Medicine and Health Sciences Commons^™

Defining Treatment-Resistant Bipolar Depression: Recommendations From The Isbd Task Force, Eduard Vieta, Roger S Mcintyre, Trisha Suppes, Tamsyn E Van Rheenen, Balwinder Singh, Kamilla Woznica Miskowiak, Allan H Young, Lakshmi N Yatham, Kyooseob Ha, Michael Berk, Holly A Swartz, Chantal Henry, Maja Pantovic Stefanovic, Gerard Anmella Diaz, Aysegul Ozerdem, Wiesław J Cubała, Diego Hidalgo-Mazzei, Mauricio Tohen, Isabella Pacchiarotti, Paula Villela Nunes, Carlos Lopez-Jaramillo, Ana Gonzalez-Pinto, Paolo Brambilla, Robert Post, Jair C Soares, Michael Bauer, Ana C Andreazza, Xavier Justes Fradera, Montserrat Cosials-Lopez, Giovanna Fico

Faculty, Staff and Student Publications

Objective: Despite the availability of approved treatments, a substantial proportion of patients with bipolar disorder experience treatment-resistant bipolar depression (TRBD), characterized by persistent depressive symptoms unresponsive to standard therapies. However, a universally accepted definition of TRBD is lacking. This consensus document, developed by the International Society for Bipolar Disorders (ISBD) Task Force on TRBD, aims to provide a standardized definition of TRBD to facilitate clinical trials, research, and treatment strategies.

Methods: The Task Force employed a literature review, clinical trials analysis, and expert consensus meetings to define TRBD.

Results: TRBD was defined as the failure to achieve a significant and …

An Exciting Future For Microbial Molecular Biology And Physiology, Andrew A Bridges, Leah Guthrie, Mckenzie Lehman, Elizabeth H Kellogg, Samantha Wellington Miranda, Andrew Pountain, Anthony L Shiver, Andrew Varble, Molecular Biology And Physiology Community Of The Council On Microbial Sciences, Heidi B Kaplan, Elizabeth A Shank, Gisela Storz

Faculty, Staff and Student Publications

Continuous advances in technologies ranging from deep sequencing and genetic manipulation to mass spectrometry, single cell imaging, and structural biology have led to previously unimaginable advances in our understanding of microbial physiology and the molecular mechanisms underlying microbial responses in a multitude of environments. Simultaneously, these advances are revealing how much more there is to learn. At the 2024 virtual retreat of the Molecular Biology and Physiology (MBP) Community of the Council on Microbial Sciences (COMS) of the American Society for Microbiology (ASM), eight early-career investigators, along with retreat attendees, discussed some of these astounding advances, as well as the …

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

Rowan-Virtua School of Osteopathic Medicine Departmental Research

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

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 …

The Swib Domain-Containing Dna Topoisomerase I Of Chlamydia Trachomatis Mediates Dna Relaxation, Li Shen, Abigail R. Swoboda, Caitlynn Diggs, Shomita Ferdous, Andrew Terrebonne, Amanda Santos, Noel Wolf, Luis Lorenzo Carvajal, Guangming Zhong, Scot P. Ouellette, Yuk Ching Tse-Dinh

School of Graduate Studies Faculty Publications

Chlamydia trachomatis has a DNA topoisomerase I with a unique C-terminal domain (CTD) homologous to eukaryotic SWIB domains. This study focused on determining the function of the SWIB domain-containing TopA from C. trachomatis (CtTopA). We demonstrated that, despite the lack of sequence similarity at the CTDs between CtTopA and TopA from Escherichia coli (EcTopA), full-length CtTopA removed negative DNA supercoils in vitro and complemented the growth defect of a topA mutant of E. coli. CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies. An antibody generated against the SWIB domain of CtTopA specifically recognized …

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 …

08.11.2025 Ored Connect, Liz Williamson

ORED Newsletter

F and A rates

ORED Research Reception

NSF Audit Final Resolution and Compliance Updates

Impact Of Urban Fine Particulate Matter Exposure On Cardiovascular Health, Shelby P. Briggs

Honors Theses

Air pollution, particularly exposure to fine particulate matter (PM2.5), poses a growing threat to cardiopulmonary health. PM2.5 consists of microscopic particles smaller than 2.5 microns in diameter and originates from industrial combustion, transportation, and urban dust. These particles are classified as xenobiotics and are capable of bypassing respiratory defenses to enter systemic circulation, where they cause oxidative stress, inflammation, and cardiovascular dysfunction. This study examines the effects of PM2.5 on cardiovascular function using a murine model. Male C57BL/6 mice were divided into control (saline), subchronic (10 µg), and chronic (100 µg) groups and were exposed weekly for 11 weeks via …

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 …

Health Outcomes Beyond Age 50 Years In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, Rusha Bhandari, Yan Chen, Eric J Chow, Rebecca M Howell, Lisa B Kenney, Kevin R Krull, Wendy Leisenring, Paul C Nathan, Joseph P Neglia, Kirsten K Ness, Kevin C Oeffinger, Claire Snyder, Lucie M Turcotte, F Lennie Wong, Yutaka Yasui, Gregory T Armstrong, Saro H Armenian

Faculty, Staff and Student Publications

Purpose: There are limited data on the risk for mortality and health outcomes among the increasing population of older (age >50 years) survivors of childhood cancer during this later stage in life when there is an expected increase in aging-related morbidities.

Methods: We assessed cause-specific mortality, incident new cancers, chronic health conditions (CHCs), frailty, and health status among survivors from the Childhood Cancer Survivor Study, conditional on surviving to 50 years. We calculated conditional survival rates, standardized mortality ratios (SMRs), and, for incident new cancers, cumulative burden, standardized incidence ratios (SIRs), and relative rates (RRs), compared with the general US …

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 …

Effect Of Histidine Tag On The Enzymatic Activity Of Pseudolysin And Its Interaction With The Streptomyces Metalloprotease Inhibitor (Smpi) Protein, Adewale Adeboye Adewole

Electronic Theses and Dissertations

Pseudolysin (PLN) protein is a major virulent factor in Pseudomonas aeruginosa infection. PLN belongs to the family of zinc-dependent metalloproteases. It is naturally inhibited by a smaller protein called streptomyces metalloprotease inhibitor (SMPI), secreted by Streptomyces nigrescens. Previous and current studies demonstrate that the interaction between PLN and SMPI offers unique mechanistic insights for drug development against infections caused by P. aeruginosa. This study investigated the effect of N-terminal Histidine (His) tag on the enzymatic activity of PLN and its interaction with SMPI. His-tagged PLN and SMPI proteins were expressed in bacteria and purified by affinity chromatography …

Temporomandibular Joint Osteoarthritis And Systemic Inflammation: A Cadaveric Study For Dental Insights, Nathan Kent Bs, David Patterson Bs, Alyssa Luu Bs, Samantha Pipkin Bs, Jason Ciccotelli Dpt, Phd, Jeremy James Dmd, Ms, Jessica Immonen Phd, Ms

The Journal of Integrative Physiology

The objective of this study was to determine if gross signs of cadaveric osteoarthritis (OA) have

a tendency to present systemically and if this presentation includes pathology found at the

temporomandibular joint (TMJ). Signs of OA were then correlated to gross alterations of the aorta and common carotid arteries seen with atherosclerotic cardiovascular disease. Ipsilateral synovial joints including the TMJ, knee joint, radiocarpal joint and trapeziometacarpal (TMC) joint were all assessed for signs of OA in 4 cadaveric donors (3 males; 72, 82 and 92 years-old / 1 female; 89 years-old) using a validated scale of disease severity. A Grade …

The Legal System For Influencers On Social Media Platforms: A Comparative Study, Ahmad Ibrahim Ballal Dr, Najem Riyad Al-Rabadi Dr, Ma’Moun Rashed Al-Huneiti Dr

Middle East Journal of Communication Studies

This study explores the legal regulation of social media influencers through a comparative analysis between French and Jordanian legislation. The research problem lies in the absence of a clear and comprehensive legal framework regulating influencers' growing role in shaping public opinion. Using the comparative analytical method, the study examines relevant legal texts and regulatory approaches in both jurisdictions. The findings highlight significant differences, with France enacting a specific law to govern influencer activities, while Jordan still relies on general legal provisions. The study recommends drafting a dedicated Jordanian law that outlines influencers' legal responsibilities and balances freedom of expression with …

Representations Of The Other In Hamas's Media Discourse During The "Al-Aqsa Flood" Operation: A Rhetorical Analytical Study, Enad Mamdouh Al-Zaben, Sabah Al Harahsheh Dr

Middle East Journal of Communication Studies

This study aimed to determine how the Hamas movement represented the "other" in its media discourse during the "Al-Aqsa Flood" operation. To achieve this goal, the study relied on the qualitative analytical approach, specifically rhetorical discourse analysis. The study sample included all Hamas's media spokesman speeches, between October 7, 2023, and January 1, 2024, numbering 11 speeches. The study results showed that Hamas's media discourse focused on portraying two main groups: "us" and "them." The "us" group included the Palestinian people in all their spectra. They were referred to using terms with positive connotations such as: "the steadfast," "the one …

Addressing Anxiety In The Pediatric Population: An Ot Perspective, Joshua D. Johnson, Mary Jan Greer, Wendy Tremaine, Justine Faghihifar

Summer 2025 OTD Capstone Symposium

This capstone develops and evaluates a trauma-informed training for RBTs and caregivers in outpatient ABA clinics serving children with ASD and anxiety. Grounded in MOHO, the seven-module program teaches trigger→support mapping, sensory strategies, visual tools, and brief co-regulation routines. Findings show improved knowledge and confidence, with recommendations to embed a fidelity rubric, booster sessions, and ready-to-use templates.

Examining Associations Between Street Vegetation And Child Firearm Violence At Microgeographic Locations In 3 Us Cities: A Case-Control Study, Zihan Lin, Gregory A. Wellenius, Jonathan Jay

Biological, Geological, and Environmental Faculty Publications

Background: Firearm violence is a leading cause of death among U.S. children under age 18. Urban vegetation, a vital component of the living environment, has been found to influence firearm violence, yet the relationship between different types of street vegetation and firearm violence with children as the victim at the microgeographic scale remains unclear.

Methods: We analyzed 2316 child firearm assault incidents from Los Angeles, New York City, and Philadelphia from 2015 to 2021. Using a spatial case-control approach, we matched assault locations with control locations within 1-km. For each location, we applied deep learning algorithms to Google Street View …

Enumerating Escherichia Coli (E. Coli) Concentrations And Evaluating Optical Brighteners As A Potential Indicator Of Human Wastewater Contamination In La Nana Bayou, Banita Creek, And Their Tributaries, Nacogdoches, Texas, Swastika Acharya, Matthew Mcbroom, Yuhui Weng, Yanli Zhang

Electronic Theses and Dissertations

La Nana Bayou was added to the Texas 303(d) list in 2000 after it failed to meet water quality standards set by the Texas Commission on Environmental Quality (TCEQ) for primary contact recreation due to elevated Escherichia coli (E. coli) levels. E. coli is a bacterial species commonly found in the intestines of humans and warm-blooded animals. It serves as an indicator of fecal contamination in freshwater, though its presence alone cannot identify the contamination source. Optical brighteners (OBs), chemicals found in laundry detergents, cleaning agents, toilet papers, and clothing, are unique to human wastewater. This study aimed …

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

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 …

Paediatric Fixed Drug Eruption: A Case Report Of Ofloxacin As The Culprit, Ambika Nand Jha, Varsha Ratan Gaikwad, Rabia Alam, Shivanshu Sharma, Ashok Kumar Gupta

Chulalongkorn Medical Journal

Ofloxacin, a second-generation fluoroquinolone, is a relatively rare but documented cause of fixed drug eruption (FDE), a localized cutaneous hypersensitivity reaction marked by recurrent, well-demarcated erythematous patches or macules that may develop into blisters upon re-exposure to the offending agent. The underlying mechanism is immune-mediated, involving T-cell activation, cytokine release, and keratinocyte apoptosis. A 5-year-old boy weighing 15 kg was prescribed Ofloxacin syrup (7.5 ml twice daily) and Paracetamol suspension (5 ml twice daily) for suspected enteric fever. Within two days, he developed several annular erythematous lesions on his hands and back, associated with intense itching, raising suspicion of a …

Development Of A Physiologically Based Pharmacokinetic (Pbpk) Model And Evaluation Of Antioxidant Capacity For Polypodium Leucotomos Extract, Christopher L. Basel

Doctoral Dissertations and Projects

The purpose of this study was to develop an equation to calculate the approximate concentration of active components in orally administered Polypodium leucotomos fern extract (PLE) and to develop physiologically based pharmacokinetic (PBPK) models for an active component of PLE or its metabolite to address the need for human pharmacokinetics (PK). Model differences based on ethnic groups were also investigated. This was a quantitative study using secondary data. It has been estimated that skin cancers account for approximately 40% of all human cancers and that approximately 13,000 people will die of skin cancer in 2024. People with darker skin experience …

Immunomodulatory Effects Of Gold Nanoparticles: Impacts On Immune Cells And Mechanisms Of Action, Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Traditional anti-inflammatory medications-such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs-are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we …

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 …

Racial And Ethnic Disparities In Receipt Of Guideline-Concordant Pancreatic Cancer Care Among Older Adults In The United States, Joshua Herb, Kai-Ping Liao, John K Lin, Kever A Lewis, Sharon H Giordano, Matthew H G Katz, Rebecca A Snyder

Faculty, Staff and Student Publications

Purpose: Patients racialized as Black experience a higher mortality from pancreatic cancer (PC). Worse survival outcomes may relate to differences in delivered treatment. This study examined differences in receipt of guideline-concordant care (GCC) among older adults with PC according to race and ethnicity.

Methods: Patients 65 years and older with incident PC racialized as non-Hispanic White (NH-White) or racialized as NH-Black or of Hispanic ethnicity were identified in the SEER-Medicare database from 2004 to 2019. The primary outcome was receipt of stage-specific GCC. Multivariable logistic regression identified factors associated with GCC. Oaxaca-Blinder decomposition examined the contribution of measured and unmeasured …

Information Theory Optimization Of Signals From Small-Angle Scattering Measurements, Robert P Rambo, John A Tainer

Faculty, Staff and Student Publications

Small-angle X-ray scattering (SAXS) of particles in solution informs on the conformational states and assemblies of biological macromolecules (bioSAXS) outside of cryo- and solid-state conditions. In bioSAXS, the SAXS measurement under dilute conditions is resolution limited, and through an inverse Fourier transform, the measured SAXS intensities directly relate to the physical space occupied by the particles via the P(r)-distribution. Yet, this inverse transform of SAXS data has been historically cast as an ill-posed, ill-conditioned problem requiring an indirect approach. Here, we show that through the applications of matrix and information theories, the inverse transform of SAXS intensity data is a …