Faculty Bibliography

Variable clinical behavior is seen in oral leukoplakia, a potentially malignant illness of the mouth that may be caused by etiological factors including cigarette smoking. Therefore, it is of interest to compare the features of oral leukoplakia lesions and epithelial dysplasia in 100 individuals, all of whom were either smokers or non-smokers, using a clinico-histopathological approach. Histopathological analysis was used to ascertain the extent of epithelial dysplasia after a thorough clinical evaluation that included the location, size, shape and duration of the lesion. Smokers were more likely to have leukoplakia on the buccal mucosa, whereas non-smokers tended to have lesions on the gingiva and tongue. Regardless of smoking status, histopathological investigation showed that moderate to severe dysplasia occurred in a considerable number of patients, even though mild dysplasia predominated in both groups. Thus, we show the need of biopsy and routine monitoring of all leukoplakic lesions, even while smoking is a major etiological factor for leukoplakia formation; dysplastic alterations and possible malignant risk may occur in smokers and non-smokers alike.

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:Risk assessment in high-risk cutaneous squamous cell carcinoma (HRcSCC) uses several clinicopathologic staging system tools, yet under- and over-treatment often occur. Integration of tumor biology as an independent predictor via gene expression profile (GEP) may improve risk stratification and tailor adjuvant care. OBJECTIVE:Integrate clinicopathologic risk factors with 40-GEP testing to refine risk stratification. METHODS:Integrated 40-GEP (i40-GEP) combines optimized nested predictive models and five clinicopathologic features (immunosuppression, location, differentiation, tumor diameter, and perineural invasion) with the validated 40-GEP, and reports results: Class 1A (Low Risk), Class 1B (Moderate Risk), Class 2A (High Risk), and Class 2B (Highest Risk). RESULTS:i40-GEP significantly stratifies metastatic and local recurrence (LR) risk (p<0.001) in a validation cohort (n=572), with >95% NPV for Class 1A across National Comprehensive Cancer Network subsets. The i40-GEP identified 12.9% of patients as Class 2B, with the lowest 3-year metastasis-free survival (66.2%) and a demonstrated benefit from adjuvant radiation treatment (ART). Multivariable analysis showed i40-GEP results significantly predict metastatic and LR risk more than individual clinicopathologic factors. LIMITATIONS/CONCLUSIONS:Retrospective study. CONCLUSIONS:I40-GEP accurately stratifies metastatic and LR risk in patients with HRcSCC, leading to improved clinical decision-making. Class 2B i40-GEP identifies patients most likely to benefit from ART.

INTRODUCTION/BACKGROUND:Adolescents and young adults living with HIV (AYLHIV) experience poor outcomes across the care continuum, and most reside in sub-Saharan Africa. The African Cohort Study (AFRICOS) provides an opportunity to examine HIV outcomes in this population across Kenya, Nigeria, Tanzania, and Uganda. METHODS:We conducted a cross-sectional analysis of AYLHIV aged 15-29 years, enrolled in AFRICOS 2013-2023, and on antiretroviral therapy (ART) ≥ six months. Primary outcomes were HIV viremia and 30-day ART non-adherence. Factors included HIV acquisition route, ART duration, ART class, and site. We used multivariate robust Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). Site directors were surveyed to assess youth-friendly services. RESULTS:Among 656 participants, the median age was 20.0 years (IQR 17.5-23.3); 41.6% were male, 61.6% had perinatally-acquired HIV, and median duration since HIV diagnosis was nine years. At enrollment, 83.8% had viral suppression (<200 copies/mL) and 80.2% were ART adherent. ART regimen and clinic site were associated with viral suppression: youth on integrase vs. protease inhibitor-based regimens (adjusted relative risk (aRR) 0.38, CI 0.23-0.63, p<0.001), and in Uganda (aRR 0.42, CI 0.20-0.90, p=0.026) or Kisumu, Kenya (aRR 0.40, CI 0.22-0.76, p=0.005) had lower likelihood of non-suppression. Compared to Nigeria, participants from other sites were less likely to report non-adherence (unadjusted RR 0.31-0.44). Youth-friendly service provision varied. CONCLUSIONS:Viral suppression and ART adherence were high among AYLHIV in AFRICOS. Clinic site and ART regimen were associated with outcomes, highlighting the importance of health system factors.

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.

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.

Peri-implantitis, characterized by inflammation of peri-implant tissues and progressive bone loss, remains a major biological complication affecting long-term implant success. Material composition, surface characteristics and biocompatibility influence microbial colonization, host immune response and implant durability. Therefore, it is of interest to investigate the relationship between different dental implant materials and the incidence of peri-implantitis among patients treated at a tertiary dental center. Clinical parameters including probing depth, bleeding on probing, radiographic bone loss, plaque index and type of implant material were recorded and analyzed. Data shows that surface roughness and alloy composition influence peri-implant tissue response, with implants exhibiting rougher surfaces and greater plaque accumulation showing higher inflammation levels. Thus, we show that appropriate material selection, optimized surface engineering and meticulous maintenance are essential strategies to minimize peri-implantitis risk and ensure long-term implant stability.

OBJECTIVES/OBJECTIVE:Generative artificial intelligence (AI) holds promise for creating patient education materials (PEM). However, AI-produced content is often difficult to read. Prompts for AI to write at a lower reading level either fail to meet recommended targets (≤6th grade) or demonstrate inconsistent results. We aimed to determine whether a new AI prompt for plain language would create PEMs that are easier to read, understand, and act upon. METHODS:We analyzed PEMs from two websites (HealthyChildren.org, UpToDate) and two generative AI programs (ChatGPT, Gemini). For each AI program, we used a basic prompt and an advanced prompt to generate separate documents. From these sources, we collected six sets of PEMs about five acute pediatric conditions, evaluated them using a panel of readability indices, and used ANOVA to compare average readability scores between sources. Two pediatricians assessed understandability and actionability using the Patient Education Materials Assessment Tool (PEMAT). We calculated mean PEMAT scores, with values > 70% considered understandable/actionable. RESULTS:ChatGPT (advanced prompt) created PEM with the lowest mean grade reading level (5.8; SD 0.84) and highest PEMAT scores (91% understandable, 84% actionable). Documents from generative AI using the advanced prompt and UpToDate had mean readability scores ≤ 6th grade, with significantly better readability than AI-generated documents using the basic prompt or HealthyChildren.org. All sources except HealthyChildren.org had mean understandability > 70%; AIs using the advanced prompt and UpToDate exceeded the actionability threshold. CONCLUSIONS:A plain-language prompt for generative AI created PEMs that were readable, understandable, and actionable, with comparable results across two AI programs. PRACTICE IMPLICATIONS/CONCLUSIONS:Healthcare providers can use this new plain-language prompt for generative AI programs to quickly create free, patient-friendly PEM about acute healthcare topics. As these AI programs were not trained to provide medical guidance, medical professionals should continue to review PEM prior to sharing with patients.

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.