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Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanismsThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.
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Rationale and Methods for Updated Guidelines for the Management of Penetrating Traumatic Brain Injury.Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and healthcare costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. A preliminary literature search revealed a need for updated guidelines, supported by the Brain Trauma Foundation. Methodologists experienced in TBI guidelines were recruited to support project development alongside two cochairs and a diverse steering committee. An expert multi-disciplinary workgroup was established and vetted to inform key clinical questions, to perform an evidence review and the development of recommendations relevant to pTBI. The methodological approach for the project was finalized. The development of up-to-date evidence- and consensus-based clinical care guidelines and algorithms for pTBI will provide critical guidance to care providers in the pre-hospital and emergent, medical, and surgical settings.
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Defining a Research Agenda for Layperson Prehospital Hemorrhage ControlImportance: Trauma is the leading cause of death for US individuals younger than 45 years, and uncontrolled hemorrhage is a major cause of trauma mortality. The US military's medical advancements in the field of prehospital hemorrhage control have reduced battlefield mortality by 44%. However, despite support from many national health care organizations, no integrated approach to research has been made regarding implementation, epidemiology, education, and logistics of prehospital hemorrhage control by layperson immediate responders in the civilian sector. Objective: To create a national research agenda to help guide future work for prehospital hemorrhage control by laypersons. Evidence Review: The 2-day, in-person, National Stop the Bleed (STB) Research Consensus Conference was conducted on February 27 to 28, 2019, to identify and achieve consensus on research gaps. Participants included (1) subject matter experts, (2) professional society-designated leaders, (3) representatives from the federal government, and (4) representatives from private foundations. Before the conference, participants were provided a scoping review on layperson prehospital hemorrhage control. A 3-round modified Delphi consensus process was conducted to determine high-priority research questions. The top items, with median rating of 8 or more on a Likert scale of 1 to 9 points, were identified and became part of the national STB research agenda. Findings: Forty-five participants attended the conference. In round 1, participants submitted 487 research questions. After deduplication and sorting, 162 questions remained across 5 a priori-defined themes. Two subsequent rounds of rating generated consensus on 113 high-priority, 27 uncertain-priority, and 22 low-priority questions. The final prioritized research agenda included the top 24 questions, including 8 for epidemiology and effectiveness, 4 for materials, 9 for education, 2 for global health, and 1 for health policy. Conclusions and Relevance: The National STB Research Consensus Conference identified and prioritized a national research agenda to support laypersons in reducing preventable deaths due to life-threatening hemorrhage. Investigators and funding agencies can use this agenda to guide their future work and funding priorities.