Faculty Bibliography

BACKGROUND:Carpal tunnel syndrome (CTS) and cubital tunnel syndrome (CuTS) are the most common upper extremity compressive neuropathies. Although often considered isolated conditions, they may occur concomitantly, and the clinical significance of dual compression remains poorly defined. This study evaluated whether concomitant CTS/CuTS represents a distinct clinical subgroup characterized by greater objective motor impairment compared with isolated entrapment syndromes. METHODS:Eighty-six adults evaluated between 2021 and 2025 were prospectively enrolled, including isolated CTS (n = 32), isolated CuTS (n = 26), and concomitant CTS/CuTS (n = 28). Standardized examinations assessed sensory findings and intrinsic motor strength using Medical Research Council grading. Multivariable logistic and ordinal regression analyses identified predictors of decreased intrinsic muscle strength. RESULTS: = .0471). CONCLUSIONS:Concomitant CTS/CuTS is associated with greater baseline intrinsic motor impairment despite similar sensory findings, suggesting that dual-site compression reflects greater motor involvement rather than the incidental coexistence of 2 isolated entrapment syndromes.

BACKGROUND/UNASSIGNED:Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) accounts for 6-8% of all MIs and is more common in women than men. After an episode of MINOCA, patients may experience a substantial symptom burden and reduced health-related quality of life (HRQoL). The aim of this post-hoc analysis was to describe clinical characteristics, residual symptoms and HRQoL, including sex differences in patients with a working diagnosis of MINOCA and preserved left ventricular ejection fraction (LV-EF). METHODS/UNASSIGNED:reatment in MINOCA patients (MINOCA-BAT) was an international clinical trial. Patients with a working diagnosis of MINOCA and LV-EF ≥ 40% were randomized to beta-blocker versus no beta-blocker and ACEI/ARB versus no ACEI/ARB. The trial was prematurely terminated after 192 enrolled participants (median age 59; 63% women). Clinical events, symptoms and HRQoL (EQ-5D-3L) were assessed at 7 weeks and 12 months after the index event. RESULTS/UNASSIGNED:The cohort represented a low-risk population. At one year, one patient had died, one had a re-infarction, 14% reported chest pain and 9% dyspnea. Median EQ-5D index scores did not change significantly between 7 weeks and 12 months (0.86 vs. 0.78) and were comparable to age-matched general population norms. Women reported slightly lower HRQoL than men. CONCLUSIONS/UNASSIGNED:Patients with a working diagnosis of MINOCA and preserved LV-EF constitute a low-risk population and demonstrate a favorable prognosis with symptom resolution within one year. Their HRQoL appears broadly similar to that observed in the general population, with only modest differences between the sexes.

INTRODUCTION/BACKGROUND:Gastroschisis is a congenital birth defect with a rising incidence. The herniation of intestines into the amniotic cavity leads to prenatal bowel injury, which contributes to significant postnatal morbidity and mortality. Current management focuses on postnatal interventions, though bowel injury begins in utero. Emerging interest in prenatal therapies aims to mitigate this injury and improve outcomes. However, none of these interventions has been widely adopted in clinical practice, highlighting the need for further research and validation. This protocol aims to outline the procedures to conduct a systematic scoping review of prenatal interventions to improve outcomes for gastroschisis, identifying gaps in the literature to guide future research and inform clinical practice. METHODS:This systematic scoping review will follow the PRISMA-ScR guidelines. We will include studies on prenatal interventions for gastroschisis in both human and animal models. Key databases including MEDLINE, Embase, Scopus, and others will be searched. Gray literature and clinical trial registries will also be reviewed. Studies will be screened, selected, and data extracted in duplicate using predefined criteria. Descriptive analysis will summarize findings, grouped by intervention, with outcomes presented in a narrative synthesis. DISCUSSION/CONCLUSIONS:This scoping review will be the first to systematically examine prenatal interventions for gastroschisis, addressing a growing clinical need due to its rising incidence and associated morbidity. Despite promising experimental approaches, no prenatal therapies are currently standard practice, underscoring the need for further research. This review will identify existing evidence and highlight knowledge gaps. Findings could inform the development of targeted prenatal treatments, improve clinical outcomes, and support the integration of effective interventions into routine care, ultimately reducing morbidity and mortality associated with gastroschisis. SYSTEMATIC REVIEW REGISTRATION/BACKGROUND:The review protocol has been registered within the Open Science Framework database ( https://doi.org/10.17605/OSF.IO/39DSQ ).

Neurons accumulate somatic mutations with age, but how mutation processes vary among neuronal types remains unclear. Characterizing this variability may elucidate the role of genome integrity in brain function and disease and reveal determinants of mutation rates and patterns. Using high-fidelity duplex DNA sequencing, we profiled somatic mutations across the lifespan in human cerebellar Purkinje and granule neurons, which differ markedly in size and physiology. Surprisingly, they exhibited similar substitution rates, including rates of SBS5, the body's predominant mutational signature, whose mechanism is unknown. However, their substitution patterns and insertion/deletion rates and patterns differed, with transcription associated with these differences. In surviving granule neurons from five cerebellar ataxias, we detected only a small disease effect on mutation profiles. Our work indicates that neuronal types can differ in aging-related mutagenesis and that key features distinguishing Purkinje and granule neurons are unlikely, in these neurons, to be major determinants of SBS5 activity.

BACKGROUND AIMS/UNASSIGNED:AHB-137 is a novel ASO targeting a conserved region near the 3' end of all HBV mRNA. This first-in-human phase 1 study evaluated the safety, tolerability, pharmacokinetics (PK), and antiviral efficacy in healthy subjects and chronic hepatitis B (CHB) patients. METHODS:Forty healthy subjects were randomized into four placebo-controlled single ascending dose (100-450 mg, 6:2 AHB-137:placebo) cohorts and one multiple-dose (MD; 300 mg, 6:2) cohort receiving four weekly subcutaneous doses with a Day 4 loading dose (5 doses). Twenty-four virally suppressed, HBeAg-negative CHB patients on stable nucleos(t)ide analogue therapy were enrolled: four in an open-label 300-mg MD cohort (5 doses) and 20 in two placebo-controlled 300-mg MD cohorts (4:1, stratified by baseline HBsAg), receiving an additional loading dose on Day 11 (6 doses). RESULTS:Treatment-related adverse events occurred in 73% of healthy subjects and 71% of CHB patients and were primarily mild or moderate injection-site reactions and headaches. No treatment-related serious adverse events, discontinuations, or deaths were observed. PK profiles showed rapid absorption (Tmax 2.96-5.50 h), dose-proportional exposure, no significant accumulation, long terminal half-life (150-220 h), and minimal renal excretion. In CHB patients, AHB-137 treatment led to a rapid HBsAg decline (mean 0.7-1.0 log10 IU/mL). HBsAg loss (<0.05 IU/mL) for at least one timepoint was observed in three patients, including two with baseline HBsAg <1 IU/mL and one with baseline HBsAg <1.5 IU/mL. CONCLUSIONS:In this Phase 1 study, AHB-137 demonstrated an acceptable safety profile, predictable PK, and rapid and prolonged HBsAg reductions, supporting further evaluation of dosing and treatment duration in CHB.

Freezing during Pavlovian fear conditioning is the most commonly used indicator of learned fear in rodents. Although freezing and its neural underpinnings have been widely studied, the field has largely ignored other potential indicators of learned fear. Darting, an escape-like conditioned fear response, occurs more frequently in females and is reliably predicted by a distinct behavioral phenotype: heightened shock response and decreased freezing compared to rodents that do not engage in darting. The experiments in this study sought to expand the field's understanding of conditioned fear by investigating the neural correlates of conditioned darting, focusing on the infralimbic cortex (IL) and longitudinal columns of the periaqueductal gray (PAG) due to their known roles in modulating defensive responses, including conditioned freezing. We find that fear conditioning elicits greater neural activity (measured by quantification of cFos expression) in the IL of females compared to males, but that IL activation corresponds to freezing only in Darters. We next used chemogenetic tools to excite or inhibit either the IL alone or IL-PAG projections prior to fear conditioning. IL manipulations in either direction reduced freezing in both males and females, while IL inhibition increased darting and shock response in females only, and the effects of circuit-specific manipulations were minimal. Together, our findings suggest a novel, role for the IL in driving defensive responses during fear conditioning that is not dependent on IL-PAG connectivity.

BACKGROUND:As a 6-month waiting period is required to receive exception points to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation, prompt addition to the waitlist is critical in access to LT. METHODS:Using Epic Cosmos data on patients with HCC referred for LT 1/2018-10/2024, we used modified Poisson regression to calculate rates of waitlisting. Center-level and individual (socioeconomic, geographic, and insurance) factors were measured among those who progressed. RESULTS:Among 11,422 HCC patients referred for LT at 70 centers, with median age 63 [IQR: 58, 68], 71.5% initiated evaluation and, of those who began evaluation, 57.6% were waitlisted for LT. Of those referred, patients who were older (age 70+ vs. 51-60; RR 0.77, 95% CI: 0.65-0.90, p < 0.001), on Medicaid (0.83, 95% CI: 0.71-0.97, p = 0.02), never-married (0.82, 95% CI: 0.73-0.91, p < 0.001), or low SES (Q4: 0.87, 95% CI: 0.77-0.97, p = 0.002) had lower rates of waitlisting. Among waitlisted patients, median time from referral was 3.3 months [IQR: 2.0, 5.3]. Despite adjustment for patient level covariates, there was high center-level variation in rate of waitlisting within 12 months; 13% of centers listed patients at a rate ≥ 20% below the national median. CONCLUSION/CONCLUSIONS:Only a fraction of referred patients with HCC are waitlisted for LT. High variation in access to waitlisting based on non-clinical factors suggests barriers to waitlisting that must be addressed. Centers should focus on interventions to reduce barriers to waitlisting in patients with HCC.

BACKGROUND:Transcranial photobiomodulation (t-PBM) with near-infrared light stimulates mitochondria and may have antidepressant effects. We evaluated dose-dependent effects of t-PBM on the hemodynamic blood-oxygenation-level-dependent (BOLD) power in major depressive disorder (MDD). METHODS:. t-PBM (808 nm) was delivered to the prefrontal cortex, bilaterally. fMRI was recorded at 3T before, during, and after t-PBM. We used mixed-effects linear regression to evaluate changes in BOLD power during stimulation, compared to sham. The analysis was repeated for the middle frontal gyrus (MFG), the prefrontal areas irradiated by t-PBM, and the entire brain cortex. RESULTS:We found similar results in the MFG, the prefrontal cortex directly irradiated, and the entire brain cortex: medium dose t-PBM was associated with a statistically significant increase in BOLD power, whereas low dose t-PBM was associated with a significant decrease in BOLD. There were no significant changes in BOLD power with the high (pulsed) t-PBM dose or with sham. Single administrations of any t-PBM dose did not result in significant changes in depression severity (versus sham). All 3 t-PBM doses were well tolerated. CONCLUSION/CONCLUSIONS:The acute effect of t-PBM on the hemodynamic BOLD power is robust, dose-dependent, bidirectional, and extends beyond the areas directly illuminated. These findings may provide a reference for future dose selection and clinical efficacy studies. CLINICALTRIALS/RESULTS:GOV: NCT04366258.

Children and youth seeking asylum encounter a range of unique experiences and obstacles in their efforts to secure protected immigration status. This study used a consensual qualitative research approach to analyze data that centered lived experience voice gathered from first-person interviews with 12 adults, six men, and six women aged 18-29 years, who entered the United States as minor asylum seekers. Results indicated that they experienced premigratory exposure to violence or harm, psychological distress, financial instability, and obstacles to health care. Participants also reported fear, adversity, and time spent in immigration detention centers as they sought asylum in the United States. Further, they disclosed current mental health concerns, as well as barriers to education, employment, and legal representation. Participants identified a series of effective internal and external supports they leveraged to adaptively respond to systemic challenges, described their aspirations for the future, and provided recommendations for guiding clinicians in service provision. The results of the study can inform psychologists and allied professionals about the impact of exposure to harm that asylum-seeking minors face, this population's resilience, and possible strengths-based strategies for responding to the needs of young people experiencing forced displacement and areas of potential advocacy. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PURPOSE/UNASSIGNED:The high mortality associated with metastatic colorectal cancer (mCRC) illuminates an unmet need for innovative therapeutic modalities. Radiopharmaceutical therapy (RPT) offers a potent, molecular-scale approach for managing and treating cancers with distant micrometastases. However, its clinical use in mCRC remains an unrealized opportunity. We have therefore identified the transmembrane glycoprotein mucin 13 (MUC13) as a promising antigen for developing a targeted RPT and have undertaken preclinical evaluation of its potential by utilizing a monoclonal antibody tool representative of a future class of translatable therapeutics. EXPERIMENTAL DESIGN/UNASSIGNED:The immunoreactivity and transcriptome of patients with colorectal cancer (n = 72 primary, 100 liver metastases) were characterized using annotated clinical datasets. Preclinical assessment of MUC13 as an RPT target for mCRC was then performed in mice using a monoclonal MUC13-targeted antibody C14 labeled with either zirconium-89 for positron emission tomography (PET) measurement of mCRC-associated MUC13 density or terbium-161 for targeted RPT. RESULTS/UNASSIGNED:Strong MUC13 immunoreactivity was observed in ∼70% of mCRC and was inversely correlated with overall survival (P < 0.01). MUC13 levels were visualized by PET and agreed with immunohistochemically determined antigen presence. Furthermore, MUC13-targeted RPT exhibited in vivo proof-of-concept efficacy and enhanced survival in preclinical colorectal cancer models. Resulting imaging, therapeutic, and pathologic analyses elucidated relationships between target density, therapeutic outcome, and a potential genetic signature. CONCLUSIONS/UNASSIGNED:MUC13-targeted RPT response was not only associated with radiopharmaceutical accumulation but also seemed to be balanced by DNA damage repair gene expression, suggesting a potential sensitivity signature that could complement a future clinical theranostic approach in MUC13-positive mCRC.