Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional near-infrared spectroscopy during a decision-making task in patients with major depressive disorder

Objective: Patients with major depressive disorder tend to exhibit poorer decision-making capacity than the general population, but neurobiological evidence is lacking. Functional near-infrared spectroscopy monitors changes in oxy-haemoglobin concentration in the cerebral cortex. It may provide an objective assessment of neurophysiological responses during decision-making processes. Thus, this study investigated the effect of major depressive disorder diagnosis and severity on prefrontal cortex activity during the Iowa gambling task. Methods: Right-handed healthy controls (n = 25) and patients with major depressive disorder (n = 25) were matched for age, gender, ethnicity and years of education in this cross-sectional study. Functional near-infrared spectroscopy signals and the responses made during a computerised Iowa gambling task were recorded. In addition, demographics, clinical history and symptom severity were noted. Results: Compared to healthy controls, patients with major depressive disorder had reduced haemodynamic response in several cortical regions of the frontal lobe (Hedge’s g range from 0.71 to 1.52; p values range from ⩽0.001 to 0.041). Among patients, mean oxy-haemoglobin declined with major depressive disorder severity in the right orbitofrontal cortex (Pearson’s r = −0.423; p = 0.024). Conclusion: Haemodynamic dysfunction of the prefrontal cortex during decision-making processes is associated with major depressive disorder diagnosis and severity. These neurophysiological alterations may have a role in the decision-making capacity of patients with major depressive disorder.
A mechanism‐based pharmacokinetic model of remdesivir leveraging interspecies scaling to simulate COVID‐19 treatment in humans

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) outbreak initiated the global coronavirus disease 2019 (COVID‐19) pandemic resulting in 42.9 million confirmed infections and > 1.1 million deaths worldwide as of October 26, 2020. Remdesivir is a broad‐spectrum nucleotide prodrug shown to be effective against enzootic coronaviruses. The pharmacokinetics (PKs) of remdesivir in plasma have recently been described. However, the distribution of its active metabolite nucleoside triphosphate (NTP) to the site of pulmonary infection is unknown in humans. Our objective was to use existing in vivo mouse PK data for remdesivir and its metabolites to develop a mechanism‐based model to allometrically scale and simulate the human PK of remdesivir in plasma and NTP in lung homogenate. Remdesivir and GS‐441524 concentrations in plasma and total phosphorylated nucleoside concentrations in lung homogenate from Ces1c−/− mice administered 25 or 50 mg/kg of remdesivir subcutaneously were simultaneously fit to estimate PK parameters. The mouse PK model was allometrically scaled to predict human PK parameters to simulate the clinically recommended 200 mg loading dose followed by 100 mg daily maintenance doses administered as 30‐minute intravenous infusions. Simulations of unbound remdesivir concentrations in human plasma were below 2.48 μM, the 90% maximal inhibitory concentration for SARS‐CoV‐2 inhibition in vitro. Simulations of NTP in the lungs were below high efficacy in vitro thresholds. We have identified a need for alternative dosing strategies to achieve more efficacious concentrations of NTP in human lungs, perhaps by reformulating remdesivir for direct pulmonary delivery.
Expression of HIV-1 Intron-Containing RNA in Microglia Induces Inflammatory Responses

Although peripheral viremia can be effectively suppressed with the advent of highly active antiretroviral therapy, a significant portion of HIV+ individuals still suffer from neurocognitive disorders. Despite suppressive therapy, HIV persists in various tissues, including the central nervous system (CNS), leading to chronic inflammation, the chief driver of neurocognitive disorders. ABSTRACT Chronic neuroinflammation is observed in HIV+ individuals on suppressive combination antiretroviral therapy (cART) and is thought to cause HIV-associated neurocognitive disorders. We recently reported that expression of HIV intron-containing RNA (icRNA) in productively infected monocyte-derived macrophages induces proinflammatory responses. Microglia, yolk sac-derived brain-resident tissue macrophages, are the primary HIV-1-infected cell type in the central nervous system (CNS). In this study, we tested the hypothesis that persistent expression of HIV icRNA in primary human microglia induces innate immune activation. We established multiple orthogonal primary human microglia-like cell cultures, including peripheral blood monocyte-derived microglia (MDMG) and induced pluripotent stem cell (iPSC)-derived microglia. Unlike MDMG, human iPSC-derived microglia (hiMG), which phenotypically mimic primary CNS microglia, were robustly infected with replication-competent HIV-1, and establishment of productive HIV-1 infection and de novo viral gene expression led to proinflammatory cytokine production. Blocking of HIV-1 icRNA expression, but not multiply spliced viral RNA, via either infection with virus expressing a Rev-mutant deficient for HIV icRNA nuclear export or infection in the presence of a small molecule inhibitor of the chromosome region maintenance 1 (CRM1)-mediated viral icRNA nuclear export pathway attenuated induction of innate immune responses. These studies suggest that Rev-CRM1-dependent nuclear export and cytosolic sensing of HIV-1 icRNA induces proinflammatory responses in productively infected microglia. Novel strategies targeting HIV icRNA expression specifically are needed to suppress HIV-induced neuroinflammation. IMPORTANCE Although peripheral viremia can be effectively suppressed with the advent of highly active antiretroviral therapy, a significant portion of HIV+ individuals still suffer from neurocognitive disorders. Despite suppressive therapy, HIV persists in various tissues, including the central nervous system (CNS), leading to chronic inflammation, the chief driver of neurocognitive disorders. While persistent infection has been described in CNS-resident macrophages and microglia, molecular mechanisms of how HIV infection in microglia contributes to neuronal inflammation have remained unclear. In this study, we used multiple primary human microglia-like cellular platforms and demonstrate that HIV-1 intron-containing RNA induces microglial activation and damage. Since current antiretroviral therapy does not suppress HIV-1 transcription, new therapeutics targeting HIV RNA expression may help to treat HIV-associated neurocognitive disorders.
Development and validation of a novel prognostic model for long-term overall survival in liposarcoma patients: a population-based study

Objective To construct and validate a clinically accurate and histology-specific nomogram to predict overall survival (OS) among liposarcoma (LPS) patients. Methods We retrospectively screened eligible patients with LPS diagnosed between 2004 and 2015 from the Surveillance, Epidemiology, and End Results database. We screened independent predictors for the nomogram using univariate and multivariate analyses. We then evaluated the prognostic accuracy of the nomogram by receiver operating characteristic (ROC) curve analysis and Harrell’s concordance index. The prognostic performances of the nomogram and the American Joint Committee on Cancer (AJCC) seventh edition staging system were compared using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analyses (DCA). Results A novel nomogram was developed using independent prognostic variables, which exhibited excellent predictive performances for 3- and 5-year OS according to ROC curves. The C-index proved that the proposed nomogram had better prognostic accuracy for LPS than the traditional AJCC system, while the NRI, IDI, and DCA of the nomogram indicated better clinical net benefit. Conclusions The proposed nomogram can predict 3- and 5-year OS of LPS patients with reliable accuracy and may thus help clinicians to develop appropriate clinical therapies and counseling strategies to prolong the life expectancy of these patients.
Visualizing insulin vesicle neighborhoods in β cells by cryo–electron tomography

Multiple distinct tomograms of a single β cell enable investigation of the architecture of insulin vesicle neighborhoods. Subcellular neighborhoods, comprising specific ratios of organelles and proteins, serve a multitude of biological functions and are of particular importance in secretory cells. However, the role of subcellular neighborhoods in insulin vesicle maturation is poorly understood. Here, we present single-cell multiple distinct tomogram acquisitions of β cells for in situ visualization of distinct subcellular neighborhoods that are involved in the insulin vesicle secretory pathway. We propose that these neighborhoods play an essential role in the specific function of cellular material. In the regions where we observed insulin vesicles, a measurable increase in both the fraction of cellular volume occupied by vesicles and the average size (diameter) of the vesicles was apparent as sampling moved from the area near the nucleus toward the plasma membrane. These findings describe the important role of the nanometer-scale organization of subcellular neighborhoods on insulin vesicle maturation.
The effects of vacancy and heteroatoms-doping on the stability, electronic and magnetic properties of blue phosphorene

In this work, we have systematically studied the stability, electronic structure and magnetic properties of the pristine, four defect states case of blue phosphorene and the six heteroatoms doping in blue phosphorene by first-principles calculations. In our findings, both defects and heteroatoms doping can regulate the band gap of blue phosphorene and the transition from indirect to direct band gap can be dramatically tuned by DV1BP, DV2BP and Al, Si atoms substitutional doping in blue phosphorene. The presence of defects and heteroatoms doping effectively modulates the electronic properties of blue phosphorene, rendering the defect-containing phosphorene semiconducting with a tunable band gap. Spin–orbit coupling can be induced by introducing SV-, DV- defects in blue phosphorene. The results provide theoretical guidance for future bandgap regulation and magnetism, defective and substitutional doping blue phosphorene may have potential electro-optical and electromagnetic applications.
Challenges and facilitators in supporting sustainable participation after rehabilitation: Experiences of immigrant parents and their children with disabilities

Abstract Background Children with immigrant backgrounds and disabilities have lower rates of social participation compared with their non-immigrant counterparts. However, rehabilitation programmes offer an opportunity to promote a physically active lifestyle and increase home and community participation of children with disabilities. Objectives By exploring immigrant families’ experiences of participation and associated challenges and facilitators after rehabilitation, the study intended to contribute to the development of potential pathways in supporting sustainable community-based participation. Methods The study used a qualitative approach with semi-structured interviews. Results The costs and lack of information, necessary skills, and local activities were among the barriers that families experienced after the rehabilitation. Local and rehabilitation professionals were not always aware of or prepared to address the challenges faced by families trying to become physically active. Parents expressed their needs for support and continuation of services after rehabilitation for moving towards an active lifestyle. Participation patterns among children highlighted the potential role of support contacts as facilitators for participation in physical activities among the families. Conclusions Establishing an efficient collaboration between local and rehabilitation professionals with identifying potential future challenges, adjusting the interventions, clarifying roles and responsibilities, and providing supportive follow-up services may support sustainable community-based participation among immigrant families.
PREDICTIVE-DESCRIPTIVE MODELS FOR GAS AND SOLUTE DIFFUSION COEFFICIENTS IN VARIABLY SATURATED POROUS MEDIA COUPLED TO PORE-SIZE DISTRIBUTION: III. INACTIVE PORE SPACE INTERPRETATIONS OF GAS DIFFUSIVITY

Accurate description of the soil-gas diffusion coefficient (DP) as a function of air-filled (&egr;) and total (&PHgr;) porosities is required for studies of gas transport and fate processes. After presenting predictive models for DP in repacked and undisturbed soils (Part I and II), this third paper takes a more descriptive approach allowing for the inclusion of inactive air-filled pore space, &egr;in. Three model-based interpretations of &egr;in are presented: (1) a simple power-law model (labeled Millington-Call) with the exponent (V) taken from Millington (1959; Science 130:100-102), and expanded with a constant &egr;in term (= 0.1 m3 m−3), (2) a model (SOLA) based on analogy with solute diffusion and assuming a linear increase in pore continuity from zero at the threshold air-filled porosity where gas diffusion ceases (&egr;th) to a maximum at &egr; = &PHgr;, (3) a power-law model (VIPS) assuming variable &egr;in that linearly decreases from a maximum at &egr; = &egr;th to zero at &egr; = &PHgr;. Assuming &egr;th = 0.1 m3 m−3, all three models satisfactorily predicted DP in 18 repacked soils. The difference between the three models is mainly pronounced for higher-&PHgr; soils, and each model has its own advantage. The SOLA model together with similar models for solute diffusivity allows a direct comparison of pore continuity in the soil gaseous and liquid phases, suggesting large differences in tortuosity and inactive fluid-phase between the two phases. The low-parameter Millington-Call model could account for variability in measured DP along a field transect (Yolo, California) by varying &egr;in with ±0.03 m3 m−3 and is applicable for stochastic gas transport simulations at field scale. The mathematically flexible VIPS model highly accurately fitted DP(&egr;) data for undisturbed soil, illustrating the large possible variations in &egr;th and V. The VIPS model is coupled with the van Genuchten (vG) soil-water characteristic model, yielding a closed-form expression for DP as a function of soil-water matric potential. The VIPS-vG model is useful to illustrate the combined effects of pore size distribution and inactive pore space on soil-gas diffusivity.
Caulerpa lentillifera (Sea Grapes) Improves Cardiovascular and Metabolic Health of Rats with Diet-Induced Metabolic Syndrome

Caulerpa lentillifera (sea grapes) is widely consumed in South-East Asia as a low-energy food with high contents of vitamins and minerals. This study investigated dried sea grapes containing 16.6% insoluble fibre commercially produced in Vietnam as an intervention. We hypothesised that insoluble fibre is the primary metabolite that will reverse diet-induced metabolic syndrome. Male Wistar rats (n = 48) were randomly allocated to four groups in a 16 week protocol. Two groups were fed either corn starch (C) or high-carbohydrate, high-fat (H) diets for the full 16 weeks. The other two groups received C and H diets for eight weeks and then received C. lentillifera added to these diets for the final eight weeks (CCL and HCL, respectively). High-carbohydrate, high-fat diet-fed rats developed obesity, hypertension, dyslipidaemia, fatty liver disease and increased left ventricular collagen deposition. C. lentillifera supplementation in HCL rats decreased body weight, systolic blood pressure, plasma concentrations of total cholesterol and non-esterified fatty acids, inflammatory cells in heart and liver, and visceral adiposity. The Firmicutes to Bacteroidetes ratio decreased in the gut microbiota of HCL rats. Therefore, C. lentillifera attenuated cardiovascular and metabolic symptoms of metabolic syndrome in rats, possibly by preventing infiltration of inflammatory cells together with modulating gut microbiota.
Clinical Outcomes of COVID-19 Patients with Type 2 Diabetes: A Population-Based Study in Korea.

Background The aim of this study was to evaluate clinical outcomes in coronavirus disease 2019 (COVID-19) positive patients with type 2 diabetes compared to those without diabetes in Korea. Methods We extracted claims data for patients diagnosed with COVID-19 from the National Health Insurance Service database in Korea from January 20, 2020 to March 31, 2020. We followed up this cohort until death from COVID-19 or discharge from hospital. Results A total of 5,473 patients diagnosed with COVID-19 were analyzed, including 495 with type 2 diabetes and 4,978 without diabetes. Patients with type 2 diabetes were more likely to be treated in the intensive care unit (ICU) (P<0.0001). The incidence of inhospital mortality was higher in patients with type 2 diabetes (P<0.0001). After adjustment for age, sex, insurance status, and comorbidities, odds of ICU admission (adjusted odds ratio [OR], 1.59; 95% confidence interval [CI], 1.02 to 2.49; P=0.0416) and in-hospital mortality (adjusted OR, 1.90; 95% CI, 1.13 to 3.21; P=0.0161) among patients with COVID-19 infection were significantly higher in those with type 2 diabetes. However, there was no significant difference between patients with and without type 2 diabetes in ventilator, oxygen therapy, antibiotics, antiviral drugs, antipyretics, and the incidence of pneumonia after adjustment. Conclusion COVID-19 positive patients with type 2 diabetes had poorer clinical outcomes with higher risk of ICU admission and in-hospital mortality than those without diabetes. Therefore, medical providers need to consider this more serious clinical course when planning and delivering care to type 2 diabetes patients with COVID-19 infection.
Physiological Responses of Exergaming Boxing in Adults: A Systematic Review and Meta-Analysis.

Objective: Studies investigating the effects of exergaming in available platforms are still limited. This review aims to systematically identify available studies on physiological intensities of exergaming boxing in able-bodied adults and recategorize them based on different platforms or environments. The meta-analysis further analyzes the physiological responses during exergaming boxing into a set of pooled data for any evidence of outliers, heterogeneity, or publication bias. Materials and Methods: A systematic search was conducted by using databases from Google Scholar, PubMed, and Web of Science. Population, intervention, comparison, and outcomes (PICO) and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used in the study selection process for the review. Results: From the 1534 articles examined, 16 articles were included for further analyses. Results indicated that exergaming boxing exhibits a wide range of metabolic equivalent of task (MET) values and intensity, from very light to vigorous, with elements of heterogeneity and bias detected. The Xbox® Kinect boxing platform produced higher MET (mean = 5.3) compared with the Nintendo® Wii™ boxing (mean = 3.8). Conclusion: The results of this review suggest that boxing exergames can produce intensity-adequate physical activity among younger adults that are beneficial for cardiometabolic improvements, regardless of platforms used. Exergaming boxing may be employed as an effective exercise tool to increase energy expenditure and physical activity level in young adults.
New clinical and molecular evidence linking mutations in ARSG to Usher syndrome type IV

In murine and canine animal models, mutations in the Arylsulfatase G gene (ARSG) cause a particular lysosomal storage disorder characterized by neurological phenotypes. Recently, two variants in the same gene were found to be associated with an atypical form of Usher syndrome in humans, leading to visual and auditory impairment without the involvement of the central nervous system. In this study, we identified three novel pathogenic variants in ARSG, which segregated recessively with the disease in two families from Portugal. The probands were affected with retinitis pigmentosa and sensorineural hearing loss, generally with an onset of symptoms in their fourth decade of life. Functional experiments showed that these pathogenic variants abolish the sulfatase activity of the Arylsulfatase G enzyme and impede the appropriate lysosomal localization of the protein product, which appears to be retained in the endoplasmic reticulum. Our data enable to definitely confirm that different biallelic variants in ARSG cause a specific deaf‐blindness syndrome, by abolishing the activity of the enzyme it encodes.
Dose–response relationship between protein intake and muscle mass increase: a systematic review and meta-analysis of randomized controlled trials

Background: Muscle mass is essential for health promotion and maintenance; however, consensus regarding the effectiveness of protein interventions in increasing muscle mass is still lacking. Objective: To evaluate the dose-response relationship in the effects of protein on lean body mass (or fat-free mass). Data Sources: PubMed and Ichushi-Web databases were searched. A manual search of the references of the literature included in this study and of that included in other meta-analyses was conducted. Study Selection: Randomized controlled trials evaluating the effect of supplementary protein intake on lean body mass were included. Data Extraction: Two researchers independently screened the abstracts and five, reviewed the full-texts. Results: A total of 5411 subjects in 105 articles were included. Dose-response analysis using a multivariate-adjusted spline model showed that lean body mass significantly improved with about 5 g/day of supplementary protein intake; this effect further increased with > 50 g/day supplementary protein intake. Conclusions: Increasing daily protein intake can help sustain and improve muscle mass in various populations, irrespective of sex, age, and exercise habits.
Reducing burnout and enhancing work engagement among clinicians

Supplemental digital content is available in the text. Background The Minnesota Hospital Association (MHA) recognized the impact that burnout and disengagement had on the clinician population. A clinician task force developed a conceptual framework, followed by annual surveys and a series of interventions. Features of the job demands–resources model were used as the conceptual underpinning to this analysis. Purpose The aim of this study was to assess the applicability of a clinician-driven conceptual model in understanding burnout and work engagement in the state of Minnesota. Methodology Four thousand nine hundred ninety clinicians from 94 MHA member hospitals/systems responded to a 2018 survey using a brief instrument adapted, in part, from previously validated measures. Results As hypothesized, job demands were strongly related to burnout, whereas resources were most related to work engagement. Variables from the MHA model explained 40% of variability in burnout and 24% of variability in work engagement. Variables related to burnout with the highest beta weights included having sufficient time for work (−0.266), values alignment with leaders (−0.176), and teamwork efficiency (−0.123), all ps < . 001. Variables most associated with engagement included values alignment (0.196), feeling appreciated (0.163), and autonomy (0.093), ps < . 001. Conclusion Findings support the basic premises of the proposed conceptual model. Remediable work–life conditions, such as having sufficient time to do the job, values alignment with leadership, teamwork efficiency, feeling appreciated, and clinician autonomy, manifested the strongest associations with burnout and work engagement. Practice Implications Interventions reducing job demands and strengthening resources such as values alignment, teamwork efficiency, and clinician autonomy are seen as having the greatest potential efficacy.