Digital Commons Network^™

Advanced Specificity And Sensitivity Studies Relative To A Research Use Only Transcription-Mediated Amplification-Based Assay For Treponema Pallidum Rna Detection, Trinity Krueger, Grace Kadonsky, Elizabeth Thelen, Amanda Zapp, Josephine Moore, Ahmet Muslu, Allan Pillay, Irene A Stafford, Erik Munson

Faculty, Staff and Student Publications

Preliminary experimentation has suggested that a research-use-only real-time transcription-mediated amplification assay for Treponema pallidum (RUO T. pallidum TMA) yields instances of T. pallidum nucleic acid detection that coincide with non-treponemal serology in men who have sex with men (MSM) at increased risk for sexually transmitted infection. To further characterize the specificity of RUO T. pallidum TMA testing, 3,586 rectal swab specimens reported as “not detected” by the assay generated a mean endpoint FAM fluorescence of 637.5 units. Introduction of Treponema denticola, Treponema phagedenis, and Treponema refringens nucleic acid into matrices generated mean endpoint FAM fluorescence ranging from 620.7 …

Csf-Exosomal Mirnas And Delayed Cerebral Ischemia: Insights Into Pathophysiology But No Definitive Biomarkers, Chathathayil M Shafeeque, Devin W Mcbride, Yuanqing Yan, Hussein A Zeineddine, John P Hagen, H Alex Choi, Jude P Savarraj, Ari Dienel, Spiros L Blackburn, Peeyush Kumar Thankamani

Faculty, Staff and Student Publications

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is notoriously known for its high mortality and morbidity. Approximately one-third of the patients who survive aneurysm rupture are reported to develop delayed cerebral ischemia (DCI), which contributes to a poor clinical outcome. Currently, there are no biomarkers for identifying which aSAH patients are at risk of developing DCI. We aimed to determine the feasibility of cerebrospinal fluid (CSF) exosomal microRNAs (miRNAs) for predicting DCI post-aSAH.

Methods: aSAH patients were prospectively enrolled, and CSF samples were collected at two time points (< 24 h and 72 h post-aSAH) from individuals undergoing external ventricular drainage. Exosomal miRNAs were isolated from the CSF for analysis. In the initial group of patients (discovery cohort), an exploratory analysis was conducted using a CSF panel containing 84 miRNAs, assessed by quantitative real-time PCR (RT-qPCR). Based on this analysis, 27 miRNAs were selected for further evaluation in a second group of patients (validation cohort). Among these, 10 miRNAs had previously been reported in SAH-related CSF studies, supporting their relevance for continued investigation.

Results: In this study, RT-qPCR analysis of 84 miRNAs in CSF samples from …

Development Of Emerin Mrna Lipid Nanoparticles To Rescue Myogenic Differentiation., Nicholas Marano, Liza Elif Guner, Rachel S Riley, James M Holaska

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Emery-Dreifuss muscular dystrophy 1 (EDMD1) arises from mutations in EMD. Most EDMD1 patients lack detectable emerin expression. They experience symptoms such as skeletal muscle wasting, joint contractures, and cardiac conduction defects. Currently, physicians rely on treating patient symptoms without addressing the underlying cause-lack of functional emerin protein. Thus, there is a need for therapeutic approaches that restore emerin protein expression to improve patient outcomes. One way would be to deliver emerin mRNA or protein directly to affected tissues to restore tissue homeostasis. Here, we evaluated the utility of lipid nanoparticles (LNPs) to deliver emerin mRNA to diseased cells. LNPs …

Variability In Long Covid Definitions And Validation Of Published Prevalence Rates, Lauren E. Wisk, Michelle L'Hommedieu, Kate Diaz Roldan, Imtiaz Ebna Mannan, Erica S. Spatz, Robert A. Weinstein, Arjun K. Venkatesh, Michael Gottlieb, Ryan Huebinger, Kristin L. Rising, Juan Carlos C. Montoy, Kari A. Stephens, Robert M. Rodriguez, Mandy J. Hill, Kelli N. O'Laughlin, Nicole L. Gentile, Ahamed H. Idris, Shu-Xia Li, Michelle Santangelo, Efrat R. Kean, Samuel A. Mcdonald, Kristyn Gatling, Joann G Elmore

Jefferson Center for Connected Care Faculty Papers

IMPORTANCE: Long COVID definitions vary widely, and no consensus exists on how to accurately measure its prevalence, complicating both clinical care and research.

OBJECTIVE: To assess long COVID prevalence using various definitions from published literature.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter cohort study used data from the longitudinal Innovative Support for Patients With SARS-CoV-2 Infections Registry (INSPIRE). Participants aged 18 years or older with symptoms suggestive of COVID-19 illness at the time of their index SARS-CoV-2 test enrolled at 8 sites across the US from December 11, 2020, through August 29, 2022, with follow-up surveys collected through February 28, …

Structural Basis For Membrane Microdomain Formation By A Human Stomatin Complex, Jack Stoner, Shufang Li, Ziao Fu

2020-Current year OA Pubs

Biological membranes are not just passive barriers-they actively sense and respond to mechanical forces, in part through specialized proteins embedded within them. Among these are Stomatin-family proteins, which are known to influence membrane stiffness and regulate ion channels, yet how they achieve these functions at the molecular level has remained elusive. Here, we report the 2.2 Å cryo-electron microscopy structure of the human Stomatin complex in a native membrane environment. We find that Stomatin assembles into a 16-subunit ring-shaped homo-oligomer, forming a ~12 nm-wide cage that defines a mechanically distinct, curvature-resistant membrane microdomain. While the majority of the complex exhibits …

Pride-Ftg Advances Academic Careers Of Underrepresented Early-Stage Investigators Performing Blood Disorders Research, Betty S Pace, Oluwatoyosi A Onwuemene, Athena Starlard-Davenport, Rhea-Beth Markowitz, Vahé Heboyan, Petar Datsov, Treva Rice

2020-Current year OA Pubs

Despite improvements in the diversity of the US biomedical research workforce, individuals from different racial/ethnic groups remain underrepresented. Even though mentoring is critical for career advancement, underrepresented faculty have limited opportunities. Therefore, we evaluated a multipronged mentoring approach for early-stage underrepresented faculty trained in the Programs to Increase Diversity Among Individuals Engaged in Health-Related Research-Functional and Translational Genomics of Blood Disorders (PRIDE-FTG). The selection process involved a rigorous review of applications, considering factors such as academic potential, research interests, and commitment to diversity in biomedical research. This yearlong training experience includes 2 summer institutes consisting of lectures, grant-writing workshops, and …

Tracing Sars-Cov-2 Clusters Across Local Scales Using Genomic Data, Leke Lyu, Mandev Gill, Guppy Stott, Sachin Subedi, Cody Dailey, Gabriella Veytsel, Magdy Alabady, Kayo Fujimoto, Ryker Penn, Pamela Brown, Roger Sealy, Justin Bahl

Faculty, Staff and Student Publications

A quantitative understanding of local transmission dynamics is essential for designing effective prevention strategies. In this study, we developed a computational workflow to identify viral introductions and trace locally circulating clusters. We analyzed over 26,000 SARS-CoV-2 genomes and their associated metadata, collected between January and October 2021, to explore introduction and local dispersal patterns in Greater Houston, a major metropolitan area known for its demographic diversity. Our analysis identified more than 1,000 independent introduction events, resulting in clusters of varying sizes. The majority of introductions originated from domestic sources, while international introductions occurred earlier and were associated with larger cluster …

Molecular Inflammatory Expression Profiles Associated With The Frequency Of Pain In Individuals With Sickle Cell Disease, Lana Mucalo Katunaric, Shuang Jia, Ashima Singh, Mark F. Roethle, Julie A. Panepinto, David C. Brousseau, Martin J. Hessner, Amanda M. Brandow

Department of Pediatrics Faculty Papers

Pain is the most common complication of sickle cell disease (SCD). The underlying biology of SCD pain is not well understood, which is a barrier to novel, effective analgesic and preventive therapies. A wide variability in the phenotypic expression of pain exists among individuals with SCD, despite the inheritance of a similar defective hemoglobin gene. This interindividual pain variability further complicates the ability to understand the biology and effectively treat pain. We sought to discover a biological signature comprising differentially expressed genes unique to SCD that could differentiate between individuals with varied pain frequency. We conducted plasma-induced transcription analysis from …

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 …

Assessing The Muc5b Promoter Variant In A Large Cohort Of Systemic Sclerosis-Associated Interstitial Lung Disease, Carlos Rosa-Baez, Carlos Rangel-Pelaez, Inmaculada Rodriguez-Martin, Martin Kerick, Alfredo Guillen-Del-Castillo, Carmen P Simeon-Aznar, José Luis Callejas, Alexandre E Voskuyl, Alexander Kreuter, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Lorenzo Beretta, Maureen D Mayes, Christopher P Denton, Shervin Assassi, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Objective: The common gain-of-function variant rs35705950, located in the promoter of MUC5B gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.

Methods: Samples were collected from blood/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100 Kb were obtained using genomic imputation. Subsequently, we tested their …

European And African Ancestry-Specific Plasma Protein-Qtl And Metabolite-Qtl Analyses Identify Ancestry-Specific T2d Effector Proteins And Metabolites, Chengran Yang, Priyanka Gorijala, Jigyasha Timsina, Lihua Wang, Menghan Liu, Ciyang Wang, William Brock, Yueyao Wang, Fumihiko Urano, Yun Ju Sung, Carlos Cruchaga

2020-Current year OA Pubs

In this study, we generated and integrated plasma proteomics and metabolomics with the genotype datasets of over 2300 European (EUR) and 400 African (AFR) ancestries to identify ancestry-specific multi-omics quantitative trait loci (QTLs). In total, we mapped 954 AFR pQTLs, 2848 EUR pQTLs, 65 AFR mQTLs, and 490 EUR mQTLs. We further applied these QTLs to ancestry-stratified type-2 diabetes (T2D) risk to pinpoint key proteins and metabolites underlying the disease-associated genetic loci. Using INTACT that combined trait-imputation and colocalization results, we nominated 270 proteins and 72 metabolites from the EUR set; seven proteins and one metabolite from the AFR set …

Hippocampal Avoidance During Prophylactic Cranial Irradiation For Patients With Small Cell Lung Cancer: Randomized Phase Ii/Iii Trial Nrg-Cc003, Vinai Gondi, Stephanie L Pugh, Minesh P Mehta, Jeffrey S Wefel, Wolfgang A Tomé, Alexander Y Sun, John Grecula, Kristin J Redmond, Shannon Fogh, Laurie Gaspar, Andre Konski, Joseph Bovi, Clifford G Robinson, Benjamin Corn, Gregory M Videtic, Benjamin H Lok, Harold A Yoon, John H Heinzerling, Albert S Denittis, Ronald C Mcgarry, Kiran Devisetty, Vijayananda Kundapur, Abraham J Wu, Edward C Mccarron, Isabelle Thibault, Edmund L Simon, Andrew M Baschnagel, Samir Narayan, Jondavid Pollock, Rebecca Paulus, Lisa A Kachnic

Faculty, Staff and Student Publications

Purpose: Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity.

Methods: This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF …

Polo-Like Kinase 1 Inactivation Enhances Pi3k Inhibition-Mediated Apoptosis Of Notch1-Mutant Head And Neck Squamous Cell Carcinoma, Pooja A Shah, Tuhina Mazumdar, Soma Ghosh, Lacin Yapindi, Reid T Powell, Yong S Park, Li Shen, Anne M Fernandez, Clifford C Stephan, Jing Wang, Andrew G Sikora, Jawad Kazi, Mitchell J Frederick, Faye M Johnson

Children’s Nutrition Research Center Staff Publications

PI3K inhibition causes apoptosis selectively in NOTCH1-mutant head and neck squamous cell carcinoma (HNSCC), but modest single-agent responses and acquired resistance (AR) limit the clinical efficacy of targeted agents. To address these limitations, we investigated novel combination therapies. We tested the efficacy of 5768 compounds as single agents and 139 in combination with PI3K inhibitors in sensitive and AR NOTCH1-mutant HNSCC cell lines. We generated synergy/efficacy classifications for the combinations using multiple metrics of statistical drug synergy and growth rate indices. The PLK1/PI3K combination's efficacy was validated using orthogonal in vitro methods and in two HNSCC xenograft models. Compound efficacy …

Vaccination With Acinetobacter Baumannii Adhesin Abp2d Provides Protection Against Catheter-Associated Urinary Tract Infection, Morgan R Timm, Kevin O Tamadonfar, Taylor M Nye, Jesús Bazán Villicaña, Jerome S Pinkner, Karen W Dodson, Ali H Ellebedy, Scott J Hultgren

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) contribute greatly to the burden of healthcare-associated infections. Acinetobacter baumannii is a Gram-negative bacterium with high levels of antibiotic resistance that is of increasing concern as a CAUTI pathogen. A. baumannii expresses fibrinogen-binding adhesins (Abp1D and Abp2D) that mediate biofilm formation on catheters, which become coated with fibrinogen upon insertion. Here we develop a protein subunit vaccine against the Abp1D and Abp2D receptor binding domains (RBD) and show that vaccination significantly reduces bacterial titers in a female mouse model of CAUTI. We further demonstrate that immunity to Abp2D

Assessing Buprenorphine Treatment Utilization And Samhsa Data Waiver Provider Distribution In 2021: A Real-World Analysis In California, Yun Wang, Tao Hu, Chih-Hung Chang, Matthew Heshmatipour, Jeff Jianfei Guo, Moom R Roosan, Karen A Miotto

2020-Current year OA Pubs

Qualified clinicians previously required a practitioner waiver (i.e., "DATA-waiver" or "X-waiver") to offer buprenorphine, a medication for opioid use disorder (OUD). However, many counties in the US experience fewer buprenorphine prescriptions due to factors such as "DATA-waiver" providers underutilizing their buprenorphine prescribing ability. Our study aimed to compare the availability of active buprenorphine-prescribing clinicians in California to the Substance Abuse and Mental Health Services Administration (SAMSHA)-listed DATA waived prescribers under each 5-digit ZIP Code. This study utilized the buprenorphine prescription record data in 2021 from California's Controlled Substance Utilization Review and Evaluation System (CURES). The list of the locators for …

Impact Of A Multi-Strain L. Crispatus-Based Vaginal Synbiotic On The Vaginal Microbiome: A Randomized Placebo-Controlled Trial, Jacques Ravel, Sheri Simmons, Eleni Greenwood Jaswa, Sara Gottfried, Miriam Greene, Susan Kellogg-Spadt, Dirk Gevers, Diane M. Harper

Institute of Emerging Health Professions Faculty Papers

A clinical trial of a multi-strain vaginal synbiotic (NCT05659745, registered 12/19/2022 at clinicaltrials.gov) led to an optimal vaginal microbiome dominated by L. crispatus (CST I). The synbiotic led to a significant increase in L. crispatus compared to placebo (p <  0.05), and conversion to CST I was significantly higher with the vaginal synbiotic than with placebo (90 vs 11%; p <  0.002). Mechanistically, the synbiotic reduced Gardnerella vaginalis and Candida, clinically important microbes.

Subsets Of Follicular Lymphoma 3b Have Divergent Outcomes: Results From The Prospective Multicenter Mer And Leo Cohorts, Patrizia Mondello, David Russler-Germain, Brad Kahl, Et Al.

2020-Current year OA Pubs

Follicular lymphoma (FL) 3B is considered an aggressive lymphoma, however recent studies have challenged this paradigm. Additional controversy involves the clinical implication of pure FL3B (FL3Bp) vs FL3B with concurrent diffuse large B cell lymphoma (DLBCL) (FL3Bc). To address these questions, we performed a pooled study of the MER and LEO cohorts comparing 464 newly diagnosed, R-CHOP-treated patients with FL1-2 (n = 216), FL3A (n = 170), FL3B (n = 78) and 739 DLBCL. Among FL3B patients, 19 (24%) had FL3Bc and 59 (76%) FL3Bp. Baseline characteristics and outcomes were similar between the two FL3B subtypes. Compared to FL1-3A, FL3B …

Hsp70 Is A Chaperone For Il-33 Activity In Chronic Airway Disease, Omar A. Osorio, Heather E. Raphael, Colin E. Kluender, Ghandi F. Hassan, Lucy S. Cohen, Deborah F. Steinberg, Ella Katz-Kiriakos, Morgan D. Payne, Ethan M. Luo, Jamie L. Hicks, Derek E. Byers, Jennifer Alexander-Brett

2020-Current year OA Pubs

IL-33 is a key driver of type 2 inflammation and implicated in pathology of chronic obstructive pulmonary disease (COPD) and asthma. However, the mechanism for IL-33 secretion and regulation in the context of chronic airway disease is poorly understood. We previously reported an airway disease-associated isoform IL-33Δ34 that escapes nuclear sequestration and is tonically secreted from epithelial cells. Here, we describe how this IL-33Δ34 isoform interacts with HSP70 within cells and is targeted to secretory organelles through coordinated binding to phosphatidylserine (PS) and delivered to compartments for unconventional protein secretion (CUPS). Once secreted, extracellular HSP70 (eHSP70) in complex with IL-33Δ34 …

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 …

Efficient Training Corpus Retrieval For Large Language Model Fine Tuning: A Case Study In Cancer., Avisha Das, Chiamaka Diala, Guocai Chen, Zhao Li, Rongbin Li, Omer Anjum, W Jim Zheng

Faculty, Staff and Student Publications

The objective is to create an automated knowledge extraction tool for cancer research that builds high-quality academic corpora for LLM fine-tuning while investigating its effectiveness in interleukin-6 and bladder cancer domains. To address the current gap in knowledge retrieval techniques for cancer research data collection, we propose KnowledgePipeline, a novel automated tool that incorporates diverse aspects of academic papers and metadata. Our tool integrates content, co-citations, and co-authorship networks to construct domain-specific academic corpora suitable for fine-tuning LLMs. We leverage two LLMs (GPTJ-6.7B and Galactica30B) trained on domain-specific question-answer pairs from the refined data. The system's evaluation focuses on both …

Amputation Trends Among People Who Use Drugs In The Context Of Philadelphia’S Increasingly Xylazine Adulterated Drug Supply, Rose Laurano, Monika Pogorzelska-Maziarz, Traci C. Green, Sara Beachy, Kristin L. Rising, Jeffrey K. Hom, Megan K. Reed

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: Xylazine-adulterated fentanyl has rapidly spread across the United States and has been increasingly detected in overdose deaths in Philadelphia, PA through medical examiner reports, clinical testing, and widescale drug checking. Xylazine use has been associated with wounds which may lead to amputation, but the extent of this outcome has not been explored.

METHODS: Utilizing the 10th revision of the International Classification of Diseases (ICD-10) codes, we conducted a de-identified retrospective analysis of data for patients identified with opioid related disorders (ICD-10 code F11) admitted to four different hospitals in Philadelphia, PA between 2018 and 2023. Exposure to xylazine use …

Discontinuation Rates And Predictors Of Medical Cannabis Cessation For Chronic Musculoskeletal Pain, Mohammad Khak, Sina Ramtin, Juliet Chung, Asif M. Ilyas, Ari Greis

Rothman Institute Papers

Medical cannabis (MC) is increasingly used as a treatment for chronic musculoskeletal pain, but there is limited data on factors influencing its discontinuation. This study aims to investigate the rates of MC discontinuation and explore factors influencing it in patients with chronic musculoskeletal pain. A retrospective analysis was conducted on 78 patients certified for medical cannabis over a 2 year period. Patient demographics, pain origin, and Global Physical Health (GPH) and Global Mental Health (GMH) scores were collected before intervention. Discontinuation rates were measured at three-month and one-year follow-up. Statistical analyses, including Fisher's Exact Test and two-sample t-tests, were performed …

Performance Of Dehydroepiandrosterone Sulfate And Baseline Cortisol In Assessing Adrenal Insufficiency, Ashley J Han, Malavika Suresh, Lucinda M Gruber, Alicia Algeciras-Schimnich, Sara J Achenbach, Elizabeth J Atkinson, Irina Bancos

Faculty, Staff and Students Publications

Context: Diagnosing adrenal insufficiency (AI) often requires complex testing, which can be time-consuming and expensive. Dehydroepiandrosterone sulfate (DHEAS) is a promising marker of hypothalamic-pituitary-adrenal axis function; however, its diagnostic performance has not yet been evaluated in a large-scale study.

Objective: Evaluate the performance of DHEAS and baseline cortisol in assessing AI.

Design: Single-center retrospective cohort study.

Setting: Referral center.

Patients: Adults who underwent cosyntropin stimulation testing (CST) between 2005 and 2023 and had DHEAS measured within 3 months prior to CST.

Main outcome measures: Area under receiver operating characteristic curve (AUROC) for DHEAS and baseline cortisol. Prevalence of AI based …

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 …

Advancing Workforce Development In Digital Health: A Regional Model From The Gcc, Manal Almalki, Osama El-Hassan, Jawad Ahmed, Amr Jamal, Mowafa Househ, Evelyn Hovenga, Paul Barach

College of Population Health Faculty Papers

This study examines the evolution of ZIMAM's role in the Gulf Cooperation Council's (GCC) taskforce on workforce development in digital healthcare. Established in 2016 and formalized as a non-profit organization in 2023, ZIMAM integrates international best practices, regional insights, and innovative strategies to develop a scalable digital health knowledge and skills framework. ZIMAM's methodology includes competency mapping aligned with the Skills Framework for the Information Age (SFIA), stakeholder engagement, and iterative validation to ensure relevance and adaptability. Key ZIMAM initiatives encompass the development of governance structures, capacity-building workshops, annual conferences, and recognition programs such as the ZIMAM-ELSEVIER Digital Health Awards. …

Generational Health Professional Perceptions About Artificial Intelligence Impact On Clinical Work, Karima Lalani, Kerryn Butler-Henderson, David T Marc, Susan H Fenton

Faculty, Staff and Student Publications

Whilst the evidence-base related to artificial intelligence (AI) has been growing in relation to its use and impact on healthcare, there is a lack of evidence related to the health workforce impact and no research examining the generational perceptions in relation to the health workforce and AI. This paper presents the results of a survey, which found generational differences in perceptions about the impact of AI on clinical jobs. Gen Z and Millennials were more likely to agree with statements that AI will improve their clinical decision-making skills/abilities, accomplish clinical tasks more quickly, and cause unemployment in their professional occupation. …

Enhancing Digital Health Development Through Speech Act Theory: Application To Peripartum Depression Management, Alexandra Zingg, Tavleen Singh, Michael Truong, Sahiti Myneni

Faculty, Staff and Student Publications

The peripartum period is a time of complex transition into motherhood when women may develop peripartum depression (PPD). Digital information sources can help prevent and monitor symptoms through social support and mental health knowledge. However, few studies have characterized the content and form of peer interactions in PPD online forums to inform interventions. In this paper, we present preliminary work using a dataset of 55,301 interactions to inform our digital health development. We combine manual coding for speech acts, behavioral theory mapping, and user engagement modeling to conceptualize dynamic digital education modules for PPD. Results reveal "Expressive" speech act, where …

Towards Data-Driven Science Literacy: Extracting Psycholinguistic Markers In Vaping-Related Online Peer Interactions, Michael Truong, Ahmed Abdelhameed, Tavleen Singh, Kirk Roberts, Sahiti Myneni

Faculty, Staff and Student Publications

Social media debates on e-cigarettes raise public health concerns due to evolving evidence and conflicting guidelines. We analyzed 25,127 vaping-related comments to explore how users discuss vaping-related topics. Our analysis revealed 25 topics grouped into three parent topics: positive effects of vaping, negative effects of vaping, and vaping-related news & information. Significant differences were observed in psycholinguistic characteristics with high emotional exchanges as positive and negative effects of e-cigarettes are debated. Our results can inform interventions promoting science literacy and misinformation resistance.

Histologic And Immune Characterization Of Cutaneous Immune-Related Adverse Events Induced By Immune Checkpoint Inhibitors, Omar Pacha, Anisha B Patel, Jonathan L Curry, Cara L Haymaker, Nejla Ozirmak Lermi, Dzifa Yawa Duose, Ken Chen, Joud Hajjar, Aung Naing

Faculty, Staff and Student Publications

Background: Although immune checkpoint inhibitors (ICIs) are efficacious, they often cause immune-related adverse events (irAEs), most commonly cutaneous irAEs (CirAEs). The mechanisms underlying CirAEs remain unclear.

Methods: Attempting to better understand their mechanisms and histology we conducted a prospective study of 15 patients with advanced cancers treated with ICIs who developed grade 2 or higher CirAEs. Clinical and histologic characterization of biopsy specimens of CirAEs was performed. Histologic analysis of patient biopsy specimens were subdivided by epidermal reaction patterns that included spongiotic, lichenoid, and interface dermatitis patterns. A targeted RNA expression assay was used to identify immune markers in CirAE …