Digital Commons Network^™

Dissecting Fc Signatures Of Protection In Neonates Following Maternal Influenza Vaccination In A Placebo-Controlled Trial., Carolyn M Boudreau, John S Burke, Kiel D Shuey, Caitlin Wolf, Joanne Katz, James Tielsch, Subarna Khatry, Steven C Leclerq, Janet A Englund, Helen Y Chu, Galit Alter

Global Health Faculty Publications

Influenza is an important cause of illness and morbidity for infants. Seasonal influenza vaccination during pregnancy aims to provide protection to mothers, but it can also provide immunity to infants. The precise influence of maternal vaccination on immunity in infants and how vaccine-elicited antibodies provide protection in some but not all infants is incompletely understood. We comprehensively profiled the transfer of functional antibodies and defined humoral factors contributing to immunity against influenza in a clinical trial of maternal influenza vaccination. Influenza-specific antibody subclass levels, Fc ɣ receptor (FCGR) binding levels, and antibody-dependent innate immune functions were all profiled in the …

Parasite Dynamics In Untreated Horses Through One Calendar Year, Ashley E. Steuer, Haley P. Anderson, Taylor Shepherd, Morgan Clark, Jessica A. Scare, Holli S. Gravatte, Martin K. Nielsen

Veterinary Science Faculty Publications

BACKGROUND: Horses are host to a plethora of parasites. Knowledge of the seasonality of parasite egg shedding and transmission is important for constructing parasite control programs. However, studies describing these patterns are sparse, and have largely been conducted only in the United Kingdom. This study evaluated strongylid egg shedding patterns and transmission dynamics of Strongylus vulgaris in naturally infected and untreated mares and foals through one calendar year in Kentucky, USA. The study also investigated the existence of a peri-parturient rise (PPR) in strongylid egg counts in foaling mares and collected information about Strongyloides westeri and Parascaris spp. in the …

Regulation Of The Double-Stranded Rna Response Through Adar1 Licenses Metaplastic Reprogramming In Gastric Epithelium, José B. Sáenz, Nancy Vargas, Charles J. Cho, Jason C. Mills

2020-Current year OA Pubs

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of …

Ddr1 Contributes To Kidney Inflammation And Fibrosis By Promoting The Phosphorylation Of Bcr And Stat3, Corina M. Borza, Gema Bolas, Fabian Bock, Xiuqi Zhang, Favour C Akabogu, Ming-Zhi Zhang, Mark De Caestecker, Min Yang, Haichun Yang, Ethan Lee, Leslie Gewin, Agnes B Fogo, W Hayes Mcdonald, Roy Zent, Ambra Pozzi

Open Access Publications

Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase activated by collagen, contributes to chronic kidney disease. However, its role in acute kidney injury and subsequent development of kidney fibrosis is not clear. Thus, we performed a model of severe ischemia/reperfusion-induced acute kidney injury that progressed to kidney fibrosis in WT and Ddr1-null mice. We showed that Ddr1-null mice had reduced acute tubular injury, inflammation, and tubulointerstitial fibrosis with overall decreased renal monocyte chemoattractant protein (MCP-1) levels and STAT3 activation. We identified breakpoint cluster region (BCR) protein as a phosphorylated target of DDR1 that controls MCP-1 production in renal proximal …

Regulation Of The Double-Stranded Rna Response Through Adar1 Licenses Metaplastic Reprogramming In Gastric Epithelium, José B Sáenz, Nancy Vargas, Charles J Cho, Jason C Mills

Faculty, Staff and Students Publications

Cells recognize both foreign and host-derived double-stranded RNA (dsRNA) via a signaling pathway that is usually studied in the context of viral infection. It has become increasingly clear that the sensing and handling of endogenous dsRNA is also critical for cellular differentiation and development. The adenosine RNA deaminase, ADAR1, has been implicated as a central regulator of the dsRNA response, but how regulation of the dsRNA response might mediate cell fate during injury and whether such signaling is cell intrinsic remain unclear. Here, we show that the ADAR1-mediated response to dsRNA was dramatically induced in 2 distinct injury models of …

Selective Reduction Of Astrocyte Apoe3 And Apoe4 Strongly Reduces Aβ Accumulation And Plaque-Related Pathology In A Mouse Model Of Amyloidosis, Thomas E Mahan, Chao Wang, Xin Bao, Ankit Choudhury, Jason D Ulrich, David M Holtzman

2020-Current year OA Pubs

BACKGROUND: One of the key pathological hallmarks of Alzheimer disease (AD) is the accumulation of the amyloid-β (Aβ) peptide into amyloid plaques. The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD and has been shown to influence the accumulation of Aβ in the brain in an isoform-dependent manner. ApoE can be produced by different cell types in the brain, with astrocytes being the largest producer of apoE, although reactive microglia also express high levels of apoE. While studies have shown that altering apoE levels in the brain can influence the development of Aβ plaque pathology, …

Constitutive Activation Of Canonical Wnt Signaling Disrupts Choroid Plexus Epithelial Fate, Arpan Parichha, Varun Suresh, Mallika Chatterjee, Aditya Kshirsagar, Lihi Ben-Reuven, Tsviya Olender, M Mark Taketo, Velena Radosevic, Mihaela Bobic-Rasonja, Sara Trnski, Michael J Holtzman, Nataša Jovanov-Milosevic, Orly Reiner, Shubha Tole

Open Access Publications

The choroid plexus secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the choroid plexus epithelium arises from the Wnt- expressing cortical hem. Canonical Wnt signaling pathway molecules such as nuclear β-CATENIN are expressed in the mouse and human embryonic choroid plexus epithelium indicating that this pathway is active. Point mutations in human β-CATENIN are known to result in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of choroid plexus epithelial identity and an apparent transformation of this tissue to a …

Host Tissue Proteomics Reveal Insights Into The Molecular Basis Of Schistosoma Haematobium-Induced Bladder Pathology., Derick N M Osakunor, Kenji Ishida, Olivia K Lamanna, Mario Rossi, Louis Dwomoh, Michael H. Hsieh

Urology Faculty Publications

Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology are not well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of …

Attitudes Among Healthcare Professionals Towards Cardiopulmonary Resuscitation During Covid-19., Safinaz Al-Shiakh, Quincy K Tran, Amy Caggiula, Ivan Berezowski, Basma Barnawi, Ali Pourmand

Emergency Medicine Faculty Publications

No abstract provided.

Association Of State Social And Environmental Factors With Rates Of Self-Injury Mortality And Suicide In The United States, Ian R H Rockett, Haomiao Jia, Bina Ali, Aniruddha Banerjee, Hilary S. Connery, Kurt B. Nolte, Ted Miller, Franklin M M White, Bernard D. Digregorio, G Luke Larkin, Steven Stack, Kairi Kõlves, R Kathryn Mchugh, Vijay O. Lulla, Jeralynn Cossman, Diego De Leo, Brian Hendricks, Paul S. Nestadt, James H. Berry, Gail D'Onofrio, Eric D. Caine

Pathology Research and Scholarship

IMPORTANCE: Self-injury mortality (SIM) combines suicides and the preponderance of drug misuse-related overdose fatalities. Identifying social and environmental factors associated with SIM and suicide may inform etiologic understanding and intervention design.

OBJECTIVE: To identify factors associated with interstate SIM and suicide rate variation and to assess potential for differential suicide misclassification.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a partial panel time series with underlying cause-of-death data from 50 US states and the District of Columbia for 1999-2000, 2007-2008, 2013-2014 and 2018-2019. Applying data from the Centers for Disease Control and Prevention, SIM includes all suicides and the preponderance …

Comparison Of Sexually Transmitted Infections And Adverse Perinatal Outcomes In Underserved Pregnant Patients Before Vs During The Covid-19 Pandemic In Texas, Irene A Stafford, Jennie O Coselli, Danielle F Wilson, Courtney Y Wang, Baha M Sibai

Faculty, Staff and Student Publications

This cohort study assesses the rates of sexually transmitted infections (STI) and associated adverse perinatal outcomes among underserved pregnant patients during the COVID-19 pandemic in a public health system in Southeastern Texas.

Safety And Efficacy Of Mass Drug Administration With A Single-Dose Triple-Drug Regimen Of Albendazole + Diethylcarbamazine + Ivermectin For Lymphatic Filariasis In Papua New Guinea: An Open-Label, Cluster-Randomised Trial, Livingstone Tavul, Kobie O'Brian, Gary J. Weil, Charles W. Goss, Et Al

Open Access Publications

BACKGROUND: Papua New Guinea (PNG) has a high burden of lymphatic filariasis (LF) caused by Wuchereria bancrofti, with an estimated 4.2 million people at risk of infection. A single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) has been shown to have superior efficacy in sustained clearance of microfilariae compared to diethylcarbamazine and albendazole (DA) in small clinical trials. A community-based cluster-randomised trial of DA versus IDA was conducted to compare the safety and efficacy of IDA and DA for LF in a moderately endemic, treatment-naive area in PNG.

METHODOLOGY: All consenting, eligible residents of 24 villages in Bogia district, …

Examining Rural-Urban Differences In Fatalism And Information Overload: Data From 12 Nci-Designated Cancer Centers, Jakob D Jensen, Jackilen Shannon, Ronaldo Iachan, Yangyang Deng, Sunny Jung Kim, Wendy Demark-Wahnefried, Babalola Faseru, Electra D Paskett, Jinxiang Hu, Robin C Vanderpool, Deann Lazovich, Jason A Mendoza, Sanjay Shete, Linda B Robertson, Rajesh Balkrishnan, Katherine J Briant, Benjamin Haaland, David A Haggstrom, Bernard F Fuemmeler, Rural Workgroup Of The Population Health Assessment In Cancer Center Catchment Areas Consortium

Faculty, Staff and Student Publications

BACKGROUND: Rural populations experience a disproportionate cancer burden relative to urban populations. One possibility is that rural populations are more likely to hold counterproductive cancer beliefs such as fatalism and information overload that undermine prevention and screening behaviors.

METHODS: Between 2016 and 2020, 12 U.S. cancer centers surveyed adults in their service areas using online and in-person survey instruments. Participants (

RESULTS: Compared with urban residents, rural residents were more likely to believe that (i) everything causes cancer (OR = 1.29; 95% CI, 1.17-1.43); (ii) prevention is not possible (OR = 1.34; 95% CI, 1.19-1.51); and (iii) there are too …

Randomized Phase Iii Bmt Ctn Trial Of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions In Myeloablative Hematopoietic Cell Transplantation For Hematologic Malignancies, Leo Luznik, Marcelo C Pasquini, Brent Logan, Robert J Soiffer, Juan Wu, Steven M Devine, Nancy Geller, Sergio Giralt, Helen E Heslop, Mary M Horowitz, Richard J Jones, Mark R Litzow, Adam Mendizabal, Lori Muffly, Eneida R Nemecek, Lynn O'Donnell, Richard J O'Reilly, Raquel Palencia, Johannes Schetelig, Leyla Shune, Scott R Solomon, Sumithira Vasu, Vincent T Ho, Miguel-Angel Perales

Faculty, Staff and Students Publications

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or …

Sars-Cov-2 Anti-Spike Antibodies After Vaccination In Pediatric Heart Transplantation: A First Report, Joseph A Spinner, Christopher L Julien, Lily Olayinka, William J Dreyer, Claire E Bocchini, Flor M Munoz, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.

METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.

RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a …

Importance Of The Intersection Of Age And Sex To Understand Variation In Incidence And Survival For Primary Malignant Gliomas, Gi-Ming Wang, Gino Cioffi, Nirav Patil, Kristin A Waite, Robert Lanese, Quinn T Ostrom, Carol Kruchko, Michael E Berens, James R Connor, Justin D Lathia, Joshua B Rubin, Jill S Barnholtz-Sloan

2020-Current year OA Pubs

BACKGROUND: Gliomas are the most common type of malignant brain and other CNS tumors, accounting for 80.8% of malignant primary brain and CNS tumors. They cause significant morbidity and mortality. This study investigates the intersection between age and sex to better understand variation of incidence and survival for glioma in the United States.

METHODS: Incidence data from 2000 to 2017 were obtained from CBTRUS, which obtains data from the NPCR and SEER, and survival data from the CDC's NPCR. Age-adjusted incidence rate ratios (IRR) per 100 000 were generated to compare male-to-female incidence by age group. Cox proportional hazard models …

Style Of Meal Service And Feeding Practices Among Mexican American Fathers And Mothers: An Analysis Of Video-Recorded Children’S Evening Mealtime At Home, Carlos Penilla, Jeanne M Tschann, Lauri A Pasch, Elena Flores, Julianna Deardorff, Suzanna M Martinez, Nancy F Butte, Louise C Greenspan

Children’s Nutrition Research Center Staff Publications

The aim of this study was to examine video-recorded observations of evening family mealtime at home among Mexican American children to help elucidate style of meal service, fathers' and mothers' feeding practices and child's eating behavior. Consistent with guidelines for coding behaviors, we analyzed observational data of evening mealtimes of 71 Mexican American children aged eight to 10 years. Regarding style of meal service, in almost all cases (96%), parents plated the child's food, with more available on the table or counter in 40% of the observations. Mothers almost always served the child (94%). Regarding parental feeding practices, parents used …

Longitudinal Changes In Vascular Stiffness And Heart Rate Variability Among Young Adults With Youth-Onset Type 2 Diabetes: Results From The Follow-Up Observational Treatment Options For Type 2 Diabetes In Adolescents And Youth (Today) Study, Amy S Shah, Laure El Ghormli, Samuel S Gidding, Kara S Hughan, Lorraine E Levitt Katz, Dorit Koren, Jeanie B Tryggestad, Fida Bacha, Barbara H Braffett, Silva Arslanian, Elaine M Urbina

Children’s Nutrition Research Center Staff Publications

Aims: (1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race-ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV.

Methods: Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes …

A Large-Scale Transcriptome-Wide Association Study (Twas) Of 10 Blood Cell Phenotypes Reveals Complexities Of Twas Fine-Mapping, Amanda L Tapia, Bryce T Rowland, Jonathan D Rosen, Michael Preuss, Kris Young, Misa Graff, Hélène Choquet, David J Couper, Steve Buyske, Stephanie A Bien, Eric Jorgenson, Charles Kooperberg, Ruth J F Loos, Alanna C Morrison, Kari E North, Bing Yu, Alexander P Reiner, Yun Li, Laura M Raffield

Faculty, Staff and Student Publications

Hematological measures are important intermediate clinical phenotypes for many acute and chronic diseases and are highly heritable. Although genome-wide association studies (GWAS) have identified thousands of loci containing trait-associated variants, the causal genes underlying these associations are often uncertain. To better understand the underlying genetic regulatory mechanisms, we performed a transcriptome-wide association study (TWAS) to systematically investigate the association between genetically predicted gene expression and hematological measures in 54,542 Europeans from the Genetic Epidemiology Research on Aging cohort. We found 239 significant gene-trait associations with hematological measures; we replicated 71 associations at p < 0.05 in a TWAS meta-analysis consisting of up to 35,900 Europeans from the Women's Health Initiative, Atherosclerosis Risk in Communities Study, and BioMe Biobank. Additionally, we attempted to refine this list of candidate genes by performing conditional analyses, adjusting for individual variants previously associated with hematological measures, and performed further fine-mapping of TWAS loci. To facilitate interpretation of our findings, we designed an R Shiny application to interactively visualize our TWAS results by integrating them with additional genetic data sources (GWAS, TWAS from multiple reference panels, conditional analyses, known GWAS variants, etc.). Our results and application highlight frequently overlooked TWAS challenges and illustrate the complexity of TWAS fine-mapping.

Genetic Errors Of Immunity Distinguish Pediatric Nonmalignant Lymphoproliferative Disorders, Lisa R Forbes, Olive S Eckstein, Nitya Gulati, Erin C Peckham-Gregory, Nmazuo W Ozuah, Joseph Lubega, Nader K El-Mallawany, Jennifer E Agrusa, M Cecilia Poli, Tiphanie P Vogel, Natalia S Chaimowitz, Nicholas L Rider, Emily M Mace, Jordan S Orange, Jason W Caldwell, Juan C Aldave-Becerra, Stephen Jolles, Francesco Saettini, Hey J Chong, Asbjorg Stray-Pedersen, Helen E Heslop, Kala Y Kamdar, R Helen Rouce, Donna M Muzny, Shalini N Jhangiani, Richard A Gibbs, Zeynep H Coban-Akdemir, James R Lupski, Kenneth L Mcclain, Carl E Allen, Ivan K Chinn

Faculty, Staff and Student Publications

BACKGROUND: Pediatric nonmalignant lymphoproliferative disorders (PLPDs) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD.

OBJECTIVE: The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes.

METHODS: PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant Epstein-Barr virus (EBV) infection. Fifty-one subjects from …

Breast Radiation Therapy-Related Treatment Outcomes In Patients With Or Without Germline Mutations On Multigene Panel Testing, Bhavana V Chapman, Diane Liu, Yu Shen, Oluwafikayo O Olamigoke, David S Lakomy, Angelica M Gutierrez Barrera, Shane R Stecklein, Gabriel O Sawakuchi, Scott J Bright, Isabelle Bedrosian, Jennifer K Litton, Benjamin D Smith, Wendy A Woodward, George H Perkins, Karen E Hoffman, Michael C Stauder, Eric A Strom, Banu K Arun, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing.

METHODS AND MATERIALS: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest …

Panobinostat Enhances Olaparib Efficacy By Modifying Expression Of Homologous Recombination Repair And Immune Transcripts In Ovarian Cancer, Andrew J Wilson, Vijayalaxmi G Gupta, Qi Liu, Fiona Yull, Marta A Crispens, Dineo Khabele

Open Access Publications

Histone deacetylase inhibitors (HDACi) sensitize homologous recombination (HR)-proficient human ovarian cancer cells to PARP inhibitors (PARPi). To investigate mechanisms of anti-tumor effects of combined HDACi/PARPi treatment we performed transcriptome analysis in HR- proficient human ovarian cancer cells and tested drug effects in established immunocompetent mouse ovarian cancer models. Human SKOV-3 cells were treated with vehicle (Con), olaparib (Ola), panobinostat (Pano) or Pano+Ola and RNA-seq analysis performed. DESeq2 identified differentially expressed HR repair and immune transcripts. Luciferised syngeneic mouse ovarian cancer cells (ID8-luc) were treated with the HDACi panobinostat alone or combined with olaparib and effects on cell viability, apoptosis, DNA …

Measurement Of Gender And Sexuality In The Adolescent Brain Cognitive Development (Abcd) Study, Alexandra S Potter, Hailee Jefferys, Et Al

Open Access Publications

The Adolescent Brain Cognitive Development

Construction And Validation Of Prognostic Nomogram For Metaplastic Breast Cancer, Yongfeng Li, Daobao Chen, Haojun Xuan, Mihnea P Dragomir, George A Calin, Xuli Meng, Meng Chen, Hongchuan Jin

Faculty, Staff and Student Publications

In this study we aimed to develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with metaplastic breast cancer (MBC). Data of patients diagnosed with MBC from 1973 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for OS and CSS of MBC patients. The obtained prognostic variables were combined to construct nomogram models for predicting OS and CSS in patients with MBC. Model performance was evaluated using concordance index (C-index) and calibration plots. Data from 1125 patients …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …

Efficacy And Safety Of Covid-19 Convalescent Plasma In Hospitalized Patients: A Randomized Clinical Trial, Mila B Ortigoza, Hyunah Yoon, Keith S Goldfeld, Andrea B Troxel, Johanna P Daily, Yinxiang Wu, Yi Li, Danni Wu, Gia F Cobb, Gillian Baptiste, Mary O'Keeffe, Marilou O Corpuz, Luis Ostrosky-Zeichner, Amee Amin, Ioannis M Zacharioudakis, Dushyantha T Jayaweera, Yanyun Wu, Julie V Philley, Megan S Devine, Mahalia S Desruisseaux, Alessandro D Santin, Shweta Anjan, Reeba Mathew, Bela Patel, Masayuki Nigo, Rabi Upadhyay, Tania Kupferman, Andrew N Dentino, Rahul Nanchal, Christian A Merlo, David N Hager, Kartik Chandran, Jonathan R Lai, Johanna Rivera, Chowdhury R Bikash, Gorka Lasso, Timothy P Hilbert, Monika Paroder, Andrea A Asencio, Mengling Liu, Eva Petkova, Alexander Bragat, Reza Shaker, David D Mcpherson, Ralph L Sacco, Marla J Keller, Corita R Grudzen, Judith S Hochman, Liise-Anne Pirofski, Lalitha Parameswaran, Anthony T Corcoran, Abhinav Rohatgi, Marta W Wronska, Xinyuan Wu, Ranjini Srinivasan, Fang-Ming Deng, Thomas D Filardo, Jay Pendse, Simone B Blaser, Olga Whyte, Jacqueline M Gallagher, Ololade E Thomas, Danibel Ramos, Caroline L Sturm-Reganato, Charlotte C Fong, Ivy M Daus, Arianne Gisselle Payoen, Joseph T Chiofolo, Mark T Friedman, Ding Wen Wu, Jessica L Jacobson, Jeffrey G Schneider, Uzma N Sarwar, Henry E Wang, Ryan M Huebinger, Goutham Dronavalli, Yu Bai, Carolyn Z Grimes, Karen W Eldin, Virginia E Umana, Jessica G Martin, Timothy R Heath, Fatimah O Bello, Daru Lane Ransford, Maudry Laurent-Rolle, Sheela V Shenoi, Oscar Bate Akide-Ndunge, Bipin Thapa, Jennifer L Peterson, Kelly Knauf, Shivani U Patel, Laura L Cheney, Christopher A Tormey, Jeanne E Hendrickson

Faculty, Staff and Student Publications

IMPORTANCE: There is clinical equipoise for COVID-19 convalescent plasma (CCP) use in patients hospitalized with COVID-19.

OBJECTIVE: To determine the safety and efficacy of CCP compared with placebo in hospitalized patients with COVID-19 receiving noninvasive supplemental oxygen.

DESIGN, SETTING, AND PARTICIPANTS: CONTAIN COVID-19, a randomized, double-blind, placebo-controlled trial of CCP in hospitalized adults with COVID-19, was conducted at 21 US hospitals from April 17, 2020, to March 15, 2021. The trial enrolled 941 participants who were hospitalized for 3 or less days or presented 7 or less days after symptom onset and required noninvasive oxygen supplementation.

INTERVENTIONS: A unit of …

Body Region-Specific 3d Age-Scaling Functions For Scaling Whole-Body Computed Tomography Anatomy For Pediatric Late Effects Studies, Aashish C Gupta, Constance A Owens, Suman Shrestha, Choonsik Lee, Susan A Smith, Rita E Weathers, Tucker Netherton, Peter A Balter, Stephen F Kry, David S Followill, Keith T Griffin, James P Long, Gregory T Armstrong, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose:

Radiation epidemiology studies of childhood cancer survivors treated in the pre-computed tomography (CT) era reconstruct the patients’ treatment fields on computational phantoms. For such studies, the phantoms are commonly scaled to age at the time of radiotherapy treatment because age is the generally available anthropometric parameter. Several reference size phantoms are used in such studies, but reference size phantoms are only available at discrete ages (e.g.: newborn, 1, 5, 10, 15, and Adult). When such phantoms are used for RT dose reconstructions, the nearest discrete-aged phantom is selected to represent a survivor of a specific age. In this work, …

Morphometric And Structural Analysis Of Florida Manatee Spermatozoa, Jonathan R Cowart, Danielle M Collins, Daniel L Stanton, Gerhard Van Der Horst, Iskande V Larkin

Staff and Researcher Publications

Sperm characteristics, such as sperm morphology and sperm morphometry are important in assessing sperm quality. This is especially important for the management and conservation of endangered and exotic species, like the Florida manatee, where information of this nature is extremely limited. In this study, we fill this knowledge gap to better understand the reproductive physiology of Florida manatees by conducting the first extensive analysis of sperm morphometry and ultrastructure. Sperm were retrieved from the vas deferens of nine recently deceased Florida manatees. Computer-aided sperm morphology analysis (CASMA) was used for morphometric analysis and laser-scanning confocal microscopy and electron microscopy were …

A Prospective Multicenter Evaluation Of Initial Treatment Choice In Metastatic Renal Cell Carcinoma Prior To The Immunotherapy Era: The Marcc Registry Experience, Brian A. Costello, Russell K. Pachynski, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The Metastatic Renal Cell Carcinoma (MaRCC) Registry provides prospective data on real-world treatment patterns and outcomes in patients with metastatic renal cell carcinoma (mRCC).

METHODS AND MATERIALS: Patients with mRCC and no prior systemic therapy were enrolled at academic and community sites. End of study data collection was in March 2019. Outcomes included overall survival (OS). A survey of treating physicians assessed reasons for treatment initiations and discontinuations.

RESULTS: Overall, 376 patients with mRCC initiated first-line therapy; 171 (45.5%) received pazopanib, 75 (19.9%) sunitinib, and 74 (19.7%) participated in a clinical trial. Median (95% confidence interval) OS was longest …

Evaluating Older Adults With Cognitive Dysfunction: A Qualitative Study With Emergency Clinicians, Anita N Chary, Noelle Castilla-Ojo, Christopher Joshi, Ilianna Santangelo, Christopher R Carpenter, Kei Ouchi, Aanand D Naik, Shan W Liu, Maura Kennedy

Faculty, Staff and Students Publications

BACKGROUND: Evaluating older adults with cognitive dysfunction in emergency departments (EDs) requires obtaining collateral information from sources other than the patient. Understanding the challenges emergency clinicians face in obtaining collateral information can inform development of interventions to improve geriatric emergency care and, more specifically, detection of ED delirium. The objective was to understand emergency clinicians' experiences obtaining collateral information on older adults with cognitive dysfunction, both before and during the COVID-19 pandemic.

METHODS: From February to May 2021, we conducted semi-structured interviews with a purposive sample of 22 emergency physicians and advanced practice providers from two urban academic hospitals and …