Medical Specialties Commons^™

Discovery Of A Small Molecule Tlr3 Agonist Adjuvant, Branden Lee, Danica Dong, Etsuro Nanishi, John Mark Awad, Kimia Abedi, Yoshine Saito, Francesco Borriello, Soumik Barman, Byron Brook, Aisling Kelly, Manisha Menon, Constance Marques-Mourlet, Maansi Gupta, Ida Lister, Chiwoo Oh, Kevin Lyskawa, Morgan Goetz, Kristina Walker, Wing Ki Cheng, Spencer Brightman, Pankaj Sharma, Timothy O'Meara, Katherine Chew, Daniel Vieira, Kevin Ryff, Cali Sweitzer, Sanya Thomas, Simon Van Haren, Matthew Pettengill, Hyuk-Soo Seo, Sirano Dhe-Paganon, Wei Zhang, Ofer Levy, David Dowling

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pattern-recognition receptor (PRR) agonists are valuable agents across multiple medical applications, from vaccinology to immune-oncology. However, well-defined and potent small molecule agonists for many PRRs still await discovery and development. Screening of chemical libraries of ~200,000 small molecules for maturation of human monocytic cells by quantifying NF-κB activation and cell adherence was completed. From this screen, we selected a thiazole benzamide derivative, PVP-057, for its robust immunomodulatory properties, low toxicity profile, and concentration-dependent activity. In vitro investigation of pathway and receptor activation reveals that PVP-057 is a Toll-like receptor 3 (TLR3) agonist. As a single-component adjuvant, administered intramuscularly or intradermally …

Methylene Blue Associated Retinal Toxicity, Sidra Zafar, Martin Calotti, Timothy T. Xu, Justin Muste, Theodore Bowe, Luis Acaba-Berrocal, Brian Cheng, Samir Patel, Yoshihiro Yonekawa, Jose S. Pulido, Jordan D. Deaner

Wills Eye Hospital Papers

BACKGROUND: To describe a case of inadvertent methylene blue use during pars plana vitrectomy (PPV) for an epiretinal membrane (ERM).

CASE: A 69-year-old man presented with 1 day of severe vision loss in his left eye. Two days prior to presentation, he had undergone PPV that was complicated by accidental methylene blue use. Visual acuity (VA) at presentation to our institution was CF from his baseline VA of 20/60. Optical coherence tomography (OCT) demonstrated diffuse hyperreflectivity and thickening of the inner retinal layers. The patient was started on oral prednisone with no improvement. On postoperative month 1, VA was HM. …

First Mammography Screening Participation And Breast Cancer Incidence And Mortality, Forruk Ahmed, Anna Aleksyeyeva, Oman Balan, Ashley Hassang

Publications and Research

This population-based cohort study evaluated the long-term relationship between initial participation in mammography screening and subsequent breast cancer outcomes among approximately 432,000 women in Stockholm, Sweden. Women were invited to their first screening between 1991 and 2020 at ages 40 or 50 and followed for up to 25 years through national health registries. Overall, 32% did not attend their initial screening. Non-attenders were significantly less likely to participate in later screening rounds and were more likely to be diagnosed with advanced disease, showing 1.5-fold higher odds of stage III and more than 3.5-fold higher odds of stage IV breast cancer …

Acceptability Of Active And Sham Home-Based Transcranial Direct Current Stimulation In Major Depression: Mixed Methods Qualitative Analysis In A Randomised Controlled Trial, Peter J Lagerberg, Rachel D Woodham, Sudhakar Selvaraj, Nahed Lajmi, Harriet Hobday, Gabrielle Sheehan, Ali-Reza Ghazi-Noori, Maheen Rizvi, Sarah S Kwon, Paulette Orhii, Rodrigo Machado-Vieira, Jair C Soares, Allan H Young, António R Fidalgo, Hakimeh Rezaei, Cynthia H Y Fu

Faculty, Staff and Student Publications

Purpose: Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation therapy that is a potential treatment for major depressive disorder (MDD). Acceptability impacts patient preference, treatment adherence and outcomes, however, it has typically been assessed through measures of attrition, self-reported satisfaction levels, or adverse events. We sought to explore participant acceptability using structured questionnaires and individual interviews.

Methods: Acceptability was assessed in a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of a 10-week course of home-based tDCS for MDD. Questionnaires were conducted at baseline and at the 10-week end of treatment. Participants were 174 adults (120 women) …

Hsp90 Buffers Deleterious Genetic Variations In Brca1, Brant Gracia, Xing-Han Zhang, Patricia Montes, Tin Chanh Pham, Min Huang, Junjie Chen, Georgios Ioannis Karras

Faculty, Staff and Student Publications

Protein-folding chaperone heat shock protein 90 (HSP90) buffers genetic variation in diverse organisms, but the clinical significance of HSP90 buffering in human disease remains unclear. Here, we show that HSP90 buffers mutations in the BRCT domain of BRCA1. HSP90-buffered BRCA1 mutations result in protein variants that retain interactions with partner proteins and strongly rely on HSP90 for protein stability and function in cell survival. Moreover, HSP90-buffered BRCA1 variants confer poly (ADP-ribose) polymerase (PARP) inhibitor resistance in cancer cells. Low-level HSP90 inhibition overcomes this resistance, revealing a cryptic and mutant-specific HSP90-contingent synthetic lethality. Furthermore, by stabilizing metastable variants across the entirety …

Revealing The Nervous System Requirements Of Alzheimer Disease Risk Genes In Drosophila, Jennifer M Deger, Shabab B Hannan, Mingxue Gu, Colleen E Strohlein, Lindsey D Goodman, Sasidhar Pasupuleti, Zahid Shaik, Liwen Ma, Yarong Li, Jiayang Li, Morgan C Stephens, Michal Tyrlík, Zhandong Liu, Ismael Al-Ramahi, Juan Botas, Chad A Shaw, Oguz Kanca, Hugo J Bellen, Joshua M Shulman

Faculty, Staff and Students Publications

Most Alzheimer disease (AD) susceptibility genes have poorly understood roles in the central nervous system (CNS). To address this gap, we systematically characterized 100 conserved candidate AD risk genes using a cross-species strategy in the fruit fly, Drosophila melanogaster. Genes were prioritized based primarily on human functional genomic evidence. We generated custom loss-of-function alleles for each of the conserved fly orthologs. Most of the genes are expressed in the adult brain, including 24 neuron- and 13 glia-specific expression patterns. Overall, we identify 50 candidate AD risk gene homologs with requirements for CNS structure or function, including 18 whose loss of …

Super-Fast, Super-Early: High-Frequency Oscillations May Be A Prelude To Alzheimer's Dementia In Down Syndrome, Manuel Silva-Pérez, Jeannie Chin

Faculty, Staff and Students Publications

Alzheimer's disease (AD) dementia has near full penetrance in adults with Down syndrome (DS) and is strongly linked to late-onset myoclonic epilepsy in Down syndrome (LOMEDS). However, promising biomarkers of epileptogenicity, such as high-frequency oscillations (HFOs >250 Hz), have not been studied. This study is the first to use wideband polysomnography in DS to investigate if HFOs occurred and preceded AD dementia and LOMEDS. Methods: Wideband (0.1 to 500 Hz, 2048 Hz) polysomnography was performed using the international 10–20 system. HFOs were automatically detected during slow-wave sleep, followed by manual review. Results: Fourteen individuals with DS and five age-matched euploid …

Cardiovascular Disease And Pregnancy: Clinical Outcomes From A Tertiary Center Experience In Saudi Arabia, Nouf Alanazi, Sara Abou Al-Saud, Wareef Almousa, Ghada Alshalan, Jumana Alqahtani, Munira Alsharif, Abrar Alshahrani, Hessah Alothman

Journal of the Saudi Heart Association

Cardiovascular disease complicates pregnancy and elevates maternal and fetal risks. Local data in Saudi Arabia is scarce. This study examines pregnancy outcomes in women with cardiovascular disease at a tertiary center. A retrospective cohort study of 103 cardio-obstetric patients (2015-2023) at King Khalid University Hospital. Multivariable logistic regression identified risk factors for adverse maternal and neonatal outcomes, with significance at p

Enhancing Sepsis Prevention In Long-Term Care Facilities: Development Of An Infection Prevention Sepsis Toolkit, Emmalyn A. Tuhin

Student Scholarly Projects

Objectives: The purpose of this Doctor of Nursing Practice (DNP) project was to create, validate, and refine an Evidence-Based Sepsis Prevention Toolkit to enhanced early sepsis recognition and interprofessional coordination of care within long-term care facilities (LTCFs).

Background: Sepsis remains a leading cause of mortality and preventable transfer to the hospital for the elderly residents within the LTCFs. A significant practice gap persists because sepsis in this population often presents atypically, resulting in delayed or inaccurate diagnosis and treatment.

Methods: This project was guided by the following PICOT question: For healthcare professionals caring for patients aged 65 years and older …

Improving Palliative Care Knowledge And Intentions Among Great Plains American Indians: Efficacy Results From A Randomized Clinical Trial Testing A Culture-Centric Palliative Care Message, Mary J. Isaacson, Kah Meng (Charlie) Soh, Christopher S. Wichman, Gina Johnson, Kelly Le Beaux, Semhar Michael, Lisa Sparks, Karla M. Hunter

Communication Faculty Articles and Research

Background

Methods

Results

Selenium Nanoparticles As Versatile Delivery Tools, Amir Nasrolahi Shirazi, Rajesh Vadlapatla, Ajoy Koomer, Kyle Yep, Keykavous Parang

Pharmacy Faculty Articles and Research

Selenium nanoparticles (SeNPs) have emerged as promising metal-based nanoparticles for drug delivery due to their unique physicochemical properties, intrinsic bioactivity, and biocompatibility. SeNPs offer a lower toxicity, higher bioavailability, and flexibility to be customized for surface chemistry compared to traditional selenium compounds. Advances in synthetic strategies, including chemical reduction, green biosynthesis, and surface functionalization with polymers, peptides, or ligands, have improved their stability, targeting capability, and circulation time. SeNP-based systems have demonstrated unique anticancer, antimicrobial, and anti-inflammatory activities, as they can function as drug carriers and active therapeutic agents. The surface of SeNPs has been functionalized with ligands such as …

Travel Time To Treating Facility And Mortality In Men With Prostate Cancer, Stephan M. Korn, Filippo Dagnino, Danesha Daniels, Zhiyu Qian, Hanna Zurl, Klara K. Pohl, Mei Chin Hsieh, Brenda Y. Hernandez, Andrea Piccolini, Alexander P. Cole, Amanda J. Reich, Joel S. Weissman, Quoc Dien Trinh, Hari S. Iyer

School of Public Health Faculty Publications

IMPORTANCE Geographic access to prostate cancer care may influence outcomes but is often measured using straight-line distance, which may not accurately capture the travel burden experienced by patients. OBJECTIVE To evaluate the association between estimated travel time from patients’ residence to treatment facilities and all-cause and prostate cancer–specific mortality. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the Multilevel Epidemiologic Tumor Registry for Oncology, a nationally representative, investigatorinitiated, population-based cancer registry that integrates geomasked residential and treatment facility information from multiple US state cancer registries. The study included patients aged 40 to 99 years from Hawaii, Louisiana, …

Exploring The Potential Of Martian Agriculture: Assessing Viability And Nutritional Composition Of Plants Cultivated In Martian Regolith, Abigail Ross

Honors Theses

In addition to sunlight and water, plants can utilize a small number of nutrients from the soil to biosynthesize all the materials that are needed for growth and development. However, plants require an environment where they are able to obtain those nutrients, such as iron, magnesium, potassium, sulfur, and nitrogen. Environmental factors determine the types and accessibility of nutrients available to plants. Plants then take up these nutrients from the soil to aid in biological mechanisms and the synthesis of important molecules needed for growth and development. Ascorbic acid, commonly known as Vitamin C, is a vital molecule that is …

A Distinct Pp2a Subunit Regulates Local Protein Phosphorylation At The Axon Initial Segment, Andrew P Anderson, Sanghyun Kim, Allison J Melton, Xiaoyun Ding, Wei Zhang, Alexander B Saltzman, Anna Malovannaya, Matthew N Rasband, Yudong Gao

Faculty, Staff and Students Publications

Protein phosphorylation plays a crucial role in regulating the cytoskeletal and membrane proteins at the axon initial segment (AIS). However, our knowledge of AIS-specific kinases and phosphatases is very limited. Here, we report the identification of a protein phosphatase 2A (PP2A) B55 regulatory subunit enriched at the AIS in mice: Ppp2r2c. Our results demonstrate that PP2A-B55 subunits exhibit substantial heterogeneity in their subcellular localization and function. Notably, the Ppp2r2c subunit is selectively concentrated at the AIS, and this enrichment is driven by its unique structure. Utilizing a microelectrode array system (MEA), we show that Ppp2r2c modulates neuronal activity during in …

The Perspectives And Experiences Of Prospective Parents Declining Diagnostic Prenatal Genome Sequencing In Continuing Pregnancies With Fetal Structural Anomalies, Lisa S Weingarten, Allison Rosenbaum, Jessica De Voest, Stephanie Galloway, Jessica L Giordano, Samantha Stover, Lauren E Westerfield, Grant Bonesteele, Kelly L Gilmore, Leandra Tolusso, Beatrix Wong, A Theresa Wittman, Daniel T Swarr, Nancy Leslie, Anthony Johnson, Ignatia B Van Den Veyver, Neeta L Vora, Rebecca G Clifton, Aaron B Caughey, Ronald J Wapner, Wendy K Chung

Duncan NRI Faculty and Staff Publications

Objective: This study evaluates an understudied perspective: the experiences of prospective parents who decline prenatal genome sequencing (pGS) for continuing pregnancies with fetal structural anomalies.

Method: We recruited a total cohort of 300 parents of 150 pregnancies who declined pGS, including 33 individuals who underwent an invasive procedure. These parents were invited to participate in a semi-structured interview between 1 and 15 months post-partum. We used Thematic Analysis to code and analyze interviews.

Results: We interviewed 22 parents of 16 pregnancies. Reasons for declining testing included risks of invasive procedures (n = 19, 86%), lack of prenatally actionable findings (n …

Long-Term Outcomes And Treatment Patterns In Waldenström Macroglobulinemia Patients Who Discontinue Bruton Tyrosine Kinase Inhibitor (Btki) Therapy, Karan L Chohan, Lorenzo Gensini, Sherif Seif, Xiaowen Sun, Lei Feng, Melody R Becnel, Mahmoud M Gaballa, Hans C Lee, Oren Pasvolsky, Krina K Patel, J Christine Ye, Donna M Weber, Robert Z Orlowski, Sheeba K Thomas

Faculty, Staff and Student Publications

No abstract provided.

Cdk2 Inhibition Enhances Cdk4/6 Inhibitor Antitumor Activity In Comprehensive Breast Cancer Pdx Model Screen, Nealia C House, Maxine M Chen, Sima Khazaei, Victoria Brown, Philip Ramsden, David H Peng, Sydney Moore, Liang Yuan, Rentian Wu, Fangyang Wang, Linjie Luo, Ningping Feng, Christopher A Bristow, Timothy A Yap, Khandan Keyomarsi, Joseph R Marszalek, Scott Ribich, Mikael L Rinne, Lakshmi B Muthuswamy, Kerrie L Faia

Faculty, Staff and Student Publications

Aberrant cyclin-dependent kinase 2 (CDK2) activity is implicated as a resistance mechanism to CDK4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Using preclinical patient-derived xenograft models, the CDK2i + CDK4/6i combination was active broadly across CDK4/6i-resistant and -naïve HR+ and triple-negative breast cancer models. A novel, weighted mRNA expression signature involving CCND1, CCNE1, RB1, and CDKN2A (p16) predicted response to combined inhibition of CDK2 and CDK4/6. Addition of endocrine therapy significantly enhanced antitumor activity in HR+ models, providing preclinical proof-of-concept for the broad antitumor activity of the triple combination. Early clinical data demonstrated …

Factors Influencing Immediate Post-Angiographic Occlusion Outcomes In Intracranial Aneurysms Treated With The Woven Endobridge Device: A Multi-Center Analysis And Predictive Model From The Worldwideweb Consortium, Muhammed Amir Essibayi, Mohamed Sobhi Jabal, Hasan Jamil, Hamza Adel Salim, Basel Musmar, Nimer Adeeb, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Arbaz A. Momin, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammed Said Besler, Yasin Celal Gunes, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Deepak Khatri, Neil Haranhalli, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal M. Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, David J Altschul, Adam A. Dmytriw, Worldwideweb Consortium Collaborators

Jefferson Hospital Staff Papers and Presentations

The Woven EndoBridge (WEB) device treats wide-necked bifurcation aneurysms, but occlusion rates vary. This study aims to identify factors associated with immediate WEB device occlusion. Data from patients treated with WEB devices across 36 sites were analyzed. Machine learning algorithms and ordinal regression models were developed to predict immediate incomplete occlusion for ruptured and unruptured aneurysms. The study included 1565 patients, with 436 ruptured and 1129 unruptured aneurysms. Immediate complete occlusion was achieved in 38.3% of ruptured and 32.8% of unruptured aneurysms. For ruptured aneurysms, the CatBoost classifier achieved an AUROC of 0.69. Key predictors of incomplete occlusion included pretreatment …

Patient And Procedural Factors Associated With Same-Day Discharge Following Pulsed Field Ablation For Atrial Fibrillation: Insights From The Disrupt-Af Registry., Amin Al-Ahmad, Jose Osorio, John Day, Jeremiah Wasserlauf, Devi Nair, Robert Eckart, Dwayne Campbell, Jonathan Dukes, Frank Cuoco, John Costello, Jason Zagrodzky, David Kessler, Gustavo Morales, Anil Rajendra, Saumil Oza, Amr Barakat, Anthony Magnano, Anish Amin, Joshua Silverstein, Amit Thosani, Susan M Bezenek, Paul Zei, Chang Dai, Andrea Natale, Rodney Horton

OhioHealth Research Institute Articles

BACKGROUND: Same-day discharge (SDD) after catheter ablation for atrial fibrillation (AF) may improve patient satisfaction and optimize healthcare resources. Pulsed field ablation (PFA) offers a favorable safety profile, potentially enabling broader adoption of SDD strategies.

OBJECTIVE: To evaluate site-level practice patterns and participant- and procedure-related factors associated with SDD after de novo PFA for AF.

METHODS: We analyzed data from participants in the DISRUPT-AF registry, a prospective, multicenter study evaluating ablation acute outcomes with a pentaspline PFA catheter. We examined participant and procedure characteristics associated with both SDD planning and success.

RESULTS: SDD was preplanned for 81% (1203) of all …

Reducing Storage-Related Bias In Reproductive Vitamin D Research: Towards A Stable And Reliable Biomarker Of Ovarian Vitamin D Status, Evelin E Lara-Molina, Jason M. Franasiak, Almudena Devesa-Peiro, Marina López-Nogueroles, Alberto Vázquez, David Amorós, Agustín Ballesteros, Antonio Pellicer, Patricia Sebastian-Leon, Patricia Diaz-Gimeno

SKMC Student Presentations and Publications

Background/Objectives: One of the main reasons for discrepancies in the role of vitamin D in ART could be the measurement of the conventional biomarker 25(OH)D₃. It is known that this value is affected by multiple factors, such as tissue origin, assay variability, classification criteria, and potential storage-related degradation. In this study, we investigate 24,25(OH)₂D₃ as a new biomarker to improve vitamin D assessment in women’s reproductive health, particularly regarding oocyte development. Methods: A prospective cohort study including 35 oocyte donors undergoing controlled ovarian stimulation, who were recruited between October and November 2017, was conducted. Vitamin …

The Right Kind Of Rarefaction: Coronary Microvascular Remodeling In Right Ventricle Failure, Cyrus Vahdatpour, Katharine Clapham, Steven M. Kawut, Kirk Jones, John J. Ryan, Danielle Petty, Shannon Talbot, Kimberly Dumoff, Ellen C. Keeley, Priti Lal, Andrew J. Bryant, Alex M. Parker, Jeremy A. Mazurek, Leonid Mirson, Andrew Murphy, Andrew Baird, Megan Schwietert, Alissa F. Schurr, Andrew Stein, Scott M. Hansen, Zhining Ou, Angela P. Presson, Dylan Miller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Right ventricular failure (RVF) is the primary determinant of outcomes in pulmonary hypertension (PH). Coronary microvascular dysfunction (CMD), defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF but remains poorly characterized. CMD, defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF through impaired myocardial oxygen delivery and fibrotic remodeling.

OBJECTIVES: To characterize right ventricle (RV) CMD and myocardial fibrosis in explanted human hearts and examine associations with echocardiographic and hemodynamic indices of RVF across PH subtypes.

METHODS: We retrospectively analyzed 57 adult patients who underwent orthotopic heart transplantation at 3 institutions (2023-2024). Explanted hearts were …

A Double-Edged Sword: Ethical And Psychological Implications Of Apoe Genotype Disclosure Across The Lifespan, Diego Iacono

Department of Neurology Faculty Papers

The apolipoprotein E (APOE) gene is the strongest genetic risk factor for sporadic Alzheimer’s disease (AD), with the ε4 allele increasing risk and decreasing the average age of onset. While APOE genotyping is primarily used in research or clinical settings for patients with memory concerns, interest in disclosing APOE status to asymptomatic individuals—particularly during early adulthood—is growing. This trend is fueled by the rise of direct-to-consumer genetic testing and emerging prevention-focused clinical trials. However, ethical debates remain unresolved about the potential harms of early disclosure, including anxiety, stigma, and misunderstanding of probabilistic risk. Conversely, some argue that knowledge of APOE …

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

Multi-Omic Profiling Provides Insights Into The Heterogeneity, Microenvironmental Features, And Biomarker Landscape Of Small-Cell Lung Cancer, Mingchao Xie, Miljenka Vuko, Shashank Saran, Siyu Liu, Andrew G Chambers, Hana Baakza, Helen K Angell, Felicia Ng, Carl M Gay, Robert J Cardnell, Felix J Segerer, Alma Andoni, Jaime Rodriguez-Canales, Paul M Waring, Markus Schick, J Carl Barrett, Lauren A Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Background: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

Methods: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

Results: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest …

Inhibition Of Clostridioides Difficile-Specific Dna Adenine Methyltransferase Cama By Analogs Of S‑Adenosyl‑L‑Methionine, Jujun Zhou, Youchao Deng, Dan Yu, Taraneh Hajian, Masoud Vedadi, Xing Zhang, Robert M Blumenthal, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapies, especially those inhibiting S-adenosyl-l-methionine (SAM)-dependent methylations of DNA, mRNA, and histones, have advanced rapidly in cancer treatment. However, these therapies remain underexplored for antibiotic development, despite the growing threat of antimicrobial resistance. Here, we screened a focused library of SAM analogs against the DNA adenine methyltransferase CamA specific to the enteric pathogen Clostridioides difficile. At the same time, we examined six other adenine methyltransferases, including two bacterial DNA methyltransferases and four human RNA methyltransferases having distinct RNA substrates. Compound 113 selectively inhibited CamA (IC50 = 0.15 μM). In addition, compound 67 inhibited Caulobacter crescentus CcrM …

Characterizing Circulating Rare Cells In Peripheral Blood For Detecting And Monitoring Multiple Myeloma And Precursor States, Stephanie N Shishido, Jeremy Mason, Mohamed Kamal, Sonia Maryam Setayesh, Amishi U Vora, David Berrios, Luz Yurany Moreno Rueda, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) arises from abnormal plasma cells (PCs) progressing from precursor states, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding this transition and progression to overt MM requires improved non-invasive strategies. We employed a liquid biopsy approach to detect and characterize circulating PCs across disease states in 68 patients (MGUS = 11, SMM = 21, NDMM = 19, RRMM = 17) using multi-channel immunofluorescence staining and machine learning-assisted rare event detection. PCs were identified by CD138 and B-cell maturation antigen (BCMA) expressions, with distinct phenotypic subpopulations stratifying disease states. The D | CD138 | …

Targeting Tet3 Suppresses Group 3 Medulloblastoma Stemness And Progression Via Impairing Hypomethylation Of Otx2 Super-Enhancer, Xuan Chen, Ziwei Wang, Yan Song, Yu Su, Yahui Zhao, Jiankang Li, Wei Wang, Jiao Zhang, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Yanan Wang, Fei Liu, Kaiwen Deng, Dongming Han, Zijia Liu, Meiyu Li, Liam D Hendrikse, Alexandra Rasnitsyn, Evan Y Wang, Dongyang Wang, Zhaoyang Feng, Yanong Li, Zitong Zhao, Hongyu Yuan, Youliang Sun, Yifei Jiang, Yanfeng Shi, Tao Yang, Xueling Qi, Yong Hou, Chunde Li, Yong-Qiang Liu, Yu Tian, Shuaicheng Li, Xiaoguang Qiu, Michael D Taylor, Guo Liang Li, Tao Jiang, Hailong Liu

Faculty, Staff and Students Publications

Medulloblastoma (MB), particularly Group_3 (G3-MB), remains the most aggressive subgroup due to strong stemness and therapeutic resistance. Through genome-wide DNA methylation and transcriptomic analysis of human MB samples, we identify enhancer hypomethylation as a key feature sustaining G3-MB stemness and tumor progression. Notably, hypomethylation of the Otx2 super-enhancer (SE) is a prognostic marker and potential therapeutic target for G3-MB patients. We demonstrate that disrupting Otx2 SE activity effectively reduces tumor growth in vivo, highlighting its critical role in G3-MB maintenance. TET3, recruited by OTX2, demethylates the Otx2 SE, promoting chromatin opening and sustaining tumor proliferation and stemness. To translate these …

Upper-Body Post-Activation Performance Enhancement In Mma Athletes: Load-Dependent Effects Across Multiple Explosive Tasks, Jan Strawiński, Dariusz T. Skalski, Magdalena Prończuk, Kinga Łosińska, Ewelina Lulińska, Miłosz Drozd, Maciej Kostrzewa, Adam Maszczyk, Robert K. Roczniok

Baltic Journal of Health and Physical Activity

Background: Post-activation performance enhancement (PAPE) has become a recognized method for acutely improving explosive output, particularly relevant to upper-body performance in combat sports. Objective: This study aimed to evaluate the effects of bench press conditioning activities (CAs) at different intensities (50 %, 65 %, and 80 % 1RM) on upper-body explosive performance in mixed martial arts (MMA) athletes, with emphasis on training status. Methods: Twenty-nine male MMA athletes were divided into intermediate (n = 14) and advanced (n = 15) groups. Each participant completed three CA sessions followed by a 4-minute recovery and then performed a plyometric push-up …

Saudi Heart Association Position Statement On Adult Vaccinations For Patients With Cardiovascular Diseases, Waleed Alhabeeb, Fayssal M Farahat, Majid Alshamrani, Raed Aldahash, Mohamed S. Al-Moamary, Mohammed Balghith, Yassmin Hanfi

Journal of the Saudi Heart Association

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. Individuals with CVD are particularly vulnerable to severe complications from vaccine-preventable infections; however, adult vaccination continues to be underutilized. Methods: A multidisciplinary expert panel from the Saudi Heart Association (SHA) conducted a comprehensive literature review and a series of consensus meetings to develop evidence-based recommendations for adult immunization in patients with CVD. Results and conclusions: Evidence from randomized trials, observational studies, and real-world data supports the role of vaccines in reducing the risk of major adverse cardiovascular events in individuals with CVD. The SHA recommends the implementation of age-appropriate …

Engaging Ukrainian Tf-Cbt Therapists In A Practice Skills Course To Support Their Wellbeing, Elisabeth Pollio, Esther Deblinger, Beth Cooper, Maike Garbade, Julie P Harrison, Elisa Pfeiffer

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Background: Burnout and secondary traumatic stress (STS) are common among therapists working with trauma-exposed clients, which can negatively impact them professionally and personally. The shared trauma of war exposure may put therapists at greater risk. To help support their wellbeing, an eight-session course was offered to Ukrainian therapists following training in Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). This course involves therapists personally utilizing the PRACTICE skills taught to clients in TF-CBT for professional and personal benefit.

Objective: The objective was to gather preliminary evidence on the potential impact of implementing the course with Ukrainian therapists providing TF-CBT during a period of …