Digital Commons Network^™

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 …

Video-Based Intervention To Reduce Treatment And Outcome Disparities In Adults Living With Stroke Or Transient Ischemic Attack (Virtual): Protocol For A Randomized Controlled Trial, Munachi Okpala, Chigozirim Izeogu, Mengxi Wang, Charles Green, Gabretta Cooksey, Thuy Nguyen, Sarah Cohen, Latonya Bryant, Daphne C Hernandez, Elmer V Bernstam, Michael Gonzales, Rhonda Conyers, Olasimbo Chiadika, Kristin Varacalli, Sean I Savitz, Jose-Miguel Yamal, Anjail Z Sharrief

Faculty, Staff and Student Publications

Background: Racial and ethnic disparities in post-stroke blood pressure (BP) control persist, and effective interventions to address post-stroke care inequities are needed. We designed a randomized comparative effectiveness trial to evaluate the Video-based Intervention to Reduce Treatment and Outcome Disparities in Adults Living with Stroke or Transient Ischemic Attack (VIRTUAL) model of care for post-stroke BP reduction.

Methods: The study will enroll 534 stroke survivors in a randomized trial to receive either the VIRTUAL intervention or enhanced standard care. Individuals with ischemic stroke, hemorrhagic stroke, or transient ischemic attack (TIA) are enrolled before hospital discharge and randomized (1:1) to VIRTUAL …

Extracellular Vesicles For Clinical Diagnostics: From Bulk Measurements To Single-Vesicle Analysis, Hai Linh Tran, Wenshu Zheng, David A Issadore, Hyungsoon Im, Yoon-Kyoung Cho, Yuanqing Zhang, Dingbin Liu, Yang Liu, Bo Li, Fei Liu, David Tai Wai Wong, Jiashu Sun, Kun Qian, Mei He, Meihua Wan, Yong Zeng, Ke Cheng, Tony Jun Huang, Daniel T Chiu, Luke P Lee, Lei Zheng, Andrew K Godwin, Raghu Kalluri, Steven A Soper, Tony Y Hu

Faculty, Staff and Student Publications

Extracellular vesicles (EVs) play a crucial role in intercellular communication, signaling pathways, and disease pathogenesis by transporting biomolecules such as DNA, RNA, proteins, and lipids derived from their cells of origin, and they have demonstrated substantial potential in clinical applications. Their clinical significance underscores the need for sensitive methods to fully harness their diagnostic potential. In this comprehensive review, we explore EV heterogeneity related to biogenesis, structure, content, origin, sample type, and function roles; the use of EVs as disease biomarkers; and the evolving landscape of EV measurement for clinical diagnostics, highlighting the progression from bulk measurement to single vesicle …

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 …

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

Faculty, Staff and Students Publications

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

Shared And Distinct Alterations In Brain Structure Of Youth With Internalizing Or Externalizing Disorders: Findings From The Enigma Antisocial Behavior, Adhd, Mdd, And Anxiety Working Groups, Sophie Townend, Marlene Staginnus, Yidian Gao, Nina Alexander, Volker Arolt, Tobias Banaschewski, Mark A Bellgrove, Vivek Benegal, Robert J Blair, Laura Blanco-Hinojo, Ole Jonas Boeken, Joscha Böhnlein, Sven Bölte, Linda M Bonnekoh, Daniel Brandeis, Rodrigo A Bressan, Fabian Breuer, Willem B Bruin, Jan K Buitelaar, Katie L Burkhouse, Monica E Calkins, Marta Cano, Narcis Cardoner, Hui Chen, Xianliang Chen, David R Coghill, Olivier F Colins, Colm G Connolly, Michael C Craig, Kathryn R Cullen, Udo Dannlowski, Christopher G Davey, Andrea Dietrich, Daifeng Dong, Christine M Freitag, Thomas Frodl, Liesbet Goossens, Dominik Grotegerd, Raquel E Gur, Ruben C Gur, Jan Haavik, Cindy C Hagan, Tim Hahn, Alfons O Hamm, Ben J Harrison, Catharina A Hartman, Martin J Herrmann, Tiffany C Ho, Pieter J Hoekstra, Bharath Holla, Karim Ibrahim, Andrea Jackowski, Hamidreza Jamalabadi, Yali Jiang, Tilo Kircher, Kerstin Konrad, Anna Kraus, Jonna Kuntsi, Till Langhammer, Luisa Lazaro, Elisabeth J Leehr, Ulrike Lueken, Ren Ma, Frank P Macmaster, Gisele G Manfro, Anne Martinelli, Hannah Meinert, Susanne Meinert, Jarosław M Michałowski, Qingsen Ming, Robert Moeck, Lilianne R Mujica-Parodi, Benson Mwangi, Janina Neufeld, Joel T Nigg, Ruth L O'Gorman Tuura, Hyuntaek Oh, Jaap Oosterlaan, Yannis Paloyelis, Pedro M Pan, Luca Passamonti, Wenceslao Peñate, K Luan Phan, Kerstin J Plessen, Jesus Pujol, Karl Lundin Remnélius, Francisco Rivero, Katya Rubia, Ramiro Salas, Giovanni A Salum, Theodore D Satterthwaite, Anne Schienle, Elisabeth Schrammen, Koen R J Schruers, Gunter Schumann, Arjun Sethi, Tim Silk, Norbert Skokauskas, Jordan Smoller, Jair C Soares, Lin Sørensen, Christina Stadler, Michael C Stevens, Benjamin Straube, Thomas Straube, Andreas Ströhle, Gustavo Sudre, Denis G Sukhodolsky, Kate Sully, Xiaoqiang Sun, Chad M Sylvester, Nicola Toschi, Steven J A Van Der Werff, Alasdair Vance, Robert Vermeiren, Albert Wabnegger, Xiaoping Wang, Julia Wendt, Sarah Whittle, Julian Wiemer, Anderson M Winkler, Hans U Wittchen, Mon-Ju Wu, Qiong Wu, Tony T Yang, Yunbo Yang, Shuqiao Yao, Jibiao Zhang, Jiansong Zhou, Andre Zugman, Giovana B Zunta-Soares, Peter M Zwanzger, Sophia I Thomopoulos, Neda Jahanshad, Paul M Thompson, Kevin Hilbert, Arielle Baskin-Sommers, Charlotte A M Cecil, Moji Aghajani, Daniel S Pine, Nic J A Van Der Wee, Dan J Stein, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Laura K M Han, Elena Pozzi, Lianne Schmaal, Barbara Franke, Martine Hoogman, Esther Walton, Stephane A De Brito, Graeme Fairchild, Enigma Antisocial Behavior, Anxiety, Adhd, And Mdd Working Groups

Staff and Researcher Publications

BACKGROUND: Externalizing and internalizing disorders are common in youth but are often studied separately, preventing researchers from identifying shared (i.e., transdiagnostic) alterations in brain structure. Using data from the ENIGMA Consortium, we conducted a mega-analysis to identify shared and distinct cortical and subcortical brain alterations across internalizing (anxiety disorders and depression) and externalizing disorders (attention-deficit/hyperactivity disorder [ADHD] and conduct disorder [CD]) in youth.

METHODS: 3D T1-weighted MRI data from youth (aged 4-21 years) with anxiety disorders (n=1,044), depression (n=504), ADHD (n=1,317), and CD (n=1,172), along with healthy controls (n=4,743) were analyzed. We assessed group differences in regional cortical thickness, surface …

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 …

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 …

Keap1 And Stk11/Lkb1 Alterations Enhance Vulnerability To Atr Inhibition In Kras Mutant Non-Small Cell Lung Cancer, Ana Galan-Cobo, Natalie I Vokes, Yu Qian, David Molkentine, Kavya Ramkumar, Alvaro G Paula, Marlese Pisegna, Daniel J Mcgrail, Alissa Poteete, Sungnam Cho, Minh Truong Do, Amirali Karimi, Yifan Kong, Anisha Solanki, Ankur Karmokar, Nicolas Floc'h, Adina Hughes, Rebecca Sargeant, Lucy Young, Li Shen, Gozde Kar, Caezaan Keshvani, Claudio Arrechedera, Sharia Hernandez, Katharina Schlacher, Jing Wang, Sonia Iyer, James Conway, Mohamed Reda Keddar, Marta Milo, Ilario De Toma, Susan E Critchlow, J Carl Barrett, Jan Cosaert, Alan Lau, Viia Valge-Archer, Lauren A Byers, Simon T Barry, John V Heymach

Faculty, Staff and Student Publications

KRAS mutations frequently co-occur with alterations in STK11/LKB1 and/or KEAP1, defining an aggressive subset of lung cancers resistant to immuno- and chemotherapy. While LKB1 loss is associated with vulnerability to DNA damage response-based therapies, the impact of KEAP1 alterations remains unknown. We demonstrate that KEAP1-NRF2 pathway drives a compensatory modulation of ATR-CHK1 signaling, enhancing vulnerability to ATR inhibitors (ATRi), particularly in the setting of increased replication stress associated with LKB1 loss. ATRi shows enhanced anti-tumor activity in LKB1 and/or KEAP1-deficient non-small cell lung cancer (NSCLC) models and synergizes with gemcitabine. ATRi also enhances antitumor immunity and mitigates the immunosuppressed phenotype …

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

Faculty, Staff and Students Publications

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

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 …

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 …

Mutant P53 Confers Chemoresistance By Activating Kmt5b-Mediated Dna Repair Pathway In Nasopharyngeal Carcinoma, Haidan Luo, Mo-Fan Huang, An Xu, Donghui Wang, Julian A Gingold, Jian Tu, Ruoyu Wang, Zijun Huo, Yen-Ting Chiang, Kuang-Lei Tsai, Jie Su, Danielle A Bazer, Mien-Chie Hung, Canmao Xie, Yubiao Guo, Dung-Fang Lee, Huiling Yang, Ruiying Zhao

Faculty, Staff and Student Publications

Nasopharyngeal carcinoma (NPC), a malignancy arising from the nasopharyngeal epithelium, is common in the east and southeast area of Asia. Treatments for locally advanced and recurrent NPC include chemotherapy (usually combined with 5-Fluorouracil, 5-FU) and radiotherapy, but response is limited due to chemo-resistance. p53 mutation is a critical factor for 5-FU resistance in some cancers, but its role in NPC chemo-resistance remains unclear. Here, we demonstrate that p53(R280T), a common p53 somatic mutation found in multiple NPC tumor samples, induces gain-of-function upregulation of DNA repair genes which leads to 5-FU resistance in NPC. p53(R280T) specifically upregulates the expression of DNA …

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 …

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

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.

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 …

Effects Of Treatment Integrity Level And Error Type On Dro Efficacy: A Parametric And Comparative Analysis, Paige O'Neill

Theses & Dissertations

Differential reinforcement of other behavior (DRO) is a strategy commonly used in applied contexts to address challenging behavior but can be difficult to implement with high treatment integrity. Previous research has shown that DRO may be robust despite marginal errors of commission, but the impact of differing degrees of errors and different error types during DRO is still unclear. The purpose of the current study was to conduct a parametric evaluation of treatment integrity level (100%, 80%, 60%, 40%, 20%) in DRO when implemented with combined errors (Experiment 1) and to directly compare error types (commission errors, omission errors, combined …

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 …

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

Faculty, Staff and Students Publications

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

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 …

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. …

In Vivo Prime Editing Rescues Alternating Hemiplegia Of Childhood In Mice., Alexander A Sousa, Markus Terrey, Holt A Sakai, Christine Q Simmons, Elena Arystarkhova, Natalia S Morsci, Laura C. Anderson, Jun Xie, Fabian Suri-Payer, Linda C Laux, Emmanuel Roze, Sylvie Forlani, Guangping Gao, Simon Frost, Nina Frost, Kathleen J Sweadner, Alfred L George, Cathleen Lutz, David R Liu

Faculty Research 2025

Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disorder with no disease-modifying treatment. Mutations in ATP1A3, encoding an Na⁺/K⁺ ATPase subunit, cause 70% of AHC cases. Here, we present prime editing (PE) and base editing (BE) strategies to correct ATP1A3 and Atp1a3 mutations in human cells and in two AHC mouse models. We used PE and BE to correct five prevalent ATP1A3 mutations with 43%–90% efficiency. AAV9-mediated in vivo PE corrects Atp1a3 D801N and E815K in the CNS of two AHC mouse models, yielding up to 48% DNA correction and 73% mRNA correction in bulk brain …

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. …

Development Of A Health Knowledge And Skill-Based Framework For The Digital Age, Evelyn Hovenga, Osama El-Hassan, Manal Almalki, Jawad Ahmed, Paul Barach, Mowafa Househ, Amr Jamal

College of Population Health Faculty Papers

The Gulf Cooperation Council (GCC) region is tackling a significant digital healthcare workforce skills gap by creating a computable unified digital health competency framework and repository. Digital technologies and global competency standards are leveraged to professionalize the digital health knowledge domain and facilitate the development of clear career pathways in digital health. A mixed-methods approach was employed to develop the framework. A standardized categorial structure and information model has been developed to support the creation of this computable framework for workforce evaluation and competency-based career development.

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 …

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.

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 …