Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast Growth Factor 23 and Risk of New Onset Heart Failure With Preserved or Reduced Ejection Fraction: The PREVEND Study

Background The role of fibroblast growth factor 23 (FGF23) in the development of new‐onset heart failure (HF) with reduced (HFrEF) or preserved ejection fraction (HFpEF) in the general population is unknown. Therefore, we set out to investigate associations of C‐terminal FGF23 with development of new‐onset HF and, more specifically, with HFrEF or HFpEF in a large, prospective, population‐based cohort. Methods and Results We studied 6830 participants (aged 53.8±12.1 years; 49.7% men; estimated glomerular filtration rate, 93.1±15.7 mL/min per 1.73 m2) in the community‐based PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study who were free of HF at baseline. Cross‐sectional multivariable linear regression analysis showed that ferritin (standardized β, −0.24; P<0.001) and estimated glomerular filtration rate (standardized β, −0.13; P<0.001) were the strongest independent correlates of FGF23. Multivariable Cox proportional hazard regression was used to study the association between baseline FGF23 and incident HF, HFrEF (ejection fraction ≤40%) or HFpEF (ejection fraction ≥50%). After median follow‐up of 7.4 [IQR 6.9–7.9] years, 227 individuals (3.3%) developed new‐onset HF, of whom 132 had HFrEF and 88 had HFpEF. A higher FGF23 level was associated with an increased risk of incident HF (fully adjusted hazard ratio, 1.29 [95% CI, 1.06–1.57]) and with an increased risk of incident HFrEF (fully adjusted hazard ratio, 1.31 [95% CI, 1.01–1.69]). The association between FGF23 and incident HFpEF lost statistical significance after multivariable adjustment (hazard ratio, 1.22 [95% CI, 0.87–1.71]). Conclusions Higher FGF23 is independently associated with new‐onset HFrEF in analyses fully adjusted for cardiovascular risk factors and other potential confounders. The association between FGF23 and incident HFpEF lost statistical significance upon multivariable adjustment.
Overcoming selection bias in synthetic lethality prediction

Abstract Motivation Synthetic lethality (SL) between two genes occurs when simultaneous loss of function leads to cell death. This holds great promise for developing anti-cancer therapeutics that target synthetic lethal pairs of endogenously disrupted genes. Identifying novel SL relationships through exhaustive experimental screens is challenging, due to the vast number of candidate pairs. Computational SL prediction is therefore sought to identify promising SL gene pairs for further experimentation. However, current SL prediction methods lack consideration for generalizability in the presence of selection bias in SL data. Results We show that SL data exhibit considerable gene selection bias. Our experiments designed to assess the robustness of SL prediction reveal that models driven by the topology of known SL interactions (e.g. graph, matrix factorization) are especially sensitive to selection bias. We introduce selection bias-resilient synthetic lethality (SBSL) prediction using regularized logistic regression or random forests. Each gene pair is described by 27 molecular features derived from cancer cell line, cancer patient tissue and healthy donor tissue samples. SBSL models are built and tested using approximately 8000 experimentally derived SL pairs across breast, colon, lung and ovarian cancers. Compared to other SL prediction methods, SBSL showed higher predictive performance, better generalizability and robustness to selection bias. Gene dependency, quantifying the essentiality of a gene for cell survival, contributed most to SBSL predictions. Random forests were superior to linear models in the absence of dependency features, highlighting the relevance of mutual exclusivity of somatic mutations, co-expression in healthy tissue and differential expression in tumour samples. Availability and implementation https://github.com/joanagoncalveslab/sbsl Supplementary information Supplementary data are available at Bioinformatics online.
Motor defects in a Drosophila model for spinal muscular atrophy result from SMN depletion during early neurogenesis

Spinal muscular atrophy (SMA) is the most common autosomal recessive neurodegenerative disease, and is characterised by spinal motor neuron loss, impaired motor function and, often, premature death. Mutations and deletions in the widely expressed survival motor neuron 1 (SMN1) gene cause SMA; however, the mechanisms underlying the selectivity of motor neuron degeneration are not well understood. Although SMA is degenerative in nature, SMN function during embryonic and early postnatal development appears to be essential for motor neuron survival in animal models and humans. Notwithstanding, how developmental defects contribute to the subversion of postnatal and adult motor function remains elusive. Here, in a Drosophila SMA model, we show that neurodevelopmental defects precede gross locomotor dysfunction in larvae. Furthermore, to specifically address the relevance of SMN during neurogenesis and in neurogenic cell types, we show that SMN knockdown using neuroblast-specific and pan-neuronal drivers, but not differentiated neuron or glial cell drivers, impairs adult motor function. Using targeted knockdown, we further restricted SMN manipulation in neuroblasts to a defined time window. Our aim was to express specifically in the neuronal progenitor cell types that have not formed synapses, and thus a time that precedes neuromuscular junction formation and maturation. By restoring SMN levels in these distinct neuronal population, we partially rescue the larval locomotor defects of Smn mutants. Finally, combinatorial SMN knockdown in immature and mature neurons synergistically enhances the locomotor and survival phenotypes. Our in-vivo study is the first to directly rescue the motor defects of an SMA model by expressing Smn in an identifiable population of Drosophila neuroblasts and developing neurons, highlighting that neuronal sensitivity to SMN loss may arise before synapse establishment and nerve cell maturation.
Chemsex users in Czechia: EMIS survey.

OBJECTIVES Chemsex is a phenomenon highly relevant to public health concerns. Our primary aim is to describe the Czech chemsex scene regarding substances used, sexual behaviour, mental health, sexual life satisfaction, internalization of homonegative attitudes, and prevalent chemsex patterns. METHODS The data from the European Men Who Have Sex With Men Internet Survey (EMIS) 2017 were used. The mental health of chemsex users was assessed by the Patient Health Questionnaire 4 (PHQ4), internalized homonegativity was measured using the Short Internalized Homonegativity Scale. A sample of 87 men who have sex with men (MSM) chemsex users and a comparison group of 261 MSM were selected from the total sample of 1,688 respondents. Mann-Whitney and χ2 tests were used to compare groups. RESULTS Active chemsex users made up 5% of the sample (87 of 1,688), with an average age of 37 years. Chemsex users were more likely to engage in condomless sex with non-steady partners (χ2 = 46.8, p < 0.001), and had dramatically more STIs, such as HIV (χ2 = 52.9, p < 0.001), HCV (χ2 = 25.9, p < 0.001), and syphilis (χ2 = 41.5, p < 0.001). Chemsex users frequently injected drugs (n = 19, 20%). More than half (n = 48; 55%) of chemsex users had sober sex in the last 4 weeks. Chemsex culture was associated with riskier substance use, both in terms of mode and frequency. The mental health of chemsex users in our sample did not differ significantly from the comparison group (χ2 = 0.2, p < 0.7). Chemsex users did not conceal their sexual identity more often than the comparison group, on the contrary, 69% (n = 59) of them were out to most significant others, compared to 53% (n = 134) in the comparison group (χ2 = 8.8, p < 0.05). In addition, we did not find differences in the degree of internalized homonegativity (χ2 = 0.9, p < 0.4). Chemsex users were clearly and significantly more satisfied with their sex life than the comparison group (Mann-Whitney U test, p < 0.001). CONCLUSIONS In our sample, chemsex use was not associated with a negative impact on health or wellbeing. Our results suggest that chemsex is not a homogeneous phenomenon. Many different patterns and subcultures exist, some of them are riskier, some safer than others.
Dynamic Interpretability for Model Comparison via Decision Rules

Explainable AI (XAI) methods have mostly been built to investigate and shed light on single machine learning models and are not designed to capture and explain differences between multiple models effectively. This paper addresses the challenge of understanding and explaining differences between machine learning models, which is crucial for model selection, monitoring and lifecycle management in real-world applications. We propose DeltaXplainer, a model-agnostic method for generating rule-based explanations describing the differences between two binary classifiers. To assess the effectiveness of DeltaXplainer, we conduct experiments on synthetic and real-world datasets, covering various model comparison scenarios involving different types of concept drift.
The bipolar patients’ family experiences of the outcomes of encountering stigma in Tehran: A qualitative study

Introduction: Nowadays, the most common psychological-social pressure to which bipolar patients’ families are exposed is stigma. Therefore, the present study was conducted to delve into the bipolar patients’ family experiences of the outcomes of encountering stigma. Method: The study was of qualitative type. Purposive sampling was used to select the participants from the persons suffering from bipolar disorder and their families. Twenty seven of the participants were interviewed. The main data collection instrument was semi-structured interview with open questions. Additionally, the collected data were analyzed via inductive content analysis method. The accuracy and validity of the study rooted in four factors: credibility, transferability, verifiability, and reliability. Results: Data analysis led to 1,326 primary codes, which were further categorized into five main categories as the main outcomes of encountering stigma (social deprivation, emotional and sentimental excitement, objective and behavioral reflections, family solidarity threat, and separation from society) and 21 sub-categories. Conclusion: Given then irreparable outcomes of stigma for bipolar patients’ family, it is necessary to take it into consideration. It is recommended to use media and also hygienic-treatment centers to educate different levels of society as to appropriate treatment with these patients and their families.
Target-dependent suppression of siRNA production modulates the levels of endogenous siRNAs in C. elegans germline.

Despite the prominent role of endo-siRNAs in transposon silencing, their expression is not limited to these "nonself" DNA elements. Transcripts of protein-coding genes ("self" DNA) in some cases also produce endo-siRNAs in yeast, plants, and animals (Piatek and Werner 2014). How cells distinguish these two populations of siRNAs to prevent unwanted silencing of active genes in animals is not well understood. To address this question, we inserted various self-gene or gfp fragments into an LTR retrotransposon that produces abundant siRNAs and examined the propensity of these gene fragments to produce ectopic siRNAs in C. elegans germline. We found that fragments of germline genes are generally protected from production of ectopic siRNAs. This phenomenon, which we termed "target-directed suppression of siRNA production" (or siRNA suppression), is dependent on the germline expression of target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur to naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing.
Public Valuation of Direct Restorations: A Discrete Choice Experiment

Direct posterior dental restorations are commonly provided following management of dental caries. Amalgam use has been phased down and the feasibility of a phase-out by 2030 is being explored. Alternative direct restorative materials differ in their outcomes and provision. This research aimed to elicit the UK population’s preferences for different attributes of restorations and their willingness to pay (WTP) for restorative services and outcomes. A discrete choice experiment (DCE) was designed with patient and public involvement and distributed to a representative sample of the UK general population using an online survey. Respondents answered 17 choice tasks between pairs of scenarios that varied in levels of 7 attributes (wait for filling, clinician type, filling color, length of procedure, likely discomfort after filling, average life span of filling, and cost). An opt-out (no treatment) was included. Mixed logit models were used for data analysis. Marginal WTP for attribute levels and relative attribute importance were calculated. In total, 1,002 respondents completed the DCE. Overall, respondents were willing to pay £39.52 to reduce a 6-wk wait for treatment to 2 wk, £13.55 to have treatment by a dentist rather than a therapist, £41.66 to change filling color from silvery/gray to white, £0.27 per minute of reduced treatment time, £116.52 to move from persistent to no postoperative pain, and £5.44 per year of increased restoration longevity. Ability to pay affected willingness to pay, with low-income respondents more likely to opt out of treatment and value restoration color (white) and increased longevity significantly lower than those with higher income. Clinicians should understand potential drivers of restoration choice, so they can be discussed with individual patients to obtain consent. It is important that policy makers consider general population preferences for restorative outcomes and services, with an awareness of how income affects these, when considering the potential phase-out of amalgam restorations.
Hair Microbiome Diversity within and across Primate Species

We created the most comprehensive primate hair and skin data set to date, including data from 12 nonhuman primate species sampled from 8 body regions each. We find that the nonhuman primate hair microbiome is distinct from the human hair and skin microbiomes in that it is relatively uniform—as opposed to distinct—across body regions and is most abundant in gut-, environment-, and respiratory-associated microbiota rather than human skin-associated microbiota. ABSTRACT Primate hair and skin are substrates upon which social interactions occur and are host-pathogen interfaces. While human hair and skin microbiomes display body site specificity and immunological significance, little is known about the nonhuman primate (NHP) hair microbiome. Here, we collected hair samples (n = 158) from 8 body sites across 12 NHP species housed at three zoological institutions in the United States to examine the following: (1) the diversity and composition of the primate hair microbiome and (2) the factors predicting primate hair microbiome diversity and composition. If both environmental and evolutionary factors shape the microbiome, then we expect significant differences in microbiome diversity across host body sites, sexes, institutions, and species. We found our samples contained high abundances of gut-, respiratory-, and environment-associated microbiota. In addition, multiple factors predicted microbiome diversity and composition, although host species identity outweighed sex, body site, and institution as the strongest predictor. Our results suggest that hair microbial communities are affected by both evolutionary and environmental factors and are relatively similar across nonhuman primate body sites, which differs from the human condition. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome. IMPORTANCE We created the most comprehensive primate hair and skin data set to date, including data from 12 nonhuman primate species sampled from 8 body regions each. We find that the nonhuman primate hair microbiome is distinct from the human hair and skin microbiomes in that it is relatively uniform—as opposed to distinct—across body regions and is most abundant in gut-, environment-, and respiratory-associated microbiota rather than human skin-associated microbiota. Furthermore, we found that the nonhuman primate hair microbiome varies with host species identity, host sex, host environment, and host body site, with host species identity being the strongest predictor. This result demonstrates that nonhuman primate hair microbiome diversity varies with both evolutionary and environmental factors and within and across primate species. These findings have important implications for understanding the biology and conservation of wild and captive primates and the uniqueness of the human microbiome.
Modeling bicyclist injury severity in bicycle–motor vehicle crashes that occurred in urban and rural areas: a mixed logit analysis

The purpose of this paper is to identify and compare the contributing factors to bicyclist injury severity in urban and rural areas. Two mixed logit models are developed for both the urban and rural areas separately to identify factors that significantly contribute to the injury severity outcome of bicyclists resulting from bicycle–motor vehicle crashes. Data collected from 2007 to 2014 in North Carolina are utilized for the model development. The model estimation results show that factors including bicyclist age from 25 to 54, driver age under 25, vehicle speed, and divided road are found to significantly affect the injury severity outcome of bicyclists in bicycle–motor vehicle crashes in rural areas only. In contrast, factors including drivers age over 60, van, single unit truck, head-on crash, motorist overtaking bicyclist, two-way roadway, road condition, and crash time are found to have a significant impact on the injury severity of bicyclists in urban areas only.
Validity and Reliability of the Seated Medicine Ball Throw as a Measure of Upper Body Power in Older Women

Abstract Strand, KL, Ly, AS, Barry, SS, Liscano, JA, Trebotich, TL, Martin-Diala, C, Martin, E, and Signorile, JF. Validity and reliability of the seated medicine ball throw as a measure of upper body power in older women. J Strength Cond Res 37(4): 902–908, 2023—In women, aging is associated with diminishing upper body power, which may increase the risk of falls and fall-related injury; however, the validity and reliability of clinical tests to evaluate upper body power need to be confirmed. The seated medicine ball throw (SMBT) is an upper body performance test used to monitor muscle function among older individuals. The purpose of this study was to evaluate the validity and test-retest reliability of the SMBT in older women. Thirty-five women (age = 75.15 ± 6.39 years) participated in this study. Subjects performed SMBT trials using common ball masses (SMBT4lb and SMBT3kg) over 3 sessions. Familiarization with the SMBT and chest press 1 repetition maximum (CP1RM) was provided on the first day. On day 2, subjects repeated the tests, but data were recorded. On day 3, SMBT was retested followed by an evaluation of chest press peak power (CPPP) values at 30–80% of CP1RM. Significant correlations (p ≤ 0.05) were found between the CPPP and SMBT4lb (r = 0.775, p < 0.001) and SMBT3kg (r = 0.734, p < 0.001), and SMBT distance showed expected declines with age (r = −0.724 to −0.626, p < 0.001), demonstrating its validity. High reliability between testing days was found, and Bland-Altman plots showed few points that fell outside the limits of agreement. In conclusion, the SMBT is a valid and highly reliable tool that can be used by health professionals to monitor deficits in upper body muscular power to improve treatment protocols in older women.
Swimming behavior and hydrodynamics of the Chinese cavefish Sinocyclocheilus rhinocerous and a possible role of its head horn structure

The blind troglobite cavefish Sinocyclocheilus rhinocerous lives in oligotrophic, phreatic subterranean waters and possesses a unique cranial morphology including a pronounced supra-occipital horn. We used a combined approach of laboratory observations and Computational Fluid Dynamics modeling to characterize the swimming behavior and other hydrodynamic aspects, i.e., drag coefficients and lateral line sensing distance of S. rhinocerous. Motion capture and tracking based on an Artificial Neural Network, complemented by a Particle Image Velocimetry system to map out water velocity fields, were utilized to analyze the motion of a live specimen in a laboratory aquarium. Computational Fluid Dynamics simulations on flow fields and pressure fields, based on digital models of S. rhinocerous, were also performed. These simulations were compared to analogous simulations employing models of the sympatric, large-eyed troglophile cavefish S. angustiporus. Features of the cavefish swimming behavior deduced from the both live-specimen experiments and simulations included average swimming velocities and three dimensional trajectories, estimates for drag coefficients and potential lateral line sensing distances, and mapping of the flow field around the fish. As expected, typical S. rhinocerous swimming speeds were relatively slow. The lateral line sensing distance was approximately 0.25 body lengths, which may explain the observation that specimen introduced to a new environment tend to swim parallel and near to the walls. Three-dimensional simulations demonstrate that just upstream from the region under the supra-occipital horn the equipotential of the water pressure and velocity fields are nearly vertical. Results support the hypothesis that the conspicuous cranial horn of S. rhinocerous may lead to greater stimulus of the lateral line compared to fish that do not possess such morphology.
Skin‐Inspired Thermoreceptors‐Based Electronic Skin for Biomimicking Thermal Pain Reflexes

Electronic systems possessing skin‐like morphology and functionalities (electronic skins [e‐skins]) have attracted considerable attention in recent years to provide sensory or haptic feedback in growing areas such as robotics, prosthetics, and interactive systems. However, the main focus thus far has been on the distributed pressure or force sensors. Herein a thermoreceptive e‐skin with biological systems like functionality is presented. The soft, distributed, and highly sensitive miniaturized (≈700 µm2) artificial thermoreceptors (ATRs) in the e‐skin are developed using an innovative fabrication route that involves dielectrophoretic assembly of oriented vanadium pentoxide nanowires at defined locations and high‐resolution electrohydrodynamic printing. Inspired from the skin morphology, the ATRs are embedded in a thermally insulating soft nanosilica/epoxy polymeric layer and yet they exhibit excellent thermal sensitivity (−1.1 ± 0.3% °C−1), fast response (≈1s), exceptional stability (negligible hysteresis for >5 h operation), and mechanical durability (up to 10 000 bending and twisting loading cycles). Finally, the developed e‐skin is integrated on the fingertip of a robotic hand and a biological system like reflex is demonstrated in response to temperature stimuli via localized learning at the hardware level.