Medicine and Health Sciences Commons^™

Multi-Omic Profiling Provides Insights Into The Heterogeneity, Microenvironmental Features, And Biomarker Landscape Of Small-Cell Lung Cancer, Mingchao Xie, Miljenka Vuko, Shashank Saran, Siyu Liu, Andrew G Chambers, Hana Baakza, Helen K Angell, Felicia Ng, Carl M Gay, Robert J Cardnell, Felix J Segerer, Alma Andoni, Jaime Rodriguez-Canales, Paul M Waring, Markus Schick, J Carl Barrett, Lauren A Byers, Giulia Fabbri

Faculty, Staff and Student Publications

Background: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.

Methods: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.

Results: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest …

Inhibition Of Clostridioides Difficile-Specific Dna Adenine Methyltransferase Cama By Analogs Of S‑Adenosyl‑L‑Methionine, Jujun Zhou, Youchao Deng, Dan Yu, Taraneh Hajian, Masoud Vedadi, Xing Zhang, Robert M Blumenthal, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapies, especially those inhibiting S-adenosyl-l-methionine (SAM)-dependent methylations of DNA, mRNA, and histones, have advanced rapidly in cancer treatment. However, these therapies remain underexplored for antibiotic development, despite the growing threat of antimicrobial resistance. Here, we screened a focused library of SAM analogs against the DNA adenine methyltransferase CamA specific to the enteric pathogen Clostridioides difficile. At the same time, we examined six other adenine methyltransferases, including two bacterial DNA methyltransferases and four human RNA methyltransferases having distinct RNA substrates. Compound 113 selectively inhibited CamA (IC50 = 0.15 μM). In addition, compound 67 inhibited Caulobacter crescentus CcrM …

Characterizing Circulating Rare Cells In Peripheral Blood For Detecting And Monitoring Multiple Myeloma And Precursor States, Stephanie N Shishido, Jeremy Mason, Mohamed Kamal, Sonia Maryam Setayesh, Amishi U Vora, David Berrios, Luz Yurany Moreno Rueda, Krina Patel, Elisabet E Manasanch, Robert Z Orlowski, Peter Kuhn

Faculty, Staff and Student Publications

Multiple myeloma (MM) arises from abnormal plasma cells (PCs) progressing from precursor states, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Understanding this transition and progression to overt MM requires improved non-invasive strategies. We employed a liquid biopsy approach to detect and characterize circulating PCs across disease states in 68 patients (MGUS = 11, SMM = 21, NDMM = 19, RRMM = 17) using multi-channel immunofluorescence staining and machine learning-assisted rare event detection. PCs were identified by CD138 and B-cell maturation antigen (BCMA) expressions, with distinct phenotypic subpopulations stratifying disease states. The D | CD138 | …

Hif-2-Dependent Regulation Of Pthrp And Paraneoplastic Hypercalcemia In Aggressive Clear-Cell Renal Cell Carcinoma, Arijit Mal, Bingqing Xie, Zane Gray, Charlotte Small, Susmita G Ramanand, Yunpeng Gao, Vanina Toffessi Tcheuyap, Sashi Debnath, Alana Christie, Jeffrey Miyata, Brooklyn Jackson, Hua Zhong, Boning Gao, Jay Lohrey, Naim M Maalouf, Sangeetha M Reddy, John D Minna, Ivan Pedrosa, Xiankai Sun, Ram S Mani, Payal Kapur, James Brugarolas

Faculty, Staff and Student Publications

Renal cell carcinoma (RCC) patients with hypercalcemia (HC) have worse outcomes. HC often involves PTHrP, and the role of HIF-2 is incompletely understood. Leveraging RCC tumorgraft (TG) models of HC, which were characterized by tumor cell autonomous inflamatory/immune signatures, we show that HIF-2 inhibition with PT2399 frequently normalized calcium, downregulated circulating PTHrP and reduced HIF-2 binding to the PTHLH (PTHrP) promoter. Likely contributing to the selective induction of PTHrP in a subset of HIF-2-dependent tumors, the PTHLH locus was generally more accessible in TG(HC). However, PTHLH chromatin accessibility was grossly unaffected by PT2399, unlike elsewhere (including EPO locus in a …

From Standard To Stratified: Modeling Ntcp And Ear To Personalize Daily Mv-Cbct In Radiotherapy., Duong Thanh Tai, Luong Tien Phat, Tran Trung Kien, Duong Tuan Linh, Nguyen Ngoc Anh, Nguyen Quang Hung, Peter Sandwall, Parham Alaei, David Bradley, James C L Chow

Oncology Articles

PURPOSE: To evaluate the cumulative radiobiological impact of daily megavoltage cone-beam computed tomography (MV-CBCT) imaging dose based on normal tissue complication probability (NTCP) and excess absolute risk (EAR) of secondary malignancies among radiotherapy patients treated for breast, pelvic, and head & neck cancers. This study investigated whether MV-CBCT imaging dose warrants protocol personalization according to patient age, anatomical treatment site, and organ-specific radiosensitivity.

METHODS: This retrospective study included cohorts of breast (n = 30), pelvic (n = 17), and head & neck (n = 20) cancer patients undergoing radiotherapy with daily MV-CBCT. Imaging dose distributions employing two common MV-CBCT protocols …

Integrating Spot-Scanning Proton Arc Therapy With Functional Avoidance Strategies To Reduce Pulmonary Toxicity, Yingxuan Chen, Peilin Liu, Xiaoda Cong, Edward Castillo, Richard Castillo, Inga Grills, Craig Stevens, Xiangkun Xu, Xiaoqiang Li, Yevgeniy Vinogradskiy, Xuanfeng Ding

Department of Radiation Oncology Faculty Papers

Background and purpose: Functional avoidance radiotherapy has emerged as a promising technique using functional imaging to minimize pulmonary toxicity by reducing doses to functional lung. This study aims to investigate the potential dose-volume advantages of a novel spot-scanning proton arc (SPArc) therapy for functional avoidance radiotherapy with four-dimensional computed tomography (4DCT)-based ventilation imaging.

Material and methods: Twenty-five patients from a prospective functional avoidance clinical trial treated with intensity-modulated photon radiotherapy were included. Robustly optimized intensity modulated proton therapy (IMPT) and SPArc plans were generated in RayStation. Functional lung contour was derived from the 4DCT-based ventilation imaging and utilized as an …

Incidence And Management Of Adverse Events Associated With Tebentafusp Treatment In Metastatic Uveal Melanoma: Pooled Safety Analysis Of 410 Patients, Takami Sato, Marcus O. Butler, Sophie Piperno-Neumann, Jessica C. Hassel, Paul Nathan, Alexander N. Shoushtari, Piotr Rutkowski, Richard D. Carvajal, Jean-Francois Baurain, Max Schlaak, Josep M. Piulats, Ryan J. Sullivan, Sebastian Ochsenreither, Reinhard Dummer, John M. Kirkwood, Alexandra Ikeguchi, Anthony M. Joshua, Mark R. Middleton, Ramakrishna Edukulla, Constance Pfeiffer, Joseph J. Sacco

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

PURPOSE: We conducted an integrated safety analysis from three clinical studies of tebentafusp, a first-in-class ImmTAC bispecific T-cell engager, which can redirect T cells to target glycoprotein 100-positive cells, in metastatic uveal melanoma.

EXPERIMENTAL DESIGN: HLA-A*02:01-positive patients with unresectable or metastatic uveal melanoma enrolled in three clinical trials (IMCgp100-01, IMCgp100-102, and IMCgp100-202) who received ≥1 dose of tebentafusp were included. Safety data were pooled to evaluate the profile, onset, and management of treatment-related adverse events (TRAE). Adverse events of special interest included cytokine release syndrome (CRS), acute skin reactions (ASR), and liver function test elevations. Primary prophylaxis with medications was …

A Feasibility Study Of Sexual Organ-Dose Sparing Volumetric Modulated Arc Therapy In Female Low Rectal Cancer Patients Treated With Three-Dimensional Conformal Radiation Therapy, Margaret Downes, Victoria Olsen, Andre Williams, Rendi Sheu, Maria Thor, Lucy Greenwald, Vishruta Dumane, Kristin Hsieh, Ayesha Ali, Orly Morgan, Michael Buckstein, Deborah Marshall

Department of Radiation Oncology Faculty Papers

BACKGROUND: Sexual dysfunction is a significant toxicity of pelvic radiation therapy (RT) for female rectal cancer patients and may be more common with intensity-modulated techniques compared to three-dimensional conformal radiation therapy (3D-CRT). However, limited research has evaluated dose sparing of female sexual organs at risk (OARs), particularly erectile tissues that are critical for sexual function.

PURPOSE: This feasibility study aimed to demonstrate the practicality of contouring and sparing female sexual OARs in rectal cancer RT by generating sexual organ-sparing volumetric modulated arc therapy (SO-VMAT) plans from a small 3D-CRT cohort and comparing dose distributions to guide future planning.

METHODS: Nine …

Exploring Bone Oncology In A Medically Underserved Area: A Retrospective Cohort Of Bone Metastases And Malignant Bone Neoplasia In The Rio Grande Valley, Blake C. Martin, Juan Carlos Lopez Alvarenga, Michael Sander

School of Medicine Publications

Objectives: The Rio Grande Valley (RGV) is a developing clinical research region characterized by its distinctive demographic profile that offers an opportunity to investigate diverse health issues. This pilot investigation sought to evaluate the demographic and clinical characteristics linked to bone metastases and primary malignant bone neoplasms (PMBNs) in patients from the RGV and to compare the frequency of these conditions with the US general population.

Methods: This was a retrospective chart review in which data were gathered from the University of Texas Rio Grande Valley UTHealth electronic database from January 1, 2018 to September 4, 2024. Various statistical analyses …

Monte Carlo Simulations Of Geometric Deformation Of Harrison-Anderson-Mick Applicators Used In Intraoperative Radiation Therapy, Benjamin Insley, Brett Bocian, Sam Beddar, Reza Reiazi, Patrick James Jensen, Rachael M Martin-Paulpeter, Joshua Scott Niedzielski, David Flint, Gabriel Oliveira Sawakuchi, Luis Augusto Perles

Faculty, Staff and Student Publications

Background: The Harrison-Anderson-Mick (HAM) applicator is a high-dose-rate intraoperative radiotherapy (HDR-IORT) applicator used to position Ir-192 brachytherapy sources over surgically-accessed tumor volumes or post-resection tumor beds. Because of the lack of a 3D imaging system, dwell times are optimized pre-surgery by a TG-43-based treatment planning system (TPS) that assumes a perfectly flat applicator surface surrounded by an infinite water phantom. These assumed conditions are disparate from typical treatment conditions, especially in the pelvic regions, which often involve uneven patient surfaces and superficial irradiations with little to no backscatter material.

Purpose: Develop and validate a Monte Carlo (MC) model of HDR-IORT …

Orthogonal Comparison Of Nuclear And Mitochondrial Clonal Architectures In Hematologic Malignancies, Nehali Shah

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by accumulation of mutations that disrupt hematopoietic differentiation and promote clonal expansion. Understanding how these mutations arise and evolve is essential for improving diagnosis, prognosis, and treatment stratification. Current methods are limited by either restricted genomic coverage (targeted panels) or low throughput and high cost (in single-cell whole genome sequencing, scWGS). An emerging alternative is the use of mitochondrial DNA (mtDNA) mutations as clonal markers.

This study aims to determine whether mitochondrial-derived clonal architectures correlate with nuclear-derived clonal architectures in AML, thereby evaluating mtDNA as a scalable orthogonal tool for lineage …

Detection Of Phase-Binning And Interpolation Artifacts In 4-Dimensional Computed Tomography Imaging Using Deep Learning And Rule-Based Approaches, Jorge Cisneros, Nathan H. Feldt, Yevgeniy Vinogradskiy, Richard Castillo, Edward Castillo

Department of Radiation Oncology Faculty Papers

BACKGROUND: Four-dimensional computed tomography (4DCT) imaging is a crucial component to lung cancer radiotherapy planning and enables CT-ventilation-based functional avoidance planning to mitigate radiation toxicity. However, 4DCT scans are frequently impaired by acquisition artifacts that corrupt downstream analyses that depend on lung segmentation and deformable image registration, such as CT-ventilation and dose accumulation.

PURPOSE: This study develops 3D deep learning models to identify phase-binning artifacts at the voxel level and a heuristic, rule-based method to identify interpolation slices within 4DCT images.

METHODS: We introduce a generator that systematically inserts synthetic phase-binning and interpolation artifacts into any artifact-free breathing phase obtained …

Does Reducing Videofluoroscopy Frame Rate Affect Dige/St Grades In Modified Barium Swallow Studies?, Shitong Mao, Carla L Warneke, Sheila N Buoy, Ariana J Sahli, Brinda Rao Korivi, Carly E A Barbon, Kristy K Brock, Katherine A Hutcheson

Faculty, Staff and Student Publications

Understanding the effects of reduced frame rates on the reliability of Modified Barium Swallow (MBS) ratings for swallowing safety and efficiency is essential for clinical practice. While previous research has examined frame rate (simulated pulse rates) implications concerning penetration, aspiration, and residue ratings, the impact on summary grading systems like the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) remains unclear. This study analyzed a total of 315 full MBS videos collected from 278 patients, and 76.25% of patients were diagnosed with head and neck cancer (mean age 62.51 years, SD 8.53; 12.23% female). We performed pairwise comparisons of DIGEST grades …

Tumor Intrinsic Mettl5 Modulates Atf4 Translation To Prevent T Cell-Induced Ferroptosis In Ovarian Cancer, Jiakai Hou, Cheng-Wei Ju, Nicholas A Egan, Yanjun Wei, Yunfei Wang, Minghao Dang, Tianyi Zhou, Leilei Shi, Ningbo Zheng, Si Chen, Ashley M Guerrero, Xiaofang Liang, Wanfu Wu, Areej Akhtar, Chitra Dhiman, Debanwita Roy Burman, Andro E Gerges, Mason D Flores, Han Li, Li-Sheng Zhang, Marleen Kok, Xiaobo Mao, Linghua Wang, Qin Feng, Yiwen Chen, Sanghoon Lee, Daniel J Mcgrail, Nidhi Sahni, Chuan He, Amir A Jazaeri, Weiyi Peng

Faculty, Staff and Student Publications

Poor clinical responses to immune checkpoint blockade (ICB) observed in ovarian cancer (OC) highlight an unmet need to understand the mechanisms driving immune evasion in this disease. To address this, an integrative analysis is conducted by combining in vitro genome‐wide immune screens, in vivo ICB screens, and clinical data mining, and METTL5 is identified as a crucial OC‐intrinsic factor that promotes immune resistance. Immunologically “cold” OC tumors and poor responders to ICB exhibit elevated METTL5 expression. Mechanistically, knocking out (KO) METTL5 in OC disrupts ATF4 translation by altering 18S rRNA m6A levels, leading to the downregulation of SLC7A11 and SLC3A2 …

Perceived Utility Of Genetic Carrier Screening In A Diverse Patient Population, Jack A Colleran, Meagan Choates, Syed Hashmi, Brittanie Shelton, Aranza Gonzalez Cendejas, Angela Haynes Burgess, Blair K Stevens

Faculty, Staff and Student Publications

Current reproductive guidelines call for offering expanded carrier screening (ECS) for genetic conditions. Currently available panels can include screening for carrier status of tens to hundreds of autosomal recessive and/or X-linked conditions. Clinical utility is based on alterations to reproductive decision-making, but study cohorts supporting the utility of ECS largely consist of individuals of European ancestry who are highly educated, of high income, and who often receive preconception counseling. There is a lack of research on the views of patients from diverse backgrounds. Therefore, we aimed to assess and compare perceptions of the utility of ECS and targeted carrier screening …

Kras Inhibition Activates An Actionable Cd24 "Do Not Eat Me" Signal In Pancreatic Cancer, Yongkun Wei, Minghui Liu, Er-Yen Yen, Jun Yao, Zhenzhen Xun, Phuoc T Nguyen, Xiaofei Wang, Zecheng Yang, Abdelrahman Yousef, Dean Pan, Yanqing Jin, Ching-Fei Li, Madelaine S Theardy, Jangho Park, Yiming Cai, Mitsunobu Takeda, Matthew Vasquez, Elizabeth M Park, David H Peng, Yong Zhou, Hong Zhao, Timothy P Heffernan, Andrea Viale, Huamin Wang, Stephanie S Watowich, Han Liang, Dan Zhao, Ronald A Depinho, Wantong Yao, Haoqiang Ying

Faculty, Staff and Student Publications

KRASG12C inhibitors (G12Ci) have produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the function of KRASG12C and possible G12Ci bypass mechanisms, we developed an autochthonous KRASG12C-driven PDAC model. Compared to the classical KRASG12D PDAC model, the G12C model exhibits slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRASG12C tumors produced modest impact despite stimulating a ‘hot’ tumor immune microenvironment. Immunoprofiling revealed that CD24, a ‘don’t eat me’ signal, is significantly upregulated on cancer …

Clinical Outcomes Of Adult Patients With Newly Diagnosed Mixed Phenotype Acute Leukemia, Hannah Goulart, Farhad Ravandi, Nicholas J Short, Nitin Jain, Naval Daver, Tapan M Kadia, Courtney Dinardo, Gautam Borthakur, Koichi Takahashi, Naveen Pemmaraju, Fadi G Haddad, Guillermo Montalban Bravo, Yesid Alvarado, Ghayas C Issa, Alex Bataller, Sherry Pierce, Sanam Loghavi, Guilin Tang, Sa A Wang, Beenu Thakral, Elizabeth Shpall, Richard Champlin, Issa Khouri, Partow Kebriaei, Guillermo Garcia-Manero, Koji Sasaki, Elias J Jabbour, Jayastu Senapati

Faculty, Staff and Student Publications

Purpose: Mixed phenotype acute leukemia (MPAL) is a rare clinical entity with historically poor outcomes.

Methods: We conducted a retrospective analysis of adults 18 years and older with newly diagnosed B-cell (B/M) or T-cell/myeloid (T/M) MPAL treated at our institution between 2017 and 2024.

Results: We identified 42 patients (median age 70 years); 20 (48%) had B/M MPAL, and 22 (52%) had T/M MPAL; 57% of patients had adverse risk cytogenetics, and 41% had a TP53 mutation. Sixty-two percent of patients were treated with a hybrid regimen, and 45% of patients received intensive therapy. A composite complete remission (CRc; CR …

Mecom Fusion Partner And Bone Marrow Blast Percentage Influence Outcomes Of Patients With Mecom Rearranged Acute Myeloid Leukaemia, Wei-Ying Jen, Guilin Tang, Eitan Kugler, Jennifer Croden, Koji Sasaki, Alexandre Bazinet, Alex Bataller, Guillermo Montalban-Bravo, Gautam Borthakur, Gokce A Toruner, Sanam Loghavi, Nicholas J Short, Ghayas C Issa, Ian M Bouligny, Sherry Pierce, Uday Popat, Naveen Pemmaraju, Elias Jabbour, Guillermo Garcia-Manero, Kapil Bhalla, Farhad Ravandi, Naval G Daver, Courtney D Dinardo, Hagop M Kantarjian, Tapan M Kadia

Faculty, Staff and Student Publications

MECOM rearrangements (MECOM-r) are acute myeloid leukaemia (AML)-defining, regardless of blast percentage or MECOM fusion partner. We sought to investigate if blast percentage or MECOM-r partner was associated with overall survival (OS). We included 152 adult patients with newly diagnosed MECOM-r and classified blast percentage into < 20% or ≥20% and MECOM-r partner into classic (GATA2::MECOM) or variant (others). Thirty-one per cent had < 20% blasts, with 69% having ≥20%; 57% had classic and 43% variant MECOM-r. Treatment was with intensive chemotherapy (IC) in 41% and low-intensity therapy (LIT) in 59%. Composite complete remission rates were similar between IC (50%) and LIT (48%, p = 0.99). The median OS was 17 months (95% confidence interval [CI], 12-not estimable [NE]) for < 20% blasts, compared with 9 months (95% CI, 6-10) for ≥20% blasts (p <  0.01). On multivariate analysis, ≥20% blasts were associated with worse OS (hazard ratio [HR] 1.9, [95% CI, 1.2-3.2], p <  0.01), independent of age, MECOM-r partner, additional cytogenetic abnormalities, treatment intensity, addition of venetoclax and stem cell transplant (SCT). HR for IC was 2.0 (95% CI, 1.1-3.7, p = 0.03). In < 20% blasts, variant MECOM-r was independently associated with a reduced hazard of death (HR 0.2 [95% CI, 0.1-0.8], p <  0.01). MECOM-r AML is a heterogenous entity; consideration should be given to LIT approaches.

The Pneumonia Challenge: Time To End The Global Neglect, Catia Cillóniz, Markus Fally, Scott Evans, Guinevere Dy-Agra, Pneumo-Strategy Group

Faculty, Staff and Student Publications

No abstract provided.

Differential Microrna Profiling Of Blood L1cam And Bulk Extracellular Vesicles In Bipolar Disorder, Gabriel R Fries, Salahudeen Mirza, Jun Wang, Camila N C Lima, Wei Zhang, Marcela Carbajal Tamez, Giselli Scaini, Jair C Soares, Joao Quevedo

Faculty, Staff and Student Publications

Objective: This preliminary study aimed to identify microRNA (miRNA) signatures associated with bipolar disorder (BD) by profiling blood-derived extracellular vesicles (EVs) of both putative neuronal origin and from all sources.

Method: In two parallel studies of individuals with BD and controls (CON), we characterized miRNA expression profiles of blood EVs selected for L1CAM, a putative marker of neuronal origin (n = 20 BD/20 CON), as well as bulk EVs (n = 21 BD/20 CON). For each study, analyses identified miRNAs differentially expressed between groups, followed by functional interrogation and testing for associations with clinical features.

Results: Results of …

Author Correction: Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

No abstract provided.

Evidence For Improved Dna Repair In The Long-Lived Bowhead Whale, Denis Firsanov, Max Zacher, Xiao Tian, Todd L Sformo, Yang Zhao, Gregory Tombline, J Yuyang Lu, Zhizhong Zheng, Luigi Perelli, Enrico Gurreri, Li Zhang, Jing Guo, Anatoly Korotkov, Valentin Volobaev, Seyed Ali Biashad, Zhihui Zhang, Johanna Heid, Alexander Y Maslov, Shixiang Sun, Zhuoer Wu, Jonathan Gigas, Eric C Hillpot, John C Martinez, Minseon Lee, Alyssa Williams, Abbey Gilman, Nicholas Hamilton, Ekaterina Strelkova, Ena Haseljic, Avnee Patel, Maggie E Straight, Nalani Miller, Julia Ablaeva, Lok Ming Tam, Chloé Couderc, Michael R Hoopmann, Robert L Moritz, Shingo Fujii, Amandine Pelletier, Dan J Hayman, Hongrui Liu, Yuxuan Cai, Anthony K L Leung, Zhengdong Zhang, C Bradley Nelson, Lisa M Abegglen, Joshua D Schiffman, Vadim N Gladyshev, Carlo C Maley, Mauro Modesti, Giannicola Genovese, Mirre J P Simons, Jan Vijg, Andrei Seluanov, Vera Gorbunova

Faculty, Staff and Student Publications

At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth1, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox2. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. …

Reference Dosimetry Data And Machine Performance Comparison For Tomotherapy Delivery Systems Audited By Iroc, Paige A Taylor, Hunter Mehrens, Mallory C Glenn, Fre'etta Brooks, Hayden Scott, Lian Duan, Taylor Meyers, Diana Carrasco Rojas, Michael Yang, Paola Alvarez, Jessica Lowenstein, Andrea Molineu, Stephen F Kry

Faculty, Staff and Student Publications

The aim of this work was to compare the imaging and radiation oncology core (IROC) on-site TomoTherapy dosimetry measurement results among institutions and generate a dataset of basic dosimetric properties for TomoTherapy units. Independent ion chamber measurements for nine TomoTherapy units were acquired by IROC physicists between 2008 and 2023. Measurements included percent depth dose (PDD) in a water tank and off axis factors (OAF) in a solid Polystyrene phantom. The independent measurements collected during the on-site audits for each TomoTherapy system were compared to corresponding TomoTherapy TPS calculations from the institution to assess agreement. Numeric measurement values and comparative …

Periostin Promotes Sarcoma Growth By Promoting Tumor-Associated Macrophage Migration And Differentiation, Jin-Fen Xiao, Kristin Ishaya, Emily Y Ko, Annaliese Fowler, Marina T Broz, Jlenia Guarnerio

Faculty, Staff and Student Publications

Soft-tissue sarcomas (STS) are characterized by abundant extracellular matrix (ECM) deposition, yet the functional contribution of specific ECM components remains poorly understood. In this study, we identify periostin (POSTN), a matricellular protein, as a regulator of sarcoma progression and the tumor immune microenvironment. Analysis of human sarcoma datasets revealed that high POSTN expression correlates with poor prognosis and elevated expression of ECM-related and myeloid cell–associated genes. In murine genetic models of sarcoma, tumors expressing high levels of Postn displayed enhanced expression of ECM genes and monocyte-recruiting cytokines. Functional silencing of Postnin vivo reduced tumor growth without altering tumor cell …

Bayesian Integrated Learning Of Longitudinal Dose-Response Relationships Via Decentralized Clinical Trials, Jingyi Zhang, Tuo Wang, Yongming Qu, Fangrong Yan, Suyu Liu, Ruitao Lin

Faculty, Staff and Student Publications

Decentralized clinical trials (DCTs) extend trial activities beyond traditional sites, enhancing access, convenience, efficiency, and result generalizability. They are particularly promising for chronic conditions like diabetes and obesity, which require longer study durations to evaluate drug effects. However, decentralized data collection raises concerns about increased variability and potential biases. This paper presents a novel Bayesian integrated learning procedure to analyze dose-response relationships using longitudinal data from a phase II DCT that combines centralized and decentralized data collection. We generalize a parametric exponential decay model to handle mixed data sources and apply Bayesian spike-and-slab priors to address biases and uncertainties from …

International Norms For Adult Handgrip Strength: A Systematic Review Of Data On 24 Million Adults Aged 20 To 100+ Years From 69 Countries And Regions, Grant R Tomkinson, Justin J Lang, Lukáš Rubín, Ryan Mcgrath, Bethany Gower, Terry Boyle, Marilyn G Klug, Alexandra J Mayhew, Henry T Blake, Francisco B Ortega, Cristina Cadenas-Sanchez, Costan G Magnussen, Brooklyn J Fraser, Tetsuhiro Kidokoro, Yang Liu, Kaare Christensen, Darryl P Leong

Faculty, Staff and Student Publications

Background: Muscular strength is a powerful marker of current health status and robust predictor of age-related disease and disability. Handgrip strength (HGS) using isometric dynamometry is a convenient, feasible, and widely used method of assessing muscular strength among people of all ages. While adult HGS norms have been published for many countries, no study has yet synthesized available data to produce international norms. The objective of this study was to generate international sex- and age-specific norms for absolute and body size-normalized HGS across the adult lifespan.

Methods: Systematic searches were conducted in 6 databases/web search engines (MEDLINE, SPORTDiscus, Embase, Web …

Reviewing Vascular Influences On Neuronal Migration, Cortical Development, And Neurodevelopmental Disorders: Focus On Autism, Adhd And Schizophrenia, Lalit K Ahirwar, Spiros L Blackburn, Devin W Mcbride, Peeyush Kumar T

Faculty, Staff and Student Publications

During cortical development, newly born neurons migrate radially or tangentially from their origin to expand the cortex. Simultaneously, neuron-derived factors support angiogenesis, and an elaborate network of blood cerebral vessels develops in the cortex. Traditionally, blood cerebral vessels were considered to support the growing cortex or migrating neurons by providing nutrients and oxygen. However, recent studies have shed light on Endothelial cells' influence on cortical development; they guide neuronal migration by providing molecular cues and structural support. Here, we review the current understanding of how CNS cerebral vessels support neurogenesis, neuronal migration, and the formation of the six-layer cortical structure …

Impact Of Postpartum Diagnosis On Survival Of Women With Inflammatory Breast Cancer, Jennifer H Chen, Rebecca S Slack Tidwell, Megumi Kai, Anthony Lucci, Wendy A Woodward, Helen M Johnson

Faculty, Staff and Student Publications

Background: Postpartum diagnosis of breast cancer confers increased risk of metastasis and death, possibly because of protumorigenic pathways that occur after weaning. We sought to evaluate the impact of postpartum diagnosis on survival in patients with inflammatory breast cancer (IBC).

Methods: We performed a retrospective analysis of patients with nonmetastatic IBC enrolled in a prospective registry (2007-2023). Kruskal-Wallis, χ2, and Fisher exact tests were used to compare between postpartum groups. The Kaplan-Meier method and log-rank tests were used for survival estimates.

Results: Among 320 patients with IBC, 25 (7.8%) were nulliparous, 31 (9.7%) were 0 to 5 years postpartum, 26 …

Bayesian Prediction Of Event Times Using Mixture Model For Blinded Randomized Controlled Trials, Jingyan Fu, Dan Zhao, Donia Skanji, Hua Liu, Rui Sammi Tang, Ying Yuan

Faculty, Staff and Student Publications

Accurate prediction of key milestone dates, such as the timing of interim and final analyses, is crucial in event-driven clinical trials with time-to-event endpoints. These predictions facilitate timely decision-making, enhance strategic planning and optimize resource allocation while minimizing patient exposure to potentially ineffective or harmful therapies. Existing methods for predicting event timing in blinded randomized clinical trials (RCTs) typically assume identical time-to-event distributions for the treatment and control arms, implying no treatment effect. This assumption fails when the treatment is more effective than the control, which is often the very outcome the trial seeks to detect, leading to biased predictions. …

Individualizing Nsaid Therapy In Axial Spondyloarthritis: N-Of-1 Trials With Bayesian Analysis, Mark C Hwang, Seokhun Kim, Shervin Assassi, Reyna Chavez, Joyce Samuel, Charles Green, Jon Tyson, John Reveille

Faculty, Staff and Student Publications

Objective: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease predominantly affecting the spine and sacroiliac joints. NSAIDs are first-line therapy, but individual responses vary widely. We evaluated the efficacy and patient preference of three NSAIDs (celecoxib, meloxicam and naproxen) through Bayesian N-of-1 clinical trials to optimize axSpA management.

Methods: We conducted N-of-1 trials with 42 patients meeting ASAS criteria for axSpA. Each patient was asked to complete two cycles of randomized double-blind crossover comparisons of the three NSAIDs, each for 4 weeks. The primary end point was the change in the Ankylosing Spondylitis Disease Activity Score (ASDAS). Bayesian analysis assessed …