Characterization of Hepatitis B Virus Transcripts in Chronically HBV-Infected Chimpanzees and Patients Treated with ARC-520 siRNA Demonstrates Transcriptional Silencing of cccDNA.

Full-length hepatitis B virus (HBV) transcripts of chimpanzees and patients treated with multidose (MD) HBV siRNA ARC-520 and entecavir (ETV) were characterized by single-molecule real-time (SMRT) sequencing, identifying multiple types of transcripts with the potential to encode HBx, HBsAg, HBeAg, core, and polymerase, as well as transcripts likely to be derived from dimers of dslDNA, and these differed between HBeAg-positive (HBeAg+) and HBeAg-negative (HBeAg-) individuals. HBV transcripts from the last follow-up ~30 months post-ARC-520 treatment were categorized from one HBeAg+ (one of two previously highly viremic patients that became HBeAg- upon treatment and had greatly reduced cccDNA products) and four HBeAg- patients. The previously HBeAg+ patient received a biopsy that revealed that he had 3.

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques.

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure.

Vaccination with a Replication-Dead Murine Gammaherpesvirus Lacking Viral Pathogenesis Genes Inhibits WT Virus Infection.

Gammaherpesviruses are oncogenic pathogens that establish lifelong infections. There are no FDA-approved vaccines against Epstein-Barr virus or Kaposi sarcoma herpesvirus. Murine gammaherpesvirus-68 (MHV68) infection of mice provides a system for investigating gammaherpesvirus pathogenesis and testing vaccine strategies.

Heterogeneous Ribonucleoprotein K Is a Host Regulatory Factor of Chikungunya Virus Replication in Astrocytes.

Chikungunya virus (CHIKV) is an emerging, mosquito-borne arthritic alphavirus increasingly associated with severe neurological sequelae and long-term morbidity. However, there is limited understanding of the crucial host components involved in CHIKV replicase assembly complex formation, and thus virus replication and virulence-determining factors, within the central nervous system (CNS). Furthermore, the majority of CHIKV CNS studies focus on neuronal infection, even though astrocytes represent the main cerebral target.

Cardiac Biomarkers in a Brazilian Indigenous Population Exposed to Arboviruses: A Cross-Sectional Study.

Arthropod-borne viral diseases are acute febrile illnesses, sometimes with chronic effects, that can be debilitating and even fatal worldwide, affecting particularly vulnerable populations. Indigenous communities face not only the burden of these acute febrile illnesses, but also the cardiovascular complications that are worsened by urbanization. A cross-sectional study was conducted in an Indigenous population in the Northeast Region of Brazil to explore the association between arboviral infections (dengue, chikungunya, and Zika) and cardiac biomarkers, including cardiotrophin 1, growth differentiation factor 15, lactate dehydrogenase B, fatty-acid-binding protein 3, myoglobin, N-terminal pro-B-type natriuretic peptide, cardiac troponin I, big endothelin 1, and creatine kinase-MB, along with clinical and anthropometric factors.

Predictive Efficacy of Dual Therapies Combining Integrase Strand Transfer Inhibitors with Second-Generation Non-Nucleoside Reverse Transcriptase Inhibitors Following HIV-1 Treatment Failure in Cameroon: Implications for the Use of a Long-Acting Therapeutic Strategy in Low- and Middle-Income Countries.

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients.

Tissue-Specific DNA Methylation Changes in CD8 T Cells During Chronic Simian Immunodeficiency Virus Infection of Infant Rhesus Macaques.

Robust CD8 T cell responses are critical for the control of HIV infection in both adults and children. Our understanding of the mechanisms driving these responses is based largely on studies of cells circulating in peripheral blood in adults, but the regulation of CD8 T cell responses in tissue sites is poorly understood, particularly in pediatric infections. DNA methylation is an epigenetic modification that regulates gene transcription.

A Small-Particle Aerosol Model of Ebolavirus Zaire Infection in Ferrets.

The Ebola virus (EBOV) causes severe disease in humans, and animal models are needed to evaluate the efficacy of vaccines and therapeutics. While non-human primate (NHP) and rodent EBOV infection models have been well characterized, there is a growing need for an intermediate model. Here, we provide the first report of a small-particle aerosol (AE) EBOV ferret model and disease progression compared with the intramuscular (IM) EBOV ferret model.

Enhanced Immune Response Against Echinococcus Granulosus Through a CTLA-4/B7 Affinity-Based Vaccine.

Echinococcosis is a zoonotic infectious disease that poses a significant threat to the health of individuals living in rural regions. While vaccination represents a potential strategy for disease prevention, there is currently no effective vaccine available for humans to prevent cystic echinococcosis (CE). This study aimed to design a novel multi-epitope vaccine (MEV) against Echinococcus granulosus for human use, employing immunoinformatics methods.

Scoping Review of Current Costing Literature on Interventions to Reach Zero-Dose Children in Low- and Middle-Income Countries.

A limited number of studies focus on estimating the costs of interventions to increase childhood immunization coverage in low- and middle-income countries (LMICs). Existing reviews often compare estimated costs but lack information on the methods used. The objective of this review is to summarize the methods used in costing studies that assessed interventions to reach zero-dose (ZD) children.

Association Between County-Level Social Vulnerability and Vaccine-Related Attitudes and Hesitancy Toward COVID-19 Vaccination in the United States.

Background/objectives: Understanding attitudes and behaviors related to vaccination is critical for enhancing COVID-19 vaccination acceptance and reducing disparities in vaccination coverage. This study examines disparities in vaccine-related attitudes and COVID-19 vaccine hesitancy in the United States in relation to community-level social vulnerability.

Methods: This study analyzed cross-sectional national surveys conducted repeatedly between July 2020 and August 2021 ( = 6716).

Microfluidic-Chip-Based Formulation and In Vivo Evaluations of Squalene Oil Emulsion Adjuvants for Subunit Vaccines.

Background: Adjuvants play a crucial role in improving the immunogenicity of various antigens in vaccines. Squalene-in-water emulsions are clinically established vaccine adjuvants that improve immune responses, particularly during a pandemic. Current manufacturing processes for these emulsion adjuvants include microfluidizers and homogenizers and these processes have been used to produce emulsion adjuvants to meet global demands during a pandemic.

COVID-19 Testing Behavior as a Predictor of COVID-19 Vaccination in Southeastern Louisiana: A Longitudinal Cohort Study.

Global COVID-19 vaccination effort faces the challenges of vaccine hesitancy and resistance, rooted in misinformation and institutional distrust. Addressing these barriers with customized messaging is essential, yet the relationship between vaccine hesitancy and other health-seeking behaviors, like COVID-19 testing, has been underexplored. This study assessed COVID-19 vaccine uptake in Southeastern Louisiana across 10 pharmacies and clinics in areas with historically high rates of COVID-19 infection.

Leveraging Data from a Provincial Electronic Immunization Registry to Analyze Immunization Coverage, Timeliness, and Defaulters Among 8.8 Million Children from the 2018 to 2023 Birth Cohorts in Sindh Province, Pakistan.

Background/objectives: Full immunization coverage in Pakistan remains suboptimal at 66%. An in-depth assessment is needed to understand the long-term trends in immunization and identify the extent of defaulters and associated risk factors of them being left uncovered by the immunization system.

Methods: We conducted a 5-year analysis using the Government's Provincial Electronic Immunization Registry data for the 2018-2023 birth cohorts in Sindh province.

Integrated Approaches for the Delivery of Maternal and Child Health Services with Childhood Immunization Programs in Low- and Middle-Income Countries: Systematic Review Update 2011-2020.

: The integration of maternal and child health services (MCH) with routine immunization is an important global health strategy, particularly in low- and middle-income countries (LMICs). However, evidence is lacking regarding the best practices for service integration and the effect of integration on immunization and linked health service outcomes. : We searched publication databases and gray literature for articles published between 2011 and 2020 that include approaches to integrating MCH services with immunizations during the first two years of life in LMICs.

Machine Learning and Statistical Analyses of Sensor Data Reveal Variability Between Repeated Trials in Parkinson's Disease Mobility Assessments.

Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insights into the impact of Parkinson's disease (PD) on motor control, balance, and cognitive function. We assess the test-retest reliability of these tasks in 262 PD participants and 50 controls by evaluating machine learning models based on wearable-sensor-derived measures and statistical metrics. This evaluation examines total duration, subtask duration, and other quantitative measures across two trials.

Characterization of an Inorganic Powder-Based Scintillation Detector Under a UHDR Electron Beam.

(1) Background: Ultra-high dose rate (UHDR) radiation therapy needs a reliable dosimetry solution and scintillation detectors are promising candidates. In this study, we characterized an inorganic powder-based scintillation detector under a 9 MeV UHDR electron beam. (2) Methods: A mixture of ZnS:Ag powder and optic glue was coupled to an 8 m Eska GH-4001-P polymethyl methacrylate (PMMA) optical fiber.

Detection and Quantification of DNA by Fluorophore-Induced Plasmonic Current: A Novel Sensing Approach.

We report on the detection and quantification of aqueous DNA by a fluorophore-induced plasmonic current (FIPC) sensing method. FIPC is a mechanism described by our group in the literature where a fluorophore in close proximity to a plasmonically active metal nanoparticle film (MNF) is able to couple with it, when in an excited state. This coupling produces enhanced fluorescent intensity from the fluorophore-MNF complex, and if conditions are met, a current is generated in the film that is intrinsically linked to the properties of the fluorophore in the complex.

Gemcitabine-Loaded Microbeads for Transarterial Chemoembolization of Rabbit Renal Tumor Monitored by F-FDG Positron Emission Tomography/X-Ray Computed Tomography Imaging.

Background/objectives: The purpose of this study was to develop the gemcitabine-loaded drug-eluting beads (G-DEBs) for transarterial chemoembolization (TACE) in rabbit renal tumors and to evaluate their antitumor effect using 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (F-FDG PET/CT).

Methods: DEBs were prepared by polyvinyl alcohol-based macromer crosslinked with -acryl tyrosine and ,'-methylenebis(acrylamide). Gemcitabine was loaded through ion change to obtain G-DEBs.

Mesoporous Polydopamine Nano-Bowls Demonstrate a High Entrapment Efficiency and pH-Responsive Release of Paclitaxel for Suppressing A549 Lung Cancer Cell Proliferation In Vitro.

The effectiveness of paclitaxel (PTX) in treating non-small-cell lung carcinoma (NSCLC) is restricted by its poor pharmacokinetic profile and side effects. This limitation stems from the lack of a suitable delivery vector to efficiently target cancer cells. Therefore, there is a critical need to develop an efficient carrier for the optimised delivery of PTX in NSCLC therapy.

Analysis of Interfacial Adhesion Properties Between PBT Azide Propellant Matrix and Defective AP Fillers Using Molecular Dynamics Simulations.

Filler defects and matrix crosslinking degree are the main factors affecting the interfacial adhesion properties of propellants. Improving adhesion can significantly enhance debonding resistance. In this study, all-atom molecular dynamics (MD) simulations are employed to investigate the interfacial adsorption behavior and mechanisms between ammonium perchlorate (AP) fillers and a poly(3,3-bis-azidomethyl oxetane)-tetrahydrofuran (PBT) matrix.

A Study on the Effect of Indirect Nitrate Supply on the Nitrogen Fixation Capacity of Soybean Nodules.

In this study, dual-root soybean ( L. Merr.) plants, with one side nodulated and the other nonnodulated, were used as experimental materials.

Identification and Analysis of the Plasma Membrane H-ATPase Gene Family in Cotton and Its Roles in Response to Salt Stress.

Plant plasma membrane (PM) H-ATPase functions as a proton-motive force by exporting cellular protons to establish a transmembrane chemical gradient of H ions and an accompanying electrical gradient. These gradients are crucial for plant growth and development and for plant responses to abiotic and biotic stresses. In this study, a comprehensive identification of the PM H-ATPase gene family was conducted across four cotton species.

Development and Validation of Kompetitive Allele-Specific Polymerase Chain Reaction Markers for Seed Protein Content in Soybean.

Seed protein content is a critical trait in soybean breeding, as it provides a primary source of high-quality protein for both human consumption and animal feed. This study aimed to enhance molecular marker-assisted selection for high-protein soybean varieties by developing Kompetitive Allele-Specific Polymerase Chain Reaction (KASP) markers targeted at loci associated with seed protein content. Nineteen markers with high genotyping efficacy were identified through screening.