Miracle-dz/UniFAR-FTUs huggingface dataset:
Les protéines à ancre GPI de Candida albicans dans l’interaction avec l’hôte : de l’étude de domaines solubles à la caractérisation de la protéine Rbt1

Candida albicans est un pathogene opportuniste present a l'etat commensal chez 75% de la population. Il s'agit du premier pathogene d'origine fongique (4eme cause d'infections nosocomiales) responsable d'infections superficielles chez les personnes immunocompetentes ou d'infections profondes chez les personnes immunodeprimees. Les proteines a ancre GPI (Glycosyl Phosphatidyl Inositol) de C. albicans, situees a l'interface entre la levure et les cellules de l'hote, semblent etre les plus aptes a moduler la reponse immunitaire. Au cours de cette etude, une banque de surexpression et de secretion d'une vingtaine de domaines fonctionnels putatifs issus de proteines a ancre GPI potentiellement exposees a la surface a ete construite. Le crible realise a permis d'identifier sept polypeptides impliques dans la modulation de la reponse des cellules macrophages et trois polypeptides ayant des proprietes immunogenes. Dans un deuxieme projet, nous avons demontre que la proteine a ancre GPI Rbt1 specifique des hyphes de C. albicans avait des proprietes d'adhesines aux substrats abiotiques et contribuait a la formation de biofilm et d'agregats. La caracterisation de cette proteine a permis d'apporter des donnees nouvelles concernant l'exposition en surface de proteines membranaires suivant la forme morphologique de C. albicans.
Separation of nasopharyngeal epithelial cells from carcinoma cells on 3D scaffold platforms

Scaffold microstructures were developed to mimic a three‐dimensional extracellular matrix in studying cell migration and invasion. The multiple‐layer scaffold platforms were designed to investigate cell migration and separation from top to bottom layer. Two cell lines including immortalized nasopharyngeal epithelial (NP460) cells and nasopharyngeal carcinoma (NPC43) cells with Epstein–Barr virus were compared in this study. On one‐layer platforms with trench depth of 15 µm, both NP460 and NPC43 cells were guided to migrate along the 18‐µm‐wide trenches, and exhibited random migration directions when the trench width was 10 or 50 µm. Nearly no cell was found to migrate in the 10‐µm‐wide trenches on one‐layer platforms. However, the NP460 and NPC43 cells showed very different probability in the narrow trenches on two‐layer platforms, making it possible to separate the nasopharyngeal epithelial cells from the carcinoma cells. Moreover, 1‐µm deep grating topography on the top layer inhibited NP460 cells to migrate from top ridges to the 10‐µm‐wide trenches, but promoted such behavior for NPC43 cells. The results demonstrated in This study suggest that the engineered multiple‐layer scaffold platforms could be used to separate carcinoma cells in NPC tumor as a potential treatment of NPC.
Dog Welfare, Well-Being and Behavior: Considerations for Selection, Evaluation and Suitability for Animal-Assisted Therapy

Simple Summary Benefits for humans participating in animal-assisted therapy (AAT) have been long documented; however, welfare considerations for the animal counterparts are still quite non-specific, often relating to more general concerns associated with animal-assisted interventions (AAIs). Providers of AAT have a moral and ethical obligation to extend the “Do No Harm” tenet to the animals with whom they work. Companion animals do not ask or voluntarily sign up to be a part of a therapeutic team and their natural traits of love and sociability can easily be misinterpreted and exploited. This article reviews the current state of animal-assisted interventions; it highlights the lack of sufficient evaluation processes for dogs working with AAT professionals, as well as the risks associated with not protecting the dogs’ welfare. Finally, the authors make recommendations for determining the suitability of specific dogs in the clinical setting and ensuring that the population, environment, and context of the work is amenable to the dogs’ welfare and well-being. Abstract Health care and human service providers may include dogs in formal intervention settings to positively impact human physical, cognitive and psychosocial domains. Dogs working within this context are asked to cope with a multitude of variables including settings, populations, activities, and schedules. In this article, the authors highlight how both the preparation and operation of dogs within animal-assisted therapy (AAT) differs from less structured animal-assisted activities (AAA) and more exclusive assistance animal work; the authors highlight the gaps in our knowledge in this regard, and propose an ethically sound framework for pragmatic solutions. This framework also emphasizes the need for good dog welfare to safeguard all participants. If dogs are not properly matched to a job or handler, they may be subjected to unnecessary stress, anxiety, and miscommunication that can lead to disinterest in the work, overt problematic behavioral or health outcomes, or general unsuitability. Such issues can have catastrophic outcomes for the AAT. The authors propose standards for best practices for selection, humane-based preparation and training, and ongoing evaluation to ensure the health, welfare and well-being of dogs working in AAT, which will have concomitant benefits for clients and the professionalism of the field.
Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain

Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24–32 months) versus young mice (2–4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.
Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program

Background Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.
Copula-Based Data Augmentation on a Deep Learning Architecture for Cardiac Sensor Fusion

In the wake of Big Data, traditional Machine Learning techniques are now often integrated in the clinical workflow. Despite more capable, Deep Learning methods are not equally accepted given their unsatiated need for great amounts of training data and transversal use of the same architectures in fundamentally different areas with weakly-substantiated adaptations. To address the former, a cardiorespiratory signal synthesizer was designed by conditional sampling from a multimodally trained stochastic system of Gaussian copulas integrated in a Markov chain. With respect to the latter, a multi-branch convolutional neural network architecture was conceived to learn the best cardiac sensor-fusion strategy at every abstraction layer. The network was tailored to the tasks of cycle detection and classification for different cardiac modality combinations by a synthesizer-based data augmentation training framework and Bayesian hyperparameter optimization. The synthesizer yielded highly realistic signals in the time, frequency and phase domains for both healthy and pathological heart cycles as well as artifacts of different modalities. Benchmarking suggested that the network is able to surpass previous architectures and data augmentation provided a performance boost in realistic data availability scenarios. These included insufficient training data volume, as low as 150 cycles long, artifact contamination and absence of a classification data type in training.
Fully Automated Breast Density Segmentation and Classification Using Deep Learning

Breast density estimation with visual evaluation is still challenging due to low contrast and significant fluctuations in the mammograms’ fatty tissue background. The primary key to breast density classification is to detect the dense tissues in the mammographic images correctly. Many methods have been proposed for breast density estimation; nevertheless, most of them are not fully automated. Besides, they have been badly affected by low signal-to-noise ratio and variability of density in appearance and texture. This study intends to develop a fully automated and digitalized breast tissue segmentation and classification using advanced deep learning techniques. The conditional Generative Adversarial Networks (cGAN) network is applied to segment the dense tissues in mammograms. To have a complete system for breast density classification, we propose a Convolutional Neural Network (CNN) to classify mammograms based on the standardization of Breast Imaging-Reporting and Data System (BI-RADS). The classification network is fed by the segmented masks of dense tissues generated by the cGAN network. For screening mammography, 410 images of 115 patients from the INbreast dataset were used. The proposed framework can segment the dense regions with an accuracy, Dice coefficient, Jaccard index of 98%, 88%, and 78%, respectively. Furthermore, we obtained precision, sensitivity, and specificity of 97.85%, 97.85%, and 99.28%, respectively, for breast density classification. This study’s findings are promising and show that the proposed deep learning-based techniques can produce a clinically useful computer-aided tool for breast density analysis by digital mammography.
USP7, negatively regulated by miR‐409‐5p, aggravates hypoxia‐induced cardiomyocyte injury

Hypoxia‐induced apoptosis is linked to the pathogenesis of myocardial infarction (MI) and heart failure. Ubiquitin‐specific peptidase 7 (USP7) is related to catabolic/pro‐apoptotic signaling. However, its role in cardiomyocyte injury is unclear. In this study, we aimed to investigate the role and the underlying regulatory mechanism of USP7 in MI. H9c2 cardiomyocytes were cultured in hypoxia to establish an in vitro model of myocardial hypoxic/ischemic injury. Sprague‐Dawley (SD) rats were used to establish animal models with MI. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot assays were performed to evaluate the expression levels of miR‐409‐5p, USP7, and p53, respectively. After USP7 and miR‐409‐5p were selectively regulated in H9c2 cells, the inflammatory response, apoptosis, and cell viability were detected by ELISA, flow cytometry, and MTT assay, respectively. The interaction between USP7 and miR‐409‐5p was determined by bioinformatics analysis, qRT‐PCR, Western blot, and dual‐luciferase reporter assay. LVEF, LVIDd, and LVIDs of rats after MI were also measured. USP7 expression was markedly elevated while miR‐409‐5p expression was significantly down‐regulated in H9c2 cells under hypoxic culture. Augmentation of USP7 expression led to a dramatic promotion of hypoxia‐induced apoptosis of cardiomyocytes, accompanied by an increase in the secretion of the cytokines IL‐1β, TNF‐α, and IL‐6. Myocardial injury markers LDH, cTnI, and CK‐MB expressions were also increased. Besides, overexpression of USP7 aggravated left ventricular remodeling and decreased left ventricular function of the rats. Conversely, the up‐regulation of miR‐409‐5p expression protected H9c2 cells from apoptosis and inhibited the release of cytokines and myocardial injury. Left ventricular remodeling and left ventricular function were also improved by miR‐409‐5p overexpression. Furthermore, USP7 was identified as a target of miR‐409‐5p and the overexpression of miR‐409‐5p reversed the effects of USP7 on H9c2 cells. USP7 exacerbates myocardial ischemic injury by promoting inflammation and apoptosis of cardiomyocytes, and the up‐regulation of its expression is partly caused by the down‐regulation of miR‐409‐5p expression.
The influence of COVID-19 measures in the United Kingdom on physical activity levels, perceived physical function and mood in older adults: A survey-based observational study

ABSTRACT In March 2020, the spreading Coronavirus (COVID-19) prompted the United Kingdom government to introduce a societal shutdown, accompanied by self-isolation and social-distancing measures to reduce virus transmission. In doing so, opportunities for physical activity were likely reduced, potentially causing detrimental effects to older adults. Therefore, the present study investigated the influence of the initial six weeks of lockdown on physical activity levels, perceived physical function and mood in older adults. A cross-sectional, mixed-methods, observational study was conducted using self-administered, fortnightly online surveys throughout the UK between 21st March–4 May 2020. A total of 117 participants (52 males [age: 76 ± 4 years] and 65 females [age: 76 ± 4 years]) completed all surveys. Despite lockdown restrictions, this group of older adults maintained their pre-lockdown physical activity levels, but also increased their self-reported sedentary time. Subsequently, perception of physical function was maintained across lockdown. With regards to mood; the only strong evidence for an increase in depression was for males (ps = 95.35%; >0.3 AU), although self-reported levels of depression were similar between sexes at week six. Given the link between sedentary behaviour and negative health outcomes in older adults, strategies to reduce sedentariness during the COVID-19 pandemic are required.
Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis

BH3-mimetics inhibiting anti-apoptotic BCL-2 proteins represent a novel and promising class of antitumor drugs. While the BCL-2 inhibitor venetoclax is already approved by the Food and Drug Administration, BCL-XL and MCL-1 inhibitors are currently in early clinical trials. To predict side effects of therapeutic MCL-1 inhibition on the human hematopoietic system, we used RNA interference and the small molecule inhibitor S63845 on cord blood-derived CD34+ cells. Both approaches resulted in almost complete depletion of human hematopoietic stem and progenitor cells. As a consequence, maturation into the different hematopoietic lineages was severely restricted and CD34+ cells expressing MCL-1 shRNA showed a very limited engraftment potential upon xenotransplantation. In contrast, mature blood cells survived normally in the absence of MCL-1. Combined inhibition of MCL-1 and BCL-XL resulted in synergistic effects with relevant loss of colony-forming hematopoietic stem and progenitor cells already at inhibitor concentrations of 0.1 mM each, indicating “synthetic lethality” of the two BH3- mimetics in the hematopoietic system.
Single-cell peripheral immunoprofiling of Alzheimer’s and Parkinson’s diseases

Peripheral immune responses of Alzheimer’s disease patients are uniquely different from those of healthy and disease controls. Peripheral blood mononuclear cells (PBMCs) may provide insight into the pathogenesis of Alzheimer’s disease (AD) or Parkinson’s disease (PD). We investigated PBMC samples from 132 well-characterized research participants using seven canonical immune stimulants, mass cytometric identification of 35 PBMC subsets, and single-cell quantification of 15 intracellular signaling markers, followed by machine learning model development to increase predictive power. From these, three main intracellular signaling pathways were identified specifically in PBMC subsets from people with AD versus controls: reduced activation of PLCγ2 across many cell types and stimulations and selectively variable activation of STAT1 and STAT5, depending on stimulant and cell type. Our findings functionally buttress the now multiply-validated observation that a rare coding variant in PLCG2 is associated with a decreased risk of AD. Together, these data suggest enhanced PLCγ2 activity as a potential new therapeutic target for AD with a readily accessible pharmacodynamic biomarker.
The nexus between environmental tax and carbon emissions with the roles of environmental technology and financial development

This study evaluates the impacts of renewable energy, environmental taxes, environmental technology, and financial development on carbon emissions in OECD economies from 1995 to 2015 by employing system-GMM and quantile regression approaches. Our empirical analysis indicates that environmental tax negatively affects carbon emissions; economic growth impedes environmental quality by increasing carbon emissions. Further, renewable energy consumption, environmental technology, and financial development improve environmental quality by decreasing carbon emissions. We suggest that changes in policymaking to promote sustainable economic growth and environmental quality should be prevent environmental degradation, but also inspire greater investments in new technologies and energy expertise in the renewables industry.
No Correlation Between Depth of Acetabuloplasty or Postoperative Lateral Center-Edge Angle on Midterm Outcomes of Hip Arthroscopy With Acetabuloplasty and Labral Repair

Background: The treatment of pincer deformity in hip arthroscopy remains controversial, with some authors advocating that over resection may risk early joint deterioration. The role of acetabular resection depth and postoperative acetabular morphology on postoperative outcomes has yet to be defined. Purpose/Hypothesis: This study measures the influence of acetabular resection depth and postoperative lateral center-edge angle (LCEA) on minimum 5-year patient-reported outcomes (PROs), revision rates, and conversion to total hip arthroplasty using a single surgeon’s prospective database. We hypothesized that patients with acetabular resections >10°, as measured by LCEA, or patients with postoperative LCEA outside the normal range of 25° to 35° would have lower PROs, higher revision rates, and higher conversion to total hip arthroplasty at midterm follow-up. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 192 patients who underwent primary hip arthroscopy with acetabuloplasty and labral repair by a single surgeon with a minimum 5-year follow-up met the inclusion criteria. Preoperative and postoperative LCEAs were measured on supine anteroposterior radiographs, and patients were divided into cohorts based on LCEA and acetabular resection depth. Cohorts for postoperative LCEA were <20° (dysplasia), 20° to 25° (borderline dysplasia), 25° to 35° (normal), and >35° (borderline overcoverage). Cohorts for acetabular resection depth were <5°, 5° to 10°, and >10° difference from preoperative to postoperative LCEA. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), 12-Item Short Form Health Survey, modified Harris Hip Score, Hip Outcome Score, satisfaction scores, revision rates, and conversion to arthroplasty rates. Results: Patients significantly improved in all outcome score measures at final follow-up. There were no statistically significant differences in PRO scores or conversion to total hip arthroplasty between any cohorts in the postoperative LCEA group. There were more revisions in the 25° to 35° cohort than the other cohorts (P = .02). The 5-10° resection depth cohort demonstrated a higher postoperative WOMAC score (P = .03), but otherwise no statistically significant differences were seen between resection depth cohorts in the remaining postoperative outcomes scores, revision rates, or conversion to total hip arthroplasty rates. Conclusion: Patients with postoperative LCEA values outside the normal reference range and with large resections perform similar to those with normal postoperative LCEA values and smaller resections at a minimum 5-year follow-up.