Medical Specialties Commons^™

Human Ipsc-Based Breast Cancer Model Identifies S100p-Dependent Cancer Stemness Induced By Brca1 Mutation, Jingxin Liu, Cai Zhao, Jiahao Chen, Pengguihang Zeng, Qingjian Li, Ranran Dai, Xingqiang Lai, Wenqian Song, Jianing Chen, Xixi Zhu, Xinyi Liu, Jun Sun, Jia Wang, Peihang Fang, Tengfei Wang, Wenjie Chen, Diana Guallar, Nan Cao, Jianli Zhao, Shicheng Su, Andy Peng Xiang, Yi Arial Zeng, Jie Li, Junchao Cai, Dung-Fang Lee, Jinxin Bei, Yongliang Huo, Hai Hu, Shengbao Suo, Dong-Feng Huang, Jin Bai, Junjun Ding

Faculty, Staff and Student Publications

Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline

Assessment Of Dnase Activity By Ratiometric Fluorescence Resonance Energy Transfer, Candace L Minchew, Vladimir V Didenko

Faculty, Staff and Students Publications

The present protocol describes a simple and sensitive ratiometric Förster resonance energy transfer (FRET) assay for the detection and quantitative assessment of DNase activity. Ratiometric FRET measurements make use of the ratio of donor and acceptor emission signals. The assay detects single-stranded DNA breaks using a staple-shaped, dual-tagged 38-mer FRET oligoprobe, employed as a real-time DNA cleavage sensor. The main application of the described approach is the quantitative assessment of the effects of reaction conditions, such as pH, temperature, and buffer composition, on DNase activity. Due to its ability to detect even minor and slow DNA cleavage, the assay is …

Imaging Efficacy And Safety Of Low Dose Intraventricular Tissue Plasminogen Activator In Aneurysmal Subarachnoid Hemorrhage: Case Series, Collin Liu, William W Wroe, Hussein A Zeineddine, Bryden Dawes, Michael Giordano, Aaron Mccabe, Ching-Jen Chen, Devin W Mcbride, Aaron M Gusdon, Huimahn A Choi, Spiros L Blackburn

Faculty, Staff and Student Publications

Introduction: Free hemoglobin's release into CSF from blood breakdown is a primary instigator of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Early clearance of subarachnoid blood with intrathecal (IT) fibrinolytics has shown potential to decrease incidence of DCI. However, the dosage of fibrinolytic needed is not known. We investigated the ability of low dose tissue plasminogen activator (tPA) to rapidly remove subarachnoid clot.

Material and methods: We performed a single center retrospective review of aSAH patients who received IT tPA. Dosing consistent with the CLEAR III trial for IVH was utilized-tPA (1 mg) administered every 8 h via …

Machine-Learning Driven Strategies For Adapting Immunotherapy In Metastatic Nsclc, Maliazurina B Saad, Qasem Al-Tashi, Lingzhi Hong, Vivek Verma, Wentao Li, Daniel Boiarsky, Shenduo Li, Milena Petranovic, Carol C Wu, Brett W Carter, Girish S Shroff, Tina Cascone, Xiuning Le, Yasir Y Elamin, Mehmet Altan, Simon Heeke, Ajay Sheshadri, Joe Y Chang, Percy P Lee, Zhongxing Liao, Don L Gibbons, Ara A Vaporciyan, J Jack Lee, Ignacio I Wistuba, Cara Haymaker, Seyedali Mirjalili, David Jaffray, Justin F Gainor, Yanyan Lou, Alessandro Di Federico, Federica Pecci, Mark Awad, Biagio Ricciuti, John V Heymach, Natalie I Vokes, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs), either as monotherapy (ICI-Mono) or combined with chemotherapy (ICI-Chemo), improves survival in advanced non-small cell lung cancer (NSCLC). However, prospective guidance for choosing between these options remains limited, and single-feature biomarkers like PD-L1 prove inadequate. We develop a machine learning model using clinicogenomic data from four cohorts (MD Anderson n = 750; Mayo Clinic n = 80; Dana-Farber n = 1077; Stand Up To Cancer n = 393) to predict individual benefit from adding chemotherapy. Benefit scores are calculated using five distinct functions derived from 28 genomic and 6 clinical features. Our integrated model, A-STEP (Attention-based …

A Multi-Modal Pelvic Mri Dataset For Deep Learning-Based Pelvic Organ Segmentation In Endometriosis, Xiaomin Liang, Linda A Alpuing Radilla, Kamand Khalaj, Haaniya Dawoodally, Chinmay Mokashi, Xiaoming Guan, Kirk E Roberts, Sunil A Sheth, Varaha S Tammisetti, Luca Giancardo

Faculty, Staff and Students Publications

Endometriosis affects approximately 190 million females of reproductive age worldwide. Magnetic Resonance Imaging (MRI) has been recommended as the primary non-invasive diagnostic method for endometriosis. This study presents new female pelvic MRI multicenter datasets for endometriosis and shows the baseline segmentation performance of two auto-segmentation pipelines: the self-configuring nnU-Net and RAovSeg, a custom network. The multi-sequence endometriosis MRI scans from two clinical institutions were collected. A multicenter dataset of 51 subjects with manual labels for multiple pelvic structures from three raters was used to assess interrater agreement. A second single-center dataset of 81 subjects with labels for multiple pelvic structures …

Project Evolve: An International Analysis Of Postimmunotherapy Lineage Switch, An Emergent Form Of Relapse In Leukemia, Sara K Silbert, Alexander W Rankin, Chloe N Hoang, Alexandra Semchenkova, Regina M Myers, Elena Zerkalenkova, Hao-Wei Wang, Alexandra E Kovach, Constance M Yuan, Dana Delgado Colon, Loïc Vasseur, Alex Bataller, Samuel John, Kaylyn Utley Lyons, Barbara Friedes, Anna Alonso-Saladrigues, Hisham Abdel-Azim, Estelle Balducci, Ahmed Assim Aljudi, Marie Balsat, D Nathan Biery, Aghiad Chamdin, Bill H Chang, Raymund S Cuevo, Barbara De Moerloose, David S Dickens, Ulrich Duffner, Nicolas Duployez, Firas El Chaer, Michelle Ann Elliott, Gabriele Escherich, Sneha Fernandes, Mandi R Fitzjohn, Zhubin Gahvari, Stephan A Grupp, Rui Rochelle He, Cynthia Harrison, Christopher B Hergott, Emily M Hsieh, Annette S Kim, Dennis J Kuo, Daniel P Larson, Benjamin J Lee, Thibaut Leguay, R Coleman Lindsley, Abhishek A Mangaonkar, Kerstin Mezger, Holly L Pacenta, Jing Pan, Marlie Provost, Latika Puri, Sunil S Raikar, Armando Martinez, Isabella Bristol, Kyle Murphy, Lauren Reiman, Michele Redell, Kelly Reed, Gabrielle Roth-Guepin, Jeremy Rubinstein, Süreyya Savaşan, Kristian Schafernak, Alexandra Stevens, Aimee Talleur, Naomi Torres Carapia, Jacques Vargaftig, Anant Vatsayan, Matthias Wölfl, Liping Zhao, Susana Rives, Vanessa A Fabrizio, Koji Sasaki, Ibrahim Aldoss, Nicolas Boissel, Susan R Rheingold, Kara L Davis, Sara Ghorashian, Elad Jacoby, Alexander Popov, Adam J Lamble, Nirali N Shah

Faculty, Staff and Students Publications

Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute …

Effects Of Oxygen Manipulation On Myofibroblast Phenotypic Transformation In Patients With Radiation-Induced Fibrosis, Eric Mastrolonardo, Sarah Sussman, Bo Yun, Victor Jegede, Dev Amin, Joel Rosenbloom, Andrew P. South, Voichita Bar-Ad, Peter J Wermuth, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

We tested if hyperoxic conditions can reduce the proportion of active myofibroblasts, which are assumed to be a major driver of head and neck radiation-induced fibrosis, as measured by expression levels of pro-fibrotic genes. Radiated, non-cancerous soft tissue from the head and neck and skin/soft tissue from non-radiated flap donor site were collected from each patient. Myofibroblast density was quantified using immunofluorescence staining with α-SMA and DAPI and visualisation under confocal microscopy and compared between baseline non-radiated and radiated tissue from the same patient. From each tissue specimen, fibroblast cell lines were cultured and exposed to either normoxic, hypoxic, or …

Effects Of Long Covid On Healthcare Utilization, Michael Gottlieb, Erica S. Spatz, Huihui Yu, Imtiaz Ebna Mannan, Michelle Santangelo, Caitlin Malicki, Nicole L. Gentile, Rachel E. Geyer, Alex Charlton, Jonathan W. Dyal, Joann G. Elmore, Kristyn Gatling, Mandy J. Hill, Juan Carlos C. Montoy, Kelli N. O'Laughlin, Kristin L. Rising, Sharon Saydah, Kari A. Stephens, Ralph C. Wang, Lauren E. Wisk, Arjun K. Venkatesh, Robert A. Weinstein

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: While most research on Long COVID (LC) has focused on symptoms and quality of life, there remains a critical need to better understand the effect of LC on resource utilization. This study sought to determine the type and amount of healthcare utilization among participants with versus without LC.

METHODS: This was a secondary analysis of a prospective, longitudinal, multicenter U.S. study of adult participants with symptomatic COVID-19, confirmed with testing, who completed 3-month post-infection surveys and had electronic health record data for at least 180 days pre- and post-index testing. We excluded participants with any COVID-19 infections within the …

One-Year Clinical Outcomes In Patients With Acute Coronary Syndrome Treated With Clopidogrel Versus Prasugrel Versus Ticagrelor: Results Of The Polish Registry Of Acute Coronary Syndromes (Pl-Acs), Julia M. Umińska, Michał Skrzypek, Małgorzata Ostrowska, Piotr Adamski, Aldona Kubica, Piotr Niezgoda, Robert Gajda, Marek Gierlotka, Bartosz Hudzik, Wiktor Kuliczkowski, Diana A. Gorog, Paul A. Gurbel, Jolanta Siller-Matula, Łukasz Szarpak, Michael Savage, Grzegorz Skonieczny, Udaya Tantry, Przemysław Trzeciak, Eliano P. Navarese, Jacek Kubica, Mariusz Gąsior

Division of Cardiology Faculty Papers

BACKGROUND: Efficient dual antiplatelet therapy is crucial in reducing adverse cardiovascular events in patients with acute coronary syndrome (ACS). Comparative effectiveness between clopidogrel, prasugrel, and ticagrelor remains unclear in real-world settings.

AIMS: The objective was to evaluate one-year clinical outcomes in ACS patients treated with clopidogrel, prasugrel, or ticagrelor using data from the Polish Registry of Acute Coronary Syndromes (PL-ACS).

MATERIAL AND METHODS: This retrospective cohort study analyzed 381 278 ACS patients from the PL-ACS registry from 2009 to 2022, who were treated with clopidogrel, prasugrel, or ticagrelor during hospitalization with a 12-month consistent regimen. The primary outcome was one-year …

Constitutive Il-7 Signaling Promotes Car-Nk Cell Survival In The Solid Tumor Microenvironment But Impairs Tumor Control, Matthew Dysthe, Ishwar Navin, Dayenne Van Leeuwen, Josue Pineda, Corrine Baumgartner, Cliona M Rooney, Robin Parihar

Faculty, Staff and Students Publications

Background: Adoptive transfer of chimeric antigen receptor (CAR)-expressing natural killer (NK) cells has demonstrated success against hematological malignancies. Efficacy against solid tumors has been limited by poor NK cell survival and function in the suppressive tumor microenvironment (TME). To enhance efficacy against solid tumors, stimulatory cytokines have been incorporated into CAR-NK cell therapeutic approaches. However, current cytokine strategies have limitations, including systemic toxicities, exogenous dependencies, and unwanted TME bystander effects. Here, we aimed to overcome these limitations by modifying CAR-NK cells to express a constitutively active interleukin (IL)-7 receptor, termed C7R, capable of providing intrinsic CAR-NK cell activation that does …

Impact Of Extended Reality On Robot-Assisted Surgery Training: A Systematic Review And Meta-Analysis, Michael Bickford, Fayez Alruwaili, Sara Ragab, Hanna Rothenberg, Mohammad Abedin-Nasab

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Robot-assisted surgeries (RAS) have an extremely steep learning curve. Because of this, surgeons have created many methods to practice RAS outside the operating room. These training models usually include animal or plastic models; however, extended reality simulators have recently been introduced into surgical training programs. This systematic review and meta-analysis was conducted to determine if extended reality simulators can improve the performance of robotic novices and how their performance compares to the conventional training of surgeons on surgical robots. Using the PRISMA 2020 guidelines, a systematic review was performed searching PubMed, Embase, Web of Science, and Cochrane library for studies …

Impact Of Posttransplant Cyclophosphamide-Based Gvhd Prophylaxis In Patients 70 Years And Older: An Update From Bmt Ctn 1703., Sameem Abedin, Michael J Martens, Javier Bolaños-Meade, Monzr M Al Malki, Qinghua Lian, Lyndsey Runaas, Hany Elmariah, Mahasweta Gooptu, Karilyn T Larkin, Brian C Shaffer, Alison W Loren, Melhem Solh, Amin M Alousi, Omer H Jamy, Miguel-Angel Perales, Andrew Rezvani, Ami Bhatt, Najla El Jurdi, Janny M Yao, Kristy Applegate, Leslie S Kean, Yvonne A Efebera, Ran Reshef, William Clark, Eric Leifer, Wael Saber, Mary M Horowitz, Richard J Jones, Shernan G Holtan, Mehdi Hamadani

Oncology Articles

Allogeneic hematopoietic cell transplant (allo-HCT) is underutilized in adults aged ≥70 years. Morbidity, often driven by graft-versus-host disease (GVHD), is considered a major barrier to its use. The BMT CTN 1703 trial (ClinicalTrials.gov identifier: NCT03959241) randomly assigned adults with hematologic malignancies undergoing allo-HCT after reduced intensity conditioning to receive either posttransplant cyclophosphamide, mycophenolate mofetil, and tacrolimus (PTCy) or tacrolimus and methotrexate (Tac/MTX) for GVHD prophylaxis. Overall study results revealed superior GVHD-free, relapse-free survival (GRFS) with PTCy-based prophylaxis. This analysis explored the impact of PTCy in patients aged ≥70 years enrolled in BMT CTN 1703. We analyzed outcomes for 96 patients …

Clinicopathologic Risk Factors For Post-Operative Complications After Enucleation Of Pancreatic Neoplasms, Isheeta Madeka, Steven Yi, Julia S. Evans, David Baek, Haresh V. Naringrekar, Harish Lavu, Charles J. Yeo, Avinoam Nevler, Wilbur B. Bowne

Kimmel Cancer Center Faculty Papers

BACKGROUND: Pancreatic enucleation is a parenchymal-sparing procedure used for highly select patients with pancreatic neoplasms. We aim to utilize a multi-institutional health research network platform (TriNetX) and a single, high-volume center to assess complications and identify risk factors associated with post-operative pancreatic fistulas (POPF) after pancreatic enucleation.

METHODS: A two-tiered retrospective study was conducted. We identified 423 patients from TriNetX, and 34 patients from a single-institution IRB-approved database who underwent pancreatic enucleation between 2004-2025 and 2012-2023, respectively. Univariate and multivariate analyses were performed to determine risk factors associated with post-operative complications and occurrence of POPFs.

RESULTS: In the TriNetX cohort, …

Participant Engagement In A National Longitudinal Study Of Covid-19: Insights From The Inspire Study, Kris Pui Kwan Ma, Tracy Stober, Michael Gottlieb, Rachel E. Geyer, Kristin L. Rising, Sharon Saydah, Michelle Santangelo, Kristyn Gatling, Dylan Grau, Ralph C. Wang, Juan Carlos Montoy, Ahamed Idris, Samuel Macdonald, Mandy J. Hill, Ryan Huebinger, Maria G. Prado, Nicole L. Gentile, Erica Spatz, Caitlin Maliki, Jocelyn Dorney, Joann G. Elmore, Michelle L'Hommedieu, Robert A Weinstein, Arjun K. Venkatesh, Kari A. Stephens

Department of Emergency Medicine Faculty Papers

OBJECTIVE: To examine participants' motivations and their experiences throughout a decentralized, longitudinal COVID-19 study in the U.S.

METHODS: We recruited 355 participants from the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) between November 2022 - March 2023 to answer five qualitative survey questions anonymously. We used an inductive content analysis approach to analyze the data.

RESULTS: We identified five key themes from the analysis, which reflected participants' a) motivations to join the study, b) study benefits, c) perceptions of survey questions, d) experiences with the research process, and e) preferences for disseminating research findings. Participants were motivated to …

Experience Matters: An Application Of The Operative Value Index For Lumbar Fusions, Danyal Quraishi, Advith Sarikonda, D. Mitchell Self, Steven R. Glener, Arbaz A. Momin, Emily L. Isch, Ashmal K. Sami, Matthews Lan, Nicholas Clark, Ashwini Sharan, Srinivas Prasad, Jack Jallo, Joshua Pelta-Heller, Alex R. Vaccaro, James Harrop, Ahilan Sivaganesan

Department of Neurosurgery Faculty Papers

INTRODUCTION: As healthcare systems transition to value-based care models, it is critical to understand factors influencing costs and outcomes in neurosurgery. This study utilizes Time-Driven Activity-Based Costing (TDABC) to assess the impact of surgeon experience and case volume on costs, clinical outcomes, and operative value in lumbar fusions. While TDABC has been applied in various surgical specialties, its use in neurosurgery, particularly in analyzing surgeon-specific factors, remains limited.

METHODS: A retrospective cohort study was conducted at a single center, analyzing lumbar instrumented arthrodesis procedures from 2017 to 2019. Primary variables included surgeon experience (years) and case volume (annual procedures). Confounding …

Timing Of Nodal Metastasis In Patients With Eyelid Sebaceous Carcinoma And Implications For Surveillance And Survival, Tracy Lu, Casey Anthony, Xinyang Jiang, Jing Ning, Ryan Goepfert, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: Sebaceous carcinoma (SC) is a rare cancer with periocular predilection. Studies focused on patterns and timing of nodal metastasis are scarce.Our aim is to report patterns of regional nodal metastasis in patients with eyelid SC, including results of sentinel lymph node biopsy (SLNB).

Methods: All consecutive patients with eyelid SC treated during 1999-2023 were retrospectively reviewed.All subjects had standard of care surgery for eyelid SC and regional lymph node evaluation using physical examination and ultrasonography (US) at baseline and during the surveillance period. 38 patients with negative findings on US had SLNB to rule out microscopic metastasis.The frequency and …

Longitudinal Analysis Of Gut Microbiome And Metabolome Correlates Of Response And Toxicity With Idecabtagene Vicleucel, Satabdi Saha, Lubna Rehman, Abdur Rehman, Faezeh Darbaniyan, Donna M Weber, Melody Becnel, Mahmoud Gaballa, Sheeba K Thomas, Hans C Lee, Chia-Chi Chang, Reetakshi Arora, Meghan Menges, Salvatore Corallo, Marco L Davila, Frederick L Locke, Mark R Tanner, Sattva S Neelapu, Elizabeth J Shpall, Christopher R Flowers, Robert Z Orlowski, Robert R Jenq, Michael D Jain, Christine Peterson, Doris K Hansen, Neeraj Y Saini, Krina K Patel

Faculty, Staff and Student Publications

Increasing evidence suggests that the gut microbiome may influence the responses and toxicities associated with chimeric antigen receptor T-cell (CAR-T) therapy. We conducted whole-genome shotgun sequencing on stool samples (N = 117) collected at various times from patients with multiple myeloma (n = 33) who underwent idecabtagene vicleucel (ide-cel) anti-B-cell maturation antigen CAR-T therapy. We observed a significant decrease in bacterial diversity after ide-cel infusion, along with significant differences in the bacterial composition linked to therapy response and toxicities. Specifically, we found significant enrichment of Flavonifractor plautii, Bacteroides thetaiotaomicron, Blautia fecis, and Dysosmobacter species in ide-cel responders. A notable finding …

Belumosudil Reduces Oral Chronic Graft-Versus-Host Disease Tissue Inflammation And Fibrosis: A Rockstar Companion Study, Rubina Sharma, Noa G Holtzman, Iskra Pusic, Corey Cutler, Nathaniel Treister, Rohtesh S Mehta, Amin S Alousi, Nadarajah Vigneswaran, Ayesha Javaid, Francis Boksa, Drashty P Mody, Ana C Costa-Da-Silva, Olivier Schueller, Sandrine Macé, Yu Yao, Ran Ji, Beifang Hu, Kathy Marshall, Bruce R Blazar, Stephanie J Lee, Steven Z Pavletic, Jacqueline W Mays

Faculty, Staff and Student Publications

Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 patients with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSGs], and skin) and the peripheral blood. After belumosudil treatment, reduction in …

Detection Of Oncogenic Fusions In Colorectal Cancer Using A Partner-Agnostic Next-Generation Sequencing Approach, Andrew J Pellatt, Reagan M Barnett, Sante Gnerre, Kristin Edwards, Jason A Willis, Michael J Overmann, Kanwal Raghav, Christine M Parseghian, Arvind Dasari, M Pia Morelli, Alisha Bent, Madhulika Eluri, Nicholas Hornstein, Leylah M Drusbosky, Scott Kopetz, Van K Morris

Faculty, Staff and Student Publications

Background: Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance.

Methods: We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H …

A Whole-Brain Voxel-Based Analysis Of Structural Abnormalities In Ptsd: An Enigma-Pgc Study, Cheryl R Z See, Shuqing Si, C Lexi Baird, Courtney C Haswell, Ahmed Hussain, Miranda Olff, Dick J Veltman, Jessie L Frijling, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Li Wang, Ye Zhu, Gen Li, Yuval Neria, Xi Zhu, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Jennifer S Stevens, Kerry Ressler, Negar Fani, Tanja Jovanovic, Sanne J H Van Rooij, Milissa L Kaufman, Lauren A M Lebois, Isabelle M Rosso, Elizabeth A Olson, Justin T Baker, Scott R Sponheim, Seth G Disner, Nicholas D Davenport, Amit Etkin, Adi Maron-Katz, Murray B Stein, Martha E Shenton, Dan J Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Shmuel Lissek, Hannah Berg, Thomas Straube, David Hofman, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Xin Wang, Andrew S Cotton, Erin N O'Leary, Hong Xie, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Ruth Lanius, Jean Théberge, Maria Densmore, Richard W J Neufeld, Chadi G Abdallah, Christopher L Averill, Ilan Harpaz-Rotem, Ifat Levy, John H Krystal, Elbert Geuze, Remko Van Lutterveld, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elisabeth A Wilde, Nic J A Van Der Wee, Robert R J M Vermeiren, Steven J A Van Der Werff, Katie Mclaughlin, Kelly Sambrook, Matthew Peverill, Joaquim Radua, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Anthony James, Lucia Valmaggia, Paul M Thompson, Rajendra A Morey, Matthew J Kempton

Faculty, Staff and Students Publications

Background: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

Methods: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and …

Adult Congenital Heart Disease As A Career? Examining Encouraging And Deterring Factors In The Global Achd Survey, Katia Bravo-Jaimes, M. H. D. Osama Srour, Petra Jenkins, Raquel Luna-Lopez, Oktay Tutarel, Geetha Kandavello, Carlos-Eduardo Guerrero-Chalela, Edgar García-Cruz, Judith Ackerman, Amalia Elizari, Miriam Valdez-Ramos, Blanche Cupido, Dominica Zentner, Murad Almasri, Sabrina Phillips, Christopher Mcleod, Luke Burchill, Celia Kamath, Renee Bullock-Palmer, Jonathan Windram

Department of Medicine Faculty Papers

BACKGROUND: There is a global mismatch between the number of adults with congenital heart disease and adult congenital heart disease (ACHD) cardiologists, potentially impacting patient outcomes. This survey explores factors influencing trainees and cardiologists' career choices in ACHD.

METHODS: An online, anonymous global survey on demographics, ACHD as a career choice, encouraging and deterring factors assessed via a 5-point Likert scale and open-ended questions on recommending ACHD was distributed through targeted emails and social media. Responses meeting a 75% completion criterion were analyzed using descriptive statistics and thematic analysis.

RESULTS: Among 811 included responses, most were from women (53.5%), aged …

Investigating The Necessity Of Adaptive Radiotherapy In Tomotherapy Of Head And Neck Cancer Patients, Ali Chaparian, Mahsa Kianinia, Mahnaz Roayaei, Nadia Najafizade, Abolfazl Kanani, Leili Mahani, Hamidreza Nourzadeh

Department of Radiation Oncology Faculty Papers

BACKGROUND: Anatomical variations that occur during radiation therapy in head and neck cancer (HNC) patients can lead to significant dosimetric changes. The purpose of this study is to evaluate dosimetric and volume changes in key anatomical structures for different treatment sites in HNC patients, and to determine the percentage of patients who need adaptive radiotherapy (ART) per treatment site.

METHODS: A total of 1,740 megavoltage computed tomography (MVCT) images from 58 HNC patients treated with helical tomotherapy (HT) were exported to the PreciseART™ (Accuray) software. Volume changes in the planning target volume (PTV) and the organs at risk (OARs) in …

Effects Of Maackia Amurensis Seed Lectin (Masl) On Oscc Cell Morphology, Pdpn Expression, Growth, And Motility In A Phase 1 Clinical Trial, Ariel C Yin, Cayla J Holdcraft, Tyler J Hellmig, Eamonn J Brace, David I Suster, Alan J Shienbaum, Dylan Roden, Evelyne Kalyoussef, Ghayoour Mir, Eugenio Capitle, Soly Baredes, Rabie M Shanti, Mika K Kaneko, Yukinari Kato, Hisataka Kobayashi, Aki Furusawa, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Podoplanin (PDPN) has emerged as a functionally relevant biomarker and chemotherapeutic target expressed by OSCC cells. PDPN signaling can directly increase tumor cell invasion and metastasis, and also inhibit host lymphocyte activation and immune response. Accordingly, antibodies and Maackia amurensis seed lectin (MASL) can target the PDPN receptor to inhibit OSCC cell migration and viability. However, the effects of MASL on OSCC cells in oral cancer patients has not yet been reported.

METHODS: We conducted a Phase 1 human clinical trial to examine the effects of a single 100 mg oral dose of MASL on OSCC cell morphology, PDPN …

Smartboot: Real-Time Monitoring Of Patient Activity Via Remote Edge Computing Technologies, Gozde Cay, Myeounggon Lee, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system-a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch-for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and …

Impact Of Sars-Cov-2 On Healthcare And Essential Workers: A Longitudinal Study Of Promis-29 Outcomes, Jocelyn Dorney, Imtiaz Ebna Mannan, Caitlin Malicki, Lauren E. Wisk, Joann Elmore, Kelli N. O'Laughlin, Dana Morse, Kristyn Gatling, Michael Gottlieb, Michelle Santangelo, Michelle L'Hommedieu, Nicole L. Gentile, Sharon Saydah, Mandy J. Hill, Ryan Huebinger, Katherine Riley Martin, Ahamed H. Idris, Efrat Kean, Kevin Schaeffer, Robert M. Rodriguez, Robert A. Weinstein, Erica S. Spatz, Inspire Group

Department of Emergency Medicine Faculty Papers

IMPORTANCE: The mandatory service of essential workers during the COVID-19 pandemic was associated with high job stress, increased SARS-CoV-2 exposure, and limited time for recovery following infection. Understanding outcomes for frontline workers can inform planning for future pandemics.

OBJECTIVE: To compare patient-reported outcomes by employment type and SARS-CoV-2 status.

DESIGN: Data from the INSPIRE registry, which enrolled COVID-positive and COVID-negative adults between 12/7/2020-8/29/2022 was analyzed. Patient-reported outcomes were collected quarterly over 18 months.

SETTING: Participants were recruited across eight US sites.

PARTICIPANTS: Employed INSPIRE participants who completed a short (3-month) and long-term (12-18 month) survey.

EXPOSURE: SARS-CoV-2 index status and …

Image-Based Inference Of Tumor Cell Trajectories Enables Large-Scale Cancer Progression Analysis, Yang Liu, Ling Cai, Ruichen Rong, Shidan Wang, Liwei Jia, Peiran Quan, Qin Zhou, Guanghua Xiao, Yang Xie

Faculty, Staff and Student Publications

Current approaches to estimating cell trajectories, tumor progression dynamics, and cell population diversity of tumor microenvironment often depend on single-cell RNA sequencing, which is costly and resource intensive. To address this limitation, we developed an artificial intelligence (AI) model that leverages cell morphology features and histological spatial organization to classify tumor cell differentiation status, infer cell dynamic trajectories, and quantify tumor progression from hematoxylin and eosin (H&E)-stained whole-slide images. In three independent lung adenocarcinoma cohorts, our AI-based model accurately predicted cell differential status and provided quantifiable measures of tumor progression that were prognostic of patient survival. Spatial transcriptomic integrative analyses …

A Two-Stage Dual-Task Learning Strategy For Early Prediction Of Pathological Complete Response To Neoadjuvant Chemotherapy For Breast Cancer Using Dynamic Contrast-Enhanced Magnetic Resonance Images, Bowen Jing, Jing Wang

Faculty, Staff and Student Publications

Early prediction of treatment response can facilitate personalized treatment for breast cancer patients. Studies on the I-SPY 2 clinical trial demonstrate that multi-time point dynamic contrast-enhanced magnetic resonance (DCEMR) imaging improves the accuracy of predicting pathological complete response (pCR) to chemotherapy. However, previous image-based prediction models usually rely on mid- or post-treatment images to ensure the accuracy of prediction, which may outweigh the benefit of response-based adaptive treatment strategy. Accurately predicting the pCR at the early time point is desired yet remains challenging. To improve prediction accuracy at the early time point of treatment, we proposed a two-stage dual-task learning …

Ifn-Β Production Promotes Metabolic Rewiring And Protection Against Oxidative Stress In Hepatitis Delta Virus-Infected Hepatocyte Cultures, Olga A Khomich, Patrick Giavalisco, Romain Parent, George S Krasnov, Peter Tessarz, Philip Meuleman, Rani Burm, Natalia F Zakirova, Jennifer Molle, Enkhtuul Batbold, Eyal Gottlieb, Fabien Zoulim, Alexander V Ivanov, Birke Bartosch

Faculty, Staff and Student Publications

Type I interferons are secreted in response to various stimuli and are used as a treatment for many diseases, including infections with the hepatitis B virus (HBV) and its satellite virus, hepatitis delta (HDV). HDV significantly aggravates HBV-mediated liver damage and is - in contrast to HBV - a strong inducer of interferon responses, including IFN-β. As the role of IFN- β in liver metabolism is so far ill explored, we studied its impact on hepatocyte metabolism in HDV-infected cultures. Transcriptome analysis, isotope tracing and functional tests on differentiated, HDV-infected hepatocytes showed reduction of mitochondrial TCA cycle and respiratory activity …

Patient-Centered, Theory-Based, Online Intervention To Promote A Physically Active Lifestyle For People With Multiple Sclerosis: Protocol For A Randomized Controlled Trial, Chungyi Chiu, Vaishnavi Sridharan, Mojtaba Khaliji, Md Refat Uz Zaman Sajib, Xiaotian Gao, Kathleen Zackowski

Children’s Nutrition Research Center Staff Publications

Background: People with multiple sclerosis (MS) experience life challenges due to the nature of disease progression. Although an active lifestyle has been shown effective for symptom and relapse management, most people with MS lead a sedentary lifestyle and do not reach the recommended physical activity (PA) guidelines.

Objective: This study aims to test the preliminary efficacy of a codeveloped, online self-management intervention based on the health action process approach (HAPA) adapted for people with MS to cultivate a physically active lifestyle.

Methods: The 8-week intervention program was developed using community-based participatory research based on the HAPA. The program includes increasing …

Multi-Ancestry Genome-Wide Meta-Analysis Of 56,241 Individuals Identifies Known And Novel Cross-Population And Ancestry-Specific Associations As Novel Risk Loci For Alzheimer’S Disease, Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan-Ping Lee, Jacob Haut, Kara L Hamilton-Nelson, Nicholas R Wheeler, Yi Zhao, John J Farrell, Michelle A Grunin, Yuk Yee Leung, Pavel P Kuksa, Donghe Li, Eder Lucio Da Fonseca, Jesse B Mez, Ellen L Palmer, Jagan Pillai, Richard M Sherva, Yeunjoo E Song, Xiaoling Zhang, Takeshi Ikeuchi, Taha Iqbal, Omkar Pathak, Otto Valladares, Dolly Reyes-Dumeyer, Amanda B Kuzma, Erin Abner, Larry D Adams, Perrie M Adams, Alyssa Aguirre, Marilyn S Albert, Roger L Albin, Mariet Allen, Lisa Alvarez, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Sanford Auerbach, Gayle Ayres, Clinton T Baldwin, Robert C Barber, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, Bruno A Benitez, David Bennett, John Bertelson, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James Brewer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Christopher S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Scott Chasse, Marie-Francoise Chesselet, Nathaniel A Chin, Helena C Chui, Jaeyoon Chung, Suzanne Craft, Paul K Crane, David H Cribbs, Elizabeth A Crocco, Carlos Cruchaga, Michael L Cuccaro, Munro Cullum, Eveleen Darby, Barbara Davis, Philip L De Jager, Charles Decarli, John Detoledo, Malcolm Dick, Dennis W Dickson, Beth A Dombroski, Rachelle S Doody, Ranjan Duara, Nilüfer Ertekin-Taner, Denis A Evans, Kelley M Faber, Thomas J Fairchild, Kenneth B Fallon, David W Fardo, Martin R Farlow, Victoria Fernandez-Hernandez, Steven Ferris, Robert P Friedland, Tatiana M Foroud, Matthew P Frosch, Brian Fulton-Howard, Douglas R Galasko, Adriana Gamboa, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Rodney C P Go, Alison M Goate, Thomas J Grabowski, Neill R Graff-Radford, Robert C Green, John H Growdon, Hakon Hakonarson, James Hall, Ronald L Hamilton, Oscar Harari, John Hardy, Lindy E Harrell, Elizabeth Head, Victor W Henderson, Michelle Hernandez, Timothy Hohman, Lawrence S Honig, Ryan M Huebinger, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Linda S Hynan, Laura Ibanez, Gail P Jarvik, Suman Jayadev, Lee-Way Jin, Kim Johnson, Leigh Johnson, M Ilyas Kamboh, Anna M Karydas, Mindy J Katz, John S Kauwe, Jeffrey A Kaye, C Dirk Keene, Aisha Khaleeq, Masataka Kikuchi, Ronald Kim, Janice Knebl, Neil W Kowall, Joel H Kramer, Walter A Kukull, Frank M Laferla, James J Lah, Eric B Larson, Alan Lerner, James B Leverenz, Allan I Levey, Andrew P Lieberman, Richard B Lipton, Mark Logue, Oscar L Lopez, Kathryn L Lunetta, Constantine G Lyketsos, Douglas Mains, Flanagan E Margaret, Daniel C Marson, Eden Rr Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Paul Massman, Arjun Masurkar, Wayne C Mccormick, Susan M Mccurry, Andrew N Mcdavid, Stefan Mcdonough, Ann C Mckee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, Edwin S Monuki, John C Morris, Shubhabrata Mukherjee, Amanda J Myers, Trung Nguyen, Thomas Obisesan, Sid O'Bryant, John M Olichney, Marcia Ory, Raymond Palmer, Joseph E Parisi, Henry L Paulson, Valory Pavlik, David Paydarfar, Victoria Perez, Elaine Peskind, Ronald C Petersen, Helen Petrovitch, Aimee Pierce, Marsha Polk, Wayne W Poon, Huntington Potter, Liming Qu, Mary Quiceno, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Joan S Reisch, John M Ringman, Erik D Roberson, Monica Rodriguear, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Donald R Royall, Marwan Sabbagh, A Dessa Sadovnick, Mark A Sager, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Susan H Slifer, Scott Small, Amanda G Smith, Janet P Smith, Joshua A Sonnen, Salvatore Spina, Peter St George-Hyslop, Takiyah D Starks, Robert A Stern, Alan B Stevens, Stephen M Strittmatter, David Sultzer, Russell H Swerdlow, Rudolph E Tanzi, Jeffrey L Tilson, John Q Trojanowski, Juan C Troncoso, Magda Tsolaki, Debby W Tsuang, Vivianna M Van Deerlin, Linda J Van Eldik, Jeffery M Vance, Badri N Vardarajan, Robert Vassar, Harry V Vinters, Jean-Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Patrice L Whitehead, Ellen M Wijsman, Kirk C Wilhelmsen, Benjamin Williams, Jennifer Williamson, Henrik Wilms, Thomas S Wingo, Thomas Wisniewski, Randall L Woltjer, Martin Woon, Clinton B Wright, Chuang-Kuo Wu, Steven G Younkin, Chang-En Yu, Lei Yu, Xiongwei Zhu, Brian W Kunkle, William S Bush, Akinori Miyashita, Goldie S Byrd, Li-San Wang, Lindsay A Farrer, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard D Schellenberg, Gyungah R Jun, Christiane Reitz, Adam C Naj, Alzheimer’S Disease Genetics Consortium (Adgc)

Faculty, Staff and Students Publications

Background: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis.

Results: We identify 13 loci with cross-population associations including known loci at/near CR1, …