Relative validity of an intelligent ordering system to estimate dietary intake among university students from a medical school in Shanghai, China.

BACKGROUND: Dietary assessment methods have limitations in capturing real-time eating behaviour accurately. Equipped with automated dietary-data-collection capabilities, the "intelligent ordering system" (IOS) has potential applicability in obtaining long-term consecutive, relatively detailed on-campus dietary records among university students with little resource consumption. We investigated (1) the relative validity of IOS-derived nutrient/food intakes compared to those from the 7-day food diary (7DFD); (2) whether including a supplemental food frequency questionnaire (SFFQ) improves IOS accuracy; and (3) sex differences in IOS dietary intake estimation. METHODS: Medical students (n = 221; age = 22.2 ± 2.4 years; 38.5% male and 61.5% female) completed the 7DFD and SFFQ. During the consecutive 7-day survey period, students weighed and photographed each meal before and after consumption. Then, students reviewed their 3-month diet and completed the SFFQ, which includes eight underprovided school-canteen food items (e.g., dairy, fruits, nuts). Meanwhile, 9385 IOS dietary data entries were collected. We used Spearman coefficients and linear regression models to estimate the associations among the different dietary intake assessment methods. Individual- and group-level agreement was assessed using the Wilcoxon signed-rank test, cross-classification, and Bland‒Altman analysis. RESULTS: IOS mean daily energy, protein, fat, and carbohydrate intake estimations were significantly lower (-15-20%) than those of the 7DFD. The correlation coefficients varied from 0.52 (for added sugar) to 0.88 (for soybeans and nuts), with fruits (0.37) and dairy products (0.29) showing weaker correlations. Sixty-two (milk and dairy products) to 97% (soybeans and nuts) of participants were classified into the same or adjacent dietary intake distribution quartile using both methods. The energy and macronutrient intake differences between the IOS + SFFQ and 7DFD groups decreased substantially. The separate fruit intake measurements from each assessment method did not significantly differ from each other (p > 0.05). IOS and IOS + SFFQ regression models generally yielded higher R2 values for males than for females. CONCLUSION: Despite estimation differences, the IOS can be reliable for medical student dietary habit assessment. The SFFQ is useful for measuring consumption of foods that are typically unavailable in school cafeterias, improving the overall dietary evaluation accuracy. The IOS assessment was more accurate for males than for females.

Accelerometer-measured intensity-specific physical activity, genetic risk and incident type 2 diabetes: a prospective cohort study.

OBJECTIVE: Although 30 min/day of moderate-intensity physical activity is suggested for preventing type 2 diabetes (T2D), the current recommendations exclusively rely on self-reports and rarely consider the genetic risk. We examined the prospective dose-response relationships between total/intensity-specific physical activity and incident T2D accounting for and stratified by different levels of genetic risk. METHODS: This prospective cohort study was based on 59 325 participants in the UK Biobank (mean age=61.1 years in 2013-2015). Total/intensity-specific physical activity was collected using accelerometers and linked to national registries until 30 September 2021. We examined the shape of the dose-response association between physical activity and T2D incidence using restricted cubic splines adjusted for and stratified by a polygenic risk score (based on 424 selected single nucleotide polymorphisms) using Cox proportional hazards models. RESULTS: During a median follow-up of 6.8 years, there was a strong linear dose-response association between moderate-to-vigorous-intensity physical activity (MVPA) and incident T2D, even after adjusting for genetic risk. Compared with the least active participants, the HRs (95% CI) for higher levels of MVPA were: 0.63 (0.53 to 0.75) for 5.3-25.9 min/day, 0.41 (0.34 to 0.51) for 26.0-68.4 min/day and 0.26 (0.18 to 0.38) for >68.4 min/day. While no significant multiplicative interaction between physical activity measures and genetic risk was found, we found a significant additive interaction between MVPA and genetic risk score, suggesting larger absolute risk differences by MVPA levels among those with higher genetic risk. CONCLUSION: Participation in physical activity, particularly MVPA, should be promoted especially in those with high genetic risk of T2D. There may be no minimal or maximal threshold for the benefits. This finding can inform future guidelines development and interventions to prevent T2D.

Associations of physical activity intensity with incident cardiovascular diseases and mortality among 366,566 UK adults.

BACKGROUND: The associations of the proportion of vigorous physical activity (VPA) to moderate to vigorous physical activity (MVPA) with incident cardiovascular disease (CVD) and all-cause mortality are unclear. METHODS: The present study included 366,566 participants (aged 40-69 years) without baseline CVD from the UK biobank during 2006 to 2010. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of outcomes. RESULTS: During a median 11.8 years of follow-up, among 366,566 participants (mean age [SD]: 56.0 [8.1]), 31,894 incident CVD and 19,823 total deaths were documented. Compared with no VPA, 0%-30% of VPA to MVPA was associated with 12% and 19% lower risks of incident CVD (HR, 0.88 [95% CI, 0.86-0.91]) and all-cause mortality (HR, 0.81 [95% CI, 0.78-0.84]), respectively. Furthermore, we found that the maximum reduction of risks of incident CVD and all-cause mortality occurred at performing approximately 30% of VPA to MVPA (P < 0.001). Compared with participants reporting the lowest levels of MVPA (moderate physical activity [MPA], 0-150 min/week; VPA, 0-75 min/week), those performing 150-300 min/week of MPA and ≥ 150 min/week of VPA experienced the lowest risk of incident CVD (HR, 0.87 [95% CI, 0.79-0.95]) and all-cause mortality (HR, 0.71 [95% CI, 0.63-0.80]). Interestingly, we found that smokers yielded more cardiovascular benefits than non-smokers by performing a higher volume of VPA. CONCLUSIONS: Comparing with UK adults reporting no VPA, engaging in 30% of VPA was associated with the lowest risk of incident CVD and all-cause mortality.

Correlates of Domain-Specific Physical Activity Among Older Adults in Six Low- to Middle-Income Countries: Analysis of Nationally Representative Samples From Study of Global Aging and Adult Health (SAGE) (Wave 1).

The correlates of physical activity differ across domains. The authors explored the contribution of domain-specific physical activity to total physical activity and examined how different sociodemographic and social capital-related variables are associated with different physical activity domains in older adults, using nationally representative samples from six low- to middle-income countries. Activity at work and home combined plays an important role in contributing to total physical activity, while leisure-time physical activity accounted for an extremely small proportion. Some correlates of physical activity were similar across countries, such as working status and structural social capital, while other associations were country specific. Promoting structural social capital, trust, and perceived safety may confer positive benefits on older adults' activity.

Social engagement pattern, health behaviors and subjective well-being of older adults: an international perspective using WHO-SAGE survey data.

BACKGROUND: Social engagement forms the basis of social relationships by providing a sense of belonging, social identity, and fulfillment. Previous research demonstrates that social engagement was associated with positive health behaviors among older adults. However, the results have been different across health-related behaviors, and mostly based on data from high-income countries. For example, studies from the US and UK showed that social engagement was protective against smoking, while others found social engagement encouraged more smoking in many Asian cultures. In this study, we aim to examine the association between social engagement and a range of health-related behaviors and subjective well-being among older adults in six low- to middle-income countries. METHODS: Data from the WHO Study on Global Ageing and Adult Health (SAGE Wave 1) were used. A total of 33,338 individuals aged 50 and older in China, Russia, India, Ghana, South Africa, and Mexico were included. Social engagement, tobacco use, alcohol consumption, fruit and vegetable intake, physical activity, sedentary behavior, sleep duration, depression symptoms, self-rated health status, and quality of life were assessed using established self-reported measures. Multiple logistic regression models were used to examine the relationship between social engagement and nine outcome variables, adjusting for socio-demographic characteristics. RESULTS: Lower levels of social engagement were positively related to physical inactivity, prolonged sitting time, unhealthy sleep duration, perceived depression, poor self-rated health, and low quality of life. However, the associations between social engagement and tobacco use, excessive drinking, and insufficient fruit and vegetable intake were mixed across countries. CONCLUSION: This international study found high social engagement as a potential health-promoting factor in some low- to middle-income countries. Although the impacts of social engagement on tobacco and alcohol use and diet were complicated and culture-specific, interventions at both individual and community levels should encourage healthy lifestyles through positive social engagement.

Assessing consistent condom use among migrant men who have sex with men in Shanghai, China: validation of an information-motivation-behavioural skills model.

BACKGROUND: In China, high prevalence of risky sexual behaviours and inequity in health services lead to situations in which migrant men who have sex with men face higher risk of contracting the human immunodeficiency virus. Consistent condom use is a primary means of preventing HIV infection during anal sex among MSM. This study aimed to apply the information-motivation-behavioural skills model to examine the predictors of consistent condom use among migrant MSM in Shanghai, and tested the associations between model constructs. METHODS: A cross-sectional study was conducted among 412 migrant MSM in Shanghai. Data on HIV-related information, motivation, behavioural skills, and behaviours were collected via structured questionnaires. A structural equation model was used to assess the IMB model. RESULTS: Of the 412 participants, 4.4% reported HIV-positive status, and prevalence of consistent condom use in the previous 6 months was 44.9%. A restricted IMB model provided an acceptable fit to the data. Behavioural skills were found to directly predict consistent condom use (ß = 0.629, P < 0.01). Neither information nor motivation could directly predict consistent condom use (P > 0.05), but motivation predicted it indirectly and was mediated by behavioural skills. CONCLUSION: The prevalence of consistent condom use was found to be relatively low among migrant MSM in Shanghai. The restricted IMB model was found to be a good predictor of consistent condom use among them. The results of this study indicate that intervention strategies for safer sexual behaviour should not only include information dissemination, but also emphasize motivation and behavioural skills among this population.

Understanding condom use among unmarried female migrants: a psychological and personality factors modified information-motivation-behavioral skills model.

BACKGROUND: In China, unmarried female migrants are vulnerable to sexual and reproductive health risks. One effective protection strategy is promoting consistent condom use (CCU). METHODS: We conducted a cross-sectional study to apply the information-motivation-behavioral skills (IMB) model and modified it by addition of psychological and personal factors to examine the related factors of CCU and provide suggestions for intervention among unmarried female migrants. RESULTS: Of all 903 eligible participants, only 13.8% of participants reported CCU in the past six months. Both the IMB model and the modified IMB model provided acceptable fit to the data. In both models, information had no direct or indirect influence on CCU (p > 0.05). However, behavioral skills had a positive effect on CCU (ß = 0.344, p < 0.001 and ß = 0.330, p < 0.001). Moreover, motivation contributed to CCU indirectly by affecting behavioral skills (ß = 0.800, p < 0.001) and had no direct influence (p > 0.05). In the modified model, psychological and personality factors influenced CCU directly (ß = - 0.100, p = 0.005). CONCLUSIONS: Our results highlight the importance of conducting CCU promotion among unmarried female migrants. Future intervention strategies should focus on both the traditional IMB model constructs and the added psychological and personality factors.

Sexual compulsivity and its relationship with condomless sex among unmarried female migrant workers in Shanghai, China: a cross-sectional study.

BACKGROUND: Individuals with high sexual compulsivity are preoccupied with their sexual desire to such an extent that it interferes with their normal daily life and can inhibit self-control. Previous studies have found a close association between sexual compulsivity and condomless sex among different populations; however, no studies have investigated this among unmarried female migrant workers in China. This study aimed to validate the Sexual Compulsivity Scale (SCS) for appropriate use and examine the association between sexual compulsivity and condomless sex in this target population. METHODS: In 2015, we recruited 1325 unmarried female migrant workers in Shanghai, China. Information about sociodemographics, sexual compulsivity, and condomless sex were collected using a structured questionnaire. Exploratory factor analysis and reliability analysis were performed to validate the Chinese version of the SCS. Multiple logistic regression analyses were used to examine the association between sexual compulsivity and condomless sex. RESULTS: The prevalence of condomless sex in the previous 6 months was 66.8% among all participants. The SCS was proven internally consistent for the overall scale (Cronbach's α = 0.89), and two factors, Social Disruptiveness (Cronbach's α = 0.87) and Perceived Self-Control (Cronbach's α = 0.84), were extracted. With mean total score of 18.25 (standard deviation = 4.94) after adjusting for significant sociodemographic factors, the SCS total scores (adjusted odds ratio [AOR] = 1.04, 95% confidence interval [CI] = 1.02-1.07) and two subscale scores (AOR = 1.07, 95% CI = 1.02-1.13; AOR = 1.06, 95% CI = 1.02-1.10) were all related to inconsistent condom use with partners in the previous 6 months. CONCLUSIONS: The Chinese version of the SCS was found to be well adaptable for use among unmarried Chinese female migrant workers and a potential predictor for condomless sex. In addition to safe sex interventions, counselling on managing sexually compulsivity should also be provided in this population.

Association between induced abortion and suicidal ideation among unmarried female migrant workers in three metropolitan cities in China: a cross-sectional study.

BACKGROUND: Despite reports of mental health issues, suicidality has not been closely examined among the migrant population. The association between induced abortion and suicidal ideation is unknown among unmarried female migrant workers of reproductive age in China. This study aims to examine induced abortion and suicidality among the Chinese migrant population. METHODS: We recruited 5115 unmarried female migrant workers during 2015 to 2016 from Shanghai, Beijing and Guangzhou, and collected demographic, psychosocial, reproductive and mental health information using structured questionnaires. We used logistic regression models to examine the association between lifetime induced abortion and suicidal ideation during the past year among the subjects. RESULTS: Overall, 8.2% of the subjects had suicidal ideation during the past year, and 15.5% of the subjects experienced induced abortion. Induced abortion was associated with nearly twice the odds of having past-year suicidal ideation (Odds ratio, OR = 1.89; 95% confidence interval, CI: 1.46, 2.44) after adjusting for age, education, years in the working place, tobacco use, alcohol consumption, daily internet use, attitude towards premarital pregnancy, multiple induced abortion, self-esteem, loneliness, depression, and anxiety disorders. The association was stronger in those aged > 25 (OR = 3.37, 95% CI = 2.16, 5.28), with > 5 years of stay in the working place (OR = 2.98, 95% CI = 2.02, 4.39), the non-anxiety group (OR = 2.28, 95% CI = 1.74, 3.00), and the non-depression group (OR = 2.94, 95% CI = 2.08, 4.15). CONCLUSIONS: Induced abortion was associated with increased odds for suicidal ideation among the unmarried female migrant workers in urban cities in China. More attention should be paid to the mental health of the population.

Effect of retirement on loneliness: a longitudinal comparative analysis across Australia, China and the USA.

BACKGROUND: There is evidence that the transition to retirement can bring social challenges and may increase loneliness. Few studies have examined the impact of retirement on loneliness; most have been conducted in Western countries. It is important to examine the differences in loneliness postretirement across countries to identify patterns and risk factors that might influence the health and well-being of older adults. We aimed to examine the effect of retirement on loneliness among older adults in Australia, China and the USA. METHODS: Longitudinal analysis of data from population-based samples of Australian, Chinese and American adults over 50. Lagged and fully lagged adjusted models were applied. Social engagement was examined as an effect modifier and a sensitivity analysis was conducted among urban participants. RESULTS: Retirees had a higher predicted prevalence of loneliness than non-retirees in Australia (19.4% (95% CI 18.0% to 20.9%) vs 17.0% (95% CI 15.7% to 18.4%)) and in the USA (19.3% (95% CI 17.5% to 21.1%) vs 15.7% (95% CI 14.3% to 17.3%)). These differences were significant only in the USA. In China, loneliness was significantly lower in those who had retired (10.0% (95% CI 7.9% to 12.5%) vs 17.1% (95% CI 15.7% to 18.5%)). In Australia and the USA, voluntary retirees had the lowest loneliness and involuntary retirees had the highest. Social engagement did not modify the association between retirement and loneliness. CONCLUSIONS: Our findings imply that the effect of retirement should be considered within a cultural context to inform suitable and effective strategies to alleviate loneliness.

Leisure-time physical activity and all-cause mortality and cardiovascular disease in adults with type 2 diabetes: Cross-country comparison of cohort studies.

PURPOSE: This study aimed to quantify the dose-response association and the minimal effective dose of leisure-time physical activity (PA) to prevent mortality and cardiovascular disease in adults with type 2 diabetes. METHODS: Cross-country comparison of 2 prospective cohort studies including 14,913 and 17,457 population-based adults with type 2 diabetes from the UK and China. Baseline leisure-time PA was self-reported and categorized by metabolic equivalent hours per week (MET-h/week) according to World Health Organization recommendations: none, below recommendation (>0-7.49 MET-h/week); at recommended level (7.5-14.9 MET-h/week); above recommendation (≥15 MET-h/week). Mortality and cardiovascular disease data were obtained from national registries. RESULTS: During a median follow-up of 12.4 and 9.7 years, in the UK and China cohorts, repectively, higher levels of leisure-time PA were inversely associated with all-cause (1571 and 2351 events) and cardiovascular mortality (392 and 1060 events), mostly consistent with a linear dose-response relationship. PA below, at, and above recommendations, compared with no activity, yielded all-cause mortality hazard ratios of 0.94 (95% confidence interval (95%CI): 0.79-1.12), 0.90 (95%CI: 0.74-1.10), and 0.85 (95%CI: 0.70-1.02) in British adults and 0.87 (95%CI: 0.68-1.10), 0.88 (95%CI: 0.74-1.03), and 0.77 (95%CI: 0.70-0.85) in Chinese adults. Associations with cardiovascular mortality were more pronounced in British adults (0.80 (95%CI: 0.58-1.11), 0.75 (95%CI: 0.52-1.09), and 0.69 (95%CI: 0.48-0.97)) but less pronounced in Chinese adults (1.06 (95%CI: 0.76-1.47), 1.01 (95%CI: 0.80-1.28), and 0.79 (95%CI: 0.69-0.92)). PA at recommended levels was not associated with lower rates of major adverse cardiovascular events (2345 and 4458 events). CONCLUSION: Leisure-time PA at the recommended levels was not convincingly associated with lower mortality and had no association with risk of major adverse cardiovascular events in British or Chinese adults with type 2 diabetes. Leisure-time PA above current recommendations may be needed to prevent cardiovascular disease and premature mortality in adults with type 2 diabetes.

The co-benefits of active travel interventions beyond physical activity: a systematic review.

Active travel is a widely recognised strategy for promoting active living but its co-benefits beyond increasing physical activity, such as broader health, environmental, and social benefits, have rarely been synthesised. We conducted a systematic review to examine the co-benefits of active travel interventions. Following a preregistered protocol (PROSPERO CRD42022359059), we identified 80 studies for the search period from Jan 1, 2000, to Sept 13, 2022. Across studies, there was consistent evidence that active travel interventions offered co-benefits beyond physical activity. Particularly, 25 (71%) of 35 studies favoured improved safety outcomes, 20 (67%) of 30 showed improved health, 17 (85%) of 20 supported economic benefits, 16 (84%) of 19 highlighted improved transport quality, 12 (92%) of 13 showed environmental benefits, and four (80%) of five documented social benefits. Despite the overall low-certainty evidence, mostly limited by the quasi-experimental design and natural-experimental design of many of the studies, active travel interventions offer unique opportunities to engage stakeholders across sectors to jointly address major societal issues, such as physical inactivity, traffic safety, and carbon emissions. This evidence can inform the design, implementation, and evaluation of active travel interventions.

A Holistic Way to Understand the Determinants of Physical Activity in Urban New South Wales, Australia: A Codesigned Systems Mapping Project.

BACKGROUND: To meet the World Health Organization goal of reducing physical inactivity by 15% by 2030, a multisectoral system approach is urgently needed to promote physical activity (PA). We report the process of and findings from a codesigned systems mapping project to present determinants of PA in the context of urban New South Wales, Australia. METHODS: A participatory conceptual mapping workshop was held in May 2023 with 19 participants working in education, transportation, urban planning, community, health, and sport and recreation. Initial maps were developed and refined using online feedback from the participants. Interviews were conducted with 10 additional policymakers from relevant sectors to further refine the maps. RESULTS: Two systems maps were cocreated, identifying over 100 variables influencing PA and their interconnections. Five settings emerged from the adults' map-social and community, policy, built environment and transportation, health care, and workplace-and 4 for the young people's map-family, school, transportation, and community and environment. The maps share similarities, such as regarding potential drivers within the transportation, community, and built environment sectors; however, the young people's map has a specific focus on the school setting and the adults' map on workplace and health care settings. Interviews with policymakers provided further unique insights into understanding and intervening in the PA system. CONCLUSIONS: This codesigned participatory systems mapping process, supplemented by stakeholder interviews, provided a unique opportunity to bring together stakeholders across sectors to understand the complexity within the PA system and begin to identify leverage points for tackling physical inactivity in New South Wales.

Retirement transition and smoking and drinking behaviors in older Chinese adults: Analysis from the CHARLS study.

Introduction: Smoking and drinking are important public problems and a substantial part of work culture in mainland China. However, little is known about the effect of retirement on these behaviors. Thus, this study examined the relationships between retirement transition, smoking and excessive drinking among older Chinese adults. Methods: Repeated longitudinal data from a nationally representative sample of Chinese adults were collected in 2011, 2013, 2015 and 2018. Respondents completed a structured questionnaire regarding work status and health behaviors. Modified mixed-effects Poisson regression models were used to explore the associations, with additional analyses stratified by gender. Results: Of the 10,378 participants included, 62.6% and 20.1% of men reported current smoking and excessive drinking at study entry; compared to 4.4% and 1.5% of women, respectively. There was no significant association between retirement and smoking. We found a dose-response relationship between time in retirement and excessive drinking in the adjusted model where those who retired >= 2 years ago had a 30% lower risk of excessive drinking (risk ratio (RR) = 0.70, 95% confidence interval (CI) = 0.56-0.86), and those who retired < 2 years ago had a 16% lower risk of excessive drinking (RR = 0.84, 95%CI = 0.73-0.97), compared with those who remained working. This pattern remained when analyzed separately for men and women, although not all results reached statistical significance. Discussion: Chinese older adults are more likely to reduce drinking following retirement. Such evidence supports the positive framing of retirement in public discourse and the need for workplace interventions to address excessive drinking in China.

Stair climbing, genetic predisposition, and the risk of incident type 2 diabetes: A large population-based prospective cohort study.

BACKGROUND: Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation. However, few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes (T2D). We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D. METHODS: We included 451,699 adults (mean age = 56.3 ± 8.1 years, mean ± SD; 55.2% females) without T2D at baseline in the UK Biobank and followed up to March 31, 2021. Stair climbing information was collected through the touchscreen questionnaire. Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms. RESULTS: During a median follow up of 12.1 years, 14,896 T2D cases were documented. Compared with participants who reported no stair climbing, those who climbed stairs regularly had a lower risk of incident T2D (10-50 steps/day: hazard ratio (HR) = 0.95, 95% confidence interval (95%CI): 0.89-1.00; 60-100 steps/day: HR = 0.92, 95%CI: 0.87-0.98; 110-150 steps/day: HR = 0.86, 95%CI: 0.80-0.91; >150 steps/day: HR = 0.93, 95%CI: 0.87-0.99, p for trend = 0.0007). We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk (p for interaction = 0.0004), where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110-150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk. CONCLUSION: A higher number of stairs climbed at home was associated with lower T2D incidence risk, especially among individuals with a low genetic predisposition to T2D. These findings highlight that stair climbing, as incidental physical activity, offers a simple and low-cost complement to public health interventions for T2D prevention.

A Ubiquitin-Dependent Switch on MEF2D Senses Pro-Metastatic Niche Signals to Facilitate Intrahepatic Metastasis of Liver Cancer.

Effective treatment for metastasis, a leading cause of cancer-associated death, is still lacking. To seed on a distal organ, disseminated cancer cells (DCCs) must adapt to the local tissue microenvironment. However, it remains elusive how DCCs respond the pro-metastatic niche signals. Here, systemic motif-enrichment identified myocyte enhancer factor 2D (MEF2D) as a critical sensor of niche signals to regulate DCCs adhesion and colonization, leading to intrahepatic metastasis and recurrence of liver cancer. In this context, MEF2D transactivates Itgb1 (coding ß1-integrin) and Itgb4 (coding ß4-integrin) to execute temporally unique functions, where ITGB1 recognizes extracellular matrix for early seeding, and ITGB4 acts as a novel sensor of neutrophil extracellular traps-DNA (NETs-DNA) for subsequent chemotaxis and colonization. In turn, an integrin-FAK circuit promotes a phosphorylation-dependent USP14-orchastrated deubiquitination switch to stabilize MEF2D via circumventing degradation by the E3-ubiquitin-ligase MDM2. Clinically, the USP14(pS432)-MEF2D-ITGB1/4 feedback loop is often hyper-active and indicative of inferior outcomes in human malignancies, while its blockade abrogated intrahepatic metastasis of DCCs. Together, DCCs exploit a deubiquitination-dependent switch on MEF2D to integrate niche signals in the liver mesenchyme, thereby amplifying the pro-metastatic integrin-FAK signaling. Disruption of this feedback loop is clinically applicable with fast-track potential to block microenvironmental cues driving metastasis.

Revisiting the 'physical activity paradox' in a Chinese context: Occupational physical activity and mortality in 142,302 urban working adults from the China Kadoorie Biobank study.

Background: Previous research suggests that while leisure-time physical activity (LTPA) is beneficial, occupational physical activity (OPA) may be detrimental to health, known as the 'physical activity paradox'. However, the current evidence is primarily based on data from Western countries. We examined the association of OPA with all-cause and cardiovascular disease mortality in working adults in urban China. Methods: This prospective longitudinal study was based on a sample of 142,302 urban working adults aged 30-79 years from the China Kadoorie Biobank study. Self-reported OPA (mainly sedentary, standing occupation, and manual work) was collected at baseline (year 2004-2008) and linked to death registries until 31st December 2016. Multivariable Cox proportional hazards models were used to examine the relationship between OPA and mortality outcomes, with further tests for effect modification by sex, educational attainment and LTPA. Findings: During a median follow-up of 10·2 years, 4,077 deaths occurred, of which cardiovascular disease was the primary cause for 727 deaths. Crude modelling showed that compared with the sedentary workers, manual work was associated with increased risk of all-cause mortality. However, after adjusting for socio-demographic and lifestyle variables, the association was attenuated to null (HR=1·00, 95%CI: 0·93-1·08). In subgroup analysis, higher OPA was associated with lower risk of all-cause mortality in the least educated group (HR=0·84, 95%CI: 0·75-0·95 for manual work, and HR=0·86, 95%CI: 0·75-0·99 for standing occupation), but harmful in the most educated group (HR=1·17, 95%CI: 1·01-1·36) and in those who reported regular LTPA (HR=1·20, 95%CI: 1·01-1·43). Interpretation: OPA was not associated with mortality risk in the overall sample. However, findings support the 'physical activity paradox' within better educated Chinese workers. Funding: None.

The prevalence of loneliness across 113 countries: systematic review and meta-analysis.

OBJECTIVES: To identify data availability, gaps, and patterns for population level prevalence of loneliness globally, to summarise prevalence estimates within World Health Organization regions when feasible through meta-analysis, and to examine temporal trends of loneliness in countries where data exist. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PsycINFO, and Scopus for peer reviewed literature, and Google Scholar and Open Grey for grey literature, supplemented by backward reference searching (to 1 September 2021) ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies based on nationally representative samples (n≥292), validated instruments, and prevalence data for 2000-19. Two researchers independently extracted data and assessed the risk of bias using the Joanna Briggs Institute checklist. Random effects meta-analysis was conducted in the subset of studies with relatively homogeneous research methods by measurement instrument, age group, and WHO region. RESULTS: Prevalence data were available for 113 countries or territories, according to official WHO nomenclature for regions, from 57 studies. Data were available for adolescents (12-17 years) in 77 countries or territories, young adults (18-29 years) in 30 countries, middle aged adults (30-59 years) in 32 countries, and older adults (≥60 years) in 40 countries. Data for all age groups except adolescents were lacking outside of Europe. Overall, 212 estimates for 106 countries from 24 studies were included in meta-analyses. The pooled prevalence of loneliness for adolescents ranged from 9.2% (95% confidence interval 6.8% to 12.4%) in South-East Asia to 14.4% (12.2% to 17.1%) in the Eastern Mediterranean region. For adults, meta-analysis was conducted for the European region only, and a consistent geographical pattern was shown for all adult age groups. The lowest prevalence of loneliness was consistently observed in northern European countries (2.9%, 1.8% to 4.5% for young adults; 2.7%, 2.4% to 3.0% for middle aged adults; and 5.2%, 4.2% to 6.5% for older adults) and the highest in eastern European countries (7.5%, 5.9% to 9.4% for young adults; 9.6%, 7.7% to 12.0% for middle aged adults; and 21.3%, 18.7% to 24.2% for older adults). CONCLUSION: Problematic levels of loneliness are experienced by a substantial proportion of the population in many countries. The substantial difference in data coverage between high income countries (particularly Europe) and low and middle income countries raised an important equity issue. Evidence on the temporal trends of loneliness is insufficient. The findings of this meta-analysis are limited by data scarcity and methodological heterogeneity. Loneliness should be incorporated into general health surveillance with broader geographical and age coverage, using standardised and validated measurement tools. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019131448.