DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Interpretation of user’s feedback in human-robot interaction

In this paper we will propose the use of social robots as interface between users and services in a Smart Environment. We will focus on the need for a robot to recognize the user’s feedback, in order to respond and revise its behaviour according to user’s needs. As we believe speech is a natural and immediate input channel in human-robot interaction, we will discuss the importance of recognising, besides the linguistic content of the spoken sentence, the attitude of the user towards the robot and the environment. In this way, the meaning of the user dialog will be made clear when hardly recognisable by the analysis of the utterance structure. Then, we will present the results of the application of a potential approach used for integrating the linguistic analysis with the recognition of the valence and arousal of the user’s utterance. In order to achieve this goal, we collected and analysed a corpus of data to build an interpretation model based on a Bayesian network. Then we tested the accuracy of the model using a test dataset. Results will show that the integration of the linguistic content with the recognition of some acoustic features of spoken sentences perform better in recognising the key aspects of user’s feedback

Gamma-ray pulsar glitches: a study of variability in Fermi-LAT data

Pulsars are generally acknowledged as very stable astrophysical rotators, and they gradually slow down by emitting radiation at the expense of their rotational energy. Occasionally, pulsars can undergo transient events called glitches, which consist in rapid changes in their rotational parameters and are often followed by a relaxation. During its first 15 years of operations, the NASA's Fermi Large Area Telescope (LAT) monitored the rotation of almost 300 gamma-ray pulsars and detected more than 100 glitches. On the other hand, radio observatories have detected almost 3300 radio pulsars and almost 600 glitches. In this thesis we analysed and compared the glitch activity among the gamma-ray and radio pulsar populations. Variability in the emission features correlated to glitches has been observed in a small family of radio pulsars and in the radio-quiet PSR J2021+4026, which is the only variable pulsar observed by the LAT. Here we present a novel analysis of the LAT gamma-ray pulsars consisting of a study of variability correlated with changes in the spin-down rate. We perform a maximum likelihood spectral analysis of the LAT data around detected glitches, aiming at measuring variations in the gamma-ray flux and spectral parameters. In order to study the variability in the shape of the pulse peaks, we fit the pulse profiles. This allows to infer information about variations at the state change, which ultimately relate to variations in the geometry of the emitting region

Supporting Students with a Personal Advisor

Recently, many national and international initiatives show an increasing interest in promoting distance education interventions by Universities. These directives aim at supporting students during their studies providing them with personalized solutions to their problems related not only to the fruition of on-line courses but also to orientation issues. In this paper we present a general architecture of an Embodied Conversational Agent (ECA) that has the main aim to assist students by providing personalized suggestions. This ECA represents the student interface in interacting with a Virtual University environment able to provide different types of services. In particular to support mobility, the ECA architecture has been conceived in order to run also on the student handheld device. The paper discusses the design and technical issues involved in developing this personal agent and the results of an evaluation study aiming at assessing the impact of conversational agents on the effectiveness of the interaction

Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review

first_pagesettingsOrder Article Reprints Open AccessReview Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review by Endrit Shahini 1,*ORCID,Giuseppe Pasculli 2,Antonio Giovanni Solimando 3ORCID,Claudio Tiribelli 4ORCID,Raffaele Cozzolongo 1,† andGianluigi Giannelli 5,† 1 Gastroenterology Unit, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy 2 National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy 3 Guido Baccelli Unit of Internal Medicine, Department of Precision and Regenerative Medicine and Ionian Area-(DiMePRe-J), University of Bari “A. Moro”, 70121 Bari, Italy 4 Scientific Director, Italian Liver Foundation, 34149 Trieste, Italy 5 Scientific Director, National Institute of Gastroenterology-IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. Int. J. Mol. Sci. 2023, 24(5), 4286; https://doi.org/10.3390/ijms24054286 Received: 30 January 2023 / Revised: 14 February 2023 / Accepted: 17 February 2023 / Published: 21 February 2023 (This article belongs to the Special Issue Challenges and Future Trends of Hepatocellular Carcinoma Immunotherapy) Download Browse Figures Review Reports Versions Notes Abstract The most common primary liver cancer is hepatocellular carcinoma (HCC), and its mortality rate is increasing globally. The overall 5-year survival of patients with liver cancer is currently 10–20%. Moreover, because early diagnosis can significantly improve prognosis, which is highly correlated with tumor stage, early detection of HCC is critical. International guidelines advise using α-FP biomarker with/without ultrasonography for HCC surveillance in patients with advanced liver disease. However, traditional biomarkers are sub-optimal for risk stratification of HCC development in high-risk populations, early diagnosis, prognostication, and treatment response prediction. Since about 20% of HCCs do not produce α-FP due to its biological diversity, combining α-FP with novel biomarkers can enhance HCC detection sensitivity. There is a chance to offer promising cancer management methods in high-risk populations by utilizing HCC screening strategies derived from new tumor biomarkers and prognostic scores created by combining biomarkers with distinct clinical parameters. Despite numerous efforts to identify molecules as potential biomarkers, there is no single ideal marker in HCC. When combined with other clinical parameters, the detection of some biomarkers has higher sensitivity and specificity in comparison with a single biomarker. Therefore, newer biomarkers and models, such as the Lens culinaris agglutinin-reactive fraction of Alpha-fetoprotein (α-FP), α-FP-L3, Des-γ-carboxy-prothrombin (DCP or PIVKA-II), and the GALAD score, are being used more frequently in the diagnosis and prognosis of HCC. Notably, the GALAD algorithm was effective in HCC prevention, particularly for cirrhotic patients, regardless of the cause of their liver disease. Although the role of these biomarkers in surveillance is still being researched, they may provide a more practical alternative to traditional imaging-based surveillance. Finally, looking for new diagnostic/surveillance tools may help improve patients’ survival. This review discusses the current roles of the most used biomarkers and prognostic scores that may aid in the clinical management of HCC patients

Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection

In hepatitis C virus (HCV) genotypes 2 and 3 patients, the high rate of relapse after 12 to 16 weeks of antiviral therapy is the main concern for shortening treatment duration. This study was undertaken to delineate predictors of relapse after short treatment in patients with undetectable HCV RNA at treatment week 4 (RVR), and to report in RVR patients with relapse the sustained virological response (SVR) after a second 24-week course of therapy. RVR patients received pegylated interferon (Peg-IFN) alfa-2b (1.5 microg/kg) and ribavirin (1000-1200 mg/day) for 12 weeks; those who relapsed were re-treated with the same drug doses but for the extended standard duration of 24 weeks. Logistic regression analysis was applied to delineate predictors of relapse by using age, sex, route of transmission, body mass index (BMI), serum alanine aminotransferase (ALT), HCV genotypes, serum HCV RNA levels, and platelet counts as covariates. Of 718 patients with genotypes 2 and 3 who were started on therapy, 496 (69.1%) had undetectable HCV RNA at week 4. Of them, 409 patients (82.5%, CI 79.1-85.8) attained SVR, and 67 (14.1%, CI 10.4-16.5) relapsed. At regression analysis, only platelet count less than 140,000 mm(3) [odds ratio, 2.51; confidence interval (CI), 1.49-4.20] and BMI 30 or higher (odds ratio, 1.7; CI, 1.03-2.70) were independently associated with relapse. Forty-three of 67 patients with relapse agreed to be re-treated, and an SVR was achieved in 30 (70.0%) of them. Conclusion: We recommend 12 weeks course of therapy for patients with undetectable HCV RNA at treatment week 4, providing they present with no advanced fibrosis and low BMI

Associations between serum biomarkers and non-alcoholic liver disease: Results of a clinical study of Mediterranean patients with obesity

BackgroundTransient elastography is an ultrasound-based method to detect non-alcoholic fatty liver disease (NAFLD). Despite the simultaneously rising prevalence of fatty liver and metabolic disease, further information about metabolic risk indicators of fatty liver is still necessary.MethodsA Southern Italian population sample with obesity (N = 87) was cross-sectionally explored for associations among the presence of NAFLD, assessed by FibroScan, and clinical, biochemical and anthropometric parameters. Inclusion criteria were age &amp;gt;18 years, BMI ≥ 25 kg/m2, no ongoing supplemental or drug therapy, including oral contraceptives or osteoporosis medications; exclusion criteria were pregnancy, endocrinological diseases, cardiovascular diseases, neoplasia, renal or hepatic failure, hereditary thrombocytopenia, hepatitis B (HBV) or hepatitis C virus (HCV) infection, and excess alcohol consumption.ResultsThe study sample featured a female predominance (67%, N = 60), age range 18–64 years, and 40% prevalence of NAFLD, in accordance with the fibroscan-measured controlled attenuation parameter (CAP) threshold value above 302 dB/m. Males were slightly more frequently affected by NAFLD (51.4% vs. 48.6%, p = 0.01). Insulin levels, insulin resistance (quantified by HOMA-IR), diastolic blood pressure, BMI, visceral adipose tissue (VAT), and waist circumference were significantly higher in the NAFLD subset compared to their counterparts (p &amp;lt; 0.01, p &amp;lt; 0.01, p = 0.05, p &amp;lt; 0.01, p &amp;lt; 0.01, p &amp;lt; 0.01, respectively). Uric acid (p &amp;lt; 0.01) also showed a positive trend in the NAFLD group. Other liver steatosis parameters, measured by stiffness (p &amp;lt; 0.01), fatty liver index (FLI) (p &amp;lt; 0.01) and FibroScan-AST (FAST) (p &amp;lt; 0.01), were also significantly greater in the NAFLD group. In three nested linear regression models built to assess associations between CAP values and serum uric acid levels, a single unit increase in uricemia indicated a CAP increase by 14 dB/m, after adjusting for confounders (coefficient: 14.07, 95% CI 0.6–27.54).ConclusionsClinical-metabolic screening for NAFLD cannot ignore uricemia, especially in patients with obesity.</jats:sec