Medicine and Health Sciences Commons^™

Potential Impact Of Parasites In The Transmission Of Chronic Wasting Disease, Paulina Soto, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Optimized Ultrasound Imaging Of Phase-Change Nanodroplets, Charles R Dyall, Dmitry Nevozhay, Andy Liu, Trevor M Mitcham, George J Lu, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

Phase-change nanodroplets (PCNDs) continue to generate significant research interest due to their potential to extravasate into tissue, to be targeted for molecular imaging and drug delivery, and to undergo an induced phase-change to "activated" microbubbles (MBs) for ultrasound (US) imaging. To accurately quantify molecular markers, however, one assumes a consistent proportion of PCNDs in a region of interest (ROI) are stably activated and imaged. Herein we present a framework for developing a diagnostic sequence that is optimized for PCND activation uniformity, contrast, and acquisition time. To develop this framework, activation was examined at three scales of increasing complexity: single, adjacent, …

Growth Hormone Pathway As A Prognostic And Therapeutic Biomarker In Patients With Unresectable Hepatocellular Carcinoma Treated With Radiation Therapy, Joe R Eid, Safa Kaseb, Lianchun Xiao, Ryan Sun, Mahesh Kumar Kannan, Manal Hassan, Asif Rashid, Hop S Tran Cao, Hesham M Amin, Eugene J Koay

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) has emerged as an effective local therapy option for patients with unresectable hepatocellular carcinoma (HCC) and is associated with improved overall survival (OS). However, some patients still have poor outcomes after RT, and biomarkers are needed to stratify prognostic groups. High circulating growth hormone (GH) levels promote HCC proliferation and survival and are associated with aggressive disease. In this study, we evaluated whether pretreatment GH levels are associated with OS and progression-free survival (PFS) in patients who underwent RT for unresectable HCC.

Methods and materials: Patients undergoing RT for HCC during 2017-2023 were identified from a …

Corrigendum To 'Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation' [Transplantation And Cellular Therapy 29/3 (2023) 204-204], Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

No abstract provided.

Inherited Tbx4 Frameshifting Variants Predicted To Escape Nonsense Mediated Decay In Two Families With Variable Phenotypes, Including Lethal Lung Developmental Disorders, Shruti A Pande, Hiuling Chan Joiner, Przemyslaw Szafranski, Tomasz Gambin, Michelle Wright, Qian Wang, Maiah Walters, Jan M Friedman, Jessica Saunders, Nicholas Avdimiretz, Cornelius F Boerkoel, Nahir Cortes-Santiago, Gail Deutsch, Pawel Stankiewicz

Faculty, Staff and Students Publications

Background: Pathogenic variants involving the transcription factor TBX4 gene have been associated with various skeletal and pulmonary abnormalities, including lethal lung developmental disorders (LLDD).

Methods: Whole-genome sequencing (WGS) with AI-powered platform for variant detection and interpretation followed by Sanger sequencing targeted variant segregation analysis were used. Reverse transcription quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) studies were performed to assess gene and protein expression levels, respectively.

Results: We describe two unrelated families with intrafamilial variability in the TBX4 phenotypic expressivity, including LLDDs. WGS analyses revealed two frameshift variants, c.1019del; p.(Arg340GlnfsTer40) in the penultimate exon and c.1167dup; p.(Arg390GlnfsTer30) in the last exon …

Yap Induces A Prorenewal Metabolic State In Cardiomyocytes, Lin Liu, Jeffrey D Steimle, Chang-Ru Tsai, Fansen Meng, Yuka Morikawa, Yi Zhao, Sandra Carmichael, Xiao Li, James F Martin

Faculty, Staff and Students Publications

BACKGROUND: Cardiomyocytes, as highly specialized and differentiated somatic cells, possess a limited capacity for renewal. Neonatal rodents possess the ability to regenerate cardiomyocytes after injury; however, this regenerative capacity declines rapidly with cardiomyocyte maturation, suggesting an inhibitory network between cellular maturation and cardiomyocyte proliferation. Maturing cardiomyocytes undergo a metabolic shift from predominantly glycolysis in the neonatal state to increased fatty acid oxidation in the mature state, which poses a barrier to cardiomyocyte proliferation and cardiac regenerative repair. YAP, a transcriptional cofactor regulated by the Hippo signaling pathway, promotes cardiac regenerative repair. We investigated the role of YAP in mediating metabolic …

Prodromal Lewy Body Disorder Features In Rem Sleep Behavior Disorder With Biomarker-Defined Synucleinopathy, Daniel Weintraub, Michele K York, Roseanne Dobkin, Anuprita R Nair, Ryan Kurth, David-Erick Lafontant, Chelsea Caspell-Garcia, Roy N Alcalay, Ethan G Brown, Lana M Chahine, Christopher Coffey, Tatiana Foroud, Douglas Galasko, Karl Kieburtz, Kenneth Marek, Kalpana Merchant, Brit Mollenhauer, Kathleen L Poston, Andrew Siderowf, Cristina Simonet, Tanya Simuni, Caroline M Tanner, Thomas F Tropea, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal state for Lewy body disorders and exhibits biological heterogeneity that may influence clinical expression and progression. We examined clinical features in individuals with iRBD and biomarker-defined synucleinopathy.

Methods: Parkinson's Progression Markers Initiative (PPMI) is a longitudinal, multi-center observational study. Participants included polysomnogram (PSG)-confirmed iRBD individuals who were cerebrospinal fluid (CSF) α-synuclein seed amplification assay positive with no clinical diagnosis of Parkinson's disease or dementia with Lewy bodies, along with robust healthy controls (HCs). Clinical and biological features of prodromal PD and DLB, including mild cognitive impairment (MCI), subthreshold …

A Performance And Quality Improvement Intervention Integrating Molecular Testing To Support Personalized Cancer Care In Lung And Thyroid Cancers, Suzanne Murray, Monica Augustyniak, John Vu, Elbert Y. Kuo, Manolo G. Pasia Jr., Sheri L. Rivera, Kelly M. Rodriguez, Vivek Subbiah, Patrice Lazure, Ecaterina E. Dumbrava

Advances in Cancer Education and Quality Improvement

Introduction: Molecular testing has been underutilized in the diagnosis and treatment of cancer patients, despite its potential to significantly impact clinical decision-making and resulting health outcomes.

Objectives: This project aimed to evaluate the process and impact of a performance/quality improvement (PI/QI) intervention to optimize the integration of molecular testing for patients with non-small cell lung cancer (NSCLC) or thyroid cancer (TC).

Methods: Physicians, advanced practice providers, and nurses were engaged in the PI/QI at 2 cancer centers (Site A and Site B) for up to 18 months following a pre-intervention needs assessment. Gaps identified at baseline informed …

Trends In The National Resident Matching Program: Shifting Applicant Priorities In The Setting Of Application Limits And Pass/Fail Step 1 Grading, Joshua Morrow, Siena Blackwell, Zibi Gugala, Atul Maheshwari, Peter Boedeker

Faculty, Staff and Students Publications

Purpose: This study evaluated differences in expected and observed proportions of activities, average Step 2 scores, and abstracts, publications, and presentations since the adoption of a 10-experience maximum for residency applications and pass/fail Step 1 grading.

Method: The authors queried National Resident Matching Program data for MD senior applicants from 2016 to 2024 across 22 specialties. Data included average Step 2 scores; research, work, and volunteer experiences; and number of research products for matched and unmatched students by specialty. Repeated-measures multilevel models were used to estimate the difference in observed outcome in 2024 and expected outcome based on trends from …

Global Impact Of Germline Structural Variation On The Cancer Proteome, Fengju Chen, Yiqun Zhang, Luis F Paulin, Darshan S Chandrashekar, Sooryanarayana Varambally, Fritz J Sedlazeck, Chad J Creighton

Faculty, Staff and Students Publications

Proteome and transcriptome data combined can help assess the relevance of non-coding germline variants. Here, we combine germline Structural Variants (SVs) with mass spectrometry-based proteomics on tumors from 1637 cancer patients spanning various tumor tissues of origin to determine the extent SV breakpoint patterns involve differential protein expression of nearby genes. Rare and singleton SVs disrupting protein expression of known cancer susceptibility genes collectively involve 6% of patients. About 24% of the hundreds of genes with SV-associated non-coding cis-regulatory alterations at the mRNA level are similarly associated at the protein level. Both rare and common SVs may associate with differential …

A Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

Evaluating The Utility Of Rnaseq In Prenatal Diagnostics: Expression Profiles Of Cultured Chorionic Villus And Amniotic Fluid Samples, Maria C Vladoiu, Sen Zhao, Roni Zemet, Christian M Parobek, Jefferson Cruz Sinson, Stacy Tankersley, Ignatia B Van Den Veyver, Pengfei Liu

Duncan NRI Faculty and Staff Publications

Objective: While RNAseq has enhanced variant interpretation in postnatal cases, its potential in the prenatal setting remains underexplored. This study investigates the utility of RNAseq in prenatal diagnostics by analyzing the expression profiles of cultured chorionic villus samples (cCVS) and amniotic fluid (cAF) samples.

Methods: We performed RNAseq on 25 prenatal samples (10 cCVS and 15 cAF) and compared their expression profiles with those of postnatal tissues-blood and skin fibroblasts.

Results: To evaluate the clinical relevance of gene expression in these samples, we curated a list of genes associated with fetal-onset genetic disorders (n = 375). Using this curated list …

Clingen Api Platform For Classification Of Human Genetic Variants, Neethu Shah, Tierra Farris, Arturo Alejandro Zuniga, Andrew R Jackson, Jessie Arce, Kevin Riehle, Christine G Preston, Mark E Mandell, Bryan Wulf, Gloria Cheung, Keyang Yu, Deborah I Ritter, Dubravka Jevtic, Miroslav Milinkov, Novak Martinovic, Nevena Vucinic, Aleksandar Mihajlovic, Alan F Rubin, Melissa S Cline, Marina Distefano, Malachi Griffith, Obi L Griffith, Matt W Wright, Teri E Klein, Sharon E Plon, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

In this commentary, we describe how the Clinical Genome Resource's (ClinGen's) application programming interface-based microservices accelerate growth and dissemination of knowledge about human genetic variation. By exposing findable, accessible, interoperable, reusable, and AI-ready variant data, ClinGen lays a foundation for next-generation software applications, AI systems, and variant classification workflows.

Correction: The Formation Of Tau Pore-Like Structures Is Prevalent And Cell Specific: Possible Implications For The Disease Phenotypes, Cristian A Lasagna-Reeves, Urmi Sengupta, Diana Castillo-Carranza, Julia E Gerson, Marcos Guerrero-Munoz, Juan C Troncoso, George R Jackson, Rakez Kayed

Faculty, Staff and Students Publications

This corrects the article "The formation of tau pore-like structures is prevalent and cell specific: possible implications for the disease phenotypes" in volume 2, 56.

Relative Impact Of Multidomain Lifestyle Interventions On Deficit Accumulation Frailty Over 24 Months In The U.S. Pointer Trial, Mark A Espeland, Kayloni Olson, Christy C Tangney, Darren R Gitelman, Maryjo Cleveland, Amber A Thro, Yitbarek N Demesie, Heather M Snyder, Rachel A Whitmer, Pankaja Desai, Rifat Alam, Lucia Crivelli, Thomas M Holland, Olivia Preissle, Rema Raman, Michele K York, Laura D Baker

Faculty, Staff and Students Publications

Background: Multidomain lifestyle interventions hold promise as approaches to slow aging. Deficit accumulation frailty indices (FIs) are increasingly used to capture aging processes. Frailty is highly associated with increased mortality and chronic disease risk, but the degree to which multidomain lifestyle changes impact frailty is not clear.

Methods: The U.S. Study to Protect Brain Health through Lifestyle Intervention to Reduce Risk (U.S. POINTER) was a 2-year randomized clinical trial to compare two multidomain lifestyle interventions designed to increase exercise, improve diet, and promote social and cognitive stimulating activities and health monitoring. The Structured intervention incorporated greater structure, intensity, and accountability …

Drd2 Rs6276 Polymorphism And Trait Impulsivity In Individuals With Mixed Behavioral And Substance Addictions, Gabriela Zdunek, Remigiusz Recław, Aleksandra Suchanecka, Krzysztof Chmielowiec, Dariusz Larysz, Patryk Ilków, Kinga Łosińska, Jolanta Chmielowiec, Łukasz Jaworski, Anna Grzywacz

Baltic Journal of Health and Physical Activity

Background/Objectives: Impulsivity is a key transdiagnostic trait linked to dysregulated reward processing in both behavioral and substance-related addictions, as recognized in DSM-5. Dopaminergic genes, including DRD2, may modulate individual differences in impulsivity, particularly under conditions of increased addiction vulnerability. This study examined whether the DRD2 Exon 8 rs6276 polymorphism predicts impulsivity levels in men with mixed addictive behaviors compared with healthy controls. Methods: A total of 328 males (128 with mixed behavioral and substance addictions and 200 controls) were assessed. Diagnoses were confirmed using the MINI interview, and impulsivity was measured with the Barratt Impulsiveness Scale (BIS-11). Genotyping of …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Widespread Distribution Of Alu/Alu-Mediated Genomic Rearrangement Predisposing To A Broad Range Of Mendelian Disease And Cancer In Human Populations, Ruizhi Vince Duan, Haowei Du, Shruti Pande, Ahmed K Saad, Meryem M Atik, Minal Jamsandekar, Karen J Coveler, Zain Dardas, Shalini N Jhangiani, Jennifer E Posey, Richard A Gibbs, James R Lupski

Faculty, Staff and Students Publications

Background

Genome-wide distributions of Alu elements contribute to a broad range of structural variants (SVs) through Alu/Alu-mediated genomic rearrangement (AAMR). Yet, the prevalence and characteristics of AAMR on the human genome and its scale in generating pathogenic SVs remain poorly understood.

Methods

We established a disease-focused, AAMR-SV dataset and a control dataset to comprehensively delineate the genomic landscape of Alu mutagenesis. The disease-focused dataset included 407 published pathogenic AAMR-SV alleles in 115 known genes for Mendelian disorders or traits through a literature survey. A control dataset was collected from short-read genome sequencing analyses of 100 randomly selected, healthy individuals. …

Non-Invasive Intracranial Pressure Estimation In The Intensive Care Unit: Narrative Review Of Methods And Clinical Applications, Edoardo Picetti, Daniele Guerino Biasucci, Elisa Gouvea Bogossian, Sérgio Brasil, Danilo Cardim, Marek Czosnyka, Daniel A Godoy, Gregory W J Hawryluk, Mohammad I Hirzallah, Frank A Rasulo, Carla Bittencourt Rynkowski, Andres M Rubiano, Fabio Silvio Taccone, Chiara Robba

Faculty, Staff and Students Publications

Despite invasive methods are the gold standard for intracranial pressure (ICP) measurement, several non-invasive techniques (nICP) have been proposed as surrogate, although their use remains insufficiently recognized in clinical practice. These include transcranial Doppler blood flow velocity  assessment (arterial or venous), optic nerve sheath diameter (ONSD), automated pupillometry, measurement of skull expansion and compliance, brain imaging, double-depth ophthalmic artery blood flow velocity, and ultrasound time-of-flight. The main limitations of all indirect methods are calibration and zeroing, which constrain the absolute accuracy of non-invasive ICP monitoring. For transcranial Doppler-based methods, the 95% limits of agreement are approximately ± 7-15 mmHg, while …

Ethical Controversies In Organ Procurement: A National Survey On Public Perceptions Of Thoracoabdominal Normothermic Regional Perfusion, Trevor M Bibler, Jill Oliver Robinson, Adam Omelianchuk, Tariq Nisar, Savitri Fedson, Ariel N Levchenko, Amy L Mcguire

Center for Medical Ethics and Health Policy Staff Publications

Thoracoabdominal normothermic regional perfusion (TA-NRP) would likely expand the quantity and quality of organs procured after controlled circulatory death donation in the United States, yet its ethical permissibility remains contested. We surveyed a representative sample of US adults (n = 975) with the goal of assessing their perspectives on the ethical permissibility of TA-NRP. After reading a neutral description of TA-NRP, participants judged its permissibility, reviewed 5 critic and 5 supporter arguments (in random order), and chose which argument they found most convincing. Multivariable logistic regression examined predictors of agreeing with critics. Before exposure to the arguments, 51.5% stated that …

Author Correction: 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, Astrazeneca Genomics Initiative, 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

No abstract provided.

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 …

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: …

Baseline Parp-1 Pet Imaging In Patients With Advanced Solid Tumors With Dna Damage Response Mutations, Tarek Daoud, Jiansong Chen, Peng Wei, Franklin Wong, Timothy A Yap, Lilie L Lin

Faculty, Staff and Student Publications

Purpose: Inhibitors of poly(ADP-ribose) polymerase (PARP), an enzyme with numerous roles in DNA damage response signaling, represent a class of anti-cancer drugs approved for treating solid tumors with defects in the DNA damage response. However, additional methods for identifying patients who would benefit from the use of PARP inhibitors are urgently needed. We evaluated a novel radiotracer, 18F-FluorThanatrace ([18F]-FTT), to noninvasively assess PARP activity with PET/CT before treatment and determine associations between uptake, tumor mutation status, and prior receipt of therapy including PARP inhibitors.

Methods: Fifty-two patients with solid tumors underwent whole-body (skull base to thigh) [18F]-FTT PET/CT scans before …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Tumor Flare Reaction With Brentuximab-Vedotin In Mycosis Fungoides, Rishabh Lohray, Seda Purnak, Samruddhi Arkatkar, Madeleine Duvic, Victor Prieto, Carlos Torres-Cabala, Auris Huen

Faculty, Staff and Student Publications

No abstract provided.