Chemical Actions and Uses Commons^™

Persistent Chemotherapy-Induced Peripheral Neuropathy As A Chronic Cancer Pain Syndrome: Mechanisms, Therapeutic Limitations, And Future Directions, Reed Firestone, Jamin Morrison

Department of Medicine Faculty Papers

Background/Objectives: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting complication of cancer therapy and a major contributor to chronic neuropathic pain among cancer survivors. Although traditionally managed as a treatment-related toxicity, persistent CIPN frequently persists long after chemotherapy completion and is increasingly recognized as a major survivorship and palliative care challenge. This review synthesizes current mechanistic, clinical, and translational evidence and reframes persistent CIPN as a chronic neuropathic cancer pain syndrome. Methods: A narrative review of peer-reviewed literature was conducted using PubMed/MEDLINE, Embase, and the Cochrane Library, supplemented by manual review of key references and clinical guidelines. Emphasis was placed …

Testing Elicitors Of Homologous Jadr2 Proteins To Regulate Natural Product Production, Carzon J. Williams, Emilee A. Patterson, Allison S. Walker

SPARK Symposium Presentations

The growing threat of antimicrobial resistance (AMR) has and will contribute to global economic and public health concerns in the foreseeable future leading into 2050. As mortality rates derived from AMR are projected to reach 10 million if no viable solution is found to combat it through hastened drug discovery. The use of natural products to mitigate AMRs effects is viable as more than 50% of FDA approved drugs are natural products. These natural products are synthesized by biosynthetic gene clusters (BGC), found in bacteria with a regulatory protein not allowing transcription until unbound . Current methods of eliciting the …

A Phase Ii Trial Of Defactinib Combined With Avutometinib In Patients With Metastatic Uveal Melanoma, Rino S. Seedor, Mizue Terai, Sergei A. Koshkin, Andrew E. Aplin, Marlana Orloff, Erin Sharpe-Mills, Madeleine Naccarato, Aurora Mills, Alfredo A. Molinolo, J. Silvio Gutkind, Takami Sato

Kimmel Cancer Center Faculty Papers

Background: Treatment options are limited, and outcomes remain poor for patients with metastatic uveal melanoma (MUM). We conducted an investigator-initiated, prospective, single-arm, single-institution, phase II study evaluating the combination of an FAK inhibitor (defactinib) with a RAF/MEK inhibitor (avutometinib) for the treatment of MUM. Methods: From February 2021 through January 2023, 12 patients with MUM were treated with the combination of defactinib and avutometinib. Defactinib was given 200 mg twice daily, and avutometinib was given 3.2 mg twice a week. Both drugs were given for 3 weeks on and 1 week off (28-day cycle). Disease control rate was the primary …

Exceptional Response Of Radiotherapy-Naïve Cranial Meningiomas To Dual Immune Checkpoint Blockade In Bap1 Tumor Predisposition Syndrome, Gary Gallia, Christine Hann, Calixto-Hope Lucas, Licia Pacheco Luna, David Kamson, Takami Sato

Department of Medical Oncology Faculty Papers

Meningiomas are the most common primary central nervous system tumors, and while most are benign, atypical and anaplastic variants frequently recur and have limited effective treatment options. Recent trials of PD-1 blockade in unselected meningioma cohorts have demonstrated modest activity, with low objective response rates. These findings highlight the need to identify molecular biomarkers that may predict immunotherapy sensitivity in this disease. BRCA1-associated protein 1 (BAP1) is a tumor suppressor critical for chromatin regulation and DNA repair, and germline pathogenic variants cause BAP1 tumor predisposition syndrome (BAP1-TPDS), a hereditary cancer syndrome characterized by uveal melanoma, mesothelioma, renal cell carcinoma, meningioma, …

Neurodevelopmental Effects Associated With In Utero Exposure To Bpa, Maximilian A. Nilsen, Grace A. Carlucci, Cody V. Thompson, Berfin Gul

Student Work

No abstract provided.

Structural Basis Of Anthocyanin-Mediated Modulation Of Il-2, Il-17, And Tnf-Α: A Docking And Molecular Dynamics Study, Andrey Bogoyavlenskiy, Adolat Manakbayeva, Timur Kerimov, Igor Yershov, Madina Alexyuk, Pavel Alexyuk, Vladimir Berezin, Vyacheslav Dushenkov

Publications and Research

Anthocyanins are naturally occurring flavonoid pigments widely distributed in plants and are recognized for their antioxidant and anti-inflammatory activities. However, the molecular mechanisms underlying their potential immunomodulatory effects remain poorly characterized, particularly regarding their direct interactions with key signaling cytokines. In this study, a set of selected anthocyanins was investigated using a hierarchical computational workflow targeting three major pro-inflammatory cytokines: interleukin-2 (IL-2), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Molecular docking analyses identified primulin and antirrhinin as the most favorable binders, forming stabilizing hydrogen bonds and hydrophobic interactions within predicted cytokine interaction interfaces. To further assess the stability of these …

Breaking Into Hiv-1'S Epigenetic Vault: Cure Strategies To Eliminate The Viral Reservoir, Joanna Jones, Chelsea Gunderson, Brian Wigdahl, Michael Nonnemacher

Kimmel Cancer Center Faculty Papers

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that integrates into the host cell's DNA as a provirus. Transcription from the provirus is regulated in large part by cellular proteins and epigenetic factors. These may be repressive or permissive to productive infection. The host factors that regulate this balance are therefore attractive targets for HIV-1 therapeutics. Indeed, proviral chromatin is the focus of two of the current HIV-1 cure strategies. "Shock and Kill" uses latency reversal agents to open the provirus's chromatin, promoting high levels of gene expression that induce the killing of infected cells. "Block and Lock" uses …

Infectious Retinitis Associated With Jak Inhibitors: The Ongoing Duality Of Jak Inhibitors, Jose S. Pulido, Fukutaro Mano, Marcello Casella, Susumu Ishida

Wills Eye Hospital Papers

PURPOSE: To discuss the recent evidence that Janus kinase (JAK) inhibitors can cause viral retinitis.

METHODS: A commentary on the case report in this issue and a review of cases in the literature.

RESULTS: A total of 6 cases have now been reported of cytomegalovirus retinitis associated with Jak inhibitors. Additionally, there was a case of bilateral toxoplasma retinitis and a case of herpetic scleritis.

DISCUSSION: It is important to be aware of the potential blinding complications associated with JAK inhibitors and if the patient complains of acute vision loss and/or floaters, the patient should be emergently referred to a …

A Study Of Awareness Of Antiseptics And Disinfectant Use Among Allied Health Sciences Students And Interns Of A Tertiary Care Hospital, Pooja M, Puneeth A, Sharmi Nm

Digital Journal of Clinical Medicine

Background:

Antiseptics and disinfectants are among the most vital tools in infection prevention and control (IPC), especially in healthcare settings where the risk of hospital-acquired infections (HAIs) remains a significant concern. This study aims to assess the awareness and knowledge of antiseptics and disinfectants among Allied Health Sciences (AHS) students and interns, identify knowledge gaps at different stages of training, and recommend educational interventions.

Methods:

This was a cross-sectional, questionnaire-based study conducted among 1st to 3rd-year AHS students and interns at a tertiary care hospital. Data were collected using a validated questionnaire via a Google form after obtaining approval from …

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

Molecular Profiling And Tumor Biomarker Analysis Of Gog281/Logs: A Positive Late-Phase Trial Of Trametinib For Recurrent/Persistent Low-Grade Serous Ovarian Carcinoma, Robert L. Hollis, Austin Miller, Heather A. Lankes, Kwong-Kwok Wong, William Rodgers, David Millan, Karen Carty, Robert L. Coleman, Kathleen N. Moore, Angeles Alvarez Secord, David M. O'Malley, John K. Chan, Andrea R. Hagemann, Stephanie Gaillard, Saketh R. Guntupalli, Mitchell I. Edelson, Peter G. Rose, Oliver Dorigo, Susana Banerjee, Ailith Ewing, Michael Churchman, Anil K. Sood, C. Simon Herrington, Charlie Gourley, David M. Gershenson

Abington Jefferson Health Papers

PURPOSE: Low-grade serous ovarian carcinoma (LGSOC) is a distinct form of ovarian cancer characterized by younger patient age and relative chemoresistance. The GOG281/LOGS trial (NCT02101788) investigated the efficacy of the MEK inhibitor trametinib compared with physician's choice standard-of-care (SOC) in patients with LGSOC with persistent/recurrent disease. The study demonstrated significantly improved progression-free survival (PFS) in the trametinib-treated arm.

EXPERIMENTAL DESIGN: Two hundred and sixty patients with recurrent/persistent LGSOC were enrolled and randomly assigned in GOG281. We performed molecular analysis of 170 patients with available tumor specimens, comprising whole-exome sequencing and phospho-ERK (pERK) IHC, to identify biomarkers of clinical benefit from …

Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group

School of Medicine Faculty Publications

Background Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea. Methods In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by …

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …

Cocaine Upregulates Microglial Lipid Droplet Formation Through Increasing Lipid Synthesis Activity In Vitro And In Vivo, Yan Cheng, Brooke Russell, Liam Liyang Guo, Aryan Patel, Yan Y. Sanders, Ming-Lei Guo

Department of Biomedical and Translational Sciences Faculty Publications

A novel subtype of microglia, lipid droplet accumulation microglia (LDAMs), has been identified in the aged brain, which is characterized by sustained inflammation and senescent-like phenotypes. LDAMs are deeply involved in promoting brain aging as well as the pathogenesis of multiple neurodegenerative diseases. Cocaine can alter brain lipidomic profiles, induce microglial activation, and accelerate brain aging. This suggests that cocaine might affect microglial lipid metabolism, which ultimately aggravates aging-related neurological disorders in people with addictions. In this study, we explored the effects of cocaine on microglial lipid metabolism. Our results showed that chronic cocaine administration altered brain lipid profiles and …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

Investigating The Role Of Traditional Chinese Herbal Medicine For Cancer Symptom Management In Older Adults: A Rapid Review, Isabelle C. Karshner

Honors Undergraduate Theses

Background: Patients with cancer often experience symptoms related to disease, complications, and treatment. One potential method of alleviating these symptoms is traditional Chinese herbal medications (TCHM). This rapid review explores the role of traditional Chinese herbal medications in treating cancer-related symptoms in older adults.

Purpose: The purpose of this rapid review is to gain and provide a better understanding of the effects of TCHM on cancer-symptom management in the older adult population. This review explores the association between TCHM and effects on cancer symptoms in older adults, including interactions, toxicity, and signs/symptoms of TCHM use that may be useful information …

Tramadol For Treatment Of Neurogenic Cough: A Retrospective Case Series, Benjamin Joseph Rubinstein, Sheela Saidha, John Todd Sinacori

Department of Otolaryngology (ENT) Faculty Publications

Objectives

Explore the efficacy of tramadol for neurogenic cough and describe the longitudinal treatment experience.

Methods

A retrospective case series of adults with chronic cough who were treated with tramadol for neurogenic cough. A complete response was defined as no pathologic coughing, and a partial response was defined as 50% or greater reduction in severity or frequency.

Results

Sixty-nine patients were included. 38% of patients reported a complete response with an additional 33% reporting a partial response. The most common successful dosing regimen was 50 mg BID. Age, gender, and BMI did not impact treatment response. Patients with a history …

The Effect Of Glp-1 Receptor Agonists On Reoperation Following Anterior Cervical Discectomy And Fusion, Nicholas C. Bank, Daniel Whittingslow, Sam Duggan, Joshua L. Morningstar, Douglas S. Weinberg

Student Papers, Posters & Projects

BACKGROUND: Pseudarthrosis remains a significant complication of ACDF, contributing to patient morbidity and increased healthcare costs. Glucagon-like peptide-1 receptor agonists (GLP-1RA), widely prescribed for diabetes and obesity, have been shown to reduced odds of pseudoarthrosis after ACDF. However, it remains unclear whether these reductions meaningfully translate to reduced odds of subsequent cervical surgery.

METHODS: The TriNetX United States Collaborative Network was queried for patients who underwent single- or multi-level ACDF between 2013-2023. Patients with perioperative GLP-1RA use and propensity-score-matched controls without GLP-1RA use were compared for subsequent rates of pseudoarthrosis and cervical reoperation at 6-, 12-, and 24-month intervals. Odds …

Early Intervention In Helminth Infections: Investigating Albendazole’S Effects On C. Elegans Egg Hatch Rate And Health, Giselle Domingo Diaz

Student Scholar Symposium

Over 1.5 billion of the poorest people are infected with soil-transmitted helminths (STH) such as whipworm, hookworm, and Ascaris which have devastating effects on human growth, nutrition, and cognition, perpetuating the cycle of poverty. The World Health Organization only approves four anthelmintic drugs to treat STH for mass drug administration (MDA), with Albendazole being the drug of choice. Due to these drugs only having two mechanisms of action, resistance to these drugs has been reported over the years. We aim to better understand STH susceptibility to drugs at multiple points in their life stage. Previously, the effects of Albendazole and …

Vasoactive Drug Use In Children With Community Acquired Septic Shock In Australia And New Zealand, Elliot Long, Stephen Hearps, Amanda Williams, Ben Gelbart, Warwick Butt, Thomas Rozen, Sarah Mcnab, Meredith Borland, Simon Erickson, Shefali Jani, Marino Festa, Eunicia Tan, Natalie Phillips, Sainath Raman, Amit Kochar, Subodh Ganu, Simon Craig, Anna Lithgow, Arjun Rao, Emma Whyte, Stuart Dalziel, Shane George, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Franz Babl

Department of Medicine Faculty Papers

BACKGROUND: Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis.

METHODS: Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-< 18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected.

FINDINGS: 6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall …