Study Design and Baseline Characteristics of ALIGN, a Randomized Controlled Study of Atrasentan in Patients With IgA Nephropathy.

Introduction: Endothelin A (ETA) receptor activation is a driver of proteinuria, kidney inflammation, and fibrosis in IgA nephropathy (IgAN). Atrasentan, a selective ETA receptor antagonist, has potential to reduce proteinuria and preserve kidney function in IgAN. ALIGN (NCT04573478) is a phase 3, randomized, double-blind, placebo-controlled clinical trial of atrasentan in patients with IgAN at high risk of kidney function loss.

Oral Administration of [F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study.

Purpose: This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration.

Procedures: Twelve male Wistar rats were divided into four groups and subjected to intravenous or oral [F]MC225 administration protocols: G (intravenous route), G (oral administration without fasting), G (oral administration with fasting), and G (oral administration with fasting following administration of the P-gp inhibitor tariquidar).

Investigating socioeconomic disparities in prescribing new diabetes medications in individuals with type 2 diabetes and very high cardiovascular risk in the Netherlands.

Aims: This study aims to analyze prescription patterns of new diabetes medication and assess socioeconomic disparities in their initiation among individuals with T2DM with very high cardiovascular risk.

Methods: Individuals diagnosed with T2DM and very high cardiovascular risk were identified (N = 10,768) based on general practitioner's electronic health record data. SGLT-2is and GLP-1RAs prescription patterns were examined.

Kinetic Control of Self-Assembly Pathway in Dual Dynamic Covalent Polymeric Systems.

Kinetically controlled self-assembly is garnering increasing interest in the field of supramolecular polymers and materials, yet examples involving dynamic covalent exchange remain relatively unexplored. Here we report an unexpected dynamic covalent polymeric system whose aqueous self-assembly pathway is strongly influenced by the kinetics of evaporation of water. The key design is to integrate dual dynamic covalent bonds-including disulfide bonds and boroxine/borate-into a dynamic equilibrium system of monomers, polymers, and materials.

Adverse health outcomes and health-related quality of life (HRQoL) among long-term adolescent and young adult (AYA) brain tumour survivors: results from the population-based SURVAYA study.

Purpose: Adolescent and young adult (AYA) malignant brain tumour (BT) survivors are at risk of adverse health outcomes, which may impact their health-related quality of life (HRQoL). This study aimed to investigate the (1) prevalence of physical and psychological adverse health outcomes, (2) the HRQoL, and (3) the association of adverse health outcomes and HRQoL among long-term AYA-BT survivors. Adverse health outcomes and HRQoL were compared to other AYA cancer (AYAC) survivors.

Tenascin-X deficiency causing classical-like Ehlers Danlos syndrome type 1 in humans is a significant risk factor for GI and tracheal ruptures.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

Validation of a Coarse-Grained Martini 3 Model for Molecular Oxygen.

Molecular oxygen (O) is essential for life, and continuous effort has been made to understand its pathways in cellular respiration with all-atom (AA) molecular dynamics (MD) simulations of, e.g., membrane permeation or binding to proteins.

Taylor dispersion analysis and release studies of β-carotene-loaded PLGA nanoparticles and liposomes in simulated gastrointestinal fluids.

β-Carotene (βC), a natural carotenoid, is the most important and effective vitamin A precursor, known also for its antioxidant properties. However, its poor water solubility, chemical instability, and low bioavailability limit its effectiveness as an orally delivered functional nutrient. Nanoparticle encapsulation improves βC's bioaccessibility by enhancing its stability and solubility.

Critical Steps in Shotgun Metagenomics-Based Diagnosis of Bloodstream Infections Using Nanopore Sequencing.

Shotgun metagenomics offers a broad detection of pathogens for rapid blood stream infection of pathogens but struggles with often low numbers of pathogens combined with high levels of human background DNA in clinical samples. This study aimed to develop a shotgun metagenomics protocol using blood spiked with various bacteria and to assess bacterial DNA extraction efficiency with human DNA depletion. The Blood Pathogen Kit (Molzym) was used to extract DNA from EDTA-whole blood (WB) and plasma samples, using contrived blood specimens spiked with bacteria for shotgun metagenomics diagnostics via Oxford Nanopore sequencing and PCR-based library preparation.

The Photoinduced Response of Antimony from Femtoseconds to Minutes.

As a phase change material (PCM), antimony exhibits a set of desirable properties that make it an interesting candidate for photonic memory applications. These include a large optical contrast between crystalline and amorphous solid states over a wide wavelength range. Switching between the states is possible on nanosecond timescales by applying short heating pulses.

Effect of multiple counselling contacts along the continuum of care on use of postpartum family planning in a cohort of Ethiopian women: a dose-response analysis.

Objective: Dose-response analysis of the effect of each additional contact where family planning (FP) was discussed during antenatal, delivery, postnatal or immunisation visits on the uptake of postpartum family planning (PPFP) within 12 months.

Design: A cohort where pregnant women were enrolled and reinterviewed approximately 12 months postpartum. Life table analyses examined differentials in probabilities of adopting contraception over 12 months postpartum by level of exposure to FP counselling.

Safe, effective and cost-effective oxygen saturation targets for children and adolescents with respiratory distress: protocol for a randomised controlled trial (OxyKids study).

Introduction: Little is known about the effectiveness and safety of oxygen saturation (SpO2) thresholds in children admitted with respiratory distress. The current 90%-94% threshold could lead to prolonged administration of supplemental oxygen, increased duration of hospital admissions, distress for children and families, and healthcare costs. To balance reducing unnecessary oxygen administration and preventing hypoxia, a lower SpO2 threshold of 88% for oxygen supplementation in children has been suggested.

Which clinical trial designs and statistical approaches have been used in assessments of orphan maintenance by the European Medicines Agency between 2012 and 2022? A cross-sectional study.

Objectives: In the European Union, a new orphan medicinal product must demonstrate 'significant benefit' over approved medicinal products targeting the same indication. To demonstrate a significant benefit, comparisons between the new product and the already approved medicinal products-either directly by a head-to-head comparison within a clinical trial or indirectly as a cross-trial comparison-are necessary. In this study, we investigate the types of trial designs and statistical approaches used for demonstrating a significant benefit of a new orphan medicinal product against approved comparators used between 2012 and 2022.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Floodplain forests drive fruit-eating fish diversity at the Amazon Basin-scale.

Unlike most rivers globally, nearly all lowland Amazonian rivers have unregulated flow, supporting seasonally flooded floodplain forests. Floodplain forests harbor a unique tree species assemblage adapted to flooding and specialized fauna, including fruit-eating fish that migrate seasonally into floodplains, favoring expansive floodplain areas. Frugivorous fish are forest-dependent fauna critical to forest regeneration via seed dispersal and support commercial and artisanal fisheries.

Genomic exploration of the journey of Plasmodium vivax in Latin America.

Plasmodium vivax is the predominant malaria parasite in Latin America. Its colonization history in the region is rich and complex, and is still highly debated, especially about its origin(s). Our study employed cutting-edge population genomic techniques to analyze whole genome variation from 620 P.

Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation.

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.

Variations in linear energy transfer distributions within a European proton therapy planning comparison of paediatric posterior fossa tumours.

Background And Purpose: Radiotherapy for paediatric posterior fossa tumours may cause complications in the brainstem and upper spinal cord due to high doses. With proton therapy (PT) this risk may increase due to higher relative biological effectiveness (RBE) from elevated linear energy transfer (LET). This study assesses variations in LET in the brainstem and spinal cord in proton treatment plans from European centres.

The feasibility of virtual reality therapy for upper extremity mobilization during and after intensive care unit admission.

Introduction: Early mobilization reduces long-term muscle weakness after intensive care unit (ICU) admission, but barriers (e.g., anxiety, lack of motivation) may complicate patients' adherence to exercise.