Faculty Bibliography

Critical-sized bone defects remain a significant clinical challenge, and dipyridamole (DIPY)-coated 3D-tricalcium phosphate (β-TCP) scaffolds have shown promising osteogenic efficacy in preclinical models. However, the literature on the systematic physicochemical characterization of this scaffold system, including optimization of DIPY loading parameters, release kinetics, and surface properties, is lacking. This study addresses these gaps by characterizing DIPY-loaded 3D-printed β-TCP scaffolds across solid and porous architectures, three coating concentrations (10, 100, and 1000 µM), and three coating volumes (250, 500, and 1000 µL). Under static PBS conditions, drug release over 21 days was quantifiable only at 1000 µM, and release-kinetics modeling (zero-order, Higuchi, and Korsmeyer-Peppas) was therefore restricted to this highest concentration. At 1000 µM, both scaffold types showed biphasic release profiles, with standard empirical models reasonably approximating the overall kinetics, while not fully capturing the biphasic behavior over the entire duration. Porous scaffolds showed significant volume-dependent release (p = 0.002, η

IMPORTANCE/UNASSIGNED:The 2026 American College of Cardiology/American Heart Association/Multisociety Dyslipidemia Guideline newly recommends selective use of coronary artery calcium (CAC) scoring based on a 10-year risk of 3% to less than 10% estimated with the Predicting Risk of Cardiovascular Disease EVENTS (PREVENT) atherosclerotic cardiovascular disease (ASCVD) equations. However, the utility of CAC scoring alongside the PREVENT equations for ASCVD risk estimation is not known. OBJECTIVE/UNASSIGNED:To determine the change in predictive utility when adding CAC scores to the PREVENT-ASCVD equations. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Longitudinal observational cohort study conducted at 6 sites in the United States and enrolling adult participants aged 45 to 79 years without ASCVD at baseline in the Multi-Ethnic Study of Atherosclerosis. EXPOSURES/UNASSIGNED:Ten-year ASCVD risk with the PREVENT-ASCVD equations before and after adding CAC scores. MAIN OUTCOMES/UNASSIGNED:Performance metrics for estimation of risk of fatal and nonfatal ASCVD, assessed using the Harrell C statistic, calibration, and net reclassification improvement (NRI) for newly defined ASCVD risk categories: low (<3%); borderline (3% to <5%); intermediate (5% to <10%); and high (≥10%). RESULTS/UNASSIGNED:A total of 6098 participants were included. At baseline, participant mean age was 61.4 (SD, 9.6) years, 52% were female, mean estimated 10-year ASCVD risk was 6.4% (SD, 4.8%) with the PREVENT-ASCVD base equations, and 49% had a CAC score greater than 0. During 10 years of follow-up, 366 (6%) experienced an ASCVD event. The Harrell C statistic for the PREVENT-ASCVD base equations was 0.73 (95% CI, 0.70-0.75). After adding CAC to the PREVENT-ASCVD base equations, the change in Harrell C statistic was 0.02 (95% CI, 0.01-0.03), and the categorical NRI was 0.095 (95% CI, 0.053-0.137). The calibration slope for the PREVENT-ASCVD base equations was 1.09 (95% CI, 0.93-1.25), and for the PREVENT-ASCVD base plus CAC equations was 0.92 (95% CI, 0.81-1.03). Among those at borderline risk, incident ASCVD occurred in 1.9% of those with CAC score of 0, 3.9% with CAC greater than 0 and less than 100, 7.4% with CAC 100 or greater and less than 300, and 14.3% with CAC 300 or greater. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Among US adults aged 45 to 79 years, addition of CAC score to the PREVENT-ASCVD equations across all risk groups overall only modestly improved and, in some groups, did not change model discrimination and reclassification. Reclassification results support selective use of CAC in those with borderline to intermediate risk estimated by the PREVENT-ASCVD equations.

Obesity is a known risk factor for diseases of the pancreas, including diabetes, pancreatic cancer and pancreatitis, but mechanisms remain unclear. Here we show by spatial, transcriptomic and functional profiling of human pancreatic immune cells from obese and non-obese organ donors that obesity profoundly impacts pancreatic immune homeostasis. Obesity is associated with higher density of tissue resident memory T-cells (TRM) in the exocrine pancreas which are characterized by high cytotoxic functions, and aggregate around macrophages. Single cell sequencing of pancreatic macrophages distinguishes two main subsets - FOLR2 + CD11c- foetal-derived macrophages with pro-repair and immunoregulatory function and FOLR2- CD11c+ lipid-associated macrophages with greater T-cell interactions and pro-inflammatory function. In obesity, the pancreatic macrophage landscape shifts to lower predominance of FOLR2 + CD11c- macrophages and expansion of FOLR2- CD11c+ macrophages, which interact selectively with the TRM and inflamed exocrine epithelium. Together, these results identify macrophage-T cell circuits and immune epithelial interactions that might lead to chronic pancreatic inflammation in obesity and might contribute to obesity-related pancreatic diseases.

BACKGROUND/UNASSIGNED:Asbestosis is a progressive interstitial lung disease caused by inhalation of asbestos fibres. Although asbestos use was banned in the Netherlands in 1993, new cases continue to be diagnosed. Since 2014, a national compensation system has enabled systematic assessment of asbestosis incidence and outcomes. This population-based study examined national trends in asbestosis incidence from 2014-2024 and evaluated survival and prognostic factors. METHODS/UNASSIGNED:We conducted a retrospective national cohort study including all adults (≥18 years) diagnosed with asbestosis between 2014-2024 according to Dutch Health Council criteria used for compensation. Diagnoses were established by consensus of three independent pulmonologists based on radiological evidence of diffuse pulmonary fibrosis, ≥5 fibre-years of exposure, and lung function impairment according to American Medical Association (AMA) criteria. Demographic data, lung function, work history and overall survival were collected. Incidence per 100 000 persons per year was calculated. RESULTS/UNASSIGNED:Of 1004 applicants, 476 (47.4%) met criteria for asbestosis. Median age at diagnosis was 77 years, and 98.9% were male. Annual incidence ranged from 0.115 to 0.347 per 100 000, with no significant temporal trend (Spearman rho 0.41; p=0.214). AMA class 4 was most common (44.5%) and strongly associated with mortality (hazard ratio 2.52, 95% CI 1.81-3.49). Older age also predicted poorer survival. Median survival ranged from 25.5 months (AMA 4) to 83.4 months (AMA 0-2). Time-dependent modelling showed increasing hazard over time for AMA class 4. CONCLUSIONS/UNASSIGNED:More than two decades after the asbestos ban, asbestosis incidence remains stable. AMA class and age are key predictors of survival.

BACKGROUND:Competency-based medical education aims to ensure that physicians develop the skills and knowledge necessary for independent clinical practice through graduated autonomy. Existing competencies in obstetrics and gynecology (OBGYN) residency often fail to capture higher-order transformations in clinical reasoning, professional identity, and emotional maturity. A more nuanced, applicable, and valid articulation of these developmental transitions is needed to better support resident growth and assessment. OBJECTIVE:To identify OBGYN-specific threshold concepts that represent transformative developmental milestones in training, as perceived by leaders in residency education. DESIGN/METHODS:This qualitative study used a constructivist, inductive thematic analysis approach. Interviews explored moments of significant developmental transition, areas of learner struggle, and examples of transformative learning during residency. Audio-recorded interviews were transcribed, deidentified, and independently coded by 2 reviewers using line-by-line analysis. Codes were iteratively organized into themes through consensus, with thematic saturation reached after 9 interviews. Credibility was supported through expert review, member checking, and iterative refinement. SETTING/METHODS:Semistructured, one-on-one interviews were conducted with 11 attending physicians holding formal educational leadership roles within OBGYN residency programs at 4 academic institutions in the New York City metropolitan area. RESULTS:Six threshold concepts were identified that characterize developmental transitions into OBGYN practice: recognition of clinical severity, anticipation and adjustment of surgical technique, ownership of patient care in dynamic settings, empathic collaboration and team management, confidence in independent decision-making, and advanced emotional regulation. These concepts reflected observable shifts in judgment, responsibility, teamwork, and emotional processing that educators consistently associated with readiness for independent practice. In a subsequent survey of n = 78 medical education leaders at a national conference, 90% of respondents endorsed incorporating these threshold concepts into resident assessment frameworks. CONCLUSIONS:This study identifies 6 threshold concepts that capture essential, yet under-recognized, developmental milestones in OBGYN residency training. These concepts offer a complementary framework to existing assessment systems by emphasizing transformative growth in clinical judgment, professional identity, and emotional resilience. Integrating threshold concepts into curriculum design and evaluation may enhance the ability of educators to support learners, identify developmental challenges, and promote readiness for independent practice.

BACKGROUND:Patients with breast cancer and limited English proficiency (LEP) experience barriers to care that may result in greater disease burden. We aim to evaluate breast cancer presentation and pathologic characteristics of patients with LEP compared with patients with English proficiency (EP). PATIENTS AND METHODS/METHODS:We performed an institutional review board (IRB)-approved, retrospective review of prospectively collected patient-reported data among a multilingual population evaluated within a New York City safety-net health system between 2018 and 2025. Comparative analysis and logistic regression were used. RESULTS:) compared with EP (31.2% versus 18.5%; p = 0.012) and was significantly associated with completion axillary lymph node dissection compared with EP (12.8% versus 3.6%; p = 0.0041). Patients with LEP had significantly longer time-to-therapy intervals from biopsy to first therapy compared with EP (52 versus 49 days; p = 0.041). On multivariate analysis, both LEP and delays to first therapy were significantly associated with axillary nodal metastasis. CONCLUSIONS:Patients with breast cancer and LEP were significantly more likely to have axillary nodal metastasis compared with patients with EP. Increased axillary nodal metastasis in this population may, in part, be due to lack of screening and delays to breast cancer treatment.

Saliva has emerged as a compelling liquid biopsy for the non-invasive diagnosis and monitoring of both oral and systemic diseases. Secreted by major and minor salivary glands and enriched by gingival crevicular fluid, epithelial turnover, immune mediators, microbial products, and plasma-derived constituents, saliva reflects a biologically integrated interface between local oral environments and systemic physiology. This dual origin enables detection of disease-associated signals across multiple molecular layers, including extracellular RNA, cell-free DNA, genomic and epigenetic material, proteins, metabolites, microbial signatures, and hormones. Advances in high-throughput sequencing, mass spectrometry, and ultrasensitive immunoassays have revealed that salivary analytes can capture dynamic pathological processes ranging from periodontal inflammation and dental caries to oral and head and neck cancers, as well as systemic conditions such as non-oral cancers and autoimmune, cardiometabolic, infectious, endocrine, and neurodegenerative diseases. In particular, extracellular vesicle-encapsulated RNA, cfDNA fragmentomics, and methylation patterns have expanded the diagnostic reach of saliva beyond conventional protein-based biomarkers, while integrated multi-omics approaches increasingly improve diagnostic performance. Despite this progress, clinical translation remains constrained by biological complexity, including variable glandular contributions, oral microbiome interactions, and pre-analytical variability in collection and processing. Emerging point-of-care technologies, microfluidic platforms, and artificial intelligence-driven multi-omic integration are beginning to address these limitations, enabling higher analytical sensitivity and improved disease stratification. Regulatory pathways, including in vitro diagnostic frameworks and laboratory-developed test structures, are progressively accommodating salivary assays, as demonstrated during the COVID-19 pandemic. However, widespread clinical adoption will require rigorous standardization, large-scale validation, and demonstration of clinical utility. Together, saliva-based liquid biopsy represents a rapidly evolving diagnostic paradigm with the potential to shift disease detection towards earlier, minimally invasive, and data-rich precision medicine approaches across dentistry and systemic healthcare.

BACKGROUND:Glioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults and demonstrates substantial transcriptomic heterogeneity associated with patient survival. High-dimensional genomic datasets present statistical challenges because the number of measured molecular features often exceeds the number of available patient samples. Penalized regression methods such as Least Absolute Shrinkage and Selection Operator (LASSO) regression enable simultaneous feature selection and survival modeling in these settings. METHODS:Transcriptomic expression and survival data from The Cancer Genome Atlas (TCGA) GBM cohort were analyzed using LASSO-regularized Cox proportional hazards regression implemented through the glmnet package in R. After preprocessing and sample matching, 518 tumor samples and 12,042 transcriptomic features were retained for analysis. Patients were randomly divided into training (n=414) and test (n=104) cohorts. Ten-fold cross-validation using Harrell's concordance index (C-index) was performed to identify optimal regularization parameters. Kaplan-Meier survival analysis was used to evaluate risk stratification performance, and receiver operating characteristic (ROC) analysis was performed for selected candidate genes. RESULTS:Cross-validation identified a maximum C-index of 0.583 at the optimal lambda.min regularization parameter. The final LASSO-Cox model retained 74 genes with nonzero coefficients. Two identified genes, CLEC5A and RANBP17, overlapped with previously reported GBM prognostic genes from an independent study. Kaplan-Meier analysis demonstrated significant survival separation between predicted high-risk and low-risk groups in both the training cohort (log-rank p < 0.0001) and the held-out test cohort (log-rank p < 0.05). ROC analysis of selected candidate genes demonstrated moderate discriminatory performance, with area under the curve values ranging from 0.604 to 0.701. CONCLUSIONS:LASSO-regularized Cox regression identified sparse transcriptomic features associated with survival in TCGA GBM patients. Survival stratification performance persisted in a held-out test dataset, supporting the reproducibility of the derived transcriptomic risk model. These findings demonstrate the applicability of penalized survival modeling approaches to high-dimensional cancer transcriptomic datasets and support further investigation of transcriptomic biomarkers in GBM prognosis.

PURPOSE/OBJECTIVE:Although the recombinant zoster vaccine (RZV) has demonstrated high efficacy in prevention of herpes zoster, there are concerns about its safety in patients with herpes zoster ophthalmicus with no clear evidence regarding the benefit of combining RZV with suppressive antiviral therapy. This secondary analysis of the Zoster Eye Disease Study outcomes by RZV vaccination status aims to assess potential benefit and risk of vaccination. METHODS:The Zoster Eye Disease Study was conducted at 95 sites from November 2017 to June 2024. RZV administration, both before and after enrollment, was recorded on electronic data entry forms. Five hundred twenty-seven participants were randomized to receive 12 months of double-masked daily valacyclovir 1000 mg or placebo and then followed for 18 months. In this analysis, we evaluated the impact on study outcomes within 3 months of RZV vaccination and at 12 and 18 months. RESULTS:Of the 527 participants, 122 (23.1%) received RZV, 37 (7.0%) pre-enrollment (15 on valacyclovir and 22 on placebo), and 85 (16.1%) postenrollment (41 on valacyclovir and 44 on placebo). Among participants who received RZV after enrollment, end points occurred within 3 months after the first shot in 5/85 (5.9%), including 0 (0/41, 0%) on valacyclovir and 5 (5/44, 11.4%) on placebo (P = 0.057), after the second shot in 2/50 (4.0%), including 2 (2/26, 7.7%) on valacyclovir and 0 on placebo (P = 0.491). Over the first 12 months, the time-dependent Cox regression analysis estimated a hazard ratio of 0.726 for end points comparing those with RZV vaccination with those without [95% confidence interval (CI) 0.39-1.34, P = 0.303]. Over 18 months, the HR comparing valacyclovir without RZV with placebo was 0.75 (95% CI 0.56-0.99, P = 0.046), and comparing valacyclovir with RZV with placebo was 0.51 (95% CI 0.27-0.98, P = 0.042). CONCLUSIONS:Participants who received suppressive valacyclovir treatment compared with placebo had a significantly lower likelihood of new or worsening ocular adverse events at 18 months; the effect of valacyclovir was similar regardless of administration of RZV.