Miracle-dz/UniFAR-FTUs huggingface dataset:
The effects of antihypertensive class on gout in older adults: secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

OBJECTIVES Gout is a common complication of blood pressure management and a frequently cited cause of medication nonadherence. Little trial evidence exists to inform antihypertensive selection with regard to gout risk. METHODS The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized clinical trial on the effects of first-step hypertension therapy with amlodipine, chlorthalidone, or lisinopril on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). Trial participants were linked to CMS and VA gout claims (ICD9 274.XX). We determined the effect of drug assignment on gout with Cox regression models. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) with gout. RESULTS Claims were linked to 23 964 participants (mean age 69.8 ± 6.8 years, 45% women, 31% black). Atenolol use was reported by 928 participants at the 1-month visit. Over a mean follow-up of 4.9 years, we documented 597 gout claims. Amlodipine reduced the risk of gout by 37% (hazard ratio 0.63; 95% CI 0.51--0.78) compared with chlorthalidone and by 26% (hazard ratio 0.74; 95% CI 0.58--0.94) compared with lisinopril. Lisinopril nonsignificantly lowered gout risk compared with chlorthalidone (hazard ratio 0.85; 95% CI 0.70--1.03). Atenolol use was not associated with gout risk (adjusted hazard ratio 1.18; 95% CI 0.78--1.80). Gout risk reduction was primarily observed after 1 year of follow-up. CONCLUSION Amlodipine lowered long-term gout risk compared with lisinopril or chlorthalidone. This finding may be useful in cases where gout risk is a principal concern among patients being treated for hypertension.This trial is registered at clinicaltrials.gov, number: NCT00000542.
Divergent Regulation of Myotube Formation and Gene Expression by E2 and EPA during In-Vitro Differentiation of C2C12 Myoblasts

Estrogen (E2) and polyunsaturated fatty acids (n-3PUFA) supplements independently support general wellbeing and enhance muscle regeneration in-vivo and myotube formation in-vitro. However, the combined effect of E2 and n-3PUFA on myoblast differentiation is not known. The purpose of the study was to identify whether E2 and n-3PUFA possess a synergistic effect on in-vitro myogenesis. Mouse C2C12 myoblasts, a reliable model to reiterate myogenic events in-vitro, were treated with 10nM E2 and 50μM eicosapentaenoic acid (EPA) independently or combined, for 0–24 h or 0–120 h during differentiation. Immunofluorescence, targeted qPCR and next generation sequencing (NGS) were used to characterize morphological changes and differential expression of key genes involved in the regulation of myogenesis and muscle function pathways. E2 increased estrogen receptor α (Erα) and the expression of the mitogen-activated protein kinase 11 (Mapk11) within 1 h of treatment and improved myoblast differentiation and myotube formation. A significant reduction (p < 0.001) in myotube formation and in the expression of myogenic regulatory factors Mrfs (MyoD, Myog and Myh1) and the myoblast fusion related gene, Tmem8c, was observed in the presence of EPA and the combined E2/EPA treatment. Additionally, EPA treatment at 48 h of differentiation inhibited the majority of genes associated with the myogenic and striated muscle contraction pathways. In conclusion, EPA and E2 had no synergistic effect on myotube formation in-vitro. Independently, EPA inhibited myoblast differentiation and overrides the stimulatory effect of E2 when used in combination with E2.
The Gene and Protein Expression of the Main Components of the Lipolytic System in Human Myocardium and Heart Perivascular Adipose Tissue. Effect of Coronary Atherosclerosis

The aim of our study was to examine the regulation of triacylglycerols (TG) metabolism in myocardium and heart perivascular adipose tissue in coronary atherosclerosis. Adipose triglyceride lipase (ATGL) is the major TG-hydrolase. The enzyme is activated by a protein called comparative gene identification 58 (CGI-58) and inhibited by a protein called G0/G1 switch protein 2 (G0S2). Samples of the right atrial appendage and perivascular adipose tissue were obtained from two groups of patients: 1—with multivessel coronary artery disease qualified for coronary artery bypass grafting (CAD), 2—patients with no atherosclerosis qualified for a valve replacement (NCAD). The mRNA and protein analysis of ATGL, HSL, CGI-58, G0S2, FABP4, FAT/CD36, LPL, β-HAD, CS, COX4/1, FAS, SREBP-1c, GPAT1, COX-2, 15-LO, and NFκβ were determined by using real-time PCR and Western Blot. The level of lipids (i.e., TG, diacylglycerol (DG), and FFA) was examined by GLC. We demonstrated that in myocardium coronary atherosclerosis increases only the transcript level of G0S2 and FABP4. Most importantly, ATGL, β-HAD, and COX4/1 protein expression was reduced and it was accompanied by over double the elevation in TG content in the CAD group. The fatty acid synthesis and their cellular uptake were stable in the myocardium of patients with CAD. Additionally, the expression of proteins contributing to inflammation was increased in the myocardium of patients with coronary stenosis. Finally, in the perivascular adipose tissue, the mRNA of G0S2 was elevated, whereas the protein content of FABP-4 was increased and for COX4/1 diminished. These data suggest that a reduction in ATGL protein expression leads to myocardial steatosis in patients with CAD.
Single-layered graphene/Au NPs-Based Love Wave Biosensor for Highly Sensitive and Specific Detection of Staphylococcus aureus Gene Sequence.

In this work, a single-layered graphene (SLG)/Au-nanoparticles (NPs)-based Love wave biosensor was prepared for detection of Staphylococcus aureus (S. aureus) gene sequence. Annealing process was proposed to obtain a larger-area interface with ssDNA. The sensitivity was verified by detecting S. aureus gene sequences with a linear detection ranging from 0-10 nmol/L, where the limit of detection (LOD) was only 12.4 pg/mL. The stable state of the biosensors based on SLG/Au NPs in liquid phase could be kept for more than 0.5 h (± 0.1°), and the specificity was verified by detecting non-complementary ssDNA, one/three-base mismatched ssDNA. The results of our study suggest that Love wave biosensor based on SLG/Au NPs hold great potential in clinical testing and diagnosis.
Outcome of fetal echogenic bowel: A systematic review and meta‐analysis

The main aim of this systematic review was to explore the outcome of fetuses with isolated echogenic bowel (EB) on antenatal ultrasound. Inclusion criteria were singleton pregnancies with isolated EB no associated major structural anomalies at the time of diagnosis. The outcomes observed were: chromosomal anomalies, cystic fibrosis (CF), associated structural anomalies detected only at follow‐up scans and at birth, regression during pregnancy, congenital infections, intra‐uterine (IUD), neonatal (NND) and perinatal (PND) death. Twenty‐five studies (12 971 fetuses) were included. Chromosomal anomalies occurred in 3.3% of the fetuses, mainly Trisomy 21 and aneuploidies involving the sex chromosomes. Cystic fibrosis occurred in 2.2%. Congenital infections affected 2.2%, mainly congenital Cytomegalovirus (CMV) infection. The majority of fetuses with EB experienced regression or disappearance of the EB at follow‐up scans. Associated anomalies were detected at a follow‐up scan in 1.8%. Associated anomalies were detected at birth and missed at ultrasound in 2.1% of cases. IUD occurred in 3.2% of cases while the corresponding figures for NND and PND were 0.4% and 3.1%. Fetuses with EB are at increased risk of adverse perinatal outcome, highlighting the need for a thorough antenatal management and postnatal follow‐up. Assessment during pregnancy and after birth should be performed in order to look for signs of fetal aneuploidy, congenital infections and associated structural anomalies.
Constitutive Activation of Guanylate Cyclase by the G86R GCAP1 Variant Is Due to “Locking” Cation-π Interactions that Impair the Activator-to-Inhibitor Structural Transition

Guanylate Cyclase activating protein 1 (GCAP1) mediates the Ca2+-dependent regulation of the retinal Guanylate Cyclase (GC) in photoreceptors, acting as a target inhibitor at high [Ca2+] and as an activator at low [Ca2+]. Recently, a novel missense mutation (G86R) was found in GUCA1A, the gene encoding for GCAP1, in patients diagnosed with cone-rod dystrophy. The G86R substitution was found to affect the flexibility of the hinge region connecting the N- and C-domains of GCAP1, resulting in decreased Ca2+-sensitivity and abnormally enhanced affinity for GC. Based on a structural model of GCAP1, here, we tested the hypothesis of a cation-π interaction between the positively charged R86 and the aromatic W94 as the main mechanism underlying the impaired activator-to-inhibitor conformational change. W94 was mutated to F or L, thus, resulting in the double mutants G86R+W94L/F. The double mutants showed minor structural and stability changes with respect to the single G86R mutant, as well as lower affinity for both Mg2+ and Ca2+, moreover, substitutions of W94 abolished “phase II” in Ca2+-titrations followed by intrinsic fluorescence. Interestingly, the presence of an aromatic residue in position 94 significantly increased the aggregation propensity of Ca2+-loaded GCAP1 variants. Finally, atomistic simulations of all GCAP1 variants in the presence of Ca2+ supported the presence of two cation-π interactions involving R86, which was found to act as a bridge between W94 and W21, thus, locking the hinge region in an activator-like conformation and resulting in the constitutive activation of the target under physiological conditions.
Taking the Pulse on Pediatric Simulation

Supplemental digital content is available in the text. Objectives There is abundant literature on simulation use in individual pediatric residency programs but limited overall data on simulation in US pediatric residency programs. This study sought to determine how US pediatric residency programs use simulation for teaching and assessment and the challenges programs face in their use of simulation. Methods The Association of Pediatric Program Director's Healthcare Simulation in Pediatrics Learning Community members developed a 15-multipart question survey on the use of simulation in US pediatric residency programs using best practices in survey design. The survey was distributed electronically to US pediatric residency program directors. Qualitative questions were analyzed by content analysis and quantitative questions using descriptive statistics. Results The survey response rate was 21%; respondents were disproportionately from large academic medical centers. Qualitative analysis found that respondents use simulation to teach pediatric residents in the areas of urgent/emergent situations, procedures, and communication, and common challenges to simulation implementation are time, physical resources, expertise, competing priorities, logistics, and buy-in. Quantitative analysis demonstrated that, although respondents are largely confident that their simulation programs improve resident preparedness and competence, few objectively evaluate their simulation programs. Conclusions Pediatric residency programs use simulation for similar purposes and face similar challenges. By collaborating, the resources of the national pediatric simulation community can be leveraged to collect evidence for best practices for simulation use in pediatric residency training.
Effect of epoch length on intensity classification and on accuracy of measurement under controlled conditions on treadmill: Towards a better understanding of accelerometer measurement

Purpose The aim of this study was to analyze the effect of epoch length on intensity classification during continuous and intermittent activities. Methods Ten active students exercised under controlled conditions on a treadmill for four 5-min bouts by combining two effort intensities (running and walking) and two physical activity (PA) patterns (continuous or intermittent). The testing session was designed to generate a known level of moderate to vigorous PA (MVPA) for each condition. These PA levels were used as criterion measures to compare with the accelerometer measures. Data obtained from the accelerometer were reintegrated into 1-sec, 10-sec, 30-sec and 60-sec epochs. Equivalence testing was used to examine measurement agreements between MVPA values obtained with the different epochs and the reference values. Mean absolute percent errors (MAPE) were also calculated to provide an indicator of overall measurement error. Results During the intermittent conditions, only the value obtained with the 1-sec epoch was significantly equivalent to the reference value. With longer epochs the difference increased for both intermittent conditions but in an opposite way: with longer epochs, MVPA decreased during walking but increased during running. Regarding the measurement accuracy, the pattern of variations according to the epoch length selected during the intermittent conditions was identical between walking and running: MAPE increased with the increase in epoch length. MAPE remained low only for the 1-sec epoch (7.6% and 2.7% for walking and running, respectively), increased at 31.3% and 34% for the 10-sec epoch and until near 100% with the 30- and 60-sec epoch lengths. Conclusion This study highlighted the misclassification of exercise intensity based on accelerometer measurement and described for the first time the extent and the direction of this misclassification. Moreover, we can confirm that the shorter epochs are more accurate to measure the real exercise intensity during intermittent PA whatever the intensity.
Smart Adhesive Joint with High-Definition Fiber-Optic Sensing for Automotive Applications

Structural health monitoring of fiber-reinforced composite-based joints for automotive applications during their manufacturing and on-demand assessment for its durability in working environments is critically needed. High-definition fiber-optic sensing is an effective method to measure internal strain/stress development using minimally invasive continuous sensors. The sensing fiber diameters are in the same order of magnitude when compared to reinforcement (glass, basalt, or carbon fibers) used in polymer composites. They also offer a unique ability to monitor the evolution of residual stresses after repeated thermal exposure with varying temperatures for automotive components/joints during painting using an electrophoretic painting process. In this paper, a high-definition fiber-optic sensor utilizing Rayleigh scattering is embedded within an adhesive joint between a carbon fiber-reinforced thermoset composite panel and an aluminum panel to measure spatially resolved strain development, residual strain, and thermal expansion properties during the electrophoretic paint process-simulated conditions. The strain measured by the continuous fiber-optic sensor was compared with an alternate technique using thermal digital image correlation. The fiber-optic sensor was able to identify the spatial variation of residual strains for a discontinuous carbon fiber-reinforced composite with varying local fiber orientations and resin content.
Relationships among Span, Time Allocation, and Leadership of First-line Managers and Nurse and Team Outcomes

Comparisons of raw span (i.e., number of staff who report directly to a manager) within and across organizations can misrepresent managerial capacity to support staff because managers may not allocate the same amount of time to staff contact. The purpose was to examine the influence of alternative measures of managerial span on nurse satisfaction with manager’s supervision and on multidisciplinary teamwork. The alternative measures were (a) raw span as a measure of reporting structure and (b) time in staff contact as a measure of closeness of contact by the manager. The main effects of the alternative measures, leadership, hours of operation, and other covariates on outcomes were examined. The interaction effects of the alternative measures with leadership and hours of operation were investigated. The study framework was based on Open System Theory and the boundary spanning functions of managers. A descriptive, correlational design was used to collect survey and administrative data from employees, managers, and organizations. Managerial time allocation data were collected through selflogging and validated through observation. Acute care hospitals were selected through purposive sampling. For supervision satisfaction, the final sample size was 31 first-line managers and 558 nurses. For teamwork, the final sample size was 30 first-line managers and 754 staff. The Leadership Practices Inventory, the Satisfaction with my Supervisor Scale, and the Relational
Environmental Durability Enhancement of Natural Fibres Using Plastination: A Feasibility Investigation on Bamboo

Natural fibers are gaining wide attention due to their much lower carbon footprint and economic factors compared to synthetic fibers. The moisture affinity of these lignocellulosic fibres, however, is still one of the main challenges when using them, e.g., for outdoor applications, leading to fast degradation rates. Plastination is a technique originally used for the preservation of human and animal body organs for many years, by replacing the water and fat present in the tissues with a polymer. This article investigates the feasibility of adapting such plastination to bamboo natural fibres using the S-10 room-temperature technique in order to hinder their moisture absorption ability. The effect of plastination on the mechanical properties and residual moisture content of the bamboo natural fibre samples was evaluated. Energy dispersive x-ray spectroscopy (EDS) and X-ray micro-computed tomography (Micro-CT) were employed to characterize the chemical composition and 3-dimensional morphology of the plastinated specimens. The results clearly show that, as plastination lessens the hydrophilic tendency of the bamboo fibres, it also decreases the residual moisture content and increases the tensile strength and stiffness of the fibers.
Monte Carlo simulation and thermodynamic integration applied to protein charge transfer

We introduce a combination of Monte Carlo simulation and thermodynamic integration methods to address a model problem in free energy computations, electron transfer in proteins. The feasibility of this approach is tested using the ferredoxin protein from Clostridium acidurici. The results are compared to numerical solutions of the Poisson‐Boltzmann equation and data from recent molecular dynamics simulations on charge transfer in a protein complex, the NrfHA nitrite reductase of Desulfovibrio vulgaris. Despite the conceptual and computational simplicity of the Monte Carlo approach, the data agree well with those obtained by other methods. A link to experiments is established via the cytochrome subunit of the bacterial photosynthetic reaction center of Rhodopseudomonas viridis.
Improved workflow for mass spectrometry–based metabolomics analysis of the heart

MS-based metabolomics methods are powerful techniques to map the complex and interconnected metabolic pathways of the heart; however, normalization of metabolite abundance to sample input in heart tissues remains a technical challenge. Herein, we describe an improved GC-MS–based metabolomics workflow that uses insoluble protein–derived glutamate for the normalization of metabolites within each sample and includes normalization to protein-derived amino acids to reduce biological variation and detect small metabolic changes. Moreover, glycogen is measured within the metabolomics workflow. We applied this workflow to study heart metabolism by first comparing two different methods of heart removal: the Langendorff heart method (reverse aortic perfusion) and in situ freezing of mouse heart with a modified tissue freeze-clamp approach. We then used the in situ freezing method to study the effects of acute β-adrenergic receptor stimulation (through isoproterenol (ISO) treatment) on heart metabolism. Using our workflow and within minutes, ISO reduced the levels of metabolites involved in glycogen metabolism, glycolysis, and the Krebs cycle, but the levels of pentose phosphate pathway metabolites and of many free amino acids remained unchanged. This observation was coupled to a 6-fold increase in phosphorylated adenosine nucleotide abundance. These results support the notion that ISO acutely accelerates oxidative metabolism of glucose to meet the ATP demand required to support increased heart rate and cardiac output. In summary, our MS-based metabolomics workflow enables improved quantification of cardiac metabolites and may also be compatible with other methods such as LC or capillary electrophoresis.
Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis*

A defective chondrogenic differentiation of MSC is implicated in the limited regeneration capacity of osteoarthritic cartilage. We have followed a SILAC-based proteomic strategy in combination with MALDI-MSI analysis to identify proteomic and metabolomic changes underlying MSC differentiation in OA, which could provide novel targets for therapeutic intervention. Specifically, we have described that UDP-glucuronic acid and UDP-GlcNAc synthesis pathway is affected during the chondrogenic differentiation of OA cells, which consequently may alter the production of cartilage ECM components. Graphical Abstract Highlights SILAC-based protein quantification of OA hBMSCs undergoing chondrogenesis. Spatially-resolved metabolomics by MSI of hBMSCs in chondrogenic differentiation. Differential metabolic pathways involved in OA compared to control hBMSCs. UDP-glucuronic acid/UDP-GlcNAc synthesis is decreased in chondrogenic OA hBMSCs. In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.