Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A α for targeted cancer therapy.

Eicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A (cPLAα) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLAα starting with compound GK470 (AVX235) and test their in vitro and cellular activities.

Globally scalable glacier mapping by deep learning matches expert delineation accuracy.

Accurate global glacier mapping is critical for understanding climate change impacts. Despite its importance, automated glacier mapping at a global scale remains largely unexplored. Here we address this gap and propose Glacier-VisionTransformer-U-Net (GlaViTU), a convolutional-transformer deep learning model, and five strategies for multitemporal global-scale glacier mapping using open satellite imagery.

When should doctors nudge? Nudging and preference-sensitive care.

When should doctors nudge their patients towards the treatments they think are best? If the nudge is compatible with the patient giving informed consent, then the nudge could be permissible. To be compatible with informed consent, the nudge must, at minimum: (1) not make the patient's understanding worse and (2) not make it hard for the patient to resist consenting. Arguably, many nudges will meet these criteria.

Joint effects of atrial fibrillation and prothrombotic genotypes on the risk of ischemic stroke.

Background: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Whether prothrombotic single nucleotide polymorphisms (SNPs) impact stroke risk in AF is not well known.

Objectives: To investigate the joint effects of five prothrombotic SNPs and AF on ischemic stroke risk.

Conversational repairs on Reddit: Widely initiated but often uncompleted.

Conversational repair has been proposed as a universal system for maintaining mutual understanding during social interactions. The repair system has been studied extensively in offline synchronous interactions (e.g.

Effects of ketamine and propofol on muscarinic plateau potentials in rat neocortical pyramidal cells.

Propofol and ketamine are widely used general anaesthetics, but have different effects on consciousness: propofol gives a deeply unconscious state, with little or no dream reports, whereas vivid dreams are often reported after ketamine anaesthesia. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist, while propofol is a γ-aminobutyric-acid (GABAA) receptor positive allosteric modulator, but these mechanisms do not fully explain how these drugs alter consciousness. Most previous in vitro studies of cellular mechanisms of anaesthetics have used brain slices or neurons in a nearly "comatose" state, because no "arousing" neuromodulators were added.

Transplant and Nontransplant Salvage Therapy in Pediatric Relapsed or Refractory Hodgkin Lymphoma: The EuroNet-PHL-R1 Phase 3 Nonrandomized Clinical Trial.

Importance: The current standard-of-care salvage therapy in relapsed/refractory classic Hodgkin lymphoma (cHL) includes consolidation high-dose chemotherapy (HDCT)/autologous stem cell transplant (aSCT).

Objective: To investigate whether presalvage risk factors and fludeoxyglucose-18 (FDG) positron emission tomography (PET) response to reinduction chemotherapy can guide escalation or de-escalation between HDCT/aSCT or transplant-free consolidation with radiotherapy to minimize toxic effects while maintaining high cure rates.

Design, Setting, And Participants: EuroNet-PHL-R1 was a nonrandomized clinical trial that enrolled patients younger than 18 years with first relapsed/refractory cHL across 68 sites in 13 countries in Europe between January 2007 and January 2013.

Sustainable biomethane production from waste biomass: challenges associated with process optimization in improving the yield.

Various novel technologies are currently under development aimed at improving bio-methane output to tackle challenges related to process stability, biogas production, and methane quality in the anaerobic digestion (AD) process. The management of substrate type, temperature, pH, hydraulic retention time (HRT), organic loading rate (OLR), and inoculum origin is essential for ensuring process effectiveness, minimizing inhibition, and maximizing production of biogas and methane yield. The review emphasizes sustainability, focusing on the environmental and economic benefits of anaerobic digestion, including the reduction of greenhouse gas (GHG) emissions, the minimization of landfill waste, and the provision of renewable energy sources.

FAIR data - the photon and neutron communities move together towards open science.

The topic of data storage, traceability, and data use and reuse in the years following experiments is becoming an important topic in Europe and across the world. Many scientific communities are striving to create open data by the FAIR principles. This is a requirement from the European Commission for EU-funded projects and experiments at EU-funded research infrastructures (RIs) and from many national funding agencies.

Environmental impact of an acid-forming alum shale waste rock legacy site in Norway.

Alum shale formations in Scandinavia are generally enriched in uranium (U) and, when exposed to air and water, may produce acidic rock drainage (ARD), releasing potentially harmful elements into the environment. Taraldrud is a legacy site in southeast Norway where approx. 51 000 m of alum shale was deposited in the 1980s-1990s.

Effectiveness of the PRPP Intervention after brain injury in home-based rehabilitation: Single-case experimental designs with multiple baselines.

Background: Occupational therapists strive to provide evidence-based cognitive rehabilitation for everyday functional activities in community-based rehabilitation.

Objective: In this study, we investigated the effectiveness of the Perceive, Recall, Plan and Perform (PRPP) Intervention in enhancing and maintaining task performance and cognitive strategy use during home-based rehabilitation for individuals with cognitive challenges following acquired brain injury.

Material And Methods: This study is a systematic replication of a single-case experimental designs using multiple baselines applied to three participants (67+ years old) undergoing nine PRPP Intervention sessions.

A Pollen-Based Assisted Migration for Rapid Forest Adaptation.

Climate change poses an unprecedented threat to forest ecosystems, necessitating innovative adaptation strategies. Traditional assisted migration approaches, while promising, face challenges related to environmental constraints, forestry practices, phytosanitary risks, economic barriers, and legal constraints. This has sparked debate within the scientific community, with some advocating for the broader implementation of assisted migration despite these limitations, while others emphasize the importance of local adaptation, which may not keep pace with the rapid rate of climate change.

Biomarker discovery and development of prognostic prediction model using metabolomic panel in breast cancer patients: a hybrid methodology integrating machine learning and explainable artificial intelligence.

Background: Breast cancer (BC) is a significant cause of morbidity and mortality in women. Although the important role of metabolism in the molecular pathogenesis of BC is known, there is still a need for robust metabolomic biomarkers and predictive models that will enable the detection and prognosis of BC. This study aims to identify targeted metabolomic biomarker candidates based on explainable artificial intelligence (XAI) for the specific detection of BC.

In situ detection of PD1-PD-L1 interactions as a functional predictor for response to immune checkpoint inhibition in NSCLC.

Background: Immune checkpoint inhibitors (ICIs) have transformed lung cancer treatment, yet their effectiveness appears restricted to certain patient subsets. Current clinical stratification based on PD-L1 expression offers limited predictive value. Given the mechanism of action, directly detecting spatial PD1-PD-L1 interactions might yield more precise insights into immune responses and treatment outcomes.

Growth and metabolic performance of house fly and black soldier fly larvae differ across densities and waste-based growth substrates.

Large scale production of insect larvae is considered a sustainable way to upcycle various organic waste- and by-products into more valuable food and feed products. The sustainability of insect larvae production depends on the substrates and species being used, but comparative studies that include both growth and efficiency are lacking. Here we compare larval fitness, including survival, development time, weight, substrate conversion efficiency, substrate reduction, and metabolic parameters across different combinations of densities and waste- and by-product-based substrates on the two fly species, the house fly (Musca domestica) and the black soldier fly (Hermetia illucens).

Calcaneal bone mineral assessment in elite female trail runners.

This study aimed to assess the calcaneal bone mineral density (BMD) of elite female trail runners and evaluate its reliability using a novel DXA method. It also examined the relationship between calcaneal BMD and other regions of interest to better understand bone health in this specific population. A cross-sectional study was conducted with 35 elite female trail runners from the Spanish national team.

How to Optimize Deimplementation of Sentinel Lymph Node Biopsy?

Background: The omission of sentinel lymph node biopsy in low-risk elderly breast cancer patients has been introduced in several guidelines. Despite evidence to support its safety, this recommendation has not been implemented by many clinicians. We have examined two aspects of this recommendation that may explain why sentinel lymph node biopsy continues to be performed in most of these patients.

Conference 2024: Building an innovative scientific research ecosystem for microbiome and One Health.

The Conference 2024 provides a platform to promote the development of an innovative scientific research ecosystem for microbiome and One Health. The four key components - Technology, Research (Biology), Academic journals, and Social media - form a synergistic ecosystem. Advanced technologies drive biological research, which generates novel insights that are disseminated through academic journals.

Effect of Variations of Amine Content and Network Branching on Thermomechanical Properties of Epoxy Systems.

In thermosetting epoxies, thermomechanical properties can be enhanced by conscious selection of curing agents. Full cross-linking leads to a maximum in the glass- transition temperature. However, the relation between the glass transition temperature and the epoxy matrix depends on several factors beyond the cross-linking degree, such as the molecular weight of the polymers, network organization, amount of branching, and the presence of hydrogen bonds.