Medical Genetics Commons^™

Neutrophils Unveiled In Chronic Lymphocytic Leukemia, Sheighlah Mcmanus, Priyanka Khare, Maria Teresa S Bertilaccio

Faculty, Staff and Student Publications

This review explores neutrophils' roles in chronic lymphocytic leukemia (CLL), highlighting their functions within the immune system. While neutrophils are known for fighting infections, their altered behavior in CLL significantly impacts disease progression. This review notes the reduced phagocytic abilities of neutrophils and the increased formation of neutrophil extracellular traps (NETs) in patients with CLL. It also examines the effects of CLL treatments, including chemotherapy, immunotherapy and targeted therapies, on neutrophils' count and function, stressing the need for improved strategies to manage therapy-induced immune dysfunction. This review also provides detailed information about the interactions between neutrophils and other immune elements …

International Multicenter Retrospective Study From The Ultra-Rare Sarcoma Working Group On Low-Grade Fibromyxoid Sarcoma, Sclerosing Epithelioid Fibrosarcoma, And Hybrid Forms: Outcome Of Primary Localized Disease, Claudia Giani, Abdulazeez Salawu, Silva Ljevar, Ryan A Denu, Andrea Napolitano, Emanuela Palmerini, Elizabeth A Connolly, Koichi Ogura, Daniel D Wong, Roberto Scanferla, Evan Rosenbaum, Jyoti Bajpai, Zola Chia-Chen Li, Susie Bae, Lorenzo D'Ambrosio, Steve Bialick, Andrew J Wagner, Alexander T J Lee, Hanna Koseła-Paterczyk, Giacomo G Baldi, Antonella Brunello, Yeh Chen Lee, Herbert H Loong, Sosipatros Boikos, Fernando Campos, Carlo M Cicala, Robert G Maki, Nadia Hindi, Costanza Figura, Shahd S Almohsen, Sheyaskumar Patel, Robin L Jones, Toni Ibrahim, Rooshdiya Karim, Akira Kawai, Richard Carey-Smith, Richard Boyle, Silvia M Taverna, Alexander J Lazar, Elizabeth G Demicco, Judith V M G Bovee, Angelo P Dei Tos, Christopher Fletcher, Daniel Baumhoer, Marta Sbaraglia, Inga-Marie Schaefer, Rosalba Miceli, Alessandro Gronchi, Silvia Stacchiotti

Faculty, Staff and Student Publications

The aim of the study was to report the outcome of primary localized low-grade fibromyxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), and hybrid LGFMS/SEF (H-LGFMS/SEF). Patients with primary localized LGFMS, SEF, or H-LGFMS/SEF, surgically treated with curative intent from January 2000 to September 2022, were enrolled from 14 countries and 27 institutions. Pathologic inclusion criteria were predefined by expert pathologists. The primary endpoint was overall survival (OS). Secondary endpoints were crude cumulative incidence (CCI) of local recurrence (LR), CCI of distant metastases (DM), and post-metastases OS (p-OS). Two hundred ninety-four patients (239 LGFMS, 32 SEF, and 23 H-LGFMS/SEF) were identified. …

Histopathologic Progression And Metastatic Relapse Outcomes In Small Cell Neuroendocrine Carcinomas Of The Urinary Tract, Mohammad Jad Moussa, Georges C Tabet, Arlene O Siefker-Radtke, Lianchun Xiao, Nathaniel R Wilson, Jianjun Gao, Christopher J Logothetis, Petros Grivas, Byron Lee, Amishi Y Shah, Pavlos Msaouel, Roger Li, Leticia Campos Clemente, Jianping Zhao, Nizar M Tannir, Ashish M Kamat, Donna E Hansel, Charles C Guo, Matthew T Campbell, Omar Alhalabi

Faculty, Staff and Student Publications

Introduction: Small cell neuroendocrine carcinoma of the urinary tract (SCNEC-URO) has an inferior prognosis compared to conventional urothelial carcinoma (UC). Here, we evaluate the predictors and patterns of relapse after surgery.

Materials and methods: We identified a definitive-surgery cohort (n = 224) from an institutional database of patients with cT1-T4NxM0 SCNEC-URO treated in 1985-2021. Histopathologic review was conducted by independent pathologists. Relapse event was the time-to-event outcome, and relapse probabilities were estimated using a competing risk method with cumulative incidence functions (CIFs). Fine-Gray distribution models assessed covariate associations.

Results: Most patients (161, 71.9%) received neoadjuvant chemotherapy (neoCTX). Ninety two (41%) …

Outcomes Of Patients Treated With Chemotherapy For Breast Cancer During Pregnancy Compared With Nonpregnant Breast Cancer Patients Treated With Systemic Therapy, Helen M Johnson, Juhee Song, Carla L Warneke, Ashley L Martinez, Jennifer K Litton, Oluchi C Oke

Faculty, Staff and Student Publications

Introduction: Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype.

Methods: PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible. Disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression.

Results: Among 143 PrBC and 285 nonpregnant patients, median follow-up was 11.4 years. …

A Pan-Tumor Review Of The Role Of Poly(Adenosine Diphosphate Ribose) Polymerase Inhibitors, Chadi Hage Chehade, Georges Gebrael, Nicolas Sayegh, Zeynep Irem Ozay, Arshit Narang, Tony Crispino, Talia Golan, Jennifer K Litton, Umang Swami, Kathleen N Moore, Neeraj Agarwal

Faculty, Staff and Student Publications

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical …

Outcomes With Bridging Radiation Therapy Prior To Chimeric Antigen Receptor T-Cell Therapy In Patients With Aggressive Large B-Cell Lymphomas, Gohar S Manzar, Chelsea C Pinnix, Stephanie O Dudzinski, Kathryn E Marqueen, Elaine E Cha, Lewis F Nasr, Alison K Yoder, Michael K Rooney, Paolo Strati, Sairah Ahmed, Chijioke Nze, Ranjit Nair, Luis E Fayad, Michael Wang, Loretta J Nastoupil, Jason R Westin, Christopher R Flowers, Sattva S Neelapu, Jillian R Gunther, Bouthaina S Dabaja, Susan Y Wu, Penny Q Fang

Faculty, Staff and Student Publications

Background: Select patients with relapsed/refractory aggressive B cell lymphoma may benefit from bridging radiation (bRT) prior to anti-CD19-directed chimeric antigen receptor T cell therapy (CAR-T). Here, we examined patient and treatment factors associated with outcomes and patterns of failure after bRT and CAR-T.

Methods: We retrospectively reviewed adults with diffuse large B-cell lymphoma (DLBCL) who received bRT prior to axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel between 11/2017-4/2023. Clinical/treatment characteristics, response, and toxicity were extracted. Survival was modeled using Kaplan-Meier or Cox regression models for events distributed over time, or binary logistic regression for disease response. Fisher's Exact Test or Mann-Whitney …

Relationship Between Trpm4 Rs8104571 Genotype, Circulating Trpm4 And Sur1, And Clinical Outcome Following Traumatic Brain Injury, Joseph D Krocker, Madeline E Cotton, Janet R Ashley, Jacob B Schriner, Baron K Osborn, Yao-Wei Willa Wang, Charles S Cox, Charles E Wade

Faculty, Staff and Student Publications

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients. Trauma patients with moderate to severe TBI were included in this retrospective study. rs8104571 genotyping and admission …

Mutation Of Conserved Mhc Class I Cytoplasmic Tyrosine Affects Cd8+ T Cell Priming, Effector Function, And Memory Response, Yimo Sun, Yitao Tang, Priscilla Ortiz, Barbara Nassif Rausseo, Barbara Pazdrak, Lama Elzohary, Arjun Katailiha, Amjad Talukder, Cassian Yee, Richard Eric Davis, Gregory Lizée

Faculty, Staff and Student Publications

The cytoplasmic domain of MHC class I (MHC-I) molecules contains a single, highly conserved tyrosine residue (Y320). In previous work, we found that mice expressing a Y320F-mutated form of H-2Kb had reduced capacity to generate Kb-restricted cytotoxic T lymphocyte (CTL) responses following viral infection, due at least in part to defects in endolysosomal trafficking of H-2Kb and antigen cross-presentation by dendritic cells (DCs). In this study, we investigated whether there are additional, post-presentation dependencies on Y320 for T cell priming. We engineered both human- and mouse-derived antigen-presenting cells (APCs) to express either wild-type MHC-I or variants of MHC-I containing Y320F …

Correction: Bronchoalveolar Lavage Cell Percentages As Diagnostic Markers Of Immune Checkpoint Inhibitor Pneumonitis, Mahnoor Mir, Felipe Soto, Pedro Antonio Amezcua Gomez, Rodrigo Del Rio Arroyo, Adarsh Suresh, Amber Su, Qiong Gan, John Stewart, Roberto Adachi, Diwakar D Balachandran, Lara Bashoura, Roberto F Casal, Burton F Dickey, George A Eapen, Scott E Evans, Horiana Grosu, Carlos A Jimenez, Julie Lin, David E Ost, Bruce F Sabath, Vickie R Shannon, Aung Naing, Jianjun Gao, Jia Wu, Karthik Suresh, Saadia A Faiz, Mehmet Altan, Ajay Sheshadri

Faculty, Staff and Student Publications

[This corrects the article DOI: 10.3389/fmed.2025.1582714.].

A Prospective Cohort Study On Stereotactic Radiotherapy In The Management Of Dural Recurrence Of Olfactory Neuroblastoma, Christopher D Goodman, Franco Demonte, Theresa P Nguyen, Adam S Garden, Catherine He Wang, Xin A Wang, Kevin Diao, Anna Lee, Jay Reddy, Amy Moreno, Michael Spiotto, Clifton D Fuller, David Rosenthal, Renata Ferrarotto, Shaan M Raza, Shirley Y Su, Andrew Warner, Ehab Hanna, Jack Phan

Faculty, Staff and Student Publications

Background: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population.

Methods: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed.

Results: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression …

Keygan: Synthetic Keystroke Data Generation In The Context Of Digital Phenotyping, Alejandro Acien, Aythami Morales, Luca Giancardo, Ruben Vera-Rodriguez, Ashley A Holmes, Julian Fierrez, Teresa Arroyo-Gallego

Faculty, Staff and Student Publications

Objective: This paper aims to introduce and assess KeyGAN, a generative modeling-based keystroke data synthesizer. The synthesizer is designed to generate realistic synthetic keystroke data capturing the nuances of fine motor control and cognitive processes that govern finger-keyboard kinematics, thereby paving the way to support biomarker development for psychomotor impairment due to neurodegeneration.

Methods: KeyGAN is designed with two primary objectives: (i) to ensure high realism in the synthetic distributions of the keystroke features and (ii) to analyze its ability to replicate the subtleties of natural typing for enhancing biomarker development. The quality of synthetic keystroke data produced by KeyGAN …

Comparison Of Primary Care Experiences And Outpatient Health Service Utilization Among Black And Latino Homeless-Experienced Veterans: An Analysis Of Patient-Centered Medical Homes, Melissa Chinchilla, Audrey L Jones, Aerin Derussy, Michael F Green, Lillian Gelberg, Alexander S Young, Jack Tsai, Sonya E Gabrielian, Stefan G Kertesz

Faculty, Staff and Student Publications

Objectives: To examine whether, among persons with recent homeless experience, minoritized clients rate primary care differently from non-minoritized clients in Veterans Affairs (VA) mainstream and homeless tailored clinics, through the largest survey of homeless-experienced Black, White, and Latino Veterans to date.

Methods: Surveys were collected from HEVs in Homeless-tailored Patient-Aligned Care Teams (HPACTs) and mainstream Patient Aligned Care Teams (PACTs; n = 4894). We tested multivariable associations between race/ethnicity, clinic (HPACT vs mainstream-PACT), and their interaction, on care experience ratings and service utilization.

Results: There were no major differences in care ratings by race/ethnicity; medical and social vulnerability factors were …

Racial And Ethnic Disparities In Longitudinal Trajectories Of Cardiovascular Risk Factors In Us Middle-Aged And Older Adults, Matthew E Dupre, Radha Dhingra, Hanzhang Xu, Scott M Lynch, Qing Yang, Cassie Ford, Michael D Green, Ying Xian, Ann Marie Navar, Eric D Peterson

Faculty, Staff and Student Publications

Background: Racial and ethnic disparities in cardiovascular disease (CVD) risk factors are well-documented. However, racial and ethnic differences in the longitudinal changes among multiple CVD risk factors are unknown.

Methods: We used prospective cohort data of U.S. adults aged ≥50 in the 2006-2016 Health and Retirement Study. Group-based multi-trajectory models characterized age-related trajectories of systolic blood pressure ([BP] mmHg), non-HDL cholesterol (mg/dL), diabetes mellitus (DM), and smoking. Racial and ethnic differences in the multi-trajectory profiles were examined using multinomial logistic regression. Karlson-Holm-Breen methods were used to assess factors contributing to these associations.

Results: Among 10,292 participants (median age: 61), approximately …

Consolidation Alk Tyrosine Kinase Inhibitors Versus Durvalumab Or Observation After Chemoradiation In Unresectable Stage Iii Alk-Positive Nsclc, Amin H Nassar, Ritujith Jayakrishnan, Jamie Feng, Frances Shepherd, Elio Adib, Justin M Cheung, Jessica J Lin, Yufei Liu, Steven H Lin, Kaushal Parikh, Arthi Sridhar, Purnima Shakya, Thomas J Dilling, David Kaldas, Jhanelle E Gray, Anastasiya Lobachov, Jair Bar, Heike Luders, Christian Grohe, Shruti Gupta, Ticiana Leal, Bailey Fitzgerald, Fionnuala Crowley, Yu Fujiwara, Thomas U Marron, Molly Wilgucki, Joshua Reuss, Luxi Chen, Kamya Sankar, Jacqueline V Aredo, Joel W Neal, Heather A Wakelee, Rohit Thummalapalli, Helena Yu, Ryan Whitaker, Ana Velazquez, Meera Ragavan, Alessio Cortellini, David J Kwiatkowski, Abdul Rafeh Naqash, Sarah B Goldberg, So Yeon Kim

Faculty, Staff and Student Publications

Introduction: Patients with advanced ALK-positive NSCLC typically have poor response to immunotherapy; the benefit of consolidation durvalumab in patients with unresectable stage III ALK-positive NSCLC remains unclear. Herein, we compare the efficacy and safety of consolidation ALK tyrosine kinase inhibitor (TKI) versus durvalumab or observation after concurrent chemoradiation.

Methods: We conducted a retrospective study using a multicenter study of 17 institutions globally. Patients with unresectable stage III ALK-positive NSCLC treated between 2015 and 2022 were included. Patients received ALK TKI, durvalumab, or observation after concurrent chemoradiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier method. Treatment-related …

Correlation Of Pancreatic Laminin Alpha 5 Expression With Clinical Outcomes In Total Pancreatectomy With Islet Autotransplantation, Jayachandra Kuncha, Carly M Darden, Yang Liu, Michael Lawrence, J Sebastian Danobeitia, Bashoo Naziruddin

Faculty, Staff and Student Publications

This study examines extracellular matrix (ECM) protein (ECM) expression in chronic pancreatitis (CP) patients and its correlation with graft function after total pancreatectomy with islet autologous transplantation (TPIAT). Pancreatic sections from 29 CP patients undergoing TPIAT were analyzed for ECM including pan-laminin, laminin alpha 5 (LAMA5), collagen IV, and Perlecan by immunohistochemistry and scored by the percentage positive staining area within the whole tissue area. Graft function was monitored by blood glucose and C-peptide levels. Laminin alpha 5 levels in blood plasma were greater in CP. Laminin alpha 5 expression was significantly higher in all CP patient etiological categories including …

Stim1 And Lipid Interactions At Er-Pm Contact Sites, Yuepeng Ke, Ritchel Gannaban, Junchen Liu, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated calcium (Ca2+) entry (SOCE) represents a major route of Ca2+ permeation across the plasma membrane (PM) in non-excitable cells, which plays an indispensable role in maintaining intracellular Ca2+ homeostasis. This process is orchestrated through the dynamic coupling between the endoplasmic reticulum (ER)-localized Ca2+ sensor stromal interaction molecule 1 (STIM1) and the PM-resident ORAI1 channel. Upon depletion of ER Ca2+ stores, STIM1 undergoes conformational rearrangements and oligomerization, leading to translocation of STIM1-containing ER membrane towards the PM. This movement is facilitated by the physical interaction between positively charged cytosolic domains within STIM1 and negatively charged phospholipids embedded in the PM, …

Combining Biology-Based And Mri Data-Driven Modeling To Predict Response To Neoadjuvant Chemotherapy In Patients With Triple-Negative Breast Cancer, Casey E Stowers, Chengyue Wu, Zhan Xu, Sidharth Kumar, Clinton Yam, Jong Bum Son, Jingfei Ma, Jonathan I Tamir, Gaiane M Rauch, Thomas E Yankeelov

Faculty, Staff and Student Publications

Purpose

To combine deep learning and biology-based modeling to predict the response of locally advanced, triple-negative breast cancer before initiating neoadjuvant chemotherapy (NAC).

Materials and Methods

In this retrospective study, a biology-based mathematical model of tumor response to NAC was constructed and calibrated on a patient-specific basis using imaging data from patients enrolled in the MD Anderson A Robust TNBC Evaluation FraMework to Improve Survival trial (ARTEMIS; ClinicalTrials.gov registration no. NCT02276443) between April 2018 and May 2021. To relate the calibrated parameters in the biology-based model and pretreatment MRI data, a convolutional neural network (CNN) was employed. The CNN …

Integrative Multi-Omics Approach For Improving Causal Gene Identification, Austin King, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) have been widely used to identify thousands of likely causal genes for diseases and complex traits using predicted expression models. However, most existing TWAS methods rely on gene expression alone and overlook other regulatory mechanisms of gene expression, including DNA methylation and splicing, that contribute to the genetic basis of these complex traits and diseases. Here we introduce a multi-omics method that integrates gene expression, DNA methylation, and splicing data to improve the identification of associated genes with our traits of interest. Through simulations and by analyzing genome-wide association study (GWAS) summary statistics for 24 complex …

Peripheral Administration Of Blood From Tau Transgenic Animals Exacerbates Brain Tau-Associated Pathology, Laura Vegas-Gomez, Matias Pizarro, Jesus Garcia-Martin, Maria Angeles Arredondo-Alcala, Bianca Bustamante, Carolina Gonzalez-Silva, Soledad Matus, Rodrigo Diaz-Espinoza, Antonia Gutierrez, Rodrigo Morales, Claudia Duran-Aniotz, Ines Moreno-Gonzalez

Faculty, Staff and Student Publications

The accumulation of amyloid plaques and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD). While amyloid-beta propagation through prion-like mechanisms has been extensively studied in both central and peripheral pathways, the potential spreading of tau aggregates in the periphery remains largely unexplored. Emerging evidence suggests that hyperphosphorylated tau (ptau) aggregates may propagate beyond the central nervous system, as they have been detected in peripheral tissues and biological fluids from humans and mouse models of tauopathies. However, whether peripheral ptau aggregates or other factors associated to its accumulation contribute to brain pathology remains unclear. In this study, we investigate the …

Accumulated Seizure Burden Predicts Neurodevelopmental Outcome At 36 Months Of Age In Patients With Tuberous Sclerosis Complex, S Katie Z Ihnen, Samuel Alperin, Jamie K Capal, Alexander L Cohen, Jurriaan M Peters, E Martina Bebin, Hope A Northrup, Mustafa Sahin, Darcy A Krueger

Faculty, Staff and Student Publications

Objective: Epilepsy and intellectual disability are common in tuberous sclerosis complex (TSC). Although early life seizures and intellectual disability are known to be correlated in TSC, the differential effects of age at seizure onset and accumulated seizure burden on development remain unclear.

Methods: Daily seizure diaries, serial neurodevelopmental testing, and brain magnetic resonance imaging were analyzed for 129 TSC patients followed from 0 to 36 months. We used machine learning to identify subgroups of patients based on neurodevelopmental test scores at 36 months of age and assessed the stability of those subgroups at 12 months. We tested the ability of …

Real-World Outcomes Of Upfront Autologous Hematopoietic Stem Cell Transplantation In Patients With Newly Diagnosed Multiple Myeloma With Deletion 17p, Curtis Marcoux, Oren Pasvolsky, Denái R Milton, Mark R Tanner, Qaiser Bashir, Samer Srour, Neeraj Saini, Paul Lin, Jeremy Ramdial, Yago Nieto, Guilin Tang, Hans C Lee, Krina K Patel, Partow Kebriaei, Amna Ahmed, Yosra Aljawai, Sheeba K Thomas, Robert Z Orlowski, Elizabeth J Shpall, Richard E Champlin, Muzaffar H Qazilbash

Faculty, Staff and Student Publications

Despite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. The aim of this study was to evaluate real-world outcomes in patients with newly diagnosed MM (NDMM) with del(17p) undergoing upfront autologous hematopoietic stem cell transplantation (auto-HCT). We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being …

Practical Application Of Multivendor Mri-Based R2* Mapping For Liver Iron Quantification At 15 T And 30 T, Gregory Simchick, Ruiyang Zhao, Qing Yuan, Mounes Aliyari Ghasabeh, Stefan Ruschke, Dimitrios C Karampinos, David T Harris, Raphael Do Vale Souza, Ryan J Mattison, Michael R Jeng, Ivan Pedrosa, Ihab R Kamel, Shreyas Vasanawala, Takeshi Yokoo, Scott B Reeder, Diego Hernando

Faculty, Staff and Student Publications

Background: Recent multicenter, multivendor MRI-based R2* vs. liver iron concentration (LIC) calibrations (i.e., MCMV calibrations) may facilitate broad clinical dissemination of R2*-based LIC quantification. However, these calibrations are based on a centralized offline R2* reconstruction, and their applicability with vendor-provided R2* maps is unclear.

Purpose: To determine R2* ranges of agreement between the centralized and three MRI vendors' R2* reconstructions.

Study type: Prospective.

Subjects: Two hundred and seven subjects (mean age 37.6 ± 19.6 years; 117 male) with known or suspected iron overload from four academic medical centers.

Field strength/sequence: Standardized multiecho spoiled gradient echo sequence at 1.5 T and …

Nrg Oncology White Paper On The Relative Biological Effectiveness In Proton Therapy, Harald Paganetti, Charles B Simone, Walter R Bosch, Daphne Haas-Kogan, David G Kirsch, Heng Li, Xiaoying Liang, Wei Liu, Anita Mahajan, Michael D Story, Paige A Taylor, Henning Willers, Ying Xiao, Jeffrey C Buchsbaum

Faculty, Staff and Student Publications

This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of …

Comprehensive Genomic Analysis Reveals Molecular Heterogeneity In Pediatric Alk-Positive Anaplastic Large Cell Lymphoma, Timothy I Shaw, Stanley Pounds, Xueyuan Cao, Jing Ma, Gustavo Palacios, John Mason, Sherrie Perkins, Gang Wu, Yiping Fan, Jian Wang, Xin Zhou, Alyssa Obermayer, Marsha C Kinney, Jacqueline Kraveka, Thomas Gross, John Sandlund, Jinghui Zhang, Charles Mullighan, Megan S Lim, Vasiliki Leventaki

Faculty, Staff and Student Publications

Anaplastic large cell lymphoma (ALCL) is a mature T-cell lymphoma that accounts for 10-15% of childhood lymphomas. Despite the observation that more than 90% of pediatric cases harbor the anaplastic lymphoma kinase (ALK) rearrangement resulting in aberrant ALK kinase expression, there is significant clinical, morphologic, and biological heterogeneity. To gain insights into the genomic aberrations and molecular heterogeneity within ALK-positive ALCL (ALK+ ALCL), we analyzed 46 pediatric ALK+ ALCLs by whole-exome sequencing, RNA sequencing, and DNA methylation profiling. Whole-exome sequencing found on average 25 SNV/Indel events per sample with recurring genetic events in regulators of DNA damage (TP53, MDM4), transcription …

Global Research Trends And Focus On Immunotherapy For Endometrial Cancer: A Comprehensive Bibliometric Insight And Visualization Analysis (2012–2024), Yachen Xu, Tao Wang, Xiaojing Liang, Jie Yang, Yuxiang Zhang, Shan Bao

Faculty, Staff and Student Publications

Background: This study conducted a novel systematic bibliometric and visualization analysis of global literature on immunotherapy for endometrial cancer (EC) to explore dynamic trends, research hotspots, and emerging topics, providing valuable references for future research.

Methods: Articles and reviews on EC immunotherapy published between 2012 and August 2024 were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric tools, CiteSpace and VOSviewer, were used to analyze clustering patterns and research dynamics.

Results: A total of 861 articles were contributed by 5,331 authors from 1,392 institutions across 58 countries or regions, involving 1,823 keywords. China demonstrated outstanding performance in this …

Long-Term Symptom Burden In A Young, Ambulatory Cohort After The Omicron Outbreak In China, Simeng Ren, Yumeng Tan, Hongkun Xu, Mian Wang, Rumei Xiang, Jiayue Jin, Baojin Han, Jiaheng Shi, Jingyu Zhang, Jinliang Yang, Xin Tian, Ying Li, Jiaojiao Chen, Wenzheng Zhang, Jingqi Yang, Xin Shelley Wang, Qiuling Shi, Jie Liu

Faculty, Staff and Student Publications

Introduction: At the end of 2022, an outbreak of the Omicron BF.7 and BA.5.2 subvariants of SARS-CoV-2 occurred in China. In this prospective cohort study, we investigated the pattern of development of major symptom burden and influencing factors in infected Chinese patients.

Methods: First-time infected outpatients were enrolled from December 7, 2022, to January 11, 2023 (N = 355). The prevalence of symptoms was monitored by a repeated patient-reported quantitative symptom survey over nine months.

Results: At the onset of the infection, the most prevalent symptoms (score ≥1 on a 0-10 numeric rating scale) were fatigue (91.8%), cough (91.8%), …

Characterization Of Additive Gene-Environment Interactions For Colorectal Cancer Risk, Claire E Thomas, Yi Lin, Michelle Kim, Eric S Kawaguchi, Conghui Qu, Caroline Y Um, Brigid M Lynch, Bethany Van Guelpen, Kostas Tsilidis, Robert Carreras-Torres, Franzel J B Van Duijnhoven, Lori C Sakoda, Peter T Campbell, Yu Tian, Jenny Chang-Claude, Stéphane Bézieau, Arif Budiarto, Julie R Palmer, Polly A Newcomb, Graham Casey, Loic Le Marchandz, Marios Giannakis, Christopher I Li, Andrea Gsur, Christina Newton, Mireia Obón-Santacana, Victor Moreno, Pavel Vodicka, Hermann Brenner, Michael Hoffmeister, Andrew J Pellatt, Robert E Schoen, Niki Dimou, Neil Murphy, Marc J Gunter, Sergi Castellví-Bel, Jane C Figueiredo, Andrew T Chan, Mingyang Song, Li Li, D Timothy Bishop, Stephen B Gruber, James W Baurley, Stephanie A Bien, David V Conti, Jeroen R Huyghe, Anshul Kundaje, Yu-Ru Su, Jun Wang, Temitope O Keku, Michael O Woods, Sonja I Berndt, Stephen J Chanock, Catherine M Tangen, Alicja Wolk, Andrea Burnett-Hartman, Anna H Wu, Emily White, Matthew A Devall, Virginia Díez-Obrero, David A Drew, Edward Giovannucci, Akihisa Hidaka, Andre E Kim, Juan Pablo Lewinger, John Morrison, Jennifer Ose, Nikos Papadimitriou, Bens Pardamean, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Xuechen Chen, Duncan C Thomas, Elizabeth A Platz, W James Gauderman, Ulrike Peters, Li Hsu

Faculty, Staff and Student Publications

Background: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure.

Methods: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk.

Results: There was no evidence of multiplicative interaction …

Optimization Of Proximity Labeling In Endothelial Cells: Overcoming Endogenous Biotin Interference And Cost Barriers, Ying Jiang, Kuizhi Qu, Mengjun Dai, Yan-Ning Rui, Zhen Xu

Faculty, Staff and Student Publications

Proximity labeling has become a powerful technique for mapping protein-protein interactions under physiologically relevant conditions, with TurboID offering high enzymatic activity and rapid labeling. However, its application in endothelial systems has been limited, partly due to the presence of endogenous biotin in specialized media, which reduces labeling specificity. Here, we optimized TurboID-mediated proximity labeling in brain microvascular endothelial cells by addressing two key challenges: endogenous biotin interference and cost-effective depletion. We discovered that endothelial cell medium contains substantial biotin levels, which saturate TurboID labeling and obscure the effects of exogenous biotin. Using High Capacity NeutrAvidin

Structured Personalized Oxygen And Supportive Therapies For Dyspnea In Oncology (Spot-On): A Personalized Randomized Clinical Trial Protocol, David Hui, Min Ji Kim, Saji Thomas, Gautam Sachdev, Sanjay Shete, Nisha Rathi, Nicole Hensch, Vera De La Cruz, Amy Ontai, Donald A Mahler, Jie Li, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Low-flow supplemental oxygen (LFSO), high-flow nasal cannula (HFNC), and non-invasive ventilation (NIV) are often used for palliation of dyspnea in hospitalized patients. However, it is unclear how patients prefer to use these modalities and how they can be personalized for optimal dyspnea relief. The objective of this randomized clinical trial is to compare the effect of a personalized respiratory therapist (RT)-led intervention, termed SPOT-ON, and enhanced usual care on dyspnea intensity in both hypoxemic and non-hypoxemic hospitalized patients with cancer.

Methods: In this two-arm, parallel group, partially blinded, waitlist-controlled randomized clinical trial, hospitalized patients with advanced cancer and at …

Refining Breast Cancer Genetic Risk And Biology Through Multi-Ancestry Fine-Mapping Analyses Of 192 Risk Regions, Guochong Jia, Zhishan Chen, Jie Ping, Qiuyin Cai, Ran Tao, Chao Li, Joshua A Bauer, Yuhan Xie, Stefan Ambs, Mollie E Barnard, Yu Chen, Ji-Yeob Choi, Yu-Tang Gao, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Motoki Iwasaki, Esther M John, Sun-Seog Kweon, Christopher I Li, Koichi Matsuda, Keitaro Matsuo, Katherine L Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Sue K Park, Boyoung Park, Michael F Press, Maureen Sanderson, Dale P Sandler, Chen-Yang Shen, Melissa A Troester, Song Yao, Ying Zheng, Thomas Ahearn, Abenaa M Brewster, Adeyinka Falusi, Anselm J M Hennis, Hidemi Ito, Michiaki Kubo, Eun-Sook Lee, Timothy Makumbi, Paul Ndom, Dong-Young Noh, Katie M O'Brien, Oladosu Ojengbede, Andrew F Olshan, Min-Ho Park, Sonya Reid, Taiki Yamaji, Gary Zirpoli, Ebonee N Butler, Maosheng Huang, Siew-Kee Low, John Obafunwa, Clarice R Weinberg, Haoyu Zhang, Hongyu Zhao, Michelle L Cote, Christine B Ambrosone, Dezheng Huo, Bingshan Li, Daehee Kang, Julie R Palmer, Xiao-Ou Shu, Christopher A Haiman, Xingyi Guo, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant. Analyses integrating functional genomics data identified 195 putative susceptibility genes, enriched in PI3K/AKT, TNF/NF-κB, p53 …