bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial self-stimulation and concomitant behaviors following systemic methamphetamine administration inHnrnph1mutant mice
Authors: Borrelli Kristyn N. , Langan Carly R. , Dubinsky Kyra R. , Szumlinski Karen K. , Carlezon William A. , Chartoff Elena H. , Bryant Camron D. 
Published: June 2020

ABSTRACTRationaleAddiction to methamphetamine (MA) is a major public health issue in the United States. While psychostimulant use disorders are heritable, their genetic basis remains poorly understood. We previously identified heterogeneous nuclear ribonucleoprotein H1 (Hnrnph1;H1) as a quantitative trait gene underlying sensitivity to MA-induced locomotor activity. Mice heterozygous for a frameshift deletion in the first coding exon of H1 (H1+/-) showed reduced MA phenotypes including oral self-administration, locomotor activity, dopamine release, and dose-dependent differences in MA conditioned place preference. However, the effects of H1+/-on innate and MA-modulated reward sensitivity are not known.ObjectivesWe examined innate reward sensitivity and modulation by MA in H1+/-mice via intracranial self-stimulation (ICSS).MethodsWe used intracranial self-stimulation (ICSS) of the medial forebrain bundle to assess shifts in reward sensitivity following acute, ascending doses of MA (0.5-4.0 mg/kg, i.p.) using a within-subjects design. We also assessed video-recorded behaviors during ICSS testing sessions.ResultsH1+/-mice displayed reduced normalized maximum response rates, H1+/-females showed lower normalized M50 values compared to wild-type females following MA, and H1+/-influenced ICSS responding relative to maximum baseline rates. There was a dose-dependent reduction in distance to the response wheel following MA administration, providing an additional measure of reward-related behavior.ConclusionsH1+/-mice displayed reduced reward facilitation following MA in a sex- and dose-dependent manner. This result expands upon the set of MA-induced phenotypes observed in H1+/-mice.
DUSP7 Regulates the Activity of ERK2 to Promote Proper Chromosome Alignment During Cell Division
Authors: Guo Xiao , Garcia Yenni A. , Ramirez Ivan , Velasquez Erick F. , Gao Lucy W. , Gholkar Ankur A. , Whitelegge Julian P. , Tofig Bobby , Damoiseaux Robert , Torres Jorge Z. 
Published: June 2020

SUMMARYHuman cell division is a highly regulated process that relies on the accurate capture and movement of chromosomes to the metaphase plate. Errors in the fidelity of chromosome congression and alignment can lead to improper chromosome segregation, which is correlated with aneuploidy and tumorigenesis. Here we show that the dual specificity phosphatase DUSP7 is important for regulating chromosome alignment. DUSP7 bound to ERK2 and regulated the abundance of active phospho-ERK2 through its phosphatase activity. Overexpression of DUSP7, but not catalytic dead mutants, led to a marked decrease in phopho-ERK2 and mitotic chromosome misalignment, while knockdown of DUSP7 also led to defective chromosome congression that resulted in a prolonged mitosis. Consistently, chemical inhibition of the MEK kinase that phosphorylates ERK2 or ERK2 itself led to chromosome alignment defects. Our results support a model where MEK phosphorylation and DUSP7 dephosphorylation regulate the levels of active phospho-ERK2 to promote proper cell division.
ScRNA-seq discover cell cluster change under OAB——ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway
Authors: Xiang Boyu , Hu Xiangyu , Li Haoxuan , Ma Li , Zhou Hao , Wei Ling , Fan Jue , Zheng Ji 
Published: June 2020

ABSTRACTObjectivePrevious study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance.Material and methodPubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively.ResultIn pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types.ConclusionThe disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB.
Variants in MARC1 and HSD17B13 reduce severity of NAFLD in children, perturb phospholipid metabolism, and suppress fibrotic pathways
Authors: Hudert Christian A. , Alisi Anna , Anstee Quentin M. , Crudele Annalisa , Draijer Laura G. ,   EU-PNAFLD investigators, Furse Samuel , Hengstler Jan G. , Jenkins Benjamin , Karnebeek Kylie , Kelly Deirdre A. , Koot Bart G. , Koulman Albert , Meierhofer David , Snowden Stuart G. , van Mourik Indra , Vreugdenhil Anita , Wiegand Susanna , Mann Jake P. 
Published: June 2020

AbstractBackground & aimsGenome-wide association studies in adults have identified variants in HSD17B13 and MARC1 as protective against NAFLD. It is not known if they are similarly protective in children and, more generally, whether the peri-portal inflammation of pediatric NAFLD and lobular inflammation seen in adults share common genetic influences. Therefore, we aimed to: establish if these variants are associated with NAFLD in children, and to investigate the function of these variants in hepatic metabolism using metabolomics.Methods960 children (590 with NAFLD, 394 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MARC1. Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of samples. In silico tools were used to model the effect of rs2642438G>A (p.Ala165Thr) on MARC1.Resultsrs72613567T>TA in HSD17B13 was associated with lower odds of NAFLD diagnosis (OR 0.7 (95%CI 0.6-0.9) and lower grade of portal inflammation (P<0.001) whilst rs2642438G>A in MARC1 was associated with lower grade of hepatic steatosis (P=0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective allele, whereas MARC1 levels were not affected by genotype. Both variants showed downregulation of hepatic fibrotic pathways, upregulation of retinol metabolism and perturbation of phospholipid species. Modelling suggests that p.Ala165Thr would disrupt the stability and metal-binding of MARC1.ConclusionsThere are shared genetic mechanisms between pediatric and adult NAFLD, despite their differences in histology. MARC1 and HSD17B13 are involved in phospholipid metabolism and suppress fibrosis in NAFLD.
Building comprehension to enhance vaccination intentions: Evidence from the United States and Italy
Authors: Porumbescu Greg , Cucciniello Maria , Pin Paolo , Melegaro Alessia 
Published: June 2020

AbstractBuilding on Cognitive Load Theory and the Elaboration Likelihood Model of Persuasion this study attempts to deepen our understanding of how health information campaigns related to vaccination work. We predict that including statistical information in health information campaigns will serve as a distraction that suppresses comprehension that renders the campaign less effective at persuading the public to vaccinate. Results from a survey experiment conducted on samples of US (n = 605) and Italian parents (n = 505) show support for the hypothesized relationship depends upon the form of comprehension (comprehension of how vaccines work versus comprehension of potential adverse effects of vaccinating). Specifically, both US and Italian parents show including statistical information reduces comprehension of how vaccines work, in turn reducing parents’ intentions to vaccinate themselves and their children. We find no support for the hypothesized mechanism when comprehension of potential adverse effects of vaccinating acts as the process variable.
Losing ground at the wrong time: Trends in self-reported influenza vaccination uptake in Switzerland, Health Survey 2007–2017
Authors: Zürcher Kathrin , Zwahlen Marcel , Berlin Claudia , Egger Matthias , Fenner Lukas 
Published: June 2020

AbstractObjectivesWe studied time trends in seasonal influenza vaccination and associations with socioeconomic and health-related determinants in Switzerland, overall and in people aged ≥ 65 years.DesignThree cross-sectional surveys.ParticipantsIndividuals who participated in the Swiss Health Surveys 2007, 2012, and 2017. We calculated the proportion reporting influenza vaccination in the last 12 months, and performed multivariable logistic regression analyses.ResultsThe proportion of reporting a history of influenza vaccination overall was 31.9% (95% confidence intervals [95% CI] 31.4–32.4); and dropped from 34.5% in 2007 to 28.8% in 2017. The uptake of vaccination within the past 12 months was 16% in 2007 and similar in 2012 and 2017 (around 14%). In people with chronic disease, uptake dropped from 43.8% in 2007 to 37.1% in 2012 and to 31.6% in 2017 (p<0.001). In people aged ≥ 65 years, uptake dropped from 47.8% in 2007 to 38.5% in 2012 to 36.2% in 2017 (p<0.001). Similarly, a decrease in vaccine uptake was seen in people with poor self-reported health status (39.4%, 33.1%, and 27.0%). In logistic regression, self-reported vaccination coverage decreased in the 65 to 75 years old (adjusted odds ratio (aOR) aOR 0.56, 95% Cl 0.48–0.66 between 2007 and 2012; aOR 0.89, 95% CI 0.77–1.03). Uptake was positively associated with the ≥ 65 age group, living in French-speaking and urban areas, history of smoking, bad self-reported health status, private/semiprivate health insurance, having a medical profession, and having any underlying chronic disease. Use of any alternative medicine therapy was negatively associated with influenza vaccination (aOR 0.72, 95% CI 0.67–0.80).ConclusionInfluenza vaccination coverage was low in older and chronically ill persons. Significant efforts are required in preparing for the flu season 2020/21 to reduce the double burden of COVID-19 and seasonal influenza. These efforts should include campaigns but also novel approaches using social media.Strengths and limitations of this studyData analysis of the Swiss Health Survey 2007, 2012, and 2017 focussing on influenza vaccine uptake overall and in the age group ≥65 years in Switzerland.The Swiss Health Survey is a nationwide, representative survey that is repeated every five years using the same methodology.Analyses were weighted and adjusted for a wide range of important cofactors.We calculated percent of people reporting having been vaccinated and associations between vaccination status and socio-demographic and health-related factors.Influenza vaccination status is self-reported in the Swiss Health Survey and the reliability of the data not ascertained.
THE ERA OF CORONAVIRUS; KNOWLEDGE, ATTITUDE, PRACTICES, AND BARRIERS TO HAND HYGIENE AMONG MAKERERE UNIVERSITY STUDENTS AND KATANGA COMMUNITY RESIDENTS
Authors: Nuwagaba Julius , Ashok Dave Darshit , Balizzakiwa Thomas , Kisengula Ibrahim , Nagaddya Edna Joyce , Rutayisire Meddy 
Published: June 2020

ABSTRACTBackgroundChina reported the Novel Coronavirus at the end of the year 2019 which was, later on, declared a Pandemic by the WHO. Proper hand hygiene was identified as one of the simplest most cost-effective Covid-19 control and prevention measures. It is therefore very important to understand the compliance of the community to hand hygiene.MethodA descriptive cross-sectional study was conducted among the undergraduate students of Makerere University and residents of Katanga slum from 17th to 22nd of March, 2020. An interviewer guided questionnaire with questions on knowledge, attitude, practice, and barriers to hand hygiene was used in data collection. The collected data was analyzed using Microsoft office excel 2016 and STATA 15 software. A 95% confidence interval was used and statistical significance was P<0.05.ResultsOnly 8.4% of the participants had good knowledge of hand hygiene. 11.7% of the university students had good knowledge compared to 0.9% of the Katanga residents. 29.0% of the participants had a good attitude while 50.1% had a moderate attitude to hand hygiene. University students were 6.3 times (OR: 6.3, 95%C1: (2.1 – 18.5), P=0.001) more likely to have good knowledge while Katanga residents were 3.6 times (OR: 3.6, 95%C1: (1.5 – 8.4), P=0.003) more likely to have good attitude to hand hygiene. Only 19.6% accomplished all the seven steps of handwashing. 38.4% of the participants still greeted by handshaking and 60.1% noted lack of soap as a barrier to hand hygiene and 62.9% reported having more than three barriers to hand hygiene. Participants that had been taught handwashing were more likely to have better hand hygiene knowledge and practice.ConclusionDespite a fair attitude, deficiency of knowledge coupled with many barriers such as Lack of soap hindered the Practice of proper hand hygiene. Public health involvement to promote hand hygiene must be promoted.
Pollen Explains Flu-Like and COVID-19 Seasonality
Authors: Hoogeveen Martijn J. , van Gorp Eric C.M. , Hoogeveen Ellen K. 
Published: June 2020

AbstractCurrent models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone, including associated behavior, do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral, anti-influenza and allergenic, plays a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19.We tested the Pollen-Flu Seasonality Theory for 2016–2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence.We found a highly significant inverse association of r(224) = –.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. The associations become stronger when taking into account incubation time, which satisfies the temporality criteria. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = –.48 (p < .001) when thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases.We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.
Cumulative Active and Recovery Rates Based Criterion for Gradual Lockdown Exit: A Global Observation of SARS Cov-2 Management
Authors: Raje Dhananjay V , Bajaj Abhay , Chakraborty Moumita , Purohit Hemant J 
Published: June 2020

AbstractOn March 11, 2020 the World Health Organization (WHO) had declared SARS-CoV-2 pandemic; and at present there are over 6 million cases across the globe. Based on the interim guidelines of WHO, most of the countries opted for social distancing with lockdown as the only way to control the pandemic. This led to ‘Manufacturing’ shut down, which acted as a spanner in the wheel for international supply chain leading to pressure on governments to review the protocols of the lockdown. We studied epidemiological parameters for 18 countries and obtained crossover time point referring to cumulative case active and case recovery rates and the time point for the peak positive confirmation rate in a time window of 92 days; and linked with the respective governmental decisions. For countries awaiting crossover, time series non-linear models could be used for predicting the crossover point. A sample study was carried out for India. The median time for reaching crossover for 12 countries was 37 days, while peak positive confirmation rate was 30 days after their first intervention. These countries enforced strict lockdown regulations and have shown constant improvement in their recovery rate even after crossover time point. A phase wise relaxation of lockdown is evident after crossover point in most of these countries. The crossover time point with the subsequent increasing recovery rate can be a strategy for lockdown relaxation as evident from the experiences of few countries. Also, we propose a criterion based on 28 cumulative recovery and fatality rate for micro-management of lockdown.
Circulating fibrocytes can identify people with a poor prognosis in idiopathic pulmonary fibrosis
Authors: Stewart Iain D. , Nanji Henry , Figueredo Grazziela , Fahy William A. , Maher Toby M. , Ask Antje J. , Maharaj Shyam , Ask Kjetil , Kolb Martin , Jenkins Gisli R. 
Published: June 2020

AbstractObjectiveCirculating fibrocytes are elevated in idiopathic pulmonary fibrosis, but the relationship between fibrocyte level with lung function decline and outcomes is lacking replication in prospective clinical study. We aim to validate the utility of circulating fibrocyte levels as a prognostic biomarker in idiopathic pulmonary fibrosis.MethodsWe tested associations between circulating fibrocyte levels, mortality, disease progression and longitudinal lung function in a well-defined prospective observational study of pulmonary fibrosis (PROFILE; NCT01134822). A subset of recruited participants had blood samples processed for fibrocyte measurement, with flow cytometry based on CD45 and collagen-I gating. Associations were tested using univariable and multivariable generalised linear models. Mortality data were subsequently combined with an independent cohort in a mixed-effect multilevel analysis.ResultsIn 102 participants with idiopathic pulmonary fibrosis, an empirically defined cutpoint of 2.22% was associated with a greater risk of overall mortality in adjusted analysis (Hazard Ratio 2.24 95% CI 1.06-4.72). A 2.5 fold greater risk of mortality was supported in a pooled analysis with a historic cohort for a larger sample of 162 participants of idiopathic pulmonary fibrosis, specifically (Hazard Ratio 2.49 95% CI 2.41-2.56). A previously defined mortality risk threshold of 5% circulating fibrocytes was not reproducible in this cohort, circulating fibrocytes were not significantly elevated above non-specific interstitial pneumonia or healthy controls.. We found no association of fibrocytes with lung function or disease progression.ConclusionsIn a prospective clinical cohort of idiopathic pulmonary fibrosis, circulating fibrocytes of 2.22% or above are associated with greater mortality, but do not associate with disease related decline in lung function.What is the key question?Can circulating fibrocytes provide reproducible prognostic biomarker value in fibrotic lung disease?What is the bottom line?Greater proportions of fibrocytes isolated from circulating leukocyte populations are associated with an increase risk of mortality in idiopathic pulmonary fibrosis, but no association was observed with disease related decline in lung function.Why read on?We present associations and limitations of circulating fibrocytes in the largest sample of individuals with pulmonary fibrosis, recruited into a prospective observational study, and replicate prognositic insights from a historic cohort.
Combined oropharyngeal/nasal swab is equivalent to nasopharyngeal sampling for SARS-CoV-2 diagnostic PCR
Authors: Desmet Tania , De Paepe Peter , Boelens Jerina , Coorevits Liselotte , Padalko Elizaveta , Vandendriessche Stien , Leroux-Roels Isabel , Aerssens Annelies , Callens Steven , Van Braeckel Eva , Malfait Thomas , Vermassen Frank , Verhasselt Bruno 
Published: June 2020

ABSTRACTBackgroundEarly 2020, a COVID-19 epidemic became a public health emergency of international concern. To address this pandemic broad testing with an easy, comfortable and reliable testing method is of utmost concern. The nasopharyngeal (NP) swab sampling is the reference method though hampered by international supply shortages. A new oropharyngeal/nasal (OP/N) sampling method was investigated using the more readily available throat swab.MethodsIn this prospective observational study 36 COVID-19 patients were tested with both a NP and combined OP/N swab for SARS-CoV-2 RNA by PCR. In hospitalized suspect patients, who tested negative on both swabs, extensive retesting was performed. The sensitivity of NP versus combined OP/N swab sampling on admission and the correlation between viral RNA loads recovered was investigated.Results35 patients were diagnosed with SARS-CoV-2 by means of either NP or OP/N sampling. The paired swabs were both positive in 31 patients. The one patient who tested negative on both NP and OP/N swab on admission, was ultimately diagnosed on bronchoalveolar lavage fluid. A strong correlation was found between the viral RNA loads of the paired swabs (r = 0.76; P < 0.05). The sensitivity of NP and OP/N analysis in hospitalized patients (n = 28) was 89.3% and 92.7% respectively.ConclusionsThis study demonstrates equivalence of NP and OP/N sampling for detection of SARS-CoV-2 by means of rRT-PCR. Sensitivity of both NP and OP/N sampling is very high in hospitalized patients.
Exosomes isolated from two different cell lines using three different isolation techniques show variation in physical and molecular characteristics
Authors: Dash Manish , Palaniyandi Kanagaraj , Ramalingam Satish , Sahabudeen S. , Raja N S 
Published: June 2020

AbstractExosomes are the nanoscopic lipid bi-layered extracellular vesicles with the potential to be utilized as targeted therapeutics. In our investigation, we compared three major exosome isolation techniques that were Total Exosome Isolation reagent (TEI), Protein organic solvent precipitation (PROSPR) and differential ultracentrifugation (UC) based on the biophysical and physicochemical characteristics of exosomes isolated from COLO 205 and MCF-7 cancer cell’s conditioned media with an aim to select a suitable method for translational studies. 3D image analysis and particle size distribution of exosomes from their HRTEM images depicted the morphological differences. Molecular and analytical characterization of exosomes using western blotting, Raman and ATR-FTIR spectroscopy and the multivariate analysis on the spectral data obtained, assessed for better molecular specifications and purity of particle. TEI method isolated exosomes with higher exosomal yield, purity, and recovery directly translatable into drug delivery and targeted therapeutics whereas ultracentrifuge had good recovery of particle morphology but showed particle aggregation and yielded exosomes with smaller mean size. PROSPR technique isolated a mixture of EVs, showed lower protein recovery in PAGE and western blotting but higher spectroscopic protein to lipid ratio and distinguishable EV population in multivariate analysis compared to exosomes isolated by TEI and UC. This comparative study should help in choosing a specific exosome isolation technique required for the objective of downstream applications.