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Traffic safety has been of great concern in recent years. The prediction of the severity of traffic accidents is an important part of it. The occurrence of traffic accidents shows the characteristics of uncertainty and nonlinearity because of the influence of random factors. However, most of the existing models are single machine learning (ML) models, which have limitations in accuracy and generalization. This study proposes a traffic accident severity prediction model based on a combination of XGBoost (extreme Gradient Boosting) and Backpropagation Neural Network (BPNN). Firstly, feature selection is performed using the XGBOOST model. Secondly, the selected feature is used as the input layer of BPNN. In addition, traffic accidents have class imbalance, so the total cost is minimized by using cost-sensitive algorithm. Finally, the precision, recall and area under the curve (AUC) are used to evaluate the prediction results of the model. The 2005-2014 UK traffic accident dataset is used for prediction and compared with other machine learning models. Experiments show that (1) the XGBoost-BPNN model outperformed the single XGBoost, logistic regression (LR), and Support vector machine (SVM) models in terms of AUC, recall, and precision. (2) The number of neurons, the number of hidden layers and the learning rate of a neural network model have a large impact on the prediction accuracy. Increasing the number of neurons appropriately can improve the convergence speed and prediction effect of the model. This study can provide a reference for traffic accident prevention and early warning. [ABSTRACT FROM AUTHOR]

Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is an established treatment in selected patients with peritoneal metastases, delivered in the UK in specialist centres. HIPEC can be administered via the open coliseum technique as first described by Sugarbaker (O-HIPEC) or using a closed technique (C-HIPEC). Data comparing the safety and outcomes of these different approaches is limited. This study aims to compare morbidity and mortality rates of O-HIPEC and C-HIPEC following CRS for peritoneal metastases from colorectal cancer and appendiceal tumours. Consecutive patients undergoing CRS with open (05/2019–04/2020) and closed (05/2020–04/2021) HIPEC were identified from a prospectively maintained database. Baseline data including primary pathology, HIPEC agent and major operative procedures were analysed using Chi-squared and Fishers exact tests to ensure comparability of groups. Primary outcomes were 30- and 60-day postoperative mortality and morbidity (Common Terminology Criteria for Adverse Events, CTCAE). Secondary outcomes were length of critical care and overall hospital stay. In addition, morbidity and mortality were compared between HIPEC agents (mitomycin and oxaliplatin/5-fluorouracil). 99 patients (39.3%) and 153 patients (60.7%) underwent O-HIPEC, C-HIPEC respectively. Groups were well matched for baseline demographics, pathology, and HIPEC agent. In the O-HIPEC and C-HIPEC groups respectively, the incidence of 60-day complications (CTCAE 1–4) was 40.4% vs 39.3% (chi squared 0.94) and severe complications (CTCAE 3–4) 14% vs 13% (Fisher's exact p = 1) There was no perioperative mortality but one death in each group within the follow up period. There was no difference in morbidity or mortality between those receiving mitomycin or oxaliplatin. Closed administration of HIPEC is safe with no difference in post-operative morbidity or mortality compared to open HIPEC administration. Differences in longer term oncological outcomes including overall survival and disease-free survival between open and closed HIPEC techniques are yet to be determined. [ABSTRACT FROM AUTHOR]

A modelling approach is used to investigate the impacts of disruptions to natural gas supplies on the UK energy system and the effectiveness of strategic infrastructure investments which could help to mitigate these impacts. The combined gas and electricity network model is described. It is then used to project the development of the UK gas and electricity networks out to 2030 under two different scenarios for the wider development of the UK energy system. A set of plausible gas supply disruptions associated with three major gas facilities, lasting from 5 to 90 days, are hypothesised to occur in mid-winter 2025. The impacts are assessed in terms of shortfalls in natural gas deliveries and the costs of wider adjustments to the gas and electricity networks. Finally, the benefits arising from a number of strategic, mitigating investments in facilities such as gas storage or expanded liquefied natural gas import capacity are assessed. Although a full cost-benefit analysis was not possible, efficacy is assessed in terms of the frequency with which disruptions would need to occur to justify the mitigating investments. [ABSTRACT FROM AUTHOR]

The purpose of this work is to throw new light upon the ‘ill-defined’ subject of design and its role in industrial competition. To this end the paper examines the attitudes of managers and project workers in British textile industrial companies towards the development of new products, and compares these attitudes with company performance in order to discover any significant relationships. The research is based on a cross-sectional survey of companies engaged in yarn, fabric, clothing and textile machinery design. It is an isochronous study which focuses upon the point where the four dimensions of ‘design’, ‘management’, ‘information’, and ‘computing’ meet. These dimensions are translated into three main research perspectives which focus upon three dynamic but interrelated aspects of new-product development (NPD): (1) key issues in NPD and major influences upon design, (2) priorities and problems in NPD, and (3) computing or information technology in NPD. ‘Key issues in NPD and major influences upon design’ (KI & MI) relate to the ‘global environment’ in which companies operate and form a theoretical framework for this research. Company attitudes are based on orientation towards these three perspectives. A major survey of two hundred companies carried out from July to October 1994 provided sufficient data to examine ‘company attitudes’ towards NPD and global textile/apparel development. Statistical analysis showed that there were significant relationships between company attitudes and company performance measures. [ABSTRACT FROM AUTHOR]

To explore whether there are ethnic differences in relationships among parathyroid hormone (PTH), vitamin D, and bone mineral status, 352 healthy volunteers, 60–83 years old, were studied in Shenyang, Peoples'' Republic of China (108 men, 110 women), and in Cambridge, UK (67 men, 67 women), in late winter. Early morning fasting blood and 2-h fasting urine were analyzed for 25-hydroxyvitamin D (25OH-D), PTH, and free deoxypyridinoline (DPD). Hip bone mineral status was measured using dual-energy X-ray absorptiometry (Lunar). There were significant differences (P < 0.001) in plasma 25OH-D and PTH concentrations between Shenyang and Cambridge [25OH-D nmol/L: Shenyang = 29.0 (SD 12.7), Cambridge = 35.7 (12.9)]; PTH ng/L: Shenyang = 34.3 (13.4), Cambridge = 25.2 (11.0)]. PTH was negatively related to 25OH-D in both populations. The relationship was exponential, best described by an inverse log-log equation with no break point (P < 0.001), indicating that the exponential curve did not tend toward a low plateau. PTH was higher for a given 25OH-D and decreased less with increasing 25OH-D in Shenyang than in Cambridge (country-ln25OH-D interaction, P = 0.0005). After adjusting for bone area, weight, height, age, and sex, hip bone mineral content (BMC) was significantly related to PTH concentration in Cambridge but not in Shenyang [femoral neck coefficient: Cambridge = −0.064 (SE 0.027), P = 0.02; Shenyang = −0.027 (0.028), P = 0.3; trochanter: Cambridge = −0.116 (0.034), P = 0.001; Shenyang = −0.019 (0.027), P = 0.5]. There was a significant country–lnPTH interaction at the trochanter (P = 0.02), but not at the femoral neck (P = 0.7). A weak positive association between BMC at the femoral neck and 25OH-D concentration was found in Cambridge [coefficient: 0.054 (0.028), P = 0.05] but not in Shenyang (coefficient: −0.013, P = 0.5; country–ln25OH-D interaction, P = 0.07). Urinary DPD concentration was also positively related to plasma PTH concentration in Cambridge subjects only [coefficient: 0.2 (0.08), P = 0.02]. These data suggest that although PTH increases when 25OH-D decreases, and Chinese people have a higher PTH for a given 25OH-D, older Chinese adults may be more resistant than Britons to the effects of PTH on bone. [Copyright &y& Elsevier]

• A model of anchorage strength with spread of the root plate as its main input was shown to be applicable for maize. • Increasing plant population reduced the anchorage and stem failure wind speeds, thus increasing lodging risk. • Changes in N fertiliser had a small effect on the lodging associated plant characters. • Stem and root failure wind speed were influenced most by variation in stem strength and root plate spread respectively. • Leaf area index measured at leaf 4, 6 or 8 stages was a good indicator of a crop's future risk of lodging. Lodging is a major constraint to increasing the global productivity of maize (Zea Maize L.). The objectives of this paper are to: i) describe a model for stem and root lodging in maize, ii) calibrate the anchorage strength component of the model, iii) evaluate the model's applicability by assessing its capacity to explain effects of crop husbandry on lodging risk and iv) investigate the potential to further develop the lodging model to predict lodging risk at an early enough growth stage for tactical agronomic action to minimise lodging risk. The study involved a multidisciplinary collaboration between crop scientists, wind engineers and geospatial scientists in the UK and China. Three field experiments with plant population density and nitrogen (N) fertiliser rate treatments were conducted in the UK and China to develop and test the lodging model. Plant characteristics associated with lodging were measured in the experiments after flowering. An existing model of cereal anchorage strength that uses the spread of the root plate as its primary input was demonstrated to be applicable for maize and calibrated for this crop species. The lodging model's predictions of the effects of plant population and N fertiliser on lodging risk were consistent with published observations. The lodging model calculated that increasing the plant population significantly reduced the anchorage and stem failure wind speeds in all experiments, thus increasing the risk of lodging. This effect was primarily due to increased plant population reducing the spread of the root plate and the stem strength. Changes in N fertiliser had a smaller effect on the lodging associated plant characters. A sensitivity analysis showed that stem failure wind speed was influenced most by variation in stem strength and root failure wind speed was influenced most by variation in the spread of the root plate. This study has shown that the leaf area index measured at leaf 4, 6 or 8 stages is a good indicator of a crop's future risk of lodging, which demonstrates the potential to develop the model into a practical tool for predicting lodging risk in time for tactical agronomic decisions to be made during the crop's growing period. [ABSTRACT FROM AUTHOR]

Background: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex., Methods: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models., Results: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (P interaction  < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape., Conclusions: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account., (© 2024. The Author(s).)

Objective: This study aims to prospectively examine the association between temperatures and the occurrence of type 2 diabetes (T2D)., Methods: We used the CPH models to analyze 103,215 non-diabetic participants in the UK Biobank cohort who answered questions about workplace temperature, to evaluate the survival relationship, and the interaction effects of working environmental temperature and T2D-related genetic risk scores (GRS) on the occurrence of T2D. The occurrence of T2D was assessed by hospital inpatient records. The weighted T2D-related GRS were calculated., Results: During 1,355,200.6 person-years follow-up, a total of 2436 participants were documented as having diagnosed T2D. After adjustment, compared to the comfortable group, the participants working in non-comfortable environmental temperature had greater risk of T2D (HR: 1.27, 95 %CI: 1.04 to 1.55, for cold; HR: 1.32, 95 %CI: 1.17 to 1.48 for hot; HR: 1.51, 95 %CI: 1.38 to 1.65 for alternate). Similarly, individuals exposed to different levels of genetic risk scores in alternating hot and cold work environments had a higher risk of developing type 2 diabetes., Conclusions: This study found working in single non-comfortable environmental temperatures was associated with greater risk of T2D occurrence, and exposure to alternating environmental temperatures had the highest risk of range and severity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.)

Background: Previous studies only focused on the individual social factors, without considering the overall social health patterns. The present study aimed to develop an integrated social health score (SHS) and investigate its associations with all-cause, cardiovascular disease (CVD), cancer mortality., Methods: A total of 330,716 participants (mean age 56.3 years; 52.4 % female) from UK Biobank was included between 2006 and 2010, and thereafter followed up to 2021. SHS was calculated by using information on social connections, social engagement and social support. Cox proportional hazards models was used to estimate the hazard ratios and 95 % confidence intervals (CIs) of the association between SHS and all-cause and cause-specific mortality and the 4-way decomposition was used to quantify the mediating effect of lifestyle factors., Results: During a median follow-up period of 12.4 years, 37,897 death cases were recorded, including 4347 CVD and 10,380 cancer cases. The SHS was inversely associated with the risks of all-cause, CVD and cancer mortality in a dose-dependent manner (P for trend <0.001). The association between SHS with all-cause mortality was mediated by lifestyle factors including diet score, smoking status and alcohol consumption., Conclusion: Integrated SHS was inversely associated with risks of all-cause, CVD and cancer mortality, and the associations were partially mediated by lifestyle factors. Our study highlights the importance of maintaining high levels of social health by jointly enhancing social involvement, expanding social networks, and cultivating enduring intimate relationships across the life course., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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/m 3 (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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Childhood trauma was known to increase risks of social isolation, loneliness and self-injurious thoughts and behaviors in adulthood. The aim of this study was to examine the protect and risk factors of social health, self-injurious thoughts and behaviors between adults with or without childhood trauma., Method: This was a cross-sectional study comprising of 145,043 participants enrolled in the UK Biobank. Childhood trauma was determined by the Childhood Trauma Screener. Social health included social isolation, loneliness and emotional support. Outcomes of self-injurious thoughts and behaviors included suicide ideation, suicide attempt and non-suicidal self-injury (NSSI). Demographic data, self-reported morbidities and other confounding variables were covariates. Stata 17.0 and SPSS 27.0 was used to analysis data., Results: Compared with participants without childhood trauma, there was no protective effect of emotional support for NSSI in participants with childhood trauma (β-value difference = 0.334, p = 0.008). The risk effect of loneliness for suicide ideation, suicide attempt and NSSI were also weaker in participants experiencing childhood trauma (p<0.05). Social isolation was no longer a risk factor for NSSI in all participants, while loneliness remained as a threat (p < 0.05)., Limitations: Many variables were measured using core items of the scale in UK Biobank, meanwhile, the childhood trauma data collected in adulthood may have recall bias., Conclusions: Adults reported childhood trauma were less vulnerable to self-injurious thoughts and behaviors when experiencing loneliness, but they could also not be protected from NSSI through emotional support. Emotional dysregulation caused by childhood trauma may contribute to this., Competing Interests: Declaration of competing interest All authors declared that there were no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Although previous research has indicated a correlation between smoking and the mortality rate in patients with lung cancer, the impact of early life factors on this relationship remains unclear and requires further investigation. This study aimed to investigate the hypothesis that breastfeeding reduces the risk of lung cancer-related death., Methods: The authors conducted a prospective cohort study involving 501 859 participants recruited from the United Kingdom Biobank to explore the potential association between breastfeeding and the risk of lung cancer mortality using a Cox proportional hazards model. Subsequently, the polygenic risk score for lung cancer was calculated to detect interactions between genes and the environment., Results: Over a median follow-up duration of 11.8 years, encompassing a total of 501 859 participants, breastfeeding was found to reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This association remained consistent after stratification. Furthermore, the influence of maternal smoking and breastfeeding on the risk of lung cancer mortality was significant at a high genetic risk level., Conclusion: Breastfeeding can reduce the risk of lung cancer-related death and the impact of maternal smoking on lung cancer mortality in adult offspring. This correlation has the potential to reduce the probability of lung-cancer-related deaths in subsequent generations., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort., Methods: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses., Results: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026)., Conclusions: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Aims: Evidence on weight transitions across life stages and cardiovascular diseases (CVDs) is limited. We aimed to explore weight transition patterns from birth to childhood to midlife and risk of incident CVDs., Methods: A total of 193,905 participants from the UK Biobank were included. Weight at birth, childhood, and midlife were collected at baseline (2006-2010). CVD outcomes were collected at year 2022. We constructed 27 transition patterns from birth to age 10 years to midlife. Cox proportional hazard models yielded hazard ratios (HRs) and 95% confidence intervals (CI) between weight transition patterns and CVDs. Mediation analyses were performed. Rate advancement periods (RAP) were also calculated., Results: Several weight transition patterns were clearly linked to risk of CVDs, including "Low birth weight → high weight at age 10 years → obesity at midlife" (HR 2.64, 95% CI 2.24-3.11), "Low birth weight → low weight at age 10 years → obesity at midlife" (2.27, 1.93-2.66), "High birth weight → low weight at age 10 years → obesity at midlife" (2.29, 1.96-2.67), and "High birth weight → high weight at age 10 years → obesity at midlife" (2.14, 1.89-2.42), which showed even stronger association with HF. RAPs of these patterns were 8.3-10.6 years for CVD and 10.0-13.1 for HF. 50% of the association between birth weight and CVDs was mediated by weight at midlife., Conclusions: Our findings highlight the importance of weight management throughout the life course in reducing the risk of CVDs, especially maintaining a heathy weight at midlife., Competing Interests: Declaration of competing interest All authors declare no conflict of interest for this contribution., (Copyright © 2023. Published by Elsevier Inc.)

Background : The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet is emerging as a promising candidate for preventive measures against inflammatory bowel disease (IBD), though there is currently no direct evidence from population-based studies. This study aims to bridge the gap in understanding of the association of the MIND diet with IBD risk. Methods : We utilized data from 187 490 participants in the UK Biobank who provided dietary information and were free of IBD at baseline. Dietary information was obtained using a validated web-based 24-hour dietary recall questionnaire. A MIND diet score was evaluated based on the intake of ten beneficial and five unhealthy food groups and the scores were further grouped into tertiles. The outcome of interest was incident IBD, Crohn's disease (CD), and ulcerative colitis (UC). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models adjusted for demographic characteristics, lifestyle factors, cancer history, and other dietary factors. Mediation analyses were performed to evaluate the role of systemic inflammation and metabolic disorders represented by the integrated biomarkers in the MIND diet-IBD association. Results : After a mean follow-up of 10.7 years, we documented 825 incident IBD cases (250 CD and 575 UC). The average age of the participants was 56.2 years, of which 55.0% were females. We found that greater adherence to the MIND diet, represented by a higher diet score, was associated with a lower risk of IBD (HR comparing extreme tertiles 0.74, 95% CI 0.62-0.90, p = 0.002; p for trend = 0.005), CD (HR 0.66, 95% CI 0.47-0.94, p = 0.022; p for trend = 0.023), and UC (HR 0.78, 95% CI 0.62-0.98, p = 0.031; p for trend = 0.022). The associations were partially mediated by metabolic and inflammation status (mediation proportion: 5.5-15.9%). Conclusion : We found higher adherence to the MIND diet was associated with a lower risk of IBD, and that inflammatory and metabolic conditions may play an important role in the underlying mechanistic pathways.

Study Objectives: To investigate the role of longitudinal change of sleep patterns in the incidence of cardiovascular diseases (CVD)., Methods: Based on UK Biobank, a total of 18 172 participants were enrolled. Five dimensions of healthy sleep including early chronotype, sleep 7-8 hours/day, free of insomnia, no snoring, and no frequent excessive daytime sleepiness were used to generate a healthy sleep score (HSS) ranging from 0 to 5. Corresponding to the HSS of 0-1, 2-3, and 4-5, the poor, intermediate, and healthy sleep patterns were defined. Based on changes in HSS across assessments 1 and 2, we calculated the absolute difference of HSS. For the change in sleep patterns, we categorized five profiles (stable healthy, worsening, stable intermediate, optimizing, and stable poor sleep patterns). The outcomes were incidence of CVD including coronary heart disease (CHD) and stroke. We assessed the adjusted hazard ratios and 95% confidence intervals (CIs) by Cox hazard models., Results: Compared with participants with stable poor patterns, those who improved their sleep patterns or maintained healthy sleep patterns had a 26% and 32% lower risk of CVD, respectively. Stable healthy sleep pattern was associated with a 29% and 44% reduced risk of CHD and stroke. Per unit, longitudinal increment of the HSS was related to an 8% lower risk of CVD and CHD. Compared with individuals with constant HSS, those with decreased HSS had a 13% higher risk of developing CVD., Conclusions: Optimizing sleep patterns and maintaining a healthy sleep pattern may reduce the risk of CVD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex-specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized. The association of sleep duration and predicted age followed a U-shape (All p for nonlinear <0.05). Compared with individuals who sleep for 7 h/day, the multivariable-adjusted beta of ≤5 and ≥9 h/day were 0.05 (95% CI 0.03, 0.07) and 0.03 (95% CI 0.02, 0.05) for HD, 0.08 (95% CI 0.01, 0.14) and 0.36 (95% CI 0.31, 0.41) for PA, and 0.21 (95% CI 0.12, 0.30) and 0.30 (95% CI 0.23, 0.37) for KDM. Significant independent and joint effects of sleep and cystatin C (CysC) and gamma glutamyltransferase (GGT) on predicted age metrics were future found. Similar results were observed when conducting stratification analyses. Short and long sleep duration were associated with accelerated predicted age metrics mediated by CysC and GGT., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Although the beneficial properties of vitamin D in anti-inflammation and immunity-modulation are promising in the management of inflammatory bowel disease (IBD), data were limited for the critical IBD prognosis. The association between serum vitamin D levels and the risk of bowel resection in individuals with IBD remains largely unknown., Materials and Methods: The authors performed a longitudinal cohort study among 5474 individuals with IBD in the UK Biobank. Serum 25-hydroxyvitamin D [25(OH)D] was measured using direct competitive chemiluminescent immunoassay. Bowel resection events were ascertained via national inpatient data. Multivariable-adjusted Cox proportional hazard regression was used to examine the association between serum 25(OH)D and bowel resection risk, presented with hazard ratios (HRs) and 95% CIs. Restricted cubic spline (RCS) was used to evaluate dose-response associations., Results: During a mean follow-up of 13.1 years, the authors documented 513 incident bowel resection cases. Compared to participants with vitamin D deficiency, nondeficient participants showed a significantly reduced bowel resection risk in IBD (HR 0.72, 95% CI: 0.59-0.87, P =0.001), Crohn's disease (CD, HR 0.74, 95% CI: 0.56-0.98, P =0.038), and ulcerative colitis (UC, HR 0.73, 95% CI: 0.57-0.95, P =0.020). When comparing extreme quintiles of 25(OH)D level, participants with IBD showed a 34% reduced risk of bowel resection (95% CI: 11-51%, P =0.007) and participants with UC showed a 46% reduced risk (95% CI: 19-64%, P =0.003), while this association was not significant in CD (HR 0.93, 95% CI: 0.59-1.45, P =0.740). Linear dose-response associations were observed using the RCS curve (all P -nonlinearity>0.05)., Conclusion: Increased serum level of 25(OH)D is independently associated with reduced bowel resection risk in IBD. This association was significant in UC but may not be stable in CD. Vitamin D deficiency is a risk factor for bowel resection in individuals with IBD, and may be an effective metric in predicting and risk-screening surgical events., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Walking pace is associated with risks of major chronic diseases including cancer, cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) in the general population. However, whether increasing walking pace could reduce risks of major chronic diseases in individuals with hypertension remains to be explored, and the underlying mechanism potentially mediated by low-grade inflammation is also unclear., Methods: A total of 160,470 participants with hypertension were included based on the UK Biobank. The relationships of the walking pace and low-grade inflammation with risks of major chronic diseases in individuals with hypertension were assessed by the Cox proportional hazards model. Mediation analyses were performed to investigate the contribution of low-grade inflammation to the association between walking pace and risks of major chronic diseases., Results: Individuals with hypertension at the brisk walking pace had decreased risks of overall cancer and site-specific cancers (liver, lung, and endometrial cancers), all CVD events (angina, atrial fibrillation, heart failure, myocardial infarction, peripheral vascular disease and stroke), and T2DM (hazard ratios: 0.42-0.91). Increasing low-grade inflammation was associated with higher risks of aforementioned diseases except liver cancer and atrial fibrillation. Furthermore, low-grade inflammation partially mediated associations of the walking pace with risks of lung cancer, T2DM, and all CVD events (except atrial fibrillation), with mediation proportion of 2.0%-9.8%., Conclusions: Brisk walking pace was linked to reduced risks of major chronic diseases in individuals with hypertension, partially mediated by low-grade inflammation. Improving walking pace may be beneficial for health in individuals with hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Epidemiological evidence regarding the association between air pollutants and cardiopulmonary disease, mortality in individuals with preserved ratio impaired spirometry (PRISm), and their combined effects remains unclear., Methods: We followed 36,149 participants with PRISm in the UK Biobank study. Annual concentrations of PM 2.5 , PM 10 , NO 2 , NO x , and SO 2 at residential addresses were determined using a bilinear interpolation method, accounting for address changes. A multistate model assessed the dynamic associations between air pollutants and cardiopulmonary diseases and mortality in PRISm. Quantile g-computation was used to investigate the joint effects of air pollutants., Results: Long-term exposure to PM 2.5 , PM 10 , NO 2 , NO x , and SO 2 was significantly associated with the risk of cardiopulmonary disease in PRISm. The corresponding hazard ratios (HRs) [95 % confidence intervals (95 % CIs)] per interquartile range (IQR) were 1.49 (1.43, 1.54), 1.52 (1.46, 1.57), 1.34 (1.30, 1.39), 1.30 (1.26, 1.34), and 1.44 (1.41, 1.48), respectively. For mortality, the corresponding HRs (95 % CIs) per IQR were 1.36 (1.25, 1.47), 1.35 (1.24, 1.46), 1.27 (1.18, 1.36), 1.23 (1.15, 1.31), and 1.29 (1.20, 1.39), respectively. In PRISm, quantile g-computation analysis demonstrated that a quartile increase in exposure to a mixture of all air pollutants was positively associated with the risk of cardiopulmonary disease and mortality, with HRs (95 % CIs) of 1.84 (1.76, 3.84) and 1.45 (1.32, 1.57), respectively., Conclusion: Long-term individual and joint exposure to air pollutants (PM 2.5 , PM 10 , NO 2 , NO x , and SO 2 ) might be an important risk factor for cardiopulmonary disease and mortality in high-risk populations with PRISm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms., Methods: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis., Results: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (P trend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (P trend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer., Conclusions: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators., Methods: We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5-7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV 1 %) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV 1 /FVC <0.7)., Results: Among participants who underwent baseline and follow-up spirometry, we identified 233 patients with RA and 37 735 non-RA comparators. Among never-smoking participants without an obstructive pattern, RA was significantly associated with more FEV 1 % decline (β=-0.49, p=0.04). However, in ever smokers with ≥10 pack-years, those with RA exhibited significantly less FEV 1 % decline than non-RA comparators (β=0.50, p=0.02). This difference was more pronounced among those with an obstructive pattern at baseline (β=1.12, p=0.01). Results were similar for FEV 1 /FVC decline. No difference was observed in the annual FVC% change in RA versus non-RA., Conclusions: Smokers with RA, especially those with baseline obstructive spirometric patterns, experienced lower FEV 1 % and FEV 1 /FVC decline than non-RA comparators. Conversely, never smokers with RA had more FEV 1 % decline than non-RA comparators. Future studies should investigate potential treatments and the pathogenesis of obstructive lung diseases in smokers with RA., Competing Interests: Competing interests: PAJ reports grant funding and other support from Novartis, Galapagos and Boehringer Ingelheim, unrelated to this work. MM reports institutional grant support from Bayer and Honoraria from Chickasaw Nation. MHC has received grant funding from Bayer, unrelated to this work. TJD received support from Bayer and has been part of a clinical trial funded by Genentech, unrelated to this study. PFD reports grant funding from Bristol Myers Squibb. ZW has received grant funding from Bristol-Myers Squibb and Principia/Sanofi and consulting fees from Viela Bio, Zenas BioPharma, Horizon Therapeutics, Sanofi, MedPace, BioCryst, Amgen, Nkarta, Inc, Adicet Bio, and Therapeutic’s and participation in data safety monitoring board or advisory board for Sanofi, Horizon, Novartis, Visterra/Otsuka and Shionogi, unrelated to this work. GMH reports consulting fees from Boehringer-Ingelheim, and the Gerson Lehrman Group, unrelated to this work. EKS has received grant support from Bayer and Northpond Laboratories, unrelated to this work. SYA reports consulting fees from Verona Pharmaceuticals and Vertex Pharmaceuticals and is cofounder and co-owner of Quantitative Imaging Solutions. RSJE reports contracts from Lung Biotechnology and Insmed, received a grant support from Boehringer Ingelheim and is cofounder and an equity holder of Quantitative Imaging Solutions. GRW reports grants from Boehringer Ingelheim, consultancy for Pulmonx, Janssen Pharmaceuticals, Novartis, and Vertex, and is founder and co-owner of Quantitative Imaging Solutions. JS has received research support from Bristol Myers Squibb and performed consultancy for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, Pfizer, ReCor, Sobi, and UCB, unrelated to this work. Other authors report no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain., Methods: This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as estimated glomerular filtration rate between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis., Results: During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12-1.19; HR 1.29, 95% CI 1.20-1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR 1.61, 95% CI 1.52-1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI 0.05-0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function., Conclusions: The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Peripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer's disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts., Methods: This was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates., Results: A subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels., Conclusions: These results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits., (© 2024. The Author(s).)

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.)

Remnant cholesterol (RC) has been associated with atherosclerotic cardiovascular disease, but its relationship with hypertension remains unclear. This prospective cohort study aimed to investigate the association between RC and subsequent hypertension risk. Data from the UK Biobank, comprising 295,062 participants initially free of hypertension, were analyzed. Cox proportional hazards regression assessed the association between RC quartiles and hypertension risk. Discordance analysis evaluated the risk of hypertension in discordant/concordant groups of RC and low-density lipoprotein cholesterol (LDL-C) using the difference in percentile units (>10 units). Restricted cubic spline curves were used to model the relationship between RC and hypertension risk. The mean ± SD age of participants was 55.1 ± 8.1 years, with 40.6% being men and 94.7% White. During a median follow-up of 12.8 years, 39,038 participants developed hypertension. Comparing extreme quartiles of RC, the hazard ratio (HR) for incident hypertension was 1.20 (95% CI: 1.17-1.24). After adjusting for traditional risk factors, each 1 mmol/L increase in RC levels was associated with a 27% higher risk of incident hypertension (HR: 1.27; 95% CI: 1.23-1.31). The discordant group with high RC/low LDL-C exhibited a higher risk of incident hypertension compared to the concordant group (HR: 1.06; 95% CI: 1.03-1.09). Spline curves further demonstrated a positive association between RC and the risk of incident hypertension. We concluded that elevated RC emerged as an independent risk factor of incident hypertension, extending beyond traditional risk factors. Monitoring RC levels and implementing interventions to lower RC may have potential benefits in preventing hypertension., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Abstract: Bendamustine is among the most effective chemotherapeutics for indolent B-cell non-Hodgkin lymphomas (iNHL), but trial reports of significant toxicity, including opportunistic infections and excess deaths, led to prescriber warnings. We conducted a multicenter observational study evaluating bendamustine toxicity in real-world practice. Patients receiving at least 1 dose of bendamustine with/without rituximab (R) for iNHL were included. Demographics, lymphoma and treatment details, and grade 3 to 5 adverse events (AEs) were analyzed and correlated. In total, 323 patients were enrolled from 9 National Health Service hospitals. Most patients (96%) received bendamustine-R, and 46%, R maintenance. Overall, 21.7% experienced serious AEs (SAE) related to treatment, including infections in 12%, with absolute risk highest during induction (63%), maintenance (20%), and follow-up (17%) and the relative risk highest during maintenance (54%), induction (34%), and follow-up (28%). Toxicity led to permanent treatment discontinuation for 13% of patients, and 2.8% died of bendamustine-related infections (n = 5), myelodysplastic syndrome (n = 3), and cardiac disease (n = 1). More SAEs per patient were reported in patients with mantle cell lymphoma, poor preinduction performance status (PS), poor premaintenance PS, and abnormal preinduction total globulins and in those receiving growth factors. Use of antimicrobial prophylaxis was variable, and 3 of 10 opportunistic infections occurred despite prophylaxis. In this real-world analysis, bendamustine-related deaths and treatment discontinuation were similar to those of trial populations of younger, fitter patients. Poor PS, mantle cell histology, and maintenance R were potential risk factors. Infections, including late onset events, were the most common treatment-related SAE and cause of death, warranting extended antimicrobial prophylaxis and infectious surveillance, especially for maintenance-treated patients., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Aims: This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D)., Materials and Methods: In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D., Results: During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HR RA  = 2.06, 95% CI: 1.76-2.41; HR M10  = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HR RA  = 4.46, 95% CI: 3.36-6.42; HR M10  = 3.15, 95% CI: 2.29-4.32; HR L5  = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05)., Conclusion: The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D., (© 2023 John Wiley & Sons Ltd.)

Background: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk., Methods: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model., Results: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males., Conclusions: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population., (© 2023. The Author(s).)

Background: Although many studies have reported on the associations between the amount of physical activity (PA) and the transitions of cardiometabolic multimorbidity (CMM), the evidence for PA intensity has not been fully evaluated., Objective: This study aimed to explore the impact of PA intensity on the dynamic progression of CMM., Methods: The prospective cohort of this study using data from the UK Biobank included 359,773 participants aged 37-73 years who were recruited from 22 centers between 2006 and 2010. The diagnoses of CMM, which included the copresence of type 2 diabetes (T2D), ischemic heart disease, and stroke, were obtained from first occurrence fields provided by the UK Biobank, which included data from primary care, hospital inpatient record, self-reported medical condition, and death registers. The PA intensity was assessed by the proportion of vigorous PA (VPA) to moderate to vigorous PA (MVPA). Multistate models were used to evaluate the effect of PA intensity on the dynamic progression of CMM. The first model (model A) included 5 transitions, namely free of cardiometabolic disease (CMD) to first occurrence of CMD (FCMD), free of CMD to death, FCMD to CMM, FCMD to mortality, and CMM to mortality. The other model (model B) used specific CMD, namely T2D, ischemic heart disease, and stroke, instead of FCMD and included 11 transitions in this study., Results: The mean age of the included participants (N=359,773) was 55.82 (SD 8.12) years at baseline, and 54.55% (196,271/359,773) of the participants were female. Compared with the participants with no VPA, participants with intensity levels of >0.75 to <1 for VPA to MVPA had a 13% and 27% lower risk of transition from free of CMD to FCMD (hazard ratio [HR] 0.87, 95% CI 0.83-0.91) and mortality (HR 0.73, 95% CI 0.66-0.79) in model A, respectively. The HR for the participants with no moderate PA was 0.82 (95% CI 0.73-0.92) compared with no VPA. There was a substantially protective effect of higher PA intensity on the transitions from free of CMD to T2D and from T2D to mortality, which reveals the importance of PA intensity for the transitions of T2D. More PA and greater intensity had a synergistic effect on decreasing the risk of the transitions from free of CMD to FCMD and mortality. Male participants, younger adults, adults with a higher BMI, current or previous smokers, and excessive alcohol drinkers could obtain more benefits from higher PA intensity for the lower risk of at least 1 transition from free of CMD, then to CMM, and finally to mortality., Conclusions: This study suggests that higher PA intensity is an effective measure for preventing CMM and mortality in the early period of CMM development. Relevant interventions related to higher PA intensity should be conducted., (©Bao-Peng Liu, Jia-Hui Zhu, Li-Peng Wan, Zhen-Yu Zhao, Xinting Wang, Cun-Xian Jia. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 25.09.2023.)

Objectives: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases., Design: Retrospective cohort study., Setting: UK Biobank., Participants: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex., Exposure: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank., Primary and Secondary Outcome Measures: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively., Results: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p < 0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p < 0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p < 0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p < 0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups., Conclusion: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Background: The link between ambient air pollution and the incidence of hypertension, diabetes, and chronic kidney disease (CKD) has been widely studied. However, the associations of air pollution with the dynamic progression to multimorbidity and mortality of these diseases are unknown., Methods: This study included 162,334 participants from the UK Biobank. Multimorbidity was defined as the coexistence of at least two of hypertension, diabetes, and CKD. Land use regression was used to estimate annual concentrations of particulate matter (PM 2.5 ), PM 10 , nitrogen dioxide (NO 2 ), and nitrogen oxides (NO x ). Multi-state models were used to assess the association between ambient air pollutants and the dynamic progression of hypertension, diabetes, and CKD., Results: During a median follow-up of 11.7 years, 18,496 participants experienced at least one of hypertension, diabetes, and CKD, 2216 experienced multimorbidity, and 302 died afterwards. We observed differential associations of four air pollutants on different transitions from healthy status to incident disease (hypertension, diabetes, or CKD), to multimorbidity, and to death. The hazard ratios (HRs) of each IQR increment in PM 2.5 , PM 10 , NO 2 , and NO x for the transition to incident disease were 1.07 [95 % confidence intervals (CI): 1.04, 1.09], 1.02 (1.00, 1.03), 1.07 (1.04, 1.09), and 1.05 (1.03, 1.07), but the associations with the transition to death were significant for NO x only [HR: 1.04 (95 % CI: 1.01, 1.08)]., Conclusions: Air pollution exposure might be one important determinant for the incidence and dynamic progression of hypertension, diabetes, and CKD, suggesting that more attention should be paid to ambient air pollution control in the prevention of hypertension, diabetes, and CKD, as well as their progression., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background & Aims: Physical activity, sedentary behaviour, and genetic variants have been associated with the nonalcoholic fatty liver disease (NAFLD). However, whether and how the degree of healthy activity patterns may modify the impact of genetic susceptibility on NAFLD remains unknown., Methods: Behaviour activity factors were determined according to total physical activity (TPA) and sedentary time. The polygenic risk score (PRS) was calculated by variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Cox regression was used to analyse the associations of genetic and behaviour activity factors with incident NAFLD in the UK Biobank (N = 338 087)., Results: During a median follow-up of 12.4 years, 3201 incident NAFLD cases were ascertained. Analyses of TPA and sedentary time simultaneously showed a dose-response association with the risk of NAFLD (p trend  < .001). The association of behaviour activity patterns with NAFLD varied by genetic variants. Of the subjects with high genetic risk, we observed a null protective effect of moderate or high TPA on NAFLD risk, while sitting less than three hours a day significantly decreased the risk of NAFLD (p = 3.50 × 10 -4 ). The high genetic risk of NAFLD can also be offset by the combination of moderate physical activity and shorter sedentary time. Moreover, the high genetic risk group has the greatest reduction of 10-year absolute risk (6.95 per 1000 person-years) if reaching both healthy activities., Conclusions: Moderate-to-high physical activity and favourable sedentary behaviour may be lifestyle modifications in preventing NAFLD, which could offset the harmful effect of predisposing genetic factors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Compared with adults with normal glucose metabolism, those with prediabetes tend to be frail. However, it remains poorly understood whether frailty could identify adults who are most at risk of adverse outcomes related to prediabetes., Objective: We aimed to systematically evaluate the associations between frailty, a simple health indicator, and risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), diabetes-related microvascular disease, cardiovascular disease (CVD), chronic kidney disease (CKD), eye disease, dementia, depression, and all-cause mortality in late life among middle-aged adults with prediabetes., Methods: We evaluated 38,950 adults aged 40 years to 64 years with prediabetes using the baseline survey from the UK Biobank. Frailty was assessed using the frailty phenotype (FP; range 0-5), and participants were grouped into nonfrail (FP=0), prefrail (1≤FP≤2), and frail (FP≥3). Multiple adverse outcomes (ie, T2DM, diabetes-related microvascular disease, CVD, CKD, eye disease, dementia, depression, and all-cause mortality) were ascertained during a median follow-up of 12 years. Cox proportional hazards regression models were used to estimate the associations. Several sensitivity analyses were performed to test the robustness of the results., Results: At baseline, 49.1% (19,122/38,950) and 5.9% (2289/38,950) of adults with prediabetes were identified as prefrail and frail, respectively. Both prefrailty and frailty were associated with higher risks of multiple adverse outcomes in adults with prediabetes (P for trend <.001). For instance, compared with their nonfrail counterparts, frail participants with prediabetes had a significantly higher risk (P<.001) of T2DM (hazard ratio [HR]=1.73, 95% CI 1.55-1.92), diabetes-related microvascular disease (HR=1.89, 95% CI 1.64-2.18), CVD (HR=1.66, 95% CI 1.44-1.91), CKD (HR=1.76, 95% CI 1.45-2.13), eye disease (HR=1.31, 95% CI 1.14-1.51), dementia (HR=2.03, 95% CI 1.33-3.09), depression (HR=3.01, 95% CI 2.47-3.67), and all-cause mortality (HR=1.81, 95% CI 1.51-2.16) in the multivariable-adjusted models. Furthermore, with each 1-point increase in FP score, the risk of these adverse outcomes increased by 10% to 42%. Robust results were generally observed in sensitivity analyses., Conclusions: In UK Biobank participants with prediabetes, both prefrailty and frailty are significantly associated with higher risks of multiple adverse outcomes, including T2DM, diabetes-related diseases, and all-cause mortality. Our findings suggest that frailty assessment should be incorporated into routine care for middle-aged adults with prediabetes, to improve the allocation of health care resources and reduce diabetes-related burden., (©Xingqi Cao, Xueqin Li, Jingyun Zhang, Xiaoyi Sun, Gan Yang, Yining Zhao, Shujuan Li, Emiel O Hoogendijk, Xiaofeng Wang, Yimin Zhu, Heather Allore, Thomas M Gill, Zuyun Liu. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 18.05.2023.)

Background and Aims: Ultra-processed food [UPF] consumption has been linked to globally increasing incidence and prevalence of chronic diseases, including inflammatory bowel diseases [IBD]. We aimed to investigate the association between UPF consumption and IBD incidence, prevalence, and IBD-relevant outcomes., Methods: We performed a cross-sectional and prospective cohort study in 187 854 individuals included in the national UK Biobank, using 24-h dietary recall questionnaires. Multivariable logistic regression and Cox proportional hazard regression were used to examine the association between UPFs and the prevalence and incidence risk of IBD, respectively., Results: A total of 185 849 participants with a mean age of 56.2 were included, with a mean follow-up of 9.84 years. During follow-up, 841 developed IBD (251 Crohn's disease [CD], and 590 ulcerative colitis [UC]). UPF intake in IBD patients was significantly higher: CD: odds ratio [OR] 1.94 (95% confidence interval [CI]: 1.52, 2.49, p <0.001); UC: OR 1.39 [95% CI: 1.17, 1.65, p <0.001]. Compared with low consumption, higher UPF consumption was significantly associated with incident CD: hazard ration [HR] 2.00 [95% CI: 1.32, 3.03, p = 0.001], but not UC. We also found a significant association between UPF intake and need of IBD-related surgery: HR 4.06 [95% CI: 1.52, 10.86, p = 0.005]., Conclusion: Higher intake of UPFs was associated with higher incidence of CD, but not UC. In individuals with a pre-existing diagnosis of IBD, consumption of UPFs was significantly higher compared with controls, and was associated with an increased need for IBD-related surgery. Further studies are needed to address the impact of UPF intake on disease pathogenesis and outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

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.

Objectives: In this study designed to investigate the effect of diet and gut microbiome on neuropsychiatric disorders, we explored the mechanisms of the interaction between diet and gut microbiome on the risk of neuroticism., Methods: First, using the individual genotype data from the UK Biobank cohort (N = 306 165), we calculated the polygenic risk score (PRS) based on 814 dietary habits single nucleotide polymorphisms (SNPs), 21 diet compositions SNPs and 1001 gut microbiome SNPs, respectively. Gut microbiome and diet-associated SNPs were collected from three genome-wide association studies (GWAS), including the gut microbiome (N = 3890), diet compositions (over 235 000 subjects) and dietary habits (N = 449 210). The neuroticism score was calculated by 12 questions from the Eysenck Personality Inventory Neuroticism scale. Then, regression analysis was performed to evaluate the interaction effects between diet and the gut microbiome on the risk of neuroticism., Results: Our studies demonstrated multiple candidate interactions between diet and gut microbiome, such as protein vs. Bifidobacterium (β = 4.59 × 10-3; P = 9.45 × 10-3) and fat vs. Clostridia (β = 3.67 × 10-3; P = 3.90 × 10-2). In addition, pieces of fresh fruit per day vs. Ruminococcus (β = -5.79 × 10-3, P = 1.10 × 10-3) and pieces of dried fruit per day vs. Clostridiales (β = -5.63 × 10-3, P = 1.49 × 10-3) were found to be negatively associated with neuroticism in fruit types. We also identified several positive interactions, such as tablespoons of raw vegetables per day vs. Veillonella (β = 5.92 × 10-3, P = 9.21 × 10-4) and cooked vegetables per day vs. Acidaminococcaceae (β = 5.69 × 10-3, P = 1.24 × 10-3)., Conclusions: Our results provide novel clues for understanding the roles of diet and gut microbiome in the development of neuroticism., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Genetic factors and muscle strength both contribute to the risk of major depressive disorder (MDD), but whether high muscle strength can offset the risk of MDD with different genetic risk is unknown. This study aims to examine whether a higher muscle strength is associated with lower risk of MDD regardless of genetic risk among middle-aged and older adults., Methods: This cohort study obtained data from the UK Biobank, which includes 345,621 individuals aged 40-69 years (mean (standard deviation): 56.7 (7.99) years) without baseline MDD. Polygenic risk score for MDD was categorised as low, intermediate or high. The mean of the right- and left-hand grip strength values was used in the analysis and was divided into three categories., Results: 9,753 individuals developed MDD within 2,752,461 person-years of follow-up. The multivariable adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of MDD across increased grip strength categories were 1.00, 0.72 (0.68-0.75) and 0.56 (0.53-0.59) (P for trend <0.0001). The HRs (95% CIs) of incident MDD across the genetic risk categories were 1.00, 1.11 (1.05-1.17) and 1.20 (1.13-1.28) (P for trend <0.0001); 4.07% of individuals with a high genetic risk and low grip strength developed MDD, and 1.72% of individuals with a low genetic risk and high grip strength developed MDD, with an HR (95% CI) of 0.44 (0.39-0.50)., Conclusions: Both muscle strength and genetic risk were significantly associated with incident MDD. A higher muscle strength was associated with a lower MDD risk among individuals with a high genetic risk. Improving muscle strength should be encouraged for all individuals, including individuals with high genetic risk for MDD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Evidence is limited regarding the association between lifestyles and cardiovascular disease (CVD), and the extent to which healthy lifestyles could offset the genetic risk of CVD in females with breast cancer (BC)., Methods: Females diagnosed as BC, who were free of CVD at baseline, from UK Biobank were included. Five modifiable lifestyle factors were considered to calculate the healthy lifestyle score, namely body mass index (BMI), smoking, alcohol drinking, dietary habits, and physical activity. The polygenetic risk score (PRS) was derived for coronary heart disease (CHD), ischemic stroke (IS), and heart failure (HF)., Results: In 13,348 female BC survivors, there were 986 CVD events (736 CHD, 165 IS, and 353 HF) over a median of 8.01 years of follow-up. Participants with 4-5 healthy lifestyle components were associated with a decreased risk of incident CVD (HR: 0.50; 95%CI: 0.37, 0.66), CHD (HR: 0.49; 95%CI: 0.35, 0.69), IS (HR: 0.35; 95%CI: 0.19, 0.65), and HF (HR: 0.59; 95%CI: 0.36, 0.97), compared with those with 0-1 lifestyle components. Evidence for the genetic-lifestyle interaction was observed for CHD ( p = 0.034) and HF ( p = 0.044). Among participants at high genetic risk, a healthy lifestyle was associated with a lower risk of CHD (HR: 0.37; 95%CI: 0.24, 0.56), IS (HR: 0.37; 95%CI: 0.15, 0.93) and HF (HR: 0.39; 95%CI: 0.21, 0.73)., Conclusions: Our findings suggest that BC survivors with a high genetic risk could benefit more from adherence to a healthy lifestyle in reducing CVD risk.

Background and aims : Onions have shown antidepressant effects but relevant evidence from people was limited. Thus, we aimed to explore the prospective association between onion consumption and risk of depressive symptoms in the general population. Methods : We used data from 2 cohorts: the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) cohort included 7739 participants (males, 57.6%) with a mean age of 39.5 years, and the UK Biobank included 169 806 individuals (males, 45.2%) with a mean age of 55.7 years. In the TCLSIH cohort, onion consumption was assessed by a validated food frequency questionnaire from May 2013; depressive symptoms were evaluated by the Chinese version of the Self-Rating Depression Scale (SDS scores ≥ 45) and were assessed up to 2018. In the UK Biobank, onion consumption was measured by 1-5 times validated 24-hour dietary recalls in 2006-2010; depressive symptoms were determined through the linked hospital records and death registries and were assessed up to 2018. Multivariable Cox proportional hazards models were employed to determine the association between onion consumption and risk of depressive symptoms. Results : A total of 1098 and 1924 cases of depressive symptoms were identified during 15 004 person-years and 1 243 832 person-years of follow-up in the TCLSIH cohort and the UK Biobank, respectively. After adjusting for many confounding factors, the fully adjusted HRs (95% CI) of depressive symptoms comparing the higher levels to the lowest level of onion consumption were 0.78 (0.65, 0.94), 0.73 (0.61, 0.87), and 0.77 (0.64, 0.92) in the TCLSIH cohort ( p for trend = 0.01); and were 0.79 (0.68, 0.93), 0.81 (0.69, 0.94), and 0.97 (0.85, 1.12) in the UK Biobank ( p for trend = 0.07). Similar associations were observed in the sensitivity analyses. Conclusion : Our results indicated that habitual onion consumption was associated with a lower risk of depressive symptoms in two cohorts. However, this association was not statistically significant in the highest level of onion consumption in the UK Biobank.

Although the possession of instrumentality (i.e., partner B being useful to partner A's goal pursuit) can facilitate relationship satisfaction, taking an instrumental approach (i.e., A focusing on B's usefulness and seeing B as a tool to facilitate personal goal attainment) is (often) considered as a callous and depersonalized approach to forming relationships. The current research examined whether adopting an exchange orientation amplifies the tendency for people to take an instrumental approach via the motive to maximize self-gain. Four studies (N = 1446) utilizing samples across different countries, including the United Kingdom, the United States and China, supported this hypothesis. Specifically, during relationship initiation, an exchange (vs. non-exchange) orientation made participants place higher importance on instrumentality rather than traits facilitating intimacy and bonding (Study 1). For established relationships, participants who chronically adopted an exchange orientation (Study 2) and who were temporarily induced to do so (vs. control; Study 3) were more likely to view their significant other as a tool. The final quasi-experiment (Study 4) showed that requiring or being required to offer a bride price - an embodiment of exchange orientation - predicted instrumentality in marriage and subsequently impaired relationship satisfaction. Implications are discussed., (© 2022 The British Psychological Society.)

The reemergence of monkeypoxvirus (MPXV) in 2017 after about 39 years of no reported cases in Nigeria, and the recent incidence in countries such as the United States of America, United Kingdom, Singapore, and Israel which have been reportedly linked with travelers from Africa, have heightened concern that MPXV may have emerged to occupy the vacant ecological and immunological niche created by the extinct smallpox virus. This study was carried out to identify environmental conditions and areas that are environmentally suitable (risky areas) for MPXV in southern Nigeria. One hundred and sixteen (116) spatially unique MPXV occurrence data from 2017-2021 and corresponding environmental variables were spatially modeled by a maximum entropy algorithm to evaluate the contribution of the variables to the distribution of the viral disease. A variance inflation analysis was adopted to limit the number of environmental variables and minimize multicollinearity. The five variables that contributed to the suitability model for MPXV disease are precipitation of driest quarter (47%), elevation (26%), human population density (17%), minimum temperature in December (7%), and maximum temperature in March (3%). For validation, our model had a high AUC value of 0.92 and standard deviation of 0.009 indicating that it had excellent ability to predict the suitable areas for monkeypox disease. Categorized risk classes across southern states was also identified. A total of eight states were predicted to be at high risk of monkeypox outbreak occurrence. These findings can guide policymakers in resources allocation and distribution to effectively implement targeted control measures for MPXV outbreaks in southern Nigeria., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aims to compare the differences in COVID-19 prevention and control policies adopted by the United Kingdom (UK) during the first wave (31 January 2020 to 6 September 2020) and the second wave (7 September 2020 to 12 April 2021), and analyze the effectiveness of the policies, so as to provide empirical experience for the prevention and control of COVID-19. Methods We systematically summarized the pandemic prevention and control policies of the UK from official websites and government documents, collated the epidemiological data from 31 January 2020 to 12 April 2021, and analyzed the effectiveness of the two waves of pandemic prevention and control policies., Results: The main pandemic prevention and control policies adopted by the UK include surveillance and testing measures, border control measures, community and social measures, blockade measures, health care measures, COVID-19 vaccination measure, and relaxed pandemic prevention measures. The new cases per day curve showed only one peak in the first wave and two peaks in the second wave. The number of new cases per million in the second wave was much higher than that in the first wave, and the curve fluctuated less. The difference between mortality per million was small, and the curve fluctuated widely., Conclusion: During the first and second waves of COVID-19, the UK implemented three lockdowns and managed to slow the spread of the pandemic. The UK's experience in mitigating the second wave proves that advancing COVID-19 vaccination needs to be accompanied by ongoing implementation of non-pharmacological interventions to reduce the transmission rate of infection. And a stricter lockdown ensures that the containment effect is maximized during the lockdown period. In addition, these three lockdowns featured distinct mitigation strategies and the UK's response to COVID-19 is mitigation strategy that reduce new cases in the short term, but with the risk of the pandemic rebound., (© 2022. The Author(s).)

Over the last few decades, the annual air pollutants from internal combustion engine (ICE) vehicles have dropped significantly, benefiting from the implementation of strict emission regulations and the development of vehicle technology. Nitrogen oxides (NO x ) and particulate matter (PM) emissions from transport sectors contributed more than 32% and 12% of annual total emissions. Although hazardous exhaust emissions from ICE vehicles will be reduced after the bans on ICE vehicle sales in 2030, sustainable technology development of ICE vehicles is still necessary to meet the future challenges. After-treatment retrofitting technology and Inspection/Maintenance (I/M) are particularly important measures to deal with the deterioration of engines and after-treatment systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)