Publications

STUDY OBJECTIVES: We investigate a Mamba-based deep learning approach for sleep staging on signals from ANNE One (Sibel Health, Chicago, IL), a non-intrusive dual-module wireless wearable system measuring chest electrocardiography (ECG), triaxial accelerometry, and chest temperature, and finger photoplethysmography and finger temperature.

METHODS: We obtained wearable sensor recordings from 357 adults undergoing concurrent polysomnography (PSG) at a tertiary care sleep lab. Each PSG recording was manually scored and these annotations served as ground truth labels for training and evaluation of our models. PSG and wearable sensor data were automatically aligned using their ECG channels with manual confirmation by visual inspection. We trained a Mamba-based recurrent neural network architecture on these recordings. Ensembling of model variants with similar architectures was performed.

RESULTS: After ensembling, the model attains a 3-class (wake, non rapid eye movement [NREM] sleep, rapid eye movement [REM] sleep) balanced accuracy of 84.02%, F1 score of 84.23%, Cohen's κ of 72.89%, and a Matthews correlation coefficient (MCC) score of 73.00%; a 4-class (wake, light NREM [N1/N2], deep NREM [N3], REM) balanced accuracy of 75.30%, F1 score of 74.10%, Cohen's κ of 61.51%, and MCC score of 61.95%; a 5-class (wake, N1, N2, N3, REM) balanced accuracy of 65.11%, F1 score of 66.15%, Cohen's κ of 53.23%, MCC score of 54.38%.

CONCLUSIONS: Our Mamba-based deep learning model can successfully infer major sleep stages from the ANNE One, a wearable system without electroencephalography (EEG), and can be applied to data from adults attending a tertiary care sleep clinic.

Clinical trials are contingent upon enrollment of participants who are willing to volunteer their time and effort. Many persons living with HIV (PLWH) are long-term survivors aging into midlife and thus, are at risk for medical co-morbidities such as cardiovascular disease (CVD). Many PLWH have a long-standing history of research participation, including therapeutic trials, which have informed the use of highly effective antiretroviral treatments. As increasing numbers of PLWH age, research participation remains essential to generate findings to inform clinical care and treatment guidelines for aging-associated diseases specific to this population. Our study shares findings from survey data that explored reasons for clinical research participation, including participation in a CVD risk study, among midlife PLWH. Four themes emerged from content analysis of the participant responses: health and wellness, research engagement, altruism, and personal benefit. Findings may inform strategies to enhance recruitment and retention strategies for research studies among midlife PLWH.

Multidrug resistance (MDR) of the pathogen Acinetobacter baumannii is a major challenge to global healthcare due to the limited treatment options. The emergence of MDR bacteria necessitates innovative therapeutic approaches, especially given the associated economic burden and the rapid spread of infections. Conventional treatments such as antibiotics and vaccines face significant obstacles. Antimicrobial peptides (AMPs) such as LL37 have potential as an alternative treatment due to their broad-spectrum activity and ability to target specific bacterial structures such as the outer membrane protein A (OmpA). The efficacy of AMPs can be enhanced by using nanobodies (Nbs) that bind to bacterial OmpA, guiding LL37 precisely to its target. In this study, A. baumannii OmpA (AbOmpA)-specific Nbs (NbO7 and NbO13) were efficiently isolated through magnetic-activated cell sorting-based screening of a yeast surface display library, eliminating the need for specialized equipment. Nbs exhibited specific, dose-dependent binding to the target. Conjugation of Nbs with LL37 effectively inhibited the growth of MDR A. baumannii. This approach leverages the natural antimicrobial properties of AMPs and enhances their specificity and effectiveness by targeting bacterial cell surface proteins. LL37-conjugated AbOmpA-Nbs present a promising therapeutic strategy against MDR A. baumannii and other resistant pathogens.IMPORTANCEMultidrug-resistant (MDR) Acinetobacter baumannii poses a major global health threat due to its resistance to nearly all available antibiotics and its persistence in hospital settings. This challenge underscores the urgent need for new therapeutic approaches beyond conventional drugs. In this study, we developed an innovative strategy that combines the human antimicrobial peptide LL37 with nanobodies (Nbs) targeting the outer membrane protein A (OmpA), a key virulence and survival factor of A. baumannii. OmpA-specific Nbs were efficiently isolated from a fully synthetic library using a simple, low-cost selection approach without animal immunization. When conjugated with LL37, these Nbs bound specifically to OmpA and strongly inhibited MDR A. baumannii growth in vitro. Our findings introduce a simple yet powerful platform for generating targeted Nb-peptide conjugates, offering strong potential for adaptation against other antibiotic-resistant pathogens and contributing to the development of next-generation biologics to overcome antibiotic limitations.

OBJECTIVES: To explore the complexities of eliminating race correction in clinical artificial intelligence (AI), the pitfalls of naive solutions, and to propose systematic strategies for equitable model development.

BACKGROUND AND SIGNIFICANCE: Race correction in clinical AI, as in traditional medicine, introduces biases with potentially harmful consequences. Simple removal of race from models is insufficient due to the lasting influence of historically biased data.

APPROACH: We analyze 4 standardized scenarios to demonstrate how race correction manifests in clinical AI: use of race-corrected variables, explicit inclusion of race, inference via proxy variables, and use of race-specific models.

RESULTS: For each scenario, the intuitive solution to removing race correction fails to eliminate bias, often due to legacy effects embedded in the data. More thoughtful approaches are required.

DISCUSSION: Ending race correction in clinical AI requires deliberate, context-sensitive interventions, inclusion of diverse stakeholders, and strategies to make model reasoning more transparent and auditable.

OBJECTIVE: Uveitis refers to the inflammation of the uveal tract of the eye (iris, ciliary body and choroid). In the developed world, it accounts for 10–15% of all cases of blindness. Anterior uveitis accounts is the most common form of uveitis. There is an unmet need for a topically administered non-steroidal drug to treat anterior uveitis.

METHODS: We tested two topical formulations of mycophenolate (MPA), an inhibitor of inosine monophosphate dehydrogenase (IMPDH) enzyme, as a potential steroid-sparing treatment for uveitis. We studied first the binding of MPA to a three-dimensional model of human IMPDH2 generated with AlphaFold 3. Next, we formulated mycophenolate sodium as an aqueous suspension and mycophenolate mofetil as an ointment. Permeability of mycophenolate through the corneal barrier was measured using a Franz cell assay using a goat eye cornea as the membrane. Drug concentration in the different compartments of the eye involved in anterior uveitis was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Both formulations were tested for acute ocular irritation in vivo, and efficacy in a rabbit model of uveitis.

RESULTS: The AlphaFold 3 model of IMPDH2 offered a detailed map of the MPA binding site. MPA makes hydrogen bonds to main chain atoms of S276 and G326 and side chain atoms of S276, T333 and Q441 as well as hydrophobic interactions with S276, G415 and Y430. The computational analysis shed new insights on the mechanism of mycophenolate inhibition and allosteric regulation of the enzyme. Mycophenolate was stable over 6 months in both suspension and ointment. Topical application of mycophenolate sodium 1% and 2% suspension eye drop exhibited a drug flux of 81·81ug/cm2 and 140.42 ug/cm2, respectively, through the corneal barrier, greater than 11.01 ug/cm2 and 26.54 ug/cm2 achieved with mycophenolate mofetil 1% and 2% ointments, respectively. The formulations were non-irritant to eyes of New Zealand white rabbits. No systemic clinical signs of toxicity and necropsy findings were observed. Mycophenolate sodium 2% suspension-treated group showed significant reduction (p < 0.0010) in the uveitis score with reduced leukocyte counts in the anterior chamber compared to vehicle control and was not statistically different from positive control prednisone steroid (p = 0.44).

CONCLUSION: Topical mycophenolate sodium 2% suspension could emerge as an effective non-steroidal treatment for anterior uveitis and merits clinical evaluation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12348-026-00569-y.

BACKGROUND AND OBJECTIVES: Cerebral adrenoleukodystrophy (CALD) is a common manifestation of adrenoleukodystrophy (ALD) in men. Early detection of CALD lesions through MRI screening is critical to allow for therapeutic action preventing severe disability and death. While the frequency of brain MRI monitoring has been addressed by international recommendations, no consensus currently exists regarding which MRI sequences should be used in a real-world setting for screening and follow-up of CALD lesions. The aim of this study was to establish guidelines for the MRI protocol in clinical practice and to identify priority sequences for research use, thereby promoting intercenter harmonization.

METHODS: A modified Delphi procedure was used to achieve consensus on MRI protocols for ALD screening, lesion monitoring, and research applications among experts with experience in brain imaging in ALD. Questionnaires allowed experts to indicate whether they considered sequences as core, optional, or research, or to express agreement (5-point scale ranging from completely disagree to completely agree) with specific statements. Topics where no agreement was reached were discussed during online consensus meetings.

RESULTS: Thirty experts from 9 countries participated and agreed that the core screening protocol for ALD in adults and children should include at least 3D T1-weighted, spin-echo T2-weighted, 3D fluid-attenuated inversion recovery, and diffusion-weighted imaging (DWI). Postcontrast T1-weighted imaging should be performed systematically in specific clinical scenarios. Experts supported using DWI alongside the Loes score and postcontrast imaging to assess lesion progression. A research protocol was defined, prioritizing diffusion tensor imaging, MR perfusion, and quantitative volumetric analyses.

DISCUSSION: This international project harmonizes the ALD MRI protocol, thus offering a practical framework to screen and monitor lesions, which will improve clinical decision making. It also identifies MRI sequences that should be prioritized in future research. Future research on MRI in ALD should focus on topics where no consensus has yet been reached in this project.

OBJECTIVE: This study aimed to identify the scope of VCE responsibilities as well as areas of improvement for the VCE role.

DESIGN: An 11-item free response/multiple-choice survey was distributed to prospective participants. Quantitative data was analyzed using descriptive statistics (mean and standard deviation) and qualitative methods were used to analyze free response data.

SETTING: Participants completed the survey electronically.

PARTICIPANTS: Current vice chairs of education from across the United States were recruited.

RESULTS: Twenty-five of 60 identified VCE (42% response rate) completed the survey. Responders held the VCE position for 4.7±3.2 years. The majority of respondents reported that they oversaw all educational activities in their department. Twenty-two respondents (88%) indicated that their job responsibilities were appropriate, while two (8%) felt their roles were not well-defined. Four VCE (16%) desired more control over the departmental budget for education-related activities, while two (8%) felt that their role was undermined by their Department Chairperson. Oversight and coordination of departmental education activities was the most frequently reported value for the VCE role. Eighteen respondents (72%) received compensation for their VCE role, but 7 (28%) did not.

CONCLUSIONS: The results of this survey provide insight into the responsibilities and perceived value of the VCE role in surgery. This survey also identified areas of concern which merit intradepartmental examination in order to improve the effectiveness of the VCE role at a local level.

OBJECTIVE: The objective of this study was to evaluate the impact of operator training level, specifically comparing Emergency Medicine (EM) attending physicians and residents, on the analgesic efficacy of ultrasound-guided nerve blocks (UGNBs) performed in the emergency department (ED).

METHODS: This is a secondary analysis of the National Ultrasound-Guided Nerve (NURVE) Block Registry, involving 11 U.S. EDs from January 1, 2022, to December 31, 2023. Adult patients undergoing UGNBs for acute pain or procedural analgesia were included, totaling 1595 procedures after exclusion of incomplete post-procedural pain scores. The primary outcome was percent pain reduction, with >50% defined as clinically meaningful and > 75% as substantial analgesia. Subgroup analyses were performed by operator experience and block type.

RESULTS: Attendings achieved clinically meaningful pain reduction in 80.7% of cases versus 63.4% for residents, and substantial reduction in 68.1% vs 47.7% respectively (p < 0.001). This difference persisted at the highest experience level (>20 prior blocks: 82.3% vs 71.0%, p = 0.0007) and was observed across block types, reaching significance for erector spinae plane blocks (79.6% vs 63.6%, p = 0.01). Complications were rare (0.13%), with both events in resident-performed blocks.

CONCLUSION: UGNBs performed by attendings were associated with greater analgesic success compared with those by residents, yet both groups achieved high rates of clinically meaningful pain reduction with very low complication rates. These results underscore the role of experience in UGNB efficacy while supporting the safety and effectiveness of supervised resident performance in the ED.

BACKGROUND: Professionalism is a core competency in graduate medical education, yet research examining specialty-specific professionalism perceptions between trainees and faculty remains limited, particularly regarding the influence of role and institutional culture on these perceptions. This study examined how anesthesiology trainees and attendings perceive unprofessional behavior and whether these perceptions differ based on participant characteristics.

METHODS: A multi-site cross-sectional survey was conducted at five anesthesiology residency programs from February to March 2024. Participants rated degree of unprofessionalism on19 workplace vignettes depicting potentially unprofessional behaviors using a 7-point Likert scale. Vignettes were categorized into five themes: Verbal, Supervision, Quality, Time, and Engagement. Proportional odds models examined differences in ratings based on role (trainee vs. attending), adjusting for gender, race, underrepresented status, and institution.

RESULTS: Among 369 respondents (153 trainees, 216 attendings; 35.9% response rate), perceptions varied by scenario and participant characteristics. Six vignettes were more consistently rated as unprofessional (>80% unprofessional ratings), while four showed higher variability (<50% unprofessional ratings). Significant institutional differences were observed in five vignettes (Odds ratios [ORs] <0.14 or >3.7, p < 0.0001 to 0.027). Age influenced ratings of five vignettes (ORs = 0.75, 1.68, 1.63, 1.35 and 1.31 respectively, p <0.0001 to 0.027), while gender, race and underrepresented status showed no significant differences. After adjusting for demographics, trainees and attendings differed significantly in their ratings of 10 vignettes (p <0.0001 to 0.033). Attendings rated nine scenarios as more unprofessional than trainees (ORs ranging from 0.26 to 0.50), while trainees rated only one scenario as more unprofessional than attendings (OR = 2.01).

CONCLUSIONS: Perceptions of unprofessional behavior among anesthesiology professionals vary significantly by role and institution. These findings underscore the importance of context-sensitive approaches to professionalism education that acknowledge diverse perspectives and institutional cultures while maintaining core professional standards.