Medicine and Health Sciences Commons^™

A Spatially Resolved Single-Cell Genomic Atlas Of The Adult Human Breast, Tapsi Kumar, Kevin Nee, Runmin Wei, Siyuan He, Quy H Nguyen, Shanshan Bai, Kerrigan Blake, Maren Pein, Yanwen Gong, Emi Sei, Min Hu, Anna K Casasent, Aatish Thennavan, Jianzhuo Li, Tuan Tran, Ken Chen, Benedikt Nilges, Nachiket Kashikar, Oliver Braubach, Bassem Ben Cheikh, Nadya Nikulina, Hui Chen, Mediget Teshome, Brian Menegaz, Huma Javaid, Chandandeep Nagi, Jessica Montalvan, Tatyana Lev, Sharmila Mallya, Delia F Tifrea, Robert Edwards, Erin Lin, Ritesh Parajuli, Summer Hanson, Sebastian Winocour, Alastair Thompson, Bora Lim, Devon A Lawson, Kai Kessenbrock, Nicholas Navin

Faculty, Staff and Student Publications

The adult human breast is comprised of an intricate network of epithelial ducts and lobules that are embedded in connective and adipose tissue1-3. Although most previous studies have focused on the breast epithelial system4-6, many of the non-epithelial cell types remain understudied. Here we constructed the comprehensive Human Breast Cell Atlas (HBCA) at single-cell and spatial resolution. Our single-cell transcriptomics study profiled 714,331 cells from 126 women, and 117,346 nuclei from 20 women, identifying 12 major cell types and 58 biological cell states. These data reveal abundant perivascular, endothelial and immune cell populations, and highly diverse luminal epithelial cell states. …

Ancestral Diversity In Lipoprotein(A) Studies Helps Address Evidence Gaps, Moa P Lee, Sofia F Dimos, Laura M Raffield, Zhe Wang, Anna F Ballou, Carolina G Downie, Christopher H Arehart, Adolfo Correa, Paul S De Vries, Zhaohui Du, Christopher R Gignoux, Penny Gordon-Larsen, Xiuqing Guo, Jeffrey Haessler, Annie Green Howard, Yao Hu, Helina Kassahun, Shia T Kent, J Antonio G Lopez, Keri L Monda, Kari E North, Ulrike Peters, Michael H Preuss, Stephen S Rich, Shannon L Rhodes, Jie Yao, Rina Yarosh, Michael Y Tsai, Jerome I Rotter, Charles L Kooperberg, Ruth J F Loos, Christie Ballantyne, Christy L Avery, Mariaelisa Graff

Faculty, Staff and Student Publications

INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in >1.5 billion individuals worldwide, but studies have prioritised European populations.

METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)'s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations.

RESULTS: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R

CONCLUSIONS: …

Missense Genetic Variation Of Icam1 And Incident Heart Failure, Pedro Giro, Jonathan W Cunningham, Laura Rasmussen-Torvik, Suzette J Bielinski, Nicholas B Larson, Laura A Colangelo, David R Jacobs, Myron Gross, Alex P Reiner, Donald M Lloyd-Jones, Xiuqing Guo, Kent Taylor, Muthiah Vaduganathan, Wendy S Post, Alain Bertoni, Christie Ballantyne, Amil Shah, Brian Claggett, Eric Boerwinkle, Bing Yu, Scott D Solomon, Sanjiv J Shah, Ravi B Patel

Faculty, Staff and Student Publications

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF.

METHODS AND RESULTS: We identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in …

Robotic Versus Laparoscopic Ventral Hernia Repair: Two-Year Results From A Prospective, Multicenter, Blinded Randomized Clinical Trial, Naila H Dhanani, Nicole B Lyons, Oscar A Olavarria, Karla Bernardi, Julie L Holihan, Shinil K Shah, Todd D Wilson, Michele M Loor, Lillian S Kao, Mike K Liang

Faculty, Staff and Student Publications

OBJECTIVE: Report the 2-year outcomes of a multicenter randomized controlled trial comparing robotic versus laparoscopic intraperitoneal onlay mesh ventral hernia repair.

BACKGROUND: Ventral hernia repair is one of the most common operations performed by general surgeons. To our knowledge, no studies have been published to date comparing long-term outcomes of laparoscopic versus robotic ventral hernia repair.

METHODS: The trial was registered at clinicaltrials.gov (NCT03490266). Clinical outcomes included surgical site infection, surgical site occurrence, hernia occurrence, readmission, reoperation, and mortality.

RESULTS: A total of 175 consecutive patients were approached that were deemed eligible for elective minimally invasive ventral hernia repair. In …

Knowledge Acquisition Efficacy Of A Remote Flipped Classroom On Learning About Removable Partial Dentures, Yuka Inamochi, Eiko Yoshida Kohno, Junichiro Wada, Natsuko Murakami, Atsushi Takaichi, Yuki Arai, Takeshi Ueno, Kenji Fueki, Noriyuki Wakabayashi

Faculty, Staff and Student Publications

Purpose: Coronavirus disease 2019 has forced the use of remote education worldwide. In 2020, the authors conducted a fully digitized, remote flipped (RF) classroom focusing on removable partial dentures. This study aimed to evaluate the learning outcomes of the RF classroom and compare these with those of the on-site classroom.

Methods: The fourth-year dental students in 2017-2019 attended on-site flipped classroom (OF; n=70) or on-site lecture classroom (OL; n=67), and those in 2020 (n=58) attended the RF classroom. Lecture videos and text were provided online in the OF and RF groups, while only the text was given to the OL …

A Genome-Wide Association Study Identifies 41 Loci Associated With Eicosanoid Levels, Eugene P Rhee, Aditya L Surapaneni, Pascal Schlosser, Mona Alotaibi, Yueh-Ning Yang, Josef Coresh, Mohit Jain, Susan Cheng, Bing Yu, Morgan E Grams

Faculty, Staff and Student Publications

Eicosanoids are biologically active derivatives of polyunsaturated fatty acids with broad relevance to health and disease. We report a genome-wide association study in 8406 participants of the Atherosclerosis Risk in Communities Study, identifying 41 loci associated with 92 eicosanoids and related metabolites. These findings highlight loci required for eicosanoid biosynthesis, including FADS1-3, ELOVL2, and numerous CYP450 loci. In addition, significant associations implicate a range of non-oxidative lipid metabolic processes in eicosanoid regulation, including at PKD2L1/SCD and several loci involved in fatty acyl-CoA metabolism. Further, our findings highlight select clearance mechanisms, for example, through the hepatic transporter encoded by SLCO1B1. Finally, …

Inhibition Of Microsomal Prostaglandin E2 Synthase Reduces Collagen Deposition In Melanoma Tumors And May Improve Immunotherapy Efficacy By Reducing T-Cell Exhaustion, Yasunari Fukuda, Sun-Hee Kim, Matias A Bustos, Sung-Nam Cho, Jason Roszik, Jared K Burks, Hong Kim, Dave S B Hoon, Elizabeth A Grimm, Suhendan Ekmekcioglu

Faculty, Staff and Student Publications

The arachidonic acid pathway participates in immunosuppression in various types of cancer. Our previous observation detailed that microsomal prostaglandin E2 synthase 1 (mPGES-1), an enzyme downstream of cyclooxygenase 2 (COX-2), limited antitumor immunity in melanoma; in addition, genetic depletion of mPGES-1 specifically enhanced immune checkpoint blockade therapy. The current study set out to distinguish the roles of mPGES-1 from those of COX-2 in tumor immunity and determine the potential of mPGES-1 inhibitors for reinforcing immunotherapy in melanoma. Genetic deletion of mPGES-1 showed different profiles of prostaglandin metabolites from that of COX-2 deletion. In our syngeneic mouse model, mPGES-1-deficient cells exhibited …

A Deep Learning Onion Peeling Approach To Measure Oral Epithelium Layer Number, Xinyi Zhang, Frederico O Gleber-Netto, Shidan Wang, Kevin W Jin, Donghan M Yang, Ann M Gillenwater, Jeffrey N Myers, Renata Ferrarotto, Curtis R Pickering, Guanghua Xiao

Faculty, Staff and Student Publications

Head and neck squamous cell carcinoma (HNSCC), specifically in the oral cavity (oral squamous cell carcinoma, OSCC), is a common, complex cancer that significantly affects patients' quality of life. Early diagnosis typically improves prognoses yet relies on pathologist examination of histology images that exhibit high inter- and intra-observer variation. The advent of deep learning has automated this analysis, notably with object segmentation. However, techniques for automated oral dysplasia diagnosis have been limited to shape or cell stain information, without addressing the diagnostic potential in counting the number of cell layers in the oral epithelium. Our study attempts to address this …

Recent Advances In The Treatment Of Complex Congenital Diaphragmatic Hernia-A Narrative Review, Kylie I Holden, Matthew T Harting

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Congenital diaphragmatic hernia (CDH) is an anomaly of the cardiopulmonary system maturation process that results from both a global embryopathy and concomitant mechanical compression of the cardiopulmonary system from the abdominal contents during fetal maturation. This results in pulmonary hypertension, pulmonary hypoplasia, and cardiac dysfunction, requiring intense critical care management. The patients with highest risk CDH are the most challenging, resource-intensive, and bear most of the mortality. Advances at the basic, translational, and clinical research levels are leading to novel therapies and management strategies for complex, high-risk CDH. Our objective is to review novel approaches in thinking …

Potential Toxic Elements And Their Carcinogenic And Non-Carcinogenic Risk Assessment In Some Commercially Important Fish Species From A Ramsar Site, Mohammad Belal Hossain, Md Moudud Ahmed, Yeasmin Nahar Jolly, As-Ad Ujjaman Nur, Salma Sultana, Shirin Akter, Jimmy Yu, Bilal Ahamad Paray, Takaomi Arai

Faculty, Staff and Student Publications

Potentially toxic elements (PTEs) such as Hg, As, and Pb have become concentrated in the aquatic ecosystem as a result of increased human activities. However, these substances frequently have synergistic or antagonistic effects on the human body or other animals. As a result, there are concerns world-wide that commercially available food products, especially fish, may be contaminated with hazardous elements. In this study, samples of four selected fishes, Gutum (Lepidocephalichthys guntea), Baim (Macrognathus pancalus), Baila (Glossogobius giuris), Meni (Nandus nandus) were analyzed from one of the largest freshwater wetlands (designed as a …

Artificial Intelligence Frameworks To Detect And Investigate The Pathophysiology Of Spaceflight Associated Neuro-Ocular Syndrome (Sans), Joshua Ong, Ethan Waisberg, Mouayad Masalkhi, Sharif Amit Kamran, Kemper Lowry, Prithul Sarker, Nasif Zaman, Phani Paladugu, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is a unique phenomenon that has been observed in astronauts who have undergone long-duration spaceflight (LDSF). The syndrome is characterized by distinct imaging and clinical findings including optic disc edema, hyperopic refractive shift, posterior globe flattening, and choroidal folds. SANS serves a large barrier to planetary spaceflight such as a mission to Mars and has been noted by the National Aeronautics and Space Administration (NASA) as a high risk based on its likelihood to occur and its severity to human health and mission performance. While it is a large barrier to future spaceflight, the underlying …

The New World Of Rna Diagnostics And Therapeutics, Giovanni Blandino, Roberto Dinami, Marco Marcia, Eleni Anastasiadou, Brid M Ryan, Alina Catalina Palcau, Luigi Fattore, Giulia Regazzo, Rosanna Sestito, Rossella Loria, Ana Belén Díaz Méndez, Maria Chiara Cappelletto, Claudio Pulito, Laura Monteonofrio, George A Calin, Gabriella Sozzi, Jit Kong Cheong, Ranit Aharonov, Gennaro Ciliberto

Faculty, Staff and Student Publications

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27-28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled "The New World of RNA diagnostics and therapeutics" highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.This report collected the presentations …

Automated Capture And Analysis Of Circulating Tumor Cells In Pediatric, Adolescent And Young Adult Patients With Central Nervous System Tumors, Wafik Zaky, Dristhi Ragoonanan, Izhar Batth, Long Dao, Jian Wang, Xueqing Xia, Najat C Daw, Jonathan B Gill, Soumen Khatua, Shulin Li

Faculty, Staff and Student Publications

Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral …

Phosphorylated Nuclear Dicer1 Promotes Open Chromatin State And Lineage Plasticity Of At2 Tumor Cells In Lung Adenocarcinomas, Raisa A Reyes-Castro, Shin-Yu Chen, Jacob Seemann, Samrat T Kundu, Don L Gibbons, Swathi Arur

Faculty, Staff and Student Publications

KRAS/ERK pathway phosphorylates DICER1, causing its nuclear translocation, and phosphomimetic Dicer1 contributes to tumorigenesis in mice. Mechanisms through which phospho-DICER1 regulates tumor progression remain undefined. While DICER1 canonically regulates microRNAs (miRNA) and epithelial-to-mesenchymal transition (EMT), we found that phosphorylated nuclear DICER1 (phospho-nuclear DICER1) promotes late-stage tumor progression in mice with oncogenic Kras, independent of miRNAs and EMT. Instead, we observe that the murine AT2 tumor cells exhibit altered chromatin compaction, and cells from disorganized advanced tumors, but not localized tumors, express gastric genes. Collectively, this results in subpopulations of tumor cells transitioning from a restricted alveolar to a broader …

Federated Generalized Linear Mixed Models For Collaborative Genome-Wide Association Studies, Wentao Li, Han Chen, Xiaoqian Jiang, Arif Harmanci

Faculty, Staff and Student Publications

Federated association testing is a powerful approach to conduct large-scale association studies where sites share intermediate statistics through a central server. There are, however, several standing challenges. Confounding factors like population stratification should be carefully modeled across sites. In addition, it is crucial to consider disease etiology using flexible models to prevent biases. Privacy protections for participants pose another significant challenge. Here, we propose distributed Mixed Effects Genome-wide Association study (dMEGA), a method that enables federated generalized linear mixed model-based association testing across multiple sites without explicitly sharing genotype and phenotype data. dMEGA employs a reference projection to …

Loss Of Metabolic Fitness Drives Tumor Resistance After Car-Nk Cell Therapy And Can Be Overcome By Cytokine Engineering, Li Li, Vakul Mohanty, Jinzhuang Dou, Yuefan Huang, Pinaki P Banerjee, Qi Miao, Jens G Lohr, Tushara Vijaykumar, Julia Frede, Birgit Knoechel, Luis Muniz-Feliciano, Tamara J Laskowski, Shaoheng Liang, Judy S Moyes, Vandana Nandivada, Rafet Basar, Mecit Kaplan, May Daher, Enli Liu, Ye Li, Sunil Acharya, Paul Lin, Mayra Shanley, Hind Rafei, David Marin, Stephan Mielke, Richard E Champlin, Elizabeth J Shpall, Ken Chen, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control the fate of CAR-NK cells after infusion and factors that influence tumor control remain poorly understood. We performed single-cell RNA sequencing and mass cytometry to study the heterogeneity of CAR-NK cells and their in vivo evolution after adoptive transfer, from the phase of tumor control to relapse. Using a preclinical model of noncurative lymphoma and samples from a responder and a nonresponder patient treated with CAR19/IL-15 NK cells, we observed the emergence of NK cell …

Perspectives In Melanoma: Meeting Report From The Melanoma Bridge (December 1st–3rd, 2022-Naples, Italy), Paolo A Ascierto, Sanjiv S Agarwala, Allison Betof Warner, Marc S Ernstoff, Bernard A Fox, Thomas F Gajewski, Jérôme Galon, Claus Garbe, Brian R Gastman, Jeffrey E Gershenwald, Pawel Kalinski, Michelle Krogsgaard, Rom S Leidner, Roger S Lo, Alexander M Menzies, Olivier Michielin, Poulikos I Poulikakos, Jeffrey S Weber, Corrado Caracò, Iman Osman, Igor Puzanov, Magdalena Thurin

Faculty, Staff and Student Publications

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have several potential target oncogenes for molecularly targeted therapy, such as tyrosine kinase inhibitors. Unfortunately, many patients still progress and …

A Phase Ii Clinical Trial Of Pembrolizumab Efficacy And Safety In Advanced Renal Medullary Carcinoma, Chijioke Nze, Pavlos Msaouel, Mohamed H Derbala, Bettzy Stephen, Abdulrahman Abonofal, Funda Meric-Bernstam, Nizar M Tannir, Aung Naing

Faculty, Staff and Student Publications

Background: Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC.

Methods: A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated …

Surface-Doped Zinc Gallate Colloidal Nanoparticles Exhibit Ph-Dependent Radioluminescence With Enhancement In Acidic Media, Navadeep Shrivastava, Jessa Guffie, Tamela L Moore, Burak Guzelturk, Amar S Kumbhar, Jianguo Wen, Zhiping Luo

Faculty, Staff and Student Publications

As abnormal acidic pH symbolizes dysfunctions of cells, it is highly desirable to develop pH-sensitive luminescent materials for diagnosing disease and imaging-guided therapy using high-energy radiation. Herein, we explored near-infrared-emitting Cr-doped zinc gallate ZnGa2O4 nanoparticles (NPs) in colloidal solutions with different pH levels under X-ray excitation. Ultrasmall NPs were synthesized via a facile hydrothermal method by controlling the addition of ammonium hydroxide precursor and reaction time, and structural characterization revealed Cr dopants on the surface of NPs. The synthesized NPs exhibited different photoluminescence and radioluminescence mechanisms, confirming the surface distribution of activators. It was observed that the colloidal NPs emit …

Gender Differences In A Mouse Model Of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging, Brian J Engel, Vincenzo Paolillo, Md Nasir Uddin, Kristyn A Gonzales, Kathryn M Mcginnis, Margie N Sutton, Madhavi Patnana, Brian J Grindel, Gregory J Gores, David Piwnica-Worms, Laura Beretta, Federica Pisaneschi, Seth T Gammon, Steven W Millward

Faculty, Staff and Student Publications

The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular …

Islet: Individual-Specific Reference Panel Recovery Improves Cell-Type-Specific Inference, Hao Feng, Guanqun Meng, Tong Lin, Hemang Parikh, Yue Pan, Ziyi Li, Jeffrey Krischer, Qian Li

Faculty, Staff and Student Publications

We propose a statistical framework ISLET to infer individual-specific and cell-type-specific transcriptome reference panels. ISLET models the repeatedly measured bulk gene expression data, to optimize the usage of shared information within each subject. ISLET is the first available method to achieve individual-specific reference estimation in repeated samples. Using simulation studies, we show outstanding performance of ISLET in the reference estimation and downstream cell-type-specific differentially expressed genes testing. We apply ISLET to longitudinal transcriptomes profiled from blood samples in a large observational study of young children and confirm the cell-type-specific gene signatures for pancreatic islet autoantibody. ISLET is available at https://bioconductor.org/packages/ISLET …

Clinical Evidence Of Human Pathogens Implicated In Alzheimer’S Disease Pathology And The Therapeutic Efficacy Of Antimicrobials: An Overview, Celso S G Catumbela, Vijayasree V Giridharan, Tatiana Barichello, Rodrigo Morales

Faculty, Staff and Student Publications

A wealth of pre-clinical reports and data derived from human subjects and brain autopsies suggest that microbial infections are relevant to Alzheimer's disease (AD). This has inspired the hypothesis that microbial infections increase the risk or even trigger the onset of AD. Multiple models have been developed to explain the increase in pathogenic microbes in AD patients. Although this hypothesis is well accepted in the field, it is not yet clear whether microbial neuroinvasion is a cause of AD or a consequence of the pathological changes experienced by the demented brain. Along the same line, the gut microbiome has also …

Telehealth Diagnosis Of Autism Spectrum Disorder Through Clinical Cases, Emmanuela Ojukwu, Eunice Bawafaa, Sara Afsah, Shivangi Singh, Harsimran Grewal, Zainab Raja, Emily Mckay

Faculty, Staff and Student Publications

INTRODUCTION: African, Caribbean and Black (ACB) adolescents are disproportionately affected by teen pregnancy in North America. Teen pregnancy poses risks to the quality of life of adolescent boys and girls, including physical, psychosocial and socioeconomic risks. Our review aims to explore this public health concern for ACB adolescents within North America. We aim to identify and analyse available evidence on the incidence and prevalence of, associated factors of and interventions to curtail teen pregnancy involvement (TPI) among ACB adolescent boys and girls in North America. This review will explore TPI, rather than teen pregnancy, to ensure a review of men' …

Tissue-Specific Features Of The T Cell Repertoire After Allogeneic Hematopoietic Cell Transplantation In Human And Mouse, Susan Dewolf, Yuval Elhanati, Katherine Nichols, Nicholas R Waters, Chi L Nguyen, John B Slingerland, Natasia Rodriguez, Olga Lyudovyk, Paul A Giardina, Anastasia I Kousa, Hana Andrlová, Nick Ceglia, Teng Fei, Rajya Kappagantula, Yanyun Li, Nathan Aleynick, Priscilla Baez, Rajmohan Murali, Akimasa Hayashi, Nicole Lee, Brianna Gipson, Madhumitha Rangesa, Zoe Katsamakis, Anqi Dai, Amanda G Blouin, Maria Arcila, Ignas Masilionis, Ronan Chaligne, Doris M Ponce, Heather J Landau, Ioannis Politikos, Roni Tamari, Alan M Hanash, Robert R Jenq, Sergio A Giralt, Kate A Markey, Yanming Zhang, Miguel-Angel Perales, Nicholas D Socci, Benjamin D Greenbaum, Christine A Iacobuzio-Donahue, Travis J Hollmann, Marcel R M Van Den Brink, Jonathan U Peled

Faculty, Staff and Student Publications

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood …

Comprehensive Analysis Of The Prognostic Significance Of The Trim Family In The Context Of Tp53 Mutations In Cancers, Trung Vu, Annaliese Fowler, Nami Mccarty

Faculty, Staff and Student Publications

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the

Prescribing Patterns Of Fall Risk-Increasing Drugs In Older Adults Hospitalized For Heart Failure, Esther Liu, Musarrat Nahid, Mahad Musse, Ligong Chen, Sarah N Hilmer, Andrew Zullo, Min Ji Kwak, Mark Lachs, Emily B Levitan, Monika M Safford, Parag Goyal

Faculty, Staff and Student Publications

BACKGROUND: Older adults hospitalized for heart failure (HF) are at risk for falls after discharge. One modifiable contributor to falls is fall risk-increasing drugs (FRIDs). However, the prevalence of FRIDs among older adults hospitalized for HF is unknown. We describe patterns of FRIDs use and examine predictors of a high FRID burden.

METHODS: We used the national biracial REasons for Geographic and Racial Differences in Stroke (REGARDS) study, a prospective cohort recruited from 2003-2007. We included REGARDS participants aged ≥ 65 years discharged alive after a HF hospitalization from 2003-2017. We determined FRIDs -cardiovascular (CV) and non-cardiovascular (non-CV) medications - …

Impact Of Type Of Induction Therapy On Outcomes In Older Adults With Aml After Allogeneic Stem Cell Transplantation, Nicholas J Short, Faustine Ong, Farhad Ravandi, Graciela Nogueras-Gonzalez, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Marina Konopleva, Gautam Borthakur, Betul Oran, Gheath Al-Atrash, Rohtesh Mehta, Elias J Jabbour, Musa Yilmaz, Ghayas C Issa, Abhishek Maiti, Richard E Champlin, Hagop Kantarjian, Elizabeth J Shpall, Uday Popat

Faculty, Staff and Student Publications

Although venetoclax-based lower-intensity regimens have greatly improved outcomes for older adults with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, the optimal induction for older patients with newly diagnosed AML who are suitable candidates for hematopoietic stem cell transplant (HSCT) is controversial. We retrospectively analyzed the post HSCT outcomes of 127 patients ≥60 years of age who received induction therapy at our institution with intensive chemotherapy (IC; n = 44), lower-intensity therapy (LIT) without venetoclax (n = 29), or LIT with venetoclax (n = 54) and who underwent allogeneic HSCT in the first remission. The 2-year relapse-free survival …

Agrp Neurons Are Not Indispensable For Body Weight Maintenance In Adult Mice, Jing Cai, Jing Chen, Joshua Ortiz-Guzman, Jessica Huang, Benjamin R Arenkiel, Yuchen Wang, Yan Zhang, Yuyan Shi, Qingchun Tong, Cheng Zhan

Faculty, Staff and Student Publications

In addition to their role in promoting feeding and obesity development, hypothalamic arcuate agouti-related protein/neuropeptide Y (AgRP/NPY) neurons are widely perceived to be indispensable for maintaining normal feeding and body weight in adults, and consistently, acute inhibition of AgRP neurons is known to reduce short-term food intake. Here, we adopted complementary methods to achieve nearly complete ablation of arcuate AgRP/NPY neurons in adult mice and report that lesioning arcuate AgRP/NPY neurons in adult mice causes no apparent alterations in ad libitum feeding or body weight. Consistent with previous studies, loss of AgRP/NPY neurons blunts fasting refeeding. Thus, our studies show …

Abatacept, Cenicriviroc, Or Infliximab For Treatment Of Adults Hospitalized With Covid-19 Pneumonia: A Randomized Clinical Trial, Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W Mccarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia De Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E Mcnulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa Lavange, Michael Proschan, Samuel A Bozzette, William G Powderly

Faculty, Staff and Student Publications

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and …

Dual Targeting Of Cdk4/6 And Bcl-2 Exhibits A Potent Antitumor Effect On Mantle Cell Lymphoma, Yuxuan Che, Yang Liu, Yijing Li, Joseph M Mcintosh, Alexa Jordan, Fangfang Yan, Wei Wang, Lei Nie, Heng-Huan Lee, Jingling Jin, Yixin Yao, Zhongming Zhao, Vivian Changying Jiang, Michael Wang

Faculty, Staff and Student Publications

No abstract provided.