Medicine and Health Sciences Commons^™

Phosphorylation Of Ahr By Plk1 Promotes Metastasis Of Luad Via Dio2-Th Signaling, Chaohao Li, Derek B. Allison, Daheng He, Fengyi Mao, Xinyi Wang, Piotr G. Rychahou, Ibrahim A. Imam, Yifan Kong, Qiongsi Zhang, Yanquan Zhang, Jinghui Liu, Ruixin Wang, Xiongjian Rao, Sai Wu, B. Mark Evers, Qing Shao, Chi Wang, Zhiguo Li, Xiaoqi Liu

Markey Cancer Center Faculty Publications

Metastasis of lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR), an important transcription factor, is involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, acts as an oncogene promoting the malignancy of multiple cancer types. However, the interaction between these two factors and their significance in lung cancer remain to be determined. In this study, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, leading to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses reveal that type 2 deiodinase (DIO2) is responsible for EMT and …

Synthetic Contraceptive Hormones Occlude The Ability Of Nicotine To Reduce Ethanol Consumption In Ovary-Intact Female Rats, Erin E. Maher, Ashley M. White, Ashley Craig, Shailesh N. Khatri, Percell T. Kendrick Jr., Mary E. Matocha, Emma O. Bondy, Nikhil Pallem, Grace W. Breakfield, Madison Botkins, Olivia Sweatt, William C. Griffin, Brent A. Kaplan, Jessica Jane Weafer, Joshua S. Beckmann, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Rates of tobacco and alcohol use in women are rising, and women are more vulnerable than men to escalating tobacco and alcohol use. Many women use hormonal birth control, with the oral contraceptive pill being the most prevalent. Oral contraceptives contain both a progestin (synthetic progesterone) and a synthetic estrogen (ethinyl estradiol; EE) and are contraindicated for women over 35 years who smoke. Despite this, no studies have examined how synthetic contraceptive hormones impact this pattern of polysubstance use in females. To address this critical gap in the field, we treated ovary-intact female rats with either sesame oil (vehicle), the …

Environmental Contamination Contributing To The Spread Of Vancomycin-Resistant Enterococci In Nursing Homes, Catherine Vaziri, Charles Darkoh

Faculty, Staff and Student Publications

No abstract provided.

Mosaic Chromosomal Alterations In Blood Across Ancestries Using Whole-Genome Sequencing, Yasminka A Jakubek, Ying Zhou, Adrienne Stilp, Jason Bacon, Justin W Wong, Zuhal Ozcan, Donna Arnett, Kathleen Barnes, Joshua C Bis, Eric Boerwinkle, Jennifer A Brody, April P Carson, Daniel I Chasman, Jiawen Chen, Michael Cho, Matthew P Conomos, Nancy Cox, Margaret F Doyle, Myriam Fornage, Xiuqing Guo, Sharon L R Kardia, Joshua P Lewis, Ruth J F Loos, Xiaolong Ma, Mitchell J Machiela, Taralynn M Mack, Rasika A Mathias, Braxton D Mitchell, Josyf C Mychaleckyj, Kari North, Nathan Pankratz, Patricia A Peyser, Michael H Preuss, Bruce Psaty, Laura M Raffield, Ramachandran S Vasan, Susan Redline, Stephen S Rich, Jerome I Rotter, Edwin K Silverman, Jennifer A Smith, Aaron P Smith, Margaret Taub, Kent D Taylor, Jeong Yun, Yun Li, Pinkal Desai, Alexander G Bick, Alexander P Reiner, Paul Scheet, Paul L Auer

Faculty, Staff and Student Publications

Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. …

Supportive Care For Dual Caregivers Who Care For Their Partner With Cancer And Their Young Children, Sujin Ann-Yi, Kathrin Milbury, Morgan Jones, Victoria Necroto, Meagan Whisenant, Yisheng Li, Eduardo Bruera

Faculty, Staff and Student Publications

Purpose: Advanced cancer patients and their spouses who parent minor children report parenting concerns and increased psychological distress. This single-arm trial examined the feasibility and initial evidence for efficacy of a novel parent support program.

Methods: Patients with a metastatic solid malignancy and their spouses completed self-reported assessments of psychological distress (HADS), parenting concerns (PCQ) and efficacy (CaPSE) at baseline. Both patients and spouses jointly attended the first two sessions addressing illness communication and family routines. Spouses individually attended two additional sessions focusing on caregiver support and death preparedness. All four sessions were delivered via videoconference by a licensed psychological …

Genome-Wide Interaction Analysis Of Folate For Colorectal Cancer Risk, Emmanouil Bouras, Andre E Kim, Yi Lin, John Morrison, Mengmeng Du, Demetrius Albanes, Elizabeth L Barry, James W Baurley, Sonja I Berndt, Stephanie A Bien, Timothy D Bishop, Hermann Brenner, Arif Budiarto, Andrea Burnett-Hartman, Peter T Campbell, Robert Carreras-Torres, Graham Casey, Tjeng Wawan Cenggoro, Andrew T Chan, Jenny Chang-Claude, David V Conti, Michelle Cotterchio, Matthew Devall, Virginia Diez-Obrero, Niki Dimou, David A Drew, Jane C Figueiredo, Graham G Giles, Stephen B Gruber, Marc J Gunter, Tabitha A Harrison, Akihisa Hidaka, Michael Hoffmeister, Jeroen R Huyghe, Amit D Joshi, Eric S Kawaguchi, Temitope O Keku, Anshul Kundaje, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M Lynch, Bharuno Mahesworo, Satu Männistö, Victor Moreno, Neil Murphy, Polly A Newcomb, Mireia Obón-Santacana, Jennifer Ose, Julie R Palmer, Nikos Papadimitriou, Bens Pardamean, Andrew J Pellatt, Anita R Peoples, Elizabeth A Platz, John D Potter, Lihong Qi, Conghui Qu, Gad Rennert, Edward Ruiz-Narvaez, Lori C Sakoda, Stephanie L Schmit, Anna Shcherbina, Mariana C Stern, Yu-Ru Su, Catherine M Tangen, Duncan C Thomas, Yu Tian, Caroline Y Um, Franzel Jb Van Duijnhoven, Bethany Van Guelpen, Kala Visvanathan, Jun Wang, Emily White, Alicja Wolk, Michael O Woods, Cornelia M Ulrich, Li Hsu, W James Gauderman, Ulrike Peters, Konstantinos K Tsilidis

Faculty, Staff and Student Publications

Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC.

Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk.

Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) …

Mitochondrial Health Index Correlates With Plasma Circulating Cell-Free Mitochondrial Dna In Bipolar Disorder, Rafaela C Cordeiro, Camila N C Lima, Gabriel R Fries, Giovana Zunta-Soares, Jair C Soares, João Quevedo, Giselli Scaini

Faculty, Staff and Student Publications

Although mitochondrial dysfunction is known to play an essential role in the pathophysiology of bipolar disorder (BD), there is a glaring gap in our understanding of how mitochondrial dysfunction can modulate clinical phenotypes. An emerging paradigm suggests mitochondria play an important non-energetic role in adaptation to stress, impacting cellular resilience and acting as a source of systemic allostatic load. Known as mitochondrial allostatic load, this (phenomenon) occurs when mitochondria are unable to recalibrate and maintain cell homeostasis. This study aimed to evaluate the composite mitochondrial health index (MHI) in BD subjects and non-psychiatry controls. We will also explore whether lower …

Long-Term Utilization And Benefit Of Luspatercept In Transfusion-Dependent, Erythropoiesis-Stimulating Agent-Refractory Or -Intolerant Patients With Lower-Risk Myelodysplastic Syndromes With Ring Sideroblasts, Uwe Platzbecker, Valeria Santini, Rami S Komrokji, Amer M Zeidan, Guillermo Garcia-Manero, Rena Buckstein, Dimana Miteva, Karen Keeperman, Natalia Holot, Jose Alberto Nadal, Yinzhi Lai, Sadanand Vodala, Barbara Rosettani, Ana Carolina Giuseppi, Aylin Yucel, Pierre Fenaux

Faculty, Staff and Student Publications

No abstract provided.

Style Transfer-Assisted Deep Learning Method For Kidney Segmentation At Multiphase Mri, Junyu Guo, Manu Goyal, Yin Xi, Lauren Hinojosa, Gaelle Haddad, Emin Albayrak, Ivan Pedrosa

Faculty, Staff and Student Publications

Purpose: To develop and validate a semisupervised style transfer-assisted deep learning method for automated segmentation of the kidneys using multiphase contrast-enhanced (MCE) MRI acquisitions.

Materials and methods: This retrospective, Health Insurance Portability and Accountability Act-compliant, institutional review board-approved study included 125 patients (mean age, 57.3 years; 67 male, 58 female) with renal masses. Cohort 1 consisted of 102 coronal T2-weighted MRI acquisitions and 27 MCE MRI acquisitions during the corticomedullary phase. Cohort 2 comprised 92 MCE MRI acquisitions (23 acquisitions during four phases each, including precontrast, corticomedullary, early nephrographic, and nephrographic phases). The kidneys were manually segmented on T2-weighted images. …

Circulating Micrornas And Cytokines As Prognostic Biomarkers For Doxorubicin-Induced Cardiac Injury And For Evaluating The Effectiveness Of An Exercise Intervention, Prince Jeyabal, Anchit Bhagat, Fei Wang, Michael Roth, J Andrew Livingston, Susan C Gilchrist, Jose Banchs, Michelle A T Hildebrandt, Joya Chandra, Anita Deswal, Efstratios Koutroumpakis, Jian Wang, Najat C Daw, Theresa A Honey, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Purpose: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.

Experimental design: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples …

Geographic Disparity Of Outcome In Patients With Cancer Over Decades: The Surveillance, Epidemiology, And End Results, Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C Issa, Sherry A Pierce, Kelly A Soltysiak, Martha S Tingen, Jorge E Cortes

Faculty, Staff and Student Publications

Background: Improvements in prevention, early detection, and effective cancer therapy have decreased cancer-related mortality; however, significant health disparities exist. Therefore, we investigated the impact of these disparities on survival.

Methods: In the Surveillance, Epidemiology, and End Results, we identified 784,341 patients with cancer between 1990 and 2016 in Georgia, 68,493 between 1990 and 1999; 371,353 between 2000 and 2009; and 322,932 between 2010 and 2016. We assessed the overall survival (OS) of patients with all cancers, chronic myeloid leukemia (CML), and lung cancer, given the dramatic improvement in outcomes in patients with CML since 2000 compared to the generally considerably …

Exercise Training Reduces The Inflammatory Response And Promotes Intestinal Mucosa-Associated Immunity In Lynch Syndrome, Nan Deng, Laura Reyes-Uribe, Johannes F Fahrmann, Whittney S Thoman, Mark F Munsell, Jennifer B Dennison, Eunice Murage, Ranran Wu, Ernest T Hawk, Selvi Thirumurthi, Patrick M Lynch, Christina M Dieli-Conwright, Alexander J Lazar, Sonali Jindal, Khoi Chu, Manoj Chelvanambi, Karen Basen-Engquist, Yisheng Li, Jennifer A Wargo, Florencia Mcallister, James P Allison, Padmanee Sharma, Krishna M Sinha, Samir Hanash, Susan C Gilchrist, Eduardo Vilar

Faculty, Staff and Student Publications

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers.

PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes …

Coordinated Regulation Of Myonuclear Dna Methylation, Mrna, And Mirna Levels Associates With The Metabolic Response To Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy In Female Mice, Ahmed Ismaeel, Nicholas T. Thomas, Mariah Mccashland, Sebastian Edman, Johanna T. Lanner, Vandré C. Figueiredo, Christopher S. Fry, John J. Mccarthy, Yuan Wen, Kevin A. Murach, Ferdinand Von Walden

Health, Human Performance and Recreation Faculty Publications and Presentations

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Cardiac Muscle-Restricted Partial Loss Of Nos1ap Expression Has Limited But Significant Impact On Electrocardiographic Features, Alexa Smith, Dallas Auer, Morgan Johnson, Ernesto Sanchez, Holly Ross, Christopher Ward, Aravinda Chakravarti, Ashish Kapoor

Faculty, Staff and Student Publications

Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT …

Effect Of Ultrasound On The Stability Of Partial Nitrification: Under The Interference Of Aeration Rate, Ying Xie, Yichun Zhu, Jieyuan Yang, Guangming Zhang, Shuai Tian, Junfeng Lian, Shanyan Dong

Faculty, Staff and Student Publications

The fluctuation of dissolved oxygen is one of the primary cause of disruptions to the consistent operation of partial nitrification, and the level of dissolved oxygen is mainly controlled by the aeration rate. This study investigated the influence of ultrasonic treatment on the stability of partial nitrification of activated sludge under different aeration conditions. After being treated with ultrasound (energy density = 0.20 W·mL−1, treatment time = 10 min), partial nitrification process operated stably for 67 days, with the nitrite accumulation rate above 83.89 %. The effluent contained 42.50 mg·L−1 of nitrite, much higher than the control reactor (0.30 mg·L−1). …

Economic Equity And People With Disabilities: Development And Characterization Of A Novel Index, Bhavneet Walia, Katherine Mcdonald, Joy Hammel, Lex Frieden, Michael Morris, Barry Whaley, Vinh Nguyen

Faculty, Staff and Student Publications

Here we develop two new social indices: The ADA PARC Absolute Economic Opportunity Index and the ADA PARC Relative Economic Opportunity Index. These indices allow us novel examinations of economic equity between people with and without disabilities within a U.S. State and between people with disabilities in different states using aggregations of multiple component economic indicators. These represent the first efforts to offer U.S. indices of this focus, an important development given the distinct economic needs of people with disabilities and the value in accounting for distinct national policies. The indices rely on U.S. Census and other data on economic …

Gene Variants In Bola-Dmb, Decr1, Fasn And Srebf1 Associated With Conceptus Death On Day 16 Of Pregnancy In Holstein Cows [Abstract], Carolina L. Gonzalez-Berrios, Courtney Bowden, Pablo J. Pinedo, Jeanette V. Bishop, Hana Van Campen, Thomas R. R. Hansen, Milton G. Thomas

United States Department of Agriculture Wildlife Services: Staff Publications

Investigating the influences of single nucleotide polymorphisms (SNP) associated with conceptus death (CD) on day 16 of pregnancy could distinguish cows who have inferior value for fertility traits. We hypothesized that CD is associated with SNP genotypes that disrupt maternal recognition and lead to early pregnancy loss. RNA sequences from Holstein cow pregnancies (n = 15) with normal conceptuses (Norm) or CD were subjected to SNP discovery via Qiagen CLC Genomics Workbench. Selected SNP were based on previous fertility studies, differentially expressed genes within pregnancy development analyses and proximity to SNP associated with fertility traits in the Cattle QTL …

Diverse Clinical Manifestations And Challenges Of Mucormycosis: Insights From Serial Cases, Marisa C Nielsen, Filipe M Cerqueira, Sri Bharathi Kavuri, Caitlin M Raymond, Aeman Muneeb, Andrzej S Kudlicki, Shafaq Tariq, Mingru Liu, Andrew L Routh, Suimin Qiu, Ping Ren

Faculty, Staff and Student Publications

Mucormycosis is a severe and potentially life-threatening infection caused by a group of fungi classified as mucormycetes within the scientific order Mucorales. These infections are characterized by rapid and invasive fungal growth, presenting significant treatment challenges. Here we present 5 cases encountered from 2018 to 2022 at the University of Texas Medical Branch in Galveston, Texas, including a novel Apophysomyces species. These cases illustrate the diverse clinical manifestations of mucormycosis, including pulmonary, rhino-cerebral, gastrointestinal, and soft tissue involvement. Our investigation incorporates information provided by a multidisciplinary team of clinical collaborators, emphasizing the findings from radiology, histopathology, and microbiology. Given the …

Diverse Clinical Manifestations And Challenges Of Mucormycosis: Insights From Serial Cases, Marisa C Nielsen, Filipe M Cerqueira, Sri Bharathi Kavuri, Caitlin M Raymond, Aeman Muneeb, Andrzej S Kudlicki, Shafaq Tariq, Mingru Liu, Andrew L Routh, Suimin Qiu, Ping Ren

Faculty, Staff and Student Publications

Background: Regulation of mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in aging and nutrition. For example, caloric restriction reduces mTORC1 signaling and extends lifespan, whereas nutrient abundance and obesity increase mTORC1 signaling and reduce lifespan. Skeletal muscle-specific knockout (KO) of DEP domain-containing 5 protein (DEPDC5) results in constitutively active mTORC1 signaling, muscle hypertrophy and an increase in mitochondrial respiratory capacity. The metabolic profile of skeletal muscle, in the setting of hyperactive mTORC1 signaling, is not well known.

Objectives: To determine the metabolomic and lipidomic signature in skeletal muscle from female and male wild-type (WT) and DEPDC5 …

Ensuring Trust In Genomics Research, Erman Ayday, Jaideep Vaidya, Xiaoqian Jiang, Amalio Telenti

Faculty, Staff and Student Publications

Reproducibility, transparency, representation, and privacy underpin the trust on genomics research in general and genome-wide association studies (GWAS) in particular. Concerns about these issues can be mitigated by technologies that address privacy protection, quality control, and verifiability of GWAS. However, many of the existing technological solutions have been developed in isolation and may address one aspect of reproducibility, transparency, representation, and privacy of GWAS while unknowingly impacting other aspects. As a consequence, the current patchwork of technological tools only partially and in an overlapping manner address issues with GWAS, sometimes even creating more problems. This paper addresses the progress in …

Technical/Algorithm, Stakeholder, And Society (Tass) Barriers To The Application Of Artificial Intelligence In Medicine: A Systematic Review, Linda T Li, Lauren C Haley, Alexandra K Boyd, Elmer V Bernstam

Faculty, Staff and Student Publications

Introduction: The use of artificial intelligence (AI), particularly machine learning and predictive analytics, has shown great promise in health care. Despite its strong potential, there has been limited use in health care settings. In this systematic review, we aim to determine the main barriers to successful implementation of AI in healthcare and discuss potential ways to overcome these challenges.

Methods: We conducted a literature search in PubMed (1/1/2001-1/1/2023). The search was restricted to publications in the English language, and human study subjects. We excluded articles that did not discuss AI, machine learning, predictive analytics, and barriers to the use of …

Operational Ontology For Oncology (O3): A Professional Society-Based, Multistakeholder, Consensus-Driven Informatics Standard Supporting Clinical And Research Use Of Real-World Data From Patients Treated For Cancer, Charles S Mayo, Mary U Feng, Kristy K Brock, Randi Kudner, Peter Balter, Jeffrey C Buchsbaum, Amanda Caissie, Elizabeth Covington, Emily C Daugherty, Andre L Dekker, Clifton D Fuller, Anneka L Hallstrom, David S Hong, Julian C Hong, Sophia C Kamran, Eva Katsoulakis, John Kildea, Andra V Krauze, Jon J Kruse, Tod Mcnutt, Michelle Mierzwa, Amy Moreno, Jatinder R Palta, Richard Popple, Thomas G Purdie, Susan Richardson, Gregory C Sharp, Shiraishi Satomi, Lawrence R Tarbox, Aradhana M Venkatesan, Alon Witztum, Kelly E Woods, Yuan Yao, Keyvan Farahani, Sanjay Aneja, Peter E Gabriel, Lubomire Hadjiiski, Dan Ruan, Jeffrey H Siewerdsen, Steven Bratt, Michelle Casagni, Su Chen, John C Christodouleas, Anthony Didonato, James Hayman, Rishhab Kapoor, Saul Kravitz, Sharon Sebastian, Martin Von Siebenthal, Walter Bosch, Coen Hurkmans, Sue S Yom, Ying Xiao

Faculty, Staff and Student Publications

PURPOSE: The ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), radiation oncology information systems, treatment planning systems, and other cancer care and outcomes databases. We sought to create a standardized ontology for clinical data, social determinants of health, and other radiation oncology concepts and interrelationships.

METHODS AND MATERIALS: The American Association of Physicists in Medicine's Big Data Science Committee was initiated in July 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- …

Neoadjuvant Durvalumab Alone Or Combined With Novel Immuno-Oncology Agents In Resectable Lung Cancer: The Phase Ii Neocoast Platform Trial, Tina Cascone, Gozde Kar, Jonathan D Spicer, Rosario García-Campelo, Walter Weder, Davey B Daniel, David R Spigel, Maen Hussein, Julien Mazieres, Julio Oliveira, Edwin H Yau, Alexander I Spira, Valsamo Anagnostou, Raymond Mager, Oday Hamid, Lin-Yang Cheng, Ying Zheng, Jorge Blando, Tze Heng Tan, Michael Surace, Jaime Rodriguez-Canales, Vancheswaran Gopalakrishnan, Bret R Sellman, Italia Grenga, Yee Soo-Hoo, Rakesh Kumar, Lara Mcgrath, Patrick M Forde

Faculty, Staff and Student Publications

Neoadjuvant chemoimmunotherapy improves pathologic complete response rate and event-free survival in patients with resectable non-small cell lung cancer (NSCLC) versus chemotherapy alone. NeoCOAST was the first randomized, multidrug platform trial to examine novel neoadjuvant immuno-oncology combinations for patients with resectable NSCLC, using major pathologic response (MPR) rate as the primary endpoint. Eighty-three patients received a single cycle of treatment: 26 received durvalumab (anti-PD-L1) monotherapy, 21 received durvalumab plus oleclumab (anti-CD73), 20 received durvalumab plus monalizumab (anti-NKG2A), and 16 received durvalumab plus danvatirsen (anti-STAT3 antisense oligonucleotide). MPR rates were higher for patients in the combination arms versus durvalumab alone. Safety profiles …

Comparison Of Progression-Free Survival Outcome Of Sentinel Node Biopsy Without Ultrastaging Versus Lymphadenectomy In Endometrial Cancer: A Propensity-Matched Analysis, Dahye Lee, Yoo-Na Kim, Sang Hyun Cho, Hye Soo Yoon, Young Tae Kim, Sunghoon Kim, Sang Wun Kim

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to investigate the oncologic outcomes of patients with endometrial cancer who underwent sentinel lymph node (SLN) biopsy without ultrastaging compared with that of those who underwent lymphadenectomy (LND).

METHODS: Patients with endometrial cancer who underwent staging with SLN biopsy or LND during 2006 - 2021 were analyzed using propensity score matching (PSM). SLN metastasis was examined using hematoxylin and eosin staining, without ultrastaging. Progression-free survival (PFS) was compared between the two groups before and after PSM using age, histology, and stage as covariates. Clinical variables such as recurrence patterns and lymphatic complications, were assessed.

RESULTS: After excluding …

Phase Ii Study Of Cladribine, Idarubicin, And Ara-C (Clia) With Or Without Sorafenib As Initial Therapy For Patients With Acute Myeloid Leukemia, Tapan M Kadia, Farhad Ravandi, Matteo Molica, Alex Bataller, Gautam Borthakur, Naval Daver, Elias Jabbour, Courtney D Dinardo, Naveen Pemmaraju, Nitin Jain, Alessandra Ferrajoli, Musa Ylimaz, Prithviraj Bose, Rebecca Slack Tidwell, Kayleigh R Marx, Caitlin R Rausch, Rashmi Kanagal-Shamanna, Sa Wang, Rabiul Islam, Richard Champlin, Elizabeth Shpall, Marina Konopleva, Guillermo Garcia-Manero, Hagop Kantarjian

Faculty, Staff and Student Publications

The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly-diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate-dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1-5, cytarabine (1 g/m2) on D1-5, and idarubicin (10 mg/m2) on D1-3. Sorafenib was added to the CLIA backbone for patients with FLT3-ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts-AML). …

Cell-Autonomous Effects Of Apoe4 In Restricting Microglial Response In Brain Homeostasis And Alzheimer’S Disease, Chia-Chen Liu, Na Wang, Yuanxin Chen, Yasuteru Inoue, Francis Shue, Yingxue Ren, Minghui Wang, Wenhui Qiao, Tadafumi C Ikezu, Zonghua Li, Jing Zhao, Yuka Martens, Sydney V Doss, Cassandra L Rosenberg, Suren Jeevaratnam, Lin Jia, Ana-Caroline Raulin, Fangfang Qi, Yiyang Zhu, Alla Alnobani, Joshua Knight, Yixing Chen, Cynthia Linares, Aishe Kurti, John D Fryer, Bin Zhang, Long-Jun Wu, Betty Y S Kim, Guojun Bu

Faculty, Staff and Student Publications

Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes …

Identification Of Novel Genetic Loci For Risk Of Multiple Myeloma By Functional Annotation, Angelica Macauda, Klara Briem, Alyssa Clay-Gilmour, Wendy Cozen, Asta Försti, Matteo Giaccherini, Chiara Corradi, Juan Sainz, Yasmeen Niazi, Rob Ter Horst, Yang Li, Mihai G Netea, Ulla Vogel, Kari Hemminki, Susan L Slager, Judit Varkonyi, Vibeke Andersen, Elzbieta Iskierka-Jazdzewska, Joaquin Mártinez-Lopez, Jan Zaucha, Nicola J Camp, S Vincent Rajkumar, Agnieszka Druzd-Sitek, Parveen Bhatti, Stephen J Chanock, Shaji K Kumar, Edyta Subocz, Grzegorz Mazur, Stefano Landi, Mitchell J Machiela, Andrés Jerez, Aaron D Norman, Michelle A T Hildebrandt, Katalin Kadar, Sonja I Berndt, Elad Ziv, Gabriele Buda, Arnon Nagler, Charles Dumontet, Malgorzata Raźny, Marzena Watek, Aleksandra Butrym, Norbert Grzasko, Marek Dudzinski, Malwina Rybicka-Ramos, Eva-Laure Matera, Ramón García-Sanz, Hartmut Goldschmidt, Krzysztof Jamroziak, Artur Jurczyszyn, Esther Clavero, Graham G Giles, Matteo Pelosini, Daria Zawirska, Marcin Kruszewski, Herlander Marques, Eva Haastrup, José Manuel Sánchez-Maldonado, Uta Bertsch, Marcin Rymko, Marc-Steffen Raab, Elizabeth E Brown, Jonathan N Hofmann, Celine Vachon, Daniele Campa, Federico Canzian

Faculty, Staff and Student Publications

No abstract provided.

Exosomes Modified With Anti-Mek1 Sirna Lead To An Effective Silencing Of Triple Negative Breast Cancer Cells, Débora Ferreira, Cátia Santos-Pereira, Marta Costa, Julieta Afonso, Sujuan Yang, Janine Hensel, Kathleen M Mcandrews, Adhemar Longatto-Filho, Rui Fernandes, Joana B Melo, Fátima Baltazar, João N Moreira, Raghu Kalluri, Ligia R Rodrigues

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an …

High-Dose Chemotherapy And Autologous Stem Cell Transplantation For Relapsed Or Refractory Primary Mediastinal Large B-Cell Lymphoma, Hanan Alkhaldi, Alec Reinhardt, Melissa Barnett, Suprateek Kundu, Chitra Hosing, Jeremy Ramdial, Neeraj Saini, Samer Srour, Amin Alousi, Partow Kebriaei, Uday Popat, Muzaffar Qazilbash, Richard Champlin, Elizabeth J Shpall, Allison Gulbis, Terri Lynn Shigle, Bouthaina Dabaja, Chelsea Pinnix, Sairah Ahmed, Raphael Steiner, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy with or without radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC), with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. The 60 study patients received either rituximab-BEAM (n = 37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) with or without vorinostat (n = 23), followed by ASCT. Forty-six patients received mediastinal RT, …