Medicine and Health Sciences Commons^™

Maturity-Onset Diabetes Of The Young (Mody) In A Racially/Ethnically Diverse Pediatric Population, Shilpi Relan, Guido Alarcon, Danielle Guffey, Charles G Minard, Mary E Fang, Kelly Timmons, Rona Y Sonabend, Mustafa Tosur, Maria J Redondo, Jennifer E Posey

Faculty, Staff and Students Publications

Context: Current practice guidelines recommend considering a diagnosis of maturity-onset diabetes of the young (MODY) in patients with diabetes with an affected parent but without typical features of type 1 or type 2 diabetes.

Objective: To test if these criteria apply to a real-world cohort of racially/ethnically diverse children with diabetes.

Methods: We performed a retrospective case review of electronic medical records of youth diagnosed with MODY in a large academic pediatric hospital in Southwestern United States. Cases were ascertained based on the identification of a molecular diagnosis of MODY.

Results: We studied 50 genetically confirmed cases of MODY: 60% …

A Retrospective Analysis Of Post-Stroke Rehabilitation With Real World Use Of Brain-Computer Interface, Neha K Prasad, Nikhita J Perry, Allison L Goldring, Lee A Fleisher, Leo Petrossian, Eric C Leuthardt, Lauren Souders, Seth J Wilk

2020-Current year OA Pubs

The IpsiHand™ System is an FDA-authorized, non-invasive therapy for chronic stroke-induced upper limb motor impairment that uses a brain-computer interface (BCI) to translate intent-to-move signals into hand movement. This retrospective study evaluated real-world outcomes in stroke survivors ≥ 6 months post-stroke who were prescribed IpsiHand™ and completed regular Upper Extremity Fugl-Meyer (UEFM) assessments as part of routine care. Patients were categorized as early responders (achieving the minimal clinically important difference [MCID] of 5.25 points in UEFM score by 6 weeks), intermediate responders (achieving MCID by 12 weeks but not at 6), or early non-responders (not reaching MCID by 12 weeks). …

Genomics Define Malignant Transformation In Myeloma Precursor Conditions, Francesco Maura, P Leif Bergsagel, Bachisio Ziccheddu, Shaji Kumar, Kylee Maclachlan, Andriy Derkach, Juan-Jose Garces, Ross Firestone, Esteban Braggio, Yan Asmann, Michael Durante, Benjamin T Diamond, Marios Papadimitriou, Malin Hultcrantz, Alessio Marella, Giancarlo Castellano, Akihiro Maeda, Marta Lionetti, Antonio Matera, Stefania Pioggia, Matteo Claudio Da Vià, Claudio De Magistris, Daniel Leongamornlert, Danny Deavila, Praneeth Reddy Sudalagunta, Rafael Renatino Canevarolo, Erin M Siegel, Phaedra Agius, Jamie Teer, Andrew Mcpherson, Yusuke Yamashita, Ariosto S Silva, Patrick Blaney, Rachid Baz, Krina K Patel, Peter Campbell, Gareth Morgan, Rafael Fonseca, Ola Landgren, Robert Z Orlowski, Kenneth H Shain, Niccolo Bolli, Saad Usmani, S Vincent Rajkumar

Faculty, Staff and Student Publications

Multiple myeloma (MM) is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). While these precursor conditions are asymptomatic, they are not entirely benign and carry a lifelong risk of progression to MM. Unlike other cancers defined by pathology, malignant transformation from MGUS or SMM to MM has so far relied on demonstration of clinical end-organ damage as morphology and cytogenetics cannot reliably distinguish them. In this study, using genomic data from 374 patients with MGUS or SMM (277 training, 97 validation), to our knowledge, we demonstrate for the first time the ability to identify …

Radionuclide-Stimulated Dynamic Therapy Induces Complementary Immunogenic Necroptosis And Apoptosis Cancer Cell Death Pathways, Christopher Egbulefu, Kvar Black, Xinming Su, Partha Karmakar, Lemoyne Habimana-Griffin, Gail Sudlow, Julie Prior, Ezugo Onejeme, Alex Zheleznyak, Baogang Xu, Yalin Xu, Alison Esser, Matthew Mixdorf, Evan Moss, Brad Manion, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Luke Stallings, Chidube Alagbaoso, Nathan Reed, Matthew M Gubin, Chieh-Yu Lin, Robert Schreiber, Katherine Weilbaecher, Samuel Achilefu

Faculty, Staff and Student Publications

Radionuclide-stimulated dynamic therapy (RaST) utilizes Cerenkov-radiating radiopharmaceuticals to activate light-sensitive drugs and materials, generating reactive oxygen species (ROS) that inhibit cancer progression. However, the underlying cell death mechanisms are not fully understood. Using ROS-regenerative nanophotosensitizers coated with a tumor-targeting transferrin-titanocene complex and radiolabeled 2-fluorodeoxyglucose, we found that RaST induced apoptosis and necroptosis, characterized by the activation of RIPK-1, RIPK-3, nuclear factor kappa B, and mixed lineage kinase domain-like pseudokinase, leading to membrane permeabilization, cytokine release, and the expression of immunogenic damage-associated molecular patterns. In immune-deficient breast tumor-bearing mice with adequate stroma and growth factors, RaST did not prevent tumor growth …

Comprehensive Metabolic Profiling Across Five Lifespan Stages In Murine Hippocampus And Cortex Reveals Sex-Related Variation In Age-Related Cognitive Decline, Xi Long, Wuping Liu, Changhan Chen, Qi Guo, Yidan Wang, Fang Yu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

This study employs Barnes maze behavioral assessments, untargeted liquid chromatography-mass spectrometry metabolomics, and 13C6-glucose isotopic tracing to systematically investigate cognitive function and metabolic profiles in hippocampal and cortical tissues of male and female mice across five distinct age-ranges. Behavioral analyses reveal significant cognitive decline in both sexes by 16-months-of-age, with females exhibiting more severe impairment by 23-months, demonstrating a sex-related variation. 13C6-glucose tracing analyses reveals that glucose is rapidly and preferentially metabolized toward the Tricarboxylic acid cycle over glycolysis and the pentose phosphate pathway (PPP), with metabolism rates increasing from juvenility to meet developmental demands and maintaining homeostasis into pre-elderly. …

Reducing Work-Related Screen-Time In Healthcare Workers During Leisure Time (Reduce Screen) - A Randomized Controlled Trial, Karsten Bartels, Karan Shah, Emelind Sanchez Rodriguez, Julie T Hoffman, Megan L Rolfzen, Juana Mora Valdovinos, Afton L Hassett, Daniel I Sessler

Faculty, Staff and Student Publications

The ubiquitous availability of work-related applications on personal devices makes healthcare workers prone to working during leisure time. We tested the hypothesis that an intervention to reduce work-related screen time during a weekend off reduces stress in healthcare workers in a pragmatic parallel design randomized controlled trial between November 2021 and November 2023. Healthcare workers using a smartphone with a work email application were eligible. Randomization was 1:1 to no treatment or a threefold educational intervention to: 1) activate automated responses to emails received, 2) reduce screen time, and 3) uninstall work applications from personal devices. The primary outcome was …

Optimal Murine Cd4+ T Cell Priming By Mrna-Lipid Nanoparticle Vaccines Requires Endogenous Antigen Processing, Julia E. Rood, Suh Kyung Yoon, Mary K. Heard, Stephen D. Carro, Emma J. Hedgepeth, Mary E. O'Mara, Michael J. Hogan, Nhu Le, Hiromi Muramatsu, Kieu Lam, Petra Schreiner, Coral Kasden, Hansell H. Stedman, Ryan A. Langlois, James Heyes, Norbert Pardi, Laurence C. Eisenlohr

College of Life Sciences Faculty Papers

Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines elicit robust CD4+ T cell responses, yet the mechanisms underlying this T cell priming remain unknown. Antigens presented to CD4+ T cells on major histocompatibility complex class II (MHC II) are traditionally acquired by antigen presenting cells (APCs) from extracellular sources. Here we show that vaccine specific CD4+ T cell responses instead rely on antigen directly expressed within APCs, without extracellular transit. Murine APCs treated with mRNA-LNP vaccines activate T cells more efficiently when presenting antigen produced internally, rather than acquired externally. Immunization with mRNA-LNP vaccines engineered to inhibit antigen expression in APCs results …

Elevated Trna Halves In Olfactory Epithelial Cells Of Patients With Schizophrenia, Justin T. Gumas, Megumi Shigematsu, Karin E. Borgmann-Winter, C. G. Hahn, Yohei Kirino

Computational Medicine Center Faculty Papers

Schizophrenia patients' olfactory epithelial cells contain abundant immune-activating tRNA fragments, linking small RNA biology to inflammation and suggesting avenues for diagnostics.

Glutamatergic Projection Neurons In The Basal Forebrain Underlie Learned Olfactory Associational Valence Assignments, Pey-Shyuan Chin, Zhuokun Ding, Mikhail Kochukov, Snigdha Srivastava, Elizabeth H Moss, Qingchun Tong, Benjamin R Arenkiel

Faculty, Staff and Student Publications

Sensory perception is shaped by experience, giving stimuli behavioral significance. Basal forebrain (BF) cholinergic neurons in mice, which are crucial for arousal and motivation, also regulate sensory processing. Within BF nuclei, glutamatergic (vGlut2BF) neurons receive cholinergic input and modulate behaviors, but their roles in encoding sensory significance remain unclear. Using in vivo calcium imaging, we found that vGlut2BF neurons initially poorly encoded odor identity. However, their response to conditioned odors increased following associative learning, and their population activity more distinctly encoded paired stimuli, reflecting emergent value representation. Furthermore, pairing stimulation or inhibition of vGlut2BF neurons with specific odors altered odor …

Extra-Axial Cerebrospinal Fluid Volumes From 6 To 24 Months Of Age Are Associated With Poorer Executive Function At School-Age In Children With And Without Autism, Yichi Zhang, Robert C Mckinstry, Natasha Marrus, John R Pruett Jr., Et Al.

2020-Current year OA Pubs

BACKGROUND: Abnormally increased extra-axial cerebrospinal fluid (EA-CSF) volume is present as early as 6 months in infants later diagnosed with autism and is associated with symptom severity at the age of diagnosis, but it is unknown whether early EA-CSF enlargement has long-term impacts on other clinical domains. Executive function (EF) deficits are frequently observed in children with autism and are linked with worse academic outcomes, higher anxiety, and lower adaptive functioning. The current study examines the association between EA-CSF volume at infancy and EF at school age in a longitudinally phenotyped cohort of children with either high (HL) or low …

Epigenome-Wide Association Study Meta-Analysis Of Bmi In African Americans, Kendra Ferrier, Mariaelisa Graff, Iain R Konigsberg, Maggie Stanislawski, Heather M Highland, Laura M Raffield, April P Carson, Eric Boerwinkle, Jill M Norris, Chris R Gignoux, Audrey E Hendricks, Sridharan Raghavan, Kari E North, Kristin L Young, Anne E Justice, Matthew A Allison, Mathew J Budoff, Silva Kasela, François Aguet, Joshua J Joseph, Charles Kooperberg, Stephen S Rich, Jerome I Rotter, Ethan M Lange, Leslie A Lange

Faculty, Staff and Student Publications

Despite considerable advances in identifying risk factors for obesity, gaps remain in our understanding about its etiology. Genetic variants explain only a small portion of variation in obesity-related traits such as body mass index (BMI). Epigenetic regulation, which controls gene expression and is influenced by environmental and genetic factors, may account for additional variability in BMI. Epigenetic studies of BMI have largely been conducted in European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). We conducted a sex-stratified BMI epigenome-wide association study meta-analysis in AA participants from the Jackson Heart Study (n = 1,604) and …

Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Lucinda Antonacci-Fulton, Susan K Dutcher, Et Al.

2020-Current year OA Pubs

BACKGROUND: Whole genome sequence (WGS) data in multi-ancestry samples supports discovery of low-frequency or population-specific genetic variants associated with chronic obstructive pulmonary disease (COPD) and lung function.

RESULTS: We performed single variant, structural variant, and gene-based analysis of pulmonary function (FEV

CONCLUSIONS: Large-scale multi-ancestry WGS analysis improves variant discovery and fine-mapping resolution for lung function and COPD and highlights biologically relevant genes and pathways.

The Impact Of Indigenous American-Like Ancestry On The Risk Of Acute Lymphoblastic Leukemia In Hispanic/Latino Children, Jalen Langie, Tsz Fung Chan, Wenjian Yang, Alice Y Kang, Libby Morimoto, Daniel O Stram, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Philip J Lupo, Karen R Rabin, Michael E Scheurer, Joseph L Wiemels, Jun J Yang, Adam J De Smith, Charleston W K Chiang

Faculty, Staff and Students Publications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with Hispanic/Latino children having a higher incidence of ALL than other racial/ethnic groups. Among the genetic variants previously implicated in ALL risk, a number of them were found to be enriched in Indigenous American (IA)-like ancestries and inherited by many Hispanic/Latino individuals. However, due to potential confounding from environmental factors, the association between IA-like ancestry and risk for ALL has remained unclear. In this study, we characterized the impact of IA-like ancestry on overall ALL risk and on the frequency and effect size of known risk alleles, while accounting for …

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

Genome-Wide Gene By Sleepiness Interaction Analysis For Sleep Apnea, Pavithra Nagarajan, Nuzulul Kurniansyah, Jiwon Lee, Sina A Gharib, Yushan Xu, Yiyan Zhang, Brian Spitzer, Tariq Faquih, Hufeng Zhou, Eric Boerwinkle, Han Chen, Daniel J Gottlieb, Xiuqing Guo, Nancy L Heard-Costa, Bertha A Hidalgo, Daniel Levy, Peter Y Liu, Hao Mei, Rebecca Montalvan, Sutapa Mukherjee, Kari E North, George T O'Connor, Lyle J Palmer, Sanjay R Patel, Bruce M Psaty, Shaun M Purcell, Laura M Raffield, Stephen S Rich, Jerome I Rotter, Richa Saxena, Albert V Smith, Katie L Stone, Xiaofeng Zhu, Topmed Sleep Trait Working Group, Brian E Cade, Tamar Sofer, Susan Redline, Heming Wang

Faculty, Staff and Student Publications

Study objectives: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea-a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index, a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk.

Methods: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (N = 11 619) data, followed by …

Workflow Improvements From Automated Large Vessel Occlusion Detection Algorithms Are Dependent On Care Team Engagement, Emmanuel C Ebirim, Ngoc Mai Le, Joseph N Samaha, Hussain Azeem, Ananya Iyyangar, Anjan N Ballekere, Saagar Dhanjani, Luca Giancardo, Eunyoung Lee, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Automated machine learning (ML)-based large vessel occlusion (LVO) detection algorithms have been shown to improve in-hospital workflow metrics including door-to-groin time (DTG). The degree to which care team engagement and interaction are required for these benefits remains incompletely characterized.

Methods: This analysis was conducted as a pre-planned post-hoc analysis of a randomized prospective clinical trial. ML-based LVO detection software was implemented at four comprehensive stroke centers (CSCs) from January 1, 2021, to February 27, 2022. Patients were included if they underwent endovascular thrombectomy for LVO acute ischemic stroke. ML software utilization was quantified as the total number of active …

Differential Virulence And Immune Recognition Of Klebsiella Pneumoniae O-Antigen Subtypes O2Α And O2Β, Paeton L Wantuch, Lloyd S Robinson, Cory J Knoot, Christian M Harding, David A Rosen

2020-Current year OA Pubs

No abstract provided.

Matched Unrelated Vs Haploidentical Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide, Dipenkumar Modi, Ramzi Abboud, Et Al.

2020-Current year OA Pubs

Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is now standard for matched unrelated donor (MUD) hematopoietic cell transplantation (HCT). Previous studies comparing MUD and haploidentical donor HCT using PTCy were limited in size and follow-up. We therefore performed a registry-based analysis examining the impact of donor type on HCT with PTCy. Adult patients (n = 5873) receiving MUD (n = 1973) or haploidentical (n = 3900) HCT with PTCy for acute leukemia (74.2%) or myelodysplastic syndrome (MDS; 25.8%) reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021 were included. Primary end points were 3-year …

Efficacy And Safety Of Oral Pcsk9 Inhibitor Enlicitide In Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial, Christie M Ballantyne, Laura Gellis, Jean-Claude Tardif, Puja Banka, Ann Marie Navar, Emil Andreas Asprusten, Russell Scott, Erik S G Stroes, Samar Froman, Geraldine Mendizabal, Fan Wang, Alberico L Catapano

Faculty, Staff and Students Publications

Importance: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies.

Objective: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy.

Design, setting, and participants: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least …

Self-Efficacy Change Among Diverse Family Caregivers In Dementia Care, Deborah M Oyeyemi, Erich J Greene, Yunshan Xu, David R Lee, Rafael Samper-Ternent, Maya L Lichtenstein, Alan Stevens, Jeff D Williamson, Arun S Karlamangla, Debra Saliba, David B Reuben

Faculty, Staff and Student Publications

Objectives: To determine whether changes in caregiver self-efficacy (beliefs about one's ability to manage dementia-related problems and access help) differed by caregiver race and ethnicity across all participants enrolled in a large pragmatic trial of comprehensive dementia care.

Methods: In the Dementia Care Study (D-CARE), community-dwelling older adults with dementia and their unpaid family caregivers were randomized to receive usual care, community-based, or health system-based comprehensive dementia care. Caregiver self-efficacy was assessed at baseline, 6 months, and 18 months using a 4-item scale (range 4-20, higher scores indicate greater self-efficacy). Among all caregivers, we compared least squares means for overall …

Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions And Induce Cell-Cycle Arrest, Jorge Luis Galeano Niño, Falk Ponath, Victor A Ajisafe, Clara R Becker, Andrew G Kempchinsky, Martha A Zepeda-Rivera, Javier A Gomez, Hanrui Wu, Jessica G Terrazas, Heather Bouzek, Elizabeth Cromwell, Pritha Chanana, Matthew Wong, Ashish Damania, Michael G White, Y Nancy You, Scott Kopetz, Nadim J Ajami, Jennifer A Wargo, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals …

Tet2-Mutant Clonal Hematopoiesis Enhances Macrophage Antigen Presentation And Improves Immune Checkpoint Therapy In Solid Tumors, Shelley Herbrich, Mehdi Chaib, Swetha Anandhan, Samuel W Andrewes, Ashwat Nagarajan, Baoxiang Guan, Nishant Gandhi, Jared Gilliam, Milan Radovich, Padmanee Sharma

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is detectable in upwards of 20% of patients with solid tumors and is associated with worsened prognosis; however, its role in tumor immunology and immune checkpoint therapy (ICT) is unknown. Using a bone marrow chimera model of Tet2+/mut CH in mice with solid tumors, we found the Tet2-mutant myeloid cells are abundant in the tumor microenvironment and contributed to an improved response to ICT. Mechanistically, Tet2+/mut macrophages inside the tumor act as immunogenic antigen-presenting cells that more effectively cross-prime naive CD8+ T cells in response to IFNγ. In human cohorts of 35,971 non-small cell lung cancer patients …

Characteristics And Effectiveness Of Maternal Health Interventions To Prevent Mother-To-Child Transmission (Pmtct) Of Syphilis In A Global Setting: A Scoping Review Using Intervention Mapping As A Framework, Jinni Tang, Anusha Sajja, Christine Markham, Emily T Hebert, Irene Stafford, Sheryl Dacso, Melissa F Peskin

Faculty, Staff and Student Publications

Background: Despite the availability of cost-effective treatments, maternal syphilis continues to contribute significantly to preventable stillbirths and congenital syphilis cases worldwide. This scoping review aimed to identify and characterize maternal health interventions designed to prevent mother-to-child transmission (PMTCT) of syphilis globally, using a modified Intervention Mapping (IM) framework.

Methods: We conducted a scoping review of maternal health interventions targeting PMTCT of syphilis published between January 2010 and August 2023. Searches were performed in PubMed, Medline Ovid, and Embase, supplemented by manual reference screening. Eligible studies described at least one maternal health intervention addressing syphilis PMTCT and were analyzed using a …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …

The Computationally Designed Tri2-2 Miniprotein Inhibitor Protects Against Multiple Sars-Cov-2 Omicron Variants, Jimin Lee, James Brett Case, Young-Jun Park, Rashmi Ravichandran, Daniel Asarnow, M Alejandra Tortorici, Jack T Brown, Shilpa Sanapala, Lauren Carter, David Baker, Michael S Diamond, David Veesler

2020-Current year OA Pubs

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent …

Transcriptomic Signature-Guided Depletion Of Intermediate Alveolar Epithelial Cells Ameliorates Pulmonary Fibrosis In Mice, Fei Peng, Chun-Sun Jiang, Zhen Zheng, Shahram Aliyari, Dan Shan, Aaryan Sabharwal, Qinyan Yin, Shigeki Saito, Chao He, Ivan O Rosas, Joseph A Lasky, Victor J Thannickal, Yong Zhou

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has identified intermediate epithelial states in pulmonary fibrosis, including KRT5-/KRT17+ aberrant basaloid cells in humans and Krt8+ alveolar differentiation intermediates (ADIs) in mice. Their functional contributions to fibrogenesis, however, remain unclear. Here, we introduce an RNA-sensing-dependent protein translation technology that enables selective targeting of Krt8+ ADI cells in vitro and in vivo. Transcriptomic analysis revealed Small Proline-Rich Protein 1 A (SPRR1A) mRNA as a shared marker of murine Krt8+ ADIs and human KRT5-/KRT17+ basaloid cells, distinguishing them from other lung cell populations. Using programmable RNA sensors, we demonstrated selective EGFP-labeling of Krt8+ ADI cells in vivo, …

Clinical And Dosimetric Dataset Of Time-To-Event Normal Tissue Complication Probability For Osteoradionecrosis, Natalie A West, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Renjie He, Mohamed A Naser, Katherine A Hutcheson, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Laia Humbert-Vidan

Faculty, Staff and Student Publications

Osteoradionecrosis of the jaw (ORNJ) is a radiation-induced late toxicity that can dramatically decrease patients' quality of life. Recent increases in survival rates of head and neck cancers associated with human papillomavirus (HPV) infection have resulted in a higher frequency of radiation-induced toxicities, particularly ORNJ. Recent work with Normal Tissue Complication Probability (NTCP) models and a Weibull Accelerated Failure Time (WAFT) model have further developed our understanding of ORNJ clinical/dosimetric risk factors and longitudinal features, respectively. In this data descriptor, 1129 head and neck cancer (HNC) patients received curative intent radiotherapy (RT) at MD Anderson Cancer Center and were followed …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Daily Locomotor Activity Declines With Tumor Growth And Disease Progression In Glioblastoma, Maria F Gonzalez-Aponte, Sofia V Salvatore, Anna R. Damato, Ruth Gn Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2-3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the …