Medicine and Health Sciences Commons^™

Phenome-Wide Analysis Of Copy Number Variants In 470,727 Uk Biobank Genomes, Xueqing Zoe Zou, Fengyuan Hu, Haiyi Lou, Oliver S Burren, Xiaoyin Li, Karyn Megy, Eleanor Wheeler, Qiang Wu, Santosh S Atanur, Marcin Karpinski, Douglas Loesch, Zammy Fairhurst-Hunter, Sri V V Deevi, Erin Oerton, Sean Wen, Xiao Jiang, Cecilia Salvoro, Jonathan Mitchell, Abhishek Nag, Ben Hollis, Amanda O'Neill, Jen Harrow, Stewart Macarthur, Sebastian Wasilewski, Sean O'Dell, Lifeng Tian, Katherine R Smith, Guillermo Del Angel, Margarete Fabre, Ryan S Dhindsa, Quanli Wang, Slavé Petrovski, Keren Carss

Duncan NRI Faculty and Staff Publications

Copy number variants (CNVs) are key drivers of human diversity and disease risk1. Here we evaluate the role of CNVs across a broad range of human phenotypes and diseases by analysing CNVs from 470,727 UK Biobank whole-genome sequences and conducting a variant- and gene-level phenome-wide association study (PheWAS) with 2,941 plasma protein abundance measurements, 13,336 binary clinical phenotypes and 1,911 quantitative traits. Proteomic analyses validated functional associations of CNVs with nearby genes (cis-protein quantitative trait loci; cis-pQTLs)—with deletions and duplications typically associated with reduced and increased protein levels, respectively—and uncovered previously unknown protein–protein interactions …

Long-Term Effect Of Ammonia- And Water-Based Silver Fluoride On Dentin Collagen Matrix, Merve Uctasli, Roda Seseogullari-Dirihan, Thiago Henrique Scarabello Stape, Mustafa Murat Mutluay, Arzu Tezvergil-Mutluay

School of Dentistry Faculty Research and Publications

Objective

To evaluate the long-term effect of ammonia- and water-based silver fluoride treatments on the degradation of the dentin collagen matrix.

Methods

Dentin beams (0.3x3x7mm) were demineralized (10 % H₃PO₄), rinsed and randomly distributed into six groups. Groups (n = 10 beams/group) were treated with (1) ammonia-based silver fluoride = SDF; (2) SDF + potassium iodide = KI (3) water-based silver fluoride = SF (4) SF + KI (5) KI (6) untreated demineralized dentin beams served as control. Following treatments, dry mass, modulus of elasticity and enzymatic activity were assessed. Dentin beams were incubated in calcium- …

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

Knowledgable Births: Advancing Informed Consent In Maternal Healthcare, Ella A. Forrester

Senior Theses

Background:

Informed consent is both a legal requirement and an ethical cornerstone of healthcare, ensuring that patients understand and voluntarily agree to medical treatments. However, evidence suggests that the informed consent process is often inadequately implemented in maternal healthcare settings, particularly during childbirth. While giving birth, women retain full decision-making capacity but are not consistently provided with sufficient information or support to exercise this right. Contributing factors include ineffective patient–provider communication, limited health literacy, and insufficient access to culturally responsive educational resources.

Methods:

This study aimed to address gaps in accessible prenatal education by developing an online resource platform, Know …

A Comparative Analysis Of Group Care: Trust, Professional Identity, And Health System Structure In The United Kingdom And The Netherlands, Samantha J. Kohlmann

Senior Theses

Group prenatal care (Group Care) has been associated with improved maternal experiences and select clinical outcomes, yet less is understood about how it functions within high-resource health systems and what mechanisms underlie its impact. This study examines how Group Care is implemented in the United Kingdom and the Netherlands, with particular attention to professional roles, relational dynamics, and health system context.

I employed a qualitative, comparative design and conducted four semi-structured interviews with midwife researchers involved in Group Care implementation in both countries. Data were analyzed thematically, with attention to cross-context similarities and differences.

Findings indicate that Group Care operates …

Effect Of Ginseng On Obesity And Neurogenesis, Hayden L. Withers, Claudia A. Grillo, Lawrence P. Reagan, Natalia Maciejewska, Sai V. Nallu, Jennifer L. Woodruff

Senior Theses

Obesity and major depressive disorder are two conditions with high comorbidity as well as overlapping pathophysiological mechanisms, including neuroinflammation, metabolic/endocrine dysfunction, and impaired hippocampal neurogenesis. Panax ginseng, a medicinal herb, is known to demonstrate anti-inflammatory and metabolic regulatory properties. Ginseng has demonstrated its effective antidepressant-like effects within preclinical studies, but its potential to restore neurogenesis in the context of obesity-induced depression is not clear. Within this study, male Sprague-Dawley rats were tested in either a high fat diet (HFD) or control diet (Cont) for 12 weeks and then was treated subsequently with daily intraperitoneal injections of either ginseng or saline …

Main Concept Analysis As A Predictor Of Aphasia Severity: Semantic, Phonological, And Executive Influences On Main Concept Performance, Chathurvedi Ganguru

Senior Theses

Main Concept Analysis is a discourse-based measure that captures the essential information conveyed during narrative speech and may serve as a functional indicator of communication ability in aphasia. This study will examine whether Main Concept composite scores derived from the Cinderella narrative task are associated with aphasia severity and identify the linguistic and cognitive factors that influence Main Concept performance. Participants will be drawn from the baseline cohort of the POLAR study and will include approximately 100 individuals with chronic post-stroke aphasia. Baseline measures include Western Aphasia Battery Aphasia Quotient, Pyramids and Palm Trees Test, Philadelphia Repetition Test, and Wechsler …

Burden Of Cardiovascular Disease In Pakistan – Insight From Global Burden Of Disease Study 2019, Ali Bin Jabbar, Taha Mansoor, Sana Sheikh, Tazeen Jafar, Sawera Hanif, Christian Razo, Mahboob Alam, Jamal Rana, Khurram Nasir, Salim Virani

Population Health, East Africa

Background Pakistan, currently the fifth-largest country by population globally, has experienced a population increase of over 100% since 1990. It is facing an escalating challenge from cardiovascular diseases (CVD). The Global Burden of Disease (GBD) 2019 study provides an in-depth evaluation of Pakistan's health situation since 1990, offering essential insights into the nation's overall health conditions.

Methods The data were obtained from the Global Burden of Disease Study 2019, which provides records for global, regional, and national burden of diseases. Specifically, data regarding CVD and its subtypes, morbidity, and mortality in Pakistan and globally from 1990 to 2019 were used …

Single-Center Experience Using Endologix Anatomically Fixated Endograft Device For Treatment Of Aortoiliac Occlusive Disease, Isabella Muti, Gaurang Joshi, Dawn M. Salvatore, Michael J. Nooromid, Paul J. Dimuzio, Babak Abai

Department of Surgery Faculty Papers

OBJECTIVE: The covered endovascular reconstruction of the aortic bifurcation (CERAB) technique was developed in recent years as a novel surgical intervention for aortoiliac occlusive disease (AIOD). One tool frequently used in such procedures is the anatomically fixated endograft (AFX), manufactured by Endologix. The present study aimed to review the outcomes of patients with AIOD after CERAB procedure using the Endologix AFX device.

METHODS: This is an institutional review board-approved retrospective study investigating the experience of a single center in using Endologix's AFX device as CERAB for AIOD from September 2018 to June 2024. Data were obtained from the medical records …

Initial Site Of Metastasis Influences Prognosis In Pancreatic Ductal Adenocarcinoma, Eleanor Mancheski, David Baek, Wilbur Bowne, Harish Lavu, Charles Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

INTRODUCTION: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a highly aggressive malignancy. Prior studies suggest that the initial site of metastasis may impact prognosis. This study investigates whether overall survival in mPDAC patients differs between patients first presenting with lung metastases versus those presenting with liver metastases.

METHODS: This retrospective analysis utilized the multi-institutional TriNetX database, identifying patients with histologically diagnosed PDAC who initially presented with either liver or lung metastases. Demographic, histologic, and outcome data were collected and analyzed. Patients were matched 1:1 using a nearest neighbor propensity score (PS) algorithm, and Kaplan-Meier survival analyses were performed. Cox regression was …

Mental Health Literacy Among Perinatal Healthcare Professionals In The United Arab Emirates: A Multiphase Convergent Mixedmethods Study, Rouwida Khalil Elkhalil

Dissertations

Perinatal mental disorders (PNMDs) pose a significant public health concern due to their impact on maternal well-being, infant development, and family functioning. Effective identification and management of PNMDs depend largely on the mental health literacy (MHL) of healthcare professionals, particularly those working in perinatal settings. However, MHL among perinatal healthcare professionals in the United Arab Emirates (UAE) remains underexplored. This dissertation aimed to examine and conceptualize MHL among perinatal healthcare professionals in the UAE, explore factors influencing its application in clinical practice, and inform evidence-based improvements in perinatal mental health care. A multiphase convergent mixed-methods design was employed across four …

Brain Candy: Wayne State University School Of Medicine Journal Of Arts And Culture, 13th Edition, Wayne State University School Of Medicine Gold Humanism Honor Society

Gold Humanism Honor Society

Brain Candy incorporates paintings, written pieces, and poetry from all the medical classes at Wayne State University School of Medicine to shed light on the creative process in medicine, the city of Detroit, and the experiences of health care providers. This year, the journal is organized into four sections, each of which denotes a particular time period within medical school. The first edition of Brain Candy was published online and in print in 2009, produced by a generous grant by the Gold Humanism Honor Society (GHHS). The edition featured poetry, nonfiction, short fiction, and different types of artwork. With generous …

Concerns Regarding The Efficacy Of Utilizing The Vibrational Response Of Aminocyanine Molecules To Near Infrared Light For Cancer Cell Destruction, Parsa Faghani-Eskandarkolaei, James Welsh, Seyed Ali Reza Mortazavi, Parmis Taghizadeh, Mobina Baramaki, Fatemeh Shams, Mohammed Nasir Abubakari, Seyed Mohammad Javad Mortazavi, Lembit Sihver

Informatics and Engineering Systems Faculty Publications

Recent advancements in cancer treatment have introduced the use of aminocyanine molecules, activated by near-infrared (NIR) light, to induce vibrational responses that can selectively destroy cancer cells. This commentary critically examines a study that reports a 99% efficacy of this method against human melanoma cells in vitro, and significant tumor reduction in murine models. While the findings are promising, our analysis highlights crucial oversights in the study’s implications for clinical applications. Specifically, the persistence of even a small fraction of cancer cells post-treatment poses significant risks for tumor regrowth and acquired resistance. Additionally, the study’s approach neglects the heterogeneity of …

Advancing The Understanding Of Palliative Care In Singapore: Knowledge, Attitudes, Receptiveness, And The Moderating Role Of Media Information-Seeking Preferences, Su Lin Yeo, Angel Lee, Raymond Han Lip Ng, May O. Lwin, Yumin Lin

Research Collection Lee Kong Chian School Of Business

Introduction: Despite the growing demand for palliative care, this specialized medical care remains severely underutilized, with almost 50% of countries worldwide lacking access. Given that misperceptions and stigma continue to hinder progress in healthcare policy, this study aims to examine the relationships between palliative care knowledge, attitudes, and receptiveness to better understand how public health communication can enhance awareness and understanding of the topic in Singapore. Applying the adapted knowledge-attitude-practice (KAP) model, it further extends theory by examining the moderating role of media information-seeking between knowledge and receptiveness.Methods: Mixed-mode surveys involving 1,226 participants (926 online and 300 in-person respondents), representing …

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Bridging Gaps: Enhancing Sleep And Health Disparities In Latino Families With Young Adults With Autism Using A Culturally Adapted Intervention, Antonio F Pagán, Alejandro L Pagán, Linda Hernandez, Matthew R Cribbet, Katherine A Loveland, Ron Acierno

Faculty, Staff and Student Publications

The present study examined the effects of a culturally adapted intervention, ¡Iniciando! la Adultez, on sleep and health-related quality of life (HRQoL) in Latino young adults with autism spectrum disorder (ASD) and their Spanish-speaking parents. The intervention targeted the transition to adulthood, a period associated with increased challenges in sleep and HRQoL, particularly for underserved Latino populations. Participants included 26 young adults and 38 parents who completed assessments at baseline and post-treatment. The results indicated significant improvements in several HRQoL domains for both groups, with young adults reporting enhanced emotional well-being, social functioning, and general health. Parents experienced notable improvements …

Preoperative First-Line Amlodipine In Phaeochromocytoma/Paraganglioma: Perioperative Haemodynamic Instability And Its Predictors, Chandramouli L, Saba Samad Memon, Anurag Ranjan Lila, Manjiri Karlekar, Aditya Phadte, Vijaya Sarathi, Rohit Barnabas, Sailaja Pramod Bijani, Sameer Rege, Yogesh Prabhakar Takalkar, Amala Kudalkar, Aarti Kulkarni, Nalini Shah, Tushar R Bandgar

Faculty, Staff and Student Publications

Objectives: Preoperative alpha blockade is recommended for phaeochromocytomas and paragangliomas (PPGLs), whereas evidence for calcium channel blockers remains limited. This study evaluated perioperative haemodynamic outcomes with first-line amlodipine for preoperative blockade and identified predictors of intraoperative haemodynamic instability (iHDI).

Methods/design: In this monocentric retrospective study, 35 operated PPGL patients who received preoperative first-line amlodipine (July 2021-March 2024) were analysed. Continuous intraoperative arterial pressure recordings were analysed for episodes and duration of hypertension, hypotension, and iHDI. Biochemical phenotype and tumour characteristics were assessed as predictors.

Results: The cohort (median age: 32 years; 60% female) included 32 phaeochromocytomas and 3 sympathetic paragangliomas. …

Probability Of Fentanyl Adulteration In Cocaine Selectively Decreases Cocaine Demand, Cecilia Nunez, Jin H Yoon, James Mackillop, Margaret C Wardle

Faculty, Staff and Student Publications

Fentanyl-related, cocaine-overdose deaths have drastically increased, yet research on how people who use cocaine perceive fentanyl adulteration is limited. This study developed the novel Adulterated Cocaine Purchasing Task (ACocPT), a modification of the original Cocaine Purchasing Task, to quantify how people respond to fentanyl adulteration in cocaine. In the ACocPT, participants indicated how much cocaine they would purchase when cocaine had no (0%) vs. some (10%) probability of fentanyl adulteration. Study aims were: 1) determine how possible fentanyl adulteration affects cocaine demand, and 2) determine which individual characteristics predict continued demand for cocaine despite fentanyl adulteration. This Amazon Mechanical Turk …

Factors Associated With Venous Complications In Lower Extremity Free Flap Reconstruction: A Multivariate Analysis, Bora Kahramangil, Ellen Wang, Imran Rizvi, Jessica R Nye, Kylie Swiekatowski, Alexandra Dunker, Kate Liao, Michael H Haydon, Jeffrey G Trost, Mohin A Bhadkamkar

Faculty, Staff and Student Publications

Background: Due to their dependent location, lower extremity (LE) free flaps (FFs) are at increased risk for venous complications. This study analyzes risk factors of venous complications in LE FFs.

Methods: A single-center retrospective review was conducted of adult patients undergoing LE FF reconstruction from 2016 to 2025. Variables included demographics, wound and operative characteristics, and the number of venous anastomoses. The primary outcome was venous complications, defined as a composite variable encompassing venous congestion, flap loss due to venous causes, and flap hematoma.

Results: The cohort consisted of 370 patients undergoing LE FF reconstructions. Single venous anastomosis was used …

A Treat-To-Target Approach For Obesity Management: A Post Hoc Analysis Of The Surmount-5 Trial., Carel W Le Roux, Luca Busetto, Louis Aronne, Deborah Bade Horn, Georgios K Dimitriadis, Beverly Falcon, Luis-Emilio Garcia-Perez, Elisa Gomez Valderas, Theresa Hunter Gibble, Cagri Senyucel, Julia P Dunn

Faculty, Staff and Student Publications

Introduction: With new advancements in obesity medicine, clarity on goals and expectations for successful disease management is limited. This post hoc analysis assessed application of proposed treat-to-target (TtT) thresholds for obesity to the outcome measures of SURMOUNT-5, which randomised participants with obesity to tirzepatide or semaglutide.

Methods: The proportion of participants in each treatment group reaching proposed TtT thresholds for waist to height ratio (WHtR) < 0.53, body mass index (BMI) < 27 kg/m2, or a combination was evaluated. The associations between the thresholds and achieving low disease activity to remission (meeting goals for at least four of five defined cardiometabolic risk parameters) and normalisation or improvement in SF-36v2 physical component score (PCS) from baseline to week 72 were explored.

Results: About 23.1%-33.9% of participants treated with tirzepatide and 14.2%-20.7% treated with semaglutide reached the TtT thresholds, with greater weight reduction than the overall population. About 77% of participants who reached WHtR < 0.53 achieved low disease activity to remission, with an odds ratio of 2.31 (p < 0.001) compared to those who did not reach this target. The BMI threshold was not statistically associated with the assessed outcomes for SF-36v2 PCS.

Conclusion: In this …

Correction: Prospective Trial Of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage Via Lumbar Catheter Extension (Pillar-Xt), Spiros L Blackburn, Marc A Babi, Andrew W Grande, Omar A Choudhri, Erik F Hauck, Christopher P Kellner, Michael C Giordano, Shivanand P Lad, Aaron R Mccabe

Faculty, Staff and Student Publications

This corrects the article "Prospective Trial of Cerebrospinal Fluid Filtration After Aneurysmal Subarachnoid Hemorrhage via Lumbar Catheter Extension (PILLAR-XT)" in volume 43 on page 934.

Distinct Effects Of Complement C4a And C4b Copy Numbers In Systemic Sclerosis Serological And Clinical Subtypes, Javier Martínez-López, Carlos Rangel-Peláez, Inmaculada Rodriguez-Martin, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José L Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Gianluca Moroncini, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcon-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera, Martin Kerick

Faculty, Staff and Student Publications

Objective: Complement component 4 (C4), encoded by C4A and C4B within the major histocompatibility complex (MHC) on chromosome 6, regulates the immune response and clears immune complexes. The variable copy number (CN) of C4 genes and retroviral human endogenous retrovirus K (HERV-K) element influence its function. Given the relationship of C4 CN with systemic sclerosis (SSc) risk, we assessed associations with SSc clinical and serologic subtypes.

Methods: We compared imputed C4 CNs across SSc subgroups (4,049 anticentromere positive [ACA+]; 2,200 anti-topoisomerase I [ATA+]; 577 anti-RNA polymerase [ARA+]; 1,078 triple-negative [TN] patients; 6,295 limited cutaneous SSc [lcSSc]; and 2,946 diffuse cutaneous …

Vascular Disease Patient Information Page: Hereditary Hemorrhagic Telangiectasia (Hht), Rohan R Kasthuri, Harish Eswaran, Karen Smith, Raj S Kasthuri

Faculty, Staff and Student Publications

No abstract provided.

Reply To Ozkok Et Al., Vikas Kannojiya, Akshita Sahni, Emily Eickhoff, Neha Zacharia, Nicole St Clair, Noah Schulz, Peter E Hammer, Pedro J Del Nido, Rahul H Rathod, David M Hoganson, Vijay Govindarajan

Faculty, Staff and Student Publications

No abstract provided.

Exploring Early Antifungal Activity Of Rezafungin As A Stepping-Stone For Shorter Treatment Duration For Candidemia: Pooled Analysis Of 2 Randomized Trials, Luis Ostrosky-Zeichner, Jalal A Aram, Mark Redell, George R Thompson, Oliver A Cornely, James A Mckinnell, Andrej Spec, Peter G Pappas

Faculty, Staff and Student Publications

Background: Guidelines recommend ≥2 weeks of antifungal therapy after candidemia clearance and for invasive candidiasis (IC). This post-hoc analysis evaluates Day 7 pooled data from the phase 2 STRIVE and phase 3 ReSTORE trials to explore early antifungal activity.

Methods: Adults with candidemia and/or IC received weekly rezafungin 400/200 mg or daily caspofungin 70/50 mg for ≤4 weeks. Efficacy was evaluated in the modified intent-to-treat population via all-cause mortality (ACM; primary endpoint; 20% noninferiority margin), mycological eradication, and time to negative blood culture (TTNBC) at days 7, 14, and 30 (TTNBC assessed only in patients with candidemia). Day 7 safety …

Intestinal Fungi Shape The Biology Of The Mammalian Gut, Elena Lindemann-Pérez, J Christian Pérez

Faculty, Staff and Student Publications

No abstract provided.

Identifying Sorafenib Benefit Among Patients With Hepatocellular Carcinoma: A Transcriptomic And Genomic Approach, Sun Young Yim, Hayeon Kim, Tae Hyung Kim, Sang-Hee Kang, Youngwoo Lee, Eunho Choi, Yang Jae Yoo, Seong Hee Kang, Young-Sun Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kyung Suk Yang, Yitao Tang, Bowha Sohn, Yun Seong Jeong, Hyewon Park, Han Liang, Ju-Seog Lee, Ji Hoon Kim

Faculty, Staff and Student Publications

Background & aims: Sorafenib has been a cornerstone of hepatocellular carcinoma (HCC) therapy; however, its efficacy is limited, and identifying patients who will benefit from sorafenib is challenging. We aimed to identify predictive biomarkers of sorafenib benefit in patients with HCC.

Methods: Gene expression data from 33 HCC tumors treated with sorafenib were analyzed to construct a prediction model aimed at identifying patients with greater benefit from sorafenib treatment. The robustness of the predictor was validated using gene expression data from two phase III clinical trials, IMbrave150 and STORM.

Results: The analysis of transcriptome data revealed a 50-gene signature, the …

Axillary Management After Neoadjuvant Endocrine Therapy (Net), Laura Leonard, Min Yi, Emma Wingate, Puneet Singh, Abigail Caudle, Rosa F Hwang, Isabelle Bedrosian, Vicente Valero, Jennifer Litton, Nuhad Ibrahim, Kelly K Hunt

Faculty, Staff and Student Publications

BACKGROUND: In patients with hormone receptor-positive (HR

PATIENTS AND METHODS: We performed a retrospective review of patients with clinical stage I-III, HR

RESULTS: A total of 230 patients were included; 120 (52.2%) were clinically node-negative (cN0), while 110 (47.8%) were clinically node-positive (cN+). In the cN+ group, 7.3% (8/110) had a nodal pathologic complete response (pCR). In total, 76.4% (84/110) in the cN+ group underwent axillary lymph node dissection (ALND) as the initial axillary procedure, and 90.9% (100/110) underwent ALND overall. In total, 98.3% (118/120) with cN0 disease underwent sentinel lymph node dissection (SLND), and 28 (23.7%) had positive nodes. …

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Unraveling The Nexus: Tumor Mutational Burden, Pd-L1 Expression, And Oncogenic Alterations In Non-Small Cell Lung Cancer Cytology Specimens, Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P Patel, Asif Rashid, Shun Rao, Mark J Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: PD-L1 expression and tumor mutational burden (TMB) are biomarkers for immune checkpoint inhibitor (ICI) therapy in non-small cell lung cancer (NSCLC); however, patients harboring oncogenic alterations have limited benefit from ICIs. The impact of oncogenic alterations on TMB and PD-L1 tumor proportion score in lung cytology specimens is poorly understood. Herein, the association between oncogenic alterations, TMB, and PD-L1 in NSCLC cytology specimens is explored.

Methods: Next-generation sequencing results from 312 NSCLC cytology specimens were retrospectively reviewed that interrogate 610 genes and select immuno-oncology signatures. TMB and PD-L1 immunohistochemical expression across oncogenic alterations were analyzed to explore associations.

Results: …