Miracle-dz/UniFAR-FTUs huggingface dataset:
Severe bleeding following off-pump coronary artery bypass grafting: predictive factors and risk model

BACKGROUND Severe bleeding following cardiac surgery remains a troublesome complication, but to date, there is a lack of comprehensive predictive models for the risk of severe bleeding following off-pump coronary artery bypass grafting (OPCABG). This study aims to analyze relevant indicators of severe bleeding after isolated OPCABG and establish a corresponding risk assessment model. METHODS The clinical data of 584 patients who underwent OPCABG from January 2018 to April 2020 were retrospectively analyzed. We gathered the preoperative baseline data and postoperative data immediately after intensive care unit admission and used multifactor logistic regression to screen the potential predictors of severe bleeding, upon which we established a predictive model. Using the consistency index and calibration curve, decision curve, and clinical impact curve analysis, we evaluated the performance of the model. RESULTS This study is the first to establish a risk assessment and prediction model for severe bleeding following isolated OPCABG. Eight independent risk factors were identified: male sex, aspirin/clopidogrel withdrawal time, platelet count, fibrinogen level, C-reactive protein, serum creatinine, and total bilirubin. Among the 483 patients in the training group, 138 patients (28.6%) had severe bleeding; among the 101 patients in the verification group, 25 patients (24.8%) had severe bleeding. Receiver operating characteristic (ROC) curve analysis for the internal training group revealed a convincing performance with a concordance index (C-index) of 0.859, while the area under the ROC curve for the external validation data was 0.807. Decision curve analysis showed that the model was useful for both groups. CONCLUSIONS Although there are some limitations, the model can effectively predict the probability of severe bleeding following isolated OPCABG and is therefore worthy of further exploration and verification.
Diagnosis of Chronic Kidney Disease Using Effective Classification Algorithms and Recursive Feature Elimination Techniques

Chronic kidney disease (CKD) is among the top 20 causes of death worldwide and affects approximately 10% of the world adult population. CKD is a disorder that disrupts normal kidney function. Due to the increasing number of people with CKD, effective prediction measures for the early diagnosis of CKD are required. The novelty of this study lies in developing the diagnosis system to detect chronic kidney diseases. This study assists experts in exploring preventive measures for CKD through early diagnosis using machine learning techniques. This study focused on evaluating a dataset collected from 400 patients containing 24 features. The mean and mode statistical analysis methods were used to replace the missing numerical and the nominal values. To choose the most important features, Recursive Feature Elimination (RFE) was applied. Four classification algorithms applied in this study were support vector machine (SVM), k-nearest neighbors (KNN), decision tree, and random forest. All the classification algorithms achieved promising performance. The random forest algorithm outperformed all other applied algorithms, reaching an accuracy, precision, recall, and F1-score of 100% for all measures. CKD is a serious life-threatening disease, with high rates of morbidity and mortality. Therefore, artificial intelligence techniques are of great importance in the early detection of CKD. These techniques are supportive of experts and doctors in early diagnosis to avoid developing kidney failure.
An Immune-Related Prognostic Classifier Is Associated with Diffuse Large B Cell Lymphoma Microenvironment

Background Diffuse large B cell lymphoma (DLBCL) is a life-threatening malignant tumor characterized by heterogeneous clinical, phenotypic, and molecular manifestations. Given the association between immunity and tumors, identifying a suitable immune biomarker could improve DLBCL diagnosis. Methods We systematically searched for DLBCL gene expression microarray datasets from the GEO database. Immune-related genes (IRGs) were obtained from the ImmPort database, and 318 transcription factor (TF) targets in cancer were retrieved from the Cistrome Cancer database. An immune-related classifier for DLBCL prognosis was constructed using Cox regression and LASSO analysis. To assess differences in overall survival between the low- and high-risk groups, we analyzed the tumor microenvironment (TME) and immune infiltration in DLBCL using the ESTIMATE and CIBERSORT algorithms. WGCNA was applied to study the molecular mechanisms explaining the clinical significance of our immune-related classifier and TFs. Results Eighteen IRGs were selected to construct the classifier. The multi-IRG classifier showed powerful predictive ability. Patients with a high-risk score had poor survival. Based on the AUC for three- and five-year survival, the classifier exhibited better predictive power than clinical data. Discrepancies in overall survival between the low- and high-risk score groups might be explained by differences in immune infiltration, TME, and transcriptional regulation. Conclusions Our study describes a novel prognostic IRG classifier with strong predictive power in DLBCL. Our findings provide valuable guidance for further analysis of DLBCL pathogenesis and clinical treatment.
The Role of Mitochondrial Quality Control in Cardiac Ischemia/Reperfusion Injury

A healthy mitochondrial network produces a large amount of ATP and biosynthetic intermediates to provide sufficient energy for myocardium and maintain normal cell metabolism. Mitochondria form a dynamic and interconnected network involved in various cellular metabolic signaling pathways. As mitochondria are damaged, controlling mitochondrial quantity and quality is activated by changing their morphology and tube network structure, mitophagy, and biogenesis to replenish a healthy mitochondrial network to preserve cell function. There is no doubt that mitochondrial dysfunction has become a key factor in many diseases. Ischemia/reperfusion (IR) injury is a pathological manifestation of various heart diseases. Cardiac ischemia causes temporary tissue and organelle damage. Although reperfusion is essential to compensate for nutrient deficiency, blood flow restoration inconsequently further kills the previously ischemic cardiomyocytes. To date, dysfunctional mitochondria and disturbed mitochondrial quality control have been identified as critical IR injury mechanisms. Many researchers have detected abnormal mitochondrial morphology and mitophagy, as well as aberrant levels and activity of mitochondrial biogenesis factors in the IR injury model. Although mitochondrial damage is well-known in myocardial IR injury, the causal relationship between abnormal mitochondrial quality control and IR injury has not been established. This review briefly describes the molecular mechanisms of mitochondrial quality control, summarizes our current understanding of the complex role of mitochondrial quality control in IR injury, and finally speculates on the possibility of targeted control of mitochondria and the methods available to mitigate IR injury.
Exploring the Mechanism of Berberine Intervention in Ulcerative Colitis from the Perspective of Inflammation and Immunity Based on Systemic Pharmacology

Background Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease of the colon and rectum. Recent studies found that berberine had effects on inflammatory diseases and immune diseases. Methods The PharmMapper database was used to predict the berberine potential target and GeneCards database and OMIM database were utilized to collect UC genes. The Cytoscape software was used to construct and analyze the networks and DAVID was utilized to perform enrichment analysis. Then, animal experiments were performed to validate the prediction results. The experimental rats were randomly divided into normal group (control group), model group, and berberine group. The general condition, body weight, gross morphology of colon tissue, and colonic mucosal damage index (CMDI) score were observed. The pathological changes of colon tissue were observed by H&E staining. The levels of serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-4 were detected by ELISA. The expressions of IL-1β, TNF-α, and IL-4 protein in colon tissue were detected by immunohistochemistry. Results A total of 211 Berberine's potential targets and 210 UC genes were obtained. The enrichment analysis showed that berberine may regulate inflammation, inflammatory cytokines, and their mediated inflammation signal pathways such as inflammatory bowel disease (IBD), rheumatoid arthritis, cytokine-cytokine receptor interaction, TNF, T cell receptor, Toll-like receptor, and JAK/STAT signaling pathway. Compared with the model group, the body mass of rats in the berberine group was significantly increased (P < 0.05); the general morphology and pathological changes of colon tissue were significantly improved; CMDI score, serum and colon tissue IL-1β, TNF-α content, and protein expression were decreased significantly (P < 0.05); and IL-4 content and protein expression increased significantly (P < 0.05). Conclusion Berberine can interfere with UC through related biological processes and signal pathways related to inflammation and immunity. In-depth exploration of the mechanism of berberine in the treatment of UC will provide a basis for clinical application.
Analysis of Serum MicroRNA-122 Expression at Different Stages of Chronic Hepatitis B Virus Infection

Objective To investigate the expression of microRNA-122 (miR-122) in the progression of chronic hepatitis B virus- (HBV-) infected liver diseases, thus determining the role of serum miR-122 as a marker of HBV-caused liver injury. Methods Sera were collected from patients with different stages of HBV infection (n = 63) and healthy volunteers (n = 11). And the serum miR-122 levels were detected using RT-qPCR. Moreover, an analysis was applied for identifying the specific correlation of the miR-122 level with HBV DNA, HBeAg, and ALT levels. After liver biopsy, Ishak scoring was utilized for evaluation of the fibrosis stage and the histological activity index (HAI). Results We confirmed, in the serum, increased miR-122 expression in HBV-infected patients and its highest expression in chronic HBV carriers, based on such comparison between the healthy controls and patients. The correlation analysis results were taken as confirmation of the positive relationship of miR-122 with HBV DNA (r = 0.354, P = 0.005) and ALT (r = 0.331, P = 0.009). But no correlation of this molecule with HBeAg levels was found (P = 0.187). In comparison with the HBeAg-negative patients, serum miR-122 expression showed an increase in the HBeAg-positive patients (P = 0.001). miR-122 expression, in addition, was of a significant correlation with HAI, but not with the liver fibrosis score. Conclusion The peak of the serum miR-122 expression normally occurs in the early stage of the progression from the HBV carrier phase to chronic hepatitis to cirrhosis. This molecule can be considered as a marker for evaluation of HBV-caused liver injury.
Immunopathogenesis of Dermatophytoses and Factors Leading to Recalcitrant Infections

The pathogenesis of dermatophytic infections involves the interplay of three major factors: the dermatophyte, the inherent host defense, and the adaptive host immune response. The fungal virulence factors determine the adhesion and invasion of the skin while the immune response depends on an interaction of the pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMP) with pattern recognition receptors (PRRs) of the host, which lead to a differential Th (T helper) 1, Th2, Th17, and Treg response. While anthropophilic dermatophytes Trichophyton rubrum and now increasingly by T. interdigitale subvert the immune response via mannans, zoophilic species are eliminated due to a brisk immune response. Notably, delayed-type hypersensitivity (Th1) response of T lymphocytes causes the elimination of fungal infection, while chronic disease caused by anthropophilic species corresponds to toll-like receptor 2 mediated IL (interleukin)-10 release and generation of T-regulatory cells with immunosuppressive potential. Major steps that determine the ultimate clinical course and chronicity include genetic susceptibility factors, impaired epidermal and immunological barriers, variations in the composition of sebum and sweat, carbon dioxide tension, skin pH, and topical steroid abuse. It is important to understand these multifarious aspects to surmount the problem of recalcitrant dermatophytosis when the disorder fails conventional therapeutic agents.
Outcomes of High Tibial Osteotomy With Versus Without Mesenchymal Stem Cell Augmentation: A Systematic Review and Meta-analysis

Background: The outcomes after high tibial osteotomy (HTO) with augmentation of intra-articular mesenchymal stem cell (MSCs) for medial tibiofemoral osteoarthritis remain controversial. Purpose: To pool existing studies to compare the outcomes of HTO with versus without intra-articular MSC augmentation when performed for medial tibiofemoral osteoarthritis. Study Design: Systematic review; Level of evidence, 3. Methods: The systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included were clinical studies that compared the outcomes of HTO with intra-articular MSC augmentation (MSC group) versus without (control group). Pre- and postoperative outcomes were compared between groups from measures including the Lysholm score, International Knee Documentation Committee (IKDC) score, Knee injury and Osteoarthritis Outcome Score, Hospital for Special Surgery Knee Rating Scale, Tegner score, visual analog scale for pain, arthroscopic and histological grading scales, femorotibial angle, weightbearing line, and posterior tibial slope. Results: We reviewed 4 studies with a total of 224 patients. The MSC group demonstrated significantly greater improvement versus controls in the pooled Lysholm score (weighted mean difference [WMD], 6.64; 95% CI, 0.90 to 12.39) and pooled IKDC score (WMD, 9.21; 95% CI, 4.06 to 14.36), which were within or close to the minimal clinically important difference. Radiological outcomes were similar in both groups, including the femorotibial angle (WMD, –0.01; 95% CI, –1.10 to 1.09), weightbearing line, and posterior tibial slope. The studies were homogeneous, and no publication bias was noted. Conclusion: Intra-articular MSC augmentation for HTO may modestly improve functional outcomes as compared with HTO alone. However, adequate data are lacking to make definitive conclusions regarding the effect of MSC augmentation on pain or arthroscopic and histologic grading.
Analysing electrocardiographic traits and predicting cardiac risk in UK biobank

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information.
Circulating tryptophan metabolites and risk of colon cancer: Results from case‐control and prospective cohort studies

Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case‐control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1‐SD = 0.44; 95% CI, 0.31‐0.64) and EPIC (OR per 1‐SD = 0.86; 95% CI, 0.74‐0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61‐11.3) and EPIC (OR = 2.03; 95% CI, 1.20‐3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1‐SD = 0.74; 95% CI, 0.55‐0.98), positively associated in CORSA (OR per 1‐SD = 1.79; 95% CI, 1.27‐2.52), while no association was observed in EPIC. The kynurenine‐to‐tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1‐SD = 1.38; 95% CI, 1.03‐1.84) and CORSA (OR per 1‐SD = 1.44; 95% CI, 1.06‐1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine‐to‐tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
Skeletal EWSR1‐NFATC2 sarcoma previously diagnosed as Ewing‐like adamantinoma: A case report and literature review emphasizing its unique radiological features

Ewing‐like adamantinoma (EAD) is a rare bone tumor. It remains unclear whether EAD belongs to adamantinoma, Ewing sarcoma (ES), or an independent category. Herein, we present a case of femoral sarcoma previously diagnosed as EAD in a 26‐year‐old woman. We observed amplified EWSR1 and NFATC2 fusion signals using fluorescence in situ hybridization. Prompted by its unique radiological features, we reviewed the current literature on skeletal EWSR1‐NFATC2 sarcoma (ENS) and EAD. In addition to the similar histological features, we found that both ENS and EAD displayed similar characteristic radiological features, such as the tendency to occur in the diaphysis of long bones, cortical expansion and buttressing‐type thickening, and bone surface involvement with saucer‐like erosion without cortical destruction. We believe that these unique radiological features were related to its indolent behavior. Altogether, it is possible that previously reported EAD cases may be neither ES nor the classic adamantinoma but ENS. Further studies are needed to clarify the relationship between EAD and ENS.
Inner shell spectroscopy of (η5-C5H5)2TiCl2, (η5-C5H5)TiCl3, and TiCl4

Oscillator strengths for C 1s excitation of gas phase Cp2TiCl2 and CpTiCl3 (Cp = η5-C5H5), and Cl 2p and Ti 2p excitation of gas phase Cp2TiCl2, CpTiCl3, and TiCl4 have been derived from electron e.
A randomized comparison of sample adequacy and diagnostic yield of various suction pressures in EBUS-TBNA.

INTRODUCTION The evidence for using vacuum suction during EBUS is sparse and the optimal suction pressure for obtaining adequate samples has not yet been determined. Our aim was to assess the influence of suction on the adequacy and diagnostic yield of EBUS-TBNA. MATERIAL AND METHODS This single-center, prospective, randomized, non-inferiority trial assessed whether no-suction and 10 mL suction are inferior to 20 mL suction for adequacy and diagnostic yield of EBUS-TBNA aspirates. RESULTS Three hundred twenty three lymph nodes were sampled using EBUS-TBNA. Baseline characteristics of lymph nodes were comparable in the three suction groups. The overall adequacy of EBUS-TBNA aspirates in the no-suction, 10 mL, and 20 mL suction was 90%, 83.49%, and 77.88%, respectively. The differences in adequacy were 12.1% (95% CI: 3.9-20.3) and 5.6% (95% CI: -3.3-14.5) for no-suction vs 20 mL, and 10 mL vs 20 mL suction, respectively. No-suction and 10 mL were not inferior to 20 mL suction in terms of sample adequacy. At a superiority margin of 3.92%, no-suction was superior to 20 mL suction in terms of sample adequacy (p < 0.05). The overall diagnostic yield was comparable (63.6%, 52.3%, and 57.7% in 0, 10 mL, and 20 mL, respectively; p-value was not significant). The proportion of aspirates which were predominantly bloody was similar (no-suction - 10.9%, 10 mL - 13.8%, 20 mL - 15.4%; p = 0.62). CONCLUSIONS EBUS-TBNA with or without the application of vacuum suction does not influence specimen adequacy and diagnostic yield.
Tenorio syndrome: Description of 14 novel cases and review of the clinical and molecular features

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome.
Oxypeucedanin is a mechanism-based inactivator of CYP2B6 and CYP2D6.

BACKGROUND Herbal medicine Angelica dahurica is widely employed for the treatment of rheumatism and pain relief in China. Oxypeucedanin is a major component of the herb. OBJECTIVES The objectives of this study are aimed at the investigation of mechanism-based inactivation of CYP2B6 and CYP2D6 by oxypeucedanin, characterization of the reactive metabolites associated with the enzyme inactivation, and identification of the P450s participating in the bioactivation of oxypeucedanin. METHODS Oxypeucedanin was incubated with liver microsomes or recombinant CYPs2B6 and 2D6 under designed conditions, and the enzyme activities were measured by monitoring the generation of the corresponding products. The resulting reactive intermediates were trapped with GSH and analyzed by LC-MS/MS. RESULTS Microsomal incubation with oxypeucedanin induced a time-, concentration-, and NADPH-dependent inhibition of CYPs2B6 and 2D6 with kinetic values of KI/kinact 1.82 µM/0.07 min-1 (CYP2B6) and 8.47 µM/0.044 min-1 (CYP2D6), respectively. Ticlopidine and quinidine attenuated the observed time-dependent enzyme inhibitions. An epoxide and/or γ-ketoenal intermediate(s) derived from oxypeucedanin was/were trapped in microsomal incubations. CYP3A4 was the primary enzyme involved in the bioactivation of oxypeucedanin. CONCLUSION Oxypeucedanin was a mechanism-based inactivator of CYP2B6 and CYP2D6. An epoxide and/or γ-ketoenal intermediate(s) may be responsible for the inactivation of the two enzymes.