Precision models in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents a global health challenge, and ranks among one of the most prevalent and deadliest cancers worldwide. Therapeutic advances have expanded the treatment armamentarium for patients with advanced HCC, but obstacles remain. Precision oncology, which aims to match specific therapies to patients who have tumours with particular features, holds great promise.

Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.

Cholestasis, characterized by impaired bile flow, is associated with an increased risk of cholangiocarcinoma (CCA), a malignancy originating from the biliary epithelium and hepatocytes. Hepatic nuclear receptors (NRs) are pivotal in regulating bile acid and metabolic homeostasis, and their dysregulation is implicated in cholestatic liver diseases and the progression of liver cancer. This review elucidates the role of various hepatic NRs in the pathogenesis of cholestasis-to-CCA progression.

shinyDeepDR: A user-friendly R Shiny app for predicting anti-cancer drug response using deep learning.

Advancing precision oncology requires accurate prediction of treatment response and accessible prediction models. To this end, we present shinyDeepDR, a user-friendly implementation of our innovative deep learning model, DeepDR, for predicting anti-cancer drug sensitivity. The web tool makes DeepDR more accessible to researchers without extensive programming experience.

Huntingtin loss in hepatocytes is associated with altered metabolism, adhesion, and liver zonation.

Huntington's disease arises from a toxic gain of function in the ( ) gene. As a result, many HTT-lowering therapies are being pursued in clinical studies, including those that reduce HTT RNA and protein expression in the liver. To investigate potential impacts, we characterized molecular, cellular, and metabolic impacts of chronic HTT lowering in mouse hepatocytes.

Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blinded, placebo controlled, multicenter study.

Introduction: Right ventricular (RV) function is a major determinant of outcome in patients with precapillary pulmonary hypertension (PH). We studied the effect of ranolazine on RV function over 6 months using multi-modality imaging and biochemical markers in patients with precapillary PH (groups I, III, and IV) and RV dysfunction [CMR imaging ejection fraction (EF) < 45%] in a longitudinal, randomized, double-blinded, placebo-controlled, multicenter study of ranolazine treatment.

Methods: Enrolled patients were assessed using cardiac magnetic resonance (CMR) imaging, C-acetate and -F-FDG positron emission tomography (PET), and plasma metabolomic profiling, at baseline and at the end of treatment.

Robotic Versus Conventional Minimally Invasive Esophagectomy for Esophageal Cancer: A Meta-analysis.

Objectives: To give a comprehensive review of the literature comparing perioperative outcomes and long-term survival with robotic-assisted minimally invasive esophagectomy (RAMIE) versus minimally invasive esophagectomy (MIE) for esophageal cancer.

Background: Curative minimally invasive surgical treatment for esophageal cancer includes RAMIE and conventional MIE. It remains controversial whether RAMIE is comparable to MIE.

An AGS-associated mutation in ADAR1 catalytic domain results in early-onset and MDA5-dependent encephalopathy with IFN pathway activation in the brain.

Background: Aicardi-Goutières syndrome (AGS) is a severe neurodegenerative disease with clinical features of early-onset encephalopathy and progressive loss of intellectual abilities and motor control. Gene mutations in seven protein-coding genes have been found to be associated with AGS. However, the causative role of these mutations in the early-onset neuropathogenesis has not been demonstrated in animal models, and the mechanism of neurodegeneration of AGS remains ambiguous.

Colon Interposition for Esophageal Cancer.

Esophagectomy and colon interposition in the adult patient, either for primary alimentary reconstruction or as a secondary replacement after initial resection/reconstruction for malignant or benign disease, remains a valuable tool in the thoracic surgeon's armamentarium. It is important for surgeons to remain versed in the complexities of the operation, including preoperative preparation and decision making, operative procedural and technical variations, and recognition and timely treatment of postoperative complications. In this article, we present technical details of the procedure, a review of selected published studies, long-term results, and indications and outcomes for revisional surgery.

Single-cell spatial transcriptomics reveals a dynamic control of metabolic zonation and liver regeneration by endothelial cell Wnt2 and Wnt9b.

The conclusive identity of Wnts regulating liver zonation (LZ) and regeneration (LR) remains unclear despite an undisputed role of β-catenin. Using single-cell analysis, we identified a conserved Wnt2 and Wnt9b expression in endothelial cells (ECs) in zone 3. EC-elimination of Wnt2 and Wnt9b led to both loss of β-catenin targets in zone 3, and re-appearance of zone 1 genes in zone 3, unraveling dynamicity in the LZ process.

Intestinal Barrier Dysfunction in Fatty Liver Disease: Roles of Microbiota, Mucosal Immune System, and Bile Acids.

Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of progressive liver diseases ranging from simple steatosis to steatohepatitis and fibrosis. Globally, NAFLD is the leading cause of morbidity and mortality associated with chronic liver disease, and NAFLD patients are at a higher risk of developing cirrhosis and hepatocellular carcinoma. While there is a consensus that inflammation plays a key role in promoting NAFLD progression, the underlying mechanisms are not well understood.

NOTCH-YAP1/TEAD-DNMT1 Axis Drives Hepatocyte Reprogramming Into Intrahepatic Cholangiocarcinoma.

Background & Aims: Intrahepatic cholangiocarcinoma (ICC) is a devastating liver cancer with extremely high intra- and inter-tumoral molecular heterogeneity, partly due to its diverse cellular origins. We investigated clinical relevance and the molecular mechanisms underlying hepatocyte (HC)-driven ICC development.

Methods: Expression of ICC driver genes in human diseased livers at risk for ICC development were examined.

Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial.

Introduction: A major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV).

Methods And Results: We enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of <45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment.

No Zones Left Behind: Democratic Hepatocytes Contribute to Liver Homeostasis and Repair.

Despite minimal turnover, liver cells possess immense regenerative capacity. Some studies suggest existence of a hepatocyte subset with such unique capabilities. However, in the current issue of Cell Stem Cell, three independent studies (Chen et al.

Metagenomic identification of severe pneumonia pathogens in mechanically-ventilated patients: a feasibility and clinical validity study.

Background: Metagenomic sequencing of respiratory microbial communities for pathogen identification in pneumonia may help overcome the limitations of culture-based methods. We examined the feasibility and clinical validity of rapid-turnaround metagenomics with Nanopore™ sequencing of clinical respiratory specimens.

Methods: We conducted a case-control study of mechanically-ventilated patients with pneumonia (nine culture-positive and five culture-negative) and without pneumonia (eight controls).

Correction: mTOR inhibition affects Yap1-β-catenin-induced hepatoblastoma growth and development.

[This corrects the article DOI: 10.18632/oncotarget.26668.

Laparoscopic Approach to Paraesophageal Hernia Repair.

The introduction of minimally invasive techniques to the field of foregut surgery has revolutionized the surgical approach to giant paraesophageal hernia repair. Laparoscopy has become the standard approach in patients with giant paraesophageal hernia because it has been shown to be safe and is associated with lower morbidity and mortality when compared with various open approaches. Specifically, it has been associated with decreased intraoperative blood loss, decreased complications, and reduced hospital length of stay.

Sputum Gram Stain for Bacterial Pathogen Diagnosis in Community-acquired Pneumonia: A Systematic Review and Bayesian Meta-analysis of Diagnostic Accuracy and Yield.

Background: The clinical role of sputum Gram stain (SGS) in community-acquired pneumonia (CAP) diagnosis remains controversial. A 1996 meta-analysis of the diagnostic accuracy of SGS reported heterogeneous results. To update the available evidence, we performed a systematic review and a Bayesian standard and latent-class model meta-analysis.