bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 serosurvey across multiple waves of the COVID-19 pandemic in New York City between 2020-2023
Authors: Carreño Juan Manuel , Wagner Abram L. , Monahan Brian , Floda Daniel , Gonzalez-Reiche Ana S , Tcheou Johnstone , Raskin Ariel , Bielak Dominika , Singh Gagandeep , Morris Sara , Fried Miriam , Yellin Temima , Sullivan Leeba ,   PARIS study group, Sordillo Emilia Mia , Gordon Aubree , van Bakel Harm , Simon Viviana , Krammer Florian 
Published: December 2023

ABSTRACTSero-monitoring provides context to the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and changes in population immunity following vaccine introduction. Here, we describe results of a cross-sectional hospital-based study of anti-spike seroprevalence in New York City (NYC) from February 2020 to July 2022, and a follow-up period from August 2023 to October 2023. Samples from 55,092 individuals, spanning five epidemiological waves were analyzed. Prevalence ratios (PR) were obtained using Poisson regression. Anti-spike antibody levels increased gradually over the first two waves, with a sharp increase during the 3rdwave coinciding with SARS-CoV-2 vaccination in NYC resulting in seroprevalence levels >90% by July 2022. Our data provide insights into the dynamic changes in immunity occurring in a large and diverse metropolitan community faced with a new viral pathogen and reflects the patterns of antibody responses as the pandemic transitions into an endemic stage.
Missense and Loss of Function Variants at GWAS Loci in Familial Alzheimer’s Disease
Authors: Gunasekaran Tamil Iniyan , Reyes-Dumeyer Dolly , Faber Kelley M. , Goate Alison , Boeve Brad , Cruchaga Carlos , Pericak-Vance Margaret , Haines Jonathan L. , Rosenberg Roger , Tsuang Debby , Mejia Diones Rivera , Medrano Martin , Lantigua Rafael A. , Sweet Robert A. , Bennett David A. , Wilson Robert S. , Alba Camille , Dalgard Clifton , Foroud Tatiana , Vardarajan Badri N. , Mayeux Richard 
Published: December 2023

AbstractBACKGROUNDFew rare variants have been identified in genetic loci from genome wide association studies of Alzheimer’s disease (AD), limiting understanding of mechanisms and risk assessment, and genetic counseling.METHODSUsing genome sequencing data from 197 families in The NIA Alzheimer’s Disease Family Based Study, and 214 Caribbean Hispanic families, we searched for rare coding variants within known GWAS loci from the largest published study.RESULTSEighty-six rare missense or loss of function (LoF) variants completely segregated in 17.5% of families, but in 91 (22.1%) of familiesAPOE-e4was the only variant segregating. However, in 60.3% of families neitherAPOE-e4nor missense or LoF variants were found within the GWAS loci.DISCUSSIONAlthoughAPOE-ε4and several rare variants were found to segregate in both family datasets, many families had no variant accounting for their disease. This suggests that familial AD may be the result of unidentified rare variants.
Beyond Borders: Spatial Disparities in the Mortality Burden of the Covid-19 pandemic across 569 European Regions (2020-2021)
Authors: Bonnet Florian , Grigoriev Pavel , Sauerberg Markus , Alliger Ina , Mühlichen Michael , Camarda Carlo-Giovanni 
Published: December 2023

AbstractThis article presents a detailed analysis of the global mortality burden of the COVID-19 pandemic across 569 regions in 25 European countries. We produce age and sex-specific excess mortality and present our results using Age-Standardised Years of Life Lost (ASYLL) in 2020 and 2021, as well as the cumulative impact over the two pandemic years. Employing a robust forecasting approach that considers regional diversity and provides confidence intervals, we find notable losses in 362 regions in 2020 (440 regions in 2021). Conversely, only seven regions experienced gains in 2020 (four regions in 2021). Most importantly, we estimate that eight regions suffered losses exceeding 20 years of life per 1,000 population in 2020, whereas this number increased to 75 regions in 2021. The contiguity of the regions investigated in our study also reveals the changing geographical patterns of the pandemic. While the highest excess mortality values were concentrated in the early COVID-19 outbreak areas during the initial pandemic year, a clear East-West gradient appeared in 2021, with regions of Slovakia, Hungary, and Latvia experiencing the highest losses. This research underscores the importance of regional analyses for a nuanced comprehension of the pandemic’s impact.
Clinical, laboratory, and imaging findings of stage 3-5 chronic kidney disease patients suffering from COVID-19 in Bangladesh: a prospective cross-sectional study
Authors: Ullah Ahsan , Khanam Asia , Mondal Mina , Haque Md Rezwanul , Sumon AHM Sanjedul Haque , Khan Shakila , Hoque Mohimanul , Sumon Motiur Rahman , Rahman Mohammad Meshbahur 
Published: December 2023

AbstractBackgroundChronic kidney disease (CKD) patients were susceptible to morbidity and mortality once they affected by COVID-19. These patients were more likely to develop severe disease, requiring dialysis, admission to intensive care unit. The aim of this study was to evaluate the presentations and outcomes of COVID-19 in stage 3-5 CKD patients not on dialysis.MethodsThis prospective observational study was conducted in the COVID-19 unit, at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from September 2020 to August 2021. Hospitalized RT-PCR positive COVID-19 patients with pre-existing CKD having eGFR <60 ml/min/1.73 m2but not yet on dialysis were enrolled. Clinical and laboratory parameters were recorded. Outcomes were observed till discharge from the hospital and followed up after 3 months of survived patients.ResultsOut of 109 patients, the mean age was 58.1(SD: ±15.4) years where 61.5% were male. Common co-morbid conditions were hypertension (89.0%), diabetes mellitus (58.7%) and ischemic heart disease (24.8%). Fever, cough, shortness of breath and fatigue were common presenting features. Most of the patients had moderate (41.3%) and severe (41.3%) COVID-19. Sixty-six patients (60.6%) developed AKI on CKD. Twenty patients (30.3%) required dialysis. Death occurred in 16 patients (14.7%) and 12 patient’s (11%) required ICU admission and 6 patients (9.1%) achieved baseline renal function at discharge. We identified risk factors like low haemoglobin, lymphopenia, high CRP, high procalcitonin, high LDH and low SpO2in patients who did not survive. Seventy-six patients were followed up at 3rd month where 17 patients were lost. Ten patients (27.0%) achieved baseline renal function who had persistent AKI at discharge and 34 patients (87.1%) remained stable who had stable renal function at discharge.ConclusionThe stage 3-5 chronic kidney patients with COVID-19 are vulnerable to severe to critical morbidity and mortality with higher incidence of AKI which demands a special attention to this group of patients.
Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors
Authors: Ray Christina MP , Yang Huilin , Spangler Jamie B , Mac Gabhann Feilim 
Published: December 2023

ABSTRACTThe spread of cancer from organ to organ (metastasis) is responsible for the vast majority of cancer deaths; however, most current anti-cancer drugs are designed to arrest or reverse tumor growth without directly addressing disease spread. It was recently discovered that tumor cell-secreted interleukin-6 (IL-6) and interleukin-8 (IL-8) synergize to enhance cancer metastasis in a cell-density dependent manner, and blockade of the IL-6 and IL-8 receptors (IL-6R and IL-8R) with a novel bispecific antibody, BS1, significantly reduced metastatic burden in multiple preclinical mouse models of cancer. Bispecific antibodies (BsAbs), which combine two different antigen-binding sites into one molecule, are a promising modality for drug development due to their enhanced avidity and dual targeting effects. However, while BsAbs have tremendous therapeutic potential, elucidating the mechanisms underlying their binding and inhibition will be critical for maximizing the efficacy of new BsAb treatments. Here, we describe a quantitative, computational model of the BS1 BsAb, exhibiting how modeling multivalent binding provides key insights into antibody affinity and avidity effects and can guide therapeutic design. We present detailed simulations of the monovalent and bivalent binding interactions between different antibody constructs and the IL-6 and IL-8 receptors to establish how antibody properties and system conditions impact the formation of binary (antibody-receptor) and ternary (receptor-antibody-receptor) complexes. Model results demonstrate how the balance of these complex types drives receptor inhibition, providing important and generalizable predictions for effective therapeutic design.
An evolutionary optimum amid moderate heritability in prokaryotic cell size
Authors: Secaira-Morocho Henry , Chede Abhinav , Gonzalez-de-Salceda Luis , Garcia-Pichel Ferran , Zhu Qiyun 
Published: December 2023

SummaryWe investigated the distribution and evolution of prokaryotic cell size based on a compilation of 5380 species. Size spans four orders of magnitude, from 100 nm (Mycoplasma) to more than 1 cm (Thiomargarita), however most species congregate heavily around the mean. The distribution approximates but is distinct from log-normality. Comparative phylogenetics suggested that size is heritable, yet the phylogenetic signal is moderate, and the degree of heritability is independent of taxonomic scale (i.e. fractal). Evolutionary modeling indicated the presence of an optimal cell size, corresponding to a coccus 0.70 µm in diameter, to which most species gravitate. Analyses of 1361 species with sequenced genomes showed that genomic traits contribute to size evolution moderately and synergistically. In light of our results, scaling theory, and empirical evidence, we discuss potential drivers that may expand or shrink cells around the optimum and propose a stability landscape model for prokaryotic cell size.
Emotion Dynamics in Reciprocity: Deciphering the Role of Prosocial Emotions in Social Decision-making
Authors: Kim Jaewon , Bong Su Hyun , Yoon Dayoung , Jeong Bumseok 
Published: December 2023

AbstractTo date, the relevance of prosocial emotions in social decisions based on reciprocity remains poorly understood. Expected and experienced emotions in interoceptive-social dimension, expected offers, and actual acceptance were measured in 476 participants during an ultimatum game consisting of fair, moderate, and unfair offers. We investigated whether participants adjust social decisions according to prediction errors on prosocial emotions and reciprocity. Participants’ acceptance trajectories were explained by prediction errors in dominance, valence, and reward. Participants were categorized into 4 distinct subgroups based on their patterns of reward expectation, acceptance, and emotional experiences before and after the offer. Furthermore, the relationships between prosocial emotions, social decisions, and reciprocity varied across these subgroups. This study’s measurement and analysis of multidimensional trajectories across four affect dimensions reveal that social decisions are influenced by the responder’s perception of partner’s reciprocity, as well as by the subsequent prediction error of basic and prosocial emotion.
The genome of the rayed Mediterranean limpetPatella caerulea(Linnaeus, 1758)
Authors: Halstead-Nussloch Gwyneth , Signorini Silvia Giorgia , Giulio Marco , Crocetta Fabio , Munari Marco , Torre Camilla Della , Weber Alexandra Anh-Thu 
Published: December 2023

AbstractPatella caerulea(Linnaeus, 1758) is a molluscan limpet species of the class Gastropoda. Endemic to the Mediterranean Sea, it is considered to be a keystone species in tidal and subtidal habitats due to its primary role in structuring and regulating the ecological balance of these habitats. It is currently being used as a bioindicator to assess the environmental quality of coastal marine waters and as a model species to understand adaptation to ocean acidification. Here we provide a high-quality reference genome assembly and annotation forPatella caerulea. We used a single specimen collected in the field to generate ∼30 Gb of PacBio HiFi data. The final assembly is 749.8 Mb large and contains 62 contigs, including the mitochondrial genome (14,938 bp). With an N50 of 48.8 Mb and 98% of the assembly contained in the 18 largest contigs, this assembly is near chromosome-scale. BUSCO scores were high (Mollusca: 87.8% complete; Metazoa: 97.2% complete) and similar to metrics observed for other chromosome-levelPatellagenomes, highlighting a possible bias in the Mollusca database for Patellids. We generated transcriptomic Illumina data from a second individual collected at the same locality, and used it together with protein evidence to annotate the genome. 23,938 protein coding gene models were found. By comparing this annotation with other publishedPatellaannotations, we found that the distribution and median values of exon and gene lengths was comparable to otherPatellaspecies despite different annotation approaches. The present high-qualityPatella caeruleareference genome is an important resource for future ecological and evolutionary studies.SignificanceReference genomes are essential resources for biodiversity conservation and management.Patella caerulea(Linnaeus, 1758) is a gastropod species occurring in the Mediterranean Sea that is currently used as a model to understand the impact of pollution and ocean acidification on marine biodiversity. Here we present a high-quality reference genome ofP. caerulea, that almost reaches chromosome-level contiguity. We further provide a high-quality genome annotation supported by transcriptomic evidence. This reference genome will be of interest for researchers working on the ecology and evolution of marine biodiversity. All data is available on the public database NCBI for future use by researchers.
HLA-EpiCheck : A B-cell epitope prediction tool for HLA proteins using molecular dynamics simulation data
Authors: Amaya-Ramirez Diego , Devriese Magali , Lhotte Romain , Usureau Cedric , Smail-Tabbone Malika , Taupin Jean-Luc , Devignes Marie-Dominique 
Published: December 2023

1AbstractThe Human Leukocyte Antigen (HLA) system is the main cause of organ transplant loss through the recognition of HLA proteins by Donor-Specific Antibodies (DSA). Therefore, the identification of potentially immunogenic epitopes is a key task to refine organ allocation and then to improve the survival of transplanted organs. Here, we present HLA-EpiCheck, a machine learning predictor for B-cell epitopes on HLA proteins that leverages an unprecedented dataset of high-quality molecular dynamics simulations of 207 HLA proteins. Candidate epitopes are represented as surface patches centered on solvent-accessible residues and described by a set of 18 descriptors. The descriptors include both static and dynamic properties, such as hydrophobicity, electrostatic charges, relative solvent-accessible surface area and side-chain flexibility. The HLA-EpiCheck was trained using an Extra Trees ensemble learning method and was compared to DiscoTope-3.0, a state-of-the-art B-cell epitope predictor. HLA-EpiCheck largely outperformed DiscoTope-3.0 in the task of predicting HLA epitopes. HLA-EpiCheck was also used to assess the epitope status of a subset of non-confirmed eplets. The predictions were compared to experimental data and a notable consistency was found. These results suggest that HLA-EpiCheck could be used to better define HLA matching between donor and recipient to reducede novoDSA formation and graft rejection.
Nanobodies as novel tools to monitor the mitochondrial fission factor Drp1
Authors: Froehlich Theresa , Jenner Andreas , Cavarischia-Rega Claudia , Fagbadebo Funmilayo O. , Lurz Yannic , Frecot Desiree I. , Kaiser Philipp D. , Nueske Stefan , Scholz Armin , Schäffer Erik , Garcia-Saez Ana J. , Macek Boris , Rothbauer Ulrich 
Published: December 2023

AbstractIn cells, mitochondria undergo constant fusion and fission. An essential factor for fission is the mammalian dynamin-related protein 1 (Drp1). Dysregulation of Drp1 has been linked to neurodegenerative diseases including Parkinson’s as well as cardiovascular diseases and cancer. Here, we developed nanobodies (Nbs) for proteomics, advanced microscopy and live cell imaging of Drp1. To specifically enrich endogenous Drp1 with interacting proteins for proteomics, we functionalized high-affinity Nbs as capture matrices. Furthermore, we detected Drp1 by bivalent Nbs combined with site-directed fluorophore labelling in super-resolution STORM microscopy. For real-time imaging of Drp1, we intracellularly expressed fluorescently labelled Nbs, so-called chromobodies (Cbs). To improve the signal-to-noise ratio, we further converted Cbs into a “turnover-accelerated” format. With these imaging probes, we visualized the dynamics of endogenous Drp1 upon compound-induced mitochondrial fission in living cells. Considering the wide range of research applications, the presented Nb toolset will open up new possibilities for advanced functional studies of Drp1 in disease-relevant models.
Identification of methylation markers for age and Bovine Respiratory Disease in dairy cattle
Authors: Attree E. , Griffiths B. , Panchal K. , Xia D. , Werling D. , Banos G. , Oikonomou G. , Psifidi A. 
Published: December 2023

AbstractMethylation profiles of animals is known to differ by age and disease status. Bovine respiratory disease (BRD), a complex infectious disease, primarily affects calves and has significant impact on animal welfare and the cattle industry, predominantly from production losses. BRD susceptibility is multifactorial, influenced by both environmental and genetic factors. We investigated the epigenetic profile of BRD susceptibility in calves and age-related methylation differences between healthy calves and adult dairy cows using Reduced Representation Bisulfite Sequencing (RRBS).We identified 3,452 genes within differentially methylated regions between calves and adults. Functional analysis revealed enrichment of developmental pathways including cell fate commitment and tissue morphogenesis. Between healthy and BRD affected calves, 964 genes were identified within differentially methylated regions. Immune and vasculature regulatory pathways were enriched and key candidates in BRD susceptibility involved in complement cascade regulation, vasoconstriction and respiratory cilia structure and function were identified.
Unlocking Mitochondrial Dysfunction-Associated Senescence (MiDAS) with NAD+– a Boolean Model of Mitochondrial Dynamics and Cell Cycle Control
Authors: Sizek Herbert , Deritei Dávid , Fleig Katherine , Harris Marlayna , Regan Peter L. , Glass Kimberly , Regan Erzsébet Ravasz 
Published: December 2023

AbstractThe steady accumulation of senescent cells with aging creates tissue environments that aid cancer evolution. Aging cell states are highly heterogeneous. ‘Deep senescent’ cells rely on healthy mitochondria to fuel a strong proinflammatory secretome, including cytokines, growth and transforming signals. Yet, the physiological triggers of senescence such as the reactive oxygen species (ROS) can also trigger mitochondrial dysfunction, and sufficient energy deficit to alter their secretome and cause chronic oxidative stress – a state termed Mitochondrial Dysfunction-Associated Senescence (MiDAS). Here, we offer a mechanistic hypothesis for the molecular processes leading to MiDAS, along with testable predictions. To do this we have built a Boolean regulatory network model that qualitatively captures key aspects of mitochondrial dynamics during cell cycle progression (hyper-fusion at the G1/S boundary, fission in mitosis), apoptosis (fission and dysfunction) and glucose starvation (reversible hyper-fusion), as well as MiDAS in response toSIRT3knockdown or oxidative stress. Our model reaffirms the protective role of NAD+and external pyruvate. We offer testable predictions about the growth factor- and glucose-dependence of MiDAS and its reversibility at different stages of reactive oxygen species (ROS)-induced senescence. Our model provides mechanistic insights into the distinct stages of DNA-damage induced senescence, the relationship between senescence and epithelial-to-mesenchymal transition in cancer and offers a foundation for building multiscale models of tissue aging.HighlightsBoolean regulatory network model reproducesmitochondrial dynamicsduring cell cycle progression, apoptosis, and glucose starvation.Model offers a mechanistic explanation for the positive feedback loop that locks inMitochondrial Dysfunction-Associated Senescence(MiDAS), involving autophagy-resistant, hyperfused, dysfunctional mitochondria.Model reproducesROS-mediated mitochondrial dysfunctionand suggests that MiDAS is part of the early phase of damage-induced senescence.Modelpredictsthat cancer-driving mutations that bypass the G1/S checkpoint generally increase the incidence of MiDAS, except for p53 loss.
eCV: Enhanced coefficient of variation and IDR extensions for reproducibility assessment of high-throughput experiments with multiple replicates
Authors: Gonzalez-Reymundez Agustin , Shen Kylie , Doyle Wayne , Peng Sichong , Hutt Kasey , Bruns Stephanie 
Published: December 2023

ABSTRACTMotivationReproducibility assessment is essential in extracting reliable scientific insights from highthroughput experiments. Inconsistency between technical replicates poses a challenge, particularly clear in next generation sequencing technologies based on immunoprecipitations, where the assessment of reproducibility in peak identification is a critical analytical step. While the Irreproducibility Discovery Rate (IDR) method has been instrumental in assessing reproducibility, its standard implementation is constrained to handling only two replicates. In the current era of steadily growing sample sizes, eased by multiplexing and reduced sequencing costs, highly performing methods that handle any number of replicates are desirable.ResultsWe introduce three novel methods for reproducibility assessment in high-throughput data that handle an arbitrary number of replicates. The first, general IDR (gIDR), extends the standard IDR by adapting its Expectation-Maximization (EM) algorithm to handle distributions of any dimensions dictated by the number of replicates. The second, meta-IDR (mIDR), employs a meta-analysis approach, calculating local IDR scores for all pairs of replicates and combining them using standard probability rules. The third method introduces an “enhanced” Coefficient of Variation (eCV), ranking features based on intensity and variability, using a parametric bootstrap approach to obtain an index analogous to local IDR. Comparative analysis with traditional IDR in simulated and experimental data reveals the heightened performance of the proposed multivariate alternatives under varying scenarios, thereby addressing the critical challenge of reproducibility assessment in contemporary high-throughput experiments.Availability and implementationThe described methods are implemented as an R package:https://github.com/eclipsebio/eCVContactinfo@eclipsebio.com