Digital Commons Network^™

Immunotherapy With Nebulized Pattern Recognition Receptor Agonists Restores Severe Immune Paralysis And Improves Outcomes In Mice With Influenza-Associated Pulmonary Aspergillosis, Jezreel Pantaleón García, Sebastian Wurster, Nathaniel D Albert, Uddalak Bharadwaj, Keerthi Bhoda, Vikram K Kulkarni, Mbaya Ntita, Paris Rodríguez Carstens, Madeleine Burch-Eapen, Daniela Covarrubias López, Jania Foncerrada Lizaola, Katherine E Larsen, Lauren M Matula, Seyed J Moghaddam, Yongxing Wang, Dimitrios P Kontoyiannis, Scott E Evans

Faculty, Staff and Student Publications

Influenza-associated pulmonary aspergillosis (IAPA) is a potentially deadly superinfection in patients with influenza pneumonia, especially those with severe disease, underlying immunosuppression, corticosteroid therapy, or requiring intensive care support. Given the high mortality of IAPA, adjunct immunomodulatory strategies remain a critical unmet need. Previously, the desensitization of pattern recognition pathways has been described as a hallmark of IAPA pathogenesis and a predictor of mortality in IAPA patients. Therefore, we studied the impact of nebulized Toll-like receptor 2/6/9 agonists Pam2 CSK4 (Pam2) and CpG oligodeoxynucleotides (ODNs) on infection outcomes and pulmonary immunopathology in a corticosteroid-immunosuppressed murine IAPA model. Mice with IAPA receiving …

Identifying Developmental Intellectual Disability As A Sudep Risk Marker From Epilepsy Monitoring Unit Reports Using Large Language Models, Ran Hu, Rashmie Abeysinghe, Gorbachev Jowah, Shiqiang Tao, Samden D. Lhatoo, Guo-Qiang Zhang, Licong Cui

Faculty, Staff and Student Publications

No abstract provided.

Clinical And Fundamental Research Progressions On Tumor-Infiltrating Lymphocytes Therapy In Cancer, Jiandong Hu, Mengli Jin, Weihong Feng, Barbara Nassif-Rausseo, Alexandre Reuben, Chunhua Ma, Gregory Lizee, Fenge Li

Faculty, Staff and Student Publications

Malignant tumors represent a significant threat to human health. Among the various therapeutic strategies available, cancer immunotherapy-encompassing adoptive cell transfer (ACT) and immune checkpoint blockade therapy-has emerged as a particularly promising approach following surgical resection, radiotherapy, chemotherapy, and molecular targeted therapies. This form of treatment elicits substantial antigen-specific immune responses, enhances or restores anti-tumor immunity, thereby facilitating the control and destruction of tumor cells, and yielding durable responses across a range of cancers, which can lead to the eradication of tumor lesions and the prevention of recurrence. Tumor-infiltrating lymphocytes (TILs), a subset of ACT, are characterized by their heterogeneity and …

Direct Parieto-Occipital Connectivity Of The Amygdala Via The Parahippocampal Segment Of The Cingulum Bundle, Arash Kamali, Kamand Khalaj, Atif Ali, Farbod Khalaj, Diana Kokash, Andres R Gonzalez, Michael A Jacobs, Alireza Akhbardeh, Paul E Schulz, Khader M Hasan

Faculty, Staff and Student Publications

Background

The amygdala is a key structure involved in memory, emotional processing, and sensory integration. While the cortical connectivity of the amygdala with the frontal and temporal lobes has been extensively studied, its direct connections with the parieto-occipital cortices remain underexplored. This study aims to delineate the direct connectivity between the amygdala and the parietal and occipital cortices via the parahippocampal segment of the cingulum bundle.

Methods

High-resolution diffusion-weighted imaging (DWI) tractography was performed on 30 healthy adult brains. Fiber tracking was conducted using three regions of interest (ROIs) placed in the parietal, occipital, and medial temporal lobes. A fractional …

Forward Genetic Screen In Zebrafish Identifies New Fungal Regulators That Limit Host-Protective Candida-Innate Immune Interaction, Bailey A Blair, Emma Bragdon, Gursimran Dhillon, Nnamdi Baker, Lena Stasiak, Mya Muthig, Pedro Miramon, Michael C Lorenz, Robert T Wheeler

Faculty, Staff and Student Publications

Candida is one of the most frequent causes of bloodstream infections, and our first line of defense against these invasive infections is the innate immune system. The early immune response is critical in controlling Candida albicans infection, but C. albicans has several strategies to evade host immune attack. Phagocytosis of C. albicans blocks hyphal growth, limiting host damage and virulence, but how C. albicans limits early recruitment and phagocytosis in vertebrate infection is poorly understood. To study innate immune evasion by intravital imaging, we utilized the transparent larval zebrafish infection model to screen 131 C. albicans mutants for altered …

Molecular Characterization And Predictors Of Relapse In Patients With Ph + All After Frontline Ponatinib And Blinatumomab, Nicholas J Short, Hagop Kantarjian, Ken Furudate, Nitin Jain, Farhad Ravandi, Omer Karrar, Sanam Loghavi, Lewis Nasr, Fadi G Haddad, Jayastu Senapati, Rebecca Garris, Koichi Takahashi, Elias Jabbour

Faculty, Staff and Student Publications

Background: Several studies have suggested that chemotherapy-free regimens consisting of blinatumomab and a BCR::ABL1 tyrosine kinase inhibitor are highly effective in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, the clinical and molecular characteristics that predict for relapse with these chemotherapy-free regimens are largely unknown.

Methods: We conducted a prospective phase II clinical trial of the combination of blinatumomab and ponatinib in 76 patients with newly diagnosed Ph + ALL. Patients received 12-15 doses of intrathecal chemotherapy as central nervous systemic (CNS) prophylaxis. The patterns of relapse and the clinical and molecular predictors of relapse were analyzed.

Results: With …

Role Of Systemic Therapy In Localized Renal Cell Carcinoma: Where Do We Stand And Where Are We Heading?, Deepa Raghavan, Viktoriya Gibatova, Nikhil Vojjala, Nagaishwarya Moka, Aihua Edward Yen

Faculty, Staff and Students Publications

The effectiveness of immunotherapy and targeted therapy has been well established in metastatic renal cell cancer (mRCC). These therapies demonstrated higher overall response rates and led to prolonged survival. In contrast, in localized RCC, conventional treatment is either partial or complete nephrectomy. While surgery is a curative option in early stages, high recurrence rates remain a concern, with survival rates ranging from 53% to 85%, depending on the initial stage at the time of diagnosis. Given favorable outcomes with systemic therapies in the metastatic setting, there has also been an increased interest in utilizing these therapies for the localized stage …

Spatial Epigenomic Niches Underlie Glioblastoma Cell State Plasticity, Sam Kint, Subhi Talal Younes, Shuozhen Bao, Gretchen Long, David Wouters, Erin Stephenson, Xing Lou, Mei Zhong, Di Zhang, Graham Su, Archibald Enninful, Mingyu Yang, Huey-Miin Chen, Katrina Ellestad, Colleen Anderson, Jennifer Moliterno, John Kelly, Jennifer A Chan, Alejandro Sifrim, Jiangbing Zhou, Ana Nikolic, Rong Fan, Marco Gallo

Faculty, Staff and Students Publications

IDH-wildtype glioblastoma (GBM) is an aggressive brain tumor with poor survival and few therapeutic options. Transcriptionally-defined cell states coexist in GBM and occupy defined regions of the tumor. Evidence indicates that GBM cell states are plastic, but it remains unclear if they are determined by the underlying epigenetic state and/or by microenvironmental factors. Here, we present spatially-resolved epigenomic profiling of human GBM tissues that implicate chromatin structure as a key enabler of cell plasticity. We report two epigenetically-defined and spatially-nested tumor niches. Each niche activates short-range molecular signals to maintain its own state and, surprisingly, long-range signals to reinforce …

Theta Oscillons In Behaving Rats, M S Zobaer, Nastaran Lotfi, Carli M Domenico, Clarissa Hoffman, Luca Perotti, Daoyun Ji, Yuri Dabaghian

Faculty, Staff and Students Publications

Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional θ-waves. The resemblances between θ-oscillons and the conventional θ-waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the θ-rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled …

The Genestar Manual For Biospecimen Collection Biobanking And Omics Data Generation From Commercial Space Missions, Aparna Krishnavajhala, Marie-Claude Gingras, Emmanuel Urquieta, Hsu Chao, Dilrukshi Bandaranaike, Yi Chen, Sravya Bhamidipati, Viktoriya Korchina, S Michelle Griffin, Michal M Masternak, Hannah Moreno, Javid Mohammed, Mullai Murugan, Jennifer E Posey, Jimmy H Wu, Donna Muzny, Richard A Gibbs, Harsha Doddapaneni

Faculty, Staff and Students Publications

The surge in commercial and civilian spaceflight enables the systematic and longitudinal, large-scale biospecimen collection to understand the prospective effects of space travel on human health. The Genomics and Space Medicine (Space Omics) project at BCM-HGSC involves a comprehensive biospecimen collection plan from commercial/private space flight participants. The manuscript addresses the critical gaps in the biospecimen collection process including details of the informed consent process, a provision for subjects to obtain custom CLIA-WGS reports, a data dictionary and a LIMS enabled biobank. The manuscript also discusses the biospecimens collection, processing methodologies and nucleic acid suitability for Omics data generation. Results …

Therapeutic Left-To-Right Shunting In Heart Failure, Francesco Fioretti, Ajith P Nair, Stefan D Anker, Barry A Borlaug, Dean J Kereiakes, Joann Lindenfeld, Gregg W Stone, Javed Butler

Faculty, Staff and Students Publications

Heart failure with reduced or preserved ejection fraction is associated with elevated left atrial pressure at rest due to fluid overload or during exercise, leading to pulmonary venous congestion. Even with available treatments, heart failure hospitalizations remain high, and improvements in quality-of-life scores and functional capacity are modest. Thus, there is growing interest in non-pharmacological methods to decompress the left atrium and improve heart failure symptoms and outcomes. Left-to-right shunts have emerged as a potential therapeutic option to reduce left atrial hypertension, improve quality of life, and impact long-term outcomes. This nascent field carries both potential therapeutic promise and many …

Genome-Wide Allele-Specific Expression In Multi-Tissue Samples From Healthy Male Baboons Reveals The Transcriptional Complexity Of Mammals, Ramesh Ramasamy, Muthuswamy Raveendran, R Alan Harris, Hiep D Le, Ludovic S Mure, Giorgia Benegiamo, Ouria Dkhissi-Benyahya, Howard Cooper, Jeffrey Rogers, Satchidananda Panda

Faculty, Staff and Students Publications

Allele-specific expression (ASE) is pivotal in understanding the genetic underpinnings of phenotypic variation within species, differences in disease susceptibility, and responses to environmental factors. We processed 11 different tissue types collected from 12 age-matched healthy olive baboons (Papio anubis) for genome-wide ASE analysis. By sequencing their genomes at a minimum depth of 30×, we identified over 16 million single-nucleotide variants (SNVs). We also generated long-read sequencing data, enabling the phasing of all variants present within the coding regions of 96.5% of assayable protein-coding genes as a single haplotype block. Given the extensive heterozygosity of baboons relative to humans, we could …

Author Correction: Risk-Stratified Treatment For Drug-Susceptible Pulmonary Tuberculosis, Vincent K Chang, Marjorie Z Imperial, Patrick P J Phillips, Gustavo E Velásquez, Payam Nahid, Andrew Vernon, Ekaterina V Kurbatova, Susan Swindells, Richard E Chaisson, Susan E Dorman, John L Johnson, Marc Weiner, Amina Jindani, Thomas Harrison, Erin E Sizemore, William Whitworth, Wendy Carr, Kia E Bryant, Deron Burton, Kelly E Dooley, Melissa Engle, Pheona Nsubuga, Andreas H Diacon, Nguyen Viet Nhung, Rodney Dawson, Radojka M Savic, Aids Clinical Trial Group, Tuberculosis Trials Consortium

Faculty, Staff and Student Publications

No abstract provided.

Ogg1s326c Variant Frequent In Human Populations Facilitates Inflammatory Responses Due To Its Extended Interaction With Dna Substrate, Jinling Han, Meichen Zhang, Jiakun Ge, Zhihua Ji, Jianyi Zhao, Yinchao Hu, Chunshuang Li, Yaoyao Xue, Xining Li, Haiwang Zhao, Zixu Cui, Miaomiao Tian, Xu Zheng, Dapeng Wang, Jing Wang, Min Wei, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba

Faculty, Staff and Student Publications

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1^S326C, prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1^S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1^S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but …

A Pharmacokinetic And Safety Study Of Oral Arsenic Trioxide In Patients With Acute Promyelocytic Leukemia, Farhad Ravandi, Sravanti Rangaraju, Hagop Kantarjian, Guillermo Garcia-Manero, Musa Yilmaz, Kristen Baker, Terence Hall, Joy Grabenstein, Pourab Roy, Beth A Zamboni, William C Zamboni, Erica Warlick, Michael Kelly, David A Roth, Gabriel Ghiaur

Faculty, Staff and Student Publications

SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the …

Genetic, Transcriptomic, And Epigenomic Insights Into Sjögren's Disease: An Integrative Network Investigation And Immune Diseases Comparison, Nitesh Enduru, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, …

Phase I Study Of Pomalidomide In Relapsed Or Refractory Waldenström Macroglobulinaemia, Karan L Chohan, Donna M Weber, Lei Feng, L Michael Wang, Sattva S Neelapu, Jasper Olsem, Ralph J Johnson, Claudia Morales De Partovi, Robert Z Orlowski, Sheeba K Thomas

Faculty, Staff and Student Publications

No abstract provided.

Loss Of Progesterone Receptor In Smooth Muscle Cells Has No Impact On Oviductal Contractions And Preimplantation Embryo Development†, Emily A Mcglade, Jiude Mao, Kalli K Stephens, Cayce N Rose, John P Lydon, Wipawee Winuthayanon

Faculty, Staff and Students Publications

No abstract provided.

Temporal Regulation Of Early-Stage Cytokine Expression In Diabetic Wound Healing Under Negative Pressure Wound Therapy, Hua-Sheng Chiu, Ting-Shuo Huang, Chien-Tzung Chen, Xin-Yu Lin, Po-Cheng Liao, Cai-Cin Liou, Chih-Chin Hsu, Sonal Somvanshi, Pavel Sumazin, Pang-Hung Hsu, Chi-Chin Sun, Yu-Chiau Shyu

Faculty, Staff and Students Publications

Negative pressure wound therapy (NPWT) is widely recognized for its efficacy in treating diabetic wounds, but the mechanisms involved in the wound healing process remain unclear. By examining changes in blood cytokine levels as molecular signaling precursors, we aim to provide a comprehensive cytokine profile to support adjunctive therapy research and clinical applications. A diabetic mouse wound model was established to compare cytokine profiles between NPWT-treated and standard dressing groups, identifying key signaling candidates that may facilitate wound healing. By integrating normal mouse data with large-scale cytokine analysis, we developed a time-stratified NPWT approach to track acute-phase cytokine fluctuations in …

Disruption Of Oocyte Sumoylation Impacts Critical Regulatory Processes During Folliculogenesis In Mice, Zian Liao, Tessa E Steenwinkel, Bruno Moscoso, Ernesto Salas, Bethany K Patton, Amanda Rodriguez, Anna Malovannaya, Stephanie A Pangas

Faculty, Staff and Students Publications

The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may …

Smooth Muscle Cells And Fibroblasts In The Ascending Aorta Exhibit Minor Differences Between Embryonic Origins In Angiotensin Ii-Driven Transcriptional Alterations, Sohei Ito, David B Graf, Yuriko Katsumata, Jessica J Moorleghen, Chen Zhang, Yanming Li, Scott A Lemaire, Ying H Shen, Hong S Lu, Alan Daugherty, Hisashi Sawada

Faculty, Staff and Students Publications

Thoracic aortopathy is influenced by angiotensin II (AngII) and exhibits regional heterogeneity with the ascending aorta being particularly susceptible. In this region, smooth muscle cells (SMCs) and selected fibroblasts originate from the second heart field (SHF) and cardiac neural crest (CNC). While our previous study revealed a critical role of SHF-derived cells in AngII-mediated aortopathy, the contribution of CNC-derived cells remains unclear. To investigate lineage-specific responses to AngII, Mef2c-Cre R26RmT/mG mice were infused with AngII. Ascending aortas were harvested at baseline or after 3 days of infusion, representing the prepathological phase. Cells were sorted based on their embryonic origins and …

Long-Term Outcomes Of Resolute Onyx Zotarolimus-Eluting Stents For Symptomatic Intracranial Stenosis: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Omid Shoraka, Ramesh Grandhi, Samantha Miller, Joanna Roy, Vinay Jaikumar, Basel Musmar, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Adnan H Siddiqui, Farhan Siddiq, Ameer E Hassan

Faculty, Staff and Students Publications

Background

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke. The Medtronic Resolute Onyx Zotarolimus-eluting stents (RO-ZES) are promising in preventing stroke recurrence compared with medical management (MM) and percutaneous angioplasty and stenting (PTAS) at both 30-day and one-year follow-ups. We evaluated long-term outcomes for patients treated with RO-ZES, PTAS, or MM.

Methods

A retrospective multicenter study was conducted including patients who underwent RO-ZES stenting for symptomatic ICAD between March 2018 and May 2023, with follow-up through October 2024. Propensity score-matched control groups, representing MM and PTAS, were derived from the SAMMPRIS trial. Primary outcomes included recurrence rates …

Effect Of Race On Procedural And Clinical Outcomes In Middle Meningeal Artery Embolization For Primary And Adjunctive Treatment Of Chronic Subdural Hematoma, Santiago Gomez-Paz, Mohamed M Salem, Cordell Baker, Okkes Kuybu, Georgios S Sioutas, Kate T Carroll, Mira Salih, Adam A Dmytriw, Jane Khalife, William Smith, Diego Alejandro Ortega Moreno, Robert W Regenhardt, Nicole M Cancelliere, Alejandro M Spiotta, Omar Tanweer, Christopher J Stapleton, Michael Lang, Vitor M Pereira, Aman B Patel, Adnan H Siddiqui, Elad I Levy, Christopher S Ogilvy, Daniel Tonetti, Ajith J Thomas, Visish M Srinivasan, Brian T Jankowitz, Michael R Levitt, Bradley A Gross, Jan-Karl Burkhardt, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

We investigated racial disparities in radiologic and clinical outcomes of patients after middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) with or without evacuation surgery.

Methods

This multicenter retrospective study includes consecutive patients who underwent MMAE across 11 institutions in North America (10 in the United States and 1 in Canada). Patients were stratified using self-reported racial data. Outcomes of interest were complications, treatment failure/reoperations, resolution of hematoma, and functional independence at last follow-up. Multivariable regression models were used to assess and adjust for relevant confounders.

Results

A total of 557 patients underwent 663 MMAEs, including 323 …

Dnmt3a Regulates Murine Megakaryocyte-Biased Hematopoietic Stem Cell Fate Decisions, Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna G Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel Rau, Ashlyn G Laidman, Maria N Barrachina, Estelle Carminita, Justin A Courson, Michael R Williamson, Joanne I Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando E Rumbaut, Alan R Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell

Center on Aging Staff Publications

Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has distinct consequences compared with the rest of the HSC pool. These megakaryocyte-biased …

International Multi-Center Study Of Middle Meningeal Artery Embolization For Chronic Subdural Hematoma In Cancer Patients: Efficacy, Safety, And Outcomes In A High-Risk Population, Avi A Gajjar, Mohamed M Salem, Georgios S Sioutas, Rashad Jabarkheel, Okkes Kuybu, Jane Khalife, Daniel A Tonetti, Gustavo Cortez, Adam A Dmytriw, Diego Alejandro Ortega Moreno, William Smith, Robert W Regenhardt, Kate T Carroll, Zachary A Abecassis, Juan Francisco Ruiz Rodriguez, Oleg Shekhtman, Alex Nguyen Hoang, Alexander A Khalessi, Cordell Baker, Matthias Matejka, Nicole M Cancelliere, Christoph J Griessenauer, Ramesh Grandhi, Peter Kan, Omar Tanweer, Michael R Levitt, Christopher J Stapleton, Vitor Mendes Pereira, Brian Jankowitz, Howard A Riina, Aman B Patel, Ricardo Hanel, Ajith J Thomas, Michael J Lang, Bradley A Gross, Jan-Karl Burkhardt, Visish M Srinivasan

Faculty, Staff and Students Publications

Background

Middle meningeal artery embolization (MMAE) is a promising treatment for chronic subdural hematoma (cSDH). Cancer patients are at risk for cSDH due to thrombocytopenia. The efficacy of MMAE in this population has not been studied.

Methods

We conducted a retrospective analysis of 76 patients who underwent 94 MMAEs for cSDH at 12 tertiary centers across North America and Europe between February 2018 and January 2023. We analyzed patient demographics, clinical profiles, procedural details, and outcomes. The primary outcome was cSDH progression, while secondary outcomes included radiographic resolution, mortality, 90-day functional outcomes, functional improvement, and procedural complications.

Results

Radiographic improvement …

Implementation Of Safety Restraint Chair Algorithm With De-Escalation Techniques To Decrease Restraint Time In Acute Psychiatric Unit, Chiamaka Nwadike

Doctor of Nursing Practice Final Project Abstract

Purpose: This quality improvement project aims to (1) decrease time in restraint use on the inpatient psychiatric unit through implementing the restraint chair protocol, and (2) improve staff satisfaction in using safety restraint.

Background: In acute psychiatric care, restraints are used to ensure safety, but they pose physical and psychological risks. There is an increasing recognition of the need for patient safety, including the use of de-escalation techniques that prioritize restraint chairs over bed restraints to ensure safety.

Methodology: The project follows the Plan-Do-Study-Act (PDSA) model, which supports a continuous improvement approach to implementing the restraint chair …

Risk Of Coronary Obstruction In Redo-Transcatheter Aortic Valve Replacement Between Bicuspid And Tricuspid Aortic Valves, Atsushi Okada, Syed Zaid, Miho Fukui, Evan Walser-Kuntz, Larissa I Stanberry, Marcus R Burns, John R Lesser, João L Cavalcante, Paul Sorajja, Vinayak N Bapat

Faculty, Staff and Students Publications

Background: Transcatheter aortic valve replacement (TAVR) is approved across all risk profiles, including patients with bicuspid aortic valves. These patients are generally younger, with a higher chance of reintervention.

Objectives: The aim of this study was to compare the feasibility of redo transcatheter aortic valve (TAV) between bicuspid and tricuspid aortic valves.

Methods: A computed tomographic (CT) simulation of redo-TAV was conducted using 913 post-TAVR CT studies from patients who underwent TAVR with SAPIEN 3 or SAPIEN 3 Ultra (S3; n = 623) or Evolut R, Evolut PRO, or Evolut PRO+ (Evolut; n = 290) valves. Fifty-nine cases were for …

Structural Proteomics Defines A Sequential Priming Mechanism For The Progesterone Receptor, Matthew D Mann, Min Wang, Josephine C Ferreon, Phoebe S Tsoi, Michael P Suess, Antrix Jain, Anna Malovannaya, Roberto Vera Alvarez, Bruce D Pascal, Raj Kumar, Dean P Edwards, Patrick R Griffin

Faculty, Staff and Students Publications

The progesterone receptor (PR) is a steroid-responsive nuclear receptor with two isoforms: PR-A and PR-B. Disruption of PR-A:PR-B signaling is associated with breast cancer through interactions with oncogenic co-regulatory proteins (CoRs). However, molecular details of isoform-specific PR-CoR interactions remain poorly understood. Using structural mass spectrometry, we investigate the sequential binding mechanism of purified full-length PR and intact CoRs, steroid receptor coactivator 3 (SRC3) and p300, as complexes on target DNA. Our findings reveal selective CoR NR-box binding by PR and unique interaction surfaces between PR and CoRs during complex assembly, providing a structural basis for CoR sequential binding on PR. …

Should Physicians Take The Rap? Normative Analysis Of Clinician Perspectives On Responsible Use Of 'Black Box' Ai Tools, Ben H Lang, Kristin Kostick-Quenet, Jared N Smith, Meghan Hurley, Rita Dexter, Jennifer Blumenthal-Barby

Center for Medical Ethics and Health Policy Staff Publications

Background: Increasing interest in deploying artificial intelligence tools in clinical contexts has raised several ethical questions of both normative and empirical interest. One such question in the literature is whether "responsibility gaps" (r-gaps) are created when clinicians utilize or rely on such tools for providing care, and if so, what to do about them. These gaps are particularly likely to arise when using opaque, "black box" AI tools. Compared to normative and legal analysis of AI-generated responsibility gaps in health care, little is known, empirically, about health care providers views on this issue. The present study examines clinician perspectives on …

Defining Three Principles For Credible Evidence Synthesis And Reviews In Health Professions Education, Michelle Daniel, Morris Gordon, Hussein Uraiby, Peter Boedeker, Janice Hanson, Diana Dolmans, Satid Thammasitboon

Faculty, Staff and Students Publications

As reviews become increasingly central to informing educational practice and guiding research in health professions education, the need for methodological clarity and quality has grown. This Commentary highlights three foundational principles - alignment, rigor, and transparency - that underpin high-quality reviews, regardless of type. We illustrate how these principles apply across commonly used review types, including systematic, scoping, realist, and narrative reviews. By aligning the research question with the appropriate review methodology, employing rigorous processes for evidence collection and synthesis, and maintaining transparency in methodological reporting, review teams can produce credible, transferable, and dependable findings. Embracing these principles not only …