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2. Alzheimer’s pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome

Author

Asken, Breton M., Tanner, Jeremy A., Gaynor, Leslie S., VandeVrede, Lawren, Mantyh, William G., Casaletto, Kaitlin B., Staffaroni, Adam M., Fonseca, Corrina, Shankar, Ranjani, Grant, Harli, Smith, Karen, Lago, Argentina Lario, Xu, Haiyan, La Joie, Renaud, Cobigo, Yann, Rosen, Howie, Perry, David C., Rojas, Julio C., Miller, Bruce L., Gardner, Raquel C., Wang, Kevin K. W., Kramer, Joel H., and Rabinovici, Gil D.

Published
2023
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3. Characterization and standardization of multiassay platforms for four commonly studied traumatic brain injury protein biomarkers: a TBI Endpoints Development Study

Author

Sarkis, George Anis, Zhu, Tian, Yang, Zhihui, Li, Xue, Shi, Yuan, Rubenstein, Richard, Yost, Richard A, Manley, Geoffrey T, and Wang, Kevin K

Subjects
Physical Injury - Accidents and Adverse Effects, Traumatic Brain Injury (TBI), Brain Disorders, Dementia, Traumatic Head and Spine Injury, Neurosciences, Acquired Cognitive Impairment, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Antigens, Biological Assay, Biomarkers, Brain Injuries, Traumatic, Case-Control Studies, Endpoint Determination, Glial Fibrillary Acidic Protein, Humans, Recombinant Proteins, Reference Standards, S100 Calcium Binding Protein beta Subunit, Ubiquitin Thiolesterase, tau Proteins, biomarker qualification, GFAP, neurodegeneration, protein biomarkers, S100B, Tau, traumatic brain injury, UCH-L1, Medicinal and Biomolecular Chemistry, Medical Biochemistry and Metabolomics, Clinical Sciences, Oncology & Carcinogenesis
Abstract

Aim: There is a critical need to validate biofluid-based biomarkers as diagnostic and drug development tools for traumatic brain injury (TBI). As part of the TBI Endpoints Development Initiative, we identified four potentially predictive and pharmacodynamic biomarkers for TBI: astroglial markers GFAP and S100B and the neuronal markers UCH-L1 and Tau. Materials & methods: Several commonly used platforms for these four biomarkers were identified and compared on analytic performance and ability to detect gold standard recombinant protein antigens and to pool control versus TBI cerebrospinal fluid (CSF). Results: For each marker, only some assay formats could differentiate TBI CSF from the control CSF. Also, different assays for the same biomarker reported divergent biomarker values for the same biosamples. Conclusion: Due to the variability of TBI marker assay in performance and reported values, standardization strategies are recommended when comparing reported biomarker levels across assay platforms.

Published
2021

8. Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Author

Kulbe, Jacqueline R., Jain, Sonia, Nelson, Lindsay D., Korley, Frederick K., Mukherjee, Pratik, Sun, Xiaoying, Okonkwo, David O., Giacino, Joseph T., Vassar, Mary J., Robertson, Claudia S., McCrea, Michael A., Wang, Kevin K. W., Temkin, Nancy, Mac Donald, Christine L., Taylor, Sabrina R., Ferguson, Adam R., Markowitz, Amy J., Diaz-Arrastia, Ramon, Manley, Geoffrey T., and Stein, Murray B.

Published
2022
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10. Diagnostic performance of point-of-care ubiquitin carboxy-terminal Hydrolase-L1 assay in distinguishing imaging abnormalities in traumatic brain injury: A TRACK-TBI cohort study

Author

Adeoye, Opeolu, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena, Bullock, M. Ross, Chesnut, Randall, Corrigan, John D., Crawford, Karen, Dikmen, Sureyya, Duhaime, Ann-Christine, Ellenbogen, Richard, Feeser, V Ramana, Ferguson, Adam R., Foreman, Brandon, Gardner, Raquel, Gaudette, Etienne, Giacino, Joseph, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J Claude, Hotz, Gillian, Kramer, Joel, Kreitzer, Natalie, Levin, Harvey, Lindsell, Chris, Machamer, Joan, Madden, Christopher, Martin, Alastair, McAllister, Thomas, McCrea, Michael, Merchant, Randall, Nelson, Lindsay, Ngwenya, Laura, Palacios, Eva, Perl, Daniel, Rabinowitz, Miri, Rosand, Jonathan, Sander, Angelle, Satris, Gabriella, Schnyer, David, Seabury, Seth, Toga, Arthur, Valadka, Alex, Vassar, Mary, Vespa, Paul, Zafonte, Ross, Wang, Kevin K., Munoz-Pareja, Jennifer C., Lautenslager, Lauren A., Tyndall, J. Adrian, Yang, Zhihui, Kerrigan, Maria R., Diaz-Arrastia, Ramon, Korley, Frederick K., Okonkwo, David, Puccio, Ava M., Yue, John K., Taylor, Sabrina R., Mukherjee, Pratik, Yuh, Esther L., Temkin, Nancy R., Robertson, Claudia S., Sun, Xiaoying, Jain, Sonia, Markowitz, Amy J., and Manley, Geoffrey T.

Published
2023
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12. Traumatic brain injury: progress and challenges in prevention, clinical care, and research

Author

Maas, Andrew I R, Menon, David K, Manley, Geoffrey T, Abrams, Mathew, Åkerlund, Cecilia, Andelic, Nada, Aries, Marcel, Bashford, Tom, Bell, Michael J, Bodien, Yelena G, Brett, Benjamin L, Büki, András, Chesnut, Randall M, Citerio, Giuseppe, Clark, David, Clasby, Betony, Cooper, D Jamie, Czeiter, Endre, Czosnyka, Marek, Dams-O'Connor, Kristen, De Keyser, Véronique, Diaz-Arrastia, Ramon, Ercole, Ari, van Essen, Thomas A, Falvey, Éanna, Ferguson, Adam R, Figaji, Anthony, Fitzgerald, Melinda, Foreman, Brandon, Gantner, Dashiell, Gao, Guoyi, Giacino, Joseph, Gravesteijn, Benjamin, Guiza, Fabian, Gupta, Deepak, Gurnell, Mark, Haagsma, Juanita A, Hammond, Flora M, Hawryluk, Gregory, Hutchinson, Peter, van der Jagt, Mathieu, Jain, Sonia, Jain, Swati, Jiang, Ji-yao, Kent, Hope, Kolias, Angelos, Kompanje, Erwin J O, Lecky, Fiona, Lingsma, Hester F, Maegele, Marc, Majdan, Marek, Markowitz, Amy, McCrea, Michael, Meyfroidt, Geert, Mikolić, Ana, Mondello, Stefania, Mukherjee, Pratik, Nelson, David, Nelson, Lindsay D, Newcombe, Virginia, Okonkwo, David, Orešič, Matej, Peul, Wilco, Pisică, Dana, Polinder, Suzanne, Ponsford, Jennie, Puybasset, Louis, Raj, Rahul, Robba, Chiara, Røe, Cecilie, Rosand, Jonathan, Schueler, Peter, Sharp, David J, Smielewski, Peter, Stein, Murray B, von Steinbüchel, Nicole, Stewart, William, Steyerberg, Ewout W, Stocchetti, Nino, Temkin, Nancy, Tenovuo, Olli, Theadom, Alice, Thomas, Ilias, Espin, Abel Torres, Turgeon, Alexis F, Unterberg, Andreas, Van Praag, Dominique, van Veen, Ernest, Verheyden, Jan, Vyvere, Thijs Vande, Wang, Kevin K W, Wiegers, Eveline J A, Williams, W Huw, Wilson, Lindsay, Wisniewski, Stephen R, Younsi, Alexander, Yue, John K, Yuh, Esther L, Zeiler, Frederick A, Zeldovich, Marina, and Zemek, Roger

Published
2022
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13. Prognostic value of day-of-injury plasma GFAP and UCH-L1 concentrations for predicting functional recovery after traumatic brain injury in patients from the US TRACK-TBI cohort: an observational cohort study

Author

Adeoye, Opeolu, Badatjia, Neeraj, Duhaime, Ann-Christine, Ferguson, Adam, Foreman, Brandon, Giacino, Joseph T, Gopinath, Shankar, Grandhi, Ramesh, Kitagawa, Ryan, Madden, Christopher, Merchant, Randall, McCrea, Mike, Ngwenya, Laura, Rabinowitz, Miri, Robertson, Claudia, Schnyer, David, Stein, Murray, Vassar, Mary, Wang, Vincent, Valadka, Alex, Zafonte, Ross, Korley, Frederick K, Jain, Sonia, Sun, Xiaoying, Puccio, Ava M, Yue, John K, Gardner, Raquel C, Wang, Kevin K W, Okonkwo, David O, Yuh, Esther L, Mukherjee, Pratik, Nelson, Lindsay D, Taylor, Sabrina R, Markowitz, Amy J, Diaz-Arrastia, Ramon, and Manley, Geoffrey T

Published
2022
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19. An update on diagnostic and prognostic biomarkers for traumatic brain injury

Author

Wang, Kevin K, Yang, Zhihui, Zhu, Tian, Shi, Yuan, Rubenstein, Richard, Tyndall, J Adrian, and Manley, Geoff T

Subjects
Autoimmune Disease, Physical Injury - Accidents and Adverse Effects, Neurodegenerative, Brain Disorders, Dementia, Neurosciences, Traumatic Brain Injury (TBI), Acquired Cognitive Impairment, Clinical Research, Traumatic Head and Spine Injury, 4.2 Evaluation of markers and technologies, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Injuries and accidents, Neurological, Good Health and Well Being, Biomarkers, Brain Injuries, Traumatic, Humans, Liquid Biopsy, Neuroimaging, Prognosis, Severity of Illness Index, traumatic brain injury, diagnostics, theranostics, neurotrauma, Clinical Sciences
Abstract

IntroductionTraumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.

Published
2018

21. Performance of the IMPACT and CRASH prognostic models for traumatic brain injury in a contemporary multicenter cohort: a TRACK-TBI study

Author

Yue, John K., primary, Lee, Young M., additional, Sun, Xiaoying, additional, van Essen, Thomas A., additional, Elguindy, Mahmoud M., additional, Belton, Patrick J., additional, Pisică, Dana, additional, Mikolic, Ana, additional, Deng, Hansen, additional, Kanter, John H., additional, McCrea, Michael A., additional, Bodien, Yelena G., additional, Satris, Gabriela G., additional, Wong, Justin C., additional, Ambati, Vardhaan S., additional, Grandhi, Ramesh, additional, Puccio, Ava M., additional, Mukherjee, Pratik, additional, Valadka, Alex B., additional, Tarapore, Phiroz E., additional, Huang, Michael C., additional, DiGiorgio, Anthony M., additional, Markowitz, Amy J., additional, Yuh, Esther L., additional, Okonkwo, David O., additional, Steyerberg, Ewout W., additional, Lingsma, Hester F., additional, Menon, David K., additional, Maas, Andrew I. R., additional, Jain, Sonia, additional, Manley, Geoffrey T., additional, _, _, additional, Badjatia, Neeraj, additional, Barber, Jason, additional, Chesnut, Randall M., additional, Diaz-Arrastia, Ramon, additional, Duhaime, Ann-Christine, additional, Eagle, Shawn R., additional, Etemad, Leila L., additional, Fabian, Brian, additional, Ferguson, Adam R., additional, Foreman, Brandon, additional, Gardner, Raquel C., additional, Giacino, Joseph T., additional, Gopinath, Shankar, additional, Gotthardt, Christine J., additional, Hamidi, Sabah, additional, Huie, J. Russell, additional, Keene, C. Dirk, additional, Korley, Frederick K., additional, Madhok, Debbie Y., additional, Madden, Christopher, additional, Merchant, Randall, additional, Nelson, Lindsay D., additional, Ngwenya, Laura B., additional, Robertson, Claudia S., additional, Rodgers, Richard B, additional, Schneider, Andrea L. C., additional, Schnyer, David M., additional, Stein, Murray B., additional, Taylor, Sabrina R., additional, Temkin, Nancy R., additional, Torres-Espin, Abel, additional, Tracey, Joye X., additional, Vassar, Mary J., additional, Wang, Kevin K. W., additional, and Zafonte, Ross D., additional

Published
2024
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23. The Traumatic Brain Injury Endpoints Development (TED) Initiative: Progress on a Public-Private Regulatory Collaboration To Accelerate Diagnosis and Treatment of Traumatic Brain Injury

Author

Manley, Geoffrey T, Mac Donald, Christine L, Markowitz, Amy J, Stephenson, Diane, Robbins, Ann, Gardner, Raquel C, Winkler, Ethan, Bodien, Yelena G, Taylor, Sabrina R, Yue, John K, Kannan, Lakshmi, Kumar, Allison, McCrea, Michael A, Wang, Kevin K, and the TED Investigators

Subjects
Physical Injury - Accidents and Adverse Effects, Traumatic Brain Injury (TBI), Traumatic Head and Spine Injury, Clinical Research, Brain Disorders, Neurosciences, Clinical Trials and Supportive Activities, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Injuries and accidents, biomarkers, clinical outcome measures, CT, FDA, MRI, traumatic brain injury, TED Investigators, Clinical Sciences, Neurology & Neurosurgery
Abstract

The Traumatic Brain Injury Endpoints Development (TED) Initiative is a 5-year, Department of Defense-funded project that is working toward the ultimate goal of developing better designed clinical trials, leading to more precise diagnosis, and effective treatments for traumatic brain injury (TBI). TED is comprised of leading academic clinician-scientists, along with innovative industry leaders in biotechnology and imaging technology, patient advocacy organizations, and philanthropists, working collaboratively with regulatory authorities, specifically the U.S. Food and Drug Administration (FDA). The goals of the TED Initiative are to gain consensus and validation of TBI clinical outcome assessment measures and biomarkers for endorsement by global regulatory agencies for use in drug and device development processes. This article summarizes the Initiative's Stage I progress over the first 18 months, including intensive engagement with a number of FDA divisions responsible for review and validation of biomarkers and clinical outcome assessments, progression into the prequalification phase of the FDA's Medical Device Development Tool program for a candidate set of neuroimaging biomarkers, and receipt of the FDA's Recognition of Research Importance Letter and a Letter of Support regarding TBI. Other signal achievements relate to the creation of the TED Metadataset, harmonizing study measures across eight major TBI studies, and the leadership role played by TED investigators in the conversion of the NINDS TBI Common Data Elements to Clinical Data Interchange Standards Consortium standards. This article frames both the near-term expectations and the Initiative's long-term vision to accelerate approval of treatments for patients affected by TBI in urgent need of effective therapies.

Published
2017

24. Expression Profile of the Integrin Receptor Subunits in the Guinea Pig Sclera

Author

Wang, Kevin K, Metlapally, Ravikanth, and Wildsoet, Christine F

Subjects
Allied Health and Rehabilitation Science, Biomedical and Clinical Sciences, Health Sciences, Ophthalmology and Optometry, Animals, Cells, Cultured, Disease Models, Animal, Fibroblasts, Gene Expression Profiling, Guinea Pigs, Integrins, Myopia, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Sclera, sclera, integrin, guinea pig, Ophthalmology & Optometry
Abstract

PurposeThe ocular dimensional changes in myopia reflect increased scleral remodeling, and in high myopia, loss of scleral integrity leads to biomechanical weakening and continued scleral creep. As integrins, a type of cell surface receptors, have been linked to scleral remodeling, they represent potential targets for myopia therapies. As a first step, this study aimed to characterize the integrin subunits at the messenger RNA level in the sclera of the guinea pig, a more recently added but increasingly used animal model for myopia research.MethodsPrimers for α and β integrin subunits were designed using NCBI/UCSC Genome Browser and Primer3 software tools. Total RNA was extracted from normal scleral tissue and isolated cultured scleral fibroblasts, as well as liver and lung, as reference tissues, all from guinea pig. cDNA was produced by reverse transcription, PCR was used to amplify products of predetermined sizes, and products were sequenced using standard methods.ResultsGuinea pig scleral tissue expressed all known integrin alpha subunits except αD and αE. The latter integrin subunits were also not expressed by cultured guinea pig scleral fibroblasts; however, their expression was confirmed in guinea pig liver. In addition, isolated cultured fibroblasts did not express integrin subunits αL, αM, and αX. This difference between results for cultured cells and intact sclera presumably reflects the presence in the latter of additional cell types. Both guinea pig scleral tissue and isolated scleral fibroblasts expressed all known integrin beta subunits. All results were verified through sequencing.ConclusionThe possible contributions of integrins to scleral remodeling make them plausible targets for myopia prevention. Data from this study will help guide future ex vivo and in vitro studies directed at understanding the relationship between scleral integrins and ocular growth regulation in the guinea pig model for myopia.

Published
2017

25. Screening Performance of S100 Calcium-Binding Protein B, Glial Fibrillary Acidic Protein, and Ubiquitin C-Terminal Hydrolase L1 for Intracranial Injury Within Six Hours of Injury and Beyond

Author

Trivedi, Dhanisha, Forssten, Maximilian Peter, Cao, Yang, Mohammad Ismail, Ahmad, Czeiter, Endre, Amrein, Krisztina, Kobeissy, Firas, Wang, Kevin K. W., DeSoucy, Erik, Büki, Andras, Mohseni, Shahin, Trivedi, Dhanisha, Forssten, Maximilian Peter, Cao, Yang, Mohammad Ismail, Ahmad, Czeiter, Endre, Amrein, Krisztina, Kobeissy, Firas, Wang, Kevin K. W., DeSoucy, Erik, Büki, Andras, and Mohseni, Shahin

Abstract

INTRODUCTION: The Scandinavian NeuroTrauma Committee (SNC) guidelines recommend S100B as a screening tool for early detection of Traumatic brain injury (TBI) in patients presenting with an initial Glasgow coma scale (GCS) of 14-15. The objective of the current study was to compare S100B's diagnostic performance within the recommended 6-hour window after injury, compared to GFAP and UCH-L1. The secondary outcome of interest was the ability of these biomarkers in detecting traumatic intracranial pathology beyond the 6-hour mark. METHODS: The Center-TBI core database (2014-2017) was queried for data pertaining to all TBI patients with an initial GCS of 14-15 who had a blood sample taken within 6 hours of injury in which the levels of S100B, GFAP, and UCH-L1 were measured. As a subgroup analysis, data involving patients with blood samples taken within 6-9 hours, and 9-12 hours were analyzed separately for diagnostic ability. The diagnostic ability of these biomarkers for detecting any intracranial injury was evaluated based on the area under the receiver operating characteristic curve (AUC). Each biomarker's sensitivity, specificity, and accuracy were also reported at the cutoff that maximized Youden's index. RESULTS: A total of 531 TBI patients with GCS 14-15 on admission had a blood sample taken within 6 hours, of whom 24.9% (N = 132) had radiologically confirmed intracranial injury. The AUCs of GFAP (0.86, 95% confidence interval (CI): 0.82-0.90) and UCH-L1 (0.81, 95% CI: 0.76-0.85) were statistically significantly higher than that of S100B (0.74, 95% CI: 0.69-0.79) during this time. There was no statistically significant difference in the predictive ability of S100B when sampled within 6 hours, 6-9 hours, and 9-12 hours of injury, as the p-values were >0.05 when comparing the AUCs. Overlapping AUC 95% CI suggests no benefit of a combined GFAP and UCH-L1 screening tool over GFAP during the time periods studied [ 0.87 (0.83-0.90) vs 0.86 (0.82-0.90) when sampled wi, The research leading to these results was supported by the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement no 602150 (CENTER-TBI). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from One Mind(USA), Integra Life Sciences (USA), and Neuro Trauma Sciences (US) and, Stroke for bundet, (SE).

Published
2024
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30. Correction to: Association of day-of-injury plasma glial fibrillary acidic protein concentration and six-month posttraumatic stress disorder in patients with mild traumatic brain injury

Author

Kulbe, Jacqueline R., Jain, Sonia, Nelson, Lindsay D., Korley, Frederick K., Mukherjee, Pratik, Sun, Xiaoying, Okonkwo, David O., Giacino, Joseph T., Vassar, Mary J., Robertson, Claudia S., McCrea, Michael A., Wang, Kevin K. W., Temkin, Nancy, Mac Donald, Christine L., Taylor, Sabrina R., Ferguson, Adam R., Markowitz, Amy J., Diaz-Arrastia, Ramon, Manley, Geoffrey T., and Stein, Murray B.

Published
2022
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35. Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the MouseScleral mi- and mRNA Profiles in Myopia Development

Author

Metlapally, Ravikanth, Park, Han Na, Chakraborty, Ranjay, Wang, Kevin K, Tan, Christopher C, Light, Jacob G, Pardue, Machelle T, and Wildsoet, Christine F

Subjects
Biomedical and Clinical Sciences, Ophthalmology and Optometry, Eye Disease and Disorders of Vision, Genetics, Biotechnology, Human Genome, 1.1 Normal biological development and functioning, Underpinning research, Animals, Disease Models, Animal, Gene Expression Regulation, Genome-Wide Association Study, Mice, Mice, Inbred C57BL, MicroRNAs, Myopia, RNA, Messenger, Real-Time Polymerase Chain Reaction, Refraction, Ocular, Sclera, Sensory Deprivation, Tomography, Optical Coherence, microarray, microRNA, mouse, myopia, sclera, Biological Sciences, Medical and Health Sciences, Ophthalmology & Optometry, Ophthalmology and optometry
Abstract

PurposeMicroRNA (miRNAs) have been previously implicated in scleral remodeling in normal eye growth. They have the potential to be therapeutic targets for prevention/retardation of exaggerated eye growth in myopia by modulating scleral matrix remodeling. To explore this potential, genome-wide miRNA and messenger RNA (mRNA) scleral profiles in myopic and control eyes from mice were studied.MethodsC57BL/6J mice (n = 7; P28) reared under a 12L:12D cycle were form-deprived (FD) unilaterally for 2 weeks. Refractive error and axial length changes were measured using photorefraction and 1310-nm spectral-domain optical coherence tomography, respectively. Scleral RNA samples from FD and fellow control eyes were processed for microarray assay. Statistical analyses were performed using National Institute of Aging array analysis tool; group comparisons were made using ANOVA, and gene ontologies were identified using software available on the Web. Findings were confirmed using quantitative PCR in a separate group of mice (n = 7).ResultsForm-deprived eyes showed myopic shifts in refractive error (-2.02 ± 0.47 D; P < 0.01). Comparison of the scleral RNA profiles of test eyes with those of control eyes revealed 54 differentially expressed miRNAs and 261 mRNAs fold-change >1.25 (maximum fold change = 1.63 and 2.7 for miRNAs and mRNAs, respectively) (P < 0.05; minimum, P = 0.0001). Significant ontologies showing gene over-representation (P < 0.05) included intermediate filament organization, scaffold protein binding, detection of stimuli, calcium ion, G protein, and phototransduction. Significant differential expression of Let-7a and miR-16-2, and Smok4a, Prph2, and Gnat1 were confirmed.ConclusionsScleral mi- and mRNAs showed differential expression linked to myopia, supporting the involvement of miRNAs in eye growth regulation. The observed general trend of relatively small fold-changes suggests a tightly controlled, regulatory mechanism for scleral gene expression.

Published
2016

37. Functional connectivity, tissue microstructure and T2 at 11.1 Tesla distinguishes neuroadaptive differences in two traumatic brain injury models in rats: A Translational Outcomes Project in NeuroTrauma (TOP-NT) UG3 phase study

Author

Kommireddy, Rohan S., primary, Mehra, Shray, additional, Pompilus, Marjory, additional, Arja, R. Daniel, additional, Zhu, Tian, additional, Yang, Zhihui, additional, Fu, Yueqiang, additional, Zhu, Jiepei, additional, Kobeissy, Firas, additional, Wang, Kevin K. W., additional, and Febo, Marcelo, additional

Published
2023
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40. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study

Author

Ackerlund, Cecilia, Amrein, Krisztina, Andelic, Nada, Andreassen, Lasse, Anke, Audny, Antoni, Anna, Audibert, Gérard, Auslands, Kaspars, Azouvi, Philippe, Azzolini, Maria Luisa, Badenes, Rafael, Bartels, Ronald, Barzó, Pál, Beauvais, Romuald, Beer, Ronny, Bellander, Bo-Michael, Belli, Antonio, Benali, Habib, Berardino, Maurizio, Beretta, Luigi, Blaabjerg, Morten, Bragge, Peter, Brazinova, Alexandra, Brinck, Vibeke, Brooker, Joanne, Brorsson, Camilla, Buki, Andras, Bullinger, Monika, Cabeleira, Manuel, Caccioppola, Alessio, Calappi, Emiliana, Calvi, Maria Rosa, Cameron, Peter, Carbayo Lozano, Guillermo, Carbonara, Marco, Castaño-León, Ana M, Chevallard, Giorgio, Chieregato, Arturo, Cnossen, Maryse, Coburn, Mark, Coles, Jonathan, Cooper, Jamie D, Correia, Marta, Čović, Amra, Curry, Nicola, Czeiter, Endre, Czosnyka, Marek, Dahyot-Fizelier, Claire, Dawes, Helen, Degos, Vincent, Della Corte, Francesco, den Boogert, Hugo, Depreitere, Bart, Dijkland, Simone, Đilvesi, Đula, Dixit, Abhishek, Donoghue, Emma, Dreier, Jens, Dulière, Guy-Loup, Ercole, Ari, Esser, Patrick, Ezer, Erzsébet, Fabricius, Martin, Feigin, Valery L, Foks, Kelly, Frisvold, Shirin, Furmanov, Alex, Gagliardo, Pablo, Galanaud, Damien, Gantner, Dashiell, Gao, Guoyi, George, Pradeep, Ghuysen, Alexandre, Giga, Lelde, Glocker, Ben, Golubović, Jagoš, Gomez, Pedro A, Gratz, Johannes, Gravesteijn, Benjamin, Grossi, Francesca, Gruen, Russell L, Gupta, Deepak, Haagsma, Juanita A., Haitsma, Iain, Helbok, Raimund, Helseth, Eirik, Horton, Lindsay, Huijben, Jilske, Hutchinson, Peter J, Jacobs, Bram, Jankowski, Stefan, Jarrett, Mike, Jiang, Ji-yao, Jones, Kelly, Karan, Mladen, Kolias, Angelos G, Kompanje, Erwin, Kondziella, Daniel, Koraropoulos, Evgenios, Koskinen, Lars-Owe, Kovács, Noémi, Lagares, Alfonso, Lanyon, Linda, Laureys, Steven, Lefering, Rolf, Legrand, Valerie, Lejeune, Aurelie, Levi, Leon, Lightfoot, Roger, Lozano, Angels, Maegele, Marc, Majdan, Marek, Manara, Alex, Maréchal, Hugues, Martino, Costanza, Mattern, Julia, McMahon, Catherine, Melegh, Béla, Menovsky, Tomas, Mulazzi, Davide, Muraleedharan, Visakh, Murray, Lynnette, Nair, Nandesh, Negru, Ancuta, Newcombe, Virginia, Nieboer, Daan, Noirhomme, Quentin, Nyirádi, József, Oddo, Mauro, Oresic, Matej, Ortolano, Fabrizio, Otesile, Olubukola, Palotie, Aarno, Parizel, Paul M, Payen, Jean-François, Perera, Natascha, Perlbarg, Vincent, Persona, Paolo, Piippo-Karjalainen, Anna, Pili Floury, Sébastien, Pirinen, Matti, Ples, Horia, Polinder, Suzanne, Pomposo, Inigo, Posti, Jussi P, Puybasset, Louis, Rădoi, Andreea, Ragauskas, Arminas, Raj, Rahul, Rambadagalla, Malinka, Real, Ruben, Rhodes, Jonathan, Richardson, Sylvia, Richter, Sophie, Ripatti, Samuli, Rocka, Saulius, Roe, Cecilie, Roise, Olav, Rosand, Jonathan, Rosenfeld, Jeffrey V, Rosenlund, Christina, Rosenthal, Guy, Rossaint, Rolf, Rossi, Sandra, Rueckert, Daniel, Rusnák, Martin, Sahuquillo, Juan, Sakowitz, Oliver, Sanchez-Porras, Renan, Sandor, Janos, Schäfer, Nadine, Schmidt, Silke, Schoechl, Herbert, Schoonman, Guus, Schou, Rico Frederik, Schwendenwein, Elisabeth, Skandsen, Toril, Smielewski, Peter, Sorinola, Abayomi, Stamatakis, Emmanuel, Stanworth, Simon, Stevanovic, Ana, Stevens, Robert, Stewart, William, Sundström, Nina, Synnot, Anneliese, Takala, Riikka, Tamás, Viktória, Tamosuitis, Tomas, Taylor, Mark Steven, Te Ao, Braden, Tenovuo, Olli, Theadom, Alice, Thomas, Matt, Tibboel, Dick, Timmers, Marjolijn, Tolias, Christos, Trapani, Tony, Tudora, Cristina Maria, Vajkoczy, Peter, Valeinis, Egils, Vallance, Shirley, Vámos, Zoltán, van der Naalt, Joukje, Van der Steen, Gregory, van Dijck, Jeroen T J M, van Essen, Thomas A., Van Hecke, Wim, van Heugten, Caroline, Van Praag, Dominique, van Wijk, Roel P J, Vande Vyvere, Thijs, Vanhaudenhuyse, Audrey, Vargiolu, Alessia, Vega, Emmanuel, Velt, Kimberley, Verheyden, Jan, Vespa, Paul M, Vik, Anne, Vilcinis, Rimantas, Volovici, Victor, Voormolen, Daphne, Vulekovic, Petar, Wang, Kevin K W, Williams, Guy, Wilson, Lindsay, Winzeck, Stefan, Wolf, Stefan, Yang, Zhihui, Ylén, Peter, Younsi, Alexander, Zeiler, Frederick A, Zelinkova, Veronika, Ziverte, Agate, Zoerle, Tommaso, Steyerberg, Ewout W, Wiegers, Eveline, Sewalt, Charlie, Citerio, Giuseppe, De Keyser, Véronique, Kunzmann, Kevin, Lecky, Fiona, Lingsma, Hester, Manley, Geoffrey, Nelson, David, Peul, Wilco, Stocchetti, Nino, von Steinbüchel, Nicole, Maas, Andrew I R, and Menon, David K

Published
2019
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41. Association between plasma GFAP concentrations and MRI abnormalities in patients with CT-negative traumatic brain injury in the TRACK-TBI cohort: a prospective multicentre study

Author

Adeoye, Opeolu M, Badjatia, Neeraj, Boase, Kim, Bodien, Yelena G, Bullock, Malcom R, Chesnut, Randall M, Corrigan, John D, Crawford, Karen, Dikmen, Sureyya S, Duhaime, Ann-Christine, Ellenbogen, Richard G, Feeser, Venkata, Foreman, Brandon, Gardner, Raquel C, Gaudette, Etienne, Giacino, Joseph T, Goldman, Dana P, Gonzalez, Luis, Gopinath, Shankar, Gullapalli, Rao, Hemphill, J C, Hotz, Gillian, Kramer, Joel H, Kreitzer, Natalie P, Levin, Harvey S, Lindsell, Christopher J, Machamer, Joan, Madden, Christopher J, Martin, Alastair J, McAllister, Thomas W, McCrea, Michael, Merchant, Randall, Nelson, Lindsay D, Noel, Florence, Palacios, Eva M, Perl, Daniel P, Puccio, Ava M, Rabinowitz, Miri, Robertson, Claudia S, Rosand, Jonathan, Sander, Angelle M, Satris, Gabriela G, Schnyer, David M, Seabury, Seth A, Sherer, Mark, Stein, Murray B, Temkin, Nancy R, Toga, Arthur W, Valadka, Alex B, Vassar, Mary J, Vespa, Paul M, Yuh, Esther L, Zafonte, Ross, Yue, John K, Korley, Frederick K, Winkler, Ethan A, Sun, Xiaoying, Puffer, Ross C, Deng, Hansen, Choy, Winward, Chandra, Ankush, Taylor, Sabrina R, Ferguson, Adam R, Huie, J Russell, Mukherjee, Pratik, Wang, Kevin K W, Diaz-Arrastia, Ramon, Okonkwo, David O, Jain, Sonia, and Manley, Geoffrey T

Published
2019
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42. Functional Selection of Tau Oligomerization‐Inhibiting Aptamers.

Author

Wang, Bang, Pan, Xiaoshu, Teng, I‐Ting, Li, Xiaowei, Kobeissy, Firas, Wu, Zo‐Yu, Zhu, Jiepei, Cai, Guangzheng, Yan, He, Yan, Xin, Liang, Mingwei, Yu, Fahong, Lu, Jianrong, Yang, Zunyi, Biondi, Elisa, Haskins, William, Cao, Y. Charles, Benner, Steven A., Tan, Weihong, and Wang, Kevin K.

Subjects
TAU proteins, APTAMERS, ALZHEIMER'S disease, TAUOPATHIES, ARACHIDONIC acid, MICROTUBULE-associated proteins, NEURODEGENERATION
Abstract

Pathological hyperphosphorylation and aggregation of microtubule‐associated Tau protein contribute to Alzheimer's Disease (AD) and other related tauopathies. Currently, no cure exists for Alzheimer's Disease. Aptamers offer significant potential as next‐generation therapeutics in biotechnology and the treatment of neurological disorders. Traditional aptamer selection methods for Tau protein focus on binding affinity rather than interference with pathological Tau. In this study, we developed a new selection strategy to enrich DNA aptamers that bind to surviving monomeric Tau protein under conditions that would typically promote Tau aggregation. Employing this approach, we identified a set of aptamer candidates. Notably, BW1c demonstrates a high binding affinity (Kd=6.6 nM) to Tau protein and effectively inhibits arachidonic acid (AA)‐induced Tau protein oligomerization and aggregation. Additionally, it inhibits GSK3β‐mediated Tau hyperphosphorylation in cell‐free systems and okadaic acid‐mediated Tau hyperphosphorylation in cellular milieu. Lastly, retro‐orbital injection of BW1c tau aptamer shows the ability to cross the blood brain barrier and gain access to neuronal cell body. Through further refinement and development, these Tau aptamers may pave the way for a first‐in‐class neurotherapeutic to mitigate tauopathy‐associated neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

Published
2024
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43. 349. The impact of Vancomycin dosing by area under the curve over minimal inhibitory concentration (AUC/MIC) versus Trough levels on cumulative Vancomycin dosage and incidence of Acute Kidney Injury (AKI) in patients admitted to intensive care units (ICU)

Author

Sahu, Aniruddha, primary, Wang, Kevin K, additional, Jurasinski, Philip, additional, Kulkarni, Salil, additional, Weihs, Sayo, additional, Mizusawa, Masako, additional, and Bamberger, David, additional

Published
2023
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47. Autoantibodies in central nervous system trauma: new frontiers for diagnosis and prognosis biomarkers

Author

Kobeissy, Firas H., primary, Ahmad, Fatima, additional, Shaito, Abdullah, additional, Hasan, Hiba, additional, Hady, Samar Abdel, additional, Nasrallah, Leila, additional, Shaito, Nour, additional, Hassan, Houssein Hajj, additional, Zibara, Kazem, additional, Yadikar, Hamad, additional, Yang, Zhihui, additional, Istanbouli, Ayah, additional, and Wang, Kevin K., additional

Published
2020
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48. Neuropsychological testing

Author

Brennan, Jeffrey, primary, Wang, Kevin K., additional, Rubenstein, Richard, additional, Robertson, Claudia S., additional, and Levin, Harvey, additional

Published
2020
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