{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:00:31Z","timestamp":1792144831253,"version":"4.4.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hoffmann-La Roche Ltd, Basel, Switzerland","award":["WA25046"],"award-info":[{"award-number":["WA25046"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary progressive multiple sclerosis (PPMS) affects 10\u201315% of multiple sclerosis patients and presents significant variability in the rate of disability progression. Identifying key biological features and patients at higher risk for fast progression is crucial to develop and optimize treatment strategies. Peripheral blood cell transcriptome has the potential to provide valuable information to predict patients\u2019 outcomes. In this study, we utilized a machine learning framework applied to the baseline blood transcriptional profiles and brain MRI radiological enumerations to develop prognostic models. These models aim to identify PPMS patients likely to experience significant disease progression and who could benefit from early treatment intervention. RNA-sequence analysis was performed on total RNA extracted from peripheral blood mononuclear cells of PPMS patients in the placebo arm of the ORATORIO clinical trial (NCT01412333), using Illumina NovaSeq S2. Cross-validation algorithms from Partek Genome Suite (www.partek.com) were applied to predict disability progression and brain volume loss over 120\u2005weeks. For disability progression prediction, we analysed blood RNA samples from 135 PPMS patients (61 females and 74 males) with a mean \u00b1 standard error age of 44.0 \u00b1 0.7 years, disease duration of 5.9 \u00b1 0.32 years and a median baseline Expanded Disability Status Scale (EDSS) score of 4.3 (range 3.5\u20136.5). Over the 120-week study, 39.3% (53\/135) of patients reached the disability progression end-point, with an average EDSS score increase of 1.3 \u00b1 0.16. For brain volume loss prediction, blood RNA samples from 94 PPMS patients (41 females and 53 males), mean \u00b1 standard error age of 43.7 \u00b1 0.7 years and a median baseline EDSS of 4.0 (range 3.0\u20136.5) were used. Sixty-seven per cent (63\/94) experienced significant brain volume loss. For the prediction of disability progression, we developed a two-level procedure. In the first level, a 10-gene predictor achieved a classification accuracy of 70.9 \u00b1 4.5% in identifying patients reaching the disability end-point within 120\u2005weeks. In the second level, a four-gene classifier distinguished between fast and slow disability progression with a 506-day cut-off, achieving 74.1 \u00b1 5.2% accuracy. For brain volume loss prediction, a 12-gene classifier reached an accuracy of 70.2 \u00b1 6.7%, which improved to 74.1 \u00b1 5.2% when combined with baseline brain MRI measurements. In conclusion, our study demonstrates that blood transcriptome data, alone or combined with baseline brain MRI metrics, can effectively predict disability progression and brain volume loss in PPMS patients.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae427","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T11:20:26Z","timestamp":1736335226000},"source":"Crossref","is-referenced-by-count":10,"title":["Machine learning\u2013based prediction of disease progression in primary progressive multiple sclerosis"],"prefix":"10.1093","volume":"7","author":[{"given":"Michael","family":"Gurevich","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]},{"name":"Sackler School of Medicine, Tel-Aviv University , Tel Aviv 6139601 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Zilkha-Falb","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Sherman","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Research & Development, , South San Francisco, CA 94080 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Usdin","sequence":"additional","affiliation":[{"name":"Genentech, Inc. Research & Development, , South San Francisco, CA 94080 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Raposo","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Basel, Hoffmann-La Roche Ltd. , Basel 4070 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licinio","family":"Craveiro","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Basel, Hoffmann-La Roche Ltd. , Basel 4070 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Sonis","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Magalashvili","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shay","family":"Menascu","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]},{"name":"Sackler School of Medicine, Tel-Aviv University , Tel Aviv 6139601 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dolev","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]},{"name":"Sackler School of Medicine, Tel-Aviv University , Tel Aviv 6139601 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Achiron","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center , Ramat-Gan 5262 ,","place":["Israel"]},{"name":"Sackler School of Medicine, Tel-Aviv University , Tel Aviv 6139601 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"issue":"10","key":"2025010811201326400_fcae427-B1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S1474-4422(07)70243-0","article-title":"Primary-progressive multiple sclerosis [published correction appears in Lancet Neurol. 2009 Aug;8(8):699]","volume":"6","author":"Miller","year":"2007","journal-title":"Lancet Neurol"},{"issue":"4\u20135","key":"2025010811201326400_fcae427-B2","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.autrev.2014.01.012","article-title":"Revised diagnostic criteria of multiple sclerosis","volume":"13","author":"Milo","year":"2014","journal-title":"Autoimmun Rev"},{"issue":"1","key":"2025010811201326400_fcae427-B3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1177\/13524585211059766","article-title":"Charting a global research strategy for progressive MS-An international progressive MS Alliance proposal","volume":"28","author":"Thompson","year":"2022","journal-title":"Mult Scler"},{"issue":"1","key":"2025010811201326400_fcae427-B4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1136\/jnnp-2014-307791","article-title":"Modelling the natural history of primary progressive multiple sclerosis","volume":"86","author":"Harding","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"Suppl 1","key":"2025010811201326400_fcae427-B5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000367614","article-title":"New multiple sclerosis phenotypic classification","volume":"72","author":"Lublin","year":"2014","journal-title":"Eur Neurol"},{"key":"2025010811201326400_fcae427-B6","doi-asserted-by":"crossref","first-page":"102814","DOI":"10.1016\/j.msard.2021.102814","article-title":"Definitions of primary-progressive multiple sclerosis trajectories by rate of clinical disability progression","volume":"50","author":"Achiron","year":"2021","journal-title":"Mult Scler Relat Disord"},{"issue":"3","key":"2025010811201326400_fcae427-B7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1056\/NEJMoa1606468","article-title":"Ocrelizumab versus placebo in primary progressive multiple sclerosis","volume":"376","author":"Montalban","year":"2017","journal-title":"N Engl J Med"},{"issue":"3","key":"2025010811201326400_fcae427-B8","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1002\/acn3.51732","article-title":"Real-world evaluation of ocrelizumab in multiple sclerosis: A systematic review","volume":"10","author":"Montalban","year":"2023","journal-title":"Ann Clin Transl Neurol"},{"issue":"9","key":"2025010811201326400_fcae427-B9","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1093\/brain\/awz212","article-title":"Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis","volume":"142","author":"Elliott","year":"2019","journal-title":"Brain"},{"key":"2025010811201326400_fcae427-B10","doi-asserted-by":"crossref","article-title":"Predicting upper limb disability progression in primary progressive multiple sclerosis using machine learning and statistical methods","author":"Mostafa","DOI":"10.1109\/BIBM52615.2021.9669665"},{"issue":"6","key":"2025010811201326400_fcae427-B11","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ana.21375","article-title":"Predicting progression in primary progressive multiple sclerosis: A 10-year multicenter study","volume":"63","author":"Khaleeli","year":"2008","journal-title":"Ann Neurol"},{"issue":"3","key":"2025010811201326400_fcae427-B12","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/acn3.534","article-title":"Brain atrophy and disability worsening in primary progressive multiple sclerosis: Insights from the INFORMS study","volume":"5","author":"Miller","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"issue":"11","key":"2025010811201326400_fcae427-B13","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1093\/brain\/awx250","article-title":"Long-term disability progression in primary progressive multiple sclerosis: A 15-year study","volume":"140","author":"Rocca","year":"2017","journal-title":"Brain"},{"key":"2025010811201326400_fcae427-B14","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.clinph.2022.02.019","article-title":"Prognostic biomarkers in primary progressive multiple sclerosis: Validating and scrutinizing multimodal evoked potentials","volume":"137","author":"Hardmeier","year":"2022","journal-title":"Clin Neurophysiol"},{"issue":"153","key":"2025010811201326400_fcae427-B15","doi-asserted-by":"crossref","first-page":"153ra131","DOI":"10.1126\/scitranslmed.3004186","article-title":"An RNA profile identifies two subsets of multiple sclerosis patients differing in disease activity","volume":"4","author":"Ottoboni","year":"2012","journal-title":"Sci Transl Med"},{"issue":"2","key":"2025010811201326400_fcae427-B16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/j.1365-2249.2007.03405.x","article-title":"Zinc-ion binding and cytokine activity regulation pathways predicts outcome in relapsing-remitting multiple sclerosis","volume":"149","author":"Achiron","year":"2007","journal-title":"Clin Exp Immunol"},{"key":"2025010811201326400_fcae427-B17","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1755-8794-2-46","article-title":"Prediction of acute multiple sclerosis relapses by transcription levels of peripheral blood cells","volume":"2","author":"Gurevich","year":"2009","journal-title":"BMC Med Genomics"},{"issue":"2","key":"2025010811201326400_fcae427-B18","doi-asserted-by":"crossref","first-page":"e0280515","DOI":"10.1371\/journal.pone.0280515","article-title":"Faster progression to multiple sclerosis disability is linked to neuronal pathways associated with neurodegeneration: An ethnicity study","volume":"18","author":"Harari","year":"2023","journal-title":"PLoS One"},{"key":"2025010811201326400_fcae427-B19","doi-asserted-by":"crossref","first-page":"579683","DOI":"10.3389\/fneur.2020.579683","article-title":"Development and validation of a five-gene signature to predict relapse-free survival in multiple sclerosis","volume":"11","author":"Ye","year":"2020","journal-title":"Front Neurol"},{"issue":"15 Suppl","key":"2025010811201326400_fcae427-B20","article-title":"Transcriptional profiling of primary progressive multiple sclerosis patients identifies fast and slow progression patterns (P1.321)","volume":"90","author":"Gurevich","year":"2018","journal-title":"Neurology"},{"issue":"1","key":"2025010811201326400_fcae427-B21","first-page":"10","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnetjournal"},{"issue":"1","key":"2025010811201326400_fcae427-B22","doi-asserted-by":"crossref","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"},{"issue":"2","key":"2025010811201326400_fcae427-B23","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2013a Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"issue":"12","key":"2025010811201326400_fcae427-B24","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"issue":"19","key":"2025010811201326400_fcae427-B25","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1093\/bioinformatics\/bts480","article-title":"Snakemake\u2013A scalable bioinformatics workflow engine [published correction appears in Bioinformatics. 2018 Oct 15;34(20):3600]","volume":"28","author":"K\u00f6ster","year":"2012","journal-title":"Bioinformatics"},{"issue":"7906","key":"2025010811201326400_fcae427-B26","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41586-022-04554-y","article-title":"Brain charts for the human lifespan [published correction appears in Nature. 2022 Oct;610(7931):E6]","volume":"604","author":"Bethlehem","year":"2022","journal-title":"Nature"},{"issue":"1","key":"2025010811201326400_fcae427-B27","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13317-019-0117-5","article-title":"Brain atrophy in multiple sclerosis: Mechanisms, clinical relevance and treatment options","volume":"10","author":"Andravizou","year":"2019","journal-title":"Auto Immun Highlights"},{"issue":"3","key":"2025010811201326400_fcae427-B28","doi-asserted-by":"crossref","first-page":"e92761","DOI":"10.1371\/journal.pone.0092761","article-title":"Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review","volume":"9","author":"Stellmann","year":"2014","journal-title":"PLoS One"},{"issue":"10","key":"2025010811201326400_fcae427-B29","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1161\/ATVBAHA.116.307610","article-title":"Endothelial cell junctional adhesion molecules: Role and regulation of expression in inflammation","volume":"36","author":"Reglero-Real","year":"2016","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"8","key":"2025010811201326400_fcae427-B30","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/ni.2062","article-title":"The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo","volume":"12","author":"Woodfin","year":"2011","journal-title":"Nat Immunol"},{"issue":"1","key":"2025010811201326400_fcae427-B31","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1677\/JOE-07-0145","article-title":"High glucose enhances lipopolysaccharide-stimulated CD14 expression in U937 mononuclear cells by increasing nuclear factor kappaB and AP-1 activities","volume":"196","author":"Nareika","year":"2008","journal-title":"J Endocrinol"},{"issue":"7","key":"2025010811201326400_fcae427-B32","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.4049\/jimmunol.180.7.5067","article-title":"High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes","volume":"180","author":"Youn","year":"2008","journal-title":"J Immunol"},{"issue":"3","key":"2025010811201326400_fcae427-B33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0167-4781(01)00337-2","article-title":"Nucleotide sequence and cell cycle-associated differential expression of ZF5128, a novel Kruppel type zinc finger protein gene","volume":"1522","author":"Rue","year":"2001","journal-title":"Biochim Biophys Acta"},{"issue":"10","key":"2025010811201326400_fcae427-B34","doi-asserted-by":"crossref","first-page":"7252","DOI":"10.1074\/jbc.M112.416792","article-title":"Dyrk2-associated EDD-DDB1-VprBP E3 ligase inhibits telomerase by TERT degradation","volume":"288","author":"Jung","year":"2013","journal-title":"J Biol Chem"},{"key":"2025010811201326400_fcae427-B35","doi-asserted-by":"crossref","first-page":"615131","DOI":"10.3389\/fcell.2020.615131","article-title":"Inflammation and Wnt signaling: Target for immunomodulatory therapy?","volume":"8","author":"Jridi","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"12","key":"2025010811201326400_fcae427-B36","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1097\/TP.0000000000001393","article-title":"Wnt signaling as master regulator of T-lymphocyte responses: Implications for transplant therapy","volume":"100","author":"Staal","year":"2016","journal-title":"Transplantation"},{"key":"2025010811201326400_fcae427-B37","doi-asserted-by":"crossref","first-page":"958677","DOI":"10.3389\/fimmu.2022.958677","article-title":"PHACTR1, a coronary artery disease risk gene, mediates endothelial dysfunction","volume":"13","author":"Ma","year":"2022","journal-title":"Front Immunol"},{"issue":"2","key":"2025010811201326400_fcae427-B38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1097\/MED.0000000000000046","article-title":"Scavenger receptor class B type I and immune dysfunctions","volume":"21","author":"Zheng","year":"2014","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"2025010811201326400_fcae427-B39","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.2741\/2281","article-title":"The role of TRAIL\/TRAIL receptors in central nervous system pathology","volume":"12","author":"Aktas","year":"2007","journal-title":"Front Biosci"},{"issue":"9","key":"2025010811201326400_fcae427-B40","doi-asserted-by":"crossref","first-page":"5259","DOI":"10.4049\/jimmunol.0902797","article-title":"Dual effects of TRAIL in suppression of autoimmunity: The inhibition of Th1 cells and the promotion of regulatory T cells","volume":"185","author":"Ikeda","year":"2010","journal-title":"J Immunol"},{"issue":"4","key":"2025010811201326400_fcae427-B41","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.4049\/jimmunol.174.4.1888","article-title":"Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand","volume":"174","author":"Hirata","year":"2005","journal-title":"J Immunol"},{"issue":"31","key":"2025010811201326400_fcae427-B42","doi-asserted-by":"crossref","first-page":"eabh2169","DOI":"10.1126\/sciadv.abh2169","article-title":"A single-cell type transcriptomics map of human tissues","volume":"7","author":"Karlsson","year":"2021","journal-title":"Sci Adv"},{"issue":"1","key":"2025010811201326400_fcae427-B43","doi-asserted-by":"crossref","first-page":"194","DOI":"10.3390\/biomedicines11010194","article-title":"The inflammatory gene PYCARD of the entorhinal cortex as an early diagnostic target for Alzheimer\u2019s disease","volume":"11","author":"Liu","year":"2023","journal-title":"Biomedicines"},{"issue":"11","key":"2025010811201326400_fcae427-B44","doi-asserted-by":"crossref","first-page":"5056","DOI":"10.1172\/JCI97912","article-title":"Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure","volume":"128","author":"Armacki","year":"2018","journal-title":"J Clin Invest"},{"issue":"45","key":"2025010811201326400_fcae427-B45","doi-asserted-by":"crossref","first-page":"6536","DOI":"10.1038\/sj.onc.1210476","article-title":"Thirty-eight-negative kinase 1 (TNK1) facilitates TNFalpha-induced apoptosis by blocking NF-kappaB activation","volume":"26","author":"Azoitei","year":"2007","journal-title":"Oncogene"},{"key":"2025010811201326400_fcae427-B46","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.intimp.2018.09.014","article-title":"Polymorphisms in the angiotensin I converting enzyme (ACE) gene are associated with multiple sclerosis risk and response to interferon-\u03b2 treatment","volume":"64","author":"Yaeghmaie","year":"2018","journal-title":"Int Immunopharmacol"},{"issue":"8","key":"2025010811201326400_fcae427-B47","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1001\/archneur.1997.00550200068012","article-title":"Serum angiotensin-converting enzyme in multiple sclerosis","volume":"54","author":"Constantinescu","year":"1997","journal-title":"Arch Neurol"},{"issue":"8","key":"2025010811201326400_fcae427-B48","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1172\/JCI41709","article-title":"Angiotensin II sustains brain inflammation in mice via TGF-beta","volume":"120","author":"Lanz","year":"2010","journal-title":"J Clin Invest"},{"issue":"11","key":"2025010811201326400_fcae427-B49","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1111\/j.1349-7006.2011.02061.x","article-title":"MAFIP is a tumor suppressor in cervical cancer that inhibits activation of the nuclear factor-kappa B pathway","volume":"102","author":"Li","year":"2011","journal-title":"Cancer Sci"},{"issue":"3","key":"2025010811201326400_fcae427-B50","first-page":"a001271","article-title":"NF-kappaB in the nervous system [published correction appears in Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a001271]","volume":"1","author":"Kaltschmidt","year":"2009","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"5","key":"2025010811201326400_fcae427-B51","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.3390\/antiox12051037","article-title":"Tetrahydrobiopterin: Beyond its traditional role as a cofactor","volume":"12","author":"Eichwald","year":"2023","journal-title":"Antioxidants (Basel)"},{"issue":"7732","key":"2025010811201326400_fcae427-B52","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/s41586-018-0701-2","article-title":"The metabolite BH4 controls T cell proliferation in autoimmunity and cancer [published correction appears in Nature. 2019 Aug;572(7769):E18]","volume":"563","author":"Cronin","year":"2018","journal-title":"Nature"},{"key":"2025010811201326400_fcae427-B53","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.brainres.2007.01.001","article-title":"Sepiapterin reductase expression is increased in Parkinson's disease brain tissue","volume":"1139","author":"Tobin","year":"2007","journal-title":"Brain Res"},{"issue":"2","key":"2025010811201326400_fcae427-B54","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2174\/1389200024605082","article-title":"Neopterin as a marker for immune system activation","volume":"3","author":"Murr","year":"2002","journal-title":"Curr Drug Metab"},{"issue":"1","key":"2025010811201326400_fcae427-B55","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41398-020-00930-2","article-title":"Genome-wide association study of cognitive function in diverse Hispanics\/Latinos: Results from the Hispanic Community Health Study\/Study of Latinos","volume":"10","author":"Jian","year":"2020","journal-title":"Transl Psychiatry"},{"key":"2025010811201326400_fcae427-B56","doi-asserted-by":"crossref","first-page":"117289","DOI":"10.1016\/j.neuroimage.2020.117289","article-title":"Associations between cognitive and brain volume changes in cognitively normal older adults","volume":"223","author":"Armstrong","year":"2020","journal-title":"Neuroimage"},{"issue":"11","key":"2025010811201326400_fcae427-B57","first-page":"637","article-title":"Brain volume is associated with cognition in MS","volume":"18","author":"Lempriere","year":"2022","journal-title":"Nat Rev Neurol"},{"issue":"3","key":"2025010811201326400_fcae427-B58","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3233\/JAD-141989","article-title":"Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer\u2019s disease","volume":"44","author":"Humphries","year":"2015","journal-title":"J Alzheimers Dis"},{"issue":"37","key":"2025010811201326400_fcae427-B59","doi-asserted-by":"crossref","first-page":"13638","DOI":"10.1074\/jbc.RA119.008903","article-title":"Magnesium transporter 1 (MAGT1) deficiency causes selective defects in N-linked glycosylation and expression of immune-response genes","volume":"294","author":"Matsuda-Lennikov","year":"2019","journal-title":"J Biol Chem"},{"issue":"8","key":"2025010811201326400_fcae427-B60","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.4049\/jimmunol.1701467","article-title":"Cutting edge: Imbalanced cation homeostasis in MAGT1-deficient B cells dysregulates B cell development and signaling in mice","volume":"200","author":"Gotru","year":"2018","journal-title":"J Immunol"},{"issue":"6","key":"2025010811201326400_fcae427-B61","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1021\/acs.jproteome.3c00015","article-title":"Deciphering the properties and functions of glycoproteins using quantitative proteomics","volume":"22","author":"Xu","year":"2023","journal-title":"J Proteome Res"},{"issue":"12","key":"2025010811201326400_fcae427-B62","doi-asserted-by":"crossref","first-page":"e164118","DOI":"10.1172\/JCI164118","article-title":"Deficiency in the omega-3 lysolipid transporter Mfsd2a leads to aberrant oligodendrocyte lineage development and hypomyelination","volume":"133","author":"Sengottuvel","year":"2023","journal-title":"J Clin Invest"},{"issue":"7501","key":"2025010811201326400_fcae427-B63","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature13241","article-title":"Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid","volume":"509","author":"Nguyen","year":"2014","journal-title":"Nature"},{"key":"2025010811201326400_fcae427-B64","doi-asserted-by":"crossref","first-page":"2329048X19880647","DOI":"10.1177\/2329048X19880647","article-title":"A novel SLC1A4 mutation (p.Y191*) causes spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) with seizure disorder","volume":"6","author":"Abdelrahman","year":"2019","journal-title":"Child Neurol Open"},{"key":"2025010811201326400_fcae427-B65","doi-asserted-by":"crossref","first-page":"107283","DOI":"10.1016\/j.clineuro.2022.107283","article-title":"A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation","volume":"218","author":"Sarigecili","year":"2022","journal-title":"Clin Neurol Neurosurg"},{"issue":"2","key":"2025010811201326400_fcae427-B66","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.4049\/jimmunol.179.2.1210","article-title":"The human endogenous retrovirus envelope glycoprotein, syncytin-1, regulates neuroinflammation and its receptor expression in multiple sclerosis: A role for endoplasmic reticulum chaperones in astrocytes","volume":"179","author":"Antony","year":"2007","journal-title":"J Immunol"},{"issue":"1","key":"2025010811201326400_fcae427-B67","first-page":"93","article-title":"Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis","volume":"87","author":"De Stefano","year":"2016","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"2025010811201326400_fcae427-B68","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1177\/1352458517742739","article-title":"Pathological cut-offs of global and regional brain volume loss in multiple sclerosis","volume":"25","author":"Uher","year":"2019","journal-title":"Mult Scler J"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/1\/fcae427\/61372684\/fcae427.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/1\/fcae427\/61372684\/fcae427.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T11:20:52Z","timestamp":1736335252000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcae427\/7945313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":68,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,12,24]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcae427","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2024,12,24]]},"article-number":"fcae427"}}