bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Seroprevalence among First Responders in the District of Columbia, May – July 2020
Authors: Reuben Jacqueline , Sherman Adrienne , Ellison James A. , Gunn Jayleen K. L. , Tran Anthony , McCarroll Matthew , Raj Pushker , Lloyd Patricia , Iyengar Preetha , Johnson-Clarke Fern , Davies-Cole John , Nesbitt LaQuandra 
Published: November 2020

AbstractFirst responders are at increased risk of occupational exposure to SARS-CoV-2 while providing frontline support to communities during the COVID-19 pandemic. In the District of Columbia (DC), first responders were among the first people exposed to and infected with SARS-CoV-2, with over 200 first responders diagnosed with COVID-19 by May 15, 2020. From June – July 2020, DC Health conducted a serologic survey to estimate SARS-CoV-2 seroprevalence and assess risk factors and occupational exposures among a convenience sample of first responders in DC. Of the 310 first responders tested, 3.5% (n = 11) had anti-SARS-CoV-2 antibodies. Seropositivity varied by occupation, with 4.8% (3/62) of firefighters; 3.6% (8/220) of police officers; and no paramedics (0/10) or administration and support staff (0/18) testing positive. Type and consistency of personal protective equipment (PPE) use also varied: all paramedics (n=10) reported wearing a N95 respirator all or most of the time, compared to 83.3% of firefighters, 38.8% of police officers, and 23.5% of administration and support staff (p<0.001). All paramedics reported wearing gloves all or most of the time, compared to 80.0% of firefighters, 27.8% of administration and support staff, and 24.3% of police (p<0.001). The relatively low seroprevalence among first responders highlights the benefits of continuous training on and reinforcement of the proper use of PPE while performing job duties to mitigate potential transmission within and between first responders and the community.SummaryUnderstanding occupational exposure to and infection with SARS-CoV-2 among first responders is important for workforce planning and emergency preparedness and response. Seroprevalence among first responders (3.5%; 11/310) who participated in a survey conducted by the District of Columbia Department of Health (DC Health) from May 28 – July 15 was 48% lower than reported in the DC community (6.7%; 876/12990). The lower prevalence of SARS-CoV-2 among first responders highlights the importance of continuous training on and reinforcement of the proper use of personal protective equipment (PPE). Proper use of PPE is a critical mitigation strategy to reduce transmission among and between first responders and the community.
Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder
Authors: Mundy Jessica , Hübel Christopher , Gelernter Joel , Levey Daniel , Murray Robin M. , Skelton Megan , Stein Murray B. ,   The Million Veteran Program,   Post Traumatic Stress Disorder Working Group of the Psychiatric Genomics Consortium, Vassos Evangelos , Breen Gerome , Coleman Jonathan R. I. 
Published: November 2020

AbstractBackgroundPosttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences following psychological trauma exposure. The disorders have high genetic overlap. We investigated whether the genetics of PTSD were associated with reported trauma in individuals with MDD. Since trauma is associated with recurrent MDD, we also investigated whether the genetics of PTSD were associated with episode recurrence.MethodsGenetic correlations were estimated between PTSD and MDD in the presence and MDD in the absence of reported exposure to psychological trauma, and recurrent and single-episode MDD, based on genetic data from UK Biobank Mental Health Questionnaire respondents (N=157,358). Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and Million Veteran Program. Polygenic risk scores were generated to investigate whether individuals with MDD who have higher genetic risk for PTSD were more likely to report psychological trauma than those with lower genetic risk.ResultsIndividuals with MDD with a higher genetic risk for PTSD were significantly more likely to report exposure to psychological trauma than those with lower risk [OR=1.06 (1.03-1.09) Empricial p<0.001]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in the absence of reported psychological trauma [rg differences = ∼0.2, p<0.008]. Participants who had experienced recurrent depressive episodes reported significantly higher trauma rates than participants who had experienced a single episode [chisquare>167, p<0.001].ConclusionsGenetic risk for PTSD in individuals with MDD may influence the way in which traumatic life events are perceived, responded to and reported.
Regional Anesthesia use in Pediatric Burn Surgery: A Retrospective Observational Cohort Study
Authors: Richman M , Berman J , Ross EM 
Published: November 2020

AbstractApproximately 77,000 children 16 years or less suffered burn injuries in the United States in 2018. Treatment, reconstruction, and rehabilitation are painful experiences. For some, the experience triggers post-traumatic stress disorder (PTSD) and/or a chronic pain syndrome. Given the role pain plays as a major secondary disease, it must be addressed to achieve optimal healing. Regional anesthesia has been used extensively to manage postoperative pain and reduce the need for opioids following other surgical procedures in children. Nevertheless, regional anesthesia has not yet been widely used in pediatric burn care. We present a demonstration project utilizing regional anesthesia in 15 pediatric burn patients over an eight-month period. Our results indicate that the use of regional anesthesia reliably reduces perioperative pain and opioid requirements in the immediate peri-operative period. In this cohort, 93% of patients scored a 0/10 on a FLACC scale for pain by post-anesthesia care unit (PACU) discharge, with an average PACU stay of 70 minutes. Thirty-three percent of patients received no opioids, and the average opioid dose was only 0.06mg/kg morphine equivalents. We conclude that regional anesthesia can be used to improve patient comfort and decrease opioid requirement.
Base-substitution mutation rate across the nuclear genome ofAlpheussnapping shrimp and the timing of isolation by the Isthmus of Panama
Authors: Silliman Katherine , Indorf Jane L. , Knowlton Nancy , Browne William E. , Hurt Carla 
Published: November 2020

AbstractThe formation of the Isthmus of Panama and final closure of the Central American Seaway (CAS) provides an independent calibration point for examining the rate of DNA substitutions. This vicariant event has been widely used to estimate the substitution rate across mitochondrial genomes and to date evolutionary events in other taxonomic groups. Nuclear sequence data is increasingly being used to complement mitochondrial datasets for phylogenetic and evolutionary investigations; these studies would benefit from information regarding the rate and pattern of DNA substitutions derived from the nuclear genome. To estimate this genomewide neutral mutation rate (μ), genotype-by-sequencing (GBS) datasets were generated for three transisthmian species pairs inAlpheussnapping shrimp. Using a Bayesian coalescent approach (G-PhoCS) applied to 44,960 GBS loci, we estimated μ to be 2.64E-9 substitutions/site/year, when calibrated with the closure of the CAS at 3 Ma. This estimate is remarkably similar to experimentally derived mutation rates in model arthropod systems, strengthening the argument for a recent closure of the CAS. To our knowledge this is the first use of transisthmian species pairs to calibrate the rate of molecular evolution from GBS data.
Vessel compression biases red blood cell partitioning at bifurcations in a haematocrit-dependent manner: implications for tumour blood flow
Authors: Enjalbert Romain , Hardman David , Krüger Timm , Bernabeu Miguel O. 
Published: November 2020

AbstractThe tumour microenvironment is abnormal and associated with tumour tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumours is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumour decompression to improved tumour oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumour vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a haematocrit-dependent and flowrate-independent manner. We identify RBC focussing due to cross-streamline migration as the mechanism responsible and characterise the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of haemodilution in tumour vascular networks and oxygen homogenisation following pharmacological solid tumour decompression.
IP3/Ca2+signals regulate larval to pupal transition under nutrient stress through the H3K36 methyltransferase dSET2
Authors: Mitra Rishav , Richhariya Shlesha , Jayakumar Siddharth , Notani Dimple , Hasan Gaiti 
Published: November 2020

AbstractPersistent loss of dietary protein usually signals a shutdown of key metabolic pathways. InDrosophilalarvae, that have crossed “critical weight” and can pupariate to form viable adults, such a metabolic shut-down would needlessly lead to death. IP3/Ca2+signals in certain interneurons (vGlutVGN6341) allowDrosophilalarvae to pupariate on a protein-deficient diet by partially circumventing this shutdown through upregulation of neuropeptide signaling and the expression of ecdysone synthesis genes. Here we show that IP3/Ca2+signals invGlutVGN6341neurons drive expression ofdSET2, aDrosophilaHistone 3 Lysine 36 methyltransferase. Further,dSET2expression is required for larvae to pupariate in the absence of dietary protein. IP3/Ca2+signal-drivendSET2expression upregulates key Ca2+signaling genes through a novel positive feedback loop. Transcriptomic studies coupled with analysis of existing ChIP-seq datasets identified genes from larval and pupal stages, that normally exhibit robust H3K36 trimethyl marks on their gene bodies and concomitantly undergo stronger downregulation by knockdown of either an intracellular Ca2+release channel the IP3R or dSET2. IP3/Ca2+signals thus regulate gene expression through dSET2 mediated H3K36 marks on select neuronal genes for the larval to pupal transition.
Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies
Authors: Lake Alice V. R. , Smith Claire E. L. , Natarajan Subaashini , Basu Basudha , Best Sunayna K. , Stevenson Thomas , Trowbridge Rachel , Grellscheid Sushma N. , Bond Jacquelyn , Foster Richard , Johnson Colin A. 
Published: November 2020

AbstractPrimary cilia are microtubule-based organelles that act as cellular antennae to mediate vertebrate development and growth factor signalling. Defects in primary cilia result in a group of inherited developmental conditions known as ciliopathies. Ciliopathies often present with cystic kidney disease, a major cause of early renal failure that requires renal replacement therapies. Currently, only one drug, Tolvaptan, is licensed to slow the decline of renal function for the ciliopathy polycystic kidney disease. Novel therapeutic interventions for these conditions remain a pressing clinical need.We screened clinical development compounds for positive effects on cilia formation and function and identified fasudil hydrochloride as the top hit. Fasudil is a generic, off-patent drug that is a potent but broadly selective Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor. In a parallel whole genome siRNA-based reverse genetics phenotypic screen of positive modulators of cilia formation, we identified ROCK2 as the target molecule. We demonstrate that ROCK2 is a key mediator of cilium formation and function through effects on actin cytoskeleton remodelling. Our results indicate that specific ROCK2 inhibitors such as belumosudil (KD-025) could be repurposed for pharmacological intervention in cystic kidney disease. We propose that ROCK2 inhibition represents a novel, disease-modifying therapeutic approach for heterogeneous ciliopathies.
The selfing syndrome overshadows other differences when comparing fitness acrossCapsellaspecies
Authors: Orsucci Marion , Vanikiotis Theofilos , Guerrina Maria , Duan Tianlin , Glémin Sylvain , Lascoux Martin 
Published: November 2020

SUMMARYSelf-fertilization has recurrently evolved from outcrossing. Self-fertilization provides an advantage in the short-term as individuals do not require a mate to reproduce, but self-fertilization is also associated with both decreased genetic diversity and accumulation of weakly deleterious mutations, which could, however, be alleviated in polyploid selfers. If pollinators are not limited, individual fitness is thus expected to be higher in outcrossers than in selfers. We measured several life history traits in fourCapsellaspecies under two different treatments (disturbed and undisturbed) to assess the effects of mating system and ploidy level on reproductive, vegetative and phenological traits. The experiment was carried out outdoor in Northwest Greece, within the range of the obligate outcrossing species,C. grandiflora, so it could be naturally pollinated and its fitness directly compared to that of its self-fertilizing relatives. Disturbance of the environment did not affect the phenotype in any of the four species. However, for most traits the obligate outcrossing species performed better than all selfing ones. In contrast, polyploidy did not seem to confer an advantage in terms of survival or reproduction compared to diploidy. Finally, plants from Asia and northern Europe had lower performances than accessions from southern Europe and the Middle-East.
An unexpected donor in the adaptive introgression candidate Helianthus annuus subsp. texanus
Authors: Owens Gregory. L , Todesco Marco , Bercovich Natalia , Légaré Jean-Sébastien , Mitchell Nora , Whitney Kenneth D. , Rieseberg Loren H. 
Published: November 2020

AbstractHybridization is widely acknowledged as an important mechanism of acquiring adaptive variation. In Texas, the sunflower Helianthus annuus subsp. texanus is thought to have acquired herbivore resistance and morphological traits via introgression from a local congener, H. debilis. Here we test this hypothesis using whole genome sequencing data from across the entire range of H. annuus and possible donor species, as well as phenotypic data from a common garden study. We find that although it is morphologically convergent with H. debilis, H. a. texanus has conflicting signals of introgression. Genome wide tests (Patterson’s D and TreeMix) only find evidence of introgression from H. argophyllus (sister species to H. annuus and also sympatric), but not H. debilis, with the exception of one individual of 109 analysed. We further scanned the genome for localized signals of introgression using PCAdmix and found minimal but non-zero introgression from H. debilis and significant introgression from H. argophyllus. Putative introgressions mainly occur in high recombination regions as predicted by theory if introgressed ancestry contains maladaptive alleles. To reconcile the disparate findings of our analyses, we discuss potential test-specific confounding features, including introgression from other taxa. Given the paucity of introgression from H. debilis, we argue that the morphological convergence observed in Texas is likely independent of introgression.
Effect size, sample size and power of forced swim test assays in mice: Guidelines for investigators to optimize reproducibility
Authors: Smalheiser Neil R. , Graetz Elena E. , Yu Zhou , Wang Jing 
Published: November 2020

AbstractA recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test putative antidepressants. Whether the mice were assayed in a naïve state vs. in a model of depression or stress, and whether the mice were given test agents vs. known antidepressants regarded as positive controls, the mean effect sizes seen in the experiments were indeed extremely large (1.5 – 2.5 in Cohen’s d units); most of the experiments utilized 7-10 animals per group which did have adequate power to reliably detect effects of this magnitude. We propose that this may at least partially explain why investigators using the FST do not perceive intuitively that their experimental designs fall short -- even though proper prospective design would require ~21-26 animals per group to detect, at a minimum, large effects (0.8 in Cohen’s d units) when the true effect of a test agent is unknown. Our data provide explicit parameters and guidance for investigators seeking to carry out prospective power estimation for the FST. More generally, altering the real-life behavior of scientists in planning their experiments may require developing educational tools that allow them to actively visualize the inter-relationships among effect size, sample size, statistical power, and replicability in a direct and intuitive manner.
Dependence of perceptual saccadic suppression on peri-saccadic image flow properties and luminance contrast polarity
Authors: Baumann Matthias P. , Idrees Saad , Münch Thomas A , Hafed Ziad M. 
Published: November 2020

AbstractAcross saccades, perceptual detectability of brief visual stimuli is strongly diminished. We recently observed that this perceptual suppression phenomenon is jumpstarted in the retina, suggesting that the phenomenon might be significantly more visual in nature than normally acknowledged. Here, we explicitly compared saccadic suppression strength when saccades were made across a uniform image of constant luminance versus when saccades were made across image patches of different luminance, width, and trans-saccadic luminance polarity. We measured perceptual contrast thresholds of human subjects for brief peri-saccadic flashes of positive (luminance increments) or negative (luminance decrements) polarity. Perceptual thresholds were >6-7 times higher when saccades translated a luminance stripe or edge across the retina than when saccades were made over a completely uniform image patch. Critically, both background luminance and flash luminance polarity relative to the background strongly modulated peri-saccadic contrast thresholds. In addition, all of these very same visual dependencies also occurred in the absence of any saccades, but with qualitatively similar rapid translations of image patches across the retina. Our results support the notion that perceptual saccadic suppression may be fundamentally a visual phenomenon, and they motivate neurophysiological and theoretical investigations on the role of saccadic eye movement commands in modulating its properties.
Digestion, fermentation, and pathogen anti-adhesive properties of the hMO-mimic di-fucosyl-β-cyclodextrin
Authors: Verkhnyatskaya Stella A. , Kong Chunli , Klostermann Cynthia , Schols Henk A. , de Vos Paul , Walvoort Marthe T.C. 
Published: November 2020

AbstractScopeHuman milk is widely acknowledged as the best food for infants, and that is not just because of nutritional features. Human milk also contains a plethora of bioactive molecules, including a large set of human milk oligosaccharides (hMOs). Especially fucosylated hMOs have received attention for their anti-adhesive effects on pathogens by preventing attachment to the intestinal wall. Because hMOs are generally challenging to produce in sufficient quantities to study and ultimately apply in (medical) infant formula, hMO mimics are interesting compounds to produce and evaluate for their biological effects.Methods and resultsWe investigated the digestion, fermentation, and pathogen anti-adhesive capacity of the novel hMO mimic di-fucosyl-β-cyclodextrin (DFβCD). We establish that DFβCD is not digested by α-amylase and also resists fermentation by the microbiota from a 9 month-old infant. In addition, we reveal that DFβCD blocks adhesion of enterotoxigenic E. coli (ETEC) to Caco-2 cells, especially when DFβCD is pre-incubated with ETEC prior to addition to the Caco-2 cells.ConclusionOur results suggests that DFβCD functions through a decoy effect. We expect that our results inspire the generation and biological evaluation of other fucosylated hMOs and mimics, to obtain a comprehensive overview of the anti-adhesive power of fucosylated glycans.
Type VI secretion system killing by commensal Neisseria is influenced by the spatial dynamics of bacteria
Authors: Custodio Rafael , Ford Rhian M. , Ellison Cara J. , Liu Guangyu , Mickute Gerda , Tang Christoph M. , Exley Rachel M. 
Published: November 2020

ABSTRACTType VI Secretion Systems (T6SS) are widespread in bacteria and can dictate the development and organisation of polymicrobial ecosystems by mediating contact dependent killing. In Neisseria species, including Neisseria cinerea a commensal of the human respiratory tract, interbacterial contacts are mediated by Type four pili (Tfp) which promote formation of aggregates and govern the spatial dynamics of growing Neisseria microcolonies. Here we show that N. cinerea expresses a plasmid-encoded T6SS that is active and can limit growth of related pathogens. We explored the impact of Tfp expression on N. cinerea T6SS-dependent killing and show that expression of Tfp by prey strains enhances their susceptibility to T6SS, by keeping them in close proximity of T6SS-wielding attacker strains. Our findings have important implications for understanding how spatial constraints during contact-dependent antagonism can shape the evolution of microbial communities.
Microstructural underpinnings and macroscale functional implications of temporal lobe connectivity gradients
Authors: Vos de Wael Reinder , Royer Jessica , Tavakol Shahin , Wang Yezhou , Paquola Casey , Benkarim Oualid , Eichert Nicole , Larivière Sara , Misic Bratislav , Smallwood Jonathan , Valk Sofie L. , Bernhardt Boris C. 
Published: November 2020

AbstractThe temporal lobe is implicated in higher cognitive processes and is one of the regions that underwent substantial reorganization during primate evolution. Its functions are instantiated, in part, by its complex layout of structural connections. This study identified low-dimensional representations of structural connectivity variations in human temporal cortex and explored their microstructural underpinnings and associations to macroscale function. We identified three eigenmodes which described gradients in structural connectivity. These gradients reflected interregional variations in cortical microstructure derived from quantitative MRI and post-mortem histology. Gradient-informed models accurately predicted macroscale measures of temporal lobe function. Gradients aligned closely with established measures of functional reconfiguration and areal expansion between macaques and humans, highlighting the important role evolution has played in shaping temporal lobe function. Our results provide robust evidence for three axes of structural connectivity in human temporal cortex with consistent microstructural underpinnings and contributions to large-scale brain network function.