Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of rivaroxaban in patients with non-valvular atrial fibrillation and end-stage kidney disease: A systematic review and meta-analysis

Background Nowadays, the number of patients with non-valvular atrial fibrillation (NVAF) complicated by end-stage renal disease (ESKD) is increasing. There are significant challenges in anticoagulation with prescription drugs because of the high risk of bleeding and embolism among these patients. However, no randomized controlled trials (RCTs) of warfarin in combination with any non-vitamin K oral anticoagulant (NOACs) have been performed in patients with baseline creatinine clearance (CrCl) <25 ml/min, which makes it difficult to justify the use of anticoagulants in such patients. Then, we aimed to collect and summarize all evidence to enable the anticoagulation of rivaroxaban, which is less cleared by the kidneys, in patients with severe renal insufficiency and to complement and improve the evidence on the use of rivaroxaban for anticoagulation. Methods The present systematic review and meta-analysis searched the databases of PubMed, Embase, the Cochrane Library, CNKI, CBM, and Google Scholar for relevant studies from inception to 1 June 2022, with the restriction of English and Chinese. Eligible cohort studies and RCTs that reported efficacy outcomes [composite of stroke and systemic embolism (SSE), ischemic stroke (ICS), and systemic embolization] or safety outcomes [major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding (GIB)] of rivaroxaban in NVAF patients with ESKD were enrolled. Two authors completed the data extraction and quality assessment work, respectively. The Cochrane Collaboration tool for assessing the risk of bias was used for RCTs, and the NEW-Castle Ottawa scale was used for study quality assessment for cohort studies. Dichotomous variables were calculated as risk factors with 95% confidence intervals (CIs), and meta-analysis was performed to probe the effect of research design, rivaroxaban dose, and controlled drug factors on outcomes. Results In total, three studies were included for meta-analysis, involving 6,071 NVAF patients with ESKD, and two studies were included for qualitative analysis. All included studies were at low risk of bias. A meta-analysis demonstrated that mix-dose rivaroxaban caused no statistical discrepancy in the occurrence of thrombotic and bleeding events when compared to the control group (embolism, LogOR: −0.64, 95% CI: −1.05 to −0.23, P:0.25; bleeding, LogOR: −0.33, 95% CI: −0.63 to −0.03, P:0.15), and low-dose rivaroxaban produced similar results (embolism, LogOR: −1.04, 95% CI: −2.15 to 0.07, P:0.61; bleeding, LogOR: −0.81, 95% CI: −1.19 to −0.44, P:0.93). Conclusion In this study, low-dose rivaroxaban (10 mg, once a day) may benefit more than warfarin in patients with NVAF and ESKD. Systematic review registration https://www.crd. york.ac. uk/prospero/#recordDetails, identifier CRD42022330973.
Assessment, life circumstances, curriculum and skills: Barriers and enablers to student mental wellbeing in distance learning

Student mental wellbeing is increasingly a priority for universities, and this is particularly critical in a distance learning context. Studies have found that studying, academic pressure, university culture and systems can affect students’ mental health. There are increasing calls for universities to take a compassionate, holistic approach to supporting student wellbeing, and identify the barriers that are created by university cultures, systems, pedagogies, curricula, tuition and assessment practices. This study aimed to identify barriers and enablers to student mental wellbeing in distance learning, and students’ recommendations for changes to be made. Using a student survey (N = 584), we identified that assessment and life circumstances were the most significant barriers, while the greatest enablers were building study skills, the people in students’ lives, and curriculum and module content. The study revealed significant demographic differences in how students experience barriers and enablers, and how likely they feel they are to benefit from solutions. Students with disclosed mental health difficulties were consistently more likely to experience barriers than students without a disclosure, while enablers were experienced by all demographic groups. The study concludes that assessment should be prioritised as an area for action.
A qualitative study exploring the perceived effects of veterinarians' mental health on provision of care

Introduction Veterinary medicine is a rewarding, yet demanding profession with a myriad of occupational stressors that can impact the mental health of veterinarians. Stress, mental health outcomes, and associated risk factors amongst veterinarians have been well-researched. Much less research has investigated how high stress and/or poor mental health can impact veterinarians' provision of care. Methods One-on-one research interviews were conducted with 25 veterinarians at a Canadian veterinary conference in July 2016 and verbatim transcripts were produced from the audio recordings. The research team collaboratively analyzed the interviews using thematic analysis. Results Five themes described the perceived impacts of high stress and/or poor mental health: perceived negative impacts on interactions with (1) co-workers and (2) clients; (3) reduced concentration; (4) difficulty in decision making; and (5) reduced quality of care. Discussion These results highlight the perceived impacts of self-reported high stress and/or poor mental health on veterinary team dynamics, the potential to impact case outcomes, and possibly endanger patient safety. Interventions to help mitigate the impacts of high stress and poor mental health are discussed.
Relationship between gut microbiota and Chinook salmon (Oncorhynchus tshawytscha) health and growth performance in freshwater recirculating aquaculture systems

Gut microbiota play important roles in fish health and growth performance and the microbiome in fish has been shown to be a biomarker for stress. In this study, we surveyed the change of Chinook salmon (Oncorhynchus tshawytscha) gut and water microbiota in freshwater recirculating aquaculture systems (RAS) for 7 months and evaluated how gut microbial communities were influenced by fish health and growth performance. The gut microbial diversity significantly increased in parallel with the growth of the fish. The dominant gut microbiota shifted from a predominance of Firmicutes to Proteobacteria, while Proteobacteria constantly dominated the water microbiota. Photobacterium sp. was persistently the major gut microbial community member during the whole experiment and was identified as the core gut microbiota for freshwater farmed Chinook salmon. No significant variation in gut microbial diversity and composition was observed among fish with different growth performance. At the end of the trial, 36 out of 78 fish had fluid in their swim bladders. These fish had gut microbiomes containing elevated proportions of Enterococcus, Stenotrophomonas, Aeromonas, and Raoultella. Our study supports the growing body of knowledge about the beneficial microbiota associated with modern salmon aquaculture systems and provides additional information on possible links between dysbiosis and gut microbiota for Chinook salmon.
Bioequivalence study of ipratropium bromide inhalation aerosol using PBPK modelling

Aims Systemic pharmacokinetic (PK) studies can reflect the overall exposure of orally inhaled drug Products (OIDPs) in the blood after inhalation into the lung and can be used to evaluate the bioequivalence of test and reference products. The aim of this article is: (1) to study the PK characteristics and bioequivalence of ipratropium bromide (IB) inhalation aerosol, reference and test products in healthy Chinese subjects; (2) to establish a physiologically based pharmacokinetic (PBPK) model and verify the accuracy of the model in predicting bioequivalence; (3) attempt to use the model to predict the regional distribution of particles in the lung after inhalation, and discuss the effect of gastrointestinal drug absorption of IB on systemic exposure. Methods The study involved two clinical studies. Clinical study-1 (registration number: CTR20201284) was used with non-clinical data to construct and validate a PBPK model in the B2O simulator, a web-based virtual drug development platform. This model assessed different test and reference products’ bioequivalence. Results were compared to a second clinical study (Clinical study-2: registration number CTR20202291). The particles’ regional distribution in the lung and the gastrointestinal absorption effect on systemic exposure were discussed based on the simulation results. Results The established PBPK model successfully simulated the in vivo PK characteristics of IB inhalation aerosol, with r2 close to 1. Gastrointestinal absorption had a negligible effect on systemic exposure. Particles accumulated in the alveolar area were cleared within an hour, followed by particles in the bronchioles and bronchi. Conclusion This model provided a reliable method for exploring the correlation between in vitro and in vivo PK studies of IB inhalation aerosols. According to the simulation results, the test and reference products were bioequivalent.
Revisiting fruit and vegetable determinants: Evidence from Latin America

Introduction In the past decade, the public health discussion regarding fruit and vegetable (FV) consumption has been dominated by economic and physical accessibility. Methods Using an online survey in four Latin American countries, we applied a set of tobit models to compare the determinants of desirable and current consumption of FV levels for satisfied and unsatisfied respondents. Results We found that, even when consuming less than five FV portions a day, most of the respondents were satisfied with their current FV consumption level. Satisfied respondents consumed significantly more FV than unsatisfied ones. In general, the desirable and current consumption of FV levels were associated with different sets of determinants, while years of education were relevant in both cases. Finally, in a hypothetical case where unsatisfied respondents would not face any physical or economic access restrictions, unsatisfied respondents would not reach the goal of five FV portions a day. Discussion Assuming that physical and economic access improved, this would automatically increase FV to reach the five-a-day recommendation may be inaccurate in some cases. We also need to take mental access into account. We may ask how to improve the desirable level of FVs and then how to close the gap between the current and desirable FV levels.
Understanding mental health through computers: An introduction to computational psychiatry

Computational psychiatry recently established itself as a new tool in the study of mental disorders and problems. Integration of different levels of analysis is creating computational phenotypes with clinical and research values, and constructing a way to arrive at precision psychiatry are part of this new branch. It conceptualizes the brain as a computational organ that receives from the environment parameters to respond to challenges through calculations and algorithms in continuous feedback and feedforward loops with a permanent degree of uncertainty. Through this conception, one can seize an understanding of the cerebral and mental processes in the form of theories or hypotheses based on data. Using these approximations, a better understanding of the disorder and its different determinant factors facilitates the diagnostics and treatment by having an individual, ecologic, and holistic approach. It is a tool that can be used to homologate and integrate multiple sources of information given by several theoretical models. In conclusion, it helps psychiatry achieve precision and reproducibility, which can help the mental health field achieve significant advancement. This article is a narrative review of the basis of the functioning of computational psychiatry with a critical analysis of its concepts.
Computationally-feasible uncertainty quantification in model-based landslide risk assessment

Introduction: Increasing complexity and capacity of computational physics-based landslide run-out modelling yielded highly efficient model-based decision support tools, e.g. landslide susceptibility or run-out maps, or geohazard risk assessments. A reliable, robust and reproducible development of such tools requires a thorough quantification of uncertainties, which are present in every step of computational workflow from input data, such as topography or release zone, to modelling framework used, e.g. numerical error. Methodology: Well-established methods from reliability analysis such as Point Estimate Method (PEM) or Monte Carlo Simulations (MCS) can be used to investigate the uncertainty of model outputs. While PEM requires less computational resources, it does not capture all the details of the uncertain output. MCS tackles this problem, but creates a computational bottleneck. A comparative study is presented herein by conducting multiple forward simulations of landslide run-out for a synthetic and a real-world test case, which are used to construct Gaussian process emulators as a surrogate model to facilitate high-throughput tasks. Results: It was demonstrated that PEM and MCS provide similar expectancies, while the variance and skewness differ, in terms of post-processed scalar outputs, such as impact area or a point-wise flow height. Spatial distribution of the flow height was clearly affected by the choice of method used in uncertainty quantification. Discussion: If only expectancies are to be assessed then one can work with computationally-cheap PEM, yet MCS has to be used when higher order moments are needed. In that case physics-based machine learning techniques, such as Gaussian process emulation, provide strategies to tackle the computational bottleneck. It can be further suggested that computational-feasibility of MCS used in landslide risk assessment can be significantly improved by using surrogate modelling. It should also be noted that the gain in compute time by using Gaussian process emulation critically depends on the computational effort needed to produce the training dataset for emulation by conducting simulations.
How systemic cognition enables epistemic engineering

Epistemic engineering arises as systems and their parts develop functionality that is construed as valid knowledge. By hypothesis, epistemic engineering is a basic evolutionary principle. It ensures that not only living systems identify the differences that make differences but also ensure that distributed control enables them to construct epistemic change. In tracking such outcomes in human life, we stress that humans act within poly-centered, distributed systems. Similar to how people can act as inert parts of a system, they also actively bring forth intents and vicariant effects. Human cognitive agents use the systemic function to construct epistemic novelties. In the illustration, we used a published experimental study of a cyborg cockroach to consider how an evoneered system enables a human subject to perform as an adaptor with some “thought control” over the animal. Within a wide system, brains enable the techniques to arise ex novo as they attune to the dictates of a device. Human parts act as adaptors that simplify the task. In scaling up, we turn to a case of organizational cognition. We track how adaptor functions spread when drone-based data are brought to the maintenance department of a Danish utility company. While pivoting on how system operators combine experience with the use of software, their expertise sets off epistemically engineered results across the company and beyond. Vicariant effects emerge under the poly-centered control of brains, persons, equipment, and institutional wholes. As a part of culture, epistemic engineering works by reducing entropy.
Neurocognitive effects of binge drinking on verbal episodic memory. An ERP study in university students

Background: Verbal memory may be affected by engagement in alcohol binge drinking during youth, according to the findings of neuropsychological studies. However, little is known about the dynamics of the neural activity underlying this cognitive process in young, heavy drinkers. Aims: To investigate brain event-related potentials associated with cued recall from episodic memory in binge drinkers and controls. Methods: Seventy first-year university students were classified as binge drinkers (32: 17 female) or controls (38: 18 female). The participants completed a verbal paired associates learning task during electroencephalogram (EEG) recording. ERPs elicited by old and new word pairs were extracted from the cued-recall phase of the task by using Principal Component Analysis. Subjects also performed a standardized neuropsychological verbal learning test. Results: Two of the three event-related potentials components indicating old/new memory effects provided evidence for anomalies associated with binge drinking. The old/new effects were absent in the binge drinkers in the two subsequent posterior components, identified with the late parietal component and the late posterior negativity The late frontal component revealed similar old/new effects in both groups. Binge drinkers showed similar behavioural performance to controls in the verbal paired associates task, but performed poorly in the more demanding short-term cued-recall trial of a neuropsychological standardized test. Conclusion: Event-related potentials elicited during a verbal cued-recall task revealed differences in brain functioning between young binge drinkers and controls that may underlie emergent deficits in episodic memory linked to alcohol abuse. The brain activity of binge drinkers suggests alterations in the hippocampal - posterior parietal cortex circuitry subserving recognition and recollection of the cue context and generation of the solution, in relation to verbal information shallowly memorised.
Pyridoxine biosynthesis protein MoPdx1 affects the development and pathogenicity of Magnaporthe oryzae

B vitamins are essential micro-organic compounds for the development of humans and animals. Vitamin B6 comprises a group of components including pyridoxine, pyridoxal, and pyridoxamine. In addition, vitamin B6 acts as the coenzymes in amino acid biosynthesis, decarboxylation, racemic reactions, and other biological processes. In this study, we found that the expressions of a gene encoding pyridoxine biosynthesis protein (PDX1) were significantly upregulated in the early infectious stages in M. oryzae. Furthermore, deletion of MoPDX1 slowed vegetative growth on different media, especially on MM media, and the growth defect was rescued when MoPdx1-protein was expressed in mutants strains and when commercial VB6 (pyridoxine) was added exogenously. However, VB6 content in different strains cultured in CM media has no significant difference, suggested that MoPdx1 was involved in de novo VB6 biosynthesis not in uptake process, and VB6 regulates the vegetative growth of M. oryzae. The ΔMopdx1 mutants presented abnormal appressorium turgor, slowed invasive growth and reduced virulence on rice seedlings and sheath cells. MoPdx1 was located in the cytoplasm and present in spore and germ tubes at 14 hours post inoculation (hpi) and then transferred into the appressorium at 24 hpi. Addition of VB6 in the conidial suspentions could rescue the defects of appressorium turgor pressure at 14 hpi or 24 hpi, invasive growth and pathogenicity of the MoPDX1 deletion mutants. Indicated that MoPdx1 affected the appressorium turgor pressure, invasive growth and virulence mainly depended on de novo VB6, and VB6 was biosynthesized in conidia, then transported into the appressorium, which play important roles in substances transportation from conidia to appressorium thus to regulate the appressorium turgor pressure. However, deletion of MoPDX1 did not affect the ability that scavenge ROS produced by rice cells, and the mutant strains were unable to activate host defense responses. In addition, co-immunoprecipitation (Co-IP) assays investigating potential MoPdx1-interacting proteins suggested that MoPdx1 might take part in multiple pathways, especially in the ribosome and in biosynthesis of some substances. These results indicate that vitamins are involved in the development and pathogenicity of M. oryzae.
A long non-coding RNA that harbors a SNP associated with type 2 diabetes regulates the expression of TGM2 gene in pancreatic beta cells

Introduction Most of the disease-associated single nucleotide polymorphisms (SNPs) lie in non- coding regions of the human genome. Many of these variants have been predicted to impact the expression and function of long non-coding RNAs (lncRNA), but the contribution of these molecules to the development of complex diseases remains to be clarified. Methods Here, we performed a genetic association study between a SNP located in a lncRNA known as LncTGM2 and the risk of developing type 2 diabetes (T2D), and analyzed its implication in disease pathogenesis at pancreatic beta cell level. Genetic association study was performed on human samples linking the rs2076380 polymorphism with T2D and glycemic traits. The pancreatic beta cell line EndoC-bH1 was employed for functional studies based on LncTGM2 silencing and overexpression experiments. Human pancreatic islets were used for eQTL analysis. Results We have identified a genetic association between LncTGM2 and T2D risk. Functional characterization of the LncTGM2 revealed its implication in the transcriptional regulation of TGM2, coding for a transglutaminase. The T2Dassociated risk allele in LncTGM2 disrupts the secondary structure of this lncRNA, affecting its stability and the expression of TGM2 in pancreatic beta cells. Diminished LncTGM2 in human beta cells impairs glucose-stimulated insulin release. Conclusions These findings provide novel information on the molecular mechanisms by which T2D-associated SNPs in lncRNAs may contribute to disease, paving the way for the development of new therapies based on the modulation of lncRNAs.