Medicine and Health Sciences Commons^™

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 …

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through Sfrp4 Signaling, Joseph Rupert, Lingyi Cai, Alexes C Daquinag, Dimitris Anastassiou, Mikhail G Kolonin

Faculty, Staff and Student Publications

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis.

Methods: To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells.

Results: Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix …

Dynamic Fib-4 Score Changes And Hcc Risk In Patients With Masld And Elevated Liver Enzymes: A Nationwide Cohort Study, Yee Hui Yeo, Hsiu J Ho, Tsai-Wei Huang, Teng-Yu Lee, Ju Dong Yang, George Cholankeril, Chien-Jen Chen, Hawi-I Yang, Chuen-Fei Chen, Hung-Chuen Chang, Chun-Ying Wu

Faculty, Staff and Students Publications

Introduction: Hepatocellular carcinoma (HCC) can develop in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis, especially in those with elevated liver enzymes. However, there is currently no low-cost, scalable screening tool for this population. To address this need, we investigated the association between serial changes in FIB-4 (fibrosis-4) scores over a 3-year period and the risk of developing HCC in a large, diverse cohort of patients with MASLD without cirrhosis.

Methods: This study utilized a nationwide cohort from the National Health Insurance Research Database (NHIRD), including 810,698 patients with MASLD who had demographic and laboratory data at baseline …

Chek2 Loss Endows Chemotherapy Resistance To Hematopoietic Stem Cells, Jing Zhou, Tianyuan Hu, Dian Li, Sanming Li, Minhua Li, Xiangguo Shi, Daisuke Nakada

Faculty, Staff and Students Publications

Individuals with history of chemo- or radiotherapy frequently exhibit somatic mosaicism in the blood, often involving mutations in genes responsible for DNA damage responses (DDR), such as CHEK2. However, the mechanisms by which CHEK2 mutations promote the expansion of mutant cells following chemo- or radiotherapy remain poorly understood. Here, we demonstrate that loss of CHEK2 confers resistance to chemotherapy in hematopoietic stem and progenitor cells (HSPCs). Through a CRISPR-based screen, we identified CHEK2 as a gene whose loss enhances resistance to cytotoxic chemotherapies. A complementary drug screen revealed that CHEK2-mutant cells are also resistant to DNA hypomethylating agents. Chek2-deficient HSPCs …

Germline Hla Heterozygosity Is Associated With Decreased Lung Cancer Risk, Taotao Tan, Vikram R Shaw, Jinyoung Byun, Hyun-Sung Lee, Younghun Han, Yafang Li, Rayjean J Hung, David C Christiani, Xin-An Wang, Mattias Johansson, Xiangjun Xiao, David Zaridze, Stig Egil Bojesen, Sanjay Shete, Demetrios Albanes, Melinda C Aldrich, Adonina Tardon, Guillermo Fernandez-Tardon, Loïc Le Marchand, Gad Rennert, Heike Bickeböller, H-Erich Wichmann, Angela Risch, John K Field, Michael Davies, Penella Woll, Lambertus A Kiemeney, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Mikael Johansson, Kjell Grankvist, Matthew B Schabath, Angeline Andrew, Philip Lazarus, Susanne M Arnold, Dakai Zhu, Maria Teresa Landi, James Mckay, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

Heterozygosity at human leukocyte antigen (HLA) loci may improve lung cancer immunosurveillance by increasing recognition of the tumor by the immune system. Previous studies utilizing data from population-level biobanks, such as the United Kingdom Biobank and FinnGen, have identified an association between germline HLA class-II heterozygosity and reduced lung cancer risk in smokers. In the present study, we evaluate the association between HLA heterozygosity and lung cancer in a large case-control study (15,302 cases; 14,580 controls) with imputed HLA allele-type information, comparing differences in HLA heterozygosity between smokers and non-smokers, amongst lung cancer subtypes, and at 2- and 4-digit HLA …

Excess Risk Of Fracture In Incident Parkinson's Disease Medicare Beneficiaries, Alejandra Camacho-Soto, Irene M Faust, Brittany Krzyzanowski, Jordan A Killion, Kassu M Beyene, Edward F Ellerbeck, Jacob J Sosnoff, Brad A Racette

2020-Current year OA Pubs

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by both motor and non-motor symptoms. Falls and fractures are common in advanced PD but the risk of fractures in newly diagnosed people with PD and the impact of treatment with levodopa is understudied.

METHODS: We investigated the risk of fractures among Medicare beneficiaries with incident PD age ≥ 67 compared to controls. Among PD cases only with continuous Part D medication coverage, we examined the effect of levodopa treatment on fracture risk. We identified incident PD cases (N = 68,150) within a population-based sample of 2017 Medicare …

P-78. Susceptibility Of Omadacycline In Bone And Joint Infections: Pathogen Susceptibility And Regimen Decisions From An Ongoing Randomized Controlled Trial, Amy Y. Kang, Evelyn A. Flores, Donna Phan Tran, Buchen (Olivia) Han, Isabel Payan, Guarina Garcia Delgado, Loren G. Miller

Pharmacy Faculty Articles and Research

Background   Treatment of Bone and joint infections (BJIs) with oral antibiotics may have benefits compared to IV therapy. Yet oral treatment options may be limited by lack of options due to antibiotic-resistant pathogens and tolerability concerns. Omadacycline has in vitro activity against common BJI pathogens, including MRSA and most Enterobacterales. However, real-world susceptibility data and implications for oral therapy are limited.   Methods

We conducted a descriptive analysis of data from adult patients enrolled to date in an open-label, randomized controlled trial of comparing omadacycline-containing antibiotic regimen vs. standard of care (SOC) antibiotics for BJIs. Omadaycline susceptibility was assessed on available …

686. Antibiotic Prescribing For Urinary Tract Infections In Outpatient Settings: A Multicenter Assessment Based On The Five Ds Of Stewardship, Amy Y. Kang, Oliver Tan, Sunwoo Oh, Nikki Derleth, Megan Shieh, Helen Vu, Inna Tagarino, Audrey Harrington, Deborah Kupferwasser, Loren G. Miller

Pharmacy Faculty Articles and Research

Background   Urinary tract infections (UTIs) are a leading cause of outpatient antibiotic use. Prior studies have documented inappropriate prescribing during outpatient UTI visits, but few have assessed intervention opportunities using a structured stewardship framework. We evaluated UTI prescribing practices in a healthcare system using the Five Ds framework: Diagnosis, Drug, Dose, Duration, and De-escalation.   Methods

We conducted a retrospective study across 4 medical centers and > 20 outpatient clinics within the Los Angeles County Department of Health Services, the second largest U.S. safety net healthcare system. To ensure adequate representation across sites while maintaining feasibility for manual chart review, we reviewed …

Blood Product Transfusion And Coagulopathy In Children With Traumatic Brain Injury: A Narrative Review., Robert Marcel T. Huibonhoa, Niranjan Vijayakumar, Daniel Kelly, Oliver Karam, Madhuradhar Chegondi

Manuscripts, Articles, Book Chapters and Other Papers

Traumatic brain injury (TBI) is a leading cause of critical illness and mortality in children. Transfusion of blood products, a common intervention in the management of pediatric TBI, has important implications for related principles, including trauma-induced coagulopathy, cerebral perfusion, and cerebral oxygen delivery. Knowledge gaps persist due to the limited availability of pediatric-specific data regarding blood product transfusion in TBI. In particular, there is a lack of prospective studies defining appropriate specific laboratory thresholds and transfusion targets, as well as insufficient evidence to guide the weighing of potential benefits against transfusion-related risks in this population. Although blood product transfusion in …

Effect Of Remineralization And Resin Infiltration On Microhardness, Mineral Content And Cervical Microleakage Of Restored Demineralized Enamel, Sara Adel Botros, Caroline Maged Massieh

Dentistry

No abstract provided.

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 …

Large-Scale Blood Pressure Gwas Accounting For Gene-Depression Interactions In 564,680 Individuals From Diverse Populations, Songmi Lee, Clint L Miller, Amy R Bentley, Michael R Brown, Pavithra Nagarajan, Raymond Noordam, John L Morrison, Karen Schwander, Kenneth Westerman, Minjung Kho, Aldi T Kraja, Paul S De Vries, Farah Ammous, Hughes Aschard, Traci M Bartz, Anh Do, Charles T Dupont, Mary F Feitosa, Valborg Gudmundsdottir, Xiuqing Guo, Sarah E Harris, Keiko Hikino, Zhijie Huang, Christophe Lefevre, Leo-Pekka Lyytikäinen, Yuri Milaneschi, Giuseppe Giovanni Nardone, Aurora Santin, Helena Schmidt, Botong Shen, Tamar Sofer, Quan Sun, Ye An Tan, Jingxian Tang, Sébastien Thériault, Peter J Van Der Most, Erin B Ware, Stefan Weiss, Wang Ya Xing, Chenglong Yu, Wei Zhao, Md Abu Yusuf Ansari, Pramod Anugu, John R Attia, Lydia A Bazzano, Joshua C Bis, Max Breyer, Brian Cade, Guanjie Chen, Stacey Collins, Janie Corley, Gail Davies, Marcus Dörr, Jiawen Du, Todd L Edwards, Tariq Faquih, Jessica D Faul, Alison E Fohner, Amanda M Fretts, Srushti Gangireddy, Adam Gepner, Mariaelisa Graff, Edith Hofer, Georg Homuth, Michelle M Hood, Xu Jie, Mika Kähönen, Sharon L R Kardia, Carrie A Karvonen-Gutierrez, Lenore J Launer, Daniel Levy, Maitreiyi Maheshwari, Lisa W Martin, Koichi Matsuda, John J Mcneil, Ilja M Nolte, Tomo Okochi, Laura M Raffield, Olli T Raitakari, Lorenz Risch, Martin Risch, Ana Diez Roux, Edward A Ruiz-Narvaez, Tom C Russ, Takeo Saito, Pamela J Schreiner, Rodney J Scott, James Shikany, Jennifer A Smith, Harold Snieder, Beatrice Spedicati, E Shyong Tai, Adele M Taylor, Kent D Taylor, Paola Tesolin, Rob M Van Dam, Rujia Wang, Wei Wenbin, Tian Xie, Jie Yao, Kristin L Young, Ruiyuan Zhang, Alan B Zonderman, Biobank Japan Project, Lifelines Cohort Study, Maria Pina Concas, David Conen, Simon R Cox, Michele K Evans, Ervin R Fox, Lisa De Las Fuentes, Ayush Giri, Giorgia Girotto, Hans J Grabe, Charles Gu, Vilmundur Gudnason, Sioban D Harlow, Elizabeth Holliday, Jonas B Jost, Paul Lacaze, Seunggeun Lee, Terho Lehtimäki, Changwei Li, Ching-Ti Liu, Alanna C Morrison, Kari E North, Brenda W J H Penninx, Patricia A Peyser, Michael M Province, Bruce M Psaty, Susan Redline, Frits R Rosendaal, Charles N Rotimi, Jerome I Rotter, Reinhold Schmidt, Xueling Sim, Chikashi Terao, David R Weir, Xiaofeng Zhu, Nora Franceschini, Jeffrey R O'Connell, Cashell E Jaquish, Heming Wang, Alisa Manning, Patricia B Munroe, Dabeeru C Rao, Han Chen, W James Gauderman, Laura J Bierut, Thomas W Winkler, Myriam Fornage

Faculty, Staff and Student Publications

Gene-environment interactions may enhance our understanding of blood pressure (BP) biology. We conducted a meta-analysis of multi-population genome-wide association studies (GWASs) of BP traits accounting for gene-depressive symptomatology (DEPR) interactions. Our study included 564,680 adults from 67 cohorts and four population backgrounds: African (5%), Asian (7%), European (85%), and Hispanic (3%). We discovered seven previously unreported BP loci showing gene-DEPR interaction. These loci mapped to genes implicated in neurogenesis (TGFA and CASP3), lipid metabolism (ACSL1), neuronal apoptosis (CASP3), and synaptic activity (CNTN6 and DBI). We also showed evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between …

Secure Distributed Multiple Imputation Enables Missing Data Inference For Private Data Proprietors, Haris Smajlović, Yi Lian, Qi Long, Ibrahim Numanagić, Xiaoqian Jiang

Faculty, Staff and Student Publications

Scattered between many healthcare providers across the US, Electronic Health Records (EHR) are extensively used for research purposes. Collaboration and sharing of EHRs between multiple institutions often provide access to more diverse datasets and a chance to conduct comprehensive studies. However, these collaboration efforts are usually hindered by privacy issues that render the pooling of such data at a centralized database impossible. Furthermore, EHRs are often incomplete and require statistical imputation prior to the study. To enable collaborative studies on top of incomplete, private EHRs, here we provide a provably secure solution built with secure multiparty computation (SMC) that provides …

Association Of Neighborhood Economic Trajectories And Risk Of Mortality Among Older Adults, Erika Figueroa-Solis, Qian Xiao

Faculty, Staff and Student Publications

Background

Lower neighborhood socioeconomic status (SES) and decline in neighborhood SES have been linked to detrimental health outcomes, such as cardiovascular disease (CVD), cancer, and mortality. However, few studies have investigated distinct types of neighborhood economic trajectories in relation to mortality. We examined the association between the recently developed multidimensional measure of neighborhood trajectories and mortality in older adults enrolled in the National Institutes of Health-AARP Diet and Health Study (NIH-AARP).

Methods

Neighborhoods were classified into five groups based on economic change patterns from 2000 to 2016 using American Community Survey data: Stability, Growth, Displacement, Abandonment, and Poverty Concentration. Mortality …

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 …

Identification Of Cadm1 As An Immunotherapeutic Target And Evaluation Of A Novel Cadm1-Targeting Antibody-Drug Conjugate In Preclinical Osteosarcoma Models, Yifei Wang, Zhongting Zhang, Caterina Longo, Wendong Zhang, Qi Wang, Amer Najjar, Xiangjun Tian, Rossana N Lazcano Segura, Michael E Roth, Jonathan Gill, Douglas J Harrison, Zhaohui Xu, Yanhua Yi, Xin Zhou, Sylvester Jusu, Timothy M Stearns, Steven B Neuhauser, Carol J Bult, Jing Wang, Alexander J Lazar, Richard Gorlick

Faculty, Staff and Student Publications

Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in patients with several solid and hematologic malignancies. Our comprehensive surfaceome profiling approach previously identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC. We tested a CADM1-targeting ADC with a tesirine payload (SG3249) in vitro in osteosarcoma, rhabdomyosarcoma, and neuroblastoma patient-derived xenograft cell lines. In vivo, we tested six CADM1-expressing osteosarcoma …

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 …

Il-18 Metabolically Reprograms Car-Expressing Natural Killer T Cells And Enhances Their Antitumor Activity, Gabriel A Barragán Bravo, David A De La Cerda, Elisa Landoni, Kshiti Dholakia, Piotr Humeniuk, Leidy D Caraballo Galva, Ying Wang, Gengwen Tian, Boning Yang, Linjie Guo, Michael S Wood, Xavier Rios, Xin Xu, Amy N Courtney, Erica J Di Pierro, Joan Jacob, Yi-Han Li, Akshaya Adaikkalavan, Norihiro Watanabe, Sufeng Mao, George Miles, Gianpietro Dotti, Leonid S Metelitsa

Faculty, Staff and Students Publications

Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR) immunotherapies. Transgenic cytokine expression can enhance cellular therapy potency, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this, we generated retroviral constructs expressing IL-15 and/or IL-18 with an inducible caspase 9 safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased CAR-NKT cytotoxicity, proliferation, and cytokine secretion in vitro compared to IL-15 alone. IL-18 also enhanced GPC3.CAR and CD19.CAR NKT activity against hepatocellular …

Plasma Proteomics And Incident Coronary Heart Disease, Matthew P Huber, Jennifer A Brody, Colleen M Sitlani, Thomas R Austin, Usman A Tahir, Shuliang Deng, Devendra Meena, Jingsha Chen, Kunihiro Matsushita, Christie M Ballantyne, Josef Coresh, Robert E Gerszten, Russell P Tracy, Ting Ye, Bruce M Psaty, Joshua C Bis, James S Floyd

Faculty, Staff and Students Publications

Background: Systematic profiling of plasma proteins in population studies offers a complementary approach to discovery of novel risk factors and may provide new insights into the causes of coronary heart disease.

Methods: To explore relationships between the circulating proteome and coronary heart disease (CHD), we evaluated associations of 4780 plasma proteins with incident CHD in the Cardiovascular Health Study (CHS, N=2856, 575 CHD events) and replicated significant associations in the Atherosclerosis Risk in Communities Study (ARIC, N = 10456; 1375 events).

Results: We find that 11 proteins significantly associate with incident CHD after adjusting for risk factors; and eight significantly …

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, …

Broad Laboratory Testing Does Not Show Utility For Telogen Effluvium: A Retrospective Analysis Of 22-Million Laboratory Results Using Trinetx, Zachary J.K. Neubauer, Shari R. Lipner

Student Papers, Posters & Projects

No abstract provided.

Sociodemographic And Hiv-Related Characteristics Associated With Mental Health Diagnoses Among People Living With Hiv, Monique J. Brown Ph.D., Mph, Jiayang Xiao, Xueying Yang Ph.D., Bankole Olatosi Ph.D., Sharon Weissman, Xiaoming Li Ph.D., Jiajia Zhang Ph.D.

Faculty Publications

Mental health diagnoses have been linked to poor HIV treatment outcomes and poorer quality of life among people living with HIV (PLWH). Therefore, this study aimed to investigate the association between sociodemographic and HIV-related characteristics, and common and serious mental health disorders among PLWH in South Carolina (SC). Data were obtained from the integrated system of statewide electronic health record (EHR) data in SC (2006–2019; N = 8,124). Multivariable logistic regression models were used to determine the associations between sociodemographic and HIV-related characteristics, and common mental health disorders and serious mental health disorders. Among the study population, 4% were 60 …

Repair Techniques For Acute Rupture Of The Patellar Tendon: A Systematic Review, Gaston Davis, Harrison S. Fellheimer, Christian Mccormick, Kevin B. Freedman

Rothman Institute Papers

BACKGROUND: Multiple techniques exist to repair acute tears of the patellar tendon. Surgical repair is required to reestablish full function of the extensor mechanism of the knee, and optimal results typically occur when the tear is repaired acutely.

PURPOSE: To systematically review the literature to evaluate treatment outcomes and complication rates after acute surgical repair of patellar tendon ruptures using suture anchor repair, transosseous repair, and end-to-end repair.

STUDY DESIGN: Scoping review; Level of evidence, 4.

METHODS: A systematic review was performed to analyze outcomes after patellar tendon repair in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews …

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 …

The Yeh Pilus Adhesin Is Equipped With An Α-Helical Flap Motif, Which Contributes To Pectin Adherence, Kevin O Tamadonfar, Roger D Klein, Edward D B Lopatto, Maxwell I Zimmerman, Philippe N Azimzadeh, Denise A Sanick, Justin R Porter, Jesus Bazan Villicana, Jerome S Pinkner, Bo Huey Chiang, Nathaniel C Gualberto, Karen W Dodson, Michael L Patnode, George M H Et Al., Gregory R Bowman, Scott J Hultgren

2020-Current year OA Pubs

The Yeh chaperone-usher pathway (CUP) pilus adhesin is encoded in one-half of all

Assessment Of Body Fat Percentage In Emirati Females: A Comparative Analysis Of Bia Vs. Dxa, Dalia Haroun, Aseel Ehsanallah

All Works

Introduction: Obesity is a significant health issue in the UAE. Accurate body composition assessment is crucial for managing obesity-related health risks. This study aimed to evaluate the agreement between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) in measuring body composition among Emirati females. Methods: This cross-sectional study involved 95 healthy Emirati females aged 17–27 years. Paired samples t-tests, correlation analyses, and Bland-Altman plots were used to compare the two methods (BIA vs. DXA). Results: BIA significantly underestimated % fat and fat mass (FM) while overestimating fat-free mass (FFM) compared to DXA. The mean difference in % fat was …

Prognostic Value Of Baseline Qfr In Single-Vessel Intermediate Coronary Stenosis, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S. Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Xin Huang, Ning Guo

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: The prognostic value of baseline Quantitative Flow Ratio (QFR) in real-world patients remains unclear. This study aimed to evaluate the prognostic value of baseline QFR and its three-tier model-low, grey-zone, and high QFR-in patients with single-vessel intermediate stenosis.

METHODS: This retrospective study included 478 patients with QFR between 0.70 and 0.90 who underwent coronary angiography between May and June 2023. Patients were stratified into Low (0.70-0.74), Grey-Zone (0.75-0.85), and High (0.86-0.90) QFR groups. The primary endpoint was major adverse cardiac events (MACE); the key secondary endpoint was target vessel failure (TVF). Kaplan-Meier and Cox proportional hazards models …