Neural network fitness functions for a musical IGA

This paper describes recent enhancements to GenJam, a genetic algorithm-based model of a novice jazz musician learning to improvise. After presenting an overview and update of the current interactive version of GenJam, we focus on efforts to augment its human fitness function with a neural network, in an attempt to ease the fitness bottleneck inherent in musical IGAs. Specifically, a cascade correlation technique was used with data taken from populations of musical ideas trained by human mentors interactively. We conclude with a discussion of why this approach failed, and we speculate on approaches that might work

The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2) and an increased synthesis of prostaglandin E2 (PGE2). The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN) and/or nucleot(s)ide analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ''historical'' interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies

The pharmacology and activity of non-steroidal anti-inflammatory drugs (NSAIDs): a review of their use as an adjuvant treatment in patients with HBV and HCV chronic hepatitis

Introduction: Different DNA and RNA viruses exploit common strategies to support their persistence and replication in infected individuals. In particular, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause major health problems worldwide. These pathogens exert an immunosuppressive role by inducing the persistent activation of cyclooxygenase-2 (COX-2) and an increased synthesis of prostaglandin E2 (PGE2). The suppression of this proinflammatory network by non-steroidal anti-inflammatory drugs (NSAIDs) has been proposed as a therapeutic approach to decrease viral replication. Materials and methods: In this review, the role of inflammation in the support of viral replication and NSAIDs and ketoprofen pharmacology are briefly discussed. In addition, studies that have investigated the use of NSAIDs for the treatment of HBV and HCV chronic hepatitis, which were identified by a systematic literature search of PubMed and MEDLINE, are reported. Results: To date, pegylated-interferon (PEG-IFN) and/or nucleot(s)ide analogues and PEG-IFN and ribavirin remain the standard therapy for HBV and HCV chronic hepatitis, respectively. Discussion: The use of NSAIDs in patients with chronic viral hepatitis has only a ‘‘historical’’ interest. Nevertheless, the possible usefulness of ketoprofen with PEG-IFN and ribavirin for HCVinfected patients, non-responders to standard therapy or with genotype 1, should be evaluated in future clinical studies

Deregulation of microRNA expression in peripheral blood mononuclear cells from patients with HCV-related malignancies

Background and aim: Hepatocellular carcinoma is one of the major causes of death due to cancer worldwide, and its association with hepatitis C virus infection has been definitively established. Hepatitis C virus is also involved in the pathogenesis of non-Hodgkin\u2019s lymphoma. This is the only virus infecting humans that is able to induce two different malignancies. We analyzed the expression levels of a panel of microRNA in peripheral blood mononuclear cells of patients with hepatitis C virus-related malignancies in order to find a disease-associated deregulation and identify specific biomarkers. Methods: We tested peripheral blood mononuclear cells isolated from patients with hepatocellular carcinoma, non-Hodgkin\u2019s lymphoma, hepatitis C virus without malignancies and healthy subjects for a panel of microRNA selected on the basis of previous studies. MicroRNA expression was evaluated by real-time PCR. Results: Our results showed an upregulation of miRNA-21 and downregulation of miRNA-26b in hepatocellular carcinoma and non-Hodgkin\u2019s lymphoma patients compared to controls (p\ua0<\ua00.001). Deregulation of miRNA-16 and miRNA-155 was limited to lymphoma patients. Conclusions: This study shows that some microRNAs are differently expressed in peripheral blood mononuclear cells from hepatitis C virus patients who develop hepatocellular carcinoma or lymphoma, while others share a common behavior. Thus, analysis of the expression of microRNAs could be a noninvasive marker of hepatitis C virus-related carcinogenesis. This analysis could be a suitable tool for identifying the existence of a malignancy and also discriminating between these two hepatitis C virus-related cancers

Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and whenever possible at baseline (N= 70). Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P= 2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure. Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring