Miracle-dz/UniFAR-FTUs huggingface dataset:
Gonadectomy and dehydroepiandrosterone (DHEA) do not modulate disease progression in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis

Abstract Epidemiological studies have shown a higher incidence of amyotrophic lateral sclerosis (ALS) in men than women. Interestingly, there are clear gender differences in disease onset and progression in rodent models of familial ALS overexpressing mutated human superoxide dismutase-1 (SOD1-G93A). In the present study we sought to determine whether the alterations of serum steroid levels by gonadectomy or chronic treatment of neuroprotective neurosteroids can modulate disease onset and progression in a rat model of ALS (SOD1-G93A transgenic rats). Presymptomatic SOD1-G93A rats were gonadectomized or treated with a neurosteroid dehydroepiandrosterone (DHEA) using silastic tubing implants. Disease onset and progression of the animals were determined by the routine analyses of locomotor testing using the Basso-Beattie-Bresnahan (BBB) score. Although sexual dimorphism was observed in intact and gonadectomized SOD1-G93A rats, there was no significant effect of gonadectomy on disease onset and progression. DHEA treatment did not alter disease progression or survival in SOD1-G93A rats. Our results indicate that gonadal steroids or neurosteroids are not one of the possible modulators for the occurrence or disease progression in a rat model of ALS. Further analysis will be necessary to understand how sexual dimorphism is involved in ALS disease progression.
Differential interactions of missing in metastasis and insulin receptor tyrosine kinase substrate with RAB proteins in the endocytosis of CXCR4

Missing in metastasis (MIM), an inverse Bin–Amphiphysin–Rvs (I-BAR) domain protein, promotes endocytosis of C-X-C chemokine receptor 4 (CXCR4) in mammalian cells. In response to the CXCR4 ligand stromal cell–derived factor 1 (SDF-1 or CXCL12), MIM associates with RAS-related GTP-binding protein 7 (RAB7) 30 min after stimulation. However, RAB7's role in MIM function remains undefined. Here we show that RNAi-mediated suppression of RAB7 expression in human HeLa cells has little effect on the binding of MIM to RAB5 and on the recruitment of CXCR4 to early endosomes but effectively abolishes MIM-mediated CXCR4 degradation, chemotactic response, and sorting into late endosomes and lysosomes. To determine whether I-BAR domain proteins interact with RAB7, we examined cells expressing insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein bearing an Src homology 3 (SH3) domain. We observed that both MIM and IRTKS interact with RAB5 at an early response to SDF-1 and that IRTKS binds poorly to RAB7 but strongly to RAB11 at a later time point. Moreover, IRTKS overexpression reduced CXCR4 internalization and enhanced the chemotactic response to SDF-1. Interestingly, deletion of the SH3 domain in IRTKS abolished the IRTKS–RAB11 interaction and promoted CXCR4 degradation. Furthermore, the SH3 domain was required for selective targeting of MIM–IRTKS fusion proteins by both RAB7 and RAB11. Hence, to the best of our knowledge, our results provide first evidence that the SH3 domain is critical in the regulation of specific endocytic pathways by I-BAR domain proteins.
Carotid Near-Occlusion: A Comprehensive Review, Part 1—Definition, Terminology, and Diagnosis

Carotid near-occlusion is distal luminal collapse of the internal carotid artery beyond a tight stenosis. Calculating percentage stenosis for carotid near-occlusion is fallacious, and near-occlusion assessment is advised before measuring for percentage stenosis. This systematic review presents what is known about carotid near-occlusion and focuses on definition, terminology, and diagnosis. SUMMARY: Carotid near-occlusion is distal ICA luminal collapse beyond a tight stenosis, where the distal lumen should not be used for calculating percentage stenosis. Near-occlusion with full ICA collapse is well-known, with a threadlike lumen. However, near-occlusion without collapse is often subtle and can be overlooked as a usual severe stenosis. More than 10 different terms have been used to describe near-occlusion, sometimes causing confusion. This systematic review presents what is known about carotid near-occlusion. In this first part, the foci are definition, terminology, and diagnosis.
Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients

Delayed hemolytic transfusion reactions (DHTRs) are serious complications of RBC transfusion that can occur in previously alloimmunized patients. Patients who require episodic transfusions during heightened inflammatory states, such as patients with sickle cell disease (SCD), are particularly prone to alloimmunization and developing DHTRs with hyperhemolysis. While efforts to mitigate these hemolytic episodes via immunosuppressive drugs can be employed, the relative efficacy of various treatment options remains incompletely understood.
Advanced glycation end-products disrupt human endothelial cells redox homeostasis: new insights into reactive oxygen species production

Abstract Advanced glycation end-products (AGEs) trigger multiple metabolic disorders in the vessel wall that may in turn lead to endothelial dysfunction. The molecular mechanisms by which AGEs generate these effects are not completely understood. Oxidative stress plays a key role in the development of deleterious effects that occur in endothelium during diabetes. Our main objectives were to further understand how AGEs contribute to reactive oxygen species (ROS) overproduction in endothelial cells and to evaluate the protective effect of an antioxidant plant extract. The human endothelial cell line EA.hy926 was treated with native or modified bovine serum albumin (respectively BSA and BSA-AGEs). To monitor free radicals formation, we used H2DCF-DA, dihydroethidium (DHE), DAF-FM-DA and MitoSOX Red dyes. To investigate potential sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondrial inhibitors were used. The regulation of different types of ROS by the polyphenol-rich extract from the medicinal plant Doratoxylon apetalum was also studied for a therapeutic perspective. BSA-AGEs exhibited not only less antioxidant properties than BSA, but also pro-oxidant effects. The degree of albumin glycoxidation directly influenced oxidative stress through a possible communication between NADPH oxidase and mitochondria. D. apetalum significantly decreased intracellular hydrogen peroxide and superoxide anions mainly detected by H2DCF-DA and DHE respectively. Our results suggest that BSA-AGEs promote a marked oxidative stress mediated at least by NADPH oxidase and mitochondria. D. apetalum plant extract appeared to be an effective antioxidant compound to protect endothelial cells.
Does integral affect influence intentions to use artificial intelligence for skin cancer screening? A test of the affect heuristic

Abstract Objective: This study investigated how affect influences people’s processing of messages about risks and benefits of using autonomous artificial intelligence (AI) technology to screen for skin cancer. We examined integral affect (emotion derived during decision making) separately from incidental affect (extraneous mood states). Design: Using the affect heuristic framework, we randomly assigned 273 participants to conditions featuring risk (high, low, uncertain) or benefit (high, low, uncertain) messages about AI. Following ‘affect-as-spotlight’, we also explored whether people’s integral affect towards skin cancer moderated the relationship between risk/benefit messages and AI screening intentions. Outcomes: Perceived risk, perceived benefit, positive and negative affect toward AI, intention to use AI screening. Results: After controlling for incidental affect and risk perceptions, we found that compared to low risk messages, uncertain risk messages increased participants’ negative affect toward AI, decreased positive affect toward AI, increased AI risk evaluations and reduced AI benefit evaluations. Perceptual variables significantly mediated participants’ intentions to use AI for risk messages but not benefit messages. No moderation effects were found. Conclusions: Results suggest extending the affect heuristic framework to include uncertain risk conditions. Integral AI affect influenced people’s interpretation of messages, which then impacted likelihood to use AI technology for health.
Environment risk factors have different impact on bipolar and psychotic disorders: an analysis of MHGP survey

AP-HP, DHU PePSY, Hôpitaux universitaires Henri-Mondor, Pôle de Psychiatrie, Créteil 94000, France; Inserm, U955, team 15, Créteil 94000, France; Fondation FondaMental, Créteil 94000, France; UPEC, Université Paris-Est, Faculté de médecine, Créteil 94000, France; Paris Diderot Université – Paris VII, 5 Rue Thomas Mann, 75013 Paris, France; Univ. Lille, CNRS UMR 9193-PsyCHIC-SCALab, & CHU Lille, Pôle de Psychiatrie, Unité CURE, F-59000 Lille, France; Fédération régionale de recherche en santé mentale (F2RSM) Nord-Pas-de-Calais; F-59000 Lille, France; EPSM Lille Métropole; Centre Collaborateur de l’Organisation Mondiale de la Santé pour la recherche et la formation en santé mentale; Équipe Eceve Inserm UMR 1123, Lille, France and King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK
Social media addiction and social media reactions: The implications for job performance

ABSTRACT We investigate the intersection of social media and the workplace, focusing on job performance impacts of employees’ social media addictions and social media reactions through work–family balance and burnout. The research model is grounded in conservation of resources theory, which suggests social media compulsions and emotional reactions to co-worker’s social media posts will deplete employees’ energetic and constructive resources, making it difficult to achieve work-family balance and increasing the likelihood of job burnout, and will ultimately degrade job performance. A sample of 326 full-time employees revealed a negative relationship between social media addiction and work-family balance and a positive relationship between social media reactions and job burnout. Balance and burnout mediated the relationship between social media and job performance such that social media addiction was negatively related to job performance through work–family balance, and social media reactions were negatively related to performance through burnout and work–family conflict.
Who Are High Users of Hospitals in Canada? Findings From a Population-Based Study

Background Dying people and older people have often been thought of as high users of hospitals, but current population-based evidence is needed to confirm or refute this claim. Purpose Quantitative population-based study designed to identify and describe hospital patients who are high users. Methods Data for all 2014–2015 Canadian hospital patients (excluding Quebec) were analyzed to identify and describe high users through descriptive-comparative and regression analysis tests. Results Only a small proportion of patients are high users in relation to multiple admissions or 30+ inpatient days of care, and with considerable diversity among them and relatively few of these advanced in age or dying in hospital. Conclusions Relatively few patients are high users of hospitals. These people are most often under age 65, so they have the potential to be ill and high users for many years. Flagging would enable individualized care planning to reduce illness exacerbations or slow disease progression and address other risk factors for long or repeat hospitalizations.
Elevated myonuclear density during skeletal muscle hypertrophy in response to training is reversed during detraining.

Myonuclei gained during exercise-induced skeletal muscle hypertrophy may be long-lasting and could facilitate future muscle adaptability after deconditioning, a concept colloquially termed "muscle memory. " The evidence for this is limited, mostly due to the lack of a murine exercise-training paradigm that is nonsurgical and reversible. To address this limitation, we developed a novel progressive weighted-wheel-running (PoWeR) model of murine exercise training to test whether myonuclei gained during exercise persist after detraining. We hypothesized that myonuclei acquired during training-induced hypertrophy would remain following loss of muscle mass with detraining. Singly housed female C57BL/6J mice performed 8 wk of PoWeR, while another group performed 8 wk of PoWeR followed by 12 wk of detraining. Age-matched sedentary cage-dwelling mice served as untrained controls. Eight weeks of PoWeR yielded significant plantaris muscle fiber hypertrophy, a shift to a more oxidative phenotype, and greater myonuclear density than untrained mice. After 12 wk of detraining, the plantaris muscle returned to an untrained phenotype with fewer myonuclei. A finding of fewer myonuclei simultaneously with plantaris deconditioning argues against a muscle memory mechanism mediated by elevated myonuclear density in primarily fast-twitch muscle. PoWeR is a novel, practical, and easy-to-deploy approach for eliciting robust hypertrophy in mice, and our findings can inform future research on the mechanisms underlying skeletal muscle adaptive potential and muscle memory.
Trends in hepatocellular carcinoma due to non-alcoholic fatty liver disease

ABSTRACT Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and is associated with hepatocellular carcinoma (HCC), the most frequent malignant liver tumor. The increasing prevalence of obesity and diabetes is influencing the epidemiology of HCC with the most dramatic increases in NAFLD-related HCC seen in Western countries. Although cirrhosis is the major risk factor for HCC in NAFLD, there is increasing recognition that NAFLD-HCC occurs in the absence of cirrhosis. Areas covered: The epidemiology of NAFLD related HCC and its impact on changing the incidence of HCC globally. We overview risk factors for NAFLD-HCC in the presence and absence of cirrhosis and examine trends in liver transplantation (LT) related to NAFLD-HCC. Expert commentary: The incidence of NAFLD-related cirrhosis will continue to rise globally in parallel with risk factors of obesity and diabetes. Consequently, NAFLD-related HCC will become an increasingly important cause of liver-related morbidity and mortality and a common indication for LT worldwide. Further identification of risk factors for NAFLD-HCC and effective treatments for NAFLD are required to reduce this future burden of disease.
Eliciting Postactivation Potentiation With Hang Cleans Depends on the Recovery Duration and the Individual's 1 Repetition Maximum Strength

Abstract Dinsdale, AJ and Bissas, A. Eliciting postactivation potentiation with hang cleans depends on the recovery duration and the individual's 1 repetition maximum strength. J Strength Cond Res 35(7): 1817–1824, 2021—Acutely coupling biomechanically similar resistance exercises (e.g., back squats) with subsequent explosive movements (e.g., countermovement jumps [CMJs]) can elicit an enhancement in explosive force and power production, which is known as postactivation potentiation (PAP). However, limited information exists with regard to the coupling of hang cleans with the CMJ. The purpose of this study was to determine the effectiveness of the hang clean at eliciting PAP through the systematic appraisal of the implemented recovery interval. Twelve explosively trained male track and field athletes completed 8 randomized protocols. These consisted of a structured warm-up, 3 baseline CMJs performed on a force platform, 3 reps of hang cleans set at 90% of 1 repetition maximum (1RM), a randomized rest, and 3 post-CMJs. The rest intervals were set at 0 (T0), 1 (T1), 2 (T2), 3 (T3), 4 (T4), 5 (T5), and 6 (T6) minutes after completing the hang cleans. A repeated-measures analysis of variance showed that the hang cleans did not elicit PAP, although there were significant (p < 0.05) decreases in jump height (JH) for T0 (−4%), T2 (−3%), and T3 (−3.3%). Interestingly, when splitting the subjects based on absolute 1RM hang clean (above 80 kg = strong and below 80 kg = weak), significant differences (p < 0.05) in JH were observed between the groups at T1 (strong −1.2% and weak +3.8%) and T5 (strong +5.1% and weak −1.9%). Our results suggest that to elicit PAP when using hang-clean protocols, it is important to establish first the function between individual strength levels and recovery duration as this may lead to contrasting optimal performance windows for different explosively trained athletes.
Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study.

BACKGROUND Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). OBJECTIVES The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. METHODS We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. RESULTS We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. CONCLUSIONS The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.
Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in octogenarian patients with non-valvular atrial fibrillation

Background and objective Elderly patients with atrial fibrillation (AF) are known to have a high risk of stroke and bleeding. We investigated the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in octogenarian patients with non-valvular AF compared with warfarin. Methods A total of 687 octogenarian patients with AF who were administered NOACs (n = 403) or warfarin (n = 284) for stroke prevention between 2012 and 2016 were included. Thromboembolic (TE) events (stroke or systemic embolism), major bleeding events, and all-cause death were analyzed. Results The NOACs group (age 83.4±3.2 years, women 52.4%, CHA2DS2-VASc score 5.0±1.8) comprised 141 dabigatran, 158 rivaroxaban, and 104 apixaban users. Most patients from the NOACs group had been prescribed a reduced dose of medication (85.6%). During 14±18 months of follow-up periods, there were 19 TE events and 18 major bleeding events. Patients with NOAC showed a lower risk of TE (1.84 vs. 2.71 per 100 person-years, hazard ration [HR] 0.134, 95% confidence interval [CI] 0.038–0.479, P = 0.002), major bleeding (1.48 vs. 2.72 per 100 person-years, HR 0.110, 95% CI 0.024–0.493, P = 0.001), and all-cause death (2.57 vs. 3.50 per 100 person-years, HR 0.298, 95% CI 0.108–0.824, P = 0.020). Conclusion In octogenarian Asian patients with AF, NOACs might be associated with lower risks of thromboembolic events, major bleeding, and all-cause death than warfarin. Although most patients had received reduced doses, on-label use of NOACs was effective and safe.
Intrauterine Undernourishment Alters TH1/TH2 Cytokine Balance and Attenuates Lung Allergic Inflammation in Wistar Rats

IL-4 produced by Th2 cells can block cytokine production by Th1 cells, and Th1 IFN-γ is known to counterregulate Th2 immune response, inhibiting allergic eosinophilia. As intrauterine undernutrition can attenuate lung inflammation, we investigated the influence of intrauterine undernourishment on the Th1/Th2 cytokine balance and allergic lung inflammation. Intrauterine undernourished offspring were obtained from dams fed 50% of the nourished diet of their counterparts and were immunized at 9 weeks of age. We evaluated the cell counts and cytokine protein expression in the bronchoalveolar lavage, mucus production and collagen deposition, and cytokine gene expression and transcription factors in lung tissue 21 days after ovalbumin immunization. Intrauterine undernourishment significantly reduced inflammatory cell airway infiltration, mucus secretion and collagen deposition, in rats immunized and challenged. Intrauterine undernourished rats also exhibited an altered cytokine expression profile, including higher TNF-α and IL-1β expression and lower IL-6 expression than well-nourished rats following immunization and challenge. Furthermore, the intrauterine undernourished group showed reduced ratios of the IL-4/IFN-γ and the transcription factors GATA-3/T-Bet after immunization and challenge. We suggest that the attenuated allergic lung inflammation observed in intrauterine undernourished rats is related to an altered Th1/Th2 cytokine balance resulting from a reduced GATA-3/T-bet ratio.
The disordered plant dehydrin Lti30 protects the membrane during water-related stress by cross-linking lipids

Dehydrins are intrinsically disordered proteins, generally expressed in plants as a response to embryogenesis and water-related stress. Their suggested functions are in membrane stabilization and cell protection. All dehydrins contain at least one copy of the highly conserved K-segment, proposed to be a membrane-binding motif. The dehydrin Lti30 (Arabidopsis thaliana) is up-regulated during cold and drought stress conditions and comprises six K-segments, each with two adjacent histidines. Lti30 interacts with the membrane electrostatically via pH-dependent protonation of the histidines. In this work, we seek a molecular understanding of the membrane interaction mechanism of Lti30 by determining the diffusion and molecular organization of Lti30 on model membrane systems by imaging total internal reflection– fluorescence correlation spectroscopy (ITIR-FCS) and molecular dynamics (MD) simulations. The dependence of the diffusion coefficient explored by ITIR-FCS together with MD simulations yields insights into Lti30 binding, domain partitioning, and aggregation. The effect of Lti30 on membrane lipid diffusion was studied on fluorescently labeled supported lipid bilayers of different lipid compositions at mechanistically important pH conditions. In parallel, we compared the mode of diffusion for short individual K-segment peptides. The results indicate that Lti30 binds the lipid bilayer via electrostatics, which restricts the mobility of lipids and bound protein molecules. At low pH, Lti30 binding induced lipid microdomain formation as well as protein aggregation, which could be correlated with one another. Moreover, at physiological pH, Lti30 forms nanoscale aggregates when proximal to the membrane suggesting that Lti30 may protect the cell by “cross-linking” the membrane lipids.