Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by abnormal thickening of the heart muscle and affects approximately 1 in 500 individuals. Variants in MYBPC3 are among the most common genetic causes. Prior studies suggest that biological sex influences disease expression, with earlier onset in males and delayed presentation in females. This study investigates sex based differences in patients with HCM carrying pathogenic or likely pathogenic MYBPC3 variants. Data was obtained from the UCLA Cardiovascular Genetics Database. A total of 64 affected individuals were analyzed. Variables included sex, age at genetic testing, variant type, and clinical history. Variants were categorized by molecular consequence, and age distributions and clinical features were compared by sex. Truncating variants, including frameshift and nonsense mutations, accounted for the largest proportion of variants observed. The average age at testing was 45 years for males and 53 years for females, indicating an approximately 8 year difference. Arrhythmias were observed in nearly half of patients, and many required advanced cardiac interventions. Structural features such as septal hypertrophy and outflow tract obstruction were common. These findings support the role of MYBPC3 loss of function in disease and sex related differences in disease timing or clinical recognition. Understanding these differences may improve risk assessment and inform more personalized approaches to diagnosis and management of HCM.

ONECUT2 (OC2) is a transcription factor that functions as a master regulator in the setting of metastatic castration-resistant prostate cancer and is associated with neuroendocrine differentiation and a treatment-resistant phenotype. This study aims to determine whether forced expression of OC2 in primary prostate epithelial cells is sufficient to induce a malignant phenotype in regenerated tissue grafts. Prostate tissue was procured from surgical specimens in accordance with an institutional review board–approved protocol. Benign tissue was macrodissected and dissociated into single cells for tissue regeneration assays. Transduction with lentivirus containing OC2 cDNA versus color marker controls was performed and expression was confirmed via western blot. Organoid cultures were maintained for 10 days in vitro, followed by retrieval and subcutaneous injection into immunocompromised mice. Xenografts were retrieved after 5 weeks and analyzed for tubular formation and marker expression. Immunostaining confirmed expression of OC2 in xenografts. There was no clear evidence of malignant transformation, however, more abundant tubule formation and possible increased expression of phosphorylated Rb, and phosphorylated AKT was observed. Further studies are needed to evaluate the role of OC2 in early prostate tumorigenesis.

Chronic Kidney Disease (CKD) is a long-term condition characterized by progressive kidney damage and a gradual decline in the kidneys’ ability to filter waste from the blood. Although CKD affects 37 million people worldwide, about 87% of affected adults are unaware that they have this condition, which can lead to delays in diagnosis and treatment. Various health systems have implemented a range of strategies to identify patients with undiagnosed CKD, including the use of electronic health record-based ICD coding and laboratory values. Over the past decade, more advanced tools, such as natural language processing, machine learning, and artificial intelligence, have also been incorporated. However, current approaches vary considerably in their accuracy, how CKD is defined over time (chronicity), and consistency across patient populations. In this scoping review, we aim to characterize the spectrum of data-driven CKD screening tools that are currently being developed. This includes analyzing their performance, strengths, limitations, and gaps in early CKD detection. We also discuss how the use of library resources, including collaboration with medical librarian Robert Johnson, has supported our work, as well as the broader value of medical library resources in undergraduate research. This review will directly inform the work of QI Scholar Dr. Shaya Nikfar in developing an EHR-based AI tool for early CKD detection. Ultimately, these efforts aim to improve early identification of CKD and help prevent disease progression.

Molecular subphenotyping is effective for risk stratification in critically ill patients but has largely been derived from a limited set of pro- and anti-inflammatory cytokines and chemokines. Here, we analyzed expression of 250 inflammation related biomarkers from pediatric patients (n=84) in the CAF-PINT study of heart and lung failure using a NULISA panel to more comprehensively discriminate latent class subphenotypes (n=42 hyperinflamed, n=42 hypoinflamed). We compared a significant outlier marker CCL20 with known subphenotype markers (IL-6, IL-10) using receiver operating characteristic (ROC) curves built from single marker linear regression models and DeLong tests. We validated these results using rapid immunoassays on critically ill, pediatric patients (n=116, n=59 hyperinflamed, n=57 hypoinflamed) from the PALI study. In CAF-PINT, CCL20 was most enriched among hyperinflammatory patients in differential analysis (FDR=8.2e-15) and a penalized regression model (Odds Ratio=1.70) and had better discrimination (AUC=0.952) than IL-6 (AUC=0.893, DeLong p=0.04) and IL-10 (AUC=0.887, DeLong p=0.09). CCL20 was validated as a better model (AUC=0.908) than IL-6 (AUC=0.723, DeLong p=0.001) and IL-10 (AUC=0.735, DeLong p=0.002) in PALI. CCL20, chemoattractant for dendritic cells and B and T lymphocytes, discriminates molecular subphenotypes better than IL-6 and IL-10 in two cohorts of critically ill children suggesting prognostic and mechanistic significance of the novel marker in systemic inflammation and treatment heterogeneity.

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide. In the US, it is the second leading cause of cancer-related mortality among women and the leading cause of cancer death among Hispanic and African American women. Approximately 70% of BCs express estrogen receptors alpha (ER𝛂), a key driver of tumor growth and progression. Although endocrine therapies significantly reduce recurrence and improve survival, resistance remains a major clinical challenge. A primary mechanism of resistance involves somatic mutations in the ESR1 gene, particularly Y537S and D538G, which promote ligand-independent ER signaling and reduce responsiveness to therapies such as aromatase inhibitors and tamoxifen. We have developed novel oral selective estrogen receptor degraders (SERDs) designed to degrade both WT and mutant ER𝛂. We assessed their anti-tumor activity through proliferation assays and protein/mRNA analysis. Treatment with these SERDs significantly reduced cell proliferation in a dose-dependent manner. (P<0.01) and decreased ER𝛂 protein and ESR1 levels across both WT and mutant models. ER𝛂 knockdown abrogated drug activity, confirming an ER𝛂 dependent mechanism. Notably, SERD JD128 demonstrated strong in-vivo efficacy in MCF7-Y537S xenograft models and enhanced T-cell infiltration within the tumor microenvironment. These findings highlight the therapeutic potential of next generation SERDs in overcoming endocrine resistance.