Exposomics: a review of methodologies, applications, and future directions in molecular medicine.

The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.

Pro-inflammatory dietary pattern and the risk of female gout: sex-specific findings from three prospective cohort studies.

Objective: We aimed to determine whether a pro-inflammatory dietary pattern (mechanism-based diet) is associated with incident female gout among two large cohorts of US women.

Methods: We prospectively followed 79,104 women from Nurses' Health Study (NHS; 1984-2016) and 93,454 women from NHSII (1991-2017); 45,445 men from Health Professionals Follow-up Study (1986-2016) served as a comparison cohort. Validated food frequency questionnaires were used to calculate Empirical Dietary Inflammatory Pattern (EDIP; food-based index predictive of circulating inflammatory biomarkers) scores every 4-years.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

FABP4 as a therapeutic host target controlling SARS-CoV-2 infection.

Host metabolic fitness is a critical determinant of infectious disease outcomes. Obesity, aging, and other related metabolic disorders are recognized as high-risk disease modifiers for respiratory infections, including coronavirus infections, though the underlying mechanisms remain unknown. Our study highlights fatty acid-binding protein 4 (FABP4), a key regulator of metabolic dysfunction and inflammation, as a modulator of SARS-CoV-2 pathogenesis, correlating strongly with disease severity in COVID-19 patients.

Bundled measures for China's food system transformation reveal social and environmental co-benefits.

Food systems are essential for the achievement of the United Nations Sustainable Development Goals in China. Here, using an integrated assessment modelling framework that considers country-specific pathways and covers 18 indicators, we find that most social and environmental targets for the Chinese food system under current trends are not aligned with the United Nations Agenda 2030. We further quantify the impacts of multiple measures, revealing potential trade-offs in pursuing strategies aimed at public health, environmental sustainability and livelihood improvement in isolation.

From physical activity patterns to cognitive status: development and validation of novel digital biomarkers for cognitive assessment in older adults.

Background: This study aims to investigate the associations between signal-level physical activity (PA) features derived from wrist accelerometry data and cognitive status in older adults, and to evaluate their potential predictive value when combined with demographics.

Methods: We analyzed PA data from 3,363 older adults (NHATS: n = 747; NHANES: n = 2,616), with each participant contributing a complete 3-day continuous activity sequence. We extracted the most relevant PA features associated with cognitive function using feature engineering and recursive feature elimination.

Analysis of longitudinal social media for monitoring symptoms during a pandemic.

Objective: Current studies leveraging social media data for disease monitoring face challenges like noisy colloquial language and insufficient tracking of user disease progression in longitudinal data settings. This study aims to develop a pipeline for collecting, cleaning, and analyzing large-scale longitudinal social media data for disease monitoring, with a focus on COVID-19 pandemic.

Materials And Methods: This pipeline initiates by screening COVID-19 cases from tweets spanning February 1, 2020, to April 30, 2022.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Background: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions.

Objective: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality.

Methods: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others.

Deep imaging of LepR stromal cells in optically cleared murine bone hemisections.

Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR stromal cells, within optically cleared bone hemisections.

Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models.

Human challenge experiments could accelerate tuberculosis vaccine development. This requires a safe Mycobacterium tuberculosis (Mtb) strain that can both replicate in the host and be reliably cleared. Here we genetically engineered Mtb strains encoding up to three kill switches: two mycobacteriophage lysin operons negatively regulated by tetracycline and a degron domain-NadE fusion, which induces ClpC1-dependent degradation of the essential enzyme NadE, negatively regulated by trimethoprim.

TSLP acts on regulatory T cells to maintain their identity and limit allergic inflammation.

Thymic stromal lymphopoietin (TSLP) is a type I cytokine that promotes allergic responses and mediates type 2 immunity. A balance between effector T cells (T), which drive the immune response, and regulatory T cells (T), which suppress the response, is required for proper immune homeostasis. Here, we report that TSLP differentially acts on T versus T to balance type 2 immunity.

High-Density Lipoprotein Lipid and Protein Cargo and Cholesterol Efflux Capacity Before and After Bariatric Surgery.

Background: Cholesterol efflux capacity (CEC) of HDL (high-density lipoprotein) is inversely associated with incident cardiovascular events, independent of HDL cholesterol. Obesity is characterized by low HDL cholesterol and impaired HDL function, such as CEC. Bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), broadly leads to improved cardiovascular outcomes, but impacts on risk factors differ by procedure, with greater improvements in weight loss, blood pressure, and glycemic control after RYGB, but greater improvements in HDL cholesterol and CEC levels after SG.

Supramolecular gel with enhanced immunomodulatory effects presents a minimally invasive treatment strategy for eosinophilic chronic rhinosinusitis.

Background: Chronic rhinosinusitis (CRS) is an inflammatory disease characterized by persistent immune dysregulation, which presents considerable limitations in current medical therapy.

Objects: This study investigates a supramolecular gel (PSPD), which aims to minimize systemic adverse effects through local injection, provide long-lasting anti-inflammatory effects, and modulate the mucosal immune microenvironment.

Methods: The properties of PSPD were evaluated using rheological experiments.

Singapore's COVID-19 Genomic Surveillance Programme: Strategies and Insights From a Pandemic Year.

Background: During the COVID-19 pandemic, genomic surveillance was crucial for monitoring virus spread and identifying variants. Effective surveillance helped understand transmission dynamics. Singapore had success in combating COVID-19 through its surveillance programmes.

Using a two sample Mendelian randomization approach to explore the causal relationship between erectile dysfunction and lung function.

Background: Recently, some observational studies have suggested potential associations between erectile dysfunction (ED) and respiratory function. However, the underlying biological mechanisms and causal relationships between ED and lung function require further investigation. This study aimed to explore the causalities between ED and lung function traits.

Exploring autism spectrum disorder and co-occurring trait associations to elucidate multivariate genetic mechanisms and insights.

Background: Autism spectrum disorder (ASD) is a partially heritable neurodevelopmental trait, and people with ASD may also have other co-occurring trait such as ADHD, anxiety disorders, depression, mental health issues, learning difficulty, physical health traits and communication challenges. The concomitant development of ASD and other neurological traits is assumed to result from a complex interplay between genetics and the environment. However, only a limited number of studies have performed multivariate genome-wide association studies (GWAS) for ASD.

Cannabidiol for Scan-Related Anxiety in Women With Advanced Breast Cancer: A Randomized Clinical Trial.

Importance: Early evidence from studies outside of oncology has suggested that cannabidiol (CBD) may have anxiolytic effects without neuropsychiatric risks. An understanding of oral CBD in patients with cancer-related anxiety is urgently needed.

Objective: To determine whether a single 400-mg oral dose of a US Food and Drug Administration-approved CBD improves clinical anxiety in an oncologic population.

Associations of PFAS concentrations during pregnancy and midlife with bone health in midlife: Cross-sectional and prospective findings from Project Viva.

Background: PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown.

Methods: We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

The effect of chelation on bone Pb stores in Pb poisoned children.

Background: Lead exposure remains a key problem for children during development. One treatment for lead poisoning is chelation - a topic that remains controversial with varied results. Bone lead serves as a marker of total body burden of lead and encompasses between 60-90% of lead storage in children.