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Blood samples were collected from collegiate athletes at preseason (baseline), within 6\u00a0h of concussion injury, and at four additional prescribed time points spanning 24\u00a0h to 6\u00a0months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s40279-023-01951-9","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T06:02:55Z","timestamp":1699423375000},"page":"1021-1032","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium 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PLoS ONE. 2017;12(9): e0183113. https:\/\/doi.org\/10.1371\/journal.pone.0183113.","journal-title":"PLoS ONE"}],"container-title":["Sports Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40279-023-01951-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40279-023-01951-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40279-023-01951-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T02:47:54Z","timestamp":1733885274000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40279-023-01951-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["1951"],"URL":"https:\/\/doi.org\/10.1007\/s40279-023-01951-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1753658\/v1","asserted-by":"object"}]},"ISSN":["0112-1642","1179-2035"],"issn-type":[{"value":"0112-1642","type":"print"},{"value":"1179-2035","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"assertion":[{"value":"8 October 2023","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This publication was made possible, in part, with support from the Grand Alliance Concussion Assessment, Research, and Education (CARE) Consortium, funded, in part by the National Collegiate Athletic Association (NCAA) and the Department of Defense (DOD). The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702\u20135014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Combat Casualty Care Research Program, endorsed by the Department of Defense, through the Joint Program Committee 6\/ Combat Casualty Care Research Program\u2014Psychological Health and Traumatic Brain Injury Program under Award No. W81XWH1420151. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Sequencing analysis was carried out in the Center for Medical Genomics at Indiana University School of Medicine, which is partially supported by the Indiana University Grand Challenges Precision Health Initiative. This project was also supported, in part, by the Indiana Clinical and Translational Sciences Institute funded, in part by Grant Number UL1TR002529 from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award. Biospecimens were stored in the CTSI Specimen Storage Facility, which is supported, in part, by grant NIH\/NCRR RR020128.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"Steven Broglio, Thomas McAllister, and Michael McCrea received funding from the NCAA and the Department of Defense to complete this investigation and to cover travel costs related to the study. Paul Pasquina is an employee of the Department of Defense, and has previously received other Department of Defense-related grants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"Patient metadata and gene expression data in the form of raw counts are accessible as part of CARE 1.0 on the Federal Interagency Traumatic Brain Injury Research Informatics System (FITBIR, fitbir.nih.gov). Raw sequence data are available on dbGap (accession number is pending). Criteria for access are determined by each of the entities hosting the data and the governance of their respective regulatory committees.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data Availability"}},{"value":"Ethics approval was granted by the Medical College of Wisconsin Institutional Review Board #2 (PRO00023196) as a Continuing Progress Report (CPR00024178) on 10 October 2022. This study was completed following approval from respective local Institutional Review Boards and the Human Research Protection Office at the US Army Medical Research and Material Command. All study operations were in accordance with the standards outlined in the Declaration of Helsinki.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Written informed consent was obtained from all participants included in the study.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"Not applicable.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"Computer code is available from the authors upon request.","order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code Availability"}},{"value":"Conceptualization, ES and YL; acquisition of data, AB, AJS, CG, DC, JJ, GM, JG JM, KG, KLC, MAM, MH, PFP, SJS, SMD, SPB, SR, and TWM; data curation, ES, KNN, LDR, and MDM; methodology, ES, KNN, JH, JR, and TWM; analysis and interpretation of data, ES, JH, JLR, JR, LDR, YL, and ZZ; resources, MAM, PFP, SPB, TMF, and TWM; writing\u2014original draft, ES and JLR; writing\u2014review and editing, AB, AJS, ES, GM, JH, JLR, JM, JR, KLC, KNN, LDR, MAM, MDM, PFP, SJS, SMD, SPB, SR, TMF, TWM, YL, and ZZ; study supervision, MAM, PFP, SB, TWM, and YL All authors read and approved the final version.","order":9,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author Contributions"}}]}}