bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a nationwide Internet-based health survey in workers during the COVID-19 pandemic in 2020
Authors: Fujino Yoshihisa , Ishimaru Tomohiro , Eguchi Hisashi , Tsuji Mayumi , Tateishi Seiichiro , Ogami Akira , Mori Koji , Matsuda Shinya ,   for the CORoNaWork project
Published: February 2021

AbstractThe ever-changing social implications of the COVID-19 pandemic have resulted in an urgent need to understand the working environments and health status of workers. We conducted a nationwide Internet-based health survey in Japanese workers in December 2020, in the midst the country’s “third wave” of COVID-19 infection. Of 33,087 surveys collected, 6,051 were determined to have invalid responses. The 27,036 surveys included in the study were balanced in terms of geographical area, participant sex, and type of work, according to the sampling plan. Men were more likely than women to have telecommuted, while women were more likely to have resigned since April 2020. Moreover, 40% and 9.1% of respondents had a K6 score of 5 or higher and 13 or higher, respectively, they did not exhibit extremely poor health. The present study describes the protocol used to conduct an Internet-based health survey in workers and a summary of its results during a period when COVID-19 was spreading rapidly in Japan. In the future, we plan to use this survey to examine the impact of COVID-19 on workers’ work styles and health.
Estimating the Population Benefits of Blood Pressure Lowering: A Wide-Angled Mendelian Randomization Study in UK Biobank
Authors: Higgins Hannah , Mason Amy M. , Larsson Susanna C. , Gill Dipender , Langenberg Claudia , Burgess Stephen 
Published: February 2021

AbstractBackgroundThe causal relevance of elevated blood pressure for several cardiovascular diseases is uncertain, as is the population impact of blood pressure lowering on risk of cardiovascular diseases more broadly. This study systematically assesses evidence of causality for various cardiovascular diseases in a two-sample Mendelian randomization framework, and estimates the potential reduction in the prevalence of these diseases attributable to long-term population shifts in the distribution of systolic blood pressure (SBP).Methods and ResultsWe investigated associations of genetically-predicted SBP as predicted by 256 genetic variants with 21 cardiovascular diseases in UK Biobank, a population-based cohort of UK residents. The sample consisted of 376,703 participants of European ancestry aged 40-69 years at baseline. Genetically-predicted SBP was positively associated with 14 of the outcomes (p<0.002), including dilated cardiomyopathy, endocarditis, peripheral vascular disease, and rheumatic heart disease. Using genetic variation to estimate the long-term impact of blood pressure lowering on disease, population reductions in SBP were predicted to result in an overall 16.9% (95% confidence interval (CI): 12.2-21.3%) decrease in morbidity for a 5 mmHg decrease from a population mean of 137.7 mmHg, 30.8% (95% CI: 22.8-38.0%) for a 10 mmHg decrease, and 56.2% (95% CI: 43.7-65.9%) decrease for a 22.7 mmHg decrease in SBP (22.7 mmHg represents a shift from the current mean SBP to 115 mmHg).ConclusionsRisk of many cardiovascular diseases is influenced by long-term differences in SBP. The burden of a broad range of CVDs could be substantially reduced by long-term population-wide reductions in the distribution of blood pressure.
Exponential increase in neutralizing and spike specific antibodies following vaccination of COVID-19 convalescent plasma donors
Authors: Vickers Molly A. , Sariol Alan , Leon Judith , Ehlers Alexandra , Locher Aaron V. , Dubay Kerry A. , Collins Laura , Voss Dena , Odle Abby E. , Holida Myrl , Merrill Anna E. , Perlman Stanley , Knudson C. Michael 
Published: February 2021

AbstractBackgroundWith the recent approval of COVID-19 vaccines, recovered COVID-19 subjects who are vaccinated may be ideal candidates to donate COVID-19 convalescent plasma (CCP).Case SeriesThree recovered COVID-19 patients were screened to donate CCP. All had molecularly confirmed COVID-19, and all were antibody positive by chemiluminescence immunoassay (DiaSorin) prior to vaccination. All were tested again for antibodies 11 to 21 days after they received the first dose of the vaccine (Pfizer). All showed dramatic increases (∼50 fold) in spike-specific antibody levels and had at least a 20-fold increase in the IC50 neutralizing antibody titer based on plaque reduction neutralization testing (PRNT). The spike-specific antibody levels following vaccination were significantly higher than those seen in any non-vaccinated COVID-19 subjects tested to date at our facility.ConclusionSpike-specific and neutralizing antibodies demonstrated dramatic increases following a single vaccination post COVID-19 infection which significantly exceeded values seen with COVID-19 infection alone. Recovered COVID-19 subjects who are vaccinated may make ideal candidates for CCP donation.
Mental Health, Substance Use, and Suicidal Ideation Among Unpaid Caregivers in the United States During the COVID-19 Pandemic: Relationships to Age, Race/Ethnicity, Employment, and Caregiver Intensity
Authors: Czeisler Mark É , Drane Alexandra , Winnay Sarah S , Capodilupo Emily R , Czeisler Charles A , Rajaratnam Shantha MW , Howard Mark E 
Published: February 2021

AbstractObjectivesTo estimate the prevalence of unpaid caregiving during the coronavirus disease 2019 (COVID-19) pandemic, and to identify factors associated with adverse mental health symptoms, substance use, and suicidal ideation in this population, which provides critical support in health care systems by providing care to older adults and those with chronic conditions.MethodsIn June 2020, Internet-based surveys with questions about demographics, caregiving responsibilities, and mental health were administered to US adults aged ≥18 years. Demographic quota sampling and survey weighting to improve cross-sectional sample representativeness of age, gender, and race/ethnicity. Prevalence ratios for adverse mental health symptoms were estimated using multivariable Poisson regressions.ResultsOf 9,896 eligible invited adults, 5,412 (54.7%) completed surveys; 5,011 (92.6%) respondents met screening criteria and were analysed, including 1,362 (27.2%) caregivers. Caregivers had higher prevalences of adverse mental health symptoms than non-caregivers, including anxiety or depressive disorder symptoms (57.6% vs 21.5%, respectively, p<0.0001) having recently seriously considered suicide (33.4% vs 3.7%, p<0.0001). Symptoms were more common among caregivers who were young vs older adults (e.g., aged 18–24 vs ≥65 years, aPR 2.75, 95% CI 1.95–3.88, p<0.0001), Hispanic or Latino vs non-Hispanic White (1.14, 1.04–1.25, p=0.0044), living with vs without disabilities (1.18, 1.10–1.26, p<0.0001), and with moderate and high vs low Caregiver Intensity Index scores (2.31, 1.65–3.23; 2.81, 2.00–3.94; both p<0.0001). Suicidal ideation was more prevalent among non-Hispanic Black vs non-Hispanic White caregivers (1.48, 1.15–1.90, p=0.0022).ConclusionsCaregivers, who accounted for one in four US adult respondents in this nationally representative sample, more commonly reported adverse mental health symptoms than non-caregivers. Increased visibility of and access to mental health care resources are urgently needed to address mental health challenges of caregiving.
Recruitment location influences bias and uncertainty in SARS-CoV-2 seroprevalence estimates
Authors: Brown Tyler S. , de Salazar Munoz Pablo Martinez , Bhatia Abhishek , Bunda Bridget , Williams Ellen K. , Bor David , Miller James S. , Mohareb Amir M. , Thierauf Julia , Yang Wenxin , Villalba Julian , Naranbai Vivek , Beltran Wilfredo Garcia , Miller Tyler E. , Kress Doug , Stelljes Kristen , Johnson Keith , Larremore Daniel B. , Lennerz Jochen , Iafrate A. John , Balsari Satchit , Buckee Caroline O. , Grad Yonatan H. 
Published: February 2021

AbstractThe initial phase of the COVID-19 pandemic in the US was marked by limited diagnostic testing, resulting in the need for seroprevalence studies to estimate cumulative incidence and define epidemic dynamics. In lieu of systematic representational surveillance, venue-based sampling was often used to rapidly estimate a community’s seroprevalence. However, biases and uncertainty due to site selection and use of convenience samples are poorly understood. Using data from a SARS-CoV-2 serosurveillance study we performed in Somerville, Massachusetts, we found that the uncertainty in seroprevalence estimates depends on how well sampling intensity matches the known or expected geographic distribution of seropositive individuals in the study area. We use GPS-estimated foot traffic to measure and account for these sources of bias. Our results demonstrated that study-site selection informed by mobility patterns can markedly improve seroprevalence estimates. Such data should be used in the design and interpretation of venue-based serosurveillance studies.
Age-related heterogeneity in immune responses to SARS-CoV-2 vaccine BNT162b2
Authors: Collier Dami A. , Ferreira Isabella A.T.M. , Kotagiri Prasanti , Datir Rawlings , Lim Eleanor , Touzier Emma , Meng Bo , Abdullahi Adam ,   The CITIID-NIHR BioResource COVID-19 Collaboration, Elmer Anne , Kingston Nathalie , Graves Barbara , Gresley Emma Le , Caputo Daniela , Smith Kenneth GC , Bradley John R. , Ceron-Gutierrez Lourdes , Cortes-Acevedo Paulina , Barcenas-Morales Gabriela , Linterman Michelle , McCoy Laura , Davis Chris , Thomson Emma , Lyons Paul A. , McKinney Eoin , Doffinger Rainer , Wills Mark , Gupta Ravindra K. 
Published: February 2021

AbstractTwo dose mRNA vaccination provides excellent protection against SARS-CoV-2. However, there are few data on vaccine efficacy in elderly individuals above the age of 801. Additionally, new variants of concern (VOC) with reduced sensitivity to neutralising antibodies have raised fears for vulnerable groups. Here we assessed humoral and cellular immune responses following vaccination with mRNA vaccine BNT162b22 in elderly participants prospectively recruited from the community and younger health care workers. Median age was 72 years and 51% were females amongst 140 participants. Neutralising antibody responses after the first vaccine dose diminished with increasing age, with a marked drop in participants over 80 years old. Sera from participants below and above 80 showed significantly lower neutralisation potency against B.1.1.7, B.1.351 and P.1. variants of concern as compared to wild type. Those over 80 were more likely to lack any neutralisation against VOC compared to younger participants following first dose. The adjusted odds ratio for inadequate neutralisation activity against the B.1.1.7, P.1 and B.1.351 variant in the older versus younger age group was 4.3 (95% CI 2.0-9.3, p<0.001), 6.7 (95% CI 1.7-26.3, p=0.008) and 1.7 (95% CI 0.5-5.7, p=0.41). Binding IgG and IgA antibodies were lower in the elderly, as was the frequency of SARS-CoV-2 Spike specific B-memory cells. We observed a trend towards lower somatic hypermutation in participants with suboptimal neutralisation, and elderly participants demonstrated clear reduction in class switched somatic hypermutation, driven by the IgA1/2 isotype. SARS-CoV-2 Spike specific T-cell IFNγ and IL-2 responses fell with increasing age, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high risk population that warrant specific measures in order to mitigate against vaccine failure, particularly where variants of concern are circulating.
Affective neural signatures do not distinguish women with emotion dysregulation from healthy controls: A mega-analysis across three task-based fMRI studies
Authors: Sicorello M. , Herzog J. , Wager T.D. , Ende G. , Müller-Engelmann M. , Herpertz S.C. , Bohus M. , Schmahl C. , Paret C. , Niedtfeld I. 
Published: February 2021

AbstractPathophysiological models are urgently needed for personalized treatments of mental disorders. However, most potential neural markers for psychopathology are limited by low interpretability, prohibiting reverse inference from brain measures to clinical symptoms and traits. Neural signatures—i.e. multivariate brain-patterns trained to be both sensitive and specific to a construct of interest—might alleviate this problem, but are rarely applied to mental disorders. We tested whether previously developed neural signatures for negative affect and discrete emotions distinguish between healthy individuals and those with mental disorders characterized by emotion dysregulation, i.e. Borderline Personality Disorder (BPD) and complex Post-traumatic Stress Disorder (cPTSD). In three different fMRI studies, a total sample of 192 women (49 BPD, 62 cPTSD, 81 healthy controls) were shown pictures of scenes with negative or neutral content. Based on pathophysiological models, we hypothesized higher negative and lower positive reactivity of neural emotion signatures in participants with emotion dysregulation. The expression of neural signatures differed strongly between neutral and negative pictures (average Cohen’s d = 1.17). Nevertheless, a mega-analysis on individual participant data showed no differences in the reactivity of neural signatures between participants with and without emotion dysregulation. Confidence intervals ruled out even small effect sizes in the hypothesized direction and were further supported by Bayes factors. Overall, these results support the validity of neural signatures for emotional states during fMRI tasks, but raise important questions concerning their link to individual differences in emotion dysregulation.
Deep Learning Prediction of Biomarkers from Echocardiogram Videos
Authors: Hughes J Weston , Yuan Neal , He Bryan , Ouyang Jiahong , Ebinger Joseph , Botting Patrick , Lee Jasper , Theurer John , Tooley James E. , Neiman Koen , Lungren Matthew P. , Liang David , Schnittger Ingela , Harrington Bob , Chen Jonathan H. , Ashley Euan A. , Cheng Susan , Ouyang David , Zou James Y. 
Published: February 2021

AbstractLaboratory blood testing is routinely used to assay biomarkers to provide information on physiologic state beyond what clinicians can evaluate from interpreting medical imaging. We hypothesized that deep learning interpretation of echocardiogram videos can provide additional value in understanding disease states and can predict common biomarkers results. Using 70,066 echocardiograms and associated biomarker results from 39,460 patients, we developed EchoNet-Labs, a video-based deep learning algorithm to predict anemia, elevated B-type natriuretic peptide (BNP), troponin I, and blood urea nitrogen (BUN), and abnormal levels in ten additional lab tests. On held-out test data across different healthcare systems, EchoNet-Labs achieved an area under the curve (AUC) of 0.80 in predicting anemia, 0.82 in predicting elevated BNP, 0.75 in predicting elevated troponin I, and 0.69 in predicting elevated BUN. We further demonstrate the utility of the model in predicting abnormalities in 10 additional lab tests. We investigate the features necessary for EchoNet-Labs to make successful predictions and identify potential prediction mechanisms for each biomarker using well-known and novel explainability techniques. These results show that deep learning applied to diagnostic imaging can provide additional clinical value and identify phenotypic information beyond current imaging interpretation methods.
Age-related susceptibility to insulin resistance is due to a combination of CPT1B decline and lipid overload
Authors: Vieira-Lara Marcel A. , Dommerholt Marleen B. , Zhang Wenxuan , Blankestijn Maaike , Wolters Justina C. , Abegaz Fentaw , Gerding Albert , van der Veen Ydwine , van Dijk Theo H. , van Os Ronald , Reijngoud Dirk-Jan , Jonker Johan W. , Kruit Janine K. , Bakker Barbara M. 
Published: February 2021

AbstractBACKGROUNDAdvanced age increases the susceptibility to diet-induced insulin resistance (IR). A key driver of this phenomenon is lipid accumulation in the skeletal muscle. It is debated, however, whether this is due to dietary lipid overload or decline of mitochondrial function. To address the interplay of diet and age in the flexibility of muscle lipid and glucose handling, we put young and aged mice on a low- or high-fat diet (HFD).RESULTSAs expected, aged mice were more susceptible to IR when given a HFD than young mice. The HFD induced intramuscular lipid accumulation specifically in aged mice, including C18:0-containing ceramides and diacylglycerols. This was reflected by the mitochondrial β-oxidation capacity, which was upregulated by the HFD in young, but not in old mice. Conspicuously, most β-oxidation proteins were upregulated by the HFD in both groups, but carnitine palmitoyltransferase 1B (CPT1B) declined in aged animals. Computational modelling traced the flux control mostly to CPT1B, suggesting a CPT1B-driven loss of flexibility to the HFD with age. Finally, in old animals glycolytic protein levels were reduced and less flexible to the diet.CONCLUSIONWe conclude that intramuscular lipid accumulation and decreased insulin sensitivity are not due to age-related mitochondrial dysfunction or nutritional overload alone, but rather to their interaction. Moreover, we identify CPT1B as a potential target to counteract age-dependent intramuscular lipid accumulation and thereby IR.
The epigenetic landscape in purified myonuclei from fast and slow muscles
Authors: Bengtsen Mads , Winje Ivan Myhre , Eftestøl Einar , Landskron Johannes , Sun Chengyi , Domanska Diana , Millay Douglas P. , Meza-Zepeda Leonardo , Gundersen Kristian 
Published: February 2021

AbstractMuscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of chromatin environment by ChIP-Seq in two muscle extremes, the almost completely fast/glycolytic extensor digitorum longus (EDL) and slow/oxidative soleus muscles. Muscle is a heterogeneous tissue where less than 60% of the nuclei are inside muscle fibers. Since cellular homogeneity is critical in epigenome-wide association studies we devised a new method for purifying skeletal muscle nuclei from whole tissue based on the nuclear envelope protein Pericentriolar material 1 (PCM1) being a specific marker for myonuclei. Using antibody labeling and a magnetic-assisted sorting approach we were able to sort out myonuclei with 95% purity. The sorting eliminated influence from other cell types in the tissue and improved the myo-specific signal. A genome-wide comparison of the epigenetic landscape in EDL and soleus reflected the functional properties of the two muscles each with a distinct regulatory program involving distal enhancers, including a glycolytic super-enhancer in the EDL. The two muscles are also regulated by different sets of transcription factors; e.g. in soleus binding sites for MEF2C, NFATC2 and PPARA were enriched, while in EDL MYOD1 and SOX1 binding sites were found to be overrepresented. In addition, novel factors for muscle regulation such as MAF, ZFX and ZBTB14 were identified.
Habitat complexity in organic olive orchards modulates the abundance of natural enemies but not the attraction to plant species
Authors: Álvarez Hugo Alejandro , Morente Marina , Ruano Francisca 
Published: February 2021

AbstractSemi-natural habitat complexity and organic management could affect the abundance and diversity of natural enemies and pollinators in olive orchards. Nonetheless, in such agroecosystems the effect of plant structure, plant richness, and plant attraction on the arthropod fauna has been poorly documented. Here we evaluate the influence of those effects jointly as an expression of arthropod abundance and richness in olive trees, ground cover, and adjacent vegetation within organic olive orchards. For this, we used generalized linear models and non-metric multidimensional scaling (NMDS) integrating generalized additive models. Our results suggest that natural enemies and pollinators are mainly attracted toA. radiatus,D. catholica, andL. longirrostriswithin ground cover andG. cinerea speciosa,Q. rotundifolia,R. officinalis,T. zygis gracilis, andU. parvifloruswithin adjacent vegetation. Accordingly, habitat complexity showed a positive relationship with the abundance of key families of natural enemies and pollinators but not with the number of taxa. NMDS showed that plant richness and plant arrangement and scattering affected the key families differently, suggesting that each key family responds to their individual needs for plant resources but forming groups modulated by complexity. This pattern was especially seeing in predators and omnivores. Our findings support that the higher the plant richness and structure of a semi natural-habitat within an olive orchard, the higher the abundance and richness of a given arthropod community (a pattern found in natural ecosystems). The information presented here can be used by producers and technicians to increase the presence and abundance of natural enemies and pollinators within organic olive orchards, and thus improve the ecosystem services provided by semi-natural habitats.Graphical abstract
Inhibitory synaptic transmission is impaired at higher extracellular Ca2+concentrations inScn1a+/−mouse model of Dravet syndrome
Authors: Uchino Kouya , Kawano Hiroyuki , Tanaka Yasuyoshi , Adaniya Yuna , Asahara Ai , Deshimaru Masanobu , Kubota Kaori , Watanabe Takuya , Katsurabayashi Shutaro , Iwasaki Katsunori , Hirose Shinichi 
Published: February 2021

ABSTRACTDravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in theSCN1Agene, which encodes a subunit of Na+channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar betweenScn1aknock-in neurons (Scn1a+/–neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower inScn1a+/–neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower inScn1a+/–neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca2+concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced inScn1a+/–neurons, while the sensitivity of inhibitory synapses to extracellular Ca2+concentrations is markedly increased. These data suggest that Ca2+tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.