A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation.

Immunity that controls parasitemia and inflammation during Plasmodium falciparum (Pf) malaria can be acquired with repeated infections. A limited understanding of this complex immune response impedes the development of vaccines and adjunctive therapies. We conducted a prospective systems biology study of children who differed in their ability to control parasitemia and fever following Pf infection. By integrating whole-blood transcriptomics, flow-cytometric analysis, and plasma cytokine and antibody profiles, we demonstrate that a pre-infection signature of B cell enrichment, upregulation of T helper type 1 (Th1) and Th2 cell-associated pathways, including interferon responses, and p53 activation associated with control of malarial fever and coordinated with Pf-specific immunoglobulin G (IgG) and Fc receptor activation to control parasitemia. Our hypothesis-generating approach identified host molecules that may contribute to differential clinical outcomes during Pf infection. As a proof of concept, we have shown that enhanced p53 expression in monocytes attenuated Plasmodium-induced inflammation and predicted protection from fever.

Detection and Clearance of Type-Specific and Phylogenetically Related Genital Human Papillomavirus Infections in Young Women in New Heterosexual Relationships.

BACKGROUND: Understanding the natural history of human papillomavirus (HPV) infections is essential to cervical cancer prevention planning. We estimated HPV type-specific infection detection and clearance in young women. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) study is a prospective cohort of 502 college-age women who recently initiated a heterosexual relationship. We tested vaginal samples collected at 6 clinical visits over 24 months for 36 HPV types. Using rates and Kaplan-Meier analysis, we estimated time-to-event statistics with 95% confidence intervals (CIs) for detection of incident infections and clearance of incident and present-at-baseline infections (separately). We conducted analyses at the woman- and HPV-levels, with HPV types grouped by phylogenetic relatedness. RESULTS: By 24 months, we detected incident infections in 40.4% (CI, 33.4%-48.4%) of women. Incident subgenus 1 (43.4; CI, 33.6-56.4), 2 (47.1; CI, 39.9-55.5), and 3 (46.6; CI, 37.7-57.7) infections cleared at similar rates per 1000 infection-months. We observed similar homogeny in HPV-level clearance rates among present-at-baseline infections. CONCLUSIONS: Our analyses provide type-specific infection natural history estimates for cervical cancer prevention planning. HPV-level analyses did not clearly indicate that high oncogenic risk subgenus 2 infections persist longer than their low oncogenic risk subgenera 1 and 3 counterparts.

Household Transmission Dynamics of Asymptomatic SARS-CoV-2-Infected Children: A Multinational, Controlled Case-Ascertained Prospective Study.

BACKGROUND: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described. METHODS: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up. RESULTS: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC. CONCLUSIONS: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC.

Effectiveness of the 2023-2024 Formulation of the COVID-19 Messenger RNA Vaccine.

BACKGROUND: The purpose of this study was to evaluate whether the 2023-2024 formulation of the coronavirus disease 2019 (COVID-19) messenger RNA vaccine protects against COVID-19. METHODS: Cleveland Clinic employees when the 2023-2024 formulation of the COVID-19 messenger RNA vaccine became available to employees were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. RESULTS: Among 48 210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (hazard ratio = .58; 95% confidence interval [CI] = .49-.68; P < .001), and lower risk but one that did not reach statistical significance after (hazard ratio = .81; 95% CI = .65-1.01; P = .06). Estimated vaccine effectiveness was 42% (95% CI = 32-51) before the JN.1 lineage became dominant, and 19% (95% CI = -1-35) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage and increased with the number of vaccine doses previously received. CONCLUSIONS: The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Perturbations in the blood metabolome up to a decade before prostate cancer diagnosis in 4387 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition.

Measuring pre-diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with prostate cancer risk. Metabolites were measured by liquid chromatography-mass spectrometry. Multivariable-adjusted conditional logistic regression was used to estimate the odds ratio per standard deviation increase in log metabolite concentration and metabolite patterns (OR1SD) for prostate cancer overall, and for advanced, high-grade, aggressive. We corrected for multiple testing using the Benjamini-Hochberg method. Overall, there were no associations between specific metabolites or metabolite patterns and overall, aggressive, or high-grade prostate cancer that passed the multiple testing threshold (padj <0.05). Six phosphatidylcholines (PCs) were inversely associated with advanced prostate cancer diagnosed at or within 10 years of blood collection. metabolite patterns 1 (64 PCs and three hydroxysphingomyelins) and 2 (two acylcarnitines, glutamate, ornithine, and taurine) were also inversely associated with advanced prostate cancer; when stratified by follow-up time, these associations were observed for diagnoses at or within 10 years of recruitment (OR1SD 0.80, 95% CI 0.66-0.96 and 0.76, 0.59-0.97, respectively) but were weaker after longer follow-up (0.95, 0.82-1.10 and 0.85, 0.67-1.06). Pattern 3 (8 lyso PCs) was associated with prostate cancer death (0.82, 0.68-0.98). Our results suggest that the plasma metabolite profile changes in response to the presence of prostate cancer up to a decade before detection of advanced-stage disease.

The Puerto Rico Young Adults' Stress, Contextual, Behavioral & Cardiometabolic Risk (PR-OUTLOOK) Study: Design and Methods.

The Puerto Rico (PR) Young Adults' Stress, Contextual, Behavioral & Cardiometabolic Risk Study (PR-OUTLOOK) is investigating overall and component-specific cardiovascular health (CVH) and cardiovascular disease (CVD) risk factors in a sample of young (age 18-29) Puerto Rican adults in PR (target n=3,000) and examining relationships between individual-, family/social- and neighborhood-level stress and resilience factors and CVH and CVD risk factors. The study is conducting standardized measurements of CVH and CVD risk factors and demographic, behavioral, psychosocial, neighborhood, and contextual variables and establishing a biorepository of blood, saliva, urine, stool, and hair samples. The assessment methods are aligned with other National Heart, Lung, and Blood Institute funded studies: the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) of adults 30-75 years, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the Boston Puerto Rican Health Study (BPRHS), and the Coronary Artery Risk Development in Young Adults (CARDIA). PR-OUTLOOK data and its biorepository will facilitate future longitudinal studies of the temporality of associations between stress and resilient factors and CVH and CVD risk factors among young Puerto Ricans, with remarkable potential for advancing the scientific understanding of these conditions in a high-risk but understudied young population.

Characterization and trajectories of hematological parameters prior to severe COVID-19 based on a large-scale prospective health checkup cohort in western China: a longitudinal study of 13-year follow-up.

BACKGROUND: The relaxation of the "zero-COVID" policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19. METHODS: Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells. RESULTS: A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066-18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046-1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341-0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009-6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P < 0.05). CONCLUSIONS: Our findings might help decision-makers and clinicians to classify different risk groups of population due to outbreaks including COVID-19. They could not only optimize the allocation of medical resources, but also help them be more proactive instead of reactive to long COVID-19 or even other outbreaks in the future.

Sleep and liver function biomarkers in relation to risk of incident liver cancer: a nationwide prospective cohort study.

BACKGROUND: To assess the largely undetermined separate and joint effects of sleep and liver function biomarkers on liver cancer. METHODS: Data of 356,894 participants without cancer at baseline in the UK Biobank were analyzed. Sleep score was evaluated using five sleep traits (sleep duration, chronotype, insomnia, snoring, and excessive daytime sleepiness) and dichotomized into healthy or unhealthy sleep. Circulating liver function biomarkers were measured. Cox proportional hazard model was performed to investigate the independent and joint associations of sleep and liver function biomarkers with liver cancer incidence. RESULTS: After a median follow-up time of 13.1 years, 394 cases of incident liver cancer were documented. The multivariable-adjusted hazard ratio (HR) for liver cancer was 1.46 (95% confidence interval: 1.15-1.85) associated with unhealthy sleep (vs. healthy sleep), and was 1.17 (1.15-1.20), 1.20 (1.18-1.22), 1.69 (1.47-1.93), 1.06 (1.06-1.07), 1.08 (1.07-1.09), 1.81 (1.37-2.39), or 0.29 (0.18-0.46) associated with each 10-unit increase in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total protein (TP), or albumin (ALB), respectively. Individuals with unhealthy sleep and high (≥ median) ALT, AST, TBIL, GGT, ALP, or TP or low (< median) ALB level had the highest HR of 3.65 (2.43-5.48), 4.03 (2.69-6.03), 1.97 (1.40-2.77), 4.69 (2.98-7.37), 2.51 (1.75-3.59), 2.09 (1.51-2.89), or 2.22 (1.55-3.17) for liver cancer, respectively. Significant additive interaction of unhealthy sleep with high TP level on liver cancer was observed with relative excess risk due to an interaction of 0.80 (0.19-1.41). CONCLUSIONS: Unhealthy sleep was associated with an increased risk of liver cancer, especially in participants with lower ALB levels or higher levels of ALT, AST, TBIL, GGT, ALP, or particularly TP.

Trait impulsivity is associated with an increased risk of type 2 diabetes incidence in adults over 8 years of follow-up: results from the NutriNet-Santé cohort.

BACKGROUND: Type 2 diabetes is one of the most prevalent and preventable diseases worldwide and impulsivity, a psychological trait characterized by making quick decisions without forethought, has been suggested as a key feature for health-related conditions. However, there have been no studies examining the relationships between impulsivity and the incidence of type 2 diabetes and our aim was to assess the prospective association between trait impulsivity and the risk of developing type 2 diabetes. METHODS: A prospective observational study design was conducted between May 2014 and February 2023 within the NutriNet-Santé cohort. A web-based platform was used to collect data from the French adult population, with voluntary enrollment and participation. Of the 157,591 adults (≥ 18 years old) participating in the NutriNet-Santé study when impulsivity was assessed, 109,214 participants were excluded due to prevalent type 1 or 2 diabetes or missing data for impulsivity or follow-up data for type 2 diabetes. Trait impulsivity, and the attention, motor, and non-planning subfactors, were assessed at baseline using the Barratt Impulsiveness Scale 11. Incident type 2 diabetes was ascertained through follow-up. Medical information was reviewed by NutriNet-Santé physician experts to ascertain incident diabetes cases based on the ICD-10. Cox regression models, using hazard ratios and 95% confidence intervals (HR [95% CI]), were performed to evaluate associations between impulsivity per 1 standard deviation increment and type 2 diabetes risk, adjusting by recognized confounders. RESULTS: Of the 48,377 individuals studied (women 77.6%; age at baseline = 50.6 year ± 14.5 years), 556 individuals developed type 2 diabetes over a median follow-up of 7.78 (IQR: 3.97-8.49) years. Baseline impulsivity was associated with an increased risk of type 2 diabetes incidence (HR = 1.10 [1.02, 1.20]). The motor impulsivity subfactor was positively associated with type 2 diabetes risk (HR = 1.14 [1.04, 1.24]), whereas no associations were found for attention and non-planning impulsivity subfactors. CONCLUSIONS: Trait impulsivity was associated with an increased type 2 diabetes risk, mainly driven by the motor impulsivity subfactor. If these results are replicated in other populations and settings, trait impulsivity may become an important psychological risk factor to be considered in the prevention of type 2 diabetes. COHORT REGISTRATION: Name of registry: The NutriNet-Santé Study. A Web-based Prospective Cohort Study of the Relationship Between Nutrition and Health and of Dietary Patterns and Nutritional Status Predictors. Cohort registration number: NCT03335644. Date of registration: October 11, 2017. URL: https://clinicaltrials.gov/ct2/show/NCT03335644.

Adulthood weight changes, body mass index in youth, genetic susceptibility and risk of atrial fibrillation: a population-based cohort study.

BACKGROUND: Epidemiological evidence on weight change and atrial fibrillation (AF) remains limited and inconsistent. Previous studies on body mass index (BMI) in youth and AF rarely considered subsequent BMI. This study aimed to assess the associations of AF with weight change and BMI in youth, as well as modified effect by genetic susceptibility of AF. METHODS: The study included 21,761 individuals (mean age 57.8 years) from the Malmö Diet and Cancer cohort. Weight information was obtained at three time points, including recalled weight at age 20 years, measured weight at baseline (middle adulthood), and reported weight at 5-year follow-up examination (late middle adulthood). A weighted genetic risk score of AF was created using 134 variants. RESULTS: During a median follow-up of 23.2 years, a total of 4038 participants developed AF. The association between weight change from early to middle adulthood and AF risk was modified by sex (Pinteraction = 0.004); weight loss was associated with a lower AF risk in females, but not in males. Conversely, weight gain was positively associated with AF risk in a linear manner in females, whereas increased AF risk appeared only when weight gain exceeded a threshold in males. Participants with weight gain of > 5 kg from middle to late middle adulthood had a 19% higher risk of AF relative to those with stable weight, whereas weight loss showed a null association. Compared to individuals with a lower BMI at age 20 years, those with a BMI above 25 kg/m2 had an increased risk of AF (HR = 1.14; 95% CI: 1.02-1.28), after controlling for baseline BMI; this association was more pronounced in males or those with a lower genetic risk of AF. CONCLUSIONS: Weight gain in middle adulthood was associated with higher AF risk. Weight loss from early to middle adulthood, but not from middle to late middle adulthood, was associated with a lower risk of AF only in females. Higher BMI in youth was associated with an increased risk of AF, particularly among males or those with a lower genetic risk of AF.

Air pollution and risk of 32 health conditions: outcome-wide analyses in a population-based prospective cohort in Southwest China.

BACKGROUND: Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions. METHODS: A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD. RESULTS: Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62-1.89), hypertensive diseases (1.49, 1.38-1.62), cardiac arrests (1.52, 1.30-1.77), arrhythmia (1.76, 1.44-2.15), cerebrovascular diseases (1.86, 1.65-2.10), stroke (1.77, 1.54-2.03), ischemic stroke (1.85, 1.61-2.12), atherosclerosis (1.77, 1.57-1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15-1.51), pneumonia (1.37, 1.16-1.61), inflammatory bowel diseases (1.34, 1.16-1.55), liver diseases (1.59, 1.43-1.77), type 2 diabetes (1.48, 1.26-1.73), lipoprotein metabolism disorders (2.20, 1.96-2.47), purine metabolism disorders (1.61, 1.38-1.88), anemia (1.29, 1.15-1.45), sleep disorders (1.54, 1.33-1.78), renal failure (1.44, 1.21-1.72), kidney stone (1.27, 1.13-1.43), osteoarthritis (2.18, 2.00-2.39), osteoporosis (1.36, 1.14-1.61). OM had max weights for joint effects of AP on many conditions. CONCLUSIONS: Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

Daytime napping and the risk of gastric cancer: the JACC Study.

BACKGROUND: Gastric cancer is a major cause of morbidity and mortality in Japan and worldwide. Emerging literature has suggested unfavorable health outcomes associated with daytime napping. Herein, we aimed to investigate the association between daytime napping and the risk of gastric cancer among Japanese people. METHODS: This prospective cohort study included 49,037 participants, aged 40-79 years, from the Japan Collaborative Cohort Study (JACC Study). Participants with positive cancer history and those who reported night or rotational shift work were excluded. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident gastric cancer among daytime nappers. RESULTS: Within 650,040 person-years (median = 13.7 years) of follow-up, 1,164 participants developed gastric cancer. Daytime napping was associated with the increased risk of gastric cancer in the multivariable-adjusted model: HR (95% CI) = 1.14 (1.01, 1.29). The excess risk did not significantly differ across sexes, age groups (<65 and ≥65 years), and employment status (employed and unemployed) (p-interactions > 0.40). However, sleep duration modified this effect: HRs (95% CIs) = 1.66 (1.23, 2.23) in sleep duration ≤6 h/night versus 1.06 (0.93, 1.21) in sleep duration >6 h/night (p-interaction = 0.006). CONCLUSION: Daytime napping was associated with increased gastric cancer risk, especially among those who reported short sleep duration.

Educational level and characteristics of invasive breast cancer: findings from a French prospective cohort.

PURPOSE: Breast cancer (BC) characteristics are known to influence patients survival. Social differences have been reported by previous studies for those characteristics but questions persist because of inconsistent conclusions. We aimed to investigate the impact of education on BC stage, grade, and hormone receptor (HR) status, while adjusting for potential confounders including a broad set of health behaviors, anthropometric measures, and reproductive factors. METHODS: In the French E3N cohort, 5236 women developed a primary invasive BC for which there was available information on stage, grade, and HR status. No multivariate analyses was performed for BC stage based on the lack of association in bivariate analyses. Odds ratios and confidence intervals were estimated using multinomial logistic regression models for BC grade or binomial logistic regression models for HR status of BC. RESULTS: Women with a lower education were diagnosed with higher grade BC compared to women with a higher education (1.32 [1.12; 1.57]). This association was slightly attenuated after adjustment for covariates independently and more strongly affected in the fully adjusted model (1.20 [0.99; 1.45]). A significant association was observed between lower education and HR- status of BC (1.20 [1.02; 1.42]) attenuated after adjustment for age at first childbirth (1.12 [0.95; 1.33]). CONCLUSION: In this cohort, education was associated with BC grade and HR status but not stage at diagnosis. The link between education and BC grade was not entirely explained by the different adjustments. A specific mechanism could be at play and deserves further investigations.

Association between the cumulative average triglyceride glucose-body mass index and cardiovascular disease incidence among the middle-aged and older population: a prospective nationwide cohort study in China.

BACKGROUND: Findings from earlier research have established that insulin resistance (IR) is implicated in atherosclerosis progression, representing a noteworthy risk factor for cardiovascular disease (CVD). Recently, the triglyceride glucose-body mass index (TyG-BMI) has been introduced as a straightforward and robust alternative indicator for early detection of IR. Nevertheless, there is a scarcity of studies that have examined the capability of TyG-BMI for predicting incident CVD. Consequently, the core objective of this study was to determine whether the cumulative average TyG-BMI correlated with CVD incidence. METHODS: All data was sourced from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the cumulative average TyG-BMI, determined by the average of TyG-BMI values for the baseline and follow-up investigations (Wave 1 in 2011, Wave 3 in 2015, respectively). The calculation of TyG-BMI involved a combination of triglyceride, fasting blood glucose, and body mass index. The primary outcome was incident CVD. Logistic regression analyses as well as restricted cubic spline (RCS) regression analyses were performed for examining the association between the cumulative average TyG-BMI and CVD incidence. RESULTS: In all, 5,418 participants were enrolled in our analysis, with 2,904 (53.6%) being female, and a mean (standard deviation, SD) age of 59.6 (8.8) years. The mean (SD) cumulative average TyG-BMI among all participants was 204.9 (35.7). Totally, during a 4-year follow-up, 543 (10.0%) participants developed CVD. The fully adjusted logistic regression analysis revealed a significant association between the cumulative average TyG-BMI and incident CVD [odds ratio (OR), 95% confidence interval (CI): 1.168, 1.040-1.310, per 1 SD increase]. The RCS regression analysis displayed a positive, linear association of the cumulative average TyG-BMI with CVD incidence (P for overall = 0.038, P for nonlinear = 0.436). CONCLUSIONS: Our study revealed a noteworthy correlation between the cumulative average TyG-BMI and incident CVD among the middle-aged and older population. The cumulative average TyG-BMI emerges as a valuable tool that may enhance the primary prevention and treatment of CVD.

Longitudinal cardiovascular health measured by life's essential 8 metrics with incident diabetes: A 13-year prospective cohort study.

AIMS: To investigate the associations of baseline and longitudinal cardiovascular health (CVH) measured by 'Life's Essential 8' (LE8) metrics with the risk of diabetes in Chinese people with normoglycaemia or prediabetes. MATERIALS AND METHODS: A total 86,149 participants without diabetes were enroled from the Kailuan study and were stratified by baseline glycaemic status (normoglycaemia or prediabetes). Cardiovascular health score ranged from 0 to 100 points was categorised into low (0-49), middle (50-79), and high (80-100) CVH status. Cox regressions were used to assess the associations of baseline and time-updated CVH status with incident diabetes in the overall cohort and across baseline glycaemic statuses. RESULTS: During a median follow-up of 12.94 (interquartile rage: 12.48-13.16) years, we identified 13,097 (15.20%) cases of incident diabetes. Baseline and time-updated high CVH status was associated with a lower risk of diabetes, the corresponding hazard ratio (HR) versus low CVH status was 0.27 (95% confidence interval [CI], 0.23-0.31) and 0.26 (95% CI, 0.23-0.30) in the overall cohort, respectively. Additionally, the effect of high CVH on diabetes was more prominent in participants with normoglycaemia than those with prediabetes (P < 0.0001), with an HR of 0.26 (95% CI, 0.22-0.31) versus 0.50 (95% CI, 0.41-0.62) for baseline CVH, and 0.25 (95% CI, 0.21-0.30) versus 0.39 (95% CI, 0.32-0.48) for time-updated CVH. CONCLUSIONS: Elevated baseline and longitudinal CVH score assessed by LE8 metrics is associated with a lower risk of subsequent diabetes, especially in normoglycaemic adults.

Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus.

BACKGROUND: Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D-metabolite pattern with a risk of progression to T2D among high-risk women with a history of gestational diabetes mellitus (GDM). METHODS: The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age-matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1-5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. RESULTS: The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR] = 23.1 [95% CI = 8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR = 2.7 per SD [95% CI = 1.9, 3.7], p < 0.0001). CONCLUSIONS: A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

Regular use of paracetamol and risk of liver cancer: a prospective cohort study.

BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. CONCLUSION: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.

APOE Genotype Modifies the Association between Midlife Adherence to the Planetary Healthy Diet and Cognitive Function in Later Life among Chinese Adults in Singapore.

BACKGROUND: It remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype. OBJECTIVES: We aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE ε4 allele could modify this association. METHODS: The study included 16,736 participants from the Singapore Chinese Health Study. The PHD score was calculated using data from a validated 165-item food frequency questionnaire at baseline (1993-1998), with higher scores indicating greater adherence to the PHD. Cognitive function was assessed by the Singapore-modified Mini-Mental State Examination at follow-up 3 visits (2014-2016). A subset of 9313 participants had APOE genotype data. Logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), with adjustment for potential confounders. RESULTS: We identified 2397 (14.3%) cases of poor cognitive function. In the total population, OR (95% CI) of poor cognitive function for each one-SD increment in the PHD score was 0.89 (0.85, 0.93). Carriers of APOE ε4 allele had increased risk of poor cognitive function (OR: 1.36, 95% CI: 1.15, 1.61). There was a significant interaction between the PHD score and the APOE ε4 allele (P-interaction = 0.042). Each one-SD increment in the PHD score was significantly associated with lower risk of poor cognitive function (OR: 0.89; 95% CI: 0.83, 0.96) in non-carriers of APOE ε4 allele, but not in APOE ε4 allele carriers (OR: 1.04, 95% CI: 0.89, 1.23). CONCLUSIONS: Midlife adherence to the PHD was associated with reduced risk of poor cognitive function in later life. However, this was not observed in carriers of APOE ε4 allele who had higher risk of poor cognitive function.

Length of Overnight Fasting and 6-year Weight Change in the Cancer Prevention Study-3.

BACKGROUND: Longer overnight fasting (ONF) is a potential strategy for weight control. Although promising, the evidence from large population-based studies is limited. OBJECTIVES: To examine the association of self-reported ONF duration with 3- and 6-y weight change in the American Cancer Society's Cancer Prevention Study-3 prospective cohort. METHODS: United States adult Cancer Prevention Study-3 participants completed a 24-h validated meal and snack timing and frequency grid (weekday and weekend) in 2015, from which weighted ONF hours were calculated. Participants reported body weight in 2015, 2018, and 2021. Three- and 6-y weight change (kg, and % body weight) were assessed. RESULTS: Among 104,420 mostly female (78.5%) participants aged 52.7 ± 9.5 (standard deviation) y followed for 6 y, a 1-h increase in ONF length was associated with a small but statistically significant reduction in weight gain over 3- and 6-y periods [multivariable-adjusted mean difference in % body weight = -0.02, 95% confidence interval (CI): -0.05, -0.00, P = 0.03 and -0.04, 95% CI: -0.07, -0.01, P < 0.01, respectively]. The mean difference of 6-y % reduction in weight gain was slightly greater among individuals with overweight (-0.05, 95% CI: -0.10, 0.00, P = 0.05) and obesity (-0.06, 95% CI: -0.12, 0.01, P = 0.08) compared with those with healthy body mass index (-0.03, 95% CI:-0.07, 0.01, P = 0.13) or underweight (0.16, 95% CI: -0.04, 0.36, P = 0.13, Pinteraction < 0.0001). Stronger associations were observed among those ≤55 y than 56+ (P < 0.001), and those with higher waist circumference (Pinteraction < 0.0001) but not by sex or earlier/later fasting period. CONCLUSIONS: Longer ONF was associated with slightly lower body weight in adult males and females over 6 y that was stronger among those with overweight or obesity, higher waist circumference, and those aged ≤55 y. The magnitude of weight change, although in the hypothesized direction, suggests that prolonged ONF may have modest impact on weight control over time.

Dietary Intake of (Poly)phenols and Risk of All-Cause and Cause-Specific Mortality in the Mexican Teachers' Cohort Study.

BACKGROUND: Observational studies have reported that total (poly)phenol intake is associated with a reduction in all-cause and cardiovascular mortality, but mainly from high-income countries, where (poly)phenol intake may differ from that of low- and middle-income countries. OBJECTIVES: Our objective was to evaluate the association between the intake of total, all classes, and subclasses of (poly)phenols and risk of all-cause and cause-specific mortality in a Mexican cohort. METHODS: We used data from the Mexican Teachers' Cohort, which included 95,313 adult females. After a median follow-up of 11.2 y, 1725 deaths were reported, including 674 from cancer and 282 from cardiovascular diseases. (Poly)phenol intake was estimated using a validated food frequency questionnaire and the Phenol-Explorer database. Multivariable Cox models were applied to estimate the association between (poly)phenol intake and all-cause mortality and competitive risk models for cause-specific mortality. RESULTS: Comparing extreme quartiles, total (poly)phenol intake was associated with lower risk of all-cause [hazard ratio (HR)Q4vs.Q1: 0.88; 95% CI: 0.76, 0.99; P-trend = 0.01] and cancer mortality (HRQ4vs.Q1: 0.81; 95% CI: 0.64, 0.99; P-trend = 0.02). Among (poly)phenol classes, phenolic acids, particularly hydroxycinnamic acids from coffee, showed an inverse association with all-cause (HRQ4vs.Q1: 0.79; 95% CI: 0.69, 0.91; P-trend = 0.002) and cancer mortality (HRQ4vs.Q1: 0.75; 95% CI: 0.61, 0.94; P-trend = 0.03). No associations were observed with flavonoids or with cardiovascular mortality. CONCLUSION: Our study suggests that high (poly)phenol intake, primarily consisting of phenolic acids such as hydroxycinnamic acids, may have a protective effect on overall and cancer mortality. Null associations for flavonoid intake might be due to the potential underestimation of their intake in this population.