A taxonomy of the factors contributing to the overtreatment of cancer patients at the end of life. What is the problem? Why does it happen? How can it be addressed?

Many patients with cancer approaching the end of life (EOL) continue to receive treatments that are unlikely to provide meaningful clinical benefit, potentially causing more harm than good. This is called overtreatment at the EOL. Overtreatment harms patients by causing side-effects, increasing health care costs, delaying important discussions about and preparation for EOL care, and occasionally accelerating death.

The benefits of Lactiplantibacillus plantarum: from immunomodulator to vaccine vector.

Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum, is one of the lactic acid bacteria commonly used in fermentation.

A novel super-resolution STED microscopy analysis approach to observe spatial MCU and MICU1 distribution dynamics in cells.

The uptake of Ca by mitochondria is an important and tightly controlled process in various tissues. Even small changes in the key proteins involved in this process can lead to significant cellular dysfunction and, ultimately, cell death. In this study, we used stimulated emission depletion (STED) microscopy and developed an unbiased approach to monitor the sub-mitochondrial distribution and dynamics of the mitochondrial calcium uniporter (MCU) and mitochondrial calcium uptake 1 (MICU1) under resting and stimulated conditions.

Homopregnane-type ferrocene-steroid conjugates exhibit immunomodulatory activity.

Numerous compounds with useful biological activities were previously prepared by tethering ferrocene to natural product scaffolds. Some conjugates of ferrocene and steroids in particular were demonstrated to act as both potent and selective antiproliferative agents. Motivated by a lack of structural diversity in the pregnane series of conjugates, we performed chemical modifications of several naturally occurring progestogens, their biosynthetic precursors and chemically related derivatives so as to obtain conjugates 1-8, in which the steroid skeleton and ferrocene core are linked by the steroid sidechain.

Decoding Salience: A Functional Magnetic Resonance Imaging Investigation of Reward and Contextual Unexpectedness in Memory Encoding and Retrieval.

The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 Participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating their distinct and interactive effects on memory encoding while undergoing high-resolution fMRI. By using advanced image processing techniques tailored to examine midbrain and brainstem nuclei with high precision, our study additionally aimed to elucidate differential activation patterns in subcortical nuclei in response to reward-associated and contextually unexpected stimuli, including distinct pathways involving in particular dopaminergic modulation.

Meta-analyses of the effects of high-intensity interval training in elite athletes - part II: relationships between the mean effects on various performance measures.

Introduction: Our recent meta-analyses have demonstrated that high-intensity interval training (HIIT) causes a range of mean changes in various measures and predictors of endurance and sprint performance in athletes. Here, we extend the analyses to relationships between mean changes of these measures and consider implications for understanding and improving HIIT that were not apparent in the previous analyses.

Methods: The data were mean changes from HIIT with highly trained endurance and elite other (mainly team sport) athletes in studies where two or more measures or predictors of performance were available.

Biosecurity measures reducing spp. and hepatitis E virus prevalence in pig farms-a systematic review and meta-analysis.

spp. and hepatitis E virus (HEV) are significant foodborne zoonotic pathogens that impact the health of livestock, farmers, and the general public. This study aimed to identify biosecurity measures (BSMs) against these pathogens on swine farms in Europe, the United States, and Canada.

Facile development of carbon nanotube (CNT)-based flexible thermoelectric materials for energy-harvesting applications.

In this study, we investigate the thermoelectric properties of functionalized multi-walled carbon nanotubes (F-MWCNTs) dispersed over a flexible substrate through a facile vacuum filtration route. To improve their interfacial adhesion and dispersion, F-MWCNTs underwent hot-pressing. The heat-treatment has improved the nanotubes' connections and subsequently reduced porosity as well, which results in an increasing electrical conductivity upon increasing temperature of hot-pressing.

'We need to be part of the solution': lessons from the 2024 PPRI Conference on ensuring access to affordable medicines through innovative policies.

On 25-26 April 2024, the 5th PPRI (Pharmaceutical Pricing and Reimbursement Information) Conference on ensuring equitable access to affordable medicines took place in Vienna (Austria). Twenty-four accepted contributions were presented either as oral presentations or posters, adding to invited keynote lectures, stakeholder debates and workshops. The global multi-stakeholder audience discussed a range of approaches in pharmaceutical policies, which have the potential to successfully and sustainably address current and future challenges in ensuring patient access to affordable medicines globally.

Prediabetes and diabetes mellitus type II after ischemic stroke.

Introduction: The progression of diabetes status in post-stroke patients remains under-investigated, particularly regarding new treatments for type II diabetes mellitus (DM II), like glucagon-like peptide 1 receptor agonists (GLP-1-RA) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, which have not been studied in the post-stroke setting.

Patients And Methods: Eight hundred eighty-four consecutive ischemic stroke patients recruited to our prospective STROKE-CARD Registry were assessed concerning their glycemic status at baseline (normoglycemia, prediabetes, DM II) and change over time within 1 year follow-up. Multivariate logistic regression was performed to identify factors associated with transitioning from normoglycemia to prediabetes or DM II.

Transforming precision medicine: The potential of the clinical artificial intelligent single-cell framework.

The editorial, "Clinical and translational mode of single-cell measurements: An artificial intelligent single-cell," introduces the innovative clinical artificial intelligence single-cell (caiSC) system, which merges AI with single-cell informatics to advance real-time diagnostics, disease monitoring, and treatment prediction. By combining clinical data and multimodal molecular inputs, caiSC facilitates personalized medicine, promising enhanced diagnostic precision and tailored therapeutic approaches. Despite its potential, caiSC lacks comprehensive data coverage across cell types and diseases, presenting challenges in data quality and model robustness.

The Effect of Accessibility of Insoluble Substrate on the Overall Kinetics of Enzymatic Degradation.

The enzymatic reaction kinetics on cellulose and other solid substrates is limited by the access of the enzyme to the reactive substrate sites. We introduce a general model in which the reaction rate is determined by the active surface area, and the resulting kinetics consequently reflects the evolving relationship between the exposed substrate surface and the remaining substrate volume. Two factors influencing the overall surface-to-volume ratio are considered: the shape of the substrate particles, characterized by a single numerical parameter related to its dimensionality, and the distribution of the particle sizes.

An In Vitro Nutritional Evaluation of Mixed Silages of Drought-Impaired Grass and Sugar Beet Pulp With or Without Silage Inoculants.

Increasing droughts adversely affect grasslands, diminishing the availability and quality of forages for ruminants. We have recently shown that mixed ensiling of drought-impaired grass (DIG) with sugar beet pulp (SBP) improved the conservation and feed value of silage. The application of silage additives may further improve the ruminal degradability, which may thereby shape the fermentation and microbiome in the rumen when those silages are tested as part of dairy diets.

Marsilea: an intuitive generalized paradigm for composable visualizations.

Biological data visualization is challenged by the growing complexity of datasets. Traditional single-data plots or simple juxtapositions often fail to fully capture dataset intricacies and interrelations. To address this, we introduce "cross-layout," a novel visualization paradigm that integrates multiple plot types in a cross-like structure, with a central main plot surrounded by secondary plots for enhanced contextualization and interrelation insights.

External validation of AI-based scoring systems in the ICU: a systematic review and meta-analysis.

Background: Machine learning (ML) is increasingly used to predict clinical deterioration in intensive care unit (ICU) patients through scoring systems. Although promising, such algorithms often overfit their training cohort and perform worse at new hospitals. Thus, external validation is a critical - but frequently overlooked - step to establish the reliability of predicted risk scores to translate them into clinical practice.

Joint EANM/EANO/RANO/SNMMI practice guideline/procedure standard for PET imaging of brain metastases: version 1.0.

This joint practice guideline/procedure standard was collaboratively developed by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI), the European Association of Neuro-Oncology (EANO), and the PET task force of the Response Assessment in Neurooncology Working Group (PET/RANO). Brain metastases are the most common malignant central nervous system (CNS) tumors. PET imaging with radiolabeled amino acids and to lesser extent [F]FDG has gained considerable importance in the assessment of brain metastases, especially for the differential diagnosis between recurrent metastases and treatment-related changes which remains a limitation using conventional MRI.

Mechanism of mammalian transcriptional repression by noncoding RNA.

Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryogenic-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation.

Engineering covalent small molecule-RNA complexes in living cells.

Covalent labeling of RNA in living cells poses many challenges. Here we describe a structure-guided approach to engineer covalent RNA aptamer-ligand complexes. The key is to modify the cognate ligand with an electrophilic handle that allows it to react with a guanine at the RNA binding site.

Heterogeneities in landed costs of traded grains and oilseeds contribute to unequal access to food.

Despite the growing accessibility of international grain and oilseed markets, high production costs and trade frictions are still prevalent, contributing to regional heterogeneities in the landed cost of grain imports. Here we quantify the landed cost for six grain commodities across 3,500 administrative regions, capturing regional cost differences to produce grain and transport it across international borders. We find large heterogeneities in the costs of imported grain, which are highest in Oceania, Central America and landlocked Africa.

Long-term effect of photodynamic therapy on choroidal vascularity index versus choroidal thickness as biomarkers for chronic central serous chorioretinopathy.

Objective: To investigate the long-term impact of half-fluence photodynamic therapy (PDT) on chorioretinal architecture in chronic central serous chorioretinopathy (cCSCR) through novel choroidal vascularity index (CVI) versus previously established subfoveal choroidal thickness (SFCT).

Methods: This post-hoc analysis included prospectively collected swept-source optical coherence tomography (SS-OCT) images of a total of 29 cCSCR and fellow eyes (FE), acquired before, one and 12 months after PDT. CVI, total choroidal area (TCA), luminal area (LA) and stromal area (SA) were calculated using validated binarization technique.