Human cerebrovascular function in health and disease: insights from integrative approaches

Abstract Background The marked increase in the size of the brain, and consequently, in neural processing capability, throughout human evolution is the basis of the higher cognitive function in humans. However, greater neural, and thus information processing capability, comes at a significant metabolic cost; despite its relatively small size, the modern human brain consumes almost a quarter of the glucose and oxygen supply in the human body. Fortunately, several vascular mechanisms ensure sufficient delivery of glucose and oxygen to the active neural tissue (neurovascular coupling), prompt removal of neural metabolic by-products (cerebral vasoreactivity), and constant global blood supply despite daily variations in perfusion pressure (cerebral autoregulation). The aim of this review is to provide an integrated overview of the available data on these vascular mechanisms and their underlying physiology. We also briefly review modern experimental approaches to assess these mechanisms in humans, and further highlight the importance of these mechanisms for humans’ evolutionary success by providing examples of their healthy adaptations as well as pathophysiological alterations. Conclusions Data reviewed in this paper demonstrate the importance of the cerebrovascular function to support humans’ unique ability to form new and different interactions with each other and their surroundings. This highlights that there is much insight into the neural and cognitive functions that could be gleaned from interrogating the cerebrovascular function

Characterization of Million Veteran Program (MVP) enrollees with Comprehensive Traumatic Brain Injury Evaluation (CTBIE) data: An analysis of neurobehavioral symptoms

The purpose of this study was to examine neurobehavioral symptom reporting in a large sample of military veterans (N = 12,144) who completed the Comprehensive Traumatic Brain Injury Evaluation (CTBIE) and enrolled in the VA's Million Veteran Program (MVP). The CTBIE is a clinician-administered interview that assesses for historical, deployment-related traumatic brain injury (TBI) and evaluates symptoms using the Neurobehavioral Symptom Inventory (NSI). Clinicians completing the CTBIE made clinical determinations about participants' (1) TBI diagnostic status (i.e., CTBIE+ or CTBIE-) and (2) current symptom etiology (i.e., Symptom Resolution, TBI, Behavioral Health, Comorbid TBI + Behavioral Health [Comorbid], or Other). We evaluated the association of TBI diagnostic status and symptom etiology group with neurobehavioral symptoms. Results showed a significant association between TBI diagnostic status and all NSI variables, with CTBIE+ veterans endorsing greater symptoms than CTBIE- veterans. There was also a significant association between symptom etiology group and all NSI variables; specifically, the Comorbid and Behavioral Health groups generally endorsed significantly greater symptoms compared to the other groups. Follow-up analyses showed that relative to the Symptom Resolution group, the Comorbid and Behavioral Health groups had increased odds of severe/very severe cognitive and affective symptoms, whereas the TBI and Other groups did not. Finally, presence of psychiatric symptoms, pain, post-traumatic amnesia, loss of consciousness, and blast exposure significantly predicted Comorbid symptom etiology group membership. Findings from this large epidemiologic MVP study have relevant clinical implications and further highlight the importance of prioritizing integrated behavioral health interventions for this vulnerable population

CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

BackgroundThe Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.ResultsPerformance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic.ConclusionsResults show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead

Data from an International Multi-Centre Study of Statistics and Mathematics Anxieties and Related Variables in University Students (the SMARVUS Dataset)

This large, international dataset contains survey responses from N = 12,570 students from 100 universities in 35 countries, collected in 21 languages. We measured anxieties (statistics, mathematics, test, trait, social interaction, performance, creativity, intolerance of uncertainty, and fear of negative evaluation), self-efficacy, persistence, and the cognitive reflection test, and collected demographics, previous mathematics grades, self-reported and official statistics grades, and statistics module details. Data reuse potential is broad, including testing links between anxieties and statistics/mathematics education factors, and examining instruments’ psychometric properties across different languages and contexts. Data and metadata are stored on the Open Science Framework website (https://osf.io/mhg94/)

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field