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Background The incidence of stroke places a heavy burden on both society and individuals. Activity is closely related to cardiovascular health. This study aimed to investigate the relationship between the varying domains of PA, like occupation-related Physical Activity (OPA), transportation-related Physical Activity (TPA), leisure-time Physical Activity (LTPA), and Sedentary Activity (SA) with stroke. Methods Our analysis included 30,400 participants aged 20+ years from 2007 to 2018 National Health and Nutrition Examination Survey (NHANES). Stroke was identified based on the participant's self-reported diagnoses from previous medical consultations, and PA and SA were self-reported. Multivariable logistic and restricted cubic spline models were used to assess the associations. Results Participants achieving PA guidelines (performing PA more than 150 min/week) were 35.7% less likely to have a stroke based on both the total PA (odds ratio [OR] 0.643, 95% confidence interval [CI] 0.523-0.790) and LTPA (OR 0.643, 95% CI 0.514-0.805), while OPA or TPA did not demonstrate lower stroke risk. Furthermore, participants with less than 7.5 h/day SA levels were 21.6% (OR 0.784, 95% CI 0.665-0.925) less likely to have a stroke. The intensities of total PA and LTPA exhibited nonlinear U-shaped associations with stroke risk. In contrast, those of OPA and TPA showed negative linear associations, while SA intensities were positively linearly correlated with stroke risk. Conclusions LTPA, but not OPA or TPA, was associated with a lower risk of stroke at any amount, suggesting that significant cardiovascular health would benefit from increased PA. Additionally, the positive association between SA and stroke indicated that prolonged sitting was detrimental to cardiovascular health. Overall, increased PA within a reasonable range reduces the risk of stroke, while increased SA elevates it.

Skillful subseasonal forecasts are crucial for various sectors of society but pose a grand scientific challenge. Recently, machine learning based weather forecasting models outperform the most successful numerical weather predictions generated by the European Centre for Medium-Range Weather Forecasts (ECMWF), but have not yet surpassed conventional models at subseasonal timescales. This paper introduces FuXi Subseasonal-to-Seasonal (FuXi-S2S), a machine learning model that provides global daily mean forecasts up to 42 days, encompassing five upper-air atmospheric variables at 13 pressure levels and 11 surface variables. FuXi-S2S, trained on 72 years of daily statistics from ECMWF ERA5 reanalysis data, outperforms the ECMWF's state-of-the-art Subseasonal-to-Seasonal model in ensemble mean and ensemble forecasts for total precipitation and outgoing longwave radiation, notably enhancing global precipitation forecast. The improved performance of FuXi-S2S can be primarily attributed to its superior capability to capture forecast uncertainty and accurately predict the Madden-Julian Oscillation (MJO), extending the skillful MJO prediction from 30 days to 36 days. Moreover, FuXi-S2S not only captures realistic teleconnections associated with the MJO, but also emerges as a valuable tool for discovering precursor signals, offering researchers insights and potentially establishing a new paradigm in Earth system science research.

Protein-protein interactions are of great importance in biochemical processes. Accurate prediction of protein-protein interaction sites (PPIs) is crucial for our understanding of biological mechanism. Although numerous approaches have been developed recently and achieved gratifying results, there are still two limitations: (1) Most existing models have excavated a number of useful input features, but failed to take coevolutionary features into account, which could provide clues for inter-residue relationships; (2) The attention-based models only allocate attention weights for neighboring residues, instead of doing it globally, which may limit the model's prediction performance since some residues being far away from the target residues might also matter. We propose a coevolution-enhanced global attention neural network, a sequence-based deep learning model for PPIs prediction, called CoGANPPIS. Specifically, CoGANPPIS utilizes three layers in parallel for feature extraction: (1) Local-level representation aggregation layer, which aggregates the neighboring residues' features as the local feature representation; (2) Global-level representation learning layer, which employs a novel coevolution-enhanced global attention mechanism to allocate attention weights to all residues on the same protein sequences; (3) Coevolutionary information learning layer, which applies CNN & pooling to coevolutionary information to obtain the coevolutionary profile representation. Then, the three outputs are concatenated and passed into several fully connected layers for the final prediction. Extensive experiments on two benchmark datasets have been conducted, demonstrating that our proposed model achieves the state-of-the-art performance.

When the Covid-19 pandemic enters dangerous new phase, whether and when to take aggressive public health interventions to slow down the spread of COVID-19. To develop the artificial intelligence (AI) inspired methods for real-time forecasting and evaluating intervention strategies to curb the spread of Covid-19 in the World. A modified auto-encoder for modeling the transmission dynamics of the epidemics is developed and applied to the surveillance data of cumulative and new Covid-19 cases and deaths from WHO, as of March 16, 2020. The average errors of 5-step forecasting were 2.5%. The total peak number of cumulative cases and new cases, and the maximum number of cumulative cases in the world with later intervention (comprehensive public health intervention is implemented 4 weeks later) could reach 75,249,909, 10,086,085, and 255,392,154, respectively. The case ending time was January 10, 2021. However, the total peak number of cumulative cases and new cases and the maximum number of cumulative cases in the world with one week later intervention were reduced to 951,799, 108,853 and 1,530,276, respectively. Duration time of the Covid-19 spread would be reduced from 356 days to 232 days. The case ending time was September 8, 2020. We observed that delaying intervention for one month caused the maximum number of cumulative cases to increase 166.89 times, and the number of deaths increase from 53,560 to 8,938,725. We will face disastrous consequences if immediate action to intervene is not taken., Comment: 28 pages, 5 figures and 5 tables. arXiv admin note: text overlap with arXiv:2002.07112

BACKGROUND An alternative to epidemiological models for transmission dynamics of Covid-19 in China, we propose the artificial intelligence (AI)-inspired methods for real-time forecasting of Covid-19 to estimate the size, lengths and ending time of Covid-19 across China. METHODS We developed a modified stacked auto-encoder for modeling the transmission dynamics of the epidemics. We applied this model to real-time forecasting the confirmed cases of Covid-19 across China. The data were collected from January 11 to February 27, 2020 by WHO. We used the latent variables in the auto-encoder and clustering algorithms to group the provinces/cities for investigating the transmission structure. RESULTS We forecasted curves of cumulative confirmed cases of Covid-19 across China from Jan 20, 2020 to April 20, 2020. Using the multiple-step forecasting, the estimated average errors of 6-step, 7-step, 8-step, 9-step and 10-step forecasting were 1.64%, 2.27%, 2.14%, 2.08%, 0.73%, respectively. We predicted that the time points of the provinces/cities entering the plateau of the forecasted transmission dynamic curves varied, ranging from Jan 21 to April 19, 2020. The 34 provinces/cities were grouped into 9 clusters. CONCLUSIONS The accuracy of the AI-based methods for forecasting the trajectory of Covid-19 was high. We predicted that the epidemics of Covid-19 will be over by the middle of April. If the data are reliable and there are no second transmissions, we can accurately forecast the transmission dynamics of the Covid-19 across the provinces/cities in China. The AI-inspired methods are a powerful tool for helping public health planning and policymaking., Comment: 14 pages, 5 figures, 1 table

Background: Although Alzheimer's disease (AD) is a central nervous system disease and type 2 diabetes mellitus (T2DM) is a metabolic disorder, an increasing number of genetic epidemiological studies show clear link between AD and T2DM. The current approach to uncovering the shared pathways between AD and T2DM involves association analysis; however, such analyses lack power to discover the mechanisms of the diseases. Methods: We develop novel statistical methods to shift the current paradigm of genetic analysis from association analysis to deep causal inference for uncovering the shared mechanisms between AD and T2DM, and develop pipelines to infer multilevel omics causal networks which lead to shifting the current paradigm of genetic analysis from genetic analysis alone to integrated causal genomic, epigenomic, transcriptional and phenotypic data analysis. To discover common causal paths from genetic variants to AD and T2DM, we also develop algorithms that can automatically search the causal paths from genetic variants to diseases and Results: The proposed methods and algorithms are applied to ROSMAP dataset with 432 individuals who simultaneously had genotype, RNA-seq, DNA methylation and some phenotypes. We construct multi-omics causal networks and identify 13 shared causal genes, 16 shared causal pathways between AD and T2DM, and 754 gene expression and 101 gene methylation nodes that were connected to both AD and T2DM in multi-omics causal networks. Conclusions: The results of application of the proposed pipelines for identifying causal paths to real data analysis of AD and T2DM provided strong evidence to support the link between AD and T2DM and unraveled causal mechanism to explain this link., Comment: 53 pages

The mainstream of research in genetics, epigenetics and imaging data analysis focuses on statistical association or exploring statistical dependence between variables. Despite their significant progresses in genetic research, understanding the etiology and mechanism of complex phenotypes remains elusive. Using association analysis as a major analytical platform for the complex data analysis is a key issue that hampers the theoretic development of genomic science and its application in practice. Causal inference is an essential component for the discovery of mechanical relationships among complex phenotypes. Many researchers suggest making the transition from association to causation. Despite its fundamental role in science, engineering and biomedicine, the traditional methods for causal inference require at least three variables. However, quantitative genetic analysis such as QTL, eQTL, mQTL, and genomic-imaging data analysis requires exploring the causal relationships between two variables. This paper will focus on bivariate causal discovery. We will introduce independence of cause and mechanism (ICM) as a basic principle for causal inference, algorithmic information theory and additive noise model (ANM) as major tools for bivariate causal discovery. Large-scale simulations will be performed to evaluate the feasibility of the ANM for bivariate causal discovery. To further evaluate their performance for causal inference, the ANM will be applied to the construction of gene regulatory networks. Also, the ANM will be applied to trait-imaging data analysis to illustrate three scenarios: presence of both causation and association, presence of association while absence of causation, and presence of causation, while lack of association between two variables.