bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of timing of a population level intervention on COVID-19 mortality
Authors: Johnston Jasper S. , Johnston Eloïse S. , Johnston Sebastian L. 
Published: April 2020

AbstractCOVID-19 poses an immense and immediate threat to global public health. Population level interventions (PLIs) impact this threat, with estimable large effects on reducing mortality. Many countries worldwide have currently zero/low mortality and many have yet to implement such PLIs. The importance of timing of PLI implementation on mortality outcomes is poorly understood. We extracted cumulative daily country-specific COVID-19 mortality for France, Germany, Italy, Spain and the UK to examine country-specific mortality trends and found that all five countries experienced COVID-19 mortality epidemics initially of exponential nature. We estimated the magnitude of effect on mortality of the nationwide PLI implemented on day 18 of Italy’s mortality epidemic and assessed the importance of timing of PLI implementation by computing the effect of implementation of a PLI of this magnitude at various times on subsequent mortality. The nationwide PLI in Italy saved an estimated 6,170 lives by day 30 of the Italian epidemic. Implementing a PLI with this effect magnitude in a country of 60 million people on the day of the first death, and on days 7, 10, 14 and 17 thereafter, compared to implementation on day 18, resulted in substantially greater numbers of lives saved. Implementation on day 1 resulted in an additional 3,477 lives saved, 6,955 intensive care unit admissions and 52,162 hospital admissions prevented, beyond that achieved by implementation on day 18. PLI implementation earlier than day 18 substantially enhances benefit. Intervention on the day of the first mortality event in a country achieves the greatest benefit.
Measure what matters: counts of hospitalized patients are a better metric for health system capacity planning for a reopening
Authors: Kashyap Sehj , Gombar Saurabh , Yadlowsky Steve , Callahan Alison , Fries Jason , Pinsky Benjamin A , Shah Nigam H 
Published: April 2020

AbstractResponding to the COVID-19 pandemic requires accurate forecasting of health system capacity requirements using readily available inputs. We examined whether testing and hospitalization data could help quantify the anticipated burden on the health system given shelter-in-place (SIP) order.We find a marked slowdown in the hospitalization rate within ten days of SIP even as cases continued to rise. We also find a shift towards younger patients in the age distribution of those testing positive for COVID-19 over the four weeks of SIP. The impact of this shift is a divergence between increasing positive case confirmations and slowing new hospitalizations, both of which affects the demand on health systems.Without using local hospitalization rates and the age distribution of positive patients, current models are likely to overestimate the resource burden of COVID-19. It is imperative that health systems start using these data to quantify effects of SIP and aid reopening planning.
Weight Sensitivity of Temporal SNR Metrics in multi-echo fMRI
Authors: Liu Thomas T. , Li Bochao , Chen Conan , Fernandez Brice , Yang Baolian , Banerjee Suchandrima 
Published: April 2020

AbstractPurposeIn multi-echo fMRI (ME-fMRI), various weighting schemes have been proposed for the combination of the data across echoes. Here we introduce a framework that facilitates a deeper understanding of the weight dependence of temporal SNR measures in ME-fMRI.Theory and MethodsWe examine two metrics that have been used to characterize ME-fMRI performance: temporal SNR (tSNR) and multi-echo temporal (metSNR). Both metrics can be described using the generalized Rayleigh quotient (GRQ) and are predicted to be relatively insensitive to the weights when there is a high degree of similarity between a metric-specific matrix in the GRQ numerator and a metricindependent covariance matrix in the GRQ denominator. The application of the GRQ framework to experimental data is demonstrated using a resting-state fMRI dataset acquired with a multi-echo multi-band EPI sequence.ResultsIn the example dataset, similarities between the covariance matrix and the metSNR and tSNR numerator matrices are highest in grey matter (GM) and cerebrospinal fluid (CSF) voxels, respectively. For representative GM and CSF voxels that exhibit high matrix similarity values, the metSNR and tSNR values, respectively, are both within 4% of their optimal values across a range of weighting schemes. However, there is a fundamental tradeoff, with a high degree of weight sensitivity in the tSNR and metSNR metrics for the representative GM and CSF voxels, respectively. Geometric insight into the observed weight dependencies is provided through a graphical interpretation of the GRQ.ConclusionA GRQ framework can provide insight into the factors that determine the weight sensitivity of tSNR and metSNR measures in ME-fMRI.
A flexible target-specific anti-infection therapeutic platform that can be applied to different microbial species
Authors: Mitsunaga Makoto , Ito Kimihiro , Nishimura Takashi , Miyata Hironori , Mizunoe Yoshimitsu , Kobayashi Hisataka , Iwase Tadayuki 
Published: April 2020

AbstractThe emergence of new microbial pathogens, including drug-resistant strains, complicates treatment, thereby threatening global health. We demonstrated a photoimmuno-antimicrobial strategy (PIAS) that eliminated antibody-targets using a photo-activated anti-pathogen antibody generating mechanical stress that damaged the target’s binding sites. PIAS is effective against many pathogens, including methicillin-resistantStaphylococcus aureus(MRSA), the fungal pathogenCandida albicans, and viral particles irrespective of their species or drug-resistance status. Animal experiments demonstrated that PIAS saved mice from fatal infections; microbiome and histochemical analyses indicated no apparent effect on normal host microflora and tissues in PIAS-treated mice. Resistance to PIAS was not observed during the eight years of this study. As a new type of anti-infection therapy, PIAS may contribute to advances in anti-infection strategies.
RiboDiPA: A Novel tool for differential pattern analysis in Ribo-seq data
Authors: Li Keren , Hope Matthew , Wang Xiaozhong A. , Wang Ji-Ping 
Published: April 2020

AbstractRibosome profiling (also known as Ribo-seq) has become an important technique to investigate changes in translation across a wide variety of contexts. Ribo-seq data not only provides the abundance of ribosomes bound to transcripts, but also positional information across transcripts that could be indicative of differences in translation dynamics between conditions. While many computational tools exist for the analysis of Ribo-seq data, including those that assess differences in translational efficiency between conditions, no tool currently exists for rigorous test of the pattern differences in ribosome footprint. In this paper we propose a novel approach together with an R package, RiboDiPA, forDifferentialPPatternAnalysis of Ribo-seq data. RiboDiPA allows for quick identification of genes with statistically significant differences in ribosome occupancy patterns for model organisms ranging from yeast to mammals. We show that differential pattern analysis reveals information that is distinct and complimentary to the existing methods that focus on translational efficiency analysis. Using both simulated Ribo-seq footprint data and two benchmark data sets, we illustrate that RiboDiPA can not only uncover meaningful global translational differences between conditions, but also the detailed differential ribosome binding patterns to a single codon resolution.
Impairments in Hippocampal Place Cell Sequences during Errors in Spatial Memory
Authors: Zheng Chenguang , Hwaun Ernie , Colgin Laura Lee 
Published: April 2020

ABSTRACTTheta and gamma rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We used a delayed match-to-place memory task to investigate whether such coordination of hippocampal place cell sequences is disrupted when memory errors occur. As rats approached a learned reward location, place cell sequences represented paths extending toward the reward location during correct trials. During error trials, paths coded by place cell sequences were significantly shorter as rats approached incorrect stop locations, with place cell sequences starting at a significantly delayed phase of the theta cycle. During rest, place cell sequences replayed representations of paths that were highly likely to end at the correct reward location during correct but not error trials. The relationship between place cell sequences and gamma rhythms, however, did not differ between correct and error trials. These results suggest that coordination of place cell sequences by theta rhythms and sharp wave-ripples is important for successful spatial memory.
Reactive Oxygen Species Modulate Activity-Dependent AMPA Receptor Transport inC. elegans
Authors: Doser Rachel L. , Amberg Gregory C. , Hoerndli Frederic J. 
Published: April 2020

ABSTRACTThe AMPA subtype of synaptic glutamate receptors (AMPARs) play an essential role in cognition. Their function, numbers and change at synapses during synaptic plasticity, is tightly regulated by neuronal activity. Although we know that long-distance transport of AMPARs is essential for this regulation, we don’t understand the regulatory mechanisms of it. Neuronal transmission is a metabolically demanding process in which ATP consumption and production are tightly coupled and regulated. Aerobic ATP synthesis unavoidably produces reactive oxygen species (ROS), such as hydrogen peroxide, which are known modulators of calcium signaling. Although a role for calcium signaling in AMPAR transport has been described, there is little understanding of the mechanisms involved and no known link to physiological ROS signaling. Here, using real-timein vivoimaging of AMPAR transport in the intactC. elegansnervous system, we demonstrate that long-distance synaptic AMPAR transport is bidirectionally regulated by calcium influx and activation of calcium/calmodulin-dependent protein kinase II. Quantifyingin vivocalcium dynamics revealed that modest, physiological increases in ROS decrease calcium transients inC. elegansglutamatergic neurons. By combining genetic and pharmacological manipulation of ROS levels and calcium influx, we reveal a mechanism in which physiological increases in ROS cause a decrease in synaptic AMPAR transport and delivery by modulating activity-dependent calcium signaling. Taken together, our results identify a novel role for oxidant signaling in the regulation of synaptic AMPAR transport and delivery, which in turn could be critical for coupling the metabolic demands of neuronal activity with excitatory neurotransmission.SIGNIFICANCE AND IMPACTSynaptic AMPARs are critical for excitatory synaptic transmission. The disruption of their synaptic localization and numbers is associated with numerous psychiatric, neurological, and neurodegenerative conditions. However, very little is known about the regulatory mechanisms controlling transport and delivery of AMPAR to synapses. Here, we describe a novel physiological signaling mechanism in which ROS, such as hydrogen peroxide, modulate AMPAR transport by modifying activity-dependent calcium influx. Our findings provide the first evidence in support of a mechanistic link between physiological ROS signaling, AMPAR transport, localization, and excitatory transmission. Of potential therapeutic importance, dysregulation of intracellular calcium and ROS signaling is implicated in the pathogenesis of several neurodegenerative disorders including Alzheimer’s and Parkinson’s disease.
Repeatability and reproducibility assessment in a large-scale population-based microbiota study: case study on human milk microbiota
Authors: Moossavi Shirin , Fehr Kelsey , Moraes Theo J. , Khafipour Ehsan , Azad Meghan B. 
Published: April 2020

AbstractBackgroundQuality control including assessment of batch variabilities and confirmation of repeatability and reproducibility are integral component of high throughput omics studies including microbiome research. Batch effects can mask true biological results and/or result in irreproducible conclusions and interpretations. Low biomass samples in microbiome research are prone to reagent contamination; yet, quality control procedures for low biomass samples in large-scale microbiome studies are not well established.ResultsIn this study we have proposed a framework for an in-depth step-by-step approach to address this gap. The framework consists of three independent stages: 1) verification of sequencing accuracy by assessing technical repeatability and reproducibility of the results using mock communities and biological controls; 2) contaminant removal and batch variability correction by applying a two-tier strategy using statistical algorithms (e.g.decontam) followed by comparison of the data structure between batches; and 3) corroborating the repeatability and reproducibility of microbiome composition and downstream statistical analysis. Using this approach on the milk microbiota data from the CHILD Cohort generated in two batches (extracted and sequenced in 2016 and 2019), we were able to identify potential reagent contaminants that were missed with standard algorithms, and substantially reduce contaminant-induced batch variability. Additionally, we confirmed the repeatability and reproducibility of our reslults in each batch before merging them for downstream analysis.ConclusionThis study provides important insight to advance quality control efforts in low biomass microbiome research. Within-study quality control that takes advantage of the data structure (i.e.differential prevalence of contaminants between batches) would enhance the overall reliability and reproducibility of research in this field.
Disease-associated mutations in TRPM3 render the channel overactive via two distinct mechanisms
Authors: Zhao Siyuan , Yudin Yevgen , Rohacs Tibor 
Published: April 2020

ABSTRACTTransient Receptor Potential Melastatin 3 (TRPM3) is a Ca2+permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations however were not reported. Here we show that both disease-associated mutations of TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease.
Recovery and Community Succession of theZostera marinaRhizobiome After Transplantation
Authors: Wang Lu , English Mary K. , Tomas Fiona , Mueller Ryan S. 
Published: April 2020

AbstractSeagrasses can form mutualisms with their microbiomes that facilitate the exchange of energy sources, nutrients, and hormones, and ultimately impact plant stress resistance. Little is known about community succession within the belowground seagrass microbiome after disturbance and its potential role in the plant’s recovery after transplantation. We transplantedZostera marinashoots with and without an intact rhizosphere and cultivated plants for four weeks while characterizing microbiome recovery and effects on plant traits. Rhizosphere and root microbiomes were compositionally distinct, likely representing discrete microbial niches. Furthermore, microbiomes of washed transplants were initially different from those of sod transplants, and recovered to resemble an undisturbed state within fourteen days. Conspicuously, changes in microbial communities of washed transplants corresponded with changes in rhizosphere sediment mass and root biomass, highlighting the strength and responsive nature of the relationship between plants, their microbiome, and the environment. Potential mutualistic microbes that were enriched over time include those that function in the cycling and turnover of sulfur, nitrogen, and plant-derived carbon in the rhizosphere environment. These findings highlight the importance and resiliency of the seagrass microbiome after disturbance. Consideration of the microbiome will have meaningful implications on habitat restoration practices.ImportanceSeagrasses are important coastal species that are declining globally, and transplantation can be used to combat these declines. However, the bacterial communities associated with seagrass rhizospheres and roots (the microbiome) are often disturbed or removed completely prior to transplantation. The seagrass microbiome benefits seagrasses through metabolite, nutrient, and phytohormone exchange, and contributes to the ecosystem services of seagrass meadows by cycling sulfur, nitrogen, and carbon. This experiment aimed to characterize the importance and resilience of the seagrass belowground microbiome by transplantingZostera marinawith and without intact rhizospheres and tracking microbiome and plant morphological recovery over four weeks. We found the seagrass microbiome to be resilient to transplantation disturbance, recovering after fourteen days. Additionally, microbiome recovery was linked with seagrass morphology, coinciding with increases in rhizosphere sediment mass and root biomass. Results of this study can be used to include microbiome responses in informing future restoration work.
Mendelian randomization analysis revealed causal effects from gut microbiota to abdominal obesity
Authors: Xu Qian , Zhang Shan-Shan , Pei Yu-Fang , Ni Jing-Jing , Zhang Lei , Wang Rui-Rui , Weng Yu-Jing , Cui Xun , Wei Xin-Tong 
Published: April 2020

ABSTRACTAlthough recent studies have revealed the association between the gut microbiota and obesity, the causality remains elusive. We performed a Mendelian Randomization (MR) analysis to determine whether there is a causal relationship between gut microbiota and abdominal obesity. We used a two-sample MR approach to assess the causal effect from gut microbiota to obesity based on genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics of gut microbiota obtained from UK-twins cohort (N=1,126) were used as discovery sample exposure, and the GWAS summary statistics from the Genetic Environmental Microbial (GEM) project (N=1,098) were used as replication sample exposure. Trunk fat mass (TFM) summary statistics from the UK Biobank (UKB) cohort (N=330,762) were used as outcome. Bacteria were grouped into taxa features at family level. A total of 16 families were analyzed in the discovery sample. FamilyBarnesiellaceaewas associated with TFM at the nominal significance level (b=-3.81×10−4,P=1.96×10−3). The causal association was successfully replicated in the replication sample (b=-7.34×10−3,P=2.77×10−2). Our findings provided evidence of causal relationship from microbiota to fat development, and may be helpful in selecting potential causal bacteria for manipulating candidate gut microbiota to therapy obesity.IMPORTANCEObesity, as a global public health problem, is one of the most important risk factors contributing to the overall global burden of disease, and is associated with an increased risk of cardiovascular disease, type 2 diabetes, and certain cancers. Recent studies have shown that gut microbiota is closely related to the development of obesity, but the causal relationship is unclear. Therefore, it is necessary to identify the causality between gut microbiota and obesity. The significance of our research is in identifying the causal relationship from specific bacteria to fat development, which will provide the new insights into the microbiota mediated the fat development mechanism.
Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients
Authors: Buscarini Elisabetta , Manfredi Guido , Brambilla Gianfranco , Menozzi Fernanda , Londoni Claudio , Alicante Saverio , Iiritano Elena , Romeo Samanta , Pedaci Marianna , Benelli Gianpaolo , Canetta Ciro , Lapiana Giuseppe , Merli Guido , Scartabellati Alessandro , Viganò Giovanni , Sfogliarini Roberto , Melilli Giovanni , Assandri Roberto , Cazzato Daniele , Rossi Davide Sebastiano , Usai Susanna , Tramacere Irene , Pellegata Germano , Lauria Giuseppe 
Published: April 2020

ABSTRACTObjectiveTo assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients.DesignSince February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. were recorded.ResultsGI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-… days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms.ConclusionsGI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.