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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 Aug 2025

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 Aug 2025

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 …


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 Aug 2025

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.


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 Aug 2025

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 Aug 2025

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 …


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. Aug 2025

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 Aug 2025

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 Aug 2025

Micbg406a Polymorphism Reduces Risk Of Mechanical Ventilation And Death During Viral Acute Lung Injury, Harry Pickering, Narges Alipanah-Lechner, Ernie Chen, Dylan Duchen, Holden T Maecker, Seunghee Kim-Schulze, Ruth R Montgomery, Chris Cotsapas, Hanno Steen, Florian Krammer, Charles R Langelier, Ofer Levy, Lindsey R Baden, Esther Melamed, Lauren Ir Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Charles B Cairns, Elias K Haddad, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, David J Erle, Joanna Schaenmann, Al Ozonoff, Bjoern Peters, Steven H Kleinstein, Alison D Augustine, Joann Diray-Arce, Patrice M Becker, Nadine Rouphael, Matthew C Altman, Steve Bosinger, Walter Eckalbar, Carolyn S Calfee, Oscar A Aguilar, Elaine F Reed, John R Greenland, Daniel R Calabrese

Faculty, Staff and Students Publications

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


Dual-Function Polyester Nanoparticles For Amplified Anti-Inflammatory Effects, Ingrid M Heyns, Abiodun T Wahab, Raghu Ganugula, David Sheikh-Hamad, M N V Ravi Kumar, Meenakshi Arora Aug 2025

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 …


Generational Health Professional Perceptions About Artificial Intelligence Impact On Clinical Work, Karima Lalani, Kerryn Butler-Henderson, David T Marc, Susan H Fenton Aug 2025

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. …


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 Aug 2025

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 Aug 2025

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.


Discontinuation Rates And Predictors Of Medical Cannabis Cessation For Chronic Musculoskeletal Pain, Mohammad Khak, Sina Ramtin, Juliet Chung, Asif M. Ilyas, Ari Greis Aug 2025

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 …


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 Aug 2025

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 Aug 2025

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 Aug 2025

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 Aug 2025

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 …


Frontline Acalabrutinib, Lenalidomide And Rituximab For Advanced Stage Follicular Lymphoma With High Tumor Burden: Phase Ii Trial, Paolo Strati, Lei Feng, Jason R Westin, Ranjit Nair, Luis E Fayad, Maria A Rodriguez, Dai Chihara, Luis Malpica, Jared Henderson, Mariana Gallardo, Marissa Rivera, Iris Wang, Anastasiia Bolshakova, Anastasia Radko, David Kurtz, Stefan K Alig, Christopher R Flowers, Ash A Alizadeh, Sattva S Neelapu Aug 2025

Frontline Acalabrutinib, Lenalidomide And Rituximab For Advanced Stage Follicular Lymphoma With High Tumor Burden: Phase Ii Trial, Paolo Strati, Lei Feng, Jason R Westin, Ranjit Nair, Luis E Fayad, Maria A Rodriguez, Dai Chihara, Luis Malpica, Jared Henderson, Mariana Gallardo, Marissa Rivera, Iris Wang, Anastasiia Bolshakova, Anastasia Radko, David Kurtz, Stefan K Alig, Christopher R Flowers, Ash A Alizadeh, Sattva S Neelapu

Faculty, Staff and Student Publications

This phase II trial aims to determine the efficacy and safety of frontline acalabrutinib, lenalidomide and rituximab for patients with advanced stage follicular lymphoma (FL) and high tumor burden. The primary endpoint was best complete response (CR) rate; the secondary endpoints were overall response rate (ORR), duration of response measured as CR at 30 months (CR30), progression of disease at 24 months (POD24) rate, progression-free survival (PFS), overall survival and safety. Twenty-four patients with previously untreated FL were included in this phase 2 single arm study (NCT04404088). The most common grade 3-4 adverse events were neutropenia (58%) and …


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 Aug 2025

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 …


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 Aug 2025

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 …


Urinary Pneumococcal Serotype Detection Among Children With And Without Community-Acquired Pneumonia, Lilliam Ambroggio, Lindsay R Grant, Jillian M Cotter, Samuel R Dominguez, Daniel Olson, Sara R Saporta-Keating, Cody Bender, Mohammad Ali, Kathleen Grice, Gonzalo Lerner, Michael W Pride, Ashley Miller, Maria J Tort, Annaellis Vaughan, Elizabeth Temte, Alec Edid, Alejandro Cané, Kristina G Hulten, Jill Stein, Bradford D Gessner, Edwin J Asturias Aug 2025

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

Faculty, Staff and Students Publications

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

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


Tet2-Mutant Myeloid Cells Mitigate Alzheimer’S Disease Progression Via Cns Infiltration And Enhanced Phagocytosis In Mice, Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra Mcdonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde, Caitlyn Vlasschaert, Marco M Buttigieg, Chih-Wei Fan, Saul Carcamo, Ruoqiong Cao, Daniel E Kennedy, Arushana A Maknojia, Apoorva Thatavarty, Josaura V Fernandez Sanchez, Hind Bouzid, Surabi Veeraragavan, Susan Crocker, Margaret A Goodell, Antony Rodriguez, Siddhartha Jaiswal, Michael J Rauh, Eirini P Papapetrou, Samuele G Marro, Katherine Y King Aug 2025

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 …


Feasibility And Preliminary Efficacy Of A Lymphedema And Fibrosis Self-Management Program For Head And Neck Cancer Survivors: A Pilot Randomized Controlled Trial, Jie Deng, Barbara Murphy, Lucy Andersen, Erin Mcmenamin, John Lukens, Joy Cohn, Karthik Rajasekaran, Ryan Quinn, Bryan Spinelli, Alexander Lin Aug 2025

Feasibility And Preliminary Efficacy Of A Lymphedema And Fibrosis Self-Management Program For Head And Neck Cancer Survivors: A Pilot Randomized Controlled Trial, Jie Deng, Barbara Murphy, Lucy Andersen, Erin Mcmenamin, John Lukens, Joy Cohn, Karthik Rajasekaran, Ryan Quinn, Bryan Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

OBJECTIVES: Survivors of head and neck cancer (HNC) are at high risk for developing lymphedema and fibrosis (LEF). Once diagnosed with LEF, survivors must engage in a lifelong program of self-care to minimize long-term adverse effects. However, evidence-based LEF self-management (SM) programs are lacking. To fill this void, we developed and pilot-tested a LEF-SM program for HNC survivors.

MATERIALS AND METHODS: The LEF-SM Program was developed using the Information-Motivation-Behavioral Skills model of health behavior change as a framework. The program was pilot tested in a three-group randomized controlled trial evaluating feasibility and preliminary efficacy. Fifty-nine participants were randomized to: Usual …


Sulfated Dietary Fiber Protects Gut Microbiota From Antibiotics, Fuqing Wu, Xiaoqian Annie Yu, David Angeles-Albores, Susan E Erdman, Eric J Alm Aug 2025

Sulfated Dietary Fiber Protects Gut Microbiota From Antibiotics, Fuqing Wu, Xiaoqian Annie Yu, David Angeles-Albores, Susan E Erdman, Eric J Alm

Faculty, Staff and Student Publications

Background: Antibiotics, while essential for combating pathogens, also disrupt commensal bacteria, leading to gut microbiota imbalance and associated diseases. However, strategies to mitigate such collateral damage remain largely underexplored.

Result: In this study, we found that fucoidan, a marine polysaccharide derived from brown seaweed, provides broad-spectrum growth protection against multiple classes of antibiotics for human gut microbial isolates in vitro and for fecal communities ex vivo. This protective effect is dependent on the structural integrity, molecular weight, and sulfur content of the polysaccharide. Transcriptomic analysis showed that while fucoidan had minimal impact on baseline gene expression, it counteracted about 60% …


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 Aug 2025

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 …


Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang Aug 2025

Exploring Factors Affecting The Adoption And Use Of Digital Health Technologies Among Older Adults With Cancer: A Qualitative Study, Misun Hwang, Youmin Cho, Katie Gahn, Heidi Mason, Milisa Manojlovich, Yang Gong, Yun Jiang

Faculty, Staff and Student Publications

Purpose: Although digital health technologies (DHTs) are promising to improve health outcomes in older adults with cancer, the low adoption and limited use remain significant gaps in their effective digital health care. Little is known about their concerns about adopting and using DHTs in routine life, particularly in the continued use phase. This study aims to explore factors affecting the initial adoption and continued use of DHTs among older adults with cancer.

Methods: A secondary analysis of qualitative data was conducted based on interviews with 21 older adults (≥ 65 years) with breast, prostate, lung, or colorectal cancer. The transcripts …


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 Aug 2025

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) …


Iodine-Promoted Oxidative Cross-Coupling For The Synthesis Of (E)-2-(3-Oxo-3-Phenylprop-1-En-1-Yl)-3-Phenylquinazolin-4(3 H)-One Via C-H Activation: Development Of Synthetic Tlx Agonists, Lingaiah Maram, Puhan Zhao, Thomas Koelblen, Lamees Hegazy, Thomas P Burris, Bahaa Elgendy Aug 2025

Iodine-Promoted Oxidative Cross-Coupling For The Synthesis Of (E)-2-(3-Oxo-3-Phenylprop-1-En-1-Yl)-3-Phenylquinazolin-4(3 H)-One Via C-H Activation: Development Of Synthetic Tlx Agonists, Lingaiah Maram, Puhan Zhao, Thomas Koelblen, Lamees Hegazy, Thomas P Burris, Bahaa Elgendy

2020-Current year OA Pubs

We report the development of an efficient iodine-promoted oxidative cross-coupling reaction for the synthesis of (


Hand Hygiene Knowledge, Attitudes, Practices, And Hand Dirtiness Of Primary School Students Before And After A Behavioral Change Intervention During The Covid-19 Pandemic, Belize 2022-2023, Anh N Ly, Christina Craig, Kelsey Mcdavid, Dian Maheia, Yolanda Gongora, Francis Morey, Russell Manzanero, Alexandra Medley, Allison Stewart, Allison Lino, Ramiro Quezada, Rosalva Blanco, Vickie Romero, Gerhaldine Morazan, Ella Hawes, Oluwadara Okeremi, Kanako Ishida, Matthew Lozier, Kristy O Murray Aug 2025

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

Faculty, Staff and Students Publications

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


Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U. Rehman, Carol J. Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W. Scherer, Ingo Helbig, Amita Sehgal Aug 2025

Rare Variants In Bmal1 Are Associated With A Neurodevelopmental Syndrome, Vishnu Anand Cuddapah, Dechun Chen, Bumsik Cho, Rebecca Moore, Mohnish Suri, Hana Safraou, Frederic Tran-Mau-Them, Ashley Wilson, Jacqueline Odgis, Atteeq U. Rehman, Carol J. Saunders, Shiva Ganesan, Vaidehi Jobanputra, Stephen W. Scherer, Ingo Helbig, Amita Sehgal

Manuscripts, Articles, Book Chapters and Other Papers

Through international gene-matching efforts, we identified 10 individuals with ultrarare heterozygous variants, including 5 de novo variants, in BMAL1, a core component of the molecular clock. Instead of an isolated circadian phenotype seen with disease-causing variants in other molecular clock genes, all individuals carrying BMAL1 variants surprisingly share a clinical syndrome manifest as developmental delay and autism spectrum disorder, with variably penetrant sleep disturbances, seizures, and marfanoid habitus. Variants were functionally tested in cultured cells using a Per2-promoter driven luciferase reporter and revealed both loss-of-function and gain-of-function changes in circadian rhythms. The tested BMAL1 variants disrupted PER2 mRNA …