Faculty Bibliography

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.

Objective Pediatric traumas are high-stakes yet relatively low-frequency events, limiting resident exposure and learning. We developed a low-cost, accessible virtual reality (VR) experience using 360-degree video to supplement pediatric trauma education and explored resident perceptions of its usability, relevance, and educational value. Methods We performed a mixed-methods descriptive study at an academic pediatric emergency department. Residents used VR headsets to experience a simulated pediatric blunt abdominal trauma resuscitation which was created with 360-degree video equipment. Interactive access points embedded within the video allowed for review of pediatric-specific considerations and Advanced Trauma Life Support concepts. Pediatric and Emergency Medicine residents provided feedback via anonymous survey with five-point Likert items assessing comfort, ease of use, usefulness, applicability, and interest in curricular integrations. Free-text responses and semi-structured interviews underwent qualitative analysis to extract themes. Results Forty-two residents completed the surveys. Most reported the experience was comfortable (n=40, 95.2%) and easy to use (n=42, 100%). Participants rated VR as useful compared with traditional resources (n=42, 100%) and applicable to clinical care (n=41, 97.6%). The majority supported incorporation of VR into the curriculum (n=38, 90.5%) and 69.0% (n=29) would use headsets for independent learning. Qualitative themes highlighted realism, improved appreciation of team dynamics, and the ability to pause for reflection. Learners requested greater interactivity and embedded knowledge checks. Conclusion A 360-degree video VR experience was a feasible and positively perceived supplementary educational modality for pediatric trauma training. Learners valued its immersive and flexible format. Our findings reflect learner perceptions rather than objective educational outcomes. Future studies should evaluate effects on knowledge acquisition, behavioral performance, long-term retention, and patient-centered clinical outcomes.

BACKGROUND:Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation has been associated with clinically significant graft and organ toxicity at the standard dose (50 mg/kg/day on days +3, +4). We conducted a two-center retrospective cohort analysis to assess outcomes after a uniform dose reduction to 40 mg/kg/day on days +3, +4 (PTCy 40-40). OBJECTIVES/OBJECTIVE:The primary objectives were to evaluate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and relapse. Secondary objectives included assessment of organ toxicity, engraftment, non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS). STUDY DESIGN/METHODS:Patients receiving PTCy 40-40 from 11/2020 to 3/2025 at two academic centers were included. Exclusion criteria were history of aplasia after chimeric antigen receptor T-cell therapy as indication for HCT or history of prior HCT complicated by GF. Only the initial HCT was included for patients who had > 1 allogeneic HCT with PTCy. Patients received cyclophosphamide at a dose of 40 mg/kg/day on days +3, +4 after peripheral blood allogeneic HCT. RESULTS:115 patients received PTCy 40-40. Most patients received reduced-intensity conditioning (80%) from matched unrelated donors (63%). Median follow-up was 9.0 months (range, 4.9-28.8). Median time to neutrophil and platelet engraftment was 14 (range, 11-27) and 19 days (range, 15-55), respectively, with one case of primary graft failure and few cardiac, renal, or hepatic events of interest. Cumulative incidence of grades 2-4 aGVHD by day +180 was 13% (95% CI 8-20), with only one grade 3-4 case. Cumulative incidence of moderate-severe cGVHD by 12 months was 13% (95% CI 7-22). At 12 months, relapse was 18% (95% CI 10-27), NRM 5% (95% CI 2-10), PFS 77% (95% CI 66-85), and OS 84% (95% CI 74-91). CONCLUSION/CONCLUSIONS:PTCy 40-40 resulted in low rates of GVHD, toxicity events of interest, and NRM, with excellent 12-month PFS and OS. Our findings from this two-center retrospective cohort analysis suggest that PTCy 40-40 is safe and effective for GVHD prophylaxis after MAC or RIC HCT from any donor type.

In the contemporary era of minimally invasive surgery, injectable biomaterial scaffolds have demonstrated significant potential in bone tissue engineering (BTE). Completely injectable hydrogel substratum with microscale bone graft particulates delivered through a needle-shaped orifice shifts a new paradigm for surgical interventions in clinical settings. Despite growing interest in biopolymer-based BTE systems, clinically applicable delivery platforms and a mechanistic understanding of cell-material interactions remain limited. This study developed a dual-syringe auto-mix system capable of generating an in situ cross-linking hydrogel-mineral construct composed of gelatin-hydroxyphenyl propionic acid, hyaluronic acid-tyramine, horseradish peroxidase, hydrogen peroxide, and calcium phosphate particles of varying sizes. Material distribution, rheological and mechanical properties, and swelling were characterized. Goat bone marrow-derived mesenchymal stem cells served as the basis for examining how the composite affected cell viability, morphology, proliferation, contractility, osteogenic differentiation, mineralization, and chemotactic behavior. To determine whether these biological findings were supported mechanically, an ex vivo cone-beam computed tomography model was used to evaluate volumetric stability and resistance to deformation at the graft-host interface. Cross-linking established a stable internal microarchitecture while remaining compatible with cell viability and nutrient-dependent survival. Formation of the gelatin-hyaluronan (GH) network significantly increased the storage modulus relative to gelatin (G) alone, whereas subsequent calcium phosphate incorporation (GH-CP) preserved this mechanical competence while attenuating the volumetric expansion of GH. These physical characteristics were accompanied by more organized cell morphology, enhanced osteogenic differentiation, and mineral deposition throughout a larger portion of the matrix. Heterogeneous interpenetrating gap striation (HIGS) appeared in regions of cellular aggregation and matrix deposition, and a new conceptualization of the osteogenic phenomenon, termed cling osteogenesis, has been proposed. These outcomes support an intricate relationship between early mechanical stabilization, mechanotransduction, and osteogenesis in injectable hydrogel-mineral systems.

OBJECTIVES/OBJECTIVE:To evaluate the effect of a proprietary motion artifact correction algorithm on CBCT spatial resolution using an in vitro phantom model. STUDY DESIGN/METHODS:Fifty CBCT scans were acquired with a ProMax 3D unit using a point spread function phantom mounted on a motorized turntable. Ten protocols were tested, including no motion and induced motion up to 9 degrees, with and without activation of the correction algorithm. Spatial resolution was assessed using full width at half maximum (FWHM), surface plots, fast Fourier transforms, pairwise comparisons, and Bland-Altman analysis. RESULTS:Motion increased FWHM values and distorted the point spread function, with greater irregularity as motion magnitude increased. The correction algorithm produced partial improvement in selected motion protocols, particularly at lower motion magnitudes, but the effect was inconsistent across all motion conditions and measurement directions. In the no-motion protocol, activation of the algorithm introduced slight unsharpness and increased heterogeneity in the high-frequency domain. CONCLUSION/CONCLUSIONS:Patient motion degrades CBCT spatial resolution. The proprietary correction algorithm may provide partial improvement under selected conditions, particularly at lower motion magnitudes, but it does not replace the need for careful patient stabilization during image acquisition and should be used cautiously when motion is unlikely.

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.

INTRODUCTION/BACKGROUND:Down syndrome (DS) is caused by a complete or partial trisomy of chromosome 21, resulting in variable intellectual disabilities and a high risk for early-onset Alzheimer's disease (DS-AD). Dysregulation of the mammalian target of rapamycin (mTOR) and insulin (INS) signaling pathways has been reported in DS. We hypothesized that upstream alterations in these two pathways contribute to hippocampal dysfunction in DS-AD. METHODS:We used spatial transcriptomics and localized proteomic techniques to examine mTOR/INS signaling pathways in subregions of the hippocampus in post mortem tissue from individuals with DS-AD and age-matched neurotypical controls. RESULTS:mTOR pathways were significantly altered in specific hippocampal subfields in DS-AD, and INS pathways were significantly altered in dentate granule neurons. DISCUSSION/CONCLUSIONS:These preliminary spatial transcriptomics and localized proteomics findings demonstrate an interplay between select hippocampal mTOR/INS pathways and cellular populations, suggesting potential novel drug targets and early biomarkers for DS.

PURPOSE/OBJECTIVE:To evaluate interobserver agreement between 2 experienced corneal specialists in classifying eyes as normal (N), keratoconus-suspect (KCN-S), or keratoconic (KCN) using Scheimpflug tomography, and to assess the discriminatory performance of tomographic asymmetry indices. METHODS:A total of 206 eyes from 103 participants (15-25 years) underwent Scheimpflug corneal tomography. Two experienced corneal specialists independently classified each eye based solely on four-map displays, without access to quantitative tomographic indices (BAD-D, ISV, IHD, IVA). Interobserver agreement was assessed using Cohen κ statistic. Discriminatory performance was evaluated by receiver operating characteristic (ROC) analysis and area under the curve (AUC), with observer classifications retrospectively compared with BAD-D, ISV, IHD, and IVA. RESULTS:Interobserver agreement was moderate (κ = 0.40, P <0.01). Agreement between observer classifications and BAD-D was substantial for observer 1 (κ = 0.70, P <0.01) and fair for observer 2 (κ = 0.35, P <0.01). Among the evaluated indices, BAD-D demonstrated the highest discriminatory performance (AUC = 0.94 and 0.85 using observer 1 and observer 2 classifications, respectively). In expert consensus cases, BAD-D achieved an AUC of 0.97. A BAD-D threshold of 1.10 yielded 90% sensitivity and 90% specificity. CONCLUSIONS:Moderate interobserver agreement highlights the diagnostic uncertainty of identifying early keratoconus-suspect eyes and may contribute to variability in reported keratoconus prevalence. Among the evaluated tomographic indices, BAD-D showed the strongest agreement with expert classifications and the greatest discriminatory ability, supporting its use as an adjunctive tool for early screening in young individuals.