Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available....Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.Methods:We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings,version 3.0(ACMG SF v3.0),list in the genomes of 57,933 Icelanders.We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database,the frequency of variants,and their associations with disease to create a manually curated set of actionable genotypes(variants).We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers.展开更多
Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available....Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.Methods:We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings,version 3.0(ACMG SF v3.0),list in the genomes of 57,933 Icelanders.We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database,the frequency of variants,and their associations with disease to create a manually curated set of actionable genotypes(variants).We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers.展开更多
Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available....Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.展开更多
How organizations analyze and use data for decision-making has been changed by cognitive computing and artificial intelligence (AI). Cognitive computing solutions can translate enormous amounts of data into valuable i...How organizations analyze and use data for decision-making has been changed by cognitive computing and artificial intelligence (AI). Cognitive computing solutions can translate enormous amounts of data into valuable insights by utilizing the power of cutting-edge algorithms and machine learning, empowering enterprises to make deft decisions quickly and efficiently. This article explores the idea of cognitive computing and AI in decision-making, emphasizing its function in converting unvalued data into valuable knowledge. It details the advantages of utilizing these technologies, such as greater productivity, accuracy, and efficiency. Businesses may use cognitive computing and AI to their advantage to obtain a competitive edge in today’s data-driven world by knowing their capabilities and possibilities [1].展开更多
Many companies like credit card, insurance, bank, retail industry require direct marketing. Data mining can help those institutes to set marketing goal. Data mining techniques have good prospects in their target audie...Many companies like credit card, insurance, bank, retail industry require direct marketing. Data mining can help those institutes to set marketing goal. Data mining techniques have good prospects in their target audiences and improve the likelihood of response. In this work we have investigated two data mining techniques: the Naive Bayes and the C4.5 decision tree algorithms. The goal of this work is to predict whether a client will subscribe a term deposit. We also made comparative study of performance of those two algorithms. Publicly available UCI data is used to train and test the performance of the algorithms. Besides, we extract actionable knowledge from decision tree that focuses to take interesting and important decision in business area.展开更多
Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western ...Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western populations.This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.Methods:This study included 5,534 consecutive CRC patients from the Genecast database.Genomic profiling was performed using a panel of 769 cancer-related genes.Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.Results:Among 5,534 CRC patients,54(0.98%)had actionable gene fusions,with NTRK1/2/3 being the most common fusion(0.38%),accounting for 38.9%(21/54)of those with fusions.Actionable gene fusion enrichment was higher in patients with microsatellite instability-high(MSI-H)(6.7%vs.0.5%,P<0.001),RAS/BRAF wildtype(2.0%vs.0.2%,P<0.001)and RNF43 mutation(7.7%vs.0.4%,P<0.001)than in patients with microsatellite stability/MSI-low,RAS/BRAF mutation and RNF43 wildtype,respectively.When these markers were combined,the fusion detection rate increased.Among patients with RAS/BRAF wildtype and MSI-H,fusions were detected in 20.3%of patients.The fusion detection rate further increased to 37.5%when RNF43 mutation was added.The fusion detection rate was also higher in colon cancer than in rectal cancer.No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast,cBioPortal,and ChimerSeq databases.Conclusions:Approximately 1%of the unselected Chinese CRC population carries actionable gene fusions,mostly involving NTRK.Actionable gene fusions are more prevalent in MSI-H,RAS/BRAF wildtype,or RNF43-mutated CRC,as well as in colon cancer.Mapping of these molecular markers can markedly increase the fusion detection rate,which can help clinicians select candidates for fusion testing and targeted therapy.展开更多
Background Despite the increasing focus on strengthening One Health capacity building on global level,challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region.Rec...Background Despite the increasing focus on strengthening One Health capacity building on global level,challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region.Recognizing these gaps,the One Health Action Commission(OHAC)was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact.Main text This viewpoint describes the agenda of,and motivation for,the recently formed OHAC.Recognizing the urgent need for evidence to support the formulation of necessary action plans,OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses,antimicrobial resistance,addressing food safety,and to enhance capacity building for context-sensitive One Health implementation.Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders,OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge,distilled practical experience and actionable policy advice,guided by strong ethical principles of One Health.展开更多
Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutati...Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutations,tyrosine kinase inhibitors developed against EGFR,ALK,RET,BRAF,ROS1,NTRK,MET,and KRAS,exhibit substantial antitumor activity and have been incorporated into standard treatment regimens.Additionally,numerous novel therapies,including immunotherapy and antibody-drug conjugate therapy,have been found to benefit patients with NSCLC.This review summarizes current advancements in targeted therapy for NSCLC,according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.展开更多
Introduction Neurosurgical emergencies such as spontaneous intracerebral hemorrhage(ICH),traumatic brain injury(TBI),and acute brain herniation are among the most time-sensitive and high-stakes conditions in modern me...Introduction Neurosurgical emergencies such as spontaneous intracerebral hemorrhage(ICH),traumatic brain injury(TBI),and acute brain herniation are among the most time-sensitive and high-stakes conditions in modern medicine.Clinical decisions often must be made within minutes,yet these decisions are traditionally guided by limited information,heuristic reasoning,and past experience.In this context,the rise of medical data mining and real-time analytics offers a transformative opportunity:to extract actionable intelligence from the flood of clinical,imaging,and physiological data already being collected,and to use this intelligence to guide care in real time[1–3](Figure 1).展开更多
The cybersecurity report provides unstructured actionable cyber threat intelligence(CTI)with detailed threat attack procedures and indicators of compromise(IOCs),e.g.,malware hash or URL(uniform resource locator)of co...The cybersecurity report provides unstructured actionable cyber threat intelligence(CTI)with detailed threat attack procedures and indicators of compromise(IOCs),e.g.,malware hash or URL(uniform resource locator)of command and control server.The actionable CTI,integrated into intrusion detection systems,can not only prioritize the most urgent threats based on the campaign stages of attack vectors(i.e.,IOCs)but also take appropriate mitigation measures based on contextual information of the alerts.However,the dramatic growth in the number of cybersecurity reports makes it nearly impossible for security professionals to find an efficient way to use these massive amounts of threat intelligence.In this paper,we propose a trigger-enhanced actionable CTI discovery system(TriCTI)to portray a relationship between IOCs and campaign stages and generate actionable CTI from cybersecurity reports through natural language processing(NLP)technology.Specifically,we introduce the“campaign trigger”for an effective explanation of the campaign stages to improve the performance of the classification model.The campaign trigger phrases are the keywords in the sentence that imply the campaign stage.The trained final trigger vectors have similar space representations with the keywords in the unseen sentence and will help correct classification by increasing the weight of the keywords.We also meticulously devise a data augmentation specifically for cybersecurity training sets to cope with the challenge of the scarcity of annotation data sets.Compared with state-of-the-art text classification models,such as BERT,the trigger-enhanced classification model has better performance with accuracy(86.99%)and F1 score(87.02%).We run TriCTI on more than 29k cybersecurity reports,from which we automatically and efficiently collect 113,543 actionable CTI.In particular,we verify the actionability of discovered CTI by using large-scale field data from VirusTotal(VT).The results demonstrate that the threat intelligence provided by VT lacks a part of the threat context for IOCs,such as the Actions on Objectives campaign stage.As a comparison,our proposed method can completely identify the actionable CTI in all campaign stages.Accordingly,cyber threats can be identified and resisted at any campaign stage with the discovered actionable CTI.展开更多
为了规避网络广告延时效应带来的不确定性风险,企业往往会采用效果付费(cost per action, CPA)方式进行网络推广。本文在CPA模式下研究考虑延时效应的供应链网络广告决策与协调问题。首先,建立含有时间延迟的品牌信誉动态模型和效果依...为了规避网络广告延时效应带来的不确定性风险,企业往往会采用效果付费(cost per action, CPA)方式进行网络推广。本文在CPA模式下研究考虑延时效应的供应链网络广告决策与协调问题。首先,建立含有时间延迟的品牌信誉动态模型和效果依赖的网络广告投入成本模型,并构建CPA模式下供应链网络广告微分博弈模型,再利用最优控制理论求解得到分散式决策与集中式决策下供应链系统的最优网络广告策略、定价策略、品牌信誉以及利润。其次,对决策结果进行综合比较分析,明确供应链系统的最佳决策机制,参照最佳决策供应链系统,设计一种动态批发价格契约,使供应链实现完美协调。最后,通过数值算例验证研究结果的有效性,对网络广告投入、品牌信誉、利润以及协调参数进行灵敏度分析。研究发现,与传统广告研究结论不同,CPA模式下制造商的最优网络广告投入高度依赖于时间,且遵循“逐降-早停”原则;CPA模式下短暂的网络广告延时效应和良好的销售效果可以增加双方合作的积极性,进而企业倾向于整体获利最大的集中式决策机制。本文研究成果为供应链企业网络推广实践提供了重要的理论指导。展开更多
Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for...Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.展开更多
Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-targe...Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.展开更多
The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of ...The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.展开更多
In this paper,we study the Bowen entropy of stable sets in positive entropy G-system of amenable group actions.The lower bound of the Bowen entropy of these sets are estimated.
Although amazing progress has been made in ma- chine learning to achieve high generalization accuracy and ef- ficiency, there is still very limited work on deriving meaning- ful decision-making actions from the result...Although amazing progress has been made in ma- chine learning to achieve high generalization accuracy and ef- ficiency, there is still very limited work on deriving meaning- ful decision-making actions from the resulting models. How- ever, in many applications such as advertisement, recommen- dation systems, social networks, customer relationship man- agement, and clinical prediction, the users need not only ac- curate prediction, but also suggestions on actions to achieve a desirable goal （e.g., high ads hit rates） or avert an unde- sirable predicted result （e.g., clinical deterioration）. Existing works for extracting such actionability are few and limited to simple models such as a decision tree. The dilemma is that those models with high accuracy are often more complex and harder to extract actionability from. In this paper, we propose an effective method to extract ac- tionable knowledge from additive tree models （ATMs）, one of the most widely used and best off-the-shelf classifiers. We rigorously formulate the optimal actionable planning （OAP） problem for a given ATM, which is to extract an action- able plan for a given input so that it can achieve a desirable output while maximizing the net profit. Based on a state space graph formulation, we first propose an optimal heuris- tic search method which intends to find an optimal solution. Then, we also present a sub-optimal heuristic search with an admissible and consistent heuristic function which can re- markably improve the efficiency of the algorithm. Our exper- imental results demonstrate the effectiveness and efficiency of the proposed algorithms on several real datasets in the application domain of personal credit and banking.展开更多
In the last few years,scholars have continued to refine the understanding of conservatism through cultural psychology.The application of Symbolic Action Theory,particularly Ernst Boesch’s framework,remains central to...In the last few years,scholars have continued to refine the understanding of conservatism through cultural psychology.The application of Symbolic Action Theory,particularly Ernst Boesch’s framework,remains central to discussions,illustrating how conservatism is not merely a political stance but a dynamic system of behaviors that reinforces societal values through symbolic actions(Kölbl,2020).Additionally,recent studies have highlighted the interaction between cultural conservatism and collective identity,with particular focus on how conservatism can manifest in diverse cultural settings(Yilmaz&Alper,2019).Research also underscores the relevance of symbolic politics in shaping both individual attitudes and broader political actions,contributing to the understanding of how symbolic meanings sustain social conservatism in different cultural contexts(Chin&Levey,2022).展开更多
On the morning of May 31st,the parallel forum"Ecological Actions to Carry Forward the Shared Values of Mankind,"as part of the 4th Dialogue on Exchanges and Mutual Learning among Civilisations,was held in Du...On the morning of May 31st,the parallel forum"Ecological Actions to Carry Forward the Shared Values of Mankind,"as part of the 4th Dialogue on Exchanges and Mutual Learning among Civilisations,was held in Dunhuang.More than 50 experts and scholars from different countries,including China,Kenya and Japan,engaged in indepth discussions on the theme.展开更多
ln order to improve the level of investment promotion and redouble effortsto enhance services,on February l9th,the 2025 Action Plan for StabilizingForeign lnvestment was released,proposing 20 measures in four aspects....ln order to improve the level of investment promotion and redouble effortsto enhance services,on February l9th,the 2025 Action Plan for StabilizingForeign lnvestment was released,proposing 20 measures in four aspects.Cur-rently,with increasing uncertainties in the external environment,China facesmultple difficulties and challenges in attracting foreign investment.展开更多
A Green Lifestyle The Double Take column looks at a single topic from an African and Chinese perspective.This month,we explore how personal actions are related to sustainable development.
文摘Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.Methods:We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings,version 3.0(ACMG SF v3.0),list in the genomes of 57,933 Icelanders.We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database,the frequency of variants,and their associations with disease to create a manually curated set of actionable genotypes(variants).We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers.
文摘Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.Methods:We assessed the prevalence of coding and splice variants in genes on the ACMG Secondary Findings,version 3.0(ACMG SF v3.0),list in the genomes of 57,933 Icelanders.We assigned pathogenicity to all reviewed variants using reported evidence in the ClinVar database,the frequency of variants,and their associations with disease to create a manually curated set of actionable genotypes(variants).We assessed the relationship between these genotypes and life span and further examined the specific causes of death among carriers.
文摘Background:In 2021,the American College of Medical Genetics and Genomics(ACMG)recommended reporting actionable genotypes in 73 genes associated with diseases for which preventive or therapeutic measures are available.Evaluations of the association of actionable genotypes in these genes with life span are currently lacking.
文摘How organizations analyze and use data for decision-making has been changed by cognitive computing and artificial intelligence (AI). Cognitive computing solutions can translate enormous amounts of data into valuable insights by utilizing the power of cutting-edge algorithms and machine learning, empowering enterprises to make deft decisions quickly and efficiently. This article explores the idea of cognitive computing and AI in decision-making, emphasizing its function in converting unvalued data into valuable knowledge. It details the advantages of utilizing these technologies, such as greater productivity, accuracy, and efficiency. Businesses may use cognitive computing and AI to their advantage to obtain a competitive edge in today’s data-driven world by knowing their capabilities and possibilities [1].
文摘Many companies like credit card, insurance, bank, retail industry require direct marketing. Data mining can help those institutes to set marketing goal. Data mining techniques have good prospects in their target audiences and improve the likelihood of response. In this work we have investigated two data mining techniques: the Naive Bayes and the C4.5 decision tree algorithms. The goal of this work is to predict whether a client will subscribe a term deposit. We also made comparative study of performance of those two algorithms. Publicly available UCI data is used to train and test the performance of the algorithms. Besides, we extract actionable knowledge from decision tree that focuses to take interesting and important decision in business area.
基金supported by the capital health research and development of special(2022-2-7083).
文摘Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western populations.This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.Methods:This study included 5,534 consecutive CRC patients from the Genecast database.Genomic profiling was performed using a panel of 769 cancer-related genes.Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.Results:Among 5,534 CRC patients,54(0.98%)had actionable gene fusions,with NTRK1/2/3 being the most common fusion(0.38%),accounting for 38.9%(21/54)of those with fusions.Actionable gene fusion enrichment was higher in patients with microsatellite instability-high(MSI-H)(6.7%vs.0.5%,P<0.001),RAS/BRAF wildtype(2.0%vs.0.2%,P<0.001)and RNF43 mutation(7.7%vs.0.4%,P<0.001)than in patients with microsatellite stability/MSI-low,RAS/BRAF mutation and RNF43 wildtype,respectively.When these markers were combined,the fusion detection rate increased.Among patients with RAS/BRAF wildtype and MSI-H,fusions were detected in 20.3%of patients.The fusion detection rate further increased to 37.5%when RNF43 mutation was added.The fusion detection rate was also higher in colon cancer than in rectal cancer.No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast,cBioPortal,and ChimerSeq databases.Conclusions:Approximately 1%of the unselected Chinese CRC population carries actionable gene fusions,mostly involving NTRK.Actionable gene fusions are more prevalent in MSI-H,RAS/BRAF wildtype,or RNF43-mutated CRC,as well as in colon cancer.Mapping of these molecular markers can markedly increase the fusion detection rate,which can help clinicians select candidates for fusion testing and targeted therapy.
基金supported in whole by the Bill&Melinda Gates Foundation(No.INV-046218)
文摘Background Despite the increasing focus on strengthening One Health capacity building on global level,challenges remain in devising and implementing real-world interventions particularly in the Asia-Pacific region.Recognizing these gaps,the One Health Action Commission(OHAC)was established as an academic community for One Health action with an emphasis on research agenda setting to identify actions for highest impact.Main text This viewpoint describes the agenda of,and motivation for,the recently formed OHAC.Recognizing the urgent need for evidence to support the formulation of necessary action plans,OHAC advocates the adoption of both bottom-up and top-down approaches to identify the current gaps in combating zoonoses,antimicrobial resistance,addressing food safety,and to enhance capacity building for context-sensitive One Health implementation.Conclusions By promoting broader engagement and connection of multidisciplinary stakeholders,OHAC envisions a collaborative global platform for the generation of innovative One Health knowledge,distilled practical experience and actionable policy advice,guided by strong ethical principles of One Health.
基金funded by the National Natural Science Foundation of China(Grant no.82172776)Tianjin Health Research Project(Grant no.TJWJ2023XK005)Tianjin Science and Technology Plan Project(Grant no.24ZXGZSY00010).
文摘Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutations,tyrosine kinase inhibitors developed against EGFR,ALK,RET,BRAF,ROS1,NTRK,MET,and KRAS,exhibit substantial antitumor activity and have been incorporated into standard treatment regimens.Additionally,numerous novel therapies,including immunotherapy and antibody-drug conjugate therapy,have been found to benefit patients with NSCLC.This review summarizes current advancements in targeted therapy for NSCLC,according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.
文摘Introduction Neurosurgical emergencies such as spontaneous intracerebral hemorrhage(ICH),traumatic brain injury(TBI),and acute brain herniation are among the most time-sensitive and high-stakes conditions in modern medicine.Clinical decisions often must be made within minutes,yet these decisions are traditionally guided by limited information,heuristic reasoning,and past experience.In this context,the rise of medical data mining and real-time analytics offers a transformative opportunity:to extract actionable intelligence from the flood of clinical,imaging,and physiological data already being collected,and to use this intelligence to guide care in real time[1–3](Figure 1).
基金Our research was supported by the National Key Research and Development Program of China(Nos.2019QY1301,2018YFB0805005,2018YFC0824801).
文摘The cybersecurity report provides unstructured actionable cyber threat intelligence(CTI)with detailed threat attack procedures and indicators of compromise(IOCs),e.g.,malware hash or URL(uniform resource locator)of command and control server.The actionable CTI,integrated into intrusion detection systems,can not only prioritize the most urgent threats based on the campaign stages of attack vectors(i.e.,IOCs)but also take appropriate mitigation measures based on contextual information of the alerts.However,the dramatic growth in the number of cybersecurity reports makes it nearly impossible for security professionals to find an efficient way to use these massive amounts of threat intelligence.In this paper,we propose a trigger-enhanced actionable CTI discovery system(TriCTI)to portray a relationship between IOCs and campaign stages and generate actionable CTI from cybersecurity reports through natural language processing(NLP)technology.Specifically,we introduce the“campaign trigger”for an effective explanation of the campaign stages to improve the performance of the classification model.The campaign trigger phrases are the keywords in the sentence that imply the campaign stage.The trained final trigger vectors have similar space representations with the keywords in the unseen sentence and will help correct classification by increasing the weight of the keywords.We also meticulously devise a data augmentation specifically for cybersecurity training sets to cope with the challenge of the scarcity of annotation data sets.Compared with state-of-the-art text classification models,such as BERT,the trigger-enhanced classification model has better performance with accuracy(86.99%)and F1 score(87.02%).We run TriCTI on more than 29k cybersecurity reports,from which we automatically and efficiently collect 113,543 actionable CTI.In particular,we verify the actionability of discovered CTI by using large-scale field data from VirusTotal(VT).The results demonstrate that the threat intelligence provided by VT lacks a part of the threat context for IOCs,such as the Actions on Objectives campaign stage.As a comparison,our proposed method can completely identify the actionable CTI in all campaign stages.Accordingly,cyber threats can be identified and resisted at any campaign stage with the discovered actionable CTI.
文摘为了规避网络广告延时效应带来的不确定性风险,企业往往会采用效果付费(cost per action, CPA)方式进行网络推广。本文在CPA模式下研究考虑延时效应的供应链网络广告决策与协调问题。首先,建立含有时间延迟的品牌信誉动态模型和效果依赖的网络广告投入成本模型,并构建CPA模式下供应链网络广告微分博弈模型,再利用最优控制理论求解得到分散式决策与集中式决策下供应链系统的最优网络广告策略、定价策略、品牌信誉以及利润。其次,对决策结果进行综合比较分析,明确供应链系统的最佳决策机制,参照最佳决策供应链系统,设计一种动态批发价格契约,使供应链实现完美协调。最后,通过数值算例验证研究结果的有效性,对网络广告投入、品牌信誉、利润以及协调参数进行灵敏度分析。研究发现,与传统广告研究结论不同,CPA模式下制造商的最优网络广告投入高度依赖于时间,且遵循“逐降-早停”原则;CPA模式下短暂的网络广告延时效应和良好的销售效果可以增加双方合作的积极性,进而企业倾向于整体获利最大的集中式决策机制。本文研究成果为供应链企业网络推广实践提供了重要的理论指导。
基金supported by the Science and Technology Innovation Program of Hunan Province(No.2022RC1168)National Natural Science Foundation of China(Nos.82322073,82173846,82304533)+12 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)China Postdoctoral Science Foundation(No.2021M702215)Oriental Scholars of Shanghai Universities(No.TP2022081)Jiangxi Province Thousand Talents Program(No.jxsq2023102168)Young Talent Lifting Project of China Association of Chinese Medicine(No.CACM-(2021-QNRC2-A08))Shanghai Rising-Star Program(No.22QA1409100)Shanghai Sailing Program(No.22YF1445000)2021 Shanghai Science and Technology Innovation Action Plan(No.21S11902800)Three-year Action Plan for Shanghai TCM Development and Inheritance Program(Nos.ZY(2021-2023)-0208,ZY(2021-2023)-0401)High level Key Discipline of National Administration of Traditional Chinese Medicine(No.71)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology。
文摘Despite ongoing advancements in cancer treatment,the emergence of primary and acquired resistance poses a significant challenge for both traditional chemotherapy and immune checkpoint blockade therapies.The demand for targeted therapeutics for multidrug-resistant cancer is more important than ever.Peptides,as emerging alternatives to current anticancer drugs,offer exquisite versatility in facilitating the design of novel oncology drugs,with the core superiorities of good biocompatibility and a low tendency to induce drug resistance.This review comprehensively introduces the pharmacological mechanisms of peptide-based drugs and strategies for overcoming multidrug resistance(MDR)in cancers,including inducing cell membrane lysis,targeting organelles,activating anticancer immune responses,enhancing drug uptake,targeting ATP-binding cassette(ABC)transporters,and targeting B-cell lymphoma-2(BCL-2)family proteins.Additionally,the current clinical applications of representative peptides in combating MDR cancers and their potential directions for medicinal chemistry research have been thoroughly discussed.This review offers essential insights into the novel treatment approaches for MDR cancers and highlights the trends and perspectives in this field.
基金supported by the National Natural Science Foundation of China(Grant Nos.:32271292,31872723,32200778,and 22377089)the Jiangsu Students Innovation and Entrepre-neurship Training Program,China(Program No.:202210285081Z)+6 种基金the Project of MOE Key Laboratory of Geriatric Diseases and Immunology,China(Project No.:JYN202404)Proj-ect Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Natural Science Foundation of Jiangsu Province,China(Project No.:BK20220494)Suzhou Medical and Health Technology Innovation Project,China(Grant No.:SKY2022107)the Clinical Research Center of Neuro-logical Disease in The Second Affiliated Hospital of Soochow University,China(Grant No.:ND2022A04)State Key Laboratory of Drug Research(Grant No.:SKLDR-2023-KF-05)Jiangsu Shuang-chuang Program for Doctor,Young Science Talents Promotion Project of Jiangsu Science and Technology Association(Program No.:TJ-2023-019)Young Science Talents Promotion Project of Suzhou Science and Technology Association,Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases,and startup funding(Grant Nos.:NH21500221,NH21500122,and NH21500123)to Qifei Cong.
文摘Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the“therapeutic module”of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.
基金Supported by The College Students’Innovation and Entrepreneurship Competition,No.2024cxcy504 and No.202410459164.
文摘The study by Yang et al presents a comprehensive investigation into the thera-peutic potential of curcumin for gastric cancer(GC).Using network pharma-cology,the researchers identified 48 curcumin-related genes,31 of which overlap with GC targets.Key genes,including ESR1,EGFR,CYP3A4,MAPK14,CYP1A2,and CYP2B6,are linked to poor survival in GC patients.Molecular docking con-firmed strong binding affinity of curcumin to these genes.In vitro experiments demonstrated that curcumin effectively inhibits the growth and proliferation of BGC-823,suggesting its therapeutic potential in GC through multiple targets and pathways.
基金Supported by NSFC(No.11861010),also supported by NSFC(No.12171175),also supported by NSFC(No.12261006)NSF of Guangxi Province(No.2018GXNSFFA281008)Project of Guangxi First Class Disciplines of Statistics(No.GJKY-2022-01)。
文摘In this paper,we study the Bowen entropy of stable sets in positive entropy G-system of amenable group actions.The lower bound of the Bowen entropy of these sets are estimated.
基金This work was supported in part by China Postdoctoral Science Foundation （2013M531527）, the Fundamental Research Funds for the Central Universities （0110000037）, the National Natural Science Foun- dation of China （Grant Nos. 61502412, 61033009, and 61175057）, Natural Science Foundation of the Jiangsu Province （BK20150459）, Natural Science Foundation of the Jiangsu Higher Education Institutions （15KJB520036）, National Science Foundation, United States （IIS-0534699, IIS-0713109, CNS-1017701）, and a Microsoft Research New Faculty Fellowship.
文摘Although amazing progress has been made in ma- chine learning to achieve high generalization accuracy and ef- ficiency, there is still very limited work on deriving meaning- ful decision-making actions from the resulting models. How- ever, in many applications such as advertisement, recommen- dation systems, social networks, customer relationship man- agement, and clinical prediction, the users need not only ac- curate prediction, but also suggestions on actions to achieve a desirable goal （e.g., high ads hit rates） or avert an unde- sirable predicted result （e.g., clinical deterioration）. Existing works for extracting such actionability are few and limited to simple models such as a decision tree. The dilemma is that those models with high accuracy are often more complex and harder to extract actionability from. In this paper, we propose an effective method to extract ac- tionable knowledge from additive tree models （ATMs）, one of the most widely used and best off-the-shelf classifiers. We rigorously formulate the optimal actionable planning （OAP） problem for a given ATM, which is to extract an action- able plan for a given input so that it can achieve a desirable output while maximizing the net profit. Based on a state space graph formulation, we first propose an optimal heuris- tic search method which intends to find an optimal solution. Then, we also present a sub-optimal heuristic search with an admissible and consistent heuristic function which can re- markably improve the efficiency of the algorithm. Our exper- imental results demonstrate the effectiveness and efficiency of the proposed algorithms on several real datasets in the application domain of personal credit and banking.
基金supported by the Philosophy and Social Science Research Fund of Zhejiang Province(Grant No.24ZJQN095YB)the Educational and Teaching Reform Project of HDU-ITMO Joint Institute(Grant No.SGJ2023JG007).
文摘In the last few years,scholars have continued to refine the understanding of conservatism through cultural psychology.The application of Symbolic Action Theory,particularly Ernst Boesch’s framework,remains central to discussions,illustrating how conservatism is not merely a political stance but a dynamic system of behaviors that reinforces societal values through symbolic actions(Kölbl,2020).Additionally,recent studies have highlighted the interaction between cultural conservatism and collective identity,with particular focus on how conservatism can manifest in diverse cultural settings(Yilmaz&Alper,2019).Research also underscores the relevance of symbolic politics in shaping both individual attitudes and broader political actions,contributing to the understanding of how symbolic meanings sustain social conservatism in different cultural contexts(Chin&Levey,2022).
文摘On the morning of May 31st,the parallel forum"Ecological Actions to Carry Forward the Shared Values of Mankind,"as part of the 4th Dialogue on Exchanges and Mutual Learning among Civilisations,was held in Dunhuang.More than 50 experts and scholars from different countries,including China,Kenya and Japan,engaged in indepth discussions on the theme.
文摘ln order to improve the level of investment promotion and redouble effortsto enhance services,on February l9th,the 2025 Action Plan for StabilizingForeign lnvestment was released,proposing 20 measures in four aspects.Cur-rently,with increasing uncertainties in the external environment,China facesmultple difficulties and challenges in attracting foreign investment.
文摘A Green Lifestyle The Double Take column looks at a single topic from an African and Chinese perspective.This month,we explore how personal actions are related to sustainable development.
