Association of Serum Afamin Concentrations With Kidney Failure in Patients With CKD: Findings From the German CKD Cohort Study.

Rationale & Objective: Afamin is a vitamin E-binding glycoprotein primarily expressed in liver and kidney. This study investigated whether serum afamin concentrations are associated with kidney function and incident kidney failure.

Study Design: Prospective cohort study with 6.

Mutations in tumor suppressor genes Vhl and Rassf1a cause DNA damage, chromosomal instability and induce gene expression changes characteristic of clear cell renal cell carcinoma.

RASSF1A is frequently biallelically inactivated in clear cell renal cell carcinoma (ccRCC) due to loss of chromosome 3p and promoter hypermethylation. Here we investigated the cellular and molecular consequences of single and combined deletion of the Rassf1a and Vhl tumor suppressor genes to model the common ccRCC genotype of combined loss of function of RASSF1A and VHL. In mouse embryonic fibroblasts and in primary kidney epithelial cells, double deletion of Rassf1a and Vhl caused chromosomal segregation defects and increased formation of micronuclei, demonstrating that pVHL and RASSF1A function to maintain genomic integrity.

Predicting cisplatin tolerability in older adults with head and neck cancer - Insights for improved chemoradiation outcomes.

Purpose: Cumulative cisplatin doses of ≥ 200 mg/m improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m cisplatin during chemoradiation.

Methods: 366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed.

Modeling heterogeneity in the progression of chronic kidney disease.

Cohort studies with comprehensive follow-up periods that track patients with chronic kidney disease (CKD) and gather extensive health data are important for understanding the diverse progression patterns of CKD. This review explores the potential of emerging analytical techniques that can be applied in addition to conventional analysis approaches to enhance CKD research, by offering more detailed insights into disease progression. To maximize the insights available from CKD cohort data with extended follow-up, we examined two advanced approaches: analysis of disease trajectories and of recurrent events.

Assessing the Effectiveness of metaHelper: A Randomized Controlled Trial of a Web Application for Statistical Transformations in Meta-Analysis.

Objective: To test whether the use of a web application (www.metaHelper.eu) can reduce errors and time needed for statistical transformations commonly performed for meta-analysis.

Inotropes for the prevention of low cardiac output syndrome and mortality for paediatric patients undergoing surgery for congenital heart disease: a network meta-analysis.

Background: Paediatric patients undergoing surgery for congenital heart disease (CHD) are at risk for postoperative low cardiac output syndrome (LCOS) and mortality. LCOS affects up to 25% of children after heart surgery. It consists of reduced myocardial function and increases postoperative morbidity, prolongs mechanical ventilation, and lengthens the duration of intensive care unit (ICU) stay.

RTF: an R package for modelling time course data.

Summary: The retarded transient function (RTF) approach serves as a complementary method to ordinary differential equations (ODEs) for modelling dynamics typically observed in cellular signalling processes. We introduce an R package that implements the RTF approach, originally implemented within the MATLAB-based Data2Dynamics modelling framework. This package facilitates the modelling of time and dose dependencies, and it includes the possibility of model reduction to minimize overfitting.

Evaluation of risk for bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation with myeloablative conditioning regimens.

Bronchiolitis obliterans syndrome (BOS), as chronic manifestation of graft-versus-host disease (GVHD), is a debilitating complication leading to lung function deterioration in patients after allogeneic hematopoietic cell transplantation (allo-HCT). In the present study, we evaluated BOS development risk in patients after receiving myeloablative conditioning (MAC) regimens. We performed a retrospective analysis of patients undergoing allo-HCT, who received MAC with busulfan/cyclophosphamid (BuCy, n = 175) busulfan/fludarabin (FluBu4, n = 29) or thiotepa/busulfan/fludarabine (TBF MAC, n = 37).

Post-Estimation Shrinkage in Full and Selected Linear Regression Models in Low-Dimensional Data Revisited.

The fit of a regression model to new data is often worse due to overfitting. Analysts use variable selection techniques to develop parsimonious regression models, which may introduce bias into regression estimates. Shrinkage methods have been proposed to mitigate overfitting and reduce bias in estimates.

Meta-Analysis of Diagnostic Accuracy Studies With Multiple Thresholds: Comparison of Approaches in a Simulation Study.

The development of methods for the meta-analysis of diagnostic test accuracy (DTA) studies is still an active area of research. While methods for the standard case where each study reports a single pair of sensitivity and specificity are nearly routinely applied nowadays, methods to meta-analyze receiver operating characteristic (ROC) curves are not widely used. This situation is more complex, as each primary DTA study may report on several pairs of sensitivity and specificity, each corresponding to a different threshold.

Association between substituting macronutrients and all-cause mortality: a network meta-analysis of prospective observational studies.

Background: Suboptimal diet quality is a key risk factor for premature death. Assuming relatively stable energy intake among individuals, changes in nutrient intakes occur by exchanging different nutrients. Therefore we aimed to examine the association of isocaloric substitution of dietary (macro)nutrients with all-cause mortality using network meta-analysis (NMA).

Construct prognostic models of multiple myeloma with pathway information incorporated.

Multiple myeloma (MM) is a hematological disease exhibiting aberrant clonal expansion of cancerous plasma cells in the bone marrow. The effects of treatments for MM vary between patients, highlighting the importance of developing prognostic models for informed therapeutic decision-making. Most previous models were constructed at the gene level, ignoring the fact that the dysfunction of the pathway is closely associated with disease development and progression.

User-Centered Evaluation of the Wearable Walker Lower Limb Exoskeleton; Preliminary Assessment Based on the Experience Protocol.

Using lower limb exoskeletons provides potential advantages in terms of productivity and safety associated with reduced stress. However, complex issues in human-robot interactions are still open, such as the physiological effects of exoskeletons and the impact on the user's subjective experience. In this work, an innovative exoskeleton, the , is assessed using the EXPERIENCE benchmarking protocol from the EUROBENCH project.

Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development.

FoPraNet-BW: An Infrastructure for Clinical Studies in Practice-Based Research Networks in the German Health System.

General practice-based research networks have become an integral tool to gain medical knowledge from primary care in many countries. For this purpose, a scalable IT-infrastructure is presented considering the limiting peculiarities in the German health system and enabling GPs to participate in clinical studies based on their patient population. The infrastructure consists of a central study management server and local clients for each practice.

Extrarenal manifestations in inherited kidney diseases.

Monogenic kidney diseases result from an abundance of potential genes carrying pathogenic variants. These conditions are primarily recognized for manifesting as kidney disorders, defined as an impairment of the structure and/or function of the kidneys. However, the impact of these genetic disorders extends far beyond the kidneys, giving rise to a diverse spectrum of extrarenal manifestations.

The membrane transporter SLC25A48 enables transport of choline into human mitochondria.

Choline has important physiological functions as a precursor for essential cell components, signaling molecules, phospholipids, and the neurotransmitter acetylcholine. Choline is a water-soluble charged molecule requiring transport proteins to cross biological membranes. Although transporters continue to be identified, membrane transport of choline is incompletely understood and knowledge about choline transport into intracellular organelles such as mitochondria remains limited.

The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies.

The pathogenesis of gout involves a series of steps beginning with hyperuricaemia, followed by the deposition of monosodium urate crystal in articular structures and culminating in an innate immune response, mediated by the NLRP3 inflammasome, to the deposited crystals. Large genome-wide association studies (GWAS) of serum urate levels initially identified the genetic variants with the strongest effects, mapping mainly to genes that encode urate transporters in the kidney and gut. Other GWAS highlighted the importance of uncommon genetic variants.

Protection from prior natural infection vs. vaccination against SARS-CoV-2-a statistical note to avoid biased interpretation.

Introduction: The fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection rate).

Methods: In order to compare protection rates after infection and vaccination, researchers consider different effect measures such as 1 minus hazard ratio, 1 minus odds ratio, or 1 minus risk ratio.

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.