Maternal smoking during pregnancy could accelerate aging in the adulthood: evidence from a perspective study in UK Biobank.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is significantly linked to the short- or long-term health of offspring. However, little research has examined whether MSDP affect the aging rate of offspring. METHODS: This study used questionnaires to determine out whether the participants' mothers smoked when they were pregnant. For evaluating aging rate, we used the following several outcome measures: telomere length, frailty index, cognitive function, homeostatic dysregulation score, KDM-age, age-related hospitalization rate, premature death, and life expectancy. RESULT: After adjusting for covariates, we found that the offspring of the MSDP group had significantly shorter telomere length in adulthood by 0.8 % (ß = -0.008,95%CI:-0.009 to -0.006) compared with non-MSDP group. Compared to the non-MSDP group, participants in MSDP group showed higher levels of homeostatic dysregulation (ß = 0.015,95%CI: 0.007-0.024) and were frailer (ß = 0.008,95%CI:0.007-0.009). The KDM age increased by 0.100 due to MSDP (ß = 0.100,95 % CI:0.018-0.181), and the age acceleration of KDM algorithm also increases significantly (ß = 0.101, 95%CI:0.020-0.183). Additionally, we found that the risk of aging-related hospitalizations was significantly higher than the non-MSDP group by 10.4 %(HR = 1.104,95%CI:1.066-1.144). Moreover, MSDP group had a 12.2 % increased risk of all-cause premature mortality (HR = 1.122,95%CI:1.064-1.182) and a significant risk of lung cancer-specific premature mortality increased by 55.4 %(HR = 1.554,95%CI:1.346-1.793). In addition, participants in the MSDP group had significantly decreased cognitive function and shorter life expectancies than those in non-MSDP group. CONCLUSION: Our findings indicated a significant association between MSPD and accelerated aging, elevated hospitalization rates, increased premature mortality rates, and reduced life expectancies in offspring.

Exploring pleiotropy in Mendelian randomisation analyses: What are genetic variants associated with 'cigarette smoking initiation' really capturing?

Genetic variants used as instruments for exposures in Mendelian randomisation (MR) analyses may have horizontal pleiotropic effects (i.e., influence outcomes via pathways other than through the exposure), which can undermine the validity of results. We examined the extent of this using smoking behaviours as an example. We first ran a phenome-wide association study in UK Biobank, using a smoking initiation genetic instrument. From the most strongly associated phenotypes, we selected those we considered could either plausibly or not plausibly be caused by smoking. We examined associations between genetic instruments for smoking initiation, smoking heaviness and lifetime smoking and these phenotypes in UK Biobank and the Avon Longitudinal Study of Parents and Children (ALSPAC). We conducted negative control analyses among never smokers, including children. We found evidence that smoking-related genetic instruments were associated with phenotypes not plausibly caused by smoking in UK Biobank and (to a lesser extent) ALSPAC. We observed associations with phenotypes among never smokers. Our results demonstrate that smoking-related genetic risk scores are associated with unexpected phenotypes that are less plausibly downstream of smoking. This may reflect horizontal pleiotropy in these genetic risk scores, and we would encourage researchers to exercise caution this when using these and genetic risk scores for other complex behavioural exposures. We outline approaches that could be taken to consider this and overcome issues caused by potential horizontal pleiotropy, for example, in genetically informed causal inference analyses (e.g., MR) it is important to consider negative control outcomes and triangulation approaches, to avoid arriving at incorrect conclusions.

Negative Emotions Are Associated With Older Self-perceived Age: A Cross-section Study From the UK Biobank.

BACKGROUND: Prior research has indicated a potential connection between psychological stress and how individuals perceive their own age. Building on this foundation, the current study explores the relationship between negative emotions and self-perceived age. METHODS: We conducted a cross-sectional analysis using data from the UK Biobank, a comprehensive cohort study representing the UK population. The analysis included 347 892 participants, aged between 39 and 73 years, of which 184 765 were women, accounting for 53.1% of the sample. Participants were categorized into three groups based on their self-perceived age: feeling younger than their chronological age (group Younger), feeling older than their chronological age (group Older), and feeling as old as their actual age (group Same). To investigate the relationship between negative emotions and self-perceived age, we utilized a multinomial logistic regression model with the Younger group serving as the reference category. RESULTS: Of 347 892 participants, after adjusted for covariates, the results showed that participants with irritability, nervous feelings, worrier/anxious feelings or fed-up feelings, worry too long and loneliness/isolation are more likely to be rated as "about your age" or "older than you are," with "younger than you are" as the reference group, indicating that negative emotions may influence one's self-perceived age. Among those negative emotions, irritability has the most significant impact self-perceived age, with the odds ratios (ORs) being 1.44 (95% CI: 1.35-1.54) and 1.11 (95% CI: 1.09-1.14). CONCLUSION: Negative emotions are associated with older self-perceived age, and irritability has the greatest impact. Further studies analyzing self-perceived age are needed to take psychological factors into consideration.

The Perils of Partnership: Interactions Between Public Health England, Drinkaware, and the Portman Group Surrounding the Drink Free Days Campaign.

BACKGROUND: There is growing evidence that the alcohol industry seeks to obstruct public health policies that might affect future alcohol sales. In parallel, the alcohol industry funds organisations that engage in "responsible drinking" campaigns. Evidence is growing that the content and delivery of such campaigns serves industry, rather than public health interests, yet these organizations continue to be the subject of partnerships with government health departments. This study aimed to examine the nature and potential impacts of such partnerships by analysing the practices of the alcohol industry-funded charity Drinkaware during the establishment of the Drink Free Days campaign. METHODS: A case study based on an inductive analysis of documents revealed by freedom of information (FoI) request regarding communications between Drinkaware, Public Health England (PHE), and the Portman Group, in the years running up to, and during, the Drink Free Days campaign, a partnership between alcohol industry-funded charity Drinkware, and PHE. RESULTS: This study reveals a range of less visible, system-level effects of such partnerships for government departments and civil society. The tensions observed, as exhibited by discrepancies between internal and external communications, the emphasis on managing and mitigating the perception of negative consequences, and the links to wider alcohol industry initiatives and bodies, suggest the need for wider considerations of organizational conflicts of interest, and of possible indirect, harmful consequences to policy-making. These include the marginalization of other civil society voices, the displacing of more effective policy options, and strategic alignment with other industry lobbying activities. CONCLUSION: The findings have implications for how public health practitioners and health organisations might better weigh the potential trade-offs of partnership in the context of health promotion campaigns.

Female-specific association between the APOE E4 allele and age at diagnosis of glaucoma in UK Biobank.

OBJECTIVE: To explore the impact of the apolipoprotein E (APOE) E4 allele in the gender-specific aging process in glaucoma by illustrating the interaction between risk factors, including the APOE E4 allele, gender and intraocular pressure (IOP), for age at diagnosis (AAD) of glaucoma. DESIGN: A cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis. Data were analyzed in December 2023. PARTICIPANTS: 2,236 glaucoma patients and 103,232 controls. METHODS: We evaluated multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele (0: absence; 1: presence), and IOP using linear mixed model (LMM) analyses across groups stratified by AAD of mean age of menopause (50 years) and gender. MAIN OUTCOMES MEASURES: AAD of glaucoma, APOE E4 allele and IOP. RESULTS: Glaucoma patients were older and had a higher percentage of males and a higher mean IOP compared to controls (all P < 0.001). Further stratifying the glaucoma patients by AAD of 50 and gender, lower IOP (Model 1 adjusted by age, ßIOP=-0.096±0.041, P=0.019) and positive APOE E4 allele (Model 2 adjusted by age and IOP, ße4=1.093±0.488, P=0.026) were associated with an older AAD in females with an AAD < 50 years under univariate LMM. In multivariate LMM adjusted by age (Model 3), the effect size of both factors increased in the multivariate model as the beta-value increased. (ßIOP=-0.111±0.040, P=0.007; ße4=1.235±0.485, P=0.012) (Model 1 vs Model 3: P=0.011). In females with an AAD ≥50 years, only positive APOE E4 allele (adjusted by age and IOP, ße4=-1.121±0.412, P=0.007) was associated with a younger AAD. In males, only higher IOP was associated with an older AAD in those with an AAD ≥50 years (ßIOP=0.088±0.032, P=0.006). CONCLUSIONS: APOE E4 allele may initially delay and later accelerate the development of glaucoma in females around the transition period of 50 years, which is the mean age of menopause, and importantly, this is independent of IOP. Understanding the specific transition states and modifiable factors within each age phase is crucial for developing interventions or strategies that promote healthy aging.

Serum Uric Acid Levels Associated with Outcomes of Neurodegenerative Disorders and Brain Health: Findings from the UK Biobank.

BACKGROUND: The relationship between serum uric acid (SUA) levels and brain-related health remains uncertain. OBJECTIVES: This study aimed to investigate the relationship between SUA levels and some neurodegenerative disorders and brain structure. DESIGN: A longitudinal study. SETTING AND PARTICIPANTS: 384,517 participants who did not have stroke, dementia, and Parkinsonism, with complete urate testes and covariates were included. MEASUREMENTS: Cox proportional hazards models, competing risk models, and restricted cubic spine models were applied. RESULTS: During the median follow-up time of 12.7 years (interquartile range [IQR]:12.0, 13.5), 7821 (2.0%) participants developed stroke, 5103 (1.3%) participants developed dementia, and 2341 (0.6%) participants developed Parkinsonism. Nonlinear relationships were identified between SUA levels and stroke (J-shaped), dementia, and Parkinsonism (U-shaped). SUA levels of 4.2 mg/dl, 6.4 mg/dl, and 6.6 mg/dl yielded the lowest risk of stroke, dementia, and Parkinsonism, respectively. Besides, we found high SUA levels reduced the volumes of total brain, grey matter, white matter, grey matter in the hippocampus, and hippocampus, but increased lateral-ventricle volume. Inflammation accounted for 9.1% and 10.0% in the association of SUA with stroke and lateral-ventricle volume. CONCLUSIONS: Lower SUA levels increased the risk of Parkinsonism, while both lower and higher SUA levels were positively associated with increased risk of stroke and dementia. Moreover, high SUA levels reduced brain structure volumes. Our findings suggest the association between SUA levels and brain-related disorders and highlight the importance of SUA management.

Nonlinear relationships of circulating polyunsaturated fatty acids with the complications of liver cirrhosis: A prospective, longitudinal cohort study.

BACKGROUND & AIMS: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear. METHODS: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma. RESULTS: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92]). CONCLUSIONS: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose.

Precision breeding in agriculture and food systems in the United Kingdom.

In recent years there have been major advances in precision breeding technologies, such as gene editing, that offer promising solutions to revolutionise global crop production and tackle the pressing issues in food systems. The UK has leading expertise in genomics, and research is already taking place to develop crops with improved resilience to climate change, resistance to disease and less reliance on chemical inputs. In March 2023, the Genetic Technology (Precision Breeding) Act received Royal Assent and passed into UK law. It provides a framework from which to build more proportionate regulations for plants and animals made using genetic technologies which contain genetic changes that could also arise through traditional breeding-known as 'Precision Bred Organisms'. New legislation and the utilization of UK world-leading research could help to enhance the efficiency of breeding systems and enable the development of plants and animals that are healthier, better for the environment and more resilient to climate change.

Associations of childhood and adulthood body size, and child-to-adult body size change with adult telomere length.

AIM: To comprehensively examine the associations of childhood and adulthood body size, and child-to-adult body size change with adult leucocyte telomere length (LTL). METHODS: We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fat mass index (FMI), and fat-free mass index (FFMI). RESULTS: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (-0.0086 [-0.0017, -0.0004]). Adulthood BMI (-0.0286 [-0.0315, -0.0258]), WC (-0.0271 [-0.0303, -0.0238]), WHR (-0.0269 [-0.0308, -0.0230]) and FMI (-0.0396 [-0.0438, -0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. CONCLUSIONS: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight.

Associations of very low Lipoprotein(a) levels with risks of new-onset diabetes and non-alcoholic liver disease.

Background and aims: We aimed to study the association of very low serum Lipoprotein(a) [Lp(a)] concentrations with new-onset type 2 diabetes (T2D) and non-alcoholic liver disease (NAFLD) in the context of statin usage in the UK Biobank, a large prospective population cohort. Methods: Using an extended biomarker dataset, we identified 47,362 participants with very low Lp(a) concentrations (<3.8 nmol/L) from a total of 451,479 participants. With a median follow-up of 12.3 years, we assessed the risk of new-onset cardiometabolic diseases in participants stratified by statin usage with Cox proportional hazards models. We performed two-sample Mendelian randomization MR analyses to test causal relationship between genetically predicted Lp(a) and T2D and NAFLD. Results: Taking the participants with Lp(a) within reportable range as the reference group, the hazard ratios (HR) for T2D were 1.07 (95 % confidence interval, CI 1.01-1.13) and for NAFLD 1.30 (95 % CI 1.20-1.41) respectively for participants with very low Lp(a) (<3.8 nmol/L). The risk for new-onset T2D was higher in participants using statins (adjusted HR 1.15; 95 % CI 1.05-1.27). The risk estimates for new-onset NAFLD were comparable in the analysis stratified by statin use. There was no evidence for causal links between genetically predicted Lp(a) and T2D nor NAFLD in two-sample MR analyses. Conclusions: Very low Lp(a) was associated with higher risks of T2D and NAFLD in a prospective analysis of the UK Biobank. The association with T2D was influenced by lipid lowering medication usage. MR analyses did not support causality for these inverse associations.

Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank.

BACKGROUND: Triglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated. METHODS: This study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI. RESULTS: Over a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08-1.35), 1.21 (95% CI 1.08-1.35), and 1.30 (95% CI 1.16-1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20-1.52). CONCLUSIONS: TyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Sex and population differences in the cardiometabolic continuum: a machine learning study using the UK Biobank and ELSA-Brasil cohorts.

BACKGROUND: The temporal relationships across cardiometabolic diseases (CMDs) were recently conceptualized as the cardiometabolic continuum (CMC), sequence of cardiovascular events that stem from gene-environmental interactions, unhealthy lifestyle influences, and metabolic diseases such as diabetes, and hypertension. While the physiological pathways linking metabolic and cardiovascular diseases have been investigated, the study of the sex and population differences in the CMC have still not been described. METHODS: We present a machine learning approach to model the CMC and investigate sex and population differences in two distinct cohorts: the UK Biobank (17,700 participants) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) (7162 participants). We consider the following CMDs: hypertension (Hyp), diabetes (DM), heart diseases (HD: angina, myocardial infarction, or heart failure), and stroke (STK). For the identification of the CMC patterns, individual trajectories with the time of disease occurrence were clustered using k-means. Based on clinical, sociodemographic, and lifestyle characteristics, we built multiclass random forest classifiers and used the SHAP methodology to evaluate feature importance. RESULTS: Five CMC patterns were identified across both sexes and cohorts: EarlyHyp, FirstDM, FirstHD, Healthy, and LateHyp, named according to prevalence and disease occurrence time that depicted around 95%, 78%, 75%, 88% and 99% of individuals, respectively. Within the UK Biobank, more women were classified in the Healthy cluster and more men in all others. In the EarlyHyp and LateHyp clusters, isolated hypertension occurred earlier among women. Smoking habits and education had high importance and clear directionality for both sexes. For ELSA-Brasil, more men were classified in the Healthy cluster and more women in the FirstDM. The diabetes occurrence time when followed by hypertension was lower among women. Education and ethnicity had high importance and clear directionality for women, while for men these features were smoking, alcohol, and coffee consumption. CONCLUSIONS: There are clear sex differences in the CMC that varied across the UK and Brazilian cohorts. In particular, disadvantages regarding incidence and the time to onset of diseases were more pronounced in Brazil, against woman. The results show the need to strengthen public health policies to prevent and control the time course of CMD, with an emphasis on women.

Geospatial AI solution to monitor and mitigate increasing adverse ecological and hydrological impacts of climate change in Uttarakhand Himalaya (India).

Though climate change and its adverse ecological and geohydrological impacts are being experienced across the world in all types of ecosystems but as far as the Himalaya mountain ecosystem is concerned, the rate of climate change and subsequent impacts have reached an alarming stage due to anthropogenic and technogenic intervention on natural process and now need most effective and less time taking management strategy. Addressing this burning environmental problem, a geospatial artificial intelligence (GeoAI) technique-based case study is presented here from one of the most densely populated and urbanized regions of Himalaya mountain, viz Uttarakhand Himalaya, which is also called central Himalaya. The results of the study suggest that due to quite a high rate of climate change, the climatic zones shifting towards higher altitudes at the average rate of 5.6 2 m/year, causing several adverse ecological impacts in terms of decreasing quality dense temperate forest cover (0.05%/year), snow cover (0.02%/year), water bodies (0.01%/year), agricultural land (0.31%/year), and horticultural land (0.01%/year). Conversion of these eco-friendly land use land cover into barren land, fallow land, and built-up land causes geohydrological consequences of climate change in terms of decreasing rainy days (1%/year), drying perennial springs (0.20%/year), perennial streams (0.11%/year), decreasing spring and stream discharge during non-monsoon season, increased extreme rainfall events (6-8%/year), and subsequent surface runoff during monsoon season. Further, the study advocates that the degraded geohydrological process has resulted in an increased frequency of disaster events (floods, cloudbursts, landslides. etc.) with a 3% (12 events) annual rate, causing great loss of environment, infrastructure, lives, and economy each year. Therefore, it has been very urgent to mitigate climate change and increase geohydrological disaster events through an integrated approach. Keep in view this, the present study proposed an integrated watershed management plan which is equally useful to be implemented across the Himalaya region and other similar ecosystems across the world.

Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank.

BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

Association between kidney function and Parkinson's disease risk: a prospective study from the UK Biobank.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. METHODS: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. RESULTS: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively. CONCLUSION: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.

PheMIME: an interactive web app and knowledge base for phenome-wide, multi-institutional multimorbidity analysis.

OBJECTIVES: To address the need for interactive visualization tools and databases in characterizing multimorbidity patterns across different populations, we developed the Phenome-wide Multi-Institutional Multimorbidity Explorer (PheMIME). This tool leverages three large-scale EHR systems to facilitate efficient analysis and visualization of disease multimorbidity, aiming to reveal both robust and novel disease associations that are consistent across different systems and to provide insight for enhancing personalized healthcare strategies. MATERIALS AND METHODS: PheMIME integrates summary statistics from phenome-wide analyses of disease multimorbidities, utilizing data from Vanderbilt University Medical Center, Mass General Brigham, and the UK Biobank. It offers interactive and multifaceted visualizations for exploring multimorbidity. Incorporating an enhanced version of associationSubgraphs, PheMIME also enables dynamic analysis and inference of disease clusters, promoting the discovery of complex multimorbidity patterns. A case study on schizophrenia demonstrates its capability for generating interactive visualizations of multimorbidity networks within and across multiple systems. Additionally, PheMIME supports diverse multimorbidity-based discoveries, detailed further in online case studies. RESULTS: The PheMIME is accessible at https://prod.tbilab.org/PheMIME/. A comprehensive tutorial and multiple case studies for demonstration are available at https://prod.tbilab.org/PheMIME_supplementary_materials/. The source code can be downloaded from https://github.com/tbilab/PheMIME. DISCUSSION: PheMIME represents a significant advancement in medical informatics, offering an efficient solution for accessing, analyzing, and interpreting the complex and noisy real-world patient data in electronic health records. CONCLUSION: PheMIME provides an extensive multimorbidity knowledge base that consolidates data from three EHR systems, and it is a novel interactive tool designed to analyze and visualize multimorbidities across multiple EHR datasets. It stands out as the first of its kind to offer extensive multimorbidity knowledge integration with substantial support for efficient online analysis and interactive visualization.

Portrait of a UK-Africa Capacity Building Initiative Consortium 2015-2022: the Cameroon, Ghana, South Africa and United Kingdom Materials Initiative (CaGSUMI) for developing materials for solar cells.

The CaGSUMI consortium was funded by the Royal Society-Department for International Development (later the Foreign, Commonwealth & Development Office) on the Africa Capacity Building Initiative programme between the years 2015 and 2022 and involved three Sub-Saharan African universities: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, University of Yaoundé I, Cameroon, and the University of Zululand, South Africa; and the University of Manchester in the United Kingdom. The project was used to cement an emergent UK-Africa network in the areas of materials chemistry related to renewable energy generation with both thin films and nanomaterials. The consortium's outputs led to numerous publications of African science in international journals, a number of graduated PhDs who went on to permanent academic positions and prestigious fellowships, the establishment of a capacity-building plan relevant to the chemistry departments in each of the African countries, and the installation of a number of first-in-kind pieces of kit for African laboratories that will keep them on a competitive footing at an international level for the next decade and more.

Cardiovascular Health, Polygenic Risk Score and Cancer Risk: A Prospective Cohort Study.

BACKGROUND: Cancer and cardiovascular disease shared common lifestyle risk factors. However, it remains unclear whether cardiovascular health (CVH) evaluated by Life's Essential 8 can predict cancer risk, and attenuate the influence of genetic susceptibility on cancer. OBJECTIVE: We aimed to evaluate independent and joint associations of CVH and polygenic risk score (PRS) with risks of overall and site-specific cancers. METHODS: We undertook a population-based cohort study based on the UK Biobank. The CVH score was constructed by physical activity, body mass index, nicotine exposure, sleep, diet, blood pressure, lipid profile, and blood glucose. PRSs were assessed individually for 18 cancer types by their independent single-nucleotide polymorphisms previously reported in genome-wide association studies. Multivariable Cox proportional hazards models were applied to explore the independent and joint associations of CVH and PRS with cancer incidence risk. The results were displayed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Compared with low CVH, high CVH was associated with decreased risks of overall cancer and the majority of common cancers, including digestive system [HRs (95% CI): 0.33 (0.23, 0.45)-0.66 (0.58, 0.75)], lung [HR (95% CI): 0.25 (0.21, 0.31)], renal [HR (95% CI): 0.42 (0.32, 0.56)], bladder [HR (95% CI): 0.55 (0.44, 0.69)], breast [HR (95% CI): 0.83 (0.74, 0.92)] and endometrial cancers [HR (95% CI): 0.39 (0.30, 0.51)]. For overall cancer in males, there was an interaction between CVH and PRS. Notably, individuals with high CVH across all levels of PRS had lower risks of overall cancer for females and eight site-specific cancers than those with low CVH and high PRS [HRs (95%CIs): 0.18 (0.12, 0.25)-0.79 (0.71, 0.87)]. CONCLUSIONS: High CVH was related to decreased risks of overall cancer and multiple cancers regardless of genetic predispositions. Our findings underscored the value of improving CVH for cancer prevention in the general population.

The association of circulating systemic inflammation with premature death and the protective role of the Mediterranean diet: a large prospective cohort study of UK biobank.

BACKGROUND: Although previous studies have identified specific circulating inflammatory markers associated with the risk of mortality, they have often overlooked the broader impact of a comprehensive inflammatory response on health outcomes. This study aims to assess the association between circulating systemic inflammation and age-related hospitalization and premature death, as well as explore the potential mediating effects of various dietary patterns on these associations. METHODS: A total of 448,574 participants enrolled in the UK Biobank study were included. Circulating C-reactive protein(CRP), white blood cell count(WBC), platelet count(Plt), and neutrophil/lymphocyte ratio(NLR) were measured, which were used to establish a weighted systemic inflammatory index of inflammation index(INFLA-Score). Dietary intake information was documented through 24-hour dietary recalls, and dietary pattern scores including Dietary Approaches to Stop Hypertension(DASH), Mediterranean(MED), and Healthy Eating Index-2020(HEI-2020) were calculated. Cox proportional hazards regression models were performed to assess the associations between INFLA-Score and age-related disease hospitalization, cause-specific and all-cause premature death. RESULTS: During a median follow-up of 12.65 years, 23,784 premature deaths were documented. After adjusting for multiple covariates, higher levels of CRP, WBC, NLR, and INFLA-Score were significantly associated with increased risks of age-related disease hospitalization(HRCRP=1.19; 95%:1.17-1.21; HRWBC=1.17; 95%:1.15-1.19; HRNLR=1.18; 95%:1.16-1.20; HRINFLA-Score=1.19; 95%:1.17-1.21) and premature death(HRCRP=1.68; 95%:1.61-1.75; HRWBC=1.23; 95%:1.18-1.27; HRNLR=1.45; 95%:1.40-1.50; HRINFLA-Score=1.58; 95%:1.52-1.64). Compared to the lowest INFLA-Score group, the highest INFLA-Score group was associated with increased values of whole-body and organ-specific biological age, and had a shortened life expectancy of 2.96 (95% CI 2.53-3.41) and 4.14 (95% CI 3.75-4.56) years at the age of 60 years in women and men, respectively. Additionally, we observed no significant association of the INFLA-Score with aging-related hospitalization and premature death among participants who were more adhering to the Mediterranean (MED) dietary pattern(HRAging-related hospitalization=1.07; 95%:0.99-1.16;HRPremature death=1.19; 95%:0.96-1.47). CONCLUSION: A higher INFLA-Score was correlated with an increased risk of age-related hospitalization and premature death. Nevertheless, adherence to a Mediterranean (MED) diet may mitigate these associations.

Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.

BACKGROUND: Accumulating evidence suggests that cardiovascular diseases and breast cancer share a number of common risk factors, however, evidence on the association between cardiovascular health (CVH) and breast cancer is limited. The present study aimed to assess the association of CVH, defined by Life's Essential 8 (LE8) and genetic risk with breast cancer incidence and mortality among premenopausal and postmenopausal women. METHODS: We used data from the UK Biobank and conducted the multivariate Cox proportional-hazards models to examine associations of LE8 score and genetic risk with breast cancer incidence and mortality. Date on LE8 score was collected between 2006 and 2010 and composed of eight components, including behavioral metrics (diet, tobacco or nicotine exposure, physical activity, and sleep health), and biological metrics (body mass index, blood lipids, blood glucose, and blood pressure). The polygenic risk score (PRS) was calculated as the sum of effect sizes of individual genetic variants multiplied by the allele dosage. RESULTS: A total of 150,566 premenopausal and postmenopausal women were included. Compared to postmenopausal women with low LE8 score, those with high LE8 score were associated with 22% lower risk of breast cancer incidence (HR: 0.78, 95% CI: 0.70-0.87) and 43% lower risk of breast cancer mortality (HR: 0.57, 95% CI: 0.36-0.90). By contrast, we did not observe the significant association among premenopausal women. Further analyses stratified by PRS categories showed that high LE8 score was associated with 28% and 71% decreased risk of breast cancer incidence (HR: 0.72, 95% CI: 0.60-0.87) and mortality (HR: 0.29, 95% CI: 0.10-0.83) compared to low LE8 score among high genetic risk groups, but no significant associations were found among low genetic risk groups. Furthermore, compared with postmenopausal women with high LE8 score and low genetic risk, those with low LE8 score and high genetic risk were associated with increased risk of breast cancer incidence (HR: 6.26, 95% CI: 4.43-8.84). CONCLUSIONS: The present study suggests that better CVH is a protective factor for both breast cancer incidence and mortality among postmenopausal women. Moreover, the risk of developing breast cancer caused by high genetic susceptibility could be largely offset by better CVH.