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Aim: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. Materials and Methods: A total of 294 815 participants without diabetes from the UK Biobank, including non‐smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. Results: During a median follow‐up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non‐smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend <.001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17–1.81) for more than 2 hours, 1.51 (1.21–1.87) for 1–2 hours, 1.58 (1.34–1.85) for 30–60 minutes, 1.86 (1.57–2.21) for 5–15 minutes and 2.01 (1.60–2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52–2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P‐interaction =.51). Conclusions: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D. [ABSTRACT FROM AUTHOR]

Aim: Women with diabetes are at higher risk of cardiovascular diseases (CVD) than men with diabetes; however, the sex difference in the association between the degree of risk factor control and the risk of CVD in patients with diabetes is unclear. Methods: In total, 17 260 participants diagnosed with diabetes from the UK Biobank were included and matched with 86 300 non‐diabetes controls based on age, sex and assessment centre. The main exposure was the number of risk factors within the target range, including glycated haemoglobin level <53 mol/mol (7%), blood pressure <140/90 mm/Hg, low‐density lipoprotein cholesterol <100 mg/dl, non‐current smoking and absence of microalbuminuria. Results: During a median follow‐up of 13.3 years, a total of 3338 incident CVD cases, including 2807 ischaemic heart disease and 793 strokes, were documented. A more stringent control of risk factors was significantly associated with a lower risk of incident CVD, and such an association was significantly stronger in women than men. Compared with non‐diabetes participants, the diabetes‐related risk of CVD appeared to be eliminated if more than three risk factors were well controlled among women and men with diabetes. Moreover, clinical biomarkers (e.g. glycated haemoglobin and blood pressure) showed greater relative importance than other factors in women, whereas socio‐economic and psychological factors (e.g. education and depression) exhibited similar relative importance to clinical biomarkers in men with diabetes. Conclusion: Our findings highlighted the importance of raising awareness of sex differences in the management of CVD risk factors among patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. Methods: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. Results: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41–0.62), 74% (HR 0.26, 95% CI 0.16–0.43) and 38% (HR 0.62, 95% CI 0.44–0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. Conclusions: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality. [ABSTRACT FROM AUTHOR]

Objective: To identify the causal role of sodium‐glucose cotransporter 2 (SGLT2) inhibition on three urological cancers. Methods: Six single nucleotide polymorphisms associated with the expression level of SLC5A2, a proxy for SGLT2 inhibition, from a recent publication were extracted. Three common urological cancers, including bladder cancer, prostate cancer and kidney cancer, were analysed. The main cohort of bladder cancer was derived from UK Biobank (1279 cases and 372,016 controls). The prostate cancer cohort was from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (79,148 cases and 61,106 controls). The kidney cancer phenotype was from the UK Biobank cohort of 463,010 individuals (1114 cases and 461,896 controls). Primary and sensitivity analysis were performed to validate the results. In vitro analysis was also incorporated to validate the Mendelian randomisation results. Results: In primary analysis, SGLT2 inhibition was associated with reduced risk of bladder cancer (OR: 0.98, 95% CI: 0.97–0.99) per unit lowering of HbA1c level. A protective association was also observed for prostate cancer with odds ratio = 0.31 (95% CI = 0.21–0.47). However, we did not discover a causal relationship between SGLT2 inhibition and kidney cancer (OR: 1.00, 95% CI: 0.99–1.00). Sensitivity analysis and in vitro validation did not support the causal role of SGLT2 inhibition in increasing cancer risk. Conclusions: We did not find any evidence that SGLT2 inhibition could increase the risk of the three cancers. Even in some analysis, SGLT2 inhibition tended to show protective effects on the three urological cancers. [ABSTRACT FROM AUTHOR]

Background: Obesity has been related to depression and adhering healthy lifestyle was beneficial to lower the risk of depression; however, little is known about the relationship between body composition and fat distribution with depression risk and the influence of body composition and fat distribution on the association of lifestyle and depression. Therefore, we aimed to investigate whether body composition and fat distribution were associated with the adverse events of depression and the relationship between lifestyle and depression. Methods: We included 330,131 participants without depression at baseline in the UK Biobank (mean age, 56.9 years; 53.83% females). The assessment of depression was sourced from health outcomes across self-report, primary care, hospital inpatient data, and death data. Body composition was determined by bioelectrical impedance. Seven lifestyles (no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, less sedentary behavior, healthy sleep pattern, and appropriate social connection) were used to generate a lifestyle score. Results: During a median of 11.7 years of follow-up, 7576 incident depression occurred. All the body composition measures were positively associated with depression risk, with the Hazard ratios (HR) for the uppermost tertile (T3) versus the lowest tertile (T1) ranging from 1.26 (95% CI: 1.15–1.39) for trunk fat-free mass (TFFM) to 1.78 (1.62–1.97) for leg fat percentage (LFP). In addition, we found significant interactions between fat mass-related indices, especially leg fat mass (LFM) (p = 1.65 × 10−9), and lifestyle score on the risk of depression, for which the beneficial associations of a healthy lifestyle with the risk of depression were more evident among participants with low body fat measurement. Conclusions: High levels of body composition measures were associated with an increased depression risk. Adverse body composition measures may weaken the link between a healthy lifestyle and a reduced risk of depression. [ABSTRACT FROM AUTHOR]

Aims To investigate the prospective associations of the loneliness and social isolation scales with cardiovascular disease (CVD) risk in diabetes patients and compare the relative importance of loneliness and social isolation with traditional risk factors. Also, the interactions of loneliness or isolation with the degree of risk factor control in relation to CVD risk were evaluated. Methods and results A total of 18 509 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess loneliness and isolation levels, respectively. The degree of risk factor control was defined as numbers of glycated hemoglobin (HbA1c), blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), smoking, and kidney condition controlled within the target range. During a mean follow-up of 10.7 years, 3247 total CVD incidents were documented, including 2771 coronary heart disease and 701 strokes. In the fully adjusted model, compared with participants with the lowest loneliness score (zero), hazard ratios (95% confidence interval) for CVD were 1.11 (1.02 and 1.20) and 1.26 (1.11 and 1.42) for participants with a loneliness scale of 1 and 2, respectively (P -trend < 0.001). No significant associations were observed for social isolation. Loneliness ranked higher in relative strength for predicting CVD than the lifestyle risk factors in diabetes patients. A significant additive interaction between loneliness and the degree of risk factor control on the risk of CVD was observed (P for additive interaction = 0.005). Conclusion Among diabetes patients, loneliness, but not social isolation scale, is associated with a higher risk of CVD and shows an additive interaction with the degree of risk factor control. [ABSTRACT FROM AUTHOR]

Background Previous studies on alcohol drinking and health largely have ignored the potential impact of the timing of drinking. Objectives We aimed to investigate the joint associations of the timing of alcohol intake with respect to meals (i.e. with meals or outside of meals) and the amount of alcohol consumed with the risk of type 2 diabetes (T2D). Methods A total of 312,388 current drinkers from the UK Biobank without T2D at baseline were included. Cox proportional hazards models were used to examine the association between the timing of alcohol intake with respect to meals and the risk of T2D. Results During a median of 10.9 y of follow-up, 8598 incident cases of T2D were documented. After adjustment for covariates and the amount of alcohol consumed, consuming alcohol with meals was significantly associated with a 12% lower risk of T2D (HR: 0.88; 95% CI: 0.83, 0.93) than was consuming alcohol outside of meals. In addition, we found that the timing of alcohol intake with respect to meals significantly modified the relations between the amount of alcohol consumed and risk of T2D (P -interaction = 0.017); the beneficial association of moderate drinking with T2D risk was only observed in participants who consumed alcohol with meals, but not in others. Further analyses on various types of alcoholic beverages indicated that the beneficial associations between alcohol drinking with meals and T2D were mainly driven by wine consumption. Moreover, we found that when consumed together with meals, drinking more wine, rather than other alcoholic beverages, was related to lower concentrations of C-reactive protein. Conclusions In current drinkers, moderate drinking of alcohol, especially wine, with meals is associated with a lower risk of T2D. [ABSTRACT FROM AUTHOR]

Aims We analyzed whether the frequency of adding salt to foods was associated with the hazard of premature mortality and life expectancy. Methods and results A total of 501 379 participants from UK biobank who completed the questionnaire on the frequency of adding salt to foods at baseline. The information on the frequency of adding salt to foods (do not include salt used in cooking) was collected through a touch-screen questionnaire at baseline. We found graded relationships between higher frequency of adding salt to foods and higher concentrations of spot urinary sodium or estimated 24-h sodium excretion. During a median of 9.0 years of follow-up, 18 474 premature deaths were documented. The multivariable hazard ratios [95% confidence interval (CI)] of all-cause premature mortality across the increasing frequency of adding salt to foods were 1.00 (reference), 1.02 (0.99, 1.06), 1.07 (1.02, 1.11), and 1.28 (1.20, 1.35) (P -trend < 0.001). We found that intakes of fruits and vegetables significantly modified the associations between the frequency of adding salt to foods and all-cause premature mortality, which were more pronounced in participants with low intakes than those with high intakes of these foods (P -interaction = 0.02). In addition, compared with the never/rarely group, always adding salt to foods was related to 1.50 (95% CI, 0.72–2.30) and 2.28 (95% CI, 1.66–2.90) years lower life expectancy at the age of 50 years in women and men, respectively. Conclusions Our findings indicate that higher frequency of adding salt to foods is associated with a higher hazard of all-cause premature mortality and lower life expectancy. [ABSTRACT FROM AUTHOR]

Background and aims: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all‐cause and cause‐specific mortality, and measure whether such associations are modified by genetic variations. Design Prospective cohort study. Setting: UK Biobank. Participants: A total of 360 937 participants aged between 37 and 73 years were enrolled in 2006–10 and ‐followed‐up to 2018. Measurements The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking‐associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all‐cause and cause‐specific mortality. Findings We identified 15 968 deaths [9022 from cancer and 5092 from cardiovascular disease (CVD)] over a median of 11.36 years' follow‐up. For all‐cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three and four were 1.23 [95% confidence intervals (CI) = 1.18–1.29), 1.66 (95% CI = 1.59–1.75), 3.33 (95% CI = 3.17–3.51) and 5.76 (95% CI = 4.66–7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45–58% reduced risk of all‐cause death compared with high PSB. Analysis of population‐attributable risk percentage indicated that 21.9, 19.1 and 24.7% of all‐cause‐, cancer‐ and CVD‐specific death could have been avoided if all ever smokers initiated smoking after age 18 years, smoked < 20 cigarettes/day and quit smoking. Conclusions: The panoramic smoking burden, based on smoking initiation, age of initiation, heaviness of smoking and smoking cessation, appears to be associated with all‐cause and cause‐specific mortality in a gradient manner with increasing panoramic smoking burden independent of other traditional and genetic risk factors. [ABSTRACT FROM AUTHOR]

Background: Individual unhealthy sleep behaviours have been associated with increased risks of all‐cause mortality and deaths due to cardiovascular disease (CVD) or cancer. The evidence regarding the association of sleep patterns with these risks is limited. Objective: To examine the associations of sleep patterns with all‐cause, CVD and cancer mortality in a large prospective cohort. Methods: This prospective cohort study included 283,443 adults from UK Biobank without CVD and cancer at baseline. We created a healthy sleep score and sleep patterns combining five individual sleep behaviours. Results: During a mean (standard deviation) of 8.9 (1.1) years (2.5 million person‐years) of follow up, a total of 7936 all‐cause deaths, 762 CVD‐caused deaths, and 4540 cancer‐caused deaths occurred during follow up. One point increase of the healthy sleep score was associated with a 4–11% lower risk of all‐cause mortality (Hazard Ratio [HR], 0.94; 95% CI, 0.92–0.96), CVD mortality (HR, 0.89; 95% CI, 0.83–0.95) and cancer mortality (HR, 0.96; 95% CI, 0.93–0.99), with adjustment for age, sex, assessment centres, smoking status, alcohol intake status, socioeconomic status and physical activity. Compared with participants with an unfavourable sleep pattern, those with a favourable sleep pattern had 24–42% lower risks of all‐cause and CVD mortality. The association with all‐cause mortality tended to be stronger among underweight participants and those with insufficient physical activity. Conclusions: A healthy sleep pattern was associated with lower risks of all‐cause mortality and mortality from CVD and cancer. Our findings highlight the importance of improving overall sleep behaviours in lowering mortality. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence has linked sleep behaviors with the risk of cardiac arrhythmias. The various sleep behaviors are typically correlated; however, most of the previous studies only focused on the individual sleep behavior, without considering the overall sleep patterns.Objectives: The purpose of this study was to prospectively investigate the associations between a healthy sleep pattern with the risks of cardiac arrhythmias.Methods: A total of 403,187 participants from UK Biobank were included. A healthy sleep pattern was defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Weighted genetic risk score for atrial fibrillation was calculated.Results: The healthy sleep pattern was significantly associated with lower risks of atrial fibrillation/flutter (AF) (HR comparing extreme categories: 0.71; 95% CI: 0.64-0.80) and bradyarrhythmia (HR: 0.65; 95% CI: 0.54-0.77), but not ventricular arrhythmias, after adjustment for demographic, lifestyle, and genetic risk factors. Compared with individuals with a healthy sleep score of 0-1 (poor sleep group), those with a healthy sleep score of 5 had a 29% and 35% lower risk of developing AF and bradyarrhythmia, respectively. Additionally, the genetic predisposition to AF significantly modified the association of the healthy sleep pattern with the risk of AF (P interaction = 0.017). The inverse association of the healthy sleep pattern with the risk of AF was stronger among those with a lower genetic risk of AF.Conclusions: Our results indicate that a healthy sleep pattern is associated with lower risks of AF and bradyarrhythmia, independent of traditional risk factors, and the association with AF is modified by genetic susceptibility. [ABSTRACT FROM AUTHOR]

Background: Air pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship.Methods and Findings: A total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m2. Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 μm (PM2.5), between 2.5 μm and 10 μm (PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants.Conclusions: We found that various air pollutants PM2.5, PM2.5-10, NO2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity. [ABSTRACT FROM AUTHOR]

Aims  Little is known about the relation between the long-term joint exposure to various ambient air pollutants and the incidence of heart failure (HF). We aimed to assess the joint association of various air pollutants with HF risk and examine the modification effect of the genetic susceptibility. Methods and results  This study included 432 530 participants free of HF, atrial fibrillation, or coronary heart disease in the UK Biobank study. All participants were enrolled from 2006 to 2010 and followed up to 2018. The information on particulate matter (PM) with diameters ≤2.5 µm (PM2.5), ≤10 µm (PM10), and between 2.5 and 10 µm (PM2.5–10) as well as nitrogen oxides (NO2 and NO x ) was collected. We newly proposed an air pollution score to assess the joint exposure to the five air pollutants through summing each pollutant concentration weighted by the regression coefficients with HF from single-pollutant models. We also calculated the weighted genetic risk score of HF. During a median of 10.1 years (4 346 642 person-years) of follow-up, we documented 4201 incident HF. The hazard ratios (HRs) [95% confidence interval (CI)] of HF for a 10 µg/m3 increase in PM2.5, PM10, PM2.5–10, NO2, and NO x were 1.85 (1.34–2.55), 1.61 (1.30–2.00), 1.13 (0.80–1.59), 1.10 (1.04–1.15), and 1.04 (1.02–1.06), respectively. We found that the air pollution score was associated with an increased risk of incident HF in a dose–response fashion. The HRs (95% CI) of HF were 1.16 (1.05–1.28), 1.19 (1.08–1.32), 1.21 (1.09–1.35), and 1.31 (1.17–1.48) in higher quintile groups compared with the lowest quintile of the air pollution score (P trend <0.001). In addition, we observed that the elevated risk of HF associated with a higher air pollution score was strengthened by the genetic susceptibility to HF. Conclusion  Our results indicate that the long-term joint exposure to various air pollutants including PM2.5, PM10, PM2.5–10, NO2, and NO x is associated with an elevated risk of incident HF in an additive manner. Our findings highlight the importance to comprehensively assess various air pollutants in relation to the HF risk. [ABSTRACT FROM AUTHOR]

Fish oil supplementation is widely used for reducing serum triglycerides (TAGs) but has mixed effects on other circulating cardiovascular biomarkers. Many genetic polymorphisms have been associated with blood lipids, including high- and low-density-lipoprotein cholesterol (HDL-C, LDL-C), total cholesterol, and TAGs. Here, the gene-diet interaction effects of fish oil supplementation on these lipids were analyzed in a discovery cohort of up to 73,962 UK Biobank participants, using a 1-degree-of-freedom (1df) test for interaction effects and a 2-degrees-of-freedom (2df) test to jointly analyze interaction and main effects. Associations with P < 1×10−6 in either test (26,157; 18,300 unique variants) were advanced to replication in up to 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Replicated associations reaching 1df P < 0.05 (2,175; 1,763 unique variants) were used in meta-analyses. We found 13 replicated and 159 non-replicated (UK Biobank only) loci with significant 2df joint tests that were predominantly driven by main effects and have been previously reported. Four novel interaction loci were identified with 1df P < 5×10−8 in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A>G; minor allele frequency = 0.041), shows exclusively interaction effects. The minor allele is significantly associated with decreased TAGs in individuals with fish oil supplementation, but with increased TAGs in those without supplementation. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue; connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Our study identifies novel gene-diet interaction effects for four genetic loci, whose effects on blood lipids are modified by fish oil supplementation. These findings highlight the need and possibility for personalized nutrition. Author summary: We utilized the unprecedentedly large genotype and phenotype dataset in the UK Biobank to perform a genome-wide association study (GWAS) which accounts for the interplay between genotype and dietary intake. We examined the interaction effects of fish oil supplementation on levels of blood lipids (LDL-C, HDL-C, TAGs, and total cholesterol). Our findings were replicated in the Atherosclerosis Risk in Communities (ARIC) Study. We found that at the genetic variant rs112803755 (A>G), the minor allele (G) is associated with a decrease in TAGs among individuals with fish oil supplementation, but is associated with an increase in TAGs among those without supplementation. In other words, only individuals carrying the minor allele benefit from fish oil supplementation in reducing TAG levels. We further analyzed rs112803755 with functional genomics data from the Genotype-Tissue Expression (GTEx) project to identify potential target genes, and found a connexin coding gene which has been previously reported to respond to cellular omega-3 levels. This research suggests that inter-personal variation in TAG response to fish oil supplementation is in part explained by genotype, and that fish oil dose adjustment based on genotype should be investigated as a means to protect against cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Context: Dietary fiber intake may relate to bone health.Objective: To investigate whether dietary fiber intake is associated with bone mineral density (BMD), and the modification effect of genetic variations related to gut microbiota-derived short-chain fatty acids (SCFAs).Design: The associations of dietary fiber intake with estimated BMD derived from heel ultrasound and fractures were assessed in 224 630 and 384 134 participants from the UK Biobank.Setting: UK Biobank.Main Outcome Measures: Estimated BMD derived from heel ultrasound.Results: Higher dietary fiber intake (per standard deviation) was significantly associated with higher heel-BMD (β [standard error] = 0.0047 [0.0003], P = 1.10 × 10-54). Similarly significant associations were observed for all the fiber subtypes including cereal, fruit (dried and raw), and vegetable (cooked and raw) (all P < .05). A positive association was found in both women and men but more marked among men except for dietary fiber in cooked vegetables (all Pinteraction < .05). A protective association was found between dietary fiber intake and hip fracture (hazard ratio, 95% confidence interval: 0.94, 0.89-0.99; P = 3.0 × 10-2). In addition, the association between dietary fiber and heel BMD was modified by genetically determined SCFA propionate production (Pinteraction = 5.1 × 10-3). The protective association between dietary fiber and heel BMD was more pronounced among participants with lower genetically determined propionate production.Conclusions: Our results indicate that greater intakes of total dietary fiber and subtypes from various food sources are associated with higher heel-BMD. Participants with lower genetically determined propionate production may benefit more from taking more dietary fiber. [ABSTRACT FROM AUTHOR]

Objective: Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D and whether such association was modified by sleep behaviors.Research Design and Methods: The study included 350,211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns.Results: During a median follow-up of 8.1 years, we documented 6,940 case subjects with incident T2D. We found that serum 25OHD was significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR) (95% CI) per 10 nmol/L increase was 0.88 (0.87-0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction = 0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction = 0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D.Conclusions: Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D, and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor. [ABSTRACT FROM AUTHOR]

Objective: Glucosamine is a widely used supplement typically taken for osteoarthritis and joint pain. Emerging evidence suggests potential links of glucosamine with glucose metabolism, inflammation, and cardiometabolic risk. We prospectively analyzed the association of habitual glucosamine use with risk of type 2 diabetes (T2D) and assessed whether genetic susceptibility and inflammation status might modify the association.Research Design and Methods: This study analyzed 404,508 participants from the UK Biobank who were free of diabetes, cancer, or cardiovascular disease at baseline and completed the questionnaire on supplement use. Cox proportional hazards models were used to evaluate the association between habitual use of glucosamine and risk of incident T2D.Results: During a median of 8.1 years of follow-up, 7,228 incident cases of T2D were documented. Glucosamine use was associated with a significantly lower risk of T2D (hazard ratio 0.83, 95% CI 0.78-0.89) after adjustment for age, sex, BMI, race, center, Townsend deprivation index, lifestyle factors, history of disease, and other supplement use. This inverse association was more pronounced in participants with a higher blood level of baseline C-reactive protein than in those with a lower level of this inflammation marker (P-interaction = 0.02). A genetic risk score for T2D did not modify this association (P-interaction = 0.99).Conclusions: Our findings indicate that glucosamine use is associated with a lower risk of incident T2D. [ABSTRACT FROM AUTHOR]

Background: We recently found that the frequency of adding salt to foods could reflect a person's long-term salt taste preference and sodium intake, and was significantly related to life expectancy.Objective: We analyzed whether the frequency of adding salt to foods was associated with incident cardiovascular disease (CVD) risk.Methods: This study included 176,570 adults in UK Biobank who were initially free of CVD. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident CVD events.Results: During a median of 11.8 years of follow-up, 9,963 total CVD events, 6,993 ischemic heart disease (IHD) cases, 2,007 stroke cases, and 2,269 heart failure cases were documented. Lower frequency of adding salt to foods was significantly associated with lower risk of total CVD events after adjustment for covariates and the DASH (Dietary Approaches to Stop Hypertension) diet (a modified DASH score was used without considering sodium intake). Compared with the group of always adding salt to foods, the adjusted HRs were 0.81 (95% CI: 0.73-0.90), 0.79 (95% CI: 0.71-0.87), and 0.77 (95% CI: 0.70-0.84) across the groups of usually, sometimes, and never/rarely, respectively (P trend < 0.001). Among the subtypes of CVD, adding salt showed the strongest association with heart failure (P trend <0.001), followed by IHD (P trend < 0.001), but was not associated with stroke. We found that participants who combined a DASH-style diet with the lowest frequency of adding salt had the lowest CVD risk.Conclusions: Our findings indicate that lower frequency of adding salt to foods is associated with lower risk of CVD, particularly heart failure and IHD. [ABSTRACT FROM AUTHOR]

Rainfall-induced landslides can originate as a result of distinct hydro-mechanical processes, such as soil-strength degradation, flow liquefaction (Buscarnera and di Prisco, 2013), groundwater level rise, among others, thus posing challenges for the development of landslide susceptibility zonation models (Lizarraga et al., 2017). Among them is the presence of unsaturated layered deposits, which markedly influences the infiltration process and conditions the timing and location of slope instabilities. This contribution presents a spatially-distributed model for landslide susceptibility in shallow layered slopes. The framework relies on a vectorized finite element (FE) algorithm that performs simulations of vertical infiltration and slope stability in unsaturated soils and provides flexibility to efficiently allocate the computational cost associated with layers of variable thickness and/or complex stratigraphy (Lizarraga and Buscarnera, 2018). To illustrate the capabilities of the proposed methodology, a series of documented shallow landslides that occurred in a region covered by stratified volcanic deposits is analyzed. The results indicate that variations of hydraulic conductivity in adjacent layers promotes the development of transient spikes of pore pressure that can initiate slope failure. Such effects have important implications in the spatio-temporal predictions of landslide triggering and computed failure depths, leading to an improved performance over the landscape when compared with results based on homogeneous slopes. The proposed framework provides an important step towards the development of robust, physically-based models for regional landslide hazard assessment.References:Buscarnera, G. and Di Prisco, C., 2013. Soil stability and flow slides in unsaturated shallow slopes: Can saturation events trigger liquefaction processes?. Géotechnique, 63(10), pp.801-817.Lizárraga, J.J., Frattini, P., Crosta, G.B. and Buscarnera, G., 2017. Regional-scale modelling of shallow landslides with different initiation mechanisms: Sliding versus liquefaction. Engineering Geology, 228, pp.346-356.Lizárraga, J.J. and Buscarnera, G., Spatially distributed modeling of rainfall-induced landslides in shallow layered slopes. Landslides, pp.1-11. [ABSTRACT FROM AUTHOR]

Background: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort. The physical-psychosocial frailty was evaluated based on seven indicators including weight loss, exhaustion, physical activity, walking pace, grip strength, social isolation, and loneliness. The outcomes were premature mortality from all causes, cancer, CVD, and other causes. Cox proportional hazards models were used to assess the associations between the physical-psychosocial frailty and premature mortality.During a median follow-up period of 12.7 years, we recorded 20,328 premature deaths. Each additional increment in the physical-psychosocial frailty index was associated with a 26% (HR 1.26, 95% CI 1.24–1.28), 10% (HR 1.10, 95% CI 1.08–1.12), 30% (HR 1.30, 95% CI 1.26–1.33), and 44% (HR 1.44, 95% CI 1.41–1.47) higher risk of all-cause, cancer, cardiovascular, and other-cause premature mortality, respectively. Compared with participants with the physical-psychosocial frailty index of 0, those with the index ≥ 4 had a 2.67 (95% CI 2.49–2.87)-fold higher risk of all-cause premature mortality. Slow walking pace and social isolation were the top two strongest predictors for all-cause premature mortality. In addition, we found that lower body mass index (BMI), age, smoking status, and dietary quality modified the associations of physical-psychosocial frailty with all-cause premature mortality (P-interaction < 0.05).In this cohort study of UK Biobank participants, joint physical-psychosocial frailty is significantly associated with risks of all-cause and cause-specific premature mortality, highlighting the importance to jointly assess physical and psychosocial factors in determining aging-related health.Design: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort. The physical-psychosocial frailty was evaluated based on seven indicators including weight loss, exhaustion, physical activity, walking pace, grip strength, social isolation, and loneliness. The outcomes were premature mortality from all causes, cancer, CVD, and other causes. Cox proportional hazards models were used to assess the associations between the physical-psychosocial frailty and premature mortality.During a median follow-up period of 12.7 years, we recorded 20,328 premature deaths. Each additional increment in the physical-psychosocial frailty index was associated with a 26% (HR 1.26, 95% CI 1.24–1.28), 10% (HR 1.10, 95% CI 1.08–1.12), 30% (HR 1.30, 95% CI 1.26–1.33), and 44% (HR 1.44, 95% CI 1.41–1.47) higher risk of all-cause, cancer, cardiovascular, and other-cause premature mortality, respectively. Compared with participants with the physical-psychosocial frailty index of 0, those with the index ≥ 4 had a 2.67 (95% CI 2.49–2.87)-fold higher risk of all-cause premature mortality. Slow walking pace and social isolation were the top two strongest predictors for all-cause premature mortality. In addition, we found that lower body mass index (BMI), age, smoking status, and dietary quality modified the associations of physical-psychosocial frailty with all-cause premature mortality (P-interaction < 0.05).In this cohort study of UK Biobank participants, joint physical-psychosocial frailty is significantly associated with risks of all-cause and cause-specific premature mortality, highlighting the importance to jointly assess physical and psychosocial factors in determining aging-related health.Key Results: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort. The physical-psychosocial frailty was evaluated based on seven indicators including weight loss, exhaustion, physical activity, walking pace, grip strength, social isolation, and loneliness. The outcomes were premature mortality from all causes, cancer, CVD, and other causes. Cox proportional hazards models were used to assess the associations between the physical-psychosocial frailty and premature mortality.During a median follow-up period of 12.7 years, we recorded 20,328 premature deaths. Each additional increment in the physical-psychosocial frailty index was associated with a 26% (HR 1.26, 95% CI 1.24–1.28), 10% (HR 1.10, 95% CI 1.08–1.12), 30% (HR 1.30, 95% CI 1.26–1.33), and 44% (HR 1.44, 95% CI 1.41–1.47) higher risk of all-cause, cancer, cardiovascular, and other-cause premature mortality, respectively. Compared with participants with the physical-psychosocial frailty index of 0, those with the index ≥ 4 had a 2.67 (95% CI 2.49–2.87)-fold higher risk of all-cause premature mortality. Slow walking pace and social isolation were the top two strongest predictors for all-cause premature mortality. In addition, we found that lower body mass index (BMI), age, smoking status, and dietary quality modified the associations of physical-psychosocial frailty with all-cause premature mortality (P-interaction < 0.05).In this cohort study of UK Biobank participants, joint physical-psychosocial frailty is significantly associated with risks of all-cause and cause-specific premature mortality, highlighting the importance to jointly assess physical and psychosocial factors in determining aging-related health.Conclusions: The importance of integrating physical and psychosocial factors in assessing frailty -health outcomes has been increasingly acknowledged, while the related evidence is lacking. We sought to investigate the associations of joint physical-psychosocial frailty with risk of premature mortality and evaluate the relative importance of individual physical and psychosocial factors.A total of 381,295 participants with no history of cancer or cardiovascular disease (CVD) were recruited from the UK Biobank cohort. The physical-psychosocial frailty was evaluated based on seven indicators including weight loss, exhaustion, physical activity, walking pace, grip strength, social isolation, and loneliness. The outcomes were premature mortality from all causes, cancer, CVD, and other causes. Cox proportional hazards models were used to assess the associations between the physical-psychosocial frailty and premature mortality.During a median follow-up period of 12.7 years, we recorded 20,328 premature deaths. Each additional increment in the physical-psychosocial frailty index was associated with a 26% (HR 1.26, 95% CI 1.24–1.28), 10% (HR 1.10, 95% CI 1.08–1.12), 30% (HR 1.30, 95% CI 1.26–1.33), and 44% (HR 1.44, 95% CI 1.41–1.47) higher risk of all-cause, cancer, cardiovascular, and other-cause premature mortality, respectively. Compared with participants with the physical-psychosocial frailty index of 0, those with the index ≥ 4 had a 2.67 (95% CI 2.49–2.87)-fold higher risk of all-cause premature mortality. Slow walking pace and social isolation were the top two strongest predictors for all-cause premature mortality. In addition, we found that lower body mass index (BMI), age, smoking status, and dietary quality modified the associations of physical-psychosocial frailty with all-cause premature mortality (P-interaction < 0.05).In this cohort study of UK Biobank participants, joint physical-psychosocial frailty is significantly associated with risks of all-cause and cause-specific premature mortality, highlighting the importance to jointly assess physical and psychosocial factors in determining aging-related health. [ABSTRACT FROM AUTHOR]

Effect modification of integrated neighborhood environment on associations of air pollution with mortality remained unclear. We analyzed data from UK biobank prospective study (n = 421,650, median 12.5 years follow-up) to examine disparities of mortality risk associated with air pollution among varied neighborhood settings. Fine particulate matter (PM 2.5), PM 10 and nitrogen dioxide (NO 2) were measured and assigned to each participants' address. Diverse ecological and societal settings of neighborhoods were integrated with principal component analysis and categorized into disadvantaged, intermediate and advantaged levels. We estimated mortality risk associated with air pollution across diverse neighborhoods using Cox regression. We calculated community-level proportions of mortality attributable to air pollutants. There was evidence of higher all-cause and respiratory disease mortality risk associated with PM 2.5 and NO 2 among those in disadvantaged neighborhoods. In disadvantaged communities, air pollutants explained larger proportions of deaths and such disparities persisted over past decades. Across 2010–2021, reducing PM 2.5 and NO 2 to 10 μg/m3 (World Health Organization limits) would save 87,000 (52,000−120,000) and 91,000 (37,000−145,000) deaths of populations aged ≥ 40 years, with 150 000 deaths occurred in disadvantaged neighborhood settings. These findings suggested that disadvantaged neighborhoods can exacerbate mortality risk associated with air pollution. [Display omitted] • Societal and ecological neighborhoods modify the health effects of air pollution. • Disadvantaged neighborhoods exacerbate mortality risk associated with air pollution. • Neighborhood disparities of air pollution-linked mortality persisted in past decades. • Interventions of air pollution may be prioritized to disadvantaged neighborhoods. [ABSTRACT FROM AUTHOR]

Little is known about the associations between perinatal exposure to maternal smoking and cardiovascular disease (CVD) incidence in offspring, and whether such associations are modified by adulthood and genetically determined smoking behaviors. A total of 414,588 participants without CVD at baseline were included from the UK Biobank in 2006–2010 and followed up through 2018. Cox-proportional hazard models were used to examine the association of perinatal maternal smoking with CVD, and both multiplicative and additive interaction analyses were performed to investigate the modification effects of own smoking behaviors. During a median follow-up of 8.93 years, we observed 10,860 incident CVD events, including 7006 myocardial infarction (MI) and 4147 stroke. We found that perinatal exposure to maternal smoking was associated with increased risks of CVD (HR: 1.10; 95% CI: 1.05–1.14), MI (1.10; 1.05–1.16) and stroke (1.10; 1.03–1.18). In addition, we observed significant interactions between perinatal exposure to maternal smoking and adulthood exposure to own smoking on CVD and MI on both the multiplicative and additive scales (all p < 0.05). The attributable proportions due to additive interaction between perinatal and adulthood exposure to smoking were 14% (9%–19%) for CVD and 16% (10%–22%) for MI, respectively. Perinatal exposure to maternal smoking also showed an interaction with genetically determined smoking on MI (p < 0.05), but no interactions were found on the total CVD and stroke. Our results indicate that perinatal exposure to maternal smoking is associated with increased risks of CVD events, and such relations are modified by adulthood smoking behaviors. [Display omitted] • Perinatal maternal smoking was associated with increased cardiovascular disease (CVD) risks in offspring. • Such associations were modified by adulthood smoking behaviors. • Simultaneous avoidance of both perinatal and adulthood exposure to smoking may further prevent CVD. [ABSTRACT FROM AUTHOR]

Aims: Although smoking is a well-known risk factor for atrial fibrillation (AF), the association of smoking timing with AF risk remains unclear. This study aimed to prospectively investigate the association of smoking timing with the risk of incident AF and test the modification effect of genetic susceptibility., Methods and Results: A total of 305 627 participants with detailed information for time from waking to the first cigarette were enrolled from UK Biobank database. The Cox proportional hazard model was employed to assess the relationship between smoking timing and AF risk. The weighted genetic risk score for AF was calculated. Over a median 12.2-year follow-up, 13 410 AF cases were documented. Compared with non-smokers, time from waking to the first cigarette showed gradient inverse associations with the risk of incident AF (P-trend <0.001). The adjusted hazard ratio related to smoking timing was 1.13 [95% confidence interval (CI): 0.96-1.34] for >120 min, 1.20 (95% CI: 1.01-1.42) for 61-120 min, 1.34 (95% CI: 1.19-1.51) for 30-60 min, 1.43 (95% CI: 1.26-1.63) for 5-15 min, and 1.49 (95% CI: 1.24-1.63) for <5 min, respectively. Additionally, we found that the increased risk of AF related to shorter time from waking to the first cigarette was strengthened by the genetic susceptibility to AF., Conclusion: Our findings suggest gradient inverse association between time from waking to the first cigarette and risk of incident AF, and the association is strengthened by the genetic susceptibility to AF., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage., Objective: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks., Study Design: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety., Results: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03)., Conclusion: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Although smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the time smoking is initiated after awakening each day and CKD remains largely unstudied. This study examined the association between this timing and the risk of CKD, and the potential interactions of smoking timing with other risk factors for the occurrence of CKD., Study Design: Observational cohort study., Setting & Participants: A total of 32,776 participants in the UK Biobank with complete data on the time from waking to the first cigarette and free of prevalent CKD were included., Exposure: Time from waking to the first cigarette., Outcome: Incident CKD cases., Analytical Approach: Cox proportional hazards regression was used to investigate the associations between the time smoking is initiated each day and the risk of CKD. The potential interactions of smoking timing with risk factors in relationship to CKD risk were assessed on both multiplicative and additive scales., Results: During a median follow-up period of 12 years, 940 incident CKD cases occurred. Shorter durations of time from waking to the first cigarette were associated with a higher risk of incident CKD (P trend=0.01). Compared with>120 minutes, the adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI, 0.92-1.80) for 61-120 minutes, 1.48 (95% CI, 1.11-1.96) for 30-60 minutes, 1.36 (95% CI, 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI, 1.22-2.37) for<5 minutes, respectively. Furthermore, there was a significant additive interaction and multiplicative interactions between the timing of smoking and a healthy diet score (P for additive interaction=0.01; P for multiplicative interaction = 0.004)., Limitations: Generalizability, possible residual confounding, limiting causal inference., Conclusions: These findings reveal a significant association between the shorter time from waking to the first cigarette and a higher CKD risk. The magnitude of these associations was greater in the setting of an unhealthy diet., Plain-Language Summary: This study explored the association of the daily timing of first cigarette smoking and the occurrence of kidney disease. Further, we addressed whether this association was influenced by the quality of the diet. The study found that smoking very soon after waking, especially when combined with a poorer quality diet, was associated with a significantly increased risk of developing chronic kidney disease. This research emphasizes the value of healthier lifestyle choices for kidney health., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate the extent to which joint risk factor control might attenuate the excess risk of chronic kidney disease (CKD) in participants with obesity., Patients and Methods: We included a total of 97 538 participants who were obese at baseline and matched 97 538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on six major CKD risk factors, including blood pressure, glycated haemoglobin, low-density lipoprotein cholesterol, albuminuria, smoking and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD, following participants from their baseline assessment until the occurrence of CKD, death, or the end of the follow-up period., Results: Among participants with obesity, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (hazard ratio: 0.89; 95% confidence interval: 0.86-0.91) reduced risk of CKD among participants with obesity, with the optimal controlling of all six risk factors associated with a 49% (hazard ratio: 0.51; 95% confidence interval: 0.43-0.61) decrease in risk of CKD. Furthermore, in individuals with obesity who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared with normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared with women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to non-users (p interaction  = 0.017, 0.033 and 0.014, respectively)., Conclusion: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among individuals with obesity. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity., (© 2024 John Wiley & Sons Ltd.)

Background: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors., Methods: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures., Results: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001)., Conclusions: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in LS BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65 yr., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To characterize and validate the subtypes of type 2 diabetes (T2D) using a novel clustering algorithm and to further assess their associations with the risk of incident cardiovascular disease (CVD) events., Methods: Unsupervised k-means clustering based on glycated hemoglobin level, age at onset of T2D, body mass index, and estimated glomerular filtration rate was conducted among participants with T2D from the UK Biobank (March 13, 2006, to October 1, 2010) and replicated in the All of Us cohort (May 30, 2017, to April 1, 2021)., Results: Five distinct T2D clusters were identified in the UK Biobank and validated in the All of Us cohort, characterizing the phenotypically heterogeneous subtypes. With a median follow-up of 11.69 years for patients with T2D in the UK Biobank, risks of incident CVD events varied considerably between the clusters after adjustment for potential confounders and multiple testing (all P<.001). With cluster 1 characterized by early onset of T2D and mild abnormalities of other variables as the reference, patients in cluster 5 characterized by poor renal function had the highest risk of CVD events (hazard ratio [95% CI], 1.72 [1.45 to 2.03], 2.41 [1.93 to 3.02], and 1.62 [1.35 to 1.94] for composite CVD event, CVD mortality, and CVD incidence, respectively; all P<.001), followed by cluster 4 characterized by poor glycemic control and cluster 3 characterized by severe obesity. No consistently significant difference was found between cluster 2 characterized by late onset of T2D and cluster 1., Conclusion: Our study, using a novel clustering algorithm to identify robust subtypes of T2D, found heterogeneous associations with incident CVD risk among patients with diabetes., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The average life expectancy has increased substantially in the past few decades in most industrialized countries; however, not all of the increased life expectancy is being spent in optimal health, especially among individuals with low socioeconomic status., Objective: To quantify the associations between levels of cardiovascular health (CVH), estimated by the American Heart Association's Life's Essential 8 (LE8) metrics, with life expectancy free of major chronic disease, including cardiovascular disease (CVD), diabetes, cancer, and dementia, in UK adults., Design, Setting, and Participants: This cohort study included 135 199 adults in the UK Biobank study who were initially free of major chronic disease and had complete data on LE8 metrics. Data analyses were performed in August 2022., Exposures: Cardiovascular health levels, as estimated by LE8 score. The LE8 score, which consists of 8 components: (1) diet, (2) physical activity, (3) tobacco/nicotine exposure, (4) sleep, (5) body mass index, (6) non-high-density lipoprotein cholesterol, (7) blood glucose, and (8) blood pressure. The CVH level was evaluated at baseline and categorized into low (LE8 score <50), moderate (LE8 score ≥50 but <80), and high (LE8 score ≥80) levels., Main Outcomes and Measures: The primary outcome was the life expectancy free of 4 major chronic diseases (CVD, diabetes, cancer, and dementia)., Results: Of the 135 199 adults (44.7% men; mean [SD] age, 55.4 [7.9] years) included in the study, a total of 4712, 48 955, and 6748 men had low, moderate, and high CVH levels, respectively, and the corresponding numbers for women were 3661, 52 192, and 18 931. At age 50 years, the estimated disease-free years were 21.5 (95% CI, 21.0-22.0), 25.5 (95% CI, 25.4-25.6), and 28.4 (95% CI, 27.8-29.0) for men with low, moderate, and high CVH levels, respectively; the corresponding estimated disease-free years at age 50 years for women were 24.2 (95% CI, 23.5-24.8), 30.5 (95% CI, 30.4-30.6), and 33.6 (95% CI, 33.1-34.0). Equivalently, men with moderate or high CVH levels lived on average 4.0 (95% CI, 3.4-4.5) or 6.9 (95% CI, 6.1-7.7) longer years free of chronic disease, respectively, at age 50 years, compared with men with low CVH levels. The corresponding longer years lived free of disease for women were 6.3 (95% CI, 5.6-7.0) or 9.4 (95% CI, 8.5-10.2). For participants with high CVH level, there was not a statistically significant difference in disease-free life expectancy between participants with low and other socioeconomic status., Conclusions and Relevance: In this cohort study, a high level of CVH, evaluated using the LE8 metrics, was associated with longer life expectancy free of major chronic diseases and may contribute to narrowing socioeconomic health inequalities in both men and women.

Background: Journal Impact Factor™ (JIF) is often used to evaluate the relative reputation and quality of academic journals in their respective fields, and can greatly influence the quality and scope of subsequent manuscript submissions. Therefore, many if not all academic journals are interested in increasing their JIF , to improve their academic impact., Aim: To determine the importance of the integrity of the editorial and publication process in improving the academic influence of academic journals and the JIF of academic journals., Methods: In this paper, we describe our statistical analysis of bibliometric factors - including the 2021 JIFs released in the Journal Citation Report™ 2022, discipline rankings, received and published articles in 2019-2021, and webpage visits and downloads - for seven journals published by Baishideng Publishing Group (Baishideng) and indexed in Science Citation Index Expanded™; ultimately, we introduce and discuss the editing and publishing processes of Baishideng's journals in their entirety, as they form the basis for our objective of safeguarding and bolstering integrity in academic publication., Results: For the seven journals assessed, their 2021 JIFs were basically unchanged from 2020, with the current metric ranging from 5.374 for World Journal of Gastroenterology ( WJG ) to 1.534 for World Journal of Clinical Cases ( WJCC ). Further assessments of the journals' bibliometrics from 2019 to 2020, showed that World Journal of Stem Cells has the highest self-citation rate (1.43%) and World Journal of Gastrointestinal Surgery has the lowest (0.21%). Additionally, the total 3012 articles published during this period were cited by more than 20000 articles in approximately 8000 academic journals. Of note, the 1102 articles published in WJG were cited by articles in 3059 journals, among which 171 journals have a JIF of > 10, including internationally renowned academic journals such as CA-A Cancer Journal for Clinicians (2021 JIF 286.130, record count: 1) , Lancet (2021 JIF 202.731, record count: 4) , Nature Reviews Immunology (2021 JIF 108.555, record count: 2), Nature Reviews Gastroenterology & Hepatology (2021 JIF 73.082, record count: 9), Lancet Gastroenterology & Hepatology (2021 JIF 45.042, record count: 8), Gastroenterology (2021 JIF 33.883, record count: 19), and Gut (2021 JIF 31.793, record count: 21). This suggests that Baishideng's journals have been widely recognized for their academic quality. In the Reference Citation Analysis ( RCA ) database, all seven Baishideng-published journals obtained a 2022 Journal Article Influence Index ( JAII ). For example, WJG has a 2022 JAII of 22.048, ranking 18 th out of 102 journals in the field of gastroenterology & hepatology in the RCA , with 469909 total citations (6/102) and 21313 total articles (5/102). The numbers of manuscripts received and published in 2021 were both higher than those in 2019-2020. For example, WJCC received a total of 3650 manuscripts in 2021, which is 91.1% higher than those in 2019-2020 (average: 1910 papers/year). In 2021, WJCC published 1296 articles, representing an increase of 105.1% compared to those in 2019-2020 (average: 632 articles/year). The numbers of webpage visits and downloads received by the seven journals have increased year by year. For example, the number of total visits received by WJG in 2019-2021 was 1974052 in 2019, 2317835 in 2020 (increased by 17.4% compared with that in 2019), and 2652555 in 2021 (increased by 4.4% compared with that in 2020). The visitors were from more than 220 countries and regions worldwide, such as the United States, China, and the United Kingdom. Open access (OA) plays a vital role in improving the quality, efficiency, transparency, and integrity of academic journal publishing. From 2019 to 2021, a total of 5543 OA articles were published in the seven journals, of which 2083 (37.6%) were invited and published free-of-charge. During the same period, 1683 articles were published in WJG , and the authors were from more than 70 countries and regions. For the total 5543 articles published in the seven journals from 2019 to 2021, 3903 article quality tracking reports were received after the online publication of these articles. The quality of the articles was further evaluated through the Baishideng's article quality and author evaluation tracking system, with 4655 articles (84.0%) having received author evaluation and feedback, which contributes to tracking metrics for authors' satisfaction with the collective publication processes. From March 25, 2021 to June 28, 2022, the seven journals received a total of 424 reader evaluations and 229 letters from readers; this subsequent reader engagement demonstrates that the popularity of the published articles and the volume of their readership audience were improved through the reader evaluation system., Conclusion: Ultimately, the findings from our bibliometric assessments indicate that establishing, promoting and actively practicing processes that safeguard and bolster the integrity of the editing and publication process also help to improve the academic influence of academic journals, which itself is the cornerstone for improving JIF., Competing Interests: Conflict-of-interest statement: The authors are employees of the Baishideng Publishing Group Inc and declare that they have no other real or potential conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To examine the association of a healthy sleep pattern, characterized by sleep of 7 to 8 h/d, morning person, no insomnia, no frequent snoring, and no daytime sleepiness, with the risk of chronic kidney disease (CKD)., Methods: We included 392,218 European adults, aged 38 to 73 years, who were free of CKD at recruitment between March 13, 2006, and October 1, 2010, from the UK Biobank study. Data on sleep behaviors were collected through questionnaires at recruitment. Cox proportional hazards regression models were used to assess the relations between the healthy sleep score and risk of CKD., Results: We identified 18,842 incident CKD cases after a mean follow-up of 11.1 (SD 2.2) years. The healthy sleep score was inversely associated with the risk of CKD in a dose-dependent manner (P for trend, <.001). Compared with the participants with a poor sleep pattern (score of 0-1), the multivariate adjusted hazard ratio of CKD was 0.77 (95% CI, 0.71 to 0.84) for those with the healthiest sleep pattern (score of 5). In addition, we found that the inverse association was stronger in individuals without history of hypertension compared with individuals with hypertension at baseline (P for interaction, .003) and in those 60 years of age or younger compared with their older counterparts (P for interaction, <.001)., Conclusion: Our data suggest that adherence to an overall healthy sleep pattern is associated with a lower risk of CKD, especially for individuals without history of hypertension and those who are younger., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Educational attainment has been associated with drinking behaviors in observation studies. We performed Mendelian randomization analysis to determine whether educational attainment causally affected drinking behaviors, including amount of alcohol intakes (in total and various types), drinking frequency, and drinking with or without meals among 334,507 white British participants from the UK Biobank cohort. We found that genetically instrumented higher education (1 additional year) was significantly related to higher total amount of alcohol intake (inverse-variance weighted method (IVW): beta = 0.44, 95% confidence interval (CI) 0.40-0.49, P = 1.57E-93). The causal relations with total amount and frequency of alcohol drinking were more evident among women. In analyses of different types of alcohol, higher educational attainment showed the strongest causal relation with more consumption of red wine (IVW beta = 0.34, 95% CI 0.32-0.36, P = 2.65E-247), followed by white wine/champagne, in a gender-specific manner. An inverse association was found for beer/cider and spirits. In addition, we found that 1 additional year of educational attainment was causally related to higher drinking frequency (IVW beta = 0.54, 95% CI 0.51-0.57, P = 4.87E-230) and a higher likelihood to take alcohol with meals (IVW: odds ratio (OR) = 3.10, 95% CI 2.93-3.29, P = 0.00E + 00). The results indicate causal relations of higher education with intake of more total alcohol especially red wine, and less beer/cider and spirits, more frequent drinking, and drinking with meals, suggesting the importance of improving drinking behaviors, especially among people with higher education., (© 2019. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Maternal smoking (MS) is associated with low birthweight (BW) but adult obesity in offspring, however, it remains unknown whether it modifies offspring's genetic susceptibility to obesity on BW, adult body weight, and birth-to-adulthood body weight tracking pattern., Methods: This study included 246,759 UK Biobank participants with information on MS, BW (kg), adult body weight and BMI (kg/m 2 ). Individual polygenetic score (PGS) was created on the basis of 97 BMI-associated genetic loci. We calculated individual birth-to-adulthood percentile change, and body weight tracking patterns that combined BW levels (<2.5, 2.5-4.0, and ≥4.0 as low, normal and high BW [LBW, NBW, and HBW]) and adulthood obesity status (≥30 as obesity [OB] and <30 as non-obesity [NOB]), including LBW-to-OB, LBW-to-NOB, NBW-to-OB, NBW-to-NOB, HBW-to-OB, and HBW-to-NOB., Results: Participants exposed to MS had a 0.108 kg lower BW (95% CI, -0.114 to -0.102), a 1.418 kg higher adult body weight (95% CI, 1.291-1.545), and a 6.91 greater percentile increase of body weight from birth to adulthood (95% CI, 6.62-7.21), compared with those nonexposed (all P < 0.001). In comparison to participants of NBW-to-NOB, MS was associated with an approximately twofold higher risk of LBW-to-OB (odds ratio [OR] 1.98, 95% CI 1.87-2.10), and a reduced likelihood of HBW-to-NOB (0.85, 95% CI 0.82-0.88). The increases in BW, adult body weight, and birth-to-adulthood percentile change per increment of 10 BMI-PGS were 0.021 vs. 0.012, 2.50 vs. 2.11, and 4.03 vs. 3.55, respectively, for participants exposed vs. nonexposed to MS (all P interaction  < 0.05)., Conclusion: Our results indicate that exposure to MS is associated with an increased risk of transition from low BW-to-adulthood obesity, and reduced likelihood of change from high BW-to-normal adult body weight. MS may modify the relation of genetic susceptibility to obesity and body weight in offspring.

A new COVID-19 epidemic model with media coverage and quarantine is constructed. The model allows for the susceptibles to the unconscious and conscious susceptible compartment. First, mathematical analyses establish that the global dynamics of the spread of the COVID-19 infectious disease are completely determined by the basic reproduction number R 0 . If R 0 ≤ 1, then the disease free equilibrium is globally asymptotically stable. If R 0 > 1, the endemic equilibrium is globally asymptotically stable. Second, the unknown parameters of model are estimated by the MCMC algorithm on the basis of the total confirmed new cases from February 1, 2020 to March 23, 2020 in the UK. We also estimate that the basic reproduction number is R 0 = 4.2816(95%CI: (3.8882, 4.6750)). Without the most restrictive measures, we forecast that the COVID-19 epidemic will peak on June 2 (95%CI: (May 23, June 13)) (Figure 3a) and the number of infected individuals is more than 70% of UK population. In order to determine the key parameters of the model, sensitivity analysis are also explored. Finally, our results show reducing contact is effective against the spread of the disease. We suggest that the stringent containment strategies should be adopted in the UK.