Miracle-dz/UniFAR-FTUs huggingface dataset:
Early life stress induces dysregulation of the heme pathway in adult mice

Early life stress (ELS) is associated with cardiovascular disease (CVD) risk in adulthood, but the underlying vascular mechanisms are poorly understood. Increased hemoglobin and heme have recently been implicated to mediate endothelial dysfunction in several vascular diseases. Chronic physiological stress is associated with alterations in the heme pathway that have been well‐described in the literature. However, very little is known about the heme pathway with exposure to ELS or chronic psychosocial stress. Utilizing a mouse model of ELS, maternal separation with early weaning (MSEW), we previously reported that MSEW induces endothelial dysfunction via increased superoxide production. We reasoned that heme dysregulation may be one of the culprits induced by MSEW and sustained throughout adulthood; thus, we hypothesized that MSEW induces heme dysfunction. We investigated whether circulating levels of heme, a circulating pro‐oxidant mediator, are increased by MSEW and examined the role of the heme metabolic pathway and heme homeostasis in this process. We found that circulating levels of heme are increased in mice exposed to MSEW and that plasma from MSEW mice stimulated higher superoxide production in cultured mouse aortic endothelial cells (MAECs) compared to plasma from normally reared mice. The heme scavenger hemopexin blunted this enhanced superoxide production. Splenic haptoglobin abundance was significantly lower and hemoglobin levels per red blood cell were significantly higher in MSEW versus control mice. These findings lead us to propose that ELS induces increased circulating heme through dysregulation of the haptoglobin‐hemoglobin system representing a mechanistic link between ELS and CVD risk in adulthood.
Efficacy, Safety, and Pharmacodynamic Effects of the Bruton’s Tyrosine Kinase Inhibitor Fenebrutinib (GDC‐0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial

Fenebrutinib (GDC‐0853) is a noncovalent, oral, and highly selective inhibitor of Bruton’s tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo‐controlled study.
Initial Training for Mental Health Peer Support Workers: Systematized Review and International Delphi Consultation

Background Initial training is essential for the mental health peer support worker (PSW) role. Training needs to incorporate recent advances in digital peer support and the increase of peer support work roles internationally. There is a lack of evidence on training topics that are important for initial peer support work training and on which training topics can be provided on the internet. Objective The objective of this study is to establish consensus levels about the content of initial training for mental health PSWs and the extent to which each identified topic can be delivered over the internet. Methods A systematized review was conducted to identify a preliminary list of training topics from existing training manuals. Three rounds of Delphi consultation were then conducted to establish the importance and web-based deliverability of each topic. In round 1, participants were asked to rate the training topics for importance, and the topic list was refined. In rounds 2 and 3, participants were asked to rate each topic for importance and the extent to which they could be delivered over the internet. Results The systematized review identified 32 training manuals from 14 countries: Argentina, Australia, Brazil, Canada, Chile, Germany, Ireland, the Netherlands, Norway, Scotland, Sweden, Uganda, the United Kingdom, and the United States. These were synthesized to develop a preliminary list of 18 topics. The Delphi consultation involved 110 participants (49 PSWs, 36 managers, and 25 researchers) from 21 countries (14 high-income, 5 middle-income, and 2 low-income countries). After the Delphi consultation (round 1: n=110; round 2: n=89; and round 3: n=82), 20 training topics (18 universal and 2 context-specific) were identified. There was a strong consensus about the importance of five topics: lived experience as an asset, ethics, PSW well-being, and PSW role focus on recovery and communication, with a moderate consensus for all other topics apart from the knowledge of mental health. There was no clear pattern of differences among PSW, manager, and researcher ratings of importance or between responses from participants in countries with different resource levels. All training topics were identified with a strong consensus as being deliverable through blended web-based and face-to-face training (rating 1) or fully deliverable on the internet with moderation (rating 2), with none identified as only deliverable through face-to-face teaching (rating 0) or deliverable fully on the web as a stand-alone course without moderation (rating 3). Conclusions The 20 training topics identified can be recommended for inclusion in the curriculum of initial training programs for PSWs. Further research on web-based delivery of initial training is needed to understand the role of web-based moderation and whether web-based training better prepares recipients to deliver web-based peer support.
Relationship Between Residual Mitral Regurgitation and Clinical and Quality-of-Life Outcomes After Transcatheter and Medical Treatments in Heart Failure

Supplemental Digital Content is available in the text. Background: In the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation), among 614 patients with heart failure with 3+ or 4+ secondary mitral regurgitation (MR), transcatheter mitral valve repair (TMVr) with the MitraClip reduced MR, heart failure hospitalizations, and mortality and improved quality of life compared with guideline-directed medical therapy (GDMT) alone. We aimed to examine the prognostic relationship between MR reduction and outcomes after TMVr and GDMT alone. Methods: Outcomes in COAPT between 30 days and 2 years were examined on the basis of the severity of residual MR at 30 days. Results: TMVr-treated patients had less severe residual MR at 30 days than GDMT-treated patients (0/1+, 2+, and 3+/4+: 72.9%, 19.9%, and 7.2% versus 8.2%, 26.1%, and 65.8%, respectively [P<0.0001]). The rate of composite death or heart failure hospitalizations between 30 days and 2 years was lower in patients with 30-day residual MR of 0/1+ and 2+ compared with patients with 30-day residual MR of 3+/4+ (37.7% versus 49.5% versus 72.2%, respectively [P<0.0001]). This relationship was consistent in the TMVr and GDMT arms (Pinteraction=0.92). The improvement in Kansas City Cardiomyopathy Questionnaire score from baseline to 30 days was maintained between 30 days and 2 years in patients with 30-day MR ≤2+ but deteriorated in those with 30-day MR 3+/4+ (–0.3±1.7 versus –9.4±4.6 [P=0.0008]) consistently in both groups (Pinteraction=0.95). Conclusions: In the COAPT trial, reduced MR at 30 days was associated with greater freedom from death or heart failure hospitalizations and improved quality of life through 2-year follow-up whether the MR reduction was achieved by TMVr or GDMT. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT01626079.
Natural antioxidants attenuate mycolactone toxicity to RAW 264.7 macrophages

Mycobacterium ulcerans produces a macrolide exotoxin, mycolactone which suppresses immune cells activity, is toxic to most cells and the key virulence factor in the pathogenesis of Buruli ulcer disease. Mycolactone is reported to mediate the production of reactive oxygen species in keratinocytes; cells that play critical role in wound healing. Increased levels of reactive oxygen species have been shown to disrupt the well-ordered process of wound repair; hence, the function of wound-healing cells such as macrophages, keratinocytes, and fibroblast could be impaired in the presence of the reactive oxygen species mediator, mycolactone. To ensure regeneration of tissues in chronic ulcers, with proper and timely healing of the wounds, natural antioxidants that can combat the effects of induced reactive oxygen species in wound-healing cells ought to be investigated. Reactive oxygen species activity was determined in mycolactone-treated RAW 264.7 macrophages and the scavenging ability of the antioxidants (ascorbic acid, gallic acid, and green tea kombucha) against mycolactone-induced reactive oxygen species (superoxide anions) was assessed using fluorescein probe (DCF-DA) and nitroblue tetrazolium dye. Cytotoxicity of the antioxidants, mycolactone, and the protective effect of the antioxidants on the cells upon treatment with mycolactone were determined using the Alamar blue assay. The expression levels of endogenous antioxidant enzyme genes (superoxide dismutase, catalase, and glutathione peroxidase) in response to mycolactone-mediated reactive oxygen species were determined using RT-qPCR. Mycolactone induced the production of reactive oxygen species in RAW 264.7 macrophages, and the resulting superoxide anions were scavenged by some of the antioxidants. The selected endogenous antioxidant enzyme genes in the macrophages were upregulated in the presence of the antioxidants and mycolactone. The exogenously supplied ascorbic acid and green tea kombucha offered moderate protection to the macrophages against the toxicity of mycolactone. We conclude that the results provide insights into alternate and adjunct therapeutic approaches in Buruli ulcer treatment, which could significantly attenuate the toxicity of the pathogenic factor; mycolactone.
Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics

Polygenic risk scores (PRSs) assess the individual genetic propensity to a condition by combining sparse information scattered across genetic loci, often displaying small effect sizes. Most PRSs are constructed in European‐ancestry populations, limiting their use in other ethnicities. Here we constructed and validated a PRS for late‐onset Alzheimer's Disease (LOAD) in Caribbean Hispanics (CH).
Automatic Diagnosis of Ocular Toxoplasmosis from Fundus Images with Residual Neural Networks

Ocular toxoplasmosis (OT) is commonly diagnosed through the analysis of fundus images of the eye by a specialist. Despite Deep Learning being widely used to process and recognize pathologies in medical images, the diagnosis of ocular toxoplasmosis(OT) has not yet received much attention. A predictive computational model is a valuable time-saving option if used as a support tool for the diagnosis of OT. It could also help diagnose atypical cases, being particularly useful for ophthalmologists who have less experience. In this work, we propose the use of a deep learning model to perform automatic diagnosis of ocular toxoplasmosis from images of the eye fundus. A pretrained residual neural network is fine-tuned on a dataset of samples collected at the medical center of Hospital de Clínicas in Asunción, Paraguay. With sensitivity and specificity rates equal to 94% and 93%,respectively, the results show that the proposed model is highly promising. In order to replicate the results and advance further in this area of research, an open data set of images of the eye fundus labeled by ophthalmologists is made available.
My Kind of Guy: Social Dominance Orientation, Hierarchy-Relevance, and Tolerance of Racist Job Candidates

Social psychology suggests that racism, as captured by explicit prejudice and racial discrimination, is perceived negatively in the United States. However, considering the hierarchy-enhancing nature of racism, it may be that negative perceptions of racism are attenuated among perceivers high in anti-egalitarian sentiment. The reported studies support this, suggesting that racist candidates were tolerated more and had relatively greater hireability ratings as a function of perceivers’ social dominance orientation (SDO; Studies 1–4). Candidate race did not impact these evaluations—only the hierarchy relevance of their actions did (i.e., whether the candidate’s behavior was hierarchy enhancing or had no clear implication for the hierarchy; Study 2). Furthermore, anti-racist candidates (e.g., those displaying hierarchy-attenuating behavior) were tolerated less and had lower hireability ratings as a function of perceivers’ SDO (Study 3). Finally, the perceived intentionality of the candidate’s actions affected tolerance toward them as a function of SDO. This suggests hierarchy relevance impacts evaluative outcomes.
The 24-Hour Movement Guidelines and Body Composition Among Youth Receiving Special Education Services in the United States.

BACKGROUND The purposes of this study were to examine the proportions of youth receiving special education services in the United States who individually and jointly met physical activity, screen time, and sleep duration guidelines, and to examine the impact of meeting none, one, two, and three of the guidelines on overweight and obesity. METHODS This cross-sectional analysis utilized data from the 2016 to 2017 National Survey for Children's Health data set on 3582 youth aged 10-17 years who received special education services. The frequency of the participants' compliance with the 24-hour movement guidelines and body weight status (based on the age- and sex-specific percentile cutoffs) were estimated. Meeting guidelines was defined as: 9-11 hours/night (5-13 y) or 8-10 hours/night (14-17 y) of sleep, ≤120 minutes per day of screen time, and ≥60 minutes per day of moderate to vigorous physical activity. A multinomial logistic regression analysis was conducted to estimate the impact of meeting none, one, two, or three guidelines on body weight status, adjusted for potential confounders. RESULTS Overall, 8.1% of youth met all three guidelines, 42.0% met two guidelines, 38.0% met one guideline, and 11.9% did not meet any guideline. Meeting all three guidelines was associated with an approximately 50% decreased likelihood of overweight than meeting no guideline, or sleep or screen time guidelines independently. CONCLUSIONS This study extends the 24-hour movement framework to children receiving special education services and should prompt the continued study of its utility for understanding health disparities experienced by this population.
An entry risk assessment of African horse sickness virus into the controlled area of South Africa through the legal movement of equids

South Africa is endemic for African horse sickness (AHS), an important health and trade-sensitive disease of equids. The country is zoned with movement control measures facilitating an AHS-free controlled area in the south-west. Our objective was to quantitatively establish the risk of entry of AHS virus into the AHS controlled area through the legal movement of horses. Outcomes were subcategorised to evaluate movement pathway, temporal, and spatial differences in risk. A ‘no-control’ scenario allowed for evaluation of the impact of control measures. Using 2019 movement and AHS case data, and country-wide census data, a stochastic model was developed establishing local municipality level entry risk of AHSV at monthly intervals. These were aggregated to annual probability of entry. Sensitivity analysis evaluated model variables on their impact on the conditional means of the probability of entry. The median monthly probability of entry of AHSV into the controlled area of South Africa ranged from 0.75% (June) to 5.73% (February), with the annual median probability of entry estimated at 20.21% (95% CI: 15.89%-28.89%). The annual risk of AHSV entry compared well with the annual probability of introduction of AHS into the controlled area, which is ~10% based on the last 20 years of outbreak data. Direct non-quarantine movements made up most movements and accounted for most of the risk of entry. Spatial analysis showed that, even though reported case totals were zero throughout 2019 in the Western Cape, horses originating from this province still pose a risk that should not be ignored. Control measures decrease risk by a factor of 2.8 on an annual basis. Not only do the outcomes of this study inform domestic control, they can also be used for scientifically justified trade decision making, since in-country movement control forms a key component of export protocols.
Prevalence of Disability Associated With Head Injury With Loss of Consciousness in Adults in the United States

Objective To provide nationally representative prevalence estimates of disability associated with prior head injury with loss of consciousness in the United States and to examine associations between prior head injury and disability. Methods This was a cross-sectional analysis of 7,390 participants ≥40 years of age in the 2011–2014 National Health and Nutrition Examination Surveys (NHANES). Head injury with loss of consciousness was assessed by self-report. Domains of disability were assessed with a standardized structured questionnaire and measured grip strength. Logistic and linear regression models adjusted for demographic, socioeconomic/behavioral, and medical comorbidity variables were used. Multiple imputation was used to account for missing covariate data. Results Mean age of participants was 58 years; 53% were female; 71% were non-Hispanic White; and 16% had a history of head injury with loss of consciousness. Overall, participants with a history of head injury had higher prevalence of disability in at least 1 domain of functioning compared to individuals without head injury (47.4% vs 38.6%, p < 0.001), with the highest prevalence of disability in the domains of mobility and work productivity. In fully adjusted models, head injury was significantly positively associated with disability in all domains assessed on the standardized questionnaire (all p < 0.05). Participants with head injury had greater grip strength (all p < 0.05). Conclusions We found that 47.4% of individuals ≥40 years of age in the United States with a history of head injury are living with disability in at least 1 domain of functioning, corresponding to 11.4 million affected individuals. This significant burden of disability suggests that efforts are needed to improve functioning among individuals with head injury.
Preparation and characterization of silk fibroin/poly(l-lactide-co-ε-caprolactone) nanofibrous membranes for tissue engineering applications

In recent years, silk fibroin has become one of the most promising tissue engineering materials because of its excellent cytocompatibility. Poly(l-lactide-co-ε-caprolactone), the copolymer of poly(l-lactide) and poly(ε-caprolactone), possesses good mechanical properties, and its degradation rates can be manipulated by varying the ratio of the constituent polymers. In this study, in order to combine their respective characteristics, silk fibroin/poly(l-lactide-co-ε-caprolactone) nanofibrous membranes were fabricated through electrospinning with different mass ratios of 100:0, 75:25, 50:50, 25:75, and 0:100. The surface properties, thermodynamic properties, mechanical properties, and cytocompatibility of silk fibroin/poly(l-lactide-co-ε-caprolactone) blended membranes were evaluated, and an optimal blending ratio was identified. The results showed that the silk fibroin/poly(l-lactide-co-ε-caprolactone) blended membranes containing 75% of silk fibroin and 25% of poly(l-lactide-co-ε-caprolactone) achieved the most improved performances compared with the single-component membranes or the blended membranes with other mixing ratios. The results from this study indicated that 75/25 silk fibroin/poly(l-lactide-co-ε-caprolactone) blended membranes which combined the advantages of poly(l-lactide-co-ε-caprolactone) and silk fibroin might be a suitable candidate material for use in tissue engineering.
Time‐restricted eating and concurrent exercise training reduces fat mass and increases lean mass in overweight and obese adults

The purpose of this study was to determine whether time‐restricted eating (TRE), also known as time‐restricted feeding, was an effective dietary strategy for reducing fat mass and preserving fat‐free mass while evaluating changes in cardiometabolic biomarkers, hormones, muscle performance, energy intake, and macronutrient intake after aerobic and resistance exercise training in physically inactive and overweight or obese adults. This study was a randomized, controlled trial. Overweight and obese adults (mean ± SD; age: 44 ± 7 years; body mass index [BMI]: 29.6 ± 2.6 kg/m2; female: 85.7%) were randomly assigned to a TRE or normal eating (NE) dietary strategy group. The TRE participants consumed all calories between 12:00 p.m. and 8:00 p.m. , whereas NE participants maintained their dietary habits. Both groups completed 8 weeks of aerobic exercise and supervised resistance training. Body composition, muscle performance, energy intake, macronutrient intake, physical activity, and physiological variables were assessed. A total of 21 participants completed the study (NE: n = 10; TRE: n = 11). A mild energy restriction was observed for TRE (~300 kcal/day, 14.5%) and NE (~250 kcal/day, 11.4%). Losses of total body mass were significantly greater for TRE (3.3%) relative to NE (0.2%) pre‐ to post‐intervention, of which TRE had significantly greater losses of fat mass (9.0%) compared to NE (3.3%). Lean mass increased during the intervention for both TRE (0.6%) and NE (1.9%), with no group differences. These data support the use of TRE and concurrent exercise training as a short‐term dietary strategy for reducing fat mass and increasing lean mass in overweight and obese adults.
Reply to: Neurofilament Light Chain in Patients with COVID‐19 and Bacterial Pneumonia

injury. Corroborating our results, recent reports have shown low to intermediate NfL levels in COVID-19 patients as compared to other infectious diseases, for example, bacterial pneumonia and sepsis. 3 Thus, with respect to changes of NfL levels, our own data and current evidence do not indicate commonly occurring neuronal damage in COVID-19. However, differences in cohort composition, such as incidence of delirium or acute kidney injury, could explain the observations made by Sutter and colleagues. As recently reported, delirium itself is associated with NfL elevation and cognitive impairment independent of infection. Furthermore, renal dysfunction might also have influenced NfL levels. In conclusion, we agree with the authors’ statement that prospective studies testing the cognitive outcome of COVID-19 patients are needed to evaluate the prognostic value of NfL levels for neuronal injury during acute SARS-CoV-2 infection. Nonetheless, at this stage, we caution against interpreting the NfL data shown by Sutter et al. as indicating COVID-19–specific neuronal damage.