Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemothe...BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.展开更多
Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollbac...Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.展开更多
Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the sta...Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the states of afile system when roll-backing the running of a program, so there are many restrictionson file accesses in existent fault-tolerance systems. SCR algorithm, an algorithmbased on atomic operation and consistent schedule, which can restore the states offile systems, is presented in this paper. In the SCR algorithm, system calls on filesystems are classified into idem-potent operations and non-idem-potent operations.A non-idem-potent operation modifies a file system's states, while an idem-potentoperation does not. SCR algorithm tracks changes of the file system states. It logseach non-idem-potent operation used by user programs and the information that canrestore the operation in disks. When check-pointing roll-backing the program, SCRalgorithm will revert the file system states to the last checkpoint time. By usingSCR algorithm, users are allowed to use any file operation in their programs.展开更多
Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in Februa...Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.展开更多
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
文摘BACKGROUND Cardiovascular diseases and cancer are leading causes of morbidity and mortality.Patients with malignancies are at increased risk for cardiovascular complications including acute coronary syndromes,chemotherapy or radiation therapy related complications and cardiac metastasis.CASE SUMMARY We present a case of a 47-year-old female with metastatic cancer on immuno-therapy presented with anterior ST elevation myocardial infarction followed by emergent percutaneous coronary intervention in the left anterior descending artery.Echocardiography after 72 hours showed thickening of inferior wall and cardiac magnetic resonance depicted inflammation and necrosis attributable to either cardiac metastasis or immunotherapy induced myocarditis.Biopsy was not performed because of treatment with antiplatelet drugs and a definite diagnosis was achieved after probationary administration of high-dose intravenous methyl-prednisolone that led to recovery.CONCLUSION In patients with malignancy,chemotherapy-induced cardiovascular complications and cardiac metastasis are common concerns and may coexist with common acute cardiovascular diseases including acute coronary syndromes.In such cases clinical suspicion aided by multimodality imaging is crucial for the diagnosis.A multidisciplinary team approach is required for prompt initiation of the appro-priate treatment.
基金Project supported by the National "863" High-tech Program of China.
文摘Network of workstations (NOW) now becomes one of the main trends of parallel computing. But for long-running scientific programs, it needs effective fault tolerance for its changing property. Checkpointing and rollback recovery is a solution to this problem. First the main problems upon rollback recovery are discussed, the different checkpointing techniques for NOW are analyzed, and then the design and implementation of ChaRM (checkpoint-based rollback recovery and process migration) system are described. The comparison of three coordinated checkpointing systems is given.
文摘Fault-tolerance is very important in cluster computing and has beenimplemented in many famous cluster-computing systems using checkpoint/restartmechanisms. But existent check-pointing algorithms cannot restore the states of afile system when roll-backing the running of a program, so there are many restrictionson file accesses in existent fault-tolerance systems. SCR algorithm, an algorithmbased on atomic operation and consistent schedule, which can restore the states offile systems, is presented in this paper. In the SCR algorithm, system calls on filesystems are classified into idem-potent operations and non-idem-potent operations.A non-idem-potent operation modifies a file system's states, while an idem-potentoperation does not. SCR algorithm tracks changes of the file system states. It logseach non-idem-potent operation used by user programs and the information that canrestore the operation in disks. When check-pointing roll-backing the program, SCRalgorithm will revert the file system states to the last checkpoint time. By usingSCR algorithm, users are allowed to use any file operation in their programs.
文摘Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.
