Ocular toxicity, distribution, and shedding of intravitreal AAV-eqIL-10 in horses.

Non-infectious uveitis (NIU) is a painful recurrent disease affecting 2%-5% of horses. Current treatments require frequent administration with associated adverse events. In a previous study, intravitreal (IVT) adeno-associated virus (AAV) harboring equine interleukin-10 (eqIL-10) cDNA inhibited experimental uveitis in rats.

Qualitative Study of Health Care Team Perception of the Benefits and Limitations of Remote Symptom Monitoring.

Purpose: Remote symptom monitoring (RSM) using electronic patient-reported outcomes (ePROS) connects patients and health care teams between appointments. Patient-perceived benefits and drawbacks of RSM are well-known, but health care team members' perceptions are less clear.

Methods: Health care team members from the University of Alabama at Birmingham and the University of South Alabama Health Mitchell Cancer Institute participated in semi-structured qualitative interviews to explore their experiences and perspectives on RSM benefits and limitations.

Toxicology study of a tissue anchoring paclitaxel prodrug.

Background: Local drug presentation made possible by drug-eluting depots provides benefits for a vast array of diseases, including cancer, microbial infection, and wound healing. Drug-eluting depots provide sustained drug release of therapeutics directly at disease sites with tunable kinetics, remove the need for drugs to access disease sites from circulation, and reduce the side effects associated with systemic therapy. Recently, we introduced an entirely novel approach to local drug presentation named Tissue-Reactive Anchoring Pharmaceuticals (TRAPs).

Patient, Caregiver, and Clinician Perspectives on the Time Burdens of Cancer Care.

Importance: Cancer and its care impose significant time commitments on patients and care partners. The oncology community has only recently conceptualized these commitments and the associated burden as the "time toxicity" of cancer care. As the concept gains traction, there is a critical need to fundamentally understand the perspectives of multiple stakeholders on the time burdens of cancer care.

A qualitative systematic review of the impact of hearing on quality of life.

Purpose: Hearing loss, deafness, and other hearing-related conditions can significantly impact quality of life; numerous qualitative studies have sought to describe these impacts. Synthesis of these findings may provide additional or more robust insights.

Methods: A qualitative systematic review of studies reporting qualitative data relating to the impact of hearing problems on adults' health-related quality of life.

Patient-Perceived Benefits and Limitations of Standard of Care Remote Symptom Monitoring During Cancer Treatment.

Introduction: Remote symptom monitoring (RSM) allows patients to electronically self-report symptoms to their healthcare team for individual management. Clinical trials have demonstrated overarching benefits; however, little is known regarding patient-perceived benefits and limitations of RSM programs used during patient care.

Methods: This prospective qualitative study from December 2021 to May 2023 included patients with cancer participating in standard-of-care RSM at the University of Alabama at Birmingham (UAB) in Birmingham, AL, and the Univeristy of South Alabama (USA) Health Mitchell Cancer Institute (MCI) in Mobile, AL.

Implementation of ePROs Into Multidisciplinary Tumor Board Discussions for Patients With Pancreatic Cancer: The INSPIRE Intervention.

Background: The incorporation of electronic patient-reported outcomes (ePROs), such as the Geriatric Assessment (GA) and treatment preferences, into decision-making for pancreatic cancer has been limited by clinician- and system-level barriers concerning workflow. We hypothesized that ePRO inclusion within multidisciplinary tumor boards (MDTBs) would circumvent barriers and provide a venue for systematic consideration of critical patient-provided information.

Patients And Methods: The INtegrating Systematic PatIent-Reported Evaluations (INSPIRE) intervention consists of (1) patient survey completion, including GA and patient preferences, and (2) screensharing patient ePROs during MDTBs.

Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease with a fatal outcome. There is accumulating evidence of a prominent role of glia in the pathology of HD, and we investigated this by conducting single nuclear RNA sequencing (snRNAseq) of human post mortem brain in four differentially affected regions; caudate nucleus, frontal cortex, hippocampus and cerebellum. Across 127,205 nuclei from donors with HD and age/sex matched controls, we found heterogeneity of glia which is altered in HD.

Corrigendum: Neurocognitive health in LGBTQIA+ older adults: current state of research and recommendations.

[This corrects the article DOI: 10.3389/fnhum.2024.

Urinary biomarkers of environmental exposures and asthma morbidity in a school inner city asthma study.

Background: The burden of pediatric asthma and other allergic diseases is not evenly distributed among United States populations.

Objective: To determine whether urinary biomarkers are associated with asthma morbidity, and if associations vary by child race, ethnicity and sex.

Methods: This study includes n = 152 children with physician-diagnosed asthma who participated in the School Inner-City Asthma Intervention Study (SICAS-2).

Improved therapeutic efficacy in two mouse models of methylmalonic acidemia (MMA) using a second-generation mRNA therapy.

Isolated methylmalonic acidemia/aciduria (MMA) due to MMUT enzyme deficiency is an ultra-rare pediatric disease with high morbidity and mortality, with no approved disease-altering therapies. Previous publications showed that systemic treatment with a codon-optimized mRNA encoding wild-type human MMUT (MMUT) is a promising strategy for treatment of MMA. We developed a second-generation drug product, mRNA-3705, comprised of an mRNA encoding the MMUT enzyme formulated in a lipid nanoparticle (LNP) with incorporation of enhancements over the previous clinical candidate mRNA-3704.

Recommendations for Clinicians to Combat Environmental Disparities in Pediatric Asthma: A Review.

Topic Importance: Asthma is a common and complex lung disease in children, with disproportionally higher prevalence and related adverse outcomes among children in racial and ethnic minority groups and of lower socioeconomic position. Environmental factors, including unhealthy housing and school-based exposures, can contribute to increased asthma morbidity and widening disparities. This underscores a significant environmental justice issue and suggests the need for clinical interventions to reduce sources of environmental exposures and ultimately diminish the observed disparities in childhood asthma.

Selecting PedsQL items to derive the PedsUtil health state classification system to measure health utilities in children.

Background: There is a lack of preference-based health-related quality of life (HRQoL) measures that consistently value health across a full range of child age groups. The PedsQL is a generic HRQoL instrument validated for children 2-18 years, but it is not preference-based. The objective of this study was to derive the PedsUtil health state classification system from the PedsQL as a basis for a preference-based HRQoL measure for children.

Biodistribution of lipid nanoparticle, eGFP mRNA and translated protein following subcutaneous administration in mouse.

Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation. Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA.

Assessing the association between quantity and quality of family caregiver participation in decision-making clinical encounters on patient activation in the metastatic breast cancer setting.

Objective: Caregivers support individuals undergoing cancer treatment by assisting with activities, managing care, navigating healthcare systems, and communicating with care teams. We explored the quality and quantity of caregiver participation during recorded decision-making clinical appointments in women with metastatic breast cancer.

Methods: This was a convergent parallel mixed methods study that utilized qualitative and quantitative data collection and analysis.

Phenotypic and spatial heterogeneity of brain myeloid cells after stroke is associated with cell ontogeny, tissue damage, and brain connectivity.

Acute stroke triggers extensive changes to myeloid immune cell populations in the brain that may be targets for limiting brain damage and enhancing repair. Immunomodulatory approaches will be most effective with precise manipulation of discrete myeloid cell phenotypes in time and space. Here, we investigate how stroke alters mononuclear myeloid cell composition and phenotypes at single-cell resolution and key spatial patterns.

Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2 migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration.

Six-month pain and function outcome expectations were established for total knee arthroplasty using the smallest worthwhile effect.

Introduction: Interpretations of patient-reported outcome measures following knee arthroplasty lack context and typically do not account for costs, risks and benefits compared to an alternative treatment. The primary purpose of our paper is to estimate expectations patients have for pain and function destination outcome, six-months following surgery relative to the outcome expected if knee arthroplasty was not done. Secondary purposes were to determine if statistically significant changes in the smallest worthwhile six-month outcome occurred following an interactive discussion and to assess the construct validity of the expected six-month outcome obtained at baseline.

Rare Case of Lower Gastrointestinal Bleeding Secondary to Miliary Tuberculosis in the United States.

Tuberculosis (TB) remains a significant global health challenge. Miliary TB is a rare manifestation of TB that involves systemic lymphohematogenous dissemination of infection and presents diagnostic challenges due to its often asymptomatic or non-specific nature. This case report documents a rare occurrence of gastrointestinal (GI) bleeding secondary to miliary TB without pulmonary symptoms in an 81-year-old Filipino-American male living in the United States.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Background: Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2.

Macrophage-fibroblast JAK/STAT dependent crosstalk promotes liver metastatic outgrowth in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease for which better therapies are urgently needed. Fibroblasts and macrophages are heterogeneous cell populations able to enhance metastasis, but the role of a macrophage-fibroblast crosstalk in regulating their pro-metastatic functions remains poorly understood. Here we deconvolve how macrophages regulate metastasis-associated fibroblast (MAF) heterogeneity in the liver.