Faculty Bibliography

PURPOSE/OBJECTIVE:This study evaluated the extent of prostate displacement during SBRT on an MRI Linac using comprehensive motion management (CMM) and identified variables associated with intrafraction motion (IFM). METHODS:212 patients with clinically localized prostate cancer were treated with 5-fraction SBRT on a 1.5 T MR-Linac where IFM was continuously tracked and gated by CMM. Pre-beam positional shifts were identified from MRI registration prior to beam delivery. Intrafraction positional variability during beam delivery was evaluated, and multivariable analysis identified variables associated with IFM. RESULTS:In 614 fractions (62.7%), a > 1.5 mm pre-beam positional shift led to an adapt-to-position (ATP) plan correction. Mean anterior-posterior and superior-inferior pre-beam shifts were 2.2 mm and 2.1 mm, respectively. For 962 evaluable fractions, the median beam-on-time was 13.7 min with a mean duty cycle of 95.8%. Sustained > 3 mm displacement was observed in 520 fractions (54.1%) with a median cumulative duration of 24 s; >5 mm displacement was observed in 209 fractions (21.7%) with a median duration of 12.4 s. The ATS + ATP workflow was associated with reduced odds of sustained > 3 mm motion (p = 0.035), while older age was associated with increased odds (p = 0.011). CONCLUSIONS:Significant prostate shifts can occur immediately prior to and during radiation beam delivery, frequently exceeding applied margins and potentially leading to tumor underdosage. Continuous motion tracking and gating during prostate SBRT is an important tool in reducing IFM and enhance treatment delivery accuracy.

The microbiome has been described as the last human "organ" and is currently the topic of great research interest worldwide. The application of culture-independent methods, like 16S ribosomal next-generation sequencing, has offered researchers the opportunity to identify bacterial populations that were impossible to detect previously using conventional culture methods. Further standardization of these new approaches to characterizing the microbiome is desirable. The present review discusses the mounting evidence suggesting that alterations in the microbiome and microbial metabolites, such as short-chain fatty acids in the gut, mouth, and ocular surface, may play a key role in the pathogenesis of ocular pathologies such as ocular surface disease, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy. Clarifying the probable role of the microbiome in ocular diseases would not only offer valuable insights into pathogenesis but could also enable the development of novel therapeutic approaches. As yet, microbial-based therapeutic applications in ophthalmology are limited. Nevertheless, recently emerging strategies utilizing probiotics and prebiotics, or even fecal transplantation to regulate microbiome composition, offer promising research avenues for developing future innovative therapies for ocular diseases. Further studies employing standardized methodological protocols are needed to ensure the reproducibility of results and to eventually unlock the precise links between the microbiome and the eye.

OBJECTIVE:This study was undertaken to evaluate whether seizure freedom in pregnancy predicts seizure freedom in the postpartum period in women with epilepsy (WWE). Prior studies have shown that seizure freedom prior to conception strongly predicts seizure freedom during pregnancy. The postpartum period is considered especially vulnerable to recurrent seizures given rapid hormonal changes, shifting antiseizure medication pharmacokinetics, and disrupted sleep. There is a lack of sufficient data on whether seizure freedom during pregnancy predicts postpartum outcomes. METHODS:Pregnant WWE (aged 14-45 years) were enrolled at <20 weeks gestation in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study. Participants completed electronic daily seizure and medication diaries with study visits each trimester, and at 6-12 weeks and 6 and 9 months postpartum. Participants also reported retrospective seizure frequency for the 9 months preconception. We used logistic regression to assess whether seizure freedom during pregnancy predicted seizure freedom postpartum, with additional analyses by seizure types. In participants with seizures during pregnancy, we evaluated median percent change in seizure frequency. RESULTS:This analysis included 331 pregnant WWE. Overall, 60.7% were seizure-free during pregnancy and 61.0% postpartum. Seizure freedom during pregnancy strongly predicted seizure freedom postpartum (odds ratio [OR] = 6.78, 95% confidence interval [CI] = 4.15-11.1, p < .0001), with a predictive value of 78% (95% CI = 72%-84%). Retrospectively reported preconception seizure freedom was also independently associated with postpartum seizure freedom (OR = 5.84, 95% CI = 3.57-9.58, p < .0001). Long-term seizure freedom during pregnancy and preconception was associated with 85% postpartum seizure freedom, whereas long-term presence of seizures was associated with only 36% postpartum seizure freedom. There were no significant differences by seizure type. Among participants with seizures during pregnancy, median postpartum seizure frequency declined by 77% (interquartile range = seizure-free to 31% reduced). SIGNIFICANCE/CONCLUSIONS:Our data demonstrated that seizure freedom during pregnancy was a robust predictor of seizure freedom during the postpartum period. These data can be used to counsel patients about seizure risk in the postpartum period.

The 2025 World Allergy Organization (WAO) Guidelines for the Classification, Diagnosis, and Treatment of Hereditary Angioedema (HAE) with Consideration of Worldwide Disparities provide a comprehensive, evidence-informed, and globally applicable framework for the care of this rare and potentially life-threatening disorder. HAE is a genetic disease characterized by recurrent episodes of subcutaneous and submucosal swelling, most commonly mediated by bradykinin, and is associated with substantial morbidity, impaired quality of life, and a lifelong risk of fatal laryngeal edema. The Guidelines were developed by an international panel of 40 experts from 22 countries, with representation from all world regions, reflecting the commitment of WAO to geographic diversity, inclusiveness, and global relevance. The development process for these guidelines followed a structured and transparent methodology that integrated systematic literature review, appraisal of real-world evidence, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework adapted for rare diseases, complemented by a formal Delphi consensus process. This approach was specifically designed to address the limitations of conventional evidence hierarchies in rare disorders, while ensuring clinical applicability across heterogeneous healthcare systems and resource settings. A central element of the guidelines is an updated classification of HAE based on underlying pathophysiology and disease endotypes. The traditional distinction between HAE types 1 and 2 is unified under the term HAE with C1 inhibitor deficiency (HAE-C1-INH), reflecting shared biological mechanisms and management principles. The guidelines also recognize an expanding spectrum of HAE with normal C1 inhibitor (HAE-nC1-INH), including forms associated with pathogenic variants in F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6, CPN1, and DAB2IP, as well as cases with currently unidentified genetic causes. The diagnostic strategy emphasizes early clinical recognition based on characteristic features, including recurrent angioedema without urticaria, abdominal or laryngeal involvement, early symptom onset, and family history. A simplified diagnostic algorithm is proposed, prioritizing the C1 inhibitor functional assay as the preferred initial test when performed in a reliable specialized laboratory. Alternative diagnostic pathways are outlined for settings with limited access to specialized testing, including pragmatic combinations of biochemical assays and selective use of genetic testing, particularly relevant for HAE-nC1-INH and family screening. Management recommendations address on-demand treatment of acute attacks, short-term prophylaxis, and individualized long-term prophylaxis. Universal access to on-demand therapy is emphasized for all patients with confirmed HAE, including those who are asymptomatic, given the unpredictable nature of attacks and lifelong risk. Long-term prophylaxis is addressed within a treat-to-target framework aimed at achieving complete disease control and sustained improvement in health-related quality of life, with regular reassessment and shared decision-making. Empowering patients and caregivers through structured education, access to appropriate medications, and integration with specialized referral centers is associated with earlier treatment, reduced healthcare utilization, and improved equity of care and reduced avoidable morbidity and mortality worldwide. The 2025 WAO Guidelines for Hereditary Angioedema establish an evidence-informed, patient-centered, and forward-looking framework for the classification, diagnosis, and management of HAE. By integrating advances in pathophysiology, diagnostics, and therapeutics with global expert consensus and real-world considerations, the guidelines aim to support consistent, equitable, and high-quality care for patients with HAE across regions and healthcare systems.

PURPOSE/OBJECTIVE:To develop a novel single-shot radial echo planar imaging (ss-rEPI) technique for rapid, distortion-free brain imaging in functional MRI experiments. METHODS:* mapping and QSM. Visual BOLD fMRI experiments were conducted and evaluated against Cartesian EPI measurements. RESULTS:* measurements. CONCLUSION/CONCLUSIONS:modeling is critical for ss-rEPI performance. Advanced reconstruction techniques and self-calibration methods could further enhance its speed, performance, and applicability across diverse MRI techniques.

PURPOSE/UNASSIGNED:Optical character recognition (OCR), a process that converts printed or handwritten text into machine-readable form, is widely used in assistive technology for people with blindness and low vision. Yet most evaluations rely on static datasets that do not reflect the challenges of mobile use. This study evaluated how OCR performance changes under static and walking conditions relevant to real-world navigation. METHODS/UNASSIGNED:Static tests varied distance from 1-7 metres and viewing angle from 0°-75°. Dynamic tests examined the impact of motion by varying walking speed from 0.8 m/s to 1.8 m/s and compared head-mounted, shoulder-mounted, and handheld positions. We evaluated a smartphone and smart glasses, including the phone's main and ultra-wide cameras, across four OCR engines: Google Vision, PaddleOCR 3.0, EasyOCR, and Tesseract. Dynamic tests used PaddleOCR 3.0. Accuracy was computed at the character level using the Levenshtein ratio against manually defined ground truth. RESULTS/UNASSIGNED:Recognition accuracy declined with increased walking speed and wider viewing angles. Google Vision achieved the highest overall accuracy, with PaddleOCR close behind as the strongest open-source alternative. Across devices, the phone's main camera achieved the highest accuracy, and a shoulder-mounted placement yielded the highest average among body positions; however, differences among shoulder, head, and hand were not statistically significant. CONCLUSION/UNASSIGNED:OCR performance depends on the recognition engine, camera hardware, field of view, device placement, and user motion. OCR systems for navigation should be evaluated under dynamic, mobility-relevant conditions rather than static images alone and designed to balance coverage, recognition accuracy, and practical deployment.

Quasisymmetric icosahedral viral capsids achieve larger sizes than possible with strictly symmetric icosahedra by tessellating pentagons and hexagons using a single subunit that adopts different conformations in symmetrically non-equivalent locations^1,2. Recapitulating such quasisymmetric architectures through computational design is a considerable challenge in nanomaterials engineering. Here we introduce a computational design strategy based on geometric frustration to generate two-component, quasisymmetric protein cages with customizable properties. We designed complementary trimeric and dimeric protein components that co-assemble into positively curved local hexagonal assemblies. Hexagonal lattices cannot tile spherical surfaces; instead, the components form closed sphere-like cage assemblies through incorporation of curvature-inducing pentagonal defects, as evidenced by electron microscopy. By designing dimers that encode different local curvatures, we programmed cage dimensions ranging from 40 to over 200 nm in diameter and with molecular weights from 2 MDa to over 50 MDa, comparable with natural virus capsids. We further functionalized these large cages with additional protein domains to enable ribonucleoprotein cargo loading and cellular uptake. Fluorescently labelled cage assemblies expressed in mammalian cells function as rheological probes and cargo recruiters, enabling a systematic study of size-dependent cytoplasmic diffusion and protein localization. Thus, the quasi-symmetry that has long fascinated structural biologists can now be achieved by computational protein design, with immediate applications to biologics delivery and molecular cell biology.

PURPOSE/OBJECTIVE:Nonsteroidal anti-inflammatory drugs (NSAIDs) increase fluid retention and the risk of heart failure (HF). The NSAIDs are commonly used in total hip arthroplasty (THA) as part of a modern multimodal pain protocol, but the risk of selective cyclooxygenase-2 (COX-2)-preferential NSAIDs in THA for Type 2 diabetes mellitus (T2DM) patients, who have an increased risk for cardiac disease, is not well understood. This study aimed to compare rates of new-onset HF following THA in T2DM patients receiving perioperative meloxicam or celecoxib. METHODS:A retrospective review was conducted of 18,142 patients who underwent primary elective THA. Data included demographics, perioperative aspirin, meloxicam and celecoxib use, T2DM diagnosis, and development of new-onset postoperative HF. Cohorts were separated based on the presence of a T2DM diagnosis and use of meloxicam or celecoxib. Propensity-matching controlled for age, American Society of Anesthesiologists score, and perioperative aspirin use. Rates of HF within T2DM patients who utilized peri-THA meloxicam versus celecoxib were compared. RESULTS:Of patients who utilized meloxicam or celecoxib, T2DM patients experience new-onset postoperative HF at higher rates than non-diabetics (6.1 [T2DM] versus 2.8% [non-T2DM], P < 0.001). Within the T2DM patients, the patients who utilized celecoxib developed HF at higher rates than T2DM patients who utilized meloxicam (4.0 [meloxicam] versus 7.1% [celecoxib], P = 0.013). CONCLUSIONS:Patients who have T2DM experience a higher incidence of new-onset postoperative HF compared to non-diabetics following perioperative selective NSAID use for THA. Additionally, T2DM patients developed HF at a greater rate when treated with perioperative celecoxib versus meloxicam. Given that both agents were associated with HF events in this high-risk population, caution is warranted when prescribing selective NSAIDs in T2DM patients undergoing THA. Risk-benefit considerations and individualized perioperative pain management strategies should be carefully considered.

Treatment selection in breast cancer is guided by risk assessment using molecular subtypes and clinicopathological characteristics. However, current approaches lack the precision required for optimal clinical decision-making. To address this, we use data from 8161 patients to develop and evaluate an AI test integrating digital pathology with clinical data. The AI test provides a robust method for predicting disease-free interval (C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p < 0.001]). In a direct comparison, the AI test displays numerically higher discrimination (C-index: 0.67 [0.61-0.74]) than the standard-of-care 21-gene assay (C-index: 0.61 [0.49-0.73]). Across molecular subtypes, the AI test demonstrates robust prognostic performance, including in triple negative breast cancer (C-index: 0.71 [0.62-0.81], HR: 3.81 [2.35-6.17, p=0.02]), where no guideline-recommended assays currently exist. These findings highlight the potential of AI-based pathology tests as a promising tool for improved risk stratification across all major subtypes, with implications for clinical decision-making.

BACKGROUND/UNASSIGNED:Heart failure is an increasingly common comorbidity among people with HIV infection, complicating care and heightening the vulnerability of this population to social adversity (SA). However, the impact of different SA domains on outcomes in this population remains poorly understood. METHODS/UNASSIGNED:We analyzed data on people with HIV infection and heart failure from the NYC 4H (NYC Health + Hospitals HIV-Heart Failure) cohort. Baseline multidimensional SA was assessed by licensed clinical social workers using standardized evaluations and grouped into 5 domains: economic hardship, health care access barriers, neighborhood or built environment instability, social support challenge, and psychobehavioral instability. We used multivariable adjusted Cox models to estimate hazard ratios (HRs) of all-cause, cardiovascular, and infection-related mortality and logistic regression to estimate odds ratios of 6-month rehospitalization risk. RESULTS/UNASSIGNED:Among 1044 participants (62.9% male; mean age, 61.6 years), 601 (58%) reported at least 1 SA: economic hardship (n=130), limited health care access (n=155), unstable housing (n=129), social support challenge (n=179), or psychobehavioral instability (n=438). Over a mean follow-up of 3.8 years, exposure to any SA was associated with higher all-cause mortality (HR, 4.32 [95% CI, 3.03-6.14]), cardiovascular mortality (HR, 4.05 [95% CI, 2.17-6.83]), and infection-related mortality (HR, 2.37 [95% CI, 1.23-4.56]). Social support challenge (HR, 2.19 [95% CI, 1.35-3.55]) and psychobehavioral instability (HR, 1.96 [95% CI, 1.24-3.11]) were associated with higher cardiovascular mortality. Economic hardship (HR, 2.40 [95% CI, 1.22-4.70]) and social support challenge (HR, 3.09 [95% CI, 1.75-5.48]) were associated with higher infection-related mortality. Compared with patients without SA, those with environmental instability, psychobehavioral instability, or social support challenges had a 73% (adjusted odds ratio, 1.73 [95% CI, 1.15-2.06]), 75% (adjusted odds ratio, 1.75 [95% CI, 1.31-2.35]), and 44% (adjusted odds ratio, 1.44 [95% CI, 1.00-2.06]) higher risk of rehospitalization within 6 months, respectively. CONCLUSIONS/UNASSIGNED:SA was significantly associated with mortality and rehospitalization among people with HIV infection and heart failure, with domain-specific pathways influencing specific outcomes. Multidimensional assessment of SA may offer a framework for domain-specific risk stratification in people with HIV infection and heart failure.