Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study.

BACKGROUND: Micro- and nanoplastics (MNPs) are emerging pollutants of concern with ubiquitous presence in global ecosystems. MNPs pose potential implications for human health; however, the health impacts of MNP exposures are not yet understood. Recent evidence suggests that MNPs can cross the placental barrier, underlying the urgent need to understand their impact on reproductive health and development. OBJECTIVE: The Actionable eUropean ROadmap for early-life health Risk Assessment of micro- and nanoplastics (AURORA) project will investigate MNP exposures and their biological and health effects during pregnancy and early life, which are critical periods due to heightened vulnerability to environmental stressors. The AURORA project will enhance exposure assessment capabilities for measuring MNPs, MNP-associated chemicals, and plastic additives in human tissues, including placenta and blood. METHODS: In this interdisciplinary project, we will advance methods for in-depth characterization and scalable chemical analytical strategies, enabling high-resolution and large-scale toxicological, exposure assessment, and epidemiological studies. The AURORA project performs observational studies to investigate determinants and health impacts of MNPs by including 800 mother-child pairs from 2 existing birth cohorts and 110 women of reproductive age from a newly established cohort. This will be complemented by toxicological studies using a tiered-testing approach and epidemiological investigations to evaluate associations between maternal and prenatal MNP exposures and health perturbations, such as placental function, immune-inflammatory responses, oxidative stress, accelerated aging, endocrine disruption, and child growth and development. The ultimate goal of the AURORA project is to create an MNP risk assessment framework and identify the remaining knowledge gaps and priorities needed to comprehensively assess the impact of MNPs on early-life health. RESULTS: In the first 3 years of this 5-year project (2021-2026), progress was made toward all objectives. This includes completion of recruitment and data collection for new and existing cohorts, development of analytical methodological protocols, and initiation of the toxicological tiered assessments. As of September 2024, data analysis is ongoing and results are expected to be published starting in 2025. CONCLUSIONS: As plastic pollution increases globally, it is imperative to understand the impact of MNPs on human health, particularly during vulnerable developmental stages such as early life. The contributions of the AURORA project will inform future risk assessment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/63176.

Time-varying exposure to food retailers and cardiovascular disease hospitalization and mortality in the netherlands: a nationwide prospective cohort study.

BACKGROUND: Very few studies to date investigated the prospective association of changes in exposure to the food environment with cardiovascular disease (CVD) risk. We aim to explore if time-varying exposure to the food environment was associated with hospitalization and mortality due to total and specific types of CVD in The Netherlands. METHODS: In this prospective cohort study, 4,641,435 Dutch adults aged 35 + years who did not change residence in 2002-2018 were identified through registry data. Exposure to the food environment was defined as time-varying Food Environment Healthiness Index (FEHI) scores (range: - 5 to 5) and time-varying kernel density of specific food retailers (e.g., fast food outlets, supermarkets) around the home location between 2004 and 2018. The main outcome measures were hospitalization and mortality due to overall CVD, stroke, HF, and CHD occurring between 2004 and 2020, based on hospital and death registries. RESULTS: In Cox regression models, each unit increase in the FEHI was associated with a lower hospitalization and mortality of CVD (hospitalization hazard ratio (HRh) = 0.90 (0.89 to 0.91), mortality hazard ratio (HRm) = 0.85 (0.82 to 0.89)), CHD (HRh = 0.88 (0.85 to 0.91), HRm = 0.80 (0.75 to 0.86)), stroke (HRh = 0.89 (0.84 to 0.93)), HRm = 0.89 (0.82 to 0.98)), and HF (HRh = 0.90 (0.84-0.96), HRm = 0.84 (0.76 to 0.92)). Increased density of local food shops, fast food outlets, supermarkets, and convenience stores and decreased density of food delivery outlets and restaurants were associated with a higher risk of CVD, CHD, stroke, and HF hospitalization and mortality. CONCLUSIONS: In this observational longitudinal study, changes in exposure to a healthier food environment over 14 years were associated with a risk reduction in CVD hospitalization and mortality, in particular in urbanized areas and for younger adults and those with higher incomes.

Reconceptualizing and Defining Exposomics within Environmental Health: Expanding the Scope of Health Research.

BACKGROUND: Exposomics, the study of the exposome, is flourishing, but the field is not well defined. The term "exposome" refers to all environmental influences and associated biological responses throughout the lifespan. However, this definition is very similar to that of the term "environment"-the external elements and conditions that surround and affect the life and development of an organism. Consequently, the exposome seems to be nothing more than a synonym for the environment, and exposomics a synonym for environmental research. As a result, some have rebranded their "standard" environmental health research with the neologistic exposome term, whereas others ignore or seek to abandon the seemingly redundant concept of the exposome. OBJECTIVES: We argue that exposomics needs to sharpen its mission focus to counteract this apparent redundancy. Exposomics should be defined as a research program in environmental health aimed at enabling a comprehensive and discovery-driven approach to identifying environmental determinants of human health. Similar to the aim of the Human Genome Project, exposomics aims to analyze the complete complexity of exposures and their corresponding biological responses. Exposomics' primary premise is that the existence of undiscovered, potentially interconnected, nongenetic (environmental) risk factors for health necessitates a comprehensive discovery-driven analysis approach. DISCUSSION: We argue that exposomics researchers should adopt our reconceptualization of exposomics and focus on the productiveness and integrity of their research program: its purpose and principles. We suggest that exposomics researchers should coordinate the writing of reviews that assess the program's productiveness and integrity, as well as provide a platform for exposomics researchers to define their vision for the field. https://doi.org/10.1289/EHP14509.

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

Socioeconomic Inequalities in the External Exposome in European Cohorts: The EXPANSE Project.

Socioeconomic inequalities in the exposome have been found to be complex and highly context-specific, but studies have not been conducted in large population-wide cohorts from multiple countries. This study aims to examine the external exposome, encompassing individual and environmental factors influencing health over the life course, and to perform dimension reduction to derive interpretable characterization of the external exposome for multicountry epidemiological studies. Analyzing data from over 25 million individuals across seven European countries including 12 administrative and traditional cohorts, we utilized domain-specific principal component analysis (PCA) to define the external exposome, focusing on air pollution, the built environment, and air temperature. We conducted linear regression to estimate the association between individual- and area-level socioeconomic position and each domain of the external exposome. Consistent exposure patterns were observed within countries, indicating the representativeness of traditional cohorts for air pollution and the built environment. However, cohorts with limited geographical coverage and Southern European countries displayed lower temperature variability, especially in the cold season, compared to Northern European countries and cohorts including a wide range of urban and rural areas. The individual- and area-level socioeconomic determinants (i.e., education, income, and unemployment rate) of the urban exposome exhibited significant variability across the European region, with area-level indicators showing stronger associations than individual variables. While the PCA approach facilitated common interpretations of the external exposome for air pollution and the built environment, it was less effective for air temperature. The diverse socioeconomic determinants suggest regional variations in environmental health inequities, emphasizing the need for targeted interventions across European countries.

Associations of night shift work with weight gain among female nurses in The Netherlands: results of a prospective cohort study.

OBJECTIVE: This study aimed to prospectively investigate associations of working night shifts with weight gain in the Nightingale Study, a large cohort of female nurses. METHODS: This study included 36 273 registered nurses, who completed questionnaires in 2011 and 2017. Cumulative number of nights, mean number of nights/month and consecutive number of nights/month in 2007-2011 were assessed. We used Poisson regression to estimate multivariable-adjusted incidence rate ratios (IRR) of >5% weight gain from 2011 to 2017 among all participants and assess risk of development of overweight/obesity (BMI≥25 kg/m2) among women with healthy baseline body mass index. The reference group consisted of women who never worked nights. RESULTS: Overall, working night shifts in 2007-2011 was associated with >5% weight gain [IRR 1.07, 95% confidence interval (CI) 1.01-1.13]. Associations differed by menopausal status in 2011, with an increased risk of gaining >5% weight limited to postmenopausal women who worked nights (IRR 1.23, 95% CI 1.10-1.38). Postmenopausal women had an increased risk of >5% weight gain when they worked on average ≥4 nights/month (4-5: IRR 1.29, 95% CI 1.09-1.52, ≥6: IRR 1.27, 95% CI 1.11-1.47) or ≥4 consecutive nights/month (IRR 1.37, 95% CI 1.19-1.58), compared to postmenopausal women who never worked nights. For postmenopausal women with healthy weight at baseline, night shift work was associated with an increased risk of overweight/obesity at follow-up (IRR 1.24, 95% CI 1.03-1.50). CONCLUSIONS: Working night shifts was associated with a slightly increased risk of weight gain and overweight/obesity development among women who were postmenopausal at study inclusion. Our findings emphasize the importance of health promotion to maintain a healthy weight among (postmenopausal) night workers.

Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (ptrend = .003) and cumulative exposure (ptrend = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL.

Spatiotemporal modeling of occupational particulate matter using personal low-cost sensor and indoor location tracking data.

Occupational exposure to particulate matter (PM) can result in multiple adverse health effects and should be minimized to protect workers' health. PM exposure at the workplace can be complex with many potential sources and fluctuations over time, making it difficult to control. Dynamic maps that visualize how PM is distributed throughout a workplace over time can help in gaining better insights into when and where exposure occurs. This study explored the use of spatiotemporal modeling followed by kriging for the development of dynamic PM concentration maps in an experimental setting and a workplace setting. Data was collected using personal low-cost PM sensors and an indoor location tracking system, mounted on a moving robot or worker. Maps were generated for an experimental study with one simulated robot worker and a workplace study with four workers. Cross-validation was performed to evaluate the performance and robustness of three types of spatiotemporal models (metric, separable, and summetric) and, as an additional external validation, model estimates were compared with measurements from sensors that were placed stationary in the laboratory or workplace. Spatiotemporal models and maps were generated for both the experimental and workplace studies, with average root mean squared error (RMSE) from 10-fold cross-validation ranging from 7-12 and 73-127 µg/m3, respectively. Workplace models were relatively more robust compared to the experimental study (relative SD ranging from 8-14% of the average RMSE vs. 27-56%, respectively), presumably due to the larger number of parallel measurements. Model estimates showed low to moderate fits compared to stationary sensor measurements (R2 ranging from 0.1-0.5), indicating maps should be interpreted with caution and only used indicatively. Together, these findings show the feasibility of using spatiotemporal modeling for generating dynamic concentration maps based on personal data. The described method could be applied for exposure characterization within comparable study designs or can be expanded further, for example by developing real-time, location-based worker feedback systems, as efficient tools to visualize and communicate exposure risks.

Evaluation of risk prediction models to select lung cancer screening participants in Europe: a prospective cohort consortium analysis.

BACKGROUND: Lung cancer risk prediction models might efficiently identify individuals who should be offered lung cancer screening. However, their performance has not been comprehensively evaluated in Europe. We aimed to externally validate and evaluate the performance of several risk prediction models that predict lung cancer incidence or mortality in prospective European cohorts. METHODS: We analysed 240 137 participants aged 45-80 years with a current or former smoking history from nine European countries in four prospective cohorts from the pooled database of the Lung Cancer Cohort Consortium: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland), the Nord-Trøndelag Health Study (Norway), CONSTANCES (France), and the European Prospective Investigation into Cancer and Nutrition (Denmark, Germany, Italy, Spain, Sweden, the Netherlands, and Norway). We evaluated ten lung cancer risk models, which comprised the Bach, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 model (PLCOm2012), the Lung Cancer Risk Assessment Tool (LCRAT), the Lung Cancer Death Risk Assessment Tool (LCDRAT), the Nord-Trøndelag Health Study (HUNT), the Optimized Early Warning Model for Lung Cancer Risk (OWL), the University College London-Death (UCLD), the University College London-Incidence (UCLI), the Liverpool Lung Project version 2 (LLP version 2), and the Liverpool Lung Project version 3 (LLP version 3) models. We quantified model calibration as the ratio of expected to observed cases or deaths and discrimination using the area under the receiver operating characteristic curve (AUC). For each model, we also identified risk thresholds that would screen the same number of individuals as each of the US Preventive Services Task Force 2021 (USPSTF-2021), the US Preventive Services Task Force 2013 (USPSTF-2013), and the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) criteria. FINDINGS: Among the participants, 1734 lung cancer cases and 1072 lung cancer deaths occurred within five years of enrolment. Most models had reasonable calibration in most countries, although the LLP version 2 overpredicted risk by more than 50% in eight countries (expected to observed ≥1·50). The PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI models showed similar discrimination in most countries, with AUCs ranging from 0·68 (95% CI 0·59-0·77) to 0·83 (0·78-0·89), whereas the LLP version 2 and LLP version 3 showed lower discrimination, with AUCs ranging from 0·64 (95% CI 0·57-0·72) to 0·78 (0·74-0·83). When pooling data from all countries (but excluding the HUNT cohort), 33·9% (73 313 of 216 387) of individuals were eligible by USPSTF-2021 criteria, which included 74·8% (1185) of lung cancers and 76·3% (730) of lung cancer deaths occurring over 5 years. Fewer individuals were selected by USPSTF-2013 and NELSON criteria. After applying thresholds to select a population of equal size to USPSTF-2021, the PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI, models identified 77·6%-79·1% of future cases, although they selected slightly older individuals compared with USPSTF-2021 criteria. Results were similar for USPSTF-2013 and NELSON. INTERPRETATION: Several lung cancer risk prediction models showed good performance in European countries and might improve the efficiency of lung cancer screening if used in place of categorical eligibility criteria. FUNDING: US National Cancer Institute, l'Institut National du Cancer, Cancer Research UK.

Expanded PAH analysis of household air pollution in a rural region of China with high lung cancer incidence.

The domestic combustion of locally sourced smoky (bituminous) coal in Xuanwei and Fuyuan counties, China, is responsible for some of the highest lung cancer rates in the world. Recent research has pointed to methylated PAHs (mPAHs), particularly 5-methylchrysene (5MC), within coal combustion products as a driving factor. Here we describe measurements of mPAHs in Xuanwei and Fuyuan derived from controlled burnings (i.e., water boiling tests, WBT, n = 27) representing exposures during stove use, and an exposure assessment (EA) study (n = 116) representing 24 h weighted exposures. Using smoky coal has led to significantly higher concentrations of known and likely human carcinogens than using smokeless coal, including 5MC (3.7 ng/m3 vs. 1.0 ng/m3 for EA samples and 100.8 ng/m3 vs. 2.2 ng/m3 for WBT samples), benzo[a]pyrene (38.0 ng/m3 vs. 7.9 ng/m3 for EA samples and 455.3 ng/m3 vs. 12.0 ng/m3 for WBT samples) and 7,12-dimethylbenz[a]anthracene (1.9 ng/m3 vs. 0.2 ng/m3 for EA samples and 47.7 ng/m3 vs. 0.6 ng/m3 for WBT samples). Mixed effect models for both EA samples and WBT samples revealed clear variation in mPAHs concentrations depending on smoky coal source while stove ventilation was consistently found to reduce measured concentrations (by up to nine fold and 65 fold for EA and WBT samples respectively when using smoky coal). Fuel type had a larger influence on mPAHs concentrations than stove type. These findings indicate that users of smoky coal experience exposure to many PAHs, including known and suspected human carcinogens (especially during cooking activities), many of which are not routinely tested for. Collectively, this provides insights into the potential etiologies of lung cancer in the region and further highlights the importance of targeting clean fuel transitions and stove refinements as the final goal for reducing household air pollution and its associated health risks.

Reduced ovarian cholesterol and steroid biosynthesis along with increased inflammation are associated with high DEHP metabolite levels in human ovarian follicular fluids.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) is known to have endocrine-disrupting properties mediated by its many metabolites that form upon exposure in biological systems. In a previous study, we reported an inverse association between DEHP metabolites in the human ovarian follicular fluid (FF) and the responsiveness of the follicles to controlled ovarian stimulation during in vitro fertilization (IVF) treatments. Here, we explored this association further through molecular analysis of the ovarian FF samples. Ninety-six IVF patients from Swedish (N = 48) and Estonian (N = 48) infertility clinics were selected from the previous cohort (N = 333) based on the molar sum of DEHP metabolites in their FF samples to arrive at "high" (mean 7.7 ± SD 2.3 nM, N = 48) and "low" (0.8 ± 0.4 nM, N = 48) exposure groups. Extracellular miRNA levels and concentrations of 15 steroid hormones were measured across FF samples. In addition, FF somatic cells, available for the Estonian patients, were used for RNA sequencing. Differential expression (DE) and interactions between miRNA and mRNA networks revealed that the expression levels of genes in the cholesterol biosynthesis and steroidogenesis pathways were significantly decreased in the high compared to the low DEHP group. In addition, the DE miRNAs were predicted to target key enzymes within these pathways (FDR < 0.05). A decreased 17-OH-progesterone to progesterone ratio was observed in the FF of the high DEHP group (p < 0.05). Additionally, the expression levels of genes associated with inflammatory processes were elevated in the FF somatic cells, and a computational cell-type deconvolution analysis suggested an increased immune cell infiltration into the high DEHP follicles (p < 0.05). In conclusion, elevated DEHP levels in FF were associated with a significantly altered follicular milieu within human ovaries, involving a pro-inflammatory environment and reduced cholesterol metabolism, including steroid synthesis. These results contribute to our understanding of the molecular mechanisms of female reprotoxic effects of DEHP.

Occupational benzene exposure and cancer risk among Chinese men: A report from the Shanghai Men's Health Study.

BACKGROUND: Benzene exposure has been associated with increased leukemia and other cancer risk; however, epidemiological evidence is inconsistent for the latter and confounding from smoking and alcohol was rarely adjusted. METHODS: We investigated associations of occupational benzene exposure and risk of leukemia, lymphoma, myeloma, lung, stomach, liver, and kidney cancers in a population-based cohort of 61,377 men ages 40-74. A job-exposure matrix, constructed by industrial hygienists specifically for the study population, was used to derive cumulative benzene exposure from all jobs held. Cox regressions were performed to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for benzene-cancer risk associations with adjustment for potential confounders. RESULTS: Over 15-years of follow-up, 1,145 lung, 656 stomach, 445 liver, 243 kidney cancer cases, 100 leukemia, 124 lymphoma, and 46 myeloma cases were identified. Benzene exposure >550mg/m3 was associated with increased leukemia (aHR=2.3, 95%CI=1.1-4.5), lung (aHR=1.2, 95%CI=1.0-1.6), and stomach (aHR=1.4, 95%CI=1.0-1.9) cancer risk; benzene-exposure was associated with early cancer diagnosis age. The benzene-leukemia and -stomach cancer associations followed a linear dose-response pattern (Plinear=0.016 and 0.023), whereas benzene-lung cancer association was evident at higher exposure levels (Pnon-linear=0.027). Alcohol consumption modified the benzene-leukemia association (HR=3.0, 95%CI=1.1-8.3 for drinkers, aHR=0.9, 95%CI=0.4-2.0 for non-drinkers, Pinteraction=0.047). CONCLUSIONS: Benzene exposure was associated with increased leukemia, stomach, and lung cancer risk. Alcohol consumption may modify the benzene-leukemia association, although estimates are imprecise. IMPACT: Our study provides additional evidence that benzene exposure increases cancer risk beyond leukemia, information important for policymakers to develop programs to mitigate cancer risk among benzene-exposed workers.

Chronotype in relation to shift work: A cohort study among 37,731 female nurses.

Chronotype may affect tolerance for circadian disruption induced by shift work. This study examines the association between chronotype, self-reported sleep timing, shift type preference, and sleep problems among nurses, and studies chronotype stability over time. The study included 37,731 Dutch female nurses who completed a baseline (2011) and follow-up questionnaire (2017), with information on shift work (e.g., job history, shift type preference [collected in 2017 only]), and sleep characteristics (e.g., chronotype, preferred sleep-wake time in a work-free period [collected in 2017 only], and sleep problems between working days according to Medical Outcomes Study-Sleep Problem Index II [MOS-SPI-II]). The association between chronotype and sleep timing was examined using (age-adjusted) linear regression. Associations between chronotype and shift type preference and sleep problems (MOS-SPI-II >30) were examined using ordered logistic and Poisson regression, respectively. With later chronotype, midsleep time increased (definite evening vs. intermediate types [reference]: ß = 55 min, 95% confidence interval [95% CI]: 54-55), the odds ratio (OR) for 1-point increase in preference for night (2.68; 95% CI: 2.48-2.90) and evening shifts increased (OR 2.20; 95% CI: 2.03-2.38), while the odds for day (OR 0.17; 95% CI: 0.16-0.18) and morning shifts (OR 0.22; 95% CI: 0.21-0.24) decreased. Intermediate chronotype was associated with fewer sleep problems (median MOS-SPI-II = 27.2, p < 0.01), compared with definite morning (28.9) and evening types (31.7). This study shows that chronotype is associated with sleep-wake times in a work-free period, shift type preference, and sleep problems in nurses. Future studies on the association of shift work-induced circadian disruption and health outcomes should therefore consider chronotype as effect-modifier.

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. METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson's disease, non-vascular dementia, Alzheimer's disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates. RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 µg/m3, respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson's disease and MS. Inverse associations were found for Alzheimer's disease. CONCLUSION: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer's disease.

Pre-diagnostic plasma advanced glycation end-products and soluble receptor for advanced glycation end-products and mortality in colorectal cancer patients.

Advanced glycation end-products (AGEs), formed endogenously or obtained exogenously from diet, may contribute to chronic inflammation, intracellular signaling alterations, and pathogenesis of several chronic diseases including colorectal cancer (CRC). However, the role of AGEs in CRC survival is less known. The associations of pre-diagnostic circulating AGEs and their soluble receptor (sRAGE) with CRC-specific and overall mortality were estimated using multivariable-adjusted Cox proportional hazards regression among 1369 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Concentrations of major plasma AGEs, Nε-[carboxy-methyl]lysine (CML), Nε-[carboxy-ethyl]lysine (CEL) and Nδ-[5-hydro-5-methyl-4-imidazolon-2-yl]-ornithine (MG-H1), were measured using ultra-performance liquid chromatography mass-spectrometry. sRAGE was assessed by enzyme-linked immunosorbent assay. Over a mean follow-up period of 96 months, 693 deaths occurred of which 541 were due to CRC. Individual and combined AGEs were not statistically significantly associated with CRC-specific or overall mortality. However, there was a possible interaction by sex for CEL (Pinteraction = .05). Participants with higher sRAGE had a higher risk of dying from CRC (HRQ5vs.Q1 = 1.67, 95% CI: 1.21-2.30, Ptrend = .02) or any cause (HRQ5vs.Q1 = 1.38, 95% CI: 1.05-1.83, Ptrend = .09). These associations tended to be stronger among cases with diabetes (Pinteraction = .03) and pre-diabetes (Pinteraction <.01) before CRC diagnosis. Pre-diagnostic AGEs were not associated with CRC-specific and overall mortality in individuals with CRC. However, a positive association was observed for sRAGE. Our findings may stimulate further research on the role of AGEs and sRAGE in survival among cancer patients with special emphasis on potential effect modifications by sex and diabetes.

Per- and polyfluoroalkyl substances (PFAS) exposure and thyroid cancer: Systematic review and meta-analysis.

Per- and polyfluoroalkyl substances (PFAS) exposure is a potential risk factor for thyroid cancer and may be a contributor to the increasing thyroid cancer incidence rates. A systematic review and meta-analysis was performed to summarize all human studies to date investigating the association between PFAS exposure and thyroid cancer. A search of the National Library of Medicine and National Institutes of Health PubMed and Scopus databases was done to identify relevant articles published in English through January 2024. Studies reporting the association between PFAS exposure and thyroid cancer using odds ratios (OR) were included in the meta-analysis with summary estimate calculated using a random effects model (n=5). Perfluorooctanoic acid (PFOA) was the most investigated PFAS. Results of the included studies varied, ranging from significant positive to significant negative associations with thyroid cancer incidence for different PFAS. Meta-analyses of PFOA, Perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS) were not significant. This comprehensive review of the current literature highlights the limited knowledge and inconsistent results of this association. Large longitudinal cohort studies with varying time between sample collection and thyroid cancer diagnosis are needed to better understand the role of PFAS exposure on thyroid carcinogenesis.

Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

Hyperlocal Air Pollution Mapping: A Scalable Transfer Learning LUR Approach for Mobile Monitoring.

Addressing the challenge of mapping hyperlocal air pollution in areas without local monitoring, we evaluated unsupervised transfer learning-based land-use regression (LUR) models developed using mobile monitoring data from other cities: CORrelation ALignment (Coral) and its inverse distance-weighted modification (IDW_Coral). These models mitigated domain shifts and transferred patterns learned from mobile air quality monitoring campaigns in Copenhagen and Rotterdam to estimate annual average air pollution levels in Amsterdam (50m road segments) without involving any Amsterdam measurements in model development. For nitrogen dioxide (NO2), IDW_Coral outperformed Copenhagen and Rotterdam LUR models directly applied to Amsterdam, achieving MAE (4.47 µg/m3) and RMSE (5.36 µg/m3) comparable to a locally fitted LUR model (AMS_SLR) developed using Amsterdam mobile measurements collected for 160 days. IDW_Coral yielded an R2 of 0.35, similar to that of the AMS_SLR based on 20 collection days, suggesting a minimum requirement of 20-day mobile monitoring to capture city-specific insights. For ultrafine particles (UFP), IDW_Coral's citywide predictions strongly correlated with previously published mixed-effect models fitted with 160-day Amsterdam measurements (Pearson correlation of 0.71 for UFP and 0.72 for NO2). IDW_Coral demands no direct measurements in the target area, showcasing its potential for large-scale applications and offering significant economic efficiencies in executing mobile monitoring campaigns.