{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:22:38Z","timestamp":1782966158750,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NICHD NIH","award":["ZIA HD008988"],"award-info":[{"award-number":["ZIA HD008988"]}]},{"name":"NICHD NIH","award":["ZIA HD008989"],"award-info":[{"award-number":["ZIA HD008989"]}]},{"name":"Together Strong Foundation","award":["ZIA HD008988"],"award-info":[{"award-number":["ZIA HD008988"]}]},{"name":"Together Strong Foundation","award":["ZIA HD008989"],"award-info":[{"award-number":["ZIA HD008989"]}]},{"name":"Ara Parseghian Medical Research Foundation","award":["ZIA HD008988"],"award-info":[{"award-number":["ZIA HD008988"]}]},{"name":"Ara Parseghian Medical Research Foundation","award":["ZIA HD008989"],"award-info":[{"award-number":["ZIA HD008989"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Niemann-Pick disease type C1 (NPC1) is a lysosomal disorder due to impaired intracellular cholesterol transport out of the endolysosomal compartment. Marked heterogeneity has been observed in individuals with the same NPC1 genotype, thus suggesting a significant effect of modifier genes. Prior work demonstrated that decreased SOAT1 activity decreased disease severity in an NPC1 mouse model. Thus, we hypothesized that a polymorphism associated with decreased SOAT1 expression might influence the NPC1 phenotype. Phenotyping and genomic sequencing of 117 individuals with NPC1 was performed as part of a Natural History trial. Phenotyping included determination of disease severity and disease burden. Significant clinical heterogeneity is present in individuals homozygous for the NPC1I1061T variant and in siblings. Analysis of the SOAT1 polymorphism, rs1044925 (A&gt;C), showed a significant association of the C-allele with earlier age of neurological onset. The C-allele may be associated with a higher Annualized Severity Index Score as well as increased frequency of liver disease and seizures. A polymorphism associated with decreased expression of SOAT1 appears to be a genetic modifier of the NPC1 phenotype. This finding is consistent with prior data showing decreased phenotypic severity in Npc1-\/-:Soat1-\/- mice and supports efforts to investigate the potential of SOAT1 inhibitors as a potential therapy for NPC1.<\/jats:p>","DOI":"10.3390\/ijms25084217","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T03:29:04Z","timestamp":1712806144000},"page":"4217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sterol O-Acyltransferase 1 (SOAT1): A Genetic Modifier of Niemann-Pick Disease, Type C1"],"prefix":"10.3390","volume":"25","author":[{"given":"Nicole Y.","family":"Farhat","sequence":"first","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6578-2537","authenticated-orcid":false,"given":"Derek","family":"Alexander","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-1043","authenticated-orcid":false,"given":"Kyli","family":"McKee","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Iben","sequence":"additional","affiliation":[{"name":"Molecular Genomics Core, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-1281","authenticated-orcid":false,"given":"Jorge L.","family":"Rodriguez-Gil","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Wassif","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-5941","authenticated-orcid":false,"given":"Niamh X.","family":"Cawley","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Balch","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9397-0046","authenticated-orcid":false,"given":"Forbes D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/BF02983018","article-title":"The relative importance of principal and modifying genes in determining some human diseases","volume":"41","author":"Haldane","year":"1941","journal-title":"J. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nbt.3514","article-title":"Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases","volume":"34","author":"Chen","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/gim.2017.50","article-title":"Assessment of the ExAC data set for the presence of individuals with pathogenic genotypes implicated in severe Mendelian pediatric disorders","volume":"19","author":"Zhu","year":"2017","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s00439-008-0560-2","article-title":"Identifying modifier genes of monogenic disease: Strategies and difficulties","volume":"124","author":"Genin","year":"2008","journal-title":"Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rahit, K., and Tarailo-Graovac, M. (2020). Genetic Modifiers and Rare Mendelian Disease. Genes, 11.","DOI":"10.3390\/genes11030239"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-030-14265-0_8","article-title":"Insights into the Molecular Mechanisms of Cholesterol Binding to the NPC1 and NPC2 Proteins","volume":"1135","author":"Cologna","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","first-page":"E336","article-title":"Cholesterol balance and metabolism in mice with loss of function of Niemann-Pick C protein","volume":"276","author":"Xie","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1750-1172-5-16","article-title":"Niemann-Pick disease type C","volume":"5","author":"Vanier","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.37349\/ent.2021.00012","article-title":"Advancing Diagnosis and Treatment of Niemann-Pick C disease through Biomarker Discovery","volume":"1","author":"Jiang","year":"2021","journal-title":"Explor. Neuroprotective Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1212\/CPJ.0000000000000399","article-title":"Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update","volume":"7","author":"Patterson","year":"2017","journal-title":"Neurol. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/ajmg.b.30969","article-title":"Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C","volume":"153B","author":"Yanjanin","year":"2010","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41525-023-00365-w","article-title":"Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): A need for precision medicine","volume":"8","author":"Szenfeld","year":"2023","journal-title":"NPJ Genom. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/ana.10266","article-title":"Niemann-Pick type C disease: Accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity","volume":"52","author":"Saito","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1002\/ajmg.a.35395","article-title":"Apolipoprotein E genotype and neurological disease onset in Niemann-Pick disease, type C1","volume":"158A","author":"Fu","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1001\/jamaneurol.2020.3241","article-title":"Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1","volume":"77","author":"Solomon","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13023-020-01363-2","article-title":"Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: A final report of the NPC Registry","volume":"15","author":"Patterson","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s13023-018-0844-0","article-title":"Miglustat in Niemann-Pick disease type C patients: A review","volume":"13","author":"Pineda","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/jimd.12245","article-title":"Long-term survival outcomes of patients with Niemann-Pick disease type C receiving miglustat treatment: A large retrospective observational study","volume":"43","author":"Patterson","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23842","DOI":"10.1074\/jbc.M111.227645","article-title":"An \u201cexacerbate-reverse\u201d strategy in yeast identifies histone deacetylase inhibition as a correction for cholesterol and sphingolipid transport defects in human Niemann-Pick type C disease","volume":"286","author":"Munkacsi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1073\/pnas.1014890108","article-title":"Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts","volume":"108","author":"Pipalia","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1093\/hmg\/ddy117","article-title":"High-content screen for modifiers of Niemann-Pick type C disease in patient cells","volume":"27","author":"Pugach","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2009.05.009","article-title":"Identification of cholesterol-regulating genes by targeted RNAi screening","volume":"10","author":"Bartz","year":"2009","journal-title":"Cell Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25152564221114513","DOI":"10.1177\/25152564221114513","article-title":"Sorting (Nexin-13) out Novel Insights into Endolysosomal Cholesterol Export","volume":"5","author":"Lu","year":"2022","journal-title":"Contact"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8091","DOI":"10.1523\/JNEUROSCI.4173-14.2015","article-title":"A murine Niemann-Pick C1 I1061T knock-in model recapitulates the pathological features of the most prevalent human disease allele","volume":"35","author":"Praggastis","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"dmm042614","DOI":"10.1242\/dmm.042614","article-title":"Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1","volume":"13","author":"Baxter","year":"2020","journal-title":"Dis. Model. Mech."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bbrc.2011.08.096","article-title":"Npc1 deficiency in the C57BL\/6J genetic background enhances Niemann-Pick disease type C spleen pathology","volume":"413","author":"Parra","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s003350010013","article-title":"A modifier of Niemann Pick C 1 maps to mouse chromosome 19","volume":"11","author":"Zhang","year":"2000","journal-title":"Mamm. Genome"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/S0960-9822(03)00531-1","article-title":"Cholesterol accumulation in NPC1-deficient neurons is ganglioside dependent","volume":"13","author":"McGlynn","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"161","DOI":"10.14348\/molcells.2014.2347","article-title":"Inhibition of GM3 synthase attenuates neuropathology of Niemann-Pick disease Type C. by affecting sphingolipid metabolism","volume":"37","author":"Lee","year":"2014","journal-title":"Mol. Cells."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1523\/JNEUROSCI.5282-06.2007","article-title":"Endosomal accumulation of Toll-like receptor 4 causes constitutive secretion of cytokines and activation of signal transducers and activators of transcription in Niemann-Pick disease type C (NPC) fibroblasts: A potential basis for glial cell activation in the NPC brain","volume":"27","author":"Suzuki","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/1742-2094-9-216","article-title":"Complement is dispensable for neurodegeneration in Niemann-Pick disease type C","volume":"9","author":"Lopez","year":"2012","journal-title":"J. Neuroinflammation."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1093\/hmg\/dds126","article-title":"Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C","volume":"21","author":"Lopez","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41586-021-03762-2","article-title":"Tonic prime-boost of STING signalling mediates Niemann-Pick disease type C","volume":"596","author":"Chu","year":"2021","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/s41556-023-01339-x","article-title":"Innate immune sensing of lysosomal dysfunction drives multiple lysosomal storage disorders","volume":"26","author":"Wang","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.nbd.2011.01.028","article-title":"Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis","volume":"42","author":"Nunes","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1093\/hmg\/ddn423","article-title":"Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis","volume":"18","author":"Pacheco","year":"2009","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Marques, A.R., Aten, J., Ottenhoff, R., van Roomen, C.P., Herrera Moro, D., Claessen, N., Vinueza Veloz, M.F., Zhou, K., Lin, Z., and Mirzaian, M. (2015). Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135889"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e2201646119","DOI":"10.1073\/pnas.2201646119","article-title":"Acat1\/Soat1 knockout extends the mutant Npc1 mouse lifespan and ameliorates functional deficiencies in multiple organelles of mutant cells","volume":"119","author":"Rogers","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"G454","DOI":"10.1152\/ajpgi.00124.2018","article-title":"Niemann-Pick C1-deficient mice lacking sterol O-acyltransferase 2 have less hepatic cholesterol entrapment and improved liver function","volume":"315","author":"Lopez","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1476-511X-9-139","article-title":"Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations","volume":"9","author":"Wu","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1476-511X-11-9","article-title":"Sex-specific association of ACAT-1 rs1044925 SNP and serum lipid levels in the hypercholesterolemic subjects","volume":"11","author":"Wu","year":"2012","journal-title":"Lipids Health Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"89055","DOI":"10.18632\/oncotarget.21649","article-title":"ACAT-1 gene polymorphism is associated with increased susceptibility to coronary artery disease in Chinese Han population: A case-control study","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s12035-020-02162-3","article-title":"Relationship Between Genetic Variants of ACAT1 and APOE with the Susceptibility to Dementia (SADEM Study)","volume":"58","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000105164","article-title":"Study on the association between SOAT1 polymorphisms, Alzheimer\u2019s disease risk and the level of CSF biomarkers","volume":"24","author":"Helisalmi","year":"2007","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neulet.2005.06.020","article-title":"Association between acyl-coenzyme A: Cholesterol acyltransferase gene and risk for Alzheimer\u2019s disease in Chinese","volume":"388","author":"Zhao","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_46","unstructured":"Brunner, F.S.M. (2006). Effects of a SOAT1 Haplotype on SOAT1 mRNA Expression and on the Risk for Sporadic Alzheimer\u2019s Disease, Swill Federal Institute of Technology Zurich."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101225","DOI":"10.1016\/j.plipres.2023.101225","article-title":"The Niemann-Pick type diseases\u2014A synopsis of inborn errors in sphingolipid and cholesterol metabolism","volume":"90","author":"Pfrieger","year":"2023","journal-title":"Prog. Lipid Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13023-018-0880-9","article-title":"Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials","volume":"13","author":"Mengel","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1186\/s13023-021-02115-6","article-title":"International consensus on clinical severity scale use in evaluating Niemann-Pick disease Type C in paediatric and adult patients: Results from a Delphi Study","volume":"16","author":"Evans","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13023-021-01719-2","article-title":"Validation of the 5-domain Niemann-Pick type C Clinical Severity Scale","volume":"16","author":"Patterson","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1086\/302626","article-title":"Niemann-Pick C1 disease: The I1061T substitution is a frequent mutant allele in patients of Western European descent and correlates with a classic juvenile phenotype","volume":"65","author":"Millat","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1172\/JCI72835","article-title":"Relative acidic compartment volume as a lysosomal storage disorder-associated biomarker","volume":"124","author":"Speak","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1038\/s41598-022-06112-y","article-title":"Correlation of age of onset and clinical severity in Niemann-Pick disease type C1 with lysosomal abnormalities and gene expression","volume":"12","author":"Baxter","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:26:07Z","timestamp":1760106367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,11]]},"references-count":54,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084217"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084217","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,11]]}}}