{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T14:29:27Z","timestamp":1786717767251,"version":"build-2736575974"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study examined the ability of established brain biomarkers, glial fibrillary acid protein (GFAP), neuro-filament light chain (NFL), ubiquitin carboxy hydrolase-L1(UCH-L1), tau, and phosphorylated tau (p-tau), and novel biomarkers from blood collected sub-acutely after concussion to determine prediction of persisting post-concussion symptoms (PPCS) beyond 3\u202fmonths. We hypothesized that a combination of established and novel proteins would predict high PPCS burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Adolescents 11 to 17.99\u202fyears with a concussion based on Concussion In Sport Group (CISG) criteria were eligible. Participants were assessed 7\u201335\u202fdays post-injury (baseline) and then reassessed at 3\u202fmonths (follow-up) for persistent post-concussion symptoms (PPCS) using the Post-Concussion Symptom Inventory, 2nd Edition (PCSI-2). A total of 155 participants (78 females, 77 males) with both blood biomarkers and 3-month symptom data were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Plasma proteins collected sub-acutely (7\u201335\u202fdays post concussion) were quantified by both Quanterix and the Olink Explore platform, and compared between participants with the highest and lowest quartiles of PPCS severity at follow-up (85\u201395\u202fdays post concussion) using the PCSI-2. An exhaustive best-subsets logistic regression strategy was executed following clinical and biological pre-filtering to identify parsimonious multivariable configurations of protein biomarkers distinguishing individuals with high and low PPCS at follow-up. A stratified 10-fold cross-validation framework was implemented to evaluate model generalizability and safeguard against overfitting, while bootstrapping was used to calculate confidence intervals. Ingenuity Pathway Analysis (IPA) was performed to generate hypotheses of molecular pathways implicated in PPCS pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>None of the brain biomarkers collected sub-acutley were significantly different in PPCS-high and PPCS-low groups at 90-day follow-up. No Olink proteins survived multiple testing correction, but a cross-validated multivariable model, including Tripartite Motif Containing 39 (TRIM39)\u202f+\u202fSclerostin (SOST)\u202f+\u202fTranscription factor Dp family member 3 (TFDP3)\u202f+\u202fTNF receptor superfamily member 9 (TNFRSF9)\u202f+\u202fLeptin (LEP)\u202f+\u202fPrune Homolog 2 With BCH Domain (PRUNE2)\u202f+\u202fTrimethylguanosine Synthase 1 (TGS1)\u202f+\u202fEPCAM (Epithelial Cell Adhesion Molecule) distinguished high PPCS at follow-up with an area under the curve (AUC) of 0.86 (95% CI 0.80\u20130.92). IPA identified three significant networks associated with PPCS: (a) cardiovascular and neurological disease, organismal injury, and abnormalities (score\u202f=\u202f45; 28 focus molecules); (b) connective tissue disorders, inflammatory disease, and organismal injury and abnormalities (score\u202f=\u202f41; 26 focus molecules); and (c) connective tissue development and function, embryonic development, and organismal development (score\u202f=\u202f41; 26 focus molecules).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests the possibility to utilize novel biomarkers discovered by high throughput proteomic analysis to predict high PPCS. Future research should further develop precision of unique biomarker profiles and prolonged symptomatology in adolescents\u2019 post-concussion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1872460","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:28:02Z","timestamp":1786714082000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory proteomic biomarker combinations associated with post-concussion symptoms following a concussion in adolescents"],"prefix":"10.3389","volume":"17","author":[{"given":"Jessica","family":"Gill","sequence":"first","affiliation":[{"name":"School of Nursing and School of Medicine, Department of Neurology, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arum","family":"Lim","sequence":"additional","affiliation":[{"name":"School of Nursing, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Bickart","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijung","family":"Yun","sequence":"additional","affiliation":[{"name":"School of Nursing, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Yun","sequence":"additional","affiliation":[{"name":"School of Nursing, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Alice","sequence":"additional","affiliation":[{"name":"School of Nursing, Johns Hopkins University","place":["Baltimore, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Miles","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, Wake Forest University School of Medicine","place":["Winston-Salem, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara PD","family":"Chrisman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington, and Seattle Children\u2019s Research Institute","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychologist, Division of Pediatric Neuropsychology, Children's National Hospital","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Munro","family":"Cullum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Neurology, and Neurological Surgery, University of Texas Southwestern Medical Center","place":["Dallas, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence J.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Utah","place":["Salt Lake City, UT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Gioia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Psychiatry, George Washington University School of Medicine","place":["Washington, DC, United States"]},{"name":"Children\u2019s National Hospital","place":["Washington, DC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick P.","family":"Rivara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Washington, and Seattle Children\u2019s Research Institute","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Giza","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Neurosurgery, UCLA School of Medicine, University of California Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Bazarian","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Neurology, University of Rochester Medical Center","place":["Rochester, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7602","DOI":"10.3390\/ijerph17207602","article-title":"Academic performance following sport-related concussions in children and adolescents: a 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