bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning with Objective Serum Markers and Algorithmic Deep Learning Computed Tomography Scan Analysis for Classification of Brain Injury
Authors: Rafter Daniel , Li Zhuliu , Schaaf Tory , Gault Kristen , Thorpe Maxwell , Venkatesh Shivani , Edpuganti Radhika , Song Tianci , Kuang Rui , Samadani Uzma 
Published: February 2021

AbstractBackgroundBrain injury is pathophysiologically diverse, with many cases presenting with mixed pathologies. Utilizing objective measures to investigate the pathophysiology of injury would aid in understanding prognosis and targeting therapeutics.ObjectiveThe goal of this study is to develop a traumatic brain injury classification scheme based on open source deep learning computer tomography (CT) analysis and the two serum biomarkers, glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal L1 (UCH-L1).MethodsMachine learning was utilized to develop a novel algorithm capable of classifying the type of brain injury based on a CT scan analysis algorithm and GFAP and UCH-L1 concentrations. Injury was stratified into one of four groups: spontaneous hemorrhage, oxygen deprivation, trauma resulting in vascular injury or high-velocity trauma with negative CT scan.Outcomes100 research subjects were enrolled. Using a combination of CT analysis and serum markers, the subjects with CT positive trauma were distinguishable from those with spontaneous hemorrhage, ischemic injury, CT negative trauma and controls with AUCs of 0.96, 0.99., 0.98 and 1.00 respectively. Ischemic injury was distinguishable from CT positive trauma with an AUC of 0.98. All forms of brain injury could be distinguished from controls with AUC = 1.00.DiscussionAn open source algorithmic CT scan analysis algorithm and serum biomarkers accurately classified the nature of brain injury across major etiologies. Further implementation of such algorithms and addition of other objective measures will enable better prognostication of injury and improved development of therapeutics.
Prevalence of cardiovascular risk factors in osteoarthritis patients derived from primary care records: a systematic review of observational studies
Authors: Huang Xiaoyang , Wilkie Ross , Mamas Mamas A , Yu Dahai 
Published: February 2021

AbstractBackgroundPeople with osteoarthritis are at a high risk of cardiovascular disease (CVD). Detecting CVD risk factors in this high-risk population will help to improve CVD outcomes. Primary care electronic health records (EHRs) provide opportunities for the surveillance of CVD risk factors in the osteoarthritis population. This paper aimed to systematically review evidence of prevalence estimates of CVD risk factors in people with osteoarthritis derived from primary care EHRs.MethodsEight databases including MEDLINE were systematically searched to January 2019. Observational studies using primary care EHRs data to estimate the prevalence of six CVD risk factors in people with osteoarthritis were included. A narrative review was conducted to summarise study results.ResultsSix studies were identified. High heterogeneity between studies prevented the calculation of pooled estimates. One study reported the prevalence of smoking (12.5%); five reported hypertension (range: 19.7%-55.5%); four reported obesity (range: 34.4%-51.6%); two reported dyslipidaemia (6.0%, 13.3%); five reported diabetes (range: 5.2%-18.6%); and one reported chronic kidney disease (1.8%) in people with osteoarthritis. One study reported a higher prevalence of hypertension (Odds Ratio (OR) 1.25, 95% confidence interval (CI) 1.19-1.32), obesity (OR 2.44, 95%CI 2.33-2.55), dyslipidaemia (OR 1.24, 95%CI 1.14-1.35) and diabetes (1.11, 95%CI 1.02-1.22) in the osteoarthritis population compared with the matched non-osteoarthritis population.ConclusionsFrom studies identified in this review that had used primary care EHRs, prevalence estimates of CVD risk factors were higher in people with osteoarthritis compared with those without. These estimates may provide baseline frequency of CVD risk factors in osteoarthritis patients in primary care, although this is limited by the small number of studies and high heterogeneity. Further studies of frequency, using primary care EHRs, will help to answer whether this data source can be used for evaluating approaches to manage CVD risk factors in osteoarthritis patients.Subject AreaPrimary care research
A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples
Authors: Sancilio Amelia , D’Aquila Richard , McNally Elizabeth M. , Velez Matt E , Ison Michael G. , Demonbreun Alexis R. , McDade Thomas W. 
Published: February 2021

ABSTRACTBackgroundThe spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample.MethodsSamples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV).ResultsDilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples.ConclusionsLarge-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.
Soluble guanylate cyclase stimulation mitigates skeletal and cardiac muscle dysfunction in a mdx model of Duchenne muscular dystrophy
Authors: Zhang Ling , Xu Yuanyuan , Yousefi Keyvan , Irion Camila I. , Alvarez Roger A. , Krishnan Shalini M. , Stasch Johannes-Peter , Martinez Eliana C. , Buys Emmanuel S. , Sandner Peter , Shehadeh Lina A. , Percival Justin M. 
Published: February 2021

AbstractThe impairment of neuronal nitric oxide synthase (nNOS) signaling contributes to disease pathology in the muscle wasting disorder Duchenne muscular dystrophy (DMD). nNOS signal propagation occurs through nitric oxide sensitive soluble guanylate cyclase (sGC), a critical source of cyclic guanosine monophosphate (cGMP) in muscle. Although both nNOS and sGC activity are impaired in DMD patients, little is known about sGC as a therapeutic target. In this study, we tested the hypothesis that stimulating sGC activity with the allosteric agonist BAY41-8543 mitigates striated muscle pathology in the mdx4cv mouse model of DMD. In contrast to DMD patients, mdx mice exhibited greater basal sGC activity than wild type controls with preservation of cGMP levels due partly to upregulation of sGC in some muscles. Stimulating sGC activity in mdx mice with BAY41-8543 substantially reduced skeletal muscle damage, macrophage densities and inflammation and significantly increased resistance to contraction-induced fatigue. BAY41-8543 also enhancedin vivodiaphragm function while reducing breathing irregularities suggesting improved respiratory function. BAY41-8543 attenuated cardiac hypertrophic remodeling, fibrosis and diastolic dysfunction including left atrium enlargement in aged mdx mice. Overall, sGC stimulation significantly mitigated skeletal and cardio-respiratory dysfunction in mdx4cv mice. Importantly, this study provides compelling pre-clinical evidence supporting sGC as a novel target in DMD and the repurposing of FDA-approved sGC stimulators, such as riociguat and veraciguat, as a novel therapeutic approach for DMD.
Gene co-expression network reveals highly conserved, well-regulated anti-ageing mechanisms in old ant queens
Authors: Harrison Mark C. , Niño Luisa M. Jaimes , Rodrigues Marisa Almeida , Ryll Judith , Flatt Thomas , Oettler Jan , Bornberg-Bauer Erich 
Published: February 2021

AbstractEvolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called ‘selection shadow’, due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant,Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in oldC. obscuriorqueens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.Significance StatementUnderstanding the exceptional longevity of ant queens and how they defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory and molecular biology of ageing. In this study we offer several clues as to how this occurs on a molecular level inC. obscuriorqueens. Specifically, we believe a reduction in the selection shadow due to low extrinsic mortality, has allowed the evolution of well-regulated anti-ageing mechanisms. Consequently, we suggest several promising starting points for future research into the poorly understood phenomenon of extreme longevity in ant queens. Making progress in this field will not only allow us to better understand longevity and fertility in social insects but may also offer interesting research strategies for human ageing.
Multispecies site occupancy modeling and study design for spatially replicated environmental DNA metabarcoding
Authors: Fukaya Keiichi , Kondo Natsuko Ito , Matsuzaki Shin-Ichiro S. , Kadoya Taku 
Published: February 2021

AbstractEnvironmental DNA (eDNA) metabarcoding has become widely applied to gauge biodiversity in a noninvasive and cost-efficient manner. The detection of species using eDNA metabarcoding is, however, imperfect owing to various factors that can cause false negatives in the inherent multi-stage workflow.Imperfect detection in the multi-stage workflow of eDNA metabarcoding also raises an issue of study design: namely, how available resources should be allocated among the different stages to optimize survey efficiency.Here, we propose a variant of the multispecies site occupancy model for eDNA metabar-coding studies where samples are collected at multiple sites within a region of interest. This model describes the variation in sequence reads, the unique output of the high-throughput sequencers, in terms of the hierarchical workflow of eDNA metabarcoding and interspecific heterogeneity, allowing the decomposition of the sources of variation in the detectability of species throughout the different stages of the workflow. We also introduced a Bayesian decision analysis framework to identify the study design that optimizes the efficiency of species detection with a limited budget.An application of the model to freshwater fish communities in the Lake Kasumigaura watershed, in Japan, highlighted a remarkable inhomogeneity in the detectability of species, indicating a potential risk of the biased detection of specific species. Species with lower site occupancy probabilities tended to be difficult to detect as they had lower capture probabilities and lower dominance of the sequences. The expected abundance of sequence reads was predicted to vary by up to 23.5 times between species.An analysis of the study design suggested that ensuring multiple within-site replications of the environmental samples is preferred in order to achieve better species detection efficiency, provided that a throughput of tens of thousands of sequence reads was secured.The proposed framework makes the application of eDNA metabarcoding more error-tolerant, allowing ecologists to monitor ecological communities more efficiently.
Changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19 pandemic in Spain
Authors: García-Esquinas Esther , Ortolá Rosario , Gine-Vázquez Iago , Carnicero José A , Mañas Asier , Lara Elvira , Alvarez-Bustos Alejandro , Vicente-Rodriguez German , Sotos-Prieto Mercedes , Olaya Beatriz , José Garcia-Garcia Francisco , Gusi Narcis , Banegas Jose R. , Rodríguez-Gómez Irene , Struijk Ellen A. , Martínez-Gómez David , Lana Alberto , María Haro Josep , Ayuso-Mateos José L. , Rodríguez-Mañas Leocadio , Ara Ignacio , Miret Marta , Rodríguez-Artalejo F 
Published: February 2021

AbstractBackgroundWe aimed to examine main changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19.MethodsWe used prospective data from 3041 participants in four cohorts of community-dwelling individuals aged ≥65 years in Spain. Data were obtained using validated questionnaires through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning the COVID-19 lockdown. Lineal or multinomial, as appropriate, regression models with adjustment for the main confounders were used to assess changes in the outcome variables from the pre-pandemic to the confinement period, and to identify their associated factors.ResultsOn average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Several subgroups of individuals were at increased risk of developing unhealthier lifestyles or mental health decline with confinement: (i)-males (for physical activity and sedentariness), (ii)-those with greater social isolation (for diet, physical activity, mental health), (iii)-feelings of loneliness (for diet, sleep quality, mental health), (iv)-poor housing conditions (for diet, physical activity, TV viewing time), (v)-unhealthy sleep duration (for physical activity and sedentariness), and (vi-worse overall health or chronic morbidities (for physical activity, screen time, mental health). On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement.ConclusionsThe lockdown during the first wave of the COVID-19 in Spain, which was one of the most restrictive in Europe, only led to minor average changes in health behaviors among older adults. However, mental health was moderately affected. If another lockdown were imposed on this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, poor housing conditions and chronic morbidities, because of their greater vulnerability to the enacted movement restrictions
Assessment of the suitability of marker fragments DNA sequences of the internal transcribed spacer region (ITS), beta-tubulin gene (TUB) and elongation factor (EF1) genes for diagnostics ofFusarium tricinctumspecies complex in Russian in grain products
Authors: Shchukovskaya A. 
Published: February 2021

AbstractBy results of laboratory researches from plant samples of grain crops speciesFusarium avenaceum, Fusarium tricinctumandFusarium acuminatumrelated toFusarium tricinctumspecies complex were isolated and identified, based on cultural and morphological characteristics, molecular-genetic analysis of 3 DNA fragments was performed: internal transcribed spacer (ITS) site, beta-tubulin gene site (TUB), elongation factor gene site (EF1) showed insignificant intraspecific and interspecific variability at ITS and EF1 sites, which may negatively affect the reliability of target species identification, TUB site was more effective for distinguishing and identifying the studied species, due to significant intraspecific and interspecific variability
Microbial tryptophan catabolism affects the vector competence ofAnopheles
Authors: Feng Yuebiao , Peng Yeqing , Wen Han , Song Xiumei , An Yanpeng , Tang Huiru , Wang Jingwen 
Published: February 2021

AbstractThe influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota ofAnopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3‐hydroxykynurenine (3‐HK) and xanthurenic acid (XA). Of these, 3‐HK impairs the structure of peritrophic matrix (PM), thereby promotingPlasmodium bergheiinfection. Among the major gut microbiota inAn. stephensi, Pseudomonas alcaligenesplays a role in catabolizing 3‐HK as revealed by whole genome sequencing and LC‐MS metabolic analysis. The genome ofP. alcaligenesencodes kynureninase (KynU) that is responsible for the conversion of 3‐HK to 3‐Hydroxyanthranilic acid (3‐HAA). Mutation of this gene abrogates the ability ofP. alcaligenesto metabolize 3‐HK, which in turn abolishes its role on PM protection. Colonization ofAn. stephensiwith KynU mutatedP. alcaligenesfails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.
Cerebral cortical communication overshadows computational energy-use, but these combine to predict synapse number
Authors: Levy William B , Calvert Victoria G. 
Published: February 2021

Darwinian evolution tends to produce energy-efficient outcomes. On the other hand, energy limits computation, be it neural and probabilistic or digital and logical. Taking a particular energy-efficient viewpoint, we define neural computation and make use of an energy-constrained, computational function. This function can be optimized over a variable that is proportional to the number of synapses per neuron. This function also implies a specific distinction between ATP-consuming processes, especially computationper sevs the communication processes including action potentials and transmitter release. Thus to apply this mathematical function requires an energy audit with a partitioning of energy consumption that differs from earlier work. The audit points out that, rather than the oft-quoted 20 watts of glucose available to the brain (1, 2), the fraction partitioned to cortical computation is only 0.1 watts of ATP. On the other hand at 3.5 watts, long-distance communication costs are 35-fold greater. Other novel quantifications include (i) a finding that the biological vs ideal values of neural computational efficiency differ by a factor of 108and (ii) two predictions ofN, the number of synaptic transmissions needed to fire a neuron (2500 vs 2000).Significance StatementEngineers hold up the human brain as a low energy form of computation. However from the simplest physical viewpoint, a neuron’s computation cost is remarkably larger than the best possible bits/J – off by a factor of 108. Here we explicate, in the context of energy consumption, a definition of neural computation that is optimal given explicit constraints. The plausibility of this definition as Nature’s perspective is supported by an energy-audit of the human brain. The audit itself requires certain novel perspectives and calculations revealing that communication costs are 35-fold computational costs.
Deletion of Small Ubiquitin-like Modifier-1 Attenuates Behavioral and Anatomical Deficits by Enhancing Functional Autophagic Activities in Huntington Disease
Authors: Ramírez-Jarquín Uri Nimrod , Sharma Manish , Shahani Neelam , Subramaniam Srinivasa 
Published: February 2021

ABSTRACTMutant HTT (mHTT) associated with Huntington disease (HD) affects the central nervous system by prominent atrophy in the striatum and promotes psychiatric, cognitive, and choreiform movements, although the exact mechanism remains obscure. Previous studies have shown that SUMO1 (Small Ubiquitin-like Modifier-1) modification of mHTT promotes cellular toxicity, but the in vivo role and functions of SUMO1 in HD pathogenesis are unclear. Here, we report that SUMO1 deletion in Q175DN HD-het knock-in mice (HD mice) prevented age-dependent HD-like motor and neurological impairments and suppressed the striatal atrophy and inflammatory response. SUMO1 deletion caused a drastic reduction in soluble mHtt levels and nuclear and extracellular mHtt inclusions, while increasing cytoplasmic inclusions in the striatum of HD mice. SUMO1 deletion also enhanced autophagic activity, characterized by augmented interactions between mHTT inclusions and a lysosomal marker (LAMP1), increased LC3B/LAMP1 interaction, and decreased sequestosome-1 (p62) and mHTT and diminished p62/LAMP1 interactions in DARPP-32–positive medium spiny neurons (MSNs) in HD mice. Depletion of SUMO1 in an HD cell model also diminished the mHtt levels and enhanced autophagy flux. In addition, the SUMOylation inhibitor ginkgolic acid strongly enhanced autophagy and diminished mHTT levels in human HD fibroblasts. These results indicate that SUMO is a critical therapeutic target in HD and that blocking SUMO may ameliorate HD pathogenesis by improving autophagy activities.