Deciphering the Oncogenic Landscape of Hepatocytes Through Integrated Single-Nucleus and Bulk RNA-Seq of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality, while the hepatocyte mechanisms driving oncogenesis remains poorly understood. In this study, single-nucleus RNA sequencing of samples from 22 HCC patients revealed 10 distinct hepatocyte subtypes, including beneficial Hep0, predominantly malignant Hep2, and immunosuppressive Hep9. These subtypes were strongly associated with patient prognosis, confirmed in TCGA-LIHC and Fudan HCC cohorts through hepatocyte composition deconvolution.

Multifaceted analysis of noncoding and coding de novo variants implicates NOTCH signaling pathway in tetralogy of Fallot in Chinese population.

Tetralogy of Fallot (TOF) is the most common cyanotic heart defect in neonates. While there is compelling evidence of genetic contribution to the etiology of TOF, the contribution of noncoding variants to the development of the defect remains unexplored. Potentially damaging noncoding de novo variants (NC DNVs) were detected from 141 Chinese nonsyndromic TOF trios (CHN-TOF) and compared with those detected in the Pediatric Cardiac Genomics Consortium (PCGC).

Genetics of biliary atresia: Approaches, pathological insights and challenges.

Biliary atresia (BA) is a severe neonatal cholestatic disorder marked by fibro-obliteration of the extrahepatic and intrahepatic bile ducts. It is the most common cause of pediatric end-stage liver disease and the leading indication for liver transplantation in children. There is significant heterogeneity in the etiology, involving various genetic and environmental factors such as viral infection, immune dysregulation and genetic predisposition to defective hepatobiliary development.

Multiomics and Artificial Intelligence for Personalized Nutritional Management of Diabetes in Patients Undergoing Peritoneal Dialysis.

Managing diabetes in patients on peritoneal dialysis (PD) is challenging due to the combined effects of dietary glucose, glucose from dialysate, and other medical complications. Advances in technology that enable continuous biological data collection are transforming traditional management approaches. This review explores how multiomics technologies and artificial intelligence (AI) are enhancing glucose management in this patient population.

Dysregulated Activation of Hippo-YAP1 Signaling Induces Oxidative Stress and Aberrant Development of Intrahepatic Biliary Cells in Biliary Atresia.

The canonical Hippo-YAP1 signaling pathway is crucial for liver development and regeneration, but its role in repair and regeneration of intrahepatic bile duct in biliary atresia (BA) remains largely unknown. YAP1 expression in the liver tissues of patients with BA and Rhesus rotavirus-induced experimental BA mouse models were examined using quantitative reverse transcriptase-PCR and double immunofluorescence. Mouse EpCAM-expressing cell-derived liver organoids were generated and treated with Hippo-YAP1 pathway activators (Xmu-mp-1 and TRULI) or an inhibitor (Peptide17).

Abnormally activated wingless/integrated signaling modulates tumor-associated macrophage polarization and potentially promotes hepatocarcinoma cell growth.

In this article, we comment on the article by Huang . The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer. Tumor-associated macrophages (TAMs), primarily of the M2 subtype, are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways, including the wingless/integrated (Wnt) pathway.

Animal and organoid models to elucidate the anti-fibrotic effect of steroid on biliary atresia.

Purpose: We performed animal and organoid study to evaluate the anti-fibrotic effect of steroid on biliary atresia (BA) and the underlying patho-mechanism.

Methods: BA animal models were created by inoculation of mice on post-natal day 1 with rhesus rotavirus (RRV). They received either 20 µl phosphate-buffered saline (PBS) or steroid from day 21 to day 34.

Ethnic and seasonal variations in FGF-23 and markers of chronic kidney disease-mineral and bone disorder.

Background: Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions.

Methods: We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study.

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes.

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes.

QTc Interval Prolongation Is Independently Associated with FGF23 and Predicts Mortality in Predialysis Chronic Kidney Disease.

Introduction: QTc interval prolongation is increasingly frequent as chronic kidney disease (CKD) advances and predicts death in dialysis. However, predictors and mortality risk in predialysis CKD are understudied. FGF23 induces left ventricular hypertrophy (LVH) which is associated with QTc interval prolongation and death, suggesting a possible pathway from FGF23 to death that entails LVH and QTc prolongation.

BNT162b2 versus mRNA-1273 Third Dose COVID-19 Vaccine in Patients with CKD and Maintenance Dialysis Patients.

Background: There is a lack of randomized controlled trial data regarding differences in immunogenicity of varying coronavirus disease 2019 (COVID-19) mRNA vaccine regimens in CKD populations.

Methods: We conducted a randomized controlled trial at three kidney centers in Toronto, Ontario, Canada, evaluating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody response after third dose vaccination. Participants ( n =273) with CKD not on dialysis or receiving dialysis were randomized 1:1 to third dose 30- µ g BNT162b2 (Pfizer-BioNTech) or 100- µ g mRNA-1273 (Moderna).

Artificial intelligence-based approaches for the detection and prioritization of genomic mutations in congenital surgical diseases.

Genetic mutations are critical factors leading to congenital surgical diseases and can be identified through genomic analysis. Early and accurate identification of genetic mutations underlying these conditions is vital for clinical diagnosis and effective treatment. In recent years, artificial intelligence (AI) has been widely applied for analyzing genomic data in various clinical settings, including congenital surgical diseases.

The Current Proceedings of PSC-Based Liver Fibrosis Therapy.

Liver fibrosis was initially considered to be an irreversible process which will eventually lead to the occurrence of liver cancer. So far there has been no effective therapeutic approach to treat liver fibrosis although scientists have put tremendous efforts into the underlying mechanisms of this disease. Therefore, in-depth research on novel and safe treatments of liver fibrosis is of great significance to human health.

Amyloidoses in Onco-Nephrology Practice: A Multidisciplinary Case-Based Conference Report.

Introduction And Objective: Amyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes.

Transcriptomics of Hirschsprung disease patient-derived enteric neural crest cells reveals a role for oxidative phosphorylation.

Hirschsprung disease is characterized by the absence of enteric neurons caused by the defects of enteric neural crest cells, leading to intestinal obstruction. Here, using induced pluripotent stem cell-based models of Hirschsprung and single-cell transcriptomic analysis, we identify a gene set of 118 genes commonly dysregulated in all patient enteric neural crest cells, and suggest HDAC1 may be a key regulator of these genes. Furthermore, upregulation of RNA splicing mediators and enhanced alternative splicing events are associated with severe form of Hirschsprung.

Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids.

Background: Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients.

Determining the Longitudinal Serologic Response to COVID-19 Vaccination in the Chronic Kidney Disease Population: A Clinical Research Protocol.

Background: People living with chronic kidney disease (CKD) have been disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic, including higher rates of infection, hospitalization, and death. Data on responsiveness to COVID-19 vaccination strategies and immunogenicity are limited, yet required to inform vaccination strategies in this at-risk population.

Objective: The objective of this study is to characterize the longitudinal serologic response to COVID-19 vaccination.

Functional patency rates of arteriovenous fistula of a retrospective cohort study from one of the biggest centers in Canada.

Background: The main barriers to arterio-venous fistula (AVF) utilization are primary failure, long maturation duration, and low secondary patency rates.

Methods: In this retrospective cohort study, primary, secondary, functional primary, and functional secondary patency rates were calculated and compared between two age groups (< 75 years and >  = 75 years) and between radiocephalic (RC-) and upper arm (UA-) AVFs, and factors determining the duration of functional secondary patency were evaluated.

Results: Between 2016 and 2020, 206 predialysis patients whose AVFs had been created previously initiated renal replacement treatment.

Genetics of Hirschsprung's disease.

Hirschsprung's disease (HSCR) is a classical model of enteric neuropathy, occurring in approximately 2-2.8 in 10,000 newborns. It is the commonest form of congenital bowel obstruction and is characterized by the absence of enteric ganglia in distal colon.

Bioengineering Liver Organoids for Diseases Modelling and Transplantation.

Organoids as three-dimension (3D) cellular organizations partially mimic the physiological functions and micro-architecture of native tissues and organs, holding great potential for clinical applications. Advances in the identification of essential factors including physical cues and biochemical signals for controlling organoid development have contributed to the success of growing liver organoids from liver tissue and stem/progenitor cells. However, to recapitulate the physiological properties and the architecture of a native liver, one has to generate liver organoids that contain all the major liver cell types in correct proportions and relative 3D locations as found in a native liver.

Whole genome sequencing reveals epistasis effects within RET for Hirschsprung disease.

Common variants in RET and NRG1 have been associated with Hirschsprung disease (HSCR), a congenital disorder characterised by incomplete innervation of distal gut, in East Asian (EA) populations. However, the allelic effects so far identified do not fully explain its heritability, suggesting the presence of epistasis, where effect of one genetic variant differs depending on other (modifier) variants. Few instances of epistasis have been documented in complex diseases due to modelling complexity and data challenges.