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To evaluate the effect of vitamin D3 supplementation on cancer mortality in the general population and on prognosis in cancer patients, a systematic review and meta-analysis of randomised, placebo-controlled trials (RCTs) and individual patient data (IPD) was conducted. Overall, 14 RCTs with a total of 104,727 participants (2015 cancer deaths) were identified and 7 RCTs, including 90 % of all study participants (n = 94,068), could be included in the IPD meta-analyses. The main meta-analysis of the 14 RCTs yielded a statistically non-significant reduction in cancer mortality by 6 % (risk ratio (RR) [95%-confidence interval (95%CI)]: 0.94 [0.86-1.02]). Subgroup analyses revealed a 12 % lower cancer mortality in the vitamin D3 group compared with the placebo group in 10 trials with a daily dosing regimen (RR [95%CI]: 0.88 [0.78-0.98]), whereas no mortality reduction was seen in 4 trials using a bolus regimen (RR [95%CI]: 1.07 [0.91-1.24]; p-value for interaction: 0.042). The IPD meta-analysis (RR [95%CI]: 0.93 [0.84; 1.02]) confirmed the finding of all trials. The IPD were used to test effect modification by age, sex, body mass index, ethnicity, baseline serum 25-hydroxyvitamin D concentration, adherence and cancer-related factors but no statistically significant findings were obtained in meta-analyses of all trials. When restricted to trials with daily dosing in a post-hoc analysis, adults aged ≥ 70 years (RR [95%CI]: 0.83 [0.77; 0.98]) and subjects with vitamin D3 therapy initiation before cancer diagnosis (RR [95%CI]: 0.87 [0.69; 0.99]) appeared to benefit most from daily vitamin D3 supplementation. Measurements of baseline 25-hydroxyvitamin D levels and inclusion of other than non-Hispanic White adults were too sparse in the trials to draw conclusions. Results for all-cause and cancer-specific survival of participants with cancer were comparable to those obtained in the general population for cancer mortality. In conclusion, vitamin D3 did not reduce cancer mortality in the main meta-analysis of all RCTs because the observed risk reduction by 6 % was not statistically significant. However, a subgroup analysis revealed that vitamin D3 administered daily, in contrast to bolus supplementation, reduced cancer mortality by 12 %.

UNLABELLED: We aimed to explore whether higher levels of residential greenness were related to lower odds of disabilities in activities of daily living (ADL) and instrumental activities of daily living (IADL). METHODS: We included older adults 65 years of age or older from the Chinese Longitudinal Healthy Longevity Survey. Our exposure was Normalized Difference Vegetation Index in 500 m radius around residence. Our outcome was ADL and IADL. We used binary logistic regression and mixed-effects logistic regression to estimate the odds of ADL and IADL disabilities. RESULTS: A total of 36,803 and 32,316 participants were included for the analysis of ADL and IADL, with 71.6% free of ADL disability and 47.3% free of IADL disability. In the logistic regression model, compared with the participants living in the lowest quartile of residential greenness, those in the highest quartile had a 28% (odds ratio [OR] = 0.72; 95% confidence interval [CI] = 0.65, 0.79) lower odds of ADL disability and a 14% (OR = 0.86; 95% CI = 0.77, 0.95) lower odds of IADL disability. A similar association was found in the mixed-effects logistic regression models. During the follow-up period, 5,004 and 4,880 healthy participants developed ADL and IADL disabilities. Per 0.1-unit increase in baseline annual average Normalized Difference Vegetation Index (NDVI) was related to an OR of 0.95 of developing ADL disability (95% CI = 0.93, 0.98) and IADL disability (95% CI = 0.91, 0.98). CONCLUSIONS: Our study suggests that increasing green space is associated with lower odds of ADL and IADL disabilities, which may reduce caregiver burden of long-term care for Chinese older adults.

BACKGROUND: Exposure to natural vegetation, or greenness, might affect health through several pathways, including increased physical activity and social engagement, improved mental health, and reductions in exposure to air pollution, extreme temperatures, and noise. Few studies of the effects of greenness have focused on Asia, and, to the best of our knowledge, no study has assessed the effect on vulnerable oldest-old populations. We assessed the association between residential greenness and mortality in an older cohort in China. METHODS: We used five waves (February, 2000-October, 2014) of the China Longitudinal Healthy Longevity Survey (CLHLS), a prospective cohort representative of the general older population in China. We assessed exposure to greenness through satellite-derived Normalised Difference Vegetation Index (NDVI) values in the 250 m and 1250 m radius around the residential address for each individual included in the study. We calculated contemporaneous NDVI values, cumulative NDVI values, and changes in NDVI from the start of the study over time. The health outcome of the study was all-cause mortality, excluding accidental deaths. Mortality rate ratios were estimated with Cox proportional hazards models, adjusted for age, sex, ethnicity, marital status, geographical region, childhood and adult socioeconomic status, social and leisure activity, smoking status, alcohol consumption, and physical activity. FINDINGS: Among 23 754 individuals (mean age at baseline 93 years [SD 7·5]) totaling 80 001 person-years, we observed 18 948 deaths during 14 years of follow-up, between June, 2000, and December, 2014. Individuals in the highest quartile of contemporaneous NDVI values had 27% lower mortality than those in the lowest quartile for the 250 m radius (hazard ratio [HR] 0·73, 95% CI 0·70-0·76), and 30% lower mortality for the 1250 m radius (0·70, 0·67-0·74). No clear association was observed for cumulative NDVI measurements and mortality. We did not detect an association between area-level changes in NDVI and mortality. INTERPRETATION: Our research suggests that proximity to more green space is associated with increased longevity, which has policy implications for the national blueprint of ecological civilisation and preparation for an ageing society in China. FUNDING: Bill & Melinda Gates Foundation, US National Institute on Aging, US National Institute of Health, Natural Science Foundation of China, UN Population Fund, China Social Sciences Foundation, and Hong Kong Research Grants Council.

Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs) and expansive symmetric cell divisions (SCDs) by governing Inscuteable (mInsc), a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1). Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG) but instead causes more basal cap cells to divide via SCD, at the expense of ACD, leading to more stem cells and larger outgrowths. Together, our studies provide insight into how the number of mammary stem cells is regulated by the extracellular cue SLIT2.

Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes. The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %). Adherence to a Mediterranean diet score (MDS), Dietary Approaches to Stop Hypertension (DASH) score, overall plant-based diet (PDI), healthful (hPDI) and unhealthful plant-based diet index (uPDI) was derived from a food frequency questionnaire and associated with cardiovascular risk factors, kidney function, and neuropathy using multivariable linear regression analysis. Differences in dietary pattern adherence between endotypes were assessed using generalized mixed models. People with MARD showed the highest, those with SIDD and MOD the lowest adherence to the hPDI. Adherence to the MDS, DASH, overall PDI, and hPDI was inversely associated with high-sensitivity C-reactive protein (hsCRP) among people with MARD (β (95%CI): −9.18 % (−15.61; −2.26); −13.61 % (−24.17; −1.58); −19.15 % (−34.28; −0.53); −16.10 % (−28.81; −1.12), respectively). Adherence to the PDIs was associated with LDL cholesterol among people with SAID, SIRD, and MOD. Minor differences in dietary pattern adherence (in particular for hPDI) and associations with markers of diabetes-related complications (e.g. hsCRP) were observed between endotypes. So far, evidence is insufficient to derive endotype-specific dietary recommendations. Clinicaltrials.gov: NCT01055093. • The diabetes endotypes showed minor differences in adherence to dietary patterns. • Associations of dietary patterns with cardiovascular risk factors varied among them. • Evidence is still insufficient to derive endotype-specific dietary recommendations. [ABSTRACT FROM AUTHOR]