Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy.

Background And Aims: The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied.

Methods: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated.

Change in Liver Function in Durvalumab Plus Tremelimumab Treatment for Unresectable Hepatocellular Carcinoma.

Background/aim: Maintaining liver function throughout the treatment of hepatocellular carcinoma (HCC) is crucial, yet the impact of durvalumab plus tremelimumab (DT) treatment on liver function is not well understood. This multicenter study aimed to examine the changes in liver function during DT treatment.

Patients And Methods: This nationwide multicenter study included 80 patients who received DT treatment for unresectable HCC.

Region-specific activation in the accumbens nucleus by itch with modified scratch efficacy in mice - a model-free multivariate analysis.

Itch is a protective/defensive function with divalent motivational drives. Itch itself elicits an unpleasant experience, which triggers the urge to scratch, relieving the itchiness. Still, it can also result in dissatisfaction when the scratch is too intense and painful or unsatisfactory due to insufficient scratch effect.

Measurement of paracentral stereopsis using a new method with the binocular open perimeter imovifa in normal adults.

Purpose: No method to quantitatively evaluate stereopsis within the 15º visual field has been clinically established. We developed a program to measure paracentral stereopsis and evaluated its feasibility in visually normal participants.

Study Design: Experimental investigation METHODS: Ten visually normal volunteers with stereopsis of 60 arcseconds or better were included.

Cholesterol-binding motifs in STING that control endoplasmic reticulum retention mediate anti-tumoral activity of cholesterol-lowering compounds.

The cGAS-STING pathway plays a crucial role in anti-tumoral responses by activating inflammation and reprogramming the tumour microenvironment. Upon activation, STING traffics from the endoplasmic reticulum (ER) to Golgi, allowing signalling complex assembly and induction of interferon and inflammatory cytokines. Here we report that cGAMP stimulation leads to a transient decline in ER cholesterol levels, mediated by Sterol O-Acyltransferase 1-dependent cholesterol esterification.

Estimation of internal-exposure contribution in radiation dose exposure for boron neutron capture therapy.

Although boron neutron capture therapy (BNCT) causes minor damage to normal cells owing to the nuclear reactions induced by neutrons with major elements of tissues such as hydrogen and nitrogen, it is useful to estimate the accurate exposure dose for radiation protection. This study aims to estimate the contribution of internal exposure in radiation exposure dose for BNCT. The study was performed by referring to clinical studies at a reactor-based BNCT facility on the basis of computational dosimetry.

SAM68 directs STING signaling to apoptosis in macrophages.

DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription.

The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation.

Pattern recognition receptors (PRRs) induce host defense but can also induce exacerbated inflammatory responses. This raises the question of whether other mechanisms are also involved in early host defense. Using transcriptome analysis of disrupted transcripts in herpes simplex virus (HSV)-infected cells, we find that HSV infection disrupts the hypoxia-inducible factor (HIF) transcription network in neurons and epithelial cells.

Growth and Dispersion Control of SnO Nanocrystals Employing an Amino Acid Ester Hydrochloride in Solution Synthesis: Microstructures and Photovoltaic Applications.

Tin oxide (SnO) is a technologically important semiconductor with versatile applications. In particular, attention is being paid to nanostructured SnO materials for use as a part of the constituents in perovskite solar cells (PSCs), an emerging renewable energy technology. This is mainly because SnO has high electron mobility, making it favorable for use in the electron transport layer (ETL) in these devices, in which SnO thin films play a role in extracting electrons from the adjacent light-absorber, i.

An IKBKE variant conferring functional cGAS/STING pathway deficiency and susceptibility to recurrent HSV-2 meningitis.

The mechanisms underlying susceptibility to recurrent herpes simplex virus type 2 (HSV-2) meningitis remain incompletely understood. In a patient experiencing multiple episodes of HSV-2 meningitis, we identified a monoallelic variant in the IKBKE gene, which encodes the IKKε kinase involved in induction of antiviral IFN genes. Patient cells displayed impaired induction of IFN-β1 (IFNB1) expression upon infection with HSV-2 or stimulation with double-stranded DNA (dsDNA) and failed to induce phosphorylation of STING, an activation marker of the DNA-sensing cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway.

Biochemical and biophysical characterization of the RAS family small GTPase protein DiRAS3.

DiRAS3, also called ARHI, is a RAS (sub)family small GTPase protein that shares 50-60% sequence identity with H-, K-, and N-RAS, with substitutions in key conserved G-box motifs and a unique 34 amino acid extension at its N-terminus. Unlike the RAS proto-oncogenes, DiRAS3 exhibits tumor suppressor properties. DiRAS3 function has been studied through genetics and cell biology, but there has been a lack of understanding of the biochemical and biophysical properties of the protein, likely due to its instability and poor solubility.

Indirect CRISPR screening with photoconversion revealed key factors of drug resistance with cell-cell interactions.

Comprehensive screenings to clarify indirect cell-cell interactions, such as those in the tumor microenvironment, especially comprehensive assessments of supporting cells' effects, are challenging. Therefore, in this study, indirect CRISPR screening for drug resistance with cell-cell interactions was invented. The photoconvertible fluorescent protein Dendra2 was inducted to supporting cells and explored the drug resistance responsible factors of supporting cells with CRISPR screenings.

Effects on survival of the adverse event of atezolizumab plus bevacizumab for hepatocellular carcinoma: a multicenter study by the Japan Red Cross Liver Study Group.

This study aimed to describe the real-world efficacy and safety of the combination therapy of atezolizumab and bevacizumab (Atezo/Bev) for unresectable hepatocellular carcinoma (HCC). This retrospective analysis of a multicenter registry cohort included 268 patients treated with Atezo/Bev. The incidence of adverse events (AE) and its impact on overall survival (OS) and progression-free survival (PFS) were analyzed.

Optimal threshold of alpha-fetoprotein response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Alpha-fetoprotein (AFP) response (relative decline in AFP) is associated with imaging response evaluated by response evaluation criteria in solid tumors ver1.1 (RECIST) and survival in treatment for hepatocellular carcinoma (HCC). However, the optimal threshold of AFP response is still unknown, especially in atezolizumab and bevacizumab (Atez/Bev) treatment.

Usefulness of neutrophil-to-lymphocyte ratio in predicting progression and survival outcomes after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

Aim: We investigated pretreatment neutrophil-to-lymphocyte ratio (NLR) for predicting survival outcomes of atezolizumab plus bevacizumab therapy for hepatocellular carcinoma (HCC) and determined the predictive ability of combined liver reserve-NLR.

Methods: This retrospective, multicenter study enrolled 242 patients receiving atezolizumab plus bevacizumab for unresectable HCC. Pretreatment NLR <2.

Fluorescence-enhanced Si photodiodes for ultraviolet C rays (UVC) measurements.

The ultraviolet C rays (UVC, wavelength λ = 100-280 nm) light generated by a Hg lamp (λ = 254 nm) and UVC light-emitting diodes (LEDs, λ = 265 and 275 nm) was detected using a fluorescence-enhanced silicon photodiode (FE-PD). Ce-doped yttrium aluminum garnet (YAG:Ce), YAG:Pr, YAG:Eu, YAG:Tb, YAG:Cr, AlO:Ti, AlO:Cr, MgAlO:Ti, MgAlO:Cr, MgAlO:Mn, and commercial fluorescent acrylic resins were tested as phosphor sources to enhance the output signal intensity of the FE-PD irradiated with UVC light. The resulting output signal intensity increased linearly with the UVC light strength, which was adjusted by raising the input current of the UVC LEDs from 0 to 40 mA.

Association Between Toileting Independence and Higher Brain Functions in Post-Stroke Inpatients: A Cross-Sectional Study.

Objectives: We aimed to cross-sectionally examine and clarify the types of higher brain functions associated with toileting independence in post-stroke inpatients.

Materials And Methods: From November 2017 to October 2020, 51 participants were selected from a database of post-stroke inpatients in a Japanese hospital; the selected participants had missing data. The objective variable was the independence of toileting and toilet transfer in the Functional Independence Measure; independence was set at 6 points or more.

Manufacturing a TiO-Based Semiconductor Film with Nanofluid Pool Boiling and Sintering Processes toward Solar-Cell Applications.

For the first time, nanofluid boiling was applied as a process for the creation of a semiconductor TiO nanoparticle film that can be deposited onto a conductive substrate (F-doped SnO glass: FTO). A steel-base device designed for pool boiling was used to deposit a TiO-based nanofluid consisting of nanoparticles with an average size of about 20 nm. The boiling of the nanofluid directly on the FTO glass substrate allowed for the deposition of the nanoparticles onto the FTO surface.

Real-world clinical outcomes of sofosbuvir and velpatasvir treatment in HCV genotype 1- and 2-infected patients with decompensated cirrhosis: A nationwide multicenter study by the Japanese Red Cross Liver Study Group.

The real-world virological efficacy and safety of interferon-free direct-acting antiviral (DAA) therapy with sofosbuvir (SOF) and velpatasvir (VEL) were assessed in hepatitis C virus (HCV) genotype 1- and 2-infected patients with decompensated cirrhosis. A total of 65 patients with HCV-related decompensated cirrhosis (Child-Pugh score of 7 points or more) who were treated with the SOF/VEL regimen were enrolled. The sustained virological response (SVR) rate and safety profile were analyzed.

Hydrosilane-Mediated Electrochemical Reduction of Amides.

Electrochemical reduction of amides was achieved by using a hydrosilane without any toxic or expensive metals. The key reactive ketyl radical intermediate was generated by cathodic reduction. Continuous reaction with anodically generated silyl radicals or zinc bromide resulted in chemoselective deoxygenation to give the corresponding amines.