Long-term exposure to air pollution and risk of dementia among older individuals of a Danish nationwide administrative cohort.

Background: Increasing evidence associates air pollution with dementia, but some pollutants and susceptible groups are understudied.

Methods: We followed all Danish residents aged ≥60 years as of 1-1-2000, without prior dementia, until 12-31-2018 for dementia incidence identified via hospital contact or prescription. We assessed annual mean levels of fine particulate matter (PM), nitrogen dioxide (NO), and black carbon (BC) in 2010 utilizing European-wide hybrid land-use regression models, at baseline (2000) residential addresses.

Comparison of air pollution mortality effect estimates using different long-term exposure assessment modelling methods.

Introduction: Epidemiological studies have used different approaches to assess long-term exposure to ambient air pollution. Little is known about how different exposure models affect health effect estimates in these studies. The aim of this study was to compare air pollution mortality effect estimates in an administrative cohort in the Netherlands based on different exposure assessment methods for black carbon (BC), nitrogen dioxide (NO), ultrafine particles (UFP), and particulate matter <2.

Comparison of air pollution exposure assessment methods and the association with children's respiratory health.

Introduction: Epidemiological studies of the associations of long-term exposure to outdoor air pollution with asthma onset and lung function in children have used different exposure assessment methods. Little is known about how these different methods affect the magnitude of the effect estimates. The aim of this study was to compare associations of long-term air pollution exposures, estimated with different exposure assessment methods, with asthma incidence and lung function.

Birth Outcomes among Infants Born between 2006 and 2018 after Maternal Exposure during Pregnancy to Ultrafine Particles from Aviation around a Large International Airport in the Netherlands.

Background: People who live near airports are exposed to higher concentrations of ultrafine particles (UFPs) from aviation. Pregnant women and their fetuses, in particular, are considered to be highly susceptible to environmental exposures.

Objective: Using existing national databases, we investigated associations between adverse birth outcomes and exposure to UFPs from aviation (UFP-aviation) at the residential address during pregnancy.

First-in-class ultralong-target-residence-time p38α inhibitors as a mitosis-targeted therapy for colorectal cancer.

Colorectal cancer (CRC) constitutes the second leading cause of cancer-related death worldwide and advanced CRCs are resistant to targeted therapies, chemotherapies and immunotherapies. p38α (Mapk14) has been suggested as a therapeutic target in CRC; however, available p38α inhibitors only allow for insufficient target inhibition. Here we describe a unique class of p38α inhibitors with ultralong target residence times (designated ULTR-p38i) that robustly inhibit p38α downstream signaling and induce distinct biological phenotypes.

Air pollution exposure and mortality from neurodegenerative diseases in the Netherlands: A population-based cohort study.

Background: Long-term exposure to ambient air pollution has been linked with all-cause mortality and cardiovascular and respiratory diseases. Suggestive associations between ambient air pollutants and neurodegeneration have also been reported, but due to the small effect and relatively rare outcomes evidence is yet inconclusive. Our aim was to investigate the associations between long-term air pollution exposure and mortality from neurodegenerative diseases.

Beyond the Runway: Respiratory health effects of ultrafine particles from aviation in children.

Aviation has been shown to cause high particle number concentrations (PNC) in areas surrounding major airports. Particle size distribution and composition differ from motorized traffic. The objective was to study short-term effects of aviation-related UFP on respiratory health in children.

Long-Term Exposure to Low-Level and Mortality: Investigation of Heterogeneity by Harmonizing Analyses in Large Cohort Studies in Canada, United States, and Europe.

Background: Studies across the globe generally reported increased mortality risks associated with particulate matter with aerodynamic diameter () exposure with large heterogeneity in the magnitude of reported associations and the shape of concentration-response functions (CRFs). We aimed to evaluate the impact of key study design factors (including confounders, applied exposure model, population age, and outcome definition) on effect estimates by harmonizing analyses on three previously published large studies in Canada [Mortality-Air Pollution Associations in Low Exposure Environments (MAPLE), 1991-2016], the United States (Medicare, 2000-2016), and Europe [Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), 2000-2016] as much as possible.

Methods: We harmonized the study populations to individuals years of age, applied the same satellite-derived exposure estimates, and selected the same sets of potential confounders and the same outcome.

Putative Cancer Stem Cell Markers are Frequently Expressed by Melanoma Cells and but are also Present in Benign Differentiated Cells.

Background: Currently, there remains an incomplete view of cancer stem cells (CSCs) in solid tumours.

Methods: We studied a panel of putative CSC surface markers (ALDH1A1, ABCG2, CD44v7/8, CD44v10, CD133, CD271, and Nestin) in 40 established melanoma cell lines and four early-passage melanoma strains by flow cytometry. We additionally examined 40 formalin-fixed paraffin-embedded melanoma tissues using immunofluorescence microscopy.

Protocol for establishing a coculture with fibroblasts and colorectal cancer organoids.

The tumor microenvironment is essential for mediating drug resistance and tumor progression. Here, we present a coculture system, which enables drug testing of colorectal cancer organoids and fibroblasts without additional matrix components such as Matrigel or basement membrane extracts. First, we describe steps to use a readout for high-throughput drug testing using a luminescence-based viability assay.

Exploring associations between residential exposure to pesticides and birth outcomes using the Dutch birth registry.

Background: Maternal occupational exposure to pesticides has been linked to adverse birth outcomes but associations with residential pesticide exposures are inconclusive.

Objectives: To explore associations between residential exposure to specific pesticides and birth outcomes using individual level exposure and pregnancy/birth data.

Methods: From all 2009-2013 singleton births in the Dutch birth registry, we selected mothers > 16 years old living in non-urban areas, who had complete address history and changed addresses at most once during pregnancy (N = 339,947).

Predicting self-perceived general health status using machine learning: an external exposome study.

Background: Self-perceived general health (SPGH) is a general health indicator commonly used in epidemiological research and is associated with a wide range of exposures from different domains. However, most studies on SPGH only investigated a limited set of exposures and did not take the entire external exposome into account. We aimed to develop predictive models for SPGH based on exposome datasets using machine learning techniques and identify the most important predictors of poor SPGH status.

Long-term exposure to ultrafine particles and natural and cause-specific mortality.

Background: Health implications of long-term exposure to ubiquitously present ultrafine particles (UFP) are uncertain. The aim of this study was to investigate the associations between long-term UFP exposure and natural and cause-specific mortality (including cardiovascular disease (CVD), respiratory disease, and lung cancer) in the Netherlands.

Methods: A Dutch national cohort of 10.

Association between exposure to multiple air pollutants, transportation noise and cause-specific mortality in adults in Switzerland.

Background: Long-term exposure to air pollution and noise is detrimental to health; but studies that evaluated both remain limited. This study explores associations with natural and cause-specific mortality for a range of air pollutants and transportation noise.

Methods: Over 4 million adults in Switzerland were followed from 2000 to 2014.

Comparison of traditional Cox regression and causal modeling to investigate the association between long-term air pollution exposure and natural-cause mortality within European cohorts.

Most studies investigating the health effects of long-term exposure to air pollution used traditional regression models, although causal inference approaches have been proposed as alternative. However, few studies have applied causal models and comparisons with traditional methods are sparse. We therefore compared the associations between natural-cause mortality and exposure to fine particulate matter (PM) and nitrogen dioxide (NO) using traditional Cox and causal models in a large multicenter cohort setting.

Mortality and Morbidity Effects of Long-Term Exposure to Low-Level PM, BC, NO, and O: An Analysis of European Cohorts in the ELAPSE Project.

Introduction: Epidemiological cohort studies have consistently found associations between long-term exposure to outdoor air pollution and a range of morbidity and mortality endpoints. Recent evaluations by the World Health Organization and the Global Burden of Disease study have suggested that these associations may be nonlinear and may persist at very low concentrations. Studies conducted in North America in particular have suggested that associations with mortality persisted at concentrations of particulate matter with an aerodynamic diameter of less than 2.

Using random forest to identify longitudinal predictors of health in a 30-year cohort study.

Due to the wealth of exposome data from longitudinal cohort studies that is currently available, the need for methods to adequately analyze these data is growing. We propose an approach in which machine learning is used to identify longitudinal exposome-related predictors of health, and illustrate its potential through an application. Our application involves studying the relation between exposome and self-perceived health based on the 30-year running Doetinchem Cohort Study.

Long-term exposure to air pollution and mortality in a Danish nationwide administrative cohort study: Beyond mortality from cardiopulmonary disease and lung cancer.

Background: The association between long-term exposure to air pollution and mortality from cardiorespiratory diseases is well established, yet the evidence for other diseases remains limited.

Objectives: To examine the associations of long-term exposure to air pollution with mortality from diabetes, dementia, psychiatric disorders, chronic kidney disease (CKD), asthma, acute lower respiratory infection (ALRI), as well as mortality from all-natural and cardiorespiratory causes in the Danish nationwide administrative cohort.

Methods: We followed all residents aged ≥ 30 years (3,083,227) in Denmark from 1 January 2000 until 31 December 2017.

Green space, air pollution, traffic noise and mental wellbeing throughout adolescence: Findings from the PIAMA study.

Background: Green space, air pollution and traffic noise exposure may be associated with mental health in adolescents. We assessed the associations of long-term exposure to residential green space, ambient air pollution and traffic noise with mental wellbeing from age 11 to 20 years.

Methods: We included 3059 participants of the Dutch PIAMA birth cohort who completed the five-item Mental Health Inventory (MHI-5) at ages 11, 14, 17 and/or 20 years.

Triple Targeting of HER Receptors Overcomes Heregulin-mediated Resistance to EGFR Blockade in Colorectal Cancer.

Current treatment options for patients with advanced colorectal cancers include anti-EGFR/HER1 therapy with the blocking antibody cetuximab. Although a subset of patients with KRAS WT disease initially respond to the treatment, resistance develops in almost all cases. Relapse has been associated with the production of the ligand heregulin (HRG) and/or compensatory signaling involving the receptor tyrosine kinases HER2 and HER3.

Residential proximity to livestock animals and mortality from respiratory diseases in The Netherlands: A prospective census-based cohort study.

Background: There is increasing evidence of associations between residential proximity to livestock farms and respiratory morbidity, but less is known about potential effects on respiratory mortality among residents.

Objectives: We aimed to assess potential associations between respiratory mortality and residential proximity to (intensive) livestock farming.

Methods: In DUELS, a national census-based cohort, we selected all inhabitants from rural and semi-urban areas of the Netherlands, aged ≥30 years and living at the same address for five years up to baseline (2004).