Digital Commons Network^™

A Comparative Analysis Of Helical Tomotherapy Planning With Active Versus Total Bone Marrow Sparing Using Dual-Energy Computed Tomography, April E. Premo

Masters Projects

Purpose: This study aims to compare helical tomotherapy (HT) plans using active bone marrow (ABM) sparing contouring versus traditional bone marrow (BM) sparing contouring using dual-energy computed tomography (DECT) in the treatment of gynecologic (GYN) cancers. The goal is to evaluate the effects of using ABM contours in optimization on organs at risk (OAR) and planning target volumes (PTVs).

Methods: The study involved creating HT plans for GYN cancer patients, utilizing both ABM and BM contouring techniques. DECT was used to distinguish between active and inactive bone marrow. Dosimetric comparisons were made between BM and ABM sparing plans. Statistical analyses …

Tumour-Intrinsic Endomembrane Trafficking By Arf6 Shapes An Immunosuppressive Microenvironment That Drives Melanomagenesis And Response To Checkpoint Blockade Therapy, Yinshen Wee, Junhua Wang, Emily C Wilson, Coulson P Rich, Aaron Rogers, Zongzhong Tong, Evelyn Degroot, Y N Vashisht Gopal, Michael A Davies, H Atakan Ekiz, Joshua K H Tay, Chris Stubben, Kenneth M Boucher, Juan M Oviedo, Keke C Fairfax, Matthew A Williams, Sheri L Holmen, Roger K Wolff, Allie H Grossmann

Faculty, Staff and Student Publications

Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with …

Translational Modeling-Based Evidence For Enhanced Efficacy Of Standard-Of-Care Drugs In Combination With Anti-Microrna-155 In Non-Small-Cell Lung Cancer, Prashant Dogra, Vrushaly Shinglot, Javier Ruiz-Ramírez, Joseph Cave, Joseph D Butner, Carmine Schiavone, Dan G Duda, Ahmed O Kaseb, Caroline Chung, Eugene J Koay, Vittorio Cristini, Bulent Ozpolat, George A Calin, Zhihui Wang

Faculty, Staff and Student Publications

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.

METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.

RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg …

Plan Comparison Of Hybrid Dynamic Conformal Arc Therapy (Hdcat) And 3-Dimensional Conformal Radiation Therapy (3dcrt) In Palliative Treatment Of Thoracic Spine Tumors, Maria Juchartz

Masters Projects

Abstract

Introduction

When cancer spreads from its place of origin to a new location, it is termed ‘metastatic’. Metastatic cancer is often not curable, however palliative care can be given. One common method of palliation is in the form of radiation therapy. A common site of metastasis is in the thoracic spine, which has several nearby organs that can make treatment planning difficult. These treatments often consist of three-dimensional conformal radiotherapy methods. The purpose of this study was to compare the traditional 3DCRT techniques to a hybrid dynamic conformal arc technique. HDCAT has been used in previous studies, however none …

Kinesin Facilitates Phenotypic Targeting Of Therapeutic Resistance In Advanced Prostate Cancer, Maddison Archer, Diane Begemann, Edgar Gonzalez-Kozlova, Prerna R Nepali, Estefania Labanca, Peter Shepherd, Navneet Dogra, Nora Navone, Natasha Kyprianou

Faculty, Staff and Student Publications

Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes in patients with metastatic castration-resistant prostate cancer. Previous work showed that dynamic interconversions between epithelial-mesenchymal transition to mesenchymal-epithelial transition defines the phenotypic landscape of prostate tumors, as a potential driver of the emergence of therapeutic resistance. In this study, we use in vitro and in vivo preclinical MDA PCa patient-derived xenograft models of resistant human prostate cancer to determine molecular mechanisms of cross-resistance between antiandrogen therapy and taxane chemotherapy, underlying the therapeutically resistant phenotype. Transcriptomic profiling revealed that resistant and sensitive prostate cancer C4-2B cells have a unique differential …

Brca1-Mediated Dual Regulation Of Ferroptosis Exposes A Vulnerability To Gpx4 And Parp Co-Inhibition In Brca1-Deficient Cancers, Guang Lei, Chao Mao, Amber D Horbath, Yuelong Yan, Shirong Cai, Jun Yao, Yan Jiang, Mingchuang Sun, Xiaoguang Liu, Jun Cheng, Zhihao Xu, Hyemin Lee, Qidong Li, Zhengze Lu, Li Zhuang, Mei-Kuang Chen, Anagha Alapati, Timothy A Yap, Mien-Chie Hung, Mingjian James You, Helen Piwnica-Worms, Boyi Gan

Faculty, Staff and Student Publications

Resistance to poly (ADP-ribose) polymerase inhibitors (PARPi) limits the therapeutic efficacy of PARP inhibition in treating breast cancer susceptibility gene 1 (BRCA1)-deficient cancers. Here we reveal that BRCA1 has a dual role in regulating ferroptosis. BRCA1 promotes the transcription of voltage-dependent anion channel 3 (VDAC3) and glutathione peroxidase 4 (GPX4); consequently, BRCA1 deficiency promotes cellular resistance to erastin-induced ferroptosis but sensitizes cancer cells to ferroptosis induced by GPX4 inhibitors (GPX4i). In addition, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and defective GPX4 induction unleash potent ferroptosis in BRCA1-deficient cancer cells upon PARPi and GPX4i …

Rosiglitazone And Trametinib Exhibit Potent Anti-Tumor Activity In A Mouse Model Of Muscle Invasive Bladder Cancer, Sakina A Plumber, Tiffany Tate, Hikmat Al-Ahmadie, Xiao Chen, Woonyoung Choi, Merve Basar, Chao Lu, Aaron Viny, Ekatherina Batourina, Jiaqi Li, Kristjan Gretarsson, Besmira Alija, Andrei Molotkov, Gregory Wiessner, Byron Hing Lung Lee, James Mckiernan, David J Mcconkey, Colin Dinney, Bogdan Czerniak, Cathy Lee Mendelsohn

Faculty, Staff and Student Publications

Muscle invasive bladder cancers (BCs) can be divided into 2 major subgroups-basal/squamous (BASQ) tumors and luminal tumors. Since Pparg has low or undetectable expression in BASQ tumors, we tested the effects of rosiglitazone, Pparg agonist, in a mouse model of BASQ BC. We find that rosiglitazone reduces proliferation while treatment with rosiglitazone plus trametinib, a MEK inhibitor, induces apoptosis and reduces tumor volume by 91% after 1 month. Rosiglitazone and trametinib also induce a shift from BASQ to luminal differentiation in tumors, which our analysis suggests is mediated by retinoid signaling, a pathway known to drive the luminal differentiation program. …

Znf397 Deficiency Triggers Tet2-Driven Lineage Plasticity And Ar-Targeted Therapy Resistance In Prostate Cancer, Yaru Xu, Yuqiu Yang, Zhaoning Wang, Martin Sjöström, Yuyin Jiang, Yitao Tang, Siyuan Cheng, Su Deng, Choushi Wang, Julisa Gonzalez, Nickolas A Johnson, Xiang Li, Xiaoling Li, Lauren A Metang, Atreyi Mukherji, Quanhui Xu, Carla R Tirado, Garrett Wainwright, Xinzhe Yu, Spencer Barnes, Mia Hofstad, Yu Chen, Hong Zhu, Ariella B Hanker, Ganesh V Raj, Guanghui Zhu, Housheng H He, Zhao Wang, Carlos L Arteaga, Han Liang, Felix Y Feng, Yunguan Wang, Tao Wang, Ping Mu

Faculty, Staff and Students Publications

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our …

Lipid Droplet-Associated Hydrolase Mobilizes Stores Of Liver X Receptor Sterol Ligands And Protects Against Atherosclerosis, Young-Hwa Goo, Janeesh Plakkal Ayyappan, Francis D Cheeran, Sushant Bangru, Pradip K Saha, Paula Baar, Sabine Schulz, Todd A Lydic, Bernhard Spengler, Andreas H Wagner, Auinash Kalsotra, Vijay K Yechoor, Antoni Paul

Faculty, Staff and Students Publications

Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression …

Caspase-2 Is Essential For Proliferation And Self-Renewal Of Nucleophosmin-Mutated Acute Myeloid Leukemia, Dharaniya Sakthivel, Alexandra N Brown-Suedel, Karla E Lopez, Suruchi Salgar, Luiza E Coutinho, Francesca Keane, Shixia Huang, Kenneth Mc Sherry, Chloé I Charendoff, Kevin P Dunne, Dexter J Robichaux, Alexander Vargas-Hernández, Baochau Le, Crystal S Shin, Alexandre F Carisey, Marcin Poreba, Jonathan M Flanagan, Lisa Bouchier-Hayes

Faculty, Staff and Students Publications

Mutation in nucleophosmin (NPM1) causes relocalization of this normally nucleolar protein to the cytoplasm (NPM1c+). Despite NPM1 mutation being the most common driver mutation in cytogenetically normal adult acute myeloid leukemia (AML), the mechanisms of NPM1c+-induced leukemogenesis remain unclear. Caspase-2 is a proapoptotic protein activated by NPM1 in the nucleolus. Here, we show that caspase-2 is also activated by NPM1c+ in the cytoplasm and DNA damage–induced apoptosis is caspase-2 dependent in NPM1c+ but not in NPM1wt AML cells. Strikingly, in NPM1c+ cells, caspase-2 loss results in profound cell cycle arrest, differentiation, and down-regulation of stem cell pathways that regulate …

Parameter Estimation For Stroke Patients Using Brain Ct Perfusion Imaging With Deep Temporal Convolutional Neural Network, Shake Ibna Abir

Masters Theses & Specialist Projects

Acute ischemic stroke, caused by cerebral artery blockage, is a leading cause of long-term disability and mortality. Effective management relies on accurate, timely assessments from neuroimaging data. Computed tomography perfusion (CTP) imaging is crucial in evaluating stroke patients, offering detailed maps of cerebral perfusion to identify irreversibly damaged tissue and at-risk areas. This detailed assessment is essential for informed therapeutic decisions.

Key perfusion parameters derived from CTP imaging, including cerebral blood volume (CBV), cerebral blood flow (CBF), time to peak (TTP), and mean transit time (MTT), are crucial for understanding the extent and nature of cerebral ischemia, providing valuable insights …

Adult-Onset T-Cell Acute Lymphoblastic Lymphoma-Leukemia Presenting With Petechial Rash: A Case Report., Kelly Kimball, Vissy Elad, Edward J Hamad, Christopher Wasco

Oncology Articles

T-cell acute lymphoblastic lymphoma-leukemia (T-ALL) is a rare neoplastic disease with presenting symptoms that are often non-specific. As such, accurate diagnosis requires high clinical suspicion and assessment of bone marrow aspirate with flow cytometry and morphology. While remission is achievable in most patients, the five-year survival rate is only 48% despite treatment. The standard chemotherapy regimen is referred to as hyper-CVAD, where CVAD stands for cyclophosphamide, vincristine sulfate, Adriamycin (doxorubicin), methotrexate, and dexamethasone. In this study, we describe a 38-year-old female who presented with atraumatic abdominal bruising and a petechial rash on the upper and lower extremities. Imaging revealed a …

Lactoferrin And Lysozyme To Promote Nutritional, Clinical And Enteric Recovery: A Protocol For A Factorial, Blinded, Placebo-Controlled Randomised Trial Among Children With Diarrhoea And Malnutrition (The Boresha Afya Trial), Ruchi Tiwari, Kirkby Tickell, Emily Yoshioka, Joyce Otieno, Adeel Shah, Barbra Richardson, Lucia Keter, Maureen Okello, Churchil Nyabinda, Indi Trehan

Paediatrics and Child Health, East Africa

Introduction: Children with moderate or severe wasting are at particularly high risk of recurrent or persistent diarrhoea, nutritional deterioration and death following a diarrhoeal episode. Lactoferrin and lysozyme are nutritional supplements that may reduce the risk of recurrent diarrhoeal episodes and accelerate nutritional recovery by treating or preventing underlying enteric infections and/or improving enteric function.

Methods and analysis: In this factorial, blinded, placebo-controlled randomised trial, we aim to determine the efficacy of lactoferrin and lysozyme supplementation in decreasing diarrhoea incidence and improving nutritional recovery in Kenyan children convalescing from comorbid diarrhoea and wasting. Six hundred children aged 6–24 months with …

The Precise-Dyad Neurodevelopmental Substudy Protocol: Neurodevelopmental Risk In Children Of Mothers With Pregnancy Complications, Dorcas Magai, Jaya Chandna, Marie-Laure Volvert, Rachel Craik, Hawanatu Jah, Agnes Msoka, Amina Abubakar, Angela Koech, Grace Mwashigadi, Marleen Temmerman

Centre of Excellence in Women and Child Health

Background: Over 250 million children are not reaching their developmental potential globally. The impact of prenatal factors and their interplay with postnatal environmental factors on child neurodevelopment, is still unclear—particularly in low- and middle-income settings. This study aims to understand the impact of pregnancy complications as well as environmental, psychosocial, and biological predictors on neurodevelopmental trajectories. Open Peer Review Approval Status 1 2 version 2 (revision) 05 Aug 2024 view view version 1 09 Nov 2023 view view Kimford Meador, Stanford University School of Medicine, Palo Alto, CA,, USA 1. Page 1 of 21 Wellcome Open Research 2024, 8:508 Last …

Scaling Up, Sustaining, And Enhancing School-Based Sexuality Education Programs In Resource-Constrained And Conservative Contexts: Replicable Lessons From Positive-Deviant Countries, Chandra Mouli, Michielsen Kristien, Gogoi Aparajita, Nair M, Ziauddin Mohammed, Hadi S, Ijaz A, Rubio Auriolesh, Marleen Temmerman

Centre of Excellence in Women and Child Health

Despite considerable efforts, progress in the implementationof sexuality education (SE) has been uneven. This study identi-fied six “positive-deviant” low- and middle-income countries,i.e., countries that had scaled up, sustained and enhancedtheir SE programs when many others—in similar social, cul-tural and economic circumstances—were not able to do so. Inother words, they were significantly and consistently moresuccessful than the norm. Countries were shortlisted using avalidated framework and were analyzed using three other vali-dated frameworks on political priority setting, scaling up, andstakeholder engagement. The study found that India, Pakistan,Nigeria, Senegal, Mexico, and Uruguay had scaled up (eithernationwide or in some states/provinces), sustained andenhanced their …

Safety And Feasibility Of Third-Party Cytotoxic T Lymphocytes For High-Risk Patients With Covid-19, Dolores Grosso, John L. Wagner, Allyson O'Connor, Kaitlyn Keck, Yanping Huang, Zi-Xuan Wang, Hilary Mehler, Benjamin Leiby, Phyllis Flomenberg, Usama Gergis, Neda Nikbakht, Michael Morris, Julie Karp, Alexis R. Peedin, Neal Flomenberg

COVID-19 Papers, Posters, and Presentations

Cytotoxic T lymphocytes (CTLs) destroy virally infected cells and are critical for the elimination of viral infections such as those caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Delayed and dysfunctional adaptive immune responses to SARS-CoV-2 are associated with poor outcomes. Treatment with allogeneic SARS-CoV-2-specific CTLs may enhance cellular immunity in high-risk patients providing a safe, direct mechanism of treatment. Thirty high-risk ambulatory patients with COVID-19 were enrolled in a phase 1 trial assessing the safety of third party, SARS-CoV-2-specific CTLs. Twelve interventional patients, 6 of whom were immunocompromised, matched the HLA-A∗02:01 restriction of the CTLs and received …

379. Sglt Inhibitors: The Biology Of Sglt Inhibition With Dr. Katherine Tuttle, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

Issue 10: Pulmonary & Critical Care Insider, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 10

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The Pulmonary & Critical Care Insider newsletter was created by Dr. Bharat Bajantri, MD and Sarah Ellsworth, MLS in 2023 as a form of current awareness for current practice at our hospital, Parkview Health.

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Topics:

VIEWPOINTS:

Biologics for treating uncontrolled severe asthma

Don't you quit on cannot quit smokers.

Paxlovid may not be your magic bullet for Covid-19 infection.

ORIGINAL STUDY SUMMARY

The DanGer Trial

The ACCESS Trial

The PREOXI …

A Retrospective Comparison Between Analytical Anisotropic Algorithm (Aaa) And Acuros Xb (Axb) Calculation Algorithms Concerning The Left Anterior Descending Coronary Artery Radiation Dose In Left Breast Cancer Patients Utilizing Deep Inspiration Breath Hold, Melissa Wilkinson

Masters Projects

Abstract

Background: Minimizing radiation exposure to the left anterior descending coronary artery (LAD) is crucial during left-sided breast cancer radiation therapy to prevent cardiac complications. Dose calculation algorithms can significantly impact the estimated LAD dose. This study investigates the differences between the Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) algorithms in LAD dose calculations.

Methods: Thirty patients treated with radiation therapy after breast-conserving surgery were included. Dosimetric data for LAD, including mean and maximum dose, was calculated using AAA and AXB algorithms. The results were compared using statistical analysis.

Results: Statistically significant reductions in mean LAD dose were observed …

High-Dose Intravenous Vitamin C Combined With Docetaxel In Men With Metastatic Castration-Resistant Prostate Cancer: A Randomized Placebo-Controlled Phase Ii Trial, Channing Paller, Marianna Zahurak, Adel Mandl, Nicole Metri, Aliya Lalji, Elisabeth Heath, William Kelly, Christopher Hoimes, Pedro Barata, Jason Taksey, Dominique Garrison, Kartick Patra, Ginger Milne, Nicole Anders, Julie Nauroth, Jennifer Durham, Catherine Marshall, Mark Markowski, Mario Eisenberger, Emmanuel Antonarakis, Michael Carducci, Samuel Denmeade, Mark Levine

Department of Medicine Faculty Papers

UNLABELLED: High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate …

Development Of An Egg-Specific Mass Spectrometry Targeted Method For Processed Food Matrices, Liyun Zhang

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Egg is a major food allergen in the United States, causing symptoms from mild reactions to severe anaphylaxis. An egg-free diet remains the only management approach for egg allergy. Therefore, individuals and families living with egg allergies rely heavily on allergen statements on packaged food products for informed food choices. Currently, no labeling regulations exist for unintentionally introduced allergens, posing risks to consumers with egg allergies. Therefore, it is critical to have an accurate and reliable detection method in allergen control and management to determine the concentration of total protein from allergenic food sources. Traditional enzyme-linked immunosorbent assays are routinely …

Child And Caregiver’ Perspective On Barriers To Asthma Management At A Tertiary Referral Hospital In Kenya, Joan Kwesigabo Ahimbisibwe

Master of Medicine in Paediatrics and Child Health

Background: Asthma is one of the most common chronic conditions in children, with significant morbidity and mortality, especially in Africa. Achieving adequate asthma control in children remains challenging due to gaps between standard recommended management strategies and treatment practices. This study explored barriers to asthma management as perceived by children and their caregivers in a private tertiary care setting in Kenya.

Methods: An exploratory phenomenological qualitative study was conducted at Aga Khan University Hospital (AKUH), Nairobi. Children aged 6–18 years with a confirmed diagnosis of asthma and their caregivers were recruited. Participants had been receiving treatment for at …

Genomic Insights Into Pediatric Intestinal Inflammatory And Eosinophilic Disorders Using Single-Cell Rna-Sequencing., Marissa R. Keever-Keigher, Lisa Harvey, Veronica Williams, Carrie A Vyhlidal, Atif A Ahmed, Jeffrey J. Johnston, Daniel A. Louiselle, Elin Grundberg, Tomi Pastinen, Craig A. Friesen, Rachel Chevalier, Craig Smail, Valentina Shakhnovich

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis.

METHODS: This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potential markers of …

Women's Experience Of Cancer Treatment During Covid-19 On The Texas-Mexico Border, Kayla E. Castañeda

Nursing Theses and Dissertations

The COVID-19 pandemic exposed existing racial, ethnic, socioeconomic, geographic, and gender disparities in cancer care and highlighted the need for more research in understudied populations. No studies have elucidated the experience of women living on the Texas-Mexico border receiving cancer treatment during the pandemic. This study explored the lived experience of receiving cancer treatment during the COVID-19 pandemic in 2020 for women living on the Texas-Mexico border and identified participants' self-identified unmet needs while receiving cancer treatment during the COVID-19 pandemic on the Texas-Mexico border. Following IRB approval and informed consent, ten women living on the Texas-Mexico border who received …

Association Between Time From Surgery To Radiation Therapy And Multimodality Treatment Outcomes In Hpv+ Head And Neck Cancer: A Multi-Institutional Cohort Experience, Muneeb Niazi, Ryan Miller, Ryann Kolb, Wenyan Ji, Alicia Lozano, Monica Ahrens, Alexandra Hanlon, Max Pickles, Andrew Song, Voichita Bar-Ad, Neil Hockstein, Sujung Park, Adam Raben, Gaurav Shukla

Department of Radiation Oncology Faculty Papers

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. Methods: We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time …

Preschool Executive Control And Adolescent Dietary Outcomes: Highlighting The Role Of Context, Marla Lopez

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Research has identified executive control (EC) as an important predictor of dietary outcomes among youth. Executive control in preschool age has been shown to predict important outcomes across development for youth, indicating that good, foundational EC abilities are associated with successful development in later life. Dietary outcomes across adolescence, an important transitional period for establishing healthy eating behaviors, are understudied. Therefore, the current study sought to link two critical developmental periods, examining how preschool EC is associated with dietary trajectories across adolescence. Further, the study aimed to identify how contextual factors, specifically indices of socio-economic status and the home and …

Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between …

Poly(Adp-Ribose) Polymerase-1 Regulates Pyroptosis Independent Function Of Nlrp3 Inflammasome In Neutrophil Extracellular Trap Formation, Louis J Delinois, Atul Sharma, Ashwin K Ramesh, Laurel D Boatright, Qun Li, Rong Xu, Hongbo R Luo, Bibhuti B Mishra, Jyotika Sharma

Faculty, Staff and Student Publications

Neutrophil extracellular traps (NETs) function to control infectious agents as well as to propagate inflammatory response in a variety of disease conditions. DNA damage associated with chromatin decondensation and NACHT domain-leucine-rich repeat-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation have emerged as crucial events in NET formation, but the link between the two processes is unknown. In this study, we demonstrate that poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, regulates NET formation triggered by NLRP3 inflammasome activation in neutrophils. Activation of mouse neutrophils with canonical NLRP3 stimulants LPS and nigericin induced NET formation, which was significantly abrogated by pharmacological …

Mechanism And Rational Combinations With Gp-2250, A Novel Oxathiazine Derivative, In Ovarian Cancer, Mark S Kim, Deanna Glassman, Katelyn F Handley, Adrian Lankenau Ahumada, Nicholas B Jennings, Emine Bayraktar, Katherine Foster, Robiya Joseph, Sanghoon Lee, Robert L Coleman, Anil K Sood

Faculty, Staff and Student Publications

BACKGROUND: GP-2250, a novel analog of taurultam (TRLT), has emerged as a potent anti-neoplastic drug; however, the mechanisms underlying its effects are not well understood. Here, we investigated the mechanism of action and the biological effects of GP-2250 using in vitro and in vivo models.

METHODS: We carried out a series of in vitro (MTT assay, Annexin V/PI assay, colony formation assay, reverse-phase protein array [RPPA], and HRLC/IC analysis) to determine the biological activity of GP-2250 and investigate the mechanism of action. In vivo experiments were carried out to determine the therapeutic efficacy of GP-2250 alone and in combination with …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …