{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:27:41Z","timestamp":1785421661144,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["The APC was funded by Medical University of Lodz, Poland"],"award-info":[{"award-number":["The APC was funded by Medical University of Lodz, Poland"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]},{"award":["The APC was funded by Medical University of Lodz, Poland"],"award-info":[{"award-number":["The APC was funded by Medical University of Lodz, Poland"]}],"id":[{"id":"https:\/\/ror.org\/02t4ekc95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mellitus, subsequent symptoms are associated with optic nerve atrophy, followed by central nervous system atrophy. Methods: The aim of the study was to analyse magnetic resonance images (MRI) of the brain in combination with single-voxel magnetic resonance spectroscopy (MRS) and to assess the copy number of mitochondrial DNA (mtDNA-CN) in 10 patients with WFS compared with a control group of 17 healthy individuals. Results: A significant decrease in the amount of selected metabolites was observed in WFS patients compared to controls in all assessed brain regions (pons, cerebellum, white matter, thalamus, and hippocampus). For three metabolites, Glutamate (Glu), Glutamate + Glutamine (Glx) and total N-acetylaspartate (TNAA), significant differences in concentrations were found between the study groups in almost all matrices evaluating specific areas of the brain (p &lt; 0.011), with the exception of a trend toward reduced TNAA in the hippocampus (p = 0.065). In addition, patients with WFS had a significant decrease in the mitochondrial-to-nuclear DNA ratio compared to controls (p &lt; 0.0003). Some metabolites, such as N-acetylaspartate and total N-acetylaspartate, showed strong correlations with specific regions of the visual pathway on MRI scans in patients with WFS. Conclusions: Selected brain metabolites and mtDNA-CN may become potential markers of WFS, and the results of this study may be used to define indicators for future therapeutic strategies.<\/jats:p>","DOI":"10.3390\/metabo16040281","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:01:22Z","timestamp":1776686482000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selected Brain Metabolites and Mitochondrial DNA Copy Number as Potential Markers of Ongoing Neurodegeneration in Patients with Wolfram Syndrome"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8959-5757","authenticated-orcid":false,"given":"Ewa","family":"Zmys\u0142owska-Polakowska","sequence":"first","affiliation":[{"name":"Department of Endodontics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-278X","authenticated-orcid":false,"given":"Tomasz","family":"P\u0142oszaj","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-2397","authenticated-orcid":false,"given":"Sebastian","family":"Skoczylas","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8779-3907","authenticated-orcid":false,"given":"Julia","family":"Grzybowska-Adamowicz","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dobromi\u0142a","family":"Bara\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Polish Mother\u2019s Memorial Hospital-Research Institute, Rzogowska Str. 281\/289, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-369X","authenticated-orcid":false,"given":"Katarzyna","family":"Matera","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Polish Mother\u2019s Memorial Hospital-Research Institute, Rzogowska Str. 281\/289, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0171-8594","authenticated-orcid":false,"given":"Aleksandra","family":"Palaty\u0144ska-Ulatowska","sequence":"additional","affiliation":[{"name":"Department of Endodontics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2714-5851","authenticated-orcid":false,"given":"Wojciech","family":"M\u0142ynarski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8781-4469","authenticated-orcid":false,"given":"Agnieszka","family":"Zmys\u0142owska","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3729-0518","authenticated-orcid":false,"given":"Michal","family":"Ciborowski","sequence":"additional","affiliation":[{"name":"Metabolomics and Proteomics Laboratory, Clinical Research Centre, Medical University of Bialystok, Waszyngtona Str. 17, 15-369 Bialystok, Poland"},{"name":"Department of Medical Biochemistry, Medical University of Bialystok, Mickiewicza Str. 2C, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rigoli, L., Caruso, V., Salzano, G., and Lombardo, F. (2022). Wolfram Syndrome 1: From Genetics to Therapy. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19063225"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1458\u22121463","DOI":"10.1016\/S0140-6736(95)92473-6","article-title":"Neurodegeneration and diabetes: UK nationwide study of Wolfram (DIDMOAD) syndrome","volume":"346","author":"Barrett","year":"1995","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/2441","article-title":"A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)","volume":"20","author":"Inoue","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/gim.2012.180","article-title":"Genotypic classification of patients with Wolfram syndrome: Insights into the natural history of the disease and correlation with phenotype","volume":"15","author":"Nunes","year":"2013","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lee, E.M., Verma, M., Palaniappan, N., Pope, E.M., Lee, S., Blacher, L., Neerumalla, P., An, W., Campbell, T., and Brown, C. (2023). Genotype and clinical characteristics of patients with Wolfram syndrome and WFS1-related disorders. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.1198171"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1750-1172-8-64","article-title":"Phenotypic characteristics of early Wolfram syndrome","volume":"8","author":"Marshall","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Farmer, A., Aym\u00e9, S., de Heredia, M.L., Maffei, P., McCafferty, S., M\u0142ynarski, W., Nunes, V., Parkinson, K., Paquis-Flucklinger, V., and Rohayem, J. (2013). EURO-WABB: An EU rare diseases registry for Wolfram syndrome, Alstrom syndrome and Bardet-Biedl syndrome. BMC Pediatr., 13.","DOI":"10.1186\/1471-2431-13-130"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbr.2016.04.011","article-title":"Variability in the effect of antidepressants upon Wfs1-deficient mice is dependent on the drugs\u2019 mechanism of actions","volume":"308","author":"Reimets","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e001379","DOI":"10.1136\/bmjdrc-2020-001379","article-title":"Serum microRNA as indicators of Wolfram syndrome\u2019s progression in neuroimaging studies","volume":"8","author":"Zmyslowska","year":"2020","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_10","first-page":"e145188","article-title":"A phase Ib\/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome","volume":"6","author":"Abreu","year":"2021","journal-title":"JCI Insight"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wang, G., Li, Z.A., Chen, L., Lugar, H., and Hershey, T. (2025). Clinical trials for Wolfram syndrome neurodegeneration: Novel design, endpoints, and analysis models. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0321598"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e091495","DOI":"10.1136\/bmjopen-2024-091495","article-title":"Sodium valproate, a potential repurposed treatment for the neurodegeneration in Wolfram syndrome (TREATWOLFRAM): Trial protocol for a pivotal multicentre, randomised double-blind controlled trial","volume":"15","author":"Dias","year":"2025","journal-title":"BMJ Open"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.2337\/dc14-1898","article-title":"Retinal thinning as a marker of disease progression in patients with Wolfram syndrome","volume":"38","author":"Zmyslowska","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ajo.2022.07.003","article-title":"Longitudinal Changes in Vision and Retinal Morphology in Wolfram Syndrome","volume":"243","author":"Samara","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hershey, T., Lugar, H.M., Shimony, J.S., Rutlin, J., Koller, J.M., Perantie, D.C., Paciorkowski, A.R., Eisenstein, S.A., Permutt, M.A., and Washington University Wolfram Study Group (2012). Early brain vulnerability in Wolfram syndrome. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040604"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.3174\/ajnr.A6831","article-title":"Longitudinal Assessment of Neuroradiologic Features in Wolfram Syndrome","volume":"41","author":"Samara","year":"2020","journal-title":"Am. J. Neuroradiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Simo, J., Lugar, H.M., Miller, E., Wilf-Yarkoni, A., Goldberg, Y., Kocaa\u011fa, A., Ito, S., Cocozza, S., Frontino, G., and Baldoli, C. (2025). Expanding the spectrum of white matter abnormalities in Wolfram syndrome: A retrospective review. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1623314"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4000","DOI":"10.1021\/acs.jproteome.7b00401","article-title":"Serum Metabolic Fingerprinting Identified Putatively Annotated Sphinganine Isomer as a Biomarker of Wolfram Syndrome","volume":"16","author":"Zmyslowska","year":"2017","journal-title":"J. Proteome Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zmys\u0142owska-Polakowska, E., P\u0142oszaj, T., Skoczylas, S., Mojsak, P., Ciborowski, M., Kretowski, A., Lukomska-Szymanska, M., Szadkowska, A., Mlynarski, W., and Zmys\u0142owska, A. (2023). Evaluation of the Oral Bacterial Genome and Metabolites in Patients with Wolfram Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065596"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.neurobiolaging.2025.11.003","article-title":"1H-MR spectroscopy biomarkers are associated with plasma-derived biomarkers of amyloid-\u03b2 and tau in the early phase of AD continuum","volume":"158","author":"Kara","year":"2026","journal-title":"Neurobiol. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2025.10.014","article-title":"Neurobiochemical alterations in patients with idiopathic Parkinson\u2019s disease in sensorimotor cortex using 1H-MRS","volume":"588","author":"Kumari","year":"2025","journal-title":"Neuroscience"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s00415-025-13422-4","article-title":"Clinical characteristics, cerebellar MR spectroscopy and response to 3,4-diaminopyridine in spinocerebellar ataxia 27B: The Sheffield Ataxia Centre experience","volume":"272","author":"Chukwuocha","year":"2025","journal-title":"J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s13195-024-01601-w","article-title":"Blood-derived mitochondrial DNA copy number is associated with Alzheimer disease, Alzheimer-related biomarkers and serum metabolites","volume":"16","author":"Tong","year":"2024","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cerantonio, A., Citrigno, L., Greco, B.M., De Benedittis, S., Passarino, G., Maletta, R., Qualtieri, A., Montesanto, A., Spadafora, P., and Cavalcanti, F. (2024). The Role of Mitochondrial Copy Number in Neurodegenerative Diseases: Present Insights and Future Directions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116062"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"110877","DOI":"10.1016\/j.diabres.2023.110877","article-title":"Mitochondrial DNA copy number in adults with and without Type 1 diabetes","volume":"203","author":"Jenkins","year":"2023","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1365-2265.2011.04102.x","article-title":"Wolfram syndrome in the Polish population: Novel mutations and genotype-phenotype correlation","volume":"75","author":"Zmyslowska","year":"2011","journal-title":"Clin. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Waszczykowska, A., Jeziorny, K., Bara\u0144ska, D., Matera, K., Pyziak-Skupien, A., Ciborowski, M., and Zmys\u0142owska, A. (2023). Searching for Effective Methods of Diagnosing Nervous System Lesions in Patients with Alstr\u00f6m and Bardet-Biedl Syndromes. Genes, 14.","DOI":"10.3390\/genes14091784"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/dmcn.14040","article-title":"Optical coherence tomography and magnetic resonance imaging visual pathway evaluation in Wolfram syndrome","volume":"61","author":"Zmyslowska","year":"2019","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-4939-1875-1_3","article-title":"PCR based determination of mitochondrial DNA copy number in multiple species","volume":"Volume 1241","author":"Rooney","year":"2015","journal-title":"Mitochondrial Regulation"},{"key":"ref_30","unstructured":"Adam, M.P., Bick, S., and Mirzaa, G.M. (2009). WFS1 Spectrum Disorder. GeneReviews\u00ae, University of Washington."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hnilicova, P., Kantorova, E., Sutovsky, S., Grofik, M., Zelenak, K., Kurca, E., Zilka, N., Parvanovova, P., and Kolisek, M. (2023). Imaging Methods Applicable in the Diagnostics of Alzheimer\u2019s Disease, Considering the Involvement of Insulin Resistance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043325"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11064-013-1199-5","article-title":"A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra","volume":"39","author":"Rae","year":"2014","journal-title":"Neurochem. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Grossmann, J., Grend\u00e1r, M., Hnilicov\u00e1, P., Kov\u00e1\u010dikov\u00e1, N., Kotul\u2019ov\u00e1, L., Bogner, W., Kur\u010da, E., and Kantorov\u00e1, E. (2025). Digit Span Tests Are More Sensitive than SDMT for Detecting Working Memory Impairment and Correlate with Metabolic Alterations in White Matter and Deep Gray Matter Nuclei in Multiple Sclerosis: A GABA-Edited Magnetic Resonance Spectroscopy Study. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202507.2165.v1"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kara, F., Neyal, N., Kamykowski, M.G., Schwarz, C.G., Kendall-Thomas, J., Morrison, H.A., Senjem, M.L., Przybelski, S.A., Fought, A.J., and Port, J.D. (2025). Decoding Thalamic Glial Interplay in Multiple Sclerosis Through Proton Magnetic Resonance Spectroscopy and Positron Emission Tomography. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26178656"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1148\/radiol.13130531","article-title":"Clinical proton MR spectroscopy in central nervous system disorders","volume":"270","author":"Oz","year":"2014","journal-title":"Radiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Montanaro, D., Vavla, M., Frijia, F., Coi, A., Baratto, A., Pasquariello, R., Stefan, C., and Martinuzzi, A. (2024). Metabolite profile in hereditary spastic paraplegia analyzed using magnetic resonance spectroscopy: A cross-sectional analysis in a longitudinal study. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1416093"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jaapos.2014.07.162","article-title":"Ophtalmologic correlates of disease severity in children and adolescents with Wolfram syndrome","volume":"18","author":"Hoekel","year":"2014","journal-title":"J. AAPOS"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1002\/oby.20332","article-title":"Dyslipidemia links obesity to early cerebral neurochemical alterations","volume":"21","author":"Haley","year":"2013","journal-title":"Obesity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.encep.2019.06.002","article-title":"R\u00f4le de l\u2019impulsivit\u00e9 dans la relation entre surpoids et TDAH chez l\u2019enfant: \u00e9tude exploratoire des caract\u00e9ristiques cliniques, neuropsychologiques et neurobiochimiques [Impulsivity and obesity in children with Attention Deficit Hyperactivity Disorder: A clinical, neuropsychological and magnetic resonance spectroscopy exploratory study]","volume":"45","author":"Lachal","year":"2019","journal-title":"L\u2019Encephale"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.parkreldis.2014.12.030","article-title":"Evidence for polymerase gamma, POLG1 variation in reduced mitochondrial DNA copy number in Parkinson\u2019s disease","volume":"21","author":"Gui","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.mito.2014.05.001","article-title":"Reduction in mitochondrial DNA copy number in peripheral leukocytes after onset of Huntington\u2019s disease","volume":"17","author":"Petersen","year":"2014","journal-title":"Mitochondrion"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6143","DOI":"10.1038\/s41467-024-50502-x","article-title":"ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome","volume":"15","author":"Liiv","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1111\/jdi.70152","article-title":"Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism","volume":"16","author":"Luo","year":"2025","journal-title":"J. Diabetes Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/joim.13242","article-title":"Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals","volume":"290","author":"Fazzini","year":"2021","journal-title":"J. Intern. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/4\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:38:36Z","timestamp":1776832716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/4\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["metabo16040281"],"URL":"https:\/\/doi.org\/10.3390\/metabo16040281","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}