Lysosomal damage due to cholesterol accumulation triggers immunogenic cell death.

Cholesterol serves as a vital lipid that regulates numerous physiological processes. Nonetheless, its role in regulating cell death processes remains incompletely understood. In this study, we investigated the role of cholesterol trafficking in immunogenic cell death.

Impact of the COVID-19 pandemic on mortality and health services utilization costs of patients diagnosed with lung cancer.

Introduction: Healthcare service disruptions due to the COVID-19 pandemic may have caused worse health outcomes and resulted in more expensive treatments for patients diagnosed with lung cancer in Alberta, Canada.

Methods: A population-based retrospective cohort design was used to compare 1-year survival, mortality, and health services utilization costs of patients diagnosed with lung cancer pre- (March 17th, 2018 to March 16th, 2019), intra- (March 17th, 2020 to March 16th, 2021), and post-pandemic (March 17th, 2021 to March 16th, 2022). Kaplan-Meier curves and Cox regressions were used for estimating survival and hazard ratios.

Towards an assessment of psychosocial work factors in a multi-level mental health intervention in the workplace: results from the MENTUPP pilot-study.

Background: Mental health in the workplace is a growing concern for enterprises and policy makers. MENTUPP is a multi-level mental health intervention implemented in small and medium size enterprises from three work sectors in nine countries. This pilot study aimed to evaluate the feasibility, delivery, and instruments for the MENTUPP intervention to inform the planning of a clustered randomized controlled trial.

Innovation Pipeline: A framework for value-based decision making.

The concept of value-based healthcare and focus on health outcomes is not new. While these ideas have been shared for decades, health systems still struggle to implement value-based decision making. This article describes the Innovation Pipeline, a framework that embeds value-based decision making in a healthcare organization.

The effects of different types of organisational workplace mental health interventions on mental health and wellbeing in healthcare workers: a systematic review.

Objective: To determine if and which types of organisational interventions conducted in small and medium size enterprises (SMEs) in healthcare are effective on mental health and wellbeing.

Methods: Following PRISMA guidelines, we searched six scientific databases, assessed the methodological quality of eligible studies using QATQS and grouped them into six organisational intervention types for narrative synthesis. Only controlled studies with at least one follow-up were eligible.

Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation.

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS.

Synergistic effect of sildenafil combined with controlled hypothermia to alleviate microglial activation after neonatal hypoxia-ischemia in rats.

Background And Purpose: The only validated treatment to prevent brain damage associated with hypoxia-ischemia (HI) encephalopathy of the newborn is controlled hypothermia with limited benefits. Additional putative neuroprotective drug candidates include sildenafil citrate, a phosphodiesterase-type 5 inhibitor. The main objective of this preclinical study is to assess its ability to reduce HI-induced neuroinflammation, in particular through its potential effect on microglial activation.

An ensemble of bias-adjusted CMIP6 climate simulations based on a high-resolution North American reanalysis.

ESPO-G6-R2 v1.0 is a set of statistically downscaled and bias-adjusted climate simulations based on the Coupled Model Intercomparison Project 6 (CMIP6) models. The dataset is composed of daily timeseries of three variables: daily maximum temperature, daily minimum temperature and daily precipitation.

Implementing a complex mental health intervention in occupational settings: process evaluation of the MENTUPP pilot study.

Background: According to the Medical Research Council (MRC) framework, the theorisation of how multilevel, multicomponent interventions work and the understanding of their interaction with their implementation context are necessary to be able to evaluate them beyond their complexity. More research is needed to provide good examples following this approach in order to produce evidence-based information on implementation practices.

Objectives: This article reports on the results of the process evaluation of a complex mental health intervention in small and medium enterprises (SMEs) tested through a pilot study.

3,4-dimethoxychalcone induces autophagy and reduces neointimal hyperplasia and aortic lesions in mouse models of atherosclerosis.

Autophagy inducers can prevent cardiovascular aging and age-associated diseases including atherosclerosis. Therefore, we hypothesized that autophagy-inducing compounds that act on atherosclerosis-relevant cells might have a protective role in the development of atherosclerosis. Here we identified 3,4-dimethoxychalcone (3,4-DC) as an inducer of autophagy in several cell lines from endothelial, myocardial and myeloid/macrophagic origin, as demonstrated by the aggregation of the autophagosome marker GFP-LC3 in the cytoplasm of cells, as well as the downregulation of its nuclear pool indicative of autophagic flux.

Phenotypic and proteomic characterization of the human erythroid progenitor continuum reveal dynamic changes in cell cycle and in metabolic pathways.

Human erythropoiesis is a complex process leading to the production of 2.5 million red blood cells per second. Following commitment of hematopoietic stem cells to the erythroid lineage, this process can be divided into three distinct stages: erythroid progenitor differentiation, terminal erythropoiesis, and reticulocyte maturation.

Insights into the Evolution of Ohnologous Sequences and Their Epigenetic Marks Post-WGD in Malus Domestica.

A Whole Genome Duplication (WGD) event occurred several Ma in a Rosaceae ancestor, giving rise to the Maloideae subfamily which includes today many pome fruits such as pear (Pyrus communis) and apple (Malus domestica). This complete and well-conserved genome duplication makes the apple an organism of choice to study the early evolutionary events occurring to ohnologous chromosome fragments. In this study, we investigated gene sequence evolution and expression, transposable elements (TE) density, and DNA methylation level.

Implementation and evaluation of a multi-level mental health promotion intervention for the workplace (MENTUPP): study protocol for a cluster randomised controlled trial.

Background: Well-organised and managed workplaces can be a source of wellbeing. The construction, healthcare and information and communication technology sectors are characterised by work-related stressors (e.g.

Outcome assessment of a complex mental health intervention in the workplace. Results from the MENTUPP pilot study.

Objective: Multicomponent interventions are recommendable to achieve the greatest mental health benefits, but are difficult to evaluate due to their complexity. Defining long-term outcomes, arising from a Theory of Change (ToC) and testing them in a pilot phase, is a useful approach to plan a comprehensive and meaningful evaluation later on. This article reports on the pilot results of an outcome evaluation of a complex mental health intervention and examines whether appropriate evaluation measures and indicators have been selected ahead of a clustered randomised control trial (cRCT).

Identification of Small Molecules Affecting the Secretion of Therapeutic Antibodies with the Retention Using Selective Hook (RUSH) System.

Unlocking cell secretion capacity is of paramount interest for the pharmaceutical industry focused on biologics. Here, we leveraged retention using a selective hook (RUSH) system for the identification of human osteosarcoma U2OS cell secretion modulators, through automated, high-throughput screening of small compound libraries. We created a U2OS cell line which co-expresses a variant of streptavidin addressed to the lumen-facing membrane of the endoplasmic reticulum (ER) and a recombinant anti-PD-L1 antibody.

A feasibility study of psychological first aid as a supportive intervention among police officers exposed to traumatic events.

Introduction: Police officers are often exposed to traumatic events, which can induce psychological distress and increase the risk of developing post-traumatic stress injuries. To date, little is known about support and prevention of traumatic events in police organizations. Psychological first aid (PFA) has been promoted as a promising solution to prevent psychological distress following exposure to a traumatic event.

Transcriptomic and proteomic studies suggest the establishment of advanced zonation-like profiles in human-induced pluripotent stem cell-derived liver sinusoidal endothelial cells and carboxypeptidase M-positive liver progenitor cells cocultured in a fluidic microenvironment.

Aim: Hepatic zonation is a physiological feature of the liver, known to be key in the regulation of the metabolism of nutrients and xenobiotics and the biotransformation of numerous substances. However, the reproduction of this phenomenon remains challenging in vitro as only part of the processes involved in the orchestration and maintenance of zonation are fully understood. The recent advances in organ-on-chip technologies, which allow for the integration of multicellular 3D tissues in a dynamic microenvironment, could offer solutions for the reproduction of zonation within a single culture vessel.

Preliminary inter-port study of the quality of environments using physiological responses of invertebrates exposed to chronic trace element and organic contamination in Corsica (Mediterranean Sea).

Port areas are socio-ecosystems impacted by chronic mixture pollution. Some marine species benefit from living there and may be studied to define the ecological state of such environments. In this study, the risks of chronic chemical contamination and its consequences on three marine molluscs were evaluated in North Corsica (France) port areas.

On the possibility of decolonising planetary health: exploring new geographies for collaboration.

Decolonial planetary health aspires to centre the diversity and importance of Indigenous thought and stewardship. In this Viewpoint, we explore research in planetary health across holistic worldviews and western scientific approaches. We base our examination of decolonising interventions in planetary health by exploring how global trajectories play out in British Columbia, Canada.