bluuebunny/crossref_metadata_2025_split huggingface dataset:
The complete genome sequence of five historical Escherichia coli sequence type (ST)1193 strains reveals insights into an emerging pathogen
Authors: White Rhys T. , Ashcroft Melinda A. , Bauer Michelle J. , Bell Jan , Butkiewicz Dominika , Álvarez-Fraga Laura , Gibson Justine S. , Kidsley Amanda K. , Mollinger Joanne L. , Peters Kate M. , Phan Minh-Duy , Roberts Leah W. , Rogers Benjamin A. , Schembri Mark A. , Trott Darren J. , Turnidge John , Forde Brian M. , Beatson Scott A. 
Published: August 2024

Fluoroquinolone-resistant Escherichia coli sequence type (ST)1193 is a profound, emerging lineage associated with systemic, urinary tract, and neonatal infections. Humans, companion animals, and the environment are reservoirs for ST1193, which has been disseminated globally. Following its detection in 2007, ST1193 has been identified repeatedly amongst fluoroquinolone-resistant clones in Australia. However, despite the growing importance of ST1193, only three complete genomes are published in the literature, none of which are from Australia. Here we expand on the available ST1193 resources with the complete genomes of five ST1193 strains sequenced using Oxford Nanopore Technologies and Illumina. Using in silico genotyping, we found that all strains were multi-drug resistant, including resistances to fluoroquinolones and cephalosporins. In vitro antibiotic susceptibility testing mostly correlated with individual genotypes. The exception was MS8320, which had additional in vitro resistance to piperacillin/tazobactam, ampicillin/sulbactam, cefazolin and doripenem (carbapenem). Further investigation identified seven additional copies of an IS26 transposable unit carrying a blaTEM-1B beta-lactamase gene, suggesting this tandem amplification is associated with extended resistance phenotypes. Uropathogenicity factors, including three separate siderophore-encoding loci, were conserved in chromosomal and plasmid regions. Using all complete genomes, we further elucidated the recombination events surrounding the previously described K5/K1 capsular loci switch. Phenotypic confirmation of differing capsules in Australian ST1193 strains, coupled with genetic analysis revealing insertions downstream of the capsular locus, underscored the genetic distinctions between K5 and K1 capsule encoding strains. This study provides five new reference ST1193 genomes from Australia. These include the earliest complete K5-capsule ST1193 genomes on record (collected 2007), alongside our reference genome (MS10858); a clinical isolate obtained early during the ST1193 expansion and representative of the predominant K1-associated clade. These findings lay the foundations for further genomic and molecular analyses that may help understand the underlying reasons for the rapid global expansion of ST1193.
Antenatal corticosteroids for pregnant women at risk of preterm labor in low- and middle-income countries: utilization and facility readiness
Authors: Yang Wen-Chien , Arsenault Catherine , Fan Victoria Y. , Leslie Hannah H. , Farooq Fouzia , Pembe Andrea B. , Getachew Theodros , Smith Emily R. 
Published: August 2024

ABSTRACTBackgroundAntenatal corticosteroids (ACS) use among pregnant women with a high likelihood of preterm labor improves newborn survival. ACS adoption in low– and middle-income countries (LMICs) remains limited. Giving ACS in inadequately equipped settings could be harmful to mothers and newborns. Thus, health facilities have to demontrate readiness to administer ACS. However, the degree to which health systems are ready is unknown.ObjectiveWe assessed facility readiness to administer ACS based on the 2022 WHO recommendations on ACS use and ACS utilization.MethodsThe study used Service Provision Assessment surveys administered between 2013 and 2022 in nine LMICs. The primary outcome was whether facilities had ever provided ACS. We also assessed injectable corticosteroid (dexamethasone or betamethasone) availability and facility readiness to administer ACS. We used a total of 35 indicators, grouped into four readiness categories based on the WHO recommendations, to measure facility readiness.FindingsAcross eight countries with comparable sampling strategies, only 10.7% (median, range 6.7% – 35.2%) of facilities had ever provided ACS; one-fourth (median 25.3%, range 4.6% – 61.5%) of facilities had injectable corticosteroids available at the time of the survey; overall readiness indices were low ranging from 8.1% for Bangladesh to 32.9% for Senegal. Across four readiness categories, the readiness index was the lowest for criterion 1 (ability to assess gestational age accurately and identify a high likelihood of preterm birth) (7.3%), followed by criterion 2 (ability to identify maternal infections) (24.8%), criterion 4 (ability to provide adequate preterm care) (31.3%), and criterion 3 (ability to provide adequate childbirth care) (32.9%).ConclusionWe proposed a strategy for measuring facility readiness to implement one of the most effective interventions to improve neonatal survival. Countries should operationalize readiness measurement, improve facilities readiness to deliver this life-saving intervention, and encourage ACS uptake by targeting facilities that are well-equipped.
Buruli ulcer Community Health Education and Medical Screening (BU-CHEMS) in Ga South District, Ghana
Authors: Narh Charles A. , Tetteh Edwin ,   NSPA-NMIMR
Published: August 2024

PROJECT SUMMARYBackgroundThe National Service Personnel Association of the Noguchi Memorial Institute for Medical Research (NSPA-NMIMR) carries out an annual community outreach project comprising health education and medical screening for some of the diseases that the institute works on. Therefore, the NSPA 2009/2010 group (40 personnel) conducted Buruli ulcer community health education and medical screening (BU-CHEMS) in the Ga South District of Ghana in July 2010.MethodBU is caused bymycobacterium ulcerans, and starts as a painless nodule, which can progress to ulcer, particularly on the upper and lower extremities. BU is often associated with witchcraft in some Ghanaian communities, and as a result, some patients reluctantly seek medical treatment. Therefore, prior to the screening program, the NSPA and medical staff from the Obom Health Centre showed video documentaries on BU as a way of educating and dispelling myths about the disease. This was followed by screening for nodules and ulcers among 2,500 people, mostly children in primary schools, residing in four endemic communities in the Ga South District. Other medical screening activities included blood group/pressure tests, Body Mass Index (BMI) and body temperature checks.Results and conclusionSuspected cases of BU (N=33) ranging from nodules, plagues, oedema and ulcers of the disease on various parts of the body including the lower and upper extremities were identified, and samples were sent to NMIMR for PCR confirmation. All the PCR-positive cases (78%), including children (<15 years, 88%) were referred to the Obom Health Center for clinical treatment. The BU-CHEMS organized by NSPA 2009/2010 group (with sponsorship from corporate organizations) contributed to NMIMR mandate: improving the health and wellbeing of Ghanaians and mankind through focused and relevant quality biomedical research, human resource development and support of national public health activities.
Association of quantified cardiovascular health with all-cause mortality in prediabetic patients
Authors: Chen Aomiao , He Qiuyu , Wu Yichuan , Chen Jiaqi , Ma Xiaoqin , Hu Lingyuan , Wang Geningyue , Wang Zhuotong , Zheng Zongji , Jia Yijie 
Published: August 2024

AbstractAim:We aimed to explore the association between all-cause mortality and cardiovascular health (CVH) lifestyle interventions (as accurately quantified by Life’s essential 8) in prediabetic patients and to observe the dose-response relationship of the potential association.Methods and Participants:The retrospective study included 5344 participants with prediabetes (age: 52.9 ±15.8 years; (51.6% of men)). The Life’s essential 8 (LE8) score includes four health indicators and four health behaviors. We calculated Cox proportional hazard ratios (HRS) for all-cause mortality in subgroups of high CVH (≥80), low CVH (≤50), and moderate CVH (50-79) based on the CVH quantification score of LE8, and explored the dose-response relationship of potential associations. We also performed separate analyses of the associations of all-cause mortality with each LE8 components and CVH health behaviors and indicators.Results:In the median follow-up period of 8.33 years, 658 deaths occurred. Compared with participants with high CVH, the covariate-adjusted HR(95%CI) for participants with moderate and low CVH were 2.55(1.23-5.31) and 3.92 (1.70-9.02), respectively. There was a dose-response relationship between the improvement of CVH status and the reduction of all-cause mortality (P-overall < 0.0001, P-nonliner = 0.7989). The improvement of CVH health behaviors has a more significant protective effect on patients with prediabetes than CVH health indicators.Conclusion:High CVH status, quantified by LE8, has a significant effect on preventing mortality outcomes in prediabetic adults in the U.S.
Public health impact of current and proposed age-expanded perennial malaria chemoprevention: a modelling study
Authors: Sen Swapnoleena , Braunack-Mayer Lydia , Kelly Sherrie L , Masserey Thiery , Malinga Josephine , Moehrle Joerg J , Penny Melissa A 
Published: August 2024

AbstractIn 2022, the World Health Organization extended their guidelines for perennial malaria chemoprevention (PMC) from infants to children up to 24 months old. However, evidence for PMC’s public health impact is primarily limited to children under 15 months. Further research is needed to assess the public health impact and cost-effectiveness of PMC, and the added benefit of further age-expansion. We integrated an individual-based model of malaria with pharmacological models of drug action to address these questions for PMC and a proposed age-expanded schedule (PMC+, for children 03-36 months). Across prevalence settings of 5-70% and different drug sensitivity assumptions, we predicted PMC and PMC+’s median efficacy of 18.6%(12.2-25.0%) and 21.9%(14.3-29.5%) against clinical disease and 9.0%(2.0-16.0%) and 10.8%(3.2-18.4%) against severe malaria, respectively, in children under three years. PMC’s total impact outweighed risk of delayed malaria in children up to age five and remained cost-effective when delivered through the Expanded Program on Immunization.
Widespread male sterility and trioecy in androdioeciousMercurialis annua: an account of its distribution, its genetic basis, and estimates of its morph-specific fitness components
Authors: Nguyen M. T. , Martignier T. , Pannell J. R. 
Published: August 2024

PremiseAngiosperms range from hermaphroditism through gynodioecy and androdioecy to dioecy. ‘Trioecy’, where females and males coexist with hermaphrodites, is rare. Recently, trioecy was documented in hexaploid populations of the wind-pollinated herb Mercurialis annua in Spain.MethodsWe surveyed the frequency of males, hermaphrodites and females inM. annuaacross its distribution in the Iberian Peninsula, tracked sex-ratio variation in several populations over consecutive generations, and assessed evidence for pollen limitation. In a common garden, we estimated male, female and hermaphrodite fitness. We used controlled crosses to infer the genetic basis of male sterility. Finally, we compared predictions of a deterministic model with the distribution of observed sex ratios in the field based on our fitness estimates and the inferred genetics of sex determination.Key resultsTrioecy is widespread in Spanish and Portuguese populations ofM. annua. Males are determined by a dominant (Y-linked) allele, and female expression results from the interaction between cytoplasmic male sterility and multiple nuclear male sterility restorers partially linked to the male determiner. Male pollen production is approximately 12 times while female seed production is less than 1.12 times that of hermaphrodites. The distribution of sex ratios in natural populations conforms with predictions of our deterministic simulations.ConclusionsOur study documents and accounts for a clear case of trioecy in which sex is determined by both maternally and biparentally inherited genes.
IL-27 Stablizes Myc-Mediated Transcription In Memory-Fated, Vaccine-Elicited CD8+ T Cells
Authors: Thompson Scott B. , Harbell Michael , Manalastas John , Ivanova Daria L. , Riemondy Kent A , Lasda Erika , Chen Vincent , Hesselberth Jay R. , Phan Anthony , Christian David , Hunter Christopher A. , Brunetti Tonya , Gapin Laurent , Klarquist Jared , Kedl Ross M. 
Published: August 2024

ABSTRACTProtection from pathogens relies on both humoral (antibody-mediated) and cellular (T cell-mediated) responses. While infections robustly elicit both types of immunity, currently approved vaccine adjuvants largely fail to induce T cell responses on par with that instigated by infections. Our goal was to investigate the transcriptional programming that supports the formation of CD8+T cells elicited by subunit vaccines compared to those elicited by infections. Our data show that vaccine-elicited T cells represent a transcriptionally unique subset of activated T cells with high proliferative capacity and a memory cell fate. This relies on IL-27 signaling, which stabilizes c-Myc and thereby supports the biomass acquisition necessary for clonal expansion. Collectively, our findings reveal that subunit vaccine-elicited T cells uniquely combine aspects of both memory and effector T cell subsets, and selectively utilize IL-27 signaling to sustain the clonal expansion of cells dedicated to a memory fate.One Sentence SummaryIn contrast to infection, subunit vaccines induce a distinct population of CD8+ T cells with memory fate characteristics which maintain their proliferative capacity during the expansion phase through IL-27 receptor signaling.
Bayesianp-curve Mixture Models as a Tool to Dissociate Effect Size and Effect Prevalence
Authors: Veillette John P. , Nusbaum Howard C. 
Published: August 2024

AbstractMuch research in the behavioral sciences aims to characterize the “typical” person. A statistically significant group-averaged effect size is often interpreted as evidence that the typical person shows an effect, but that is only true under certain distributional assumptions for which explicit evidence is rarely presented. Mean effect size varies with bothwithin-participant effect sizeandpopulation prevalence(proportion of population showing effect). Few studies consider how prevalence affects mean effect size estimates and existing estimators of prevalence are, conversely, confounded by uncertainty about effect size. We introduce a widely applicable Bayesian method, thep-curve mixture model, that jointly estimates prevalence and effect size by probabilistically clustering participant-level data based on their likelihood under a null distribution. Our approach, for which we provide a software tool, outperforms existing prevalence estimation methods when effect size is uncertain and is sensitive to differences in prevalence or effect size across groups or conditions.
Deep Learning Reaction Network: a machine learning framework for modeling time resolved data
Authors: Alagna Nicolò , Dúzs Brigitta , Köppl Heinz , Walther Andreas , Gerber Susanne 
Published: August 2024

AbstractModel-based analysis is essential for extracting information about chemical reaction kinetics in full detail from time-resolved data sets. Such analysis combines experimental hypotheses of the process with mathematical models related to the system’s physical mechanisms. This combination can provide a concise description of complex system dynamics and extrapolate kinetic model parameters, such as kinetic pathways, time constants, and species amplitudes. However, the process leading to the final kinetic model requires several intermediate steps in which different assumptions and models are tested, even using different experimental data sets. This approach requires considerable experience in modeling and data comprehension, as poor decisions at any stage of time-resolved data analysis (such as time-resolved spectra and agarose gel electrophoresis) can lead to an incorrect or incomplete kinetic model, resulting in inaccurate model parameters and amplitudes. The Deep Learning Reaction Network (DLRN) can rapidly provide a kinetic reaction network, time constants, and amplitude for the system, with comparable performance and, in part, even better than a classical fitting analysis. Additionally, DLRN works in scenarios in which the initial state is a non-emitting dark state and for multiple timescales. The utility of DLRN is also shown for more than one 2D system, as it performed well for both spectral and time-resolved agarose gel electrophoresis data.
Towards an eco-epidemiological framework for managing freshwater crayfish communities confronted with crayfish plague
Authors: Bozzuto Claudio , Schmidt-Posthaus Heike , Adrian-Kalchhauser Irene , Pisano Simone Roberto Rolando 
Published: August 2024

AbstractWildlife diseases figure prominently among the main causes of biodiversity loss worldwide. Especially fungal and fungus-like pathogens are on the rise, wreaking havoc across the tree of life by threatening species persistence and destabilizing ecosystems. A worrisome example are freshwater crayfish species in Eurasia and Oceania, facing the dual challenge of introduced competitive crayfish species and an introduced water mold (Aphanomyces astaci) causing crayfish plague.A. astacilocally extinguishes susceptible native crayfish populations, while non-native individuals (mostly from North America) remain largely unaffected. Despite its significant impact and its ∼150 years of presence in Europe, studies and disease management recommendations for crayfish plague that are firmly rooted in epidemiological theory are scarce. Here, we present a practical eco-epidemiological framework to understand how multi-species crayfish communities react to crayfish plague introductions. The framework is based on the observation that the dynamics of crayfish communities are mainly determined by life-history characteristics, within- and among-species competition, effects of generalist predators (including fishing), and host-pathogen interactions. From this ecological and epidemiological context, we derive fundamental epidemiological metrics, single-host species and community-level basic reproduction numbers (R0). We investigate how host species densities affect the likelihood of a disease outbreak in a crayfish community, and we demonstrate that a community’sR0value is simply the sum of the community’s single-host speciesR0values, adjusted for competition and predation. We further demonstrate howR0can be used to guide preventative and mitigation actions for crayfish communities. For example, we show howR0expressions – even without a detailed parametrization – can be used to construct regional risk rankings for different crayfish communities, for an effective allocation of resources to local conservation plans. Our eco-epidemiological framework will also be of interest to the management of other aquatic host-pathogen systems with water-borne pathogen transmission as the main route of pathogen spread.
PROSER1 Modulates DNA Demethylation through Dual Mechanisms to Prevent Syndromic Developmental Malformations
Authors: Fleming Anna , Knatko Elena V. , Li Xiang , Zoch Ansgar , Heckhausen Zoe , Stransky Stephanie , Brenes Alejandro J. , Sidoli Simone , Hajkova Petra , O’Carroll Dónal , Rasmussen Kasper D. 
Published: August 2024

ABSTRACTThe link between DNA methylation and neurodevelopmental disorders is well established. However, how DNA methylation is fine-tuned – ensuring precise gene expression and developmental fidelity – remains poorly understood. PROSER1, a known TET2 interactor, was recently linked to a severe neurodevelopmental disorder. Here, we demonstrate that PROSER1 interacts with all TET enzymes and stabilizes chromatin-boundTET-OGT-PROSER1-DBHS (TOPD) complexes, which regulate DNA demethylation and developmental gene expression. Surprisingly, we find that PROSER1 also sequesters TET enzymes, preventing widespread demethylation and transposable element de-repression. Our findings identify PROSER1 as a key factor which both positively and negatively regulates DNA demethylation essential for mammalian neurodevelopment.
SMURF1/2 are novel regulators of WNK1 stability
Authors: Jaykumar Ankita B. , Plumber Sakina , Binns Derk , Wichaidit Chonlarat , Luby-Phelps Katherine , Cobb Melanie H. 
Published: August 2024

AbstractAngiogenesis is essential for remodeling and repairing existing vessels, and this process requires signaling pathways including those controlled by transforming growth factor beta (TGF-β). We have previously reported crosstalk between TGF-β and the protein kinase With No lysine (K) 1 (WNK1). Homozygous disruption of the gene encoding WNK1 results in lethality in mice near embryonic day E12 due to impaired angiogenesis and this defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase Oxidative Stress-Responsive 1 (OSR1). However, molecular processes regulated via a collaboration between TGF-β and WNK1/OSR1 are not well understood. Here we show that WNK1 interacts with the E3 ubiquitin ligases SMURF1/2. In addition, we discovered that WNK1 regulates SMURF1/2 protein stability and vice versa. We also demonstrate that WNK1 activity regulates TGF-β receptor levels, in turn, controlling TGF-β signaling.
Pollen Partners: The Symbiotic Microbes ofPinus radiataPollen
Authors: Armstrong C , Ganasamurthy S , Walker K , Mercier C , Wakelin S 
Published: August 2024

AbstractPollen, a crucial source of nutrients and energy for pollinators. It also provides a unique habitat for ecological microbiota. Previous research on the microbiome of pollen has largely focussed on angiosperm systems, with limited research into coniferous gymnosperms. This study characterises the pollen microbiome associated with one of the world’s most widely grown tree species,Pinus radiata. Trees were sampled from locations across Canterbury, New Zealand, with repeated collections in 2020 and 2021. Metabolomic analysis revealed the main compounds present onP. radiatapollen to be amino acids (principally proline), and carbohydrates (fructose, glucose, and sucrose). Although phenolic compounds such as ρ-coumaric acid and catechin, and terpenoids such as dehydroabietic acid, were present at low concentrations, their strong bioactive natures mean they may be important in filtering of microbiome communities on pollen.Pinus radiatapollen was found to host a microbiome dominated by fungi; this directly contrasts with those for many angiosperm species. Geographic range and sampling years were evaluated as secondary drivers of microbiome assembly. Neither sampling location nor annual variation had a significant impact on the fungal component of the pine pollen microbiome, which was remarkably stable/conserved among samples. However, some bacterial taxa exhibited sensitivity to geographic distances and yearly variations, suggesting a secondary role for some. A core microbiome was identified inP. radiatapollen, characterized by a consistent presence of specific fungal and bacterial taxa across samples. While the dominant phyla, Proteobacteria and Ascomycota, align with findings from other pollen microbiome studies, unique core members were unidentified at genus level. This tree species-specific microbiome assembly emphasizes the crucial role of the host plant in shaping the pollen microbiome. These findings contribute to a deeper understanding of pollen microbiomes in gymnosperms, shedding light on the need to look further at their ecological and functional roles.