Digital Commons Network^™

Psychedelic Psychotherapy And The Mental Health Crisis: A Historical And Scientific Review, Dylan Kunkel, Neil Levens, Charles Schumpert

Senior Theses

The global mental health crisis continues to expose the limitations of traditional psychiatric treatments for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). As conventional antidepressants offer modest remission rates and delayed efficacy, interest has grown in the therapeutic potential of psychedelic compounds. This thesis explores psychedelic psychotherapy through both a historical and scientific lens, tracing its roots from ancient ceremonial practices to modern clinical trials. It also provides context behind the neurobiological mechanisms by which psychedelics like psilocybin, LSD, ketamine, MDMA, and DMT affect mood and cognition. These compounds appear to reduce default mode network (DMN) connectivity, increase …

Semi-Parametric Testing For Ordinal Treatment Effects In Time-To-Event Data Via Dynamic Dirichlet Process Mixtures Of The Inverse-Gaussian Distribution., Jonathan A Race, Amy S Ruppert, Yvonne Efebera, Michael L Pennell

Ambulatory and Primary Care Articles

Time-to-event data often violate the proportional hazards assumption under which the log-rank test is optimal. Such violations are especially common in the sphere of biological and medical data where heterogeneity due to unmeasured covariates or time varying effects are common. A variety of parametric survival models have been proposed in the literature which make more appropriate assumptions on the hazard function, at least for certain applications. One such model is derived from the first hitting time paradigm which assumes that a subject's event time is determined by a latent stochastic process reaching a threshold value. Several random effects specifications of …

The Interaction Between Antithrombin And Endothelial Heparan Sulfate Mitigates Pulmonary Thromboinflammation After Trauma And Hemorrhagic Shock, Maria Del Pilar Huby Vidaurre, Ava K Mokhtari, Baron K Osborn, Bryan A Cotton, Yao-Wei Wang, Yongmei Xu, Katelyn Arnold, Jian Liu, Jillian R Richter, Jessica C Cardenas

Faculty, Staff and Student Publications

Introduction:

Trauma and hemorrhagic shock (T/HS) are associated with multiple organ injury. Antithrombin (AT) has anti-inflammatory and organ protective activity through its interaction with endothelial heparan sulfate containing a 3-O-sulfate modification. Our objective was to examine the effects of T/HS on 3-O-sulfated (3-OS) heparan sulfate expression and determine whether AT-heparan sulfate interactions are necessary for its anti-inflammatory properties.

Methods:

Male Sprague Dawley rats underwent laparotomy, gut distension and fixed-pressure hemorrhagic shock (HS) and resuscitation. Liquid chromatography-coupled mass spectrometry analyses were performed to measure pulmonary and plasma heparan sulfate di/tetrasaccharides. Pulmonary mRNA levels were assessed by nCounter …

Measles Is Just A Harbinger

Faculty, Staff and Student Publications

No abstract provided.

Destructive And Protective Effects And Therapeutic Targets Of Il-36 Family Cytokines In Dry Eye Disease, Jing Lin, Ning Gao, Zhao Liu, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li

Faculty, Staff and Students Publications

Purpose: To explore the destructive and protective effects and therapeutic targets of IL-36 cytokines in dry eye disease using a murine dry eye model.

Methods: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls. A topical challenge model was performed in normal mice with exogenous rmIL-36α, rhIL-38 and 2 % ectoine, or PBS vehicle. IL-36 cytokine expression was assessed by RT-qPCR and immunofluorescent (IF) staining. Corneal epithelial damage was evaluated by corneal smoothness score, Oregon Green Dextran (OGD) fluorescent staining, and tight junction barrier.

Results: All members of the IL-36 …

Single-Nucleus Transcriptional Profiling Of The Placenta Reveals The Syncytiotrophoblast Stress Response To Covid-19, Diana R O'Day, Akihiko Miyauchi, Kadeshia M Campbell, Natalie Lanners, Jeffery A Goldstein, Connor Yee, Neil J Mckenna, Ronald J Parchem, Jacqueline G Parchem

Faculty, Staff and Students Publications

Background: COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology and function is unclear.

Objective: This study aimed to determine the effects of maternal COVID-19 on placental syncytiotrophoblasts using single-nucleus transcriptional profiling and to compare placental stress responses in COVID-19 and preeclampsia.

Study design: For transcriptional characterization of syncytiotrophoblasts, we used the single-nucleus RNA sequencing platform, single-cell combinatorial indexing RNA sequencing (sci-RNA-seq3), to profile placental villi and fetal membranes from unvaccinated patients with symptomatic COVID-19 at birth (n = 4), gestational age-matched controls (n = 4), and a case of …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

Endogenous Dna Damage At Sites Of Terminated Transcripts, Sadeieh Nimer, Alice X Wen, Jennifer A Halliday, Devon M Fitzgerald, Qian Mei, Ralf B Nehring, Mary Crum, Stanislav G Kozmin, Jun Xia, Matthew B Cooke, Yin Zhai, David Bates, Lei Li, P J Hastings, Irina Artsimovitch, Christophe Herman, Patrick M Sung, Kyle M Miller, Susan M Rosenberg

Faculty, Staff and Students Publications

DNA damage promotes mutations that fuel cancer, aging, and neurodegenerative diseases1–3, but surprisingly, the causes and types of damage remain largely unknown. There are three identified mechanisms that damage DNA during transcription: RNA polymerase (RNAP) colliding with DNA-replication machinery head-on and co-directionally4–6, and R-loop-induced DNA breakage7–10. Here, we identify DNA-damage reaction intermediates11,12 uncharacterized previously in living cells, and uncover a surprising fourth transcription-related source: endogenous DNA damage at sites of terminated transcripts. We engineered proteins to capture single-stranded (ss)DNA ends with 3'-polarity, in both bacterial …

Clinical Management And Therapeutic Optimization Of Patients With Heart Failure With Reduced Ejection Fraction And Low Blood Pressure. A Clinical Consensus Statement Of The Heart Failure Association (Hfa) Of The Esc, Mark C Petrie, Michael Böhm, Marianna Adamo, Wilfried Mullens, Gianluigi Savarese, Mehmet Birhan Yilmaz, Offer Amir, Antoni Bayes-Genis, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, Alexandre Mebazaa, Jose L Merino, Brenda Moura, Piotr Ponikowski, Petar Seferovic, Giuseppe M C Rosano, Marco Metra

Faculty, Staff and Students Publications

Despite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of …

Statin Use Is Associated With Protection Against Acute Cholangitis In Patients With Primary Sclerosing Cholangitis: A Multicenter Retrospective Cohort Study, Joseph Rathkey, Samir Khan, Soumya Murag, Robert Lerrigo, Ahmad Kamal, Ajitha Mannalithara, Prasun Jalal, Aijaz Ahmed, John Vierling, Aparna Goel, Sidhartha R Sinha

Faculty, Staff and Students Publications

Introduction: Patients with primary sclerosing cholangitis (PSC) are at increased risk of acute cholangitis. The epidemiological risks of cholangitis are poorly studied despite the high morbidity associated with this infection. The aim of this study was to understand the impact of statins on acute cholangitis in PSC.

Methods: This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with the development of cholangitis were identified using multivariable Cox regression.

Results: The patients were predominantly male (68.7%) with a median age at enrollment of 48 …

Anaplastic Meningioma In A 6-Year-Old With Somatic Yap1::Maml2 Fusion And Multiple Endocrine Neoplasia Type 4 (Men4) Syndrome, Andrea R Gilbert, Eva M Galvan, Achint K Singh, Angshumoy Roy, George Miles, Jacquelyn Reuther, Donna M Muzny, Bo Yuan, Shashikant Kulkarni, Christine Eng, Sarah Scollon, Shawn Gessay, Amy L Mcguire, D Williams Parsons, Gail E Tomlinson, Sharon E Plon, Shafqat Shah

Faculty, Staff and Students Publications

Meningiomas are the most common primary brain tumors in adults but much less frequent in children. Many subtypes exist, including anaplastic (malignant) meningioma, which accounts for less than 20% of pediatric tumors. Meningiomas can arise in association with cancer predisposition syndromes due to germline variants in genes such as NF2, MEN1 and SMARCE1. This report describes a 6-year-old boy diagnosed with anaplastic meningioma who was treated with surgery and focal radiation therapy. The family consented to participate in the Texas KidsCanSeq clinical genomics study. Analysis of germline and tumor samples detected a single germline finding of a CDKN1B pathogenic frameshift …

Functional Connectomics Reveals General Wiring Rule In Mouse Visual Cortex, Eric Y Wang, Brendan Celii, Christos Papadopoulos, Andersen Chang, Alexander B Kunin, Dat Tran, Jiakun Fu, Zhiwei Ding, Saumil Patel, Lydia Ntanavara, Rachel Froebe, Kayla Ponder, Taliah Muhammad, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Wenjing Yin, Szi-Chieh Yu, Dimitri Yatsenko, Emmanouil Froudarakis, Fabian Sinz, Krešimir Josić, Robert Rosenbaum, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Edgar Y Walker, Xaq Pitkow, Jacob Reimer, Andreas S Tolias

Faculty, Staff and Students Publications

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain computes. In mouse primary visual cortex, excitatory neurons with similar response properties are more likely to be synaptically connected1–8; however, broader connectivity rules remain unknown. Here we leverage the millimetre-scale MICrONS dataset to analyse synaptic connectivity and functional properties of neurons across cortical layers and areas. Our results reveal that neurons with similar response properties are preferentially connected within and across layers and areas—including feedback connections—supporting the universality of ‘like-to-like’ connectivity across the visual hierarchy. Using a validated digital twin model, …

Mapping The Transcriptional And Epigenetic Landscape Of Organotypic Endothelial Diversity In The Developing And Adult Mouse, William B Gillespie, James F Martin, Joshua D Wythe

Faculty, Staff and Students Publications

The vascular endothelium features unique molecular and functional properties across different vessel types, such as between arteries, veins and capillaries, as well as between different organs, such as the leaky sinusoidal endothelium of the liver versus the impermeable vessels of the brain. However, the transcriptional networks governing endothelial organ specialization remain unclear. Here we profile the accessible chromatin and transcriptional landscapes of the endothelium from the mouse liver, lung, heart, kidney, brain and retina, across developmental time, to identify potential transcriptional regulators of endothelial heterogeneity. We then determine which of these putative regulators are conserved in human brain endothelial cells, …

International Multispecialty Expert Physician Preoperative Identification Of Extranodal Extension In Patients With Oropharyngeal Cancer Using Computed Tomography: Prospective Blinded Human Inter-Observer Performance Evaluation, Cem Dede, Nicolette Taku, Renjie He, Mohamed A Naser, Christina S Sharafi, Antti Mäkitie, Benjamin H Kann, Kimmo Kaski, Jaakko Sahlsten, Joel Jaskari, Moran Amit, Gregory M Chronowski, Eduardo M Diaz, Adam S Garden, Ryan P Goepfert, Jeffrey P Guenette, G Brandon Gunn, Jussi Hirvonen, Frank Hoebers, Katherine A Hutcheson, Nandita Guha-Thakurta, Jason Johnson, Diana Kaya, Shekhar D Khanpara, Kristofer Nyman, Stephen Y Lai, Miriam Lango, Kim O Learned, Anna Lee, Carol M Lewis, Anastasios Maniakas, Amy C Moreno, Jeffrey N Myers, Jack Phan, Kristen B Pytynia, David I Rosenthal, Vlad C Sandulache, Dawid Schellingerhout, Shalin J Shah, Andrew G Sikora, Abdallah S R Mohamed, Melissa M Chen, Clifton D Fuller, Multidisciplinary Oropharyngeal Cancer Extra‐Nodal Extension (Opc Ene) Assessment Working Group

Faculty, Staff and Students Publications

Background: Pathologic extranodal extension (pENE) is a crucial prognostic factor in oropharyngeal cancer (OPC), but determining pENE from imaging has high inter-observer variability. The role of clinician specialty in the accuracy of imaging-detected extranodal extension (iENE) remains unclear. The purpose of this study is to assess the influence of clinician specialty on the accuracy of preoperative iENE detection in human papillomavirus (HPV)-positive OPC using computed tomography (CT) imaging.

Methods: This prospective observational study evaluated pretherapy CT images from 24 HPV-positive OPC patients (30 scans, including duplicates). Thirty-four expert observers (11 radiologists, 12 surgeons, 11 radiation oncologists) assessed iENE and reported …

Playbook Workflow Builder: Interactive Construction Of Bioinformatics Workflows, Giacomo B Marino, Anna I Byrd, Mano R Maurya, Sumana Srinivasan, Keyang Yu, Varduhi Petrosyan, Matthew E Roth, Miroslav Milinkov, Charles Hadley King, Jeet Kiran Vora, Jonathon Keeney, Christopher Nemarich, William Khan, Alexander Lachmann, Nasheath Ahmed, Alexandra Agris, Juncheng Pan, Srinivasan Ramachandran, Eoin Fahy, Emmanuel Esquivel, Aleksandar Mihajlovic, Bosko Jevtic, Vuk Milinovic, Sean Kim, Patrick Mcneely, Tianyi Wang, Eric Wenger, Miguel A Brown, Alexander Sickler, Yuankun Zhu, Sherry L Jenkins, Philip D Blood, Deanne M Taylor, Adam C Resnick, Raja Mazumder, Aleksandar Milosavljevic, Shankar Subramaniam, Avi Ma'ayan

Faculty, Staff and Students Publications

The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large …

Defining The Transcriptional Basis Of Organ-Specific Endothelial Cell Specialization

Faculty, Staff and Students Publications

Blood vessels feature extensive phenotypic and functional differences that help them meet the unique nutritive and energetic demands of the specific organ they reside in. Profiling the chromatin and transcriptional landscape of several organs identified novel gene regulatory networks that determine endothelial cell organ specialization in mammals.

Acute Kidney Injury In Severe Alcohol-Associated Hepatitis Treated With Anakinra Plus Zinc Or Prednisone, Douglas A Simonetto, Amon Asgharpour, Muhammad Y Jan, Qing Tang, Yunpeng Yu, Yang Li, Moyinoluwa Taiwo, Prashanth Thevkar Nagesh, Srinivasan Dasarathy, Patrick S Kamath, Craig J Mcclain, Naga Chalasani, Gyongyi Szabo, Ramon Bataller, Mack Mitchell, Wajahat Z Mehal, Laura E Nagy, Vijay H Shah, Samer Gawrieh, Arun J Sanyal

Faculty, Staff and Students Publications

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Soluble Mesothelin-Related Peptide As A Prognosticator In Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy, Sung Wook Kang, Jong Min Choi, Ji Seon Shim, Claire Lee, Priyanka Ranchod, Peter Jindra, Maheshwari Ramineni, Meera Patel, R Taylor Ripley, Shawn S Groth, Shanda H Blackmon, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Students Publications

Background: Immune checkpoint therapy (ICT) has significantly impacted the treatment of malignant pleural mesothelioma (MPM). Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.

Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of mesothelin and PD-L1. Both univariable and …

Recent Advances In The Management Of Pediatric Cholestatic Liver Diseases, Rima Fawaz, Alisha M Mavis, Debora Kogan-Liberman, Saeed Mohammad, Sarah A Taylor

Faculty, Staff and Students Publications

Pediatric cholestatic liver diseases are rare conditions that can result from multiple specific underlying etiologies. Among the most common etiologies of pediatric cholestatic liver diseases are biliary atresia, Alagille syndrome (ALGS), and inherited disorders of bile acid transport. These diseases are characterized by episodic or chronic unremitting cholestasis. Due to the chronicity of these conditions, it is imperative to optimize medical management to improve patient quality of life, provide nutritional support, and reduce bile acid toxicity in efforts to slow disease progression. Cholestatic liver diseases remain the leading cause of pediatric liver transplantation, as many underlying disease etiologies have no …

Rapid Diagnostic Sequencing Of Stool Dna Using Targeted Nanopore Sequencing In Patients With A Pulmonary Tuberculosis Diagnosis, Doctor Sibandze, Abigail Seeger, Maia Madison, Anca Vasiliu, Durbin Mulengwa, Clement Gascua, Mangaliso Ziyane, Sindisiwe Dlamini, Gugu Maphalala, Eric Bortz, Alexander Kay, Christoph Lange, Viola Dreyer, Tanja Niemann, Stefan Niemann, Andrew Dinardo, Anna Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

Background: Approximately 1.25 million individuals died of tuberculosis in 2023, in part due to ineffective treatment. In patients with paucibacillary tuberculosis, microbiologic confirmation and drug resistance testing via respiratory specimens is challenging; hence, stool samples are increasingly used for microbiologic confirmation. Targeted next-generation sequencing (tNGS) of stool DNA may improve detection of drug-resistant (DR) tuberculosis, helping patients receive appropriate treatments.

Methods: We assessed the ability of a nanopore tNGS approach using stool to detect drug resistance in a prospective, nested cohort of consecutive participants in Eswatini with pulmonary tuberculosis confirmed via sputum culture or sputum GeneXpert Ultra from 2020 to …

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

Foraging Animals Use Dynamic Bayesian Updating To Model Meta-Uncertainty In Environment Representations, Daeyeol Lee, Caleb Kemere, Matthew Mcginley

Faculty, Staff and Students Publications

Foraging theory predicts animal behavior in many contexts. In patch-based foraging behaviors, the marginal value theorem (MVT) gives the optimal strategy for deterministic environments whose parameters are fully known to the forager. In natural settings, environmental parameters exhibit variability and are only partially known to the animal based on its experience, creating uncertainty. Models of uncertainty in foraging are well established. However, natural environments also exhibit unpredicted changes in their statistics. As a result, animals must ascertain whether the currently observed quality of the environment is consistent with their internal models, or whether something has changed, creating meta-uncertainty. Behavioral strategies …

Guideline-Directed Medical Therapy And Outcomes In The Ischemia Trial, Ying Lu, Susanna Stevens, William E Boden, Kreton Mavromatis, Jason Linefsky, Rajesh G Nair, Olga Bockeria, Gilbert Gosselin, Gian P Perna, Elena Demchenko, David Foo, Michael D Shapiro, Mary Ann Champagne, Christie Ballantyne, Peter Mccullough, Jose Luis Lopez-Sendon, Frank Rockhold, Frank Harrell, Yves Rosenberg, Gregg W Stone, Sripal Bangalore, Harmony R Reynolds, John A Spertus, Judith S Hochman

Faculty, Staff and Students Publications

Background: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain.

Objectives: This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes.

Methods: This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals …

The Internist's Post V.1 N.13, The University Of Texas Rio Grande Valley. School Of Medicine, Jian Garcia Cruz, Julio Javier Perez Rodriguez, Ramon Elizondo Romo, Barbara Malaga-Espinoza, Carlos Alejos Aguero, Osiris Fernandez, Edgar Dorsey Trevino, Diana Othon Martinez, Roque Mifuji Lira, Martha Solis, Cesar Gutierrez

School of Medicine Publications

No abstract provided.

A Novel Method For Semi-Quantitative Detection Of Hpv16 And Hpv18 Mrna With A Low-Cost, Open-Source Fluorimeter, Kathryn A Kundrod, Mary E Natoli, Chelsey A Smith, Jackson B Coole, Megan M Chang, Emilie Newsham Novak, Elizabeth Chiao, Elizabeth A Stier, Jane R Montealegre, Michael E Scheurer, Philip E Castle, Kathleen M Schmeler, Rebecca R Richards-Kortum

Center for Medical Ethics and Health Policy Staff Publications

Despite global calls to eliminate cervical cancer, rates of cervical cancer incidence and mortality remain high in resource-limited settings, where it is challenging to implement and sustain screening, diagnosis, and treatment programs. The presence of high-risk HPV mRNA in cervical cells is a sensitive and specific biomarker of cervical precancer. Yet, current testing methods are too costly and complex for use in resource-limited settings. Here, we present a novel method for semi-quantitative detection of HPV16 and HPV18 mRNA with minimal infrastructure requirements. The assay relies on isothermal reverse transcription recombinase polymerase amplification (RT-RPA) with real-time fluorescence readout, demonstrated on rugged, …

Comparing Rituximab And Cyclophosphamide In Induction Therapy For Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An Archive Registry Cohort Study, Brett Klamer, Kimberly A Morishita, Adam Huber, Alvaro Orjuela, Barbara Eberhard, Charlotte Myrup, Dana Gerstbacher, Dirk Foell, Eslam Al-Abadi, Flora Mcerlane, Kathryn Cook, Linda Wagner-Weiner, Melissa Elder, L Nandini Moorthy, Paul Dancey, Rae Yeung, Raju Khubchandani, Samundeeswari Deepak, Sirirat Charuvanij, Stacey Tarvin, Susan Shenoi, Tamara Tanner, Kelly Brown, David A Cabral, Archive Investigators Network Within The Pedvas Initiative

Faculty, Staff and Students Publications

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index …

Clinical And Genetic Delineation Of Autosomal Recessive And Dominant Actl6b-Related Developmental Brain Disorders, Stephanie Efthymiou, Antonella Riva, Dana Marafi, Maha S Zaki, Mohnish Suri, Roberto Dominguez, Hasnaa M Elbendary, Shahryar Alavi, Mohamed S Abdel-Hamid, Heba Morsy, Frederic Tran Mau-Them, Mathilde Nizon, Pavel Tesner, Lukáš Ryba, Faisal Zafar, Nuzhat Rana, Nebal W Saadi, Zahra Firoozfar, Pinar Gencpinar, Bulent Unay, Canan Ustun, Ange-Line Bruel, Christine Coubes, Jennifer Stefanich, Ozlem Sezer, Emanuele Agolini, Antonio Novelli, Gessica Vasco, Donatella Lettori, Mathieu Milh, Laurent Villard, Shimriet Zeidler, Henry Opperman, Vincent Strehlow, Mahmoud Y Issa, Hebatallah El Khassab, Prem Chand, Shahnaz Ibrahim, Ali Rashidi-Nezhad, Mohammad Miryounesi, Pegah Larki, Jennifer Morrison, Ingrid Cristian, Isabelle Thiffault, Nicole L Bertsch, Grace J Noh, John Pappas, Ellen Moran, Nikolaos M Marinakis, Joanne Traeger-Synodinos, Susan Hosseini, Mohammad Reza Abbaszadegan, Roseline Caumes, Lisenka E L M Vissers, Maedeh Neshatdoust, Mostafa Montazer Zohour, Elmostafa El Fahime, Christina Canavati, Lara Kamal, Moien Kanaan, Omar Askander, Victoria Voinova, Olga Levchenko, Shahzhad Haider, Sara S Halbach, Rayana Elias Maia, Salehi Mansoor, Vivek Jain, Sanjukta Tawde, Viveka Santhosh R Challa, Vykuntaraju K Gowda, Varunvenkat M Srinivasan, Lucas Alves Victor, Benito Pinero-Banos, Jennifer Hague, Heba Ahmed Elawady, Adelia Maria De Miranda Henriques-Souza, Huma Arshad Cheema, Muhammad Nadeem Anjum, Sara Idkaidak, Firas Alqarajeh, Osama Atawneh, Hagar Mor-Shaked, Tamar Harel, Giovanni Zifarelli, Peter Bauer, Fernando Kok, Joao Paulo Kitajima, Fabiola Monteiro, Juliana Josahkian, Gaetan Lesca, Nicolas Chatron, Dorothe Ville, David Murphy, Jeffrey L Neul, Sureni V Mullegama, Amber Begtrup, Isabella Herman, Tadahiro Mitani, Jennifer E Posey, Chee Geap Tay, Iram Javed, Lucinda Carr, Farah Kanani, Fiona Beecroft, Lee Hane, Elsayed Abdelkreem, Milan Macek, Luciana Bispo, Marwa Abd Elmaksoud, Farzad Hashemi-Gorji, Davut Pehlivan, David J Amor, Rami Abou Jamra, Wendy K Chung, Eshan Ghayoor Karimiani, Philippe M Campeau, Fowzan S Alkuraya, Alistair T Pagnamenta, Joseph G Gleeson, James R Lupski, Pasquale Striano, Andres Moreno-De-Luca, Denis L J Lafontaine, Henry Houlden, Reza Maroofian

Faculty, Staff and Students Publications

Purpose: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

Methods: We identified 105 affected individuals, including 39 previously reported cases, and systematically analyzed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

Results: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability, infantile intractable seizures, absent speech, autistic features, dystonia, …

Endothelial Micu1 Protects Against Vascular Inflammation And Atherosclerosis By Inhibiting Mitochondrial Calcium Uptake, Meiming Su, Qingze He, Zhidan Zhang, Zhenghong Liu, Zhihua Wang, Hui Jiang, Li Wang, Shuai Guo, Yiming Xu, Yuqing Huo, Clint L Miller, Maciej Banach, Yu Huang, Paul C Evans, Jaroslav Pelisek, Giovanni G Camici, Bradford C Berk, Stefan Offermanns, Junbo Ge, Suowen Xu, Jianping Weng

Faculty, Staff and Students Publications

Mitochondrial dysfunction fuels vascular inflammation and atherosclerosis. Mitochondrial calcium uptake 1 (MICU1) maintains mitochondrial Ca2+ homeostasis. However, the role of MICU1 in vascular inflammation and atherosclerosis remains unknown. Here, we report that endothelial MICU1 prevents vascular inflammation and atherosclerosis by maintaining mitochondrial homeostasis. We observed that vascular inflammation was aggravated in endothelial cell–specific Micu1 knockout mice (Micu1ECKO) and attenuated in endothelial cell–specific Micu1 transgenic mice (Micu1ECTg). Furthermore, hypercholesterolemic Micu1ECKO mice also showed accelerated development of atherosclerosis, while Micu1ECTg mice were protected against atherosclerosis. Mechanistically, MICU1 depletion increased mitochondrial Ca2+ influx, thereby decreasing the expression …

Klf4 Enhances Transplantation-Induced Hematopoiesis By Inhibiting Tlrs And Noncanonical Nfκb Signaling At A Steady State, Taylor J Chen, Saptarsi Shai, Wa Du, Monica Puppi, Barry Zorman, Sumazin Pavel, H Daniel Lacorazza

Faculty, Staff and Students Publications

The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and …