Development and Assessment of a Deceased Donor Organ Recovery Workshop for Surgical Fellows.

OBJECTIVE: To assess the impact of a deceased donor organ procurement training workshop on the transplant fellow's confidence and proficiency in organ recovery. This pilot workshop was designed to address the current gap in the transplant fellow's training in North America. DESIGN: Participants' confidence and competence in deceased donor organ recovery were assessed pre- and postworkshop (immediate, 1- and 6-month) using a survey questionnaire. Participants' responses were compared using T-test and Wilcoxon tests before and after the workshop. PARTICIPANTS: The hepatopancreatobiliary-transplant fellows from the University of Toronto participated in the workshop. RESULTS: Seven fellows participated, with 57% reported very limited exposure to deceased donor operations in the past year. Fellows' confidence improved significantly immediately postworkshop (69% vs. 85%, p = <0.05), persisting at 1 month (86%, p = <0.05) and 6 months (91%, p = <0.05). Competence scores also demonstrated improvement postworkshop (88% vs. 78%, p = 0.3), remaining constant at 1 month (88%, p = 0.18), and further increasing at 6 months (92%, p = 0.19). CONCLUSION: This pilot study represents a notable step as the first workshop tailored for transplant fellows in Canada, demonstrating sustained improvement in both confidence and competence for deceased donor organ procurements. The study is limited by results from a single center and small sample size, impacting the generalizability of findings. However, the workshop addresses variability in transplant fellows' exposure and confidence levels, emphasizing the importance of structured training in organ procurement to enhance skills and readiness for real-time procedures.

An exploratory study of functional brain activity associated with gross motor function improvement in children with unilateral cerebral palsy.

PURPOSE: Identify relations of gross motor function and primary motor cortex (M1) functional activity pre and post gross motor interventions for children with unilateral cerebral palsy (UCP). METHODS: Thirteen children with UCP completed a gross motor intervention. Pre/post-intervention functional MRI outcomes included the laterality index (LI), activation volume, and spatial overlap of M1 activation during active ankle dorsiflexion. Advanced gross motor function (Challenge) was assessed pre/post-intervention, and 2-6 months later. Bivariate correlations and linear regression assessed relations between neuroimaging and motor function. RESULTS: Mean pre-intervention M1 activity was contralateral during dominant (LI = +0.85, SD 0.21) but variable during the affected (LI = +0.43, SD 0.57) ankle dorsiflexion. Changes in motor function and neuroimaging outcomes were not significantly associated. However, smaller affected ankle activation and less spatial overlap between ankle activations pre-intervention predicted Challenge improvements post-intervention (adjusted R2 = 0.74, p = .001.). CONCLUSIONS: This exploratory study identified pre-intervention neuroimaging predictors of post-intervention improvements in advanced gross motor function.

The Impact of the American Association of Thoracic Surgery on Clinical Trial Development by Cardiothoracic Surgeons.

OBJECTIVE: Clinical trials play a critical role in the rapidly evolving field of cardiothoracic surgery and the American Association of Thoracic Surgery (AATS) Clinical Trials Methods Course has provided a biannual symposium led by preeminent surgeons with vast experience in planning, conducting and analyzing surgical clinical trials. This study hypothesizes that participation in the course is associated with future success in clinical trial leadership. METHODS: A list of course attendees (2014-2022) was queried in "ClinicalTrials.gov", a database of clinical trials funded by the United States Health and Human Services and the National Institutes of Health. The type of clinical trial and publications from the trial were collected. Demographic information about the participants were collected from faculty pages. RESULTS: A total of 107 participants from various professional backgrounds attended the AATS Clinical Trials course and led 91 clinical trials. The average time to starting a clinical trial after attending the workshop was 3.04 years for participants who had not already been involved with a trial. Of the 107 participants, 36 (36/107; 33.6%) were either the principal investigator or a sub-investigator for 91 clinical trials. CONCLUSIONS: The AATS Clinical Trials course provides participants the tools for successfully leading surgical clinical trials. Although participation has been limited, those who attend the course and lead a clinical trial do so within approximately 3 years. The Clinical Trials course provides an excellent return on investment and the AATS should continue sponsorship of this program as it supports the develop of future leaders in cardiothoracic surgery.

Magnetoelectric nanodiscs enable wireless transgene-free neuromodulation.

Deep brain stimulation with implanted electrodes has transformed neuroscience studies and treatment of neurological and psychiatric conditions. Discovering less invasive alternatives to deep brain stimulation could expand its clinical and research applications. Nanomaterial-mediated transduction of magnetic fields into electric potentials has been explored as a means for remote neuromodulation. Here we synthesize magnetoelectric nanodiscs (MENDs) with a core-double-shell Fe3O4-CoFe2O4-BaTiO3 architecture (250 nm diameter and 50 nm thickness) with efficient magnetoelectric coupling. We find robust responses to magnetic field stimulation in neurons decorated with MENDs at a density of 1 µg mm-2 despite individual-particle potentials below the neuronal excitation threshold. We propose a model for repetitive subthreshold depolarization that, combined with cable theory, supports our observations in vitro and informs magnetoelectric stimulation in vivo. Injected into the ventral tegmental area or the subthalamic nucleus of genetically intact mice at concentrations of 1 mg ml-1, MENDs enable remote control of reward or motor behaviours, respectively. These findings set the stage for mechanistic optimization of magnetoelectric neuromodulation towards applications in neuroscience research.

Signal sequences target enzymes and structural proteins to bacterial microcompartments and are critical for microcompartment formation.

Spatial organization of pathway enzymes has emerged as a promising tool to address several challenges in metabolic engineering, such as flux imbalances and off-target product formation. Bacterial microcompartments (MCPs) are a spatial organization strategy used natively by many bacteria to encapsulate metabolic pathways that produce toxic, volatile intermediates. Several recent studies have focused on engineering MCPs to encapsulate heterologous pathways of interest, but how this engineering affects MCP assembly and function is poorly understood. In this study, we investigated the role of signal sequences, short domains that target proteins to the MCP core, in the assembly of 1,2-propanediol utilization (Pdu) MCPs. We characterized two novel Pdu signal sequences on the structural proteins PduM and PduB, which constitutes the first report of metabolosome signal sequences on structural proteins rather than enzymes. We then explored the role of enzymatic and structural Pdu signal sequences on MCP assembly by deleting their encoding sequences from the genome alone and in combination. Deleting enzymatic signal sequences decreased MCP formation, but this defect could be recovered in some cases by overexpressing genes encoding the knocked-out signal sequence fused to a heterologous protein. By contrast, deleting structural signal sequences caused similar defects to knocking out the genes encoding the full length PduM and PduB proteins. Our results contribute to a growing understanding of how MCPs form and function in bacteria and provide strategies to mitigate assembly disruption when encapsulating heterologous pathways in MCPs.

CSF1-dependent macrophage support matrisome and epithelial stress-induced keratin remodeling in Eosinophilic esophagitis.

Atopic diseases such as Eosinophilic Esophagitis (EoE) often progress into fibrosis (FS-EoE), compromising organ function with limited targeted treatment options. Mechanistic understanding of FS-EoE progression is confounded by the lack of preclinical models and the heavy focus of research on eosinophils themselves. We found that macrophage accumulation precedes esophageal fibrosis in FS-EoE patients. We developed a FS-EoE model via chronic administration of oxazalone allergen, in a transgenic mouse over-expressing esophageal epithelial hIL-5 (L2-IL5OXA). These mice display striking histopathologic features congruent with that found in FS-EoE patients. Unbiased proteomic analysis, using a unique extracellular-matrix (ECM) focused technique, identified an inflammation-reactive provisional basal lamina membrane signature and this was validated in two independent EoE patient RNA-sequencing/proteomic cohorts, supporting model significance. A wound healing signature was also observed involving hemostasis-associated molecules previously unnoted in EoE. We further identified the ECM glycoprotein, Tenascin-C (TNC), and the stress-responsive keratin-16 (KRT16) as IL-4 and IL-13 responsive mediators, acting as biomarkers of FS-EoE. To mechanistically address how the immune infiltrate shapes FS-EoE progression, we phenotyped the major immune cell subsets that coalesce with fibrosis in both the L2-IL5OXA mice and in FS-EoE patients. We found that macrophage are required for matrisome and cytoskeletal remodeling. Importantly, we show that macrophage accumulation precedes esophageal fibrosis and provide a novel therapeutic target in FS-EoE as their depletion with anti-CSF1 attenuated reactive matrisome and cytoskeletal changes. Thus, macrophage-based treatments and the exploration of TNC and KRT16 as biomarkers may provide novel therapeutic options for patients with fibrostenosis.

Implementation and Evaluation of an Academic Development Rotation for Surgery Residents.

OBJECTIVE: To describe the design, implementation, and evaluation of a two-week rotation intended to enhance junior surgical residents' preparation for their dedicated professional development time (PDT) and academic careers. DESIGN: As part of a multifaceted effort to promote residents' academic development, we designed a two-week, nonclinical "Academic Development Block" (ADB) rotation for postgraduate year (PGY)-2 and -3 residents. During this rotation, residents meet with clinical, research, and peer mentors and work on academic activities, with relevant deliverables specific to each class year. We analyzed feedback from postrotation surveys and interviews, which were inductively coded and thematically analyzed, and data on resident grant applications and earnings before and after implementation. SETTING: The general surgery residency program at a major urban, university-affiliated academic medical center. ADBs were first implemented in 2021. PARTICIPANTS: A total of 39 PGY-2 and PGY-3 residents rotated through the program with 51 ADBs over the first two years of implementation. RESULTS: Surveys indicated overwhelmingly positive perceptions on the value of ADBs, including the amount of structure and resources available. Free-response and interview themes indicated appreciation for time to meet with mentors, develop ideas, and complete academic work. Residents believed the ADB rotation accelerated their transition into PDT and was a marker of institutional commitment. Areas for improvement pertained to the timing of ADBs and pairing of mentors. Both cohorts who participated in at least 1 ADB had higher proportions of residents who successfully applied for grants and a greater amount of total funding awarded compared to all 4 of the most recent cohorts prior to implementation. CONCLUSIONS: A short academic development rotation protected from clinical responsibilities is a well-regarded intervention to help residents refine their career goals and prepare for their PDT. Similar initiatives may be of interest to residency programs seeking to foster their residents' academic career development.

Quantitative susceptibility and T1 ρ mapping of knee articular cartilage at 3T.

T1 ρ and Quantitative Susceptibility Mapping (QSM) are evolving as substrates for quantifying the progressive nature of knee osteoarthritis. Objective: To evaluate the effects of spin lock time combinations on depth-dependent T1 ρ estimation, in adjunct to QSM, and characterize the degree of shared variance in QSM and T1 ρ for the quantitative measurement of articular cartilage. Design: Twenty healthy participants (10 â€‹M/10F, 22.2 â€‹± â€‹3.4 years) underwent bilateral knee MRI using T1 ρ MAPPS sequences with varying TSLs ([0-120] ms), along with a 3D spoiled gradient echo for QSM. Five total TSL combinations were used for T1 ρ computation, and direct depth-based comparison. Depth-wide variance was assessed in comparison to QSM as a basis to assess for depth-specific variation in T1 ρ computations across healthy cartilage. Results: Longer T1 ρ relaxation times were observed for TSL combinations with higher spin lock times. Depth-specific differences were documented for both QSM and T1 ρ , with most change found at ∼60% depth of the cartilage, relative to the surface. Direct squared linear correlation revealed that most T1 ρ TSL combinations can explain over 30% of the variability in QSM, suggesting inherent shared sensitivity to cartilage microstructure. Conclusions: T1 ρ mapping is subjective to the spin lock time combinations used for computation of relaxation times. When paired with QSM, both similarities and differences in signal sensitivity may be complementary to capture depth-wide changes in articular cartilage.

CelltypeR: A flow cytometry pipeline to characterize single cells from brain organoids.

Motivated by the cellular heterogeneity in complex tissues, particularly in brain and induced pluripotent stem cell (iPSC)-derived brain models, we developed a complete workflow to reproducibly characterize cell types in complex tissues. Our approach combines a flow cytometry (FC) antibody panel with our computational pipeline CelltypeR, enabling dataset aligning, unsupervised clustering optimization, cell type annotating, and statistical comparisons. Applied to human iPSC derived midbrain organoids, it successfully identified the major brain cell types. We performed fluorescence-activated cell sorting of CelltypeR-defined astrocytes, radial glia, and neurons, exploring transcriptional states by single-cell RNA sequencing. Among the sorted neurons, we identified subgroups of dopamine neurons: one reminiscent of substantia nigra cells most vulnerable in Parkinson's disease. Finally, we used our workflow to track cell types across a time course of organoid differentiation. Overall, our adaptable analysis framework provides a generalizable method for reproducibly identifying cell types across FC datasets in complex tissues.

Electrostatic Dissipation in 3D-Printable Silicone.

In this report, we describe the incorporation of single-walled carbon nanotubes (CNTs) into 3D printable siloxane elastomers for electrostatic dissipation. The composite was characterized, focusing on how rheological and mechanical properties of the siloxane are affected at various CNT loading levels. Electrical properties were also characterized to develop materials with effective electrostatic dissipation. We demonstrate that low loadings (<1 wt %) of CNTs can be sufficiently dispersed into silicone resins that can be 3D printed, and the resulting material shows a significant improvement in electrostatic dissipation through the reduction in electrical resistivity with minimal effect on its mechanical properties.

Forensic intelligence in Australia and New Zealand: Status and future directions.

Forensic science is underutilised. Operating models restricted to the support of court outcomes do not address core requirements of contemporary policing and public security, which are to disrupt criminal activity and prevent crime. Forensic intelligence (FORINT) is a principal means of enhancing the role of forensic science, emphasising proactivity and cross-case, cross-crime domain insights. To catalyse implementation, a FORINT Specialist Advisory Group (SAG) has been established under the Australia & New Zealand Policing Advisory Agency (ANZPAA) National Institute of Forensic Science (NIFS). The SAG has established a concept of operations with four lines of effort - namely, to (i) promote awareness and consistency, (ii) shape the workforce, (iii) develop information management frameworks and (iv) guide operational implementation. This aims to shift Australia & New Zealand from its present state (of substantial interagency variability) to a state of widespread, consistent and effective FORINT delivery in terms of: (a) culture, (b) information management, (c) education & training, and (d) organisation & operating environment. There are risks to implementing FORINT, in terms of privacy/confidentiality, bias/misinterpretation, and resource impost. However, these are not necessarily FORINT-specific, and solutions or mitigations exist. Moreover, these issues are outweighed by the risks of not implementing FORINT - such as a failure to reveal threats, missed opportunities, and poor resource efficiency. This paper is a call to arms. For policing and laboratories - now is the time to implement and entrench FORINT. For academia - now is the time to build foundations for this future. For supporting industries - now is the time to develop partnerships and facilitate delivery.

Charting Diagnostic Safety: Exploring Patient-Provider Discordance in Medical Record Documentation.

BACKGROUND: The 21st Century Cures Act enables patients to access their medical records, thus providing a unique opportunity to engage patients in their diagnostic journey. OBJECTIVE: To explore the concordance between patients' self-reported diagnostic concerns and clinician-interpreted information in their electronic health records. DESIGN: We conducted a mixed-methods analysis of a cohort of 467 patients who completed a structured data collection instrument (the Safer Dx Patient) to identify diagnostic concerns while reviewing their clinician's notes. We conducted a qualitative content analysis of open-ended responses on both the tools and the case summaries. Two clinical chart reviewers, blinded to patient-reported diagnostic concerns, independently conducted chart reviews using a different structured instrument (the Revised Safer Dx Instrument) to identify diagnostic concerns and generate case summaries. The primary outcome variable was chart review-identified diagnostic concerns. Multivariate logistic regression tested whether the primary outcome was concordant with patient-reported diagnostic concerns. SETTING: Geisinger, a large integrated healthcare organization in rural and semi-urban Pennsylvania. PARTICIPANTS: Cohort of adult patients actively using patient portals and identified as "at-risk" for diagnostic concerns using an electronic trigger algorithm based on unexpected visit patterns in a primary care setting. RESULTS: In 467 cohort patients, chart review identified 31 (6.4%) diagnostic concerns, of which only 11 (21.5%) overlapped with 51 patient-reported diagnostic concerns. Content analysis revealed several areas of discordant understanding of the diagnostic process between clinicians and patients. Multivariate logistic regression analysis showed that clinician-identified diagnostic concerns were associated with patients who self-reported "I feel I was incorrectly diagnosed during my visit" (odds ratio 1.65, 95% CI 1.17-2.3, p < 0.05). CONCLUSION: Patients and clinicians appear to have certain differences in their mental models of what is considered a diagnostic concern. Efforts to integrate patient perspectives and experiences with the diagnostic process can lead to better measurement of diagnostic safety.

Implicit Race Bias in Pediatric Patients: Understanding Patient Perspectives.

INTRODUCTION: Implicit racial bias has been well studied in adults, including among orthopaedic surgeons, through the Implicit Association Test (IAT). Recent studies suggest implicit race bias is also present among children. Explicit racial preference has been studied in children through The Clark Doll Test since the 1930s. The purpose of this study was to determine whether implicit and explicit racial biases are present among pediatric orthopaedic patients. METHODS: A prospective, cross-sectional survey was administered to pediatric orthopaedic patients aged 7 to 18 years at clinics in a tertiary pediatric hospital setting. The survey included a Clark Doll Test to determine whether pediatric patients expressed explicit bias, followed by a race IAT to determine whether pediatric patients expressed implicit bias. Preference and magnitude of implicit bias as demonstrated on the IAT was calculated using standard D-scores. RESULTS: A total of 96 patients were consented and included in this study. Overall, pediatric patients demonstrated a slight pro-White implicit bias (M = 0.22) on IAT testing. Pediatric patients who identified as White or European American and Hispanic or Latinx both had the strongest pro-White implicit bias (M = 0.35). Patients who identified as Black or African American demonstrated no implicit racial bias (M = -0.13) on IAT testing. No notable explicit bias was observed in participants of any racial background. DISCUSSION: This study contributes evidence that pediatric orthopaedic patients express implicit racial bias on IAT testing, with an overall slight pro-White bias. It also provides insight into the dissociation of implicit and explicit racial bias in childhood and adolescence. CONCLUSION: We encourage future research on implicit bias among pediatric patients in the orthopaedic community to provide a better understanding and possible solutions to bias-related challenges in health care.

Firefighter- and fire department-level barriers and promoters of physical activity and fitness among volunteer firefighters: a qualitative study using semi-structured interviews.

OBJECTIVE: To describe volunteer firefighters' perspectives on how firefighter- and fire department-level factors influence their physical activity and fitness. METHODS: Firefighters (n = 28) were interviewed, stratified by their years of firefighting, using an interview guide. Thematic analysis and systematic coding were employed to analyze the interview transcripts. RESULTS: Five themes were identified: (1) health and firefighting performance; (2) firefighter time and availability; (3) responsibility of the fire department to support volunteer members' physical fitness; (4) fire training drills as a form of functional physical activity, and (5) fitness initiatives at the department. Interviewing by years of experience showed varied perspectives which converged towards similar conclusions. CONCLUSIONS: Incorporating fitness discussions into department meetings and trainings, and identifying fitness advocates within the department, may contribute to overcoming barriers to physical fitness among volunteer firefighters.

Fluorescence labeling strategies for cell surface expression of TRPV1.

Regulation of ion channel expression on the plasma membrane is a major determinant of neuronal excitability, and identifying the underlying mechanisms of this expression is critical to our understanding of neurons. Here, we present two orthogonal strategies to label extracellular sites of the ion channel TRPV1 that minimally perturb its function. We use the amber codon suppression technique to introduce a non-canonical amino acid (ncAA) with tetrazine click chemistry, compatible with a trans-cyclooctene coupled fluorescent dye. Additionally, by inserting the circularly permutated HaloTag (cpHaloTag) in an extracellular loop of TRPV1, we can incorporate a fluorescent dye of our choosing. Optimization of ncAA insertion sites was accomplished by screening residue positions between the S1 and S2 transmembrane domains with elevated missense variants in the human population. We identified T468 as a rapid labeling site (∼5 min) based on functional and biochemical assays in HEK293T/17 cells. Through adapting linker lengths and backbone placement of cpHaloTag on the extracellular side of TRPV1, we generated a fully functional channel construct, TRPV1exCellHalo, with intact wild-type gating properties. We used TRPV1exCellHalo in a single molecule experiment to track TRPV1 on the cell surface and validate studies that show decreased mobility of the channel upon activation. The application of these extracellular label TRPV1 (exCellTRPV1) constructs to track surface localization of the channel will shed significant light on the mechanisms regulating its expression and provide a general scheme to introduce similar modifications to other cell surface receptors.

Evaluation of Rhode Island's Early Geographic COVID-19 Vaccine Prioritization Policy.

Objectives. To determine whether geographic prioritization of limited COVID-19 vaccine supply was effective for reducing geographic disparities in case rates. Methods. Rhode Island allocated a portion of the initial COVID-19 vaccine supply to residents of Central Falls, a community already affected by structural policies and inadequate systems that perpetuate health inequities and experiencing disproportionately high COVID-19 morbidity and mortality. The policy was implemented with a culturally and linguistically appropriate community engagement plan and was intended to reduce observed disparities. Using a Bayesian causal analysis with population surveillance data, we evaluated the impact of this prioritization policy on recorded cases over the subsequent 16 weeks. Results. Early geographic prioritization of Central Falls accelerated vaccine uptake, averting an estimated 520 cases (95% confidence interval = 22, 1418) over 16 weeks and reducing cases by approximately 34% during this period (520 averted vs 1519 expected without early prioritization). Conclusions. Early geographic prioritization increased vaccine uptake and reduced cases in Central Falls, thereby reducing geographic disparities. Public Health Implications. Public health institutions should consider geographic prioritization of limited vaccine supply to reduce geographic disparities in case rates. (Am J Public Health. 2024;114(S7):S580-S589. https://doi.org/10.2105/AJPH.2024.307741).

Bacteroides ovatus alleviates dysbiotic microbiota-induced graft-versus-host disease.

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus.

Differential neural mechanisms for movement adaptations following neuromuscular training in young female athletes with a history of sports-related concussion.

Sports-related concussion (SRC) in adolescent athletes is associated with an increased risk of subsequent lower extremity injury. Neuromuscular training (NMT) has shown promise for reducing lower extremity injuries following SRC, however, neural adaptations in response to changes in lower extremity biomechanics following NMT in athletes with a history of SRC (HxSRC) remains poorly understood. Therefore, the purpose of this study was to identify changes in neural activity associated with lower extremity movement adaptations following a six-week NMT intervention in athletes with a HxSRC. Thirty-two right-hand/foot-dominant female adolescent athletes (16 with self-reported HxSRC, 16 age- and anthropometrically-matched controls) completed a bilateral leg press task with 3D motion analysis during functional magnetic resonance imaging (fMRI). Movement adaptations were defined as a change in frontal and sagittal plane range of motion (ROM) during the fMRI bilateral leg press task. Significant pre- to post-NMT reductions were observed in the non-dominant (left) mean frontal plane ROM. Whole-brain neural correlate analysis revealed that increased cerebellar activity was significantly associated with reduced mean left-knee frontal ROM for matched controls. Exploratory within group analyses identified neural correlates in the postcentral gyrus for the HxSRC group which was associated with reduced mean left-knee frontal plane ROM. These distinct longitudinal changes provide preliminary evidence of differential neural activity associated with NMT to support knee frontal plane control in athletes with and without a HxSRC.

Metabolic dysfunction mediated by HIF-1α contributes to epithelial differentiation defects in eosinophilic esophagitis.

BACKGROUND: Investigating the contributory role that epithelial cell metabolism plays in allergic inflammation is a key factor to understanding what influences dysfunction and the pathogenesis of the allergic disease eosinophilic esophagitis (EoE). We previously highlighted that the absence of hypoxia signaling through hypoxia-inducible factor (HIF)-1α in EoE contributes to esophageal epithelial dysfunction. However, metabolic regulation by HIF-1α has not been explored in esophageal allergy. OBJECTIVES: We sought to define the role of HIF-1α-mediated metabolic dysfunction in esophageal epithelial differentiation processes and barrier function in EoE. METHODS: In RNA sequencing of EoE patient biopsy samples, we observed the expression pattern of key genes involved in mitochondrial metabolism/oxidative phosphorylation (OXPHOS) and glycolysis. Seahorse bioenergetics analysis was performed on EPC2-hTERT cells to decipher the metabolic processes involved in epithelial differentiation processes. In addition, air-liquid interface cultures were used to delineate metabolic dependency mechanisms required for epithelial differentiation. RESULTS: Transcriptomic analysis identified an increase in genes associated with OXPHOS in patients with EoE. Epithelial origin of this signature was confirmed by complex V immunofluorescence of patient biopsy samples. Bioenergetic analysis in vitro revealed that differentiated epithelium was less reliant on OXPHOS compared with undifferentiated epithelium. Increased OXPHOS potential and reduced glycolytic capacity was mirrored in HIF1A-knockdown EPC2-hTERT cells that exhibited a significant absence of terminal markers of epithelial differentiation, including involucrin. Pharmacologic glucose transport inhibition phenocopied this, while rescue of the HIF-1α-deficient phenotype using the pan-prolyl hydroxylase inhibitor dimethyloxalylglycine resulted in restored expression of epithelial differentiation markers. CONCLUSIONS: An OXPHOS-dominated metabolic pattern in EoE patients, brought about largely by the absence of HIF-1α-mediated glycolysis, is linked with the deficit in esophageal epithelial differentiation.