bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hookworm genes encoding intestinal excreted-secreted proteins are transcriptionally upregulated in response to the host’s immune system
Authors: Schwarz Erich M. , Noon Jason B. , Chicca Jeffrey D. , Garceau Carli , Li Hanchen , Antoshechkin Igor , Ilík Vladislav , Pafčo Barbora , Weeks Amy M. , Homan E. Jane , Ostroff Gary R. , Aroian Raffi V. 
Published: February 2025

AbstractHookworms are intestinal parasitic nematodes that chronically infect ∼500 million people, with reinfection common even after clearance by drugs. How infecting hookworms successfully overcome host protective mechanisms is unclear, but it may involve hookworm proteins that digest host tissues, or counteract the host’s immune system, or both. To find such proteins in the zoonotic hookwormAncylostoma ceylanicum, we identified hookworm genes encoding excreted-secreted (ES) proteins, hookworm genes preferentially expressed in the hookworm intestine, and hookworm genes whose transcription is stimulated by the host immune system. We collected ES proteins from adult hookworms harvested from hamsters; mass spectrometry identified 565A. ceylanicumgenes encoding ES proteins. We also used RNA-seq to identifyA. ceylanicumgenes expressed both in young adults (12 days post-infection) and in intestinal and non-intestinal tissues dissected from mature adults (19 days post-infection), with hamster hosts that either had normal immune systems or were immunosuppressed by dexamethasone. In adultA. ceylanicum, we observed 1,670 and 1,196 genes with intestine- and non-intestine-biased expression, respectively. Comparing hookworm gene activity in normal versus immunosuppressed hosts, we observed almost no changes of gene activity in 12-day young adults or non-intestinal 19-day adult tissues. However, in intestinal 19-day adult tissues, we observed 1,951 positively immunoregulated genes (upregulated at least two-fold in normal hosts versus immunosuppressed hosts), and 137 genes that were negatively immunoregulated. Thus, immunoregulation was observed primarily in mature adult hookworm intestine directly exposed to host blood; it may include hookworm genes activated in response to the host immune system in order to neutralize the host immune system. We observed 153 ES genes showing positive immunoregulation in 19-day adult intestine; of these genes, 69 had ES gene homologs in the closely related hookwormAncylostoma caninum, 24 in the human hookwormNecator americanus, and 24 in the more distantly related strongylid parasiteHaemonchus contortus. Such a mixture of rapidly evolving and conserved genes could comprise virulence factors enabling infection, provide new targets for drugs or vaccines against hookworm, and aid in developing therapies for autoimmune diseases.
Host serine proteases and antiviral innate immunity as potential therapeutic targets in influenza A virus infection-induced COPD exacerbations
Authors: Bai Haiqing , Rodas Melissa , Si Longlong , Man Yuncheng , Ji Jie , Plebani Roberto , Mercer Johnathan D. , Powers Rani K. , Belgur Chaitra , Jiang Amanda , Hall Sean R. R. , Prantil-Baun Rachelle , Ingber Donald E. 
Published: February 2025

ABSTRACTLung manifestations of chronic obstructive pulmonary disease (COPD) are often exacerbated by influenza A virus infections; however, the underlying mechanisms remain largely unknown and hence, therapeutic options are limited. Using a physiologically relevant human lung airway-on-a-chip (Airway Chip) microfluidic culture model lined with human airway epithelium from COPD or healthy donors interfaced with pulmonary microvascular endothelium, we observed that Airway Chips lined with COPD epithelium exhibit an increased sensitivity to influenza virus infection, as is observed clinically in COPD patients. Differentiated COPD airway epithelial cells display increased inflammatory cytokine production, barrier function loss, and mucus accumulation upon virus infection. Transcriptomic analysis revealed gene expression profiles characterized by upregulation of serine proteases that may facilitate viral entry and downregulation of interferon-related genes associated with antiviral immune responses. Importantly, treatment of influenza virus-infected COPD epithelium with a protease inhibitor, nafamostat, ameliorated the disease phenotype as evidenced by dampened viral replication, reduced mucus accumulation, and improved tissue barrier integrity. These findings suggest that targeting host serine proteases may represent a promising therapeutic avenue against influenza-afflicted COPD exacerbations.
ImputeBench: Benchmarking Single Imputation Methods
Authors: Richter Robin , Tavares Juliana F. , Miloschewski Anne , Breteler Monique M. B. , Mukherjee Sach 
Published: February 2025

AbstractBiomedical data often contain missing values and in many applications missing value imputation (MVI) is an important part of the data analysis work-flow. However, the performance of MVI methods depends on details of the joint distribution of data and missingness patterns that are typically unknown in practice, making ana priorichoice of MVI method challenging. Furthermore, technical assumptions underlying MVI methods can be hard to directly verify in practice. Motivated by these issues, in this paper, we propose an approach for the context-specific selection of MVI methods. Due to the fact that different methods may work well in different cases we argue for a move away from a “one size fits all” view and put forward in this paper a standardized, empirical approach in which MVI methods are benchmarked in the specific context of a problem of interest. We connect our work to the large body of MVI research, along the way refining definitions of missing at random and missing not at random and providing a detailed review of existing work on benchmarking. Our approach can be tailored to reflect specific assumptions on missingness patterns, allowing for application in diverse applied problems. Furthermore, in addition to using real data, we study benchmarking via data simulation spanning a broad range of properties, such as latent factors, non-linearity and multi-modality, with interpretable simulation parameters that are amenable to user specification. The approaches we propose can be used to (i) select an MVI method for a given data set or (ii) benchmark a novel MVI method across a range of regimes. Alongside the general protocol, we provide a specific, reproducible implementation (in the R-packageImputeBench, available under github.com/richterrob/ImputeBench) that gives users a ready-to-use tool for MVI selection and assessment. We illustrate the use ofImputeBenchto study the behaviour of a range of existing imputation methods (k-nn, soft impute, missForest, MICE) in the context of real data from an ongoing large-scale population-level study.
Accidental and Regulated Cell Death in Yeast Colony Biofilms
Authors: Netherwood Daniel J. , Tam Alexander K. Y. , Gourlay Campbell W. , Knežević Tea , Gardner Jennifer M. , Jiranek Vladimir , Binder Benjamin J. , Green J. Edward F. 
Published: February 2025

AbstractThe yeast speciesSaccharomyces cerevisiaeis one of the most intensively studied organisms on the planet due to being an excellent eukaryotic model organism in molecular and cell biology. In this work, we investigate the growth and morphology of yeast colony biofilms, where proliferating yeast cells reside within a self-produced extracellular matrix. This research area has garnered significant scientific interest due to its applicability in the biological and biomedical sectors. A central feature of yeast colony biofilm expansion is cellular demise, which is onset by one of two independent mechanisms: either accidental cell death (ACD) or regulated cell death (RCD). In this article, we generalise a recently developed continuum model for the nutrient-limited growth of a yeast colony biofilm to include the effects of ACD and RCD. This new model involves a system of four coupled nonlinear reaction–diffusion equations for the yeast-cell density, the nutrient concentration, and two species of dead cells. Numerical solutions of the spatially one and two-dimensional governing equations reveal the impact that ACD and RCD have on expansion speed, morphology and cell distribution within the colony biofilm. Our results show good qualitative agreement with our own experiments.
Genetic liability to physical health conditions influences comorbidities in individuals with severe mental illness
Authors: Kappel Djenifer B. , Smart Sophie E. , Owen Michael J. , O’Donovan Michael C. , Pardiñas Antonio F. , Walters James T. R. 
Published: February 2025

AbstractBackgroundIndividuals with severe mental illness (SMI), including schizophrenia and bipolar disorder, have elevated rates of physical health conditions, leading to increased morbidity and mortality. While environmental factors such as adverse effects of medication and lifestyle changes contribute to this burden, the role of genetic liability to physical health conditions remains underexplored. We assessed whether genetic risk for physical health conditions influences comorbidities in individuals with SMI and compared these effects to those observed in the general population.MethodsWe utilized data from two SMI cohorts from the UK: CardiffCOGS (n=721) and the National Centre for Mental Health (NCMH; n=1011). We tested whether polygenic risk scores (PRS) for six physical health conditions (high cholesterol, type 2 diabetes, hypertension, asthma, heart disease, and rheumatoid arthritis) were associated with having the corresponding condition in those with SMI. Models were adjusted for demographic and clinical covariates. Associations between psychiatric PRSs (schizophrenia, bipolar disorder, major depressive disorder, and ADHD) and presence of physical comorbidities were also evaluated.ResultsPRS for physical health conditions were associated with the presence of the corresponding conditions in SMI cohorts, with effect sizes comparable to those reported in the general population. Adjustments for environmental factors had minimal impact on these associations. Psychiatric PRS showed weaker and less consistent associations with physical comorbidities.DiscussionThis study provides robust evidence supporting the role of genetic risk in the development of common physical health conditions in individuals with SMI. Our findings indicate that the occurrence of physical health comorbidities was much more strongly associated with genetic liability to physical health conditions, than with psychiatric genetic liability. The genetic risk for physical health conditions contributes additively to environmental and clinical factors in driving comorbidities among individuals with SMI. These findings indicate there would be value in incorporating genetic risk information into predictive algorithms for physical health comorbidities in those with SMI, and that PRS should be included in research studies developing and validating such algorithms.
High agreement between lean mass assessed by dual-energy X-ray absorptiometry and bioelectrical impedance analysis across the adult lifespan
Authors: Kristensen T. , Kamper R.S. , Haddock B. , Nygaard H. , Nørst T. , Hovind P. , Suetta C. 
Published: February 2025

AbstractBackgroundBioelectrical impedance analysis (BIA) is considered a portable alternative to Dual-energy X-ray absorptiometry (DXA) when assessing deficient muscle mass, a major concern for older adults associated with increased risks of falls, fractures, disability, and mortality. However, several studies have demonstrated that BIA overestimates muscle mass in the older population and that estimates of muscle mass may depend on the BIA and DXA devices utilized. This study aims to describe the concordance between lean mass assessed by DXA and BIA across the adult population.MethodsThis study is based on data from the Copenhagen Sarcopenia Study, a cross-sectional study of 1127 healthy participants aged 22-92 years with complete measurements of lean mass from both DXA (iDXA, GE Lunar) and BIA (Inbody 770). Relative appendicular lean mass (ALM) was calculated by normalizing ALM to height2to account for allometric differences in body size.ResultsFor the total cohort, linear regression models showed a strong correlation between BIA and DXA for ALM (R2= 0.92) and relative ALM (R2= 0.83). A small, yet consistent, bias of relative ALM values was observed where BIA measures were on average 0.25±0.50 kg/m2higher compared to measurements by DXA. The bias was consistent across age groups with a mean difference in relative ALM of 0.24±0.50 kg/m2, and 0.26±0.49 kg/m2for younger participants, and older participants, respectively.ConclusionBIA is a reliable alternative to DXA for assessing muscle mass, in both younger, and older adults. The findings indicate that with simple correction models for ALM and relative ALM, BIA can be a practical and accessible tool in clinical settings where DXA is unavailable. These models make BIA particularly useful for diagnosing sarcopenia, allowing for early detection and management regardless of age.Key messagesBioelectrical impedance analysis (BIA) is considered a portable alternative to Dual-energy X-ray absorptiometry (DXA) when assessing deficient muscle mass, a major concern for older adults and is associated with increased risks of falls, fractures, disability, and mortality. However, several studies have demonstrated that BIA overestimates muscle mass in the older population and estimates of muscle mass may depend on the BIA and DXA devices utilized. By applying the models of regression equations developed in this study, clinicians can improve the accuracy of BIA measurements, making BIA a practical alternative to DXA in clinical settings where DXA is not accessible. These findings are especially relevant for the early detection and management of sarcopenia in older adults, allowing for timely interventions to preserve muscle function and reduce the risk of adverse health outcomes.
Evolution of Pandemic Cholera at its Global Source
Authors: Barton Amber , Afrad Mokibul Hassan , Taylor-Brown Alyce , Singh Nisha , Thakur Chetan , Islam Taufiqul , Rahman Sadia Isfat Ara , Akhtar Marjahan , Begum Yasmin Ara , Bhuiyan Taufiqur Rahman , Khan Ashraful Islam , Taneja Neelam , Thomson Nicholas R. , Qadri Firdausi 
Published: February 2025

AbstractThe seventh pandemic of cholera, caused by the 7thPandemic El Tor Lineage (7PET)Vibrio cholerae, was previously shown to have emanated in three global waves from the Bay of Bengal, bordering Bangladesh and India. However, the respective roles of the Ganges delta and basin regions in seeding these global pandemic waves were not known. We find that while there are transmission events between Bangladesh and India,V. choleraewithin the two countries has largely evolved separately over the past 20 years, contained by national borders rather than following hydrological features such as the Ganges delta and basin. Evolution within Bangladesh was distinct from that seen in India, involving rapid gain and loss of genes and mobile genetic elements, particularly those involved in phage defence. The loss/gain of these anti-phage elements mirrored loss/gain of anti-defence systems in lytic phage ICP1. Importantly, the loss of these systems was associated with increased risk of severe disease and transmission outside of Bangladesh. Here we show that the Ganges basin, falling across Bangladesh and Northern India, rather than the Ganges delta, acts as a global launch pad for pandemic disease. This completely shifts our understanding of Bangladesh as the purported global source of cholera, and the role of phage in controlling spread of lineages within the current seventh pandemic.
Association of Pre-pregnancy Mental Health Disorders with Hypertensive Disorders of Pregnancy
Authors: Ncube Collette N. , Choi Minhyuk , Barnard-Mayers Ruby , Zimmerman Scott C. , Vodovozov Shelli , Glymour M. Maria , Parker Samantha E. 
Published: February 2025

ABSTRACTBackgroundHypertensive disorders of pregnancy (HDP) affect nearly 10% of pregnancies in the U.S. and are known to increase risk of severe maternal morbidity and later life cardiovascular disease and stroke. Mental health disorders are common among pregnant individuals and have been linked to high blood pressure and adverse pregnancy outcomes. However, there is limited research investigating the association between history of mental health conditions and HDP.ObjectivesWe aimed to assess the association of pre-pregnancy mental health disorders with HDP.MethodsWe used the NIHAll of UsResearch Program, which began enrollment in May 2018 and linked participants’ electronic health records (EHRs). First pregnancies with conception dates between October 2015 and September 2021 were identified from EHRs. Risk of HDP was examined among pregnancies of at least 20 weeks of gestation. We assessed the association between a pre-pregnancy mental health diagnosis and the risk of HDP using log-binomial regression models, estimating risk ratios (RR) and 95% confidence intervals, adjusted for racial and ethnic group and maternal age. We examined early pregnancy loss as a secondary outcome among all identified pregnancies. Results were stratified by the timing of pregnancy start relative to enrollment in theAll of Uscohort.ResultsAmong 11,756 pregnancies that occurred prior to study enrollment, we observed a 20% increased risk of HDP associated with pre-pregnancy anxiety and depression (RR 1.20, 95% CI 1.05,1.36) and a 50% increased risk of early pregnancy loss associated with pre-pregnancy anxiety and depression (RR 1.49, 95% CI 1.36,1.64). Among 2,358 pregnancies occurring after enrollment, findings for HDP were generally similar, but associations with early pregnancy loss were attenuated, with imprecise estimates.ConclusionsPrior mental health disorder diagnoses were associated with a modest increase in risk of HDP and early pregnancy loss.SYNOPSISStudy questionDo pre-pregnancy mental health disorders increase the risk of pregnancy loss or hypertensive disorders of pregnancy (HDP)?What’s already knownFew studies have evaluated pre-pregnancy mental health disorders and pregnancy loss. Findings from prior studies of the association between mental health disorders and HDP are inconsistent, with mental health status often ascertained in early pregnancy thus masking the temporal relationship with HDP.What this study addsIn this study, which leverages theAll of UsResearch Program cohort, we report an increased risk of HDP associated with pre-pregnancy mental health disorders. Additionally, we found an increased risk of early pregnancy loss associated with pre-pregnancy mental health disorders, suggesting our results may underestimate the risk associated with HDP having conditioned on later gestations.
A public resource of 15 genomically characterised representative strains ofShigella sonnei
Authors: Miles Sydney L. , Hawkey Jane , Vezina Ben , Torraca Vincenzo , Jenkins Claire , Weill François-Xavier , Baker Stephen , Baker Kate S. , Mostowy Serge , Holt Kathryn E. 
Published: February 2025

AbstractShigella sonneiis rapidly emerging as the dominant agent of shigellosis, an enteric disease responsible for a significant burden of morbidity and mortality worldwide. Whole-genome sequencing ofS. sonneiisolated over the last three decades has revealed phylogenomic diversity within the population and the emergence of multiple lineages associated with distinct epidemiological patterns such as resistance to critical antimicrobials and/or transmission within different groups. However most experimental work onS. sonneibiology and pathogenicity has focused on a single laboratory strain (53G), which is phylogenetically distant from currently circulating strains. Here we introduce a set of 15 phylogenetically diverse and epidemiologically relevantS. sonneiisolates made available through publicly accessible culture collections as a resource for laboratory science. We present their complete whole-genome sequences, including the pINV invasion plasmid (missing from a large proportion of public genome data due to loss during laboratory culture). Finally, the characterisation and comparison of these complete genome sequences highlight evidence for ongoing adaptive evolution inS. sonnei, featuring the accumulation of insertion sequences, gene pseudogenisation and structural variation.Significance as a BioResource to the communityGenomic analysis ofShigellahas historically been challenging due to presence of hundreds of repetitive sequence elements (which can cause fragmented assemblies) and loss of the pINV invasion plasmid (essential to virulence) during laboratory culture. Furthermore, most experimental work onS. sonneipathogenicity uses a lab strain that is phylogenetically distant from circulating isolates. To supportS. sonneiexperimental andin silicoresearch and increase its relevance to current clinical problems, we report here the complete, high-quality genome sequences of 15S. sonneiisolates, each selected to represent distinct sub-clades of epidemiological interest. We also make the corresponding strains publicly available in national reference culture collections.Data summaryAll sequencing reads and complete assemblies have been deposited into the National Center for Biotechnology Information (NCBI) database (accessions to be determined). Genome assemblies and Bakta annotations used in the analysis can be found in Figshare (https://doi.org/10.6084/m9.figshare.28302986) together with Mauve multiple-sequence alignments for the chromosome and pINV plasmid sequences, and genome-scale metabolic models produced for each strain.Pure cultures of all strains were deposited in the publicly accessible National Collection of Type Cultures (NCTC, UK) or the “Collection de l’Institut Pasteur” (CIP, France) (accessions to be determined).
CDK9 interacts with a RanGTP-NEMP1-Importin β complex to regulate erythroid enucleation
Authors: Newton Lucas M. , Lim Krystle Y. B. , Abeid Donia Y. , Wölwer Christina B. , Johnson Chad J. , Russell Sarah M. , Hawkins Edwin D. , Humbert Patrick O. 
Published: February 2025

AbstractErythroid enucleation is the final stage of erythroid terminal differentiation and involves the separation of an orthochromatic erythroblast into two daughter cells; a pyrenocyte containing the extruded nucleus, and the other a reticulocyte that will become a red blood cell. Our previous work identified CDK9 as a regulator of erythroid enucleation that appears to act independently of its known role in regulating RNA polymerase II transcription, suggesting the potential for a new CDK9 role. Using a co-immunoprecipitation and mass spectrometry approach, we have identified the interactome of CDK9 in differentiating erythroblasts. We show that CDK9 interacts with a RanGTP-NEMP1-Importin β complex during erythroid terminal differentiation, and inhibition of importin β in erythroblasts blocks erythroid enucleation. Using imaging analysis and functional assays of enucleating erythroblasts, we show that CDK9 and importin β co-locate at a critical site of activity opposite to the nucleus before nuclear extrusion and we describe a novel finding that physically links CDK9 and importin β activity prior to CaM/Ca2+signalling and subsequent F-actin activity to achieve enucleation.Key PointsImportin β physically interacts with CDK9 in erythroid cells and is a novel regulator of erythroid enucleationFunctional assays show that CDK9 and importin β act prior to calcium-dependent actin-mediated nuclear extrusion