Miracle-dz/UniFAR-FTUs huggingface dataset:
Population genetic structure and geographical variation in Neotricula aperta (Gastropoda: Pomatiopsidae), the snail intermediate host of Schistosoma mekongi (Digenea: Schistosomatidae)

Background Neotricula aperta is the snail-intermediate host of the parasitic blood-fluke Schistosoma mekongi which causes Mekong schistosomiasis in Cambodia and the Lao PDR. Despite numerous phylogenetic studies only one DNA-sequence based population-genetic study of N. aperta had been published, and the origin, structure and persistence of N. aperta were poorly understood. Consequently, a phylogenetic and population genetic study was performed, with addition of new data to pre-existing DNA-sequences for N. aperta from remote and inaccessible habitats, including one new taxon from Laos and 505 bp of additional DNA-sequence for all sampled taxa,. Principal findings Spatial Principal Component Analysis revealed the presence of significant spatial-genetic clustering. Genetic-distance-based clustering indicated four populations with near perfect match to a priori defined ecogeographical regions. Spring-dwelling taxa were found to form an ecological isolate relative to other N. aperta. The poor dispersal capabilities suggested by spatial-genetic analyses were confirmed by Bayesian inference of migration rates. Population divergence time estimation implied a mid-Miocene colonisation of the present range, with immediate and rapid radiation in each ecogeographical region. Estimated effective population sizes were large (120–310 thousand). Conclusions The strong spatial-genetic structure confirmed the poor dispersal capabilities of N. aperta—suggesting human-mediated reintroduction of disease to controlled areas as the primary reason for control failure. The isolation of the spring-dwelling taxa and ecogeographical structure suggests adaptation of sub-populations to different habitats; the epidemiological significance of this needs investigation. The large effective population sizes indicate that the high population densities observed in surveyed habitats are also present in inaccessible areas; affording great potential for recrudescence driven by animal-reservoir transmission in remote streams. Mid-Miocene colonisation implies heterochronous evolution of these snails and associated schistosomes and suggests against coevolution of snail and parasite. Heterochronicity favours ecological factors as shapers of host-parasite specificity and greater potential for escape from schistosomiasis control through host-switching.
Cholesterol Metabolism: A Potential Therapeutic Target in Glioblastoma

Glioblastoma is a highly lethal adult brain tumor with no effective treatments. In this review, we discuss the potential to target cholesterol metabolism as a new strategy for treating glioblastomas. Twenty percent of cholesterol in the body is in the brain, yet the brain is unique among organs in that it has no access to dietary cholesterol and must synthesize it de novo. This suggests that therapies targeting cholesterol synthesis in brain tumors might render their effects without compromising cell viability in other organs. We will describe cholesterol synthesis and homeostatic feedback pathways in normal brain and brain tumors, as well as various strategies for targeting these pathways for therapeutic intervention.
Development of a perceived exertion scale for dogs using selected physiologic parameters

OBJECTIVE To develop a perceived exertion scale for dogs exercising on a treadmill and to assess intra- and inter-observer variability. MATERIALS AND METHODS Fifteen healthy client-owned dogs participated in paired exercise trials. Measurements of lactate, glucose, heart rate, temperature, respiratory rate and regional tissue oximetry were obtained before, during and after exercise. Perceived exertion scale scores were recorded during exercise and using video recordings to evaluate inter-observer variability. Correlations were evaluated using the Spearman's non-parametric method. RESULTS Thirteen dogs completed both trials. Dogs walked or trotted on the treadmill with an average perceived exertion score of 2 in both trials. Holter heart rate was positively correlated with perceived exertion scale scores from all observers for both trials. In trial 1, plasma glucose decreased in association with increase in perceived exertion and, in trial 2, cutaneous oximetry decreased, respiratory rate increased and temperature increased with increases on the perceived exertion scale. Inter-observer perceived exertion scale scores were positively correlated in both trials. There was no intra-observer variability between trials. CLINICAL SIGNIFICANCE The perceived exertion scale correlated with the measured physiologic parameters in dogs exercising at mild to moderate intensity. The perceived exertion scale was consistent and repeatable but larger study numbers and further validation are needed before it can be widely applied.
Work productivity of people with a psychiatric disability working in social firms.

BACKGROUND Several factors impact work productivity in employees with a psychiatric condition. OBJECTIVE In the context of social firms (SFs) the goal of this study is to test a theoretical model to predict work productivity across time, while considering worker and workplace factors. METHODS 222 people with a psychiatric disability employed in SFs were enrolled in a longitudinal study (6 month follow up) and completed the baseline battery of questionnaires on health (severity of symptoms), individual (self-esteem as a worker) and organizational factors (organizational constraints and supervisory support), and their work productivity (also measured at follow-up). Path analysis was used to test the hypothetical model, assessing individual and organizational factors in the context of social firms that could facilitate or hamper work productivity in the immediate term (T1), as well as the stability of work productivity in the middle/long term (T2 or 6 month follow up). RESULTS Work productivity of people with a psychiatric disability was affected negatively by severity of the symptoms, organizational constraints, and positively by self- esteem as a worker at T1. The stability of work productivity was significant across time (T2). Supervisor support was only related to work productivity at 6 month follow-up. CONCLUSIONS The results highlight the importance of the supportive workplaces for people with mental disorders that SFs provide, and the stability of work productivity across time. Supervisor support seems to have a delayed impact on work productivity. In future studies, researchers could determine how individual and organizational variables influence job tenure of employees with a psychiatric disability.
Disgust assessment: Factorial structure and psychometric properties of the French version of the Disgust Propension and Sensibility Scale Revised-12

The present study examined the internal and external validity of the French version of the 12-item Disgust Propensity and Sensitivity Scale-Revised (DPSS-12) in a nonclinical sample from the general population. Two hundred and eighty-two participants completed the DPSSf-12 questionnaire as well as the Anxiety Sensitivity Index (ASI), Anxiety Trait (STAI B), Obsessional Belief Questionnaire 44 items (OBQ 44), Obsessive Compulsive Inventory-Revised (OCI-R) and Positive and Negative Affect Schedule (PANAS). Confirmatory Factor Analysis supported a 2-factor structure after two sensitivity items were removed. The 10-item scale showed good internal consistency, construct validity and test-retest reliability. These adequate psychometric properties make the DPSSf-10 appropriate for use by researchers and practitioners.
Robust Depth Estimation for Light Field Microscopy

Light field technologies have seen a rise in recent years and microscopy is a field where such technology has had a deep impact. The possibility to provide spatial and angular information at the same time and in a single shot brings several advantages and allows for new applications. A common goal in these applications is the calculation of a depth map to reconstruct the three-dimensional geometry of the scene. Many approaches are applicable, but most of them cannot achieve high accuracy because of the nature of such images: biological samples are usually poor in features and do not exhibit sharp colors like natural scene. Due to such conditions, standard approaches result in noisy depth maps. In this work, a robust approach is proposed where accurate depth maps can be produced exploiting the information recorded in the light field, in particular, images produced with Fourier integral Microscope. The proposed approach can be divided into three main parts. Initially, it creates two cost volumes using different focal cues, namely correspondences and defocus. Secondly, it applies filtering methods that exploit multi-scale and super-pixels cost aggregation to reduce noise and enhance the accuracy. Finally, it merges the two cost volumes and extracts a depth map through multi-label optimization.
Switching strategies in the recent era of antiretroviral therapy

ABSTRACT Introduction: Although antiretroviral therapy is highly effective, many patients may benefit from switching strategies. Rapid advances in the development of new antiretroviral drugs could enhance the success of these approaches. In this review, we build on a previous review from 2014 and summarize the current options for switching strategies in virologically suppressed HIV-infected patients. Areas covered: We conduct a critical analysis of scientific evidence for various switching strategies used in the modern era of antiretroviral therapy, as well as reasons for these approaches, other considerations to be taken into account, and alternative strategies. Expert opinion: Current antiretroviral regimens are effective and well tolerated in HIV patients. A number of options may provide benefit to patients, even virologically suppressed patients, possibly enhancing adherence and avoiding adverse effects and toxicities. Cost reduction may also be an important goal of switching strategies. The present scenario is excellent, as many good antiretroviral compounds and regimens allow clinicians to further improve on effective treatments now used in routine practice. Even the current paradigm of triple-drug regimens as the standard of care could change, at least in some patients.
A Comparison of Multilevel Imputation Schemes for Random Coefficient Models: Fully Conditional Specification and Joint Model Imputation with Random Covariance Matrices

Abstract Literature addressing missing data handling for random coefficient models is particularly scant, and the few studies to date have focused on the fully conditional specification framework and “reverse random coefficient” imputation. Although it has not received much attention in the literature, a joint modeling strategy that uses random within-cluster covariance matrices to preserve cluster-specific associations is a promising alternative for random coefficient analyses. This study is apparently the first to directly compare these procedures. Analytic results suggest that both imputation procedures can introduce bias-inducing incompatibilities with a random coefficient analysis model. Problems with fully conditional specification result from an incorrect distributional assumption, whereas joint imputation uses an underparameterized model that assumes uncorrelated intercepts and slopes. Monte Carlo simulations suggest that biases from these issues are tolerable if the missing data rate is 10% or lower and the sample is composed of at least 30 clusters with 15 observations per group. Furthermore, fully conditional specification tends to be superior with intraclass correlations that are typical of crosssectional data (e.g., ICC = .10), whereas the joint model is preferable with high values typical of longitudinal designs (e.g., ICC = .50).
Satisfaction and Needs in Serious Mental Illness and Autism Spectrum Disorder: The REHABase Psychosocial Rehabilitation Project.

OBJECTIVE: The REHABase project is a French observational, prospective, and multicenter cohort study of serious mental illness and autism spectrum disorder (ASD), launched in 2016 for a planned minimum duration of 15 years. The aim is to characterize the care and quality-of-life needs of participants. This article presents initial results from data collection. METHODS: Psychosocial, cognitive, and functional data were collected at baseline, annually, and after rehabilitation care. Data from the baseline evaluation on diagnoses, medications, well-being, insight, life satisfaction, and care needs are presented. The clinical profiles of REHABase participants with serious mental illness or ASD were assessed in relation to their level of satisfaction with life and well-being in nine life dimensions and their needs, according to their stage of recovery in a five-stage model. RESULTS: Baseline data were collected for 1,397 participants between January 2016 and August 2018. Main diagnoses were schizophrenia spectrum disorder (49%); ASD (13%); and personality (12%), bipolar (9%), and major depressive (6%) disorders. More than 50% of participants reported needs for care or interventions in four of nine dimensions: employment, cognitive functioning, symptom management, and interpersonal relationships. Nearly half of participants were not in the active stages of recovery (stages 4 and 5), and even those considered to have reached the final stage continued to require help in several areas. CONCLUSIONS: Most participants had already received psychiatric care for several years, and most remained dissatisfied with their social and emotional life and their psychological well-being.
Dynamic structural biology at the protein membrane interface

Since I started doing scientific research, I've been fascinated by the interplay of protein structure and dynamics and how they together mediate protein function. A particular area of interest has been in understanding the mechanistic basis of how lipid-signaling enzymes function on membrane surfaces. In this award lecture article, I will describe my laboratory's studies on the structure and dynamics of lipid-signaling enzymes on membrane surfaces. This is important, as many lipid-signaling enzymes are regulated through dynamic regulatory mechanisms that control their enzymatic activity. This article will discuss my continued enthusiasm in using a synergistic application of hydrogen–deuterium exchange MS (HDX–MS) with other structural biology techniques to probe the mechanistic basis for how membrane-localized signaling enzymes are regulated and how these approaches can be used to understand how they are misregulated in disease. I will discuss specific examples of how we have used HDX–MS to study phosphoinositide kinases and the protein kinase Akt. An important focus will be on a description of how HDX–MS can be used as a powerful tool to optimize the design of constructs for X-ray crystallography and EM. The use of a diverse toolbox of biophysical methods has revealed novel insight into the complex and varied regulatory networks that control the function of lipid-signaling enzymes and enabled unique insight into the mechanics of membrane recruitment.
Sex-Specific Co-expression Networks and Sex-Biased Gene Expression in the Salmonid Brook Charr Salvelinus fontinalis

Networks of co-expressed genes produce complex phenotypes associated with functional novelty. Sex differences in gene expression levels or in the structure of gene co-expression networks can cause sexual dimorphism and may resolve sexually antagonistic selection. Here we used RNA-sequencing in the salmonid Brook Charr Salvelinus fontinalis to characterize sex-specific co-expression networks in the liver of 47 female and 53 male offspring. In both networks, modules were characterized for functional enrichment, hub gene identification, and associations with 15 growth, reproduction, and stress-related phenotypes. Modules were then evaluated for preservation in the opposite sex, and in the congener Arctic Charr Salvelinus alpinus. Overall, more transcripts were assigned to a module in the female network than in the male network, which coincided with higher inter-individual gene expression and phenotype variation in the females. Most modules were preserved between sexes and species, including those involved in conserved cellular processes (e.g., translation, immune pathways). However, two sex-specific male modules were identified, and these may contribute to sexual dimorphism. To compare with the network analysis, differentially expressed transcripts were identified between the sexes, revealing a total of 16% of expressed transcripts as sex-biased. For both sexes, there was no overrepresentation of sex-biased genes or sex-specific modules on the putative sex chromosome. Sex-biased transcripts were also not overrepresented in sex-specific modules, and in fact highly male-biased transcripts were enriched in preserved modules. Comparative network analysis and differential expression analyses identified different aspects of sex differences in gene expression, and both provided new insights on the genes underlying sexual dimorphism in the salmonid Brook Charr.
Prognostic and diagnostic significance of circRNAs expression in hepatocellular carcinoma patients: A meta‐analysis

Circular RNAs (circRNAs) as novel biomarkers are widely investigated in various cancers. The aim of our study was to reveal the clinicopathological, prognostic, and diagnostic features of circRNAs in human hepatocellular carcinoma (HCC). A systematical search was conducted on PubMed, Scopus, Web of Science (WOS), EMBASE, and the Cochrane Library databases. Eligible studies reporting on the association among circRNAs and clinicopathological, prognostic, diagnostic values of HCC patients were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to assess clinicopathological parameters, sensitivity, and specificity, and hazard ratios (HRs) were to evaluate overall survival (OS). 17 eligible studies which included 7 for clinicopathological features, 10 for prognosis, and 8 for diagnosis were in our study. As for clinicopathological parameters, high expression of oncogenic circRNAs had a significant association with poor clinicopathological features and tumor‐suppressor circRNAs proved the contrary. In terms of the prognostic values, oncogenic circRNAs had a negative influence on overall survival (OS: HR = 3.39, 95%Cl: 2.59‐4.19), and high expression of tumor‐suppressor circRNAs was relevant to improved survival outcomes (OS: HR = 0.46, 95%Cl: 0.37‐0.56). The pooled diagnostic outcomes indicated an area under the curve (AUC) of 0.84, with sensitivity of 82% and specificity of 72% in discriminating HCC from controls. Our study indicates that circRNAs may be important biomarkers for prognostic and diagnostic values of HCC.
Effectiveness of seasonal influenza vaccination of children in Senegal during a year of vaccine mismatch: a cluster-randomized trial.

Background Population effects of influenza vaccination of children have not been extensively studied, especially in tropical developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of inactivated influenza vaccine, trivalent (IIV3). Methods In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for high-coverage vaccination of children aged 6 months through 10 years with 2008-09 northern hemisphere IIV3 or inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza. Results Between May 23 and July 11, 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until May 28, 2010. Four unrelated serious adverse events were identified. Among vaccinees, total effectiveness against illness caused by seasonal influenza virus (presumed all drifted A/H3N2 based on antigenic characterization data) circulating at high rates among children was 43.6% (95% CI, 18.6% to 60.9%). Indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI, -22.0% to 41.3%). Total effectiveness against illness caused by pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI, -177.2% to 16.6%). Conclusions IIV3 provided statistically significant, moderate protection to children in Senegal against circulating pre-2010 seasonal influenza strains but not against A/H1N1pdm09 not included in the vaccine. No indirect effects were measured. Further study in low resource populations is warranted.
Seeking allosteric networks in PDZ domains

Abstract Ever since Ranganathan and coworkers subjected the covariation of amino acid residues in the postsynaptic density-95/Discs large/Zonula occludens 1 (PDZ) domain family to a statistical correlation analysis, PDZ domains have represented a paradigmatic family to explore single domain protein allostery. Nevertheless, several theoretical and experimental studies in the past two decades have contributed contradicting results with regard to structural localization of the allosteric networks, or even questioned their actual existence in PDZ domains. In this review, we first describe theoretical and experimental approaches that were used to probe the energetic network(s) in PDZ domains. We then compare the proposed networks for two well-studied PDZ domains namely the third PDZ domain from PSD-95 and the second PDZ domain from PTP-BL. Our analysis highlights the contradiction between the different methods and calls for additional work to better understand these allosteric phenomena.
Pregnancy and cardiovascular risk

We read with great interest the study by Li et al. In their meta-analysis of cohort studies, the authors conclude that ever parity is related to cardiovascular disease risk and that there is an association between the number of pregnancies and the risk of cardiovascular disease. In our view, this conclusion might deliver a dangerous message and is not supported by the data. First, these authors have previously described associations of parity with obesity and diabetes that could explain, at least in part, these findings. Second, a welldesigned large study not included in the present metaanalysis, adjusted for confounders as cardiovascular risk factors and lifestyle, found no consistent relationships between parity and total, ischaemic heart disease or stroke mortality. Third, beneficial effects of pregnancy in the cardiovascular system have been described, and the number of previous pregnancies is independently associated with better survival in women with heart failure. There is an insufficient birth rate in western countries and many others, and the consequences of having so few children include population loss, increased aging and economic and affective impoverishment. This demographic suicide is already a brutal problem and we, as physicians, should be extremely careful before rushing to embrace theories that might make pregnancy less appealing for many women.