{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T21:46:30Z","timestamp":1783201590817,"version":"3.54.6"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T00:00:00Z","timestamp":1583366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS097549"],"award-info":[{"award-number":["R01NS097549"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS069545"],"award-info":[{"award-number":["U01NS069545"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Traumatic brain injury (TBI) can cause biochemical and metabolomic alterations in the brain tissue and serum. These alterations can be used for diagnosis and prognosis of TBI. Here, the serum concentrations of seventeen amino acids (AA) were studied for their potential utility as biomarkers of TBI. Twenty-five female, 4-week-old piglets received diffuse (n = 13) or focal (n = 12) TBI. Blood samples were obtained both pre-injury and at either 24-h or 4-days post-TBI. To find a robust panel of biomarkers, the results of focal and diffuse TBIs were combined and multivariate logistic regression analysis, coupled with the best subset selection technique and repeated k-fold cross-validation method, was used to perform a thorough search of all possible subsets of AAs. The combination of serum glycine, taurine, and ornithine was optimal for TBI diagnosis, with 80% sensitivity and 86% overall prediction rate, and showed excellent TBI diagnostic performance, with 100% sensitivity and 78% overall prediction rate, on a separate validation dataset including four uninjured and five injured animals. We found that combinations of biomarkers outperformed any single biomarker. We propose this 3-AA serum biomarker panel to diagnose mild-to-moderate focal\/diffuse TBI. The systematic approaches implemented herein can be used for combining parameters from various TBI assessments to develop\/evaluate optimal multi-factorial diagnostic\/prognostic TBI metrics.<\/jats:p>","DOI":"10.3390\/ijms21051786","type":"journal-article","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T07:33:46Z","timestamp":1583480026000},"page":"1786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Using Serum Amino Acids to Predict Traumatic Brain Injury: A Systematic Approach to Utilize Multiple Biomarkers"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-2447","authenticated-orcid":false,"given":"Marzieh","family":"Hajiaghamemar","sequence":"first","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd","family":"Kilbaugh","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1694-4562","authenticated-orcid":false,"given":"Kristy B.","family":"Arbogast","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Injury Research and Prevention, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-4270","authenticated-orcid":false,"given":"Christina L.","family":"Master","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Center for Injury Research and Prevention, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"},{"name":"Sports Medicine and Performance Center, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan S.","family":"Margulies","sequence":"additional","affiliation":[{"name":"Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.expneurol.2019.04.019","article-title":"Toward development of clinically translatable diagnostic and prognostic metrics of traumatic brain injury using animal models: A review and a look forward","volume":"318","author":"Hajiaghamemar","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4928","DOI":"10.1007\/s12035-017-0687-z","article-title":"Traumatic brain injury alters the metabolism and facilitates Alzheimer\u2019s disease in a murine model","volume":"55","author":"Lou","year":"2018","journal-title":"Mol. 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