Probability of Achieving Bone Mineral Density Treatment Goals with Denosumab Treatment in Postmenopausal Women with Osteoporosis.

Bone mineral density (BMD) levels achieved on osteoporosis treatment are predictive of subsequent fracture risk, and T-score > -2.5 has been proposed as a minimum treatment target for women with osteoporosis. Knowing the likelihood of attaining target T-scores with different medications for different baseline BMD levels can help determine appropriate initial treatment for individual patients.

Bayesian Borrowing With Multiple Heterogeneous Historical Studies Using Order Restricted Normalized Power Prior.

The recent U.S. Food and Drug Administration guidance on complex innovative trial designs acknowledges the use of Bayesian strategies to incorporate historical information based on clinical expertise and data similarity.

Evaluating sex and line differences in successive negative contrast and ethanol consumption using alcohol preferring and high alcohol drinking rats.

Background: The loss of a job or relationship are a couple of examples of unexpected reward loss. Life events, such as these can induce negative emotional reactions (e.g.

Interferon-Stimulated Genes and Immune Metabolites as Broad-Spectrum Biomarkers for Viral Infections.

The type I interferon (IFN-I) response is a critical component of the immune defense against various viral pathogens, triggering the expression of hundreds of interferon-stimulated genes (ISGs). These ISGs encode proteins with diverse antiviral functions, targeting various stages of viral replication and restricting infection spread. Beyond their antiviral functions, ISGs and associated immune metabolites have emerged as promising broad-spectrum biomarkers that can differentiate viral infections from other conditions.

High-Throughput Oxford Nanopore Sequencing Unveils Complex Viral Population in Kansas Wheat: Implications for Sustainable Virus Management.

Wheat viruses are major yield-reducing factors, with mixed infections causing substantial economic losses. Determining field virus populations is crucial for effective management and developing virus-resistant cultivars. This study utilized the high-throughput Oxford Nanopore sequencing technique (ONT) to characterize wheat viral populations in major wheat-growing counties of Kansas from 2019 to 2021.

Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines.

The betacoronavirus genus contains five of the seven human coronaviruses, making it a particularly critical area of research to prepare for future viral emergence. We utilized three human betacoronaviruses, one from each subgenus-HCoV-OC43 (embecovirus), SARS-CoV-2 (sarbecovirus), and MERS-CoV (merbecovirus)-, to study betacoronavirus interactions with the PKR-like ER kinase (PERK) pathway of the integrated stress response (ISR)/unfolded protein response (UPR). The PERK pathway becomes activated by an abundance of unfolded proteins within the endoplasmic reticulum (ER), leading to phosphorylation of eIF2α and translational attenuation.

Animal Models of Non-Respiratory, Post-Acute Sequelae of COVID-19.

Post-acute sequelae of COVID-19 (PASC) are a diverse set of symptoms and syndromes driven by dysfunction of multiple organ systems that can persist for years and negatively impact the quality of life for millions of individuals. We currently lack specific therapeutics for patients with PASC, due in part to an incomplete understanding of its pathogenesis, especially for non-pulmonary sequelae. Here, we discuss three animal models that have been utilized to investigate PASC: non-human primates (NHPs), hamsters, and mice.

Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates.

Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.

Co-Infection of Mosquitoes with Rift Valley Fever Phlebovirus Strains Results in Efficient Viral Reassortment.

Rift Valley fever phlebovirus (RVFV) is a zoonotic mosquito-borne pathogen endemic to sub-Saharan Africa and the Arabian Peninsula which causes Rift Valley fever in ruminant livestock and humans. Co-infection with divergent viral strains can produce reassortment among the L, S, and M segments of the RVFV genome. Reassortment events can produce novel genotypes with altered virulence, transmission dynamics, and/or mosquito host range.

Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection.

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.

Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease.

Enterovirus-D68 (EV68) continues to present as a global health issue causing respiratory illness and outbreaks associated with long-lasting neurological disease, with no antivirals or specific treatment options. The development of antiviral therapeutics, such as small-molecule inhibitors that target conserved proteins like the enteroviral 3C protease, remains to be achieved. While various 3C inhibitors have been investigated, their design does not consider the potential emergence of drug resistance mutations.

Comparative Adsorption of Porcine Reproductive and Respiratory Syndrome Virus Strains to Minnesota Soils.

Porcine reproductive and respiratory syndrome (PRRS) is an endemic disease affecting the swine industry. The disease is caused by the PRRS virus (PRRSV). Despite extensive biosecurity and control measures, the persistence and seasonality of the virus have raised questions about the virus's environmental dynamics during the fall season when the yearly epidemic onset begins and when crop harvesting and manure incorporation into the field occur.

The Genes of Nigerian Marek's Disease Virus (MDV) Field Isolates Contain Mutations Common to Both European and US High Virulence Strains.

Background: Marek's disease (MD) is a pathology affecting chickens caused by Marek's disease virus (MDV), an acute transforming alphaherpesvirus of the genus . MD is characterized by paralysis, immune suppression, and the rapid formation of T-cell (primarily CD4+) lymphomas. Over the last 50 years, losses due to MDV infection have been controlled worldwide through vaccination; however, these live-attenuated vaccines are non-sterilizing and potentially contributed to the virulence evolution of MDV field strains.

Modeling BK Virus Infection in Renal Transplant Recipients.

Kidney transplant recipients require a lifelong protocol of immunosuppressive therapy to prevent graft rejection. However, these same medications leave them susceptible to opportunistic infections. One pathogen of particular concern is human polyomavirus 1, also known as BK virus (BKPyV).

Unveiling the Molecular Architecture of HBV Spherical Subviral Particles: Structure, Symmetry, and Lipid Dynamics.

Since the discovery of the Australia antigen, now known as the hepatitis B surface antigen (HBsAg), significant research has been conducted to elucidate its physical, chemical, structural, and functional properties. Subviral particles (SVPs) containing HBsAg are highly immunogenic, non-infectious entities that have not only revolutionized vaccine development but also provided critical insights into HBV immune evasion and viral assembly. Recent advances in cryo-electron microscopy (cryo-EM) have uncovered the heterogeneity and dynamic nature of spherical HBV SVPs, emphasizing the essential role of lipid-protein interactions in maintaining particle stability.

eEF-2K Deficiency Boosts the Virus-Specific Effector CD8 T Cell Responses During Viral Infection.

In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8 T cells without compromising the development of VACV-specific memory CD8 T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8 T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase.

Activity of Various Cathepsin Proteases and Enrichment of Klotho Protein in the Urine and Urinary Extracellular Vesicles After SARS-CoV-2 Infection.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for causing the Coronavirus disease 2019 (COVID-19) outbreak. While mutations cause the emergence of new variants, the ancestral SARS-CoV-2 strain is unique among other strains. Various clinical parameters, the activity of cathepsin proteases, and the concentration of various proteins were measured in urine samples from COVID-19-negative participants and COVID-19-positive participants.

Evaluating Neural Network Performance in Predicting Disease Status and Tissue Source of JC Polyomavirus from Patient Isolates Based on the Hypervariable Region of the Viral Genome.

JC polyomavirus (JCPyV) establishes a persistent, asymptomatic kidney infection in most of the population. However, JCPyV can reactivate in immunocompromised individuals and cause progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease with no approved treatment. Mutations in the hypervariable non-coding control region (NCCR) of the JCPyV genome have been linked to disease outcomes and neuropathogenesis, yet few metanalyses document these associations.

Identifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic .

Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Single Exposure to Low-Intensity Focused Ultrasound Causes Biphasic Opening of the Blood-Brain Barrier Through Secondary Mechanisms.

The blood-brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood.

Inhibition of Endothelial Cell Tube Formation by Anti-Vascular Endothelial Growth Factor/Anti-Angiopoietin-2 RNA Nanoparticles.

RNA nanoparticles, derived from the packaging RNA three-way junction motif (pRNA-3WJ) of the bacteriophage phi29 DNA packaging motor, have been demonstrated to be thermodynamically and chemically stable, with promise as a nanodelivery system. : A previous study showed that RNA nanoparticles with antiangiogenic aptamers (anti-vascular endothelial growth factor (VEGF) and anti-angiopoietin-2 (Ang2) aptamers) inhibited cell proliferation via WST-1 assay. To further investigate the antiangiogenic potential of these RNA nanoparticles, a modified three-dimensional (3D) spheroid sprouting assay model of human umbilical vein endothelial cells was utilized in the present study.

Pharmacokinetic Evaluation of Neutral Sphinghomyelinase2 (nSMase2) Inhibitor Prodrugs in Mice and Dogs.

: Extracellular vesicles (EVs) can carry pathological cargo, contributing to disease progression. The enzyme neutral sphingomyelinase 2 (nSMase2) plays a critical role in EV biogenesis, making it a promising therapeutic target. Our lab previously identified a potent and selective inhibitor of nSMase2, named DPTIP (IC = 30 nM).

Evaluation of Biologics ACE2/Ang(1-7) Encapsulated in Plant Cells for FDA Approval: Safety and Toxicology Studies.

For several decades, protein drugs (biologics) made in cell cultures have been delivered as sterile injections, decreasing their affordability and patient preference. Angiotensin Converting Enzyme 2 (ACE2) gum is the first engineered human blood protein expressed in plant cells approved by the FDA without the need for purification and is a cold-chain and noninvasive drug delivery. This biologic is currently being evaluated in human clinical studies to debulk SARS-CoV-2 in the oral cavity to reduce coronavirus infection/transmission (NCT00543318).

Global Transcriptomic Analysis of Inbred Lines Reveal Candidate Genes for Response to Maize Lethal Necrosis.

Maize lethal necrosis (MLN) is a significant threat to food security in Sub-Saharan Africa (SSA), with limited commercial inbred lines displaying tolerance. This study analyzed the transcriptomes of four commercially used maize inbred lines and a non-adapted inbred line, all with varying response levels to MLN. RNA-Seq revealed differentially expressed genes in response to infection by maize chlorotic mottle virus (MCMV) and sugarcane mosaic virus (SCMV), the causative agents of MLN.