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Background & Aims We investigated the association between interferon λ 3 ( IFNL3 ) genotype (also known as interleukin 28B) and response to IFNα therapy in patients with chronic hepatitis D virus (HDV) infection. Methods We studied IFNL3 genotypes of 32 patients (19 men; median age, 42.5 y) with chronic HDV infection. Nineteen patients (59%) were treated with pegylated IFNα and 13 patients (41%) were treated with standard IFNα, for at least 12 months. Levels of HDV RNA were measured before the initiation of treatment and every 6 months thereafter; patients were followed up for a median time of 16 months (range, 6–164 mo) after treatment ended. We used real-time polymerase chain reaction to classify the IFNL3 polymorphism rs12979860 as CC, CT, or TT, and rs8099917 as TT, GT, or GG. A virologic response was defined as undetectable HDV RNA in serum, and a sustained virologic response (SVR) was defined as undetectable HDV RNA after cessation of treatment until the end of the follow-up period. We evaluated the association between IFNL3 polymorphism and treatment response using univariate and multivariate analyses. Results After treatment, a response was achieved in 16 patients (50%) and an SVR was achieved in 9 (28%). The percentages of patients with CC, CT, and TT at rs12979860 were 47%, 47%, and 6%, respectively; the percentages of patients with TT, GT, and GG at rs8099917 were 69%, 28%, and 3%, respectively. Rates of SVR were 27%, 27%, and 50% in patients with CC, CT, TT at rs12979860 ( P = .78 for CC vs CT vs TT) and 36%, 11%, and 0% in patients with TT, GT, and GG at rs8099917 ( P = .30 for TT vs GT vs GG). Conclusions The IFNL3 polymorphisms rs12979860 and rs8099917 do not significantly affect responses of patients with chronic HDV infection to treatment with IFNα. [ABSTRACT FROM AUTHOR]

Conventional microphone array implementations aim to lock onto a source with given location and if required, tracking it. It is a challenge to identify the intended source when the location of the source is unknown and interference exists in the same environment. In this study we combine speaker verification and microphone array processing techniques to localize and maximize gain on the intended speaker under the assumption of open acoustic field. We exploit the steering capability of the microphone array for more accurate speaker verification. Our first contribution is a new N-Gram based and computationally efficient feature for detecting an intended speaker. When the source and interference are localized, microphone array can be tuned further to reduce noise and increase the gain. Our second contribution is this integrated algorithm for speaker verification and localization. In the context of this study we developed SharpEar, an open source environment that simulates propagation of sound emanating from multiple sources. Our third and last contribution is this simulation environment, which is open source and available to researchers of the field. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease (COVID-19) is a highly contagious disease caused by the SARS-CoV-2 virus, leading severe acute respiratory syndrome in patients. Although various antiviral drugs and their combinations have been tried so far against SARS-CoV-2 and they have shown some effectiveness, there is still a need for safe and cost-effective binding inhibitors in the fight against COVID-19. Therefore, phytochemicals in nature can be a quick solution due to their wide therapeutic spectrum and strong antiviral, anti-inflammatory, and antioxidant properties. In this context, the low toxicity, and high pharmacokinetic properties of curcumin, which is a natural phytochemical, as well as the easy synthesizing of its derivatives reveal the need for investigation of its various derivatives as inhibitors against coronaviruses. The present study focused on curcumin derivatives with reliable ADME profile and high molecular binding potency to different SARS-CoV-2 target enzymes (3CLPro, PLpro, NSP7/8/12, NSP7/8/12 +RNA, NSP15, NSP16, Spike, Spike+ACE). In the molecular docking studies, the best binding scores for the 22 proposed curcumin derivatives were obtained for the PLpro protein. Furthermore, MD simulations were performed for high-affinity ligand-PLpro protein complexes and subsequently, Lys157, Glu161, Asp164, Arg166, Glu167, Met208, Pro247, Pro248, Tyr264, Tyr273 and Asp302 residues of PLpro was determined to play key role for ligand binding by Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) analysis. The results of the study promise that the proposed curcumin derivatives can be potent inhibitors against SARS-CoV-2 and be converted into pharmaceutical drugs. It is also expected that the findings may provide guiding insights to future design studies for synthesizing different antiviral derivatives of phytochemicals. [Display omitted] • The proposed curcumin derivatives have reliable ADME profile. • High molecular binding potentials were observed on different SARS-CoV-2 target enzymes for curcumin derivatives. • The proposed curcumin derivatives are most effective on PLpro. • Molecular dynamics simulation showed that the curcumin derivatives exhibit strong interactions. • MM-PBSA calculations identified key residues of PLpro in binding curcumin derivatives. [ABSTRACT FROM AUTHOR]

Summary Objectives Serum alanine aminotransferase (ALT) is a controversial marker for disease monitoring in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. The aim of this study was to determine the fibrosis stage and histological activity index (HAI) in HBeAg-negative CHB patients with persistently normal ALT (PNALT) and high serum HBV DNA (≥2000 IU/ml) and to investigate clinical risk factors for the requirement of treatment through the examination of liver biopsy specimens. Methods HBeAg-negative CHB patients with PNALT (≤40 IU/l) and high serum HBV DNA (≥2000 IU/ml) were included. HBV fibrosis stage and HAI were scored according to the Ishak system. Multivariate logistic regression analysis was used to estimate the independent risk factors for fibrosis stage ≥2 and/or HAI ≥6. Receiver operating characteristic curve analysis was used to determine an optimal age cut-off for liver biopsy. Results A total 120 patients were enrolled. These patients had a mean HBV DNA level of 123 680 ± 494 500 IU/ml; the HBV DNA load was 2000–20 000 IU/ml in 68 patients (56.6%) and ≥20 000 IU/ml in 52 (43.4%). Eighteen patients (15%) had moderate-to-severe histological activity (HAI ≥6). Forty-three patients (35.9%) had a fibrosis stage ≥2. Forty-eight patients (40%) had a fibrosis stage ≥2 and/or HAI ≥6. On multivariate logistic regression analysis, independent variables associated with fibrosis stage ≥2 and/or HAI ≥6 included age and HBV DNA viral load. Patients with HBV DNA 2000–20 000 IU/ml were more likely to require treatment compared to those with a viral load ≥20 000 IU/ml. The optimal age cut-off to predict fibrosis stage ≥2 and/or HAI ≥6 was 46 years. Conclusions Significant liver damage was detected in 40% of CHB patients with PNALT and high HBV DNA upon biopsy. Age and HBV DNA viral load were independent predictors of significant liver damage. A biopsy to determine the degree of liver damage is advisable for CHB patients older than 46 years. [ABSTRACT FROM AUTHOR]