bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggressive conflict impacts path integration in homing desert ants
Authors: Bollig Antonio , Freire Marília , Bücking Konrad , Kühnapfel Jana , Knaden Markus 
Published: November 2024

SummaryThe desert antCataglyphis fortisinhabits the salt pans of Tunisia, which are characterized by a lack of precipitation, extreme heat, and the complete absence of landmarks perceivable to humans. The individually foraging ants use path integration to find their way back to their nest (Müller and Wehner 1988, Wehner and Müller 2006, Müller and Wehner 2007, Wehner 2008). Additionally, the ants make use of other sensory cues, mainly visual and olfactory landmarks (Wehner and Raber 1979, Wehner et al. 1996, Steck et al. 2009, Buehlmann et al. 2011, Buehlmann et al. 2012, Wehner 2020), to form a robust toolkit for navigation. Since cooperation during foraging is negligible forC. fortis, the impact of intraspecific contact on its navigation has not yet been investigated. Our data suggests thatC. fortisconsiders intraspecific contact, or social cues, to further augment navigation. We show that contact with foreign conspecifics reduces trust in path integration thus broadening search patterns to optimize homing success. Furthermore, we explore the question of how ants navigate their surroundings without having aggressive encounters with neighboring nests and propose a navigational mechanism that might help ants avoid aggressive encounters with individuals of foreign colonies.
MuMu: a sample multiplexing protocol for droplet-based simultaneous single nuclei RNA- and ATAC-seq systems
Authors: Li Zhen , Haydar Tarik F. 
Published: November 2024

SummarySample multiplexing is a common approach to reduce experimental cost and technical batch effect. Here, we present a protocol that for the first time allows the pooling of single nuclei from multiple biological samples prior to performing simultaneous single nuclei RNA-seq and ATAC-seq, which we termMultiplexedMultiome (MuMu). We describe steps for assembling the custom Tn5 transposome, performing the transposition reaction, nuclei pooling, sequencing library preparation, and sequencing data pre-processing. This protocol will greatly reduce the cost of sn-Multiome.Graphical abstract
Emulating randomized controlled trials of long-acting insulins and cardiovascular events using real-world data for patients with type 2 diabetes
Authors: Wang Wanning , Reynier Pauline , Webster-Clark Michael , Yu Oriana HY , Brunetti Vanessa , Filion Kristian B. 
Published: November 2024

ABSTRACTAimsRandomized controlled trials (RCTs) have high internal validity but often have limited generalizability. To our knowledge, there are no studies examining potential differences between RCTs and real-world data in patient characteristics and risk of major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM) treated with long-acting insulin analogues.MethodsWe emulated the DEVOTE trial of insulin degludec vs glargine among patients with T2DM using data from the United Kingdom’s Clinical Practice Research Datalink. DEVOTE eligible and ineligible subpopulations were created. Cox proportional hazards models with inverse probability of treatment weighting were used to estimate hazard ratios (HRs) and corresponding confidence intervals (CIs) for MACE comparing new users of insulin degludec to new users of insulin glargine overall and in the eligible/ineligible subpopulations.ResultsThere were 10,430 patients in the overall population, 5,280 in the DEVOTE eligible population, and 5,150 in the DEVOTE ineligible population. The overall (HR: 1.36, 95% CI: 0.83, 1.86) and DEVOTE eligible populations (HR: 1.07, 95% CI: 0.63, 1.58) were compatible with findings from the DEVOTE trial (HR: 0.91, 95% CI: 0.78, 1.06) for the risk of MACE. Due to a low number of events the DEVOTE ineligible population had deviations in point estimates and wider CIs (HR: 2.19, 95% CI: 0.30, 3.83).ConclusionThe risk of MACE among patients with T2DM newly prescribed insulin degludec compared to insulin glargine was consistent between the overall population and the DEVOTE eligible subpopulation, while the DEVOTE ineligible population had discrepant point estimates.Twitter SummaryOur study emulated the DEVOTE trial using RWD. Half of the RWD population would be eligible for the trial. RWD and RCTs had compatible effect estimate for risk of major cardiovascular outcomes.
Epigenetic Age Monitoring in Professional Soccer Players for Tracking Recovery and the Effects of Strenuous Exercise
Authors: Brooke Robert T , Kocher Thomas , Zauner Roland , Gordevicius Juozas , Milčiūtė Milda , Nowakowski Marc , Haser Christian , Blobel Thomas , Sieland Johanna , Langhoff Daniel , Banzer Winfried , Horvath Steve , Pfab Florian 
Published: November 2024

AbstractElite sports have become increasingly professionalized and personalized, with soccer players facing a high number of games per season. This trend presents significant challenges in optimizing training for peak performance and requires rigorous monitoring of athletes to prevent overload and reduce injury risks. The emerging field of epigenetic clocks offers promising new pathways for developing useful biomarkers that enhance training management. This study investigates the effects of intense physical activity on epigenetic age markers in professional soccer players. We analyzed DNA methylation data from saliva samples collected before and after physical activity. Vigorous physical activity was found to rejuvenate epigenetic clocks, with significant decreases in DNAmGrimAge2 and DNAmFitAge observed immediately after games. Among player subgroups, midfielders exhibited the most substantial epigenetic rejuvenation effect following games. Additionally, the study suggests a potential link between DNA methylation patterns and injury occurrence. Overall, our study suggests that DNA methylation based biomarkers may have applications in monitoring athlete performance and managing physical stress.
Blood methylation biomarkers are associated with diabetic kidney disease progression in type 1 diabetes
Authors: Syreeni Anna , Dahlström Emma H. , Smyth Laura J. , Hill Claire , Mutter Stefan , Gupta Yogesh , Harjutsalo Valma , Chen Zhuo , Natarajan Rama , Krolewski Andrzej S. , Hirschhorn Joel N. , Florez Jose C. ,   GENIE consortium, Maxwell Alexander P. , Groop Per-Henrik , McKnight Amy Jayne , Sandholm Niina 
Published: November 2024

AbstractBackgroundDNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort.MethodsWe analysed baseline blood sample-derived DNA methylation (Illumina’s EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.73m2(early DKD progression group; median follow-up 13.1 years) or end-stage kidney disease (ESKD) (late DKD progression group; median follow-up 8.4 years). We conducted two epigenome-wide association studies (EWASs) on DKD progression and sought methylation quantitative trait loci (meQTLs) for the lead CpGs to estimate genetic contribution.ResultsAltogether, 14 methylation sites were associated with DKD progression (P<9.4×10−8). Methylation at cg01730944 nearCDKN1Cand at other CpGs associated with early DKD progression were not correlated with baseline eGFR, whereas late progression CpGs were strongly associated. Importantly, 13 of 14 CpGs could be linked to a gene showing differential expression in DKD or chronic kidney disease. Higher methylation at the lead CpG cg17944885, a frequent finding in eGFR EWASs, was associated with ESKD risk (HR [95% CI] = 2.15 [1.79, 2.58]). Additionally, we replicated meQTLs for cg17944885 and identified ten novel meQTL variants for other CpGs. Furthermore, survival models including the significant CpG sites showed increased predictive performance on top of clinical risk factors.ConclusionsOur EWAS on early DKD progression identified a podocyte-specificCDKN1Clocus. EWAS on late progression proposed novel CpGs for ESKD risk and confirmed previously known sites for kidney function. Since DNA methylation signals could improve disease course prediction, a combination of blood-derived methylation sites could serve as a potential prognostic biomarker.
PADI4 minor haplotype as risk factor for excessive NET formation and associated wound healing disorders in diabetes mellitus
Authors: Ehnert Sabrina , Hemmann Philipp , Ihle Christoph , Linnemann Caren , Mück Jonas , Anastasiou Panagiota-Georgia , Lobmann Ralf , Blumenstock Gunnar , Pscherer Stefan , Fritsche Andreas , Baumgartner Heiko , Histing Tina , Rollmann Mika F. , Nussler Andreas K. 
Published: November 2024

AbstractDiabetes mellitus (DM) complicates wound healing, partly due to excessive neutrophil extracellular trap (NET) formation, a process regulated by the enzyme peptidyl-arginine deiminase 4 (PADI4). Circulating NET markers can predict the healing outcome of chronic wounds, but may not allow enough time for intervention as the accumulated NETs may have already damaged the tissue. In search for an early detectable risk marker, this study aimed at relating PADI4 haplotype, to PADI4 expression, NET formation and clinical outcomes,i.a.infections, delayed wound and bone healing, in 687 surgical patients (44.7% with DM). Pre-surgical PADI4 expression was 9.4-fold higher in patients with DM, especially those with complicated wound healing. The study linked PADI4 haplotypes to NET formation and clinical outcomes, finding that neutrophils with the PADI4 minor haplotype had higher PADI4 mRNA and protein levels and more rapidly produced a larger amount of NETs than neutrophils with the PADI4 major haplotype. Patients with DM and the PADI4 minor haplotype experienced the highest rates of delayed wound healing and infections. Our findings suggest that the PADI4 haplotype influences neutrophil behavior and clinical outcomes, making it a potential biomarker to screen patients with DM for their risk of developing wound healing complications.Graphical Abstract
Deteriorated mechanics of left ventricular diastolic filling one year after coronary artery bypass grafting
Authors: Norderfeldt Joakim , Sundqvist Martin G , Maret Eva , Löfström Ulrika , Corbascio Matthias , Hage Camilla , Ekström Mattias , Wallén Håkan , Lyngå Patrik , Persson Bengt , Persson Hans E , Linde Cecilia , Marlevi David , Eriksson Maria J , Ugander Martin 
Published: November 2024

AbstractBackgroundIschemic heart disease impairs left ventricular (LV) diastolic function, but little is known about changes in the mechanical properties of LV relaxation following coronary artery bypass grafting (CABG).ObjectivesThis study aimed to explore if and how the mechanics of LV filling change following CABG.MethodsPatients underwent transthoracic echocardiography before and one year after elective CABG. Mitral inflow E-waves were analyzed using the parameterized diastolic filling (PDF) method, allowing for quantification of mechanical properties of diastolic function.ResultsAmong patients (n=96, 10% female, median [interquartile range] age 68 [62–74] years), LV ejection fraction (LVEF) at baseline was 59 [53–63] %. At follow-up, there was an increase in the PDF-derived measures of myocardial stiffness, damping, peak driving and resistive forces, and filling energy, together with increase in left atrial (LA) volume index, and a decrease in LA conduit and contractile strains and tricuspid annular plane systolic excursion (p<0.001 for all). There was no change in heart rate, LV size, LVEF, E/é ratio, or LV filling efficiency. Furthermore, there were no differences in the mechanics of LV filling in patients when grouped according to baseline LVEF, or the number of revascularized coronary arteries.ConclusionsOne year after CABG, there was consistent deterioration in the mechanics of diastolic filling assessed using comprehensive conventional and mechanistic evaluation. Revascularization with CABG may worsen diastolic function one year after CABG. However, causes and significance of these changes remain to be further investigated.Abstract FigureCentral illustration.Deterioration in LV diastolic properties one year after CABG.Overview of background, study design, methods and main results. Abbreviations: LV – Left Ventricular; CABG – Coronary artery bypass graft surgery; CMR – Cardiovascular magnetic resonance; ECHO – transthoracic echocardiography.
Do Researchers Consider the Inter-relationship Between Time to Assessment and Admission Severity in Acute Stroke?
Authors: Lu Zewen , Gittins Matthew , Kishore Amit K , Smith Craig J , Vail Andy 
Published: November 2024

AbstractBackgroundStroke severity, often quantified by NIHSS at admission, evolves and may influence patients’ time to hospital arrival. The inclusion of timing in stroke severity assessment remains unclear in stroke research. Oversight of time to assessment can affect prognostic model interpretation, acute clinical decision-making, and the design of future clinical trials by considering admission severity in the context of time since symptom onset.AimsThis study aimed to assess whether and, if so, how stroke researchers account for time from symptom onset to admission severity assessment in their analyses. We sought to compare this with approaches used by perinatal researchers, considering a similar statistical relationship between gestational age and birth weight.Summary of reviewTwo reviewers systematically reviewed papers in leading specialty journals published in 2019 using NIHSS at admission and birth weight respectively as an explanatory factor in the statistical analysis. We targeted a minimum of 50 articles from each field to ensure 90% to identify approaches used in 5% or more of studies.A total of 111 studies were included. Perinatal researchers considered the temporal variable gestational age more often than time to assessment in stroke studies (89% vs. 7%, chi-squared p<0.001). It was consequently included more often (56% vs. 5%, chi-squared p<0.001). Four methods, including stratification, distribution, regression and combined approaches, were found. Time to assessment was only included as a continuous (n=2) or categorical (n=1) factor alongside admission NIHSS in three studies. Methods for covariate selection, essential for the interpretation of statistical models, were rarely specified.ConclusionsFew researchers explore the inter-relationship between baseline severity and time to assessment in stroke prognostication, in sharp contrast to consideration of timing in perinatal studies. Future research will investigate whether time to assessment or serial NIHSS in the hyper-acute phase could benefit both clinical practice and stroke research.
Extensive antagonistic variants across human genome
Authors: Bian Beilei , Hivert Valentin , Wray Naomi R , McRae Allan F 
Published: November 2024

AbstractPleiotropic conflict, where a genetic locus has antagonistic effects on different traits, is a common phenomenon observed in animals and plants. While pleiotropy has been widely reported in humans, there is no systematic study of pleiotropic conflict in humans. Here, we leverage GWAS summary statistics of complex diseases and traits derived from large-scale population cohorts to identify pleiotropic regions with conflicting effects. Through a multi-trait colocalization approach, we identified 219 independent regions containing variants showing pleiotropic conflict, which cover ∼11.4% of linkage disequilibrium blocks in the human genome. Antagonistic variants are observed to be enriched for SNPs with intermediate minor allele frequencies and antagonistic regions show signatures of positive/balancing selection. Our results suggest that antagonistic variants are pervasive in humans and indicate their role in maintaining phenotypic and genetic diversity in humans.
Gaussian Process Emulation for Modeling Dengue Outbreak Dynamics
Authors: Langmüller Anna M. , Chandrasekher Kiran A. , Haller Benjamin C. , Champer Samuel E. , Murdock Courtney C. , Messer Philipp W. 
Published: November 2024

AbstractEpidemiological models that aim for a high degree of biological realism by simulating every individual in a population are unavoidably complex, with many free parameters, which makes systematic explorations of their dynamics computationally challenging. This study investigates the potential of Gaussian Process emulation to overcome this obstacle. To simulate disease dynamics, we developed an individual-based model of dengue transmission that includes factors such as social structure, seasonality, and variation in human movement. We trained three Gaussian Process surrogate models on three outcomes: outbreak probability, maximum incidence, and epidemic duration. These models enable the rapid prediction of outcomes at any point in the eight-dimensional parameter space of the original model. Our analysis revealed that average infectivity and average human mobility are key drivers of these epidemiological metrics, while the seasonal timing of the first infection can influence the course of the epidemic outbreak. We use a dataset comprising more than 1,000 dengue epidemics observed over 12 years in Colombia to calibrate our Gaussian Process model and evaluate its predictive power. The calibrated Gaussian Process model identifies a subset of municipalities with consistently higher average infectivity estimates, highlighting them as promising areas for targeted public health interventions. Overall, this work underscores the potential of Gaussian Process emulation to enable the use of more complex individual-based models in epidemiology, allowing a higher degree of realism and accuracy that should increase our ability to control important diseases such as dengue.
Preparedness of Sub-Saharan African Countries to Address Climate Change and Health Impact: A Scoping Review
Authors: Kilungo Aminata , Chukwuonye Godsgift N. , Okpanachi Victor , Hussein Mohamed 
Published: November 2024

AbstractClimate change severely threatens global public health, with sub-Saharan Africa (SSA) projected to experience profound impacts. This scoping review aimed to provide a comprehensive overview of current research on climate change and its health implications in SSA while identifying research gaps and outlining the necessary resources and policy interventions to strengthen public health resilience in the region. Literature was retrieved from four databases (PubMed, Scopus, Embase and Web of Science) using the keywords “climate change,” “health,” and “sub-Saharan Africa”. A total of 7851 journal articles were identified from the initial search, and after screening, 153 studies were included for review. The included studies were published between January 2001 and August 2024. Although extensive studies have been conducted on extreme heat (71 studies), drought (45 studies), extreme precipitation events (52 studies), and flooding (34 studies), important themes such as air quality (10 studies), chemical water quality (8 studies) and natural disasters (8) have been understudied. Additionally, this scoping review revealed a geographical gap in climate change and health studies, as only 24 out of 53 countries in sub-Saharan Africa were represented. The key deficiencies identified include limited funding, technological constraints, inadequate climate policies, and a lack of community-focused adaptation plans. Moreover, this review highlights the urgent need for resilient healthcare systems capable of addressing climate-related health risks effectively. Addressing these gaps is essential for developing targeted strategies to mitigate climate change’s health impacts and increase resilience in SSA communities. This review aims to inform policymakers, researchers, and stakeholders about critical areas requiring attention and investment by enhancing our understanding of these challenges and gaps. Strengthening research capacities, fostering collaboration, and implementing evidence-based policies are imperative steps toward achieving sustainable health outcomes in the face of a changing climate in sub-Saharan Africa.
Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors
Authors: Wood Eilidh M. , Hornaday Kylie K. , Newton Matthew , Wang Melinda , Wood Stephen L. , Slater Donna M. 
Published: November 2024

AbstractProstaglandins and other related molecules in the eicosanoid family have long been implicated in the process of both term and preterm labour. Although, exactly which eicosanoids are involved and whether they have utility as biomarkers for labour, remains to be shown. The objective of this study was to determine whether urinary prostaglandins and related molecules a) change with labour and/or cervical changes, at term and preterm, and/or b) are associated with timing of delivery in individuals with threatened preterm labour. Pregnant individuals were recruited into the following groups: n=32 term non-labour, n=49 term labour, n=15 preterm non-labour controls, n=43 threatened preterm labour with preterm delivery, and n=44 threatened preterm labour with term delivery. Metabolites of prostaglandins PGE2, PGF2α, PGD2, and PGI2as well as 8-isoprostane were measured by ELISA. In addition, 147 eicosanoids were measured in a small (n=24) subset of these samples using a mass-spectrometry based targeted lipidomics panel. At term labour prostaglandin PGF2αand PGE2and PGF2αmetabolites were increased compared to term non-labour. There were no changes in any prostaglandin metabolites prior to labour onset. Prostaglandin I2metabolite was lower in individuals with threatened preterm labour who delivered preterm compared to those who went on to deliver at term. In our discovery cohort, we identified 20 additional eicosanoids as highly expressed in maternal urine, include members of the prostaglandin, hydroxyeicosatetraenoic acid (HETE), epoxyeicosatrienoic acid (EET), dihydroxy-octadecenoic acid (DiHOME), dihydroxy-eicosatrienoic acid (diHETrE), isoprostane, and nitro fatty acid eicosanoid families. In conclusion, we did not identify any prostaglandins that would have utility as predictors for term or preterm labour, however, we have identified diverse eicosanoids that have not been previously explored in the context of pregnancy and labour, highlighting novel areas for biomarker research.