Faculty Bibliography

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.

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.

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

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.

OBJECTIVES/OBJECTIVE:Laser and light-based therapies are widely used in dermatology, yet patients with inflammatory dermatoses are often excluded from cosmetic procedures due to concerns for disease exacerbation. This systematic review evaluated the safety and efficacy of these modalities to inform their use. METHODS:A PRISMA-guided search of PubMed, Embase, ClinicalTrials.gov, and Scopus from inception through March 1, 2026 identified studies of adults with psoriasis, atopic dermatitis, lichen sclerosus, lichen planus pigmentosus, frontal fibrosing alopecia, or cutaneous sarcoidosis treated with laser or light-based therapies. Eligible studies reported clinical outcomes and adverse events; reviews and studies without attributable outcomes were excluded. Risk of bias was assessed qualitatively, and results were synthesized descriptively. RESULTS:Fifty-seven studies including over 900 patients were analyzed, with the strongest evidence in psoriasis and lichen sclerosus. Across conditions and device types, therapies consistently demonstrated clinical improvement and were generally well tolerated. Adverse effects were predominantly localized and transient, including erythema, edema, blistering, and pigmentary changes. Serious adverse events were rare, with only isolated cases of koebnerization or disease worsening reported. Limitations include heterogeneity and predominance of small or non-randomized studies. CONCLUSIONS:These findings suggest that, in appropriately selected patients, laser and light-based therapies are safe and do not consistently precipitate disease exacerbation.

OBJECTIVE:Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, meta-analyses were performed estimating age-specific incidence of SLE by sex, race, and ethnicity. METHODS:The CDC network of SLE registries includes five state-based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002-2018. Registries provided age-specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person-years, stratified by sex, race, and ethnicity for the meta-analyses. RESULTS:Incidence rates among women were highest for those aged 30-39 (12.7, 95%CI: 9.5-16.8), while rates among men were highest for those aged 60-69 (2.1, 95%CI: 1.3-3.4). Black women aged 20-39 had the highest SLE incidence rates (23.6, 95%CI: 20.7-26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8-15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4-15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30-39 years. CONCLUSIONS:This study provides comprehensive sex- and race-specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

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.

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.

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.