bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA-sequence and epigenomic determinants of local rates of transcription elongation
Authors: Liu Lingjie , Zhao Yixin , Siepel Adam 
Published: December 2023

AbstractAcross all branches of life, transcription elongation is a crucial, regulated phase in gene expression. Many recent studies in eukaryotes have focused on the regulation of promoter-proximal pausing of RNA Polymerase II (Pol II), but rates of productive elongation also vary substantially throughout the gene body, both within and across genes. Here, we introduce a probabilistic model for systematically evaluating potential determinants of the local elongation rate based on nascent RNA sequencing (NRS) data. Our model is derived from a unified model for both the kinetics of Pol II movement along the DNA template and the generation of NRS read counts at steady state. It allows for a continuously variable elongation rate along the gene body, with the rate at each nucleotide defined by a generalized linear relationship with nearby genomic and epigenomic features. High-dimensional feature vectors are accommodated through a sparse-regression extension. We show with simulations that the model allows accurate detection of associated features and accurate prediction of local elongation rates. In an analysis of public PRO-seq and epigenomic data, we identify several features that are strongly associated with reductions in the local elongation rate, including DNA methylation, splice sites, RNA stem-loops, CTCF binding sites, and several histone marks, including H3K36me3 and H4K20me1. By contrast, low-complexity sequences and H3K79me2 marks are associated with increases in elongation rate. In an analysis of DNAk-mers, we find that cytosine nucleotides are strongly associated with reductions in local elongation rate, particularly when preceded by guanines and followed by adenines or thymines. Increases in elongation rate are associated with thymines and A+T-richk-mers. These associations are generally shared across cell types, and by considering them our model is effective at predicting features of held-out PRO-seq data. Overall, our analysis is the first to permit genome-wide predictions of relative nucleotide-specific elongation rates based on complex sets of genomic and epigenomic covariates. We have made predictions available for the K562, CD14+, MCF-7, and HeLa-S3 cell types in a UCSC Genome Browser track.
High throughput screening of Leaf Economics traits in six wine grape varieties
Authors: Cui Boya , Mariani Rachel , Cathline Kimberley A. , Robertson Gavin , Martin Adam R. 
Published: December 2023

AbstractReflectance spectroscopy has become a powerful tool for non-destructive and high- throughput phenotyping in crops. Emerging evidence indicates that this technique allows for estimation of multiple leaf traits across large numbers of samples, while alleviating the constraints associated with traditional field- or lab-based approaches. While the ability of reflectance spectroscopy to predict leaf traits across species and ecosystems has received considerable attention, whether or not this technique can be applied to quantify within species trait variation have not been extensively explored. Employing reflectance spectroscopy to quantify intraspecific variation in functional traits is especially appealing in the field of agroecology, where it may present an approach for better understanding crop performance, fitness, and trait-based responses to managed and unmanaged environmental conditions. We tested if reflectance spectroscopy coupled with Partial Least Square Regression (PLSR) predicts rates of photosynthetic carbon assimilation (Amax), Rubisco carboxylation (Vcmax), electron transport (Jmax), leaf mass per area (LMA), and leaf nitrogen (N), across six wine grape (Vitis vinifera) varieties (Cabernet Franc, Cabernet Sauvignon, Merlot, Pinot Noir, Viognier, Sauvignon Blanc). Our PLSR models showed strong capability in predicting intraspecific trait variation, explaining 55%, 58%, 62%, and 64% of the variation in observedJmax,Vcmax, leaf N, and LMA values, respectively. However, predictions ofAmaxwere less strong, with reflectance spectra explaining only 29% of the variation in this trait. Our results indicate that trait variation within species and crops is less well-predicted by reflectance spectroscopy, than trait variation that exists among species. However, our results indicate that reflectance spectroscopy still presents a viable technique for quantifying trait variation and plant responses to environmental change in agroecosystems.
Genome-wide QTL mapping across three tissues highlights several Alzheimer’s and Parkinson’s disease loci potentially acting via DNA methylation
Authors: Ohlei Olena , Sommerer Yasmine , Dobricic Valerija , Homann Jan , Deecke Laura , Schilling Marcel , Bartrés-Faz David , Cattaneo Gabriele , Düzel Sandra , Fjell Anders M. , Lindenberger Ulman , Pascual-Leone Álvaro , Sabet Sanaz Sedghpour , Solé-Padullés Cristina , Tormos Josep M. , Vetter Valentin M. , Walhovd Kristine B. , Wesse Tanja , Wittig Michael , Franke Andre , Demuth Ilja , Lill Christina M. , Bertram Lars 
Published: December 2023

AbstractDNA methylation (DNAm) is an epigenetic mark with essential roles in disease development and predisposition. Here, we created genome-wide maps of methylation quantitative trait loci (meQTL) in three peripheral tissues and used Mendelian randomization (MR) analyses to assess the potential causal relationships between DNAm and risk for two common neurodegenerative disorders, i.e. Alzheimer’s disease (AD) and Parkinson’s disease (PD). Genome-wide single nucleotide polymorphism (SNP; ∼5.5M sites) and DNAm (∼850K CpG sites) data were generated from whole blood (n=1,058), buccal (n=1,527) and saliva (n=837) specimens. We identified between 11 and 15 million genome-wide significant (p<10-14) SNP-CpG associations in each tissue. Combining these meQTL GWAS results with recent AD/PD GWAS summary statistics by MR strongly suggests that the previously described associations betweenPSMC3,PICALM, andTSPAN14and AD may be founded on differential DNAm in or near these genes. In addition, there is strong, albeit less unequivocal, support for causal links between DNAm atPRDM7in AD as well as atKANSL1/MAPTin AD and PD. Our study adds valuable insights on AD/PD pathogenesis by combining two high-resolution “omics” domains, and the meQTL data shared along with this publication will allow like-minded analyses in other diseases.
Psychometric analysis of the modified Covid-19 Yorkshire Rehabilitation Scale (C19-YRSm) in a prospective multicentre study
Authors: Smith Adam B. , Greenwood Darren C. , Horton Mike , Osborne Thomas , Goodwin Madeline , Lawrence Román Rocha , Winch Darren , Williams Paul , Milne Ruairidh ,   the LOCOMOTION consortium, Sivan Manoj 
Published: December 2023

AbstractBckgroundLong COVID is a novel multisystem clinical syndrome affecting millions of individuals worldwide. The modified COVID-19 Yorkshire Rehabilitation Scale (C19-YRSm) is a condition-specific patient-reported outcome measure designed for assessment and monitoring of people with Long COVID (LC).ObjectivesTo evaluate the psychometric properties of the C19-YRSm in a prospective sample of people with Long COVID.Methods1314 patients attending UK specialist Long COVID clinics completed C19-YRSm and EQ-5D-5L longitudinally. Scale characteristics were derived for C19-YRSm subscales (Symptom Severity, SS; Functional Disability, FD; and Overall Health, OH) and internal consistency (Cronbach’s alpha). Convergent validity was assessed using the FACIT-Fatigue scale. Known groups validity was assessed for the Other Symptoms (OS) subscale as tertiles, hospitalisation and intensive care admission. Responsiveness and test-retest reliability was evaluated for C19-YRSm subscales and EQ-5D-5L. The minimal important difference (MID) and minimal clinically important difference (MCID) were estimated. Confirmatory factor analysis was applied to determine the instrument’s two-factor structure.ResultsC19-YRSm demonstrated good scale characteristic properties. Item-total correlations were between 0.37 to 0.65 (for SS and FD), with good internal reliability (Cronbach’s alphas >0.8). Item correlations between subscales ranged between 0.46 to 0.72. Convergent validity with FACIT was good (−0.46 to −0.62). The three subscales discriminated between different levels of symptom burden (p<0.001), and between patients admitted to hospital and intensive care. There was moderate responsiveness for the three subscales ranging from 0.22 (OH) to 0.50 (SS) and was greater than the EQ-5D-5L. Test-retest reliability was good for both SS 0.86 and FD 0.78. MID was 2 for SS, 2 for FD, and 1 for OH; MCID was 4 for both the SS and FD. The factor analysis supported the two-factor SS and FD structure.ConclusionsThe C19-YRSm is a condition-specific, reliable, valid, and responsive patient-reported outcome measure for Long COVID.Key messagesWhat is already known on this topicLong Covid or Post-COVID-19 syndrome is a multisystem, fluctuating condition. C19-YRSm is literature’s first condition-specific patient reported outcome measure which needed validation in a large population sample.What this study addsC19-YRSm is a valid, reliable, responsive and easy to administer measure which is able to show clinically meaningful change in the status of the condition in people living with Long Covid.How this study might affect research, practice or policyC19-YRSm can be used in clinical and research settings to reliably capture the condition trajectory and the effect of interventions and also help inform clinical policy.
Individual effect of diet on postprandial glycemic response and its relationship with gut microbiome profile in healthy subjects: protocol for a series of randomized N-of-1 trials
Authors: Zamparette C.P. , Teixeira B.L. , Cruz G.N.F. , Filho V. B. , De Oliveira L.F.V. 
Published: December 2023

AbstractBackgroundType 2 diabetes causes over a million deaths annually, ranking in the top ten causes of death worldwide. Glycemic control through dietary adequacy is essential for treatment success and disease prevention. Recent evidence indicates that the glycemic response to various foods varies from individual to individual. The intestinal microbiome is seen as a potential key player, mediating the effect of foods on glycemic response. By design, however, most published studies cannot separate variation in the individual treatment effects (ITE) of different diets from within-individual variability of glycemic responses. In this context, the present study aims to assess the heterogeneity in the ITE of diet on glycemic response and investigate the relevance of the intestinal microbiome profile as a predictor of this heterogeneity.MethodsThis study is a series of N-of-1 randomized clinical trials. Each participant will undergo five treatment cycles of two prescribed diets (low-carb versus vegan) in one of two randomly chosen treatment sequences (ABBABAABBA or BAABABBAAB). The primary outcome is the positive incremental area-under-the-curve (iAUC) of the postprandial interstitial fluid glucose measured within 2 hours of meal consumption. The trial plans to recruit 80 healthy volunteers with ages between 18 and 60. Fecal samples will be collected at baseline for microbiome analysis by metagenomics shotgun technique. Random effects linear models will be used for the primary analysis.DiscussionWhile significant variation of individual effects warrants personalized interventions, it is well-known that glycemic responses to the same food, in the same individual, vary from occasion to occasion. Yet, most clinical studies are based on designs that are incapable of separating ITE variation from within-individual variability. This is a major limitation since the personalization of dietary interventions is only justified by clinically relevant heterogeneity of individual-level effects. In this study, if significant ITE variation is indeed observed, then we will also be able to estimate the relationship between the intestinal microbiome and the expected diet effects. This is essential to identify predictive biomarkers, which can identify those who intrinsically benefit the most from which diet, going beyond pure associations with glycemic response. Conversely, observing negligible ITE variation in a large series of N-of-1 trials would cast major doubts on the relevance of personalizing dietary interventions for glycemic control. Therefore, the present study represents a major step toward understanding the clinical value of microbiome-driven precision nutrition.
A Phenome-wide association study of genetically determined nicotine metabolism reveals novel links with health-related outcomes
Authors: Buchwald Jadwiga , Lehtimäki Terho , Raitakari Olli , Salomaa Veikko , Kaprio Jaakko , Pirinen Matti 
Published: December 2023

AbstractBackgroundFaster nicotine metabolism, defined as the nicotine metabolite ratio (NMR), is known to associate with heavier smoking and challenges in smoking cessation. However, the broader health implications of genetically determined nicotine metabolism are not well characterized.MethodsWe performed a hypothesis-free phenome-wide association study (PheWAS) of over 21,000 outcome variables from UK Biobank (UKB) to explore how the NMR (measured as the 3-hydroxycotinine-to-cotinine ratio) associates with the phenome. As the exposure variable, we used a genetic score for faster nicotine metabolism based on 10 putative causal genetic variants, explaining 33.8 % of the variance in the NMR. We analysed ever and never smokers separately to assess whether a causal pathway through nicotine metabolism is plausible.ResultsA total of 57 outcome variables reached phenome-wide significance at a false discovery rate of 5 %. We observed expected associations with several phenotypes related to smoking and nicotine, but could not replicate prior findings on cessation. Importantly, we found novel associations between genetically determined faster nicotine metabolism and adverse health outcomes, including unfavourable liver enzyme and lipid values, as well as increased caffeine consumption. These associations did not appear to differ between ever and never smokers, suggesting the corresponding pathways may not involve nicotine metabolism. No favourable health outcomes were linked to genetically determined faster nicotine metabolism.ConclusionsOur findings support a possibility that a future smoking cessation therapy converting fast metabolizers of nicotine to slower ones could work without adverse side effects and potentially even provide other health-related benefits.
The effect of leisure activities on quality-of-life scores for children with complex needs: A service evaluation in Wales, UK
Authors: McGrath Nicole , Astill Fiona , Collins Bethan , Maguire Sabine , Kemp Alison , Hurt Lisa 
Published: December 2023

AbstractPurposeRecent guidance has resulted in an increased level of interest in the wellbeing of children and young people, including those with complex needs. Evaluation of quality of life in this population is notoriously difficult, but has become increasingly vital when assessing the value of a service.MethodsA previously validated tool, Quality of life Inventory-Disability (QI-Disability), was used in conjunction with parental reports on quality-of-life measures for children and young people before and after 6 and 12 months of attending specialist leisure activities provided by a charity (Sparkle) at children’s centres in South Wales.ResultsQI-Disability scores improved overall after 6 and 12 months of attending Sparkle club activities. However, the only statistically significant improvement was in the QI-Disability positive emotions domain. Parental reports also confirmed that children and young people were making progress towards their personal goals.ConclusionCollecting evaluation data within real-world services is challenging but essential. This paper uses quality-of-life measures to demonstrate how leisure activities provided by Sparkle improve scores for children with disabilities, including evidence of the perceived value for children, young people and parents.Plain English summaryThere is little previous research evaluating specialist leisure activities provided for children and young people with disabilities within real-world services. This evaluation aimed to find out if specialist leisure activities improved wellbeing scores for children with complex needs. We used parent-report questionnaires to measure changes to children’s quality of life whilst accessing these leisure activities. We found there is a benefit to children and young people with complex needs and their families when they participate in specialist leisure activities, and children experienced more positive emotions after accessing for 6 months.
Antibodies toAedes aegyptiD7L salivary proteins as a new serological tool to estimate human exposure toAedesmosquitoes
Authors: Chea Sophana , Willen Laura , Nhek Sreynik , Ly Piseth , Tang Kristina , Oristian James , Salas-Carrillo Roberto , Ponce Aiyana , Leon Paola Carolina Valenzuela , Kong Dara , Ly Sokna , Sath Ratanak , Lon Chanthap , Leang Rithea , Huy Rekol , Yek Christina , Valenzuela Jesus G. , Calvo Eric , Manning Jessica E. , Oliveira Fabiano 
Published: December 2023

1AbstractIntroductionAedes spp.are the most prolific mosquito vectors in the world. Found on every continent, they can effectively transmit various arboviruses, including the dengue virus which continues to cause outbreaks worldwide and is spreading into previously non-endemic areas. The lack of widely available dengue vaccines accentuates the importance of targeted vector control strategies to reduce the dengue burden. High-throughput sensitive tools to estimate human-mosquito contact and evaluate vector control interventions are lacking. We propose a novel serological tool that allows rapid screening of large human cohorts for exposure to potentially infectious mosquitoes and effective targeting of vector control.MethodsWe tested 563 serum samples from a longitudinal pediatric cohort study previously conducted in Cambodia. Children enrolled in the study were dengue-naïve at baseline and were followed biannually for dengue incidence for two years. We used Western blotting and enzyme-linked immunosorbent assays to identify the most immunogenicAedes aegyptisalivary proteins and measure total anti-Ae. AegyptiIgG.ResultsWe found a strong correlation (rs=0.86) between the combined IgG responses against AeD7L1 and AeD7L2 recombinant proteins and those to whole salivary gland homogenate. We observed seasonal fluctuations of AeD7L1+2 IgG responses, corresponding toAedes spp.abundance in the region, and no cross-reactivity withCulex quinquefasciatusandAnopheles dirusmosquitoes. The baseline median AeD7L1+2 IgG responses for young children were higher in those who developed asymptomatic dengue versus those who developed symptomatic dengue.ConclusionThe IgG response against AeD7L1+2 recombinant proteins is a highly sensitive andAedesspecific marker of human exposure toAedesbites that can facilitate standardization of future serosurveys and epidemiological studies by its ability to provide a robust estimation of human-mosquito contact in a high-throughput fashion.
Connectivity at home: A data-driven connectivity modeling framework for home range movements in heterogeneous landscapes
Authors: Merkens Lisa , Mimet Anne , Bae Soyeon , Fairbairn Andrew , Mühlbauer Maximilian , Lauppe Elio , Mesarek Florian , Stauffer-Bescher Daniel , Hauck Thomas E. , Weisser Wolfgang W. 
Published: December 2023

AbstractLandscape connectivity analyses can serve landscape planning with designing functional conservation networks. However, existing frameworks face challenges, such as achieving consistency between integrated data and modeled processes, implementing data-driven parameterization, and addressing connectivity within the home range. We propose restricting connectivity analyses to the home range scale to better relate landscape resistance, barrier effects and resource accessibility to daily movements and home range establishment.We introduce a home range connectivity modeling framework that allows deriving important connectivity parameters empirically. We identify areas that can support home ranges based on available resources and calculate resource patch accessibility using graph and circuit theory. Resistance values, patch isolation distances, and connectivity metrics are selected from statistical models using movement data. We demonstrate the framework’s utility through a case study on urban blackbirds and increase its applicability by testing whether the use of simple presence/absence data without additional movement data, and the use of a coarser resolution affect the estimation of parameter values.In statistical analyses, the local connectivity showed a strong significant positive association with the probability of blackbird movement (β = 0.23, p < 0.005). We uncover that the connectivity parameters are better assessed with graph theory-derived metrics when parametrized with movement data. We find a high barrier effect of high buildings and a moderate barrier effect of lower buildings and streets on blackbird movement. However, when assessed with presence/absence data, model parametrization can result in similar values only when using circuit theory metrics. Changing the resolution from 10 to 30 m has minimal impact on parametrization results with movement data.Our study showcases a data-driven parameterization using statistical model selection, which addresses several of the main limitations of recent connectivity modeling approaches. Presence/absence data and coarser resolution can be used judiciously, but independently. Restricting analyses to home ranges yields valuable insights into home range ecology, landscape impacts on movement in highly heterogeneous landscapes, and species distribution.
Complex life cycles and parasite-mediated trophic cascades drive species coexistence and the maintenance of genetic diversity
Authors: Hijar-Islas Ana C. , Mon Père Nathaniel V. , Huang Weini , Eizaguirre Christophe 
Published: December 2023

AbstractEcological and evolutionary processes shape the dynamics of species interactions, yet the drivers of eco-evolutionary feedback remain elusive. Here, we developed an individual-based model of a coevolving predator-prey-parasite system, in which predators can be infected by trophically transmitted parasites. We combined host-parasite coevolution with prey-predator interactions at an individual level, hence integrating evolutionary and ecological processes. We show that species coexist more when parasite-mediated selection is weak on both the predator and the prey. Population size and genotypic diversity of the parasite are highest at intermediate parasite-mediated selection on the predator and no parasite-mediated selection on the prey. Interestingly, we show that the evolution of super-resistant genotypes, where host genotypes have resistant alleles in all loci, is driven by interspecific interactions rather than by the population size of the host species. Overall, host-parasite coevolution shapes the direction of interspecific ecological interactions which, in turn, determine species coexistence and community diversity in a complex system.