Miracle-dz/UniFAR-FTUs huggingface dataset:
Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study.

CONTEXT Several observational studies and meta-analyses have reported increased mortality of patients taking sulfonylurea and insulin. The impact of patient profiles and concomitant therapies often remains unclear. OBJECTIVE The objective of the study was to quantify survival of patients after starting glucose-lowering agents (GLAs) and compare it with control subjects, matched for risk profiles and concomitant therapies. DESIGN This was a retrospective, controlled, cohort study. SETTING The study is based on health expenditure records of the largest Belgian health mutual insurer, covering more than 4.4 million people. PATIENTS A total of 115 896 patients starting metformin, sulfonylurea, or insulin (alone or in combination) between January 2003 and December 2007 participated in the study. Control subjects without GLA therapy were matched for age, gender, history of cardiovascular events, and therapy with antihypertensives, statins and blood platelet aggregation inhibitors. INTERVENTION(S) There were no interventions. MAIN OUTCOME MEASURE Five-year survival after the start of GLA was measured. RESULTS Profiles of patients using different GLAs varied, with patients on sulfonylurea being oldest and patients on insulin having more frequently a history of cardiovascular disease. Excess mortality differed across GLA therapies compared with matched controls without GLAs, even after adjusting for observable characteristics. Only metformin monotherapy was not associated with an increased 5-year mortality compared with matched controls, whereas individuals on a combination of sulfonylurea and insulin had the highest mortality risks. Age and concomitant use of statins strongly affect survival. CONCLUSIONS Differences exist in 5-year survival of patients on GLA, at least partly driven by the risk profile of the individuals themselves. Metformin use was associated with lowest 5-year mortality risk and statins dramatically lowered 5-year mortality throughout all cohorts.
Treatment with Sildenafil Improves Insulin Sensitivity in Prediabetes: A Randomized, Controlled Trial.

CONTEXT Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance. OBJECTIVE The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function. DESIGN This was a randomized, double-blind, placebo-controlled study. SETTING This trial was conducted at Vanderbilt Clinical Research Center. PARTICIPANTS Participants included overweight individuals with prediabetes. INTERVENTIONS Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment. MAIN OUTCOME MEASURES The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion. RESULT Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation. CONCLUSIONS Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
Impact of depression on sexual dysfunction and HRQoL in CAD patients

BackgroundThe aim of this study was to assess the impact of the depression on sexual dysfunction and the health-related quality of life (HRQoL) in coronary artery disease (CAD) patients admitted for cardiovascular rehabilitation within 3 months after an acute myocardial infarction (AMI). Methods. In all, 745 consecutive CAD patients (502 men and 243 women, aged 60.9 ± 9.3 years) admitted for cardiovascular rehabilitation within 3 months after an AMI, were enrolled in the study and divided into 4 groups according to Beck depression inventory (BDI) score range. HRQoL was estimated using the SF-36 questionnaire for total QoL and dimensions for physical and mental health [physical and mental component summary scores (PCS, MCS)]. Sexual dysfunction was assessed using the ASEX scale.ResultsThe HRQoL decreased following the range of depression, as demonstrated for significantly higher PCS in minimal compared to mild, moderate and severe depression groups (P<0.001). The MCS was significantly higher in minimal compared to mild, moderate and severe depression groups (P<0.001). The ASEX score was significantly higher in minimal, compared to mild, moderate and severe depression groups, as well as in mild and moderate compared to severe depression group. A significant association was found between depression score range and age, self-reported regular exercise, type 2 diabetes mellitus, and cigarette smoking.ConclusionsDepression significantly affected HRQoL and sexual dysfunction in CAD patients, as demonstrated by the significant decrease of PCS, MCS, and significant increase of ASEX score following the range of the depression according to BDI.
A Faith-Based Integrated Substance Abuse and HIV Prevention Program for Rural African American Adolescents

The purpose of this daylong workshop was to reach consensus about a prevention program to decrease risk and increase resiliency behaviors associated with substance abuse and HIV among rural adolescents in faith-based settings. The process and outcomes of the workshop are described. Workshop participants validated and prioritized risk and resiliency factors associated with substance abuse and HIV infection and used these to decide between potential prevention programs. A substance abuse (All Stars) program and an HIV (Be Proud! Be Responsible! ) curriculum were selected and integrated. Consensus was reached that the implementation team should consist of adults and adolescents.
Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood.

CONTEXT Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. OBJECTIVE The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. DESIGN AND SETTING In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group. MAIN OUTCOME MEASURE The degrees of steatosis of NAFLD were determined by ultrasonography. RESULTS The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P < .05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P < .05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. CONCLUSIONS Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.
Non‐medical palliative care and education to improve end‐of‐life care at geriatric health services facilities: A nationwide questionnaire survey of chief nurses

Background: Geriatric health services facilities (GHSF) are expected to assume a growing role in caring for the dying elderly. However, research in this area has so far been scant. The purpose of the present study is to reveal the status of non‐medical palliative care and staff education aiming at improving and enhancing end‐of‐life care at GHSF.
Fast DOA Estimation Algorithm Based on a Combination of an Orthogonal Projection and Noise Pseudo-Eigenvector Approach

This paper presents a new fast direction of arrival (DOA) estimation technique, using both the projection spectrum and the eigenspectrum. First, the rough DOA range is selected using the projection spectrum; then, a linear matrix equation is used to acquire a noise pseudo-eigenvector. Finally, the fine DOA estimation is obtained from an eigenspectrum approach based on the noise pseudo-eigenvector. Without the need to form the covariance matrix from a block of the array data and without a prior knowledge of the number of incoming signals, reduced complexity is achieved, in contrast to conventional subspace-based algorithms. Simulation results show that the proposed algorithm has a good resolution performance and deals well with both uncorrelated and correlated signals. Since the new approach can reduce computational complexity while maintaining better or similar resolution capability, it may provide wider application prospects in real-time DOA estimation when contrasted to other comparable methods.
Child-adult differences in muscle strength and activation pattern during isometric elbow flexion and extension.

Muscle strength and activation were compared in boys and men during maximal voluntary elbow flexion and extension contractions. Peak torque, peak rate of torque development (d/dmax), rate of muscle activation, and electromechanical delay (EMD) were measured in 15 boys (aged 9.7 +/- 1.6 years) and 16 men (aged 22.1 +/- 2.8 years). During flexion, peak torque was significantly lower in boys than in men (19.5 +/- 5.8 vs. 68.5 +/- 11.0 Nm, respectively; p < 0.05), even when controlling for upper-arm cross-sectional area (CSA), and peak electromyography activity. Boys also exhibited a lower normalized d/dmax (7.2 +/- 1.7 vs. 9.5 +/- 1.6 (Nm.s-1). (Nm-1), respectively; p < 0.05) and a significantly longer EMD (75.5 +/- 28.4 vs. 47.6 +/- 17.5 ms, respectively). The pattern was similar for extension, except that group differences in peak torque were no longer significant when normalized for CSA. These results suggest that children may be less able to recruit or fully utilize their higher-threshold motor units, resulting in lower dimensionally normalized maximal torque and rate of torque development.
Lipid rafts, microdomain heterogeneity and inter‐organelle contacts: Impacts on membrane preparation for proteomic studies

In recent years, there has been considerable interest in mapping the protein content of isolated organelles using mass spectrometry. However, many subcellular compartments are highly dynamic with diverse and intricate architectures that are not always preserved during membrane isolation procedures. Furthermore, lateral heterogeneities in intra‐membrane lipid and protein concentrations underlie the formation of membrane microdomains, trafficking vesicles and inter‐membrane contacts. These complexities in membrane organisation have important consequences for the design of membrane preparation strategies and test the very concept of organelle purity. We illustrate how some of these biological considerations are relevant to membrane preparation and assess the numerous potential pitfalls in attempting to purify organelles from mammalian cells.
PRC1 components exhibit different binding kinetics in Polycomb bodies

Polycomb group (PcG) proteins keep the memory of cell identity by maintaining the repression of numerous target genes. They accumulate into nuclear foci called Polycomb bodies, which function in Drosophila cells as silencing compartments where PcG target genes convene. PcG proteins also exert their activities elsewhere in the nucleoplasm. In mammalian cells, the dynamic organisation and function of Polycomb bodies remain to be determined.
Fat adaptation in well-trained athletes: effects on cell metabolism.

The performance of prolonged (>90 min), continuous, endurance exercise is limited by endogenous carbohydrate (CHO) stores. Accordingly, for many decades, sports nutritionists and exercise physiologists have proposed a number of diet-training strategies that have the potential to increase fatty acid availability and rates of lipid oxidation and thereby attenuate the rate of glycogen utilization during exercise. Because the acute ingestion of exogenous substrates (primarily CHO) during exercise has little effect on the rates of muscle glycogenolysis, recent studies have focused on short-term (<1-2 weeks) diet-training interventions that increase endogenous substrate stores (i.e., muscle glycogen and lipids) and alter patterns of substrate utilization during exercise. One such strategy is "fat adaptation", an intervention in which well-trained endurance athletes consume a high-fat, low-CHO diet for up to 2 weeks while undertaking their normal training and then immediately follow this by CHO restoration (consuming a high-CHO diet and tapering for 1-3 days before a major endurance event). Compared with an isoenergetic CHO diet for the same intervention period, this "dietary periodization" protocol increases the rate of whole-body and muscle fat oxidation while attenuating the rate of muscle glycogenolysis during submaximal exercise. Of note is that these metabolic perturbations favouring the oxidation of fat persist even in the face of restored endogenous CHO stores and increased exogenous CHO availability. Here we review the current knowledge of some of the potential mechanisms by which skeletal muscle sustains high rates of fat oxidation in the face of high exogenous and endogenous CHO availability.
Association between exercise hemodynamics and changes in local vascular function following acute exercise.

Skeletal muscle contractions are associated with physical stimuli that act upon muscle vasculature, including increased shear stress and blood pressure. It is unclear if acute dynamic exercise alters local vascular function. The purpose of this study was to examine the role of exercise hemodynamics on the effects of acute exercise on vascular function, as evaluated by brachial artery flow-mediated dilation (FMD). Healthy individuals (n = 14; age, 18-34 years) performed 30 min of handgrip exercise at fast and slow contractions. Blood pressure during exercise was measured using a Vasotrac system (Medwave Inc.), while shear rate during exercise and FMD at rest and after 30 min of recovery from exercise were measured in the brachial artery of the active arm using Doppler ultrasound. Estimated contractile work was correlated with blood pressure (r = 0.61, p < 0.01) and retrograde shear rate (r = -0.78, p < 0.01). As a result, blood pressure was higher (p < 0.05) and oscillatory shear index was lower (p < 0.05) during slow as compared with fast contractions. On average, FMD was unchanged following fast contractions (5.4 ± 3.4%dilation to 6.1 ± 3.8%dilation; p = 0.19), but significantly reduced following slow contractions (6.9 ± 4.2%dilation to 3.6 ± 2.5%dilation; p = 0.01). Within slow contractions, subgroup analysis revealed blood pressure to associate with the change in FMD; such that individuals with mean blood pressure >100 mm Hg (range, 102-139 mm Hg) during exercise had larger decreases in FMD than individuals with lower exercise blood pressure. These results indicate that impaired local vascular function following acute exercise with high contractile activity is associated with blood pressure stimuli in healthy individuals.
The localisation of the apical Par/Cdc42 polarity module is specifically affected in microvillus inclusion disease

Microvillus inclusion disease (MVID) is a genetic disorder affecting intestinal absorption. It is caused by mutations in MYO5B or syntaxin 3 (STX3) affecting apical membrane trafficking. Morphologically, MVID is characterised by a depletion of apical microvilli and the formation of microvillus inclusions inside the cells, suggesting a loss of polarity. To investigate this hypothesis, we examined the location of essential apical polarity determinants in five MVID patients.
Introduction of macarpine as a novel cell‐permeant DNA dye for live cell imaging and flow cytometry sorting

Macarpine (MA) is a quaternary benzophenanthridine plant alkaloid isolated from Macleaya microcarpa or Stylophorum lasiocarpum. Benzophenanthridine alkaloids are interesting natural products that display antiproliferative, antimicrobial, antifungal and anti‐inflammatory activities, and also fluorescence properties. In a previous study, we demonstrated that thanks to its ability to interact with DNA and its spectral properties MA could be used as a supravital DNA probe for fluorescence microscopy and flow cytometry including analyses of the cell cycle. In this study, we evaluated the suitability of MA as a DNA dye for time‐lapse microscopy and flow‐cytometric cell sorting.
Thyroid Function Tests in the Reference Range and Fracture: Individual Participant Analysis of Prospective Cohorts

Context Hyperthyroidism is associated with increased fracture risk, but it is not clear if lower thyroid-stimulating hormone (TSH) and higher free thyroxine (FT4) in euthyroid individuals are associated with fracture risk. Objective To evaluate the association of TSH and FT4 with incident fractures in euthyroid individuals. Design Individual participant data analysis. Setting Thirteen prospective cohort studies with baseline examinations between 1981 and 2002. Participants Adults with baseline TSH 0.45 to 4.49 mIU/L. Main Outcome Measures Primary outcome was incident hip fracture. Secondary outcomes were any, nonvertebral, and vertebral fractures. Results were presented as hazard ratios (HRs) with 95% confidence interval (CI) adjusted for age and sex. For clinical relevance, we studied TSH according to five categories: 0.45 to 0.99 mIU/L; 1.00 to 1.49 mIU/L; 1.50 to 2.49 mIU/L; 2.50 to 3.49 mIU/L; and 3.50 to 4.49 mIU/L (reference). FT4 was assessed as study-specific standard deviation increase, because assays varied between cohorts. Results During 659,059 person-years, 2,565 out of 56,835 participants had hip fracture (4.5%; 12 studies with data on hip fracture). The pooled adjusted HR (95% CI) for hip fracture was 1.25 (1.05 to 1.49) for TSH 0.45 to 0.99 mIU/L, 1.19 (1.01 to 1.41) for TSH 1.00 to 1.49 mIU/L, 1.09 (0.93 to 1.28) for TSH 1.50 to 2.49 mIU/L, and 1.12 (0.94 to 1.33) for TSH 2.50 to 3.49 mIU/L (P for trend = 0.004). Hip fracture was also associated with FT4 [HR (95% CI) 1.22 (1.11 to 1.35) per one standard deviation increase in FT4]. FT4 only was associated with any and nonvertebral fractures. Results remained similar in sensitivity analyses. Conclusions Among euthyroid adults, lower TSH and higher FT4 are associated with an increased risk of hip fracture. These findings may help refine the definition of optimal ranges of thyroid function tests.
A comparison of the relationship of 14 performance-based measures with frailty in older women.

The purpose of this study was to determine which performance measures of physical function are most closely related to frailty and whether physical function is different across levels of frailty. Fifty-three community-dwelling Greek women (63-100 years) participated in this study. Participants were divided into 3 tertiles based on level of frailty as calculated from a frailty index (FI): lowest FI group (<0.19 FI), intermediate FI group (0.19-0.36 FI), and highest FI group (>0.36 FI). Performance measures tested were handgrip and knee extension muscle strength and fatigue, upper and lower body muscular endurance, walking performance, agility, and dynamic balance. The greatest proportion of variance in the FI was explained by combining all performance-based measures of physical function. The performance measures that were most closely related to frailty yet different across levels of frailty were ambulatory mobility, lower body muscular endurance, and nondominant handgrip strength. Walking at a preferred pace had the strongest relationship to frailty rather than walking at maximal pace. Grip strength of the nondominant hand had a stronger correlation with frailty compared with the dominant hand. The FI was a better predictor of physical function than chronological age. The decline in physical function accelerated after the intermediate FI tertile. Definitions of frailty need to combine performance-based measures that can identify impairments in various domains of physical function. The assessment protocols of these measures are important.
Underestimating a serving size may lead to increased food consumption when using Canada ’ s Food Guide

It is unclear whether Canadians accurately estimate serving sizes and the number of servings in their diet as intended by Canada’s Food Guide (CFG). The objective of this study was to determine if participants can accurately quantify the size of 1 serving and the number of servings consumed per day. White, Black, South Asian, and East Asian adults (n = 145) estimated the quantity of food that constituted 1 CFG serving, and used CFG to estimate the number of servings that they consumed from their 24-h dietary recall. Participants estimated 1 serving size of vegetables and fruit (+43%) and grains (+55%) to be larger than CFG serving sizes (p ≤ 0.05); meat alternatives (–33%) and cheese (–31%) to be smaller than a CFG serving size (p ≤ 0.05); and chicken, carrots, and milk servings accurately (p > 0.05). Serving size estimates were positively correlated with the amount of food participants regularly consumed at 1 meal (p < 0.001). From their food records, all ethnicities estimated that they consumed fewer servings of vegetables and fruit (–15%), grains (–28%), and meat and alternatives (–14%) than they actually consumed, and more servings of milk and alternatives (+26%, p ≤ 0.05) than they actually consumed. Consequently, 68% of participants believed they needed to increase consumption by greater than 200 kcal to meet CFG recommendations. In conclusion, estimating serving sizes to be larger than what is defined by CFG may inadvertently lead to estimating that fewer servings were consumed and overeating if Canadians follow CFG recommendations without guidance. Thus, revision to CFG or greater public education regarding the dietary guidelines is warranted.