Pulmonology Commons^™

Regulation Of Myogenesis By Mechanomir-200c/Foxo3 Axis, Junaith S Mohamed, Aladin M Boriek

Faculty, Staff and Students Publications

Cyclic mechanical stretch has been shown to inhibit myoblast differentiation while promoting proliferation. However, the underlying molecular mechanisms are not well understood. Here, we report that mechanical stretch inhibits the differentiation of mouse primary myoblasts by promoting the cell cycle program and by inhibiting the expression of the myogenic regulator MyoD. Stretch alters the miRNA expression profile as evidenced by miRNA microarray analysis. We identified miR-200c as one of the highly downregulated mechanosensitive miRNAs (mechanomiRs) whose expression level was increased during differentiation. This suggests that mechanomiRs-200c is a myogenic miRNA. Overexpression of mechanomiR-200c revoked the effect of stretch on myoblast …

Oxygen Saturation Targeting In The Neonatal Intensive Care Unit, Faeq Almudares, Bheru Gandhi, Jonathan Davies, Xanthi Couroucli, Natalie Villafranco, Nidhy Paulose Varghese, Milenka Cuevas Guaman, Charleta Guillory, Binoy Shivanna

Faculty, Staff and Students Publications

Oxygen (O2) is vital for cellular development, function, proliferation, and repair, underscoring its critical role in organogenesis. Both hypoxia (reduced tissue O2) and hyperoxia (excess tissue O2), when prolonged, can trigger inflammation and oxidative stress, contributing to acute and long-term cardiopulmonary and neurodevelopmental morbidity. In sick neonates, immature defense mechanisms and coexisting morbidities demand nuanced and sometimes opposing strategies for O2 saturation targets and therapeutic titration. Most current neonatal O2 targeting guidelines are based on animal models or small clinical studies, resulting in recommendations with limited evidence. This narrative review aims to provide an updated overview of the physiological roles …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

Targeting S1pr2 In Sepsis, One Fragmented Mitochondrion At A Time, Chao He, Jennifer L Larson-Casey

Faculty, Staff and Students Publications

No abstract provided.

Airway Immune Signatures In Severe And Fatal Infection With Covid-19, Naresh Doni Jayavelu, Jing Jing Qi, Slim Fourati, Farrah Kheradmand, Charles R Langelier, Lauren I R Ehrlich, Joann Diray-Arce, Annmarie Hoch, Monica Kraft, Patrice M Becker, Matthew C Altman, Ruth R Montgomery

Faculty, Staff and Students Publications

No abstract provided.

Secreted Phosphoprotein 1 In Lung Diseases, Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He

Faculty, Staff and Students Publications

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Gut Dysbiosis Patterns In Cvid Patients With Noninfectious Complications Observed In A Germ-Free Mouse Model Through Fecal Microbiota Transplantation, Joud Hajjar, Anita Y Voigt, Margaret E Conner, Alton G Swennes, Stephanie Fowler, Chadi Calarge, Danielle D Mendonca, Dominique Armstrong, Chen-Yen Chang, Jolan E Walter, Manish J Butte, Tor Savidge, Julia Oh, Farrah Kheradmand, Joseph F Petrosino

Faculty, Staff and Students Publications

Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes

A Fatal Triad: Concurrent Pulmonary Infections With Candida, Mucorales, And Aspergillus In An Immunocompromised Patient With Underlying Vasculitis And Diabetes, Paridhi Ghai, Kavitha Gopalratnam

Posters

We present a case of disseminated fungal disease involving simultaneous infections with Candida, Mucorales, and Aspergillus.

Discharge Practice Variability In Pediatric Chronic Home Invasive Ventilation, Guillermo Beltran-Ale, Ryne Simpson, Terri Magruder, Ajay S Kasi, Amit Agarwal, Jake A Kaslow

Faculty, Staff and Students Publications

Introduction: The Pediatric Mechanical Ventilation Society is a collaboration of pediatric pulmonologists with a focus on pediatric chronic home invasive ventilation (PCHIV). Since the initial discharge on PCHIV is not always directed by pediatric pulmonologists, we sought to understand how this variability between centers impact adherence to American Thoracic Society (ATS) guidelines for PCHIV.

Methods: A survey was distributed to pediatric pulmonologists across multiple platforms inquiring about discharging practices for PCHIV and adherence to six of the nine ATS recommendations for PCHIV. Two subgroups were created based on common practices - discharge by pediatric pulmonologists from a non-ICU unit (pulmonary …

Successful Flexible Bronchoscopic Extraction Of A Dental Foreign Body Aspirated Into The Left Mainstem Bronchus, Alexys Bolden, Hayden Cooper, Lynnetta Payne, Mark Coomes, Mark Cooper

Marshall Journal of Medicine

Foreign body aspiration (FBA) is a potentially life-threatening emergency that commonly occurs in children but varies widely in clinical presentation. Rapid diagnosis and intervention are of the utmost importance to prevent complications such as airway obstruction, infection, and lung injury. While uncommon in adults, most encountered causes occur in the setting of intoxication, neuromuscular weakness, or iatrogenic dental work. Those with dental prostheses are especially susceptible due to the partially attached nature, rendering the risk of accidental dislodgement. This report discusses an uncommon case wherein an 82-year-old male aspirated a dental bridge into his left mainstem bronchus during routine dental …

Liposomes As Imaging Agents Of Inflammation And Oxidative Stress In Bone Implants, Delia Danila, Patricia S Pardo, R Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production …

Impact Of Shift Length On Burnout And Job Or Life Satisfaction Among Allied Healthcare Professionals, Tareq F. Alotaibi, Abdulmohsen Altayyar, Muteb Al Muflih, Nawaf Alqahtani, Naif Alhawiti, Badi A. Alotaibi, Sami Al Ossaimi, Hassan Y. Aljohani, Mobarak Alqahtani, Taha Ismaeil, Mohammed Al Qahtani, Saleh Al Garni

Internet Journal of Allied Health Sciences and Practice

Abstract: Background/Objectives: Healthcare professionals are critical to community well-being, but the 12-versus 8-hour shifts on their stress and burnout are unclear. This study examines the effects of work patterns on the quality of life, job satisfaction, and burnout among allied healthcare professionals. Method: a validated questionnaire was used. A descriptive analysis, independent samples t-test and Mann–Whitney U test were used, and the significance level was p < 0.05. Results: Among the 340 participants, the mean age was 28 years, and most were women (63.5%), single (58%), and worked 8-hour shifts (54.4%). Most (78%) of the participants reported their job satisfaction …

Early Nintedanib Deployment In Covid-19 Interstitial Lung Disease (Endcov-I): Study Protocol Of A Randomised, Double-Blind, Placebo-Controlled Trial, Valeria Santibanez, Aditi Mathur, Jigna Zatakia, Nicole Ng, Michele Cohen, Emilia Bagiella, Stacey-Ann Brown, Ivan O Rosas, Nina M Patel, Amy Olson, Peide Li, Maria Padilla

Faculty, Staff and Students Publications

Introduction: In December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute lung injury evolving to chronic fibrosing interstitial lung disease. While nintedanib, a tyrosine-kinase inhibitor, shows promise in treating progressive fibrotic lung disease, limited randomised trial data exists for post-COVID-19-induced lung injury. We hypothesise that treatment with nintedanib may attenuate advancement to the fibrotic stages, offering a potential avenue for improving outcomes in this specific patient subset.

Methods and analysis: We describe the design of a multicentre, randomised, double-blind, placebo-controlled …

Single Dose Nivolumab And Ipilimumab Treatment Causing Complete And Durable Response In Extensive Stage - Small Cell Lung Cancer Complicated By Severe Sensory Autoimmune Neuropathy, Aaron Lobo Md, Nur Rahman Md, Nicholas Blondin Md, Neal Fischbach

Posters

The use of immune checkpoint inhibitors (ICI) in recent years has increasingly emerged as a second-line treatment in the management of extensive-stage small cell lung cancer (ES-SCLC) compared to conventional chemotherapy alone.

The use of combined ICI therapy by inhibiting two distinct pathways in patients with ES-SCLC has been evaluated in clinical trials. The increase incidence of immune related adverse events (Ir-AE) in these trials due to excessive immune system activation or multiple organ disorders has posed serious clinical challenges.

Here we report a dramatic and durable response to combined immune checkpoint blockade without chemotherapy and discuss the relationship between …

Pulmonary Function Testing In Pediatric Allogeneic Stem Cell Transplant Recipients To Monitor For Bronchiolitis Obliterans Syndrome: A Systematic Review, William A Gower, Maximiliano Tamae-Kakazu, Shivanthan Shanthikumar, Saumini Srinivasan, Erin E Reardon, Amisha V Barochia, Edward Charbek, Charlotte Calvo, Pi Chun Cheng, Shailendra Das, Stella M Davies, Jessica Gross, Ajay Sheshadri, Christoper T Towe, Samuel B Goldfarb, Narayan P Iyer

Faculty, Staff and Students Publications

Background: Bronchiolitis obliterans syndrome (BOS) represents a significant source of morbidity and non-relapse mortality among children and young adults treated with allogeneic hematopoietic stem cell transplantation (aHSCT). Pulmonary function testing (PFT) pre- and post-aHSCT may allow for pre-symptomatic detection of BOS, and thus early intervention. Current guidelines and practices vary regarding which tests to perform and timing relative to transplant. A systematic review evaluating PFT before and after pediatric aHSCT was conducted to inform American Thoracic Society clinical practice guidelines on detection of BOS.

Objective: To determine the optimal approach to conducting PFT prior to and after pediatric aHSCT.

Study …

Advances In Idiopathic Pulmonary Fibrosis Diagnosis And Treatment, Hongli Liu, Jiaxi Shen, Chao He

Faculty, Staff and Students Publications

Significant advances have been made in diagnosing and treating idiopathic pulmonary fibrosis (IPF) in the last decade. The incidence and prevalence of IPF are increasing, and morbidity and mortality remain high despite the two Food and Drug Administration (FDA)-approved medications, pirfenidone and nintedanib. Hence, there is an urgent need to develop new diagnostic tools and effective therapeutics to improve early, accurate diagnosis of IPF and halt or reverse the progression of fibrosis with a better safety profile. New diagnostic tools such as transbronchial cryobiopsy and genomic classifier require less tissue and generally have good safety profiles, and they have been …

Chronic Hepatitis And Hemophagocytic Lymphohistiocytosis Associated With Systemic Chronic Active Epstein-Barr Virus Disease, Emmanuel Palomera-Tejeda, Lauren Shaffer, Michael Shi, Nagasri Shankar, Roshan Raza, George Cholankeril

Faculty, Staff and Students Publications

Systemic chronic active Epstein-Barr virus (EBV) disease is a rare, delayed, and life-threatening complication of EBV infection. It is characterized by persistent viremia and a mononucleosis-like syndrome with multisystemic involvement because of lymphocytic tissue infiltration. We present the case of an 82-year-old woman without known immunodeficiency who presented with abnormal liver enzymes and interstitial pneumonia. Investigations revealed hyperferritinemia, elevated soluble interleukin-2 receptor levels, hypofibrinogenemia, and hepatosplenomegaly, consistent with hemophagocytic lymphohistiocytosis, as well as a high EBV viral load. Liver biopsy demonstrated portal chronic lymphocytic inflammation and positive EBV in situ hybridization, suggesting systemic chronic active Epstein-Barr virus disease as the …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …

Clinical Characteristics Of Patients With Copd And Comorbid Depression And Anxiety: Data From A National Multicenter Cohort Study, Jing Gennie Wang, Sonali Bose, Janet T Holbrook, Lin Nan, Michelle N Eakin, Abebaw M Yohannes, Robert A Wise, Nicola A Hanania

Faculty, Staff and Students Publications

Background: Most studies on mental health among individuals with chronic obstructive pulmonary disease (COPD) utilize screening questionnaires, which detect psychiatric symptoms, but cannot be used to diagnose depression/anxiety disorders. We utilized the Mini-International Neuropsychiatric Interview (MINI) to identify depression/anxiety disorders meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria and described associated disease burden in people with COPD.

Methods: This is a cross-sectional, secondary analysis of a multicenter study designed to evaluate anxiety questionnaires in COPD patients. Research coordinators administered both the MINI and screening questionnaires to determine participants who met diagnostic criteria for depression/anxiety …

Peripheral Extracellular Vesicles For Diagnosis And Prognosis Of Resectable Lung Cancer: The Lucex Study Protocol, Jorge Rodríguez-Sanz, Nadia Muñoz-González, José Pablo Cubero, Pablo Ordoñez, Victoria Gil, Raquel Langarita, Myriam Ruiz, Marta Forner, Marta Marín-Oto, Elisabet Vera, Pedro Baptista, Francesca Polverino, Juan Antonio Domingo, Javier García-Tirado, José María Marin, David Sanz-Rubio

Faculty, Staff and Students Publications

Background/Objectives: Lung cancer is the primary cause of cancer-related deaths. Most patients are typically diagnosed at advanced stages. Low-dose computed tomography (LDCT) has been proven to reduce lung cancer mortality, but screening programs using LDCT are associated with a high number of false positives and unnecessary thoracotomies. It is therefore imperative that a certain diagnosis is refined, especially in cases of solitary pulmonary nodules that are difficult to technically access for an accurate preoperative diagnosis. Extracellular vesicles (EVs) involved in intercellular communication may be an innovative biomarker for diagnosis and therapeutic strategies in lung cancer, regarding their ability to carry …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Skewed Adaptive Immune Responses Are Involved In Alpha-1 Antitrypsin Deficiency Emphysema, Joselyn Rojas-Quintero, Scott A Ochsner, Hyun-Sung Lee, Christine Cong, Alan Waich Cohen, Adrianne S Colborg, Konstantin Tsoyi, Maria C Basil, Edward Cantu, Ivan O Rosas, Neil J Mckenna, Raúl San-José Estépar, Igor Barjaktarevic, Andrew A Wilson, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …