9culaire des Maladies M\u00e9taboliques et de la Reproduction, H\u00f4pital Bic\u00eatre, Facult\u00e9 de M\u00e9decine Paris Saclay, INSERM U1193, 94275 Le Kremlin-Bic\u00eatre, France"},{"name":"Laboratoire de Biologie Mol\u00e9culaire National de R\u00e9f\u00e9rence-LBMR Pour les Infertilit\u00e9s G\u00e9n\u00e9tiques Chez la Femme et l\u2019Homme, H\u00f4pitaux Universitaires Paris Saclay, 94275 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e8le","family":"Cantalloube","sequence":"additional","affiliation":[{"name":"Service de Gyn\u00e9cologie-Obst\u00e9trique, 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estimation from 1990 to 2021: A systematic review and meta-analysis","volume":"2022","author":"Cox","year":"2022","journal-title":"Hum. Reprod Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"j138","DOI":"10.1136\/bmj.j138","article-title":"Treatment strategies for women with WHO group II anovulation: Systematic review and network meta-analysis","volume":"356","author":"Wang","year":"2017","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1001\/jama.2021.4788","article-title":"Diagnosis and Management of Infertility: A Review","volume":"326","author":"Carson","year":"2021","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI, Webber, L., Davies, M., Anderson, R., Bartlett, J., Braat, D., Cartwright, B., Cifkova, R., de Muinck Keizer-Schrama, S., and Hogervorst, E. (2016). ESHRE Guideline: Management of women with premature ovarian insufficiency. Hum. Reprod., 31, 926\u2013937.","DOI":"10.1093\/humrep\/dew027"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.tem.2018.03.010","article-title":"Advances in the Molecular Pathophysiology, Genetics, and Treatment of Primary Ovarian Insufficiency","volume":"29","author":"Huhtaniemi","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1080\/13697137.2019.1574738","article-title":"The global prevalence of primary ovarian insufficiency and early menopause: A meta-analysis","volume":"22","author":"Golezar","year":"2019","journal-title":"Climacteric"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Esteves, S.C., Alviggi, C., Humaidan, P., Fischer, R., Andersen, C.Y., Conforti, A., B\u00fchler, K., Sunkara, S.K., Polyzos, N.P., and Galliano, D. (2019). The POSEIDON Criteria and Its Measure of Success Through the Eyes of Clinicians and Embryologists. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00814"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s10815-014-0257-5","article-title":"Genetic associations with diminished ovarian reserve: A systematic review of the literature","volume":"31","author":"Greene","year":"2014","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1093\/humrep\/dey238","article-title":"Diminished ovarian reserve and poor response to stimulation in patients <38 years old: A quantitative but not qualitative reduction in performance","volume":"33","author":"Morin","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13048-023-01296-x","article-title":"Potential factors result in diminished ovarian reserve: A comprehensive review","volume":"16","author":"Zhu","year":"2023","journal-title":"J. Ovarian Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Heddar, A., Ogur, C., Da Costa, S., Braham, I., Billaud-Rist, L., Findikli, N., Beneteau, C., Reynaud, R., Mahmoud, K., and Legrand, S. (2022). Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine. eBioMedicine, 84.","DOI":"10.1016\/j.ebiom.2022.104246"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41591-022-02194-3","article-title":"Landscape of pathogenic mutations in premature ovarian insufficiency","volume":"29","author":"Ke","year":"2023","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13048-019-0595-0","article-title":"A novel EIF4ENIF1 mutation associated with a diminished ovarian reserve and premature ovarian insufficiency identified by whole-exome sequencing","volume":"12","author":"Zhao","year":"2019","journal-title":"J. Ovarian Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jgg.2020.09.004","article-title":"A recurrent mutation in TBPL2 causes diminished ovarian reserve and female infertility","volume":"47","author":"He","year":"2020","journal-title":"J. Genet. Genomics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1007\/s10815-022-02580-3","article-title":"Novel pathogenic splicing variants in helicase for meiosis 1 (HFM1) are associated with diminished ovarian reserve and poor pregnancy outcomes","volume":"39","author":"Yu","year":"2022","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hou, X., Zeb, A., Dil, S., Zhou, J., Zhang, H., Shi, B., Muhammad, Z., Khan, I., Zaman, Q., and Shah, W.A. (2023). A homozygous KASH5 frameshift mutation causes diminished ovarian reserve, recurrent miscarriage, and non-obstructive azoospermia in humans. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1128362"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Li, N., Xu, W., Liu, H., Zhou, R., Zou, S., Wang, S., Li, S., Yang, Z., Piao, Y., and Zhang, Y. (2023). Whole exome sequencing reveals novel variants associated with diminished ovarian reserve in young women. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1154067"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wan, Y., Hong, Z., Ma, B., He, X., Ma, L., Wang, M., and Zhang, Y. (2023). Identification of compound heterozygous variants in MSH4 as a novel genetic cause of diminished ovarian reserve. Reprod. Biol. Endocrinol., 21.","DOI":"10.1186\/s12958-023-01127-0"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/14647273.2016.1255356","article-title":"FMR1 premutation: Not only important in premature ovarian failure but also in diminished ovarian reserve","volume":"20","author":"Eslami","year":"2017","journal-title":"Hum. Fertil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.fertnstert.2016.09.032","article-title":"Distribution of the FMR1 gene in females by race\/ethnicity: Women with diminished ovarian reserve versus women with normal fertility (SWAN study)","volume":"107","author":"Pastore","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tang, R., and Yu, Q. (2020). The significance of FMR1 CGG repeats in Chinese women with premature ovarian insufficiency and diminished ovarian reserve. Reprod. Biol. Endocrinol., 18.","DOI":"10.1186\/s12958-020-00645-5"},{"key":"ref_22","first-page":"824","article-title":"Reproductive dysfunction in women with Albright\u2019s hereditary osteodystrophy","volume":"83","author":"Namnoum","year":"1998","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1056\/NEJMoa2103329","article-title":"Obesity-Associated GNAS Mutations and the Melanocortin Pathway","volume":"385","author":"Keogh","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/humupd\/dmu036","article-title":"The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders","volume":"20","author":"Persani","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/humrep\/del107","article-title":"Mutational analysis of the betaglycan gene-coding region in susceptibility for ovarian failure","volume":"21","author":"Dixit","year":"2006","journal-title":"Hum. Reprod."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.fertnstert.2006.05.080","article-title":"Mutational analysis of betaglycan\/TGF-betaRIII in premature ovarian failure","volume":"87","author":"Chand","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000015560","article-title":"Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene","volume":"89","author":"Prueitt","year":"2000","journal-title":"Cytogenet. Cell Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gioia, M., Payero, L., Salim, S., Fajish, V.G., Farnaz, A.F., Pannafino, G., Chen, J.J., Ajith, V.P., Momoh, S., and Scotland, M. (2023). Exo1 protects DNA nicks from ligation to promote crossover formation during meiosis. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002085"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1101\/gad.1060603","article-title":"Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility","volume":"17","author":"Wei","year":"2003","journal-title":"Genes. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"dgaa505","DOI":"10.1210\/clinem\/dgaa505","article-title":"Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency","volume":"105","author":"Luo","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1038\/s41467-022-33323-8","article-title":"BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency","volume":"13","author":"Wang","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3787","DOI":"10.1093\/hmg\/ddy261","article-title":"Basonuclin 1 deficiency is a cause of primary ovarian insufficiency","volume":"27","author":"Zhang","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/s41436-018-0287-y","article-title":"ATG7 and ATG9A loss-of-function variants trigger autophagy impairment and ovarian failure","volume":"21","author":"Delcour","year":"2019","journal-title":"Genet. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101073","DOI":"10.1016\/j.arr.2020.101073","article-title":"Lamin A involvement in ageing processes","volume":"62","author":"Cenni","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/S0140-6736(03)14069-X","article-title":"LMNA mutations in atypical Werner\u2019s syndrome","volume":"362","author":"Chen","year":"2003","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/ajmg.a.32627","article-title":"Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation","volume":"149A","author":"McPherson","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.ejcb.2009.06.002","article-title":"Impaired nuclear functions lead to increased senescence and inefficient differentiation in human myoblasts with a dominant p.R545C mutation in the LMNA gene","volume":"88","author":"Kandert","year":"2009","journal-title":"Eur. J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/j.1474-9726.2011.00719.x","article-title":"Retinoblastoma-independent regulation of cell proliferation and senescence by the p53-p21 axis in lamin A\/C-depleted cells","volume":"10","author":"Moiseeva","year":"2011","journal-title":"Aging Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41431-018-0294-0","article-title":"Assessment of fibroblast nuclear morphology aids interpretation of LMNA variants","volume":"27","author":"Lindsey","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Qin, Y., Guo, T., Li, G., Tang, T.-S., Zhao, S., Jiao, X., Gong, J., Gao, F., Guo, C., and Simpson, J.L. (2015). CSB-PGBD3 Mutations Cause Premature Ovarian Failure. PLoS Genet., 11.","DOI":"10.1371\/journal.pgen.1005419"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1210\/en.2019-00441","article-title":"Mitochondrial Dysfunction in Primary Ovarian Insufficiency","volume":"160","author":"Tiosano","year":"2019","journal-title":"Endocrinology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/gim.2017.35","article-title":"The clinical spectrum and natural history of early-onset diseases due to DNA polymerase gamma mutations","volume":"19","author":"Hikmat","year":"2017","journal-title":"Genet. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/13697137.2018.1467891","article-title":"Identification of the first homozygous POLG mutation causing non-syndromic ovarian dysfunction","volume":"21","author":"Chen","year":"2018","journal-title":"Climacteric"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101168","DOI":"10.1016\/j.arr.2020.101168","article-title":"Mitochondria in Ovarian Aging and Reproductive Longevity","volume":"63","author":"Chiang","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1093\/hmg\/ddy037","article-title":"Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies","volume":"27","author":"Portnoi","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1801899","DOI":"10.1183\/13993003.01899-2018","article-title":"Genetics and genomics of pulmonary arterial hypertension","volume":"53","author":"Morrell","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.maturitas.2019.10.011","article-title":"Analysis of NR5A1 in 142 patients with premature ovarian insufficiency, diminished ovarian reserve, or unexplained infertility","volume":"131","author":"Jaillard","year":"2020","journal-title":"Maturitas"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"gaab058","DOI":"10.1093\/molehr\/gaab058","article-title":"A pathogenic DMC1 frameshift mutation causes nonobstructive azoospermia but not primary ovarian insufficiency in humans","volume":"27","author":"Cao","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1002\/mrd.22076","article-title":"Regulation of the ovarian reserve by members of the transforming growth factor beta family","volume":"79","author":"Pangas","year":"2012","journal-title":"Mol. Reprod. Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"dgz226","DOI":"10.1210\/clinem\/dgz226","article-title":"BMPR1A and BMPR1B Missense Mutations Cause Primary Ovarian Insufficiency","volume":"105","author":"Renault","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1210\/me.2009-0461","article-title":"Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development","volume":"24","author":"Edson","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.fertnstert.2020.10.051","article-title":"Diminished ovarian reserve is associated with reduced euploid rates via preimplantation genetic testing for aneuploidy independently from age: Evidence for concomitant reduction in oocyte quality with quantity","volume":"115","author":"Jaswa","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.fertnstert.2022.06.008","article-title":"A diagnosis of diminished ovarian reserve does not impact embryo aneuploidy or live birth rates compared to patients with normal ovarian reserve","volume":"118","author":"Fouks","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/cge.14080","article-title":"A SPIDR homozygous nonsense pathogenic variant in isolated primary ovarian insufficiency with chromosomal instability","volume":"101","author":"Heddar","year":"2022","journal-title":"Clin. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1093\/clinchem\/hvab220","article-title":"Galaxy Is a Suitable Bioinformatics Platform for the Molecular Diagnosis of Human Genetic Disorders Using High-Throughput Sequencing Data Analysis: Five Years of Experience in a Clinical Laboratory","volume":"68","author":"Chappell","year":"2022","journal-title":"Clin. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.ajhg.2017.01.004","article-title":"InterVar: Clinical Interpretation of Genetic Variants by the 2015 ACMG-AMP Guidelines","volume":"100","author":"Li","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41431-020-00755-z","article-title":"MobiDetails: Online DNA variants interpretation","volume":"29","author":"Baux","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/11915\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:27:05Z","timestamp":1760113625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/11915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":59,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252211915"],"URL":"https:\/\/doi.org\/10.3390\/ijms252211915","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]}}}