Validation of radiolabelled exendin for beta cell imaging by ex vivo autoradiography and immunohistochemistry of human pancreas.

Background: Estimation of beta cell mass is currently restricted to evaluating pancreatic tissue samples, which provides limited information. A non-invasive imaging technique that reliably quantifies beta cell mass enables monitoring of changes of beta cell mass during the progression of diabetes mellitus and may contribute to monitoring of therapy effectiveness. We assessed the specificity of radiolabelled exendin for beta cell mass quantification in humans.

Totally endoscopic coronary artery bypass grafting: experience in 1500 patients.

Objectives: Totally endoscopic coronary artery bypass grafting (TECAB) is a minimally invasive approach to achieve surgical revascularization through a minimally invasive approach. Still, data regarding non-robotic TECAB are limited. This report presents the results of a TECAB technique using long-shafted instruments, defined as Endo-CABG, from a single-centre experience in 1500 consecutive patients.

Histology-Based Radiomics for [F]FDG PET Identifies Tissue Heterogeneity in Pancreatic Cancer.

Radiomics features can reveal hidden patterns in a tumor but usually lack an underlying biologic rationale. In this work, we aimed to investigate whether there is a correlation between radiomics features extracted from [F]FDG PET images and histologic expression patterns of a glycolytic marker, monocarboxylate transporter-4 (MCT4), in pancreatic cancer. A cohort of pancreatic ductal adenocarcinoma patients ( = 29) for whom both tumor cross sections and [F]FDG PET/CT scans were available was used to develop an [F]FDG PET radiomics signature.

Automatic quantification of tumor-stroma ratio as a prognostic marker for pancreatic cancer.

Purpose: This study aims to introduce an innovative multi-step pipeline for automatic tumor-stroma ratio (TSR) quantification as a potential prognostic marker for pancreatic cancer, addressing the limitations of existing staging systems and the lack of commonly used prognostic biomarkers.

Methods: The proposed approach involves a deep-learning-based method for the automatic segmentation of tumor epithelial cells, tumor bulk, and stroma from whole-slide images (WSIs). Models were trained using five-fold cross-validation and evaluated on an independent external test set.

A review on the safety of growth factors commonly used in cultivated meat production.

Growth factors are commonly added to cell culture media in cellular agriculture to mimic the endogenous process of proliferation and differentiation of cells. Many of these growth factors are endogenous to humans and known to be present in the edible tissues and milk of food animals. However, there is little or no information on the use of growth factors intentionally added in food production before the advent of cultivated meat.

Rational evolution for altering the ligand preference of estrogen receptor alpha.

Estrogen receptor α is commonly used in synthetic biology to control the activity of genome editing tools. The activating ligands, estrogens, however, interfere with various cellular processes, thereby limiting the applicability of this receptor. Altering its ligand preference to chemicals of choice solves this hurdle but requires adaptation of unspecified ligand-interacting residues.

Fibroblast Activation Protein-Targeted Photodynamic Therapy of Cancer-Associated Fibroblasts in Murine Models for Pancreatic Ductal Adenocarcinoma.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5 year survival of 9%. One important limiting factor for treatment efficacy is the dense tumor-supporting stroma. The cancer-associated fibroblasts in this stroma deposit excessive amounts of extracellular matrix components and anti-inflammatory mediators, which hampers the efficacy of chemo- and immunotherapies.

Effects of Nutritional Interventions in Older Adults with Malnutrition or at Risk of Malnutrition on Muscle Strength and Mortality: Results of Pooled Analyses of Individual Participant Data from Nine RCTs.

Nutritional intervention studies in older adults with malnutrition aim to improve nutritional status. Although these studies show a significant gain in body weight, there is inconsistent evidence of clinical effectiveness on muscle strength and mortality. This study aimed to examine the effects of nutritional interventions on muscle strength and risk of mortality in older adults (malnourished or at risk) and explore whether these effects are influenced by participant characteristics.

Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy.

Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation.

Imaging and photodynamic therapy of prostate cancer using a theranostic PSMA-targeting ligand.

Purpose: Incomplete resection of prostate cancer (PCa) results in increased risk of disease recurrence. Combined fluorescence-guided surgery with tumor-targeted photodynamic therapy (tPDT) may help to achieve complete tumor eradication. We developed a prostate-specific membrane antigen (PSMA) ligand consisting of a DOTA chelator for In labeling and a fluorophore/photosensitizer IRDye700DX (PSMA-N064).

Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial.

β-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the β-agonist clenbuterol (40 µg/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.

SBH17: Benchmark Database of Barrier Heights for Dissociative Chemisorption on Transition Metal Surfaces.

Accurate barriers for rate controlling elementary reactions on metal surfaces are key to understanding, controlling, and predicting the rate of heterogeneously catalyzed processes. While barrier heights for gas phase reactions have been extensively benchmarked, dissociative chemisorption barriers for the reactions of molecules on metal surfaces have received much less attention. The first database called SBH10 and containing 10 entries was recently constructed based on the specific reaction parameter approach to density functional theory (SRP-DFT) and experimental results.

Functional noninvasive detection of glycolytic pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) lacks effective treatment options beyond chemotherapy. Although molecular subtypes such as classical and QM (quasi-mesenchymal)/basal-like with transcriptome-based distinct signatures have been identified, deduced therapeutic strategies and targets remain elusive. Gene expression data show enrichment of glycolytic genes in the more aggressive and therapy-resistant QM subtype.

Acute Effects of Inorganic Nitrate Intake on Brachial and Femoral Flow-Mediated Vasodilation, and on Carotid Artery Reactivity Responses: Results of a Randomized, Double-Blinded, Placebo-Controlled Cross-Over Study in Abdominally Obese Men.

Most trials on the effects of inorganic nitrate intake have focused on only one specific aspect of the endothelial cell response to a stimulus, thereby possibly missing other important effects. The aim of the present randomized, double-blinded, placebo-controlled cross-over study was therefore to investigate in eighteen healthy abdominally obese men (18-60 years, waist circumference ≥ 102 cm) acute effects of potassium nitrate on brachial and femoral flow-mediated vasodilation (FMD), and on carotid artery reactivity (CAR) to a cold pressure test. Participants received in random order a drink providing 10 mmol potassium nitrate (i.

N/C Interactions Are Dispensable for Normal In Vivo Functioning of the Androgen Receptor in Male Mice.

The androgen receptor (AR) plays a central role in the development and maintenance of the male phenotype. The binding of androgens to the receptor induces interactions between the carboxyterminal ligand-binding domain and the highly conserved 23FQNLF27 motif in the aminoterminal domain. The role of these so-called N/C interactions in AR functioning is debated.

Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men.

Aims: Improving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men.

Methods: Eighteen apparently healthy men, aged 18-60 years and with a waist circumference ≥ 102 cm, participated in a randomized, double-blind, placebo-controlled cross-over trial.

A disease-associated missense mutation in CYP4F3 affects the metabolism of leukotriene B4 via disruption of electron transfer.

Background: Cytochrome P450 4F3 (CYP4F3) is an ω-hydroxylase that oxidizes leukotriene B4 (LTB4), prostaglandins, and fatty acid epoxides. LTB4 is synthesized by leukocytes and acts as a chemoattractant for neutrophils, making it an essential component of the innate immune system. Recently, involvement of the LTB4 pathway was reported in various immunological disorders such as asthma, arthritis, and inflammatory bowel disease.

Antizyme Inhibitor 1 Regulates Matrikine Expression and Enhances the Metastatic Potential of Aggressive Primary Prostate Cancer.

Unlabelled: Molecular drivers of metastasis in patients with high-risk localized prostate cancer are poorly understood. Therefore, we aim to study molecular drivers of metastatic progression in patients with high-risk prostate cancer. A retrospective matched case-control study of two clinico-pathologically identical groups of patients with high-risk prostate cancer was undertaken.

Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression.

Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC.

Dietary Macronutrients Do Not Differently Influence Postprandial Serum and Plasma Brain-Derived Neurotrophic Factor Concentrations: A Randomized, Double-Blind, Controlled Cross-Over Trial.

Brain-derived neurotrophic factor (BDNF) plays a role in cognition and metabolism. Specific nutrients can affect fasting BDNF concentrations, which are potentially mediated by insulin and/or glucose. Since macronutrients trigger each a different insulin and glucose response, we examined postprandial effects of meals rich in fat, carbohydrates, or protein on BDNF concentrations.

Small-molecule profiling for steroid receptor activity using a universal steroid receptor reporter assay.

A critical step in the development of novel drug candidates for the treatment of steroid related diseases is ensuring the absence of crosstalk with steroid receptors (SRs). Establishing this SR cross-reactivity profile requires multiple reporter assays as each SR associates with its unique enhancer region, a labor intensive and time-consuming approach. To overcome this need for multi-reporter assays, we established a steroid receptor inducible luciferase reporter assay (SRi-Luc) that allows side-by-side examination of agonistic and antagonistic properties of small-molecules on all steroid receptors.

Effects of L-citrulline supplementation and watermelon consumption on longer-term and postprandial vascular function and cardiometabolic risk markers: A meta-analysis of randomized controlled trials in adults.

L-citrulline may improve non-invasive vascular function and cardiometabolic risk markers through increases in L-arginine bioavailability and nitric oxide synthesis. A meta-analysis of randomized controlled trials (RCTs) was performed to examine longer-term and postprandial effects of L-citrulline supplementation and watermelon consumption on these markers for cardiovascular disease in adults. Summary estimates of weighted mean differences (WMDs) in vascular function and cardiometabolic risk markers with accompanying 95% confidence intervals (CIs) were calculated using random or fixed-effect meta-analyses.

The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation.

Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR ). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone.

An Explorative Study on Monocyte Reprogramming in the Context of Periodontitis and .

Aims: Periodontitis is an independent risk factor for cardiovascular disease, but the mechanistic link is not fully understood. In atherosclerotic cardiovascular disease, monocytes can adopt a persistent hyperresponsive phenotype, termed trained immunity. We hypothesized that periodontitis-associated bacteria can induce trained immunity in monocytes, which subsequently accelerate atherosclerosis development.