bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular epidemiology of Blastocystis in urban and periurban human populations in Arequipa, Peru
Authors: Ascuña-Durand Kasandra , Salazar-Sánchez Renzo S. , Cartillo-Neyra Ricardo , Ballón-Echegaray Jorge 
Published: June 2020

AbstractBlastocystis is one of the most common parasites found in the gut of humans and other hosts. It has a wide genetic diversity distributed around the world, predominating subtypes 1, 2 and 3 in South America countries. Nonspecific and inconsistent symptoms associated with this parasite made it controversial. The aim of this study was to estimate the prevalence of subtypes and determinate the epidemiological conditions associated with them. A total of 116 Blastocystis positive stool samples were processed by conventional PCR with Blastocystis-specific primers for subtypes 1 to 3. We identified subtype 1 (10.3%), subtype 2 (7.6%), subtype 3 (25.0%) and mixed infections (8.6%). We did not identify these Blastocystis subtypes in 48.7% of stool samples, assuming the presence of other subtypes in the zone. Any association was found between gastrointestinal symptoms and single subtype infections neither with mixed subtypes coinfections. However, our results suggest an association of Blastocystis subtype 2 and Irritable Bowel Syndrome (IBS, p=0.039). Besides, there was not an association between Blastocystis subtypes 1, 2 and 3 nor-mixed infections with epidemiological variables such as gender, age, presence of animals or vectors, places of food consumption, type of water consumption and water supply.
Combining clinical and polygenic risk improves stroke prediction among individuals with atrial fibrillation
Authors: O’Sullivan Jack W. , Shcherbina Anna , Justesen Johanne M , Turakhia Mintu , Perez Marco , Wand Hannah , Tcheandjieu Catherine , Clarke Shoa L. , Harrington Robert A. , Rivas Manuel A. , Ashley Euan A 
Published: June 2020

AbstractBackgroundAtrial fibrillation (AF) is associated with a five-fold increased risk of ischemic stroke. A portion of this risk is heritable, however current risk stratification tools (CHA2DS2-VASc) don’t include family history or genetic risk. We hypothesized that we could improve ischemic stroke prediction in patients with AF by incorporating polygenic risk scores (PRS).ObjectivesTo construct and test a PRS to predict ischemic stroke in patients with AF, both independently and integrated with clinical risk factors.MethodsUsing data from the largest available GWAS in Europeans, we combined over half a million genetic variants to construct a PRS to predict ischemic stroke in patients with AF. We externally validated this PRS in independent data from the UK Biobank (UK Biobank), both independently and integrated with clinical risk factors.ResultsThe integrated PRS and clinical risk factors risk tool had the greatest predictive ability. Compared with the currently recommended risk tool (CHA2DS2-VASc), the integrated tool significantly improved net reclassification (NRI: 2.3% (95%CI: 1.3% to 3.0%)), and fit (χ2 P =0.002). Using this improved tool, >115,000 people with AF would have improved risk classification in the US. Independently, PRS was a significant predictor of ischemic stroke in patients with AF prospectively (Hazard Ratio: 1.13 per 1 SD (95%CI: 1.06 to 1.23))). Lastly, polygenic risk scores were uncorrelated with clinical risk factors (Pearson’s correlation coefficient: −0.018).ConclusionsIn patients with AF, there appears to be a significant association between PRS and risk of ischemic stroke. The greatest predictive ability was found with the integration of PRS and clinical risk factors, however the prediction of stroke remains challenging.
Drainage of inflammatory macromolecules from brain to periphery targets the liver for macrophage infiltration
Authors: Yang Linlin , Jiménez Jessica A. , Earley Alison M. , Hamlin Victoria , Kwon Victoria , Dixon Cameron T. , Shiau Celia E. 
Published: June 2020

AbstractMany brain pathologies are associated with liver damage, but a direct link has long remained elusive. Here, we establish a new paradigm for interrogating brain-periphery interactions by leveraging zebrafish for its unparalleled access to the intact whole animal forin vivoanalysis in real time after triggering focal brain inflammation. We reveal that drainage of inflammatory macromolecules from the brain led to a strikingly robust peripheral infiltration of macrophages into the liver independent of Kupffer cells. We further demonstrate that this macrophage recruitment requires signaling from the cytokine IL-34, Toll-like receptor adaptor protein MyD88, and neutrophils. These results highlight the ability for circulation of brain-derived substances to serve as a rapid mode of communication from brain to the liver. Understanding how the brain engages the periphery at times of danger may offer new perspectives for detecting and treating brain pathologies.
SARS-CoV-2-specific antibody detection for sero-epidemiology: a multiplex analysis approach accounting for accurate seroprevalence
Authors: Hartog Gerco den , Schepp Rutger M. , Kuijer Marjan , GeurtsvanKessel Corine , van Beek Josine , Rots Nynke , Koopmans Marion P.G. , van der Klis Fiona R.M. , van Binnendijk Robert S. 
Published: June 2020

ABSTRACTBackgroundThe COVID-19 pandemic demands detailed understanding of the kinetics of antibody production induced by infection with SARS-CoV-2. We aimed to develop a high throughput multiplex assay to detect antibodies to SARS-CoV-2 to assess immunity to the virus in the general population.MethodsSpike protein subunits S1 and RBD, and Nucleoprotein were coupled to distinct microspheres. Sera collected before the emergence of SARS-CoV-2 (N=224), and of non-SARS-CoV-2 influenza-like illness (N=184), and laboratory-confirmed cases of SARS-CoV-2 infection (N=115) with various severity of COVID-19 were tested for SARS-CoV-2-specific concentrations of IgG.ResultsOur assay discriminated SARS-CoV-2-induced antibodies and those induced by other viruses. The assay obtained a specificity between 95.1 and 99.0% with a sensitivity ranging from 83.6-95.7%. By merging the test results for all 3 antigens a specificity of 100% was achieved with a sensitivity of at least 90%. Hospitalized COVID-19 patients developed higher IgG concentrations and the rate of IgG production increased faster compared to non-hospitalized cases.ConclusionsThe bead-based serological assay for quantitation of SARS-CoV-2-specific antibodies proved to be robust and can be conducted in many laboratories. Finally, we demonstrated that testing of antibodies against different antigens increases sensitivity and specificity compared to single antigen-specific IgG determination.
Modeling COVID19 mortality in the US: Community context and mobility matter
Authors: McGough Sarah F. , Gan Ryan W. , Tibshirani Robert , Meyer Anne-Marie 
Published: June 2020

AbstractThe United States has become an epicenter for the coronavirus disease 2019 (COVID-19) pandemic. However, communities have been unequally affected and evidence is growing that social determinants of health may be exacerbating the pandemic. Furthermore, the impact and timing of social distancing at the community level have yet to be fully explored. We investigated the relative associations between COVID-19 mortality and social distancing, sociodemographic makeup, economic vulnerabilities, and comorbidities in 24 counties surrounding 7 major metropolitan areas in the US using a flexible and robust time series modeling approach. We found that counties with poorer health and less wealth were associated with higher daily mortality rates compared to counties with fewer economic vulnerabilities and fewer pre-existing health conditions. Declines in mobility were associated with up to 15% lower mortality rates relative to pre-social distancing levels of mobility, but effects were lagged between 25-30 days. While we cannot estimate causal impact, this study provides insight into the association of social distancing on community mortality while accounting for key community factors. For full transparency and reproducibility, we provide all data and code used in this study.One-sentence summaryCounty-level disparities in COVID19 mortality highlight inequalities in socioeconomic and community factors and delayed effects of social distancing.
THE USE OF DENATURING SOLUTION AS COLLECTION AND TRANSPORT MEDIA TO IMPROVE SARS-COV-2 RNA DETECTION AND REDUCE INFECTION OF LABORATORY PERSONNEL
Authors: de Carvalho Alex Fiorini , Gonçalves Andreza Parreiras , de Souza Silva Thaís Bárbara , Sato Hugo Itaru , Vuitika Larissa , Bagno Flavia Fonseca , Sérgio Sarah Aparecida Rodrigues , Figueiredo Maria Marta , Rocha Raissa Prado , Fernandes Ana Paula Salles Moura , Alves Pedro Augusto , Teixeira Santuza Maria Ribeiro , da Fonseca Flavio Guimarães 
Published: June 2020

AbstractBackgroundSince the emergence of the COVID-19, health officials have struggled to devise strategies to counteract the speed of the pandemic’s spread across the globe. It became imperative to implement accurate diagnostic tests for the detection of SARS-CoV-2 RNA on respiratory samples. In many places, however, besides the limited availability of test reagents, laboratory personnel face the challenge of adapting their working routines to manipulate highly infective clinical samples. Here, we proposed the use of a virus-inactivating solution as part of a sample collection kit to decrease the infectious potential of the collected material without affecting the integrity of RNA samples used in diagnostic tests based on RT-qPCR.MethodsNasopharyngeal and oropharyngeal swab samples were collected from SARS-CoV-2-infected patients and from laboratory personnel using a commercially available viral transport solution (VTM) and the denaturing solution (DS) described here. RNA extracted from all samples was tested by RT-qPCR using probes for viral and human genes. Exposure of laboratory personnel to infective viruses was also accessed using ELISA tests.FindingsThe use of the DS did not interfere with the detection of viral genome or the endogenous human mRNA, since similar results were obtained from samples collected with VTM or DS. In addition, all tests of laboratory personnel for the presence of viral RNA and IgG antibodies against SARS-CoV-2 were negative.InterpretationThe methodology described here provides a strategy that allow high diagnostic accuracy as well as safe manipulation of clinical samples by those involved with diagnostic procedures.FundingCAPES, FAPEMIG, CNPq, MCTIC, FIOCRUZ and the UK Global Challenges Research Fund (GCRF).
Descriptive Epidemiological Assessment of the Relationship between the Global Burden of Influenza from 2017-2019 and COVID-19
Authors: Baral Stefan David , Rucinski Katherine B. , Twahirwa Rwema Jean Olivier , Rao Amrita , Menezes Neia Prata , Diouf Daouda , Kamarulzaman Adeeba , Phaswana-Mafuya Nancy , Mishra Sharmistha 
Published: June 2020

AbstractBackgroundSARS-CoV-2 and influenza are lipid-enveloped viruses with differential morbidity and mortality but shared modes of transmission. With a descriptive epidemiological framing, we assessed whether historical patterns of regional influenza burden are reflected in the observed heterogeneity in COVID-19 cases across regions of the world.MethodsWeekly surveillance data reported in FluNet from January 2017–December 2019 for influenza and World Health Organization for COVID-19 (to May 31, 2020) across the seven World Bank regions were used to assess the total and annual number of influenza and COVID-19 cases per country, within and across all regions, to generate comparative descending ranks from highest to lowest burden of disease.ResultsAcross regions, rankings of influenza and COVID-19 were relatively consistent. Europe and Central Asia and North America ranked first and second for COVID-19 and second and first for influenza, respectively. East Asia and the Pacific traditionally ranked higher for influenza with recent increases in COVID-19 consistent with influenza season. Across regions, Sub-Saharan Africa ranked amongst the least affected by both influenza and COVID-19.ConclusionConsistency in the regional distribution of the burden of COVID-19 and influenza suggest shared individual, structural, and environmental determinants of transmission. Using a descriptive epidemiological framework to assess shared regional trends for rapidly emerging respiratory pathogens with better studied respiratory infections may provide further insights into the differential impacts of non-pharmacologic interventions and intersections with environmental conditions. Ultimately, forecasting trends and informing interventions for novel respiratory pathogens like COVID-19 should leverage epidemiologic patterns in the relative burden of past respiratory pathogens as prior information.
IL-13 is a driver of COVID-19 severity
Authors: Donlan Alexandra N. , Sutherland Tara E. , Marie Chelsea , Preissner Saskia , Bradley Ben T. , Carpenter Rebecca M. , Sturek Jeffrey M. , Ma Jennie Z. , Moreau G. Brett , Donowitz Jeffrey R. , Buck Gregory A. , Serrano Myrna G. , Burgess Stacey L. , Abhyankar Mayuresh M. , Mura Cameron , Bourne Philip E. , Preissner Robert , Young Mary K. , Lyons Genevieve R. , Loomba Johanna J. , Ratcliffe Sarah J , Poulter Melinda D. , Mathers Amy J. , Day Anthony , Mann Barbara J. , Allen Judith E. , Petri William A. 
Published: June 2020

AbstractImmune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here we report that elevated interleukin-13 (IL-13) was associated with the need for mechanical ventilation in two independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab had less severe disease. In SARS-CoV-2 infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti-IL-13 treatment in infected mice, in the lung, hyaluronan synthase 1 (Has1) was the most downregulated gene and hyaluronan accumulation was decreased. Blockade of the hyaluronan receptor, CD44, reduced mortality in infected mice, supporting the importance of hyaluronan as a pathogenic mediator, and indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and hyaluronan has important implications for therapy of COVID-19 and potentially other pulmonary diseases.SummaryL-13 levels are elevated in patients with severe COVID-19. In a mouse model of disease, IL-13 neutralization results in reduced disease and lung hyaluronan deposition. Similarly, blockade of hyaluronan’s receptor, CD44, reduces disease, highlighting a novel mechanism for IL-13-mediated pathology.
SARS-CoV-2 in human milk is inactivated by Holder pasteurization but not cold storage
Authors: Walker Gregory J. , Clifford Vanessa , Bansal Nidhi , Stella Alberto Ospina , Turville Stuart , Stelzer-Braid Sacha , Klein Laura D , Rawlinson William 
Published: June 2020

ABSTRACTAs the COVID-19 pandemic evolves, human milk banks worldwide continue to provide donor human milk to vulnerable infants who lack access to mother’s own milk. Under these circumstances, ensuring the safety of donor human milk is paramount, as the risk of vertical transmission of SARS-CoV-2 is not well understood. Here, we investigate the inactivation of SARS-CoV-2 in human milk by pasteurisation, and the stability of SARS-CoV-2 in human milk under cold storage (freezing or refrigeration). Following heating to 63°C or 56°C for 30 minutes, SARS-CoV-2 replication competent (i.e. live) virus was undetected in both human milk and the control medium. Cold storage of SARS-CoV-2 in human milk (either at 4°C or - 30°C) did not significantly impact infectious viral load over a 48 hour period. Our findings demonstrate that SARS-CoV-2 can be effectively inactivated by Holder pasteurisation, and confirm that existing milk bank processes will effectively mitigate the risk of transmission of SARS-COV-2 to vulnerable infants through pasteurised donor human milk.
Simulation of COVID-19 Incubation Period and the Effect of Probability Distribution Function on Model Training Using MIMANSA
Authors: Patel Abhilasha P. , Welling Arpita A. , Vaidya Vinay G. , Kulkarni Padmaj S. 
Published: June 2020

AbstractCoronavirus disease 2019 (COVID-19) has infected people all over the world. While scientists are busy finding a vaccine and medicine, it becomes difficult to control the spread and manage patients. Mathematical models help one get a better feel for the challenges in patient management. With this in mind, our team developed a model called Multilevel Integrated Model with a Novel Systems Approach (MIMANSA) Welling et. al (2020). MIMANSA is a multi-parametric model. One of the challenges in the design of MIMANSA was to simulate the incubation period of coronavirus. The incubation period decides when virus-infected patients would show symptoms. The probability distribution function (PDF), when applied to the number of virus-infected cases, gives a good representation of the process of the incubation period. The probability distribution functions can take various forms. In this paper, we explore a variety of PDFs and their impact on parameter estimation in the MIMANSA model. For our experiments, we used Weibull, Gaussian, uniform, and Gamma distribution. To ensure a fair comparison of Weibull, Gaussian, and Gamma distribution, we matched the peak value of the distribution. Our results show that the Weibull distribution with shape 7.7 and scale 7 for 14 days gives a better training model and predictions.
Prognostic factors in spanish COVID-19 patients: A case series from barcelona
Authors: Sisó-Almirall Antoni , Kostov Belchin , Mas-Heredia Minerva , Vilanova-Rotllan Sergi , Sequeira-Aymar Ethel , Sans-Corrales Mireia , Sant-Arderiu Elisenda , Cayuelas-Redondo Laia , Martínez-Pérez Angela , Plana Noemí García , Anguita-Guimet August , Benavent-Àreu Jaume 
Published: June 2020

ABSTRACTBackgroundIn addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community.AimTo determine clinical factors of a poor prognosis in patients with COVID-19 infection.Design and SettingDescriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000.MethodExamination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction.ResultsWe included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged ≥ 65 years). The best predictors of ICU admission or death were greater age, male sex (OR=2.99; 95%CI=1.55 to 6.01), fever (OR=2.18; 95%CI=1.06 to 4.80), dyspnoea(OR=2.22; 95%CI=1.14 to 4.24), low oxygen saturation (OR=2.94; 95%CI=1.34 to 6.42), auscultatory alterations (OR=2.21; 95%CI=1.00 to 5.29), heart disease (OR=4.37; 95%CI=1.68 to 11.13), autoimmune disease (OR=4.03; 95%CI=1.41 to 11.10), diabetes (OR=4.00; 95%CI=1.89 to 8.36), hypertension (OR=3.92; 95%CI=2.07 to 7.53), bilateral pulmonary infiltrates (OR=3.56; 95%CI=1.70 to 7.96), elevated lactate-dehydrogenase (OR=3.02; 95%CI=1.30 to 7.68), elevated C-reactive protein (OR=2.94; 95%CI=1.47 to 5.97), elevated D-dimer (OR=2.66; 95%CI=1.15 to 6.51) and low platelet count (OR=2.41; 95%CI=1.12 to 5.14). Myalgia or artralgia (OR=0.28; 95%CI=0.10 to 0.66), dysgeusia (OR=0.28; 95%CI=0.05 to 0.92) and anosmia (OR=0.23; 95%CI=0.04 to 0.75) were protective factors.ConclusionDetermining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.
Hemochromatosis mutations, dementia and brain iron deposition: a prospective cohort study
Authors: Melzer David , Atkins Janice L , Pilling Luke C , Heales Christine J , Savage Sharon , Kuo Chia-Ling , Kuchel George A , Steffens David C 
Published: June 2020

ABSTRACTImportanceBrain iron deposition is common in dementia, but its causal significance is uncertain. The HFE p.C282Y homozygous mutation in European ancestry populations can lead to iron overload and hemochromatosis, mainly in males. Data on brain outcomes in homozygotes are scarce.ObjectiveTo estimate HFE variant associations with MRI features plus incident dementia diagnoses during follow-up in a large community based cohort.DesignUK Biobank cohort with follow-up in routine hospitalization records (mean 8.8 years). MRI imaging available on a participant subset scanned 2014 to 2018.SettingCommunity cohort participants across England, Wales and Scotland.ParticipantsEuropean ancestry participants (n=451,186) aged 40 to 70 years at baseline, including 2,890 p.C282Y homozygotes (predominantly without baseline haemochromatosis diagnoses). MRI scanning on 9,464 males and 10,475 females, including 40 male and 75 female p.C282Y homozygotes.ExposureHFE C282Y and H63D genetic variantsMain outcome and measuresBrain MRI site specific T2* measures (lower values associated with iron deposition) and gray matter volumes. Incident dementia diagnoses during follow-up.ResultsMale p.C282Y homozygotes had lower T2* measures in several brain areas including the thalamus (beta = -1.04 standard deviations, 95% CI -1.33 to -0.76, multiple testing adjusted p-value=4.9*10-10), putamen and hippocampus, compared to those without HFE mutations. Male homozygotes also had smaller gray matter volumes in the putamen (beta -0.80 sd, 95%CI -1.12 to - 0.47, adjusted p=2.2*10-4) and ventral striatum.Diagnoses of incident dementia (Hazard Ratio HR=2.27; 95% CI 1.36 to 3.80, p=0.002) were more common in p.C282Y homozygous men, as were delirium diagnoses (HR=2.04, CI 1.09 to 3.82, p=0.03), but there was no association with Stroke.In p.C282Y homozygote females and p.C282Y/H63D heterozygotes, MRI associations were less marked.Conclusion and RelevanceIn a community sample, men with the HFE p.C282Y homozygote genotype had more brain iron deposition, smaller specific gray matter volumes, and increased incidence of dementia. As iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.Key PointsQuestionIs the hemochromatosis HFE p.C282Y homozygous variant in men associated with brain MRI features and incident dementia?FindingsOn MRI, p.C282Y homozygote males had evidence of more iron deposition in areas including the thalamus, putamen and hippocampus, plus smaller putamen gray matter volumes, compared to men without HFE mutations. In 451,186 UK Biobank participants during the mean 8.8 year follow-up, incident dementia diagnoses were more than twice as common in the 1,294 homozygous men.MeaningAs iron overload in hemochromatosis is treatable, early intervention may prevent or limit related brain pathology in male HFE p.C282Y homozygotes.