Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneous microenvironment analysis to explore the potential regulatory role of endothelial-mesenchymal transition in idiopathic pulmonary fibrosis

Background Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease mainly caused by excessive proliferation of fibroblasts and activation of myofibroblasts. The cellular microenvironment is mainly composed of different types of cellular components and extracellular matrix (ECM), whose changes directly affect cellular heterogeneity, resulting in immensely complex cellular interactions. However, microenvironment study is mainly focused on the pathological process of tumors, and the microenvironment changes during IPF development remain unclear. Methods The current study intends to employ IPF-related single-cell sequencing and gene expression profile data to analyze the scores of different cell clusters in the IPF microenvironment, and exploit the underlying interaction between cells to illustrate the fundamental mechanism causing IPF. Results Our analysis revealed that the amount of endothelial cells was obviously decreased, and the amount of fibroblasts and myofibroblasts was increased during the development of IPF, suggesting a possible endothelial-mesenchymal transition (EndMT) process. Furthermore, we found that the hub genes obtained through IPF-related gene expression profile analysis may play a regulative role in the number and function of endothelial cells and fibroblasts/myofibroblasts during IPF. Conclusions Our research represents a valuable analysis of the cellular microenvironment, and provides a novel mechanistic insight into the pathobiology of not only EndMT in IPF, but also other traumatic fibrotic disease disorders.
High fatty liver index is an independent predictor of ischemic heart disease during a 10‐year period in a Japanese population

Fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ‐glutamyl transferase and triglycerides, is a validated surrogate marker of nonalcoholic fatty liver disease. We retrospectively investigated the relationship between FLI and the development of ischemic heart disease (IHD) during a 10‐year period.
Survival stacking with multiple data types using pseudo-observation-based-AUC loss

ABSTRACT There have been many strategies to adapt machine learning algorithms to account for right censored observations in survival data in order to build more accurate risk prediction models. These adaptions have included pre-processing steps such as pseudo-observation transformation of the survival outcome or inverse probability of censoring weighted (IPCW) bootstrapping of the observed binary indicator of an event prior to a time point of interest. These pre-processing steps allow existing or newly developed machine learning methods, which were not specifically developed with time-to-event data in mind, to be applied to right censored survival data for predicting the risk of experiencing an event. Stacking or ensemble methods can improve on risk predictions, but in general, the combination of pseudo-observation-based algorithms, IPCW bootstrapping, IPC weighting of the methods directly, and methods developed specifically for survival has not been considered in the same ensemble. In this paper, we propose an ensemble procedure based on the area under the pseudo-observation-based-time-dependent ROC curve to optimally stack predictions from any survival or survival adapted algorithm. The real application results show that our proposed method can improve on single survival based methods such as survival random forest or on other strategies that use a pre-processing step such as inverse probability of censoring weighted bagging or pseudo-observations alone.
Social media’s impact on widespread SARMs abuse

Selective Androgen Receptor Modulators (SARMs) abuse and social media prevalence is rapidly growing. Despite the paucity of literature on the clinical effects and safety profile of SARMs, abuse by recreational and professional athletes increases annually. SARMs, a World Anti-Doping Agency (WADA) prohibited performance enhancing drug (PED), display stronger tissue-selective activation of androgen signaling as compared to anabolic steroids. Published case reports and anecdotal evidence suggest liver toxicity, cardiac injury, and other adverse effects are associated with SARMs consumption. However, social media misinformation may lead individuals to believe that SARMs are safe. With no established evidence-based guidelines, we propose that treatment for SARMs abuse should mimic treatment for anabolic-steroid abuse. Health care providers and sports team members must educate themselves on the SARMs literature and social media trends to promote open dialogue and prevent SARMs abuse.
Mycophenolate mofetil for immune checkpoint inhibitor‐related hepatotoxicity relapsing during dose reduction of corticosteroid: A report of two cases and literature review

Immune checkpoint inhibitors (ICIs) sometimes cause immune‐related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high‐dose corticosteroids are usually effective in treatment of ICI‐related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI‐related liver injury that relapses under corticosteroid therapy after temporary remission.
Successful telehealth transformation of a pediatric outpatient obesity teaching program due to the COVID-19 pandemic – the “Video KiCK” program

Abstract Objectives To investigate if digital approaches can ameliorate the known consequences of social-distancing restrictions in the context of the global COVID-19 pandemic for adolescent participants originally registered for a face-to-face outpatient weight regulation program and whether video-based multiprofessional outpatient obesity therapy is successful for a group of adolescents with preexisting obesity. Methods The certified KiCK outpatient training program for children and adolescents with overweight and obesity was remodeled as a consequence of the lockdown traditional face-to-face program to a completely digital and video-based format on short notice. The virtual approach was compared with the results of the conventional program regarding metabolic parameters, body mass index standard deviation score (BMI SDS), well-being, and physical fitness. Results Sixty-nine of 77 enrolled participants for KiCK (age 8 to 17 years, BMI z score >2.0) were able and willing to participate virtually. After the first lockdown significant improvements of BMI SDS (mean 0.18; p=0.02), homeostasis model assessment (HOMA) index (mean 1.4; p=0.016), triglycerides (mean 0.18 mmol/dL; p=0.021), 6 minute-walk-test (mean 97.0 m; p=0.030, and well-being according to the World Health Organization 5 (WHO-5) questionnaire (mean 2.5; p=0.002) were found after the virtual intervention, which was comparable to the results observed previously in matched pairs data from the program during the pre-COVID period. After the end of the second lockdown weight SDS, BMI SDS, HOMA INDEX, and cholesterol were also measured reduced compared to baseline parameters measured before program initiation. Walking distance in the 6 MWT and improvement in general well-being in the WHO-5 questionnaire also persisted. Conclusions These results indicate good acceptance and efficacy of the video-intervention for youth with overweight and obesity during the lockdown, supporting the use of virtual modules in future programs after the pandemic.
The value of WNT5A as prognostic and immunological biomarker in pan-cancer

Background Finding new immune-related biomarkers is one of the promising research directions for tumor immunotherapy. The WNT5A gene could stimulate the WNT pathway and regulate the progression of various tumors. Recent studies have partially revealed the relationship between WNT5A and tumor immunity, but the correlation and underlying mechanisms in pan-cancer remain obscure. Thus, we conducted this study aiming to characterize the prognostic value and immunological portrait of WNT5A in cancer. Methods The data obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases was utilized to analyze WNT5A expression levels by Kruskal-Wallis test and correlation to prognosis by Cox regression test and Kaplan-Meier test, while the data was also used to study the association between WNT5A expression and immune microenvironment, immune neoantigens, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) in pan-cancer. Gene set enrichment analysis (GSEA) was used to clarify the relevant signaling pathways. The R package was used for data analysis and to create the plots. Results The pan-cancer analysis revealed that the expression level of WNT5A is generally elevated in most tumors (19/34, 55.88%), and high WNT5A expression was correlated with poor prognosis in esophageal carcinoma (ESCA, P<0.05), low-grade glioma (LGG, P<0.01), adrenocortical carcinoma (ACC, P<0.01), pancreatic adenocarcinoma (PAAD, P<0.01), and head and neck squamous cell carcinoma (HNSC, P<0.05). In addition, WNT5A expression was positively associated with immune infiltration, stromal score, and immune checkpoints in most cancers, and correlated to immune neoantigens, TMB, and MSI. Finally, GSEA indicated that WNT5A is implicated in the transforming growth factor β (TGFβ), Notch, and Hedgehog signaling pathways, which may be related to tumor immunity. Conclusions The expression of WNT5A is elevated in most tumors and associated with tumor prognosis. Furthermore, WNT5A is associated with tumor immunity and may be an immunological biomarker in cancer.
Investigating the ultrastructural and viscoelastic characteristics of whole blood after exposure to the heavy metals cadmium, lead and chromium, alone and in combination

ABSTRACT In recent years, heavy metal exposure has become a serious health concern as more humans are being exposed to heavy metals on a daily basis. Most of the environmental contamination and human exposure result from anthropogenic activities such as mining and smelting. The industrial and agricultural sectors also play a big role. Cigarette smoke in particular contains trace amounts of heavy metals that put chronic smokers at serious risk. Previous studies have determined that there is a strong correlation between heavy metal exposure and adverse effects on the coagulation system. The aim of this study was to investigate the effect of cadmium, lead and chromium alone and in combination on erythrocytes and fibrin networks that form part of the coagulation system as well as the viscoelastic properties of thrombus formation by using thromboelastography®. The choice of metals for this study was based on a previous study that compared the levels of metals between smokers and nonsmokers and found significantly higher levels of cadmium, lead and chromium in the platelet-rich fibrin of smoking individuals. Scanning electron microscopy analysis revealed that the cadmium and chromium combination groups caused the highest degree of echinocyte formation and fibrin network alterations. These findings were supported by the thromboelastography® analysis that indicated a significant decrease in reaction-time and split point values for the chromium-containing group, suggesting a shorter initiation time for clot formation. The findings of this study support the hypothesis that the coagulation pathway is a potential target for heavy metal toxicity.
Advances in inhaled corticosteroids for the treatment of chronic obstructive pulmonary disease: what is their value today?

ABSTRACT Introduction As of today, there is still a need to determine which COPD patients may benefit from ICS therapy, whether ICSs are useful in COPD patients without chronic bronchitis, and whether long-acting bronchodilators can reduce the risk of exacerbations in frequent exacerbators even if ICSs are not used, and whether combination therapy including ICSs is helpful in infrequent exacerbators to optimize the use of ICSs in COPD. Areas covered Herein, the authors provide an overview of use of ICS in COPD, discuss their value to the current treatment armamentarium and focus on emerged aspects on which there is no consensus. Expert opinion There is growing agreement on why, in whom, and when ICS therapy can be used in COPD, although the consensus is still lacking because of the heterogeneity of COPD. The use of BECs is only helpful in T2 inflammation, while there is a lack of biomarkers indicating the presence of T1 and T17 immunity, which is poorly responsive to ICS. Identifying ICS-sensitive endotypes using specific biomarkers that have yet to be identified and validated is likely to demonstrate that ICSs can influence the natural course of COPD in at least a subset of patients.
Upper Extremity Contralaterally Controlled Functional Electrical Stimulation Versus Neuromuscular Electrical Stimulation in Post-Stroke Individuals: A Meta-Analysis of Randomized Controlled Trials

Background Electrical stimulation has been employed as a safe and effective therapy for improving arm function after stroke. Contralaterally controlled functional electrical stimulation (CCFES) is a unique method that has progressed from application in small feasibility studies to implementation in several randomized controlled trials. However, no meta-analysis has been conducted to summarize its efficacy. Objective To summarize the effect size of CCFES through measures of upper extremity motor recovery compared with that of neuromuscular electrical stimulation (NMES). Methods The PubMed, Cochrane Library, EMBASE, Scopus, and Google Scholar databases were searched. Randomized controlled trials (RCTs) were selected and subjected to meta-analysis and risk of bias assessment. Results 6 RCTs were selected and 267 participants were included. The Upper Extremity Fugl-Meyer assessment (UEFMA) was included in all studies, the Box and Blocks test (BBT) and active range of motion (AROM) were included in 3 and 4 studies, respectively. The modified Barthel Index (mBI) and Arm Motor Abilities Test (AMAT) were included in 2 and 3 studies, respectively. The CCFES group demonstrated greater improvement than the NMES did in UEFMA (SMD = .42, 95% CI = .07–.76), BBT (SMD = .48, 95% CI = .10–.86), AROM (SMD = .54, 95% CI = .23–.86), and mBI (SMD = .54, 95% CI = .12–.97). However, the results for AMAT did not differ significantly (SMD = .34, 95% CI = −.03–.72). Conclusion Contralaterally controlled functional electrical stimulation produced greater improvements in upper extremity hemiplegia in people with stroke than NMES did. PROSPERO registration number: CRD42021245831
Identification of 4 compounds from the Pharmakon library with antifungal activity against Candida auris and species of Cryptococcus.

There is an urgent need to develop novel antifungals. In this study, we screened 1600 compounds for antifungal activity against Cryptococcus neoformans and Candida auris. We evaluated 4 promising compounds against 24 additional isolates of C. neoformans, C. auris, Cryptococcus deuterogattii, and Cryptococcus gattii. The 4 compounds, dequalinium chloride (DQC), bleomycin sulfate (BMS), pentamidine isethionate salt (PIS), and clioquinol (CLQ), varied in their efficacy against these pathogens but were generally more effective against cryptococci. The compounds exerted their antifungal effect via multiple mechanisms including interference with the capsule of cryptococci and induction of hyphal-like morphology in C. auris. Our results indicate that DQC, BMS, PIS, and CLQ represent potential prototypes for the future development of antifungals.
Epistasis Creates Invariant Sites and Modulates the Rate of Molecular Evolution

Abstract Invariant sites are a common feature of amino acid sequence evolution. The presence of invariant sites is frequently attributed to the need to preserve function through site-specific conservation of amino acid residues. Amino acid substitution models without a provision for invariant sites often fit the data significantly worse than those that allow for an excess of invariant sites beyond those predicted by models that only incorporate rate variation among sites (e.g., a Gamma distribution). An alternative is epistasis between sites to preserve residue interactions that can create invariant sites. Through computer-simulated sequence evolution, we evaluated the relative effects of site-specific preferences and site-site couplings in the generation of invariant sites and the modulation of the rate of molecular evolution. In an analysis of ten major families of protein domains with diverse sequence and functional properties, we find that the negative selection imposed by epistasis creates many more invariant sites than site-specific residue preferences alone. Further, epistasis plays an increasingly larger role in creating invariant sites over longer evolutionary periods. Epistasis also dictates rates of domain evolution over time by exerting significant additional purifying selection to preserve site couplings. These patterns illuminate the mechanistic role of epistasis in the processes underlying observed site invariance and evolutionary rates.
Clinical utility of the 'Determine HBsAg' Point-of-Care Test for Diagnosis of Hepatitis B Surface Antigen in Africa

ABSTRACT Introduction Chronic infection with hepatitis B virus (HBV) is a leading cause of morbidity and death, especially in sub-Saharan Africa (SSA), where approximately 60 million adults are infected. More than 90% of these patients are unaware of their HBV status. Areas covered Scaling-up of HBV screening programs in SSA are essential to increase diagnosis, linkage to care, and access to treatment, and will ultimately reduce HBV disease burden to achieve WHO hepatitis elimination targets. Such scale up will rely on inexpensive rapid point-of-care (POC) tests, especially in remote areas where gold standard serological assays are not routinely available. This review discusses the diagnostic performance and clinical utility of the Determine™ (Abbott, USA) hepatitis B surface Antigen (HBsAg) POC test for improving HBV screening in SSA, in light with others available HBsAg rapid tests. Expert Opinion The Determine™ HBsAg POC test has demonstrated relatively good diagnostic accuracy at the low cost, in the African field and laboratory and should be used for large scale mass screening of HBV infection in Africa.
The Proteobacterial Methanotroph Methylosinus trichosporium OB3b Remodels Membrane Lipids in Response to Phosphate Limitation

Methane is a potent greenhouse gas in the atmosphere, and its concentration has continued to increase steadily in recent decades. In the natural environment, bacteria known as methanotrophs help mitigate methane emissions at no cost to human beings. ABSTRACT Methane is a potent greenhouse gas in the atmosphere, and its concentration has continued to increase in recent decades. Aerobic methanotrophs, bacteria that use methane as the sole carbon source, are an important biological sink for methane, and they are widely distributed in the natural environment. However, relatively little is known on how methanotroph activity is regulated by nutrients, particularly phosphorus (P). P is the principal nutrient constraining plant and microbial productivity in many ecosystems, ranging from agricultural land to the open ocean. Using a model methanotrophic bacterium, Methylosinus trichosporium OB3b, we demonstrate here that this bacterium can produce P-free glycolipids to replace membrane phospholipids in response to P limitation. The formation of the glycolipid monoglucuronic acid diacylglycerol requires plcP-agt genes since the plcP-agt mutant is unable to produce this glycolipid. This plcP-agt-mediated lipid remodeling pathway appears to be important for M. trichosporium OB3b to cope with P stress, and the mutant grew significantly slower under P limitation. Interestingly, comparative genomics analysis shows that the ability to perform lipid remodeling appears to be a conserved trait in proteobacterial methanotrophs; indeed, plcP is found in all proteobacterial methanotroph genomes, and plcP transcripts from methanotrophs are readily detectable in metatranscriptomics data sets. Together, our study provides new insights into the adaptation to P limitation in this ecologically important group of bacteria. IMPORTANCE Methane is a potent greenhouse gas in the atmosphere, and its concentration has continued to increase steadily in recent decades. In the natural environment, bacteria known as methanotrophs help mitigate methane emissions at no cost to human beings. However, relatively little is known regarding how methane oxidation activity in methanotrophs is regulated by soil nutrients, particularly phosphorus. Here, we show that methanotrophs can modify their membrane in response to phosphorus limitation and that the ability to change membrane lipids is important for methanotroph activity. Genome and metatranscriptome analyses suggest that such an adaptation strategy appears to be strictly conserved in all proteobacterial methanotrophs and is used by these bacteria in the natural environment. Together, our study provides a plausible molecular mechanism for better understanding the role of phosphorus on methane oxidation in the natural environment.
Anemia, overhydration, and lower muscle strength in hemodialysis patients with protein‐energy wasting

The protein‐energy wasting (PEW) syndrome is a common complication in hemodialysis (HD) patients associated to morbidity and mortality. Our objective was to assess the prevalence of PEW and its association with erythropoietin resistance index (ERI) score, body composition by impedance, health‐related quality of life, and muscle strength.
Perceptions of practising physiotherapists in Saudi Arabia about their role in the health promotion of patients with musculoskeletal conditions: a qualitative study

Objective: This study aimed to explore physiotherapists’ perceptions in Saudi Arabia about their understanding and role in health promotion through lifestyle behaviours and risk factors assessment and management of patients with musculoskeletal pain and disabilities. Study design: Qualitative study. Method: One-to-one interviews with 12 physiotherapists (six females; mean age 34.5 ± 8) within a constructivist framework. Interviews were recorded, transcribed verbatim, and analysed using a thematic analysis approach. Result: Three themes were identified: (1) the physiotherapists’ awareness and knowledge of health promotion; (2) current practice of physiotherapists to implementing health promotion practice; and (3) the physiotherapists’ perceived barriers to implementing health promotion practice. Participants generally perceived health promotion to be within their scope of practice. However, their understanding and approaches to deliver this practice were varied and non-standardised. Some barriers to routine engagement in health promotion were identified, including time constraints, the beliefs of healthcare practitioners, and limited education and training. Conclusion: This study highlighted that physiotherapists acknowledged the role of health promotion in their practice. However, there were different explanations of the concept and it was informally practised.