Characterisation of the HollandPTC R&D proton beamline for physics and radiobiology studies.

HollandPTC is an independent outpatient center for proton therapy, scientific research, and education. Patients with different types of cancer are treated with Intensity Modulated Proton Therapy (IMPT). Additionally, the HollandPTC R&D consortium conducts scientific research into the added value and improvements of proton therapy.

Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia.

Background: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

Predictors of persistent symptoms in eosinophilic esophagitis after remission: fibrostenosis, eosinophilia, anxiety, and depression.

Eosinophilic Esophagitis (EoE) is a chronic inflammatory esophageal disorder, often associated with dysphagia, chest discomfort, and heartburn. There is limited information on persistent esophageal symptoms despite histologic remission (HR). We aimed to assess the prevalence and predictors of persistent esophageal symptoms in adult patients with EoE in HR.

Characterizing the Origins of Primary Aldosteronism.

Background: Renin-independent aldosterone production in normotensive people increases risk for developing hypertension. In parallel, normotensive adrenal glands frequently harbor aldosterone-producing micronodules with pathogenic somatic mutations known to induce primary aldosteronism (PA). A deeper understanding of these phenomena would inform the origins of PA and its role in hypertension pathogenesis.

The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice.

Background: Dichloroacetate (DCA), a pan-pyruvate dehydrogenase kinase inhibitor, ameliorates multiple pathological conditions and tissue injury and shows strong potential for clinical applications. Here, we investigated the preventive effects of DCA in a murine model of alcohol-associated liver disease.

Methods: C57BL/6J mice were subjected to the acute-on-chronic model of alcohol-associated liver disease and treated with DCA.

Real-Time Data Collection Utilizing Mobile Technology in Clinical Research: A Secondary Analysis of a Prospective Cohort.

Introduction: Clinical research faces the challenge of declining physician participation in the pursuit of advancing evidence-based medicine. This secondary analysis focuses on the interactive mobile health (mHealth) application's utility as a real-time data collection tool in clinical settings, specifically targeting cow's milk protein allergy (CMPA) management. The study assesses the mHealth application's potential to alleviate data collection inefficiencies and improve physician engagement in clinical research.

TEMPORARY REMOVAL: Content of selected nutrients and potential contaminants in prenatal multivitamins and minerals: an observational study.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.

Tumor cell-derived spermidine promotes a protumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma (GBM) microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly affect the immune system, but the mechanisms driving these interactions are not completely clear. Here, we demonstrate that the polyamine metabolite spermidine (SPD) was elevated in the GBM tumor microenvironment.

Large- and Small-Animal Studies of Safety, Pharmacokinetics, and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs.

Immune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids can offer limited relief for systemic inflammation for some organs, many patients never achieve remission, and such drugs do not cross the blood-brain barrier, making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease.

Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.

Background & Aims: In Crohn's disease, wrapping of mesenteric fat around the bowel wall, so-called "creeping fat," is highly associated with strictures. The strongest contributor to luminal narrowing in strictures is a thickening of the human intestinal muscularis propria (MP). We investigated creeping fat-derived factors and their effect on mechanisms of human intestinal MP smooth muscle cell (HIMC) hyperplasia.

Co-Design and Refinement of Curriculum-Based Foodbot Factory Intervention to Support Elementary School Nutrition Education.

Background/objectives: School-based nutrition education interventions can support the development of children's food literacy and healthy eating habits. The Foodbot Factory serious game was developed to support school nutrition education based on Canada's Food Guide and Ontario curriculum. The objective of this research was to refine the Foodbot Factory intervention to include curriculum-based lesson plans that had a high-level of acceptability by stakeholders to support implementation by teachers in classrooms.

Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.

Registry-based study comparing health-related quality of life between patients with primary rectal cancer and locally recurrent rectal cancer.

Aim: National clinical registries offer the benefits of a comprehensive dataset, particularly when linked with patient-reported outcome (PRO) data. This aim of this study was to utilise UK registry data to assess cross-sectional differences in health-related quality of life (HrQoL) in patients with primary rectal (PRC) and locally recurrent rectal cancer (LRRC).

Materials And Methods: Data were extracted from the COloRECTal cancer Repository (CORECT-R) and the Locally Recurrent Rectal Cancer - Quality of Life (LRRC-QoL) datasets.

The influence of "advancing" and "receding" colors on figure-ground perception under monocular and binocular viewing.

Research on figure-ground perception has consistently found that red images are more likely to be perceived as figure/nearer, yet the mechanisms behind this are not completely clear. The primary theories have pointed to optical chromatic aberrations or cortical mechanisms, such as the antagonistic interactions of the magno-/parvocellular (M/P) systems. Our study explored this color-biased figure-ground perception by examining the duration for which a region was perceived as figure under both binocular and monocular conditions, using all combinations of red, blue, green, and gray.

Circulating Gut Microbe-Derived Metabolites Are Associated with Hepatocellular Carcinoma.

Unlabelled: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites.

Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines.

Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range.

Methods: Adult participants were recruited at two academic centers.

The adjuvant BcfA activates antigen presenting cells through TLR4 and supports T and T1 while attenuating T2 gene programming.

Introduction: Adjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates T1/T17-polarized immune responses to protein antigens from and SARS CoV-2.

Mirtazapine to alleviate severe breathlessness in patients with COPD or interstitial lung diseases (BETTER-B): an international, multicentre, double-blind, randomised, placebo-controlled, phase 3 mixed-method trial.

Background: Breathlessness frequently becomes severe among people with respiratory disease. Mirtazapine, a widely used antidepressant, has shown promise in the modulation of respiratory sensation and the response to it, as well as reducing feelings of panic, which often accompanies breathlessness. We aimed to determine the effectiveness of mirtazapine to alleviate severe persisting breathlessness.

Relationship of Subendocardial Perfusion to Myocardial Injury, Cardiac Structure, and Clinical Outcomes Among Patients With Hypertension.

Background: Coronary microvascular dysfunction has been implicated in the development of hypertensive heart disease and heart failure, with subendocardial ischemia identified as a driver of sustained myocardial injury and fibrosis. We aimed to evaluate the relationships of subendocardial perfusion with cardiac injury, structure, and a composite of major adverse cardiac and cerebrovascular events consisting of death, heart failure hospitalization, myocardial infarction, and stroke.

Methods: Layer-specific blood flow and myocardial flow reserve (MFR; stress/rest myocardial blood flow) were assessed by N-ammonia perfusion positron emission tomography in consecutive patients with hypertension without flow-limiting coronary artery disease (summed stress score <3) imaged at Brigham and Women's Hospital (Boston, MA) from 2015 to 2021.

Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors.

Allosteric modulation is a central mechanism for metabolic regulation but has yet to be described for a gut microbiota-host interaction. Phenylacetylglutamine (PAGln), a gut microbiota-derived metabolite, has previously been clinically associated with and mechanistically linked to cardiovascular disease (CVD) and heart failure (HF). Here, using cells expressing β1- versus β2-adrenergic receptors (β1AR and β2AR), PAGln is shown to act as a negative allosteric modulator (NAM) of β2AR, but not β1AR.