bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHYSICIANS’ ADHERENCE TO GUIDELINES ON MEDICAL THERAPY FOR HEART FAILURE AND PATIENTS’ OUTCOMES IN A KENYAN REFERRAL HOSPITAL
Authors: Mucyo Willy , Shah Jasmit , Mohamed Jeilan , Varwani Mohamed Hasham , Ngunga Mzee 
Published: November 2023

ABSTRACTBackgroundAdherence to guidelines on prescription and uptitration of GDMT for HFrEF is associated with reduced mortality and hospitalization. Published data on physicians’ GDMT prescription in sub-Saharan Africa is scarce. In addition, there is a need for data on patients’ characteristics, treatment, and outcomes in this region.ObjectiveTo determine physicians’ level of adherence to guidelines on prescription and uptitration of medical therapy for HFrEF at AKUHN, a referral hospital in Nairobi, Kenya.MethodsWe reviewed 280 files of all HFrEF patients admitted over a 3-year period. Detailed patients’ characteristics and outcomes were analyzed. We calculated the Guideline Adherence Index (GAI) and the QUality of Adherence to guideline recommendations for LIFe-saving treatment in heart failure (QUALIFY) scores. From worst to best, GAI ranges from 0 to 100%, while QUALIFY scores were categorized as poor, moderate, or good.ResultsThe median age (IQR) was 63 years (53,74); 165(58.9%) were male; and 207(74.2%) were black; 98(35%) had ischemic heart disease; 153(54.6%) had hypertension, and 101(36.1%) had diabetes. At six months follow-up, 43.8% of patients had been readmitted at least once and 8.8% had died. GAI at discharge were 66.2%, 71.7%, and 42.6% for ACEI/ARNI/ARBs, B-blockers, and MRAs, respectively. At 6 months, the scores were 86.3%, 84.4%, and 61.2%, respectively. GAI for SGLT2is was 38.9% at 6 months. The proportions for good QUALIFY scores for ACEI/ARNI/ARBs, B- blockers, and MRAs were 35.8%, 38.5%, and 9.5%, respectively. Uptitration to ≥ 50% of target dose was done in 51.9%, 48.7%, and 7.9% of patients for ACEI/ARNI/ARBs, B- blockers, and MRAs, respectively.ConclusionPhysicians’ level of adherence to prescription and up-titration of GDMT was satisfactory for ACEI/ARNI/ARBs and B-blockers, however, it was poor for SGLT2is and MRAs. There is a need for regular surveys on prescription and uptitration of GDMT with a special attention to MRAs and SGLT2is.
Automated assessments can support regional Red Lists but need to be applied with caution: A case study from central Germany
Authors: Zizka Alexander , Starke-Ottich Indra , Eichenberg David , Bönsel Dirk , Zizka Georg 
Published: November 2023

AbstractAimExpert-based regional Red Lists (RL) carry conservation legislation globally. Yet, they are often difficult to reproduce and their regular compilation by a dwindling number of expert assessors burdens many regional conservation authorities. Here we batch-estimate RL indicators and extinction risk for >1,100 plant species and test the potential of this automated approach to support the expert-based RL process.LocationState of Hesse, Central GermanyMethodsFirst, we estimated current population status, short-term population trend, long-term population trend, and extinction risk by binning existing occurrence probabilities modelled at three time slices with cut-off values derived from RL methodology. Subsequently we compared the results with the latest version of the Hessian expert-based RL using summary statistics and selected example species.ResultsWe find the assessments of extinction risk to agree in c. 60% of the cases, mostly for species not threatened with extinction. Existing mismatch was by one category in most cases, but up to 6 categories in some cases (mean: 1.6 categories). Furthermore, agreement was highest for extreme categories and very abundant species.Main conclusionsAutomated assessments were simplistic for many rare and taxonomically challenging species, but we considered them more accurate than the expert assessments for species with intermediate population size and for species of anthropogenic habitats. Furthermore, the automated assessments are particularly informative for the estimation of long-term and short-term population trends, for which experts are often left to guesstimate based on little data.
Story of an infection: viral dynamics and host responses in theCaenorhabditis elegans-Orsay virus pathosystem
Authors: Castiglioni Victoria G. , Olmo-Uceda Maria J. , Villena-Giménez Ana , Muñoz-Sánchez Juan C. , Elena Santiago F. 
Published: November 2023

SUMMARYOrsay virus (OrV) is the only known natural virus affectingCaenorhabditis elegans, with minimal impact on the worm’s fitness due to its robust innate immune response. This study aimed to understand the interactions betweenC. elegansand OrV by tracking the infection’s progression during larval development. Four distinct stages of infection were identified based on viral load, with a peak in capsid- encoding RNA2 coinciding with the first signs of viral egression. Transcriptomic analysis revealed temporal changes in gene expression and functions induced by the infection. A specific set of up- regulated genes remained active throughout the infection, and genes correlated and anticorrelated with virus accumulation were identified. Responses to OrV mirrored reactions to other biotic stressors, distinguishing between virus-specific responses and broader immune responses. Additionally, mutants of early response genes and defense-related processes showed altered viral load progression, uncovering new players in the antiviral defense response.
Taking fear back into the Marginal Value Theorem: the risk-MVT and optimal boldness
Authors: Calcagno Vincent , Grognard Frédéric , Hamelin Frédéric M. , Mailleret Ludovic 
Published: November 2023

AbstractForagers exploiting heterogeneous habitats must make strategic movement decisions in order to maximize fitness. Foraging theory has produced very general formalizations of the optimal patch-leaving decisions rational individuals should make. One is Charnov’s Marginal Value Theorem (MVT), which models the sequential visit of habitat patches and their spatial distribution. The MVT has a simple intuitive graphical interpretation in terms of gain functions and travel times. However, it considers only energy gains, and the effect of predation risk on the time allocation strategy is notoriously lacking. An important development that includes predation risk was Brown’s economic treatment of optimal patch leaving decisions, the basis of giving-up density (GUD) theory, often cited as an extension of the MVT. However, it is a more abstract result that does not have the specificities or graphical appeal of the MVT. Although both successful, the two theories are cited by distinct communities and are seldom connected in texbooks. Here we formally introduce the risk-MVT (rMVT), a generalization of the MVT that can incorporate most types of predation risks. We show that Brown’s GUD-theory is equivalent to a rMVT, but applies for one type of predation risk only. The rMVT retains the structure and graphical simplicity of the MVT, but implies a shift from residence time to expected dose of risk (micromort units, as used in decision analysis) as the domain over which rates of gain are computed and maximized. Applications of the rMVT show that different types of risk can yield opposite responses of optimal strategies to an increase in the risk level, and predict differential responses of behaviours observed in experimental versus natural conditions. The risk-MVT can also be used to predict the optimal level of risk taking, or “optimal boldness”, and suggests that individuals should generally be bolder in riskier habitats.
DeepCor: Denoising fMRI Data with Contrastive Autoencoders
Authors: Zhu Yu , Aglinskas Aidas , Anzellotti Stefano 
Published: November 2023

ABSTRACTFunctional magnetic resonance imaging (fMRI) is widely used in neuroscience research. FMRI data is noisy; improving denoising methods could lead to novel discoveries. Here, we introduce and evaluate a denoising method (DeepCor) which utilizes deep generative models to disentangle and remove noise. DeepCor outperforms CompCor (a state-of-the art denoising approach) on a variety of simulated datasets. In addition, DeepCor enhances differences in connectivity between brain networks in real datasets.
Non-linear modelling of motor development in typically developing children and youth using robotic assessments
Authors: Dobri Stephan C.D. , Scott Stephen H. , Davies T. Claire 
Published: November 2023

AbstractBackgroundClinical tasks are most often used to differentiate motor performance of individuals who have impaired function. However, these are not as accurate and repeatable as robotic tasks. Additionally, motor development occurs rapidly at early ages and slows as they reach adulthood, resulting in a non-linear model of performance. There is also evidence that variability in performance changes as children and youth age. Accurate normative models of performance are necessary to identify differentiate deficiencies in motor performance and to track the efficacy of therapies.MethodsTwo-hundred and eighty-eight participants who are typically developing (ages 5-18) completed a robotic point-to-point reaching task and an object hitting task using the Kinarm Exoskeleton. Exponential or quadratic curves were fit to performance parameters generated by Kinarm to model typical performance. These models included a linear term to account for changing variability with age.ResultsMost performance parameters showed improvement with age, and none showed deterioration. Some parameters showed large changes in variability in performance with age, up to a 74% decrease in the range of typical performance.ConclusionsReduced variability occurs with age, indicating the need to account for differences in variability when developing models of typical motor performance in children and youth. Models used to identify deficits in motor performance should account for changing variability in data and changing repeatability with age to increase accuracy of identification of deficits.
Characterization of groups of informal caregivers. A cluster analysis using the example of Saxony
Authors: Tischendorf Tim , Geithner Silke , Schaal Tom 
Published: November 2023

AbstractBackgroundAs a result of demographic change, a further increase in the number of people in need of care in Germany can be expected in the future. Nursing activities performed by family members are a central component of care provision. The assumption of support services is increasingly associated with an additional physical and psychological burden on informal caregivers. The aim of this study is to identify and characterize groups of informal caregivers with regard to their well-being.MethodologyThe empirical study was based on a survey on home care in Saxony from 2019, which was intended as exploratory work to provide insights into the care situation in Saxony. The central component is a two-step cluster analysis with exclusively informal caregivers.ResultsThe net sample size for the cluster analysis comprised 178 subjects who were involved in caring for relatives. The cluster analysis revealed two groups of caregiving relatives in Saxony, which were differentiated by a different experience of stress and various sociodemographic factors.DiscussionInformal caregivers in Saxony are not a homogeneous group. Depending on various sociodemographic factors or the care effort and situation, they are confronted with different challenges in caring for relatives, which are directly reflected in their well-being. In order to achieve a targeted reduction in the burden on family caregivers, cooperation and constructive collaboration between political decision-makers, care and health insurers, and the various players in health and care provision is required.
A biomechanical switch promotes lysosomal remodelling and exocytosis in keloid fibroblasts
Authors: Ross Rosie , Guo Yiyang , Walker Rebecca N. , Bergamaschi Daniele , Shaw Tanya J. , Connelly John T. 
Published: November 2023

AbstractKeloids are a severe form of scarring for which the underlying mechanisms are poorly understood, and treatment options are limited or inconsistent. While biomechanical forces are potential drivers of keloid scarring, the direct cellular responses to mechanical cues have yet to be defined. The aim of this study was to examine the distinct responses of normal dermal fibroblasts (NDFs) and keloid-derived fibroblasts (KDFs) to changes in extracellular matrix (ECM) stiffness. When cultured on hydrogels mimicking the elasticity of normal or scarred skin, KDFs displayed greater stiffness-dependent increases in cell spreading, F-actin stress fibre formation, and focal adhesion assembly. Elevated acto-myosin contractility in KDFs disrupted the normal mechanical regulation of ECM remodelling, leading to constitutive collagen and fibronectin deposition. Transcriptional profiling identified mechanically-regulated pathways in NDFs and KDFs, including the actin cytoskeleton, Hippo signalling, and autophagy. Further analysis of the autophagy pathway revealed that autophagic flux was intact in both fibroblast populations and depended on acto-myosin contractility. However, KDFs displayed marked changes in lysosome organisation and an increase in lysosomal exocytosis, which was mediated by acto-myosin contractility. Together, these findings demonstrate that KDFs possess an intrinsic increase in cytoskeletal tension, which heightens the response to ECM mechanics and promotes lysosomal exocytosis.
Population structure and history ofMycobacterium bovisEuropean 3 clonal complex reveal transmission across ecological corridors of unrecognised importance in Portugal
Authors: Pereira André C. , Lourenço José , Themudo Gonçalo , Botelho Ana , Cunha Mónica V. 
Published: November 2023

ABSTRACTMycobacterium boviscauses animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available dataset in the country. Using phylogenetic and ecological modelling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation ofM. bovisEuropean 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 90’s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelling frequent transmission between two clusters that represent an ecological corridor of previously unrecognised importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface towards locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis ofM. bovisEu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission, and informing where efforts could be focused within the larger hotspot risk area of Portugal.IMPORTANCEEfforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed byM. boviswhole genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits.We find evidence for the co-circulation of severalM. bovisclades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognised importance forM. bovismaintenance.Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.
Phase Separation of a Novel form of Euchromatic Histone Methyltransferasel (EHMT1N/C) into cytoplasmic RNA viral Inclusion bodies facilitates their coalescence, thereby enhancing viral replication
Authors: Biligiri Kriti Kestur , Sharma Nishi Raj , Mohanty Abhishek , Sarkar Debi Prasad , Vemula Praveen Kumar , Rampalli Shravanti 
Published: November 2023

AbstractProtein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered a distinct nucleo-cytoplasmic form of Euchromatic Histone Methyltransferase1(EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus). EHMT1N/Cinteracts with cytoplasmic EHMT2 and methylates SeV-Nucleoprotein upon infection. Elevated nucleoprotein methylation during infection correlated with coalescence of small IBs into large mature platforms for efficient replication. Inhibition of EHMT activity by pharmacological inhibitors or genetic depletion of EHMT1N/Creduced the size of IBs with a concomitant reduction in replication. Since IB formation is conserved among all cytoplasmic RNA-viruses, our study will have strong implications in understanding the mechanisms regulating IB formation, discerning RNA viral pathogenesis and designing therapeutic strategies.
Implementation of an internet-based stress management program in micro- and small-sized enterprises: A study protocol for a pre-post feasibility study of the effectiveness-implementation hybrid type 2 trial
Authors: Sasaki Natsu , Shimazu Taichi , Takeno Hajime , Ogawa Sayaka , Sawada Utako , Tsutsumi Akizumi , Imamura Kotaro 
Published: November 2023

AbstractBackgroundText-based self-guided internet-based stress management programs can improve mental health among workers. However, such mental health programs have scarcely been implemented in micro– and small-sized enterprises (MSEs), which are lacking in occupational healthcare services.ObjectivesThis paper describes a study protocol for a pre-post feasibility study of an effectiveness-implementation hybrid type 2 trial of text-based internet-based programs (“WellBe-LINE”) in MSEs with less than 50 employees. This feasibility study primarily aims to evaluate trial methods for future effectiveness-implementation hybrid type 2 trials.MethodsFor this study protocol, an internet– and text-based self-care intervention program using the LINE app (a popular message tool in Japan) will be prepared according to evidence-based psychoeducational topics. Based on our online survey findings, personalized algorithms will be implemented according to employees’ gender, age, and psychological distress levels. A pre-post design feasibility study will be conducted on ten companies to evaluate trial methods (e.g., recruitment, penetration, and procedures). The primary outcome will involve individual-level penetration, defined as the proportion of the number of employees who register for the program divided by the total number of invited employees at the company. The progression criterion specifies that more than 50% of the recruited companies obtain 60% individual penetration. Finally, acceptability, appropriateness, feasibility, and cost will be measured using quantitative internet-based questionnaires and qualitative interviews.DiscussionThis pre-post feasibility study for future effectiveness-implementation hybrid type 2 trials will provide in-depth knowledge about the successful implementation of text-based, semi-personalized, self-care mental health interventions in real-world settings using both quantitative and qualitative data.ConclusionsThis feasibility study will help validate the effectiveness of text-based interventions using a widely used social networking service (SNS) tool for employees in MSEs.Trial registrationUMIN clinical trial registration: UMIN000046960 (registration date: February 21, 2022)https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000053570Contributions to the literatureInternet-based mental health interventions in micro– and small-sized enterprises have not been implemented yet.This feasibility study plans to test the implementation strategies to achieve high penetration in employees.This study can provide insights into occupational health implementation in a disadvantaged context.
Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain
Authors: Sæther Linn Sofie , Szabo Attila , Akkouh Ibrahim A. , Haatveit Beathe , Mohn Christine , Vaskinn Anja , Aukrust Pål , Ormerod Monica B. E.G. , Steen Nils Eiel , Melle Ingrid , Djurovic Srdjan , Andreassen Ole A. , Ueland Torill , Ueland Thor 
Published: November 2023

AbstractRecent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n=1235), we aimed to i) identify candidate peripheral markers (n=25) associated with cognitive domains (n=9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n=10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n=776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n=474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high inflammatory subgroup consisting predominantly of SZ in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness.