Background With global aging, cognitive impairment, including Alzheimer's disease and related dementias, has become a critical public health challenge, driving the need for convenient screening tools to facilitate early intervention. Objective This study aimed to develop an efficient and noninvasive risk assessment model for identifying potential cognitive impairment in the elderly using machine learning algorithms based on comprehensive geriatric assessment (CGA). Methods We included 1410 participants aged 50 and older from geriatric clinics and community. Feature selection was performed on the CGA indicators using a combination of expert knowledge and machine learning. Logistic regression (LR), naive Bayes, support vector machines, neural networks, and random forests were comprehensively evaluated based on common classification performance metrics. The optimal machine learning algorithms and feature subset are used to construct the final prediction model. Shapley Additive exPlanations (SHAP) was used to explain the model. Results Thirteen noninvasive predictors were identified, including 'Bathing', 'Age', 'Caregiver', 'Sleep duration', 'Homekeeping', 'Right Ear', 'Stand BWEO', 'Hobbies', 'Focusing Difficulty', 'UI effect', and 'Housework'. The LR model performed best on the test set, with an AUC of 0.877 and high accuracy (0.815), sensitivity (0.767), and specificity (0.827). The SHAP results illustrated the role of these key features in cognitive impairment, which is highly consistent with clinical knowledge.Conclusions This study identifies convenient, noninvasive predictors for screening-oriented prediction of cognitive impairment, develops an efficient machine learning model, and employs SHAP analysis for interpretation. This facilitates widespread screening, providing guidance for early detection and intervention in high-risk populations.

OBJECTIVES:Few prospective studies have investigated early-life tobacco smoke's effects on chronic gastrointestinal diseases (CGD) and multi-morbidity (CGM). We examined associations between early-life tobacco exposure and subsequent CGD or CGM development. STUDY DESIGN:This was a prospective cohort study conducted among UK Biobank. METHODS:We assessed the association between tobacco exposure in early life and incident CGD using UK Biobank data. We employed Cox models to estimate the risk of CGD, examining the separate and combined impacts of tobacco exposures in early life and pack-years. Multi-state Cox models further analyzed the impact of tobacco smoke on CGM progression. RESULTS:Our analysis involved 294,344 UK Biobank participants, with 61,472 developing CGD over a median observation period of 13.02 years. Prenatal tobacco exposure increased CGD risk by 11 % (HR = 1.11, 95 % CI: 1.09-1.13). Earlier smoking initiation was associated with higher CGD risk: adjusted HRs were 1.09 for adulthood, 1.16 for adolescence, and 1.25 for childhood initiation compared to never smokers (P trend <0.001). Childhood smoking initiation was linked to a 42 % increased risk of CGD in current smokers (HR = 1.42, 95 % CI: 1.31-1.53) and influenced transitions from incident CGD to CGM (HR = 1.30, 95 % CI: 1.12-1.51) and from healthy to CGM (HR = 1.83, 95 % CI: 1.58-2.13). Additionally, childhood smoking significantly raised mortality risk from all states: healthy (HR = 2.53, 95 % CI: 2.21-2.89), incident CGD (HR = 2.30, 95 % CI: 1.79-2.95), and CGM (HR = 1.67, 95 % CI: 1.13-2.46). CONCLUSIONS:Exposure to tobacco in early life increases the risk of developing CGD and elevates incidence and progress of CGM.

Multiple diet patterns play a crucial role in the development of colorectal cancer and its precursor, colorectal adenoma, but mediating effect of plasma metabolite profiles is unclear. A total of 95,275 participants from UK Biobank with plasma metabolomics and dietary information were analyzed. Metabolite profile scores for 14 dietary patterns were estimated through elastic net regression. Cox regression analysis assessed the associations of dietary patterns and their metabolite profile scores with colorectal tumor risk. Mediating effects of identified metabolite profile scores were estimated in the associations. Fourteen metabolite profile scores, including a range of 28 to 205 signatures, were weak to moderate correlation with dietary patterns (all p < 0.001). Multivariable Cox regression analyses revealed that five dietary patterns were significantly correlated with a decreased risk of colorectal tumor after FDR correction and adjustment for covariates. HRs (95

Introduction: Given the increase in ultra-processed food (UPF) consumption, their potential health effects have aroused concern. Whether UPF consumption is associated with cancer and cardiovascular disease mortality is debatable. This study evaluates the association of UPF consumption with mortality. Methods: A total of 108,714 U.S. adults from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (1993-2001), 208,051 UK adults from UK Biobank (2006-2010), and 41,070 U.S. adults from National Health and Nutrition Examination Survey (1999-2018) were included. Dietary data were collected by dietary questionnaire and classified using the NOVA classification. UPF consumption was expressed as the weight proportion of UPFs in total foods consumed. Cox proportional hazard models were used to calculate hazard ratios and 95% CIs. Mediation analysis was used to evaluate whether multiple metabolic pathways mediated the associations in UK Biobank. Analyses were performed in 2022-2023. Results: Combined analyses of the three cohorts showed that those with the highest quartile of UPF consumption had higher risks of all-cause mortality (hazard ratio, 1.16; 95% CI, 1.11-1.20) and cardiovascular disease mortality (hazard ratio, 1.17; 95% CI, 1.06-1.28) compared to the lowest quartile of UPF consumption. UPF consumption was not associated with cancer mortality risk. Biomarkers of liver function have the greatest mediating effects on all-cause mortality (20.3%), and biomarkers of inflammation have the greatest mediating effects on cardiovascular disease mortality (29.2%). Conclusions: Higher UPF consumption was associated with increased all-cause and cardiovascular disease mortality risk, with multiple metabolic pathways playing mediating roles. Am J Prev Med 2024;66(2):315-323. (c) 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Gastrointestinal (GI) disorders are highly prevalent and severely diminish life quality. It is yet unknown which dietary pattern is optimal for the prevention of GI disorders. Among 141 450 participants from UK Biobank with a median follow-up of 15 years, we comprehensively assessed 13 dietary patterns in relation to 6 GI disorders. Multivariable Cox proportional hazards models demonstrated that adherence to healthy diets was associated with lower risk of GI disorders, with the strongest associations observed for the Dietary Approaches to Stop Hypertension (DASH) diet (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), the Alternate Mediterranean Diet (AMED) (HRQ4 vs. Q1 = 0.85, 95% CI: 0.81, 0.88), and the Alternate Healthy Eating Index-2010 (AHEI-2010) (HRQ4 vs. Q1 = 0.86, 95% CI: 0.82, 0.89). AHEI-2010 (HRs ranging from 0.76 to 0.90) and DASH (HRs ranging from 0.75 to 0.88) showed inverse associations with every individual GI disorder. Furthermore, comorbidities decreased significantly in number with higher AMED and DASH diet scores (P for trend <0.001). Finally, the associations of AHEI-2010, AMED and DASH with GI disorders diminished most intensely after removing the component of fruits or whole grains. The combined intake of fruits and whole grains was inversely associated with the risk of overall GI disorders (HRT3 vs. T1 = 0.89, 95% CI: 0.86, 0.93). In conclusion, AHEI-2010 and DASH were the most recommended dietary patterns for the prevention of GI disorders. Fruits and whole grains are the most significant contributors to the protective effect.

Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm 22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient's condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm 22/ST46 GAS infections in China.

OBJECTIVE:Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS:The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS:During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS:Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

BackgroundHepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored.MethodsBased on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied.ResultsDifferent subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells.ConclusionWe developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.

Numerous studies have revealed associations between high intake of whole grains and reduced risk of various cancers. Yet, in recent decades, the traditional Chinese diets have been challenged by reduction in whole grains and increase in refined grains. To assess the impact of this dietary transition on cancer prevention, we analyzed the time trend of whole grain intake using nationally representative sampling data of over 15 thousand individuals from the China Health and Nutrition Survey. We applied the comparative risk assessment method to estimate the population attributable fraction of cancers due to insufficient whole grain intake from 1997 to 2011 and projected the trend of whole grain intake and the associated burden of cancers to 2035. We found a significant decrease of approximately 59% of whole grain intake in the Chinese population from 1997 to 2011. Compared with 1997, insufficient intake of whole grains was responsible for 9940 more cases of breast cancer, 12,903 more cases of colorectal cancer and 434 more cases of pancreatic cancer in 2011. Our projections suggest that if every Chinese would consume 125 g whole grain per day as recommended by the latest Chinese Dietary Guidelines, 0.63% bladder cancer, 8.98% breast cancer, 15.85% colorectal cancer, 3.86% esophageal cancer, 2.52% liver cancer and 2.22% pancreatic cancer (totaling 186,659 incident cases) could theoretically be averted by 2035. Even if everyone maintained the 2011 whole grain intake level, an estimated 8.38% of cancer events could still be prevented by 2035.

Because of tumour dependence on angiogenesis, anti-angiogenic therapy has become the most attractive area of basic and clinical study in the field of cancer research. In order to create a synergistic effect on angiogenesis and immune regulation, we designed and constructed a new type of DNA vaccine that can express VEGFR2 (vascular endothelial growth factor receptor 2) and the prostate cancer antigen IL-12 (interleukin 12) in the same reading frame. The aim of this study was to investigate the anti-tumour activity of a eukaryotic expression plasmid carrying a fusion gene of human VEGFR2 and IL-12. According to the gene sequences in GenBank, we synthesized the human VEGFR2 and IL-12 genes. VEGFR2 and IL-12 were joined by a sequence encoding a Furin recognition site and a 2A cleavage site, and the resulting fusion gene was cloned into the eukaryotic expression vector pVAX1 to construct the expression plasmid pVAX1-VEGFR2-F2A-IL-12. The expression of VEGFR2 and IL-12 could be detected in 293T cells transfected with pVAX1-VEGFR2-F2A-IL-12 by enzyme-linked immunosorbent assay. Each of these proteins, and in particular co-expression of both proteins, can result in humoral and cellular immune responses in C57BL/6 mice. After injection into the tumour-bearing mouse model, the plasmid showed stronger inhibition of tumour growth than a plasmid expressing VEGFR2 alone. Our results demonstrate that a DNA vaccine carrying a fusion gene of human VEGFR2 and IL-12 could represent a promising approach for tumour immunotherapy.