Miracle-dz/UniFAR-FTUs huggingface dataset:
Frequency and Functional Consequences of Low Appendicular Lean Mass and Sarcopenic Obesity in Patients with Asthma Referred for Pulmonary Rehabilitation

Introduction: One of the most prominent extrapulmonary manifestations in patients with chronic respiratory disease is changes in body weight and composition. However, the frequency and functional consequences of low appendicular lean mass (ALM) or sarcopenic obesity (SO) in patients with asthma are largely unknown. Therefore, the aim of the current study was to assess the frequency and functional consequences of low appendicular lean mass index (ALMI) and SO in patients with asthma. Methods: A retrospectively analyzed cross-sectional study was conducted in 687 patients with asthma (60% female, 58 ± 13 years, FEV1 76 ± 25% pred) referred for comprehensive pulmonary rehabilitation (PR). Body composition, pulmonary function, exercise capacity, quadriceps muscle function, and quality of life were assessed. Patients were classified as presenting low ALMI according to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values and as having SO according to the diagnostic procedure proposed by the 2022 ESPEN/EASO consensus. In addition, clinical outcomes between patients with normal and low ALMI or with and without SO were compared. Results: The frequency of patients classified as low ALMI was 19%, whereas 45% of the patients were obese. Among the obese patients, 29% had SO. In patients with normal weight, those with low ALMI were younger and had worse pulmonary function, exercise capacity and quadriceps muscle function than those with normal ALMI (all p < 0.05). Overweight patients with low ALMI presented poorer pulmonary function and quadriceps muscle function (both strength and total work capacity). In obese class I patients, those with low ALMI showed lower quadriceps strength and maximal oxygen uptake acquired during cardiopulmonary exercise testing. Both male and female patients with SO showed lower quadriceps muscle function and reduced maximal exercise capacity compared to non-SO asthma patients. Conclusion: Approximately one in five asthma patients presented low ALM when age-sex-BMI-specific ALMI cutoffs were applied. Obesity is common among patients with asthma referred for PR. Among the obese patients, a significant proportion presented SO. Low ALM and SO were associated with worse functional outcomes.
Traditional medicinal plants in the treatment of gastrointestinal parasites in humans: A systematic review and meta‐analysis of clinical and experimental evidence

Gastrointestinal (GI) parasites cause significant morbidity and mortality worldwide. The use of conventional antiparasitic drugs is often inhibited due to limited availability, side effects or parasite resistance. Medicinal plants can be used as alternatives or adjuncts to current antiparasitic therapies. This systematic review and meta‐analysis aimed to critically synthesise the literature on the efficacy of different plants and plant compounds against common human GI parasites and their toxicity profiles. Searches were conducted from inception to September 2021. Of 5393 screened articles, 162 were included in the qualitative synthesis (159 experimental studies and three randomised control trials [RCTs]), and three articles were included in meta‐analyses. A total of 507 plant species belonging to 126 families were tested against different parasites, and most of these (78.4%) evaluated antiparasitic efficacy in vitro. A total of 91 plant species and 34 compounds were reported as having significant in vitro efficacy against parasites. Only a few plants (n = 57) were evaluated for their toxicity before testing their antiparasitic effects. The meta‐analyses revealed strong evidence of the effectiveness of Lepidium virginicum L. against Entamoeba histolytica with a pooled mean IC50 of 198.63 μg/mL (95% CI 155.54–241.72). We present summary tables and various recommendations to direct future research.
A multivariate approach to investigate the associations of electrophysiological indices with schizophrenia clinical and functional outcome

Abstract Background Different electrophysiological (EEG) indices have been investigated as possible biomarkers of schizophrenia. However, these indices have a very limited use in clinical practice, as their associations with clinical and functional outcomes remain unclear. This study aimed to investigate the associations of multiple EEG markers with clinical variables and functional outcomes in subjects with schizophrenia (SCZs). Methods Resting-state EEGs (frequency bands and microstates) and auditory event-related potentials (MMN-P3a and N100-P3b) were recorded in 113 SCZs and 57 healthy controls (HCs) at baseline. Illness- and functioning-related variables were assessed both at baseline and at 4-year follow-up in 61 SCZs. We generated a machine-learning classifier for each EEG parameter (frequency bands, microstates, N100-P300 task, and MMN-P3a task) to identify potential markers discriminating SCZs from HCs, and a global classifier. Associations of the classifiers’ decision scores with illness- and functioning-related variables at baseline and follow-up were then investigated. Results The global classifier discriminated SCZs from HCs with an accuracy of 75.4% and its decision scores significantly correlated with negative symptoms, depression, neurocognition, and real-life functioning at 4-year follow-up. Conclusions These results suggest that a combination of multiple EEG alterations is associated with poor functional outcomes and its clinical and cognitive determinants in SCZs. These findings need replication, possibly looking at different illness stages in order to implement EEG as a possible tool for the prediction of poor functional outcome.
ORIENTING METHOD FOR OBSTACLE PROBLEMS

This paper deals with obstacle problems of type minimize R Ω F (x, v,∇v) dx subject to v ∈ W (Ω), v ≥ r in Ω, v = g on ∂Ω where Ω ⊂ R is a bounded open set and r, g ∈ W (Ω) (1 ≤ p ≤ ∞). To state some sufficient criteria for determining parts of the coincidence set C(u) = {x ∈ Ω : u(x) = r(x)} and of the non-coincidence set N (u) = {x ∈ Ω : u(x) > r(x)} of the optimal solution u to this obstacle problem, optimal solutions to some particular auxiliary problems without obstacle minimize R e ΩF (x, v,∇v) dx subject to v ∈ Ke Ω,g̃ = {v ∈ W 1,p(e Ω) : v = g̃ on ∂e Ω} are used as orienting tool. For this purpose, we do not assume any coercive assumption, but only the uniqueness of the optimal solution to auxiliary problems, which is ensured if e.g. the performance index is strictly convex in Ke .
A Novel Hybrid Global Optimization Algorithm Based on Particle Swarm Optimization and Differential Evolution

A new hybrid global optimization algorithm – PSODE is presented,which is based on the combination of the particle swarm optimization(PSO) and differential evolution(DE). PSODE is based on a two-population evolution scheme,in which the individuals of one population are evolved by PSO and the individuals of the other population are evolved by DE.The individuals both in PSO and DE are co-evolved during the algorithm execution by employing an information sharing mechanism.To further improve the proposed PSODE,a mutation mechanism is also introduced when it is strapped into a local minima.In test,four benchmark functions are used,and the performance of the proposed PSODE algorithm is compared with PSO and DE,which demonstrate that it's a powerful global optimization algorithm with rapid convergence rate,high solution quality and algorithm robustness.
Hepatitis C Virus Genotype 5 Variability in Treatment-Naïve Patients in South Africa

Introduction: Hepatitis C virus (HCV) genotype 5 was originally identified in South Africa, where it represents 35–60% of all HCV infections. There are limited data on resistance-associated variants (RAVs) in South Africa. Thus, we investigated variability within the NS3/NS4A, NS5A, and NS5B genes of treatment-naïve individuals with HCV genotype 5 infection at the Dr. George Mukhari Academic Hospital (DGMAH) in Pretoria, South Africa. Methods: Nested PCR was performed to amplify the NS3/4A, NS5A, and NS5B genes. RAVs were evaluated using the Geno2pheno tool. Results: In the NS3/4A gene, F56S and T122A were detected in one sample each. The D168E mutation was detected in 7 samples. Within the NS5A gene, the T62M mutation was detected in 2 individuals. In the NS5B gene, 8 of 12 individuals (67%) had the A421V mutation, while all 12 individuals (100%) had the S486A mutation. Discussion: RAVs were detected frequently among treatment-naïve individuals with HCV genotype 5 infection in South Africa. Thus, resistance testing may be prudent when initiating treatment of patients with genotype 5 infection. Additional population-based studies are needed to understand the prevalence of these RAVs during HCV genotype 5 infection.
Progressive Transmission of Vector Curve Data over Internet

We propose a method for multi-scale representation of curve which keeps topological relationship unchanged and elaborates the process of progressive transmission of curve data over the Internet based on this method.Firstly,the importance degree of nodes and the information about public constrain points and monotone chains are stored in a monotonous linear BLG tree structure.Then the multi-scale curve is generated in real time based on this structure and the topological relationship is maintained by an optimized monotone chains intersection algorithm.Finally,the method was used in the experiment of progressive transmission of curve data over the Internet and verified its effectiveness.
A novel mechanism regulating pyroptosis-induced fibrosis in endometriosis via lnc-MALAT1/miR-141-3p/NLRP3 pathway

Abstract Endometriosis is a chronic inflammatory disease distinguished by ectopic endometrium and fibrosis. NLRP3 inflammasome and pyroptosis are present in endometriosis. Aberrant increase of Long noncoding (Lnc)-metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays a vital role in endometriosis. However, the relationship between lnc-MALAT1, pyroptosis, and fibrosis is not completely known. In the present study, we found that the pyroptosis levels in ectopic endometrium of patients with endometriosis were significantly increased, consistent with fibrosis levels. Lipopolysaccharide (LPS) + ATP could induce pyroptosis of primary endometrial stromal cells (ESCs), thereby releasing interleukin (IL)-1β and stimulating transforming growth factor (TGF)-β1-mediated fibrosis. NLRP3 inhibitor MCC950 had the same effect as TGFβ1 inhibitor SB-431542 in suppressing the fibrosis-inducing effect of LPS + ATP in vivo and in vitro. The abnormal increase of lnc-MALAT1 in ectopic endometrium was connected with NLRP3-mediated pyroptosis and fibrosis. Leveraging bioinformatic prediction and luciferase assays combined with western blotting and quantitative reverse transcriptase-polymerase chain reaction, we validated that lnc-MALAT1 sponges miR-141-3p to promote NLRP3 expression. Silencing lnc-MALAT1 in HESCs ameliorated NLRP3-mediated pyroptosis and IL-1β release, thereby relieving TGF-β1-mediated fibrosis. Consequently, our findings suggest that lnc-MALAT1 is critical for NLRP3-induced pyroptosis and fibrosis in endometriosis through sponging miR-141-3p, which may indicate a new therapeutic target of endometriosis treatment. Summary Sentence Lnc-MALAT1 sponges miR-141-3p to deregulate its inhibitory effect on NLRP3, thus promoting endometrial stromal cell pyroptosis and exacerbating the progressive fibrosis of ectopic lesions. Graphical Abstract
Evaluation of dietary supplementation and/or herbal food consumption habits and common beliefs on their effectiveness during the COVID-19 pandemic

Since 2020, COVID-19 has affected the entire world. Various dietary supplements/herbal foods are recommended to protect against and/or treat COVID-19 through social media and conventional media platforms, although their effects are unproven. Hence, this study aimed to investigate dietary supplementation and/or herbal food consumption habits intended to protect against and/or treat COVID-19, as well as common thoughts and beliefs about these products during the COVID-19 pandemic. This cross-sectional study was conducted as an online survey via the “SurveyMonkey” platform between June and December 2021. Participants were invited to participate in the study via social media (Instagram, Twitter, Facebook, WhatsApp) and the questionnaire was administered online. A total of 1767 participants were confirmed to be eligible. Overall, 35.3% used dietary supplements/herbal foods for protection against COVID-19 and 67.1% used them for treatment. Most believed that certain dietary supplements/herbal foods have an effect on the prevention and treatment of COVID-19. According to the COVID-19 infection status, participants differed in their opinions regarding the protective effects of vitamin D supplementation against COVID-19 (P = .02). It is important to raise public awareness of this issue and to avoid the unnecessary use of dietary supplements before sufficient evidence has been presented.
Diagnostic Utility of CD200 Immunohistochemistry in Distinguishing EBV-Positive Large B-Cell Lymphoma From Classic Hodgkin Lymphoma.

OBJECTIVES Epstein-Barr virus-positive large B-cell lymphoma (EBV+ LBCL) is a heterogeneous group of diseases that may resemble classic Hodgkin lymphoma (CHL) both morphologically and immunophenotypically. However, these diseases are treated with different therapies and carry distinct prognoses. We examined CD200 expression by immunohistochemistry in EBV+ LBCL and evaluated its diagnostic utility in the differential diagnosis with CHL. METHODS CD200 immunohistochemistry was performed on archival material from 20 cases of CHL (11 EBV+, 9 EBV-), 11 cases of EBV+ LBCL, and 10 cases of diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS). Staining pattern and intensity (0-3+ scale) were recorded. RESULTS CD200 positivity was seen in Reed-Sternberg cells in 19 (95%) of 20 cases of CHL, predominantly in a strong (3+, 15/19) and diffuse (>50% of cells, 17/19) pattern. In contrast, CD200 was negative in 8 (73%) of 11 cases of EBV+ LBCL; the 3 positive cases showed 1 to 2+ staining in less than 50% of lesional cells. All cases of DLBCL NOS were negative for CD200. CONCLUSIONS CD200 may be a useful immunophenotypic marker in differentiating EBV+ LBCL from CHL, with negative to partial/weak staining favoring a diagnosis of EBV+ LBCL and strong diffuse staining favoring a diagnosis of CHL.
Intervention to reduce age bias in medical students’ decision making for the treatment of older women with breast cancer: A novel approach to bias training

Abstract Objectives: Despite NICE guidelines to ‘treat people with invasive breast cancer, irrespective of age, with surgery and appropriate systemic therapy, rather than endocrine therapy alone’, older patients receive differential treatment and experience worse outcomes. Research has evidenced the prevalence of ageism and identified the role of implicit bias in reflecting and potentially perpetuating disparities across society, including in healthcare. Yet age bias has rarely been considered as an explanatory factor in poorer outcomes for older breast cancer patients nor, consequentially, has removing age bias been considered as an approach to improving outcomes. Many organizations carry out bias training with the aim of reducing negative impacts from biased decision making, yet the few evaluations of these interventions have mostly seen small or negative effects. This study explores whether a novel intervention to address age bias leads to better quality decision making for the treatment of older women with breast cancer. Methods: An online study compared medical students’ treatment recommendations for older breast cancer patients and the reasoning for their decision making before and after a novel bias training intervention. Thirty-one medical students participated in the study. Results: The results show that the bias training intervention led medical students to make better quality decisions for older breast cancer patients. The quality of decision making was measured by decreases in age-based decision making and increased efforts to include patients in decision making. These results suggest there is value in exploring whether if anti-bias training interventions could usefully be applied in other areas of practice where older patients experience poorer outcomes. Conclusions: This study evidences that bias training improves the quality of decision making by medical students in respect of older breast cancer patients. The study findings show promise that this novel approach to bias training might usefully be applied to all medical practitioners making treatment recommendations for older patients.
Pushing the boundaries : Women teachers’ experiences of learning mathematics

This paper reports on a research project exploring women mathematics teachers’ experiences of professional learning. Adopting a life history approach, data was gathered in semi-structured interview-conversations. Initial meetings focused on teachers’ experiences of learning mathematics and of learning to teach. The views and practices of their own secondary mathematics teachers emerge as significant both in terms of informing their A-level and career choice and acting as an important frame of reference when analyzing their current teaching practice.
An Optimized Method of Collecting Murine Peripheral Blood and Dilution Correction for Accurate Blood Cell Enumeration

Accurate measurement of whole blood counts from mice is an essential quantitative tool across the fields of vascular cell biology. In particular, the measurement of platelet counts can be challenging as the process relies upon good phlebotomy technique, the inclusion of a sufficient amount of the appropriate anticoagulant, and very often dilution of the sample to meet the sample volume requirements of an automated analyzer. To minimize sample dilution, blood collection tubes pre‐coated with the anticoagulant can be used; however, these are expensive and prone to blood clotting issues. Here, we describe a simple dilution correction method that accurately calculates blood‐to‐anticoagulant dilutions to generate appropriate volumes for automated blood cell analysis while minimizing blood clotting. We also discuss some simple steps that can be incorporated into blood collection methods to avoid artefacts during blood collection. Blood count data analysis involving volume correction and clot exclusion can significantly reduce variable blood cell count values among healthy untreated littermates. It also detects subtle changes in blood cell counts, mainly of platelets and RBCs in experimental settings, which can be masked in the absence of careful and precise volume correction. Blood count analysis with volume correction precisely determines mouse whole blood cell counts for investigators. The decreased variability in cell count values reduces the number of experimental animals required for meaningful analysis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.
QPOLE: A Quick, Simple, and Cheap Alternative for POLE Sequencing in Endometrial Cancer by Multiplex Genotyping Quantitative Polymerase Chain Reaction

PURPOSE Detection of 11 pathogenic variants in the POLE gene in endometrial cancer (EC) is critically important to identify women with a good prognosis and reduce overtreatment. Currently, POLE status is determined by DNA sequencing, which can be expensive, relatively time-consuming, and unavailable in hospitals without specialized equipment and personnel. This may hamper the implementation of POLE-testing in clinical practice. To overcome this, we developed and validated a rapid, low-cost POLE hotspot test by a quantitative polymerase chain reaction (qPCR) assay, QPOLE. MATERIALS AND METHODS Primer and fluorescence-labeled 5′-nuclease probe sequences of the 11 established pathogenic POLE mutations were designed. Three assays, QPOLE-frequent for the most common mutations and QPOLE-rare-1 and QPOLE-rare-2 for the rare variants, were developed and optimized using DNA extracted from formalin-fixed paraffin-embedded tumor tissues. The simplicity of the design enables POLE status assessment within 4-6 hours after DNA isolation. An interlaboratory external validation study was performed to determine the practical feasibility of this assay. RESULTS Cutoffs for POLE wild-type, POLE-mutant, equivocal, and failed results were predefined on the basis of a subset of POLE mutants and POLE wild-types for the internal and external validation. For equivocal cases, additional DNA sequencing is recommended. Performance in 282 EC cases, of which 99 were POLE-mutated, demonstrated an overall accuracy of 98.6% (95% CI, 97.2 to 99.9), a sensitivity of 95.2% (95% CI, 90.7 to 99.8), and a specificity of 100%. After DNA sequencing of 8.8% equivocal cases, the final sensitivity and specificity were 96.0% (95% CI, 92.1 to 99.8) and 100%. External validation confirmed feasibility and accuracy. CONCLUSION QPOLE is a qPCR assay that is a quick, simple, and reliable alternative for DNA sequencing. QPOLE detects all pathogenic variants in the exonuclease domain of the POLE gene. QPOLE will make low-cost POLE-testing available for all women with EC around the globe.
Safety, tolerability, pharmacodynamics and pharmacokinetics of the soluble guanylyl cyclase activator BI 685509 in patients with diabetic kidney disease: A randomized trial

Albuminuria is associated with abnormalities in the nitric oxide (NO)–soluble guanylyl cyclase (sGC)–cyclic guanosine monophosphate pathway. We assessed safety and efficacy of the NO‐independent sGC activator BI 685509 in patients with diabetic kidney disease and albuminuria.
Omentectomy as Part of Radical Surgery for Gastric Cancer: 5-Year Follow-Up Results of a Multicenter Prospective Cohort Study

Introduction: Curative therapy for gastric cancer usually consists of perioperative chemotherapy combined with a radical (R0) gastrectomy. In addition to a modified D2 lymphadenectomy, a complete omentectomy is recommended. However, there is little evidence for a survival benefit of omentectomy. This study presents the follow-up data of the OMEGA study. Methods: This multicenter prospective cohort study included 100 consecutive patients with gastric cancer undergoing (sub)total gastrectomy with complete en bloc omentectomy and modified D2 lymphadenectomy. Primary outcome of the current study was 5-year overall survival. Patients with or without omental metastases were compared. Pathological factors associated with locoregional recurrence and/or metastases were tested with multivariable regression analysis. Results: Of 100 included patients, five had metastases in the greater omentum. Five-year overall survival was 0.0% in patients with omental metastases and 44.2% in patients without omental metastases (p = 0.001). Median overall survival time for patients with or without omental metastases was 7 months and 53 months. A (y)pT3–4 stage tumor and vasoinvasive growth were associated with locoregional recurrence and/or metastases in patients without omental metastases. Conclusion: The presence of omental metastases in gastric cancer patients who underwent potentially curative surgery was associated with impaired overall survival. Omentectomy as part of radical gastrectomy for gastric cancer might not contribute to a survival benefit in case of undetected omental metastases.