OBJECTIVE The aim of this study was to investigate the association between contrast dye stagnation in digital subtraction angiography (DSA) and ruptured aneurysm in posterior communicating artery aneurysms (PCoAs) and explore its potential as a marker for ruptured aneurysms, especially small aneurysms (<7 mm). This study was conducted because culprit aneurysms in multiple aneurysm settings, especially smaller ones, are difficult to identify using established markers. METHODS DSA data of 144 patients treated at UCLA from 2007 to 2021 were retrospectively reviewed. The stagnation sign is defined as the persistence of contrast stagnation in the lesion relative to the parent artery until the venous phase. Univariate and multivariate analyses were performed to determine the association between rupture status and stagnation sign. RESULT Ruptured PCoAs were found in 41 patients (41.4%) and stagnation sign was observed in 34 patients (34.3%). Stagnation sign was significantly associated with rupture in PCoAs with both univariate and multivariate logistic regression analysis. This association was found both when considering aneurysms of all sizes (OR 11.488, 95% CI 4.153–36.638, p < 0.0001) and small aneurysms with diameter < 7 mm (OR 9.436, 95% CI 2.280–56.117, p = 0.0013). SIGNIFICANCE This study demonstrates that stagnation sign may be an independent marker for ruptured aneurysms. In clinical settings, it may be used as a complementary marker to established markers such as aneurysm diameter and oculomotor nerve palsy occurrence.

Placenta Accreta Spectrum (PAS) is a life-threatening obstetric disorder in which the placenta abnormally attaches to the uterine wall, causing severe hemorrhage and often necessitating emergency hysterectomy. Despite its clinical severity, the mechanisms driving PAS remain poorly understood. Prior work from our lab established that PAS may arise not from aggressive trophoblast behavior, but from a failure of the maternal decidua and uterine endothelium to maintain proper tissue boundaries, creating a permissive environment for unchecked placental attachment. Building on this, the current project applies single-cell RNA sequencing (scRNA-seq) to characterize gene expression dynamics and cellular heterogeneity across PAS, placenta previa, and early-gestation samples to identify which placental cell types exhibit the earliest molecular deviations toward a PAS phenotype. Using the 10x Genomics Chromium platform and Seurat v5, we constructed a multi-patient single-cell atlas spanning anatomically defined placental regions. Following quality control, Harmony batch correction, and UMAP visualization, we annotated major cell populations including trophoblast subtypes, fibroblasts, endothelial cells, and immune populations. We then performed iterative subclustering, removing low-quality clusters and doublets to establish high-confidence subtype annotations. Ongoing work will pursue differential expression analysis and cell-cell communication modeling via CellChat to uncover the transcriptional programs underlying PAS development.

Alterations in myocardial metabolism are a defining feature that may contribute to heart failure (HF), yet the relationship between metabolic changes and cardiac remodeling remains incompletely understood. Previously, 2-hydroxyglutarate (2HG) was observed to accumulate in both rodent and human HF models. To explore if enhancing 2HG clearance could improve cardiac remodeling, we overexpressed the dehydrogenases D2HGDH (D2) and L2HGDH (L2)via AAV9 to induce degradation of 2HG in mouse hearts subjected to transverse aortic constriction (TAC). Compared to mCherry and D2 groups, the group overexpressing L2 displayed significantly reduced cardiac hypertrophy post-TAC. To investigate the stereospecific roles of 2HG, we generated the cardiomyocyte-restricted D2 knockout (D2KO) and L2 knockout (L2KO) mice. We subject the D2KO and L2KO mice to metabolomics by Liquid Chromatography-Mass Spectrometry. Both D2KO and L2KO mice show increased 2HG levels in the heart, with a strong correlation between itaconic acid and 2-hydroxyglutaric acid. The L2KO model shows an increase in imidazole propionate and hypoxanthine, yet a decrease in malonic acid. Combining the metabolomics data with proteomics data, we performed the pathway enrichment analysis, which showed that D2KO has a stronger impact on mitochondrial stress response, while L2KO has greater regulation of epigenetics. In summary, elevated 2HG is a metabolite feature of HF and this study focused on the stereospecific role of 2HG to test its potential as a therapeutic approach for HF.

Tumor vasculature exhibits structural heterogeneity—including irregular branching, dilation, and tortuosity—which can impair perfusion and contribute to hypoxia and therapeutic resistance. West-Brown-Enquist (WBE) metabolic scaling theory predicts optimal vascular branching under distinct regimes, including area-preserving behavior in larger vessels and Murray’s Law in smaller, viscous-dominated vessels. However, deviations from these principles in tumor vascular networks remain insufficiently quantified at the full graph level in clinical imaging data. We develop a computational framework that extracts vascular networks from CT imaging and maps tumor annotations into image space to identify tumor-associated vessels, enabling within-patient comparisons between tumor and non-tumor vasculature. At each bifurcation, we compute mean radius ratio, branching asymmetry, length ratio, and volumetric scaling factor, capturing deviations from idealized branching. Preliminary analyses show systematic differences in branching geometry between tumor and non-tumor vasculature, suggesting altered scaling relative to predictions. Stratified analyses across clinical T- and N-stage--where T-stage reflects primary tumor size and local invasion, and N-stage reflects regional lymph node involvement--will evaluate associations with vascular geometry, tumor progression, and nodal spread. These metrics are collected to support future theory-informed machine learning approaches linking vascular structure to perfusion and treatment response.

Recent research indicates that dietary interventions like cyclic fasting, calorie restriction, ketogenic diets, and low-protein regimens may contribute to tumor growth suppression. Evidence suggests that these starvation-based protocols can modulate the immune system. This study aims to determine the targeted fasting’s influence, a method of metabolic alteration, on the immune response within human HCC orthotopic xenografts in nude mice, specifically to enhance thermal ablation. Given that brief starvation impacts the immune microenvironment to favor antitumor responses, this experiment explores the potential of a 5-hour nocturnal fasting period (19:00–00:00) in optimizing the liver for local interventions. Accordingly, 32 HCC bearing mice were randomized into four experimental groups: fasting with ablation, fasting without ablation, ad libitum with ablation, and ad libitum without ablation. Methodologically, single-cell suspensions of dissected spleen and liver tissues are isolated utilizing tissue-disassociation buffer and a modified Lymphoprep density gradient to obtain intrasplenic and intrahepatic lymphocytes. Peripheral blood mononuclear cells (PBMC) are isolated by Lymphoprep. Multi-color flow cytometry characterizes the PBMC, hepatic, and splenic immune landscape, quantifying effector NK cells and other resident immune populations. Comparisons evaluate the effectiveness of chronometabolic manipulation in remodeling the intrahepatic microenvironment to favor inflammation for successful ablation.