Digital Commons Network^™

Pretreatment Risk Model For Radiation-Induced Lymphopenia Is Associated With Adjuvant Durvalumab Efficacy In Patients With Unresectable Stage Iii Nsclc, Peter S N Van Rossum, Pim J J Damen, Francesco Cortiula, Brian P Hobbs, Lorenzo De Marchi, Radhe Mohan, Max Peters, Famke L Schneiders, Dirk De Ruysscher, Robin Wijsman, Joost J C Verhoeff, Ting Xu, Zhongxing Liao, Steven H Lin

Faculty, Staff and Student Publications

Introduction: Severe radiation-induced lymphopenia (RIL) during concurrent chemoradiotherapy (CCRT) for NSCLC has been associated with poorer outcomes and reduced immunotherapy efficacy. Because RIL often develops late during CCRT, identifying patients at risk before treatment may be clinically relevant. This study aimed to develop and validate a nomogram based on pretreatment predictors for severe RIL, and secondarily to explore associations between predicted RIL risk and adjuvant durvalumab-associated survival.

Methods: A retrospective development cohort of consecutive patients with NSCLC treated with CCRT (2010-2019) was established, along with an independent external validation cohort from other institutions. A multivariable logistic regression model was developed …

Frequency And Self-Reported Outcomes Of Transcranial Magnetic Stimulation For Obsessive Compulsive Disorder In The U.S. And Latin America, Hala Aziz, Guadalupe Vidal-Martinez, Ogechi C Onyeka, Jacey L Anderberg, Javier Vargas-Medrano, Diana Sotelo, Demi Kourtesi, Renee M Frederick, Josselyn S Muñoz, Dayan Berrones, Vanessa Zavala Cruz, Peter Thompson, Silvina Tonarelli, Andrew D Wiese, James J Crowley, Eric A Storch

Faculty, Staff and Students Publications

Introduction: Obsessive compulsive disorder (OCD) affects about 1-2% of the global population, with roughly 30% of patients not responding to first-line treatments. Transcranial Magnetic Stimulation (TMS) has some support for treatment-resistant OCD but global use is unclear.

Methods: This study describes the frequency with which TMS was reported to be received among a large cohort of individuals who self-identified as Latino-Hispanic in Latin America and the United States. Among 3,391 participants, 76 (2.2%) had completed TMS for OCD.

Results: Recipients who received TMS exhibited more severe current and lifetime OCD symptoms compared to non-recipients. On average, participants underwent 22.61 TMS …

Merritt-Putnam Symposium | Tumor-Associated Epilepsy And Epilepsy-Associated Tumors: Exploring The Bidirectional Crosstalk Between Tumors And Seizures, Tracy A Bedrosian, Michael Wong, Erin L Heinzen, Benjamin Deneen, Catherine A Christian-Hinman

Faculty, Staff and Students Publications

Links between cancerous and noncancerous brain tumors and epilepsy have long been recognized. However, recent clinical and preclinical studies emphasize that not only do tumors impinge on surrounding brain tissue in ways that promote hyperexcitability and epileptogenesis, but that neural activity also influences tumor progression. In this review, inspired by the Merritt-Putnam Symposium of the 2025 meeting of the American Epilepsy Society, we present a cross-disciplinary dialog between cancer and epilepsy research, including discussion of tumors and epilepsies that are more prominent in pediatric versus adult populations. First, we discuss the neuropathology, genetics, and surgical outcomes of epileptogenic brain tumors, …

Supporting Evidence-Based Responses To Emotional Needs In Emphysema (Serene): Protocol For A Randomized, Open-Label Mechanistic Trial Comparing Coping Skills Training And Disease-Specific Education For Depressive Symptoms Conducted In United States Health Systems, Joanna L. Hart, Daniel Carter, Chloe Hinton, James Grilli, Lily A. Brown, Nora Brier, Yingying Lu, Casey Whitman, Michael O. Harhay, Michael Sims, Carmen Alvarez, Lisa R. Miller-Matero, C. Virginia O'Hayer

Department of Psychiatry and Human Behavior Faculty Papers

BACKGROUND: Depressive symptoms and anxiety are highly prevalent among people with chronic obstructive pulmonary disease (COPD), strongly associated with poor outcomes, and rarely recognized or treated. Integrating families into interventions may amplify supportive care treatment effects and overcome common challenges, yet this strategy is understudied. The Supporting Evidence-based Responses to Emotional Needs in Emphysema (SERENE) trial's main objective is to identify the mechanisms through which a family-partnered Coping Skills Training (CST) reduces depressive symptoms among patients with COPD, testing five putative mechanisms: family relationship quality, patient and caregiver self-efficacy, patient loneliness, and caregiver psychological distress.

METHODS: SERENE will enroll 375 …

Outcomes Of Radiation Integrated With T-Cell-Engaging Bispecific Antibodies In Relapsed/Refractory Multiple Myeloma, Heta Patel, Harper Hubbeling, Kyle Yu, Maribel Carpenter, Michael Lariviere, John Plastaras, Adam Cohen, Shivani Kapur, Dan Vogl, Adam Waxman, Edward Stadtmauer, Alfred Garfall, Sandra Susanibar-Adaniya

Student Papers, Posters & Projects

No abstract provided.

Liposclerosing Myxofibrous Tumor Of The Foot: A Case Report, Mohammad Junayed Khan, Sufiyan Mannan Ahmed, Asad Mustafa, Sairah Asghar, Mohammad Tanjim Hossain

School of Podiatric Medicine - Student Research

Statement of Purpose: This case presents a rare sclerosing-type atypical lipomatous tumor with myxomatous features—the first and only known reported case of an ALT in the foot—along with its pathology, treatment, and management.

Case Study: Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) represents the most common liposarcoma subtype, with recurrence and dedifferentiation risk influenced by tumor location. Retroperitoneal tumors recur frequently, while those in the lower extremity rarely do. Liposarcoma of the foot is exceedingly rare.

A 61-year-old male presented with a slowly enlarging, mildly tender lump on the right plantar heel. Radiographs demonstrated a 3 cm oval soft-tissue thickening without calcification. …

Midfoot Reconstruction For Avascular Necrosis Of The Navicular Bone​, Jessica Sima, Srilalitha Lanka, Merlin Sajeev, Shannon Rush, Graham Hamilton

School of Podiatric Medicine - Student Research

Background: Avascular necrosis (AVN) of the tarsal navicular, particularly with collapse, presents a complex surgical challenge due to compromised vascularity and the need to restore medial column length. This retrospective case series evaluates three distinct surgical approaches to midfoot reconstruction in patients with navicular AVN.

Methods: Three patients with navicular AVN were treated using individualized grafting strategies. Etiologies included chronic protease inhibitor use for HIV, Müller-Weiss syndrome, and post-resection of a giant cell tumor. All procedures utilized a medial utility incision with debridement to viable bleeding bone. Two cases were reconstructed using a combination of proximal tibial autograft, patellar allograft, …

Eepd1 Evolved A Unique Dna Clamping Dimer Protecting Reversed Replication Forks, Runze Shen, Altaf H Sarker, Yue Chen, Min Liu, Sunetra Roy, Andrew S Arvai, Albino Bacolla, Zamal Ahmed, Panagiotis Katsonis, Michal Hammel, Isao Kuraoka, Miaw-Sheue Tsai, Corydon Irie, Lukas Webb, Olivier Lichtarge, Chi-Lin Tsai, Susan E Tsutakawa, Katharina Schlacher, John A Tainer

Faculty, Staff and Student Publications

Exonuclease/endonuclease/phosphatase (EEP)-fold hydrolases are canonically monomeric phosphodiesterases exemplified by APE1, DNase I, and TDP2 nucleases. While EEP family domain containing protein 1 (EEPD1) acts in DNA stress responses, its proposed nuclease activities are enigmatic. Here, we integrate hybrid structural methods, evolution, biochemistry, cancer genomics, plus molecular and cell biology to define EEPD1 structure, assembly, and function at stalled DNA replication forks. Results imply EEPD1 surprisingly requires both unique EEP domain dimer and distinctive tandem Helix-hairpin-Helix [(HhH)2] domains to clamp double-stranded (ds) DNA at reversed DNA replication forks for fork protection. Small-angle X-ray Scattering (SAXS), crystal, and cryo-EM structures unveil an …

The Path Forward For T Cell Engagers In Patients With Prostate Cancer, Sumit K. Subudhi, Bilal A. Siddiqui, Kevin K. Zarrabi, William K. Kelly, Charles G. Drake

Department of Medical Oncology Faculty Papers

T cell engagers (TCEs) recruit T cells to the tumor microenvironment (TME) to induce antitumor immune responses. TCEs have demonstrated promising clinical responses in patients with metastatic castration-resistant prostate cancer and have advanced into phase 3 clinical trials. Here we provide an overview of the mechanisms of action of TCEs, including both CD3-targeted and CD28-targeted agents, and review the clinical development of these agents for prostate cancer. We propose a path forward for TCEs in prostate cancer, in which innovative clinical trials will facilitate a biological understanding of mechanisms of efficacy and toxicity to inform: (1) development of predictive biomarkers …

Winner's Curse Free Robust Mendelian Randomization With Summary Data, Zhongming Xie, Wanheng Zhang, Jingshen Wang, Chong Wu

Faculty, Staff and Student Publications

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses using summary data may still produce biased causal effect estimates due to the winner’s curse and pleiotropy issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner’s curse and screens out invalid genetic instruments with pleiotropic effects. …

Innovative Approaches For Lung Cancer Screening And Interception, Jianjun Zhang, Matthew D Park, Tej Pandya, Elaine Shum, Jia Wu, Simon Heeke, Ramin Salehi-Rad, Thomas U Marron, Zhubo Wei, Hui Li, Torsten G Blum, John V Heymach, Steven M Dubinett, Pan-Chyr Yang, Charles Swanton, Miriam Merad

Faculty, Staff and Student Publications

Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results …

Supt16h-Associated Neurodevelopmental Disorder And Neurocristopathy: Genetic And Phenotypic Spectrum, Eunhye Lee, Seungmin Sim, Hee-Jung Choi, Eugene Y Liang, Carolyn Le, Roya Bina, Ryan Cohen, Elizabeth George, Soo Yeon Kim, Gifty Bhat, Erin Falsey, Richard Sidlow, Kristin Clinard, Shay Ben-Shachar, Eleina England, Beatriz Menendez, Isabella Herman, Shelly Nielsen, Jaya Punetha, Priya Bhola, J Austin Hamm, Megan A Keeney, Nike Sitzman, Sara Berger, Lakshmi Mehta, Alison J Conn, Lilian Downie, Myla Ashfaq, Hope Northrup, Ange-Line Bruel, Sylvie Odent, Justin O Szot, Noelia Nunez Martinez, Sunju Park, Julie Refkin, Jean-Marc Good, Fabienne Maurer, Cédric Le Caignec, David J Coman, Erin Anderson, Linda J Richards, Ryan J Dean, Caleb Yang, Chulwon Choi, Byung Joon Hwang, Jin Sook Lee, William B Dobyns, Murim Choi, Elliott H Sherr, Jong-Hee Chae, Yun Kee, Emanuela Argilli

Faculty, Staff and Student Publications

SUPT16H encodes a subunit of the FACT (FAcilitates Chromatin Transcription) complex, a histone chaperone essential for maintaining chromatin integrity during transcription, replication, and DNA repair. Pathogenic de novo SUPT16H missense variants have previously been linked to neurodevelopmental disorders in eight individuals. Here, we expand the genotypic and phenotypic spectrum by identifying 24 additional individuals harboring ultrarare heterozygous missense or truncating variants, who share overlapping clinical features including intellectual disability, autism spectrum disorder, hypotonia, and characteristic craniofacial dysmorphism. To elucidate the underlying mechanisms, we generated a supt16h knockout zebrafish model using CRISPR/Cas9. The supt16h loss-of-function (LOF) model recapitulated key patient phenotypes …

External Validation Of The Proliferation Saturation Index Model In Predicting Tumour Volume Regression In Patients With Non-Small Cell Lung Cancer Undergoing Radiation Therapy, Sarah Barrett, Mohammad Zahid, Conor K Mcgarry, Heiko Enderling, Gerard M Walls, Laure Marignol

Faculty, Staff and Student Publications

Background: The Proliferation Saturation Index (PSI) model is a patient-specific mathematical model designed to simulate and predict tumour volume regression (TVR) during radiation therapy (RT) using early treatment response dynamics. This study validates the PSI model in an independent external cohort of patients with non-small cell lung cancer (NSCLC) using previously derived model parameters.

Methods: In a cohort of 71 patients, treated with definitive RT alone (55Gy/20#) tumour volume measurements extracted from 6 Cone Beam CT (CBCT) scans acquired on days 1, 2 and 3 and weekly thereafter. Model predictions of TVR at final CBCT (CBCT6) were made using tumour …

Hp1Β Recruits Ring1a To Ubiquitinate Histone H2a For Brca1-Mediated Resection Of Double-Stand Breaks, Vijaya Charaka, Raj K Pandita, Chi-Lin Tsai, Xiaoyan Wang, Sharmista Chakraborty, Kenneth S Ramos, Sandhik Nandi, Fransisca Leonard, Vipin Singh, Partha S Sarkar, Clayton R Hunt, John A Tainer, Chandrima Das, Tej K Pandita

Faculty, Staff and Student Publications

Efficient DNA double-strand break (DSB) repair by homologous recombination (HR), as initiated by BRCA1 recruitment orchestrated by histone and non-histone proteins, is critical to genome stability, replication, transcription, and cancer avoidance. Here we reveal Heterochromatin Protein1 beta (HP1β) promotes BRCA1 enrichment at DNA DSB sites in gene-rich regions, and this is impaired by HP1β depletion. We find that HP1β is specifically enriched at DSBs within gene-rich regions via its Chromo Shadow Domain (CSD) that interacts with both Chromatin Assembly Factor 1 and the RING1A ubiquitinase component of Polycomb Repressor Complex 1. The resulting protein complex facilitates BRCA1 recruitment by promoting …

Nci9673 (Part B): Etctn Randomized Phase Ii Study Of Nivolumab With Or Without Ipilimumab In Refractory, Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Kristen K Ciombor, Lianchun Xiao, Joshua K Ochieng, Enrica Marmonti, Blase Polite, Benjamin A Weinberg, John C Krauss, John Hays, Sarbajit Mukherjee, Olivia Aranha, Syma Iqbal, Tony Shields, Al B Benson, Syed Kazmi, Christopher Lieu, Howard Hochster, Jennifer Whisenant, Cara Haymaker, Cathy Eng

Faculty, Staff and Student Publications

Purpose: In the previously completed NCI9673 (part A) single-arm study, the antiprogrammed death (PD)-ligand-1 antibody nivolumab demonstrated efficacy for patients with metastatic anal cancer. In NCI9673 (Part B), we evaluated the anticytotoxic T-cell lymphocyte antigen-4 (CTLA-4) antibody ipilimumab in combination with nivolumab for patients with incurable anal cancer.

Methods: In this phase II NCI ETCTN trial, 100 patients with refractory, incurable anal cancer were randomly assigned to receive nivolumab (480 mg IV once every 4 weeks) alone or with ipilimumab (1 mg/kg IV once every 8 weeks). The primary end point was progression-free survival (PFS). Secondary endpoints included radiographic response, …

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …

Adipocyte-Specific Deletion Of Sine Oculis Homeobox Homolog 1 Inhibits Lipolysis And Reduces Skin Fibrosis, Nancy Wareing, Tingting W Mills, Scott Collum, Minghua Wu, Lucy Revercomb, René Girard, Hui Liu, Alexes Daquinag, Mikhail Kolonin, Marka Lyons, Brian Skaug, Weizhen Bi, Meer A Ali, Haniyeh Koochak, Anthony R Flores, Yuntao Yang, W Jim Zheng, William R Swindell, Shervin Assassi, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Dermal fibrosis is a cardinal feature of systemic sclerosis (SSc) for which there are limited Systemic sclerosis (SSc) is characterized by dermal fibrosis accompanied by loss of dermal white adipose tissue (DWAT), yet the mechanisms linking adipocyte depletion to fibroblast activation remain unclear. Here we identify the transcription factor SIX1 as a central regulator coupling adipogenic repression with profibrotic signaling. SIX1 expression was increased in skin biopsies from two independent SSc cohorts and localized to fibroblast and perivascular stromal cells. In mice, ubiquitous or adipocyte-specific deletion of Six1 preserved DWAT, reduced collagen accumulation, and selectively decreased pro-fibrotic mediators. In cultured …

Cml-Like Biology Is A Unifying Feature Of Myeloid/Lymphoid Neoplasms With Tyrosine Kinase Fusions In Lymphoid Blast Phase Comment On: Multilineage Involvement In Abl-Class Fusion-Positive Pediatric B-Cell Acute Lymphoblastic Leukemia: Cml-Like Biology, Wei J Wang, Shimin Hu

Faculty, Staff and Student Publications

No abstract provided.

Management Of Acute Myeloid Leukemia: A Review, Chetan Jeurkar, Lana King, David Baek, Lindsay Wilde, Gina Keiffer, Margaret Kasner

Kimmel Cancer Center Faculty Papers

Background/Objectives: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with historically poor outcomes, particularly among older adults and patients harboring high-risk molecular features. Advances in genomic profiling have enabled the development of targeted therapies, reshaping treatment algorithms beyond conventional cytarabine-anthracycline induction and hypomethylating agent-based regimens. This review summarizes current evidence and emerging therapeutic strategies across four evolving areas: menin inhibition, FLT3 inhibition, IDH inhibition and treatment approaches for TP53-mutated AML. Methods: We reviewed published clinical trials, preclinical studies, and ongoing clinical trials evaluating targeted therapies in AML. Emphasis was placed on agents with regulatory approval or substantial clinical development, …

Comparative Safety, Efficacy, And Predictors Of Complete Occlusion Of Flow Diverter Devices In The Treatment Of Unruptured Distal Anterior Cerebral Artery Aneurysms, Hamza Adel Salim, Luca Scarcia, Frédéric Clarençon, Orabi Hajjeh, Motaz Daraghma, Davide Simonato, Yan-Lin Li, Eimad Shotar, Kevin Premat, Pascal Jabbour, Stavropoula Tjoumakaris, Michael R. Gooch, Marios Psychogios, Nikos Ntoulias, Peter Sporns, Ajit S. Puri, Jasmeet Singh, Anna Luisa Kuhn, Ameer E. Hassan, Oktay Algin, Markus A. Möhlenbruch, Sophia Hohenstatt, Riccardo Russo, Mauro Bergui, Oded Goren, Matthew J. Kole, Nourou Dine Adeniran Bankole, Richard Bibi, Gregoire Boulouis, Takeshi Morimoto, Fumihiro Sakakibara, Raoul Pop, Ciprian Juravle, Joanna W. K. Ho, Ãngel Ferrario, Virginia Pujol Lereis, Jared Cooper, Chirag D. Gandhi, Giancarlo Salsano, Lucio Castellan, Arturo Consoli, Alessandro Sgreccia, Eytan Raz, Charlotte Chung, Julien Burel, Chrysanthi Papagiannaki, Umair Rasheed, Khawaja Muhammad Baqir Hassan, Hong Tao, Zhe Ji, Riitta Rautio, Matias Sinisalo, Maria Ruggiero, Elvis Lafe, Valerio Da Ros, Luigi Bellini, Joseph Domenico Gabrieli, Francesco Causin, Michael R. Levitt, Kate Carroll, Zachary Abecassis, Antonio Armando Caragliano, Sergio Lucio Vinci, Guillaume Bellanger, Christophe Cognard, Gaultier Marnat, Lisa Saleille, Nicola Limbucci, Francesco Capasso, Mariangela Piano, Claudia Rollo, Alexis Guedon, Francesco Arpaia, Andrea Romi, Fortunato Di Caterino, Alessandra Biondi, Erwah Kalsoum, Mykola Vyval, Adrien Guenego, Than Nguyen, Mohamad Abdalkader, Thibault Agripnidis, Aman B. Patel, Vitor Mendes Pereira, Maurizio Fuschi, Alessandro Pedicelli, Vivek Yedavalli, Max Wintermark, Andrea M. Alexandre, Adam A. Dmytriw, Creta Investigators

Department of Neurosurgery Faculty Papers

BACKGROUND: Flow diverters (FDs) are increasingly used for cerebral aneurysms, including distal anterior cerebral artery (DACA) aneurysms, but comparative data between devices in this challenging location are limited.

OBJECTIVE: To compare the safety and efficacy of Pipeline, Silk Vista Baby (SVB), and FRED Jr. FDs for unruptured DACA aneurysms and identify predictors of complete occlusion.

METHODS: We retrospectively analyzed 166 patients treated with FDs at 39 centers in 14 countries (2018–2022) from the CRETA registry. Outcomes included aneurysm occlusion (O’Kelly–Marotta [OKM] scale), complications, retreatment, modified Rankin Scale (mRS) scores, and independent predictors of complete occlusion using multivariable Cox regression.

RESULTS: …

Anti-Apoptotic Bcl-2 Binds To All Three Ip3r Isoforms, Thereby Limiting The Ca2+-Flux Properties Of Ip3r Homo-Tetramers, Ian De Ridder, Claire Cauwelier, Larry E Wagner Ii, Jens Loncke, Vikas Arige, Irina I Serysheva, David I Yule, Geert Bultynck

Faculty, Staff and Student Publications

Anti-apoptotic B-cell lymphoma 2 (BCL-2) controls inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca²+ signalling. As cells typically express all three IP3R isoforms in variable abundances that assemble in hetero-tetrameric channels, the specific effects of BCL-2 on each isoform remain unclear. Here, we employed a reductionist approach using HEK293 cells triple-IP3R knockout reconstituted with a single IP3R isoform to elucidate the impact of BCL-2 on Ca2+ signalling by homo-tetrameric IP3R channels. Co-immunoprecipitation experiments demonstrated that BCL-2 interacts with each IP3R isoform. Live-cell Ca²+ imaging revealed that BCL-2 overexpression suppresses Ca²+ signals evoked by any of the three IP3R isoforms. Moreover, BCL-2 overexpression impaired …

Relationships Between Clinical Symptom Scales And Eeg Biomarkers In Oud Patients, Jess Delange, Benjamin M. Latey, John Glinski, Braden Ashcraft, Jasmine Pannu, Cassidy Beatty, Lauren Knudson, Benjamin Chafetz, Bryan Fugal, Patrick Tanner Brain, N P. Griffin, Christopher Gowans, Amanda Brandaris, Amanda Page, Blake D. Harris, Sophia Delgado, Lorissa Thorpe, Kyle Bills, Andrew Payne

Annual Research Symposium

This poster examines the relationship between clinical symptom scales and electroencephalographic (EEG) biomarkers in patients with Opioid Use Disorder (OUD). Participants from inpatient substance use treatment facilities completed validated mental health and withdrawal assessments, including the COWS, PHQ-9, HAM-A, and ASRS followed by cognitive testing while undergoing 19-lead EEG recording.

Preliminary findings indicate that synthetic opioid use is associated with prolonged P300 response latency across brain regions, suggesting measurable neurophysiologic differences tied to substance type and addiction severity. The study explores how EEG metrics may complement subjective symptom reporting to provide more objective markers of addiction status, co-morbid psychiatric burden, …

Imaging In Acute Neurovascular Emergencies: Optimizing Outcomes In Large Vessel Occlusion Stroke, Chandu Goli, Rohit Patel, Elliott Beard, Anna Liles, Saeed Saleh, Aleeza Namit, Alissa Ongaco, Kevin Steed Ph.D.

Annual Research Symposium

Purpose:

Large vessel occlusion (LVO) stroke is associated with high rates of morbidity and mortality, and patient outcomes are strongly influenced by rapid identification and timely reperfusion. Advances in acute neurovascular imaging have transformed stroke care by enabling precise patient selection, extending treatment windows, and accelerating clinical workflows. The purpose of this project is to evaluate how modern neurovascular imaging strategies influence treatment selection, workflow efficiency, and clinical outcomes in patients with acute LVO stroke.

Methods:

A narrative review of peer-reviewed literature published within the past decade was conducted. The review focused on CT-based imaging (non-contrast CT, CT angiography, CT …

S6k1 Modulates Stat3 Activation To Promote Resistance To Radiotherapy In Lung Cancer, Ali Calderon-Aparicio, Noelle Francois, Tyler Grenda, Shan Xu, Olugbenga Okusanya, Jun He, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Radiotherapy is a mainstay in the management of locally advanced lung cancer; however, intrinsic and acquired radioresistance contribute to poor prognosis. S6K1, a serine/threonine kinase, regulates cell growth, protein synthesis, and survival, and is increased in tumors, which is linked to enhanced survival under therapeutic stress, including radiation. The mechanisms, however, are not fully understood. This study investigates the role of S6K1 in lung cancer radioresistance and the mechanisms involved. Intrinsic radioresistance in lung cancer cells was associated with increased S6K1 activation. Pharmacologic inhibition or genetic deletion of S6K1 enhanced radiosensitivity both in vitro and in vivo, highlighting the therapeutic …

Tumor Microenvironment Transcriptional Activity Enables Robust Stratification Of Chemotherapy Response In Triple-Negative Breast Cancer, Yaoyi Dai, Xiaoxi Pan, Shuai Guo, Shuangxi Ji, Shaolong Cao, Matthew D Montierth, Yujie Jiang, Jeffrey T Chang, Leming Shi, Shabnam Shalapour, Gloria V Echeverria, Lucy Yates, Johan Staaf, Bora Lim, Yinyin Yuan, Wenyi Wang

Faculty, Staff and Student Publications

Triple-negative breast cancer (TNBC) exhibits heterogeneous treatment responses, yet molecular subtypes based on predefined biological pathways show limited prognostic value. We introduce tumor-specific total mRNA expression (TmS), a pathway-agnostic deconvolution metric derived from matched RNA/DNA sequencing, as a robust stratification tool. Analyzing 575 TNBC patients across Western and East Asian populations, TmS outperforms established subtypes in predicting chemotherapy outcomes, stratifying patients into high TmS with favorable prognosis and low TmS with poor prognosis. Stromal enrichment with immune exclusion emerges as a universal feature of chemotherapy-resistant low-TmS tumors across all cohorts. Population-specific features distinguish Asian cohorts: high-TmS tumors exhibit cell cycle-driven …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

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 …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Metastatic Castrate-Resistant Prostate Cancer To The Penis Resulting In Malignant Priapism And Urethral Obstruction, Courtney Stewart, Joon Yau Leong, William Kevin Kelly, Mihir Shah

Department of Urology Faculty Papers

A 76-year-old male with metastatic castrate-resistant prostate cancer was found to have metastatic disease to the urethra and penis on PSMA PET scan. This resulted in constant pain due to obstruction of blood flow through the corpora cavernosum resulting in priapism and urethral obstruction. The patient underwent a radical penectomy, partial urethrectomy and perineal urethrostomy creation. Final pathology confirmed metastatic prostatic adenocarcinoma. Although rare, prostate cancer can metastasize to the corpora spongiosum or cavernosa. Treatment options are limited, and surgical excision with urinary diversion is likely to provide the most durable outcomes for one's quality of life.

Relationship Between Navigation Success, Diagnostic Accuracy, And Ventilation Strategy: Retrospective Chart Review Of 224 Consecutive Navigational Bronchoscopic Procedures Performed Under General Anesthesia, Basavana Goudra, Prarthna Chandar, Divakara Gouda, Harrison Yang, Ganan Muhunthan, Suvan Sundaresh, Michael Stuart Green

Department of Medicine Faculty Papers

Background: Navigational bronchoscopy (NB) enables precise sampling of peripheral and central pulmonary nodules using shape-sensing or electromagnetic guidance. A major challenge is anesthesia-induced atelectasis, which alters lung anatomy, reduces registration accuracy, and is known to lower diagnostic accuracy. To counteract this, ventilatory protocols such as the Ventilatory Strategy to Prevent Atelectasis (VESPA) and the Lung Navigation Ventilation Protocol (LNVP) have been recommended. Their adoption and clinical impact, however, remain uncertain. Methods: We conducted a retrospective review of 224 consecutive NB procedures performed under general anesthesia at a single academic medical center (January 2020–August 2024). Demographic, anesthetic, and ventilatory data were …