An international Delphi consensus statement on metabolic dysfunction-associated fatty liver disease and risk of chronic kidney disease.

Background: With the rising global prevalence of fatty liver disease related to metabolic dysfunction, the association of this common liver condition with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the term non-alcoholic fatty liver disease (NAFLD). The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.

Impact of liver cirrhosis, the severity of cirrhosis, and portal hypertension on the outcomes of minimally invasive left lateral sectionectomies for primary liver malignancies.

Background: The impact of cirrhosis and portal hypertension on perioperative outcomes of minimally invasive left lateral sectionectomies remains unclear. We aimed to compare the perioperative outcomes between patients with preserved and compromised liver function (noncirrhotics versus Child-Pugh A) when undergoing minimally invasive left lateral sectionectomies. In addition, we aimed to determine if the extent of cirrhosis (Child-Pugh A versus B) and the presence of portal hypertension had a significant impact on perioperative outcomes.

Impact of body mass index on perioperative outcomes of laparoscopic major hepatectomies.

Background: Data on the effect of body mass index on laparoscopic liver resections are conflicting. We performed this study to investigate the association between body mass index and postoperative outcomes after laparoscopic major hepatectomies.

Methods: This is a retrospective review of 4,348 laparoscopic major hepatectomies at 58 centers between 2005 and 2021, of which 3,383 met the study inclusion criteria.

Apoptotic cell death in disease-Current understanding of the NCCD 2023.

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions.

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis.

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1.

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect.

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration.

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.

Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches.

CORE-IBD: A Multidisciplinary International Consensus Initiative to Develop a Core Outcome Set for Randomized Controlled Trials in Inflammatory Bowel Disease.

Background & Aims: End points to determine the efficacy and safety of medical therapies for Crohn's disease (CD) and ulcerative colitis (UC) are evolving. Given the heterogeneity in current outcome measures, harmonizing end points in a core outcome set for randomized controlled trials is a priority for drug development in inflammatory bowel disease.

Methods: Candidate outcome domains and outcome measures were generated from systematic literature reviews and patient engagement surveys and interviews.

Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.

Reporting guidelines for human microbiome research: the STORMS checklist.

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome epidemiology researchers adapted guidelines for observational and genetic studies to culture-independent human microbiome studies, and also developed new reporting elements for laboratory, bioinformatics and statistical analyses tailored to microbiome studies.

Autophagy in major human diseases.

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies.

Selenium-GPX4 axis protects follicular helper T cells from ferroptosis.

Follicular helper T (T) cells are a specialized subset of CD4 T cells that essentially support germinal center responses where high-affinity and long-lived humoral immunity is generated. The regulation of T cell survival remains unclear. Here we report that T cells show intensified lipid peroxidation and altered mitochondrial morphology, resembling the features of ferroptosis, a form of programmed cell death that is driven by iron-dependent accumulation of lipid peroxidation.

Metabolomic analyses reveal new stage-specific features of COVID-19.

The current pandemic of coronavirus disease 2019 (COVID-19) has affected >160 million individuals to date, and has caused millions of deaths worldwide, at least in part due to the unclarified pathophysiology of this disease. Identifying the underlying molecular mechanisms of COVID-19 is critical to overcome this pandemic. Metabolites mirror the disease progression of an individual and can provide extensive insights into their pathophysiological significance at each stage of disease.

An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

Backgrounds & Aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology.

The metabolic hormone leptin promotes the function of T cells and supports vaccine responses.

Follicular helper T (T) cells control antibody responses by supporting antibody affinity maturation and memory formation. Inadequate T function has been found in individuals with ineffective responses to vaccines, but the mechanism underlying T regulation in vaccination is not understood. Here, we report that lower serum levels of the metabolic hormone leptin associate with reduced vaccine responses to influenza or hepatitis B virus vaccines in healthy populations.