{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:53:35Z","timestamp":1790949215804,"version":"4.1.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100018607","name":"Henan Province Science and Technology Innovation Talent Program","doi-asserted-by":"publisher","award":["LHGJ20250259"],"award-info":[{"award-number":["LHGJ20250259"]}],"id":[{"id":"10.13039\/501100018607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vestibular migraine (VM) is an underrecognized disorder characterized by episodic vertigo, often accompanied by headache. Despite its substantial prevalence and disease burden, its metabolic features remain poorly characterized, and serum biomarkers for diagnosis or activity assessment are lacking. We performed untargeted metabolomics in discovery (33 VM vs 30 healthy controls [HCs]) and replication (37 VM vs 27 HCs) cohorts, applying machine learning solely in the discovery cohort for marker selection. In the discovery cohort, 510 metabolites exhibited differential abundance (197 upregulated, 313 downregulated). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed enrichment trends for upregulated metabolites in cysteine\/methionine, histidine, and phenylalanine metabolism. Machine learning identified three candidate metabolites\u2500phenylethylamine, N-acetylserotonin, and cysteine-S-sulfate\u2500each achieving an area under the curve &amp;gt; 0.9. In the discovery cohort, cysteine-S-sulfate correlated with vertigo Visual Analog Scale scores, and phenylethylamine correlated with Headache Impact Test-6 and Generalized Anxiety Disorder-7 (GAD-7) scores. In the replication cohort, all three markers maintained differential expression and discriminative performance; additionally, cysteine-S-sulfate correlated with Dizziness Handicap Inventory scores, and phenylethylamine with GAD-7 scores. This study elucidates the metabolic landscape of VM and identifies promising serum biomarkers, though these findings warrant further validation in larger, multicenter cohorts before clinical translation.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00143","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:01:56Z","timestamp":1788768116000},"page":"5146-5158","source":"Crossref","is-referenced-by-count":0,"title":["Integrating\nMetabolomics and Machine Learning Reveals\nMetabolic Signatures and Candidate Biomarkers for Vestibular Migraine"],"prefix":"10.1021","volume":"25","author":[{"given":"Hongliang","family":"Xu","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Peking University First Hospital , , ,","place":["Beijing, China, 100034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Fang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3267-2253","authenticated-orcid":true,"given":"Liguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhengzhou University , , ,","place":["Zhengzhou, China, 450000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Peking University First Hospital , , ,","place":["Beijing, China, 100034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Lian","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-716X","authenticated-orcid":true,"given":"Yikang","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhengzhou University , , , ,","place":["Zhengzhou, Henan, China, 450052"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"11","key":"2026100208420123200_cit1","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1093\/brain\/awac264","article-title":"Vestibular\nmigraine treatment: a comprehensive practical review","volume":"145","author":"Smyth","year":"2022","journal-title":"Brain"},{"issue":"S1","key":"2026100208420123200_cit2","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1007\/s00415-015-7905-2","article-title":"Vestibular migraine: the most frequent\nentity of episodic vertigo","volume":"263","author":"Dieterich","year":"2016","journal-title":"J. Neurol."},{"issue":"8","key":"2026100208420123200_cit3","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1097\/MAO.0000000000001900","article-title":"The Epidemiology\nof Vestibular Migraine: A Population-based Survey Study","volume":"39","author":"Formeister","year":"2018","journal-title":"Otol. Neurotol."},{"issue":"4","key":"2026100208420123200_cit4","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1212\/WNL.56.4.436","article-title":"The interrelations\nof migraine, vertigo, and migrainous vertigo","volume":"56","author":"Neuhauser","year":"2001","journal-title":"Neurology"},{"issue":"5","key":"2026100208420123200_cit5","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1177\/0333102415597890","article-title":"Vestibular migraine\nin multicenter neurology clinics\naccording to the appendix criteria in the third beta edition of the\nInternational Classification of Headache Disorders","volume":"36","author":"Cho","year":"2016","journal-title":"Cephalalgia"},{"issue":"1","key":"2026100208420123200_cit6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s10194-021-01285-9","article-title":"Identification\nof disease-\nand headache-specific mediators and pathways in migraine using blood\ntranscriptomic and metabolomic analysis","volume":"22","author":"Aczel","year":"2021","journal-title":"J.\nHeadache Pain"},{"issue":"1","key":"2026100208420123200_cit7","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s10194-021-01357-w","article-title":"Metabolic profile changes in serum of migraine patients\ndetected using (1)H-NMR spectroscopy","volume":"22","author":"Harder","year":"2021","journal-title":"J. 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Neurol."},{"issue":"2","key":"2026100208420123200_cit25","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1111\/head.12293","article-title":"Histamine\nin migraine and brain","volume":"54","author":"Alstadhaug","year":"2014","journal-title":"Headache"},{"issue":"1","key":"2026100208420123200_cit26","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/head.13164","article-title":"Histamine\nand Migraine","volume":"58","author":"Yuan","year":"2018","journal-title":"Headache"},{"issue":"5","key":"2026100208420123200_cit27","doi-asserted-by":"publisher","first-page":"033310242311782","DOI":"10.1177\/03331024231178218","article-title":"Altered\ninterictal serum histamine and immunoglobulin E but unchanged tryptase\nlevels in individuals with episodic and chronic migraine","volume":"43","author":"Park","year":"2023","journal-title":"Cephalalgia"},{"issue":"10","key":"2026100208420123200_cit28","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1212\/WNL.40.10.1582","article-title":"Neuroexcitatory\nplasma amino acids are elevated in migraine","volume":"40","author":"Ferrari","year":"1990","journal-title":"Neurology"},{"issue":"3","key":"2026100208420123200_cit29","doi-asserted-by":"publisher","first-page":"345","DOI":"10.2174\/1871527314666150225144300","article-title":"Changes in Serum Amino Acids in Migraine Patients without\nand with Aura and their Possible Usefulness in the Study of Migraine\nPathogenesis","volume":"14","author":"Domitrz","year":"2015","journal-title":"CNS Neurol. 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Allergy, Asthma, Immunol."},{"issue":"1","key":"2026100208420123200_cit33","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s10194-025-02178-x","article-title":"Histamine plasma levels from dietary histidine\/histamine\nintake correlate with CGRP in trigeminal tissues","volume":"26","author":"de Mora","year":"2025","journal-title":"J. Headache Pain"},{"issue":"11","key":"2026100208420123200_cit34","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.2174\/1570159X22666240319123151","article-title":"Histaminergic\nSystem and Vestibular Function in Normal and Pathological Conditions","volume":"22","author":"Tighilet","year":"2024","journal-title":"Curr. Neuropharmacol."},{"issue":"10","key":"2026100208420123200_cit35","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1007\/s10072-015-2270-6","article-title":"Fixed combination\nof cinnarizine and dimenhydrinate in the prophylactic therapy of vestibular\nmigraine: an observational study","volume":"36","author":"Teggi","year":"2015","journal-title":"Neurol. Sci."},{"issue":"1","key":"2026100208420123200_cit36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/S0887-8994(02)00466-6","article-title":"The diet factor\nin pediatric and adolescent migraine","volume":"28","author":"Millichap","year":"2003","journal-title":"Pediatr.\nNeurol."},{"issue":"9","key":"2026100208420123200_cit37","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1212\/WNL.27.9.817","article-title":"Phenylethylamine\nand cerebral blood flow. Possible\ninvolvement of phenylethylamine in migraine","volume":"27","author":"McCulloch","year":"1977","journal-title":"Neurology"},{"issue":"1","key":"2026100208420123200_cit38","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s10194-024-01871-7","article-title":"Pediatric\nmigraine is characterized by traits of ecological\nand metabolic dysbiosis and inflammation","volume":"25","author":"Papetti","year":"2024","journal-title":"J.\nHeadache Pain"},{"issue":"7","key":"2026100208420123200_cit39","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/S1474-4422(13)70107-8","article-title":"Vestibular\nmigraine: clinical aspects\nand pathophysiology","volume":"12","author":"Furman","year":"2013","journal-title":"Lancet Neurol."},{"issue":"1","key":"2026100208420123200_cit40","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s10194-023-01708-9","article-title":"Tryptophan\nmetabolites and gut microbiota play an important role in pediatric\nmigraine diagnosis","volume":"25","author":"Liu","year":"2024","journal-title":"J. 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Headache Pain"},{"key":"2026100208420123200_cit45","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.freeradbiomed.2018.10.402","article-title":"The multiple protective\nroles and molecular mechanisms of melatonin\nand its precursor N-acetylserotonin in targeting brain injury and\nliver damage and in maintaining bone health","volume":"130","author":"Luo","year":"2019","journal-title":"Free Radical Biol. Med."},{"key":"2026100208420123200_cit46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fneur.2015.00012","article-title":"New insights\ninto pathophysiology of vestibular migraine","volume":"6","author":"Espinosa-Sanchez","year":"2015","journal-title":"Front. Neurol."},{"issue":"6","key":"2026100208420123200_cit47","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.70116","article-title":"Acute Effects of\nFour Major Trace Amines on Zebrafish Behavioral, Neurochemical, and\nNeuroendocrine Responses","volume":"169","author":"Quintanilha","year":"2025","journal-title":"J. Neurochem."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00143","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5146\/68400028\/acs.jproteome.6c00143.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5146\/68400028\/acs.jproteome.6c00143.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:52:52Z","timestamp":1790945572000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/10\/5146\/5422139\/Integrating-Metabolomics-and-Machine-Learning"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":47,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,9,7]]},"published-print":{"date-parts":[[2026,10,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00143","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}