bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved estimation of time-varying reproduction numbers at low case incidence and between epidemic waves
Authors: Parag Kris V 
Published: September 2020

AbstractWe construct a recursive Bayesian smoother, termed EpiFilter, for estimating the effective reproduction number, R, from the incidence of an infectious disease in real time and retrospectively. Our approach borrows from Kalman filtering theory, is quick and easy to compute, generalisable, deterministic and unlike many current methods, requires no change-point or window size assumptions. We model R as a flexible, hidden Markov state process and exactly solve forward-backward algorithms, to derive R estimates that incorporate all available incidence information. This unifies and extends two popular methods, EpiEstim, which considers past incidence, and the Wallinga-Teunis method, which looks forward in time. We find that this combination of maximising information and minimising assumptions significantly reduces the bias and variance of R estimates. Moreover, these properties make EpiFilter more statistically robust in periods of low incidence, where existing methods can become destabilised. As a result, EpiFilter offers improved inference of time-varying transmission patterns that are especially advantageous for assessing the risk of upcoming waves of infection in real time and at various spatial scales.Author SummaryInferring changes in the transmissibility of an infectious disease is crucial for understanding and controlling epidemic spread. The effective reproduction number, R, is widely used to assess transmissibility. R measures the average number of secondary cases caused by a primary case and has provided insight into many diseases including COVID-19. An upsurge in R can forewarn of upcoming infections, while suppression of R can indicate if public health interventions are working. Reliable estimates of temporal changes in R can contribute important evidence to policymaking. Popular R-inference methods, while powerful, can struggle when cases are few because data are noisy. This can limit detection of crucial variations in transmissibility that may occur, for example, when infections are waning or when analysing transmissibility over fine geographic scales. In this paper we improve the general reliability of R-estimates and specifically increase robustness when cases are few. By adapting principles from control engineering, we formulate EpiFilter, a novel method for inferring R in real time and retrospectively. EpiFilter can potentially double the information extracted from epidemic time-series (when compared to popular approaches), significantly filtering the noise within data to minimise both bias and uncertainty of R-estimates and enhance the detection of salient changepoints in transmissibility.
Effects of Randomized Corruption Audits on Early-Life Mortality in Brazil
Authors: Nichter Simeon , Ramos Antonio P. , Gao Leiwen , Weiss Robert E. 
Published: September 2020

AbstractBackgroundVarious studies suggest that corruption affects public health systems across the world. However, the extant literature lacks causal evidence about whether anti-corruption interventions can improve health outcomes. We examine the impact of randomized anti-corruption audits on early-life mortality in Brazil.MethodsThe Brazilian government conducted audits in 1,949 randomly selected municipalities between 2003 and 2015. To identify the causal effect of anti-corruption audits on early-life mortality, we analyse data on health outcomes from individual-level vital statistics (DATASUS) collected by Brazil’s government before and after the random audits. Data on the audit intervention are from the Controladoria-Geral da Uniao, the government agency responsible for the anti-corruption audits. Outcomes are neonatal mortality, infant mortality, child mortality, preterm births, and prenatal visits. Analyses examine aggregate effects for each outcome, as well as effects by race, cause of death, and years since the intervention.ResultsAnti-corruption audits significantly decreased early-life mortality in Brazil. Expressed in relative terms, audits reduced neonatal mortality by 6.7% (95% CI −8.3%, −5.0%), reduced infant mortality by 7.3% (−8.6%, −5.9%), and reduced child mortality by 7.3% (−8.5%, −6.0%). This reduction in early mortality was higher for nonwhite Brazilians, who face significant health disparities. Effects are greater when we look at deaths from preventable causes, and show temporal persistence with large effects even a decade after audits. In addition, analyses show that the intervention led to a 12.1% (−13.4%, −10.6%) reduction in women receiving no prenatal care, as well as a 7.4% (−9.4%, −5.5%) reduction in preterm births; these effects are likewise higher for nonwhites and are persistent over time. All effects are robust to various alternative specifications.InterpretationGovernments have the potential to improve health outcomes through anti-corruption interventions. Such interventions can reduce early-life mortality and mitigate health disparities. The impact of anti-corruption audits should be investigated in other countries, and further research should further explore the mechanisms by which combating corruption affects the health sector.
Genetically proxied inhibition of interleukin-6 signaling: opposing associations with susceptibility to COVID-19 and pneumonia
Authors: Larsson Susanna C. , Burgess Stephen , Gill Dipender 
Published: September 2020

ABSTRACTThe inflammatory cytokine interleukin-6 (IL-6) is pivotal for orchestrating the immune response. Inhibitors of IL-6 signaling are being investigated as treatments for severe coronavirus disease 2019 (COVID-19). We conducted a Mendelian randomization study investigating the effect of IL-6 signaling on susceptibility to COVID-19 and pneumonia. Our results showed that genetically proxied inhibition of IL-6 signaling was associated with reduced risk of COVID-19, but also with increased risk of pneumonia. Respiratory disease is a main feature of severe COVID-19, and the potential of IL-6 signaling inhibitors to increase risk of pneumonia warrants vigilance and caution in their application to treat COVID-19.
SARS-CoV-2 reactive antibodies in unexposed individuals revealed by a high sensitivity, low noise serologic assay
Authors: Yuen Rachel R. , Steiner Dylan , Pihl Riley M.F. , Chavez Elizabeth , Olson Alex , Baird Lillia A. , Korkmaz Filiz , Urick Patricia , Sagar Manish , Berrigan Jacob L. , Gummuluru Suryaram , Corley Ronald B. , Quillen Karen , Belkina Anna C. , Mostoslavsky Gustavo , Rifkin Ian , Kataria Yachana , Cappione Amedeo J. , Lin Nina H. , Bhadelia Nahid , Snyder-Cappione Jennifer E. 
Published: September 2020

AbstractThe COVID-19 pandemic has significantly impacted work, economy, and way of life. The SARS-CoV-2 virus displays unique features including widely varying symptoms and outcomes between infected individuals. Sensitive measurement of SARS-CoV-2 specific antibodies would provide new insight into virus transmission dynamics, pre-existing cross-reactive immunity, and the nuances of SARS-CoV-2 pathogenesis. To date, existing SARS-CoV-2 serology tests have limited utility due to insufficient detection of antibody levels lower than what is typically present after several days of symptoms. To measure lower quantities of SARS-CoV-2 IgM, IgG, and IgA with higher resolution than existing assays, we developed a new ELISA protocol with a distinct plate washing procedure and timed plate development via use of a standard curve. This ‘BU ELISA’ method exhibits very low signal from plasma or serum samples added to uncoated wells at as low as a 1:5 dilution. Use of this method revealed circulating SARS-CoV-2 receptor binding domain (RBD) and nucleocapsid protein (NP) reactive antibodies from blood samples drawn prior to May 2019. Of our prepandemic cohort, no SARS-CoV-2 RBD-reactive IgG antibodies were detected in subjects over 70 years of age, and SARS-CoV-2 NP-reactive antibodies were present at similar levels to infected subjects in some individuals and very low in others. Also, samples drawn in May 2020 from two individuals with no symptoms or no known virus exposure contained SARS-CoV-2 RBD-reactive antibodies at intermediate amounts compared with other subject groups (higher than pre-pandemic and lower than confirmed SARS-CoV-2 infected). The one asymptomatic SARS-CoV-2 convalescent subject in our study possessed comparable amounts of SARS-CoV-2 NP-specific IgM and IgG but drastically lower IgA than the symptomatic counterparts. Also, our assay detected positive signal from samples that gave negative results in a commercially available Lateral Flow Device (LFD) and the EUA approved Abbott IgG chemiluminescent microparticle immunoassay for SARS-CoV-2 antibody detection. We propose that this improved ELISA protocol, which is straightforward to perform, low cost, and uses readily available commercial reagents, is a useful tool to elucidate new information about SARS-CoV-2 infection and has promising implications for improved detection of all analytes measurable by this platform.
Comparative profiling of epigenetic modifications among individuals living in different high and low air pollution zones: A pilot study from India
Authors: Mishra Pradyumna Kumar , Bunkar Neha , Singh Radha Dutt , Kumar Rajat , Gupta Pushpendra Kumar , Tiwari Rajnarayan , Lodhi Lalit , Bhargava Arpit , Chaudhury Koel 
Published: September 2020

AbstractEpigenetic modifications act as an important bridge to regulate the complex network of gene-environment interaction. As these mechanisms determines the gene-expression patterns via regulating the transcriptomic machinery, environmental stress induced epigenetic modifications may interrupt distinct cellular functions resulting into generation of diseased phenotypes. In the present study, we used a multi-city approach to compare the epigenomic signatures of individuals living in two tiers of Indian cities categorized as low-risk and high-risk air pollution zones. The high-risk group reported marked changes in the expression levels of epigenetic modifiers (DNMT1, DNMT3a, EZH2, EHMT2 and HAT), that maintains the levels of specific epigenetic marks essential for appropriate gene functioning. These results also coincided with the observed alterations in the levels of DNA methylation (LINE-1 and % 5mC), and histone modifications (H3 and H4), among the high-risk group. In addition, higher degree of changes reported in the expression profile of a selected miRNA panel in the high-risk group indicated the probability of deregulated transcriptional machinery. This was further confirmed by the analysis of a target gene panel involved in various signalling pathways, which revealed differential expression of the gene transcripts regulating cell cycle, inflammation, cell survival, apoptosis and cell adhesion. Together, our results provide first insights of epigenetic modifications among individuals living in different high and low levels of air pollution zones of India. However, further steps to develop a point-of-care epigenomic assay for human bio-monitoring may be immensely beneficial to reduce the health burden of air pollution especially in lower-middle-income countries.
COVID-19 incidence and mortality in the Metropolitan Region, Chile: time, space, and structural factors
Authors: Dintrans Pablo Villalobos , Castillo Claudio , Fuente Felipe De La , Maddaleno Matilde 
Published: September 2020

AbstractChile has been heavily affected by the COVID-19 pandemic. This article analyzes the association of different groups of factors—demographic, health-related, and socioeconomic—on COVID-19-related outcomes. Using the municipalities of the Metropolitan Region the study looks at the role of time dynamics, space and place in cases and deaths during a 100-days period.Results show that common and idiosyncratic elements that explain the prevalence and dynamics of infections and mortality, with an important role of social determinants of health, particularly multidimensional poverty index and use of public transportation, in explaining differences in outcomes.The article contributes to the understanding of the determinants of COVID-19 outcomes in a specific region, but also highligths the need to consider time-space dynamics and social determinants as key in the analysis. The results are specially relevant for similar research in unequal settings.
Superspreaders provide essential clues for mitigation of COVID-19
Authors: Nielsen Bjarke Frost , Sneppen Kim 
Published: September 2020

AbstractAlthough coronavirus disease 2019 (COVID-19) has caused severe suffering in many countries around the world, the efficacy of non-pharmaceutical interventions such as policies of social distancing has been greater than models have predicted. Meanwhile, evidence is mounting that the pandemic is characterized by superspreading, where a small fraction account for the majority of infections. Capturing this phenomenon theoretically requires modeling at the scale of individuals. Using a mathematical model, we show that superspreading represents an Achilles’ heel of COVID-19, and drastically improves the efficacy of mitigations which reduce the personal contact number, even when this is done without changing the average social contact time.
Early Release Estimates for SARS-CoV-2 Prevalence and Antibody Response Interim Weighting for Probability-Based Sample Surveys
Authors: Bradley Heather , Fahimi Mansour , Sanchez Travis , Lopman Ben , Frankel Martin , Kelley Colleen F. , Rothenberg Richard , Siegler Aaron J , Sullivan Patrick S 
Published: September 2020

AbstractMany months into the SARS-CoV-2 pandemic, basic epidemiologic parameters describing burden of disease are lacking. To reduce selection bias in current burden of disease estimates derived from diagnostic testing data or serologic testing in convenience samples, we are conducting a national probability-based sample SARS-CoV-2 serosurvey. Sampling from a national address-based frame and using mailed recruitment materials and test kits will allow us to estimate national prevalence of SARS-CoV-2 infection and antibodies, overall and by demographic, behavioral, and clinical characteristics. Data will be weighted for unequal selection probabilities and non-response and will be adjusted to population benchmarks. Due to the urgent need for these estimates, expedited interim weighting of serosurvey responses will be undertaken to produce early release estimates, which will be published on the study website, COVIDVu.org. Here, we describe a process for computing interim survey weights and guidelines for release of interim estimates.
Mobile EEG reveals functionally dissociable dynamic processes supporting real-world ambulatory obstacle avoidance: Evidence for early proactive control
Authors: Mustile Magda , Kourtis Dimitrios , Ladouce Simon , Learmonth Gemma , Donaldson David I. , Ietswaart Magdalena 
Published: September 2020

AbstractThe ability to safely negotiate the world on foot takes years to develop in human infants, reflecting the huge cognitive demands associated with real-time dynamic planning and control of walking. Despite the importance of walking, surprisingly little is known about the neural and cognitive processes that support ambulatory motor control in humans. In particular, methodological limitations have, to date, largely prevented study of the neural processes involved in detecting and avoiding obstacles during walking. Here, using mobile EEG during real-world ambulatory obstacle avoidance, we captured the dynamic oscillatory response to changes in the environment. Time-frequency analysis of EEG data revealed clear neural markers of proactive and reactive forms of movement control (occurring before and after crossing an obstacle), visible as increases in frontal theta and centro-parietal beta power respectively. Critically, the temporal profile of changes in frontal theta allowed us to arbitrate between early selection and late correction mechanisms of proactive control: our data show that motor plans are updated as soon as an upcoming obstacle appears, rather than when the obstacle is reached, as previously thought. In addition, regardless of whether motor plans required updating, a clear beta rebound was present after obstacles were crossed, reflecting the resetting of the motor system. Overall, our use of mobile EEG during real-world walking provides novel insight into the cognitive and neural basis of dynamic motor control in humans, suggesting new routes to the monitoring and rehabilitation of motor disorders such as dyspraxia and Parkinson’s disease.
Interaction of habitat isolation and seasonality: impact of fragmentation in dynamic landscapes on local and regional population variability in meta-food chains
Authors: Stark Markus , Bach Moritz , Guill Christian 
Published: September 2020

AbstractWhile habitat loss is a known key driver of biodiversity decline, the effect of habitat fragmentation ‘per se’ is far less clear. Environmental perturbations, e.g. due to seasonality, potentially interact with effects of habitat fragmentation, thus making the latter even more difficult to assess. In order to analyze how the dynamic stability of local and metapopulations is affected by habitat fragmentation, we simulate a meta-food chain with three species on complex networks of habitat patches and evaluate the average variability of the local populations and the metapopulations as well as the level of synchronization between the patches. To account for environmental perturbations, we contrast simulations of static landscapes with simulations of dynamic landscapes, where 30 percent of the patches periodically become unavailable as habitats. We find that it depends on the parameterization of the food chain whether higher dispersal rates in less fragmented landscapes synchronize the dynamics or not. Even if the dynamics synchronize, local population variability can decrease due to indirect effects of dispersal mortality, thereby stabilizing metapopulation dynamics and reducing the risk of extinction. In dynamic landscapes, periodic external perturbations often fully synchronize the dynamics even if they act on a much slower time scale than the ecological interactions. Furthermore, they not only increase the variability of local and metapopulations, but also mostly overrule the effects of habitat fragmentation. This may explain why in nature effects of habitat fragmentation are often small and inconclusive.
The role of miR-31-5p in the development of intervertebral disc degeneration and its therapeutic potential
Authors: Zhou Yong , Su Jiqing , Deng Mingsi , Zhang Wei , Liu Dongbiao , Wang Zhengguang 
Published: September 2020

AbstractIntervertebral disc degeneration (IDD) refers to the abnormal response of cell-mediated progressive structural failure. In order to understand the molecular mechanism of the maintenance and destruction of the intervertebral disc, new IDD treatment methods are developed. Here, we first analyzed the key regulators of IDD through miRNA microarrays. The cell structure and morphology were discovered by Histological and radiographic. Then, the level of miR-31-5p was disclosed by qRT-PCR. The association between miR-31-5p and SDF-1/CXCR7 axis was discovered by 3′-Untranslated region (UTR) cloning and luciferase assay. The apoptosis of cells under different treatments was disclosed by Flow cytometer. The cell proliferation was discovered by EdU assay. Finally, the protein levels of SDF-1, CXCR7, ADAMTS-5, Col II, Aggrecan and MMP13 were discovered by Western blot. The results show that miR-31-5p is a key regulator of IDD and its level is down-regulated in IDD. Overexpression of miR-31-5p facilitates NP cell proliferation, inhibits apoptosis, facilitates ECM formation and inhibits the level of matrix degrading enzymes in NP cells. The SDF-1/CXCR7 axis is the direct target of miR-31-5p. miR-31-5p acts on IDD by regulating SDF-1/CXCR7. In vitro experiments further verified that the up-regulation of miR-31-5p prevented the development of IDD. In conclusion, overexpression of miR-31-5p can inhibit IDD by regulating SDF-1/CXCR7.
Functional dynamics of de-afferented early visual cortex in glaucoma
Authors: Prabhakaran Gokulraj T. , Al-Nosairy Khaldoon O. , Tempelmann Claus , Wagner Markus , Thieme Hagen , Hoffmann Michael B. 
Published: September 2020

AbstractfMRI studies in macular degeneration (MD) and retinitis pigmentosa (RP) demonstrated that responses in the lesion projection zones (LPZ) of V1 are task related, indicating significant limits of bottom-up visual system plasticity in MD and RP. In advanced glaucoma (GL), a prevalent eye disease and leading cause of blindness, the scope of visual system plasticity is currently unknown. We performed 3T fMRI in patients with extensive visual field defects due to GL (n=5), RP (n=2) and healthy controls (n=7; with simulated defects). Participants viewed contrast patterns drifting in 8 directions alternating with uniform gray and performed 3 tasks: (1) passive viewing (PV), (2) one-back task (OBT) and (3) fixation-dot task (FDT). During PV, they passively viewed the stimulus with central fixation, during OBT they reported the succession of the same two motion directions, and during FDT a change in the fixation color. In GL, LPZ responses of the early visual cortex (V1, V2 and V3) shifted from negative during PV to positive for OBT [p (corrected): V1(0.006); V2(0.04); V3(0.008)], while they were negative in the controls’ simulated LPZ for all stimulation conditions. For RP a similar pattern as for GL was observed. Consequently, activity in the de-afferented visual cortex in glaucoma is, similar to MD and RP, task-related. In conclusion, the lack of bottom-up plasticity appears to be a general feature of the human visual system. These insights are of importance for the development of treatment and rehabilitation schemes in glaucoma.HighlightsFunctional dynamics of early visual cortex LPZ depend on task demands in glaucomaBrain activity in deprived visual cortex suggests absence of large-scale remappingLimited scope of bottom-up plasticity is a general feature of human visual systemVisual system stability and plasticity is of relevance for therapeutic advances