Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in ...Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.展开更多
While restorative proctocolectomy with ileal pouch-anal anastomosis has significantly improved the quality of life in patients with underlying ulcerative colitis who require surgery,complications can occur.Pouchitis a...While restorative proctocolectomy with ileal pouch-anal anastomosis has significantly improved the quality of life in patients with underlying ulcerative colitis who require surgery,complications can occur.Pouchitis as the most common long-term complication represents a spectrum of disease processes ranging from acute,antibiotic-responsive type to chronic antibiotic-refractory entity.Accurate diagnosis using a combined assessment of symptoms,endoscopy and histology and the stratification of clinical phenotypes is important for treatment and prognosis the disease.The majority of patients respond favorably to antibiotic therapy.However,management of chronic antibiotic-refractory pouchitis remains a challenge.展开更多
AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess th...AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality. METHODS: From July 2003 to August 2005, 77 consecutive HCC patients underwent OLT, including 15 patients with recurrent HCC after partial hepatectomy for tumor resection (the rescue OLT group) and 62 patients with de novo OLT for HCC (the de novo OLT group). Thirty-three demographic, clinical, histological, laboratory, intra-operative and post-operative variables were analyzed. Survival was calculated by the Kaplan- Meier method. Univariable and multivariable analyses were also performed. RESULTS: The median age of the patients was 49.0 years. The median follow-up was 20 mo. Three patients (20.0%) in the rescue OLT group and 15 patients (24.2%) in the de novo OLT group died during the follow-up period (P = 0.73). The 30-day mortality of OLT was 6.7% for the rescue OLT group vs 1.6% for the de novo OLT group (P = 0.27). Cox proportional hazards model showed that pre-OLT hyperbilirubinemia, the requirement of post-OLT transfusion, the size of the tumor, and family history of HCC were significantly associated with a higher hazard for mortality. CONCLUSION: There are no significant differences in survival/mortality rates between OLT as de novo therapy and OLT as a rescue therapy for patients with hcc. Pre-OLT hyperbilirubinemia, post-OLT requirement of transfusion, large tumor size and family history of HCC are associated with a poor survival outcome.展开更多
Reinforcement learning(RL) in real-world problems requires function approximations that depend on selecting the appropriate feature representations. Representational expansion techniques can make linear approximators ...Reinforcement learning(RL) in real-world problems requires function approximations that depend on selecting the appropriate feature representations. Representational expansion techniques can make linear approximators represent value functions more effectively; however, most of these techniques function well only for low dimensional problems. In this paper, we present the greedy feature replacement(GFR), a novel online expansion technique, for value-based RL algorithms that use binary features. Given a simple initial representation, the feature representation is expanded incrementally. New feature dependencies are added automatically to the current representation and conjunctive features are used to replace current features greedily. The virtual temporal difference(TD) error is recorded for each conjunctive feature to judge whether the replacement can improve the approximation. Correctness guarantees and computational complexity analysis are provided for GFR. Experimental results in two domains show that GFR achieves much faster learning and has the capability to handle large-scale problems.展开更多
基金funded by a grant from the National Natural Science Foundation of China(81873045)the Natural Science Foundation of Fujian Province of China(2020J011115)+1 种基金the Medicine Innovation Project of Fujian Province of China(2020CXB007)the Joint Funds for the Innovation of Science and Technology(2021Y9209).
文摘Background:Ovarian cancer(OC)is a leading cause of gynecological cancer-linked deaths worldwide.Exosomal miR-1825 and its target gene C-type lectin domain family 5 member A(CLEC5A)are associated with tumorigenesis in cancers that was further probed.Methods:Exosomal miR-1825 expression in exosomes and its impact on overall survival(OS)prediction were determined using Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)data.Target genes of miR-1825 were searched in five prediction databases and prognostically significant differentially expressed genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were carried out.The ability of CLEC5A to predict OS was evaluated using univariate and multivariate Cox regression analyses and Kaplan-Meier curves.The CLEC5A expression pattern in OC was validated using immunohistochemistry.The CIBERSORT algorithm was used to compare the immune cell landscape,and the results were validated in a GEO cohort.Finally,the predicted half maximal inhibitory concentration(IC50)values for five commonly used chemotherapy agents were also compared.Results:MiR-1825 level was higher in exosomes derived from OC cells and served as a tumor suppressor.The CLEC5A gene was found to be a target of miR-1825,the upregulation of which was correlated with a poor prognosis.M2 macrophage infiltration was significantly enhanced in the CLEC5A high expression group,while T follicular helper cell infiltration was reduced in it.While the predicted IC50 for cisplatin and doxorubicin was higher in the CLEC5A high expression group,that of docetaxel,gemcitabine,and paclitaxel was lower.Conclusion:MiR-1825,a promising OC biomarker,may promote OC progression by increasing CLEC5A expression via exosome-mediated efflux from tumor cells.
基金a grant from National Institutes of Health,No.R03DK 067275 a grant from Broad Medical Research Program ofBroad Foundation
文摘While restorative proctocolectomy with ileal pouch-anal anastomosis has significantly improved the quality of life in patients with underlying ulcerative colitis who require surgery,complications can occur.Pouchitis as the most common long-term complication represents a spectrum of disease processes ranging from acute,antibiotic-responsive type to chronic antibiotic-refractory entity.Accurate diagnosis using a combined assessment of symptoms,endoscopy and histology and the stratification of clinical phenotypes is important for treatment and prognosis the disease.The majority of patients respond favorably to antibiotic therapy.However,management of chronic antibiotic-refractory pouchitis remains a challenge.
文摘AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality. METHODS: From July 2003 to August 2005, 77 consecutive HCC patients underwent OLT, including 15 patients with recurrent HCC after partial hepatectomy for tumor resection (the rescue OLT group) and 62 patients with de novo OLT for HCC (the de novo OLT group). Thirty-three demographic, clinical, histological, laboratory, intra-operative and post-operative variables were analyzed. Survival was calculated by the Kaplan- Meier method. Univariable and multivariable analyses were also performed. RESULTS: The median age of the patients was 49.0 years. The median follow-up was 20 mo. Three patients (20.0%) in the rescue OLT group and 15 patients (24.2%) in the de novo OLT group died during the follow-up period (P = 0.73). The 30-day mortality of OLT was 6.7% for the rescue OLT group vs 1.6% for the de novo OLT group (P = 0.27). Cox proportional hazards model showed that pre-OLT hyperbilirubinemia, the requirement of post-OLT transfusion, the size of the tumor, and family history of HCC were significantly associated with a higher hazard for mortality. CONCLUSION: There are no significant differences in survival/mortality rates between OLT as de novo therapy and OLT as a rescue therapy for patients with hcc. Pre-OLT hyperbilirubinemia, post-OLT requirement of transfusion, large tumor size and family history of HCC are associated with a poor survival outcome.
基金Project supported by the 12th Five-Year Defense Exploration Project of China(No.041202005)the Ph.D.Program Foundation of the Ministry of Education of China(No.20120002130007)
文摘Reinforcement learning(RL) in real-world problems requires function approximations that depend on selecting the appropriate feature representations. Representational expansion techniques can make linear approximators represent value functions more effectively; however, most of these techniques function well only for low dimensional problems. In this paper, we present the greedy feature replacement(GFR), a novel online expansion technique, for value-based RL algorithms that use binary features. Given a simple initial representation, the feature representation is expanded incrementally. New feature dependencies are added automatically to the current representation and conjunctive features are used to replace current features greedily. The virtual temporal difference(TD) error is recorded for each conjunctive feature to judge whether the replacement can improve the approximation. Correctness guarantees and computational complexity analysis are provided for GFR. Experimental results in two domains show that GFR achieves much faster learning and has the capability to handle large-scale problems.