National Analysis of Over 48,000 Veterans With HIV Demonstrates CD4/CD8 Ratio as a Risk Marker for Anal Intraepithelial Lesions and Anal Cancer.

Background: Anal squamous intraepithelial lesions are identifiable and treatable precancerous lesions that lack defined risk factors determining screening necessity.

Objective: Assess the prevalence and risk factors associated with low- and high-grade anal squamous intraepithelial lesions and anal squamous cell carcinoma.

Design: Retrospective cohort analysis of veterans with HIV between 1999-2023.

Using T-Cell Subsets to Better Characterize Immunoresiliency and Immunodeficiency in Patients with Recurrent Infections.

Background/objectives: Common Variable Immunodeficiency Disease (CVID) and other immunodeficiencies can present in subtle and variable ways. Whether or not a genetic lesion can be identified, there are not well understood biomarkers that quantitatively describe how severe a deficiency is. Here we discuss two possible ranking systems, CD4/CD8 T cell ratios and Immune Health Grades, and how such data maybe applicable to some immunodeficiencies.

Viruses tipping the scales: The role of the CD4/CD8 ratio in determining viral outcome.

Here we review recent data on how animal viruses alter the T cell dynamics, and how stressed T cell populations alter viral disease outcomes. The CD4/CD8 ratio of T cells is regulated by the thymus well into adulthood, and determined by both host genetics and environmental exposures. Human and animal data now show many chronic viral infections interact with this ratio and Immune Health Grades, but this raises new questions and justifies new experimental systems.

Risk of developing high-grade squamous intraepithelial lesions or anal cancer after anal condylomata treatment in people living with HIV.

Aim: To assess the risk and natural history of developing advanced anal disease after diagnosis of anal condyloma in people living with HIV (PLWH).

Methods: This was a single-centre retrospective cohort study of PLWH and anal condyloma from 2001 to 2021. Patients who developed advanced anal disease (AAD; anal high-grade squamous intraepithelial lesions and/or anal cancer) were compared to those who did not progress (non-AAD).

Analysis of >15 000 Solid Organ Transplant Recipients Reveals Nonanal Genitourinary HPV-related Disease as Highest Risk Predictor for Anal Squamous Intraepithelial Lesions/Anal Cancer.

Background: Solid organ transplantation is a risk predictor for virally-mediated anal squamous intraepithelial lesions and cancer (anal disease). Precancerous squamous intraepithelial lesions can be detected by screening, and treatment may prevent cancer progression. Screening recommendations are not well defined.

Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV cancer.

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus.

A Qualitative Study of Barriers to Anal Cancer Screenings in US Veterans Living with HIV.

People living with human immunodeficiency virus (HIV) are at high risk for anal cancer. Anal cancer screenings are recommended annually for US veterans with HIV. Screenings can identify treatable precursor lesions and prevent cancer development.

A Microstrip Transmission Line Biosensor to Measure the Interaction between Microliter Aqueous Solutions and 1.0-17.0 GHz Radio Frequencies.

Radio frequency (RF) biosensors are an expanding field of interest because of the ability to design noninvasive, label-free, low-production-cost sensing devices. Previous works identified the need for smaller experimental devices, requiring nanoliter to milliliter sampling volumes and increased capability of repeatable and sensitive measurement capability. The following work aims to verify a millimeter-sized, microstrip transmission line biosensor design with a microliter well operating on a broadband radio frequency range of 1.

Duration of Time CD4/CD8 Ratio is Below 0.5 is Associated with Progression to Anal Cancer in Patients with HIV and High-Grade Dysplasia.

Background: A CD4/CD8 ratio < 0.5 is associated with increased risk of advanced anal disease (AAD) but it is unknown if duration below 0.5 matters.

A translational genomics approach identifies IL10RB as the top candidate gene target for COVID-19 susceptibility.

Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that reduce COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX), and perturbagen signatures, we identified IL10RB as the top candidate gene target for COVID-19 host susceptibility.

Do immune inflammatory markers correlate with anal dysplasia and anal cancer risk in patients living with HIV?

Purpose: People living with HIV (PLWH) are at an elevated risk for developing anal cancer. As screening is invasive, markers predicting those at highest risk for anal cancer could guide individualized screening. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are surrogate inflammatory/immune markers known to correlate with cancer outcomes.

Engineering Selectivity for Reduced Toxicity of Bacterial Kinase Inhibitors Using Structure-Guided Medicinal Chemistry.

Tuberculosis is a major global public health concern, and new drugs are needed to combat both the typical form and the increasingly common drug-resistant form of this disease. The essential tuberculosis kinase PknB is an attractive drug development target because of its central importance in several critical signaling cascades. A major hurdle in kinase inhibitor development is the reduction of toxicity due to nonspecific kinase activity in host cells.

IL10RB as a key regulator of COVID-19 host susceptibility and severity.

Background: Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes and readily available compounds that reduce COVID-19 host susceptibility is a critical next step.

Methods: We integrate COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbargen signatures to identify candidate genes and compounds that reverse the predicted gene expression dysregulation associated with COVID-19 susceptibility.

Prevalence of High-Grade Anal Dysplasia and Anal Cancer in Veterans Living With HIV and CD4/CD8 Ratio as a Marker For Increased Risk: A Regional Retrospective Cohort Study.

Background: The Department of Veterans Affairs cares for the largest population of patients with HIV of any healthcare system in the United States. Screening for anal dysplasia/cancer is recommended for all veterans with HIV. Exams are invasive, burdensome, and resource intensive.

CD4/CD8 Ratio as a Novel Marker for Increased Risk of High-Grade Anal Dysplasia and Anal Cancer in HIV+ Patients: A Retrospective Cohort Study.

Background: People living with HIV are at risk for anal dysplasia/cancer. Screening/surveillance is costly and burdensome, and the frequency is not evidence based. Objective markers of increased risk of anal carcinogenesis are needed to tailor screening/surveillance.

Immune recovery in HIV-1 infected patients with sustained viral suppression under long-term antiretroviral therapy in Ethiopia.

Background: There is very little data on long-term immune recovery responses in patients on suppressive antiretroviral therapy (ART) in the setting of sub-Saharan Africa (SSA). Thus, we sought to determine CD4+ T-cell, CD8+ T-cell and CD4/CD8 ratio responses in a cohort of HIV infected individuals on sustained suppressive ART followed up for more than a decade.

Methods: The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 14 years.

Role of CD4/CD8 ratio on the incidence of tuberculosis in HIV-infected patients on antiretroviral therapy followed up for more than a decade.

Background: The role of CD4/CD8 ratio on the incidence of tuberculosis (TB) in patients on antiretroviral therapy (ART) is unknown. Thus, we sought to determine whether the CD4/CD8 ratio was associated with development of TB in a cohort of HIV infected individuals on ART followed up for more than a decade in the setting of sub-Saharan Africa (SSA).

Methods: The cohort comprised adult patients who started ART between 2001 and 2007 and followed for up to 15 years.

Anal Intraepithelial Neoplasia Screening With Anal Pap Tests: Follow-up and Corresponding Histology.

Background: Anal cytology is used as a screening tool in the detection of precancerous anal squamous lesions. Follow-up clinical examination after abnormal anal cytology is recommended. The objective of this study was to determine how often abnormal cytology was followed by a clinical examination at our institution and how often cytology predicted histologic outcome.

In Silico Screen and Structural Analysis Identifies Bacterial Kinase Inhibitors which Act with β-Lactams To Inhibit Mycobacterial Growth.

New tools and concepts are needed to combat antimicrobial resistance. Actinomycetes and firmicutes share several eukaryotic-like Ser/Thr kinases (eSTK) that offer antibiotic development opportunities, including PknB, an essential mycobacterial eSTK. Despite successful development of potent biochemical PknB inhibitors by many groups, clinically useful microbiologic activity has been elusive.

GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus.

As antibiotic resistance rises, there is a need for strategies such as antibiotic adjuvants to conserve already-established antibiotics. A family of bacterial kinases known as the penicillin-binding-protein and serine/threonine kinase-associated (PASTA) kinases has attracted attention as targets for antibiotic adjuvants for β-lactams. Here, we report that the pyrazolopyridazine GW779439X sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to various β-lactams through inhibition of the PASTA kinase Stk1.