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Introduction: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. Conclusions: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. Trial Registration: ClinicalTrial.gov identifier, NCT04070235. [ABSTRACT FROM AUTHOR]

Let U ħ (g ^) be the untwisted affinization of a symmetrizable quantum Kac-Moody algebra U ħ (g) . For ℓ ∈ C , we construct an ħ -adic quantum vertex algebra V g ^ , ħ (ℓ , 0) , and establish a one-to-one correspondence between ϕ -coordinated V g ^ , ħ (ℓ , 0) -modules and restricted U ħ (g ^) -modules of level ℓ . Suppose that ℓ is a positive integer. We construct a quotient ħ -adic quantum vertex algebra L g ^ , ħ (ℓ , 0) of V g ^ , ħ (ℓ , 0) , and establish a one-to-one correspondence between certain ϕ -coordinated L g ^ , ħ (ℓ , 0) -modules and restricted integrable U ħ (g ^) -modules of level ℓ . Suppose further that g is of finite type. We prove that L g ^ , ħ (ℓ , 0) / ħ L g ^ , ħ (ℓ , 0) is isomorphic to the simple affine vertex algebra L g ^ (ℓ , 0) . [ABSTRACT FROM AUTHOR]

Batch normalization is one of the most widely used components in deep neural networks. It can accelerate training, and boost model performance on normal samples. However, batch normalization induces vulnerability to models on adversarial examples, especially in medical images, and the reason is still not clear. In this paper, we aim to explain the vulnerability aroused by batch normalization under adversarial images. Specifically, we first discover that both natural and medical images contain a large number of trivial features, whose weights will be enlarged under adversarial attacks, and batch normalization can further enlarge their weights. Additionally, we find that batch normalization will reduce the inter-class margin of high-level features, leading to less tolerance to adversarial perturbations, thereby decreasing the model robustness. Moreover, we hypothesize that the smaller inter-class margin, the more difficult to attain the optimal classification space, which means batch normalization will restrict the performance of adversarial training. This further verifies that a narrower inter-class margin induced by batch normalization reduces the model robustness. Experiments on four benchmark datasets demonstrate our discovery, interpretation and hypothesis. [ABSTRACT FROM AUTHOR]

Objective: Adenoid or adenotonsillar hypertrophy (AATH) causes upper airway obstruction, leading to cardiovascular complications. This meta-analysis was conducted to evaluate the efficacy of adenoidectomy or adenotonsillectomy (AATE) on the cardiovascular system. Methods: Using the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE databases, we identified studies involving a comparison of preoperative and postoperative cardiovascular function in children with AATH. The Cochrane Collaboration's Review Manager 5.3 software was used for meta-analysis. Results: A total of 13 studies with 706 participants were included. The meta-analysis demonstrated a significant reduction in mean pulmonary artery pressure (mPAP) of patients after AATE compared with preoperative values. The left ventricular myocardial function index (LVMPI) and the right ventricular myocardial function index (RVMPI) showed a significant decrease after the operation. Moreover, AATE prominently increased left ventricular ejection time (LVET) and right ventricular ejection time (RVET) and reduced the left ventricular interventricular septum diameter (LVIVSD) and the right ventricular end-diastolic diameter (RVedD). There was no significant difference in mPAP, LVMPI, RVMPI, LVET, RVET, LVIVSD, and RVedD between postoperative patients and healthy children (P > 0.05). Conclusion: AATE can improve cardiovascular function in pediatric patients with AATH. Specifically, it reduces mPAP and LVMPI/RVMPI in pediatric patients. Furthermore, AATE increases LVET and RVET and reduces LVIVSD and RVedD. [ABSTRACT FROM AUTHOR]

Glioma treatment remains a challenge owing to unsatisfactory targeted chemotherapy, where the blood–brain barrier (BBB) hinders the efficient uptake of therapeutics into the brain. Vasculogenic mimicry (VM) formed by invasive glioma cells negatively affects the treatment of glioma. Herein, we developed a targeted biomimetic drug delivery system comprising a doxorubicin-loaded platelet membrane-coated nanogel (DOX@PNGs). The nanogels provide great redox/pH dual responsiveness, while the platelet membrane (PLTM) promotes stability and circulation time. In vitro cellular uptake and in vivo imaging experiments demonstrated that the DOX@PNGs delivery system could penetrate the BBB, target gliomas, and destruct VM. DOX@PNGs increased drug penetration and prolonged mouse survival time during the treatment of orthotopic gliomas. These results indicate this biomimetic drug delivery system to be promising for glioma treatment and may be clinically translated in the future. [ABSTRACT FROM AUTHOR]