Oncogene-induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice.

Leukemia relapse is a major cause of death after allogeneic hematopoietic cell transplantation (allo-HCT). We tested the potential of targeting T cell (Tc) immunoglobulin and mucin-containing molecule 3 (TIM-3) for improving graft-versus-leukemia (GVL) effects. We observed differential expression of TIM-3 ligands when hematopoietic stem cells overexpressed certain oncogenic-driver mutations.

Data-Independent Acquisition: A Milestone and Prospect in Clinical Mass Spectrometry-Based Proteomics.

Data-independent acquisition (DIA) has revolutionized the field of mass spectrometry (MS)-based proteomics over the past few years. DIA stands out for its ability to systematically sample all peptides in a given m/z range, allowing an unbiased acquisition of proteomics data. This greatly mitigates the issue of missing values and significantly enhances quantitative accuracy, precision, and reproducibility compared to many traditional methods.

Serum and Urine Metabolites and Kidney Function.

Key Points: We provide an atlas of cross-sectional and longitudinal serum and urine metabolite associations with eGFR and urine albumin-creatinine ratio in an older community-based cohort. Metabolic profiling in serum and urine provides distinct and complementary insights into disease.

Background: Metabolites represent a read-out of cellular processes underlying states of health and disease.

New insights into the hypothalamic-pituitary-thyroid axis: a transcriptome- and proteome-wide association study.

Introduction: Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic-pituitary-thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels.

Linking Basement Membrane and Slit Diaphragm in Drosophila Nephrocytes.

Key Points: nephrocytes feature a special basement membrane that may serve to model joint function of the glomerular filtration barrier. Silencing of laminin and collagen IV genes reduced the density of slit diaphragms in nephrocytes, showing a direct effect of the matrix. Matrix receptor silencing phenocopied basement membrane disruption, indicating that the matrix guides slit diaphragm position through matrix receptors.

Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP): A single center, open-label, three-arm, randomized, controlled intervention pilot trial.

Background: To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute-on-chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT).

Methods: A prospective, randomized, single-center, open-label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT).

A novel non-negative Bayesian stacking modeling method for Cancer survival prediction using high-dimensional omics data.

Background: Survival prediction using high-dimensional molecular data is a hot topic in the field of genomics and precision medicine, especially for cancer studies. Considering that carcinogenesis has a pathway-based pathogenesis, developing models using such group structures is a closer mimic of disease progression and prognosis. Many approaches can be used to integrate group information; however, most of them are single-model methods, which may account for unstable prediction.

metaGWASmanager: a toolbox for an automated workflow from phenotypes to meta-analysis in GWAS consortia.

Summary: This article introduces the metaGWASmanager, which streamlines genome-wide association studies within large-scale meta-analysis consortia. It is a toolbox for both the central consortium analysis group and participating studies to generate homogeneous phenotypes, minimize unwanted variability from inconsistent methodologies, ensure high-quality association results, and implement time-efficient quality control workflows. The toolbox features a plug-in-based approach for customization of association testing.

Interactive exploration of adverse events and multimorbidity in CKD.

Background: Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study.

Methodological biases in observational hospital studies of COVID-19 treatment effectiveness: pitfalls and potential.

Introduction: This study aims to discuss and assess the impact of three prevalent methodological biases: competing risks, immortal-time bias, and confounding bias in real-world observational studies evaluating treatment effectiveness. We use a demonstrative observational data example of COVID-19 patients to assess the impact of these biases and propose potential solutions.

Methods: We describe competing risks, immortal-time bias, and time-fixed confounding bias by evaluating treatment effectiveness in hospitalized patients with COVID-19.

Imaging Markers Derived From MRI-Based Automated Kidney Segmentation—an Analysis of Data From the German National Cohort (NAKO Gesundheitsstudie).

Background: Population-wide research on potential new imaging biomarkers of the kidney depends on accurate automated segmentation of the kidney and its compartments (cortex, medulla, and sinus).

Methods: We developed a robust deep-learning framework for kidney (sub-)segmentation based on a hierarchical, three-dimensional convolutional neural network (CNN) that was optimized for multiscale problems of combined localization and segmentation. We applied the CNN to abdominal magnetic resonance images from the population-based German National Cohort (NAKO) study.

LFK index does not reliably detect small-study effects in meta-analysis: A simulation study.

The LFK index has been promoted as an improved method to detect bias in meta-analysis. Putatively, its performance does not depend on the number of studies in the meta-analysis. We conducted a simulation study, comparing the LFK index test to three standard tests for funnel plot asymmetry in settings with smaller or larger group sample sizes.

Apolipoprotein A-IV concentrations and cancer in a large cohort of chronic kidney disease patients: results from the GCKD study.

Background: Chronic kidney disease (CKD) is highly connected to inflammation and oxidative stress. Both favour the development of cancer in CKD patients. Serum apolipoprotein A-IV (apoA-IV) concentrations are influenced by kidney function and are an early marker of kidney impairment.

Transcatheter aortic valve replacement in Germany with need for a surgical bailout.

Background: In transcatheter aortic valve replacement (TAVR), complications may force the need for a surgical bailout, but knowledge is rare about outcomes in Germany.

Methods: Using national health records, we investigated all TAVR in German hospitals between 2007 and 2020, focusing on 2018-2020. We extracted data on those interventions with need for a surgical bailout.

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII.

Purpose: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies.

Methods: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights.

Atrial fibrillation and survival on a medical intensive care unit.

Background: Atrial fibrillation (AF) is common among patients in the intensive care unit (ICU) and can be triggered by severe illness or preexisting conditions. It is debated if AF is an independent predictor of poor outcome.

Methods: Data derives from a single center retrospective registry including all patients with a stay on the medical ICU for >24 h.

Prospective Cohort Study of Soluble Urokinase Plasminogen Activation Receptor and Cardiovascular Events in Patients With CKD.

Introduction: Soluble urokinase plasminogen activation receptor (suPAR) is an immune-derived pathogenic factor for kidney and atherosclerotic disease. Whether the association between suPAR and cardiovascular (CV) outcomes is dependent on the severity of underlying kidney disease is unclear.

Methods: We measured serum suPAR levels in 4994 participants (mean age 60 years; 60% men; 36% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) 49 ml/min per 1.

Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns.

The kidney medulla is a specialized region with important homeostatic functions. It has been implicated in genetic and developmental disorders along with ischemic and drug-induced injuries. Despite its role in kidney function and disease, the medulla's baseline gene expression and epigenomic signatures have not been well described in the adult human kidney.

Meta-GWAS on PCSK9 concentrations reveals associations of novel loci outside the PCSK9 locus in White populations.

Background And Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of lipid homeostasis. A few earlier genome-wide association studies (GWAS) investigated genetic variants associated with circulating PCSK9 concentrations. However, uncertainty remains about some of the genetic loci discovered beyond the PCSK9 locus.