Biomedical Informatics Commons^™

Recurrent Somatic Copy Number Alterations And Their Association With Oncogene Expression Levels In High-Grade Ovarian Serous Carcinoma, Hillary P Esplen, Richard K Yang, Awdhesh Kalia, Zhenya Tang, Guilin Tang, L Jeffrey Medeiros, Gokce A Toruner

Faculty, Staff and Student Publications

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly …

Transforming Ovarian Cancer Care By Targeting Minimal Residual Disease, Amir A Jazaeri, Rachel Grisham, Anne Knisely, Stefani Spranger, Dmitriy Zamarin, R Tyler Hillman, Barrett C Lawson, Kathleen H Burns, Sanghoon Lee, Shannon N Westin, Enrico Moiso, Marc J Williams, Neelkanth M Bardhan, Thomas Pisanic, Ursula Matulonis, Britta Weigelt, Ieming Shih, Panagiotis A Konstantinopoulos, Stephanie Gaillard, Linghua Wang, Carol Aghajanian, Alan D D'Andrea, Paula Hammond, Sohrab Shah, Kai W Wucherpfennig, Karen H Lu

Faculty, Staff and Student Publications

Frontline treatment and resultant cure rates in patients with advanced ovarian cancer have changed little over the past several decades. Here, we outline a multidisciplinary approach aimed at gaining novel therapeutic insights by focusing on the poorly understood minimal residual disease phase of ovarian cancer that leads to eventual incurable recurrences.

Comparative Performance Analysis Of Binary Variants Of Fox Optimization Algorithm With Half-Quadratic Ensemble Ranking Method For Thyroid Cancer Detection, Rohit Sharma, Gautam Kumar Mahanti, Ganapati Panda, Adyasha Rath, Sujata Dash, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

Thyroid cancer is a life-threatening condition that arises from the cells of the thyroid gland located in the neck's frontal region just below the adam's apple. While it is not as prevalent as other types of cancer, it ranks prominently among the commonly observed cancers affecting the endocrine system. Machine learning has emerged as a valuable medical diagnostics tool specifically for detecting thyroid abnormalities. Feature selection is of vital importance in the field of machine learning as it serves to decrease the data dimensionality and concentrate on the most pertinent features. This process improves model performance, reduces training time, and …

Cd46-Adc Reduces The Engraftment Of Multiple Myeloma Patient-Derived Xenografts, Michael J Vanwyngarden, Zachary J Walker, Yang Su, Olivia Perez De Acha, Brett M Stevens, Peter A Forsberg, Tomer M Mark, William Matsui, Bin Liu, Daniel W Sherbenou

Faculty, Staff and Student Publications

An antibody-drug conjugate (ADC) targeting CD46 conjugated to monomethyl auristatin has a potent anti-myeloma effect in cell lines in vitro and in vivo, and patient samples treated ex vivo. Here, we tested if CD46-ADC may have the potential to target MM-initiating cells (MM-ICs). CD46 expression was measured on primary MM cells with a stem-like phenotype. A patient-derived xenograft (PDX) model was implemented utilizing implanted fetal bone fragments to provide a humanized microenvironment. Engraftment was monitored via serum human light chain ELISA, and at sacrifice via bone marrow and bone fragment flow cytometry. We then tested MM regeneration in PDX by …

Is The Direct Fixation Of Displaced Quadrilateral Plates In Acetabular Fractures Necessary?, Beom-Soo Kim, Ki-Cheor Bae, Chul-Hyun Cho, Kyung-Jae Lee, In Gyu Lee, Min-Gyu Lee, Byung-Woo Min

Faculty, Staff and Student Publications

Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of …

Venetoclax Abrogates The Prognostic Impact Of Splicing Factor Gene Mutations In Newly Diagnosed Acute Myeloid Leukemia, Jayastu Senapati, Samuel Urrutia, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Abhishek Maiti, Hussein A Abbas, Naval G Daver, Naveen Pemmaraju, Sherry Pierce, Kelly S Chien, Koji Sasaki, Tapan M Kadia, Danielle E Hammond, Gautam Borthakur, Keyur Patel, Farhad Ravandi, Hagop M Kantarjian, Guillermo Garcia-Manero, Courtney D Dinardo

Faculty, Staff and Student Publications

Mutations in splicing factor (SF) genes SRSF2, U2AF1, SF3B1, and ZRSR2 are now considered adverse risk in the European LeukemiaNet 2022 acute myeloid leukemia (AML) risk stratification. The prognostic impact of SF mutations in AML has been predominantly derived from younger patients treated with intensive (INT) therapy. We evaluated 994 patients with newly diagnosed AML, including 266 (27%) with a SFmut. Median age was 67 years overall, with patients with SFmut being older at 72 years. SRSF2 (n = 140, 53%) was the most common SFmut. In patients treated with INT, median relapse-free survival (RFS) (9.6 vs 21.4 months, P …

The Cancer Moonshot Immuno-Oncology Translational Network At 5: Accelerating Cancer Immunotherapies, Ananth Annapragada, Andrew G Sikora, Himangi Marathe, Song Liu, Michael Demetriou, Lawrence Fong, Jinming Gao, Donald Kufe, Zachary S Morris, Eduardo Vilar, Elad Sharon, Alan Hutson, Kunle Odunsi

Faculty, Staff and Student Publications

The Immuno-Oncology Translational Network (IOTN) was established in 2018 as part of the Cancer Moonshot. In 2022, President Joe Biden set new goals to reduce the cancer death rate by half within 25 years and improve the lives of people with cancer and cancer survivors. The IOTN is focused on accelerating translation of cancer immunology research, from bench to bedside, and improving immunotherapy outcomes across a wide array of cancers in the adult population. The unique structure and team science approach of the IOTN is designed to accelerate discovery and evaluation of novel immune-based therapeutic and prevention strategies. In this …

Synthetic Megavoltage Cone Beam Computed Tomography Image Generation For Improved Contouring Accuracy Of Cardiac Pacemakers, Hana Baroudi, Xinru Chen, Wenhua Cao, Mohammad D El Basha, Skylar Gay, Mary Peters Gronberg, Soleil Hernandez, Kai Huang, Zaphanlene Kaffey, Adam D Melancon, Raymond P Mumme, Carlos Sjogreen, January Y Tsai, Cenji Yu, Laurence E Court, Ramiro Pino, Yao Zhao

Faculty, Staff and Student Publications

In this study, we aimed to enhance the contouring accuracy of cardiac pacemakers by improving their visualization using deep learning models to predict MV CBCT images based on kV CT or CBCT images. Ten pacemakers and four thorax phantoms were included, creating a total of 35 combinations. Each combination was imaged on a Varian Halcyon (kV/MV CBCT images) and Siemens SOMATOM CT scanner (kV CT images). Two generative adversarial network (GAN)-based models, cycleGAN and conditional GAN (cGAN), were trained to generate synthetic MV (sMV) CBCT images from kV CT/CBCT images using twenty-eight datasets (80%). The pacemakers in the sMV CBCT …

Comparison Of Single-Port Laparoscopy With Other Surgical Approaches In Endometrial Cancer Surgical Staging: Propensity-Score-Matched Analysis, Sang Hyun Cho, Jung-Yun Lee, Eun Ji Nam, Sunghoon Kim, Young Tae Kim, Sang Wun Kim

Faculty, Staff and Student Publications

This single-institution, retrospective study aimed to compare the surgical outcomes of single-port, multi-port, and robot-assisted laparoscopy, as well as laparotomy, in patients with endometrial cancer who underwent surgical staging between January 2006 and December 2017. This study evaluated various parameters, including disease-free survival (DFS), overall survival (OS), recurrence rate (RR), recurrence site, and intra- and postoperative complications. Propensity score matching was performed to account for baseline characteristics, and a total of 881 patients were included in the analysis. The 3-year DFS of single-port laparoscopy was similar to that of the other groups, but laparotomy exhibited a lower 3-year DFS compared …

Author Correction: Regulation Of Hnrnpa1 By Micrornas Controls The Mir-18a-K-Ras Axis In Chemotherapy-Resistant Ovarian Cancer, Cristian Rodriguez-Aguayo, Paloma Del C Monroig, Roxana S Redis, Emine Bayraktar, Maria I Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K Sood, George A Calin, Gabriel Lopez-Berestein

Faculty, Staff and Student Publications

No abstract provided.

Efficacy Of Sotagliflozin In Adults With Type 2 Diabetes In Relation To Baseline Hemoglobin A1c, Rahul Aggarwal, Deepak L Bhatt, Michael Szarek, Christopher P Cannon, Darren K Mcguire, Silvio E Inzucchi, Renato D Lopes, Michael J Davies, Phillip Banks, Bertram Pitt, Philippe Gabriel Steg

Faculty, Staff and Student Publications

Background: The SCORED (Effect of Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk) and SOLOIST-WHF (Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure) trials demonstrated that sotagliflozin, an SGLT1 and SGLT2 inhibitor, improves outcomes in individuals with type 2 diabetes who have heart failure (HF) or kidney disease.

Objectives: We assessed the efficacy of sotagliflozin on HF clinical outcomes in individuals with differing baseline glycosylated hemoglobin (HbA1c) levels.

Methods: We included all adults from SCORED and SOLOIST-WHF. The primary …

A Randomized Phase Iii Study Of Standard Versus High-Dose Cytarabine With Or Without Vorinostat For Aml, Guillermo Garcia-Manero, Nikolai A Podoltsev, Megan Othus, John M Pagel, Jerald P Radich, Min Fang, David A Rizzieri, Guido Marcucci, Stephen A Strickland, Mark R Litzow, M Lynn Savoie, Bruno C Medeiros, Mikkael A Sekeres, Tara L Lin, Geoffrey L Uy, Bayard L Powell, Jonathan E Kolitz, Richard A Larson, Richard M Stone, David Claxton, James Essell, Selina M Luger, Sanjay R Mohan, Anna Moseley, Frederick R Appelbaum, Harry P Erba

Faculty, Staff and Student Publications

Prior experience indicated that use of higher doses of cytarabine during induction for acute myeloid leukemia (AML) with a histone deacetylase inhibitor resulted in high response rates. S1203 was a randomized multicenter trial for previously untreated patients aged 18-60 with AML which compared daunorubicin and cytarabine (DA), idarubicin with higher dose cytarabine (IA) and IA with vorinostat (IA + V). The primary endpoint was event free survival (EFS). 738 patients were randomized: 261 to each DA and IA arms and 216 to the IA + V arm. 96, 456, and 150 patients had favorable-, intermediate-, and unfavorable-risk cytogenetics, respectively. 152 …

Ischemic Bowel Associated With Newly Diagnosed Patent Foramen Ovale, Hannah Hong, Deanna Glassman, Shannon Neville Westin

Faculty, Staff and Student Publications

No abstract provided.

The Deubiquitinase Zranb1 Is An E3 Ubiquitin Ligase For Slc7a11 And Regulates Ferroptotic Resistance, Shan Huang, Qimin Zhang, Manyu Zhao, Xing Wang, Yilei Zhang, Boyi Gan, Peijing Zhang

Faculty, Staff and Student Publications

The dependency of cancer cells on iron increases their susceptibility to ferroptosis, thus providing new opportunities for patients with treatment-resistant tumors. However, we show that lipid peroxidation, a hallmark of ferroptosis, was found in various areas of patient samples, indicating the potential resistance of ferroptosis. Using whole deubiquitinases (DUBs) sgRNA screening, we found that loss of ZRANB1 confers cancer cell resistance to ferroptosis. Intriguingly, functional studies revealed that ZRANB1 ubiquitinates and represses SLC7A11 expression as an E3 ubiquitin ligase and that ZRANB1 inhibits glutathione (GSH) synthesis through SLC7A11 degradation, leading to elevated lipid peroxidation and ferroptosis. Deletion of the region …

Aptamers As Potential Therapeutic Tools For Ovarian Cancer: Advancements And Challenges, Wojciech Szymanowski, Anna Szymanowska, Anna Bielawska, Gabriel Lopez-Berestein, Cristian Rodriguez-Aguayo, Paola Amero

Faculty, Staff and Student Publications

Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug …

Identification Of Blood Protein Biomarkers Associated With Prostate Cancer Risk Using Genetic Prediction Models: Analysis Of Over 140,000 Subjects, Hua Zhong, Jingjing Zhu, Shuai Liu, Dalia H Ghoneim, Praveen Surendran, Tao Liu, Sarah Fahle, Adam Butterworth, Md Ashad Alam, Hong-Wen Deng, Herbert Yu, Chong Wu, Lang Wu

Faculty, Staff and Student Publications

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant …

Repurposing Egfr Inhibitors For Oral Cancer Pain And Opioid Tolerance, Maria Daniela Santi, Morgan Zhang, Naijiang Liu, Chi T Viet, Tongxin Xie, Dane D Jensen, Moran Amit, Huilin Pan, Yi Ye

Faculty, Staff and Student Publications

Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how …

In Situ Profiling Reveals Metabolic Alterations In The Tumor Microenvironment Of Ovarian Cancer After Chemotherapy, Sara Corvigno, Sunil Badal, Meredith L Spradlin, Michael Keating, Igor Pereira, Elaine Stur, Emine Bayraktar, Katherine I Foster, Nicholas W Bateman, Waleed Barakat, Kathleen M Darcy, Thomas P Conrads, G Larry Maxwell, Philip L Lorenzi, Susan K Lutgendorf, Yunfei Wen, Li Zhao, Premal H Thaker, Michael J Goodheart, Jinsong Liu, Nicole Fleming, Sanghoon Lee, Livia S Eberlin, Anil K Sood

Faculty, Staff and Student Publications

In this study, we investigated the metabolic alterations associated with clinical response to chemotherapy in patients with ovarian cancer. Pre- and post-neoadjuvant chemotherapy (NACT) tissues from patients with high-grade serous ovarian cancer (HGSC) who had poor response (PR) or excellent response (ER) to NACT were examined. Desorption electrospray ionization mass spectrometry (DESI-MS) was performed on sections of HGSC tissues collected according to a rigorous laparoscopic triage algorithm. Quantitative MS-based proteomics and phosphoproteomics were performed on a subgroup of pre-NACT samples. Highly abundant metabolites in the pre-NACT PR tumors were related to pyrimidine metabolism in the epithelial regions and oxygen-dependent proline …

Language Nativeness Modulates Physiological Responses To Moral Vs Immoral Concepts In Chinese-English Bilinguals: Evidence From Event-Related Potential And Psychophysiological Measures, Fei Gao, Chenggang Wu, Hengyi Fu, Kunyu Xu, Zhen Yuan

Faculty, Staff and Student Publications

Morality has been an integral part of social cognition and our daily life, and different languages may exert distinct impacts on human moral judgment. However, it remains unclear how moral concept is encoded in the bilingual brain. This study, therefore, aimed to explore the emotional and cognitive involvement of bilingual morality judgement by using combined event-related potential (ERP) and psychophysiological (including skin, heart, and pulse) measures. In the experiment, thirty-one Chinese-English bilingual participants were asked to make moral judgments in Chinese and English, respectively. Our results revealed increased early frontal N400 and decreased LPC in L1 moral concept encoding as …

Potentiation Of Apoptosis In Drug-Resistant Mantle Cell Lymphoma Cells By Mcl-1 Inhibitor Involves Downregulation Of Inhibitor Of Apoptosis Proteins, Yijing Li, Heng-Huan Lee, Vivian Changying Jiang, Yuxuan Che, Joseph Mcintosh, Alexa Jordan, Jovanny Vargas, Tianci Zhang, Fangfang Yan, Margaret Elizabeth Simmons, Wei Wang, Lei Nie, Yixin Yao, Preetesh Jain, Michael Wang, Yang Liu

Faculty, Staff and Student Publications

Bruton's tyrosine kinase inhibitors (BTKi) and CAR T-cell therapy have demonstrated tremendous clinical benefits in mantle cell lymphoma (MCL) patients, but intrinsic or acquired resistance inevitably develops. In this study, we assessed the efficacy of the highly potent and selective MCL-1 inhibitor AZD5991 in various therapy-resistant MCL cell models. AZD5991 markedly induced apoptosis in these cells. In addition to liberating BAK from the antiapoptotic MCL-1/BAK complex for the subsequent apoptosis cascade, AZD5991 downregulated inhibitor of apoptosis proteins (IAPs) through a BAK-dependent mechanism to amplify the apoptotic signal. The combination of AZD5991 with venetoclax enhanced apoptosis and reduced mitochondrial oxygen consumption …

Racial Disparities In Mit Family Translocation Renal Cell Carcinoma, Xiaofan Lu, Nassim Tawanaie Pour Sedehi, Xiaoping Su, Fangrong Yan, Omar Alhalabi, Nizar M Tannir, Gabriel G Malouf

Faculty, Staff and Student Publications

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian …

Incidence And Risk Factors For Pneumonitis Associated With Checkpoint Inhibitors In Advanced Non-Small Cell Lung Cancer: A Single Center Experience, Mehmet Altan, Felipe Soto, Linda L Zhong, Fechukwu O Akhmedzhanov, Nathaniel R Wilson, Abdulrazzak Zarifa, Aya A Albittar, Vincent Yang, Jeff Lewis, Waree Rinsurongkawong, J Jack Lee, Vadeerat Rinsurongkawong, Jianjun Zhang, Don L Gibbons, Ara A Vaporciyan, Kristofer Jennings, Fareed Khawaja, Saadia A Faiz, Vickie R Shannon, Girish Shroff, Myrna C B Godoy, Naval G Daver, Saumil Gandhi, Tito R Mendoza, Aung Naing, Carrie Daniel-Macdougall, John V Heymach, Ajay Sheshadri

Faculty, Staff and Student Publications

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially.

METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for …

Comparison Of Non-Laser And Laser Transvenous Lead Extraction: A Systematic Review And Meta-Analysis, Zaki Akhtar, Christos Kontogiannis, Georgios Georgiopoulos, Christoph T Starck, Lisa W M Leung, Sun Y Lee, Byron K Lee, Sreenivasa R K Seshasai, Manav Sohal, Mark M Gallagher

Faculty, Staff and Student Publications

AIMS: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis.

METHODS AND RESULTS: We searched Medline, Embase, Scopus, ClinicalTrials.gov, and CENTRAL databases for TLE studies published between 1991 and 2021. From the included 68 studies, safety and efficacy data were carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR), and pooled rates were synthesized from eligible studies to compare …

Microfluidic Coaxial 3d Bioprinting Of Cell-Laden Microfibers And Microtubes For Salivary Gland Tissue Engineering, Yu Yin, Ephraim J Vázquez-Rosado, Danielle Wu, Vignesh Viswananthan, Andrew Farach, Mary C Farach-Carson, Daniel A Harrington

Faculty, Staff and Student Publications

Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate …

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 …

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 …

Nanobomb Optical Coherence Elastography In Multilayered Phantoms, Maryam Hatami, Dmitry Nevozhay, Manmohan Singh, Alexander Schill, Paul Boerner, Salavat Aglyamov, Konstantin Sokolov, Kirill V Larin

Faculty, Staff and Student Publications

Many tissues are composed of layered structures, and a better understanding of the changes in the layered tissue biomechanics can enable advanced guidance and monitoring of therapy. The advent of elastography using longitudinally propagating shear waves (LSWs) has created the prospect of a high-resolution assessment of depth-dependent tissue elasticity. Laser activation of liquid-to-gas phase transition of dye-loaded perfluorocarbon (PFC) nanodroplets (a.k.a., nanobombs) can produce highly localized LSWs. This study aims to leverage the potential of photoactivation of nanobombs to incudce LSWs with very high-frequency content in wave-based optical coherence elastography (OCE) to estimate the elasticity gradient with high resolution. In …

Early Skeletal Muscle Loss In Adolescent And Young Adult Cancer Patients Treated With Anthracycline Chemotherapy, Savannah V Wooten, Fei Wang, Michael E Roth, Guanshu Liu, J Andrew Livingston, Behrang Amini, Susan C Gilchrist, Michelle Hildebrandt, Eugenie S Kleinerman

Faculty, Staff and Student Publications

BACKGROUND: Early skeletal muscle loss has been observed in adolescent and young adult (AYA) sarcoma patients undergoing treatment. Identification of individuals within the AYA populace that are at greatest risk of anthracycline-induced skeletal muscle loss is unknown. Moreover, investigations which seek out underlying causes of skeletal muscle degradation during chemotherapy are critical for understanding, preventing, and reducing chronic health conditions associated with poor skeletal muscle status.

METHODS: Computed tomography (CT) scans were used to investigate changes in skeletal muscle of 153 AYA sarcoma and Hodgkin lymphoma patients at thoracic vertebra 4 after anthracycline treatment. Images were examined at three time …

A Framework For Standardised Tissue Sampling And Processing During Resection Of Diffuse Intracranial Glioma: Joint Recommendations From Four Rano Groups, Philipp Karschnia, Marion Smits, Guido Reifenberger, Emilie Le Rhun, Benjamin M Ellingson, Norbert Galldiks, Michelle M Kim, Jason T Huse, Oliver Schnell, Patrick N Harter, Malte Mohme, Expert Rater Panel, Louisa Von Baumgarten, Nathalie L Albert, Raymond Y Huang, Minesh P Mehta, Martin Van Den Bent, Michael Weller, Michael A Vogelbaum, Susan M Chang, Mitchel S Berger, Joerg-Christian Tonn

Faculty, Staff and Student Publications

Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, …

Effect Of The Covid-19 Pandemic On The Epidemiology Of Pediatric Traumatic Brain Injury In Brazil, Leopoldo Mandic Ferreira Furtado, José Aloysio Da Costa Val Filho, Victor Da Silva Pereira, Yasmin S Coimbra, Vitor Hugo R Caldas, Anne R Magalhães, Bruna Athayde S De Carvalho, Saulo G Moreira, Antônio L Teixeira, Aline Silva De Miranda

Faculty, Staff and Student Publications

Aim: In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children’s freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children.

Materials and methods: We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic.

Results: Of the patients with …