bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical thickness estimation in individuals with cerebral small vessel disease, focal atrophy, and chronic stroke lesions
Authors: Ozzoude Miracle , Ramirez Joel , Raamana Pradeep , Holmes Melissa F. , Walker Kirstin , Scott Christopher J.M. , Goubran Maged , Kwan Donna , Tartaglia Maria C. , Beaton Derek , Saposnik Gustavo , Hassan Ayman , Lawrence-Dewar Jane , Dowlatshahi Dariush , Strother Stephen C. , Symons Sean , Bartha Robert , Swartz Richard H. , Black Sandra E. ,   on behalf of the ONDRI Investigators
Published: August 2020

ABSTRACTBackgroundRegional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases can be estimated using specialised neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures.PurposeThe main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer’s cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and cerebrovascular disease, with varying degrees of neurovascular lesions and brain atrophy.MethodsIn 155 cerebrovascular disease patients enrolled in the Ontario Neurodegenerative Disease Research Initiative (ONDRI), FreeSurfer outputs were compared between a fully automated, unmodified procedure and a corrected procedure that accounted for potential sources of error due to atrophy and neurovascular lesions. Quality control (QC) measures were obtained from both procedures. Association between cortical thickness and global cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) score was also investigated from both procedures.ResultsCorrected procedures increased ‘Acceptable’ QC ratings from 18% to 76% for the cortical ribbon and from 38% to 92% for tissue segmentation. Corrected procedures reduced ‘Fail’ ratings from 11% to 0% for the cortical ribbon and 62% to 8% for tissue segmentation. FreeSurfer-based segmentation of T1-weighted white matter hypointensities were significantly greater in the corrected procedure (5.8mL vs. 15.9mL, p<0.001). The unmodified procedure yielded no significant associations with global cognitive status, whereas the corrected procedure yielded positive associations between MoCA total score and clusters of cortical thickness in the left superior parietal (p=0.018) and left insula (p=0.04) regions. Further analyses with the corrected cortical thickness results and MoCA subscores showed a positive association between left superior parietal cortical thickness and Attention (p<0.001).ConclusionsThese findings suggest that correction procedures that account for brain atrophy and neurovascular lesions can significantly improve FreeSurfer’s segmentation results, reduce failure rates, and potentially increase sensitivity to examine brain-behaviour relationships. Future work will examine relationships between cortical thickness, cerebral small vessel disease, and neurodegenerative disease in the ONDRI study.
Immune gene expression covaries with gut microbiome composition in stickleback
Authors: Fuess Lauren , Haan Stijn den , Ling Fei , Weber Jesse N. , Steinel Natalie C. , Bolnick Daniel I. 
Published: August 2020

ABSTRACTCommensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here we leverage a large study of laboratory-raised fish from the speciesGasterosteus aculeatus(three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immunity. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated to host gene expression. These families were all tightly correlated to host expression of immune genes and processes, falling into one of three categories: those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with abundance of these taxons, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition.
Electrostatic Fields Have Strong Repellency Effects AgainstCulex pipiens
Authors: Tam Jonathan 
Published: August 2020

AbstractCurrently, the most effective mosquito repellents employ the use of the chemical N, N-Diethyl-meta-toluamide (DEET), often considered the gold standard of repellents. However, as DEET continues to be widely used, it is beginning to lose efficacy as mosquitoes gradually gain resistance to it. Additionally, DEET only protects the skin that it is applied on, and therefore, it is difficult to achieve 100% repellency for the entire body. As urbanization and climate change continue to increase the threat of widespread mosquito-borne illnesses, new forms of repellents must be developed to combat the possibility of an epidemic. Previous studies indicate that a multitude of insects, including spiders, flies, and mosquitoes, avoid electrostatic fields at sufficiently high voltages. In this study, I evaluate if electrostatic fields can be used as a potential personal repellent against mosquitoes and an alternative to chemical sprays. I found that by charging the surface of a person’s body with a high voltage (9800V) but minuscule current, I created a safe and effective method that repels mosquitoes from landing on the skin. This method has similar efficacy to DEET, with near 100% repellency after 20 minutes of charging. It also has the advantage of not needing to be reapplied and provides full-body protection, allowing greater protection to the user than DEET. These results introduce a promising method of repelling mosquitoes, that used together with present-day chemical repellents, can help provide greater protection to malaria-endemic countries.
Plasmodium falciparumincreases its investment in gametocytes in the wet season in asymptomatic individuals
Authors: Oduma Colins O. , Ogolla Sidney , Atieli Harrysone , Ondigo Bartholomew N. , Lee Ming-Chieh , Githeko Andrew K. , Dent Arlene E. , Kazura James W. , Yan Guiyun , Koepfli Cristian 
Published: August 2020

AbstractIn many regions, malaria transmission is seasonal, but it is not well understood whetherP. falciparummodulates its investment in transmission in response to seasonal vector abundance. In two sites in western Kenya (Chulaimbo and Homa Bay), we sampled 1116 asymptomatic individuals in the wet season, when vectors are abundant, and 1743 in the dry season. We screened forP. falciparumby qPCR, and gametocytes bypfs25RT-qPCR. Parasite prevalence in Chulaimbo and Homa Bay was 27.1% and 9.4% in the dry season, and 48.2% and 7.8% in the wet season respectively. Mean parasite densities did not differ between seasons (P=0.562). A contrasting pattern of gametocyte carriage was observed. In the wet season, fewer infections harbored gametocytes (22.3% vs. 33.8%,P=0.009), but densities were 3-fold higher (P<0.001). Thus, in the wet season, among gametocyte positive individuals, higher proportion of all parasites were gametocytes, reflecting an increased investment in transmission.
CRISPR Turbo Accelerated Knock Out (CRISPy TAKO) for rapidin vivoscreening of gene function
Authors: Plasil SL , Seth A , Homanics GE 
Published: August 2020

AbstractThe development of CRISPR/Cas9 technology has vastly sped up the process of genome editing by introducing a bacterial system that can be exploited for reverse genetics-based research. However, generating homozygous knockout (KO) animals using traditional CRISPR/Cas9-mediated techniques requires three generations of animals. A founder animal with a desired mutation is crossed to produce heterozygous F1 offspring which are subsequently interbred to generate homozygous F2 KO animals. This study describes a novel adaptation of the CRISPR/Cas9-mediated method to develop a homozygous gene-targeted KO animal cohort in one generation. A well-characterized ethanol-responsive gene,MyD88, was chosen as a candidate gene for generation ofMyD88-/-mice as proof of concept. Previous studies have reported changes in ethanol-related behavioral outcomes in MyD88 KO mice. Therefore, it was hypothesized that a successful one-generation KO of MyD88 should reproduce decreased responses to ethanols sedative effects, as well as increased ethanol consumption in males that were observed in previous studies. One-cell mouse embryos were simultaneously electroporated with four gRNAs targeting a critical Exon of MyD88 along with Cas9. DNA and RNA analysis of founder mice revealed a complex mix of genetic alterations, all of which were predicted to ablate MyD88 gene function. This study additionally compared responses of Mock treatment control mice generated through electroporation to controls purchased from a vendor. No substantial behavioral changes were noted between control cohorts. Overall, the CRISPR/Cas9 KO protocol reported here, which we callCRISPRTurboAcceleratedKnockOut (CRISPy TAKO), will be useful for reverse geneticin vivoscreens of gene function in whole animals.
Super-human cell death detection with biomarker-optimized neural networks
Authors: Linsley Jeremy W. , Linsley Drew A. , Lamstein Josh , Ryan Gennadi , Shah Kevan , Castello Nicholas A. , Oza Viral , Kalra Jaslin , Wang Shijie , Tokuno Zachary , Javaherian Ashkan , Serre Thomas , Finkbeiner Steven 
Published: August 2020

AbstractCell death is an essential process in biology that must be accounted for in live microscopy experiments. Nevertheless, cell death is difficult to detect without perturbing experiments with stains, dyes or biosensors that can bias experimental outcomes, lead to inconsistent results, and reduce the number of processes that can be simultaneously labelled. These additional steps also make live microscopy difficult to scale for high-throughput screening because of the cost, labor, and analysis they entail. We address this fundamental limitation of live microscopy with biomarker-optimized convolutional neural networks (BO-CNN): computer vision models trained with a ground truth biosensor that detect live cells with superhuman, 96% accuracy more than 100 times faster than previous methods. Our models learn to identify important morphological characteristics associated with cell vitality without human input or additional perturbations, and to generalize to other imaging modalities and cell types for which they have no specialized training. We demonstrate that we can interpret decisions from BO-CNN models to gain biological insight into the patterns they use to achieve superhuman accuracy. The BO-CNN approach is broadly useful for live microscopy, and affords a powerful new paradigm for advancing the state of high-throughput imaging in a variety of contexts.
Optimal policy for attention-modulated decisions explains human fixation behavior
Authors: Jang Anthony , Sharma Ravi , Drugowitsch Jan 
Published: August 2020

AbstractTraditional accumulation-to-bound decision-making models assume that all choice options are processed simultaneously with equal attention. In real life decisions, however, humans tend to alternate their visual fixation between individual items in order to efficiently gather relevant information [46, 23, 21, 12, 15]. These fixations also causally affect one’s choices, biasing them toward the longer-fixated item [38, 2, 25]. We derive a normative decision-making model in which fixating a choice item boosts information about that item. In contrast to previous models [25, 39], we assume that attention enhances the reliability of information rather than its magnitude, consistent with neurophysiological findings [3, 13, 29, 45]. Furthermore, our model actively controls fixation changes to optimize information gathering. We show that the optimal model reproduces fixation patterns and fixation-related choice biases seen in human decision-makers, and provides a Bayesian computational rationale for the fixation bias. This insight led to additional behavioral predictions that we confirmed in human behavioral data. Finally, we explore the consequences of changing the relative allocation of cognitive resources to the attended versus the unattended item, and show that decision performance is benefited by a more balanced spread of cognitive resources.
Japanese encephalitis virus capsid protein interacts with non-lipidated MAP1LC3 on replication membranes and lipid droplets
Authors: Sarkar Riya , Sharma Kiran Bala , Kumari Anita , Asthana Shailendra , Kalia Manjula 
Published: August 2020

AbstractStudies have shown that Japanese encephalitis virus (JEV), replicates on ER derived membranes that are marked by autophagosome negative non-lipidated MAP1LC3 (LC3-I). Depletion of LC3 exerts a profound inhibition on virus replication and egress. Here, we further characterize the role of LC3 in JEV replication, and through immunofluorescence and immunoprecipitation show that LC3-I interacts with the virus capsid protein in infected cells. This association was observed on capsid localized to both the replication complex and lipid droplets (LDs). JEV infection decreased the number of LDs per cell indicating a link between lipid metabolism and virus replication. This capsid-LC3 interaction was independent of the autophagy adaptor protein p62/SQSTM1. Further, no association of capsid was seen with the GABARAP protein family, suggesting that this interaction was specific for LC3. High resolution protein-protein docking studies identified a putative LC3-interacting region (LIR) in capsid,56FTAL59, and other key residues that could mediate a direct interaction between the two proteins.
Susceptibility to Residual Inhibition is Associated with Hearing Loss and Tinnitus Chronicity
Authors: Hu Suyi , Anschuetz Lukas , Hall Deborah A. , Caversaccio Marco , Wimmer Wilhelm 
Published: August 2020

AbstractResidual inhibition, i.e. the temporary suppression of tinnitus loudness after acoustic stimulation, is a frequently observed phenomenon that may have prognostic value for clinical applications. However, it is unclear in which subjects residual inhibition is more likely and how stable the suppression can be induced repeatedly. The primary aim of this work was to evaluate the effect of hearing loss and tinnitus chronicity on residual inhibition susceptibility. The secondary aim was to investigate the short-term repeatability of residual inhibition. Residual inhibition was assessed in 74 tinnitus subjects with 60-second narrowband noise stimuli in 10 consecutive trials. The subjects were assigned to groups according to their depth of suppression (substantial residual inhibition vs. comparator group). In addition, a categorization in normal hearing and hearing loss groups, related to the degree of hearing loss at the frequency corresponding to the tinnitus pitch, was made. Logistic regression was used to identify factors associated with susceptibility to residual inhibition. Repeatability of residual inhibition was assessed using mixed-effects ordinal regression including post-stimulus time and repetitions as factors. Tinnitus chronicity was not associated with residual inhibition for subjects with hearing loss, while a statistically significant negative association between tinnitus chronicity and residual inhibition susceptibility was observed in normal hearing subjects (odds ratio: 0.63; CI: 0.41 to 0.83; p = 0.0076). Moreover, repeated states of suppression can be stably induced. Our results suggest that long chronicity and residual inhibition susceptibility could be indicators for hidden lesions along the auditory pathway in subjects with normal hearing thresholds at their tinnitus frequency.
First-in-Human Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine
Authors: Keech Cheryl , Glenn Gregory M. , Albert Gary , Cho Iksung , Robertson Andreana , Reed Patricia , Neal Susan , Plested Joyce S. , Zhu Mingzhu , Cloney-Clark Shane , Zhou Haixia , Smith Gale , Patel Nita , Frieman Matthew B. , Haupt Robert E. , Logue James , McGrath Marisa , Weston Stuart , Piedra Pedro A. , Desai Chinar , Callahan Kathleen , Lewis Maggie , Price-Abbott Patricia , Formica Neil , Shinde Vivek , Fries Louis , Lickliter Jason D. , Griffin Paul , Wilkinson Bethanie 
Published: August 2020

AbstractBackgroundNVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults.MethodsThis is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses.ResultsParticipants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean ≤2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5μg NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype.ConclusionsNVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).
Insights into the first wave of the COVID-19 pandemic in Bangladesh: Lessons learned from a high-risk country
Authors: Siam Md. Hasanul Banna , Hasan Md. Mahbub , Raheem Md. Enayetur , Khan Hasinur Rahaman , Siddiqee Mahbubul H. , Hossain Mohammad Sorowar 
Published: August 2020

AbstractBackgroundSouth Asian countries including Bangladesh have been struggling to control the COVID-19 pandemic despite imposing months of lockdown and other public health measures (as of June 30, 2020). In-depth epidemiological information from these countries is lacking. From the perspective of Bangladesh, this study aims to understand the epidemiological features and gaps in public health preparedness.MethodThis study used publicly available data (8 March-30 June 2020) from the respective health departments of Bangladesh and Johns Hopkins University Coronavirus Resource Centre. Descriptive statistics was used to report the incidence, case fatality rates (CFR), and trend analysis. Spatial distribution maps were created using ArcGIS Desktop. Infection dynamics were analyzed via SIR models.FindingsIn 66 days of nationwide lockdown and other public health efforts, a total of 47,153 cases and 650 deaths were reported. However, the incidence was increased by around 50% within a week after relaxing the lockdown. Males were disproportionately affected in terms of infections (71%) and deaths (77%) than females. The CFR for males was higher than females (1.38% vs 1.01%). Over 50% of infected cases were reported among young adults (20-40-year age group). Geospatial analysis between 7 June 2020 and 20 June 2020 showed that the incidences increased 4 to 10-fold in 12 administrative districts while it decreased in the epicenter. As compared to the EU and USA, trends of the cumulative incidence were slower in South Asia with lower mortality.ConclusionOur findings on gaps in public health preparedness and epidemiological characteristics would contribute to facilitating better public health decisions for managing current and future pandemics like COVID-19 in the settings of developing countries.
Changes in health and functioning of care home residents over two decades: what can we learn from population based studies?
Authors: Barker Robert O , Hanratty Barbara , Kingston Andrew , Ramsay Sheena , Matthews Fiona E 
Published: August 2020

AbstractBackgroundCare home residents have complex care and support needs, as demonstrated by their vulnerability during the COVID-19 pandemic. There is a perception that the needs of residents have increased, but evidence is limited. We investigated changes in health and functioning of care home residents over two decades in England and Wales.MethodsWe conducted a repeated cross-sectional analysis over a 24-year period (1992-2016), using data from three longitudinal studies, the Cognitive Function and Ageing Studies (CFAS) I and II and English Longitudinal Study of Ageing (ELSA). To adjust for ageing of respondents over time results are presented for the 75-84 age group.ResultsAnalysis of 2,280 observations from 1,745 care home residents demonstrated increases in severe disability (difficulty in at least two from washing, dressing and toileting). The prevalence of severe disability increased from 63% in 1992 to 87% in 2014 (subsequent fall in 2016 although wide confidence intervals). The prevalence of complex multimorbidity (problems in at least three out of six body systems) increased within studies over time, from 33% to 54% in CFAS I/II between 1992 and 2012, and 26% to 54% in ELSA between 2006 and 2016.ConclusionOver two decades, there has been an increase in disability and the complexity of health problems amongst care home residents in England and Wales. A rise in support needs for residents places increasing demands on care home staff and health professionals. This is an important concern for policymakers when considering the impact of COVID-19 infection in care homes.Key pointsCare home residents have complex care and support needs, which has contributed to their vulnerability during the COVID-19 pandemic.Despite a perception that the needs of care home residents have increased over time, the epidemiological evidence is limited.This study demonstrates an increase in the level of disability and the complexity of health problems amongst care home residents in England and Wales over two decades.The rise in support needs for care home residents places increasing demands on care home staff and health professionals, and should be an important consideration for policymakers and service commissioners when considering the impact of current and future waves of COVID-19 infection in this setting.