A prospective longitudinal study assessing the impact of rhinovirus and bacterial infections in acute exacerbations of chronic rhinosinusitis.

Background: Acute exacerbations of chronic rhinosinusitis (AECRS) are thought to arise from common viral infections progressing to secondary bacterial infections. However, the pathophysiology of AECRS remains poorly understood due to a lack of prospective longitudinal studies.

Methods: We conducted a one-year prospective longitudinal study involving chronic rhinosinusitis (CRS) adults.

Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies.

Assessing the role of ankle and hip joint proprioceptive information in balance recovery using vibratory stimulation.

Background: Previous work suggests that proprioceptive information from ankle and hip are crucial in maintaining balance during upright standing; however, the contribution of these proprioceptive information during stepping balance recovery in not clear. The goal of the current study was to assess the role of ankle and hip proprioceptive information on balance recovery performance by manipulating type 1a afferent in muscle spindles using vibratory stimulation.

Methods: Twenty healthy young participants were recruited (age = 22.

Understanding the exposure risk of aerosolized Coccidioides in a Valley fever endemic metropolis.

Coccidioides is the fungal causative agent of Valley fever, a primarily pulmonary disease caused by inhalation of fungal arthroconidia, or spores. Although Coccidioides has been an established pathogen for 120 years and is responsible for hundreds of thousands of infections per year, little is known about when and where infectious Coccidioides arthroconidia are present within the ambient air in endemic regions. Long-term air sampling programs provide a means to investigate these characteristics across space and time.

No Evidence That Analgesic Use after COVID-19 Vaccination Negatively Impacts Antibody Responses.

Uptake of mRNA vaccines, especially booster immunizations, against COVID-19 has been lower than hoped, perhaps in part due to their reactogenicity. Analgesics might alleviate symptoms associated with vaccination, but they might also impact immune responses. We semiquantitatively measured Ab responses following COVID-19 vaccination in 2354 human participants surveyed about analgesic use after vaccination.

Determinants of B cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections.

Vaccine-induced immunity may impact subsequent responses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants.

The initial age-associated decline in early T-cell progenitors reflects fewer pre-thymic progenitors and altered signals in the bone marrow and thymus microenvironments.

Age-related thymus involution results in decreased T-cell production, contributing to increased susceptibility to pathogens and reduced vaccine responsiveness. Elucidating mechanisms underlying thymus involution will inform strategies to restore thymopoiesis with age. The thymus is colonized by circulating bone marrow (BM)-derived thymus seeding progenitors (TSPs) that differentiate into early T-cell progenitors (ETPs).

Gene Co-Expression Analysis of Multiple Brain Tissues Reveals Correlation of FAM222A Expression with Multiple Alzheimer's Disease-Related Genes.

Background: Alzheimer's disease (AD) is the most common form of dementia in the elderly marked by central nervous system (CNS) neuronal loss and amyloid plaques. FAM222A, encoding an amyloid plaque core protein, is an AD brain atrophy susceptibility gene that mediates amyloid-β aggregation. However, the expression interplay between FAM222A and other AD-related pathway genes is unclear.

T-cell cellular stress and reticulocyte signatures, but not loss of naïve T lymphocytes, characterize severe COVID-19 in older adults.

In children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old. To understand age-specific immune pathobiology of COVID-19, we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable.

T-cell cellular stress and reticulocyte signatures, but not loss of naïve T lymphocytes, characterize severe COVID-19 in older adults.

In children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old. To understand age-specific immune pathobiology of COVID-19 we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable.

Inflammatory and immune markers in HIV-infected older adults on long-term antiretroviral therapy: Persistent elevation of sCD14 and of proinflammatory effector memory T cells.

HIV-positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared with individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV-positive subjects.

Booster doses of COVID-19 vaccines for patients with haematological and solid cancer: a systematic review and individual patient data meta-analysis.

Importance: Patients with cancer have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies.

Objective: To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose.

Competent immune responses to SARS-CoV-2 variants in older adults following two doses of mRNA vaccination.

Aging is associated with a reduced magnitude of primary immune responses to vaccination. mRNA-based SARS-CoV-2 vaccines have shown efficacy in older adults but virus variant escape is still unclear. Here we analyze humoral and cellular immunity against an early-pandemic viral isolate and compare that to the P.

Markers of ventricular repolarization and overall mortality in sleep disordered breathing.

Introduction: Variability and prolongation of ventricular repolarization - measured by changes in QT interval and QT variability are independently associated with ventricular arrhythmias, sudden death, and mortality but such studies did not examine the role of sleep-disordered breathing. We aimed to determine whether sleep-disordered breathing moderated the association between measures of ventricular repolarization and overall mortality.

Methods: Eight hundred participants were randomly selected from each of the following four groups in the Sleep Heart Health Study: mild, moderate, severe or no sleep disordered breathing (n = 200 each).

Early age-related atrophy of cutaneous lymph nodes precipitates an early functional decline in skin immunity in mice with aging.

Secondary lymphoid organs (SLOs) (including the spleen and lymph nodes [LNs]) are critical both for the maintenance of naive T (TN) lymphocytes and for the initiation and coordination of immune responses. How they age, including the exact timing, extent, physiological relevance, and the nature of age-related changes, remains incompletely understood. We used “time stamping” to indelibly mark newly generated naive T cells (also known as recent thymic emigrants) (RTEs) in mice, and followed their presence, phenotype, and retention in SLOs.

NeoScore Integrates Characteristics of the Neoantigen:MHC Class I Interaction and Expression to Accurately Prioritize Immunogenic Neoantigens.

Accurate prioritization of immunogenic neoantigens is key to developing personalized cancer vaccines and distinguishing those patients likely to respond to immune checkpoint inhibition. However, there is no consensus regarding which characteristics best predict neoantigen immunogenicity, and no model to date has both high sensitivity and specificity and a significant association with survival in response to immunotherapy. We address these challenges in the prioritization of immunogenic neoantigens by (1) identifying which neoantigen characteristics best predict immunogenicity; (2) integrating these characteristics into an immunogenicity score, the NeoScore; and (3) demonstrating a significant association of the NeoScore with survival in response to immune checkpoint inhibition.

Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.

Purpose: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design.

Experimental Design: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis.

Results: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy.

Shared Gene Expression and Immune Pathway Changes Associated with Progression from Nevi to Melanoma.

There is a need to identify molecular biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. Using datasets containing gene expression for dysplastic nevi and melanoma or melanoma arising in a nevus, we performed differential gene expression analysis and regularized regression models to identify genes and pathways that were associated with progression from nevi to melanoma. A small number of genes distinguished nevi from melanoma.

Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose.

CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes.

Background: Dedifferentiated liposarcoma (DDLPS) is one of the most common soft tissue sarcoma subtypes and is devastating in the advanced/metastatic stage. Despite the observation of clinical responses to inhibitors, little is known about the immune microenvironment in relation to patient prognosis.

Methods: We performed a retrospective study of 61 patients with DDLPS.

COVID-19 Infection, Reinfection, and Vaccine Effectiveness in a Prospective Cohort of Arizona Frontline/Essential Workers: The AZ HEROES Research Protocol.

Background: The Arizona Healthcare, Emergency Response, and Other Essential workers Study (AZ HEROES) aims to examine the epidemiology of SARS-CoV-2 infection and COVID-19 illness among adults with high occupational exposure risk.

Objective: Study objectives include estimating incidence of SARS-CoV-2 infection in essential workers by symptom presentation and demographic factors, determining independent effects of occupational and community exposures on incidence of SARS-CoV-2 infection, establishing molecular and immunologic characteristics of SARS-CoV-2 infection in essential workers, describing the duration and patterns of rRT-PCR-positivity, and examining post-vaccine immunologic response.

Methods: Eligible participants include Arizona residents aged 18-85 years who work at least 20 hours per week in an occupation involving regular direct contact (within three feet) with others.

Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy.

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster.

Coronavirus Disease 2019 Symptoms and Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Positivity in a Large Survey of First Responders and Healthcare Personnel, May-July 2020.

A severe acute respiratory syndrome coronavirus 2 serosurvey among first responder/healthcare personnel showed that loss of taste/smell was most predictive of seropositivity; percent seropositivity increased with number of coronavirus disease 2019 symptoms. However, 22.9% with 9 symptoms were seronegative, and 8.

T cell-depleted cultured pediatric thymus tissue as a model for some aspects of human age-related thymus involution.

Human age-related thymus involution is characterized by loss of developing thymocytes and the thymic epithelial network that supports them, with replacement by adipose tissue. The mechanisms that drive these changes are difficult to study in vivo due to constant trafficking to and from the thymus. We hypothesized that the loss of thymocytes that occurs during human thymic organ cultures could model some aspects of thymus involution and begin to identify mechanisms that drive age-related changes in the thymic microenvironment.