bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climatic factors influence COVID-19 outbreak as revealed by worldwide mortality
Authors: Quilodrán Claudio S. , Currat Mathias , Montoya-Burgos Juan I. 
Published: April 2020

SummaryThe COVID-19 outbreak is triggering a global crisis that is challenging governments, health systems and the scientific community worldwide1. A central question in the COVID-19 pandemic is whether climatic factors modulate its progression. This information is key to epidemiologists and healthcare decision-makers for improving their management plans2. Previous attempts to assess the impact of climatic parameters have yielded ambiguous results, either because they were using geographically or temporally restricted data, or because they were comparing infection rates across countries, which were measured differently depending on local screening strategies. In March 2020, the spread of COVID-19 dramatically increased the number of countries recording deaths3, providing an opportunity to use mortality rate, which is measured more homogeneously across countries than infection rates, as a descriptor of the COVID-19 outbreak over a large latitudinal range. Here, using data recorded in 208 territories from 88 countries, we show that mortality rate is negatively influenced by warmer air temperature and positively affected by higher relative humidity. Each additional Celsius degree decreases mortality rate by ∼4%, while a 1% increase in relative humidity raises mortality rate by ∼2%. Temperature is positively correlated with UV-index, for which one unit of increase results in a ∼15% decrease in the mortality rate. We also show that other factors contribute to the dynamics of the COVID-19 outbreak, such as the proportion of vulnerable age classes in the population, access to a non-overwhelmed health system, as well as governmental travel restrictions for controlling the spread of the disease. All of them are critical factors impacting the mortality rate of COVID-19. The influence of climatic factors is a warning to all southern hemisphere countries where winter is coming soon. Northern hemisphere countries should also be warned that climatic factors alone will likely not be sufficient to contain the disease.
Estimated surge in hospitalization and intensive care due to the novel coronavirus pandemic in the Greater Toronto Area, Canada: a mathematical modeling study with application at two local area hospitals
Authors: Mishra Sharmistha , Wang Linwei , Ma Huiting , Yiu Kristy CY , Paterson J. Michael , Kim Eliane , Schull Michael J , Pequegnat Victoria , Lee Anthea , Ishiguro Lisa , Coomes Eric , Chan Adrienne , Downing Mark , Landsman David , Straus Sharon , Muller Matthew 
Published: April 2020

AbstractBackgroundA hospital-level pandemic response involves anticipating local surge in healthcare needs.MethodsWe developed a mechanistic transmission model to simulate a range of scenarios of COVID-19 spread in the Greater Toronto Area. We estimated healthcare needs against 2019 daily admissions using healthcare administrative data, and applied outputs to hospital-specific data on catchment, capacity, and baseline non-COVID admissions to estimate potential surge by day 90 at two hospitals (St. Michael’s Hospital [SMH] and St. Joseph’s Health Centre [SJHC]). We examined fast/large, default, and slow/small epidemics, wherein the default scenario (R0 2.4) resembled the early trajectory in the GTA.ResultsWithout further interventions, even a slow/small epidemic exceeded the city’s daily ICU capacity for patients without COVID-19. In a pessimistic default scenario, for SMH and SJHC to remain below their non-ICU bed capacity, they would need to reduce non-COVID inpatient care by 70% and 58% respectively. SMH would need to create 86 new ICU beds, while SJHC would need to reduce its ICU beds for non-COVID care by 72%. Uncertainty in local epidemiological features was more influential than uncertainty in clinical severity. If physical distancing reduces contacts by 20%, maximizing the diagnostic capacity or syndromic diagnoses at the community-level could avoid a surge at each hospital.InterpretationAs distribution of the city’s surge varies across hospitals over time, efforts are needed to plan and redistribute ICU care to where demand is expected. Hospital-level surge is based on community-level transmission, with community-level strategies key to mitigating each hospital’s surge.
A model-based evaluation of the efficacy of COVID-19 social distancing, testing and hospital triage policies
Authors: McCombs Audrey , Kadelka Claus 
Published: April 2020

AbstractWe present a stochastic compartmental network model of SARS-CoV-2 and COVID-19 exploring the effects of policy choices in three domains: social distancing, hospital triaging, and testing. We distinguished between high-risk and low-risk members of the population, and modeled differences in social interactions due to context, risk level, infection status, and testing status. The model incorporates many of the currently important characteristics of the disease, including overcapacity in the healthcare system and uncertainties surrounding the proportion and transmission potential of asymptomatic cases. We compared current policy guidelines from public health agencies with alternative options, and investigated the effects of policy decisions on the overall proportion of COVID-19-related deaths. Our results support current policies to contain the outbreak but also suggest possible refinements, including emphasizing the need to reduce public, random contacts more than private contacts, and testing low-risk symptomatic individuals before high-risk symptomatic individuals. Our model furthermore points to interactions among the three policy domains; the efficacy of a particular policy choice depends on other implemented policies. Finally, our results provide an explanation for why societies like Germany, with lower average rates of social contact, are more successful at containing the outbreak than highly social societies such as Italy, despite the implementation of similar policy measures.
Genetic evidence for protective effects of smoking and drinking behavior on Parkinson’s disease: A Mendelian Randomization study
Authors: Domínguez-Baleón Carmen , Ong Jue-Sheng , Scherzer Clemens R. , Rentería Miguel E. , Dong Xianjun 
Published: April 2020

ABSTRACTBackgroundObservational studies have identified correlations between environmental and lifestyle factors and Parkinson’s disease (PD). However, the causal direction of many of these relationships remains unclear.ObjectiveTo infer causal relationships between smoking and alcohol intake and PD.MethodsWe use a two-sample Mendelian randomization (MR) experimental design to infer causal relationships between smoking (initiation, age of initiation, heaviness, and cessation) and alcohol (drinks per week) consumption as exposure variables and PD as the health outcome. We also conduct sensitivity analyses, including testing for pleiotropic effects MR-Egger and MR-PRESSO, and multivariable MR to jointly model the effects of drinking and smoking behavior on PD risk.ResultsBoth alcohol intake (OR = 0.69; 95% CI 0.56-0.86; p=0.001). and smoking cessation (comparing current vs. former smokers) (IVW OR = 0.39; 95% CI 0.22 to 0.69; p=0.001) were causally associated with a reduced risk of PD. In addition, our multivariable MR results provide additional assurance that the causal association between drinks per week and PD is unlikely due to confounding by smoking behavior.ConclusionOur findings support the role of smoking as a protective factor against PD, but only when comparing current vs. former smokers. Increased alcohol intake also had a protective effect over PD risk, and the alcohol dehydrogenase 1B (ADH1B) locus is a candidate for further investigating the mechanisms underlying this association.
Copy Number Variation at 16p11.2 Imparts Transcriptional Alterations in Neural Development in an hiPSC-derived Model of Corticogenesis
Authors: Roth Julien G. , Muench Kristin L. , Asokan Aditya , Mallett Victoria M. , Gai Hui , Verma Yogendra , Weber Stephen , Charlton Carol , Fowler Jonas L. , Loh Kyle M. , Dolmetsch Ricardo E. , Palmer Theo D. 
Published: April 2020

ABSTRACTMicrodeletions and microduplications of the 16p11.2 chromosomal locus are associated with syndromic neurodevelopmental disorders and reciprocal physiological conditions such as macro/microcephaly and high/low body mass index. To facilitate cellular and molecular investigations of these phenotypes, 65 clones of human induced pluripotent stem cells (hiPSCs) were generated from 13 individuals with 16p11.2 copy number variations (CNVs). Cortical neural progenitor cells derived from these hiPSCs were profiled using RNA-Seq, which identified alterations in radial glial gene expression that precede morphological abnormalities reported at later neurodevelopmental stages. Moreover, a customizable bioinformatic strategy for the detection of random integration and expression of reprogramming vectors was developed and leveraged towards identifying a subset of “footprint”-free hiPSC clones that are available by request from the Simons Foundation Autism Research Initiative. This publicly available resource of 65 human hiPSC clones can serve as a powerful medium for probing the etiology of developmental disorders associated with 16p11.2 CNVs.
Self-reported symptoms of covid-19 including symptoms most predictive of SARS-CoV-2 infection, are heritable
Authors: Williams Frances MK , Freidin Maxim B , Mangino Massimo , Couvreur Simon , Visconti Alessia , Bowyer Ruth CE , Le Roy Caroline I , Falchi Mario , Sudre Carole , Davies Richard , Hammond Christopher , Menni Cristina , Steves Claire J , Spector Tim D 
Published: April 2020

AbstractSusceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n=2633) completing the C-19 Covid symptom tracker app allowed classical twin studies of covid-19 symptoms including predicted covid-19, a symptom-based algorithm predicting true infection derived in app users tested for SARS-CoV-2. We found heritability for fever = 41 (95% confidence intervals 12-70)%; anosmia 47 (27-67)%; delirium 49 (24-75)%; and predicted covid-19 gave heritability = 50 (29-70)%.
Cellular expression and functional roles of all 26 neurotransmitter GPCRs in theC. elegansegg-laying circuit
Authors: Fernandez Robert W. , Wei Kimberly , Wang Erin Y. , Mikalauskaite Deimante , Olson Andrew , Pepper Judy , Christie Nakeirah , Kim Seongseop , Koelle Michael R. 
Published: April 2020

SummaryMaps of the synapses made and neurotransmitters released by all neurons in model systems such asC. eleganshave left still unresolved how neural circuits integrate and respond to neurotransmitter signals. Using the egg-laying circuit ofC. elegansas a model, we mapped which cells express each of the 26 neurotransmitter G protein coupled receptors (GPCRs) of this organism and also genetically analyzed the functions of all 26 GPCRs. We found that individual neurons express many distinct receptors, epithelial cells often express neurotransmitter receptors, and receptors are often positioned to receive extrasynaptic signals. The egg-laying circuit appears to use redundancy and compensation to achieve functional robustness, as receptor knockouts reveal few defects; however, increasing receptor signaling through overexpression more efficiently reveals receptor functions. This map of neurotransmitter GPCR expression and function in the egg-laying circuit provides a model for understanding GPCR signaling in other neural circuits.
Early detection of daylengths with a feedforward circuit coregulated by circadian and diurnal cycles
Authors: Panchy Nicholas , von Arnim Albrecht G. , Hong Tian 
Published: April 2020

AbstractLight-entrained circadian clocks confer rhythmic dynamics of cellular and molecular activities to animals and plants. These intrinsic clocks allow stable anticipations to light-dark (diel) cycles. Many genes in the model plantArabidopsis thalianaare regulated by diel cycles via pathways independent of the clock, suggesting that the integration of circadian and light signals is important for the fitness of plants. Previous studies of light-clock signal integrations have focused on moderate phase adjustment of the two signals. However, dynamical features of integrations across a broad range of phases remain elusive. We recently found that phosphorylation of RIBOSOMAL PROTEIN OF THE SMALL SUBUNIT 6 (RPS6 or eS6), a ubiquitous post-translational modification across kingdoms, is influenced by the circadian clock and the light-dark (diel) cycle in an opposite manner. In order to understand this striking phenomenon and its underlying information processing capabilities, we built a mathematical model for the eS6-P control circuit. We found that the dynamics of eS6-P can be explained by a feedforward circuit with inputs from both circadian and diel cycles. Furthermore, the early-day response of this circuit with dual rhythmic inputs is sensitive to the changes in daylength, including both transient and gradual changes observed in realistic light intervals across a year, due to weather and seasons. By analyzing published gene expression data, we found that the dynamics produced by the eS6-P control circuit can be observed in the expression profiles of a large number of genes. Our work provides mechanistic insights into the complex dynamics of a ribosomal protein, and it proposes a previously underappreciated function of the circadian clock which not only prepares organisms for normal diel cycles but also helps to detect both transient and seasonal changes with a predictive power.
Ras Inhibitor CAPRI Enables Neutrophils to Chemotax Through a Higher-Concentration Range of Gradients
Authors: Xu Xuehua , Wen Xi , Moosa Amer , Bhimani Smit , Jin Tian 
Published: April 2020

AbstractNeutrophils sense and migrate through an enormous range of chemoattractant gradients through adaptation. Here, we reveal that, in human neutrophils, Calcium-promoted Ras inactivator (CAPRI) locally controls the GPCR-stimulated Ras adaptation. Human neutrophils lacking CAPRI (caprikd) exhibit chemoattractant-induced non-adaptive Ras activation; significantly increased phosphorylation of AKT, GSK3α/3β, and cofilin; and excessive actin polymerization.caprikdcells display defective chemotaxis in response to high-concentration gradients but exhibit improved chemotaxis in low- or subsensitive-concentration gradients of various chemoattractants as a result of their enhanced sensitivity. Taken together, our data reveal that CAPRI controls GPCR activation-mediated Ras adaptation and lowers the sensitivity of human neutrophils so that they are able to chemotax through a higher concentration range of chemoattractant gradients.Significance StatementNeutrophils provide first-line host defense by migrating through chemoattractant gradients to the sites of inflammation. Inappropriate recruitment and mis-regulated activation of neutrophils contribute to tissue damage and cause autoimmune and inflammatory disease. One fascinating feature of chemotactic neutrophils is their ability to migrate through an enormous concentration range of chemoattractant gradients (10−9∼ 10−5M) through “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. Our study reveals, for the first time, that the inhibitory component, CAPRI, is essential for both the sensitivity and the GPCR-mediated adaptation of human neutrophils.
Hepatocyte-specific deletion of XBP1 sensitizes mice to liver injury through hyperactivation of IRE1α
Authors: Duwaerts Caroline C. , Siao Kevin , Soon Russell K. , Her Chris , Iwawaki Takao , Kohno Kenji , Mattis Aras N. , Maher Jacquelyn J. 
Published: April 2020

AbstractX-box binding protein-1 (XBP1) is a transcription factor that plays a central role in controlling cellular responses to endoplasmic reticulum (ER) stress. Under stress conditions, the transcriptionally active form of XBP1 is generated by unique splicing ofXbp1mRNA by the ER-resident protein inositol-requiring enzyme-1 (IRE1α). Genetic deletion of XBP1 has multiple consequences: some resulting from the loss of the transcription factor per se, and others related to compensatory upstream activation of IRE1α. The objective of the current study was to investigate the effects of XBP1 deletion in adult mouse liver and determine to what extent they are direct or indirect. XBP1 was deleted specifically from hepatocytes in adultXbp1fl/flmice using AAV8-Transthyretin-Cre (Xbp1Δhep).Xbp1Δhepmice exhibited no liver disease at baseline, but developed acute biochemical and histologic liver injury in response to a dietary challenge with fructose for 4 wk. Fructose-mediated liver injury inXbp1Δhepmice coincided with heightened IRE1α activity, as demonstrated by cJun phosphorylation and regulated IRE1α -dependent RNA decay (RIDD). Activation of eIF2α was also evident, with associated up-regulation of the pro-apoptotic molecules CHOP, BIM and PUMA. To determine whether the adverse consequences of liver-specific XBP1 deletion were due to XBP1 loss or heightened IRE1α activity, we repeated a fructose challenge in mice with liver-specific deletion of both XBP1 and IRE1α (Xbp1Δhep;IRE1αΔhep).Xbp1Δhep;IRE1αΔhepmice were protected from fructose-mediated liver injury and failed to exhibit any of the signs of ER stress seen in mice lacking XBP1 alone. The protective effect of IRE1α deletion persisted even with long-term exposure to fructose.Xbp1Δhepmice developed liver fibrosis at 16 wk, butXbp1Δhep;IRE1αΔhepmice did not. Overall, the results indicate that the deleterious effects of hepatocyte-specific XBP1 deletion are due primarily to hyperactivation of IRE1α. They support further exploration of IRE1α as a contributor to acute and chronic liver diseases.
The conservation of a core virome inAedesmosquitoes across different developmental stages and continents
Authors: Shi Chenyan , Zhao Lu , Atoni Evans , Zeng Weifeng , Hu Xiaomin , Matthijnssens Jelle , Yuan Zhiming , Xia Han 
Published: April 2020

AbstractMosquitoes belonging to the genusAedescan efficiently transmit many pathogenic arboviruses, placing a great burden on public health worldwide. In addition, they also carry a number of insect specific viruses (ISVs), and it was recently suggested that some of these ISVs might form a stable species-specific “core virome” in mosquito populations. However, little is known about such a core virome in laboratory colonies and if it is present across different developmental stages. In this study, we compared the viromes in eggs, larvae, pupae and adults ofAedes albopictusmosquitoes collected from the field as well as from a lab colony. The virome in lab-derivedAe. albopictusis very stable across all stages, consistent with a vertical transmission route of these viruses, forming a “vertically transmitted core virome”. The different stages of field collectedAe. albopictusmosquitoes also contains this stable vertically transmitted core virome as well as another set of viruses shared by mosquitoes across different stages, which might be an “environment derived core virome”. Both these vertically and environmentally transmitted core viromes inAe. albopictusdeserve more attention with respect to their effects on vector competence for important medically relevant arboviruses. To further study this core set of ISVs, we screened 46 publically available SRA viral metagenomic dataset of mosquitoes belonging to the genusAedes. Some of the identified core ISVs are identified in the majority of SRAs. In addition, a novel virus, Aedes phasmavirus, is found to be distantly related to Yongsan bunyavirus 1, and the genomes of the core virus Phasi Charoen-like phasivirus is highly prevalent in the majority of the tested samples, with nucleotide identities ranging from 94% to 99%. Finally, Guadeloupe mosquito virus, and some related viruses formed three separated phylogenetic clades. How these core ISVs influence the biology of mosquito host, arboviruses infection and evolution deserve to be further explored.
Agro-industrialisation and financial intermediation in Nigeria
Authors: Adeleye Ngozi , Osabuohien Evans , Asongu Simplice 
Published: April 2020

PurposeThe study aims to analyse the role of finance in the agro-industrialisation nexus in Nigeria using annual data on manufacturing value added, agricultural value added and volume of finance availed to the agricultural sector from 1981 to 2015.Design/methodology/approachTo establish the presence of a long-run relationship, the error correction model and bounds cointegration techniques are employed. Likewise, the model is augmented to test whether the associated relationship between industrial output and agricultural output depends on access to finance by farmers with the inclusion of an interaction term.FindingsSome salient contributions to the literature are as follows: agriculture and finance are strong and positive predictors of industrialisation in the long run; in the short run, past realisations of industrial output and finance have significant asymmetric effects on industrial output; the explanatory power of agriculture decreases with the growth of the financial system; and the long-run results validate the role of finance in the agro-industrialisation nexus.Originality/valueGiven these findings, achieving growth in the agricultural sector that will induce desired industrialisation should be prioritised by the government through agencies such as the central bank, financial intermediaries and other stakeholders with a view to making agricultural financing a major concern for sustainable domestic consumption and industrial growth.
The influence of food values on post–purchase variables at food establishments
Authors: Izquierdo-Yusta Alicia , Gómez-Cantó Carmen María , Martínez-Ruiz María Pilar , Pérez-Villarreal Héctor Hugo 
Published: April 2020

PurposeThe importance of food values for the post–purchase process has not been widely studied. Most previous research in this line has focused on examining either the attributes of specific food categories, without taking the corresponding values into account, or food-purchasing attitudes and behaviour. To address this gap in the research, this paper delves deeper into the influence of food values on post–purchase variables.Design/methodology/approachSpecifically, it analyses the influence of food values on satisfaction (both with the purchase and with the establishment), switching costs and loyalty. To this end, a sample of 708 consumers, collected through online questionnaires in Spain, is analysed using various descriptive statistics and causal models.FindingsThe findings confirm the influence of food values on satisfaction and that satisfaction positively influences loyalty. Switching costs were not found to moderate the relationship between satisfaction and loyalty.Research limitations/implicationsThe survey had to be completed online, and, thus, respondents needed to have an e-mail address. This influenced the respondents' profile, since many consumers over the age of 54 do not have e-mail, do not use it, or are more reluctant to complete online surveys.Practical implicationsPurchase satisfaction was not found to affect switching costs, which reinforces the idea that loyalty can sometimes be spurious. It would thus be an indicator that, as long as consumers have no other option, they will continue to shop at the establishment. In contrast, establishment satisfaction did generate switching costs. This finding could be due to aspects such as convenience, the development and maintenance of relationships with the employees, knowledge of where products are located in the store, etc. Customers may be dissatisfied with their purchase, yet still satisfied with an establishment, which could entail very high switching costs for them and, therefore, cause them to remain loyal (albeit spuriously) to the establishment.Originality/valueThis research contributes to the literature in this field by examining the influence of food values on key post-purchase variables.