Modeling Chronic Disease Mortality by Methods From Accelerated Life Testing.

We propose a parametric model for describing chronic disease mortality from cohort data and illustrate its use for Type 2 diabetes. The model uses ideas from accelerated life testing in reliability theory and conceptualizes the occurrence of a chronic disease as putting the observational unit to an enhanced stress level, which is supposed to shorten its lifetime. It further addresses the issue of semi-competing risk, that is, the asymmetry of death and diagnosis of disease, where the disease can be diagnosed before death, but not after.

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study.

Introduction/objectives: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation.

A discrete time-to-event model for the meta-analysis of full ROC curves.

The development of new statistical models for the meta-analysis of diagnostic test accuracy studies is still an ongoing field of research, especially with respect to summary receiver operating characteristic (ROC) curves. In the recently published updated version of the "Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy", the authors point to the challenges of this kind of meta-analysis and propose two approaches. However, both of them come with some disadvantages, such as the nonstraightforward choice of priors in Bayesian models or the requirement of a two-step approach where parameters are estimated for the individual studies, followed by summarizing the results.

Effects of ACLY Inhibition on Body Weight Distribution: A Drug Target Mendelian Randomization Study.

Adenosine triphosphate-citrate lyase (ACLY) inhibition has proven clinically efficacious for low-density lipoprotein cholesterol (LDL-c) lowering and cardiovascular disease (CVD) risk reduction. Clinical and genetic evidence suggests that some LDL-c lowering strategies, such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition with statin therapy increase body weight and the risk of developing type 2 diabetes mellitus (T2DM). However, whether ACLY inhibition affects metabolic risk factors is currently unknown.

Exposure to gestational diabetes mellitus in utero impacts hippocampal functional connectivity in response to food cues in children.

Objectives: Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging (fMRI).

Slow-wave sleep drives sleep-dependent renormalization of synaptic AMPA receptor levels in the hypothalamus.

According to the synaptic homeostasis hypothesis (SHY), sleep serves to renormalize synaptic connections that have been potentiated during the prior wake phase due to ongoing encoding of information. SHY focuses on glutamatergic synaptic strength and has been supported by numerous studies examining synaptic structure and function in neocortical and hippocampal networks. However, it is unknown whether synaptic down-regulation during sleep occurs in the hypothalamus, i.

Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes.

Aim: To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves β-cell responsivity in healthy men.

Methods: In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.

Impact of peripheral thyroid hormone balance on liver fat: insights from the NutriAct trial.

Objective: Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat.

Design: 502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG).

Projecting the economic burden of type 1 and type 2 diabetes mellitus in Germany from 2010 until 2040.

Background: The aim is to estimate age- and sex-specific direct medical costs related to diagnosed type 1 and type 2 diabetes in Germany between 2010 and 2040.

Methods: Based on nationwide representative epidemiological routine data from 2010 from the statutory health insurance in Germany (almost 80% of the population's insurance) we projected age- and sex-specific healthcare expenses for type 1 and 2 diabetes considering future demographic, disease-specific and cost trends. We combine per capita healthcare cost data (obtained from aggregated claims data from an almost 7% random sample of all German people with statutory health insurance) together with the demographic structure of the German population (obtained from the Federal Statictical Office), diabetes prevalence, incidence and mortality.

Surrogate measures of first-phase insulin secretion versus reference methods intravenous glucose tolerance test and hyperglycemic clamp: a systematic review and meta-analyses.

Introduction: In this systematic review, we investigated the diagnostic accuracy of surrogate measures of insulin secretion based on fasting samples and the oral glucose tolerance test (OGTT). The first phase of insulin secretion was calculated using two gold standard methods; the hyperglycemic clamp (HGC) test and intravenous glucose tolerance test (IVGTT).

Research Design And Methods: We conducted searches in the PubMed, Cochrane Central, and Web of Science databases, the last of which was conducted at the end of June 2021.

Using the illness-death model to estimate age- and sex-standardized incidence rates of diabetes in Mexico from 2003 to 2015.

Background: We aimed to estimate the age-specific and age-standardized incidence rate of diabetes for men and women in Mexico between 2003 and 2015, and to assess the relative change in incidence of diabetes between 2003 and 2015.

Methods: We use a partial differential equation describing the illness-death model to estimate the incidence rate (IR) of diabetes for the years 2003, 2009 and 2015 based on prevalence data from National Health Surveys conducted in Mexico, the mortality rate of the Mexican general population and plausible input values for age-specific mortality rate ratios associated with diabetes.

Results: The age-standardized IR of diabetes per 1000 person years (pryr) was similar among men (IRm) and women (IRw) in the year 2003 (IRm 6.

Effect of Extract Supplementation in the Metabolic Control of People with Diabetes Mellitus Type 1: A Double-Blind Randomized Placebo-Controlled Trial.

Unlabelled: Introduction-Background: Data from experimental trials show that L. (saffron) is considered to improve glycemia, lipid profile, and blood pressure and reduce oxidative stress. So far, clinical trials have been conducted in individuals with metabolic syndrome and Diabetes Mellitus type 2 (DMT-2).

Correlating maternal and cord-blood inflammatory markers and BDNF with human fetal brain activity recorded by magnetoencephalography: An exploratory study.

Background: During gestation, the brain development of the fetus is affected by many biological markers, where inflammatory processes and neurotrophic factors have been of particular interest in the past decade.

Aim: This exploratory study is the first attempt to explore the relationships between biomarker levels in maternal and cord-blood samples and human fetal brain activity measured with non-invasive fetal magnetoencephalography (fMEG).

Method: Twenty-three women were enrolled in this study for collection of maternal serum and fMEG tracings immediately prior to their scheduled cesarean delivery.

The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.

The root cause of type 2 diabetes (T2D) is insulin resistance (IR), defined by the failure of cells to respond to circulating insulin to maintain lipid and glucose homeostasis. While the causes of whole-body insulin resistance are multifactorial, a major contributing factor is dysregulation of liver and adipose tissue function. Adipose dysfunction, particularly adipose tissue-IR (adipo-IR), plays a crucial role in the development of hepatic insulin resistance and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of T2D.

Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies.

Weight loss induced by glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual glucagon-like peptide-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor agonists is coming closer to the magnitudes achieved with surgery. However, with greater weight loss there is concern about potential side effects on muscle quantity (mass), health and function. There is heterogeneity in the reported effects of GLP-1-based therapies on lean mass changes in clinical trials: in some studies, reductions in lean mass range between 40% and 60% as a proportion of total weight lost, while other studies show lean mass reductions of approximately 15% or less of total weight lost.

Panacus: fast and exact pangenome growth and core size estimation.

Motivation: Using a single linear reference genome poses a limitation to exploring the full genomic diversity of a species. The release of a draft human pangenome underscores the increasing relevance of pangenomics to overcome these limitations. Pangenomes are commonly represented as graphs, which can represent billions of base pairs of sequence.

The Role of Activator Protein-1 Complex in Diabetes-Associated Atherosclerosis: Insights From Single-Cell RNA Sequencing.

Despite advances in treatment, atherosclerotic cardiovascular disease remains the leading cause of death in patients with diabetes. Even when risk factors are mitigated, the disease progresses, and thus, newer targets need to be identified that directly inhibit the underlying pathobiology of atherosclerosis in diabetes. A single-cell sequencing approach was used to distinguish the proatherogenic transcriptional profile in aortic cells in diabetes using a streptozotocin-induced diabetic Apoe-/- mouse model.

Mother-infant feeding interactions in mothers with and without eating disorder history: Results of a structured observational study.

Background: A growing body of evidence suggests that children of mothers with eating disorders (EDs) have a greater risk of early feeding problems. Recognizing and reacting adequately to the infant's signals during feeding is crucial for the child's development of internal and external regulatory mechanisms of food intake. Parental EDs might affect this ability.

Radiomics workflow definition & challenges - German priority program 2177 consensus statement on clinically applied radiomics.

Objectives: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation.

Materials And Methods: The consensus was achieved by a multi-stage process.

AGO, a Framework for the Reconstruction of Ancestral Syntenies and Gene Orders.

Reconstructing ancestral gene orders from the genome data of extant species is an important problem in comparative and evolutionary genomics. In a phylogenomics setting that accounts for gene family evolution through gene duplication and gene loss, the reconstruction of ancestral gene orders involves several steps, including multiple sequence alignment, the inference of reconciled gene trees, and the inference of ancestral syntenies and gene adjacencies. For each of the steps of such a process, several methods can be used and implemented using a growing corpus of, often parameterized, tools; in practice, interfacing such tools into an ancestral gene order reconstruction pipeline is far from trivial.

Family-Free Genome Comparison.

The comparison of large-scale genome structures across distinct species offers valuable insights into the species' phylogeny, genome organization, and gene associations. In this chapter, we review the family-free genome comparison tool FFGC that, relying on built-in interfaces with a sequence comparison tool (either BLAST+ or DIAMOND) and with an ILP solver (either CPLEX or Gurobi), provides several methods for analyses that do not require prior classification of genes across the studied genomes. Taking annotated genome sequences as input, FFGC is a complete workflow for genome comparison allowing not only the computation of measures of similarity and dissimilarity but also the inference of gene families, simultaneously based on sequence similarities and large-scale genomic features.

Role of lifestyle and glucagon-like peptide-1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases.

Background: The current obesity pandemic has given rise to associated comorbidities and complications, including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). During the last decade, certain glucagon-like peptide 1 receptor agonists (GLP-1RA), originally developed as antihyperglycemic drugs, also demonstrated efficacy for weight loss.

Aims: To review shared pathophysiologic features of common metabolic diseases and compare therapeutic strategies to reduce body weight and related complications.