Medicine and Health Sciences Commons^™

Macrophage Phagocytosis Of Human Norovirus-Infected Cells In An Ex Vivo Human Enteroid-Macrophage Coculture Model, Ngan Fung Li, Sue E Crawford, Sydney R Mittiga, Cristian Coarfa, Hoa Nguyen-Phuc, Budi Utama, Sarah E Blutt, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

Human norovirus (HuNoV) causes acute gastroenteritis in immunocompetent hosts and chronic infection in immunocompromised individuals. Many recent studies of replication and innate immune responses following HuNoV infection have utilized epithelium-only human intestinal enteroids (HIEs), which lack immune cells. Here, we utilized an ex vivo enteroid-macrophage coculture model consisting of HIEs and different subtypes of human peripheral blood mononuclear cell-derived macrophages to better recapitulate in vivo gut biology and explore the role of macrophages in HuNoV replication and pathogenesis. We show that HuNoV infection in HIEs polarized on Transwells leads to bilateral release of the viral genome, with predominant apical virus …

Adherence To Inhaled Corticosteroid Medications After An Asthma Exacerbation And The Risk Of Subsequent Exacerbations, Mina Khezrian, Marjan Kerkhof, Tham T Le, Tim Harrison, Tianshi David Wu, Bill Cook, Jonatan Hedberg, Kirsty Rhodes, Nicole Zubizarreta, Joshua Enxing, Trung N Tran

Faculty, Staff and Students Publications

Background: Data on the duration of improved adherence to controller medications after an exacerbation and its impact on asthma outcomes are inconsistent.

Objective: To describe levels and changes in adherence to inhaled corticosteroid (ICS)-containing medication after a severe exacerbation and the association with future exacerbation risk.

Methods: This retrospective cohort study used data from Optum's deidentified Clinformatics Data Mart Database (October 2015-December 2023). Patients with asthma, 1 or more severe exacerbations, and adherence to ICS-containing therapy (proportion of days covered [PDC]) of less than 80% in the 3 months before an exacerbation were included. Primary and secondary end points were …

Established And Emerging Asthma Biomarkers With A Focus On Biologic Trials: A Narrative Review, Philip F Lavere, Kaitlin M Phillips, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic airway inflammation with variable airflow obstruction is clinical asthma, and it arises from distinct molecular and pathological mechanisms called endotypes. Biomarkers allow for precise endotype characterization and have been used in clinical trials to design, monitor, and evaluate outcomes for asthma biologic therapies. This review will highlight the central and evolving role of biomarkers for past, present, and future asthma, with a focus on regulatory-approved biologic therapies and emerging biomarkers. Established biomarkers, including serum immunoglobulin E (IgE), blood eosinophils, the fraction of exhaled nitric oxide (FeNO), and serum periostin, helped elucidate the complex pathophysiology of the eosinophilic type 2 …

Pd-1 Inhibition For Relapse After Allogeneic Transplantation In Acute Myeloid Leukemia And Myelodysplastic Syndrome, John M Magenau, David G Frame, Mary Riwes, John Maciejewski, Sarah Anand, Attaphol Pawarode, Anamarija M Perry, Marcus Geer, Thomas Braun, Monalisa Ghosh, Pavan Reddy

Faculty, Staff and Students Publications

Relapse of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains the primary source of mortality after allogeneic hematopoietic stem cell transplantation (HCT). Targeting programmed death-1 (PD-1) for reversing T-cell exhaustion and restoring the graft-versus-leukemia (GVL) effect may have logistical advantages over donor lymphocyte infusion. In a prospective phase 1B clinical trial, pembrolizumab was administered every 3 weeks to 16 patients with AML (n = 12) and MDS (n = 4) in relapse after HCT to assess graft-versus-host disease (GVHD), clinical response, and survival. The median time to relapse after HCT was 5.5 months and the median pretreatment bone marrow …

Non-Isolated Tetralogy Of Fallot (Tof+): Exome Sequencing Efficacy And Phenotypic Expansions, Julia Volpi, Xiaonan Zhao, Nichole Owen, Tia Evans, Muriel Holder-Espinasse, Nayana Lahiri, Eleanor Sherlock, Gemma Poke, Jeroen Breckpot, Koen Devriendt, Bjorn Cools, Alfredo Brusco, Giovanni Battista Ferrero, Enrico Grosso, Pradeep Vasudevan, Sara Loddo, Antonio Novelli, Maria Cristina Digilio, Aafke Engwerda, Marrit Hitzert, Alison Male, Lucy Bownass, Ruth Newbury-Ecob, Zosia Miedzybrodzka, Ruth Armstrong, Sally Ann Lynch, Gunnar Houge, Shiyi Xiong, Seema R Lalani, Jill A Rosenfeld, Pamela N Luna, Chad A Shaw, Daryl A Scott

Faculty, Staff and Students Publications

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect (CHD). TOF may present in isolation or in conjunction with one or more non-cardiac congenital anomalies or neurodevelopmental disorders (TOF+). Uncertainty regarding the efficacy of various genetic testing strategies, and an incomplete understanding of the genetic causes of TOF+, may lead to hesitancy in recommending genetic testing, particularly, clinical exome sequencing (cES). Here, we analyzed cES data from 131 individuals with TOF+. A definitive or probable diagnosis was made for 31 individuals, yielding a diagnostic rate of 23.6% (31/131). One individual received three diagnoses. Commercially available CHD panels …

Botulinum Toxin For The Treatment Of Tremors, Steven Bellows, Joseph Jankovic

Faculty, Staff and Students Publications

Tremor, an oscillatory movement disorder, is commonly encountered in clinical practice in the setting of a variety of etiologies, such as essential tremor and Parkinson's disease. Despite its high prevalence, treatment options are somewhat limited. Oral medications are often ineffective or limited by side effects, and other treatments, such as deep brain stimulation, are more invasive and costly. Botulinum toxin (BoNT) injections are a well-established therapy in the treatment of dystonia, but its use in the treatment of tremors has not been fully explored. In this review, we discuss the available randomized controlled trials and open-label evidence for the use …

Correction: Development And Extensive Sequencing Of A Broadly-Consented Genome In A Bottle Matched Tumor-Normal Pair, Jennifer H Mcdaniel, Vaidehi Patel, Nathan D Olson, Hua-Jun He, Zhiyong He, Kenneth D Cole, Alexander A Gooden, Anthony Schmitt, Kristin Sikkink, Fritz J Sedlazeck, Harsha Doddapaneni, Shalini N Jhangiani, Donna M Muzny, Marie-Claude Gingras, Heer Mehta, Sairam Behera, Luis F Paulin, Alex R Hastie, Hung-Chun Yu, Victor Weigman, Alison Rojas, Katie Kennedy, Jamie Remington, Isai Salas-González, Mitch Sudkamp, Kelly Wiseman, Bryan R Lajoie, Shawn Levy, Miten Jain, Stuart Akeson, Giuseppe Narzisi, Zoe Steinsnyder, Catherine Reeves, Jennifer Shelton, Sarah B Kingan, Christine Lambert, Primo Baybayan, Aaron M Wenger, Ian J Mclaughlin, Aaron Adamson, Christopher Kingsley, Melanie Wescott, Young Kim, Benedict Paten, Jimin Park, Ivo Violich, Karen H Miga, Joshua Gardner, Brandy Mcnulty, Gail L Rosen, Rajiv Mccoy, Francesco Brundu, Erfan Sayyari, Konrad Scheffler, Sean Truong, Severine Catreux, Lesley Chapman Hannah, Doron Lipson, Hila Benjamin, Nika Iremadze, Ilya Soifer, Gat Krieger, Stephen Eacker, Mary Wood, Erin Cross, Greg Husar, Stephen Gross, Michael Vernich, Mikhail Kolmogorov, Tanveer Ahmad, Ayse G Keskus, Asher Bryant, Francoise Thibaud-Nissen, Jonathan Trow, Jacqueline Proszynski, Jeremy Wain Hirschberg, Krista Ryon, Christopher E Mason, Mital S Bhakta, J Zachary Sanborn, Elizabeth M Munding, Justin Wagner, Chunlin Xiao, Andrew S Liss, Justin M Zook

Faculty, Staff and Students Publications

No abstract provided.

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, 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, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

MHC class I polypeptide-related sequence B (MICB) is a ligand for NKG2D. We have shown NK cells are central to lung transplant acute lung injury (ALI) via NKG2D activation, and increased MICB in bronchoalveolar lavage predicts ALI severity. Separately, we found a MICB polymorphism (MICBG406A) is associated with decreased ALI risk. We hypothesized this polymorphism would protect against severe SARS-CoV-2 respiratory disease. We analyzed 1,036 patients hospitalized with SARS-CoV-2 infection from IMPACC. Associations between MICBG406A and outcomes were determined by linear regression or Cox proportional hazards models. We also measured immune profiles of peripheral blood and the upper and lower …

Dual-Function Polyester Nanoparticles For Amplified Anti-Inflammatory Effects, Ingrid M Heyns, Abiodun T Wahab, Raghu Ganugula, David Sheikh-Hamad, M N V Ravi Kumar, Meenakshi Arora

Faculty, Staff and Students Publications

This study investigates a dual-acting drug delivery system using naringenin (NAR) as a folate receptor ligand to enhance intestinal uptake and encapsulated NAR for combating inflammation. The dual-acting systems were tested in vitro on cisplatin-induced human kidney-2 cells and in vivo in a mouse model of cisplatin-induced acute kidney injury (AKI). NAR-loaded passive nanoparticles [P2Ns(NAR)] and dual-acting systems [P2Ns-NAR(NAR)] showed notable advantages over unformulated NAR, reducing the required dose by up to 57 and 79%, respectively. These nanoparticles modulated immune responses, restored T cell function, and shifted macrophage polarization from proinflammatory M1 to tissue-repairing M2. In addition, P2Ns-NAR(NAR) alleviated AKI …

Urinary Pneumococcal Serotype Detection Among Children With And Without Community-Acquired Pneumonia, Lilliam Ambroggio, Lindsay R Grant, Jillian M Cotter, Samuel R Dominguez, Daniel Olson, Sara R Saporta-Keating, Cody Bender, Mohammad Ali, Kathleen Grice, Gonzalo Lerner, Michael W Pride, Ashley Miller, Maria J Tort, Annaellis Vaughan, Elizabeth Temte, Alec Edid, Alejandro Cané, Kristina G Hulten, Jill Stein, Bradford D Gessner, Edwin J Asturias

Faculty, Staff and Students Publications

Background: Urinary antigen detection (UAD) assays can address diagnostic challenges with culture-based identification of S. pneumoniae. We aimed to evaluate the utility of Pfizer's UAD1 and UAD2 assays for pneumococcal serotype surveillance in children with community acquired pneumonia (CAP) or upper respiratory tract infections (URI).

Methods: From March 2021-December 2023, children 3 months to 5 years who presented to the Children's Hospital Colorado Emergency Department with respiratory symptoms were enrolled as CAP or URI; healthy children served as controls. Nasal swabs were tested for pneumococcus by PCR. UAD assays identified pneumococcal serotypes from urine. Groups were compared using descriptive statistics. …

Tet2-Mutant Myeloid Cells Mitigate Alzheimer’S Disease Progression Via Cns Infiltration And Enhanced Phagocytosis In Mice, Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra Mcdonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M Buttigieg, Chih-Wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E Kennedy, Arushana A Maknojia, Apoorva Thatavarty, Josaura V Fernandez Sanchez, Hind Bouzid, Surabi Veeraragavan, Susan Crocker, Margaret A Goodell, Antony Rodriguez, Siddhartha Jaiswal, Michael J Rauh, Eirini P Papapetrou, Samuele G Marro, Katherine Y King

Faculty, Staff and Students Publications

Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than …

Adipokines And Transitions In Metabolic Health Over Time: The Atherosclerosis Risk In Communities (Aric) Study, Bige Ozkan, Sui Zhang, Justin B Echouffo-Tcheugui, Roberta Florido, Vijay Nambi, Erin D Michos, Layla A Abushamat, Kunihiro Matsushita, Gary Gerstenblith, Roger S Blumenthal, Ron Hoogeveen, Christie M Ballantyne, Josef Coresh, Elizabeth Selvin, Chiadi E Ndumele

Faculty, Staff and Students Publications

Context: Transitions in metabolic health status over time are strongly linked to risk for cardiovascular events, particularly among individuals with obesity. Adipokines are proteins with metabolic effects, but their role in transitions in metabolic health status over time is unknown.

Objective: To evaluate the associations of adiponectin and leptin with metabolic risk transitions over time.

Methods: Among 8423 individuals who attended ARIC Visits 2 (1990-1992) and 4 (1996-1998), we evaluated prospective associations of Visit 2 levels of the adipokines adiponectin and leptin (per 1-SD higher) with 6-year transitions in metabolic health. Metabolic health was categorized as metabolically "healthy" [no metabolic …

Mri-Based Radiomics For Outcome Stratification In Pediatric Osteosarcoma, Esther Ngan, Dolores Mullikin, Ashok J Theruvath, Ananth V Annapragada, Ketan B Ghaghada, Andras A Heczey, Zbigniew A Starosolski

Faculty, Staff and Students Publications

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. \

Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor …

Botulinum Toxin For The Treatment Of Motor Tics In Children: A Case Series, Ethan Edmondson, Mariam Hull, Sukru Aras, Mered Parnes

Faculty, Staff and Students Publications

Tic disorders, including Tourette syndrome, are characterized by brief, repetitive, and patterned movements or vocalizations. Botulinum neurotoxin (BoNT) has emerged as a therapeutic option for motor tics, particularly when oral medications are insufficient or poorly tolerated. This retrospective cohort study evaluated the safety and effectiveness of botulinum neurotoxin injections in 50 pediatric patients (aged 7-18 years) with motor tic disorders treated at a tertiary pediatric movement disorders clinic between May 2019 and January 2024. Botulinum neurotoxin injections were tailored to individual symptomatology. Overall, 64% of patients reported improvement in tic severity, 36% noted no change, and 6% worsened. Response did …

Hand Hygiene Knowledge, Attitudes, Practices, And Hand Dirtiness Of Primary School Students Before And After A Behavioral Change Intervention During The Covid-19 Pandemic, Belize 2022-2023, Anh N Ly, Christina Craig, Kelsey Mcdavid, Dian Maheia, Yolanda Gongora, Francis Morey, Russell Manzanero, Alexandra Medley, Allison Stewart, Allison Lino, Ramiro Quezada, Rosalva Blanco, Vickie Romero, Gerhaldine Morazan, Ella Hawes, Oluwadara Okeremi, Kanako Ishida, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) can prevent the spread of infectious diseases and school absenteeism. However, limited data exist on HH practices at schools. Our study assesses the impact of a pilot HH intervention in 12 schools in Belize during the coronavirus disease 2019 (COVID-19) pandemic. After a national assessment of existing water, sanitation, and hygiene resources (December 2021-January 2022), 12 pilot schools were selected to evaluate an HH intervention, which included environmental nudges and HH education. Baseline assessments occurred in March 2022, the HH intervention was implemented during October 2022-May 2023, and follow-up assessments were conducted in June 2023. Student knowledge, …

Drug Development Studies Supporting Zileuton As A Parenteral Adjuvant To Attenuate Antibiotic-Associated Nephrotoxicity, Cole S Hudson, James E Smith, Linh T Vuong, Nicholas S Teran, Nazanin Pouya, David Sheikh-Hamad, Xinli Liu, Shama Kajiji, Vincent H Tam

Faculty, Staff and Students Publications

Glycopeptide, polymyxin, and aminoglycoside antibiotics are among the most commonly used agents to treat drug-resistant bacterial infections; however, their clinical use is hindered by nephrotoxicity. We previously reported that zileuton has the potential to attenuate antibiotic-associated nephrotoxicity in an animal model. Here, we further report the development of a parenteral formulation and exploration of dosing strategies for zileuton. The solubility, stability, and multi-dose safety of two zileuton formulations were evaluated. Zileuton serum and renal tissue pharmacokinetics were evaluated after a single dose and compared to steady state after 10 days. Different dosing strategies of zileuton to attenuate vancomycin-, polymyxin B-, …

Leishmania In Texas: A Contemporary One Health Scoping Review Of Vectors, Reservoirs, And Human Health, Morgan H Jibowu, Richard Chung, Nina L Tang, Sarah Guo, Leigh-Anne Lawton, Brendan J Sullivan, Dawn M Wetzel, Sarah M Gunter

Faculty, Staff and Students Publications

Leishmaniasis, a vector-borne neglected tropical disease, affects over 6.2 million people globally. Case acquisition is increasingly recognized in the United States, and in Texas, most reported cases are locally acquired and speciated to Leishmania mexicana. We conducted a scoping literature review to systematically assess contemporary research on Leishmania in humans, animals, reservoir hosts, or vectors in Texas after 2000. Out of 22 eligible studies, the most prevalent themes were case reports, followed by studies on domestic animals, reservoirs, and vectors, with several studies bridging multiple disciplines. Climate change, urbanization, and habitat encroachment appear to be driving the northward expansion …

Increased Fungal Burden In The Gastrointestinal Tract Of Brain-Dead Organ Donors, Erika J Nachman, Colleen K Ardis, A Kyle B Ardis, Javier Nieto, Madeline M Bresson, Clare M Robertson, Maggie N Seale, Nora M Villafuerte, Zhe Lyu, Eva C Preisner, Heather A Danhof, Sara C Di Rienzi, Yolanda T Becker, Robert A Britton

Faculty, Staff and Students Publications

Approximately 3% of organ transplant recipients will be diagnosed with an invasive fungal infection (IFI), with 10%-47% being fatal. The source of IFI is typically not known, but Candida spp. cause the majority of IFI cases. We obtained intestines from two types of organ donors, brain-dead (BD) (n = 7) and donation after circulatory death (DCD) (n = 5), to sample microbes from the mucosal surface and the lumen. BD donors were parenterally fed and treated with corticosteroids in the days before procurement, whereas DCD donors were enterally fed and not given corticosteroids. We found fungi present in …

Survival To Hospital Discharge In The Fetus With Moderate To Severe Mitral Regurgitation Either In Isolation Or In Combination With Aortic Valve Stenosis Or Atresia, A Fetal Heart Society Collaborative Study, Betul Yilmaz Furtun, Kavitha Pundi, Anita Moon-Grady, Nicole Cresalia, Asela Nieuwsma, Sarah K Gelehrter, Bhawna Arya, Mary T Donofrio, Christopher Statile, Ann Kavanaugh-Mchugh, Lindsay Freud, Elijah Bolin, Megan Warner, Sowmya Balasubramanian, James Strainic, Carol Wittlieb-Weber, Nelangi M Pinto, Lisa Hornberger, Shaine A Morris

Faculty, Staff and Students Publications

Background: Case series report high mortality after fetal diagnosis of moderate to severe mitral regurgitation in combination with left atrial dilation, hydrops, or restrictive atrial septum. However, overall outcomes and specific high-risk features remain unclear.

Methods: We performed a multicenter retrospective cohort study of fetuses with ≥moderate mitral regurgitation and normal cardiac connections evaluated January 1, 2005 to January 31, 2016. Fetuses undergoing fetal cardiac intervention (FCI) were described separately. We assessed associations between fetal echocardiographic features and discharge mortality using mixed logistic regression and classification and regression tree modeling, stratified by studies performed < 28 and ≥28 weeks gestational age (GA).

Results: Of 67 fetuses, 96% had …

Rescue Of Male Infertility By Human Prss55 In Transgenic Mice Establishes A Contraceptive Research Model, Courtney M Sutton, Kohei Umezu, Daisuke Mashiko, Masahito Ikawa, Irina V Larina, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of non-hormonal male contraceptives requires validated preclinical models. This study investigated whether human orthologs of two mouse testis-specific serine proteases, PRSS55 and TMPRSS12, both essential for male fertility in mice, could functionally rescue the infertility phenotypes of their respective knockout mouse lines. We generated transgenic mouse lines expressing human PRSS55 with either an extracellularly or intracellularly positioned C-terminal 3xFLAG tag (RES GPI or RES TM), and a line expressing human TMPRSS12 with a C-terminal 3xFLAG tag (T12 RES), all on their respective mouse null backgrounds. Fertility was assessed through continuous mating trials, and sperm parameters were evaluated. Both …

Grade Concept Paper 9: Rationale And Process For Creating A Grade Ontology, Paul Whaley, Brian Alper, Joanne Dehnbostel, Carlos Alva-Diaz, Stavros Antoniou, Antonio Bognanni, Javier Bracchiglione, Therese Kristine Dalsbø, Sean Grant, Jennifer Hunter, Alfonso Iorio, Malgorzata Lagisz, Harold Lehmann, Sheyu Li, Joerg Meerpohl, Saphia Mokrane, Cauê Monaco, Ignacio Neumann, Kevin Pottie, Shahab Sayfi, Nigar Sekercioglu, Jasvinder Singh, Bernardo Sousa-Pinto, Janice Tufte, Lenny Thinagaran Vasanthan, Li Wang, Jun Xia, Xiaomei Yao, Holger Schünemann

Faculty, Staff and Students Publications

Context: As the rate of research production accelerates, the ability to efficiently and unambiguously communicate judgments relating to the synthesis, evaluation, and use of scientific information becomes paramount.

Perspective: Scientific information can be viewed as a "layered infrastructure" of data, evidence, knowledge, and use. The GRADE approach serves as a de facto data standard for this infrastructure, supporting movement between layers by reducing ambiguity in claims to knowledge (in the form of judgements of certainty in the evidence when answering research questions) and level of commitment to possible solutions to problems (in the form of strength of recommendations for interventions). …

Three Things We Can Do Now To Reduce The Risk Of Avian Influenza Spillovers, Kenneth B Yeh, William P Bahnfleth, Elaine Bradford, Carol Cardona, Kristen K Coleman, Peter J Hudson, Bernadeta Dadonaite, Rebecca J Hutchins, Anthony Maresso, C Raina Macintyre, Matthew Scotch

Faculty, Staff and Students Publications

No abstract provided.

Development And Validation Of Venous Thromboembolism-Bidirectional Encoder Representations From Transformers (Vte-Bert) Natural Language Processing Model, Omid Jafari, Shengling Ma, Barbara D Lam, Jun Y Jiang, Emily Zhou, Mrinal Ranjan, Justine Ryu, Raka Bandyo, Arash Maghsoudi, Bo Peng, Christopher I Amos, Abiodun Oluyomi, Nathanael R Fillmore, Jennifer La, Ang Li

Faculty, Staff and Students Publications

Background: Accurate and rapid phenotyping of venous thromboembolism (VTE) in longitudinal studies is important. A natural language processing (NLP) tool externally validated in representative patients is lacking.

Objectives: To train and validate an efficient NLP model to detect incident VTE event.

Methods: We designed a novel NLP platform, NLPMed, to assist thrombosis researchers with data preprocessing, phenotype annotation, language model finetuning, and NLP application. Using clinical notes, discharge summaries, and radiology reports from patients with cancer at 2 healthcare institutions, we finetuned Bio_Clinical Bidirectional Encoder Representations from Transformers (BERT) to develop VTE-BERT. The new model was trained to detect acute …

Hemispherotomy For Drug-Resistant Epilepsy In Bilateral Sturge-Weber Syndrome: Illustrative Cases, Eveline Teresa Hidalgo, Eric A Grin, Yosef Dastagirzada, Nealen Laxpati, Judith Bluvstein, Julia R Schneider, Daniel Miles, Michal Tzadok, James Riviello, Howard L Weiner

Faculty, Staff and Students Publications

Background: Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by angiomas of the face, choroid, and leptomeninges. Seizures in these children often present within the first 2 years of life. SWS is typically unilateral, but bilateral SWS occurs in approximately 15% of cases. Bilateral SWS is associated with earlier seizure onset and poorer cognitive, developmental, and functional outcomes. More than half of children with SWS develop drug-resistant epilepsy requiring surgical intervention. Hemispherotomy has been established as a successful treatment for unilateral SWS, but resective surgery has traditionally not been considered a treatment option for patients with bilateral disease.

Observations: …

Limosilactobacillus Reuteri Enables Oral-To-Systemic Absorption Of Iberiotoxin For Treatment Of Collagen-Induced Arthritis In Rats, Mohamed R Kady, R Nicholas Elston, Lauren J Snyder, Jorie D Fleischman, Madilyn J Brandt, Duolong Zhu, Robert A Britton, Christine Beeton

Faculty, Staff and Students Publications

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and damage in which fibroblast-like synoviocytes (FLS) play a central role. Invasiveness and proliferation of FLS in RA is dependent on activity of the KCa1.1 potassium channel. Peptide blockers of KCa1.1, such as iberiotoxin (IbTX), can be delivered subcutaneously to treat animal models of RA. We tested whether an engineered probiotic oral delivery platform could effectively deliver IbTX systemically in a rat model of RA.

Results: A plasmid for inducible secretion of IbTX was constructed and transformed into probiotic Limosilactobacillus reuteri ATCC PTA-6475 to generate LrIbTX. No differences …

Inhibition Of Epithelial Cell Yap-Tead/Lox Signaling Attenuates Pulmonary Fibrosis In Preclinical Models, Darcy Elizabeth Wagner, Hani N Alsafadi, Nilay Mitash, Aurelien Justet, Qianjiang Hu, Ricardo Pineda, Claudia Staab-Weijnitz, Martina Korfei, Nika Gvazava, Kristin Wannemo, Ugochi Onwuka, Molly Mozurak, Adriana Estrada-Bernal, Juan Cala-Garcia, Katrin Mutze, Rita Costa, Deniz Bölükbas, John Stegmayr, Wioletta Skronska-Wasek, Stephan Klee, Chiharu Ota, Hoeke A Baarsma, Jingtao Wang, John Sembrat, Anne Hilgendorff, Jun Ding, Andreas Günther, Rachel Chambers, Ivan Rosas, Stijn De Langhe, Naftali Kaminski, Mareike Lehmann, Oliver Eickelberg, Melanie Königshoff

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX …

The Glycosyltransferase Poglut1 Regulates Muscle Stem Cell Development And Maintenance In Mice, Soomin Cho, Emilia Servián-Morilla, Victoria Navarro, Beatriz Rodriguez-Gonzalez, Youxi Yuan, Raquel Cano, Arjun A Rambhiya, Radbod Darabi, Robert S Haltiwanger, Carmen Paradas, Hamed Jafar-Nejad

Faculty, Staff and Students Publications

Mutations in protein O-glucosyltransferase 1 (POGLUT1) cause a recessive limb-girdle muscular dystrophy (LGMDR21) with reduced satellite cell number and NOTCH1 signaling in adult patient muscles and impaired myogenic capacity of patient-derived muscle progenitors. However, the in vivo roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse Poglut1 in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced Pax7 expression, abnormality in muscle extracellular matrix, and impaired muscle repair. Poglut1-deficient muscle progenitors exhibit reduced proliferation, enhanced differentiation, and accelerated fusion into myofibers. Inducible loss …

Plasminogen Mutation-Associated Thrombotic Microangiopathy And Role Of Anticoagulation: A Single Institution Case Series, Shreya Agarwal, Nicola Pozzi, Senthil Sukumar, Camila Masias, Anuja Java, Spero Cataland

Faculty, Staff and Students Publications

Background: Knowledge gaps exist regarding the role of coagulation pathway mutations such as those in the plasminogen (PLG) gene in the pathogenesis of thrombotic microangiopathy (TMA) and treatment outcomes.

Objectives: This study aims to describe the unique phenotypic features of patients with PLG mutations and perform structural mapping of the variants to enhance variant interpretation.

Methods: This was a single-center retrospective study of patients with TMA in whom genetic testing was performed between 2011 and 2023. Data were collected regarding demographics, clinical features at their first presentation, renal outcomes, genetic mutations, and recurrence for those who were found …

Generation Of Human Induced Pluripotent Stem Cell Lines From An Age-Related Macular Degeneration Patient With Hyperreflective Foci Overlying Drusen (Rfsci002-A) And An Unaffected Sibling (Rfsci001-A), Adnin Ashrafi, Wendy Runyon, Sam Hu, Ritu Kumar, Timothy Catchpole, Ajeet Singh, Rinki Ratnapriya, Karl G Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) is a leading cause of vision loss, driven by retinal pigment epithelium (RPE) and photoreceptor degeneration. A key feature is drusen accumulation between the RPE and Bruch's membrane. In intermediate AMD, hyperreflective foci (HRF)-bright intraretinal lesions visible on optical coherence tomography (OCT) imaging-serve as biomarkers of disease progression. To study HRF mechanisms, we generated induced pluripotent stem cell (iPSC) lines from an AMD patient with HRF overlying drusen (RFSC4) and their unaffected sibling (RFSC3). These iPSC models offer a platform to explore disease mechanisms and develop therapies for AMD.

Community-Engaged Medical Student Elective To Improve Knowledge And Attitudes Toward Individuals With Intellectual And Developmental Disabilities, Kathryn J Kemere, Nital Appelbaum, Priya Chandan, Elisha Acosta

Faculty, Staff and Students Publications

Individuals with intellectual and developmental disabilities (IDD) face multiple barriers to inclusion throughout life. One barrier is the medical knowledge and biases of adult healthcare providers with diagnoses traditionally associated with childhood. Medical school curricula have limited content related to IDD, and students have limited opportunities to engage with community organizations during their clinical years. Methods: We created a one-month clinical elective to address medical students' attitudes and knowledge regarding individuals with IDD using experiential learning. Students saw adult patients in our primary care clinic with a variety of IDD diagnoses and spent 30% of their time at community sites …