Biomedical Informatics Commons^™

The Study Of The Epidemiology Of Pediatric Hypertension Registry (Superhero): Rationale And Methods, Andrew M South, Victoria C Giammattei, Kiri W Bagley, Christine Y Bakhoum, William H Beasley, Morgan B Bily, Shupti Biswas, Aaron M Bridges, Rushelle L Byfield, Jessica Fallon Campbell, Rahul Chanchlani, Ashton Chen, Lucy D'Agostino Mcgowan, Stephen M Downs, Gina M Fergeson, Jason H Greenberg, Taylor A Hill-Horowitz, Elizabeth T Jensen, Mahmoud Kallash, Margret Kamel, Stefan G Kiessling, David M Kline, John R Laisure, Gang Liu, Jackson Londeree, Caroline B Lucas, Sai Sudha Mannemuddhu, Kuo-Rei Mao, Jason M Misurac, Margaret O Murphy, James T Nugent, Elizabeth A Onugha, Ashna Pudupakkam, Kathy M Redmond, Sandeep Riar, Christine B Sethna, Sahar Siddiqui, Ashley L Thumann, Stephen R Uss, Carol L Vincent, Irina V Viviano, Michael J Walsh, Blanche D White, Robert P Woroniecki, Michael Wu, Ikuyo Yamaguchi, Emily Yun, Donald J Weaver

Faculty, Staff and Students Publications

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research, such as small sample sizes, reliance on manual record review, and limited analytic methods, that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite, retrospective registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases, 10th …

Onset And Progression Of Disease In Nonhuman Primates With Pde6c Cone Disorder, Monica Ardon, Lily Nguyen, Rui Chen, Jeffrey Rogers, Tim Stout, Sara Thomasy, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: The California National Primate Research Center contains a colony of rhesus macaques with a homozygous missense mutation in PDE6C (R565Q) which causes a cone disorder similar to PDE6C achromatopsia in humans. The purposes of this study are to characterize the phenotype in PDE6C macaques in detail to determine the onset of the cone phenotype, the degree to which the phenotype progresses, if heterozygote animals have an intermediate phenotype, and if rod photoreceptor function declines over time.

METHODS: We analyzed spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and electroretinography (ERG) data from 102 eyes of 51 macaques (aged 0.25 …

Inherited Retinal Degenerations And Non-Neovascular Age-Related Macular Degeneration: Progress And Unmet Needs, Jacque L Duncan, Angela Bowman, Amy Laster, Claire Gelfman, David G Birch, Shannon E Boye, Stephen P Daiger, Lucian Del Priore, Donald J Zack, James T Handa

Faculty, Staff and Student Publications

Inherited retinal degeneration (IRD) disease and age-related macular degeneration (AMD) are leading causes of irreversible vision loss and blindness. Although significant progress has advanced the field in the past 5 years, significant challenges remain. The current article reviews the accomplishments and research advances that have fueled the development of treatments for patients with IRD and AMD, including the first approved gene-augmentation treatment for RPE65-related retinal degeneration and complement inhibition therapies to slow progression of geographic atrophy (GA) in AMD. The article outlines opportunities to address gaps and unmet needs that should lead to additional progress toward the development of treatments …

Systemic Administration Of A Site-Targeted Complement Inhibitor Attenuates Chronic Stress-Induced Social Behavior Deficits And Neuroinflammation In Mice, Amit Kumar Madeshiya, Brandi Quintanilla, Carl Whitehead, Stephen Tomlinson, Anilkumar Pillai

Faculty, Staff and Student Publications

Chronic stress, a risk factor for many neuropsychiatric conditions, causes dysregulation in the immune system in both humans and animal models. Additionally, inflammation and synapse loss have been associated with deficits in social behavior. The complement system, a key player of innate immunity, has been linked to social behavior impairments caused by chronic stress. However, it is not known whether complement inhibition can help prevent neuroinflammation and behavioral deficits caused by chronic stress. In this study, we investigated the potential of a site-targeted complement inhibitor to ameliorate chronic stress-induced changes in social behavior and inflammatory markers in the prefrontal cortex …

Private-Sector Readmissions For Inpatient Surgery In Veterans Health Administration Hospitals, Mary Vaughan Sarrazin, Yubo Gao, Carly A Jacobs, Michael A Jacobs, Susanne Schmidt, Heather Davila, Katherine Hadlandsmyth, Andrea L Strayer, John Cashy, George Wehby, Paula K Shireman, Daniel E Hall

Faculty, Staff and Student Publications

Importance: The Veterans Health Administration (VHA) reports multiple indicators of hospital surgical performance, including hospital risk-standardized 30-day readmission rates (RSRRs). Currently, most routinely reported measures do not include readmissions that occur outside VHA hospitals. The impact of readmissions outside the VHA on hospital RSRR is not known.

Objective: To measure the impact of including non-VHA readmissions on VHA hospital performance rankings for 30-day readmission.

Design, setting, and participants: This retrospective cohort study included patients aged at least 65 years from 2013 to 2019 from the Veterans Affairs Surgical Quality Improvement Program linked to patient-level data from the VHA and Medicare. …

Myeloid Activation Clears Ascites And Reveals Il27-Dependent Regression Of Metastatic Ovarian Cancer, Brennah Murphy, Taito Miyamoto, Bryan S Manning, Gauri Mirji, Alessio Ugolini, Toshitha Kannan, Kohei Hamada, Yanfang P Zhu, Daniel T Claiborne, Lu Huang, Rugang Zhang, Yulia Nefedova, Andrew Kossenkov, Filippo Veglia, Rahul Shinde, Nan Zhang

Faculty, Staff and Student Publications

Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of < 30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity. β-glucan alone cleared ascites and eliminated fluid tumor cells by inducing intraperitoneal clotting in the fluid and Dectin-1-Syk-dependent NETosis in the omentum. In omentum tumors, BI expanded a novel subset of immunostimulatory IL27+ macrophages and neutralizing IL27 impaired BI efficacy in vivo. Moreover, BI directly induced IL27 secretion in macrophages where single agent treatment did not. Finally, BI extended mouse survival in a chemoresistant model and significantly improved chemotherapy response in a chemo-sensitive model. In summary, we propose a new therapeutic strategy for the treatment of metastatic OvCa.

Rna Shielding Of P65 Is Required To Potentiate Oncogenic Inflammation In Tet2-Mutated Clonal Hematopoiesis, Nana Adjoa Ben-Crentsil, Wazim Mohammed Ismail, Maria E Balasis, Hannah Newman, Ariel Quintana, Moritz Binder, Traci Kruer, Surendra Neupane, Meghan C Ferrall-Fairbanks, Jenna Fernandez, Terra L Lasho, Christy M Finke, Mohammed L Ibrahim, Kathy L Mcgraw, Michael Wysota, Amy L Aldrich, Christopher B Ryder, Christopher T Letson, Joshua Traina, Amy F Mclemore, Nathalie Droin, Aditi Shastri, Seongseok Yun, Eric Solary, David A Sallman, Amer A Beg, Li Ma, Alexandre Gaspar-Maia, Mrinal M Patnaik, Eric Padron

Faculty, Staff and Student Publications

This work identifies MALAT1 as a requisite downstream effector of oncogenic feedforward inflammatory circuits necessary for the development of TET2-mutated CH and fulminant myeloid malignancy. We elucidate a novel mechanism by which MALAT1 "shields" p65 from dephosphorylation to potentiate this circuit and nominate MALAT1 inhibition as a future therapeutic strategy.

Steering Research On Mrna Splicing In Cancer Towards Clinical Translation, Olga Anczukow, Frédéric H-T Allain, Brittany L Angarola, Douglas L Black, Angela N Brooks, Chonghui Cheng, Ana Conesa, Edie I Crosse, Eduardo Eyras, Ernesto Guccione, Sydney X Lu, Karla M Neugebauer, Priyanka Sehgal, Xiao Song, Zuzana Tothova, Juan Valcárcel, Kevin M Weeks, Gene W Yeo, Andrei Thomas-Tikhonenko

Faculty, Staff and Students Publications

Splicing factors are affected by recurrent somatic mutations and copy number variations in several types of haematologic and solid malignancies, which is often seen as prima facie evidence that splicing aberrations can drive cancer initiation and progression. However, numerous spliceosome components also 'moonlight' in DNA repair and other cellular processes, making their precise role in cancer difficult to pinpoint. Still, few would deny that dysregulated mRNA splicing is a pervasive feature of most cancers. Correctly interpreting these molecular fingerprints can reveal novel tumour vulnerabilities and untapped therapeutic opportunities. Yet multiple technological challenges, lingering misconceptions, and outstanding questions hinder clinical translation. …

A Transgenic Mouse Model Of Down Syndrome Acute Lymphoblastic Leukemia Identifies Targetable Vulnerabilities, Jacob J Junco, Max Rochette, Michelle Alozie, Raushan Rashid, Maci Terrell, Barry Zorman, Pavel Sumazin, Lauren Rowland, Gino Dettorre, Reid T Powell, Clifford C Stephan, Peter J Davies, Margarita Martinez-Moczygemba, Jun J Yang, Karen R Rabin

Faculty, Staff and Students Publications

No abstract provided.

Testosterone Acts Through The Membrane Protein Gprc6a To Cause Cardiac Edema In Zebrafish Embryos, Vahid Zadmajid, Shayan Shahriar, Daniel A Gorelick

Faculty, Staff and Students Publications

Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants …

Development And Evaluation Of A Training Curriculum To Engage Researchers On Accessing And Analyzing The All Of Us Data, Julie R Coleman, Jasmine N Baker, Shamika Ketkar, Ashley M Butler, Laterrica Williams, Latanya Hammonds-Odie, Elizabeth G Atkinson, Debra D Murray, Brendan Lee, Kim C Worley

Faculty, Staff and Students Publications

OBJECTIVE: The All of Us Evenings with Genetics (EwG) Research Program at Baylor College of Medicine (BCM), funded to engage research scholars to work with the All of Us data, developed a training curriculum for the Researcher Workbench, the platform to access and analyze All of Us data. All of Us EwG developed the curriculum so that it could teach scholars regardless of their skills and background in programming languages and cloud computing. All of Us EwG delivered this curriculum at the first annual All of Us EwG Faculty Summit in May 2022. The curriculum was evaluated both during and …

Rfc2 May Contribute To The Pathogenicity Of Williams Syndrome Revealed In A Zebrafish Model, Ji-Won Park, Tae-Ik Choi, Tae-Yoon Kim, Yu-Ri Lee, Dilan Wellalage Don, Jaya K George-Abraham, Laurie A Robak, Cristina C Trandafir, Pengfei Liu, Jill A Rosenfeld, Tae Hyeong Kim, Florence Petit, Yoo-Mi Kim, Chong Kun Cheon, Yoonsung Lee, Cheol-Hee Kim

Faculty, Staff and Students Publications

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167-kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate …

Chatgpt Vs Expert-Guided Care Pathways For Postesophagectomy Symptom Management, Mohamad K Abou Chaar, Giovanna Grigsby-Rocca, Ming Huang, Shanda H Blackmon

Faculty, Staff and Student Publications

BACKGROUND: The objective of this study was to compare generative artificial intelligence-initiated care pathways, using ChatGPT, with expert-guided consensus-initiated care pathways from AskMayoExpert (AME) for symptom management of esophageal cancer patients after esophagectomy.

METHODS: A formal protocol for development of 9 AME care pathways was followed for specific patient-identified domains after esophagectomy for esophageal cancer. Domain scores were measured and assessed through the Upper Digestive Disease tool. These care pathways were developed by experts validated by a consensus-driven methodology. ChatGPT was used to answer specific questions similar to the AME care pathway on April 9, 2023, and March 28, 2024. …

Addressing Ethical Issues In Healthcare Artificial Intelligence Using A Lifecycle-Informed Process, Benjamin X Collins, Jean-Christophe Bélisle-Pipon, Barbara J Evans, Kadija Ferryman, Xiaoqian Jiang, Camille Nebeker, Laurie Novak, Kirk Roberts, Martin Were, Zhijun Yin, Vardit Ravitsky, Joseph Coco, Rachele Hendricks-Sturrup, Ishan Williams, Ellen W Clayton, Bradley A Malin, Bridge2ai Ethics And Trustworthy Ai Working Group

Faculty, Staff and Student Publications

OBJECTIVES: Artificial intelligence (AI) proceeds through an iterative and evaluative process of development, use, and refinement which may be characterized as a lifecycle. Within this context, stakeholders can vary in their interests and perceptions of the ethical issues associated with this rapidly evolving technology in ways that can fail to identify and avert adverse outcomes. Identifying issues throughout the AI lifecycle in a systematic manner can facilitate better-informed ethical deliberation.

MATERIALS AND METHODS: We analyzed existing lifecycles from within the current literature for ethical issues of AI in healthcare to identify themes, which we relied upon to create a lifecycle …

Targeting The Glutamine-Arginine-Proline Metabolism Axis In Cancer, Di Wang, Jiang-Jie Duan, Yu-Feng Guo, Jun-Jie Chen, Tian-Qing Chen, Jun Wang, Shi-Cang Yu

Faculty, Staff and Student Publications

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy …

Genetic Ablation Of The Isoform Γ Of Pi3k Decreases Antidepressant Efficacy Of Ketamine In Male Mice, Gabriela N Vaz, Flávia C Turcato, Isabel A V Lima, Franciele F Scarante, Melissa R Araújo, Tamires A V Brigante, Livia C M Rodrigues, Francisco S Guimarães, Jaime E C Hallak, Jose A Crippa, Antonio L Teixeira, Antonio C P De Oliveira, Alline Cristina Campos

Faculty, Staff and Student Publications

About one-third of major depressive disorder (MDD) patients demonstrate unresponsiveness to classic antidepressants, and even the clinical efficacy of fast-acting drugs such as ketamine varies significantly among patients with treatment-resistant depression. Nevertheless, the lack of suitable animal models that mimic a possible ketamine-resistant phenotype challenges the understanding of resistance to drug treatment. In this study, we showed that PI3Kγ knock-out (KO) mice do not respond to classical doses of ketamine and classical antidepressants. PI3Kγ KO mice were unresponsive to both the rapid and sustained antidepressant-like effects of a single dose of ketamine in the forced swimming test. Additionally, they were …

Off-Protocol Radiation Therapy In Phase 3 Metastatic Solid Tumor Trials, Alexander D Sherry, Timothy A Lin, Zachary R Mccaw, Esther J Beck, Ramez Kouzy, Joseph Abi Jaoude, Adina H Passy, Avital M Miller, Gabrielle S Kupferman, Clifton David Fuller, Charles R Thomas, Eugene J Koay, Chad Tang, Pavlos Msaouel, Ethan B Ludmir

Faculty, Staff and Student Publications

Purpose: Increasing data suggest that radiation therapy, particularly ablative radiation therapy, alters the natural history of metastatic disease. For patients with metastatic disease enrolled in prospective trials testing systemic therapy, the use of off-protocol radiation therapy to improve clinical symptoms or extend the duration of study systemic therapy may influence study endpoints. We sought to evaluate how often off-protocol radiation therapy was permitted among systemic therapy phase 3 trials, how often off-protocol radiation therapy is used, and whether off-protocol radiation therapy correlated with study outcomes.

Methods and materials: Two-arm, superiority-design, phase 3 randomized trials testing systemic therapy were screened from …

Prevalence, Diagnostic Features, And Medical Outcomes Of Females With Turner Syndrome With A Trisomy X Cell Line (45, X/47, Xxx): Results From The Insights Registry, Natalia Klamut, Samantha Bothwell, Alexandra E Carl, Vaneeta Bamba, Jennifer R Law, Wendy J Brickman, Karen O Klein, Roopa Kanakatti Shankar, Catherina T Pinnaro, Patricia Y Fechner, Siddharth K Prakash, Iris Gutmark-Little, Susan Howell, Nicole Tartaglia, Marybel Good, Kelly C Ranallo, Shanlee M Davis

Faculty, Staff and Student Publications

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly …

Vitamin D In Patients With Low Tumor-Burden Indolent Non-Hodgkin Lymphoma Treated With Rituximab Therapy (Ilyad): A Randomized, Phase 3 Clinical Trial, Jonathan W Friedberg, Michael T Brady, Myla Strawderman, Brad S Kahl, Izidore S Lossos, Jonathon B Cohen, Patrick M Reagan, Carla Casulo, Barbara L Averill, Andrea Baran, Grerk Sutamtewagul, Paul M Barr, John P Leonard, John M Ashton, John G Strang, Francisco Vega, Derick R Peterson, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: There is a significant association between low vitamin D levels at diagnosis of indolent B-cell lymphomas and inferior overall survival (OS). To determine whether supplemental vitamin D improves event-free survival (EFS) in these patients, we conducted a comparative double-blind study of vitamin D3 vs. placebo.

Methods: In this phase 3, randomized, double-blind, placebo-controlled trial, patients with low tumor burden follicular, marginal zone or small lymphocytic lymphoma, age 18 or older, with stage two or greater disease and no prior systemic treatment were enrolled at 7 academic cancer centers. Patients were stratified by histology and FLIPI (Follicular Lymphoma International Prognostic …

Antiangiogenic Therapy Combined With Immune Checkpoint Blockade In Urothelial Cancer: Systematic Review And Meta-Analysis, Mohammad Jad Moussa, Iuliia Kovalenko, Emanuele Crupi, Ekaterina Proskuriakova, Yimin Geng, Giuseppe Fallara, Raed Benkhadra, Daniele Raggi, Matthew T Campbell, Pavlos Msaouel, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Antiangiogenic therapy had been tested in urothelial cancer (UC) without reaching the clinic.

Objective: We provide a systematic review and meta-analysis of trials to assess efficacy of immune checkpoint inhibitors (ICI) combined with antiangiogenic agents in UC.

Methods: Following PRISMA guidelines, we searched for trials with at least one arm of patients with UC treated with ICI plus antiangiogenics. Data were analyzed with the "meta" package from R using a one-staged frequentist meta-analysis.

Results: After screening 13,708 titles and abstracts, 9 studies were selected for analysis with 14 identified cohorts comprising 621 patients: 448 were ICI-naïve (ICI-N) and 173 …

Early-Stage Extranodal Nk/T-Cell Lymphoma, Nasal Type: A Role For Elective Nodal Irradiation?, Penny Fang, Sonal S Noticewala, Susan Y Wu, Jillian R Gunther, Ethan B Ludmir, L Jeffrey Medeiros, Paolo Strati, Ranjit Nair, Chijioke Nze, Loretta J Nastoupil, Sairah Ahmed, Luis Malpica Castillo, Luis Fayad, Jason Westin, Sattva Neelapu, Christopher Flowers, Auris Huen, Swaminathan P Iyer, Bouthaina Dabaja, Chelsea C Pinnix

Faculty, Staff and Student Publications

Purpose: Extranodal NK/T-cell lymphoma (ENKTCL) is rare in the Western Hemisphere and is commonly treated with combined modality therapy (CMT).

Methods and materials: We retrospectively reviewed 35 patients treated with Ann Arbor stage I/II ENKTCL between 1994 and 2015 at a large academic cancer center in the United States.

Results: With 11.6 years median follow-up, median overall survival and progression-free survival were 13.5 and 7.5 years, respectively. Eighteen (51%) patients experienced disease relapse, with 5 regional nodal relapses, of which 2 experienced combined regional and distant relapses. All 5 regional nodal relapses occurred exclusively among patients not treated with elective …

Low Intensity Mechanical Signals Promote Proliferation In A Cell-Specific Manner: Tailoring A Non-Drug Strategy To Enhance Biomanufacturing Yields, M Ete Chan, Christopher Ashdown, Lia Strait, Sishir Pasumarthy, Abdullah Hassan, Steven Crimarco, Chanpreet Singh, Vihitaben S Patel, Gabriel Pagnotti, Omor Khan, Gunes Uzer, Clinton T Rubin

Faculty, Staff and Student Publications

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively …

Constructing Phylogenetic Trees For Microbiome Data Analysis: A Mini-Review, Ruitao Liu, Xi Qiao, Yushu Shi, Christine B Peterson, William S Bush, Fabio Cominelli, Ming Wang, Liangliang Zhang

Faculty, Staff and Student Publications

As next-generation sequencing technologies advance rapidly and the cost of metagenomic sequencing continues to decrease, researchers now face an unprecedented volume of microbiome data. This surge has stimulated the development of scalable microbiome data analysis methods and necessitated the incorporation of phylogenetic information into microbiome analysis for improved accuracy. Tools for constructing phylogenetic trees from 16S rRNA sequencing data are well-established, as the highly conserved regions of the 16S gene are limited, simplifying the identification of marker genes. In contrast, metagenomic and whole genome shotgun (WGS) sequencing involve sequencing from random fragments of the entire gene, making identification of consistent …

Healthcare Disparities, Screening, And Molecular Testing In The Changing Landscape Of Non-Small Cell Lung Cancer In The United States: A Review, Razelle Kurzrock, Aadel A Chaudhuri, David Feller-Kopman, Narjust Florez, Jed Gorden, Ignacio I Wistuba

Faculty, Staff and Student Publications

Inequitable access to care continues to hinder improvements in diagnosis and treatment of lung cancer. This review describes healthcare disparities in the changing landscape of non-small cell lung cancer (NSCLC) in the United States, focusing on racial, ethnic, sex-based, and socioeconomic trends. Furthermore, strategies to address disparities, overcome challenges, and improve patient outcomes are proposed. Barriers exist across lung cancer screening, diagnosis, and treatment regimens, varying by sex, age, race and ethnicity, geography, and socioeconomic status. Incidence and mortality rates of lung cancer are higher among Black men than White men, and incidences in young women are substantially greater than …

Artificial Intelligence Uncertainty Quantification In Radiotherapy Applications – A Scoping Review, Kareem A Wahid, Zaphanlene Y Kaffey, David P Farris, Laia Humbert-Vidan, Amy C Moreno, Mathis Rasmussen, Jintao Ren, Mohamed A Naser, Tucker J Netherton, Stine Korreman, Guha Balakrishnan, Clifton D Fuller, David Fuentes, Michael J Dohopolski

Faculty, Staff and Student Publications

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions.

Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual …

Development Of Novel Ionization Chambers For Reference Dosimetry In Electron Flash Radiotherapy, Kevin Liu, Shannon Holmes, Ahtesham Ullah Khan, Brian Hooten, Larry Dewerd, Emil Schüler, Sam Beddar

Faculty, Staff and Student Publications

Background: Reference dosimetry in ultra-high dose rate (UHDR) beamlines is significantly hindered by limitations in conventional ionization chamber design. In particular, conventional chambers suffer from severe charge collection efficiency (CCE) degradation in high dose per pulse (DPP) beams.

Purpose: The aim of this study was to optimize the design and performance of parallel plate ion chambers for use in UHDR dosimetry applications, and evaluate their potential as reference class chambers for calibration purposes. Three chamber designs were produced to determine the influence of the ion chamber response on electrode separation, field strength, and collection volume on the ion chamber response …

Pathway-Based Clustering Identifies Two Subtypes Of Cancer-Associated Fibroblasts Associated With Distinct Molecular And Clinical Features In Pancreatic Ductal Carcinoma, Hongjing Ai, Rongfang Nie, Xiaosheng Wang

Faculty, Staff and Student Publications

Existing single-cell clustering methods are based on gene expressions that are susceptible to dropout events in single-cell RNA sequencing (scRNA-seq) data. To overcome this limitation, we proposed a pathway-based clustering method for single cells (scPathClus). scPathClus first transforms single-cell gene expression matrix into pathway enrichment matrix and generates its latent feature matrix. Based on the latent feature matrix, scPathClus clusters single cells using the method of community detection. Applying scPathClus to PDAC scRNA-seq datasets, we identified two types of cancer-associated fibroblasts (CAFs), termed csCAFs and gapCAFs, which highly expressed complement system and gap junction-related pathways, respectively. Spatial transcriptome analysis revealed …

Association Of Late Eating With Colorectal Adenomas: A Cross-Sectional Study, Darbaz Adnan, Edena R Khoshaba, Mostafa Abel-Reheem, Jonathan Q Trinh, Yin Cao, Faraz Bishehsari

Faculty, Staff and Student Publications

Purpose: Colorectal cancer (CRC) is linked to lifestyle exposures. However, changes in the CRC rates among younger populations remain poorly understood and suggest the existence of yet unidentified factor(s) that may contribute to colon carcinogenesis. Here, we investigated the potential role of time of eating in the risk of pre-cancerous colonic neoplasms (tubular adenoma: TA).

Methods: We enrolled 663 participants undergoing screening colonoscopies. Data on food timing, dietary intake, sleep/wake patterns, and chronotype were collected through structured questionnaires. Late eating was defined as the consumption of food or snack within a 3-hour window of sleep onset for at least four …

Why And When Do We Invasively Restage After Neoadjuvant Chemoimmunotherapy?, Jonathan D Spicer, Tina Cascone, Murry W Wynes, Karen L Kelly

Faculty, Staff and Student Publications

No abstract provided.

Mimicking Large Spot-Scanning Radiation Fields For Proton Flash Preclinical Studies With A Robotic Motion Platform, Fada Guan, Dadi Jiang, Xiaochun Wang, Ming Yang, Kiminori Iga, Yuting Li, Lawrence Bronk, Julianna Bronk, Liang Wang, Youming Guo, Narayan Sahoo, David R Grosshans, Albert C Koong, Xiaorong R Zhu, Radhe Mohan

Faculty, Staff and Student Publications

Previously, a synchrotron-based horizontal proton beamline (87.2 MeV) was successfully commissioned to deliver radiation doses in FLASH and conventional dose rate modes to small fields and volumes. In this study, we developed a strategy to increase the effective radiation field size using a custom robotic motion platform to automatically shift the positions of biological samples. The beam was first broadened with a thin tungsten scatterer and shaped by customized brass collimators for irradiating cell/organoid cultures in 96-well plates (a 7-mm-diameter circle) or for irradiating mice (1-cm