Life Sciences Commons^™

Encouraging Or Guilt-Inducing? An Analysis Of Fitspiration Content And Its Effect On Body Image And Lifestyle Changes, Brenna Mazour

Honors Program: Senior Projects (Public)

More people are acquiring their nutrition and exercise information from social media accounts called fitspiration. Analyses of fitspiration content have found the focus to be on restrictive diets and excessive exercise that’s appearance driven. Although its intent is to inspire its consumers to change their lifestyle, many speculate that it brings upon negative body image and induces guilt. The Theory of Planned Behavior (TPB) has been used to determine why people take part in certain health behaviors, such as diets or exercise regimens posted on fitspiration. TPB shows how the characteristics of social media discourage people to use fitspiration as …

Dysphagia And Shortness-Of-Breath As Markers For Treatment Failure And Survival In Oropharyngeal Cancer After Radiation, Jarey H Wang, Vivian Salama, Lance Mccoy, Cem Dede, Temitayo Ajayi, Amy Moreno, Abdallah S R Mohamed, Katherine A Hutcheson, Clifton David Fuller, Lisanne V Van Dijk, Md Anderson Head And Neck Symptom Working Group

Faculty, Staff and Student Publications

Background: Post-treatment symptoms are a focal point of follow-up visits for head and neck cancer patients. While symptoms such as dysphagia and shortness-of-breath early after treatment may motivate additional work up, their precise association with disease control and survival outcomes is not well established.

Methods: This prospective data cohort study of 470 oropharyngeal cancer patients analyzed patient-reported swallowing, choking and shortness-of-breath symptoms at 3-to-6 months following radiotherapy to evaluate their association with overall survival and disease control. Associations between the presence of moderate-to-severe swallowing, choking and mild-to-severe shortness-of-breath and treatment outcomes were analyzed via Cox regression and Kaplan-Meier. The main …

Predictors Of Emergency Room Visits After Ambulatory Breast Cancer Surgery In The Medicare Population, Susie X Sun, Zhigang Duan, Henry M Kuerer, Sarah M Desnyder, Carrie Cunningham, Hui Zhao, Sharon H Giordano

Faculty, Staff and Student Publications

Background: Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery.

Patients and methods: Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well …

Mitochondrial Structure And Function Adaptation In Residual Triple Negative Breast Cancer Cells Surviving Chemotherapy Treatment, Mokryun L Baek, Junegoo Lee, Katherine E Pendleton, Mariah J Berner, Emily B Goff, Lin Tan, Sara A Martinez, Iqbal Mahmud, Tao Wang, Matthew D Meyer, Bora Lim, James P Barrish, Weston Porter, Philip L Lorenzi, Gloria V Echeverria

Faculty, Staff and Student Publications

Neoadjuvant chemotherapy (NACT) used for triple negative breast cancer (TNBC) eradicates tumors in ~45% of patients. Unfortunately, TNBC patients with substantial residual cancer burden have poor metastasis free and overall survival rates. We previously demonstrated mitochondrial oxidative phosphorylation (OXPHOS) was elevated and was a unique therapeutic dependency of residual TNBC cells surviving NACT. We sought to investigate the mechanism underlying this enhanced reliance on mitochondrial metabolism. Mitochondria are morphologically plastic organelles that cycle between fission and fusion to maintain mitochondrial integrity and metabolic homeostasis. The functional impact of mitochondrial structure on metabolic output is highly context dependent. Several chemotherapy agents …

Highly Synchronized Cortical Circuit Dynamics Mediate Spontaneous Pain In Mice, Weihua Ding, Lukas Fischer, Qian Chen, Ziyi Li, Liuyue Yang, Zerong You, Kun Hu, Xinbo Wu, Xue Zhou, Wei Chao, Peter Hu, Tewodros Mulugeta Dagnew, Daniel M Dubreuil, Shiyu Wang, Suyun Xia, Caroline Bao, Shengmei Zhu, Lucy Chen, Changning Wang, Brian Wainger, Peng Jin, Jianren Mao, Guoping Feng, Mark T Harnett, Shiqian Shen

Faculty, Staff and Student Publications

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized …

On Target Methods To Induce Abscopal Phenomenon For Off-Target Effects: From Happenstance To Happenings, Blessie Elizabeth Nelson, Jacob J Adashek, Steven H Lin, Vivek Subbiah

Faculty, Staff and Student Publications

Although the "abscopal phenomenon" has been described several decades ago, this phenomenon lately has been obtaining momentous traction with the dawn of immune-based therapies. There has been increased cross talk among radiation oncologists, oncologists and immunologists and consequently a surge in the number of prospective clinical trials. This must be coupled with translation work from these clinical trials to aid in eventual identification of patients who may benefit. Abscopal effects may be induced by local and systemic methods, conventional radiotherapy, particle radiation, radionucleotide methods, cryoablation and brachytherapy. These approaches have all been reported to be stimulate abscopal effect. Immune induction …

Integrative Bioinformatic Analysis Of P53 And Pathway Alterations In Two Different Lung Cancer Subtypes, Yun Zhang, Abie Williams-Villalobo, Jyotsna D Godavarthi, Faith Shakoor, Shunbin Xiong, Bin Liu

Faculty, Staff and Student Publications

Whether p53, either wild type (WT) or mutant, plays cell-specific or uniform role remains controversial. Using The Cancer Genome Atlas, we examined p53 in the lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), two lung cancers with different cellular origins and frequent p53 mutation (52% and 83%, respectively). Mutant p53 more strongly correlates with different genomic alteration and protein expression profiles in LUAD than in LUSC. p53 mutation in LUAD and LUSC is associated with multiple exacerbated clinical outcomes. Although the presence of p53 mutation does not change the survival of LUAD patients, LUSC patients containing p53 mutation exhibit …

Adding The X-Ray Bragg Reflection Physical Process In Crystal To The Geant4 Monte Carlo Simulation Toolkit, Part I: Reflection From A Crystal Slab, Fada Guan, Makoto Asai, Dirk A Bartkoski, Michael Kleckner, Ze'ev Harel, Mohammad Salehpour

Faculty, Staff and Student Publications

X-ray diffraction from a solid crystal shows the wave nature of photons. It is an important electromagnetic (EM) physics process when X-ray photons interact with a crystal. Bragg diffraction, often called Bragg reflection, is a special case of the general form of X-ray diffraction, known as Laue diffraction. When the Bragg's law is met, the incident photon beam is reflected from the crystal plane behaving as a specular reflection at the Bragg angle. However, the Bragg reflection physical process has not been integrated into the general-purpose Monte Carlo simulation toolkit Geant4 for particle physics. In the current study, we developed …

Impact Of High Neutrophil-To-Lymphocyte Ratio On Survival In Hospitalized Cancer Patients With Covid-19, Fernando A Díaz-Couselo, Santiago Flagel, Carla Nicolini, Sebastián Halac, Natalia Manzano, Marina Aguirre, Juan Rébora, Sandra Valle, Laura Noro, Chirayu Mohindroo, Florencia Mcallister, Marcelo Zylberman

Faculty, Staff and Student Publications

Neutrophil-to-lymphocyte ratio (NLR) has been studied as a prognostic factor for mortality in COVID-19 patients. Our study aimed to evaluate the association between NLR at COVID-19 diagnosis and survival during the following 90 days in hospitalized patients with solid cancer. Between May 2020 and June 2021, 120 patients were included in a retrospective cohort study. Univariable analysis showed patients with an NLR > 8.3 were associated with an increased risk of death (HR: 4.34; 95% CI: 1.74-10.84) compared to patients with NLR < 3.82 and with NLR ≥3.82 and ≤8.30 (HR: 2.89; 95% CI: 1.32-6.36). Furthermore, on multivariable analysis, NLR > 8.30 independently correlated with increased mortality. In patients with solid malignancies with COVID-19, an NLR > 8.3 is associated with …

Multi-Ancestry Genome-Wide Association Analyses Improve Resolution Of Genes And Pathways Influencing Lung Function And Chronic Obstructive Pulmonary Disease Risk, Nick Shrine, Abril G Izquierdo, Jing Chen, Richard Packer, Robert J Hall, Anna L Guyatt, Chiara Batini, Rebecca J Thompson, Chandan Pavuluri, Vidhi Malik, Brian D Hobbs, Matthew Moll, Wonji Kim, Ruth Tal-Singer, Per Bakke, Katherine A Fawcett, Catherine John, Kayesha Coley, Noemi Nicole Piga, Alfred Pozarickij, Kuang Lin, Iona Y Millwood, Zhengming Chen, Liming Li, China Kadoorie Biobank Collaborative Group, Sara R A Wijnant, Lies Lahousse, Guy Brusselle, Andre G Uitterlinden, Ani Manichaikul, Elizabeth C Oelsner, Stephen S Rich, R Graham Barr, Shona M Kerr, Veronique Vitart, Michael R Brown, Matthias Wielscher, Medea Imboden, Ayoung Jeong, Traci M Bartz, Sina A Gharib, Claudia Flexeder, Stefan Karrasch, Christian Gieger, Annette Peters, Beate Stubbe, Xiaowei Hu, Victor E Ortega, Deborah A Meyers, Eugene R Bleecker, Stacey B Gabriel, Namrata Gupta, Albert Vernon Smith, Jian'an Luan, Jing-Hua Zhao, Ailin F Hansen, Arnulf Langhammer, Cristen Willer, Laxmi Bhatta, David Porteous, Blair H Smith, Archie Campbell, Tamar Sofer, Jiwon Lee, Martha L Daviglus, Bing Yu, Elise Lim, Hanfei Xu, George T O'Connor, Gaurav Thareja, Omar M E Albagha, Qatar Genome Program Research (Qgpr) Consortium, Karsten Suhre, Raquel Granell, Tariq O Faquih, Pieter S Hiemstra, Annelies M Slats, Benjamin H Mullin, Jennie Hui, Alan James, John Beilby, Karina Patasova, Pirro Hysi, Jukka T Koskela, Annah B Wyss, Jianping Jin, Sinjini Sikdar, Mikyeong Lee, Sebastian May-Wilson, Nicola Pirastu, Katherine A Kentistou, Peter K Joshi, Paul R H J Timmers, Alexander T Williams, Robert C Free, Xueyang Wang, John L Morrison, Frank D Gilliland, Zhanghua Chen, Carol A Wang, Rachel E Foong, Sarah E Harris, Adele Taylor, Paul Redmond, James P Cook, Anubha Mahajan, Lars Lind, Teemu Palviainen, Terho Lehtimäki, Olli T Raitakari, Jaakko Kaprio, Taina Rantanen, Kirsi H Pietiläinen, Simon R Cox, Craig E Pennell, Graham L Hall, W James Gauderman, Chris Brightling, James F Wilson, Tuula Vasankari, Tarja Laitinen, Veikko Salomaa, Dennis O Mook-Kanamori, Nicholas J Timpson, Eleftheria Zeggini, Josée Dupuis, Caroline Hayward, Ben Brumpton, Claudia Langenberg, Stefan Weiss, Georg Homuth, Carsten Oliver Schmidt, Nicole Probst-Hensch, Marjo-Riitta Jarvelin, Alanna C Morrison, Ozren Polasek, Igor Rudan, Joo-Hyeon Lee, Ian Sayers, Emma L Rawlins, Frank Dudbridge, Edwin K Silverman, David P Strachan, Robin G Walters, Andrew P Morris, Stephanie J London, Michael H Cho, Louise V Wain, Ian P Hall, Martin D Tobin

Faculty, Staff and Student Publications

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of …

Causes Of Clonal Hematopoiesis: A Review, Lijin Joo, Catherine C Bradley, Steven H Lin, Paul A Scheet, Kevin T Nead

Faculty, Staff and Student Publications

PURPOSE OF REVIEW: Clonal hematopoiesis (CH) is an age-dependent process detectable using advanced sequencing technologies and is associated with multiple adverse health outcomes including cardiovascular disease and cancer. The purpose of this review is to summarize known causes of CH mutations and to identify key areas and considerations for future research on CH.

RECENT FINDINGS: Studies have identified multiple potential causes of CH mutations including smoking, cancer therapies, cardiometabolic disease, inflammation, and germline risk factors. Additionally, large-scale studies have facilitated the identification of gene-specific effects of CH mutation risk factors that may have unique downstream health implications. For example, cancer …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Immune And Pathologic Responses In Patients With Localized Prostate Cancer Who Received Daratumumab (Anti-Cd38) Or Edicotinib (Csf-1r Inhibitor), Bilal A Siddiqui, Brian F Chapin, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Ai-Di Gu, Alexsandra B Espejo, Michelle Kinder, Curtis A Pettaway, John F Ward, Rebecca S S Tidwell, Patricia Troncoso, Paul G Corn, Christopher J Logothetis, Roland Knoblauch, Natalie Hutnick, Marco Gottardis, Charles G Drake, Padmanee Sharma, Sumit K Subudhi

Faculty, Staff and Student Publications

BACKGROUND: The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.

HYPOTHESIS: Daratumumab or edicotinib will be safe and …

Respiratory And Cardiometabolic Comorbidities And Stages I To Iii Nsclc Survival: A Pooled Analysis From The International Lung Cancer Consortium, Miguel García-Pardo, Amy Chang, Sabine Schmid, Mei Dong, M Catherine Brown, David Christiani, Hilary Aurora Tindel, Paul Brennan, Chu Chen, Jie Zhang, Brid M Ryan, David Zaridze, Matthew B Schabath, Leticia Ferro Leal, Rui Manuel Reis, Adonina Tardon, Guillermo Fernández-Tardon, Sanjay S Shete, Angeline Andrew, Hermann Brenner, Wei Xu, Rayjean J Hung, Geoffrey Liu

Faculty, Staff and Student Publications

INTRODUCTION: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

METHODS: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection.

RESULTS: OS analyses used patients with NSCLC with respiratory health …

Factors That Influence Treatment Decisions: A Qualitative Study Of Racially And Ethnically Diverse Patients With Low- And Very-Low Risk Prostate Cancer, Alice Guan, Janet K Shim, Laura Allen, Mei-Chin Kuo, Kathie Lau, Zinnia Loya, James D Brooks, Peter R Carroll, Iona Cheng, Benjamin I Chung, Mindy C Derouen, Dominic L Frosch, Todd Golden, John T Leppert, Daphne Y Lichtensztajn, Qian Lu, Debora L Oh, Weiva Sieh, Michelle Wadhwa, Scarlett L Gomez, Salma Shariff-Marco

Faculty, Staff and Student Publications

BACKGROUND: Factors that influence prostate cancer treatment decisions are complex, multifaceted, and personal, and may vary by race/ethnicity. Although research has been published to quantify factors involved in decision-making, these studies have been limited to primarily white, and to a lesser extent, Black patients, and quantitative studies are limited for discerning the cultural and contextual processes that shape decision-making.

METHODS: We conducted 43 semi-structured interviews with a racially and ethnically diverse sample of patients diagnosed with low- and very-low risk prostate cancer who had undergone treatment for their prostate cancer. Interviews were transcribed, independently coded, and analyzed to identify themes …

Aapm Medical Physics Practice Guideline 13a: Hdr Brachytherapy, Part A, Susan L Richardson, Ivan M Buzurovic, Gil'ad N Cohen, Wesley S Culberson, Claire Dempsey, Bruce Libby, Christopher S Melhus, Robin A Miller, Daniel J Scanderbeg, Samantha J Simiele

Faculty, Staff and Student Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their …

Temporal Multi-Step Predictive Modeling Of Remission In Major Depressive Disorder Using Early Stage Treatment Data; Star*D Based Machine Learning Approach, Haitham Salem, Tung Huynh, Natasha Topolski, Benson Mwangi, Madhukar H Trivedi, Jair C Soares, A John Rush, Sudhakar Selvaraj

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …

Risk Analysis Of The Unity 15 T Mr-Linac Adapt-To-Position Workflow, Jiayi Liang, Paola Godoy Scripes, Neelam Tyagi, Ergys Subashi, Theresa Wunner, Nicolas Cote, Ching-Yun Chan, Angela Ng, Victoria Brennan, Kaveh Zakeri, Cassandra Wildberger, James Mechalakos

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps.

METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was …

Persistent Nociceptor Hyperactivity As A Painful Evolutionary Adaptation, Edgar T Walters, Robyn J Crook, G Gregory Neely, Theodore J Price, Ewan St John Smith

Faculty, Staff and Student Publications

Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal …

Dosimetric Response Of Gafchromic™ Ebt-Xd Film To Therapeutic Protons, Fada Guan, Xiaochun Wang, Ming Yang, Emily Draeger, Dae Han, Kiminori Iga, Fanqing Guo, Luis Perles, Yuting Li, Narayan Sahoo, Radhe Mohan, Zhe Chen

Faculty, Staff and Student Publications

The EBT-XD model of Gafchromic™ films has a broader optimal dynamic dose range, up to 40 Gy, compared with its predecessor models. This characteristic has made EBT-XD films suitable for high-dose applications, such as stereotactic body radiotherapy and stereotactic radiosurgery, as well as ultra-high dose rate FLASH radiotherapy. The purpose of the current study was to characterize the dependence of EBT-XD film response on linear energy transfer (LET) and dose rate of therapeutic protons from a synchrotron. A clinical spot-scanning proton beam was used to study LET dependence at three dose-averaged LET values of 1.0 keV/μm, 3.6 keV/μm, and 7.6 …

The Effect Direction Should Be Taken Into Account When Assessing Small-Study Effects, Zhuo Meng, Chong Wu, Lifeng Lin

Faculty, Staff and Student Publications

OBJECTIVE: Studies with statistically significant results are frequently more likely to be published than those with non-significant results. This phenomenon leads to publication bias or small-study effects and can seriously affect the validity of the conclusion from systematic reviews and meta-analyses. Small-study effects typically appear in a specific direction, depending on whether the outcome of interest is beneficial or harmful, but this direction is rarely taken into account in conventional methods.

METHODS: We propose to use directional tests to assess potential small-study effects. The tests are built on a one-sided testing framework based on the existing Egger's regression test. We …

Macrophage-Derived Mlkl In Alcohol-Associated Liver Disease: Regulation Of Phagocytosis, Xiaoqin Wu, Xiude Fan, Megan R Mcmullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z Day, Josiah E Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S Allende, Arthur J Mccullough, Jon M Jacobs, Daniel M Rotroff, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury.

APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced …

Mutant Npm1 Hijacks Transcriptional Hubs To Maintain Pathogenic Gene Programs In Acute Myeloid Leukemia, Xue Qing David Wang, Dandan Fan, Qinyu Han, Yiman Liu, Hongzhi Miao, Xinyu Wang, Qinglan Li, Dong Chen, Haley Gore, Pamela Himadewi, Gerd P Pfeifer, Tomasz Cierpicki, Jolanta Grembecka, Jianzhong Su, Shasha Chong, Liling Wan, Xiaotian Zhang

Faculty, Staff and Student Publications

Nucleophosmin (NPM1) is a ubiquitously expressed nucleolar protein with a wide range of biological functions. In 30% of acute myeloid leukemia (AML), the terminal exon of NPM1 is often found mutated, resulting in the addition of a nuclear export signal and a shift of the protein to the cytoplasm (NPM1c). AMLs carrying this mutation have aberrant expression of the HOXA/B genes, whose overexpression leads to leukemogenic transformation. Here, for the first time, we comprehensively prove that NPM1c binds to a subset of active gene promoters in NPM1c AMLs, including well-known leukemia-driving genes—HOXA/B cluster genes and MEIS1. NPM1c sustains …

Clinical Outcomes Of Combined Cervical And Transthoracic Surgical Approaches In Patients With Advanced Thyroid Cancer, Jared A Shenson, Mark E Zafereo, Mark Lee, Kevin J Contrera, Lei Feng, Mongkol Boonsripitayanon, Neil Gross, Ryan Goepfert, Anastasios Maniakas, Jennifer Rui Wang, Libby Grubbs, Ara Vaporciyan, Wayne Hofstetter, Stephen Swisher, Reza Mehran, David Rice, Boris Sepesi, Mara Antonoff, Maria Cabanillas, Naifa Busaidy, Ramona Dadu, Natalie L Silver

Faculty, Staff and Student Publications

Background: Advanced thyroid disease involving the mediastinum may be managed surgically with a combined transcervical and transthoracic approach. Contemporary analysis of this infrequently encountered cohort will aid the multidisciplinary team in personalizing treatment approaches.

Methods: Retrospective review of patients undergoing combined transcervical and transthoracic surgery for thyroid cancer at a single high-volume institution from 1994 to 2015.

Results: Thirty-eight patients with median age 59 years (range 28-76) underwent surgery without perioperative mortality. Most patients had primary disease. A majority had distant metastases outside the mediastinum but had locoregionally curable disease. Common complications were temporary (39%) and permanent (18%) hypoparathyroidism, and …

Impact Of Dose Calculation Accuracy On Inverse Linear Energy Transfer Optimization For Intensity-Modulated Proton Therapy, Mei Chen, Wenhua Cao, Pablo Yepes, Fada Guan, Falk Poenisch, Cheng Xu, Jiayi Chen, Yupeng Li, Ivan Vazquez, Ming Yang, X Ronald Zhu, Xiaodong Zhang

Faculty, Staff and Student Publications

Objective: To determine the effect of dose calculation accuracy on inverse linear energy transfer (LET) optimization for intensity-modulated proton therapy, and to determine whether adding more beams would improve the plan robustness to different dose calculation engines.

Methods: Two sets of intensity-modulated proton therapy plans using two, four, six, and nine beams were created for 10 prostate cancer patients: one set was optimized with dose constraints (DoseOpt) using the pencil beam (PB) algorithm, and the other set was optimized with additional LET constraints (LETOpt) using the Monte Carlo (MC) algorithm. Dose distributions of DoseOpt plans were then recalculated using the …

The Microbiome And Its Impact On Allogeneic Hematopoietic Cell Transplantation, Florent Malard, Robert R Jenq

Faculty, Staff and Student Publications

Allogeneic hematopoietic cell transplantation (alloHCT) is a standard curative therapy for a variety of benign and malignant hematological diseases. Previously, patients who underwent alloHCT were at high risk for complications with potentially life-threatening toxicities, including a variety of opportunistic infections as well as acute and chronic manifestations of graft-versus-host disease (GVHD), where the transplanted immune system can produce inflammatory damage to the patient. With recent advances, including newer conditioning regimens, advances in viral and fungal infection prophylaxis, and novel GVHD prophylactic and treatment strategies, improvements in clinical outcomes have steadily improved. One modality with great potential that has yet to …

Deep Learning-Based Pathology Image Analysis Predicts Cancer Progression Risk In Patients With Oral Leukoplakia, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Roberta Rayra Martins-Chaves, Ricardo Santiago Gomez, Nadarajah Vigneswaran, Arunangshu Sarkar, William N William, Vassiliki Papadimitrakopoulou, Michelle Williams, Diana Bell, Doreen Palsgrove, Justin Bishop, John V Heymach, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Scott M Lippman, Curtis Rg Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

BACKGROUND: Oral leukoplakia (OL) is associated with an increased risk for oral cancer (OC) development. Prediction of OL cancer progression may contribute to decreased OC morbidity and mortality by favoring early intervention. Current OL progression risk assessment approaches face large interobserver variability and is weakly prognostic. We hypothesized that convolutional neural networks (CNN)-based histology image analyses could accelerate the discovery of better OC progression risk models.

METHODS: Our CNN-based oral mucosa risk stratification model (OMRS) was trained to classify a set of nondysplastic oral mucosa (OM) and a set of OC H&E slides. As a result, the OMRS model could …

Use Of Contrast Media During Ct-Guided Thermal Ablation Of Colorectal Liver Metastasis For Procedure Planning Is Associated With Improved Immediate Outcomes, Iwan Paolucci, Yuan-Mao Lin, A Kyle Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to analyze the impact of using intra-procedural pre-ablation contrast-enhanced CT prior to percutaneous thermal ablation (pre-ablation CECT) of colorectal liver metastases (CLM) on local outcomes.

MATERIALS AND METHODS: This retrospective analysis of a prospectively collected liver ablation registry included 144 consecutive patients (median age 57 years IQR [49, 65], 60% men) who underwent 173 CT-guided ablation sessions for 250 CLM between October 2015 and March 2020. In addition to oncologic outcomes, technical success was retrospectively evaluated using a biomechanical deformable image registration software for 3D-minimal ablative margin (3D-MAM) quantification. Bayesian regression was used …

Physician Perspectives On Telemedicine In Radiation Oncology, Sean Maroongroge, Brian De, Kristina D Woodhouse, Roland L Bassett, Percy Lee, Elizabeth S Bloom, Grace L Smith, Steven J Frank, Jing Li, George Perkins, Prajnan Das, Albert C Koong, Benjamin D Smith, Chenyang Wang

Faculty, Staff and Student Publications

PURPOSE: Telemedicine enthusiasm and uptake in radiation oncology rapidly increased during the COVID-19 pandemic, but it is unclear if and how telemedicine should be used after the COVID-19 public health emergency ends is unclear. Herein, we report on our institution's provider experience after the mature adoption of telemedicine.

METHODS AND MATERIALS: We distributed a survey to all radiation oncology attending physicians at our institution in October 2021 to assess satisfaction, facilitators, and barriers to telemedicine implementation. We performed quantitative and qualitative analyses to characterize satisfaction and identify influencing factors whether telemedicine is employed. We calculated the average proportion of visits …

High Pulse Pressure Impairs Cerebral Artery Endothelial Function In Young, But Not Old, Mice, Nick R Winder, Emily H Reeve, Elise K Kronquist, Aleena Khurana, Byron Lee, Thuan Nguyen, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent …