Biomedical Informatics Commons^™

Efficacy And Mortality Of Rotating Sheaths Versus Laser Sheaths For Transvenous Lead Extraction: A Meta-Analysis, Sun Yong Lee, Isabel E Allen, Celso Diaz, Xiaofan Guo, Cara Pellegrini, Ramin Beygui, Ricardo Cardona-Guarache, Gregory M Marcus, Byron K Lee

Faculty, Staff and Student Publications

Background: Rotating and laser sheaths are both routinely used in transvenous lead extraction (TLE) which can lead to catastrophic complications including death. The efficacy and risk of each approach are uncertain. To perform a meta-analysis to compare success and mortality rates associated with rotating and laser sheaths.

Methods: We searched electronic academic databases for case series of consecutive patients and randomized controlled trials published 1998-2017 describing the use of rotating and laser sheaths for TLE. Among 48 studies identified, rotating sheaths included 1,094 patients with 1,955 leads in 14 studies, and laser sheaths included 7,775 patients with 12,339 leads in …

Heterozygous Midnolin Knockout Attenuates Severity Of Nonalcoholic Fatty Liver Disease In Mice Fed A Western-Style Diet High In Fat, Cholesterol, And Fructose, Soo-Mi Kweon, Jose Irimia-Dominguez, Gayeoun Kim, Patrick T Fueger, Kinji Asahina, Keith K Lai, Daniela S Allende, Quincy R Lai, Chih-Hong Lou, Walter M Tsark, Ju Dong Yang, Dominic S Ng, Ju-Seog Lee, Patrick Tso, Wendong Huang, Keane K Y Lai

Faculty, Staff and Student Publications

Although midnolin has been studied for over 20 years, its biological roles in vivo remain largely unknown, especially due to the lack of a functional animal model. Indeed, given our recent discovery that the knockdown of midnolin suppresses liver cancer cell tumorigenicity and that this antitumorigenic effect is associated with modulation of lipid metabolism, we hypothesized that knockout of midnolin in vivo could potentially protect from nonalcoholic fatty liver disease (NAFLD) which has become the most common cause of chronic liver disease in the Western world. Accordingly, in the present study, we have developed and now report on the first …

Vincristine Enhances The Efficacy Of Mek Inhibitors In Preclinical Models Of Kras-Mutant Colorectal Cancer, Susmita Ghosh, Fan Fan, Reid T Powell, Jason Roszik, Yong Sung Park, Clifford Stephan, Manu Sebastian, Lin Tan, Alexey V Sorokin, Philip L Lorenzi, Scott Kopetz, Lee M Ellis, Rajat Bhattacharya

Faculty, Staff and Student Publications

Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting mitogen-activated protein kinase kinase (MEK), a downstream mediator of RAS, have also been ineffective in colorectal cancer. To identify drugs that can enhance the efficacy of MEK inhibitors, we performed unbiased high-throughput screening using colorectal cancer spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the NCI-approved Oncology Library version …

Development And Validation Of An Automated Image-Based Deep Learning Platform For Sarcopenia Assessment In Head And Neck Cancer, Zezhong Ye, Anurag Saraf, Yashwanth Ravipati, Frank Hoebers, Paul J Catalano, Yining Zha, Anna Zapaishchykova, Jirapat Likitlersuang, Christian Guthier, Roy B Tishler, Jonathan D Schoenfeld, Danielle N Margalit, Robert I Haddad, Raymond H Mak, Mohamed Naser, Kareem A Wahid, Jaakko Sahlsten, Joel Jaskari, Kimmo Kaski, Antti A Mäkitie, Clifton D Fuller, Hugo J W L Aerts, Benjamin H Kann

Faculty, Staff and Student Publications

Importance: Sarcopenia is an established prognostic factor in patients with head and neck squamous cell carcinoma (HNSCC); the quantification of sarcopenia assessed by imaging is typically achieved through the skeletal muscle index (SMI), which can be derived from cervical skeletal muscle segmentation and cross-sectional area. However, manual muscle segmentation is labor intensive, prone to interobserver variability, and impractical for large-scale clinical use.

Objective: To develop and externally validate a fully automated image-based deep learning platform for cervical vertebral muscle segmentation and SMI calculation and evaluate associations with survival and treatment toxicity outcomes.

Design, setting, and participants: For this prognostic study, …

Myelodysplastic Syndromes: 2023 Update On Diagnosis, Risk-Stratification, And Management, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Disease overview: The myelodysplastic syndromes (MDS) are a very heterogeneous group of myeloid disorders characterized by peripheral blood cytopenias and increased risk of transformation to acute myelogenous leukemia (AML). MDS occurs more frequently in older males and in individuals with prior exposure to cytotoxic therapy.

Diagnosis: Diagnosis of MDS is based on morphological evidence of dysplasia upon visual examination of a bone marrow aspirate and biopsy. Information obtained from additional studies such as karyotype, flow cytometry, and molecular genetics is usually complementary and may help refine diagnosis. A new WHO classification of MDS was proposed in 2022. Under this classification, …

Pitfalls In Machine Learning-Based Assessment Of Tumor-Infiltrating Lymphocytes In Breast Cancer: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Jeppe Thagaard, Glenn Broeckx, David B Page, Chowdhury Arif Jahangir, Sara Verbandt, Zuzana Kos, Rajarsi Gupta, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Guray Akturk, Jonas S Almeida, Isabel Alvarado-Cabrero, Mohamed Amgad, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Eva Balslev, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Najat Bouchmaa, Octavio Burgues, Alexandros Chardas, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Anders B Dahl, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Johan Doré Hansen, Sarah N Dudgeon, Thomas Ebstrup, Mahmoud Elghazawy, Claudio Fernandez-Martín, Stephen B Fox, William M Gallagher, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Steven N Hart, Johan Hartman, Søren Hauberg, Stephen Hewitt, Akira I Hida, Hugo M Horlings, Zaheed Husain, Evangelos Hytopoulos, Sheeba Irshad, Emiel Am Janssen, Mohamed Kahila, Tatsuki R Kataoka, Kosuke Kawaguchi, Durga Kharidehal, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Amy Ly, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Arman Rahman, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Jorge S Reis-Filho, Joana M Ribeiro, David Rimm, Anne Roslind, Anne Vincent-Salomon, Manuel Salto-Tellez, Joel Saltz, Shahin Sayed, Ely Scott, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Susan Fineberg, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Paul J Van Diest, Gregory E Verghese, Giuseppe Viale, Michael Vieth, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, Reena Md Zin, Sylvia Adams, John Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Roberto Salgado, Elisabeth Specht Stovgaard

Faculty, Staff and Student Publications

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. …

Spatial Analyses Of Immune Cell Infiltration In Cancer: Current Methods And Future Directions: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, David B Page, Glenn Broeckx, Chowdhury Arif Jahangir, Sara Verbandt, Rajarsi R Gupta, Jeppe Thagaard, Reena Khiroya, Zuzana Kos, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Guray Akturk, Jonas S Almeida, Isabel Alvarado-Cabrero, Farid Azmoudeh-Ardalan, Sunil Badve, Nurkhairul Bariyah Baharun, Enrique R Bellolio, Vydehi Bheemaraju, Kim Rm Blenman, Luciana Botinelly Mendonça Fujimoto, Najat Bouchmaa, Octavio Burgues, Maggie Chon U Cheang, Francesco Ciompi, Lee Ad Cooper, An Coosemans, Germán Corredor, Flavio Luis Dantas Portela, Frederik Deman, Sandra Demaria, Sarah N Dudgeon, Mahmoud Elghazawy, Scott Ely, Claudio Fernandez-Martín, Susan Fineberg, Stephen B Fox, William M Gallagher, Jennifer M Giltnane, Sacha Gnjatic, Paula I Gonzalez-Ericsson, Anita Grigoriadis, Niels Halama, Matthew G Hanna, Aparna Harbhajanka, Alexandros Hardas, Steven N Hart, Johan Hartman, Stephen Hewitt, Akira I Hida, Hugo M Horlings, Zaheed Husain, Evangelos Hytopoulos, Sheeba Irshad, Emiel Am Janssen, Mohamed Kahila, Tatsuki R Kataoka, Kosuke Kawaguchi, Durga Kharidehal, Andrey I Khramtsov, Umay Kiraz, Pawan Kirtani, Liudmila L Kodach, Konstanty Korski, Anikó Kovács, Anne-Vibeke Laenkholm, Corinna Lang-Schwarz, Denis Larsimont, Jochen K Lennerz, Marvin Lerousseau, Xiaoxian Li, Amy Ly, Anant Madabhushi, Sai K Maley, Vidya Manur Narasimhamurthy, Douglas K Marks, Elizabeth S Mcdonald, Ravi Mehrotra, Stefan Michiels, Fayyaz Ul Amir Afsar Minhas, Shachi Mittal, David A Moore, Shamim Mushtaq, Hussain Nighat, Thomas Papathomas, Frederique Penault-Llorca, Rashindrie D Perera, Christopher J Pinard, Juan Carlos Pinto-Cardenas, Giancarlo Pruneri, Lajos Pusztai, Arman Rahman, Nasir Mahmood Rajpoot, Bernardo Leon Rapoport, Tilman T Rau, Jorge S Reis-Filho, Joana M Ribeiro, David Rimm, Anne Vincent-Salomon, Manuel Salto-Tellez, Joel Saltz, Shahin Sayed, Kalliopi P Siziopikou, Christos Sotiriou, Albrecht Stenzinger, Maher A Sughayer, Daniel Sur, Fraser Symmans, Sunao Tanaka, Timothy Taxter, Sabine Tejpar, Jonas Teuwen, E Aubrey Thompson, Trine Tramm, William T Tran, Jeroen Van Der Laak, Paul J Van Diest, Gregory E Verghese, Giuseppe Viale, Michael Vieth, Noorul Wahab, Thomas Walter, Yannick Waumans, Hannah Y Wen, Wentao Yang, Yinyin Yuan, Sylvia Adams, John Mark Seaverns Bartlett, Sibylle Loibl, Carsten Denkert, Peter Savas, Sherene Loi, Roberto Salgado, Elisabeth Specht Stovgaard

Faculty, Staff and Student Publications

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described clinical …

Generative Pre-Trained Transformers (Gpt) And Space Health: A Potential Frontier In Astronaut Health During Exploration Missions, Ethan Waisberg, Joshua Ong, Mouayad Masalkhi, Nasif Zaman, Sharif Amit Kamran, Prithul Sarker, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

In anticipation of space exploration where astronauts are traveling away from Earth, and for longer durations with an increasing communication lag, artificial intelligence (AI) frameworks such as large language learning models (LLMs) that can be trained on Earth can provide real-time answers. This emerging technology may be helpful for acute medical emergencies, particularly in austere and distant space environments. In this manuscript, we provide an overview of generative pre-trained transformer (GPT) technology, a rapidly emerging AI technology, and implications, considerations, and limitations of such technology for space health.

Predictive Model Of Liver Toxicity To Aid The Personalized Selection Of Proton Versus Photon Therapy In Hepatocellular Carcinoma, Ibrahim Chamseddine, Yejin Kim, Brian De, Issam El Naqa, Dan G Duda, John A Wolfgang, Jennifer Pursley, Jennifer Y Wo, Theodore S Hong, Harald Paganetti, Eugene J Koay, Clemens Grassberger

Faculty, Staff and Student Publications

Purpose: Our objective was to develop an externally validated model for predicting liver toxicity after radiation therapy in patients with hepatocellular carcinoma (HCC) that can integrate both photon and proton dose distributions with patient-specific characteristics.

Methods and materials: Training data consisted of all patients with HCC treated between 2008 and 2019 at our institution (n = 117, 60%/40% photon/proton). We developed a shallow convolutional neural network (CNN) to predict posttreatment liver dysfunction from the differential dose-volume histogram (DVH) and baseline liver metrics. To reduce bias and improve robustness, we used ensemble learning (CNNE). After a preregistered study analysis plan, we …

Ultrasensitive Ngs Mrd Assessment In Ph+ All: Prognostic Impact And Correlation With Rt-Pcr For Bcr::Abl1, Nicholas J Short, Elias Jabbour, Walid Macaron, Farhad Ravandi, Nitin Jain, Rashmi Kanagal-Shamanna, Keyur P Patel, Sanam Loghavi, Fadi G Haddad, Musa Yilmaz, Ghayas C Issa, Partow Kebriaei, Steven M Kornblau, Sarah Pelletier, Wilmer Flores, Jairo Matthews, Rebecca Garris, Hagop Kantarjian

Faculty, Staff and Student Publications

Reverse transcription polymerase chain reaction (RT-PCR) for BCR::ABL1 is the most common and widely accepted method of measurable residual disease (MRD) assessment in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL); however, RT-PCR may not be an optimal measure of MRD in many cases of Ph+ ALL. We evaluated the clinical impact of a highly sensitive next-generation sequencing (NGS) MRD assay (sensitivity of 10-6 ) and its correlation with RT-PCR for BCR::ABL1 in patients with Ph+ ALL. Overall, 32% of patients had a discordance between MRD assessment by RT-PCR and NGS, and 31% of patients who achieved NGS MRD negativity were …

A Spatiotemporal Notch Interaction Map From Plasma Membrane To Nucleus, Alexandre P Martin, Gary A Bradshaw, Robyn J Eisert, Emily D Egan, Lena Tveriakhina, Julia M Rogers, Andrew N Dates, Gustavo Scanavachi, Jon C Aster, Tom Kirchhausen, Marian Kalocsay, Stephen C Blacklow

Faculty, Staff and Student Publications

Notch signaling relies on ligand-induced proteolysis of the transmembrane receptor Notch to liberate a nuclear effector that drives cell fate decisions. Upon ligand binding, sequential cleavage of Notch by the transmembrane protease ADAM10 and the intracellular protease γ-secretase releases the Notch intracellular domain (NICD), which translocates to the nucleus and forms a complex that induces target gene transcription. To map the location and timing of the individual steps required for the proteolysis and movement of Notch from the plasma membrane to the nucleus, we used proximity labeling with quantitative, multiplexed mass spectrometry to monitor the interaction partners of endogenous NOTCH2 …

Retrospective Analysis Of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study By The Transatlantic Australasian Retroperitoneal Sarcoma Working Group (Tarpswg), Sangkyu Noh, Carolyn Nessim, Emily Z Keung, Christina L Roland, Dirk Strauss, Gausihi Sivarajah, Marco Fiore, Davide Biasoni, Stefano Piero Bernardo Cioffi, Winta Mehtsun, Ferdinando Carlo Maria Cananzi, Federico Sicoli, Vittorio Quagliuolo, Jun Chen, Chenghua Luo, Rebecca A Gladdy, Carol Swallow, Wendy Johnston, Samuel J Ford, Caroline Evenden, Fabio Tirotta, Max Almond, Laura Nguyen, Piotr Rutkowski, Maria Krotewicz, Elisabetta Pennacchioli, Kenneth Cardona, Adriana Gamboa, Daphne Hompes, Marleen Renard, Attila Kollár, Christoph O Ryser, Nikolaos Vassos, Chandrajit P Raut, Mark Fairweather, Dagmar Adamkova Krakorova, Sergio Quildrian, Andraz Perhavec, Eran Nizri, Jeffrey M Farma, Stephanie H Greco, Bruno Vincenzi, José Antonio González Lopez, Mireia Solans Solerdecoll, Shintaro Iwata, Suguru Fukushima, Teresa Kim, Francesco Tolomeo, Hayden Snow, Ynez Howlett-Jansen, Dimitri Tzanis, Maxim Nikulin, Alessandro Gronchi, Jason K Sicklick, Transatlantic Australasian Retroperitoneal Sarcoma Working Group

Faculty, Staff and Student Publications

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas.

BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series.

METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management.

RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of …

Quality-Adjusted Survival In Women With Gynecologic Malignancies Receiving Imrt After Surgery: A Patient Reported Outcome Study Of Nrg Oncology’S Rtog 1203, Andre Konski, Snehal Deshmukh, Ann H Klopp, Anamaria R Yeung, Shannon N Westin, J Spencer Thompson, Desiree E Doncals, Guilherme H C Cantuaria, David P D'Souza, Amy Chang, Vijayananda Kundapur, Dasarahally S Mohan, Michael L Haas, Yong Bae Kim, Catherine L Ferguson, Stephanie L Pugh, Lisa A Kachnic, Deborah W Bruner

Faculty, Staff and Student Publications

INTRODUCTION: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments.

METHODS: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS), were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1 and 3-years post RT. EQ-5D index and VAS scores along …

Artificial Mirnas Derived From Mir-181 Family Members Have Potential In Cancer Therapy Due To An Altered Spectrum Of Target Mrnas, Sergiu Chira, Cristina Ciocan, Cecilia Bica, George A Calin, Ioana Berindan-Neagoe

Faculty, Staff and Student Publications

miRNAs are a class of noncoding RNAs with gene regulation properties, and they function as key factors in cell homeostasis. The interaction of miRNAs with their target mRNAs is largely considered to rely on sequence complementarity; however, some evidence indicates that mature miRNAs can adopt diverse conformations with implications for their function. Using the oncogenic miR-181 family as a study model, we suggest that a potential relationship between the primary sequence and secondary structure of miRNAs may have an impact on the number and spectrum of targeted cellular transcripts. We further emphasize that specific alterations in miR-181 primary sequences might …

Statin Use And Chemoradiation In Esophageal Squamous Cell Carcinomas: Ready For Prime Time?, Steven H Lin

Faculty, Staff and Student Publications

No abstract provided.

Cooperative Activation Of Pdk1 And Akt By Mapk4 Enhances Cancer Growth And Resistance To Therapy, Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang

Faculty, Staff and Students Publications

Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase of the protein A, G, and C (AGC) family kinases that play important roles in regulating cancer cell proliferation, survival, and metabolism. Besides phosphorylating/activating AKT at the cell membrane in a PI3K-dependent manner, PDK1 also exhibits constitutive activity on many other AGC kinases for tumor-promoting activity. In the latter case, PDK1 protein levels dominate its activity. We previously reported that MAPK4, an atypical MAPK, can PI3K-independently promote AKT activation and tumor growth. Here, using triple-negative breast cancer (TNBC) cell models, we demonstrate that MAPK4 can also enhance PDK1 protein synthesis, thus phosphorylate/activate PDK1 …

The Case For Expanding Visual Assessments During Spaceflight, Ethan Waisberg, Joshua Ong, Mouayad Masalkhi, Nasif Zaman, Sharif Amit Kamran, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments …

Ddx41 Mutations In Patients With Non-Myeloid Hematologic Neoplasms, Fatima Zahra Jelloul, Mark J Routbort, Courtney D Dinardo, Carlos E Bueso-Ramos, Rashmi Kanagal-Shamanna, Beenu Thakral, Zhuang Zuo, C Cameron Yin, Sanam Loghavi, Chi Young Ok, Sa A Wang, Zhenya Tang, M James You, Keyur P Patel, L Jeffrey Medeiros, Andrés E Quesada

Faculty, Staff and Student Publications

No abstract provided.

Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit

Faculty, Staff and Student Publications

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …

Individual, Systemic And State Factors Associated With Provider Recommendation Of Hpv Vaccination: Findings From Nis-Teen, 2020, Ikponmwosa Osaghae, Monalisa Chandra, Rajesh Talluri, Sanjay Shete

Faculty, Staff and Student Publications

The most important determinant of HPV vaccination uptake is healthcare provider recommendation, yet not all eligible patients receive HPV vaccination recommendations. We used data from the 2020 National Immunization Survey-Teen to determine individual, systemic, and state factors associated with provider recommendation of HPV vaccination. A total of 18,534 teens were included, with 81.4% receiving provider recommendations for HPV vaccination. HPV vaccination recommendation was higher among females compared to males (AOR: 1.57; 95% CI: 1.27-1.93), teens who received a well-child exam at 11 or 12 years compared to those who did not (AOR: 2.10; 95% CI: 1.61-2.74), and teens whose mothers …

Gwas-Identified Telomere Length Associated Genetic Variants Predict Risk Of Recurrence Of Hpv-Positive Oropharyngeal Cancer After Definitive Radiotherapy, Peng Sun, Peng Wei, Hongliang Liu, Jia Wu, Neil D Gross, Andrew G Sikora, Qingyi Wei, Sanjay Shete, Mark E Zafereo, Jisheng Liu, Guojun Li

Faculty, Staff and Student Publications

Background: Lymphocyte telomere length (LTL)-related genetic variants may modulate LTL and affect recurrence of squamous cell carcinoma of the oropharynx (SCCOP).

Methods: A total of 1013 patients with incident SCCOP were recruited and genotyped for 16 genome-wide association study (GWAS)-identified TL-related polymorphisms. Of these patients, 489 had tumour HPV16 status determination. Univariate and multivariate analyses were performed to evaluate associations.

Findings: Of the 16 TL-related polymorphisms, four were significantly associated with LTL: rs1920116, rs3027234, rs6772228, and rs11125529, and the patients with putatively favourable genotypes had approximately 1.5-3 times the likelihood of shorter LTL compared with patients with the corresponding risk …

Mosaic Chromosomal Alterations Are Associated With Increased Lung Cancer Risk: Insight From The Integral-Ilcco Cohort Analysis, Chao Cheng, Wei Hong, Yafang Li, Xiangjun Xiao, James Mckay, Younghun Han, Jinyoung Byun, Bo Peng, Demetrios Albanes, Stephen Lam, Adonina Tardon, Chu Chen, Stig E Bojesen, Maria T Landi, Mattias Johansson, Angela Risch, Heike Bickeböller, H-Erich Wichmann, David C Christiani, Gad Rennert, Susanne Arnold, Gary Goodman, John K Field, Michael P A Davies, Sanjay S Shete, Loic Le Marchand, Geoffrey Liu, Rayjean J Hung, Angeline S Andrew, Lambertus A Kiemeney, Meng Zhu, Hongbing Shen, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, Angela Cox, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B Schabath, Melinda C Aldrich, Paul Brennan, Yong Li, Olga Gorlova, Ivan Gorlov, Christopher I Amos, Integral-Ilcco Lung Cancer Consortium

Faculty, Staff and Student Publications

INTRODUCTION: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer.

METHODS: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls.

RESULTS: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal …

Tmbim6 Deficiency Leads To Bone Loss By Accelerating Osteoclastogenesis, Sun-Ju Yi, You-Jee Jang, Seokchan Lee, Sung-Jin Cho, Kyuho Kang, Jae-Il Park, Han-Jung Chae, Hyung-Ryong Kim, Kyunghwan Kim

Faculty, Staff and Student Publications

TMBIM6 is an endoplasmic reticulum (ER) protein that modulates various physiological and pathological processes, including metabolism and cancer. However, its involvement in bone remodeling has not been investigated. In this study, we demonstrate that TMBIM6 serves as a crucial negative regulator of osteoclast differentiation, a process essential for bone remodeling. Our investigation of Tmbim6-knockout mice revealed an osteoporotic phenotype, and knockdown of Tmbim6 inhibited the formation of multinucleated tartrate-resistant acid phosphatase-positive cells, which are characteristic of osteoclasts. Transcriptome and immunoblot analyses uncovered that TMBIM6 exerts its inhibitory effect on osteoclastogenesis by scavenging reactive oxygen species and preventing p65 nuclear localization. …

Association Of Patient-Reported Health-Related Quality Of Life With Physician-Reported Toxicities In Adolescents And Young Adults Receiving Radiation Therapy For Cancer, Kelsey L Corrigan, Bryce B Reeve, John M Salsman, Elizabeth J Siembida, Grace L Smith, Maria C Swartz, Kamaria L Lee, Faraz Afridi, Lauren M Andring, Andrew J Bishop, Jillian R Gunther, J Andrew Livingston, Susan K Peterson, Susan K Parsons, Michael Roth

Faculty, Staff and Student Publications

PURPOSE: Radiation therapy (RT) may cause toxicities in adolescents and young adults (AYAs, age 15-39 years) with cancer. However, the range of RT-related toxicities in AYAs and the affect on health-related quality of life (HRQOL) has not been well studied. We performed a cross-sectional study in AYAs with cancer who received RT to identify RT-related toxicities and examine their impact on HRQOL.

MATERIALS AND METHODS: A total of 178 AYAs received RT and completed PROMIS HRQOL instruments from 2018 to 2022. Acute and late physician-graded Common Terminology Criteria for Adverse Events RT-related toxicities were extracted and described. Multivariable linear regression …

Biochemical And Structural Characterization Of The First-Discovered Metazoan Dna Cytosine-N4 Methyltransferase From The Bdelloid Rotifer Adineta Vaga, Jujun Zhou, John R Horton, Gundeep Kaur, Qin Chen, Xuwen Li, Fabian Mendoza, Tao Wu, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Much is known about the generation, removal, and roles of 5-methylcytosine (5mC) in eukaryote DNA, and there is a growing body of evidence regarding N6-methyladenine, but very little is known about N4-methylcytosine (4mC) in the DNA of eukaryotes. The gene for the first metazoan DNA methyltransferase generating 4mC (N4CMT) was reported and characterized recently by others, in tiny freshwater invertebrates called bdelloid rotifers. Bdelloid rotifers are ancient, apparently asexual animals, and lack canonical 5mC DNA methyltransferases. Here, we characterize the kinetic properties and structural features of the catalytic domain of the N4CMT protein from the bdelloid rotifer Adineta vaga. We …

Cardiac Substructure Radiation Dose And Risk Of Late Cardiac Disease In Survivors Of Childhood Cancer: A Report From The Childhood Cancer Survivor Study, James E Bates, Suman Shrestha, Qi Liu, Susan A Smith, Daniel A Mulrooney, Wendy Leisenring, Todd Gibson, Leslie L Robison, Eric J Chow, Kevin C Oeffinger, Gregory T Armstrong, Louis S Constine, Bradford S Hoppe, Choonsik Lee, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

PURPOSE: Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished.

METHODS: Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships.

RESULTS: The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 …

Outcomes After Definitive Treatment For Cutaneous Angiosarcomas Of The Face And Scalp: Reevaluating The Role Of Surgery And Radiation Therapy, Alison K Yoder, Ahsan S Farooqi, Cort Wernz, Aparna Subramaniam, Vinod Ravi, Ryan Goepfert, Erich M Sturgis, Devarati Mitra, Andrew J Bishop, B Ashleigh Guadagnolo

Faculty, Staff and Student Publications

INTRODUCTION: We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA).

METHODS: We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model.

RESULTS: For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained …

Predicting Severity Of Radiation Induced Lymphopenia In Individual Proton Therapy Patients For Varying Dose Rate And Fractionation Using Dynamic 4-Dimensional Blood Flow Simulations, Lucas Mccullum, Jungwook Shin, Stella Xing, Chris Beekman, Jan Schuemann, Theodore Hong, Dan Duda, Radhe Mohan, Steven H Lin, Camilo M Correa-Alfonso, Sean Domal, Julia Withrow, Wesley Bolch, Harald Paganetti, Clemens Grassberger

Faculty, Staff and Student Publications

PURPOSE: Radiation-induced lymphopenia has gained attention recently as the result of its correlation with survival in a range of indications, particularly when combining radiation therapy (RT) with immunotherapy. The purpose of this study is to use a dynamic blood circulation model combined with observed lymphocyte depletion in patients to derive the in vivo radiosensitivity of circulating lymphocytes and study the effect of RT delivery parameters.

METHODS AND MATERIALS: We assembled a cohort of 17 patients with hepatocellular carcinoma treated with proton RT alone in 15 fractions (fx) using conventional dose rates (beam-on time [BOT], 120 seconds) for whom weekly absolute …

Tp53 Gain-Of-Function Mutation Modulates The Immunosuppressive Microenvironment In Non-Hpv-Associated Oral Squamous Cell Carcinoma, Yewen Shi, Xiaoyong Ren, Shaolong Cao, Xi Chen, Bo Yuan, Fabio Henrique Brasil Da Costa, Alanis E Rodriguez Rosario, Arnoldo Corona, Chieko Michikawa, Ratna Veeramachaneni, Abdullah A Osman, Tongxin Xie, Wenyi Wang, Andrew G Sikora, Jeffrey N Myers, Roberto Rangel

Faculty, Staff and Student Publications

BACKGROUND: TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.

METHODS: Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H …

Maternal Provisioning Interacts With Incubation Temperature To Affect Hatchling Mercury Exposure In An Oviparous Reptile, Josiah M Johnson, Christopher R Smaga, Samantha L Bock, Benjamin B Parrott

Faculty, Staff and Student Publications

The thermal environment experienced by developing embryos can influence the utilization of maternally provisioned resources. Despite being particularly consequential for oviparous ectotherms, these dynamics are largely unexplored within ecotoxicological frameworks. Here, we test if incubation temperature interacts with maternally transferred mercury to affect subsequent body burdens and tissue distributions of mercury in hatchling American alligators (