Gut microbiome pattern impacts treatment response in primary biliary cholangitis.

Background: Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease. An inadequate response to ursodeoxycholic acid (UDCA) poses a high risk of progression toward end-stage liver disease. Gut dysbiosis has been implicated in PBC.

Multi-objective Bayesian optimization with enhanced features for adaptively improved glioblastoma partitioning and survival prediction.

Glioblastoma, an aggressive brain tumor prevalent in adults, exhibits heterogeneity in its microstructures and vascular patterns. The delineation of its subregions could facilitate the development of region-targeted therapies. However, current unsupervised learning techniques for this task face challenges in reliability due to fluctuations of clustering algorithms, particularly when processing data from diverse patient cohorts.

Prolonged ventricular repolarization associated with mild cognitive impairment and white matter hyperintensities: a cross-sectional study.

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.

CRIP1 regulates osteogenic differentiation of bone marrow stromal cells and pre-osteoblasts via the Wnt signaling pathway.

With the aging of the global demographic, the prevention and treatment of osteoporosis are becoming crucial issues. The gradual loss of self-renewal and osteogenic differentiation capabilities in bone marrow stromal cells (BMSCs) is one of the key factors contributing to osteoporosis. To explore the regulatory mechanisms of BMSCs differentiation, we collected bone marrow cells of femoral heads from patients undergoing total hip arthroplasty for single-cell RNA sequencing analysis.

EEF1B2 regulates bone marrow-derived mesenchymal stem cells bone-fat balance via Wnt/β-catenin signaling.

The pathological advancement of osteoporosis is caused by the uneven development of bone marrow-derived mesenchymal stem cells (BMSCs) in terms of osteogenesis and adipogenesis. While the role of EEF1B2 in intellectual disability and tumorigenesis is well established, its function in the bone-fat switch of BMSCs is still largely unexplored. During the process of osteogenic differentiation, we observed an increase in the expression of EEF1B2, while a decrease in its expression was noted during adipogenesis.

Optimising brain age estimation through transfer learning: A suite of pre-trained foundation models for improved performance and generalisability in a clinical setting.

Estimated age from brain MRI data has emerged as a promising biomarker of neurological health. However, the absence of large, diverse, and clinically representative training datasets, along with the complexity of managing heterogeneous MRI data, presents significant barriers to the development of accurate and generalisable models appropriate for clinical use. Here, we present a deep learning framework trained on routine clinical data (N up to 18,890, age range 18-96 years).

Decreased expression of GEM in osteoarthritis cartilage regulates chondrogenic differentiation via Wnt/β-catenin signaling.

Background: GEM (GTP-binding protein overexpressed in skeletal muscle) is one of the atypical small GTPase subfamily members recently identified as a regulator of cell differentiation. Abnormal chondrogenesis coupled with an imbalance in the turnover of cartilaginous matrix formation is highly relevant to the onset and progression of osteoarthritis (OA). However, how GEM regulates chondrogenic differentiation remains unexplored.

A+T rich interaction domain protein 3a (Arid3a) impairs Mertk-mediated efferocytosis in cholestasis.

Background & Aims: Macrophages are key elements in the pathogenesis of cholestatic liver diseases. Arid3a plays a prominent role in the biologic properties of hematopoietic stem cells, B lymphocytes and tumor cells, but its ability to modulate macrophage function during cholestasis remains unknown.

Methods: Gene and protein expression and cellular localization were assessed by q-PCR, immunohistochemistry, immunofluorescence staining and flow cytometry.

Temporal transcriptome features identify early skeletal commitment during human epiphysis development at single-cell resolution.

Human epiphyseal development has been mainly investigated through radiological and histological approaches, uncovering few details of cellular temporal genetic alternations. Using single-cell RNA sequencing, we investigated the dynamic transcriptome changes during post-conception weeks (PCWs) 15-25 of human distal femoral epiphysis cells. We find epiphyseal cells contain multiple subtypes distinguished by specific markers, gene signatures, Gene Ontology (GO) enrichment analysis, and gene set variation analysis (GSVA).

Multi-Modal Learning for Predicting the Genotype of Glioma.

The isocitrate dehydrogenase (IDH) gene mutation is an essential biomarker for the diagnosis and prognosis of glioma. It is promising to better predict glioma genotype by integrating focal tumor image and geometric features with brain network features derived from MRI. Convolutional neural networks show reasonable performance in predicting IDH mutation, which, however, cannot learn from non-Euclidean data, e.

Multi-UAV Path Planning in GPS and Communication Denial Environment.

This paper proposes a feature fusion algorithm for solving the path planning problem of multiple unmanned aerial vehicles (UAVs) using GPS and communication denial conditions. Due to the blockage of GPS and communication, UAVs cannot obtain the precise position of a target, which leads to the failure of path planning algorithms. This paper proposes a feature fusion proximal policy optimization (FF-PPO) algorithm based on deep reinforcement learning (DRL); the algorithm can fuse image recognition information with the original image, realizing the multi-UAV path planning algorithm without an accurate target location.

A regulatory variant at 19p13.3 is associated with primary biliary cholangitis risk and ARID3A expression.

Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the mechanism by which the 19p13.

Nonalcoholic steatohepatitis critically rewires the ischemia/reperfusion-induced dysregulation of cardiolipins and sphingolipids in mice.

Background: Lipid dysregulation plays a fundamental role in nonalcoholic steatohepatitis (NASH), which is an emerging critical risk factor that aggravates hepatic ischemia/reperfusion (I/R) injury. However, the specific lipids that mediate the aggressive I/R injury in NASH livers have not yet been identified.

Methods: The mouse model of hepatic I/R injury on NASH was established on C56B/6J mice by first feeding the mice with a Western-style diet to induce NASH, then the NASH mice were subjected to surgical procedures to induce hepatic I/R injury.

Clinical, Dermoscopic, Ultrasonographic, and Histopathologic Correlations in Kaposi's Sarcoma Lesions and Their Differential Diagnoses: A Single-Center Prospective Study.

(1) Background: Kaposi's sarcoma (KS) is an angioproliferative neoplasm typically appearing as angiomatous patches, plaques, and/or nodules on the skin. Dermoscopy and ultrasonography have been suggested as an aid in the diagnosis of KS, but there is little evidence in the literature, especially regarding its possible differential diagnoses. Our aim is to describe and compare the clinical, dermoscopic, and ultrasonographic features of KS and KS-like lesions.

Structural connectome quantifies tumour invasion and predicts survival in glioblastoma patients.

Glioblastoma is characterized by diffuse infiltration into the surrounding tissue along white matter tracts. Identifying the invisible tumour invasion beyond focal lesion promises more effective treatment, which remains a significant challenge. It is increasingly accepted that glioblastoma could widely affect brain structure and function, and further lead to reorganization of neural connectivity.

Prognostic significance of MRI-based late-course tumor volume in locoregionally advanced nasopharyngeal carcinoma.

Background: To validate tumor volume-based imaging markers for predicting local recurrence-free survival (LRFS) in locoregionally advanced nasopharyngeal carcinoma patients, who underwent induction chemotherapy followed by definitive intensity-modulated radiotherapy.

Methods: We enrolled 145 patients with stage III-IVA nasopharyngeal carcinoma in this retrospective study. Pre-treatment tumor volume (V) and late-course volume (LCV) were measured based on the MRIs scanned before treatment and during the first 3 days in the sixth week of radiotherapy, respectively.

Serum Biomarkers for Autoimmune Hepatitis Type 1: the Case for CD48 and a Review of the Literature.

In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA.

Utility of 2-Diphenylphosphoryloxy-1,3-Dienes in Multicomponent Hetero-Diels-Alder Reactions to Construct Functionalized Six-Membered Nitrogen Heterocycles.

The utility of 2-diphenylphosphoryloxy-1,3-dienes for the construction of substituted six-membered nitrogen heterocycles is presented. These dienes undergo boron trifluoride-promoted aza-Diels-Alder reactions when reacted with imines or related species formed in situ using aldehydes and amine derivatives. The stability of the dienes allows this three-component reaction to be carried out with no special precautions to eliminate water or air.

The burden associated with, and management of, difficult-to-treat depression in patients under specialist psychiatric care in the United Kingdom.

Background: Major depressive disorder (MDD) is common and often has sub-optimal response to treatment. Difficult-to-treat depression (DTD) is a new concept that describes 'depression that continues to cause significant burden despite usual treatment efforts'.

Aims: To identify patients with likely DTD in UK secondary care and examine demographic, disease and treatment data as compared with 'non-DTD' MDD patients.

Manifold Roles of Ceramide Metabolism in Non-Alcoholic Fatty Liver Disease and Liver Cancer.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder manifested in hepatic fat accumulation (hepatic steatosis) in the absence of heavy alcohol use. NAFLD consists of four major stages ranging from simple steatosis or non-alcoholic fatty liver (NAFL) to more advanced stages, non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NFLAD may further advance to hepatocellular carcinoma (HCC).

BOEC-Exo Addition Promotes In Vitro Maturation of Bovine Oocyte and Enhances the Developmental Competence of Early Embryos.

Exosomes are nano-sized vesicles with abundant nucleic acids, proteins, lipids, and other regulatory molecules. The aim of this study was to examine the effect of BOEC-Exo on bovine in vitro oocyte maturation and in vitro embryo development. We found that a 3% Exo supplementation to IVM media significantly enhanced the oocyte maturation and reduced the accumulation of ROS in MII-stage bovine oocytes.

MutT Homolog 1 Inhibitor Karonudib Attenuates Autoimmune Hepatitis by Inhibiting DNA Repair in Activated T Cells.

Autoimmune hepatitis (AIH) is an inflammatory liver disease driven by the hyperactivation of various intrahepatic antigen-specific T cells due to a breach of immune tolerance. Studies in immunometabolism demonstrate that activated T cells harbor increased levels of reactive oxygen species that cause oxidative DNA damage. In this study, we assessed the potential of DNA damage repair enzyme MutT homolog 1 (MTH1) as a therapeutic target in AIH and karonudib as a novel drug for patients with AIH.

Radiological tumor classification across imaging modality and histology.

Radiomics refers to the high-throughput extraction of quantitative features from radiological scans and is widely used to search for imaging biomarkers for prediction of clinical outcomes. Current radiomic signatures suffer from limited reproducibility and generalizability, because most features are dependent on imaging modality and tumor histology, making them sensitive to variations in scan protocol. Here, we propose novel radiological features that are specially designed to ensure compatibility across diverse tissues and imaging contrast.

Alterations in microbiota and their metabolites are associated with beneficial effects of bile acid sequestrant on icteric primary biliary Cholangitis.

: Increasing data suggests an interaction between bile acids and intestinal microbiota in the pathogenesis of primary biliary cholangitis (PBC). Bile acid sequestrants are widely used to bind bile acids in the intestinal lumen and are therefore posited to impact gut bacteria. Herein we aimed to investigate the effects of cholestyramine on the bile acid profile and gut microbiome in a cohort of icteric PBC patients.