Medicine and Health Sciences Commons^™

Intraoperative Identification Of Thyroid And Parathyroid Tissues During Human Endocrine Surgery Using The Masspec Pen, Rachel J Dehoog, Mary E King, Michael F Keating, Jialing Zhang, Marta Sans, Clara L Feider, Kyana Y Garza, Alena Bensussan, Anna Krieger, John Q Lin, Sunil Badal, Elizabeth Alore, Christopher Pirko, Kirtan Brahmbhatt, Wendong Yu, Raymon Grogan, Livia S Eberlin, James Suliburk

Faculty, Staff and Students Publications

IMPORTANCE: Intraoperative identification of tissues through gross inspection during thyroid and parathyroid surgery is challenging yet essential for preserving healthy tissue and improving outcomes for patients.

OBJECTIVE: To evaluate the performance and clinical applicability of the MasSpec Pen (MSPen) technology for discriminating thyroid, parathyroid, and lymph node tissues intraoperatively.

DESIGN, SETTING, AND PARTICIPANTS: In this diagnostic/prognostic study, the MSPen was used to analyze 184 fresh-frozen thyroid, parathyroid, and lymph node tissues in the laboratory and translated to the operating room to enable in vivo and ex vivo tissue analysis by endocrine surgeons in 102 patients undergoing thyroidectomy and parathyroidectomy procedures. …

Commentary: Aortic Arch Repair: Custom Made Versus One Size Fits All, Jaskaran S Saini, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

Structural Biology Of Mcr-1-Mediated Resistance To Polymyxin Antibiotics, Isabel Cristina Materon, Timothy Palzkill

Faculty, Staff and Students Publications

Polymyxins, a last resort antibiotic, target the outer membrane of pathogens and are used to address the increasing prevalence of multidrug-resistant Gram-negative bacteria. The plasmid-encoded enzyme MCR-1 confers polymyxin resistance to bacteria by modifying the outer membrane. Transferable resistance to polymyxins is a major concern; therefore, MCR-1 is an important drug target. In this review, we discuss recent structural and mechanistic aspects of MCR-1 function, its variants and homologs, and how they are relevant to polymyxin resistance. Specifically, we discuss work on polymyxin-mediated disruption of the outer and inner membranes, computational studies on the catalytic mechanism of MCR-1, mutagenesis and …

Single-Cell Rna Sequencing Provides New Insights Into Therapeutic Roles Of Thyroid Hormone In Idiopathic Pulmonary Fibrosis, Lan Wang, Zhongzheng Li, Ruyan Wan, Xin Pan, Bin Li, Huabin Zhao, Juntang Yang, Weiming Zhao, Shenghui Wang, Qiwen Wang, Peishuo Yan, Chi Ma, Hongmei Yuan, Mengxia Zhao, Ivan Rosas, Chen Ding, Baofa Sun, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal interstitial lung disease without an effective cure. Herein, we explore the role of 3,5,3′-triiodothyronine (T3) administration on lung alveolar regeneration and fibrosis at the single-cell level. T3 supplementation significantly altered the gene expression in fibrotic lung tissues. Immune cells were rapidly recruited into the lung after the injury; there were much more M2 macrophages than M1 macrophages in the lungs of bleomycin-treated mice; and M1 macrophages increased slightly, whereas M2 macrophages were significantly reduced after T3 treatment. T3 enhanced the resolution of pulmonary fibrosis by promoting the differentiation of Krt8+ transitional …

Texas Developmental Center For Aids Research Cfar Diversity, Equity, And Inclusion Pathway Initiative Program, Fred A Pereira, Alana D Newell, Andrew P Rice

Faculty, Staff and Students Publications

BACKGROUND: The Texas Developmental Center for AIDS Research (D-CFAR) diversity program, termed the CFAR Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI), was created in 2021 to engage high school students and graduate students from Underrepresented Minorities/Black, Indigenous, and People of Color populations.

SETTING: The Texas D-CFAR CDEIPI has partnered with 2 Texas high schools with predominantly economically disadvantaged and minority student populations-Michael E. DeBakey High School for Health Professions in Houston, TX, and the South Texas Independent School District Medical Professions High School in Olmito, TX in the Rio Grande Valley.

METHODS: A total of 370 high school student learners …

Evaluation Of An Individualized Learning Plan Template For The Transition To Residency, Amber T Pincavage, Ashish Gandhi, Eli Falk, Lauren Dimarino, Douglas Ruiz Carbajal, Uma Ayyala, Jayaram Chandrasekar, Andrew N Dentino, Allison H Ferris, Richard M Forster, Paul A Hemmer, Nancy Masucci, William D Surkis, Valerie O, John H Choe

Faculty, Staff and Students Publications

Background Specialty-specific individualized learning plans (ILPs) have been promoted to improve the undergraduate to graduate medical education transition, yet few pilots have been described.

Objective To create and report on the feasibility and acceptability of a pilot internal medicine (IM) ILP template.

Methods The ILP was created by a group of diverse IM expert stakeholders and contained questions to stimulate self-reflection and collect self-reported readiness data from incoming interns. US IM residency programs were invited to pilot the ILP with interns in spring 2022. Data was used at the programs’ discretion. The pilot was evaluated by a post-pilot survey of …

Type 1 Diabetes Genetic Risk Score Differentiates Subgroups Of Ketosis-Prone Diabetes, Deborah Osafehinti, Surya N Mulukutla, Christiane S Hampe, Ruchi Gaba, Nalini Ram, Michael N Weedon, Richard A Oram, Ashok Balasubramanyam

Faculty, Staff and Students Publications

OBJECTIVE: To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A- define the presence or absence of islet autoantibodies and β+ and β- define the presence or absence of β-cell function.

RESEARCH DESIGN AND METHODS: We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia.

RESULTS: Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+β- > A+β+ = A-β- > A-β+. GRS of A+β- KPD was lower than that of a T1D …

Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators

Faculty, Staff and Students Publications

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function …

A Retrospective Review Of Social Deprivation Index And Maternal Outcomes With Placenta Accreta Spectrum From A Single Referral Center, Alison N Goulding, Karin A Fox, Christina C Reed, Bahram Salmanian, Alireza A Shamshirsaz, Kjersti M Aagaard

Faculty, Staff and Students Publications

Objective

Little is known about how community characteristics influence placenta accreta spectrum (PAS) outcomes. Our objective was to evaluate whether adverse maternal outcomes among pregnant people (gravidae) with PAS delivering at a single referral center differ by community-level measures of social deprivation.

Study Design

We conducted a retrospective cohort study of singleton gravidae with histopathology confirmed PAS delivering from January 2011 to June 2021 at a referral center. Data abstraction collected relevant patient information, including resident zip code, which was linked to Social Deprivation Index (SDI) score (a measure of area-level social deprivation). SDI scores were divided into quartiles for …

Bioimpedance Analysis Predicts The Etiology Of Cirrhosis In A Prospective Cohort Study, Hashem B El-Serag, Ghida Akhdar, Aaron P Thrift, Michelle Luster, Saira Khaderi, Abeer Alsarraj, Hao Duong, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition.

METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease …

The New Era Of Long-Acting Antiretroviral Therapy: When And Why To Make The Switch, Melanie C Goebel, Emmanuel Guajardo, Thomas P Giordano, Shital M Patel

Faculty, Staff and Students Publications

Purpose of review: Despite the availability of safe and effective oral combination antiretroviral therapy, barriers to maintaining viral suppression remain a challenge to ending the HIV epidemic. Long-acting injectable antiretroviral therapy was developed as an alternative to daily oral therapy. This review summarizes the current literature on the efficacy of long-acting cabotegravir plus rilpivirine for the treatment of HIV-1, reasons to switch to injectable therapy, and barriers to switching.

Recent findings: Long-acting cabotegravir plus rilpivirine is safe and effective in maintaining HIV-1 virologic suppression. Ideal candidates for switching to long-acting cabotegravir plus rilpivirine are virologically suppressed on oral regimens with …

Human Intestinal Organoids As Models To Study Enteric Bacteria And Viruses, Grace Adeniyi-Ipadeola, Hephzibah Nwanosike, Sasirekha Ramani

Faculty, Staff and Students Publications

Laboratory studies of host-microbe interactions have historically been carried out using transformed cell lines and animal models. Although much has been learned from these models, recent advances in the development of multicellular, physiologically active, human intestinal organoid (HIO) cultures are allowing unprecedented discoveries of host-microbe interactions. Here, we review recent literature using HIOs as models to investigate the pathogenesis of clinically important enteric bacteria and viruses and study commensal intestinal microbes. We also discuss limitations of current HIO culture systems and how technical advances and innovative engineering approaches are providing new directions to improve the model. The studies discussed here …

Comparing Palliation Strategies For Single-Ventricle Anatomy With Transposed Great Arteries And Systemic Outflow Obstruction, Alyssa B Kalustian, Zachary A Spigel, Christopher E Greenleaf, Tam T Doan, Alejandra I Chavez, Iki Adachi, Jeffrey S Heinle, Ziyad M Binsalamah

Faculty, Staff and Student Publications

OBJECTIVE: Patients with complex single-ventricle anatomy with transposed great arteries and systemic outflow obstruction (SV-TGA-SOO) undergo varied initial palliation with ultimate goal of Fontan circulation. We examine a longitudinal experience with multiple techniques, including the largest published cohort following palliative arterial switch operation (pASO), to describe outcomes and decision-making factors.

METHODS: Neonates with SV-TGA-SOO who underwent initial surgical palliation from 1995 to 2022 at a single institution were retrospectively reviewed.

RESULTS: In total, 71 neonates with SV-TGA-SOO underwent index surgical palliation at a median age of 7 days (interquartile range, 6-10) by pASO (n = 23), pulmonary artery band (PAB) …

Hope And Optimism In Pediatric Deep Brain Stimulation: Key Stakeholder Perspectives, Natalie Dorfman, Lilly Snellman, Ynez Kerley, Kristin Kostick-Quenet, Gabriel Lazaro-Munoz, Eric A Storch, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is utilized to treat pediatric refractory dystonia and its use in pediatric patients is expected to grow. One important question concerns the impact of hope and unrealistic optimism on decision-making, especially in "last resort" intervention scenarios such as DBS for refractory conditions.

Objective: This study examined stakeholder experiences and perspectives on hope and unrealistic optimism in the context of decision-making about DBS for childhood dystonia and provides insights for clinicians seeking to implement effective communication strategies.

Materials and methods: Semi-structured interviews with clinicians (n = 29) and caregivers (n = 44) were conducted, …

Cardiac Magnetic Resonance Imaging To Determine Single Ventricle Function In A Pediatric Population Is Feasible In A Large Trial Setting: Experience From The Single Ventricle Reconstruction Trial Longitudinal Follow Up, Jon Detterich, Michael D Taylor, Timothy C Slesnick, Michael Dilorenzo, Anthony Hlavacek, Christopher Z Lam, Shagun Sachdeva, Sean M Lang, M Jay Campbell, Jennifer Gerardin, Kevin K Whitehead, Rahul H Rathod, Mark Cartoski, Shaji Menon, Felicia Trachtenberg, Russell Gongwer, Jane Newburger, Caren Goldberg, Adam L Dorfman, The Pediatric Heart Network Investigators

Faculty, Staff and Students Publications

The Single Ventricle Reconstruction (SVR) Trial was a randomized prospective trial designed to determine survival advantage of the modified Blalock-Taussig-Thomas shunt (BTTS) vs the right ventricle to pulmonary artery conduit (RVPAS) for patients with hypoplastic left heart syndrome. The primary aim of the long-term follow-up (SVRIII) was to determine the impact of shunt type on RV function. In this work, we describe the use of CMR in a large cohort follow up from the SVR Trial as a focused study of single ventricle function. The SVRIII protocol included short axis steady-state free precession imaging to assess single ventricle systolic function …

Atrial Septal Defect Closure Is Associated With Improved Clinical Status In Patients ≤ 10 Kg With Bronchopulmonary Dysplasia, Melissa K Webb, Milenka Cuevas Guaman, S Kristen Sexson Tejtel, Neil Cambronero, Ryan D Coleman, Corey A Chartan, Betul Yilmaz Furtun, Shaine A Morris, Nidhy P Varghese, Natalie M Villafranco

Faculty, Staff and Students Publications

Patients with bronchopulmonary dysplasia (BPD) have shown clinical improvement after secundum atrial septal defect (ASD) closure. We sought to determine if this post‐ASD closure improvement is secondary to the expected course in BPD patients or related to the closure itself. A novel BPD‐ASD score was created to assess patients' clinical status (higher score = worse disease) and applied to 10 BPD‐ASD inpatients weighing ≤ 10 kg who underwent ASD closure. The score and its subcomponents were retrospectively calculated serially ranging from 8 weeks pre‐ to 8 weeks post‐intervention, and pre‐ and post‐intervention score slopes were created. These slopes were compared …

Plasma Amino Acid Signatures Define Types Of Pediatric Diabetes, Mustafa Tosur, Jean W Hsu, Saima Deen, Xiaofan Huang, Danielle Guffey, Serife Uysal, Marcela Astudillo, Maria J Redondo, Farook Jahoor, Ashok Balasubramanyam

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Metabolic biomarkers with pathophysiological relevance is lacking in pediatric diabetes. We aimed to identify novel metabolic biomarkers in pediatric type 1 (T1D) and type 2 diabetes (T2D). We hypothesized that (1) targeted plasma metabolomics, focused on plasma amino acid concentrations, could identify distinctively altered patterns in children with T1D or T2D, and (2) there are specific changes in concentrations of metabolites related to branch chain amino acids (BCAA) and arginine metabolism in children with T2D.

METHODS: In a pilot study, we enrolled children with T1D (n = 15) and T2D (n = 13), and healthy controls (n …

Current Perspectives On Mass Spectrometry-Based Immunopeptidomics: The Computational Angle To Tumor Antigen Discovery, Bing Zhang, Michal Bassani-Sternberg

Faculty, Staff and Students Publications

Identification of tumor antigens presented by the human leucocyte antigen (HLA) molecules is essential for the design of effective and safe cancer immunotherapies that rely on T cell recognition and killing of tumor cells. Mass spectrometry (MS)-based immunopeptidomics enables high-throughput, direct identification of HLA-bound peptides from a variety of cell lines, tumor tissues, and healthy tissues. It involves immunoaffinity purification of HLA complexes followed by MS profiling of the extracted peptides using data-dependent acquisition, data-independent acquisition, or targeted approaches. By incorporating DNA, RNA, and ribosome sequencing data into immunopeptidomics data analysis, the proteogenomic approach provides a powerful means for identifying …

Quality Improvement Initiative To Improve Time And Adherence To Revaccination After Hematopoietic Cell Transplantation: Implementation Of A Revaccination Clinic Within The Transplantation Program, Caitlin Elgarten, Anne Wohlschlaeger, Ellen Levy, Katharine Tadley, Lei Wang, Megan Atkinson, Houston Roberson, Timothy Olson, Nancy Bunin, Jennifer Heimall, Brian Fisher, Stephan Grupp, Jason Freedman

Faculty, Staff and Students Publications

Background:

Revaccination after hematopoietic cell transplantation (HCT) is critical to prevent morbidity and mortality from vaccine preventable illnesses. While earlier re-vaccination after HCT is desirable, they may be ineffective if deployed before partial reconstitution of adaptive immunity. Increasingly, personalized approaches to re-vaccination after HCT have replaced time-based protocols in order to minimize unvaccinated time and enhance vaccine effectiveness. Furthermore, for revaccination to be maximally beneficial, compliance with, and timely delivery of the complete revaccination schedule is imperative, but rare, and there is little data on strategies to optimize vaccine delivery.

Objectives:

The global aim of our quality improvement initiative was …

Prevalence Of Pathogenic Germline Variants In Adult-Type Diffuse Glioma, Malcolm F Mcdonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, Jacob J Mandel

Faculty, Staff and Students Publications

BACKGROUND: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma.

METHODS: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected.

RESULTS: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, …

Convergent Escape Behaviour From Distinct Visual Processing Of Impending Collision In Fish And Grasshoppers, Richard B Dewell, Terri Carroll-Mikhail, Margaret R Eisenbrandt, Alexander F Mendoza, Bidisha Halder, Thomas Preuss, Fabrizio Gabbiani

Faculty, Staff and Students Publications

In animal species ranging from invertebrate to mammals, visually guided escape behaviours have been studied using looming stimuli, the two-dimensional expanding projection on a screen of an object approaching on a collision course at constant speed. The peak firing rate or membrane potential of neurons responding to looming stimuli often tracks a fixed threshold angular size of the approaching stimulus that contributes to the triggering of escape behaviours. To study whether this result holds more generally, we designed stimuli that simulate acceleration or deceleration over the course of object approach on a collision course. Under these conditions, we found that …

Bioresorbable Mesenchymal Stem Cell-Loaded Electrospun Polymeric Scaffold Inhibits Neointimal Hyperplasia Following Arteriovenous Fistula Formation In A Rat Model Of Chronic Kidney Disease, Allan John R Barcena, Joy Vanessa D Perez, Marvin R Bernardino, Jossana A Damasco, Andrea Cortes, Huckie C Del Mundo, Erin Marie D San Valentin, Carleigh Klusman, Gino Martin Canlas, Francisco M Heralde, Rony Avritscher, Natalie Fowlkes, Richard R Bouchard, Jizhong Cheng, Steven Y Huang, Marites P Melancon

Faculty, Staff and Students Publications

Bioresorbable perivascular scaffolds loaded with antiproliferative agents have been shown to enhance arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). These scaffolds, which can mimic the three-dimensional architecture of the vascular extracellular matrix, also have an untapped potential for the local delivery of cell therapies against NIH. Hence, an electrospun perivascular scaffold from polycaprolactone (PCL) to support mesenchymal stem cell (MSC) attachment and gradual elution at the AVF's outflow vein is fabricated. Chronic kidney disease (CKD) in Sprague-Dawley rats is induced by performing 5/6th nephrectomy, then AVFs for scaffold application are created. The following groups of CKD rats are …

Clinician Perspectives On Levels Of Evidence And Oversight For Deep Brain Stimulation For Treatment-Resistant Childhood Ocd, Michelle T Pham, Tiffany A Campbell, Natalie Dorfman, Laura Torgerson, Kristin Kostick-Quenet, Jennifer Blumenthal-Barby, Eric A Storch, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Approximately 10-20% of children with obsessive-compulsive disorder (OCD) have treatment-resistant presentations, and there is likely interest in developing interventions for this patient group, which may include deep brain stimulation (DBS). The World Society for Stereotactic and Functional Neurosurgery has argued that at least two successful randomized controlled trials should be available before DBS treatment for a psychiatric disorder is considered "established." The FDA approved DBS for adults with treatment-resistant OCD under a humanitarian device exemption (HDE) in 2009, which requires that a device be used to manage or treat a condition impacting 8,000 or fewer patients annually in the United …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

Hope And Optimism In Pediatric Deep Brain Stimulation: Key Stakeholder Perspectives, Natalie Dorfman, Lilly Snellman, Ynez Kerley, Kristin Kostick-Quenet, Gabriel Lazaro-Munoz, Eric A Storch, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Deep brain stimulation (DBS) is utilized to treat pediatric refractory dystonia and its use in pediatric patients is expected to grow. One important question concerns the impact of hope and unrealistic optimism on decision-making, especially in "last resort" intervention scenarios such as DBS for refractory conditions.

Objective: This study examined stakeholder experiences and perspectives on hope and unrealistic optimism in the context of decision-making about DBS for childhood dystonia and provides insights for clinicians seeking to implement effective communication strategies.

Materials and methods: Semi-structured interviews with clinicians (n = 29) and caregivers (n = 44) were conducted, …

Ethics Education For Healthcare Professionals In The Era Of Chatgpt And Other Large Language Models: Do We Still Need It?, Vasiliki Rahimzadeh, Kristin Kostick-Quenet, Jennifer Blumenthal Barby, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

In this paper, we contend with whether we still need traditional ethics education as part of healthcare professional training given the abilities of chatGPT (generative pre-trained transformer) and other large language models (LLM). We reflect on common programmatic goals to assess the current strengths and limitations of LLMs in helping to build ethics competencies among future clinicians. Through an actual case analysis, we highlight areas in which chatGPT and other LLMs are conducive to common bioethics education goals. We also comment on where such technologies remain an imperfect substitute for human-led ethics teaching and learning. Finally, we conclude that the …

Dimensionality Reduction For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Mais Al Taie, Joshua P Yung, Tucker J Netherton, Ankit B Patel, Kristy K Brock

Faculty, Staff and Student Publications

Clinically-deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these models do tend to perform well in most instances, which could exacerbate automation bias. Therefore, it is critical to detect out-of-distribution images at inference to warn the clinicians that the model likely failed. This work applies the Mahalanobis distance post hoc to the bottleneck features of a Swin UNETR model that segments the liver on T1-weighted magnetic resonance imaging. By reducing the dimensions of the bottleneck features with principal component analysis, images the model failed on were detected …

Neurodevelopmental Deficits And Cell-Type-Specific Transcriptomic Perturbations In A Mouse Model Of Hnrnpu Haploinsufficiency, Sarah A Dugger, Ryan S Dhindsa, Gabriela De Almeida Sampaio, Andrew K Ressler, Elizabeth E Rafikian, Sabrina Petri, Verity A Letts, Jiajie Teoh, Junqiang Ye, Sophie Colombo, Yueqing Peng, Mu Yang, Michael J Boland, Wayne N Frankel, David B Goldstein

Faculty, Staff and Students Publications

Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory …

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu

Faculty, Staff and Students Publications

BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.

METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.

RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …

Tnf Is A Critical Cytokine In Age-Related Dry Eye Disease, Yashaswini Kelagere, Kaitlin K Scholand, Erica N Dejong, Andrea I Boyd, Zhiyuan Yu, Roger A Astley, Michelle C Callegan, Dawn Me Bowdish, Helen P Makarenkova, Cintia S De Paiva

Faculty, Staff and Students Publications

Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), …