Miracle-dz/UniFAR-FTUs huggingface dataset:
Primary defects in lipid handling and resistance to exercise in myotubes from obese donors with and without type 2 diabetes.

Several studies have shown that human primary myotubes retain the metabolic characteristic of their donors in vitro. Others and we have demonstrated a reduced lipid turnover and fat oxidation rate in myotubes derived from obese donors without and with type 2 diabetes (T2D). Because exercise is known to increase fat oxidative capacity in skeletal muscle, we investigated if in vitro exercise could restore primary defects in lipid handling in myotubes of obese without and with T2D compared to lean non-diabetic donors. Primary myotubes cultures were derived from biopsies of lean, obese and T2D subjects. One single bout of long-duration exercise was mimicked in vitro by electrical pulse stimulation (EPS) for 24 h. Lipid handling was measured using radiolabeled palmitate, Metabolic gene expression by real-time qPCR, and proteins by western blot. We first show that myotubes from obese and T2D donors had increased uptake and incomplete oxidation of palmitate. This was associated with reduced mitochondrial respiratory chain complex II, III and IV protein expression in myotubes from obese and T2D subjects. EPS stimulated palmitate oxidation in lean donors, while myotubes from obese and T2D donors were refractory to this effect. Interestingly, EPS increased total palmitate uptake in myotubes from lean donors while myotubes from T2D donors had a reduced rate of palmitate uptake into complex lipids and triacylglycerols. Novelty: • Myotubes from obese and T2D donors are characterized by primary defects in palmitic acid handling. • Both obese and T2D myotubes are partially refractory to the beneficial effect of exercise on lipid handling.
B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma

ABSTRACT Introduction: B cell maturation antigen (BCMA) contributes to MM pathophysiology and is a target antigen for novel MM immunotherapy. Complete responses have been observed in heavily pretreated MM patients after treatment with BCMA antibody-drug conjugates (ADC), chimeric antigen receptor T, and bi-specific T cell engagers (BiTE®). These and other innovative BCMA-targeted therapies transform the treatment landscape and patient outcome in MM. Areas covered: The immunobiological rationale for targeting BCMA in MM is followed by key preclinical studies and available clinical data on efficacy and safety of therapies targeting BCMA from recent phase I/II studies. Expert opinion: BCMA is the most selective MM target antigen, and BCMA-targeted approaches have achieved high responses even in relapse and refractory MM as a monotherapy. Long-term follow-up and correlative studies using immuno-phenotyping and -sequencing will delineate mechanisms of overcoming the immunosuppressive MM bone marrow microenvironment to mediate additive or synergistic anti-MM cytotoxicity. Moreover, they will delineate cellular and molecular events underlying the development of resistance underlying relapse of disease. Most importantly, targeted BCMA-based immunotherapies used earlier in the disease course and in combination (adoptive T cell therapy, mAbs/ADCs, checkpoint and cytokine blockade, and vaccines) have great promise to achieve long-term disease control and potential cure.
The HKT Transporter Gene from Arabidopsis, AtHKT1;1, Is Dominantly Expressed in Shoot Vascular Tissue and Root Tips and Is Mild Salt Stress-Responsive

The Arabidopsis high-affinity K+ transporter (AtHKT1;1) plays roles in salt tolerance by unloading Na+ from the root xylem to the xylem parenchyma cells and/or uploading Na+ from the shoot/leaf xylem to the xylem parenchyma cells. To use this promoter for the molecular breeding of salt-tolerant plants, I evaluated the expression profile of the AtHKT1;1 promoter in detail. Approximately 1.1 kbp of sequence upstream from the start codon of AtHKT1;1 was polymerase chain reaction (PCR)-amplified, fused to the β-glucuronidase (GUS) gene, and introduced into Arabidopsis. The resultant transformants were evaluated under nonstressed and salt-stress conditions at the seedling and reproductive stages. Histochemical analysis showed that GUS activity was detected in vascular bundle tissue in roots, hypocotyls, petioles, leaves, and petals, and in root tips. GUS enzyme activity in shoots tended to be higher than that in roots at both stages. After treatment with 50 mM NaCl for 24 h, GUS transcription levels and GUS enzyme activity were enhanced in transgenic lines. These results indicate that the AtHKT1;1 promoter isolated in this study could be useful in expressing transgenes specifically in vascular tissue and root tips, and in a mild salt-stress-responsive manner. The data provide novel insights into the functions of AtHKT1;1.
Effects of Defoliation on Phenolic Concentrations, Antioxidant and Antibacterial Activity of Grape Skin Extracts of the Varieties Blaufränkisch and Merlot (Vitis vinifera L.)

Vitis vinifera L. has been highlighted by its many positive effects on human health, including antibacterial, anti-inflammatory and antioxidant activity due to its rich phytochemical content. Removing six basal leaves has great potential to influence the production of phytochemicals. The purpose of this study was to determine the impact of different terms of defoliation on the antioxidant and antibacterial activity of grape skin extracts of the Blaufränkisch and Merlot varieties. The total phenolic concentration, total and individual anthocyanin concentration, antioxidant activity and antibacterial activity on gram-positive and gram-negative human pathogens have been determined. The study was conducted on three treatments (control treatment without defoliation, defoliation immediately after bloom and defoliation before the start of the véraison phase). The results showed statistically significant enhancement of the total phenolic concentration as well as the antioxidant and antibacterial activity in both studied cultivars. Defoliation just after blooming was the preferable defoliation term in the Merlot variety for achieving the highest total anthocyanin concentration, antioxidant activity and significant increase of antibacterial activity against all four investigated bacteria. Defoliation before the start of the véraison phase was the preferable defoliation term for achieving the highest total anthocyanin concentration in the Blaufränkisch variety. In general, treatment of defoliation immediately after bloom was more beneficial compared with the defoliation before the start of the véraison phase.
High-level expression of biologically active human follicle stimulating hormone in the Chinese hamster ovary cell line by a pair of tricistronic and monocistronic vectors

Recombinant human follicle stimulating hormone (FSH), produced in Chinese hamster ovary (CHO) cells, is widely used for treatment of fertility disorders and is subject to biosimilars development. Cell lines with high specific productivities may simplify the FSH production process. Here, we used our previously established expression system based on vector p1.1 to create new cell lines secreting heterodimeric FSH protein. To this end, we linked open reading frames of both FSH subunits by the wild-type internal ribosome entry site from the encephalomyocarditis virus (EMCV IRES). Intact and double-negative for the dihydrofolate reductase CHO cells were stably transfected by the FSH-coding plasmids. Stably transfected intact cells showed higher level of the FSH secretion and were utilized for subsequent methotrexate-driven transgene amplification, which doubled their productivity. The excess of the free α-subunit was corrected by transfecting the cells by the additional p1.1-based plasmid encoding the β-subunit of the FSH. Clonal cell lines obtained secreted mostly the heterodimeric FSH and possessed specific productivities up to 12.3±1.7 pg/cell/day. Candidate clonal cell line C-P1.3-FSH-G4 maintained a constant specific productivity for at least 2 months of culturing without the section pressure. The resulting FSH protein conformed to the international pharmaceutical quality criteria as evidenced by the receptor binding kinetics, distribution pattern of hormone isoforms and biological activity. In conclusion, our expression system offers a simple and cost-effective approach to production of FSH.
Contribution of the Achilles tendon to force potentiation in a stretch–shortening cycle

ABSTRACT Muscle force during concentric contractions is potentiated by a preceding eccentric contraction: a phenomenon known as the stretch–shortening cycle (SSC) effect. Tendon elongation is often considered to be the primary factor for this force potentiation. However, direct examination of the influence of tendon elongation on the SSC effect has not been made. The aim of this study was to evaluate the contribution of tendon elongation to the SSC effect by comparing the magnitude of the SSC effect in the rat soleus with and without the Achilles tendon. The rat soleus was subjected to concentric contractions without pre-activation (CON) and concentric contractions with an eccentric pre-activation (ECC). For the ‘with-tendon’ condition, the calcaneus was rigidly fixed to a force transducer, while for the ‘without-tendon’ condition, the soleus was fixed at the muscle–tendon junction. The SSC effect was calculated as the ratio of the mechanical work done during the concentric phase for the ECC and the CON conditions. Substantial and similar (P=0.167) SSC effects were identified for the with-tendon (318±86%) and the without-tendon conditions (271±70%). The contribution of tendon elongation to the SSC effect was negligible for the rat soleus. Other factors, such as pre-activation and residual force enhancement, may cause the large SSC effects and need to be evaluated. Summary: Eliminating the Achilles tendon does not affect the stretch–shortening cycle in rat soleus muscle.
Nighttime blood pressure decline as a predictor of renal injury in patients with hypertension: a population-based cohort study

We explored whether the nighttime blood pressure (BP) decline predicts renal function decline in a population-based cohort with primary hypertension. We measured the baseline ambulatory BP and glomerular filtration rate (GFR) in a cohort of 1,042 primary hypertensive patients. We repeated the GFR measurements and calculated the rate of GFR decline after a median follow-up of 5.8 years. The estimated GFR (eGFR) declined by −0.23 to −0.20 mL/min per year as the nighttime systolic BP (SBP), diastolic BP (DBP), and mean BP decline rates increased by 1% (P < 0.001). In the fully adjusted model, the nighttime SBP, DBP, and mean BP were all related to a steeper rate of eGFR decline by −0.25 to −0.22 mL/min per 1% increase. The adjusted multivariable results indicated that the odds of an eGFR decline were reduced by 46% when the nighttime SBP decline rate increased by 1% (OR= 0.54, 95% CI: 0.46–0.62). The restricted cubic spline model indicated a non-linear dose-response relationship with the nighttime SBP, DBP, and mean BP. Nighttime BP may be an important biomarker of renal function injury in hypertensive patients.
British Society of Gastroenterology guidelines on the diagnosis and management of patients at risk of gastric adenocarcinoma

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer—in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met.
Weak correlations between body height and several brain metrics in healthy elderly subjects

The question whether body height is related to different brain size measures has recently gained renewed interest as some studies have reported that body height correlates with intelligence and several brain size measures. In this study, we re‐evaluated this question by examining the relationship between body height and different brain size measures including intracranial volume, total brain volume, total cortical surface area, total cortical volume, volume of normal‐appearing white matter, white matter hyperintensity, cortical surface area, cortical thickness, subcortical grey matter volume, cerebellar cortex and cerebellar white matter in a relatively large sample (n = 216) of physically and cognitively healthy elderly subjects (mean age 71 years, age range 65–85 years). We identified small correlations (r = .11–.19) between body height and seven out of 10 brain metrics (total brain volume, cortical surface area, cortical volume, subcortical volume, normal‐appearing white matter volume and cerebellar grey as well as white matter volumes) when controlling for sex and age. Based on these small relationships between body height and various brain size measures, we discuss the possible reasons and theoretical problems for these small relationships.
In Vitro Acquisition of Specific Small Interfering RNAs Inhibits the Expression of Some Target Genes in the Plant Ectoparasite Xiphinema index

Xiphinema index is an important plant parasitic nematode that induces direct damages and specifically transmits the Grapevine fanleaf virus, which is particularly harmful for grapevines. Genomic resources of this nematode species are still limited and no functional gene validation technology is available. RNA interference (RNAi) is a powerful technology to study gene function and here we describe the application of RNAi on several genes in X. index. Soaking the nematodes for 48 h in a suspension containing specific small interfering RNAs resulted in a partial inhibition of the accumulation of some targeted mRNA. However, low reproducible silencing efficiency was observed which could arise from X. index silencing pathway deficiencies. Indeed, essential accustomed proteins for these pathways were not found in the X. index proteome predicted from transcriptomic data. The most reproducible silencing effect was obtained when targeting the piccolo gene potentially involved in endo-exocytosis of synaptic molecules. This represents the first report of gene silencing in a nematode belonging to the Longidoridae family.
Instrumented Crutch Tip for Monitoring Force and Crutch Pitch Angle

In rehabilitation procedures related to the lower limbs, gait monitoring is an important source of information for the therapist. However, many of the approaches proposed in the literature require the use of uncomfortable and invasive devices. In this work, an instrumented tip is developed and detailed, which can be connected to any crutch. The instrumented tip provides objective data of the crutch motion, which, combined with patient movement data, might be used to monitor the daily activities or assess the recovery status of the patient. For that purpose, the tip integrates a two-axis inclinometer, a tri-axial gyroscope, and a force sensor to measure the force exerted on the crutch. In addition, a novel algorithm to estimate the pitch angle of the crutch is developed. The proposed approach is tested experimentally, obtaining acceptable accuracies and demonstrating the validity of the proposed lightweight, portable solution for gait monitoring.
Diagnostic Accuracy of Radiologic Methods for Ankle Syndesmosis Injury: A Systematic Review and Meta-Analysis

Misdiagnosis and inadequate treatment of syndesmosis could result in significant long-term morbidity including pain, instability, and degenerative changes of the ankle joint. The objective of this systematic review and meta-analysis was to determine whether radiologic tests accurately and reliably diagnose ankle syndesmosis injury. Medline, Embase, and Cochrane were searched. The database search resulted in 258 full text articles that we assessed for eligibility, we used eight studies that met all the inclusion criteria. In subgroup meta-analysis, the sensitivity analysis showed significant differences only in the MRI (Magnetic Resonance Imaging), and specificity was not statistically significant. In diagnostic meta-analysis, the pooled sensitivity and specificity were 0.528 and 0.984 for X-rays, 0.669 and 0.87 for CT (Computed Tomography), and 0.929 and 0.865 for MRI, all respectively. For sensitivity, MRI showed significantly sensitivity as higher than the other methods, and we detected no significance for specificity. Syndesmosis injuries differed significantly in the accuracy of radiological methods according to the presence of accompanied ankle fractures. In patients with fractures, simple radiography has good specificity, and CT and MRI have high sensitivity and specificity irrespective of fracture; in particular, MRI has similar accuracy to gold standard arthroscopic findings.
Resveratrol-Induced Temporal Variation in the Mechanical Properties of MCF-7 Breast Cancer Cells Investigated by Atomic Force Microscopy

Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine simultaneous variations of Young’s modulus, the maximum adhesion force, and tether formation, thereby determining cell motility and adhesiveness. Effects of treatment were measured at several time-points (0–6 h, 24 h, and 48 h); longer exposures resulted in cell death. Our results demonstrated that AFM can be efficiently used as a diagnostic tool to monitor irreversible morpho/nano-mechanical changes in cancer cells during the early steps of drug treatment.
Preparation of Validation Materials for Estimating Gluten Recovery by ELISA According to SMPR 2017.021.

Background: In September 2017, the AOAC INTERNATIONAL Stakeholder Panel for Alternative Methods adopted Standard Method Performance Requirement (SMPR®) 2017.021, "Quantitation of Wheat, Rye, and Barley Gluten in Oats," as guidance for the validation of methods for measuring gluten in oat products. The SMPR requires prospective methods to demonstrate adequate recovery (50-200%) based on the analysis of a set of reference samples. Objective: This document provides specific methods and data on the preparation of such validation materials and their analysis by an R5 ELISA kit to demonstrate the SMPR recovery estimation procedure. Methods: Seven reference samples were made by spiking wheat, rye, and barley into gluten-free oat flour at two levels, 10 and 20 mg/kg. The levels of gluten were determined by a wet chemical method based on the Codex Alimentarius definition of gluten. Results: The recoveries for wheat, rye, and barley were 122, 425, and 349%, respectively, for the R5 ELISA kit. The wet chemical method for estimating gluten in a sample of pure grain demonstrated repeatability relative SDs ranging from 1.40 to 2.75%. Conclusions: The reference materials are suitable to estimate ELISA kit responses to wheat, rye, and barley and calculate recoveries. Highlights: A series of oat flours spiked with wheat, rye, and barley flours were developed to be used as reference materials. A wet chemical method was established to estimate gluten contents based on the Codex definition. The reference materials are available for purchase to support further method development and validation.
BCG Therapy of Bladder Cancer Stimulates a Prolonged Release of the Chemoattractant CXCL10 (IP10) in Patient Urine

Background: Intra-vesical instillation of Bacille Calmette–Guérin (BCG), an attenuated strain of Mycobacterium bovis, is an effective therapy for high-grade non-muscle invasive bladder cancer (NMIBC), which provokes a local immune response resulting in 70% of patients free of relapse after three years. Because non-responder patients usually have a bad prognosis, the early identification of treatment failure is crucial. We hypothesized that, if an effective immune response was taking place in the bladder, soluble factors would be released to the urine many days after BCG instillations. Methods: An extensive panel of cytokines and chemokines released into the urine seven days after every BCG instillation was screened in a cohort of NMIBC patients over three years. Results: The determinations of the urinary concentrations of cytokines, chemokines, and creatinine showed that increasing concentrations of C-X-C motif chemokine 10 (CXCL10) also known as interferon-inducible protein 10 (IP10) could be detected during the six-week induction cycle of BCG-treated patients released into the urine by CD14+ cells. In vitro, CXCL10 facilitated the recruitment of effector immune cells after the BCG-mediated upregulation of CXCR3 in both T- and natural killer (NK)-cells. Conclusions: The high concentrations of chemokine detected one week after the encounter with mycobacteria suggest that the CXCL10 axis might be related to the intensity of the immune anti-tumor response.
Occupational Accidents in Iran: Risk Factors and Long Term Trend (2007–2016)

Background: Although much is known about the distribution of occupational accidents in the world, less is known about occupational injuries in developing countries. Therefore, the aim of this study was to investigate the trend of occupational accidents during 10 years (2007-2016) and to find factors affecting the accident outcome. Study design: A cross-sectional study. Methods: This study was done based on the data gathered by the Iranian Social Security Organization (ISSO), including demographic data (age, sex, marital status) and occupational accident characteristics (accident sector, cause, type, body part, location, time, month, and incident outcome). Result: A decreasing pattern of occupational accidents was found from 2.95 per 1000 workers in 2007 to 1.46 per 1000 workers in 2016. The mean age of injured workers was 32.97 years. The most common cause and type of accidents were incaution and lack of attention and collision, and trapping, respectively. Limbs were the most affected body parts, and less than 1% of occupational accidents resulted in death. The highest incident was seen in the industrial sector during all years. More severe accident outcomes were seen at older ages and in the male gender, married subjects, winter season, agriculture sector, and outside of work place. Conclusion: These results provide a basis for further investigations regarding data collection and accident causes. Modification of some associated factors and implementation of safety prevention programs would be useful in reducing occupational accidents in Iran.