Digital Commons Network^™

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

Enhancing The Safety And Efficacy Of Cell Therapy With Programmed Sense-And-Respond Function, Andrew J Walters, Xiaoyu Yang, Scott D Olson, Caleb J Bashor

Faculty, Staff and Student Publications

No abstract provided.

Imaging In Pelvic Exenteration-A Multidisciplinary Practice Guide From The Esgar-Sar-Esur-Pelvex Collaborative Group, Stephanie Nougaret, Doenja M J Lambregts, Geerard L Beets, Regina G H Beets-Tan, Lennart Blomqvist, David Burling, Quentin Denost, Maria A Gambacorta, Benedetta Gui, Ann Klopp, Yulia Lakhman, Kate E Maturen, Riccardo Manfredi, Iva Petkovska, Luca Russo, Atul B Shinagare, James A Stephenson, Damian Tolan, Aradhana M Venkatesan, Aaron J Quyn, Rosemarie Forstner

Faculty, Staff and Student Publications

Pelvic exenteration (PE) is a radical surgical approach designed for the curative treatment of advanced pelvic malignancies, requiring en-bloc resection of multiple pelvic organs. While the procedure is radical, it has shown promise in enhancing long-term survival and is now comparable in surgical mortality to elective resections for primary pelvic cancers. Imaging plays a crucial role in preoperative planning, with MRI, CT, and PET/CT being pivotal in assessing the extent of cancer and formulating a surgical roadmap. This paper presents clinical practice guidelines for imaging in the context of PE, developed jointly by ESGAR, SAR, ESUR, and the PelvEx Collaborative. …

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

A Qualitative Nmr And Histological Analysis Of Adipocere Formation In Different Aqueous Environments Using Sus Scrofa Models, Mia M. Sorrentino

Student Theses

Adipocere is a wax-like crust that has the potential to form over corpses in moist, humid, and anaerobic environments, preserving them in a process similar to that of mummification. The substance can be identified within 3-6 months postmortem and is characterized by the ratio of saturated fatty acids to unsaturated fatty acids. Palmitic acid and stearic acid are the most abundant in comparison to myristic and oleic acids. The goal of this study was to investigate factors affecting adipocere formation in different aqueous environments. Pork belly samples were submerged in water samples collected from different places around New York City …

Emotional Outbursts In Latinx Autistic Youth With Intact Or Non-Intact Families; Frequency, Severity, And Socio-Demographic Correlates, Sandra Lucia Masso Hernandez

Theses and Dissertations

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction, communication, and restricted repetitive behaviors. One of the core difficulties in individuals with ASD is related to emotional outbursts. Emotional outbursts (EO) are behavioral episodes in response to situations, environmental and physiological stimuli that occur in an extreme, unpleasant, sometimes aggressive way, often disproportionate to the context. Considering the impacts that EO’s can cause in populations with neurodevelopmental disorders and on the well-being and mental health of parents/caregivers, the need arises to evaluate these populations. Due to the core characteristics of ASD (such as a rigid mentality, …

Translation Of The Carcinogenic Dna Breakage-Repair Inhibition Mechanism For Hexavalent Chromium To Its Key Targets: Lung Epithelial Cells, Lung Tissue And Impacts On The Genome., Idoia Meaza Isusi

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death worldwide. Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread occupational and environmental exposure. Despite the known health risks, how Cr(VI) causes lung cancer remains unclear. This dissertation investigates the mechanisms of Cr(VI)-induced carcinogenesis. Cr(VI) causes DNA damage, specifically DNA double strand breaks, and inhibits homologous recombination repair, a high-fidelity repair pathway. Unrepaired DNA double strand breaks or those repaired through error-prone pathways, progress to chromosomal damage, and chromosome instability. The latter is a common characteristic of Cr(VI)-exposed cells, and a hallmark of lung cancer. Although the mechanism of Cr(VI)-induced …

Improving Brain Health: Exercise As A Tool For Enhancing Executive Function And Reducing Stress In Older African Americans, Destiny Ellise Ramos

Theses, Dissertations and Culminating Projects

Older African American (AA) adults face disproportionately higher risk of stress and Alzheimer's Disease and Related Dementias (ADRD) compared to other racial and ethnic groups, yet they remain underrepresented in intervention-based research. Previous research has suggested aerobic exercise may reduce stress and benefit executive functioning, which is among the first cognitive domains to be affected in ADRD; however, no studies to date have directly tested the impact of aerobic vs. non-aerobic exercise in older AAs at high risk for developing ADRD. The current study evaluated the effects of a group-based cardio dance fitness (CDF) exercise intervention versus a strength, flexibility, …

Functional Analysis Of Chromatin Remodeler Csb In Parp1/2- Mediated Oxidative Dna Lesion Repair, Rabeya Bilkis

Biomedical Sciences ETDs

The ATP-dependent chromatin remodeler Cockayne syndrome protein B (CSB) is essential for maintaining genome integrity. Mutations in CSB are the primary cause of Cockayne syndrome (CS), a premature aging disorder with severe sun sensitivity and neurodevelopmental symptoms. However, the precise mechanisms underlying the disease etiology remain poorly understood. Given the critical roles of oxidative stress in aging and neurodegenerative disorders, this research sought to determine the mechanisms of CSB’s functions in oxidative DNA damage repair.

In the first aim, we investigated how CSB participates in PARP1/2-mediated oxidative DNA repair. We showed that PARP1 and PARP2 recruit CSB to oxidized chromatin …

Variations In Sensory And Emotional Responses To Gluten-Containing And Gluten-Free Cookie Products Under Blind And Labeled Conditions, Eniola Ola, Han-Seok Seo

Food Science Faculty Publications and Presentations

The gluten-free food market is expanding rapidly. However, consumer acceptance and emotional responses to gluten-free food, especially commercially available products, have received relatively underexplored. This study aimed to determine how consumer perceptions, acceptance, and emotional responses differ between gluten-containing (C) and gluten-free (F) chocolate chip cookies from three brands under both blind and labeled conditions. In the labeled condition, 84 participants without celiac disease evaluated 3 F cookies labeled "gluten-free" and 3 C cookies presented without claims on a plain white card. In the blind condition, they tested the six cookies without labels. Participants provided hedonic ratings, Just-About-Right (JAR) ratings, …

Assessing The Implicit Prices Of Health And Wellness Product Attributes In Pet Food: A Hedonic Analysis Approach, Lonnie Hobbs Jr., Andrew Anderson

Agricultural Economics and Agribusiness Faculty Publications and Presentations

Here we examine product attributes present in dry dog food to show there exist potential price premiums and discounts associated with health and wellness attributes in dry dog food. The findings indicate price premiums are associated with attributes related to digestion and allergy care. Pricing discounts are found to be associated with immune support and dental attributes. The results of this study are anticipated to be a starting point for more sophisticated and dynamic analysis of pricing and willingness-to-pay studies in the pet food industry.

Whole-Genome Assembly And Annotation Of The Firecracker Penstemon (Penstemon Eatonii), David E. Jarvis, Mikel R. Stevens, Payton Carter, Ying Fei Lin, Kate E. Jaggi, Gabriela Jijon, Teal Kalt, Jouber Calixto, Samantha Standring, Kaitlin Torres, Kayla B. Stephensen, Hayley Mangelson, Noah H. Williams, Carolyn A. Wessinger, Peter J. Maughan, Paul B. Frandsen

Faculty Publications

The penstemons are ornamental annual flowering plants native to the Intermountain West and Rocky Mountains and commonly used for urban landscaping. Elite commercial penstemons are generally susceptible to abiotic stresses, including drought, root rot, cold, and high salinity. Firecracker penstemon (Penstemon eatonii), however, is much more tolerant to these stresses than most elite cultivars. Importantly, firecracker penstemon has been reported to hybridize with many other penstemons and therefore provides the opportunity to develop more tolerant elite cultivars through strategic crossing. To facilitate the study and utilization of firecracker penstemon, we sequenced and annotated the genome of a P. …

Precision Proteogenomics Reveals Pan-Cancer Impact Of Germline Variants, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Kathleen J Imbach, Karl R Clauser, Myvizhi Esai Selvan, Isabel Mendizabal, Yifat Geffen, Yo Akiyama, Myranda Maynard, Tomer M Yaron, Yize Li, Song Cao, Erik P Storrs, Olivia S Gonda, Adrian Gaite-Reguero, Akshay Govindan, Emily A Kawaler, Matthew A Wyczalkowski, Robert J Klein, Berk Turhan, Karsten Krug, D R Mani, Felipe Da Veiga Leprevost, Alexey I Nesvizhskii, Steven A Carr, David Fenyö, Michael A Gillette, Antonio Colaprico, Antonio Iavarone, Ana I Robles, Kuan-Lin Huang, Chandan Kumar-Sinha, François Aguet, Alexander J Lazar, Lewis C Cantley, Urko M Marigorta, Zeynep H Gümüş, Matthew H Bailey, Gad Getz, Eduard Porta-Pardo, Li Ding

Faculty, Staff and Student Publications

We investigate the impact of germline variants on cancer patients' proteomes, encompassing 1,064 individuals across 10 cancer types. We introduced an approach, "precision peptidomics," mapping 337,469 coding germline variants onto peptides from patients' mass spectrometry data, revealing their potential impact on post-translational modifications, protein stability, allele-specific expression, and protein structure by leveraging the relevant protein databases. We identified rare pathogenic and common germline variants in cancer genes potentially affecting proteomic features, including variants altering protein abundance and structure and variants in kinases (ERBB2 and MAP2K2) impacting phosphorylation. Precision peptidome analysis predicted destabilizing events in signal-regulatory protein alpha (SIRPA) and glial …

Yield And Economics Following 5 Years Of Integrated Weed Management In Cotton, Amar Godar, Jason K. Norseworthy, L. Tom Barber, Roger Farr, Ty Smith

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

The implementation of integrated weed management (IWM) practices in conventional management systems involves additional costs and can influence both short-term and long-term cotton (Gossypium hirsutum L.) yields, ultimately affecting economic viability. This study, conducted from fall 2018 to fall 2023 near Marianna, AR, evaluated four IWM practices in a large-plot, fixed-plot factorial design: zero tolerance for weed seed rain, soil inversion deep tillage every third year in the fall, a preplant terminated cereal rye cover crop, and dicamba-resistant cotton technology. Long-term economic impacts were assessed using the 5-year average cost-adjusted yield, with the base program (excluding all IWM practices) serving …

A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower

All Dissertations

This dissertation explores the value of genomic testing in precision oncology with an emphasis on how US payers conceptualize and prioritize elements of value. This research aims to address gaps in understanding payer perspectives and proposes a stakeholder-informed framework for evaluating genomic testing in oncology. To achieve this aim, the presented research investigates payer perspectives, value-based cancer care priorities, and the conceptual understanding of the value of a genetic diagnosis to establish a framework for value with the payer audience in mind. Chapter 1 outlines relevant background information relating to the genomic revolution and challenges in translating genomic testing technologies …

The Genomic Landscape And Prognostic Impact Of Kras, Stk11, And Smarca4 Mutations And Co-Mutations On Survival Outcomes In Non-Small Cell Lung Cancer, Peter Manolakos

All Dissertations

Non-small lung cancer (NSCLC) accounts for 85% of lung cancer cases, and Kirsten rat sarcoma viral oncogene homolog (KRAS), Serine/Threonine Kinase 11 (STK11), and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations and co-mutations have been increasingly recognized for their potential prognostic significance. However, clear knowledge gaps remain regarding which treatments should be selected for patients who present clinically with KRAS/STK11 or KRAS/SMARCA4 co-mutations, as outlined in Chapter 1. Despite significant clinical development advancements in immunotherapy and targeted therapy, a deeper understanding of the influence of these genomic …

Development Of A Treatment Decision Aid For Patients With Dysplastic Nevi Who Are Candidates For Re-Excision, Jaclyn N Roland-Mcgowan, Steven Caleb Freeman, Wenelia Baghoomian, Bryan T Carroll, Caroline Choi Kim, Emily Y Chu, Kelly Carter Nelson, Kevin P White, Michael E Ming, Rebecca I Hartman, Sancy A Leachman, Stephanie Mengden-Koon, Suephy C Chen, Susan M Swetter, Victor G Prieto, Elizabeth Berry, Wesley Y Yu

Faculty, Staff and Student Publications

No abstract provided.

A Comparison Of Carbon Ions Versus Protons For Integrated Mode Ion Imaging, Mikaël Simard, Ryan Fullarton, Lennart Volz, Christoph Schuy, Daniel G Robertson, Colin Baker, Christian Graeff, Charles-Antoine Collins Fekete

Faculty, Staff and Student Publications

Background: Incorporating image guidance into ion beam therapy is critical for minimizing beam range uncertainties and realizing the modality's potential. One promising avenue for image guidance is to capture transmission ion radiographs (iRads) before and/or during treatment. iRad image quality is typically maximized using a single-event imaging system, which involves tracking individual ions, albeit the approach is generally not suited to clinical beam settings. An alternative faster and clinically compatible method is integrated mode imaging, where individual pencil beam data is acquired, rather than single ion data. To evaluate the usefulness of transmission ion imaging for image guidance, it is …

Advancing Understanding And Therapeutic Strategies For Nut Sarcomas: Comprehensive Review Of The Literature And Two Cases, Carlos Torrado, Elise Nassif Haddad, Neeta Somaiah, Pavlos Msaouel, Alexander J Lazar

Faculty, Staff and Student Publications

Soft tissue sarcomas (STSs) are a group of rare cancers, among which nuclear protein in testis (NUT) sarcomas represent an ultra-rare subset driven by NUTM1 gene fusions. This article presents two unique cases of NUT sarcomas and conducts a comprehensive review of the literature to include an additional 61 cases. Our review reveals that NUT sarcoma exhibits a slightly higher incidence among women (male-to-female ratio of 1:1.03) and tends to manifest at a relatively young age (median age of 40 years). The most prevalent NUT partner genes were the MAD family in 52% of patients (33 of 63 patients, including …

Summary Of Research: Efficacy Of Trastuzumab Deruxtecan In Her2-Expressing Solid Tumors By Enrollment Her2 Ihc Status: Post Hoc Analysis Of Destiny-Pantumor02, Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Kyung Hae Jung, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam

Faculty, Staff and Student Publications

of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects …

Further Delineation Of The Scaf4-Associated Neurodevelopmental Disorder, Cosima M Schmid, Anne Gregor, Anna Ruiz, Carmen Manso Bazús, Isabella Herman, Urania Kotzaeridou, Lucie Dupuis, Katharina Steindl, Anaïs Begemann, Anita Rauch, Aude-Annick Suter, Bertrand Isidor, Sandra Mercier, Mathilde Nizon, Benjamin Cogné, Wallid Deb, Thomas Besnard, Tobias B Haack, Ruth J Falb, Amelie J Müller, Tobias Linden, Chad R Haldeman-Englert, Charlotte W Ockeloen, Francesca Mattioli, Alexandre Reymond, Nazia Ibrahim, Shagufta Naz, Elodie Lacaze, Jennifer A Bassetti, Julia Hoefele, Theresa Brunet, Korbinian M Riedhammer, Houda Z Elloumi, Richard Person, Fanggeng Zou, Juliette J Kahle, Kirsten Cremer, Axel Schmidt, Marie-Ange Delrue, Pedro M Almeida, Fabiana Ramos, Siddharth Srivastava, Aisling Quinlan, Stephen Robertson, Eva Manka, Alma Kuechler, Stephanie Spranger, Malgorzata J M Nowaczyk, Reem M Elshafie, Hind Alsharhan, Paul R Hillman, Leslie A Dunnington, Hilde M H Braakman, Shane Mckee, Angelica Moresco, Andrea-Diana Ignat, Ruth Newbury-Ecob, Guillaume Banneau, Olivier Patat, Jeffrey Kuerbitz, Susan Rzucidlo, Susan S Sell, Patricia Gordon, Sarah Schuhmann, André Reis, Yosra Halleb, Radka Stoeva, Boris Keren, Zainab Al Masseri, Zeynep Tümer, Sophia Hammer-Hansen, Sofus Krüger Sølyst, Connolly G Steigerwald, Nicolas J Abreu, Helene Faust, Amica Müller-Nedebock, Frédéric Tran Mau-Them, Heinrich Sticht, Christiane Zweier

Faculty, Staff and Student Publications

While mostly de novo truncating variants in SCAF4 were recently identified in 18 individuals with variable neurodevelopmental phenotypes, knowledge on the molecular and clinical spectrum is still limited. We assembled data on 50 novel individuals with SCAF4 variants ascertained via GeneMatcher and personal communication. With detailed evaluation of clinical data, in silico predictions and structural modeling, we further characterized the molecular and clinical spectrum of the autosomal dominant SCAF4-associated neurodevelopmental disorder. The molecular spectrum comprises 25 truncating, eight splice-site and five missense variants. While all other truncating variants were classified as pathogenic/likely pathogenic, significance of one C-terminal truncating variant, one …

Gene Promoters Are Genomically Encoded To Facilitate Histone Exchange/Incorporation, Blaine Bartholomew

Faculty, Staff and Student Publications

Gene promoters are intrinsically hardwired not only to facilitate transcription preinitiation complex formation but also the release of paused RNA polymerase by H2A.Z. A new PLOS Biology study reveals poly (dA) tracts at promoters positively stimulate H2A.Z incorporation by the SWR complex in yeast.

The Multilayered Transcriptional Architecture Of Glioblastoma Ecosystems, Masashi Nomura, Avishay Spitzer, Kevin C Johnson, Luciano Garofano, Djamel Nehar-Belaid, Alissa C Greenwald, Young Taek Oh, Frederick S Varn, Fulvio D'Angelo, Simon Gritsch, Kevin J Anderson, Simona Migliozzi, L Nicolas Gonzalez Castro, Tamrin Chowdhfury, Nicolas Robine, Catherine Reeves, Jong Bae Park, Anuja Lipsa, Frank Hertel, Anna Golebiewska, Simone P Niclou, Labeeba Nusrat, Sorcha Kellet, Sunit Das, Hyo Eun Moon, Sun Ha Paek, Franck Bielle, Alice Laurenge, Anna Luisa Di Stefano, Bertrand Mathon, Alberto Picca, Marc Sanson, Shota Tanaka, Nobuhito Saito, David M Ashley, Stephen T Keir, Keith L Ligon, Jason T Huse, W K Alfred Yung, Anna Lasorella, Roel G W Verhaak, Antonio Iavarone, Mario L Suvà, Itay Tirosh

Faculty, Staff and Student Publications

In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary and recurrent GBM samples from 59 patients using single-nucleus RNA sequencing and bulk tumor DNA sequencing to characterize GBM transcriptional heterogeneity. First, GBMs can be classified by their broad cellular composition, encompassing malignant and nonmalignant cell types. Second, in each cell type we describe the diversity of cellular states and their pathway activation, particularly an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like and cilia-like. Third, the remaining variation between GBMs highlights three baseline gene expression …

From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Danielle Wu

Faculty, Staff and Student Publications

Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5

Rna Sculpting By The Primordial Helix-Clasp-Helix-Strand-Loop (Hch-Sl) Motif Enforces Chemical Recognition Enabling Diverse Kh Domain Functions, John A Tainer, Susan E Tsutakawa

Faculty, Staff and Student Publications

In all domains of life, the ancient K homology (KH) domain superfamily is central to RNA processes including splicing, transcription, posttranscriptional gene regulation, signaling, and translation. Proteins with 1 to 15 KH domains bind single-strand (ss) RNA or DNA with base sequence specificity. Here, we examine over 40 KH domain experimental structures in complex with nucleic acid (NA) and define a novel Helix-clasp-Helix-Strand-Loop (HcH-SL) NA recognition motif binding 4 to 5 nucleotides using 10 to 18 residues. HcH-SL includes and extends the Gly-X-X-Gly (GXXG) signature sequence "clasp" that brings together two helices as an ∼90° helical corner. The first helix …

Temporal Trends Of Subsequent Central Nervous System Malignancies Among Survivors Of Childhood Cancer, Robert T Galvin, Yan Chen, Yan Yuan, Tabitha Cooney, Rebecca Howell, Michael A Arnold, Wendy Leisenring, Gregory T Armstrong, Joseph P Neglia, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: It is not known whether temporal changes in childhood cancer therapy have reduced risk of subsequent malignant neoplasms of the central nervous system (CNS), a frequently fatal late effect of cancer therapy.

Methods: Five-year survivors of primary childhood cancers diagnosed between 1970 and 1999 in the Childhood Cancer Survivor Study with CNS subsequent malignant neoplasms were identified. Cumulative incidence rates and standardized incidence ratios were compared among survivors diagnosed between 1970-1979 (n = 6223), 1980-1989 (n = 9680), and 1990-1999 (n = 8999). Multivariable models assessed risk factors for CNS subsequent malignant neoplasms.

Results: A total of 157 CNS …

Quantifying Photon Counting Detector (Pcd) Performance Using Pcd-Ct Images, Linying Zhan, Guang-Hong Chen, Ke Li

Faculty, Staff and Student Publications

Background: Photon counting detector CTs (PCD-CTs) have recently been introduced to clinical imaging. This development creates a new need for end-users to quantify and monitor the physical performance of PCDs. Traditionally, the characterization of PCD performance relied on detector counts, which are typically accessible to the manufacturer but are not usually available to clinical end-users.

Purpose: The goal of this work was to develop a new method for quantifying PCD performance using reconstructed PCD-CT images, without requiring access to the PCD counts.

Methods: The proposed method is based on a set of closed-form relationships that connect PCD-CT image noise, the …

Oral Microbiome Profile Of The Us Population, Anil K Chaturvedi, Emily Vogtmann, Jianxin Shi, Yukiko Yano, Martin J Blaser, J Gregory Caporaso, Barry I Graubard, Xing Hua, Autumn G Hullings, Lisa Kahle, Rob Knight, Shilan Li, Jody Mclean, Vaishnavi Purandare, Yunhu Wan, Neal D Freedman, Christian C Abnet

Faculty, Staff and Student Publications

Importance: The oral microbiome likely plays key roles in human health. Yet, population-representative characterizations are lacking.

Objective: To characterize the composition, diversity, and correlates of the oral microbiome in US adults.

Design, setting, and participants: This cross-sectional study analyzed data from the population-representative National Health and Nutrition Examination Survey (NHANES) from 2009 to 2012. Microbiome data were made publicly available in 2024. NHANES participants were aged 18 to 69 years and provided oral rinse samples in 1 of 2 consecutive NHANES cycles (2009-2010 and 2011-2012).

Exposures: Demographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.

Main outcomes and measures: Oral microbiome …

Phase Ii Trial Of Atezolizumab And Bevacizumab For Treatment Of Hpv-Positive Unresectable Or Metastatic Squamous Cell Carcinoma Of The Anal Canal, Van K Morris, Suyu Liu, Kangyu Lin, Haifeng Zhu, Seema Prasad, Priya Bhosale, Edwin R Parra, Ignacio Wistuba, Arjun Peddireddy, James Yao, Julia Mendoza-Perez, Mark Knafl, Scott E Woodman, Cathy Eng, Daniel Halperin

Faculty, Staff and Student Publications

Purpose: Anti-PD-L1 antibodies are associated with responses in < 25% of patients with metastatic human papillomavirus-associated malignancies. VEGF signaling causes immune evasion and immune suppression within the tumor. We evaluated the anti-PD-L1 antibody atezolizumab and anti-VEGF antibody bevacizumab for patients with unresectable, advanced anal cancer.

Patients and methods: For this phase II study, participants with previously treated, immunotherapy-naïve anal cancer received atezolizumab (1,200 mg) and bevacizumab (15 mg/kg) intravenously every 21 days. Responses were evaluated every 9 weeks (RECIST version 1.1). The primary endpoint was the best radiographic response. Median survival was estimated by Kaplan-Meier and compared for selected biomarkers (including paired pre- and on-treatment biopsies) using a log-rank test.

Results: Among 20 participants, the overall response rate was 11% [95% confidence interval (CI): 1.2-32]. Median progression-free survival and overall survival were 4.1 months (95% CI, 2.6-not …

Dose Prediction Via Deep Learning To Enhance Treatment Planning Of Lung Radiotherapy Including Simultaneous Integrated Boost Techniques, Wenhua Cao, Mary Gronberg, Stephen Bilton, Hana Baroudi, Skylar Gay, Zhongxing Liao, Karen Hoffman, Laurence E Court

Faculty, Staff and Student Publications

Background: Recent studies have shown deep learning techniques are able to predict three-dimensional (3D) dose distributions of radiotherapy treatment plans. However, their use in dose prediction for treatments with varied prescription doses including simultaneous integrated boost (SIB), that is, using multiple prescription doses within the same plan, and benefit in improving plan quality should be validated.

Purpose: To investigate the feasibility and potential benefit of using deep learning to predict dose distribution of volumetric modulated arc therapy (VMAT) including SIB techniques and improve treatment planning for patients with lung cancer.

Methods: The dose prediction model was trained with 93 retrospective …