Digital Commons Network^™

Implementation Of Clinical Practice Guidelines To Prevent Cervical Cancer: Mixed Methods Study, Oliver C Ezechi, Folahanmi T Akinsolu, Olunike R Abodunrin, Oluwabukola M Ola, Chisom Obi-Jeff, Ishak K Lawal, George U Eleje, Joseph D Tucker, Juliet I Iwelunmor

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is a common cause of death among women globally, particularly in Africa. Each year, an average of 7093 women in Nigeria die from cervical cancer. Clinical practice guidelines developed by the Society of Obstetrics and Gynecology of Nigeria (SOGON) aim to prevent cervical cancer. However, the extent of their adoption among gynecologists remains unclear.

OBJECTIVE: This study aimed to assess Nigerian gynecologists' awareness, understanding, and incorporation of the SOGON clinical practice guidelines for cervical cancer prevention in their clinical practices.

METHODS: A convergent parallel mixed methods design was used. Quantitative data were collected via a web-based and …

Clinical, Tumor, And Product Features Associated With Outcomes After Axicabtagene Ciloleucel Therapy In Follicular Lymphoma, Soumya Poddar, Jiali Yan, Gayatri Tiwari, Darawan Rinchai, Justin Budka, Wangshu Zhang, Weixin Peng, Shruti Salunkhe, Madison Davis, Qinghua Song, Sara Beygi, Harry Miao, Mike Mattie, Rhine S Shen, Caron A Jacobson, Davide Bedognetti, Simone Filosto, Sattva S Neelapu

Faculty, Staff and Student Publications

Background: Axicabtagene ciloleucel (axi-cel), anti-CD19 chimeric antigen receptor (CAR) T cell therapy, demonstrated remarkable efficacy with manageable toxicity in relapsed/refractory indolent B cell lymphomas in the ZUMA-5 trial.

Methods:Here, we report associations of product attributes, serum biomarkers, clinical features, and tumor characteristics with outcome in 124 patients with follicular lymphoma (FL).

Results: In univariate and multivariate analyses, pretreatment inflammatory markers, including TNF-α and IL-12p40, as well as total metabolic tumor volume (TMTV), associated with disease progression. Conversely, T-naive–like product phenotype associated with improved outcome, particularly in patients with high TMTV. These covariates improved risk stratification when combined with the …

Outcomes Of Patients With Newly Diagnosed Acute Myeloid Leukemia With Flt3-Tyrosine Kinase Domain Mutations: Prognostic Implications Of Npm1 Co-Mutation, Sankalp Arora, Wei-Ying Jen, Musa Yilmaz, Indraneel Deshmukh, Jayastu Senapati, Sanam Loghavi, Ghayas C Issa, Nicholas J Short, Tapan M Kadia, Courtney D Dinardo, Gautam Borthakur, Joseph Jabbour, Naveen Pemmaraju, Michael Andreeff, Koichi Takahashi, Kapil Bhalla, Uday Popat, Elizabeth J Shpall, Betul Oran, Hussein A Abbas, Guillermo Garcia-Manero, Farhad Ravandi, Hagop Kantarjian, Naval Daver

Faculty, Staff and Student Publications

Background: The prognostic impact of Fms-like tyrosine kinase 3 (FLT3)-tyrosine kinase domain (TKD) mutation in patients with acute myeloid leukemia (AML) is not well defined. The authors described outcomes of one of the largest cohorts of patients with FLT3-TKD mutated (FLT3-TKDmut) AML to date.

Methods: This retrospective study included patients with newly diagnosed AML who received frontline treatment at The University of Texas MD Anderson Cancer Center from January 2012 to March 2024 divided into two cohorts: FLT3-TKDmut AML and nucleophosmin-mutated (NPM1mut)/FLT3-TKD wild-type (FLT3-TKDwt) AML. Patients with FLT3 internal tandem duplication mutations were excluded.

Results: In total, 2922 patients were …

Beyond Smoking: A Geospatial Investigation Of Factors Associated With Lung And Bronchus Cancer Risk In Pennsylvania, Tesla D. Dubois, Daniel Wiese, Kevin A. Henry, Shannon M. Lynch

Kimmel Cancer Center Faculty Papers

INTRODUCTION: While smoking is the leading cause of lung and bronchus cancer (LBC), additional exposures have been implicated and may explain the rise in LBC among never-smokers. To better understand the spatial distribution of LBC incidence and associated risk factors, this study aims to identify geographic areas with significantly elevated incidence rates in Pennsylvania and investigate the potential underlying risk factors.

METHODS: Using cancer registry data aggregated to the census tract level, spatial scan statistics were applied to detect areas of higher-than-expected LBC incidence across the state. Associations were then tested between census tract inclusion in a high-incidence area and …

Artificial Intelligence Algorithm Predicts Response To Immune Checkpoint Inhibitors, Faisal Fa'ak, Nicolas Coudray, George Jour, Milad Ibrahim, Irineu Illa-Bochaca, Shi Qiu, Adalberto Claudio Quiros, Ke Yuan, Douglas B Johnson, David L Rimm, Jeffrey S Weber, Aristotelis Tsirigos, Iman Osman

2020-Current year OA Pubs

PURPOSE: Cancer treatment has been revolutionized by immune checkpoint inhibitors (ICI). However, a subset of patients do not respond and/or they experience significant adverse events. Attempts to integrate reliable biomarkers of ICI response as part of standard care have been hampered by limited generalizability. We previously reported our supervised machine learning (ML) model in a retrospective cohort of metastatic melanoma.

EXPERIMENTAL DESIGN: In this study, we expanded our testing to include larger cohorts of patients with melanoma accrued at several sites, including patients enrolled in clinical trials in both adjuvant and metastatic settings. We examined pretreatment hematoxylin and eosin slides …

Multidimensional Analysis Of B7 Homolog 3 Rna Expression In Small Cell Lung Cancer Molecular Subtypes, Carl M Gay, Taofeek K Owonikoko, Lauren A Byers, Noura J Choudhury, Sajid Ahmed, Zachary Cain, Xiaozhong Qian, Matthew Brentnall, Simon Heeke, Ming Poi, Sharon Wu, Charles M Rudin

Faculty, Staff and Student Publications

Purpose: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters.

Experimental design: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor …

Multimodal Spatial Transcriptomic Characterization Of Mouse Kidney Injury And Repair, Qiao Xuanyuan, Haojia Wu, Hemalatha Sundaramoorthi, Pierre Isnard, Changfeng Chen, Waleed Rahmani, Benjamin D Humphreys

2020-Current year OA Pubs

The transition from acute kidney injury to chronic kidney disease is characterized by significant changes in the cellular composition and molecular interactions within the kidney. Utilizing high-resolution Xenium and whole transcriptome Visium spatial transcriptomics platforms, we analyze over a million cells on 12 male mouse kidneys across six stages of renal injury and repair. We define and validate 20 major kidney cell populations and delineate distinct cellular neighborhoods through this multimodal spatial analysis. We further reveal a specific fibro-inflammatory niche enriched in failed-repair proximal tubule cells, fibroblasts, and immune cells, with conserved neighborhood gene signatures across mouse and human. Within …

Cortical Spectral Dynamics Of Vibrotactile Frequency Processing, Nabi Rustamov, Phillip Demarest, Zhuangyu Han, Safia Mohamud, Simon Haroutounian, Eric C Leuthardt

2020-Current year OA Pubs

While scientific research has extensively explored how the brain integrates touch and pain signals, the cerebral processing of specific vibrotactile frequencies remains poorly understood. This gap is particularly significant given clinical evidence that vibrotactile stimulation can reduce pain in both chronic pain patients and experimental settings. Our study investigated the cortical electrophysiological correlates of peripheral vibrotactile stimulation across different frequencies in healthy volunteers, with a focus on frequency-dependent patterns of neuronal activation. While electroencephalogram (EEG) was recorded, healthy participants received vibrotactile stimulation (high-frequency burst stimulation with different inter-burst intervals) to the left index fingertip at frequencies corresponding to established neural …

Genetic Deletion Of The Sodium Phosphate Cotransporter Napi2a Ameliorates Heart Failure In Mice, Hiroko Yamauchi-Sawada, Benjamin D Humphreys, Et Al.

2020-Current year OA Pubs

Apical membrane sodium transporters in renal proximal tubules, such as sodium-glucose co-transporter 2, are attractive therapeutic targets for the treatment of heart failure (HF). Sodium-phosphate co-transporter 2a (NaPi2a) is predominantly expressed in the apical membrane of proximal tubular epithelia and functions to reabsorb filtered phosphate and sodium. It currently remains unclear whether the inhibition of NaPi2a attenuates HF. We found that NaPi2a deficiency improved the cardiac phenotypes of the HF models of transverse aortic constriction (TAC) and doxorubicin (Dox) cardiotoxicity. Natriuretic and phosphaturetic effects were observed in NaPi2a-KO mice under normal conditions, resulting in low serum phosphate and fibroblast growth …

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 …

Cardiovascular Autonomic Neuropathy Defined By Indices Of Heart Rate Variability Is Associated With Cardiovascular Disease: A Longitudinal Cohort Study Of Participants With Type 1 Diabetes, Barbara H Braffett, Laure El Ghormli, Catherine Martin, Neil H White, Irl B Hirsch, Anne Bantle, Anders Carlson, Ellen Leschek, Rose Gubitosi-Klug, Elsayed Z Soliman, Adrian Vella, Bruce A Perkins, Ionut Bebu, Rodica Pop-Busui, Dcct/Edic Research Group

2020-Current year OA Pubs

BACKGROUND: To describe longitudinal prevalence and risk factors associated with cardiovascular autonomic neuropathy (CAN), defined by heart rate variability (HRV) indices, and evaluate the impact of CAN on cardiovascular disease (CVD), in adults with type 1 diabetes (T1D) from the Epidemiology of Diabetes Interventions and Complications (EDIC) study.

METHODS: Standard resting electrocardiogram (ECG) recordings were obtained annually in 997 participants (mean ± SD age 56.2 ± 6.8 years; T1D duration 34.7 ± 7.9 years; 48% female) between 2015 and 2022. The standard deviation of normally conducted R-R intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals …

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 …

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, …

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 …

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 …

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 …

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 …

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. …

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 …

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 …

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 …

Artificial Transneurons Emulate Neuronal Activity In Different Areas Of Brain Cortex, Rivu Midya, Ambarish S Pawar, Debi P Pattnaik, Eric Mooshagian, Pavel Borisov, Thomas D Albright, Lawrence H Snyder, R Stanley Williams, J Joshua Yang, Alexander G Balanov, Sergei Gepshtein, Sergey E Savel'ev

2020-Current year OA Pubs

Rapid development of memristive elements emulating biological neurons creates new opportunities for brain-like computation at low energy consumption. A first step toward mimicking complex neural computations is the analysis of single neurons and their characteristics. Here we measure and model spiking activity in artificial neurons built using diffusive memristors. We compare activity of these artificial neurons with the spiking activity of biological neurons measured in sensory, pre-motor, and motor cortical areas of the monkey (male) brain. We find that artificial neurons can operate in diverse self-sustained and noise-induced spiking regimes that correspond to the activity of different types of cortical …

Analysis Of Lifespan Across Diversity Outbred Mouse Studies Identifies Multiple Longevity-Associated Loci., Martin N Mullis, Kevin M Wright, Anil Raj, Daniel M Gatti, Peter C. Reifsnyder, Kevin Flurkey, Jonathan R Archer, Laura Robinson, Andrea Di Francesco, Karen L. Svenson, Ron Korstanje, David E Harrison, J Graham Ruby, Gary Churchill

Faculty Research 2025

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conducted a genetic mega-analysis of longevity in Diversity Outbred (DO) mice that included 2,444 animals from 3 independently conducted lifespan studies. We identified 8 loci that contributed significantly to lifespan independently of diet and drug treatment in at least one study. One of these loci also influenced lifespan in a sex-dependent manner, and we detected an additional locus with a diet-specific effect on lifespan. Collectively, these loci explained over half of the estimated heritable variation in lifespan …

Development Of A Customizable Web-Based Dashboard For Remote Blood Pressure Monitoring: Feasibility And Usability Implementation Study, Joshua Wollen, Thuy Nguyen, Charles Coton, Gina Dewildt, Gabretta Cooksey, Audrey Cohen, Nicholas Hoang, Munachi Okpala, Michael Gonzalez, Mengxi Wang, Chigozirim Izeogu, Elmer Bernstam, Charles Green, Sean Savitz, Jose-Miguel Yamal, Anjail Sharrief

Faculty, Staff and Student Publications

Background: Effective blood pressure (BP) management is essential for several disease states, including secondary stroke prevention. Remote BP monitoring used in combination with an electronic data capture (EDC) system offers potential for improved BP control for patients. While such systems currently exist, there are many patient-, provider-, and system-specific challenges these systems currently do not address. In addition, such systems are rarely described transparently and comprehensively in the literature with enough detail to be reproduced by other clinicians.

Objective: This study aims to describe the development and design of a web-based EDC system tailored for remote BP monitoring and management …

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-, …

Applying The Practical, Robust, Implementation And Sustainability Model (Prism) To A Community-Based Youth Participatory Action Research Program, Nicholas Szoko, Tyia K Wilson, Ebonie Slade, Ti'yanna Risher, Marquise Wheeler, Elizabeth Miller, Alison J Culyba

2020-Current year OA Pubs

BACKGROUND: Youth participatory action research (YPAR) represents an empowerment-based process in which youth identify and address issues in their schools and communities. YPAR has been applied in diverse settings, but evaluations of YPAR implementations using an implementation and dissemination science (IDS) framework are limited. Our goal was to use the Practical, Robust, Implementation & Sustainability Model (PRISM) to evaluate a multisite community-based YPAR program.

METHODS: We identified three community sites to implement Youth Leadership in Action (YLIA+), an eight session YPAR intervention. Any youth aged 13 and older was eligible to participate. Guided by PRISM, we collected data using: (1) …

Association Between Allostatic Load And Accelerated White Matter Brain Aging: Findings From The Uk Biobank, Li Feng, Zhenyao Ye, Zewen Du, Yezhi Pan, Travis Canida, Hongjie Ke, Song Liu, Shuo Chen, L Elliot Hong, Peter Kochunov, Jie Chen, David K Y Lei, Edmond Shenassa, Tianzhou Ma

Faculty, Staff and Student Publications

White matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting, …