Faculty Bibliography

PURPOSE/UNASSIGNED:Understanding medical students' readiness to perform basic entrustable professional activities (EPAs) informs tailored support during transition to residency. METHODS/UNASSIGNED:Night-onCall (NOC) was developed to assess medical student readiness to perform core EPAs on day one of internship. NOC is a complex, integrated simulation centered around three clinical cases. Assessments include standardized patient (SP), nurse (SN), physician attending (SA), and resident (SR) perspectives using clinical competency rating instruments mapped to EPAs and scored as Well Done (WD), Partly Done (PD) or Not Done (ND). Faculty rate clinical reasoning using a rubric evaluating written post-encounter notes as poor, beginning, competent, or strong. The ability to recognize lapses in patient safety is assessed based on written case responses. Medical librarians evaluate students' ability to formulate a clinical question and search for evidence. RESULTS/UNASSIGNED:Data was collected from 'near-graduates' from seven USA medical schools from 2020 to 2023 (n = 1116). Overall, SPs rated 75.0% of overall communication skills and only 56% of patient education items as WD. SNs rated interprofessional communication 57.0% WD, and SRs rated intraprofessional communication 61.0% WD. History gathering and physical exam skills varied by case. Faculty rated clinical reasoning as beginning (45%) or competent (44%) and librarians rated 16% of literature searches as WD. CONCLUSION/UNASSIGNED:Most near-graduates demonstrated competent basic patient communication skills but performed less well on patient education, communication with other team members, clinical reasoning, and accessing the evidence base to answer clinical questions. These overall trends, consistent across schools and year, provide benchmarks for clinical training.

INTRODUCTION/BACKGROUND:Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings. METHODS:We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy. RESULTS:Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The median follow-up time was 6 years (range 1-13). The etiology of DRE included malformations of cortical development in 14 children (60.8%), including 8 (34.8%) with schizencephaly, and secondary causes in 9 children (39.1%). Seizure frequency improved for all 23 children (100%): Engel I was achieved in 15 children (65.2%), Engel II (26.1%) in six children, and Engel III (8.7%) in two children. Patients with seizure freedom had significantly fewer preoperative seizures per day than patients with seizure recurrence. Complications occurred in six children (26.1%): 2 wound infections, 2 meningitis, 1 femoral vein thrombosis, and 1 wound hematoma with return to OR. There were no perioperative mortality and no postoperative hydrocephalus or CSF diversion. QoL-related outcomes were available for 16 children: 16/16 (100%) reported that the surgery was a worthwhile and repeatable choice, 14 (87.5%) reported improved cognitive function, the median QOLCE-16 score was 62.5 ± 21. CONCLUSION/CONCLUSIONS:Hemispherotomy for DRE in selected children is a safe and effective surgery in a public children's hospital in a low-resource setting. At last follow-up, the majority of children were seizure-free, and all children had decreased seizure frequency. Families reported improved cognitive function, improved QoL and high satisfaction with their decision to pursue this surgery.

The American Society for Gastrointestinal Endoscopy (ASGE) Technology Committee provides reviews of existing, new, or emerging endoscopic technologies that have an impact on the practice of GI endoscopy. An evidence-based methodology is used, with a MEDLINE literature search to identify pertinent clinical studies on the topic and a Manufacturer and User Facility Device Experience (U.S. Food and Drug Administration Center for Devices and Radiological Health) database search to identify the reported adverse events of a given technology. Both are supplemented by accessing the "related articles" feature of PubMed and by scrutinizing pertinent references cited by the identified studies. Controlled clinical trials are emphasized, but in many cases, data from randomized controlled trials are lacking. In such cases, large case series, preliminary clinical studies, and expert opinion are used. Technical data are gathered from traditional and web-based publications, proprietary publications, and informal communications with pertinent vendors. Technology Status Evaluation Reports are drafted by 1 or 2 members of the ASGE Technology Committee, reviewed and edited by the committee as a whole, and approved by the ASGE Governing Board. When financial guidance is indicated, the most recent coding data and list prices at the time of publication are provided. For this review, the MEDLINE database was searched through March 2025 for articles related to pancreaticobiliary stricture management. Technology Status Evaluation Reports are scientific reviews provided solely for educational and informational purposes. They are not rules and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment or payment for such treatment.

Although the largest completely symmetric closed assembly that can be built from a single building block is the 60-subunit icosahedron¹, viruses can form capsid assemblies with hundreds to thousands of identical subunits through quasisymmetry-using the same subunit in symmetrically non-equivalent locations in the assembly^2-5. Quasisymmetric one-component assemblies could have considerable advantages for delivery of biologics because of the large internal volume achieved using only a single building block, but the design of these structures is challenging because of the inherent complexity of designing chemically identical subunits to both adopt different conformations and make different interactions in the distinct symmetrically non-equivalent locations. Here we conjectured that quasisymmetry could arise from spontaneous symmetry breaking in a system of strongly interacting building blocks with programmed curvatures and show that this principle, coupled with a design approach combining a parametric representation of cage architecture with RoseTTAFold diffusion generative modelling, can generate a rich array of quasisymmetric assemblies. Electron microscopy confirmed the structures of designed 3 ≤ T ≤ 36 cages with 180-2,160 subunits and diameters from 68 nm to 220 nm, and designed 1 < T < 3 non-icosahedral clathrin-like assemblies. Cryogenic electron microscopy structure determination showed how the global symmetry breaking associated with the formation of both hexons and pentons in the T = 3 architecture arises from symmetry breaking in the designed subunit interface. Our results indicate how the detailed architecture of complex systems can be controlled by designing overall system properties, and our approach provides a roadmap for designing large quasisymmetric assemblies for biologics delivery and other applications.

OBJECTIVE:Vascular calcification (VC), characterized by abnormal calcium salts buildup in blood vessels, greatly raises the risk of adverse cardiovascular events. However, the mechanisms behind VC are not fully understood. Nogo-B, a member of the reticulon family, has been implicated in various pathological processes including intimal neovascularization, obesity, and metabolic-associated fatty liver disease. Yet, its role in VC has not been explored. APPROACH AND RESULTS/RESULTS:). An ex vivo osteogenic model employing human arteries and an in vitro osteogenic model using human aortic smooth muscle cells (HASMCs) were both created under high phosphate conditions. Nogo-B expression was significantly downregulated in calcified human and mouse aortas, as well as in high phosphate-treated HASMCs. Additionally, SMC-specific knockout of Nogo-B exacerbated VC. Conversely, overexpressing Nogo-B suppressed osteogenic differentiation of HASMCs. Mechanistically, Nogo-B inhibited VC by upregulating the expression of the amino acid transporter SLC7A11. Nogo-B strongly interacts with SLC7A11 and promotes recruitment of the deubiquitinating enzyme OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1), thereby preventing K63-linked ubiquitination of SLC7A11 at K30. Furthermore, Nogo-B-mediated upregulation of SLC7A11 boosted intracellular glutathione (GSH) synthesis, which activated NRF2. NRF2 functions as a transcriptional enhancer of SLC7A11. Ultimately, Nogo-B activated antioxidant defense and alleviated oxidative stress to suppress vascular calcification. CONCLUSION/CONCLUSIONS:This study identifies Nogo-B as a novel regulator of VC. Nogo-B stabilizes the SLC7A11 protein by modulating OTUB1-mediated deubiquitination and enhances the GSH/NRF2 signaling axis, thereby promoting glutathione synthesis, reducing oxidative stress, and inhibiting the osteogenic differentiation of VSMCs and VC progression.

OBJECTIVE:Leveraging large language models (LLM), we identified an unregistered subpopulation of individuals with World Trade Center-related exposure and lung cancer who were not previously captured in registries, and assessed how this exposure impacted patients' disease course. METHODS:Associations between exposure type and smoking history, cancer stage, mutation status, disease progression, and survival were statistically analyzed. RESULTS:The highest proportion of never-smokers was observed among residents, compared to first responders and commuters (19% and 24%; p = 0.005). Residents had more than twice the risk of disease progression (HR = 2.14, p = 0.008) and an elevated risk of death (HR = 2.43, p = 0.03). Only EGFR mutations were significantly associated with exposure type (p = 0.01). CONCLUSIONS:This work highlights that LLM can capture a greater population of WTC survivors, including genetics.

BACKGROUND:Communication failures are a leading cause of sentinel events in U.S. healthcare, often due to unclear provider contact identification. The electronic health record (EHR) system offers a solution by enabling the discrete assignment of a first contact provider (FCP), who oversees and coordinates patient care. However, adoption of this practice is inconsistent across many hospital settings. This study describes the impact of continuous learning and improvement cycles to address this challenge. METHODS:Following the Plan-Do-Study-Act (PDSA) lifecycle, we completed five quality improvement cycles. Each PDSA cycle included a technological intervention accompanied by evolving operational expectations for clinical staff. We evaluated improvement after each PDSA by measuring the percent of a hospitalized patient's time with an assigned FCP. RESULTS:FCP coverage significantly improved from a baseline average of 5.1% to 59.0% after PDSA Cycle 1 (p < 0.001), 67.4% after Cycle 2 (p < 0.001), 79.7% after Cycle 3 (p < 0.001), 87.5% after Cycle 4 (p < 0.001), and 99.4% after Cycle 5 (p < 0.001). CONCLUSION/CONCLUSIONS:Having a reliable FCP at any point during a patient's hospital admission is an important safety practice. Continuous learning and improvement cycles, driven by a strong partnership between technology and operations, led to significant and sustained improvements in FCP assignments.

IMPORTANCE/OBJECTIVE:Despite its frequent use for visualization of ureteral efflux during pelvic/abdominal surgery, there are limited data on indigo carmine pharmacokinetics and duration of blue color in postdose urine. Understanding how long the blue color persists allows the clinician to make accurate assessments of the urinary system during complex surgical procedures. OBJECTIVES/OBJECTIVE:This study observed the plasma and urinary pharmacokinetics of indigo carmine in healthy volunteers and the voided urine color. STUDY DESIGN/METHODS:This study was an open-label, randomized clinical trial in 16 healthy participants who received either a 2.5-mL or a 5.0-mL intravenous injection of indigo carmine. Blood (pre, 2, 5, 7, 10, 15, 20, 30, 40 minutes and 1, 2, 3, 4, 6, 12 hours post) and urine (predose, 0-2, 2-6, 6-12 hours post) were collected. The first postdose stool was collected. RESULTS:Plasma concentration peaked within 5 minutes, and all plasma concentrations were below the limit of quantification by 2 hours postdose. The estimated plasma half-life of indigo carmine was 12 minutes. Voided urine through 2 hours postdose was visibly discolored compared with the matched predose urine. In some cases, urine discoloration persisted through 6 hours (10/16) and 12 hours (1/16). Unchanged indigo carmine eliminated in stool was observed in 4 of 16 participants (25%). CONCLUSIONS:The short half-life and rapid urinary excretion of indigo carmine favor its clinical use for intraoperative cystoscopy and are consistent with the reported median time of 6 minutes postinjection to ureteral efflux in patients undergoing surgical procedures.

Lysosomal phospholipid degradation produces two types of metabolites, either 2-lysophospholipids with saturated fatty acids in sn-1 position or 1-lysophospholipids with unsaturated fatty acids in sn-2 position. They may either be degraded further or re-used for phospholipid synthesis. We found that LPLAT7 (LPGAT1), an acyltransferase of the endoplasmic reticulum, re-acylates specifically lysosome-derived 1-lysophospholipids that carry an unsaturated chain. The enzymatic activity of LPLAT7 was specific for stearoyl-CoA and 1-lyso-2-acyl positional isomers of unsaturated lysophospholipids. In Huh7 cells, Lplat7 knockout prevented the reacylation of 1-lysophospholipids generated by the lysosomal degradation of exogenous ²H-phosphatidylcholine. Inhibition of lysosomal phospholipid degradation reduced the abundance of 1-stearoyl-2-unsaturated PC in Huh7 cells. Lplat7 knockout blunted the loss of unsaturated lysophosphatidylcholine (LPC) in response to lysosomal inhibition, suggesting that LPLAT7 consumes unsaturated LPC formed by lysosomes. In mice, Lplat7 knockout increased the concentration of unsaturated lysophospholipids, reduced the abundance of 1-stearoyl-2-unsaturated species of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine, and inhibited the regeneration of cellular membranes. It also triggered the accumulation of triglycerides, confirming earlier reports that unsaturated lysophospholipids induce lipid droplet formation. Thus, by re-acylating unsaturated 1-lysophospholipids, LPLAT7 shifts lipid metabolism from the biogenesis of lipid droplets to the biogenesis of membranes.