The trafficking dynamics of uromodulin (UMOD), the most abundant protein in human urine, play a critical role in the pathogenesis of kidney disease. Monoallelic mutations in the UMOD gene cause autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), an incurable genetic disorder that leads to kidney failure. The disease is caused by the intracellular entrapment of mutant UMOD in kidney epithelial cells, but the precise mechanisms mediating disrupted UMOD trafficking remain elusive.
View Article and Find Full Text PDFBackground: Somali American individuals have lower cervical cancer screening rates than the U.S. general population.
View Article and Find Full Text PDFClin Genitourin Cancer
December 2024
Patients with relapsed/refractory germ cell tumors (GCT) have limited treatment options and poor survival outcomes. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient regimen for 35 patients with relapsed/refractory GCT between 2017 and 2022. Twenty-four patients received nonpalliative intent ATP, with a median of 2 lines of prior therapy, 23 (96%) having received at least 1 cisplatin-based regimen and 1 (4%) with a prior stem cell transplant.
View Article and Find Full Text PDFCochrane Database Syst Rev
October 2024
Background: Age-related macular degeneration (AMD) is a retinal disorder characterized by central retinal (macular) damage. Approximately 10% to 20% of non-exudative AMD cases progress to the exudative form, which may result in rapid deterioration of central vision. Individuals with exudative AMD (eAMD) need prompt consultation with retinal specialists to minimize the risk and extent of vision loss.
View Article and Find Full Text PDFEffective treatment of pediatric acute leukemia is dependent on accurate genomic classification, typically derived from a combination of multiple time-consuming and costly techniques such as flow cytometry, fluorescence hybridization (FISH), karyotype analysis, targeted PCR, and microarrays (Arber et al., 2016; Iacobucci & Mullighan, 2017; Narayanan & Weinberg, 2020). We investigated the feasibility of a comprehensive single-assay classification approach using long-read sequencing, with real-time genome target enrichment, to classify chromosomal abnormalities and structural variants characteristic of acute leukemia.
View Article and Find Full Text PDFThe clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy.
View Article and Find Full Text PDFOptogenetic techniques provide genetically targeted, spatially and temporally precise approaches to correlate cellular activities and physiological outcomes. In the nervous system, G protein-coupled receptors (GPCRs) have essential neuromodulatory functions through binding extracellular ligands to induce intracellular signaling cascades. In this work, we develop and validate an optogenetic tool that disrupts Gα signaling through membrane recruitment of a minimal regulator of G protein signaling (RGS) domain.
View Article and Find Full Text PDFThe presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation.
View Article and Find Full Text PDFBackground: We assessed human papillomavirus (HPV) vaccine effectiveness (VE) against anal HPV among men who have sex with men (MSM) in 2018-2023.
Methods: Residual anal specimens from MSM without HIV ages 18-45 years were tested for HPV. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between vaccination (≥1 dose) and quadrivalent vaccine (4vHPV)-type prevalence adjusting for city, race/ethnicity, and non-vaccine-type HPV prevalence, stratified by age group (18-26, 27-45).
Purpose: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications.
View Article and Find Full Text PDFThe receptor tyrosine kinase FGFR3 is frequently mutated in bladder cancer and is a validated therapeutic target. Although pan-FGFR tyrosine kinase inhibitors (TKI) have shown clinical efficacy, toxicity and acquired resistance limit the benefit of these agents. While antibody-based therapeutics can offer superior selectivity than TKIs, conventional ligand-blocking antibodies are usually ineffective inhibitors of constitutively active receptor tyrosine kinases.
View Article and Find Full Text PDFAlthough the selection interview is a standard admission practice for graduate medical education (GME) programs in the United States, there is a dearth of recent reviews on optimizing the trainee interview process, which has low reliability, high cost, and major risk of bias. To investigate the evidence base for different selection interview practices in GME. We searched 4 literature databases from inception through September 2022.
View Article and Find Full Text PDFViral vectors and lipofection-based gene therapies have dispersion-dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close-field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of "naked" plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near-field conductivity ("conductivity-clamping"-CC), increasing the efficiency of plasma membrane molecular translocation.
View Article and Find Full Text PDFJ Racial Ethn Health Disparities
June 2024
Introduction: Cervical cancer screening (CCS) among East African immigrants (EAI) in the USA is under explored. This study aimed to investigate adherence to CCS and its correlates among EAI.
Methods: We identified 1664 EAI women (25-65 years) with ≥ 1 primary care clinic visit(s) between 2017 and 2018, using University of Washington (UW) Medicine electronic health record data.
Purpose: We examined the performance of artificial intelligence chatbots on the PREview Practice Exam, an online situational judgment test for professionalism and ethics.
Methods: We used validated methodologies to calculate scores and descriptive statistics, tests, and Fisher's exact tests to compare scores by model and competency.
Results: GPT-3.
Purpose: To describe gender diversity and research productivity among medical education boards.
Methods: We examined gender, training status, and research productivity of board members of Journal Citation Reports-listed medical education journals and affiliated professional societies. We determined gender using gendered pronouns and-if unavailable-software.
People living with HIV (PLWH) are at highest risk of anal cancer and will benefit from optimized screening for early disease detection. We compared host DNA methylation markers in high-grade squamous intraepithelial lesions (HSIL) versus samples negative for intraepithelial lesions (NILM) or low-grade intraepithelial lesions (LSIL) in PLWH. We recruited PLWH identifying as male aged ≥18 years undergoing high-resolution anoscopy (HRA) in Seattle, Washington, 2015-2016.
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