{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:50:57Z","timestamp":1787165457786,"version":"build-2736575974"},"reference-count":40,"publisher":"SAGE Publications","issue":"13-14","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Concussion is a heterogeneous injury that relies predominantly on subjective symptom reports for patient assessment and treatment. Developing an objective, biological test could aid phenotypic categorization of concussion patients, leading to advances in personalized treatment. This prospective multi-center study employed saliva micro-ribonucleic acid (miRNA) levels to stratify 251 individuals with concussion into biological subgroups. Using miRNA biological clusters, our objective was to assess for differences in medical\/demographic characteristics, symptoms, and functional measures of balance and cognition. The miRNAs that best defined each cluster were used to identify physiological pathways that characterized each cluster. The 251 participants (mean age: 18\u2009\u00b1\u20097 years; 57% male) were optimally grouped into 10 clusters based on 22 miRNA levels. The clusters differed in age (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200919.1,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.024), days post-injury at the time of saliva collection (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200922.6;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.007), and number of prior concussions (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200917.6,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.040). The clusters also differed in symptom reports for fatigue (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200917.7;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.039), confusion (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200922.3;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.008), difficulty remembering (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200922.0;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.009), and trouble falling asleep (\u03c7\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u200917.2;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.046), but not objective balance or cognitive performance (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&gt;\u20090.05). The miRNAs that defined concussion clusters regulate 16 physiological pathways, including adrenergic signaling, estrogen signaling, fatty acid metabolism, GABAergic signaling, synaptic vesicle cycling, and transforming growth factor (TGF)-\u03b2 signaling. These results show that saliva miRNA levels may stratify individuals with concussion based on underlying biological perturbations that are relevant to both symptomology and pharmacological targets. If validated in a larger cohort, miRNA assessment could aid individualized, biology-driven concussion treatment.\n                  <\/jats:p>","DOI":"10.1089\/neu.2022.0018","type":"journal-article","created":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T12:55:38Z","timestamp":1649768138000},"page":"923-934","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Defining Biological Phenotypes of Mild Traumatic Brain Injury Using Saliva MicroRNA Profiles"],"prefix":"10.1177","volume":"39","author":[{"given":"Steven D.","family":"Hicks","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Leddy","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA."},{"name":"Department of Orthopedics, State University of New York at Buffalo, Buffalo, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke P.","family":"Lichak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cayce","family":"Onks","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA."},{"name":"Department of Orthopaedics and Rehabilitation, College of Medicine, Penn State University, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dretsch","sequence":"additional","affiliation":[{"name":"US Army Medical Research Directorate-West, Walter Reed Army Institute of Research, Joint Base Lewis-McChord, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Tennant","sequence":"additional","affiliation":[{"name":"Quadrant Biosciences, Inc, Syracuse, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Nadir","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, USA."},{"name":"Department of Orthopedics, State University of New York at Buffalo, Buffalo, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Olympia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA."},{"name":"Department of Emergency Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Zuckerman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayson","family":"Loeffert","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA."},{"name":"Department of Orthopaedics and Rehabilitation, College of Medicine, Penn State University, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea C.","family":"Loeffert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuck","family":"Monteith","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, Colgate University, Hamilton, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Master","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2017-097699"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2018-100338"},{"key":"e_1_3_6_4_2","article-title":"Diagnosis and management of mild traumatic brain injury in children: a systematic review","volume":"172","author":"Lumba-Brown A.","year":"2018","unstructured":"Lumba-Brown A., , Yeates K.O., , Sarmiento K., , Breiding M.J., , Haegerich T.M., , Gioia G. A., , Turner M., , Benzel E.C., , Suskauer S.J., , Giza C.C., , Joseph M., , Broomand C., , Weissman B., , Gordon W., , Wright D.W., , Moser R.S., , McAvoy K., , Ewing-Cobbs L., , Duhaime A.C., , Putukian M., , Holshouser B., , Paulk D., , Wade S.L., , Herring S.A., , Halstead M., , Keenan H.T., , Choe M., , Christian C.W., , Guskiewicz K., , Raksin P.B., , Gregory A., , Mucha A., , Taylor H.G., , Callahan J.M., , DeWitt J., , Collins M.W., , Kirkwood M.W., , Ragheb J., , Ellenbogen R.G., , Spinks T.J., , Ganiats T.G., , Sabelhaus L.J., , Altenhofen K., , Hoffman R., , Getchius T., , Gronseth G., , Donnell Z., , O'Connor R.E., , and Timmons S.D. (2018). Diagnosis and management of mild traumatic brain injury in children: a systematic review. 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(2021). Refinement of saliva microRNA biomarkers for sports-related concussion. J. Sport Health Sci. [Epub ahead of print.]","journal-title":"J. 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(2021). M-CSF, IL-6, and TGF-\u03b2 promote generation of a new subset of tissue repair macrophage for traumatic brain injury recovery. Sci. Adv. 7, eabb6260","journal-title":"Sci. Adv. 7,"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2012.2439"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.06.002"},{"key":"e_1_3_6_40_2","author":"Wilde E.A.","year":"2022","unstructured":"Wilde E.A., , Wanner I.B., , Kenney K., , Gill J., , Stone J.R., , Disner S., , Schnakers C., , Meyer R., , Prager E.M., , Haas M., , and Jeromin A. (2022). A framework to advance biomarker development in the diagnosis, outcome prediction, and treatment of traumatic brain injury. J. Neurotrauma [Epub ahead of print].","journal-title":"J. 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