Medical Specialties Commons^™

Characteristics Associated With Eurolupus Versus Modified National Institutes Of Health Cyclophosphamide Regimen Use In Children And Young Adults With Lupus Nephritis, Christine S Wang, Rebecca E Sadun, Wenru Zhou, Kristen R Miller, Stacy P Ardoin, Christine Bearer, Emily Hause, Joyce Hui-Yuen, Nicole Ling, Maria Pereira, Meredith Riebschleger, Kelly Rouster-Stevens, Aliese Sarkissian, Julia Shalen, William Daniel Soulsby, Marinka Twilt, Eveline Y Wu, Laura B Lewandowski, Scott E Wenderfer, Jennifer C Cooper

Faculty, Staff and Students Publications

Objective: To determine the demographic and clinical characteristics associated with use of the EuroLupus or modified National Institutes of Health (NIH) cyclophosphamide (CYC) regimen for treatment of lupus nephritis (LN) at North American pediatric centers.

Methods: A retrospective cohort study was conducted at 11 North American centers. Patients < 22 years of age with active LN treated with CYC using the EuroLupus or NIH regimen between July 2014 and June 2021 were included. Data were extracted via electronic medical record review. Demographic and clinical characteristics were compared at CYC initiation. A multivariable generalized estimating equation with logit link was fit to model EuroLupus use. An exchangeable correlation structure was used to account for correlation within centers. Independent variables were chosen using elastic net regression.

Results: The cohort consisted of 191 patients (85 EuroLupus, 106 NIH) with a median age of 15.3 years at CYC initiation. In multivariable analysis, characteristics significantly associated with EuroLupus regimen use (vs NIH regimen use) included more recent year of CYC initiation, longer disease duration, Hispanic ethnicity and Asian race (as compared …

Factors Associated With Child Protective Services Referrals In Young Children With Isolated Skull Fractures, Karli Breeden-Carino, Joanne N Wood, Cindy W Christian, Tagrid M Ruiz-Maldonado, Daniel M Lindberg, Angela Bachim, Lori Frasier, Terra N Frazier, Nancy S Harper, Sara E Kruczek, Farah Brink, Jennifer E Wolford, Jan Leonard, M Katherine Henry

Faculty, Staff and Students Publications

Objective: Many young children with isolated skull fractures are referred to child protective services (CPS) despite being assessed to have a low likelihood of abuse. We sought to identify factors associated with CPS referrals in this population and to quantify hospital-level variation.

Methods: We performed a multicenter retrospective cross-sectional study of children < 2 years with skull fractures with or without a small underlying intracranial hemorrhage (ICH) and no additional injuries undergoing a child abuse pediatrics (CAP) subspecialty evaluation. We explored associations between demographic factors, clinical characteristics, psychosocial risk factors, and hospital site with CPS referral status. We performed multivariable logistic regression, adjusting for transfer status and all significant covariates from unadjusted analyses. We utilized marginal standardization to calculate the estimated probability of CPS referrals at each site, adjusting for all factors in the final model.

Results: Of 528 children, 303 (57.4%) were referred to CPS, with 86.5% referred prior to CAP consultation. In multivariable logistic regression, presence of psychosocial risk factors (OR 4.00; 95% CI 2.25, 7.11), in-person CAP consult (OR 3.93; 1.61, 9.62), inflicted or no trauma history provided (OR 6.15; 3.30, …

Derivation Of Pluripotent Stem Cell Lines (Rfsci005-A, Rfsci006-A) From Siblings Harboring Identical High-Risk Complement Variants With Discordant Age-Related Macular Degeneration, Naresh Rajendran, Ajeet Singh, Wendy Runyon, Sam Hu, Ritu Kumar, Rinki Ratnapriya, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a complex disease influenced by genetic and environmental factors. Variants in the complement pathway, especially in the CFH gene, increase AMD risk, yet disease severity can differ among individuals with identical high-risk genotypes. We generated induced pluripotent stem cell (iPSC) lines from siblings carrying identical high-risk complement variants but displaying discordant AMD phenotypes. These lines provide a unique platform to study epigenetic, transcriptomic, and environmental factors driving AMD heterogeneity. By comparing differentiated retinal cells, we aim to reveal mechanisms behind variable disease susceptibility and inform personalized therapies for AMD.

Generation Of Ipscs (Rfsci007-A, Rfsci008-A) From A Patient With Early-Onset Bilateral Drusen And A Healthy Sibling For Retinal Disease Modeling, Sonali Singh, Wendy Runyon, Sam Hu, Paige Grona Kennedy, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Drusen are extracellular deposits between the retinal pigment epithelium and Bruch's membrane, commonly linked to age-related macular degeneration (AMD). However, their presence in younger individuals offers a unique opportunity to study early disease mechanisms before extensive degeneration. We generated two human induced pluripotent stem cell (hiPSC) lines from siblings' peripheral blood mononuclear cells-one with early-onset bilateral drusen and the other unaffected. This genetically matched iPSC pair enables investigation of early drusen associated pathological changes driving retinal disease development.

Soluble C5b-9 (Sc5b-9) In Pediatrics-A Clinical Assessment, Ridwan B Ibrahim, Radwa Almamoun, Sarah E Sartain, Sridevi Devaraj

Faculty, Staff and Students Publications

Background: The soluble C5b-9 (sC5b-9) is a soluble form of the Terminal Complement Complex (TCC) that is released into the circulation with elevated levels, associated with increased morbidity and mortality in patients with complement-mediated inflammatory conditions. With the advent of eculizumab and ravulizumab, proper testing for diagnoses and therapeutic monitoring is warranted.

Methods: We evaluated both the analytical and clinical performance of the Quidel Microvue sC5b-9 Plus enzyme immunoassay. Analytical performance was evaluated with precision, linearity, interference studies, and correlation with a reference laboratory. Reference intervals were established using control donor samples [n = 26; median age 18.5 years (range …

Transcriptional Coregulator Zmiz1 Modulates Estrogen Responses That Are Essential For Healthy Endometrial Function, Sylvia C Hewitt, Frank Orellana, Ryan M Marquardt, Myeongjin Yi, Cynthia J Willson, Mark Y Chiang, Yong Song, Goutham Venkata Naga Davuluri, Christopher Day, Ramakrishna Kommagani, Joseph Rodriguez, Asgerally T Fazleabas, John P Lydon, Francesco J Demayo

Faculty, Staff and Students Publications

Estrogen is a critical regulator of endometrial health. Aberrant estrogen stimulation can result in infertility, endometrial cancer, and endometriosis. Here, we identified Zinc Finger MIZ-Type Containing 1 (Zmiz1) as a coregulator of uterine estrogen signaling. ZMIZ1 is colocalized with an estrogen receptor α–binding (ESR1-binding) super enhancer. ZMIZ1 mutations are found in endometrial cancer and its RNA levels trend toward reduction in endometrium of patients with endometriosis. ZMIZ1 is dynamically expressed in human endometrial tissues during the menstrual cycle. Disrupting ZMIZ1 in cultured human endometrial stromal cells resulted in impaired cell proliferation and decidual differentiation. Ablation of Zmiz1 using …

Transoral Robotic-Assisted Removal Of A Submucosal Pyriform Sinus Foreign Body, Elisabeth Wenneker, Rebecca Doctor, Ari Schuman, Adam Szymanowski, Ray Wang

Faculty, Staff and Students Publications

Background: Submucosal foreign bodies of the medial pyriform sinus represent a challenge given limited visualization and difficult retraction with endoscopic approaches, and risk of injury to the recurrent laryngeal nerve with open approaches. Transoral robotic surgery (TORS) offers improved visualization and multiple working arms to facilitate retraction. We present a novel case utilizing the Da Vinci SP system for removal of an embedded fishbone of the medial pyriform sinus.

Results: An 84-year-old woman presented with five days of odynophagia and globus sensation after swallowing a fish bone. Non-contrast computed tomography scan revealed a 3.0 cm submucosal object within the post-cricoid …

Screening For Diabetes After Solid Organ Transplantation: A 10-Year Retrospective Study, Ridwan B Ibrahim, Sneha Kumar, Sahil Malik, Joseph A Spinner, Daniel H Leung, Sridevi Devaraj

Faculty, Staff and Students Publications

Post-transplantation diabetes mellitus (PTDM) is a common and important complication after solid organ transplantation, affecting long-term outcomes. Graft rejection, decreased patient survival, infections and increased cardiovascular risk are associated with PTDM and may arise from both transplant-related and traditional risk factors. Early screening for PTDM is crucial for early detection and management. Despite clinical guidelines recommending regular screening for PTDM, screening rates remain suboptimal. This retrospective study analyzes PTDM screening rates between January 2014-January 2024 among pediatric kidney, liver, heart and lung transplant recipients at a large quaternary academic pediatric transplant center. PTDM screening rates vary by organ type, with …

Common Severity-Based Definitions Of Bronchopulmonary Dysplasia Are Not Associated With Outpatient Morbidities, Robin L Mckinney, Antonia P Popova, Milenka Cuevas Guaman, Matthew J Kielt, Paul E Moore, Sharon A Mcgrath-Morrow, Joseph M Collaco

Faculty, Staff and Students Publications

Objectives: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth, which can have life-long effects. Commonly used definitions of BPD severity are based on respiratory support at 36 weeks post-menstrual age. The utility of these definitions for tertiary referral centers outside the initial birth hospitalization is unclear.

Study design: Retrospective cohort study of infants born < 34 weeks gestation in the BPD Collaborative registry using three common definitions of BPD severity at 36 weeks post menstrual age and associated their severity with outpatient respiratory outcomes during the first 3 years of life.

Results: BPD severity by all three definitions was applied to 608 patients. Although the definitions had different distributions of BPD severity for the cohort, a majority of participants (75.7%) had moderate/Grade 2 or severe/Grade 3 BPD irrespective of the definition. Using clustered logistic …

Decreasing Barriers To The Utilization Of Cryopreserved Sperm In Male Cancer Survivors: An Expert Review And Guide, Megan V Alexander, Hailie Ciomperlik, Anna Claire Reynolds, Allyson Nevins, Luwam Ghidei, Jordan Kassab, Kevin Campbell, John Sullivan, Michael D Jochum, Laura Detti, Terri L Woodard, Larry I Lipshultz, Laurie J Mckenzie

Faculty, Staff and Students Publications

Background: Sperm cryopreservation offers male cancer patients a critical opportunity to preserve fertility prior to gonadotoxic therapy, yet utilization of banked sperm remains modest, typically under 10%. A structured understanding of barriers across the cancer survivorship continuum is needed to support patients in utilization of cryopreserved sperm in alignment with their reproductive goals.

Materials and methods: This expert review synthesizes current evidence and clinical experience to explore the multifaceted barriers to cryopreserved sperm use and propose specific solutions. Key intervention timepoints are examined, including the post-treatment fertility return visit, long-term cryopreservation while remote from family building, readiness for family building, …

Fast And Accurate Measurement Of Small Field Dosimetry Using A Novel Scintillation Detector, Yiding Han, Jingzhu Xu, Yao Hao, Baozhou Sun

Faculty, Staff and Students Publications

Background: The most used instruments for small-field dosimetry have notable limitations, including the need for correction of output factors, limited scanning speeds, and challenges in alignment for percentage depth dose (PDD) measurements, particularly for extremely small fields. However, plastic scintillation detectors (PSDs) are an attractive alternative for small-field dosimetry due to their correction-free nature, linear dose response, and fast response time.

Purpose: This study evaluates the robustness and accuracy of the dosimetric measurements using a new water-equivalent PSD in small-field dosimetry. The study also aims to report accurate measurements of output factors, profiles, and an indirect method for measuring PDD …

Health-Related Quality Of Life After Neonatal Treatment Of Symptomatic Tetralogy Of Fallot: Insights From The Congenital Cardiac Research Collaborative, George T Nicholson, Jeffrey D Zampi, Andrew C Glatz, Bryan H Goldstein, Christopher J Petit, Yun Zhang, Courtney E Mccracken, Athar M Qureshi, Caren S Goldberg, Jennifer C Romano, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Asaad Beshish, Michael L O'Byrne, R Allen Ligon, Kathryn O Stack, Hala Q Khan, Shalin Parekh, Dawn L Ilardi

Faculty, Staff and Students Publications

To evaluate the association between initial management strategy of neonatal symptomatic Tetralogy of Fallot (sTOF) and later health-related quality of life (HRQOL) outcomes. We performed a multicenter, cross-sectional evaluation of a previously assembled cohort of infants with sTOF who underwent initial intervention at ≤ 30 days of age, between 2005 and 2017. Eligible patients’ parents/guardians completed an age-appropriate Pediatric Quality of Life Inventory, a Pediatric Quality of Life Inventory Cardiac Module Heart Disease Symptoms Scale, and a parental survey. The association between treatment strategy and HRQOL was evaluated, and the entire sTOF cohort was compared to published values for the …

The Association Between Condom Use Self-Efficacy And Condom-Decision Abdication Among College Students, Mikaela Gjoka, Madison K Firkey, Alan Z Sheinfil, Sarah E Woolf-King

Faculty, Staff and Students Publications

Objective: Condomless sex and its related consequences are a persistent problem on college campuses in the United States. This study aimed to examine the association between condom use self-efficacy and condom-decision abdication among college students, and whether this association was moderated by gender.

Participants & methods: Undergraduate college students (N = 212; 50.5% female) were recruited via Amazon Mechanical Turk as part of a larger online study that examined normative feedback for condom use.

Results: The association between condom use self-efficacy and condom-decision abdication was significantly moderated by gender (B = -0.07, p < .001), such that condom use self-efficacy was associated with condom-decision abdication in college women (B = -0.05, p < .005) but not in college men (B = .02, p = .18).

Conclusion: Findings from this study suggest that …

Reconstruction Of Traumatic Carotidcavernous Fistula Using A Covered Stent, Julio Calderon, Ravi Shastri, Guhanand Venkataraman, Mohadese Ahmadzade, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

A traumatic carotid-cavernous fistula (CCF) is a significant neurovascular condition characterized by an abnormal connection between the carotid artery and the cavernous sinus, often resulting from head trauma. This condition can lead to serious complications, necessitating effective management strategies. Endovascular treatment is the preferred approach for managing this condition. We present a case of a 23-year-old male with persistent left eye pain and redness seven months post-motor vehicle collision. Cerebral angiography confirmed a high-flow CCF with compromised intracranial flow, successfully treated with a 5 mm PK Papyrus covered stent using a novel tri-axial delivery system. This case highlights the efficacy …

Evaluating Covid-19 Severity Prediction And Immune Dynamics With Nulisaseq: Insights From The Impacc Study, Koji Abe, Tyson H Holmes, Tran T Nguyen, Seunghee Kim-Schulze, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, Ruth R Montgomery, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez-Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Joanna Schaenman, Elaine F Reed, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Holden T Maecker

Faculty, Staff and Students Publications

The National Institutes of Health-funded IMPACC (IMmunoPhenotyping Assessment in a COVID-19 Cohort) evaluated longitudinal clinical and immunological features of human patients hospitalized for COVID-19. This study focuses on comparing the novel NULISAseq assay with the Olink platform using a subset of participants to assess their efficacy in predicting COVID-19 severity and understanding immune response dynamics. Our findings reveal that NULISAseq could provide superior detectability and dynamic range across various targets. Elastic net analysis demonstrated that specific proteins, including amphiregulin, effectively predict COVID-19 severity from sera at admission (samples drawn within 96 h of admission), with a test area under the …

Administration Of A Novel Reprogramming Formula Improves Cardiac Function And Decreases Cardiac Fibrosis In A Myocardial Infarction Model, Megumi Mathison, Saliha S Pathan, Aliya Lackan, Jianchang Yang, Tamer M A Mohamed, Todd K Rosengart

Faculty, Staff and Students Publications

Background: The reprogramming of fibroblasts into (induced) cardiomyocytes offers a direct myocardial regeneration strategy for improving postinfarction myocardial function. Compared to lower-order species, human cells are relatively resistant to such reprogramming. We previously found that p63-transactivation inhibitory domain (TID; the portion of p63 that physical interacts and interferes with its activation of the epigenetic repressor HDAC1) combined with the cardio-differentiation factors Hand2 and Myocardin (HM) enhanced rat and human cell transdifferentiation. The present study sought to determine the in vivo effects of this reprogramming strategy in a rat myocardial infarction model.

Methods: Adult male and female rats underwent left anterior …

The State Of Educational Research In Cardiothoracic Surgery: A Review Of The Literature, Amirtha Shekar, Victoria Hart, John Treffalls, Travis J Miles, Todd K Rosengart, Marc R Moon, Joseph S Coselli, Lauren M Barron, Shawn S Groth, Shanda H Blackmon, Ravi K Ghanta, Dawn S Hui, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: Evolving training paradigms in cardiothoracic surgery (CTS) are changing the educational needs of integrated residents and traditional fellows. Educational research is important for evaluating specialty training. This study assessed CTS education articles to analyze their prevalence, content, and reach.

Methods: In a cross-sectional observational study of education articles published on North American CTS programs from January 2013 through December 2023, articles were identified by querying PubMed, other databases, and journals. Articles that passed an initial abstract review underwent full-text review. Articles were organized by content into 9 categories: curriculum, simulation, trainee assessment, program evaluation, wellness/burnout, diversity/inclusion, mentorship/career, outcomes, and …

Technical Pitfalls And Initial Clinical Experience Using Femoral Staggered Multibranch Thoracoabdominal Aneurysm Repair Technique, Jong Hun Park, Giuliano Giova Volpiani, Alvaro Razuk, Leonardo Ferber, Lucas Ruiter Kanamori, Bruno Pagnin Schmid, Steven Maximus, Gustavo S Oderich

Faculty, Staff and Students Publications

Total transfemoral approach may be challenging in patients with narrow aortic lumens. We describe a novel total femoral staggered multibranch thoracoabdominal aortic aneurysm repair technique (FEM-SMART) to facilitate target vessel catheterization in this population. FEM-SMART is performed using a standard off-the-shelf multibranch stent graft via a total transfemoral approach. The endograft is partially deployed to the level of the celiac axis directional branch, which is selectively catheterized via contralateral femoral access using a steerable sheath. Subsequently, staggered endograft deployment, sequential catheterization of directional branches, and target vessel stenting are performed, starting with the superior mesenteric artery, followed by the renal …

Application Of The Surgical Apgar Score To Predict Intensive Care Unit Admission And Post-Operative Outcomes In Cesarean Hysterectomy For Placenta Accreta Spectrum, Emily Root, Jacqueline Curbelo, Patrick Ramsey, Jessian L Munoz

Faculty, Staff and Students Publications

Background and Objective: Placenta Accreta Spectrum (PAS) encompasses a continuum of abnormal placentation conditions associated with significant maternal and fetal morbidity. Management of PAS requires coordinated cesarean hysterectomy. Associated morbidities include blood transfusion, coagulopathy, and intensive care unit (ICU) admission. Accurate prediction of ICU admission allows for enhanced multidisciplinary management, coordination of care and utilization of resources. Scoring systems exist in other surgical specialties that can predict the likelihood of ICU admission, but these have not been applied to an obstetric population. The SAS is a 10-point scale that has been validated for the prediction of ICU-level care requirements within …

Stage- And Smoking-Associated Microrna Expression In Lung Adenocarcinoma, Min Huang, Yimin Ge, Huiqin Chen, Caimiao Wei, David Cogdell, Cristina Ivan, Meng Chen, Wei Zhang, George A Calin, Ming Guo

Faculty, Staff and Student Publications

Background: Altered expression of microRNAs (miRNAs) is implicated in lung carcinogenesis, but little research has investigated the association of miRNA alterations with lung cancer stage or smoking status. To identify such alterations in lung adenocarcinoma, we conducted miRNA profiling.

Methods: Lung adenocarcinoma specimens and paired nonneoplastic lung tissues from 58 patients who had received no preoperative therapy and underwent tumor resection from 1991 to 2006 were collected from tumor tissue banks. Thirty (52%) of the tumors were stage I and 28 (48%) stage II or higher. Twenty-five (43%) patients were nonsmokers and 33 (57%) were smokers. To identify miRNAs of …

The Gut Microbiome In Stevens-Johnson Syndrome And Sjögren's Disease: Correlations With Dry Eye, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

Changes in gut microbial composition may influence mucosal immune responses and contribute to systemic autoimmune manifestations. In this pilot exploratory study, we investigated and compared the gut microbiome in patients with Stevens–Johnson syndrome (SJS), patients with Sjögren’s disease (SjD), and healthy controls, using next-generation sequencing (NGS), and assessed correlations with dry eye parameters. The study included 10 patients with SJS matched by age and sex to 10 healthy controls, and 10 patients with SjD matched to an additional set of 10 healthy controls. Dry eye parameters were employed to evaluate dry eye disease (DED). Microbiome profiles were determined using next-generation …

Microbial Associations And Viruses On The Risk Of Celiac Disease (Mavric): A Longitudinal Post-Hoc Case-Cohort Study, Kristian F Lynch, Eric W Triplett, Heikki Hyöty, Angelica P Ahrens, Jutta E Laiho, Joseph F Petrosino, Richard E Lloyd, Daniel Agardh

Faculty, Staff and Students Publications

Celiac disease etiopathogenesis requires genetic predisposition and exposure to gluten, yet these factors alone are not sufficient. Larger longitudinal studies are needed to determine the role of time-varying infections and gut microorganisms. The aim was to design a celiac disease case-cohort longitudinal study using The Environmental Determinants of Diabetes in the Young (TEDDY) study. By age 3-years, persistent tissue transglutaminase autoantibodies (tTGA), i.e., celiac disease autoimmunity (CDA), was confirmed in 704 of the 6132 genetically at-risk TEDDY children. Celiac disease onset (CD-onset) was defined as the age CDA developed when followed by a biopsy-proven diagnosis. A competing risk analysis on …

Developmental Stage-Dependent Transcriptomic Responses To Neonatal Intraventricular Hemorrhage, Elizabeth Wallace-Anthony, Miriam Zamorano, Hemendra J Vekaria, Braden B Oldham, Kiara P Umpornpun, Scott D Olson, Stefano Berto, Brandon A Miller

Faculty, Staff and Student Publications

Neonatal intraventricular hemorrhage (IVH) is a major complication of preterm birth, yet how developmental stage influences the brain's response to injury remains unclear. We performed single-nucleus RNA sequencing on rat brains 24 h after IVH at postnatal day 2 (PND2) or day 5 (PND5) to define transcriptional responses across cell types. We identified 42 distinct cell populations and found that PND5 brains exhibited a markedly stronger immune and inflammatory response to IVH, with a threefold increase in differentially expressed genes compared to PND2. Microglia were the most perturbed cell type at both stages, showing increased oxidative stress and polarization toward …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

Faculty, Staff and Student Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Radiologist-Validated Automatic Lumbar T1-Weighted Spinal Mri Segmentation Tool Via An Attention U-Net Algorithm, Aryan Kalluvila, Ethan Wang, Michael C Hurley, Colbey Freeman, Jason M Johnson

Faculty, Staff and Student Publications

Background/Objectives: Spinal MRI segmentation has become increasingly important with the prevalence of disc herniation and vertebral injuries. Artificial intelligence can help orthopedic surgeons and radiologists automate the process of segmentation. Currently, there are few tools for T1-weighted spinal MRI segmentation, with most focusing on T2-weighted imaging. This paper focuses on creating an automatic lumbar spinal MRI segmentation tool for T1-weighted images using deep learning.

Methods: An Attention U-Net was employed as the main algorithm because the architecture has shown success in other segmentation applications. Segmentation loss functions were compared, focusing on the difference between BCE and MSE loss. Two board-certified …

Mecp2 Interacts With The Super Elongation Complex To Regulate Transcription, Jun Young Sonn, Wonho Kim, Marta Iwanaszko, Yuki Aoi, Yan Li, Guantong Qi, Luke Parkitny, Janice L Brissette, Lorin Weiner, Juan Botas, Ismael Al-Ramahi, Ali Shilatifard, Huda Y Zoghbi

Faculty, Staff and Students Publications

Loss-of-function mutations in methyl-CpG binding protein 2 (MECP2) cause Rett syndrome. While we know that MeCP2 binds to methylated cytosines on DNA, the full breadth of the molecular mechanisms by which MeCP2 regulates gene expression remains incompletely understood. Here, using a genetic modifier screen, we identify the super elongation complex, a P-TEFb–containing elongation factor that releases promoter-proximally paused RNA polymerase II, as a genetic interactor of MECP2. MeCP2 physically interacts with SEC subunits and directly binds AFF4, the scaffold of the SEC, via the transcriptional repression domain. Furthermore, MeCP2 facilitates the binding of AFF4 on a subset …

Delphi Panel On Neuromodulation As A Treatment Strategy For Dry Eye Disease: Unlocking The Potential Of Natural Tear Production, Esen Akpek, Lyndon Jones, Kelly K Nichols, Lisa M Nijm, Stephen Pflugfelder

Faculty, Staff and Students Publications

Purpose: Chronic tear deficiency, through reduced production and/or increased evaporation, is regarded as a root cause of dry eye disease (DED). The goal of treating DED is restoration of the tear film ultimately resulting in ocular surface homeostasis. Multiple therapeutic prescription drugs to manage DED exist with varying speed of onset, overall magnitude of efficacy, and tolerability. Neuromodulation is an emerging treatment modality offering direct stimulation of natural tear production. A modified Delphi study was conducted to explore the role of neuromodulation as a treatment for DED.

Methods: Twenty DED experts participated in three rounds of structured electronic Delphi questionnaires. …

A Phase 1/2 Study Of Ds-1594 Menin Inhibitor In Relapsed/Refractory Acute Leukemias, Jayastu Senapati, Marina Konopleva, Ghayas C Issa, Elias Jabbour, Tapan Kadia, Courtney Dinardo, Gautam Borthakur, Naveen Pemmaraju, Nicholas J Short, Musa Yilmaz, Indraneel Deshmukh, Joie Alvarez, Sanam Loghavi, Guilin Tang, Hussein A Abbas, Michael Andreeff, Kapil Bhalla, Narasimha M Midde, Nabil Said, Amy Noyalis, Derek E Mires, Jing Ning, Lianchun Xiao, Farhad Ravandi, Guillermo Garcia-Manero, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

Several menin inhibitors are in development targeting menin dependent leukemias, however available preclinical results show variable level of activity. We report the phase 1 portion (to establish a recommended phase 2 dose [RP2D]) and pharmacokinetic analysis of a phase 1/2 first-in-human clinical trial of DS-1594b menin inhibitor. Eligible patients included adults (≥ 18 years of age) with relapsed/refractory (R/R) acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) including but not restricted to those with KMT2A-rearrangement (r) or NPM1 mutation. Seventeen patients at a median of age 56 years (range, 19-82 years) were treated, 15 (88%) had R/R AML, and …

Soluble Immune Factor Profiles In Blood And Csf Associated With Lrrk2 Mutations And Parkinson's Disease, Roshni Jaffery, Yuhang Zhao, Sarfraz Ahmed, Jackson G Schumacher, Jae Ahn, Leilei Shi, Yujia Wang, Yukun Tan, Jiayin Zhang, Ken Chen, Hussein Tawbi, Jian Wang, Michael A Schwarzschild, Weiyi Peng, Xiqun Chen

Faculty, Staff and Student Publications

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of …

Multimodal Cardiac Imaging Of Immune-Mediated Complications Post Heart Transplantation: A Contemporary Review, Bruno Bezerra Lima, Tam T Doan, Atilla Feher, James C Wilkinson, Marvin W Kronenberg, Chloe Carr, Malek Nayfeh, Tania Ruiz, Luke L Laws, Melissa Lou Silva, John A Wells, Leandro Slipczuk, Emily T Lippincott, John J Carr, Kaushik Amancherla, Cameron Henry, David Parra, Kelly Schlendorf, Quinn S Wells, Sean G Hughes, Jonathan Soslow

Faculty, Staff and Students Publications

Heart transplantation significantly enhances survival and quality of life for patients with end-stage heart failure. Despite advances in surgical and postoperative care, immune-mediated complications, acute graft rejection and cardiac allograft vasculopathy (CAV), remain major barriers to long-term success. Acute rejection predominantly affects early posttransplant survival, whereas CAV becomes a leading cause of mortality in later years. The gold standards for diagnosis, endomyocardial biopsy for rejection and coronary angiography for CAV, are invasive and imperfect. Noninvasive multimodality imaging is increasingly used to complement or, in selected scenarios, defer invasive testing. Echocardiography with strain detects early myocardial dysfunction when ejection fraction is …