Inhibition of NLRP3 enhances pro-apoptotic effects of FLT3 inhibition in AML.

FLT3 mutations occur in approximately 25% of all acute myeloid leukemia (AML) patients. While several FLT3 inhibitors have received FDA approval, their use is currently limited to combination therapies with chemotherapy, as resistance occurs, and efficacy decreases when the inhibitors are used alone. Given the highly heterogeneous nature of AML, there is an urgent need for novel targeted therapies that address the disease from multiple angles.

Using a clinical decision support system to reduce excess driving pressure: the ALARM trial.

Background: Patients at need for ventilation often are at risk of acute respiratory distress syndrome (ARDS). Although lung-protective ventilation strategies, including low driving pressure settings, are well known to improve outcomes, clinical practice often diverges from these strategies. A clinical decision support (CDS) system can improve adherence to current guidelines; moreover, the potential of a CDS to enhance adherence can possibly be further increased by combination with a nudge type intervention.

Time-resolved momentum microscopy with fs-XUV photons at high repetition rates with flexible energy and time resolution.

Time-resolved momentum microscopy is an emerging technique based on photoelectron spectroscopy for characterizing ultrafast electron dynamics and the out-of-equilibrium electronic structure of materials in the entire Brillouin zone with high efficiency. In this article, we introduce a setup for time-resolved momentum microscopy based on an energy-filtered momentum microscope coupled to a custom-made high-harmonic generation photon source driven by a multi-100 kHz commercial Yb-ultrafast laser that delivers fs pulses in the extreme ultraviolet range. The laser setup includes a nonlinear pulse compression stage employing spectral broadening in a Herriott-type bulk-based multi-pass cell.

A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Structured surgical training in minimally invasive esophagectomy (MIE) increases textbook outcome-a risk-adjusted learning curve.

Background: Minimally Invasive Esophagectomy (MIE) is a complex surgical procedure that has become a cornerstone in the management of esophageal cancer. This study aims to delineate the learning curve associated with MIE and its impact on patient outcomes.

Methods: A retrospective analysis was conducted on 191 patients who underwent MIE between 2015 and 2022.

Urology on a changing planet: links between climate change and urological disease.

Urological diseases and their varied forms of management warrant special attention in the setting of climate change. Regarding urological cancers, climate change will probably increase the incidence and severity of cancer diagnoses through exposures to certain environmental risk factors, while simultaneously disrupting cancer care delivery and downstream outcomes. Regarding benign urological diseases, a burgeoning body of work exists on climate-related heat waves, dehydration, urolithiasis, renal injury and infectious and vector-borne diseases.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

Radon on Mars and the Moon derived from Martian and lunar meteorites.

The radioactive gas radon-222, a fluid and aerosol tracer in Earth's lithosphere and atmosphere, can also reveal subtle rock physics processes in extraterrestrial environments, such as those involving water, but remains poorly constrained in planetary bodies due to the limited number of samples available. Here we measure the effective radium-226 concentration (EC) of six Martian and nine lunar meteorites to derive radon source terms for Martian and lunar rocks. EC values are 0.

Partially Bonded Crystals: A Pathway to Porosity and Polymorphism.

In recent years, experimental and theoretical investigations have shown that anisotropic colloids can self-organize into ordered porous monolayers, where the interplay of localized bonding sites, so-called patches, with the particle's shape is responsible for driving the systems away from close-packing and toward porosity. Until now it has been assumed that patchy particles have to be fully bonded with their neighboring particles for crystals to form, and that, if full bonding cannot be achieved due to the choice of patch placement, disordered assemblies will form instead. In contrast, we show that by deliberately displacing the patches such that full bonding is disfavored, a different route to porous crystalline monolayers emerges, where geometric frustration and partial bonding are decisive process.

The role of nutritional vitamin D in CKD-MBD in children and adults with CKD, on dialysis and after kidney transplantation - a European consensus statement.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale, clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations.

Docking Structures Induced by Substitution Motifs of Softwood Xylan at Various Cellulose Surfaces.

To understand xylan-cellulose interactions in softwood, the adsorption behavior of hexameric softwood xylan proxies with various substitutions was analyzed on the three surfaces of a hexagonal cellulose microfibril. The study found that all surfaces could bind xylan motifs, showing equally high affinity for the hydrophilic (110) and hydrophobic (100) surfaces and significantly lower affinity for the hydrophilic (11̅0) surface. Unsubstituted xylose hexamers had the highest affinity and most ordered adsorption structures, while substitutions generally reduced the affinity and regularity.

Can spatial self-organization inhibit evolutionary adaptation?

Plants often respond to drier climates by slow evolutionary adaptations from fast-growing to stress-tolerant species. These evolutionary adaptations increase the plants' resilience to droughts but involve productivity losses that bear on agriculture and food security. Plants also respond by spatial self-organization, through fast vegetation patterning involving differential plant mortality and increased water availability to the surviving plants.

Cancer-specific utility instrument for health economic evaluations: A synopsis of the EORTC QLU-C10D user manual and current validity evidence.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Utility - Core 10 Dimensions (QLU-C10D) adds a preference-based scoring algorithm to the EORTC measurement portfolio. It is built on the most widely used health-related quality of life (HRQoL) measure in oncology, the EORTC Quality of Life Questionnaire - Core 30 (QLQ-C30), allowing for the calculation of both HRQoL profiles and health utilities. This is an important advancement for integrating cancer-specific values into health economic evaluations and decision making, offering greater content validity and statistical power than some generic measures.

Caring around and through medical tests in primary care: On the role of care in the diagnostic process.

Primary care is characterised by a broad understanding of health and illness. Due to the high degree of diagnostic uncertainty in primary care, medical tests play a lesser role in this domain than in specialist medicine. However, medical testing is also becoming increasingly important in primary care, raising questions about how these technologies are integrated into everyday practice.

Assessment of potential ecological risk by metals in Ilha Grande Bay (Southeast Brazil).

This study evaluates contamination and potential ecological risk in Ilha Grande Bay (BIG) in southeastern Brazil. To achieve these objectives, we analyzed physicochemical, sediment textural, and geochemical data from 134 stations distributed throughout the bay. The results reveal significant environmental degradation in the coastal areas of Paraty, Saco do Mamanguá, Angra dos Reis City, and Abraão Cove (at Ilha Grande island).

The cost of fear: Impairments of decision-making in specific phobia.

Background: Decision-making processes may play a pivotal role in the etiology and maintenance of specific phobia. However, empirical evidence is limited. This study examined whether decision-making is only impaired in presence of fear-related stimuli or whether general impairments exist but are more pronounced in the presence of fear-related stimuli.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) of the European Association for Cardio-Thoracic Surgery Fourth report: Focus on standardized outcome ratios.

Objectives: This fourth report aimed to provide insights into patient characteristics, outcomes, and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centers in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry.

Methods: All registered patients receiving durable mechanical circulatory support up to August 2024 were included. Expected number of events were predicted using penalized logistic regression.

Theoretical Study on Adsorption of Halogenated Benzenes on Montmorillonites Modified With M(I)/M(II) Cations.

Halogenated benzenes (HBs) are hydrophobic organic chemicals belonging to persistent organic pollutants. Owing to their persistence, they represent a serious problem in environmental contamination, specifically of soils and sediments. One of the most important physical processes determining the fate of HBs in soils is adsorption to main soil components such as soil organic matter and soil minerals.

Milestone events in recessive dystrophic epidermolysis bullosa (RDEB): findings of the PEBLES Study.

Background: In recessive dystrophic epidermolysis bullosa (RDEB), complications like oesophageal strictures, hand contractures, cardiomyopathy and cutaneous squamous cell carcinoma (SCC) may develop, necessitating procedures such as oesophageal dilatation (OD), gastrostomy tube placement and hand surgery.

Objectives: To determine prevalence and age of onset of milestone events by RDEB subtype, specifically dysphagia, first OD, first gastrostomy tube, first hand surgery, cardiomyopathy, first SCC and death.

Methods: The Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) is a register study of individuals with RDEB which records comprehensive EB- and non-EB-related health information.