An extensive benchmark study on biomedical text generation and mining with ChatGPT.

MOTIVATION: In recent years, the development of natural language process (NLP) technologies and deep learning hardware has led to significant improvement in large language models (LLMs). The ChatGPT, the state-of-the-art LLM built on GPT-3.5 and GPT-4, shows excellent capabilities in general language understanding and reasoning. Researchers also tested the GPTs on a variety of NLP-related tasks and benchmarks and got excellent results. With exciting performance on daily chat, researchers began to explore the capacity of ChatGPT on expertise that requires professional education for human and we are interested in the biomedical domain. RESULTS: To evaluate the performance of ChatGPT on biomedical-related tasks, this article presents a comprehensive benchmark study on the use of ChatGPT for biomedical corpus, including article abstracts, clinical trials description, biomedical questions, and so on. Typical NLP tasks like named entity recognization, relation extraction, sentence similarity, question and answering, and document classification are included. Overall, ChatGPT got a BLURB score of 58.50 while the state-of-the-art model had a score of 84.30. Through a series of experiments, we demonstrated the effectiveness and versatility of ChatGPT in biomedical text understanding, reasoning and generation, and the limitation of ChatGPT build on GPT-3.5. AVAILABILITY AND IMPLEMENTATION: All the datasets are available from BLURB benchmark https://microsoft.github.io/BLURB/index.html. The prompts are described in the article.

Changes in physical activity and all-cause mortality in the oldest old population: Findings from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

BACKGROUND: Insufficient or decreasing physical activity is common in older adults. Most studies on physical activity changes and mortality were conducted in adults younger than 80 years old in developed countries. We aimed to investigate the relationship between changes in physical activity and longevity in the oldest old (80 years or older) population using the Chinese Longitudinal Healthy Longevity Survey. METHODS: Participants aged 80 or older at baseline were categorized into four groups: 1) remaining physically inactive (n = 14,287), 2) remaining physically active (n = 5411), 3) shifting from being inactive to active (n = 1364), and 4) shifting from being active to inactive (n = 1401). We fitted accelerated failure time Weibull survival regression models, adjusting for baseline sociodemographics, lifestyle factors and disease status. We further examined whether the associations differed by subgroups. RESULTS: A total of 15,707 participants died during follow-up (median duration of follow-up = 3.0 years). Compared with participants who remained physically inactive, those who remained active (fully adjusted event time ratio (ETR): 1.14, 95%CI: 1.11-1.17) or shifted from being inactive to active (fully adjusted ETR: 1.14, 95%CI: 1.08-1.20) had statistically significant longer survival time. No significant association was observed between remaining physically inactive and shifting from being active to inactive. Subgroup analyses showed consistent associations in nearly all strata. CONCLUSION: Maintaining frequent physical activity or shifting from being physically inactive to active was consistently associated with longer survival time in the oldest old population. Our findings provide evidence for encouraging older adults to regularly engage in physical activity to gain longevity benefits.

Healthy eating and all-cause mortality among Chinese aged 80 years or older.

BACKGROUND: There is little evidence of the influence of dietary patterns on mortality risk among adults 80 years or older ("oldest-old"). We evaluated the association between the Simplified Healthy Eating index (SHE-index) and mortality among Chinese oldest-old. METHODS: Population-based cohort study from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 1998-2014, n = 35 927), conducted in 22 Chinese provinces, were pooled for analysis. The first seven waves of the CLHLS (1998, 2000, 2002, 2005, 2008-09, 2011-12, and 2013-2014) were utilized, with follow-up to the last wave (2018) (range 0-21 years). The SHE-index was collected in each wave, and was constructed from intake frequency of nine dietary variables, with a higher score indicating better diet quality. Cox proportional hazards model with dietary patterns as a time-varying exposure was employed to analyze the relationship between SHE-index and mortality. RESULTS: At baseline, the median age of all participants was 92 years (25th percentile, 85 years; 75th percentile, 100 years). In multivariable models, the hazard ratios (95% confidence intervals) for SHE-index quartile 2, quartile 3 and quartile 4 versus quartile1 were 0.91 (0.88, 0.93), 0.89 (0.86, 0.92) and 0.82 (0.78, 0.85), respectively. Results were generally consistent for men and women and in a large number of sensitivity analyses. CONCLUSIONS: Healthier eating patterns were associated with a significant reduction in the risk of all-cause mortality among Chinese oldest-old, lending support to the importance of life-long adherence to healthy diet into advanced old age.

Retinal microvascular changes in white matter hyperintensities investigated by swept source optical coherence tomography angiography.

BACKGRO: To assess the microvascular changes in the macular region and the foveal avascular zone (FAZ) area in participants with white matter hyperintensities (WMHs) using swept source optical coherence tomography angiography (SS OCTA). METHODS: This cross-sectional study included a total of 23 WMH participants (45 eyes) and 20 age-matched healthy participants (40 eyes). SS OCTA (VG200; SVision Imaging, Ltd., Luoyang, China) was used to assess the retinal vessel density (VD) and the FAZ area. VD was measured in the superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) within a 6 × 6-mm scan centred on the macula using a 5-mm Macula circle. The FAZ area was automatically measured on the inner retina layer within a 3 × 3-mm scan in the macular region. RESULTS: There was no significant difference in VD in the SVP between the two groups. However, VD in both the ICP and DCP was significantly decreased in WMH participants (P = 0.028, P = 0.016). The FAZ area was significantly enlarged in WMH participants (P = 0.030). The signal quality was significantly lower in WMH participants (P < 0.001). CONCLUSIONS: This study suggested that WMH participants have retinal microvascular and foveal avascular zone area changes compared with healthy controls. Further longitudinal studies with larger sample sizes are warranted to identify the value of our findings in the early evaluation of WMHs.

Association between indoor ventilation frequency and cognitive function among community-dwelling older adults in China: results from the Chinese longitudinal healthy longevity survey.

BACKGROUNDS: Emerging evidence suggested that indoor air pollution caused long-term adverse effects on cognitive function among older adults who spend more than 85% of their time indoors. Although high indoor ventilation can mitigate the effect of indoor air pollution on cognition among the younger population, limited evidence revealed the association between indoor ventilation and cognition among older adults. METHODS: A total of 11,853 participants aged 65 and over (female, 54.5%; mean age, 83.6 years) were included from the 2017-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Indoor ventilation frequency was measured by the self-reported frequency of opening windows per week in each season. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Multivariate Poisson regression with robust error variance was applied to assess the association between overall indoor ventilation frequency and cognitive function. We fitted in two adjusted models: Model 1 was adjusted for demographic; model 2 was further adjusted for lifestyle, socioeconomic status, health conditions, and environmental factors. The same models were also applied to measure the association between seasonal indoor ventilation frequency and cognitive function. RESULTS: Of 11,853 older adults, 3035 (25.6%) had cognitive impairment. A high overall indoor ventilation frequency (indoor ventilation frequency: 6-8) was significantly associated with a 9% lower likelihood of cognitive impairment than low overall indoor ventilation frequency (indoor ventilation frequency: 0-3) among Chinese older adults [Relative risk (RR): 0.91, 95% Confidential Interval (CI): 0.83-0.99] in the full adjusted model. In the subgroup analysis in four seasons, high and intermediate indoor ventilation frequency in winter were significantly associated with 8% (RR: 0.92; 95%CI: 0.86-0.99) and 16% (RR: 0.84; 95%CI: 0.78-0.90) lower probability of cognitive impairment than low indoor ventilation frequency in the fully adjusted model among Chinese older adults, respectively. CONCLUSIONS: In this nationally representative cohort, a higher frequency of house ventilation by opening windows was significantly associated with a lower risk of cognitive impairment among Chinese older adults aged 65 and over. These results offered robust evidence for policymaking and health intervention to prevent older adults from cognitive impairment or dementia in developing regions.

Women's Participation in Cardiovascular Clinical Trials From 2010 to 2017.

BACKGROUND: Cardiovascular disease is the leading cause of death among women worldwide, yet, women have historically been underrepresented in cardiovascular trials. METHODS: We systematically assessed the participation of women in completed cardiovascular trials registered in ClinicalTrials.gov between 2010 and 2017, and extracted publicly available information including disease type, sponsor type, country, trial size, intervention type, and the demographic characteristics of trial participants. We calculated the female-to-male ratio for each trial and determined the prevalence-adjusted estimates for participation of women by dividing the percentage of women among trial participants by the percentage of women in the disease population (participation prevalence ratio; a ratio of 0.8 to 1.2 suggests comparable prevalence and good representation). RESULTS: We identified 740 completed cardiovascular trials including a total of 862 652 adults, of whom 38.2% were women. The median female-to-male ratio of each trial was 0.51 (25th quartile, 0.32; 75th quartile, 0.90) overall and varied by age group (1.02 in ≤55 year old group versus 0.40 in the 61- to 65-year-old group), type of intervention (0.44 for procedural trials versus 0.78 for lifestyle intervention trials), disease type (0.34 for acute coronary syndrome versus 3.20 for pulmonary hypertension), region (0.45 for Western Pacific versus 0.55 for the Americas), funding/sponsor type (0.14 for government-funded versus 0.73 for multiple sponsors), and trial size (0.56 for smaller [n≤47] versus 0.49 for larger [n≥399] trials). Relative to their prevalence in the disease population, participation prevalence ratio was higher than 0.8 for hypertension, pulmonary arterial hypertension and lower (participation prevalence ratio 0.48 to 0.78) for arrhythmia, coronary heart disease, acute coronary syndrome, and heart failure trials. The most recent time period (2013 to 2017) saw significant increases in participation prevalence ratios for stroke (P=0.007) and heart failure (P=0.01) trials compared with previous periods. CONCLUSIONS: Among cardiovascular trials in the current decade, men still predominate overall, but the representation of women varies with disease and trial characteristics, and has improved in stroke and heart failure trials.

Association of APOE ε4 genotype and lifestyle with cognitive function among Chinese adults aged 80 years and older: A cross-sectional study.

BACKGROUND: Apolipoprotein E (APOE) ε4 is the single most important genetic risk factor for cognitive impairment and Alzheimer disease (AD), while lifestyle factors such as smoking, drinking, diet, and physical activity also have impact on cognition. The goal of the study is to investigate whether the association between lifestyle and cognition varies by APOE genotype among the oldest old. METHODS AND FINDINGS: We used the cross-sectional data including 6,160 oldest old (aged 80 years old or older) from the genetic substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) which is a national wide cohort study that began in 1998 with follow-up surveys every 2-3 years. Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score less than 18. Healthy lifestyle profile was classified into 3 groups by a composite measure including smoking, alcohol consumption, dietary pattern, physical activity, and body weight. APOE genotype was categorized as APOE ε4 carriers versus noncarriers. We examined the associations of cognitive impairment with lifestyle profile and APOE genotype using multivariable logistic regressions, controlling for age, sex, education, marital status, residence, disability, and numbers of chronic conditions. The mean age of our study sample was 90.1 (standard deviation [SD], 7.2) years (range 80-113); 57.6% were women, and 17.5% were APOE ε4 carriers. The mean MMSE score was 21.4 (SD: 9.2), and 25.0% had cognitive impairment. Compared with those with an unhealthy lifestyle, participants with intermediate and healthy lifestyle profiles were associated with 28% (95% confidence interval [CI]: 16%-38%, P < 0.001) and 55% (95% CI: 44%-64%, P < 0.001) lower adjusted odds of cognitive impairment. Carrying the APOE ε4 allele was associated with 17% higher odds (95% CI: 1%-31%, P = 0.042) of being cognitively impaired in the adjusted model. The association between lifestyle profiles and cognitive function did not vary significantly by APOE ε4 genotype (noncarriers: 0.47 [0.37-0.60] healthy versus unhealthy; carriers: 0.33 [0.18-0.58], P for interaction = 0.30). The main limitation was the lifestyle measurements were self-reported and were nonspecific. Generalizability of the findings is another limitation because the study sample was from the oldest old in China, with unique characteristics such as low body weight compared to populations in high-income countries. CONCLUSIONS: In this study, we observed that healthier lifestyle was associated with better cognitive function among the oldest old regardless of APOE genotype. Our findings may inform the cognitive outlook for those oldest old with high genetic risk of cognitive impairment.

Association between body mass index, its change and cognitive impairment among Chinese older adults: a community-based, 9-year prospective cohort study.

To examine the association of baseline body mass index (BMI) and BMI change with cognitive impairment among older adults in China. The study included data from the Chinese Longitudinal Healthy Longevity Study, a national community-based prospective cohort study from 2002 to 2018. Baseline BMI and BMI change were available for 12,027 adults aged older than 65 years. Cognitive impairment was defined as Chinese version of the Mini Mental State Examination score lower than 18. Multivariable Cox proportional hazard model was used. Among 12,027 participants (mean age was 81.23 years old and 47.48% were male), the proportion of underweight, normal, overweight and obese at baseline was 33.87%, 51.39%, 11.39% and 3.34%, respectively. During an average of 5.9 years' follow-up, 3086 participants (4.35 per 100 person-years) with incident cognitive impairment were identified. Compared with normal weight group, adjusted hazard ratio (AHR) for cognitive impairment was 0.86 (95% CI 0.75-0.99) among overweight group, whereas corresponding AHR was 1.02 (95% CI 0.94-1.10) in underweight and 1.01 (95% CI 0.80-1.28) in obese participants. Large weight loss (< -10%) was significantly associated with an increased risk of cognitive impairment (AHR, 1.42, 95% CI 1.29-1.56), compared to stable weight status group (-5% ~ 5%). In the restricted cubic spline models, BMI change showed a reverse J-shaped association with cognitive impairment. BMI-defined overweight, but not obesity, was associated with a lower risk of cognitive impairment among elderly Chinese adults, while large weight loss was associated with an increased risk. These findings are consistent with weight loss in the prodromal phase of dementia.

Changes in Levels and Determinants of Maternal Health Service Utilization in Ethiopia: Comparative Analysis of Two Rounds Ethiopian Demographic and Health Surveys.

BACKGROUND: Antenatal care (ANC), delivery by skilled birth attendants, and postnatal care (PNC) are critical components of maternal health services for reducing maternal mortality. The study aimed to compare the utilization of maternal health services in the two most recent rounds of Ethiopia Demographic and Health Surveys (EDHS) and identify the factors influencing the utilization of these services using the 2016 EDHS. METHODS: Two rounds of EDHS data in 2011 and 2016 were used to estimate the proportion of women who had ANC, delivered by skilled birth attendants, and had a postnatal checkup and other characteristics of the surveyed population. The most recent round of data-the 2016 EDHS-was used to examine the socio-cultural and reproductive health factors associated with the three maternal health services utilization. Chi-square tests and multivariate logistic regression analyses with adjusted Odds Ratios (AOR) were conducted using Stata 15.0. RESULTS: The use of ANC services and skilled birth attendants increased significantly between 2011 and 2016 EDHS, utilization of ANC services increased from 34.0 to 65.5%, and use of skilled birth attendants increased from 11.7 to 35.9%, respectively. The use of postnatal care decreased from 9.3 to 6.9%. Utilization of maternal health service was significantly associated with urban residence, Protestant religion, Oromo ethnicity, more education, more household wealth, and less parity. Furthermore, women who had ANC visits during pregnancy were more likely to subsequently use skilled birth attendants (AOR 5.5, p < 0.001) and PNC (AOR 2.9, p < 0.001). CONCLUSION: The study highlighted the inequalities in the utilization of maternal health services between rural and urban areas, and the need of addressing the social, economic, and physical barriers that prevent women from using these services. Further, programs should be targeted at promoting the use of professional birth and postnatal services in Ethiopia.

Short-term air pollution exposure is associated with hospital length of stay and hospitalization costs among inpatients with type 2 diabetes: a hospital-based study.

Air pollution is a risk factor for type 2 diabetes (T2D), exerting heavy economic burden on both individuals and societies. However, there is no apparent report regarding the influence of air pollutants such as particulate matter (PM2.5 and PM10), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and ozone (O3) on financial burden to individuals and societies suffering from T2D. This study aimed to determine whether short-term (no more than 16 d) air pollution exposure was associated with T2D-related length of stay (LOS) and hospitalization expenses incurred by patients. This investigation examined 2840 T2D patients hospitalized from December 17, 2013 to May 31, 2016 in China. Multiple linear regression analysis was applied to determine the association between short-term (no more than 16 d) ambient air pollution, LOS, and hospitalization expenses, controlling for age, gender, ethnicity, marital status, and weather conditions. Sulfur dioxide (SO2) and carbon monoxide (CO) were significantly positively while nitrogen dioxide (NO2) was negatively associated with presence of T2D, LOS, and expenses. A 10-µg/m3 rise in 16-d (lag 0-15) average concentrations of SO2 and CO prior to hospitalization was correlated with a significant elevation in LOS and elevation in expenses in T2D patients. However, a 10-µg/m3 rise in 16-d average NO2 was associated with marked negative alterations in LOS and hospital costs in T2D patients. Taken together, data demonstrate that exposure to air pollutants impacts differently on LOS and hospitalization costs for T2D patients. This is the first apparent report regarding the correlation between air pollution exposure and clinical costs of T2D in China. It is of interest that air pollutants affected T2D patients differently as evidenced by LOS and clinical expenses where SO2 and CO exhibited a positive adverse relationship in contrast to NO2.

Development and evaluation of an efficient heterologous gene knock-in reporter system in Lactococcus lactis.

BACKGROUND: Lactococcus lactis is a food grade probiotics and widely used to express heterologous proteins. Generally, target genes are knocked into the L. lactis genome through double-crossover recombination to express heterologous proteins stably. However, creating marker-less heterologous genes knocked-in clones is laborious. In this study, an efficient heterologous gene knock-in reporter system was developed in L. lactis NZ9000. RESULTS: Our knock-in reporter system consists of a temperature-sensitive plasmid pJW and a recombinant L. lactis strain named NZB. The pJW contains homologous arms, and was constructed to knock-in heterologous genes at a fixed locus of NZ9000 genome. lacZ (ß-galactosidase) gene was knocked into the chromosome of NZ9000 as a counter-selective marker through the plasmid pJW to generate NZB. The engineered NZB strain formed blue colonies on X-Gal plate. The desired double-crossover mutants formed white colonies distinctive from the predominantly blue colonies (parental and plasmid-integrated clones) when the embedded lacZ was replaced with the target heterologous genes carried by pJW in NZB. CONCLUSIONS: By using the system, the heterologous gene knocked-in clones are screened by colony phenotype change rather than by checking colonies individually. Our new knock-in reporter system provides an efficient method to create heterologous genes knocked-in clones.

Notch Signaling in Endothelial Cells: Is It the Therapeutic Target for Vascular Neointimal Hyperplasia?

Blood vessels respond to injury through a healing process that includes neointimal hyperplasia. The vascular endothelium is a monolayer of cells that separates the outer vascular wall from the inner circulating blood. The disruption and exposure of endothelial cells (ECs) to subintimal components initiate the neointimal formation. ECs not only act as a highly selective barrier to prevent early pathological changes of neointimal hyperplasia, but also synthesize and release molecules to maintain vascular homeostasis. After vascular injury, ECs exhibit varied responses, including proliferation, regeneration, apoptosis, phenotypic switching, interacting with other cells by direct contact or secreted molecules and the change of barrier function. This brief review presents the functional role of the evolutionarily-conserved Notch pathway in neointimal hyperplasia, notably by regulating endothelial cell functions (proliferation, regeneration, apoptosis, differentiation, cell-cell interaction). Understanding endothelial cell biology should help us define methods to prompt cell proliferation, prevent cell apoptosis and dysfunction, block neointimal hyperplasia and vessel narrowing.

Machine learning-based prediction of infarct size in patients with ST-segment elevation myocardial infarction: A multi-center study.

BACKGROUND: Cardiac magnetic resonance imaging (CMR) is the gold standard for measuring infarct size (IS). However, this method is expensive and requires a specially trained technologist to administer. We therefore sought to quantify the IS using machine learning (ML) based analysis on clinical features, which is a convenient and cost-effective alternative to CMR. METHODS AND RESULTS: We included 315 STEMI patients with CMR examined one week after morbidity in final analysis. After feature selection by XGBoost on fifty-six clinical features, we used five ML algorithms (random forest (RF), light gradient boosting decision machine, deep forest, deep neural network, and stacking) to predict IS with 26 (selected by XGBoost with information gain greater than average level of 56 features) and the top 10 features, during which 5-fold cross-validation were used to train and optimize models. We then evaluated the value of actual and ML-IS for the prediction of adverse remodeling. Our finding indicates that MLs outperform the linear regression in predicting IS. Specifically, the RF with five predictors identified by the exhaustive method performed better than linear regression (LR) with 10 indicators (R2 of RF: 0.8; LR: 0). The finding also shows that both actual and ML-IS were independently associated with adverse remodeling. ML-IS ≥ 21% was associated with a twofold increase in the risk of LV remodeling (P < 0.01) compared with patients with reference IS (1st tertile). CONCLUSION: ML-based methods can predict IS with widely available clinical features, which provide a proof-of-concept tool to quantitatively assess acute phase IS.

Pharmacophoric-constrained heterogeneous graph transformer model for molecular property prediction.

Informative representation of molecules is a crucial prerequisite in AI-driven drug design and discovery. Pharmacophore information including functional groups and chemical reactions can indicate molecular properties, which have not been fully exploited by prior atom-based molecular graph representation. To obtain a more informative representation of molecules for better molecule property prediction, we propose the Pharmacophoric-constrained Heterogeneous Graph Transformer (PharmHGT). We design a pharmacophoric-constrained multi-views molecular representation graph, enabling PharmHGT to extract vital chemical information from functional substructures and chemical reactions. With a carefully designed pharmacophoric-constrained multi-view molecular representation graph, PharmHGT can learn more chemical information from molecular functional substructures and chemical reaction information. Extensive downstream experiments prove that PharmHGT achieves remarkably superior performance over the state-of-the-art models the performance of our model is up to 1.55% in ROC-AUC and 0.272 in RMSE higher than the best baseline model) on molecular properties prediction. The ablation study and case study show that our proposed molecular graph representation method and heterogeneous graph transformer model can better capture the pharmacophoric structure and chemical information features. Further visualization studies also indicated a better representation capacity achieved by our model.

Evaluating the effectiveness and cost-effectiveness of free influenza vaccination policy for older adults in Yinzhou, China: Study protocol of a real-world analyses.

BACKGROUND: Influenza causes excessive morbidity and mortality among older adults. While influenza vaccine provides protection against its infection, the vaccination coverage in China among older adults has been very low. Previous evidence on the cost-effectiveness of government-sponsored free influenza vaccination programs in China was primarily based on literature data, which might not always reflect real-world patient populations. The Yinzhou Health Information System (YHIS) is a regional database that captures electronic health records, insurance claims data, etc. for all residents in Yinzhou district, Zhejiang province, China. We will use YHIS to study the effectiveness, influenza-related direct medical cost and cost-effectiveness analysis (CEA) of the free influenza vaccination program for older adults. In this paper, we describe the study design and innovations in detail. METHODS: We will establish a retrospective cohort of permanent older residents aged 65 and over, using YHIS between 2016 and 2021. We will estimate the vaccine coverage rate, influenza incidence rate and influenza-related direct medical cost from 2016 to 2021. Regression discontinuity will be used to estimate vaccine effectiveness for the 2020/2021 season. We will build a decision tree model to compare the cost-effectiveness of three influenza vaccination options (free trivalent influenza vaccine, free quadrivalent influenza vaccine, and no policy) from both societal and health system perspectives. Parameter inputs will be gathered from both YHIS and published literature. We will calculate the incremental cost-effectiveness ratio with cost and quality-adjusted life years (QALYs) discounted at 5 % annually. DISCUSSION: Our CEA solidifies multiple sources including regional real-world data and literature for a rigorous evaluation of the government-sponsored free influenza vaccination program. The results will provide real-world evidence from real-world data on the cost-effectiveness of a real-world policy. Our findings are expected to support evidence-based policy making and to promote health for older adults.

Pre-Training of Equivariant Graph Matching Networks with Conformation Flexibility for Drug Binding.

The latest biological findings observe that the motionless "lock-and-key" theory is not generally applicable and that changes in atomic sites and binding pose can provide important information for understanding drug binding. However, the computational expenditure limits the growth of protein trajectory-related studies, thus hindering the possibility of supervised learning. A spatial-temporal pre-training method based on the modified equivariant graph matching networks, dubbed ProtMD which has two specially designed self-supervised learning tasks: atom-level prompt-based denoising generative task and conformation-level snapshot ordering task to seize the flexibility information inside molecular dynamics (MD) trajectories with very fine temporal resolutions is presented. The ProtMD can grant the encoder network the capacity to capture the time-dependent geometric mobility of conformations along MD trajectories. Two downstream tasks are chosen to verify the effectiveness of ProtMD through linear detection and task-specific fine-tuning. A huge improvement from current state-of-the-art methods, with a decrease of 4.3% in root mean square error for the binding affinity problem and an average increase of 13.8% in the area under receiver operating characteristic curve and the area under the precision-recall curve for the ligand efficacy problem is observed. The results demonstrate a strong correlation between the magnitude of conformation's motion in the 3D space and the strength with which the ligand binds with its receptor.

Aldehyde dehydrogenase 2 rs671 polymorphism and multiple diseases: protocol for a quantitative umbrella review of meta-analyses.

BACKGROUND: The mutant allele (*2) of aldehyde dehydrogenase type 2 (ALDH2) caused by a single nucleotide variant (rs671) inhibits enzymatic activity and is associated with multiple diseases. In recent years, an explosive number of original studies and meta-analyses have been conducted to examine the associations of ALDH2 rs671 polymorphism with diseases. Due to conflicting results, the overall associations of ALDH2 rs671 polymorphism and multiple diseases remain unclear. METHODS: A quantitative umbrella review will be conducted on meta-analyses of genetic association studies to examine the pleiotropic effects of ALDH2 rs671, mainly including cardio-cerebral vascular disease, diabetes mellitus, cancer, neurodegenerative disease, and alcohol-induced medical disease. A search of relevant literature according to comprehensive search strategies will be performed on studies published before July 1st, 2022 in PubMed, MEDLINE Ovid, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Study selection, data extraction, methodology quality assessment, and strength of evidence assessment will be conducted by two reviewers independently and in duplicate. Included meta-analyses will be grouped by outcomes. Data conflicts and overlap between meta-analyses will be managed through updated standardized and customized methods including the calculation of CCA for study selection reference, application of Doi plots to assess small-study effects and others. Evidence from included meta-analyses will be quantitatively synthesized by overlap-corrected analyses and meta-analysis using primary studies. DISCUSSION: This umbrella review is expected to generate systematic evidence on the association between ALDH2 rs671 and diseases. Specific approaches were developed to address key challenges in conducting an umbrella review, including assessment tools of methodology and evidence quality of meta-analyses, methods to manage overlap between meta-analyses, a "stop-light" plot to summarize key findings. These approaches provide applicable methods for future umbrella reviews of meta-analyses on genetic association studies. TRIAL REGISTRATION: CRD42021223812.

Mediation analysis of leisure activities on the association between cognitive function and mortality: a longitudinal study of 42,942 Chinese adults 65 years and older.

OBJECTIVES: Previous studies have established associations of cognitive function and leisure activities with mortality. This study aimed to evaluate whether leisure activities causally mediate these associations. METHODS: This longitudinal study included 42,246 participants aged over 65 years from the Chinese Longitudinal Healthy Longevity Survey. The Mini-Mental State Examination and a self-reported scale were used to measure cognitive status and leisure activities, respectively. We examined the associations of cognitive function and leisure activities with mortality using Cox proportional hazards models. Causal mediation analysis was used to assess whether leisure activities mediated the association between cognitive function and mortality. RESULTS: Cognitive function and leisure activities were inversely associated with mortality. Leisure activities accounted for 28.3% (95% confidence interval [CI], 25.6 to 31.1) of the total effect of cognitive function and mortality. A higher mediated proportion (PM) was observed for physical leisure activities (PM, 20.1%; 95% CI, 18.0 to 22.3) than for social leisure activities (PM, 17.7%; 95% CI, 15.7 to 19.7). The mediating effect was higher among participants at younger ages (PM, 41.5%; 95% CI, 21.3 to 65.4), those with higher education levels (PM, 30.5%; 95% CI, 25.3 to 36.2), and residents of rural China (PM, 42.5%; 95% CI, 25.4 to 62.5). CONCLUSIONS: Cognitive function was associated with inverse mortality. Leisure activities significantly mediated this association. Participation in leisure activities at the early stages of mild cognitive impairment could reduce the risk of mortality, which has a major impact on interventional strategies for healthy aging.

The association between self-rated health and all-cause mortality and explanatory factors in China's oldest-old population.

Background: Self-rated health (SRH) is considered a condensed summary of information about bodily conditions that involves people's biological, cognitive, and cultural status, but has been under-studied in the oldest old population. This study aimed to investigate the association between SRH and all-cause mortality among the oldest-old population in China and to explore potential explanatory factors in this association. Methods: The study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018 and included 30 222 participants aged 80 years or older (ie, the oldest old) in the analysis. We used Cox models to assess the association between SRH and mortality in this population and its subgroups, and used the Percentage Excess Risk Mediated approach to identify potential contributing factors. Results: After adjustment of confounders, people with "good" "neutral", and "bad/very bad" SRH were significantly associated with 8% (95% confidence interval (CI) = 3%-13%), 23% (95% CI = 18%-29%), and 52% (95% CI = 44%-61%) higher hazard of mortality respectively, compared with those with "very good" SRH. The significant SRH-mortality associations were exclusive to men and those with at least primary education. The adjustment of "regular physical activity", "leisure activity", "activities of daily living (ADL)", and "cognitive function" all led to noticeable attenuation to the SRH-mortality association, with "leisure activity" causing the most attenuation (64.9%) in the "Good SRH" group. Conclusions: Self-rated health is significantly associated with all-cause mortality among the oldest old population in China, particularly among men and the educated, and is considerably explained by regular physical activity, leisure activity, ADL, and cognitive function. We advocate the use of SRH as a simple and efficient tool in research and (potentially) health care practices.

Interaction of greenness and polygenic risk score of Alzheimer's disease on risk of cognitive impairment.

Studies have shown contact with nature has positive psychological, neurological, and cognitive benefits. Whether the built environment can affect genetic predisposition of Alzheimer's disease (AD) should be explored. We aimed to examine whether greenness around the residential environment can modify the effect of genetic AD risk on cognitive function. We used a genetic sub-study of the Chinese Longitudinal Healthy Longevity Survey including 1199 older adults (mean age: 100.3 ± 3.4 years) aged 90 years old or older. We used Polygenic Risk Score (PRS) to quantify the genetic AD risk and two types of measurements based on Normalized Difference Vegetation Index (NDVI) to access the residential greenness (contemporaneous and annual average NDVI). Contemporaneous NDVI values were the NDVI value collected at the corresponding survey, and the annual average NDVI was the average value of NDVI during the year before the corresponding survey. We defined cognitive impairment as having a Mini-Mental State Examination score below 25. In the multivariable logistics regression models, contemporaneous NDVI and genetic AD risk were associated with cognitive impairment. Among those with low genetic AD risk, the risk of cognitive impairment was lower in those living around higher greenness (contemporaneous NDVI OR: 0.55, 95% CI: [0.34, 0.86]; Pinteraction: 0.071; annual average NDVI OR: 0.49, 95% CI: [0.31, 0.79]; Pinteraction: 0.040). We did not observe significant associations between greenness and cognitive impairment among those with high genetic AD risk. Prevention efforts using PRS warrant a higher granularity of environmental exposures and biological etiology data.