Towards silent and efficient flight by combining bioinspired owl feather serrations with cicada wing geometry.

As natural predators, owls fly with astonishing stealth due to the serrated feather morphology that produces advantageous flow characteristics. Traditionally, these serrations are tailored for airfoil edges with simple two-dimensional patterns, limiting their effect on noise reduction while negotiating tradeoffs in aerodynamic performance. Conversely, the intricately structured wings of cicadas have evolved for effective flapping, presenting a potential blueprint for alleviating these aerodynamic limitations.

Factors Influencing Admission Decisions in Skilled Nursing Facilities: Retrospective Quantitative Study.

Background: Occupancy rates within skilled nursing facilities (SNFs) in the United States have reached a record low. Understanding drivers of occupancy, including admission decisions, is critical for assessing the recovery of the long-term care sector as a whole. We provide the first comprehensive analysis of financial, clinical, and operational factors that impact whether a patient referral to an SNF is accepted or denied, using a large health informatics database.

Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine.

The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N = 12) and a carbamazepine study (N = 12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose.

Phase 1 study of safety, pharmacokinetics, and antiviral activity of SARS-CoV-2 neutralizing monoclonal antibody ABBV-47D11 in patients with COVID-19.

ABBV-47D11 is a neutralizing monoclonal antibody that targets a mutationally conserved hydrophobic pocket distal to the ACE2 binding site of SARS-CoV-2. This first-in-human safety, pharmacokinetics, and antiviral pharmacodynamic assessment in patients with COVID-19 provide an initial evaluation of this antibody that may allow further development. This multicenter, randomized, double-blind, and placebo-controlled single ascending dose study of ABBV-47D11 (180, 600, or 2400 mg) as an intravenous infusion, was in hospitalized and non-hospitalized (confined) adults with mild to moderate COVID-19.

Description of antibiotic use variability among US nursing homes using electronic health record data.

Background: Antibiotics are frequently prescribed in nursing homes; national data describing facility-level antibiotic use are lacking. The objective of this analysis was to describe variability in antibiotic use in nursing homes across the United States using electronic health record orders.

Methods: A retrospective cohort study of antibiotic orders for 309,884 residents in 1,664 US nursing homes in 2016 were included in the analysis.

Biomarkers for the clinical development of antiviral therapies.

With the morbidity and mortality associated with the COVID-19 pandemic that we are witnessing this year, the risks posed by emerging viral diseases to global health are all too obvious. This pandemic highlights the importance of antiviral drug discovery, which targets emerging viral pathogens, as well as existing pathogenic viruses that undergo continuous evolution. Drug discovery and development is a long and resource intensive process; however, the use of biomarkers can accelerate clinical development of antivirals by providing information regarding diagnosis of specific viral infections, status of infection, potential safety parameters, and antiviral responses.

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers.

Backgrounds: Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).

Methods: Biobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied.

Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial.

Background & Aims: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis.

Methods: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial.

Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered With Human Immunodeficiency Virus Antiretrovirals.

Background: Treatment of patients coinfected with hepatitis C and human immunodeficiency viruses (HCV; HIV) requires careful consideration of potential drug-drug interactions between HCV direct-acting antiviral agents (DAA) and HIV antiretrovirals. Glecaprevir/pibrentasvir is a fixed-dose combination of an NS3/4A protease inhibitor and an NS5A inhibitor approved for the treatment of chronic HCV genotype 1-6 infection, including patients with HIV coinfection.

Methods: A series of phase 1 studies was conducted to evaluate potential interactions of glecaprevir and pibrentasvir with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, abacavir/dolutegravir/lamivudine, raltegravir, rilpivirine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir, or efavirenz/emtricitabine/tenofovir disoproxil fumarate.

Safety and Pharmacokinetics of Glecaprevir/Pibrentasvir in Adults With Chronic Genotype 1-6 Hepatitis C Virus Infections and Compensated Liver Disease.

Background: Untreated, chronic hepatitis C virus (HCV) infection may lead to progressive liver damage, which can be mitigated by successful treatment. This integrated analysis reports the safety, efficacy, and pharmacokinetics (PK) of the ribavirin-free, direct-acting, antiviral, fixed-dose combination of glecaprevir/pibrentasvir (G/P) in patients with chronic HCV genotype 1-6 infections and compensated liver disease, including patients with chronic kidney disease stages 4 or 5 (CKD 4/5).

Methods: Data from 9 Phase II and III clinical trials, assessing the efficacy and safety of G/P treatment for 8-16 weeks, were included.

Glecaprevir/pibrentasvir in patients with chronic HCV and recent drug use: An integrated analysis of 7 phase III studies.

Background: Injection drug use is the primary mode of transmission for hepatitis C virus (HCV), and treatment guidelines recommend treating HCV-infected people who use drugs; however, concerns about adherence, effectiveness, and reinfection have impeded treatment uptake.

Methods: Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir (G/P) in patients chronically infected with HCV genotypes 1-6. Patients had compensated liver disease, with or without cirrhosis, and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon.

Glecaprevir/Pibrentasvir in patients with chronic HCV genotype 3 infection: An integrated phase 2/3 analysis.

Glecaprevir coformulated with pibrentasvir (G/P) is approved to treat hepatitis C virus (HCV) infection and was highly efficacious in phase 2 and 3 studies. Treating HCV genotype (GT) 3 infection remains a priority, as these patients are harder to cure and at a greater risk for liver steatosis, fibrosis progression and hepatocellular carcinoma. Data were pooled from five phase 2 or 3 trials that evaluated 8-, 12- and 16-week G/P in patients with chronic HCV GT3 infection.

High SVR12 with 8-week and 12-week glecaprevir/pibrentasvir therapy: An integrated analysis of HCV genotype 1-6 patients without cirrhosis.

Background & Aims: Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. In nine phase II or III clinical trials, G/P therapy achieved rates of sustained virologic response 12 weeks after treatment (SVR12) of 93-100% across all six major HCV genotypes (GTs). An integrated efficacy analysis of 8- and 12-week G/P therapy in patients without cirrhosis with HCV GT 1-6 infection was performed.

Interactions between the Hepatitis C Virus Nonstructural 2 Protein and Host Adaptor Proteins 1 and 4 Orchestrate Virus Release.

Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting.

Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection.

Background: Glecaprevir and pibrentasvir are direct-acting antiviral agents with pangenotypic activity and a high barrier to resistance. We evaluated the efficacy and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C virus (HCV) genotype 1 or 3 infection.

Methods: We conducted two phase 3, randomized, open-label, multicenter trials.

Glecaprevir/pibrentasvir for hepatitis C virus genotype 3 patients with cirrhosis and/or prior treatment experience: A partially randomized phase 3 clinical trial.

This study assessed the efficacy and safety of ribavirin-free coformulated glecaprevir/pibrentasvir (G/P) in patients with hepatitis C virus genotype 3 infection with prior treatment experience and/or compensated cirrhosis, a patient population with limited treatment options. SURVEYOR-II, Part 3 was a partially randomized, open-label, multicenter, phase 3 study. Treatment-experienced (prior interferon or pegylated interferon ± ribavirin or sofosbuvir plus ribavirin ± pegylated interferon therapy) patients without cirrhosis were randomized 1:1 to receive 12 or 16 weeks of G/P (300 mg/120 mg) once daily.

Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis.

Background & Aims: Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.

Methods: SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1-6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin.

Anticancer kinase inhibitors impair intracellular viral trafficking and exert broad-spectrum antiviral effects.

Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown.

High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis.

Background & Aims: The combination of ABT-493 (NS3/4A protease inhibitor) plus ABT-530 (NS5A inhibitor) has shown high rates of sustained virologic response at post-treatment week 12 (SVR12) in noncirrhotic patients infected with hepatitis C virus (HCV) genotypes (GTs) 1-6. We describe 2 open-label phase 2 studies investigating the efficacy and safety of ABT-493 plus ABT-530 with or without ribavirin (RBV) in GT1- or GT3-infected patients with compensated cirrhosis.

Methods: Patients with GT1 infection received 200 mg ABT-493 plus 120 mg ABT-530 for 12 weeks.

B-cell receptors expressed by lymphomas of hepatitis C virus (HCV)-infected patients rarely react with the viral proteins.

Chronic hepatitis C virus (HCV) infection has been implicated in the induction and maintenance of B-cell lymphomas. The strongest evidence for this derives from clinical observations of tumor regressions upon antiviral treatments. Here we used multiple methods to test the hypothesis that the expansion of HCV-specific B cells gives rise to lymphomas.

Telephone triage service data for detection of influenza-like illness.

Background: Surveillance for influenza and influenza-like illness (ILI) is important for guiding public health prevention programs to mitigate the morbidity and mortality caused by influenza, including pandemic influenza. Nontraditional sources of data for influenza and ILI surveillance are of interest to public health authorities if their validity can be established.

Methods/principal Findings: National telephone triage call data were collected through automated means for purposes of syndromic surveillance.

Electrocardiographic determination of culprit lesion site in patients with acute coronary events.

Purpose: The purpose of our study was to determine the ability of electrocardiographic (ECG) criteria derived from prior angiographic-ECG correlative studies to identify life-threatening coronary artery obstructive lesions.

Methods: We studied 128 consecutive patients referred from the emergency department for emergent coronary angiography for symptoms and ECG changes suggesting an acute coronary event. Using ECG criteria derived from prior studies, we attempted to predict not only the vessel housing the culprit lesion, but whether the lesion was located proximally in that vessel, and then determined the positive and negative predictive values (PPV and NPV) of the criteria used.