Metabolic dysfunction-associated steatohepatitis (MASH) is a major global chronic liver disease without approved pharmacotherapy. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show therapeutic promise due to their multi-faceted metabolic benefits, but their efficacy on histological endpoints in MASH requires definitive synthesis.

Sarcomas are rare, genomically heterogeneous malignancies for which prognosis has remained poor and largely unchanged over recent decades. Patient-derived xenograft (PDX) models are an important tool for cancer research, but their availability and utility remain limited in sarcoma. Here, we establish the SGH sarcoma PDX biobank, a living multi-omics resource comprising 155 xenografts from 132 patients across 11 sarcoma histotypes, with osteosarcoma as the predominant subtype. This cohort is enriched for high-risk sarcomas characterized by poor prognosis and widespread copy-number alterations. Using this biobank, we show that extrachromosomal DNA (ecDNA) frequently drives high-level oncogene amplification in osteosarcoma and that MYC ecDNA may underlie aggressive disease trajectories. Analyses of paired patient and PDX samples demonstrate that ecDNA is preferentially retained over intrachromosomal amplicons during engraftment and is stably maintained in PDX models. In addition, the PDX models largely recapitulate the histopathological and molecular features of their matched patient tumors while exhibiting distinct clonal evolutionary trajectories during engraftment. Finally, we identified potentially actionable genomic alterations within this PDX cohort, demonstrated genotype-matched targeted therapy in a KRAS G12C-mutant PDX model, and prioritized several candidate antibody-drug conjugate targets. Together, this resource provides a platform for biological discovery and preclinical precision oncology for sarcoma.

There is limited literature addressing work-life challenges caregivers face while working in pharmacy academia. Identifying these challenges and solutions can help increase their well-being and retention. Caregiving responsibilities vary from short-term support required during an acute illness or following an accident, to long-term care for an individual that can extend over months to years, such as aging parents, partners, family members, or children with chronic illnesses, conditions, or diseases. Pharmacy faculty and staff serving as caregivers face challenges such as the cognitive load associated with managing caretaking needs with workplace tasks and responsibilities. They also face challenges related to support networks that may diminish while fulfilling caretaking responsibilities resulting from decreased time, decreased attendance at work, or privacy concerns. This lack of a support network can lead to increased stress and burnout and decreased job retention. Potential solutions include fostering a supportive environment, increasing communication, conducting needs assessments, exploring flexible work arrangements and tailoring solutions, pausing promotion clocks and evaluations, facilitating support networks, and recognizing post-caregiving needs. Colleges and Schools of Pharmacy that proactively acknowledge and support caregiving as a reality, foster greater faculty and staff well-being, retention, and overall positive and nurturing cultures.

Allergic asthma is characterized by airway hypersensitivity to various allergens and chronic airway inflammation. The mechanisms underlying such a prolonged and broad-responsive airway hypersensitivity remain not fully understood. In this study, we systematically investigated the role of allergen-induced trained immunity in tissue resident alveolar macrophages (AMs) and its impact on long-lasting airway hypersensitivity. Here, we utilized flow cytometry and single-cell transcriptomics to analyze immune cell dynamics in murine asthma model, and we compare the differences between allergen-experienced AMs and naïve AMs. Specifically, we introduce and delve into the concept of allergen-induced trained immunity within these particular cells (Trained alveolar macrophages, Tr-AMs). Our findings demonstrated that Tr-AMs preferentially produce pro-eosinophilic chemokines upon subsequent allergen exposure and, therefore, induce exacerbated eosinophilic inflammation in the lung. The induction of Tr-AMs was potentially associated with their interactions with other immune cells, such as natural killer cells, dendritic cells, and Th2 cells. Both IFN-γ and IL-4 are critical for AM activation, we found that their simultaneous action on AMs induced the development of an MHCII+ CD206+ Tr-AM phenotype, which was specialized in producing pro-eosinophilic chemokines, including CCL24 (eotaxin-2) and CCL5 (RANTES). This study highlights the establishment and roles of Tr-AMs in pro-asthmatic airway hypersensitivity, providing a new understanding of the pathogenesis and recurrence of allergic asthma.

Pediatric submandibular sialolithiasis with a salivary cutaneous fistula is exceptionally rare. A 15-year-old boy presented with a 4-month history of a persistent right submandibular inflammatory lesion with a central opening and hypergranulation despite previous incision and drainage. Contrast-enhanced computed tomography demonstrated a 10.8 mm distal Wharton duct stone, a 34 mm inflammatory lesion extending toward the skin, and marked atrophy of the right submandibular gland. Because of persistent inflammation, fistula formation, and severe glandular atrophy, the fistulous tract and affected gland were excised. Histopathology demonstrated chronic ulceration with acute and chronic inflammation; an excised lymph node showed reactive hyperplasia. At 4 months, the fistula had resolved without recurrent inflammation. Although gland-preserving treatment should be considered in children, gland excision may be appropriate in advanced disease with marked glandular atrophy and persistent fistula formation.