Miracle-dz/UniFAR-FTUs huggingface dataset:
JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis

Dermatomyositis is an acquired auto-immune disease characterized by skin lesions and muscle-specific pathological features such as perifascicular muscle fibre atrophy and vasculopathy. Dermatomyositis patients display an upregulation of type I interferon-inducible genes in muscle fibres, endothelial cells, skin and peripheral blood. However, the effect of type I interferon on muscle tissue has not yet been determined. Our aim was to study the pathogenicity of type I interferon in vitro and to evaluate the efficacy of the type I interferon pathway blockade for therapeutic purposes. The activation of type I interferon in differentiating myoblasts abolished myotube formation with reduced myogenin expression while in differentiated myotubes, we observed a reduction in surface area and an upregulation of atrophy-associated genes. In vitro endothelial cells exposure to type I interferon disrupted vascular network organization. All the pathogenic effects observed in vitro were abolished by ruxolitinib. Finally, four refractory dermatomyositis patients were treated with ruxolitinib and improvement ensued in skin lesions, muscle weakness and a reduced serum type I interferon levels and interferon-inducbile genes scores. We propose JAK inhibition as a mechanism-based treatment for dermatomyositis, a finding that is relevant for the design of future clinical trials targeting dermatomyositis.
Training Classifiers with Natural Language Explanations

Training accurate classifiers requires many labels, but each label provides only limited information (one bit for binary classification). In this work, we propose BabbleLabble, a framework for training classifiers in which an annotator provides a natural language explanation for each labeling decision. A semantic parser converts these explanations into programmatic labeling functions that generate noisy labels for an arbitrary amount of unlabeled data, which is used to train a classifier. On three relation extraction tasks, we find that users are able to train classifiers with comparable F1 scores from 5-100 faster by providing explanations instead of just labels. Furthermore, given the inherent imperfection of labeling functions, we find that a simple rule-based semantic parser suffices.
Interprofessional education in mental health: An opportunity to reduce mental illness stigma

ABSTRACT Mental illness stigma is a common problem in healthcare students and professionals in addition to the general public. Stigma is associated with numerous negative outcomes and hence there is an urgent need to address it. This article explores the potential for interprofessional education (IPE) to emerge as a strategy to reduce mental illness stigma amongst healthcare students and professionals. Most anti-stigma strategies use a combination of knowledge and contact (with a person with lived experience) to change attitudes towards mental illness. Not surprisingly interprofessional educators are well acquainted with theory and learning approaches for attitude change as they are already used in IPE to address learners’ attitudes and perceptions of themselves, other professions, and/or teamwork. This article, through an analysis of IPE pedagogy and learning methods, identifies opportunities to address mental illness stigma with application of the conditions that facilitate stigma reduction. The goal of this article is to raise awareness of the issue of mental illness stigma amongst healthcare students and professionals and to highlight interprofessional education as an untapped opportunity for change.
Effect of Vitamin C and Vitamin E on Mercuric Chloride -Induced Reproductive Toxicity in Male Rats

To evaluate the protective effects of Vitamin C and Vitamin E against Mercuric chloride -induced reproductive toxicity and to study the mechanisms underlying these effects. Male Wistar rats were orally administered mercuric chloride (10 mg/100 gm b.wt), (10 mg/100 gm b.wt) of mercuric chloride + (40 mg/100 gm b.wt) of Vitamin C and (10 mg/100 gm b.wt) of mercuric chloride + (20 mg/100 gm b.wt) of Vitamin E were administered orally to male albino rats for 30 days. Treatments with either Vitamin C or Vitamin E resulted in a significant protection of reproductive function. Both vitamins reduced the extent of mercuric chloride-induced reproductive toxicity, as evidenced by decrease in sperm abnormality and increase in sperm motility. Mercuric chloride-induced alterations in testis lipid peroxidation (MDA) were also markedly improved by test vitamins, and mercuric chloride -induced alterations in the testis antioxidation defense system were profoundly prevented by vitamins. In groups, where mercuric chloride was combined with either Vitamin C or Vitamin E, antioxidation enzymes like superoxide dismutase (SOD), reduced glutathione (GSH), and catalase (CAT) were significantly elevated compared to the mercuric chloride-treated group. The results provide further insight into the mechanisms of mercuric chloride-induced reproductive toxicity and confirm the antioxidant potential of both Vitamin C and Vitamin E.
Electrospinning of highly concentrated albumin patches by using auxiliary polymers for laser-assisted vascular anastomosis

Background and objective. Electrospun meshes have been extensively investigated for tissue engineering and drug delivery. The application of this technology is of interest for laser-assisted vascular anastomosis (LAVA) due to the possibility to bind and stabilize macromolecules in fibers. Materials and methods. We prepared bovine serum albumin (BSA) blend microfibers from the auxiliary proteins polyethylene oxide (PEO), polycaprolactone (PCL), polyvinyl alcohol (PVA) and gelatin. The thickness and weight of the resulting patches were measured and the morphological characteristics were observed by scanning electron microscopy. Thereafter, layered patches were prepared by spinning the BSA/polymer layer on top of a light absorbing layer made of indocyanine green and PCL. The effect of the material composition of the electrospun patches on the behavior during LAVA, the bonding strength and the resulting thermal damage were investigated. Results. The bonding strength of the tissue fusion increased with higher BSA amounts in the patch. By using PEO, a ratio of 85/15 (w/w) of BSA/PEO was stable during electrospinning, leading to a shear strength that was similar to patches that were soaked in liquid BSA (20.7 ± 4.1 mN mm−2 and 20.3 ± 4.1 mN mm−2, respectively). The handling during LAVA was however drastically improved by using a layered patch made from BSA/PEO. Thermal damage was similar compared to previous solder materials. Conclusion. This study investigated the maximum amount of BSA possible in electrospun polymer fibers made from PEO, PCL, PVA and gelatin. Both, the process of electrospinning and the performance during ex vivo LAVA, makes the BSA/PEO blend a promising material for LAVA.
Histone deacetylase inhibition inhibits brachial plexus avulsion‐induced neuropathic pain

Introduction: Neuropathic pain induced by brachial plexus avulsion (BPA) is a pathological condition. We hypothesized that inhibition of histone deacetylase (HDAC) could suppress BPA‐induced neuropathic pain through inhibition of transient reception potential (TRP) overexpression and protein kinase B (Akt)‐mediated mammalian target of rapamycin (mTOR) activation. Methods: We generated a rat BPA model; administered HDAC inhibitor tricostatin A (TSA) for 7 days postsurgery; and assessed the effects on HDAC expression, Akt phosphorylation, neuroinflammation, and mTOR activation. Results: TSA treatment alleviated BPA‐induced mechanical hyperalgesia, suppressed Akt phosphorylation, and increased HDAC. We found suppressed proinflammatory cytokine levels, TRPV1 and TRPM8 expression, and mTOR activity in TSA‐treated BPA rats. Discussion: Our results suggest that altered HDAC and Akt signaling are involved in BPA‐induced neuropathic pain and that inhibition of HDAC could be an effective therapeutic approach in reducing neuropathic pain. Muscle Nerve 58: 434–440, 2018
Sagittal Spinal Alignment in Adult Spinal Deformity: An Overview of Current Concepts and a Critical Analysis Review

Changes in spinal alignment trigger several compensatory changes in the pelvis and lower extremities to maintain upright posture. Activating these mechanisms of compensation may require increased energy expenditure to maintain upright posture.The Scoliosis Research Society-Schwab Adult Spinal Deformity (ASD) classification system allows for a uniform classification and discussion of ASD. A higher sagittal deformity classifier is associated with increased disability.Age-related changes in spinal alignment are important to consider when setting alignment goals for deformity correction. Less-aggressive correction should be considered in older patients because of their increased risk for complications.A structured approach to the treatment of ASD consists of 6 steps: (1) find and quantify the driver of deformity, (2) evaluate how deformity impacts global alignment, (3) define alignment targets, (4) determine spinal flexibility, (5) choose a surgical strategy, and (6) execute this strategy intraoperatively in a controlled fashion.
SOME OSTROWSKI TYPE INEQUALITIES FOR QUASI-CONVEX FUNCTIONS WITH APPLICATIONS TO SPECIAL MEANS

for any x, y ∈ [a, b] and λ ∈ [0, 1] . Clearly, any convex function is a quasi-convex function. Furthermore, there exist quasi-convex functions which are not convex (see [10]). For refinements inequalities concerning quasi-convex functions, see [2], [3], [9] and [10]. Recently, Alomari et al. [2] established several inequalities for functions whose first derivatives in absolute value are quasi-convex. Namely, the authors obtained the following results:
Beating the Omega Clock: An Optimal Stopping Problem with Random Time-Horizon Under Spectrally Negative Lévy Models

We study the optimal stopping of an American call option in a random time-horizon under exponential spectrally negative L\'evy models. The random time-horizon is modeled as the so-called Omega default clock in insurance, which is the first time when the occupation time of the underlying L\'evy process below a level $y$, exceeds an independent exponential random variable with mean $1/q>0$. We show that the shape of the value function varies qualitatively with different values of $q$ and $y$. In particular, we show that for certain values of $q$ and $y$, some quantitatively different but traditional up-crossing strategies are still optimal, while for other values we may have two disconnected continuation regions, resulting in the optimality of two-sided exit strategies. By deriving the joint distribution of the discounting factor and the underlying process under a random discount rate, we give a complete characterization of all optimal exercising thresholds. Finally, we present an example with a compound Poisson process plus a drifted Brownian motion.
Interexaminer Variance of Median Nerve Compound Muscle Action Potential Measurements in Hand Position With and Without Fixation in Plaster

Objectives: We examined how hand fixation affects interexaminer variance in measuring compound muscle action potential (CMAP) during nerve conduction studies of the median nerve. Methods: Subjects comprised 6 experienced examiners [1 woman and 5 men; mean (SD) age, 38.3 ± 8.5 years; range, 28-46 years]. The standardized median nerve motor conduction setting was used for electromyography. The mean of 5 serial stimulations was taken as 1 examination for each subject. Distal latency, conduction velocity, and peak-to-peak amplitude of CMAP were measured as parameters. Subjects were examined without hand fixation and with hands fixed in prepared plaster molds. Results: Fixation yielded significantly decreased coefficient of variance for CMAP amplitude (5.0% ± 3.4%) compared with measurement without fixation (8.4% ± 3.7%; P = 0.028). No differences in distal latencies or conduction velocities were evident between fixation and nonfixation. Conclusions: This study provides quantitative evidence for empirical observations that hand fixation might decrease CMAP variability in median nerve studies.
Prevalence of Serious Bacterial Infections in Return Visits to the Emergency Department Among Infants Aged 90 Days or Younger

ObjectiveThe main objective of this study was to describe the epidemiology of return visits (RVs) in well-appearing infants to an urban emergency department (ED) who were evaluated for serious bacterial infection (SBI) at their index ED visit. MethodsWe conducted a retrospective chart review on infants aged 90 days and younger who were evaluated for SBI at their initial ED visit from 2003 through 2009. A parent database of all febrile infants evaluated for SBI was queried to identify patients who had an RV within 7 days of the index visit. We collected demographic variables including age, sex, and past medical history as well as laboratory test results including white blood cell count, blood, urine, and cerebrospinal fluid cultures and viral studies. ResultsOf eligible febrile infants, 10.8% (350/3220) had an RV to the ED within 7 days. The prevalence of SBI in the RV cohort was 6.0% (21/350), which included 1.7% (6/350) bacteremia, 3.7% (13/350) urinary tract infection, and 0.6% (2/350) combined urinary tract infection and bacteremia. The blood culture contamination rate was 88%. ConclusionsInfants aged 90 days or younger who are evaluated for SBI have high RV rates. A substantial number of RVs are due to contaminated blood cultures. Future studies should be conducted to identify predictors for false-positive blood cultures.
Scalable Bayesian variable selection for structured high‐dimensional data

Variable selection for structured covariates lying on an underlying known graph is a problem motivated by practical applications, and has been a topic of increasing interest. However, most of the existing methods may not be scalable to high‐dimensional settings involving tens of thousands of variables lying on known pathways such as the case in genomics studies. We propose an adaptive Bayesian shrinkage approach which incorporates prior network information by smoothing the shrinkage parameters for connected variables in the graph, so that the corresponding coefficients have a similar degree of shrinkage. We fit our model via a computationally efficient expectation maximization algorithm which scalable to high‐dimensional settings ( p∼100,000 ). Theoretical properties for fixed as well as increasing dimensions are established, even when the number of variables increases faster than the sample size. We demonstrate the advantages of our approach in terms of variable selection, prediction, and computational scalability via a simulation study, and apply the method to a cancer genomics study.
A temporal and morphological framework for flower development in Antirrhinum majus

The entire course of flower development in Antirrhinum majus L. , from initiation to maturity, is described in terms of regular time intervals. Floral meristem and bud morphology was determined by scanning electron microscopy for a sequence of 58 plastochrons. These can be grouped to define 15 stages or 7 phases of development, providing a temporal framework for gene expression and key morphological events, such as the formation of the complex corolla. The time course is also used to estimate overall growth rates of sepals and petals. Sepals initially grow at a constant rate, but growth rate gradually declines at later stages and sepal growth eventually arrests before flower development is complete. Petals initially grow at a similar rate to that of early sepals, but this growth rate is maintained for a longer period, accounting for the larger size of mature petals relative to sepals. Comparisons with Arabidopsis indicate that the duration of growth also makes an important contribution to variation in flower size.
Estimation of Relative Load From Bar Velocity in the Full Back Squat Exercise

Abstract The use of bar velocity to estimate relative load in the back squat exercise was examined. 80 strength-trained men performed a progressive loading test to determine their one-repetition maximum (1RM) and load-velocity relationship. Mean (MV), mean propulsive (MPV) and peak (PV) velocity measures of the concentric phase were analyzed. Both MV and MPV showed a very close relationship to %1RM (R2=0.96), whereas a weaker association (R2=0.79) and larger SEE (0.14 vs. 0.06 m·s−1) were found for PV. Prediction equations to estimate load from velocity were obtained. When dividing the sample into 3 groups of different relative strength (1RM/body mass), no differences were found between groups for the MPV attained against each %1RM. MV attained with the 1RM was 0.32±0.03 m·s−1. The propulsive phase accounted for ~82% of concentric duration at 40% 1RM, and progressively increased until reaching 100% at 1RM. Provided that repetitions are performed at maximal intended velocity, a good estimation of load (%1RM) can be obtained from mean velocity as soon as the first repetition is completed. This finding provides an alternative to the often demanding, time-consuming and interfering 1RM or nRM tests and allows implementing a velocity-based resistance training approach.
KINEMATIC ANALYSIS OF BICYCLE PEDALLING USING 2D AND 3D MOTION CAPTURE SYSTEMS

The main purpose was to test the validity and sensibility of two motion capture systems (sophisticated 3D vs low-cost 2D) to analyse angular kinematics during pedalling. Twelve trained cyclists participated, and were analysed in three different saddle heights at a random order: their preferred one, 2% lower and 2% higher. High correlations were found between 2D and 3D systems in all the measured variables. The 2D system was sensitive as the 3D to detect small changes in saddle height. In conclusion, the 2D motion capture system is valid and sensitive for angular kinematic analysis in the sagittal plane. It underestimated 2-3o hip and knee extensions, without differences in the ankle extension, while joint flexion were also underestimated 3-4o, 2o and 1o, respectively. Additionally, pedalling symmetry between left and right sides could be assumed.
Combined effects of PEGylation and particle size on uptake of PLGA particles by macrophage cells

Objective: At the present study, relationship between phagocytosis of PLGA particles and combined effects of particle size and surface PEGylation was investigated. Materials and Methods: Microspheres and nanospheres (3500 nm and 700 nm) were prepared from three types of PLGA polymers (non-PEGylated and PEGylation percents of 9% and 15%). These particles were prepared by solvent evaporation method. All particles were labeled with FITC-Albumin. Interaction of particles with J744.A. 1 mouse macrophage cells, was evaluated in the absence or presence of 7% of the serum by flowcytometry method. Results: The study revealed more phagocytosis of nanospheres. In the presence of the serum, PEGylated particles were phagocytosed less than non-PEGylated particles. For nanospheres, this difference was significant (P<0/05) and their uptake was affected by PEGylation degree. In the case of microsphere formulation, PEGylation did not affect the cell uptake. In the serum-free medium, the bigger particles had more cell uptake rate than smaller ones but the cell uptake rate was not influenced by PEGylation. Conclusion: The results indicated that in nanosized particles both size and PEgylation degree could affect the phagocytosis, but in micron sized particles just size, and not the PEGylation degree, could affect this.
Bacteria‐induced susceptibility to Candida albicans super‐infection in mice via monocyte methyltransferase Setdb2

Systemic bacterial infections are prone to secondary Candida albicans super‐infection. However, the molecular mechanisms involved remain poorly understood. In this study, a model comprising sublethal cecal ligation and puncture plus C. albicans intravenous injection was applied to mimic the situation in super‐infection. Compared with mice without systemic bacterial infection, mice with systemic bacterial infection had lower antifungal gene expression (including Il1b, Tnf, Il6, Ifnb, Ifng, Cxcl1, and Ccr2) in monocytes and less inflammatory monocytes and neutrophils infiltrating into the kidney when challenged with C. albicans. Further, lentivirus‐mediated Setdb2‐knockout and overexpression experiments verified that Setdb2 levels in monocytes correlated negatively with antifungal gene expression and survival rates. Transcriptional repression was probably achieved by Setdb2 through H3 methylation at lysine 9 in promoter regions of these antifungal genes.
Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease

Background: This study explored the feasible efficacy and safety of the Spore Powder of Ganoderma Lucidum (SPGL) for treating patients with Alzheimer disease (AD). Methods: Forty-two eligible patients with AD were recruited. These patients were randomly allocated to an intervention group and a control group equally. The patients in the intervention group underwent SPGL, whereas the subjects in the control received placebo. All patients were treated for a total of 6 weeks. The primary outcome was measured by Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog). The secondary outcomes were measured by the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Neuropsychiatric Index (NPI). The adverse events were also recorded during the treatment period. Results: At the end of the treatment, GLSP did not show more encouraging outcomes in symptoms improvement, measured by the ADAS-cog (P = .31), and NPI (P = .79); and quality of life enhancement, measured by the WHOQOL-BREF (physical, P = .62; psychological, P = .69; social relationships, P = .75; environment, P = .82; overall quality of life, P = .74), compared with the control group. In addition, all adverse events were mild, and no significant differences were found between 2 groups. Conclusion: The results of this study did not find the promising efficacy of SPGL for the treatment of AD after 6-week treatment. It may be because of the relative short-term of intervention. Future clinical trials with larger sample size and longer treatment period are urgently needed.
Deep Subseafloor Fungi as an Untapped Reservoir of Amphipathic Antimicrobial Compounds

The evolving global threat of antimicrobial resistance requires a deep renewal of the antibiotic arsenal including the isolation and characterization of new drugs. Underexplored marine ecosystems may represent an untapped reservoir of novel bioactive molecules. Deep-sea fungi isolated from a record-depth sediment core of almost 2000 m below the seafloor were investigated for antimicrobial activities. This antimicrobial screening, using 16 microbial targets, revealed 33% of filamentous fungi synthesizing bioactive compounds with activities against pathogenic bacteria and fungi. Interestingly, occurrence of antimicrobial producing isolates was well correlated with the complexity of the habitat (in term of microbial richness), as higher antimicrobial activities were obtained at specific layers of the sediment core. It clearly highlights complex deep-sea habitats as chemical battlefields where synthesis of numerous bioactive compounds appears critical for microbial competition. The six most promising deep subseafloor fungal isolates were selected for the production and extraction of bioactive compounds. Depending on the fungal isolates, antimicrobial compounds were only biosynthesized in semi-liquid or solid-state conditions as no antimicrobial activities were ever detected using liquid fermentation. An exception was made for one fungal isolate, and the extraction procedure designed to extract amphipathic compounds was successful and highlighted the amphiphilic profile of the bioactive metabolites.