Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease mechanisms.The herbal medicine Qingjin Yiqi granules(QJYQ)constitute a cli...Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease mechanisms.The herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely unknown.This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.Methods:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS cases.Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug targets.Furthermore,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.Results:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by 2011.Causal graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of CFS.Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in CFS.The major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual screening.Conclusions:Our integrated analytical framework combining epidemiological,genetic,and in silico data provides a novel strategy for elucidating complex disease mechanisms,such as CFS,and informing models of action of traditional Chinese medicines,such as QJYQ.Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.展开更多
The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant...The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.展开更多
Physics-informed neural networks(PINNs)have become an attractive machine learning framework for obtaining solutions to partial differential equations(PDEs).PINNs embed initial,boundary,and PDE constraints into the los...Physics-informed neural networks(PINNs)have become an attractive machine learning framework for obtaining solutions to partial differential equations(PDEs).PINNs embed initial,boundary,and PDE constraints into the loss function.The performance of PINNs is generally affected by both training and sampling.Specifically,training methods focus on how to overcome the training difficulties caused by the special PDE residual loss of PINNs,and sampling methods are concerned with the location and distribution of the sampling points upon which evaluations of PDE residual loss are accomplished.However,a common problem among these original PINNs is that they omit special temporal information utilization during the training or sampling stages when dealing with an important PDE category,namely,time-dependent PDEs,where temporal information plays a key role in the algorithms used.There is one method,called Causal PINN,that considers temporal causality at the training level but not special temporal utilization at the sampling level.Incorporating temporal knowledge into sampling remains to be studied.To fill this gap,we propose a novel temporal causality-based adaptive sampling method that dynamically determines the sampling ratio according to both PDE residual and temporal causality.By designing a sampling ratio determined by both residual loss and temporal causality to control the number and location of sampled points in each temporal sub-domain,we provide a practical solution by incorporating temporal information into sampling.Numerical experiments of several nonlinear time-dependent PDEs,including the Cahn–Hilliard,Korteweg–de Vries,Allen–Cahn and wave equations,show that our proposed sampling method can improve the performance.We demonstrate that using such a relatively simple sampling method can improve prediction performance by up to two orders of magnitude compared with the results from other methods,especially when points are limited.展开更多
BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certai...BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.展开更多
BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship bet...BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.展开更多
People learn causal relations since childhood using counterfactual reasoning. Counterfactual reasoning uses counterfactual examples which take the form of “what if this has happened differently”. Counterfactual exam...People learn causal relations since childhood using counterfactual reasoning. Counterfactual reasoning uses counterfactual examples which take the form of “what if this has happened differently”. Counterfactual examples are also the basis of counterfactual explanation in explainable artificial intelligence (XAI). However, a framework that relies solely on optimization algorithms to find and present counterfactual samples cannot help users gain a deeper understanding of the system. Without a way to verify their understanding, the users can even be misled by such explanations. Such limitations can be overcome through an interactive and iterative framework that allows the users to explore their desired “what-if” scenarios. The purpose of our research is to develop such a framework. In this paper, we present our “what-if” XAI framework (WiXAI), which visualizes the artificial intelligence (AI) classification model from the perspective of the user’s sample and guides their “what-if” exploration. We also formulated how to use the WiXAI framework to generate counterfactuals and understand the feature-feature and feature-output relations in-depth for a local sample. These relations help move the users toward causal understanding.展开更多
Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims...Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims We aim to assess shared genetics and potential associations between ADHD and T2D.Methods We performed genetic correlation,two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D.The genome-wide association study(GWAS)summary results of T2D(80154 cases and 853816 controls),ADHD2019(20183 cases and 35191 controls from the 2019 GWAS ADHD dataset)and ADHD2022(38691 cases and 275986 controls from the 2022 GWAS ADHD dataset)were used for the analyses.The T2D dataset was obtained from the DIAGRAM Consortium.The ADHD datasets were obtained from the Psychiatric Genomics Consortium.We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset.Moreover,molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D.Results T2D has positive genetic correlations with ADHD2019(rg=0.33)and ADHD2022(rg=0.31).Genetic liability to ADHD2019 was associated with an increased risk for T2D(odds ratio(OR):1.30,p<0.001),while genetic liability to ADHD2022 had a suggestive causal effect on T2D(OR:1.30,p=0.086).Genetic liability to T2D was associated with a higher risk for ADHD2019(OR:1.05,p=0.001)and ADHD2022(OR:1.03,p<0.001).The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022.T2D and ADHD2022 have three overlapping loci.Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways.Conclusions Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.展开更多
BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems ...BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.展开更多
Regression is a widely used econometric tool in research. In observational studies, based on a number of assumptions, regression-based statistical control methods attempt to analyze the causation between treatment and...Regression is a widely used econometric tool in research. In observational studies, based on a number of assumptions, regression-based statistical control methods attempt to analyze the causation between treatment and outcome by adding control variables. However, this approach may not produce reliable estimates of causal effects. In addition to the shortcomings of the method, this lack of confidence is mainly related to ambiguous formulations in econometrics, such as the definition of selection bias, selection of core control variables, and method of testing for robustness. Within the framework of the causal models, we clarify the assumption of causal inference using regression-based statistical controls, as described in econometrics, and discuss how to select core control variables to satisfy this assumption and conduct robustness tests for regression estimates.展开更多
Cross-document relation extraction(RE),as an extension of information extraction,requires integrating information from multiple documents retrieved from open domains with a large number of irrelevant or confusing nois...Cross-document relation extraction(RE),as an extension of information extraction,requires integrating information from multiple documents retrieved from open domains with a large number of irrelevant or confusing noisy texts.Previous studies focus on the attention mechanism to construct the connection between different text features through semantic similarity.However,similarity-based methods cannot distinguish valid information from highly similar retrieved documents well.How to design an effective algorithm to implement aggregated reasoning in confusing information with similar features still remains an open issue.To address this problem,we design a novel local-toglobal causal reasoning(LGCR)network for cross-document RE,which enables efficient distinguishing,filtering and global reasoning on complex information from a causal perspective.Specifically,we propose a local causal estimation algorithm to estimate the causal effect,which is the first trial to use the causal reasoning independent of feature similarity to distinguish between confusing and valid information in cross-document RE.Furthermore,based on the causal effect,we propose a causality guided global reasoning algorithm to filter the confusing information and achieve global reasoning.Experimental results under the closed and the open settings of the large-scale dataset Cod RED demonstrate our LGCR network significantly outperforms the state-ofthe-art methods and validate the effectiveness of causal reasoning in confusing information processing.展开更多
This paper explores the asymmetric effect of COVID-19 pandemic news,as measured by the coronavirus indices(Panic,Hype,Fake News,Sentiment,Infodemic,and Media Coverage),on the cryptocurrency market.Using daily data fro...This paper explores the asymmetric effect of COVID-19 pandemic news,as measured by the coronavirus indices(Panic,Hype,Fake News,Sentiment,Infodemic,and Media Coverage),on the cryptocurrency market.Using daily data from January 2020 to September 2021 and the exponential generalized autoregressive conditional heter-oskedasticity model,the results revealed that both adverse and optimistic news had the same effect on Bitcoin returns,indicating fear of missing out behavior does not prevail.Furthermore,when the nonlinear autoregressive distributed lag model is esti-mated,both positive and negative shocks in pandemic indices promote Bitcoin’s daily changes;thus,Bitcoin is resistant to the SARS-CoV-2 pandemic crisis and may serve as a hedge during market turmoil.The analysis of frequency domain causality supports a unidirectional causality running from the Coronavirus Fake News Index and Sentiment Index to Bitcoin returns,whereas daily fluctuations in the Bitcoin price Granger affect the Coronavirus Panic Index and the Hype Index.These findings may have significant policy implications for investors and governments because they highlight the impor-tance of news during turbulent times.The empirical results indicate that pandemic news could significantly influence Bitcoin’s price.展开更多
BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown...BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown.AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies(GWAS)of the European population were identified as genetic instrument variants.GWAS statistics for individuals with UC(6968 patients and 20464 controls;adults)and CD(5956 patients and 14927 controls;adults)were obtained from the International IBD Genetics Consortium.GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium(2565 patients and 14745 controls;adults)and FinnGen project(20992 patients and 197800 controls;adults),respectively.Inverse-variance weighted was applied to assess the causal relationship,and the results were strengthened by heterogeneity,pleiotropy and leave-one-out analyses.RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety[odds ratio:1.071(95%confidence interval:1.009-1.135),P=0.023],while genetic susceptibility to CD was not associated with anxiety.Genetic susceptibility to anxiety was not associated with UC or CD.No heterogeneity or pleiotropy was observed,and the leave-one-out analysis excluded the potential influence of a particular variant.CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.展开更多
Propensity score (PS) adjustment can control confounding effects and reduce bias when estimating treatment effects in non-randomized trials or observational studies. PS methods are becoming increasingly used to estima...Propensity score (PS) adjustment can control confounding effects and reduce bias when estimating treatment effects in non-randomized trials or observational studies. PS methods are becoming increasingly used to estimate causal effects, including when the sample size is small compared to the number of confounders. With numerous confounders, quasi-complete separation can easily occur in logistic regression used for estimating the PS, but this has not been addressed. We focused on a Bayesian PS method to address the limitations of quasi-complete separation faced by small trials. Bayesian methods are useful because they estimate the PS and causal effects simultaneously while considering the uncertainty of the PS by modelling it as a latent variable. In this study, we conducted simulations to evaluate the performance of Bayesian simultaneous PS estimation by considering the specification of prior distributions for model comparison. We propose a method to improve predictive performance with discrete outcomes in small trials. We found that the specification of prior distributions assigned to logistic regression coefficients was more important in the second step than in the first step, even when there was a quasi-complete separation in the first step. Assigning Cauchy (0, 2.5) to coefficients improved the predictive performance for estimating causal effects and improving the balancing properties of the confounder.展开更多
Chinese film Little Big Woman takes the father’s funeral as the main line to tell the story of family affection and real-life emotional entanglements.In the narrative with multiple clues,we go back to find the hidden...Chinese film Little Big Woman takes the father’s funeral as the main line to tell the story of family affection and real-life emotional entanglements.In the narrative with multiple clues,we go back to find the hidden reasons,and the gradually clear reflection of the past is related to the real situation of the characters.Causal cycle narrative is not only a narrative strategy,but also a narrative logic with deep Chinese traditional cultural and philosophical connotations.展开更多
After the 21st century,high school history learning will focus on teachers promoting the twelve-year state education.In recent years,in line with the changes in the new 108-year social curriculum,supporting strategies...After the 21st century,high school history learning will focus on teachers promoting the twelve-year state education.In recent years,in line with the changes in the new 108-year social curriculum,supporting strategies have been proposed:such as literacy orientation,inquiry and practice,learning process archives,and the structural direction of the controversial Chinese history into East Asian history.Historical learning has indeed had a great impact on the people’s national spiritual education and the development of historical consciousness in Taiwan’s education policy.This is the reason Taiwan’s Ministry of Education strives to improve students’historical literacy and connotation application abilities.When developing a learning policy,both external and internal learning factors need to be considered.The external aspect deals with the reasons for learning:Is learning for the purpose of using or accumulating historical wisdom in daily life to learn from the past and the present,on the other hand,to test the content of the course and the degree of absorption;or is it specifically for exams or other enlightenment purposes.The internal aspect involves those most affected by the policy:students and teachers.After studying and observing high school history learning policies for decades,some alternative future visions for history learning were found in the method of reflection on future research-the conclusion is that history is interestingly revitalized,and the preferred future is thematic history.According to the famous futurology scholar Sohail Inayatuallah’s proposal:the causal layering model.It helps understand how Taiwan’s historical policies operate.And how teachers and students on the front line respond to changes and take future actions.The key is to change the future:in the process of building an alternative future,whether the internal and external mix has changed or whether you want to try new things and expand your horizons.In fact,the difficulty of teaching lies in students’cooperation and conscious learning.Therefore,in the analysis of learning through alternative futures,is it possible to distinguish between internal and external situations and methods such as:1.Internal:Is education centered on teachers?Or is it student-centered?2.External:Does the Ministry of Education prioritize testing,or encourage teachers to adopt interactive communication and integrate education into the curriculum?Therefore,what is the function and inspiration of studying high school history and life?If thematic history teaching is used:teachers can use thematic learning methods to help students focus on causal relationships,the causes of turning points,or the evolution process of the beginning and end of events.This is more advantageous for testing based on the application topic,and it is easy to test how much understanding and understanding of history?Has an activating effect.By studying history in high school,using the“CLA(Causal layered analysis)”method of future studies,you can enter the stage of worldview exploration with the goal of improving professional depth and emotional level,and use it in your own understanding and utilization of history.Based on research,some insights into the prospects and thinking of learning history in high schools are provided:1.Facing the impact of declining birthrate,Taiwan needs a macro perspective to improve its future competitiveness and look forward to a new perspective on world history,using futuristic cause-and-effect level analysis to combine world changes with daily life applications.2.The study of history in high schools should go into a systematic construction:understand its cause-and-effect relationships and global trends,so teachers play a professional and future role in controlling the use of new information and technology.3.In the future,humans may develop more“intelligent”needs.As a reference from history or to explore the preferred path for the future,there will also be a greater need to innovate and meet challenges.4.Studying high school history has entered the professional field.Through self-exploration,it can be transformed into life affairs and establish the concept and value of lifelong learning.5.In studying the“history of high school learning”,have new prospects for the future of education.Through professional knowledge such as“trend theory and causal hierarchy analysis”of futurology,pursue new horizons and visions,making future education full of hope and possibility.展开更多
基金supported by an internal fund from Macao Polytechnic University(RP/FCSD-02/2022).
文摘Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease mechanisms.The herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely unknown.This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.Methods:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS cases.Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug targets.Furthermore,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.Results:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by 2011.Causal graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of CFS.Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in CFS.The major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual screening.Conclusions:Our integrated analytical framework combining epidemiological,genetic,and in silico data provides a novel strategy for elucidating complex disease mechanisms,such as CFS,and informing models of action of traditional Chinese medicines,such as QJYQ.Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.
基金supported by the National Natural Science Foundation of China(Grant No.82173601)Yili&Jiangsu Joint Institute of Health(Grant No.yl2021ms02).
文摘The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.
基金Project supported by the Key National Natural Science Foundation of China(Grant No.62136005)the National Natural Science Foundation of China(Grant Nos.61922087,61906201,and 62006238)。
文摘Physics-informed neural networks(PINNs)have become an attractive machine learning framework for obtaining solutions to partial differential equations(PDEs).PINNs embed initial,boundary,and PDE constraints into the loss function.The performance of PINNs is generally affected by both training and sampling.Specifically,training methods focus on how to overcome the training difficulties caused by the special PDE residual loss of PINNs,and sampling methods are concerned with the location and distribution of the sampling points upon which evaluations of PDE residual loss are accomplished.However,a common problem among these original PINNs is that they omit special temporal information utilization during the training or sampling stages when dealing with an important PDE category,namely,time-dependent PDEs,where temporal information plays a key role in the algorithms used.There is one method,called Causal PINN,that considers temporal causality at the training level but not special temporal utilization at the sampling level.Incorporating temporal knowledge into sampling remains to be studied.To fill this gap,we propose a novel temporal causality-based adaptive sampling method that dynamically determines the sampling ratio according to both PDE residual and temporal causality.By designing a sampling ratio determined by both residual loss and temporal causality to control the number and location of sampled points in each temporal sub-domain,we provide a practical solution by incorporating temporal information into sampling.Numerical experiments of several nonlinear time-dependent PDEs,including the Cahn–Hilliard,Korteweg–de Vries,Allen–Cahn and wave equations,show that our proposed sampling method can improve the performance.We demonstrate that using such a relatively simple sampling method can improve prediction performance by up to two orders of magnitude compared with the results from other methods,especially when points are limited.
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
基金Supported by Doctoral Research Fund Project of Henan Provincial Hospital of Traditional Chinese Medicine,No.2022BSJJ10.
文摘BACKGROUND Despite being one of the most prevalent sleep disorders,obstructive sleep apnea hypoventilation syndrome(OSAHS)has limited information on its immunologic foundation.The immunological underpinnings of certain major psychiatric diseases have been uncovered in recent years thanks to the extensive use of genome-wide association studies(GWAS)and genotyping techniques using highdensity genetic markers(e.g.,SNP or CNVs).But this tactic hasn't yet been applied to OSAHS.Using a Mendelian randomization analysis,we analyzed the causal link between immune cells and the illness in order to comprehend the immunological bases of OSAHS.AIM To investigate the immune cells'association with OSAHS via genetic methods,guiding future clinical research.METHODS A comprehensive two-sample mendelian randomization study was conducted to investigate the causal relationship between immune cell characteristics and OSAHS.Summary statistics for each immune cell feature were obtained from the GWAS catalog.Information on 731 immune cell properties,such as morphologic parameters,median fluorescence intensity,absolute cellular,and relative cellular,was compiled using publicly available genetic databases.The results'robustness,heterogeneity,and horizontal pleiotropy were confirmed using extensive sensitivity examination.RESULTS Following false discovery rate(FDR)correction,no statistically significant effect of OSAHS on immunophenotypes was observed.However,two lymphocyte subsets were found to have a significant association with the risk of OSAHS:Basophil%CD33dim HLA DR-CD66b-(OR=1.03,95%CI=1.01-1.03,P<0.001);CD38 on IgD+CD24-B cell(OR=1.04,95%CI=1.02-1.04,P=0.019).CONCLUSION This study shows a strong link between immune cells and OSAHS through a gene approach,thus offering direction for potential future medical research.
文摘BACKGROUND Vitamin deficiencies are linked to various eye diseases,and the influence of vitamin D on cataract formation has been noted in prior research.However,detailed investigations into the causal relationship between 25-(OH)D status and cataract development remain scarce.AIM To explore a possible causal link between cataracts and vitamin D.METHODS In this study,we explored the causal link between 25-(OH)D levels and cataract development using Mendelian randomization.Our analytical approach included inverse-variance weighting(IVW),MR-Egger,weighted median,simple mode,and weighted mode methods.The primary analyses utilized IVW with random effects,supplemented by sensitivity and heterogeneity tests using both IVW and MR-Egger.MR-Egger was also applied for pleiotropy testing.Additionally,a leave-one-out analysis helped identify potentially impactful single-nucleotide polymorphisms.RESULTS The analysis revealed a positive association between 25-(OH)D levels and the risk of developing cataracts(OR=1.11,95%CI:1.00-1.22;P=0.032).The heterogeneity test revealed that our IVW analysis exhibited minimal heterogeneity(P>0.05),and the pleiotropy test findings confirmed the absence of pleiotropy within our IVW analysis(P>0.05).Furthermore,a search of the human genotype-phenotype association database failed to identify any potentially relevant risk-factor single nucleotide polymorphisms.CONCLUSION There is a potential causal link between 25-(OH)D levels and the development of cataracts,suggesting that greater 25-(OH)D levels may be a contributing risk factor for cataract formation.Further experimental research is required to confirm these findings.
文摘People learn causal relations since childhood using counterfactual reasoning. Counterfactual reasoning uses counterfactual examples which take the form of “what if this has happened differently”. Counterfactual examples are also the basis of counterfactual explanation in explainable artificial intelligence (XAI). However, a framework that relies solely on optimization algorithms to find and present counterfactual samples cannot help users gain a deeper understanding of the system. Without a way to verify their understanding, the users can even be misled by such explanations. Such limitations can be overcome through an interactive and iterative framework that allows the users to explore their desired “what-if” scenarios. The purpose of our research is to develop such a framework. In this paper, we present our “what-if” XAI framework (WiXAI), which visualizes the artificial intelligence (AI) classification model from the perspective of the user’s sample and guides their “what-if” exploration. We also formulated how to use the WiXAI framework to generate counterfactuals and understand the feature-feature and feature-output relations in-depth for a local sample. These relations help move the users toward causal understanding.
文摘Background Type 2 diabetes(T2D)is a chronic metabolic disorder with high comorbidity with mental disorders.The genetic links between attention-deficit/hyperactivity disorder(ADHD)and T2D have yet to be elucidated.Aims We aim to assess shared genetics and potential associations between ADHD and T2D.Methods We performed genetic correlation,two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D.The genome-wide association study(GWAS)summary results of T2D(80154 cases and 853816 controls),ADHD2019(20183 cases and 35191 controls from the 2019 GWAS ADHD dataset)and ADHD2022(38691 cases and 275986 controls from the 2022 GWAS ADHD dataset)were used for the analyses.The T2D dataset was obtained from the DIAGRAM Consortium.The ADHD datasets were obtained from the Psychiatric Genomics Consortium.We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset.Moreover,molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D.Results T2D has positive genetic correlations with ADHD2019(rg=0.33)and ADHD2022(rg=0.31).Genetic liability to ADHD2019 was associated with an increased risk for T2D(odds ratio(OR):1.30,p<0.001),while genetic liability to ADHD2022 had a suggestive causal effect on T2D(OR:1.30,p=0.086).Genetic liability to T2D was associated with a higher risk for ADHD2019(OR:1.05,p=0.001)and ADHD2022(OR:1.03,p<0.001).The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022.T2D and ADHD2022 have three overlapping loci.Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways.Conclusions Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.
基金Supported by National Natural Science Foundation of China,No.82174363.
文摘BACKGROUND Gastroesophageal reflux disease(GERD)affects approximately 13% of the global population.However,the pathogenesis of GERD has not been fully elucidated.The development of metabolomics as a branch of systems biology in recent years has opened up new avenues for the investigation of disease processes.As a powerful statistical tool,Mendelian randomization(MR)is widely used to explore the causal relationship between exposure and outcome.AIM To analyze of the relationship between 486 blood metabolites and GERD.METHODS Two-sample MR analysis was used to assess the causal relationship between blood metabolites and GERD.A genome-wide association study(GWAS)of 486 metabolites was the exposure,and two different GWAS datasets of GERD were used as endpoints for the base analysis and replication and meta-analysis.Bonferroni correction is used to determine causal correlation features(P<1.03×10^(-4)).The results were subjected to sensitivity analysis to assess heterogeneity and pleiotropy.Using the MR Steiger filtration method to detect whether there is a reverse causal relationship between metabolites and GERD.In addition,metabolic pathway analysis was conducted using the online database based MetaboAnalyst 5.0 software.RESULTS In MR analysis,four blood metabolites are negatively correlated with GERD:Levulinate(4-oxovalerate),stearate(18:0),adrenate(22:4n6)and p-acetamidophenylglucuronide.However,we also found a positive correlation between four blood metabolites and GERD:Kynurenine,1-linoleoylglycerophosphoethanolamine,butyrylcarnitine and guanosine.And bonferroni correction showed that butyrylcarnitine(odd ratio 1.10,95% confidence interval:1.05-1.16,P=7.71×10^(-5))was the most reliable causal metabolite.In addition,one significant pathways,the"glycerophospholipid metabolism"pathway,can be involved in the pathogenesis of GERD.CONCLUSION Our study found through the integration of genomics and metabolomics that butyrylcarnitine may be a potential biomarker for GERD,which will help further elucidate the pathogenesis of GERD and better guide its treatment.At the same time,this also contributes to early screening and prevention of GERD.However,the results of this study require further confirmation from both basic and clinical real-world studies.
基金This research was funded by the National Natural Science Foundation of China(Grant No.72074060).
文摘Regression is a widely used econometric tool in research. In observational studies, based on a number of assumptions, regression-based statistical control methods attempt to analyze the causation between treatment and outcome by adding control variables. However, this approach may not produce reliable estimates of causal effects. In addition to the shortcomings of the method, this lack of confidence is mainly related to ambiguous formulations in econometrics, such as the definition of selection bias, selection of core control variables, and method of testing for robustness. Within the framework of the causal models, we clarify the assumption of causal inference using regression-based statistical controls, as described in econometrics, and discuss how to select core control variables to satisfy this assumption and conduct robustness tests for regression estimates.
基金supported in part by the National Key Research and Development Program of China(2022ZD0116405)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA27030300)the Key Research Program of the Chinese Academy of Sciences(ZDBS-SSW-JSC006)。
文摘Cross-document relation extraction(RE),as an extension of information extraction,requires integrating information from multiple documents retrieved from open domains with a large number of irrelevant or confusing noisy texts.Previous studies focus on the attention mechanism to construct the connection between different text features through semantic similarity.However,similarity-based methods cannot distinguish valid information from highly similar retrieved documents well.How to design an effective algorithm to implement aggregated reasoning in confusing information with similar features still remains an open issue.To address this problem,we design a novel local-toglobal causal reasoning(LGCR)network for cross-document RE,which enables efficient distinguishing,filtering and global reasoning on complex information from a causal perspective.Specifically,we propose a local causal estimation algorithm to estimate the causal effect,which is the first trial to use the causal reasoning independent of feature similarity to distinguish between confusing and valid information in cross-document RE.Furthermore,based on the causal effect,we propose a causality guided global reasoning algorithm to filter the confusing information and achieve global reasoning.Experimental results under the closed and the open settings of the large-scale dataset Cod RED demonstrate our LGCR network significantly outperforms the state-ofthe-art methods and validate the effectiveness of causal reasoning in confusing information processing.
文摘This paper explores the asymmetric effect of COVID-19 pandemic news,as measured by the coronavirus indices(Panic,Hype,Fake News,Sentiment,Infodemic,and Media Coverage),on the cryptocurrency market.Using daily data from January 2020 to September 2021 and the exponential generalized autoregressive conditional heter-oskedasticity model,the results revealed that both adverse and optimistic news had the same effect on Bitcoin returns,indicating fear of missing out behavior does not prevail.Furthermore,when the nonlinear autoregressive distributed lag model is esti-mated,both positive and negative shocks in pandemic indices promote Bitcoin’s daily changes;thus,Bitcoin is resistant to the SARS-CoV-2 pandemic crisis and may serve as a hedge during market turmoil.The analysis of frequency domain causality supports a unidirectional causality running from the Coronavirus Fake News Index and Sentiment Index to Bitcoin returns,whereas daily fluctuations in the Bitcoin price Granger affect the Coronavirus Panic Index and the Hype Index.These findings may have significant policy implications for investors and governments because they highlight the impor-tance of news during turbulent times.The empirical results indicate that pandemic news could significantly influence Bitcoin’s price.
基金Supported by China Postdoctoral Science Foundation,No.2021M701614Guangdong Basic and Applied Basic Research Foundation,No.2022A1515111063,No.2022A1515111045Foundation of Guangdong Provincial People’s Hospital,No.8200010545。
文摘BACKGROUND Anxiety is common in patients with inflammatory bowel disease(IBD),including those with ulcerative colitis(UC)and Crohn’s disease(CD);however,the causal relationship between IBD and anxiety remains unknown.AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.METHODS Single nucleotide polymorphisms retrieved from genome-wide association studies(GWAS)of the European population were identified as genetic instrument variants.GWAS statistics for individuals with UC(6968 patients and 20464 controls;adults)and CD(5956 patients and 14927 controls;adults)were obtained from the International IBD Genetics Consortium.GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium(2565 patients and 14745 controls;adults)and FinnGen project(20992 patients and 197800 controls;adults),respectively.Inverse-variance weighted was applied to assess the causal relationship,and the results were strengthened by heterogeneity,pleiotropy and leave-one-out analyses.RESULTS Genetic susceptibility to UC was associated with an increased risk of anxiety[odds ratio:1.071(95%confidence interval:1.009-1.135),P=0.023],while genetic susceptibility to CD was not associated with anxiety.Genetic susceptibility to anxiety was not associated with UC or CD.No heterogeneity or pleiotropy was observed,and the leave-one-out analysis excluded the potential influence of a particular variant.CONCLUSION This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.
文摘Propensity score (PS) adjustment can control confounding effects and reduce bias when estimating treatment effects in non-randomized trials or observational studies. PS methods are becoming increasingly used to estimate causal effects, including when the sample size is small compared to the number of confounders. With numerous confounders, quasi-complete separation can easily occur in logistic regression used for estimating the PS, but this has not been addressed. We focused on a Bayesian PS method to address the limitations of quasi-complete separation faced by small trials. Bayesian methods are useful because they estimate the PS and causal effects simultaneously while considering the uncertainty of the PS by modelling it as a latent variable. In this study, we conducted simulations to evaluate the performance of Bayesian simultaneous PS estimation by considering the specification of prior distributions for model comparison. We propose a method to improve predictive performance with discrete outcomes in small trials. We found that the specification of prior distributions assigned to logistic regression coefficients was more important in the second step than in the first step, even when there was a quasi-complete separation in the first step. Assigning Cauchy (0, 2.5) to coefficients improved the predictive performance for estimating causal effects and improving the balancing properties of the confounder.
文摘Chinese film Little Big Woman takes the father’s funeral as the main line to tell the story of family affection and real-life emotional entanglements.In the narrative with multiple clues,we go back to find the hidden reasons,and the gradually clear reflection of the past is related to the real situation of the characters.Causal cycle narrative is not only a narrative strategy,but also a narrative logic with deep Chinese traditional cultural and philosophical connotations.
文摘After the 21st century,high school history learning will focus on teachers promoting the twelve-year state education.In recent years,in line with the changes in the new 108-year social curriculum,supporting strategies have been proposed:such as literacy orientation,inquiry and practice,learning process archives,and the structural direction of the controversial Chinese history into East Asian history.Historical learning has indeed had a great impact on the people’s national spiritual education and the development of historical consciousness in Taiwan’s education policy.This is the reason Taiwan’s Ministry of Education strives to improve students’historical literacy and connotation application abilities.When developing a learning policy,both external and internal learning factors need to be considered.The external aspect deals with the reasons for learning:Is learning for the purpose of using or accumulating historical wisdom in daily life to learn from the past and the present,on the other hand,to test the content of the course and the degree of absorption;or is it specifically for exams or other enlightenment purposes.The internal aspect involves those most affected by the policy:students and teachers.After studying and observing high school history learning policies for decades,some alternative future visions for history learning were found in the method of reflection on future research-the conclusion is that history is interestingly revitalized,and the preferred future is thematic history.According to the famous futurology scholar Sohail Inayatuallah’s proposal:the causal layering model.It helps understand how Taiwan’s historical policies operate.And how teachers and students on the front line respond to changes and take future actions.The key is to change the future:in the process of building an alternative future,whether the internal and external mix has changed or whether you want to try new things and expand your horizons.In fact,the difficulty of teaching lies in students’cooperation and conscious learning.Therefore,in the analysis of learning through alternative futures,is it possible to distinguish between internal and external situations and methods such as:1.Internal:Is education centered on teachers?Or is it student-centered?2.External:Does the Ministry of Education prioritize testing,or encourage teachers to adopt interactive communication and integrate education into the curriculum?Therefore,what is the function and inspiration of studying high school history and life?If thematic history teaching is used:teachers can use thematic learning methods to help students focus on causal relationships,the causes of turning points,or the evolution process of the beginning and end of events.This is more advantageous for testing based on the application topic,and it is easy to test how much understanding and understanding of history?Has an activating effect.By studying history in high school,using the“CLA(Causal layered analysis)”method of future studies,you can enter the stage of worldview exploration with the goal of improving professional depth and emotional level,and use it in your own understanding and utilization of history.Based on research,some insights into the prospects and thinking of learning history in high schools are provided:1.Facing the impact of declining birthrate,Taiwan needs a macro perspective to improve its future competitiveness and look forward to a new perspective on world history,using futuristic cause-and-effect level analysis to combine world changes with daily life applications.2.The study of history in high schools should go into a systematic construction:understand its cause-and-effect relationships and global trends,so teachers play a professional and future role in controlling the use of new information and technology.3.In the future,humans may develop more“intelligent”needs.As a reference from history or to explore the preferred path for the future,there will also be a greater need to innovate and meet challenges.4.Studying high school history has entered the professional field.Through self-exploration,it can be transformed into life affairs and establish the concept and value of lifelong learning.5.In studying the“history of high school learning”,have new prospects for the future of education.Through professional knowledge such as“trend theory and causal hierarchy analysis”of futurology,pursue new horizons and visions,making future education full of hope and possibility.