bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composite trait Mendelian Randomization reveals distinct metabolic and lifestyle consequences of differences in body shape
Authors: Sulc Jonathan , Sonrel Anthony , Mounier Ninon , Auwerx Chiara , Marouli Eirini , Darrous Liza , Draganski Bogdan , Kilpeläinen Tuomas O. , Joshi Peter , Loos Ruth J.F. , Kutalik Zoltán 
Published: September 2020

AbstractObesity is a major risk factor for a wide range of cardiometabolic diseases, however the impact of specific aspects of body morphology remains poorly understood. We combined the GWAS summary statistics of fourteen anthropometric traits from UK Biobank through principal component analysis to reveal four major independent axes summarizing 99% of genetically driven variation in body shape and size: overall body size, adiposity, predisposition to abdominal fat deposition, and lean mass. Enrichment analyses suggest that body size and adiposity are affected by genes involved in neuronal signaling, whereas body fat distribution and lean mass are dependent on genes involved in morphogenesis and energy homeostasis. Using Mendelian randomization, we found that although both body size and adiposity contribute to the consequences of BMI, many of their effects are distinct, such as body size increasing the risk of diseases of the veins (b ≥ 0.044, p ≤ 8.9*10-10) and cardiac arrhythmia (b = 0.06, p = 4.2*10-17) while adiposity instead increased the risk of ischemic heart disease (b = 0.079, p = 8.2*10-21). The body mass-neutral component predisposing to abdominal fat deposition, likely reflecting a shift from subcutaneous to visceral fat, exhibited health effects that were weaker but specifically linked to lipotoxicity, such as ischemic heart disease (b = 0.067, p = 9.4*10-14) and diabetes (b = 0.082, p = 5.9*10-19). Combining their predicted effects significantly improved the prediction of obesity-related diseases, even when applied out-of-population (p < 10-10). The presented decomposition approach sheds light on the biological mechanisms underlying the remarkably heterogeneous nature of body morphology as well as its consequences on health and lifestyle.
Exploring linkages between drought and HIV treatment adherence in Africa: A Systematic Review
Authors: Orievulu Kingsley , Ayeb-Karlsson Sonja , Ngema Sthembile , Baisley Kathy , Tanser Frank , Ngwenya Nothando , Seeley Janet , Hanekom Willem , Herbst Kobus , Kniveton Dominic , Iwuji Collins 
Published: September 2020

AbstractClimate change is directly and indirectly linked to human health, including through access to treatment and care. Our systematic review presents a ‘systems’ understanding of the nexus between drought and antiretroviral treatment (ART) adherence in HIV-positive individuals in the African setting. Narrative synthesis of 111 studies retrieved from Web of Science, PubMed/Medline, and PsycINFO suggests that economic and livelihoods conditions, comorbidities and ART regimens, human mobility, and psycho-behavioural dispositions and support systems interact in complex ways in the drought-ART adherence nexus in Africa. Economic and livelihood-related challenges appear to impose the strongest impact on human interactions, actions and systems that culminate in non-adherence. Indeed, the complex pathways identified by our systems approach emphasise the need for more integrated research approaches to understanding this phenomenon and develop interventions.
COVID-19 hospitalizations in Brazil’s Unified Health System (SUS)
Authors: de Andrade Carla Lourenço Tavares , de Aguiar Pereira Claudia Cristina , Martins Mônica , Lima Sheyla Maria Lemos , Portela Margareth Crisóstomo 
Published: September 2020

AbstractObjectiveTo study the profile of hospitalizations due to COVID-19 in the Unified Health System (SUS) in Brazil and to identify factors associated with hospital mortality related to the disease.MethodsCross-sectional study, based on secondary data on COVID-19 hospitalizations that occurred in SUS, between the last days of February and June. Patients aged 18 years or older, with primary or secondary diagnoses indicative of COVID-19 were included. Bivariate analyses were performed and generalized linear mixed models (GLMM) were estimated with random effects intercept. The modeling followed three steps, including: attributes of the patients; elements of the care process; and characteristics of the hospital and place of hospitalization.Results89,405 hospitalizations were observed, of which 24.4% resulted in death. COVID-19 patients hospitalized in SUS were predominantly male (56.5%), with a mean age of 58.9 years. The length of stay ranged from less than 24 hours to 114 days, with a mean of 6.9 (±6.5) days. Of the total number of hospitalizations, 22.6% reported ICU use. The chances of hospital death among men were 16.8% higher than among women and increased with age. Black individuals had a higher chance of death. The behavior of the Charlson and Elixhauser indices was consistent with the hypothesis of a higher risk of death among patients with comorbidities, and obesity had an independent effect on increasing this risk. Some states had a higher risk of hospital death from COVID-19, such as Amazonas and Rio de Janeiro. The chances of hospital death were 72.1% higher in municipalities with at least 100,000 inhabitants and being hospitalized in the municipality of residence was a protective factor.ConclusionThere was wide variation in hospital COVID-19 mortality in the SUS, associated with demographic and clinical factors, social inequality and differences in the structure of services and quality of health care.
Swab pooling for large-scale RT-qPCR screening of SARS-CoV-2
Authors: Paula Christoff Ana , Cruz Giuliano Netto Flores , Sereia Aline Fernanda Rodrigues , Boberg Dellyana Rodrigues , Bastiani Daniela Carolina de , Yamanaka Laís Eiko , Fongaro Gislaine , Stoco Patrícia Hermes , Bazzo Maria Luiza , Grisard Edmundo Carlos , Hernandes Camila , de Oliveira Luiz Felipe Valter 
Published: September 2020

AbstractPool testing has been proposed as an alternative for large-scale SARS-CoV-2 screening. However, dilution factors proportional to the number of pooled samples have been a source of major concern regarding its diagnostic performance. Further, sample pooling can lead to increased laboratory workload and operational complexity. Therefore, pooling strategies that minimize sample dilution, loss of sensitivity, and laboratory overload are needed to allow reliable and large-scale screenings of SARS-CoV-2. Here, we describe a pooling procedure in which nasopharyngeal swabs are pooled together at the time of sample collection (swab pooling), decreasing laboratory manipulation and minimizing dilution of the viral RNA present in the samples. Paired analysis of pooled and individual samples from 613 patients revealed 94 positive individual tests. Having individual testing as a reference, no false-positives or false-negatives were observed for swab pooling. A Bayesian model estimated a sensitivity of 99% (Cr.I. 96.9% to 100%) and a specificity of 99.8% (Cr.I. 99.4% to 100%) for the swab pooling procedure. Data from additional 18,922 patients screened with swab pooling were included for further quantitative analysis. Mean Cq differences between individual and corresponding pool samples ranged from 0.1 Cq (Cr.I. –0.98 to 1.17) to 2.09 Cq (Cr.I. 1.24 to 2.94). Overall, 19,535 asymptomatic and presymptomatic patients were screened using 4,400 RT-qPCR assays, resulting in 246 positive patients (positivity rate 1.26%). This corresponds to an increase of 4.4 times in laboratory capacity and a reduction of 77% in required tests. Finally, these data demonstrate that swab pooling can significantly minimize sample dilution and sensitivity issues commonly seen in its traditional counterpart. Therefore, swab pooling represents a major alternative for reliable and large-scale screening of SARS-CoV-2 in low prevalence populations.
Assessment of COVID-19 Pandemic in Nepal: A Lockdown Scenario Analysis
Authors: Sharma Kusum , Banstola Amrit , Parajuli Rishi Ram 
Published: September 2020

AbstractThe Government of Nepal issued a nationwide lockdown from 24 March to 21 July 2020, prohibiting domestic and international travels, closure of the border and non-essential services. There were only two confirmed cases from 610 Reverse Transcription Polymerase Chain Reaction (RT-PCR) tests and no fatalities when the government introduced nationwide lockdown. This study aimed to explore the overall scenario of COVID-19 including spatial distribution of cases; government efforts, and impact on public health, socio-economy, and education during the lockdown in Nepal. We collated and analysed data using official figures from the Nepalese Ministry of Health and Population. Nepal had performed 7,791 RT-PCR tests for COVID-19, the highest number of tests during the lockdown. It has recorded its highest daily rise in coronavirus infections with a total of 740 new cases from the total of 4,483 RT-PCR tests performed on a single day. Nepal had reported a total of 17,994 positive cases and 40 deaths at the end of lockdown. The spatial distribution clearly shows that the cases were rapidly spreading from the southern part of the country where most points of entry and exit from India are located. To contain the spread of the virus, the government has also initiated various preventive measures and strategies during the lockdown. The Government of Nepal needs to allocate more resources, increase its capacity to test and trace, establish dedicated isolation and quarantine facility and impose local restrictions such as a local lockdown based on risk assessment rather than a nationwide lockdown.
Inter-specific Variability in Demographic Processes Affects Abundance-Occupancy Relationships
Authors: Şen Bilgecan , Akçakaya H. Reşit 
Published: September 2020

AbstractSpecies with large local abundances tend to occupy more sites. One of the mechanisms proposed to explain this widely reported inter-specific relationship is a cross-scale hypothesis based on dynamics at the population level. Called the vital rates mechanism, it uses within-population demographic processes of population growth and density dependence to predict when inter-specific abundance-occupancy relationships can arise and when these relationships can weaken and even turn negative. Even though the vital rates mechanism is mathematically simple, its predictions has never been tested directly because of the difficulty estimating the demographic parameters involved. Here, using a recently introduced mark-recapture analysis method, we show that there is a weakly positive relationship between abundance and occupancy among 17 bird species. Our results are consistent with the predictions of the vital rate mechanism regarding the demographic processes that are expected to weaken this relationship. Specifically, we find that intrinsic growth rate and local abundance are weakly correlated; and density dependence strength shows considerable variation across species. Variability in density dependence strength is related to variability in species-level local average abundance and intrinsic growth rate; species with lower growth rate have higher abundance and are strongly regulated by density dependent processes, especially acting on survival rates. Species with higher growth rate, on average, have lower abundance and are more weakly regulated by density dependent processes especially acting on fecundity. More generally, our findings support a cross scale mechanism of macroecological abundance-occupancy relationship emerging from density-dependent dynamics at the population level.
A SARS-CoV-2 – host proximity interactome
Authors: Samavarchi-Tehrani Payman , Abdouni Hala , Knight James D.R. , Astori Audrey , Samson Reuben , Lin Zhen-Yuan , Kim Dae-Kyum , Knapp Jennifer J. , St-Germain Jonathan , Go Christopher D. , Larsen Brett , Wong Cassandra J. , Cassonnet Patricia , Demeret Caroline , Jacob Yves , Roth Frederick P. , Raught Brian , Gingras Anne-Claude 
Published: September 2020

AbstractViral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.
No evidence for differential gene expression in major depressive disorder PBMCs, but robust evidence of elevated biological ageing
Authors: Cole John J. , McColl Alison , Shaw Robin , Lynall Mary-Ellen , Cowen Philip J , de Boer Peter , Drevets Wayne C , Harrison Neil , Pariante Carmine , Pointon Linda ,   NIMA consortium, Goodyear Carl , Bullmore Edward , Cavanagh Jonathan 
Published: September 2020

AbstractBackgroundThe increasingly compelling data supporting the involvement of immunobiological mechanisms in Major Depressive Disorder (MDD) might provide some explanation of the variance in this heterogeneous condition. Peripheral blood measures of cytokines and chemokines constitute the bulk of evidence with consistent meta-analytic data implicating raised proinflammatory cytokines such as IL6, IL1β and TNF. Among the potential mechanisms linking immunobiological changes to affective neurobiology is the accelerated biological ageing seen in MDD, particularly via the senescence associated secretory phenotype (SASP). However, the cellular source of immunobiological markers remains unclear.AimsPre-clinical evidence suggests a role for peripheral blood mononuclear cells (PBMC), thus here we aimed to explore the transcriptomic profile using RNA sequencing in PBMCs in a clinical sample of people with various levels of depression and treatment response comparing it with that in healthy controls (HCs).MethodTranscriptomic analysis of peripheral blood mononuclear cells.ResultsThe data showed no robust signal differentiating MDD and HCs. There was, however, significant evidence of elevated biological ageing in MDD vs HC.ConclusionsFuture work should endeavour to expand clinical sample sizes and reduce clinical heterogeneity. The exploration of RNA-seq signatures in other leukocyte populations and advances in RNA sequencing at the level of the single cell may help uncover more subtle differences. However, currently the subtlety of any PBMC signature mitigates against its convincing use as a diagnostic or predictive biomarker.HighlightsPBMCs showed no differential transcriptomic signature between depressed cases and healthy controls suggesting that the cellular source of the immune signature seen in depression may be from a different cell group.There was significant evidence of accelerated biological ageing in major depression compared to healthy controls.
Using human genetics to understand the causes and consequences of circulating cardiac troponin I in the general population
Authors: Moksnes Marta R , Røsjø Helge , Richmond Anne , Lyngbakken Magnus N , Graham Sarah E , Hansen Ailin Falkmo , Wolford Brooke N , Taliun Sarah A Gagliano , LeFaive Jonathon , Rasheed Humaira , Thomas Laurent F , Zhou Wei , Surakka Ida , Douville Nicholas J , Campbell Archie , Porteous David J , Welsh Paul , Sattar Naveed , Smith George Davey , Fritsche Lars G , Nielsen Jonas B , Åsvold Bjørn Olav , Hveem Kristian , Hayward Caroline , Willer Cristen J , Brumpton Ben M , Omland Torbjørn 
Published: September 2020

AbstractCirculating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes is unclear. We combine data from the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study and perform a genome-wide association study of highsensitivity cTnI concentrations with 48 115 individuals.We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes:CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1andLMAN1. Using two-sample Mendelian randomization we confirmed the non-causal role of cTnI in acute myocardial infarction, but could not rule out a causal role for cTnI in heart failure. Using genetically informed methods for causal inference of cTnI helps inform the role and value of measuring cTnI in the general population.
Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability
Authors: Georgakis Marios K. , van der Laan Sander W. , Asare Yaw , Mekke Joost M. , Haitjema Saskia , Schoneveld Arjan H. , de Kleijn Dominique P.V. , de Borst Gert J. , Pasterkamp Gerard , Dichgans Martin 
Published: September 2020

AbstractMonocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental,1–6genetic,7and observational8,9data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations with histopathological, molecular, and clinical features of plaque vulnerability. MCP-1 plaque levels were associated with histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) as well as molecular markers of plaque inflammation and matrix turnover, clinical plaque instability, and periprocedural stroke during plaque removal. Collectively, our findings highlight a role of MCP-1 in human plaque vulnerability and suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.
Nucleo-cytoplasmic shuttling of splicing factor SRSF1 is required for development and cilia function
Authors: Haward Fiona , Maslon Magdalena M. , Yeyati Patricia L. , Bellora Nicolas , Hansen Jan N. , Aitken Stuart , Lawson Jennifer , von Kriegsheim Alex , Wachten Dagmar , Mill Pleasantine , Adams Ian R. , Cáceres Javier F. 
Published: September 2020

AbstractShuttling RNA-binding proteins coordinate nuclear and cytoplasmic steps of gene expression. The SR family proteins regulate RNA splicing in the nucleus and a subset of them, including SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) inSrsf1to create a mouse model harboring an SRSF1 protein that is retained exclusively in the nucleus.Srsf1NRS/NRSmutants displayed small body size, hydrocephalus and immotile sperm, all traits associated with ciliary defects. We observed reduced translation of a subset of mRNAs and decreased abundance of proteins involved in multiciliogenesis, with disruption of ciliary ultrastructure and motility in cells derived from this mouse model. These results demonstrate that SRSF1 shuttling is used to reprogram gene expression networks in the context of high cellular demands, as observed here, during motile ciliogenesis.
Preclinical efficacy and safety analysis of gamma-irradiated inactivated SARS-CoV-2 vaccine candidates
Authors: Sir Karakus Gozde , Tastan Cihan , Dilek Kancagi Derya , Yurtsever Bulut , Tumentemur Gamze , Demir Sevda , Dilek Turan Raife , Abanuz Selen , Cakirsoy Didem , Seyis Utku , Ozer Samed , Elibol Omer , Elek Muhammer , Ertop Gurcan , Arbak Serap , Acikel Elmas Merve , Hemsinlioglu Cansu , Sesin Kocagoz Ayse , Hatirnaz Ng Ozden , Akyoney Sezer , Sahin Ilayda , Ozbek Ugur , Telci Dilek , Sahin Fikrettin , Yalcin Koray , Ratip Siret , Ovali Ercument 
Published: September 2020

AbstractCOVID-19 outbreak caused by SARS-CoV-2 created an unprecedented health crisis since there is no vaccine for this novel virus. Therefore, SARS-CoV-2 vaccines have become crucial for reducing morbidity and mortality. In this study, in vitro and in vivo safety and efficacy analyzes of lyophilized vaccine candidates inactivated by gamma-irradiation were performed. The candidate vaccines in this study were OZG-3861 version 1 (V1), an inactivated SARS-CoV-2 virus vaccine, and SK-01 version 1 (V1), a GM-CSF adjuvant added vaccine. The candidate vaccines were applied intradermally to BALB/c mice to assess toxicity and immunogenicity. Preliminary results in vaccinated mice are reported in this study. Especially, the vaccine models containing GM-CSF caused significant antibody production with neutralization capacity in absence of the antibody-dependent enhancement feature, when considered in terms of T and B cell responses. Another important finding was that the presence of adjuvant was more important in T cell in comparison with B cell response. Vaccinated mice showed T cell response upon restimulation with whole inactivated SARS-CoV-2 or peptide pool. This study shows that the vaccines are effective and leads us to start the challenge test to investigate the gamma-irradiated inactivated vaccine candidates for infective SARS-CoV-2 virus in humanized ACE2+ mice.
Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA
Authors: Ali Neserin , Turkiewicz Aleksandra , Hughes Velocity , Folkesson Elin , Tjörnstand Jon , Neuman Paul , Önnerfjord Patrik , Englund Martin 
Published: September 2020

AbstractThe underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group.More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.