Digital Commons Network^™

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 …

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 …

Onset And Exacerbation Of Obsessive-Compulsive Disorder In The Perinatal Period, Jack Samuels, Mary Kimmel, Janice Krasnow, Rashelle Musci, Paul S Nestadt, Lauren M Osborne, Eric A Storch, Jonathan S Abramowitz, Gerald Nestadt

Faculty, Staff and Students Publications

Purpose: Obsessive-compulsive disorder (OCD) can emerge during pregnancy and the postpartum and may adversely affect mother and newborn. However, little is known about potential risk factors for the onset of OCD in the perinatal period. Therefore, we investigated the onset of diagnosed DSM-5 OCD in women followed from the second trimester of pregnancy to 6-months postpartum.

Methods: We followed 256 women from the 20-24th week of pregnancy to 6-month postpartum. Participants had psychiatric diagnostic interviews at baseline and 6-month postpartum and completed self-report instruments. We compared women with and without incident OCD on sociodemographic characteristics and clinical features.

Results: Of …

Attitudes Toward Patients' Safety Among Healthcare Professionals In The United Arab Emirates: A Cross-Sectional Study, Moien Khan, Amiri Sohrab, Iffat Elbarazi, Mohammed Salaheldin Elsayed, Reem Al Falasi, Debasish Kar

Peninsula Medical School

This research aims to investigate healthcare professionals’ (HCPs) attitudes towards patient safety and to explore the role ofvarious work-related factors that could be the barriers to safety-events reporting to modify these attitudes. A cross-sectionalsurvey was conducted, involving 629 HCPs who are working across health care sectors in the United Arab Emirates. HCPs in theUnited Arab Emirates, comprising 71.5% women and 27.8% men, displayed a generally positive attitude towards patient safety(mean score = 3.91). Sub-comparisons indicated high scores for team functioning (4.58 ± 0.62) and low scores for professionalincompetence as an error cause (2.86 ± 0.50). Common barriers to reporting safety …

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.

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 …

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 …

The Impact Of Skin Tone On Performance Of Pulse Oximeters Used By Nhs England Covid Oximetry @Home Scheme: Measurement And Diagnostic Accuracy Study, Exakt Study Investigators, Daniel S Martin, James C Doidge, Doug Gould, Tasnin Shahid, Alex Cowden, Walton N Charles, Amelia Francis Johnson, Roger Garrett, Catherine Mbema, Olusegun Olusanya, Eugene Healy, Kathryn Rowan, Paul Mouncey, David A Harrison

Peninsula Medical School

OBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.

DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).

SETTING: Twenty four intensive care units in England between June 2022 and August 2024.

PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.

INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) …

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 …

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.

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 …

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 …

Unlocking The Potential Of Citrulline Malate: A Pilot Study, Fabiola E. Bejarano, Elisa L. Milkie, Parker Andersen, Jenevieve L. Roper Facsm

International Journal of Exercise Science: Conference Proceedings

Citrulline malate (CM) is an ergogenic aid hypothesized to improve exercise performance by promoting nitric oxide (NO) production resulting in increased vasodilation, blood flow, and oxygen and nutrient delivery to working muscles. It is also thought to increase the synthesis of ATP and aerobic efficiency via malate and the TCA cycle. Prior research demonstrates improvements in upper and lower body submaximal resistance training exercise performance in females; however, limited research exists on the effects of CM supplementation on submaximal aerobic exercise performance in females. PURPOSE: Determine the effects of acute CM supplementation on submaximal time-trial (TT) performance in females. …

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 …

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 …

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 …

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 …

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, …

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 …

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 …

Antecedent Enhancer Activity Predicts Future Susceptibility To Seizures In Mice, Benjamin D Boros, Mariam A Gachechiladze, Juanru Guo, Dylan A Galloway, Shayna M Mueller, Mark Shabsovich, Allen Yen, Xuhua Chen, Alexander J Cammack, Tao Shen, Robi D Mitra, Joseph D Dougherty, Timothy M Miller

2020-Current year OA Pubs

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci …

Gh Alters Lymphatic Vessels In Female Mice And Stat5 Phosphorylation In Human Lymphatic Endothelial Cells, Christopher Walsh, Emily Scott, Elise Wagner, Jerome Walsh, Shashank Reddy, Arshad Ahmad, Reetobrata Basu, Eva Sevick-Muraca, Rich Brody, Uday Sandbhor, Sebastian Neggers, John J Kopchick

The Brown Foundation: Institute of Molecular Medicine

Disruption of lymphatic function underlies a broad spectrum of inflammatory and metabolic disorders, yet the hormonal pathways that regulate lymphatic biology remain poorly defined. GH, which is implicated in similar disease states, has an unclear role in lymphatic homeostasis. To address this gap, we investigated how chronic alterations in GH signaling alter lymphatic structure and function. Using transgenic mouse lines with increased, decreased, or absent GH action, we quantified the effect of GH on lymphatic pumping rate and lymphangiogenic remodeling during wound healing using near-infrared fluorescent imaging. We also measured markers of lymphatic endothelial cells using Western blot and immunohistochemistry …

Comparison Of Surgery And Medicine On The Impact Of Diverticulitis (Cosmid) Trial: A Protocol For A Pragmatic Randomised Study Of Diverticulitis Treatment In The Usa, Mariam N Hantouli, Robert H Schmicker, Janice E Tufte, Fadwa G Ali, Robert D Bennett, Jessica N Cohan, Bryan A Comstock, Thomas Curran, Giana H Davidson, Samuel Eisenstein, Katherine N Fischkoff, Fergal J Fleming, Irena Gribovskaja-Rupp, Mehraneh Dorna Jafari, Larry G Kessler, Mukta K Krane, Sarah O Lawrence, James T Mccormick, Stefanos G Millas, Arden M Morris, Kelsey M Pullar, Caroline E Reinke, Julia T Saraidaridis, Vlad V Simianu, Suzanne P Watkins, Nicole B White, Elizabeth C Wick, Nicole Wieghard, David R Flum, Thomas E Read

Faculty, Staff and Student Publications

Introduction: Each year, millions of people experience recurrent diverticulitis episodes. Elective sigmoid colon resection reduces the risk of recurrence, but The American Society of Colon and Rectal Surgeons recommends individualising surgical decisions based on the impact of the condition on a patient's quality of life (QoL). However, no threshold for QoL impairment has been established to guide decision-making, and evidence comparing elective colectomy with medical management in terms of QoL limitation is limited. To address these gaps and to guide treatment decision-making, we designed the Comparison of Surgery and Medicine on the Impact of Diverticulitis (COSMID) trial.The COSMID trial is …

Assessing The Effects Of Ehealth Literacy And The Area Deprivation Index On Barriers To Electronic Patient Portal Use For Orthopedic Surgery: Cross-Sectional Observational Study, Audrey Lynn Litvak, Nicholas Lin, Kelly Hynes, Jason Strelzow, Jeffrey G Stepan

2020-Current year OA Pubs

BACKGROUND: As electronic patient portals (EPPs) continue to gain popularity and systems transition to online tools for scheduling, communication, and telehealth, patients without access or skills to use these tools may be overlooked.

OBJECTIVE: This study analyzed patient and neighborhood-level factors, including eHealth literacy level and the Area Deprivation Index (ADI), that may limit EPP access for orthopedic surgery.

METHODS: A cross-sectional, survey-based study was performed at a single urban tertiary academic medical center in the United States across foot and ankle, hand and upper extremity, and orthopedic trauma subspecialty clinics from June 21, 2022, to August 12, 2022. Survey …