Miracle-dz/UniFAR-FTUs huggingface dataset:
Metformin protects cardiomyocytes against oxygen-glucose deprivation injury by promoting autophagic flux through AMPK pathway

Abstract Metformin has been shown to protect myocardial ischaemia/reperfusion or hypoxia/reoxygenation injury. In our current study, we investigated the effects of metformin on autophagy and its possible underlying mechanisms in in vivo myocardial infarction (MI) model and in vitro oxygen-glucose deprivation (OGD) model. A rat model of MI was made by ligating coronary artery in vivo study. Metformin (200 mg/kg/day) could improve cardiac function, prevent rats from MI-induced injury by reducing myocardial infarct size and apoptosis. Moreover, metformin furtherly promoted autophagy by increasing the protein expression of LC3-II, ATG5, ATG7 and Beclin1, and by involving AMPK pathway during MI. H9c2 cells were treated with metformin (4 mM) in vitro study to assess its effects after exposure to OGD. Metformin increased cell viability and inhibited OGD-induced LDH synthesis and cell apoptosis. Furthermore, metformin increased autophagosome formations as well as expression of autophagy-related proteins, promoted autophagic flux. In addition, metformin augmented the protein level of Bcl-2 and diminished the protein levels of Bax and cleaved caspase-3. Metformin also upregulated p-AMPK expression. Nevertheless, the above-mentioned effects of metformin on H9c2 cells were remarkably eliminated by compound C (an AMPK inhibitor). In summary, we displayed that metformin protected cardiomyocytes against OGD-induced injury and apoptosis by promoting autophagic flux through the AMPK pathway.
Probing the Local Site Disorder and Distortion in Pyrochlore High-Entropy Oxides.

High-entropy oxides (HEOs) have attracted great interest in diverse fields because of their inherent opportunities to tailor and combine materials functionalities. The control of local order/disorder in the class is by extension a grand challenge toward realizing their vast potential. Here we report the first examples of pyrochlore HEOs with five M-site cations, for Nd2M2O7, in which the local structure has been investigated by neutron diffraction and pair distribution function (PDF) analysis. The average structure of the pyrochlores is found to be orthorhombic Imma, in agreement with radius-ratio rules governing the structural archetype. The computed PDFs from density functional theory relaxed special quasirandom structure models are compared with real space PDFs in this work to evaluate M-site order/disorder. Reverse Monte Carlo combined with ab initio molecular dynamics and Metropolis Monte Carlo simulations demonstrates that Nd2(Ta0.2Sc0.2Sn0.2Hf0.2Zr0.2)2O7 is synthesized with its M-site local to nanoscale order highly randomized/disordered, while Nd2(Ti0.2Nb0.2Sn0.2Hf0.2Zr0.2)2O7+x exhibits a strong distortion of the TiO6 octahedron and small degree of Ti chemical short-range order (SRO) on the subnanometer scale. Calculations suggest that this may be intrinsic, energetically favored SRO rather than due to sample processing. These results offer an important demonstration that the engineered variation of participating ions in HEOs, even among those with very similar radii, provides richly diverse opportunities to control local order/disorder motifs-and therefore materials properties for future designs. This work also hints at the exquisite level of detail that may be needed in computational and experimental data analysis to guide structure-property tuning in the emerging HEO materials class.
Temperature-dependent quantum yields for O(3P) and O(1D) production from photolysis of O3 at 248 nm

A pulsed laser photolysis–resonance fluorescence technique was employed independently by two laboratories to measure ΦO3P, the quantum yield for production of O(3P) from O3 photolysis at 248 nm, between 196 and 427 K. The agreement between the two studies is very good, and the combined results are adequately represented by the function ΦO3P= (0.115 ± 0.030) × exp((35 ± 60)/T) where the uncertainties are 2σ. Within experimental uncertainties, the new results are in agreement with previously reported room temperature results as well as with the single previous temperature dependence study, and greatly reduce the uncertainties in ΦO3P(T) and ΦO1D(T) (=1− ΦO3P(T)) especially at temperatures other than room temperature. The yield of O(3P) in the reaction of O(1D) with O3 is shown to be greater than unity at room temperature and below, and to increase slightly with decreasing temperature.
Overweight, Obesity, and Late-Life Sarcopenia Among Men With Cardiovascular Disease, Israel

Introduction Little is known about the association between obesity and sarcopenia — age-related loss of muscle mass and function — among patients with cardiovascular disease. We investigated the association between overweight, obesity, and sarcopenia among community-dwelling men in Israel with cardiovascular disease. Methods A subset of 337 men (mean age at baseline 56.7 [SD, 6.5]) who previously (1990–1997) participated in the Bezafibrate Infarction Prevention trial underwent a neurovascular evaluation as part of the Bezafibrate Infarction Prevention Neurocognitive Study 15.0 (SD, 3.0) years after baseline and a sarcopenia evaluation 19.9 (SD, 1.0) years after baseline. We applied a multinomial logistic model to estimate odds ratios and 95% CIs for 3 categories of sarcopenia: no evidence of sarcopenia (ie, robust), probable sarcopenia, and sarcopenia. Results We found sarcopenia among 54.3% of participants with obesity (body mass index [BMI, in kg/m2] ≥30.0), 37.0% of participants who were overweight (25.0 ≤ BMI ≤29.9), and 24.8% of participants with normal weight (BMI 18.5 to 24.9). In a comparison of BMI ≥25.0 and BMI <25.0, adjusting for covariates, the odds ratio of having probable sarcopenia was 3.27 (95% CI, 1.68–6.36) and having sarcopenia was 5.31 (95% CI, 2.50–11.27). Conclusion We found a positive association between obesity and late-life sarcopenia and suggest that obesity might be an important modifiable risk factor related to sarcopenia among men with cardiovascular disease.
Improving Hospital Glucometrics, Workflow, and Outcomes with a Computerized Intravenous Insulin Dose Calculator Built into the Electronic Health Record

Objective: To adjust for dynamic insulin requirements in critically ill patients, intravenous (IV) insulin infusions allow for titration of the dose according to a prespecified algorithm. Despite the adaptability of IV insulin protocols, human involvement in dose calculation allows for error. We integrated a previously validated IV insulin calculator into our electronic health record (Epic) and instituted it in the cardiovascular intensive care unit (CVICU). We aim to describe the design of the calculator, the implementation process, and evaluate the calculator’s impact. Method: Employing an aggressive training program and user acceptance testing prior to significant elbow support at the time of institution, we successfully integrated the insulin calculator in our CVICU. We evaluated the glucometrics before and after implementation as well as nursing satisfaction following calculator implementation. Results: Overall, our implementation led to increased frequency of blood sugar at various glycemic targets, a trend toward less hypoglycemia or hyperglycemia. For severe hypoglycemia, our preintervention cohort had 0.02% of blood sugars less than 40 mg/dL but no blood sugars less than 40 mg/dL were identified in our patient’s postintervention. For the CVICU target blood glucose of 70-180 mg/dL, 87.97% blood sugars at baseline met goal compared to 91.39% at one month, 91.24% at three months, and 90.87% at six months postintervention. Conclusion: By utilizing an aggressive education campaign championing superusers and making adjustments to the calculator based on early problems that were encountered, we were able to improve glycemic control and limit glucose variability at our institution.
Circadian regulation of transporter expression and implications for drug disposition

ABSTRACT Introduction: Solute Carrier (SLC) and ATP-binding cassette (ABC) transporters expressed in the intestine, liver, and kidney determine the absorption, distribution, and excretion of drugs. In addition, most molecular and cellular processes show circadian rhythmicity controlled by circadian clocks that leads to diurnal variations in the pharmacokinetics and pharmacodynamics of many drugs and affects their therapeutic efficacy and toxicity. Area covered: This review provides an overview of the current knowledge on the circadian rhythmicity of drug transporters and the molecular mechanisms of their circadian control. Evidence for coupling drug transporters to circadian oscillators and the plausible candidates conveying circadian clock signals to target drug transporters, particularly transcription factors operating as the output of clock genes, is discussed. Expert opinion: The circadian machinery has been demonstrated to interact with the uptake and efflux of various drug transporters. The evidence supports the concept that diurnal changes that affect drug transporters may influence the pharmacokinetics of the drugs. However, more systematic studies are required to better define the timing of pharmacologically important drug transporter regulation and determine tissue- and sex-dependent differences. Finally, the transfer of knowledge based on the results and conclusions obtained primarily from animal models will require careful validation before it is applied to humans.
Patient and Provider Decision-Making Experiences: A Qualitative Study

The purpose of this qualitative descriptive study was to explore patient and provider experiences in making health care decisions. A convenience sample of primary care patients and providers was engaged in face-to-face and telephone interviews, to elicit participants’ experiences in making health care decisions. Three main themes were identified in the data: Involvement, including being in control and accepting responsibility; seeking and confirming Information; and establishing communication and negotiating trust in the patient-provider Relationship. Themes identified in the data describe the elements involved in health care decision-making, and depict the relationship between patient and provider as being central to the making of health care decisions. In addition, the subthemes of control and negotiation merit additional in-depth exploration to illuminate the implicit and explicit expressions of hierarchy in the patient-provider relationship, as this hierarchy appears to hinder efforts at sharing decisions in health care encounters.
Point mutation in the stop codon of MAV_RS14660 increases the growth rate of Mycobacterium avium subspecies hominissuis

Mycobacterium avium subspecies hominissuis (MAH) is a pathogen that causes various non-tuberculous mycobacterial diseases in humans and animals worldwide. Among the genus, MAH is characterized by relatively slow growth. Here, we isolated a rapidly growing variant of the MAH 104 strain. The variant strain (named N104) exhibited an enhanced growth rate and higher motility compared to the parent MAH 104 strain (P104). Whole-genome sequencing analysis of N104 revealed the loss of the stop codon of MAV_RS14660 due to a single nucleotide replacement, resulting in the substitution of the codon for tryptophan. Notably, exclusion of the stop codon ligated the open reading frames and caused the fusion of two adjacent proteins. A revertant parent strain, in which a mutation was introduced to restore the stop codon, revealed that elimination of the stop codon in MAV_RS14660 was responsible for the N104 phenotype. Furthermore, we analysed the phenotypes of the parent and mutated strains by determining the functions of the MAV_RS14660 and MAV_RS14655 coding regions flanking the stop codon. The mutant strains, expected to express a fusion protein, exhibited increased resistance to antimicrobial drugs and exogenous copper toxicity compared to that of the parent strains. These findings suggest that the fusion of the MAV_RS14660- and MAV_RS14655-encoding regions in the mutant N104 strain could be related to the modified functions of these intrinsic proteins.
Molar mass characterization of hydrophilic copolymers, 1 Size exclusion chromatography of neutral and anionic (meth)acrylate copolymers

Abstract A robust and reproducible method for the molar mass analysis of neutral and anionic copolymers based on methacrylic acid and different (meth)acrylates has been developed. Size exclusion chromatography (SEC) using a novel polyester- based packing as the stationary phase and dimethylacetamide (DMAC) as the mobile phase yields highly accurate results for copolymers with a methacrylic acid content up to 50 wt. -%. To suppress the different polar and ionic interactions between the sample molecules, the stationary phase and the eluent, DMAC was modified with LiBr and acetic acid. Calibrating the SEC system with poly(methyl methacrylate) of narrow polydispersity, molar masses were obtained that are in good agreement with data obtained by SEC-MALLS (multi-angle laser light scattering) and SEC measurements of methylated samples. The reproducibility and the robustness of the novel method were proven by running similar samples in three different laboratories and for an extended period of two weeks.
Nephrology Dialysis Transplantation Transmission routes of HCV infection in dialysis

Nosocomial transmission of hepatitis C virus (HCV) to haemodialysed patients, strongly suspected in epidemiological studies, has recently been unequivocally demonstrated by molecular virology reports. Potential transmission mechanisms include staff hands, dialysis monitors, and equipment items shared between patients. The respective involvement of each of these vectors in HCV transmission has not been determined. There is no conclusive data on the reality of HCV transmission by dialyser re-use. Prevention of HCV transmission relies on the use of erythropoietin, blood donor screening for anti-HCV antibodies and the application of'Universal Precautions' (Atlanta CDC). In contrast, isolation of anti-HCV-positive dialysed patients does not appear to be warranted by prospective studies, as it might increase the risk of co-infection by different HCV strains, would entail additional costs and be at best partially effective. Recent data have shown that HCV transmission may be prevented by the observance of the 'Universal Precautions' without having to isolate HCV+ patients. Risk factors of HCV seropositivity in dialysed
Non-operative orthobiologic use for rotator cuff disorders and glenohumeral osteoarthritis: A systematic review.

BACKGROUND Shoulder pain from rotator cuff pathology and glenohumeral osteoarthritis is a common entity encountered in musculoskeletal practices. Orthobiologic agents are being increasingly used as a treatment option and understanding their safety and efficacy is necessary. OBJECTIVE To systematically evaluate the available evidence for orthobiologic use in rotator cuff and glenohumeral pathology. METHODS A systematic review was undertaken following PRISMA guidelines. Randomized clinical trials (RCTs) and prospective cohort studies evaluating non-operative treatment with prolotherapy, platelet-rich plasma (PRP), or medicinal signaling cells (MSCs) for rotator cuff pathology and glenohumeral osteoarthritis were included. Bias risk assessments used were the Cochrane tool and Newcastle-Ottawa score. RESULTS The search yielded 852 potential articles, of which 20 met the inclusion criteria with a breakdown of 5 prolotherapy, 13 PRP, and 2 MSC. Sixteen studies were RCTs and 4 were cohort studies. Six studies were deemed "low risk of bias or good quality". Efficacy results were mixed, and no serious adverse events were reported from orthobiologic treatment. CONCLUSIONS Orthobiologics offer a relatively safe management option with inconclusive evidence for or against its use for rotator cuff pathology. No studies on glenohumeral osteoarthritis met the inclusion criteria. Adoption of standardized preparation reporting and consistent use of functional outcome measures is imperative for future studies to consider.
The relevance of nanotechnology, hepato-protective agents in reducing the toxicity and augmenting the bioavailability of isotretinoin

Abstract Acne Vulgaris is one of the most common chronic inflammatory skin disorders that affect majority of teen-agers worldwide. Isotretinoin (ITT) is the drug of choice in the management of acne, but, it suffers from serious side-effects including hepatotoxicity, and some psychological disturbances following its oral intake. The objective of this study was to develop and optimize ITT loaded nanoemulsions (ITT-SNEDDS) and to incorporate resveratrol (RSV)in optimum formulation to decrease ITT side effects The ITT solubility was first tested in various essential oils, surfactants, and co-surfactants to select the essential nanoemulsion ingredients. Mixture design was applied to study the effect of independent variables and their interactions on the selected dependent responses. The developed ITT-SNEDDS were characterized for their globule size and ex vivo permeation. The optimized batch was further loaded with RSV and evaluated for in vitro and ex vivo permeation and for in vivo hepatotoxicity. The developed ITT-SNEDDS exhibited globule size below 300 nm, up to 272.27 ± 7.12 mcg/cm2.h and 61.27 ± 2.83% of steady-state flux (JSS) and permeability % respectively. Optimum formulation consisted of 0.15 g oil mixture, 0.6 g of surfactant (Labrasol), and 0.250 g co-surfactant (Transcutol). Permeability studies confirmed the enhanced permeation percentage of ITT (40.77 ± 1.18%), and RSV (29.94 ± 2.02%) from optimized formulation, with enhanced steady-state flux (JSS). In vivo studies demonstrated the superior hepatoprotective activity of optimized formulation compared to a different drug formulations and marketed product. Therefore, RVS loaded ITT-SNEDDS might be a successful strategy for acne management with improved action, and minimum side effects.
l-Citrullinium perchlorate

In the title compound, C6H14N3O3+·ClO4−, the citrullinium residue forms a strong O—H⋯O hydrogen bonds with the terminal O atom of a symmetry-related residue. This residue has a gauche I-trans-trans-trans conformation. The crystal structure is stabilized by an N—H⋯O hydrogen-bonding network. The perchlorate anion is linked to the cation, forming chains along the a axis.
Double 15‐nm‐wide metal gates 10 nm apart and 70 nm thick on GaAs

A method that can fabricate two narrow but thick metal lines separated by a small gap on a bulk semiconductor substrate is described. By opening a 40‐nm‐wide trench in a single layer of 70‐nm‐thick polymethylmethacrylate resist on GaAs using high resolution electron beam lithography, and by double shadow evaporations and a lift‐off, two 15‐nm‐wide metal lines 10 nm apart and 70 nm thick were fabricated on a bulk GaAs substrate. The pitch size of the double metal lines is 25 nm. This is a factor of 2 smaller than the previous smallest pitch size on bulk semiconductors. It is found that the width and spacing of the two lines are uniform over tens of microns. It is also found that metals shadow evaporated on top of the resist can be removed successfully by a lift‐off, even though they were connected to the metals in the resist trenches. These results suggest that using this method metal lines with even finer linewidth (<15 nm) can be achieved on a bulk semiconductor substrate.
Comparison of Second- and Third-Generation Parathyroid Hormone Test Results in Patients with Chronic Kidney Disease

Background In patients with chronic kidney disease (CKD), secondary hyperparathyroidism is assessed by measuring serum parathyroid hormone (PTH) levels. Well-established, recommended, second-generation intact parathyroid hormone (iPTH) tests are typical; rarely are more recent third-generation PTH 1–84 assays used. The agreement between results of the 2 tests in patients with CKD has not been sufficiently defined. Material/Methods This study aimed to compare Roche second- and third-generation PTH assays by establishing a quantitative relationship between the results of assays in patients with CKD and assessing degree of their correlation with kidney function and calcium-phosphate and bone metabolism parameters. In 205 patients with stages 3 to 5D CKD and 30 healthy controls, we measured levels of iPTH and PTH (1–84), creatinine, urea, cystatin C, calcium, inorganic phosphate, magnesium, alkaline phosphatase, bone alkaline phosphatase, osteocalcin, and β-CrossLaps. Results The third-generation PTH assay results were more than 40% lower than those obtained with the second-generation test in patients undergoing dialysis and approximately 30% lower in patients in the pre-dialysis period. PTH concentrations determined with both assays were almost to the same extent correlated with calcium-phosphate and bone metabolism parameters, and renal function indices. Formulas have been developed enabling 2-way conversion of PTH results determined with both the second- and third-generation PTH assays: For dialyzed patients, PTH (1–84)=0.5181iPTH+18.0595. Serum osteocalcin, β-CrossLaps, and total calcium were independent predictors of PTH levels. Conclusions Correcting for the established quantitative differences, the second-and third-generation PTH tests can be used interchangeably, given the almost identical pathophysiological correlations of their results with calcium-phosphate and bone metabolism parameters.
Extrasynaptic acetylcholine signaling through a muscarinic receptor regulates cell migration

Significance Although ACh is best known for its role in neurotransmission, it also plays a role in cell migration. ACh promotes various cell migrations in vitro, but little is known how it affects cell migration inside an organism where multiple environmental cues are involved. We investigated the migration of an epithelial cell in C. elegans, the gonad leader cell, which expresses a muscarinic acetylcholine receptor. This leader cell migrates closely along the animal’s nerve cords and uses ACh secreted from cholinergic neurons. The muscarinic receptor helps the leader cell stay on its migratory path, but its overactivation causes a reversal in cell orientation. The leader cell may use the muscarinic receptor to adjust its orientation to stay on its migratory path. Acetylcholine (ACh) promotes various cell migrations in vitro, but there are few investigations into this nonsynaptic role of ACh signaling in vivo. Here we investigate the function of a muscarinic receptor on an epithelial cell migration in Caenorhabditis elegans. We show that the migratory gonad leader cell, the linker cell (LC), uses an M1/M3/M5-like muscarinic ACh receptor GAR-3 to receive extrasynaptic ACh signaling from cholinergic neurons for its migration. Either the loss of the GAR-3 receptor in the LC or the inhibition of ACh release from cholinergic neurons resulted in migratory path defects. The overactivation of the GAR-3 muscarinic receptor caused the LC to reverse its orientation through its downstream effectors Gαq/egl-30, PLCβ/egl-8, and TRIO/unc-73. This reversal response only occurred in the fourth larval stage, which corresponds to the developmental time when the GAR-3::yellow fluorescent protein receptor in the membrane relocalizes from a uniform to an asymmetric distribution. These findings suggest a role for the GAR-3 muscarinic receptor in determining the direction of LC migration.