Journal of neurotrauma
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Journal of neurotrauma · Jun 2021
Operation Brain Trauma Therapy (OBTT): the use of machine learning to re-assess patterns of multivariate functional recovery following fluid percussion injury.
Traumatic brain injury (TBI) is a leading cause of death and disability. Yet, despite immense research efforts, treatment options remain elusive. Translational failures in TBI are often attributed to the heterogeneity of the TBI population and limited methods to capture these individual variabilities. ⋯ In all but one of the possible pairwise combinations of minocycline, levetiracetam, erythropoietin, nicotinamide, and amantadine, the baseline was outperformed by one or more supervised classifiers, the exception being nicotinamide versus amantadine. Further, when the same methods were employed to assess different doses of the same treatment, the ML classifiers had greater difficulty in understanding which treatment each sample received. Our data serve as a critical first step toward identifying optimal treatments for specific subgroups of samples that are dependent on factors such as types and severity of traumatic injuries, as well as informing the prediction of therapeutic combinations that may lead to greater treatment effects than individual therapies.
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Journal of neurotrauma · Jun 2021
Interactive TutorialAssessment of compression driven shock tube designs in replicating free-field blast conditions for TBI studies.
Compression driven shock tubes are indispensable in studies of blast-induced traumatic brain injury (bTBI). The ability of shock tubes in faithfully recreating free-field blast conditions is of enormous interest and has a direct impact on injury outcomes. Toward this end, the evolution of blast wave inside and outside of the compression driven shock tube has been studied using validated, finite element based shock tube models. ⋯ Locations outside the shock tube are affected by jet-wind effects because of the sudden expansion, barring a narrow region at the exit. For the desired overpressure yield inferred in bTBI, obtaining positive phase durations of <1 msec inside the shock tube, which are sought for studies in rodents, is challenging. Overall, these results underscore that replicating free-field blast conditions using a shock tube involves tradeoffs that need to be weighed carefully and their effect on injury outcomes should be evaluated during laboratory bTBI investigations.
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Journal of neurotrauma · Jun 2021
Differential DNA methylation of the genes for amyloid precursor protein, tau and neurofilaments in human traumatic brain injury.
Traumatic brain injury (TBI) is an established risk factor for neurodegenerative disorders and dementias. Epigenetic modifications, such as DNA methylation, may alter the expression of genes without altering the DNA sequence in response to environmental factors. We hypothesized that DNA methylation changes may occur in the injured human brain and be implicated in the neurodegenerative aftermath of TBI. ⋯ Among the top 20 differentially methylated CpG sites, 11 were in the APP gene. In addition, the EWAS evaluating 828,888 CpG sites revealed 308 differentially methylated CpG sites in genes related to cellular/anatomical structure development, cell differentiation, and anatomical morphogenesis. These preliminary findings provide the first evidence of an altered DNA methylome in the injured human brain, and may have implications for the neurodegenerative disorders associated with TBI.
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Journal of neurotrauma · Jun 2021
Imaging markers for the characterization of grey and white matter changes from acute to chronic stages after experimental traumatic brain injury.
Despite clinical symptoms, a large majority of people with mild traumatic brain injury (TBI) have normal computed tomography (CT) and magnetic resonance imaging (MRI) scans. Therefore, present-day neuroimaging tools are insufficient to diagnose or classify low grades of TBI. Advanced neuroimaging techniques, such as diffusion-weighted and functional MRI, may yield novel biomarkers that may aid in the diagnosis of TBI. ⋯ No significant changes in individual outcome measures were detected after mild TBI. However, multivariate analysis showed a significant additive contribution of diffusion parameters in the distinction between control and different grades of TBI-affected brains. Therefore, combining multiple imaging markers may increase the sensitivity for TBI-related pathology.
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Journal of neurotrauma · Jun 2021
Multicenter StudyMissing data in prediction research: A five step approach for multiple imputation, illustrated in the CENTER-TBI study.
In medical research, missing data is common. In acute diseases, such as traumatic brain injury (TBI), even well-conducted prospective studies may suffer from missing data in baseline characteristics and outcomes. Statistical models may simply drop patients with any missing values, potentially leaving a selected subset of the original cohort. ⋯ We hereto propose a five-step approach, centered around single and multiple imputation: 1) explore the missing data patterns; 2) choose a method of imputation; 3) perform imputation; 4) assess diagnostics of the imputation; and 5) analyze the imputed data sets. We illustrate these five steps with the estimation and validation of the IMPACT (International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury) prognostic model in 1375 patients from the CENTER-TBI database, included in 53 centers across 17 countries, with moderate or severe TBI in the prospective European CENTER-TBI study. Future prediction modeling studies in acute diseases may benefit from following the suggested five steps for optimal statistical analysis and interpretation, after maximal effort has been made to minimize missing data.