TY - JOUR AU - Albala, Bruce AU - Appelmans, Eline AU - Burress, Ramona AU - De, Santi Susan AU - Devins, Theresa AU - Klein, Gregory AU - Logovinsky, Veronika AU - Novak, Gerald P. AU - Ribeiro, Kim AU - Schmidt, Mark E. AU - Schwarz, Adam J. AU - Scott, David AU - Shcherbinin, Sergey AU - Siemers, Eric AU - Travaglia, Alessio AU - Weber, Christopher J. AU - White, Leah AU - Wolf-Rodda, Julie AU - Vasanthakumar, Aparna TI - The Alzheimer's Disease Neuroimaging Initiative and the role and contributions of the Private Partners Scientific Board (PPSB) JF - ALZHEIMERS & DEMENTIA J2 - ALZHEIMERS DEMENT VL - 20 PY - 2024 IS - 1 SP - 695 EP - 708 PG - 14 SN - 1552-5260 DO - 10.1002/alz.13483 UR - https://m2.mtmt.hu/api/publication/34238857 ID - 34238857 N1 - Funding Agency and Grant Number: The authors would like to acknowledge the invaluable input and support provided by our colleagues and collaborators Maria C. Carrillo (Alzheimerapos;s Association), Rebecca Edelmayer (Alzheimerapos;s Association), Michael Wiener (ADNI Principal Investiga; Fujirebio [U01 AG024904]; Meso Scale Diagnostics - Alzheimerapos;s Disease Neuroimaging Initiative (ADNI; National Institutes of Health) [W81XWH-12-2-0012]; DOD ADNI (Department of Defense); National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimerapos;s Association; Alzheimerapos;s Drug Discovery Foundation; Araclon Biotech; Biogen; CereSpir, Inc.; Cogstate; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; Janssen Alzheimer Immunotherapy Research amp; Development, LLC; Johnson amp; Johnson Pharmaceutical Research amp; Development LLC; Lumosity; Merck amp; Co., Inc.; Meso Scale Diagnostics, LLC; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; ADNI clinical sites in Canada; Foundation for the National Institutes of Health; Northern California Institute for Research and Education Funding text: The authors would like to acknowledge the invaluable input and support provided by our colleagues and collaborators Maria C. Carrillo (Alzheimer & apos;s Association), Rebecca Edelmayer (Alzheimer & apos;s Association), Michael Wiener (ADNI Principal Investigator-UCSF), John Hsaio (National Institute on Aging), Laurie Ryan (National Institute on Aging), Tolga Turan (Abbvie), Archana Iyer (Abbvie), Fedik Rahimov (Abbvie), Miguel Mendoza (Roche), Martin Guess (Roche), Laura Lenzo (Roche), Fujirebio, EUROIMMUN, Meso Scale Diagnostics, and Saladax/Siemens. ELECSYS is a trademark of Roche. We are grateful for the leadership of the late Dr. John Trojanowski as the co-lead of the ADNI biofluid biomarker core and for helping the biofluid biomarker working group achieve its goals. Data collection and sharing for this project was funded by the Alzheimer & apos;s Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie; Alzheimer & apos;s Association; Alzheimer & apos;s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Saladax/Siemens; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer & apos;s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California on the website USC.LONI.ADNI. AbbVie participated in the interpretation of data, review, and approval of the publication. There is no relevant funding to report for this work. AB - The Alzheimer's Disease Neuroimaging Initiative (ADNI) Private Partners Scientific Board (PPSB) encompasses members from industry, biotechnology, diagnostic, and non-profit organizations that have until recently been managed by the Foundation for the National Institutes of Health (FNIH) and provided financial and scientific support to ADNI programs. In this article, we review some of the major activities undertaken by the PPSB, focusing on those supporting the most recently completed National Institute on Aging grant, ADNI3, and the impact it has had on streamlining biomarker discovery and validation in Alzheimer's disease. We also provide a perspective on the gaps that may be filled with future PPSB activities as part of ADNI4 and beyond. LA - English DB - MTMT ER - TY - JOUR AU - Freire, M.A.M. AU - Rocha, G.S. AU - Bittencourt, L.O. AU - Falcao, D. AU - Lima, R.R. AU - Cavalcanti, J.R.L.P. TI - Cellular and Molecular Pathophysiology of Traumatic Brain Injury: What Have We Learned So Far? JF - BIOLOGY-BASEL J2 - BIOLOGY-BASEL VL - 12 PY - 2023 IS - 8 SN - 2079-7737 DO - 10.3390/biology12081139 UR - https://m2.mtmt.hu/api/publication/34181781 ID - 34181781 N1 - Export Date: 9 October 2023 LA - English DB - MTMT ER - TY - JOUR AU - Harris, Georgia AU - Stickland, Clarissa A. AU - Lim, Matthias AU - Goldberg, Oppenheimer Pola TI - Raman Spectroscopy Spectral Fingerprints of Biomarkers of Traumatic Brain Injury JF - CELLS J2 - CELLS-BASEL VL - 12 PY - 2023 IS - 22 PG - 28 SN - 2073-4409 DO - 10.3390/cells12222589 UR - https://m2.mtmt.hu/api/publication/34511399 ID - 34511399 N1 - Funding Agency and Grant Number: Wellcome Trust Funding text: No Statement Available AB - Traumatic brain injury (TBI) affects millions of people of all ages around the globe. TBI is notoriously hard to diagnose at the point of care, resulting in incorrect patient management, avoidable death and disability, long-term neurodegenerative complications, and increased costs. It is vital to develop timely, alternative diagnostics for TBI to assist triage and clinical decision-making, complementary to current techniques such as neuroimaging and cognitive assessment. These could deliver rapid, quantitative TBI detection, by obtaining information on biochemical changes from patient's biofluids. If available, this would reduce mis-triage, save healthcare providers costs (both over- and under-triage are expensive) and improve outcomes by guiding early management. Herein, we utilize Raman spectroscopy-based detection to profile a panel of 18 raw (human, animal, and synthetically derived) TBI-indicative biomarkers (N-acetyl-aspartic acid (NAA), Ganglioside, Glutathione (GSH), Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase L1 (UCHL1), Cholesterol, D-Serine, Sphingomyelin, Sulfatides, Cardiolipin, Interleukin-6 (IL-6), S100B, Galactocerebroside, Beta-D-(+)-Glucose, Myo-Inositol, Interleukin-18 (IL-18), Neurofilament Light Chain (NFL)) and their aqueous solution. The subsequently derived unique spectral reference library, exploiting four excitation lasers of 514, 633, 785, and 830 nm, will aid the development of rapid, non-destructive, and label-free spectroscopy-based neuro-diagnostic technologies. These biomolecules, released during cellular damage, provide additional means of diagnosing TBI and assessing the severity of injury. The spectroscopic temporal profiles of the studied biofluid neuro-markers are classed according to their acute, sub-acute, and chronic temporal injury phases and we have further generated detailed peak assignment tables for each brain-specific biomolecule within each injury phase. The intensity ratios of significant peaks, yielding the combined unique spectroscopic barcode for each brain-injury marker, are compared to assess variance between lasers, with the smallest variance found for UCHL1 (sigma 2 = 0.000164) and the highest for sulfatide (sigma 2 = 0.158). Overall, this work paves the way for defining and setting the most appropriate diagnostic time window for detection following brain injury. Further rapid and specific detection of these biomarkers, from easily accessible biofluids, would not only enable the triage of TBI, predict outcomes, indicate the progress of recovery, and save healthcare providers costs, but also cement the potential of Raman-based spectroscopy as a powerful tool for neurodiagnostics. LA - English DB - MTMT ER - TY - JOUR AU - Harris, Georgia AU - Rickard, Jonathan James Stanley AU - Butt, Gibran AU - Kelleher, Liam AU - Blanch, Richard James AU - Cooper, Jonathan AU - Oppenheimer, Pola Goldberg TI - Review: Emerging Eye-Based Diagnostic Technologies for Traumatic Brain Injury JF - IEEE REVIEWS IN BIOMEDICAL ENGINEERING J2 - IEEE REV BIOMED ENG VL - 16 PY - 2023 SP - 530 EP - 559 PG - 30 SN - 1937-3333 DO - 10.1109/RBME.2022.3161352 UR - https://m2.mtmt.hu/api/publication/33858664 ID - 33858664 N1 - Funding Agency and Grant Number: Wellcome Trust [174ISSFPP]; Royal Academy of Engineering [RF1415\14\28]; Defence Science and Technology Laboratories [DSTLX-1000098511]; EPSRC [EP/V029983/1] Funding text: This work was supported in part by the Wellcome Trust under Grant 174ISSFPP, in part by the Royal Academy of Engineering under Grant RF1415\14\28, in part by the Defence Science and Technology Laboratories under Grant DSTLX-1000098511, and also in part by the financial support of this work by the EPSRC under Grant EP/V029983/1. AB - The study of ocular manifestations of neurodegenerative disorders, Oculomics, is a growing field of investigation for early diagnostics, enabling structural and chemical biomarkers to be monitored overtime to predict prognosis. Traumatic brain injury (TBI) triggers a cascade of events harmful to the brain, which can lead to neurodegeneration. TBI, termed the "silent epidemic" is becoming a leading cause of death and disability worldwide. There is currently no effective diagnostic tool for TBI, and yet, early-intervention is known to considerably shorten hospital stays, improve outcomes, fasten neurological recovery and lower mortality rates, highlighting the unmet need for techniques capable of rapid and accurate point-of-care diagnostics, implemented in the earliest stages. This review focuses on the latest advances in the main neuropathophysiological responses and the achievements and shortfalls of TBI diagnostic methods. Validated and emerging TBI-indicative biomarkers are outlined and linked to ocular neuro-disorders. Methods detecting structural and chemical ocular responses to TBI are categorised along with prospective chemical and physical sensing techniques. Particular attention is drawn to the potential of Raman spectroscopy as a non-invasive sensing of neurological molecular signatures in the ocular projections of the brain, laying the platform for the first tangible path towards alternative point-of-care diagnostic technologies for TBI LA - English DB - MTMT ER - TY - JOUR AU - Li, Zhigang AU - Quan, Bingxuan AU - Li, Xiuyan AU - Xiong, Wei AU - Peng, Zhibin AU - Liu, Jingsong AU - Wang, Yansong TI - A proteomic and phosphoproteomic landscape of spinal cord injury JF - NEUROSCIENCE LETTERS J2 - NEUROSCI LETT VL - 814 PY - 2023 PG - 9 SN - 0304-3940 DO - 10.1016/j.neulet.2023.137449 UR - https://m2.mtmt.hu/api/publication/34238858 ID - 34238858 N1 - Funding Agency and Grant Number: Natural Science Foundation of China [81871781]; Key Project of Natural Science Foundation of Heilongjiang Province of China [ZD2021H003]; Natural Science Foundation of Inner Mongolia Autonomous Region [2023LHMS08071] Funding text: The study was funded by Natural Science Foundation of China (Project No. 81871781) , Key Project of Natural Science Foundation of Heilongjiang Province of China (Project No. ZD2021H003) and Natural Science Foundation of Inner Mongolia Autonomous Region (Project No. 2023LHMS08071) . AB - Spinal cord injury (SCI) is a devastating trauma of the central nervous system, with high levels of morbidity, disability, and mortality. To explore the underlying mechanism of SCI, we analyzed the proteome and phosphoproteome of rats at one week after SCI. We identified 465 up-regulated and 129 down-regulated differentially expressed proteins (DEPs), as well as 184 up-regulated and 40 down-regulated differentially expressed phosphoproteins (DEPPs). Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these proteins from the perspectives of cell component, biological process, and molecular function. We also found a lot of enriched functional pathways such as GABAergic synapse pathway, ErbB signaling pathway, tight junction, adherens junction. The integrated analysis of proteomics and phosphoproteomics yielded 22 differently expressed co-identified proteins of DEPs and DEPPs, which revealed strongly correlative patterns. These findings may help clarify the potential mechanisms of trauma and repair in SCI and may guide the development of novel treatments. LA - English DB - MTMT ER - TY - JOUR AU - Rauchman, Steven H. AU - Pinkhasov, Aaron AU - Gulkarov, Shelly AU - Placantonakis, Dimitris G. AU - De, Leon Joshua AU - Reiss, Allison B. TI - Maximizing the Clinical Value of Blood-Based Biomarkers for Mild Traumatic Brain Injury JF - DIAGNOSTICS J2 - DIAGNOSTICS VL - 13 PY - 2023 IS - 21 PG - 14 SN - 2075-4418 DO - 10.3390/diagnostics13213330 UR - https://m2.mtmt.hu/api/publication/34430418 ID - 34430418 N1 - Funding Agency and Grant Number: Herb and Evelyn Abrams Family Amyloid Research Fund Funding text: We thank Robert Buescher, Lynn Drucker, and Edmonds Bafford. We also thank The Herb and Evelyn Abrams Family Amyloid Research Fund. The original art in Figure 1 is by Elizabeth Castronovo. AB - Mild traumatic brain injury (TBI) and concussion can have serious consequences that develop over time with unpredictable levels of recovery. Millions of concussions occur yearly, and a substantial number result in lingering symptoms, loss of productivity, and lower quality of life. The diagnosis may not be made for multiple reasons, including due to patient hesitancy to undergo neuroimaging and inability of imaging to detect minimal damage. Biomarkers could fill this gap, but the time needed to send blood to a laboratory for analysis made this impractical until point-of-care measurement became available. A handheld blood test is now on the market for diagnosis of concussion based on the specific blood biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl terminal hydrolase L1 (UCH-L1). This paper discusses rapid blood biomarker assessment for mild TBI and its implications in improving prediction of TBI course, avoiding repeated head trauma, and its potential role in assessing new therapeutic options. Although we focus on the Abbott i-STAT TBI plasma test because it is the first to be FDA-cleared, our discussion applies to any comparable test systems that may become available in the future. The difficulties in changing emergency department protocols to include new technology are addressed. LA - English DB - MTMT ER - TY - JOUR AU - Helmrich, Isabel R A Retel AU - Czeiter, Endre AU - Amrein, Krisztina AU - Büki, András AU - Lingsma, Hester F AU - Menon, David K AU - Mondello, Stefania AU - Steyerberg, Ewout W AU - von Steinbüchel, Nicole AU - Wang, Kevin K W AU - Wilson, Lindsay AU - Xu, Haiyan AU - Yang, Zhihui AU - van Klaveren, David AU - Maas, Andrew I R TI - Incremental prognostic value of acute serum biomarkers for functional outcome after traumatic brain injury (CENTER-TBI): an observational cohort study JF - LANCET NEUROLOGY J2 - LANCET NEUROL VL - 21 PY - 2022 IS - 9 SP - 792 EP - 802 PG - 11 SN - 1474-4422 DO - 10.1016/S1474-4422(22)00218-6 UR - https://m2.mtmt.hu/api/publication/33051550 ID - 33051550 N1 - Funding Agency and Grant Number: European Union's Seventh Framework Programme; Hannelore Kohl Stiftung; OneMind; Integra LifeSciences; NeuroTrauma Sciences Funding text: European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences AB - Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome.We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure.Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009-0·020) and R2 by 4·9% (3·6-6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48-65% for IMPACT and 30-34% for CRASH prognostic models.Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers-particularly UCH-L1-in established prognostic models.European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences. LA - English DB - MTMT ER - TY - JOUR AU - Kocheril, Philip A. AU - Moore, Shepard C. AU - Lenz, Kiersten D. AU - Mukundan, Harshini AU - Lilley, Laura M. TI - Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review JF - BIOMARKER INSIGHTS J2 - BIOMARKER INSIGHTS VL - 17 PY - 2022 PG - 18 SN - 1177-2719 DO - 10.1177/11772719221105145 UR - https://m2.mtmt.hu/api/publication/33047483 ID - 33047483 N1 - Funding Agency and Grant Number: National Nuclear Security Administration of the U.S. Department of Energy [89233218CNA000001]; Samitaur Medical Technologies Inc. Funding text: The authors gratefully acknowledge Mr. Davis Bobbitt for helpful discussions in the planning stages of the review. Figures were created with BioRender.com. This work was performed at the Los Alamos National Laboratory, which is operated by Triad National Security, LLC, for the National Nuclear Security Administration of the U.S. Department of Energy (Contract No. 89233218CNA000001). Many thanks to Samitaur Medical Technologies Inc., Mr. and Mrs. Frederick and Laurie Samitaur Smith for their support of TBI research. AB - Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others present with persistent symptoms that can cause disability, neuropsychological trauma, and even death. Understanding, diagnosing. and treating TBI is extremely complex for many reasons, including the variable biomechanics of head impact. differences in severity and location of injury, and individual patient characteristics. Because of these confounding factors, the development of reliable diagnostics and targeted treatments for brain injury remains elusive. We argue that the development of effective diagnostic and therapeutic strategies for TBI requires a deep understanding of human neurophysiology at the molecular level and that the framework of multiomics may provide some effective solutions for the diagnosis and treatment of this challenging condition. To this end, we present here a comprehensive review of TBI biomarker candidates from across the multiomic disciplines and compare them with known signatures associated with other neuropsychological conditions, including Alzheimer's disease and Parkinson's disease. We believe that this integrated view will facilitate a deeper understanding of the pathophysiology of TBI and its potential links to other neurological diseases. LA - English DB - MTMT ER - TY - JOUR AU - Lilley, Laura M. AU - Sanche, Steven AU - Moore, Shepard C. AU - Salemi, Michelle R. AU - Vu, Dung AU - Iyer, Srinivas AU - Hengartner, Nicolas W. AU - Mukundan, Harshini TI - Methods to capture proteomic and metabolomic signatures from cerebrospinal fluid and serum of healthy individuals JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-022-16598-1 UR - https://m2.mtmt.hu/api/publication/33460358 ID - 33460358 N1 - Export Date: 21 January 2023 AB - Discovery of reliable signatures for the empirical diagnosis of neurological diseases-both infectious and non-infectious-remains unrealized. One of the primary challenges encountered in such studies is the lack of a comprehensive database representative of a signature background that exists in healthy individuals, and against which an aberrant event can be assessed. For neurological insults and injuries, it is important to understand the normal profile in the neuronal (cerebrospinal fluid) and systemic fluids (e.g., blood). Here, we present the first comparative multi-omic human database of signatures derived from a population of 30 individuals (15 males, 15 females, 23-74 years) of serum and cerebrospinal fluid. In addition to empirical signatures, we also assigned common pathways between serum and CSF. Together, our findings provide a cohort against which aberrant signature profiles in individuals with neurological injuries/disease can be assessed-providing a pathway for comprehensive diagnostics and therapeutics discovery. LA - English DB - MTMT ER - TY - JOUR AU - Mainali, Shraddha AU - Aiyagari, Venkatesh AU - Alexander, Sheila AU - Bodien, Yelena AU - Boerwinkle, Varina AU - Boly, Melanie AU - Brown, Emery AU - Brown, Jeremy AU - Claassen, Jan AU - Edlow, Brian L. AU - Fink, Erika L. AU - Fins, Joseph J. AU - Foreman, Brandon AU - Frontera, Jennifer AU - Geocadin, Romergryko G. AU - Giacino, Joseph AU - Gilmore, Emily J. AU - Gosseries, Olivia AU - Hammond, Flora AU - Helbok, Raimund AU - Hemphill, J. Claude AU - Hirsch, Karen AU - Kim, Keri AU - Laureys, Steven AU - Lewis, Ariane AU - Ling, Geoffrey AU - Livesay, Sarah L. AU - McCredie, Victoria AU - McNett, Molly AU - Menon, David AU - Molteni, Erika AU - Olson, DaiWai AU - O'Phelan, Kristine AU - Park, Soojin AU - Polizzotto, Len AU - Provencio, Jose Javier AU - Puybasset, Louis AU - Rao, Chethan P. Venkatasubba AU - Robertson, Courtney AU - Rohaut, Benjamin AU - Rubin, Michael AU - Sharshar, Tarek AU - Shutter, Lori AU - Silva, Gisele Sampaio AU - Smith, Wade AU - Stevens, Robert D. AU - Thibaut, Aurore AU - Vespa, Paul AU - Wagner, Amy K. AU - Ziai, Wendy C. AU - Zink, Elizabeth AU - Suarez, Jose I TI - Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness JF - NEUROCRITICAL CARE J2 - NEUROCRIT CARE VL - 37 PY - 2022 IS - 1 SP - 326 EP - 350 PG - 25 SN - 1541-6933 DO - 10.1007/s12028-022-01505-3 UR - https://m2.mtmt.hu/api/publication/32993758 ID - 32993758 N1 - Export Date: 3 August 2022 AB - This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article. LA - English DB - MTMT ER - TY - JOUR AU - Osmanlioglu, Yusuf AU - Parker, Drew AU - Alappatt, Jacob A. AU - Gugger, James J. AU - Diaz-Arrastia, Ramon R. AU - Whyte, John AU - Kim, Junghoon J. AU - Verma, Ragini TI - Connectomic assessment of injury burden and longitudinal structural network alterations in moderate-to-severe traumatic brain injury JF - HUMAN BRAIN MAPPING J2 - HUM BRAIN MAPP VL - 43 PY - 2022 IS - 13 SP - 3944 EP - 3957 PG - 14 SN - 1065-9471 DO - 10.1002/hbm.25894 UR - https://m2.mtmt.hu/api/publication/33460359 ID - 33460359 N1 - Export Date: 21 January 2023 CODEN: HBMAE AB - Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network-wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been relatively limited. In this study, we propose a novel connectomic measure that we call network normality score (NNS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate-to-severe TBI patients, we demonstrate that structural network topology of patients is more heterogeneous and significantly different than that of healthy controls at 3 months postinjury, where dissimilarity further increases up to 12 months. We also show that NNS captures injury burden as quantified by posttraumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally, we compare NNS to major graph theory measures used in TBI literature and demonstrate the superiority of NNS in characterizing the disease. LA - English DB - MTMT ER - TY - JOUR AU - Van, Der Naalt J. AU - Jacobs, B. TI - Highlights mild traumatic brain injury 2021 JF - CURRENT OPINION IN ANAESTHESIOLOGY J2 - CURR OPIN ANESTHESIO VL - 35 PY - 2022 IS - 5 SP - 577 EP - 582 PG - 6 SN - 0952-7907 DO - 10.1097/ACO.0000000000001177 UR - https://m2.mtmt.hu/api/publication/33110370 ID - 33110370 N1 - Export Date: 26 September 2022 CODEN: COAEE Correspondence Address: Van Der Naalt, J.; Department of Neurology AB51, Hanzeplein 1, Netherlands; email: j.van.der.naalt@umcg.nl AB - PurposeMild traumatic brain injury (TBI) is one of the most common causes of morbidity worldwide. Patients at risk of unfavourable outcome may benefit from additional attention and help but identification of these patients necessitates the development of diagnostic methods to assess indices of brain injury at an early stage. The aim of this overview is to highlight studies that reflect the growing scientific attention to the early diagnosis and prognostication of mild TBI.Recent findingsThe value of serum biomarkers for the diagnosis of TBI severity has been acknowledged in recent studies. The diagnostic and prognostic utility of several biomarkers of brain injury, such as glial fibrillary acidic protein, and of inflammation, such as interleukin (IL)-6 and IL-10, holds promise for application in daily clinical practice in a point-of-care platform. Besides head CT imaging, early advanced MRI brain imaging has been reported as a tool for assessment of injury severity and prognostication. The introduction of direct oral anticoagulants (DOACs) has raised new challenges for the treatment of intracranial traumatic haemorrhage at the Emergency Department.SummaryPromising findings of new diagnostic markers of brain injury severity highlight the potential prognostic value of serum biomarkers and early MRI imaging. The accurate assessment of patients at risk of incomplete recovery after mTBI will enhance more timely and individualized treatment. © 2022 Lippincott Williams and Wilkins. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Wu, Taotao AU - Rifkin, Jared A. AU - Rayfield, Adam C. AU - Anderson, Erin D. AU - Panzer, Matthew B. AU - Meaney, David F. TI - Concussion Prone Scenarios: A Multi-Dimensional Exploration in Impact Directions, Brain Morphology, and Network Architectures Using Computational Models JF - ANNALS OF BIOMEDICAL ENGINEERING J2 - ANN BIOMED ENG VL - 50 PY - 2022 IS - 11 SP - 1423 EP - 1436 PG - 14 SN - 0090-6964 DO - 10.1007/s10439-022-03085-x UR - https://m2.mtmt.hu/api/publication/33460357 ID - 33460357 N1 - Export Date: 21 January 2023 CODEN: ABMEC AB - While individual susceptibility to traumatic brain injury (TBI) has been speculated, past work does not provide an analysis considering how physical features of an individual's brain (e.g., brain size, shape), impact direction, and brain network features can holistically contribute to the risk of suffering a TBI from an impact. This work investigated each of these features simultaneously using computational modeling and analyses of simulated functional connectivity. Unlike the past studies that assess the severity of TBI based on the quantification of brain tissue damage (e.g., principal strain), we approached the brain as a complex network in which neuronal oscillations orchestrate to produce normal brain function (estimated by functional connectivity) and, to this end, both the anatomical damage location and its topological characteristics within the brain network contribute to the severity of brain function disruption and injury. To represent the variations in the population, we analyzed a publicly available database of brain imaging data and selected five distinct network architectures, seven different brain sizes, and three uniaxial head rotational conditions to study the consequences of 74 virtual impact scenarios. Results show impact direction produces the most significant change in connections across brain areas (structural connectome) and the functional coupling of activity across these brain areas (functional connectivity). Axial rotations were more injurious than those with sagittal and coronal rotations when the head kinematics were the same for each condition. When the impact direction was held constant, brain network architecture showed a significantly different vulnerability across axial and sagittal, but not coronal rotations. As expected, brain size significantly affected the expected change in structural and functional connectivity after impact. Together, these results provided groupings of predicted vulnerability to impact-a subgroup of male brain architectures exposed to axial impacts were most vulnerable, while a subgroup of female brain architectures was the most tolerant to the sagittal impacts studied. These findings lay essential groundwork for subject-specific analyses of concussion and provide invaluable guidance for designing personalized protection equipment. LA - English DB - MTMT ER - TY - JOUR AU - Agoston, Denes V. TI - COVID-19 and Traumatic Brain Injury (TBI); What We Can Learn From the Viral Pandemic to Better Understand the Biology of TBI, Improve Diagnostics and Develop Evidence-Based Treatments JF - FRONTIERS IN NEUROLOGY J2 - FRONT NEUR VL - 12 PY - 2021 PG - 6 SN - 1664-2295 DO - 10.3389/fneur.2021.752937 UR - https://m2.mtmt.hu/api/publication/32998924 ID - 32998924 N1 - Export Date: 21 January 2023 LA - English DB - MTMT ER - TY - JOUR AU - Carmichael, J. AU - Hicks, A.J. AU - Spitz, G. AU - Gould, K.R. AU - Ponsford, J. TI - Moderators of gene-outcome associations following traumatic brain injury JF - NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS J2 - NEUROSCI BIOBEHAV R VL - 130 PY - 2021 SP - 107 EP - 124 PG - 18 SN - 0149-7634 DO - 10.1016/j.neubiorev.2021.08.015 UR - https://m2.mtmt.hu/api/publication/32195759 ID - 32195759 N1 - Monash-Epworth Rehabilitation Research Centre, Epworth HealthCare, Melbourne, Australia Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Australia Export Date: 13 September 2021 CODEN: NBRED Correspondence Address: Carmichael, J.; Monash-Epworth Rehabilitation Research Centre, 185–187 Hoddle Street, Australia; email: jai.carmichael@monash.edu LA - English DB - MTMT ER - TY - JOUR AU - Gradisek, Primoz AU - Carrara, Greta AU - Antiga, Luca AU - Bottazzi, Barbara AU - Chieregato, Arturo AU - Csomós, Ákos AU - Fainardi, Enrico AU - Filekovic, Suada AU - Fleming, Joanne AU - Hadjisavvas, Andreas AU - Kaps, Rafael AU - Kyprianou, Theodoros AU - Latini, Roberto AU - Lazar, Isaac AU - Masson, Serge AU - Mikaszewska-Sokolewicz, Malgorzata AU - Novelli, Deborah AU - Paci, Giulia AU - Xirouchaki, Nektaria AU - Zanier, Elisa AU - Nattino, Giovanni AU - Bertolini, Guido TI - Prognostic Value of a Combination of Circulating Biomarkers in Critically Ill Patients with Traumatic Brain Injury: Results from the European CREACTIVE Study JF - JOURNAL OF NEUROTRAUMA J2 - J NEUROTRAUM VL - 38 PY - 2021 IS - 19 SP - 2667 EP - 2676 PG - 10 SN - 0897-7151 DO - 10.1089/neu.2021.0066 UR - https://m2.mtmt.hu/api/publication/32193801 ID - 32193801 N1 - Funding Agency and Grant Number: European UnionEuropean Commission [602714] Funding text: The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement number 602714. AB - Individualized patient care is essential to reduce the global burden of traumatic brain injury (TBI). This pilot study focused on TBI patients admitted to intensive care units (ICUs) and aimed at identifying patterns of circulating biomarkers associated with the disability level at 6 months from injury, measured by the extended Glasgow Outcome Scale (GOS-E). The concentration of 107 biomarkers, including proteins related to inflammation, innate immunity, TBI, and central nervous system, were quantified in blood samples collected on ICU admission from 80 patients. Patients were randomly selected among those prospectively enrolled in the Collaborative Research on Acute Traumatic Brain Injury in Intensive Care Medicine in Europe (CREACTIVE) observational study. Six biomarkers were selected to be associated with indicators of primary or secondary brain injury: three glial proteins (glial cell-derived neurotrophic factor, glial fibrillary acidic protein, and S100 calcium-binding protein B) and three cytokines (stem cell factor, fibroblast growth factor [FGF] 23 and FGF19). The subjects were grouped into three clusters according to the expression of these proteins. The distribution of the 6-month GOS-E was significantly different across clusters (p < 0.001). In two clusters, the number of 6-month deaths or vegetative states was significantly lower than expected, as calculated according to a customization of the corticosteroid randomization after significant head injury (CRASH) scores (observed/expected [O/E] events = 0.00, 95% confidence interval [CI]: 0.00-0.90 and 0.00, 95% CI: 0.00-0.94). In one cluster, less-than-expected unfavorable outcomes (O/E = 0.50, 95% CI: 0.05-0.95) and more-than-expected good recoveries (O/E = 1.55, 95% CI: 1.05-2.06) were observed. The improved prognostic accuracy of the pattern of these six circulating biomarkers at ICU admission upon established clinical parameters and computed tomography results needs validation in larger, independent cohorts. Nonetheless, the results of this pilot study are promising and will prompt further research in personalized medicine for TBI patients. LA - English DB - MTMT ER - TY - JOUR AU - Czeiter, Endre AU - Amrein, Krisztina AU - Gravesteijn, Benjamin Y AU - Lecky, Fiona AU - Menon, David K AU - Mondello, Stefania AU - Newcombe, Virginia F J AU - Richter, Sophie AU - Steyerberg, Ewout W AU - Vyvere, Thijs Vande AU - Verheyden, Jan AU - Xu, Haiyan AU - Yang, Zhihui AU - Maas, Andrew I R AU - Wang, Kevin K W AU - Büki, András TI - Blood biomarkers on admission in acute traumatic brain injury : Relations to severity, CT findings and care path in the CENTER-TBI study JF - EBIOMEDICINE J2 - EBIOMEDICINE VL - 56 PY - 2020 PG - 11 SN - 2352-3964 DO - 10.1016/j.ebiom.2020.102785 UR - https://m2.mtmt.hu/api/publication/31328719 ID - 31328719 N1 - * Megosztott szerzőség AB - Serum biomarkers may inform and improve care in traumatic brain injury (TBI). We aimed to correlate serum biomarkers with clinical severity, care path and imaging abnormalities in TBI, and explore their incremental value over clinical characteristics in predicting computed tomographic (CT) abnormalities.We analyzed six serum biomarkers (S100B, NSE, GFAP, UCH-L1, NFL and t-tau) obtained <24 h post-injury from 2867 patients with any severity of TBI in the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) Core Study, a prospective, multicenter, cohort study. Univariable and multivariable logistic regression analyses were performed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals.All biomarkers scaled with clinical severity and care path (ER only, ward admission, or ICU), and with presence of CT abnormalities. GFAP achieved the highest discrimination for predicting CT abnormalities (AUC 0•89 [95%CI: 0•87-0•90]), with a 99% likelihood of better discriminating CT-positive patients than clinical characteristics used in contemporary decision rules. In patients with mild TBI, GFAP also showed incremental diagnostic value: discrimination increased from 0•84 [95%CI: 0•83-0•86] to 0•89 [95%CI: 0•87-0•90] when GFAP was included. Results were consistent across strata, and injury severity. Combinations of biomarkers did not improve discrimination compared to GFAP alone.Currently available biomarkers reflect injury severity, and serum GFAP, measured within 24 h after injury, outperforms clinical characteristics in predicting CT abnormalities. Our results support the further development of serum GFAP assays towards implementation in clinical practice, for which robust clinical assay platforms are required.CENTER-TBI study was supported by the European Union 7th Framework program (EC grant 602150). LA - English DB - MTMT ER - TY - JOUR AU - Fidali, Brian C. AU - Stevens, Robert D. AU - Claassen, Jan TI - Novel approaches to prediction in severe brain injury JF - CURRENT OPINION IN NEUROLOGY J2 - CURR OPIN NEUROL VL - 33 PY - 2020 IS - 6 SP - 669 EP - 675 PG - 7 SN - 1350-7540 DO - 10.1097/WCO.0000000000000875 UR - https://m2.mtmt.hu/api/publication/32519800 ID - 32519800 N1 - Funding Agency and Grant Number: NIH [UG3NS106937, R01 NS106014, R03 NS112760]; Johns Hopkins University; DANA Foundation; James S. McDonnell Foundation Funding text: RDS is supported by grant funding from the NIH UG3NS106937 and by a Discovery Award from Johns Hopkins University; JC is supported by grant funding from the NIH R01 NS106014 and R03 NS112760, the DANA Foundation and the James S. McDonnell Foundation. AB - Purpose of review Recovery after severe brain injury is variable and challenging to accurately predict at the individual patient level. This review highlights new developments in clinical prognostication with a special focus on the prediction of consciousness and increasing reliance on methods from data science. Recent findings Recent research has leveraged serum biomarkers, quantitative electroencephalography, MRI, and physiological time-series to build models for recovery prediction. The analysis of high-resolution data and the integration of features from different modalities can be approached with efficient computational techniques. Advances in neurophysiology and neuroimaging, in combination with computational methods, represent a novel paradigm for prediction of consciousness and functional recovery after severe brain injury. Research is needed to produce reliable, patient-level predictions that could meaningfully impact clinical decision making. LA - English DB - MTMT ER -