Medical Specialties Commons^™

Improved Synthesis And Anticancer Activity Of A Potent Neuronal Nitric Oxide Synthase Inhibitor, Dhananjayan Vasu, Cory T. Reidl, Eric Wang, Sun Yang, Richard B. Silverman

Pharmacy Faculty Articles and Research

An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Correction Of T-Cell Repertoire And Autoimmune Diabetes In Nod Mice By Non-Myeloablative T-Cell Depleted Allogeneic Hsct, Rakefet Sidlik Muskatel, Bar Nathansohn-Levi, Shlomit Reich-Zeliger, Michal Mark, Liat Stoler-Barak, Chava Rosen, Irit Milman-Krentsis, Esther Bachar Lustig, Robert Pete Gale, Nir Friedman, Yair Reisner

Faculty, Staff and Student Publications

The induction of partial tolerance toward pancreatic autoantigens in the treatment of type 1 diabetes mellitus (T1DM) can be attained by autologous hematopoietic stem cell transplantation (HSCT). However, most patients treated by autologous HSCT eventually relapse. Furthermore, allogeneic HSCT which could potentially provide a durable non-autoimmune T-cell receptor (TCR) repertoire is associated with a substantial risk for transplant-related mortality. We have previously demonstrated an effective approach for attaining engraftment without graft versus host disease (GVHD) of allogeneic T-cell depleted HSCT, following non-myeloablative conditioning, using donor-derived anti-3rd party central memory CD8 veto T cells (Tcm). In the present study, we investigated …

Open-Label, Expanded-Access Study Of A Bioengineered Allogeneic Cellularized Construct In Adults With Deep Partial- Thickness Burns, Angela Gibson, Victor Joe, Joshua Carson, Jeff Litt, Jeffrey Carter, James Holmes

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Adipose Derived Stem Cell Paracrine Factor Release In Smokers Vs Non Smokers With Burn Injuries, Paige Deville, Alison Smith, Herbert Phelan, Jeffrey Carter, Olivia Warren, Cameron Fontenot

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

The Rising Use Of Fire As A Weapon, Jason Woods, Jeffrey Carter, Kathe Conlon, Carl Flores, Randy Kearns

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Characteristics Of Verified And Designated Burn Centers, Jeffrey Carter, Randy Kearns, Elle Lovick, Erica Murata, Bart Phillips

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Donor Site Reduction With Combined Use Of Bromelain Enzymatic Debridement And Autologous Skin Cell Suspension, Steven A. Kahn, Jeffrey E. Carter, Gabriel G. Gaweda, Elizabeth Halicki, William L. Hickerson, Ashley Hink, James H. Holmes, Deepak Ozhathil, Narayan Raghava

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

An Exploratory Study On Strategies Adopted By Parents Who Use E-Cigarettes To Negotiate Risk Perceptions Of Their Children's Secondhand Exposure And Parental Role Modeling, Joon Kyung Nam, Jesse P Zatloff, Su-Wei Wong, Hsien-Chang Lin, Wei-Chung Su, Anne Buu

Faculty, Staff and Student Publications

Existing health messages mainly targeted youth susceptible to vaping or parents who do not have much knowledge about e-cigarettes. This study makes a unique contribution by conducting the first in-depth investigation of e-cigarette-using parents' risk perceptions and parental role modeling and how these two factors affect their vaping behaviors at home or implementation of any strategies to reduce their children's risk. Fifteen parents who used e-cigarettes participated in a semi-structured interview. Interview transcripts were coded and analyzed through a deductive approach of thematic analysis. This study demonstrates the need to develop and disseminate future health messages for e-cigarette-using parents who …

Immunologic Predictors For Clinical Responses During Immune Checkpoint Blockade In Patients With Myelodysplastic Syndromes, Sung-Eun Lee, Feng Wang, Maison Grefe, Abel Trujillo-Ocampo, Wilfredo Ruiz-Vasquez, Koichi Takahashi, Hussein A Abbas, Pamella Borges, Dinler Amaral Antunes, Gheath Al-Atrash, Naval Daver, Jeffrey J Molldrem, Andrew Futreal, Guillermo Garcia-Manero, Jin S Im

Faculty, Staff and Student Publications

PURPOSE: The aim of this study is to determine immune-related biomarkers to predict effective antitumor immunity in myelodysplastic syndrome (MDS) during immunotherapy (IMT, αCTLA-4, and/or αPD-1 antibodies) and/or hypomethylating agent (HMA).

EXPERIMENTAL DESIGN: Peripheral blood samples from 55 patients with MDS were assessed for immune subsets, T-cell receptor (TCR) repertoire, mutations in 295 acute myeloid leukemia (AML)/MDS-related genes, and immune-related gene expression profiling before and after the first treatment.

RESULTS: Clinical responders treated with IMT ± HMA but not HMA alone showed a significant expansion of central memory (CM) CD8+ T cells, diverse TCRβ repertoire pretreatment with increased clonality and …

An Opportunity To Increase Collaborative Science In Fetal, Infant, And Toddler Neuroimaging, Marta Korom, M Catalina Camacho, Aiden Ford, Hana Taha, Dustin Scheinost, Marisa Spann, Kelly A Vaughn

Faculty, Staff and Student Publications

The field of fetal, infant, and toddler (FIT) neuroimaging research—including magnetic resonance imaging (MRI), electroencephalography (EEG), magnetoencephalography, and functional near-infrared spectroscopy, among others—offers pioneering insights into early brain development and has grown in popularity over the past 2 decades. In broader neuroimaging research, multisite collaborative projects, data sharing, and open-source code have increasingly become the norm, fostering big data, consensus standards, and rapid knowledge transfer and development. Given the aforementioned benefits, along with recent initiatives from funding agencies to support multisite and multimodal FIT neuroimaging studies, the FIT field now has the opportunity to establish sustainable, collaborative, and open science …

Structural Insights Into Ligand Recognition And Selectivity Of Somatostatin Receptors, Corey F Hryc, Venkata K P S Mallampalli, Evgeniy I Bovshik, Stavros Azinas, Guizhen Fan, Irina I Serysheva, Genevieve C Sparagna, Matthew L Baker, Eugenia Mileykovskaya, William Dowhan

Faculty, Staff and Student Publications

Cardiolipin is a hallmark phospholipid of mitochondrial membranes. Despite established significance of cardiolipin in supporting respiratory supercomplex organization, a mechanistic understanding of this lipid-protein interaction is still lacking. To address the essential role of cardiolipin in supercomplex organization, we report cryo-EM structures of a wild type supercomplex (IV

Telehealth Clinical Appropriateness And Quality, Lulu Wang, Anthony Fabiano, Arjun K. Venkatesh, Nick Patel, Judd E. Hollander

Department of Emergency Medicine Faculty Papers

Contrary to common perception, telehealth is not simply a substitute for in-person care. With an array of modalities—live audio–video, asynchronous patient communication, and remote patient monitoring, to name a few—telehealth creates entirely new avenues of care delivery (Table 1). Although our current care model is reactive—relying on episodic visits to an office or hospital—telehealth allows us to be proactive, filling in the gaps to provide a continuum of care. Widespread uptake of telehealth has created fertile ground for long-overdue health system reform. In this study, we describe essential next steps: redefine telehealth clinical appropriateness, evolve payment models, provide necessary training, …

Effects Of Prenatal Pesticide Exposure On The Fetal Brain And Placenta Transcriptomes In A Rodent Model, Corina Lesseur, Kirtan Kaur, Sean D Kelly, Karen Hermetz, Randy Williams, Ke Hao, Carmen J Marsit, W Michael Caudle, Jia Chen

Faculty, Staff and Student Publications

Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6 J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5 mg/kg, a pyrethroid, deltamethrin (DM), at 3 mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational …

Surgeons’ Knowledge Regarding Perioperative Pain Management In Patients With Opioid Use Disorder: A Survey Among 260 Members Of The American College Of Surgeons, Caroline E Crocker, Romana Sharmeen, Thu T Tran, Amir M Khan, Wen Li, Joseph L Alcorn

Faculty, Staff and Student Publications

Surfactant protein A (SP-A) has important roles in innate immunity and modulation of pulmonary and extrapulmonary inflammation. Given SP-A has been detected in rat and human brain, we sought to determine if SP-A has a role in modulating inflammation in the neonatal mouse brain. Neonatal wildtype (WT) and SP-A-deficient (SP-A

Clinically Stable Covid-19 Patients Presenting To Acute Unscheduled Episodic Care Venues Have Increased Risk Of Hospitalization: Secondary Analysis Of A Randomized Control Trial, Joseph Bledsoe, Scott C Woller, Maria Brooks, Frank C Sciurba, Jerry A Krishnan, Deborah Martin, Peter Hou, Janet Y Lin, Andrei Kindzelski, Eileen Handberg, Bridget-Anne Kirwan, Elaine Zaharris, Lauren Castro, Nancy L Shapiro, Carl J Pepine, Sarah Majercik, Zhuxuan Fu, Yongqi Zhong, Vidya Venugopal, Yu-Hsuan Lai, Paul M Ridker, Jean M Connors

Faculty, Staff and Student Publications

BACKGROUND: Assessment for risks associated with acute stable COVID-19 is important to optimize clinical trial enrollment and target patients for scarce therapeutics. To assess whether healthcare system engagement location is an independent predictor of outcomes we performed a secondary analysis of the ACTIV-4B Outpatient Thrombosis Prevention trial.

METHODS: A secondary analysis of the ACTIV-4B trial that was conducted at 52 US sites between September 2020 and August 2021. Participants were enrolled through acute unscheduled episodic care (AUEC) enrollment location (emergency department, or urgent care clinic visit) compared to minimal contact (MC) enrollment (electronic contact from test center lists of positive …

Secondary Immunohistochemical Analysis Of Viable Cells As Determined By Hematoxylin And Eosin Staining, Bonnie Carney, Cameron D'Orio, Jeffrey Shupp, Jeffrey Carter, William Hickerson, James Holmes, Herbert Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Glutamatergic Cerebellar Neurons Differentially Contribute To The Acquisition Of Motor And Social Behaviors, Meike E Van Der Heijden, Alejandro G Rey Hipolito, Linda H Kim, Dominic J Kizek, Ross M Perez, Tao Lin, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Insults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social …

Kras Hijacks The Mirna Regulatory Pathway In Cancer, Angelina S Bortoletto, Ronald J Parchem

Faculty, Staff and Students Publications

Extensive studies have focused on the misregulation of individual miRNAs in cancer. More recently, mutations in the miRNA biogenesis and processing machinery have been implicated in several malignancies. Such mutations can lead to global miRNA misregulation, which may promote many of the well-known hallmarks of cancer. Interestingly, recent evidence also suggests that oncogenic Kristen rat sarcoma viral oncogene homolog (KRAS) mutations act in part by modulating the activity of members of the miRNA regulatory pathway. Here, we highlight the vital role mutations in the miRNA core machinery play in promoting malignant transformation. Furthermore, we discuss how mutant KRAS can simultaneously …

Cardiac Pericytes Mediate The Remodeling Response To Myocardial Infarction, Pearl Quijada, Shuin Park, Peng Zhao, Kamal Ss Kolluri, David Wong, Kevin D Shih, Kai Fang, Arash Pezhouman, Lingjun Wang, Ali Daraei, Matthew D Tran, Elle M Rathbun, Kimberly N Burgos Villar, Maria L Garcia-Hernandez, Thanh Td Pham, Charles J Lowenstein, M Luisa Iruela-Arispe, S Thomas Carmichael, Eric M Small, Reza Ardehali

Faculty, Staff and Students Publications

Despite the prevalence of pericytes in the microvasculature of the heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that pericytes migrated to the injury site and expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq of cardiac pericytes at various time points after MI revealed the temporally regulated induction of genes related to vascular permeability, extracellular matrix production, basement membrane degradation, and TGF-β signaling. Deleting TGF-β receptor 1 in chondroitin sulfate proteoglycan 4-expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading to a transient improvement in the cardiac …

Ragd Auto-Activating Mutations Impair Mit/Tfe Activity In Kidney Tubulopathy And Cardiomyopathy Syndrome, Irene Sambri, Marco Ferniani, Giulia Campostrini, Marialuisa Testa, Viviana Meraviglia, Mariana E G De Araujo, Ladislav Dokládal, Claudia Vilardo, Jlenia Monfregola, Nicolina Zampelli, Francesca Del Vecchio Blanco, Annalaura Torella, Carolina Ruosi, Simona Fecarotta, Giancarlo Parenti, Leopoldo Staiano, Milena Bellin, Lukas A Huber, Claudio De Virgilio, Francesco Trepiccione, Vincenzo Nigro, Andrea Ballabio

Duncan NRI Faculty and Staff Publications

Heterozygous mutations in the gene encoding RagD GTPase were shown to cause a novel autosomal dominant condition characterized by kidney tubulopathy and cardiomyopathy. We previously demonstrated that RagD, and its paralogue RagC, mediate a non-canonical mTORC1 signaling pathway that inhibits the activity of TFEB and TFE3, transcription factors of the MiT/TFE family and master regulators of lysosomal biogenesis and autophagy. Here we show that RagD mutations causing kidney tubulopathy and cardiomyopathy are "auto- activating", even in the absence of Folliculin, the GAP responsible for RagC/D activation, and cause constitutive phosphorylation of TFEB and TFE3 by mTORC1, without affecting the phosphorylation …

Burn Injury Assessment Study (Bias): Is There Room To Improve?, Jeffrey Carter, Herbert Phelan, John Friedstat, William Hickerson, James Holmes, James Hwang, Steven Kahn, Alisa Savetamal, Jeffrey Shupp

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Autologous Skin Cell Suspensions For Reconstruction Of Nonthermal Soft Tissue Wounds: A Case Series, Paige Deville, Elle Lovick, Jeffrey Carter, Herbert Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Injury To Intervention: Is There Another Opportunity To Improve Burn Care?, William L. Hickerson, Jeffrey E. Carter, John Friedstat, James H. Holmes, James Hwang, Steven A. Kahn, Herbert A. Phelan, Alisa Savetamal

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Access To Burn Care: A 10 Year Perspective Of Burn Centers In The U.S, Elle Lovick, Jeffrey Carter, Herbert Phelan, Randy Kearns, Bart Phillips, William Hickerson

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

A Pilot Study Of Hand Autografts Treated With Autologous Skin Cell Suspension, Paige Deville, Jeffrey E. Carter, Madeline Lechtenberg, Herbert A. Phelan

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16 - 19, 2023, Dallas, TX

Select Survey Of Human Cadaver Skin Allograft Utilization By 21 Senior Academic Burn Surgeons, William Hickerson, Franco Aveau, Narayan Iyer, James Jeng, Victor Joe

School of Medicine Faculty Publications

55th Annual Meeting of the American Burn Association, ABA 2023, May 16-19,2023, Dallas, TX

Feature Selection From Clinical Surveys Using Semantic Textual Similarity, Benjamin Warner

McKelvey School of Engineering Graduate Student Theses & Dissertations

Survey data collected from human subjects can contain a high number of features while having a comparatively low quantity of examples. Machine learning models that attempt to predict outcomes from survey data under these conditions can overfit and result in poor generalizability. One remedy to this issue is feature selection, which attempts to select an optimal subset of features to learn upon. A relatively unexplored source of information in the feature selection process is the usage of textual names of features, which may be semantically indicative of which features are relevant to a target outcome. The relationships between feature names …

Observations On The Present And The Future Of Hip Surgery, Alberto Di Martino

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

A Systematic Literature Review Of Telehealth For Health Equity In Pediatric And Women's Health Care: Promise Vs Reality, Sharanya Chandu

Honors Scholar Theses

Background: Telehealth interventions can transform the healthcare system to improve accessibility, quality of care, and outcomes for women’s obstetric health.

Objective: This literature review seeks to summarize current research to understand the effect of telehealth on women’s obstetrics and gynecology outcomes.

Methods: A literature review was conducted following the PRISMA methodology to identify a set of papers containing information related to obstetrics and maternal health. The search terms used identified telehealth or telemedicine interventions used for obstetric, maternal, or prenatal care from the period 2013-2023. 19 articles were identified and reviewed.

Results: The literature review considered three primary aspects from …