bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can social vulnerability indices predict county trauma fatality rates?
Authors: Phelos Heather M. , Deeb Andrew-Paul , Brown Joshua B. 
Published: April 2021

BACKGROUND
Social vulnerability indices were created to measure resiliency to environmental disasters based on socioeconomic and population characteristics of discrete geographic regions. They are composed of multiple validated constructs that can also potentially identify geographically vulnerable populations after injury. Our objective was to determine if these indices correlate with injury fatality rates in the US.

METHODS
We evaluated three social vulnerability indices: The Hazards & Vulnerability Research Institute’s Social Vulnerability Index (SoVI), the Center for Disease Control’s Social Vulnerability Index (SVI), and the Economic Innovation Group’s Distressed Community Index (DCI). We analyzed SVI subindices and common individual census variables as indicators of socioeconomic status. Outcomes included age-adjusted county-level overall, firearm, and motor vehicle collision deaths per 100,000 population. Linear regression determined the association of injury fatality rates with the SoVI, SVI, and DCI. Bivariate choropleth mapping identified geographic variation and spatial autocorrelation of overall fatality, SoVI, and DCI.

RESULTS
A total of 3,137 US counties were included. Only 24.6% of counties fell into the same vulnerability quintile for all three indices. Despite this, all indices were associated with increasing fatality rates for overall, firearm, and motor vehicle collision fatality. The DCI performed best by model fit, explanation of variance, and diagnostic performance on overall injury fatality. There is significant geographic variation in SoVI, DCI, and injury fatality rates at the county level across the United States, with moderate spatial autocorrelation of SoVI (Moran’s I, 0.35; p < 0.01) and high autocorrelation of injury fatality rates (Moran’s I, 0.77; p < 0.01) and DCI (Moran’s I, 0.53; p < 0.01).

CONCLUSION
While the indices contribute unique information, higher social vulnerability is associated with higher injury fatality across all indices. These indices may be useful in the epidemiologic and geographic assessment of injury-related fatality rates. Further study is warranted to determine if these indices outperform traditional measures of socioeconomic status and related constructs used in trauma research.

LEVEL OF EVIDENCE
Epidemiological, level IV.
Physician-staffed ambulance and increased in-hospital mortality of hypotensive trauma patients following prolonged prehospital stay: A nationwide study
Authors: Yamamoto Ryo , Suzuki Masaru , Yoshizawa Jo , Nishida Yusho , Junichi Sasaki 
Published: April 2021

BACKGROUND
The benefits of physician-staffed emergency medical services (EMS) for trauma patients remain unclear because of the conflicting results on survival. Some studies suggested potential delays in definitive hemostasis due to prolonged prehospital stay when physicians are dispatched to the scene. We examined hypotensive trauma patients who were transported by ambulance, with the hypothesis that physician-staffed ambulances would be associated with increased in-hospital mortality, compared with EMS personnel-staffed ambulances.

METHODS
A retrospective cohort study that included hypotensive trauma patients (systolic blood pressure ≤ 90 mm Hg at the scene) transported by ambulance was conducted using the Japan Trauma Data Bank (2004–2019). Physician-staffed ambulances are capable of resuscitative procedures, such as thoracotomy and surgical airway management, while EMS personnel-staffed ambulances could only provide advanced life support. In-hospital mortality and prehospital time until the hospital arrival were compared between patients who were classified based on the type of ambulance. Inverse probability weighting was conducted to adjust baseline characteristics including age, sex, comorbidities, mechanism of injury, vital signs at the scene, injury severity, and ambulance dispatch time.

RESULTS
Among 14,652 patients eligible for the study, 738 were transported by a physician-staffed ambulance. In-hospital mortality was higher in the physician-staffed ambulance than in the EMS personnel-staffed ambulance (201/699 [28.8%] vs. 2287/13,090 [17.5%]; odds ratio, 1.90 [1.61–2.26]; adjusted odds ratio, 1.22 [1.14–1.30]; p < 0.01), and the physician-staffed ambulance showed longer prehospital time (50 [36–66] vs. 37 [29–48] min, difference = 12 [11–12] min, p < 0.01). Such potential harm of the physician-staffed ambulance was only observed among patients who arrived at the hospital with persistent hypotension (systolic blood pressure < 90 mm Hg on hospital arrival) in subgroup analyses.

CONCLUSION
Physician-staffed ambulances were associated with prolonged prehospital stay and increased in-hospital mortality among hypotensive trauma patients compared with EMS personnel-staffed ambulance.

LEVEL OF EVIDENCE
Therapeutic, level IV.
Evaluating the impact of keeping indoor dining closed on COVID-19 rates among large US cities: a quasi-experimental design
Authors: Schnake-Mahl Alina S. , O’Leary Gabriella , Mullachery Pricila H. , Vaidya Vaishnavi , Connor Gabrielle , Rollins Heather , Kolker Jennifer , Diez Roux Ana V. , Bilal Usama 
Published: April 2021

AbstractObjectiveIndoor dining is one of the potential key drivers of COVID-19 transmission. We leverage the heterogeneity in state government preemption of city indoor dining closures, to estimate the impact of keeping indoor dining closed on COVID-19 incidence.MethodsWe obtained case rates and city/state re-opening dates from March to October 2020 in 11 U.S. cities. We categorized cities as (treatment) cities that were allowed by the state to reopen but kept indoor dining closed; and (comparison) cities that would have kept indoor dining closed but were preempted by their state and had to reopen indoor dining.ResultsKeeping indoor dining closed was associated with a 43% (IRR=0.57, 95% CI 0.46 to 0.69) decline in COVID-19 incidence over 4-weeks compared with cities that reopened indoor dining. These results were consistent after testing alternative modeling strategies.ConclusionsKeeping indoor dining closed contributes to reductions in COVID-19 spread.Policy ImplicationsEvidence of the relationship between indoor dining and COVID-19 incidence can inform state and local decisions to restrict indoor dining as a tailored strategy to reduce COVID-19 incidence.
Establishment of local adaptation in partly self-fertilizing populations
Authors: Trickovic Bogi , Glémin Sylvain 
Published: April 2021

AbstractPopulations often inhabit multiple ecological patches and thus experience divergent selection, which can lead to local adaptation if migration is not strong enough to swamp locally adapted alleles. Conditions for the establishment of a locally advantageous allele have been studied in randomly mating populations. However, many species reproduce, at least partially, through self-fertilization, and how selfing affects local adaptation remains unclear and debated. Using a two-patch branching process formalism, we obtained a closed-form approximation under weak selection for the probability of establishment of a locally advantageous allele (P) for arbitrary selfing rate and dominance level, where selection is allowed to act on viability or fecundity, and migration can occur via seed or pollen dispersal. This solution is compared to diffusion approximation and used to investigate the consequences of a shift in a mating system onP, and the establishment of protected polymorphism. We find that selfing can either increase or decreaseP, depending on the patterns of dominance in the two patches, and has conflicting effects on local adaptation. Globally, selfing favors local adaptation when locally advantageous alleles are (partially) recessive, when selection between patches is asymmetrical and when migration occurs through pollen rather than seed dispersal. These results establish a rigorous theoretical background to study heterogeneous selection and local adaptation in partially selfing species.
Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: Protocol for a cohort study in Montreal, Canada
Authors: Zinszer K , McKinnon B , Bourque N , Zahreddine M , Charland K , Papenburg J , Fortin G , Hamelin ME , Saucier A , Apostolatos A , Pierce L , Savard-Lamothe A , Carbonneau Julie , Conrod P , Haley N , Laurin I , Boivin G , De Serres G , Quach C 
Published: April 2021

ABSTRACTBackgroundFurther evidence is needed to understand the contribution of schools and daycares to the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Étude de séroprévalence (EnCORE) study will estimate the seroprevalence and seroconversion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and socio-demographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes.MethodsThis study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children age 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot (DBS), at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include socio-demographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts, and health and lifestyle information. Logistic regression using generalized estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering.DiscussionThe results of the EnCORE study will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares, which is critical for decisions regarding school attendance and the management of school outbreaks through the remainder of this school year and beyond.
Distinct nociresponsive region in mouse primary somatosensory cortex
Authors: Osaki Hironobu , Kanaya Moeko , Ueta Yoshifumi , Miyata Mariko 
Published: April 2021

AbstractNociception, somatic discriminative aspects of pain, is represented in the primary somatosensory cortex (S1), as is touch, but the separation and the interaction of the two modalities within S1 remain unclear. Here, we show the spatially-distinct tactile and nociceptive processing in the granular barrel field (BF) and the adjacent dysgranular region (Dys) in mouse S1. Simultaneous recording of the multiunit activity across subregions reveals that Dys responses are selective to noxious input whereas those of BF are to tactile input. At the single neuron level, nociceptive information is represented separately from the tactile information in Dys layer 2/3. In contrast, both modalities are converged in a layer 5 neuron in each region. Interestingly, the two modalities interfere with each other in both regions. We further demonstrate that Dys, but not BF, activity is critically involved in neuropathic pain and pain behavior, and thus provide evidence that Dys is a center specialized for nociception in S1.
Environmental selection and epistasis in an empirical phenotype-environment-fitness landscape
Authors: Chen J.Z. , Fowler D.M. , Tokuriki N. 
Published: April 2021

AbstractFitness landscapes, mappings of genotype/phenotype to their effects on fitness, are invaluable concepts in evolutionary biochemistry. Though widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype of VIM-2 β-lactamase across a 64-fold range of ampicillin concentrations. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account. We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, suggesting the evolution of VIM-2 can be predicted based on the selection environment. Our landscape provides new quantitative knowledge on the evolution of the β-lactamases and proteins in general, particularly their evolutionary dynamics under sub-inhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of nonspecific epistasis.One Sentence SummaryAn empirical fitness landscape discloses the environmental dependence of mutational effects in VIM-2 β-lactamase.
Aging alters the metabolic flux signature of the ER unfolded protein responsein vivoin mice
Authors: Schneider Catherine P. , Peng Lucy , Yuen Samuel , Halstead John , Palacios Hector , Nyangau Edna , Mohammed Hussein , Ziari Naveed , Frakes Ashley E. , Dillin Andrew , Hellerstein Marc K. 
Published: April 2021

AbstractAge is a risk factor for numerous diseases, including neurodegenerative diseases, cancers, and diabetes. Loss of protein homeostasis is a central hallmark of aging. Activation of the endoplasmic reticulum unfolded protein response (UPRER) includes changes in protein translation and membrane lipid synthesis. Using stable isotope labeling, a “signature” of the UPRERin vivoin mouse liver was developed by inducing ER stress and measuring rates of both proteome-wide translation andde novolipogenesis. Several changes in protein synthesis across ontologies were noted with age, including a more dramatic suppression of translation under ER stress in aged mice as compared to young mice. Binding immunoglobulin protein (BiP) synthesis rates and mRNA levels were increased more in aged than young mice.De novolipogenesis rates decreased under ER stress conditions in aged mice, including both triglyceride and phospholipid fractions. In young mice, only a significant reduction was seen in the triglyceride fraction. These data indicate that aged mice have an exaggerated response to ER stress, which may indicate that the aging renders the UPRERless effective in resolving proteotoxic stress.
Learning interpretable cellular responses to complex perturbations in high-throughput screens
Authors: Lotfollahi Mohammad , Susmelj Anna Klimovskaia , De Donno Carlo , Ji Yuge , Ibarra Ignacio L. , Wolf F. Alexander , Yakubova Nafissa , Theis Fabian J. , Lopez-Paz David 
Published: April 2021

AbstractRecent advances in multiplexed single-cell transcriptomics experiments are facilitating the high-throughput study of drug and genetic perturbations. However, an exhaustive exploration of the combinatorial perturbation space is experimentally unfeasible, so computational methods are needed to predict, interpret, and prioritize perturbations. Here, we present the compositional perturbation autoencoder (CPA), which combines the interpretability of linear models with the flexibility of deep-learning approaches for single-cell response modeling. CPA encodes and learns transcriptional drug responses across different cell type, dose, and drug combinations. The model produces easy-to-interpret embeddings for drugs and cell types, which enables drug similarity analysis and predictions for unseen dosage and drug combinations. We show that CPA accurately models single-cell perturbations across compounds, doses, species, and time. We further demonstrate that CPA predicts combinatorial genetic interactions of several types, implying that it captures features that distinguish different interaction programs. Finally, we demonstrate that CPA can generatein-silico5,329 missing genetic combination perturbations (97.6% of all possibilities) with diverse genetic interactions. We envision our model will facilitate efficient experimental design and hypothesis generation by enablingin-silicoresponse prediction at the single-cell level, and thus accelerate therapeutic applications using single-cell technologies.
A curated collection of human vaccination response signatures
Authors: Smith Kenneth C. , Chawla Daniel G. , Dhillon Bhavjinder K. , Ji Zhou , Vita Randi , van der Leest Eva C. , Weng Jing Yi (Jessica) , Tang Ernest , Abid Amani ,   The Human Immunology Project Consortium (HIPC), Peters Bjoern , Hancock Robert E.W. , Floratos Aris , Kleinstein Steven H. 
Published: April 2021

AbstractRecent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications identifying “immune signatures”. Unfortunately, these are often described within text, figures, or tables in a format not amenable to computational processing, thus severely hampering our ability to fully exploit this information. Here we present a data model to represent immune signatures, along with the Human Immunology Project Consortium (HIPC) Dashboard (www.hipc-dashboard.org), a web-enabled application to facilitate signature access and querying. The data model captures the biological response components (e.g., genes, proteins, cell types or metabolites) and metadata describing the context under which the signature was identified using standardized terms from established resources (e.g., HGNC, Protein Ontology, Cell Ontology). We have manually curated a collection of >600 immune signatures from >60 published studies profiling human vaccination responses for the current release. The system will aid in building a broader understanding of the human immune response to stimuli by enabling researchers to easily access and interrogate published immune signatures.
Profiling the transcallosal response of rat motor cortex evoked by contralateral optogenetic stimulation of glutamatergic cortical neurons
Authors: Skoven Christian Stald , Tomasevic Leo , Kvitsiani Duda , Pakkenberg Bente , Dyrby Tim Bjørn , Siebner Hartwig Roman 
Published: April 2021

AbstractBackgroundEfficient interhemispheric integration of neural activity between left and right primary motor cortex (M1) is critical for inter-limb motor control.ObjectiveWe employed optogenetic stimulation to establish a framework for probing transcallosal M1-M1 interactions in rats.MethodsIn male rats, we optogenetically stimulated glutamatergic neurons in right M1 and recorded the transcallosally evoked potential with chronically implanted electrodes in contralateral left M1 during dexmedetomidine anesthesia. We systematically varied the stimulation intensity and duration to characterize the relationship between stimulation parameters in right M1 and the characteristics of the evoked intracortical potentials in left M1.ResultsOptogenetic stimulation of right M1 consistently evoked a transcallosal response in left M1 with a consistent negative peak (N1) that sometimes was preceded by a smaller positive peak (P1). Higher stimulation intensity or longer stimulation duration gradually increased N1 amplitude and reduced N1 variability across trials. Median N1 latencies remained stable, once stimulation elicited a reliable N1 peak and did not display a systematic shortening with increasing stimulation intensity or duration.ConclusionsOptogenetically stimulated glutamatergic neurons in M1 can reliably evoke a transcallosal response in anesthetized rats and can be used to characterize the relationship between “stimulation dose” and “response magnitude” (i.e., the gain function) of transcallosal M1-to-M1 glutamatergic connections. Detailed knowledge of the stimulus-response relationship is needed to optimize the efficacy of optogenetic stimulation. Since transcallosal M1-M1 interactions can also be probed non-invasively with transcranial magnetic stimulation in humans, our optogenetic stimulation approach bears translational potential for studying how unilateral M1 stimulation can induce interhemispheric plasticity.
Passive receptor dissociation driven by porin threading establishes active colicin transport throughEscherichia coliOmpF
Authors: Francis Marie-Louise R. , Webby Melissa N. , Housden Nicholas G. , Kaminska Renata , Elliston Emma , Chinthammit Boonyaporn , Lukoyanova Natalya , Kleanthous Colin 
Published: April 2021

SUMMARYBacteria deploy weapons to kill their neighbours during competition for resources and aid survival within microbiomes. Colicins were the first antibacterial system identified yet how these bacteriocins cross the outer membrane of Escherichia coli is unknown. Here, by solving the structures of translocation intermediates and imaging toxin import, we uncover the mechanism by which the Tol-dependent nuclease colicin E9 (ColE9) crosses the outer membrane. We show that threading of ColE9’s disordered domain through two pores of the trimeric porin OmpF causes the colicin to disengage from its primary receptor, BtuB, and reorganise the translocon either side of the membrane. These rearrangements prime the toxin for import through the lumen of a single OmpF subunit, which is driven by the proton motive force-linked TolQ-TolR-TolA-TolB assembly. Our study explains why OmpF is a better translocator than OmpC and reconciles the mechanisms by which Ton- and Tol- dependent bacteriocins cross the bacterial outer membrane.
Hippocampal theta sequences in REM sleep during spatial learning
Authors: Zielinski Mark C. , Shin Justin D. , Jadhav Shantanu P. 
Published: April 2021

ABSTRACTRapid eye movement (REM) sleep is known to play a role in hippocampally-dependent memory, yet the activity and development of hippocampal neuronal ensembles during this state is not well understood. Here we investigated patterning of CA1 place cell activity by theta oscillations, a shared electrophysiological hallmark of both waking behavior and REM sleep, in male rats learning a spatial memory task. We report the existence of REM theta sequences, sequential reactivations of place cells in REM theta that parallel waking theta sequences. REM and wake theta sequences develop rapidly with experience, recapitulating behavioral sequences of compressed space in forward and reverse directions throughout learning. REM sleep exhibited a balance of forward and reverse sequences in contrast to predominantly forward wake theta sequences. Finally, we found that a CA1 neuronal population known to shift preferred theta phases in REM exhibited differential participation in wake and REM theta sequences. In particular, this phase-shifting population showed an increased contribution to REM theta sequence representations after behavioral performance asymptotes and the task is learned, supporting a previously hypothesized role in depotentiation. These findings suggest a role for REM associated theta sequences in state dependent memory functions of the hippocampal circuit, providing evidence that REM sleep is associated with sequence reactivation that can support consolidation of representations necessary for memory guided behavior.