Medical Specialties Commons^™

Diagnostic Accuracy Of Artificial Intelligence For Detecting Gastrointestinal Luminal Pathologies: A Systematic Review And Meta-Analysis, Om Parkash, Asra Tus Saleha Siddiqui, Uswa Jiwani, Fahad Rind, Zahra Ali Padhani, Arjumand Rizvi, Zahra Hoodbhoy, Jai K. Das

Section of Gastroenterology

Background: Artificial Intelligence (AI) holds considerable promise for diagnostics in the field of gastroenterology. This systematic review and meta-analysis aims to assess the diagnostic accuracy of AI models compared with the gold standard of experts and histopathology for the diagnosis of various gastrointestinal (GI) luminal pathologies including polyps, neoplasms, and inflammatory bowel disease.
Methods: We searched PubMed, CINAHL, Wiley Cochrane Library, and Web of Science electronic databases to identify studies assessing the diagnostic performance of AI models for GI luminal pathologies. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. …

Mitochondrial Protective Effects Caused By The Administration Of Mefenamic Acid In Sepsis, Diogo Dominguini, Monique Michels, Leticia B Wessler, Emilio L Streck, Tatiana Barichello, Felipe Dal-Pizzol

Faculty, Staff and Student Publications

The pathophysiology of sepsis may involve the activation of the NOD-type receptor containing the pyrin-3 domain (NLPR-3), mitochondrial and oxidative damages. One of the primary essential oxidation products is 8-oxoguanine (8-oxoG), and its accumulation in mitochondrial DNA (mtDNA) induces cell dysfunction and death, leading to the hypothesis that mtDNA integrity is crucial for maintaining neuronal function during sepsis. In sepsis, the modulation of NLRP-3 activation is critical, and mefenamic acid (MFA) is a potent drug that can reduce inflammasome activity, attenuating the acute cerebral inflammatory process. Thus, this study aimed to evaluate the administration of MFA and its implications for …

Locus Of Control In Athletic Training, Brittany James, Lindsey E. Eberman, Kenneth E. Games, Matthew J. Rivera

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Purpose: Locus of control (LOC) is the level of control an individual feels they have over the outcomes in their life; work locus of control (WLOC) is the control someone feels over their work. Both LOC and WLOC can be internally or externally affected and influence athletic trainers’ ability to change their clinical circumstances. The purpose of this study was to explore athletic trainers’ LOC and WLOC.

Method: Cross-sectional web-based survey. Two validated surveys were used to measure locus of control and work locus of control in athletic trainers along with the collection of 8 demographic variables. Results: Of …

Creatively Capturing Structure And Energy: Zero Balancing's Essential Elements (Article & Video), Lisa Bardarson

Journal of Transformative Touch

Through the creative use of coloring, I am devising a way to document Zero Balancing’s two foundational elements, structure and energy and the changes that occur following a ZB session. I believe this experiential activity will be a creative fulcrum, helping the client connect more effectively with the deepest part of themselves thereby experiencing greater ease and freedom from their issues. As the activity of coloring is a “right brain”/ creative endeavor, I believe it can serve to enhance a client’s expanded state of consciousness, one of the hallmarks of a Zero Balancing session, as well as improve their overall …

Deep Learning Algorithm Reveals Probabilities Of Stage-Specific Time To Conversion In Individuals With Neurodegenerative Disease Late, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng

Sanders-Brown Center on Aging Faculty Publications

Introduction: Limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) is a recently defined neurodegenerative disease. Currently, there is no effective way to make a prognosis of time to stage-specific future conversions at an individual level.

Methods: After using the Kaplan–Meier estimation and log-rank test to confirm the heterogeneity of LATE progression, we developed a deep learning–based approach to assess the stage-specific probabilities of time to LATE conversions for different subjects.

Results: Our approach could accurately estimate the disease incidence and transition to next stages: the concordance index was at least 82% and the integrated Brier score …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

Metformin Increases Natural Killer Cell Functions In Head And Neck Squamous Cell Carcinoma Through Cxcl1 Inhibition, Mckenzie Crist, Benyamin Yaniv, Sarah Palackdharry, Maria A. Lehn, Mario Medvedovic, Timothy Stone, Shuchi Gulati, Vidhya Karivedu, Michael Borchers, Bethany Fuhrman, Audrey Crago, Joseph Curry, Ubaldo Martinez-Outschoorn, Vinita Takiar, Trisha M. Wise-Draper

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Metformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in our phase 1 clinical trial (NCT02325401). Metformin is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) and natural killer T cells, including results from two phase I open-label studies in patients with HNSCC treated with metformin (NCT02325401, NCT02083692).

METHODS: Peripheral blood was collected before and after metformin treatment or from newly diagnosed patients with HNSCC. Peripheral immune cell …

Impact Of Moral Injury On Work Performance In Nurses Following The Covid-19 Surges, Annette Callis, Trisha Saul, Ross Bindler

Articles, Abstracts, and Reports

Background

Moral Injury (MI) was defined by Jonathan Shay in 1994 as committing acts that betray one’s moral compass in high-stakes situations, while under the authority of another, that severely affect one’s well-being. MI was measured solely in the military prior to the COVID pandemic.

Aims

1.Explore the relationship between moral injury (MI) and perceived work performance in hospital nurses following the pandemic surges. 2. Determine relationships between MI and select participant demographics and between work performance and select demographics.

Sample

A convenience sample of 191 nurses from seven Southern California Hospitals participated in the study from March to June …

Characterization Of Bcma Expression In Circulating Rare Single Cells Of Patients With Plasma Cell Neoplasms, Libere J Ndacayisaba, Kate E Rappard, Stephanie N Shishido, Sonia M Setayesh, Guilin Tang, Pei Lin, Nicholas Matsumoto, Ching-Ju Hsu, Rafael Nevarez, Carmen Ruiz Velasco, Amin Naghdloo, Eric Yang, Kevin Kelly, James Hicks, Jeremy Mason, Robert Z Orlowski, Elisabet E Manasanch, Peter Kuhn

Faculty, Staff and Student Publications

B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients' blood could enable early disease profiling and therapy response monitoring. Here, we report …

Antibiotic Exposure Does Not Impact Immune Checkpoint Blockade Response In Msi-H/Dmmr Metastatic Colorectal Cancer: A Single-Center Experience, Victoria Serpas Higbie, Jane Rogers, Hyunsoo Hwang, Wei Qiao, Lianchun Xiao, Arvind Dasari, Kerri Mola-Rudd, Van K Morris, Robert A Wolff, Kanwal Raghav, Ryan Huey, Christine Parseghian, Jason Willis, Scott Kopetz, Michael J Overman, Benny Johnson

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has improved outcomes for patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors. However, not all MSI-H/dMMR patients will exhibit the same ICB efficacy. Previous studies suggest that concomitant antibiotic use while receiving ICB may result in poorer outcomes. We aimed to evaluate this association in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC).

MATERIALS AND METHODS: A single-site, retrospective review of 57 patients with MSI-H/dMMR mCRC that received ICB was completed. Data collected included patient demographics, ICB information, and antibiotic use. Antibiotic exposure was considered from 90 days prior to ICB through 6 weeks …

Metabolic Pathways Enriched According To Erg Status Are Associated With Biochemical Recurrence In Hispanic/Latino Patients With Prostate Cancer, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Melody C. Baddoo, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Marcela Nuñez Lemus, Martha Lucía Serrano, Jovanny Zabaleta, Alba L. Combita, María Carolina Sanabria-Salas

School of Medicine Faculty Publications

Background: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed …

Injury To The Posterior Horn Of The Lateral Meniscus From A Misplaced Tibial Tunnel For Anterior Cruciate Ligament Reconstruction: A Case Report, Amar S Vadhera, Jonathan S Lee, Harsh Singh, Safa Gursoy, Kyle N Kunze, Nikhil N Verma, Jorge Chahla

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND Posterior meniscal root avulsions can cause meniscal extrusion, joint space narrowing, and progressive knee arthritis. Iatrogenic posterior meniscal root avulsions after malpositioning of the transtibial tunnels during anterior cruciate ligament (ACL) reconstruction can account for poor long-term outcomes seen in some patients following ACL reconstruction. Therefore, correct transtibial tunnel placement during ACL reconstruction is essential to avoid iatrogenic meniscal damage. CASE REPORT A 32-year-old man presented with 1 year of right knee pain and instability following a non-contact twisting injury sustained while playing soccer. An ACL tear with no meniscal involvement was diagnosed at an outside institution. A double-bundle …

Microrna Analysis In Maternal Blood Of Pregnancies With Preterm Premature Rupture Of Membranes Reveals A Distinct Expression Profile, Michail Spiliopoulos, Andrew Haddad, Huda B Al-Kouatly, Saeed Haleema, Michael J Paidas, Sara N Iqbal, Robert I Glazer

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To determine the expression profile of microRNAs in the peripheral blood of pregnant women with preterm premature rupture of membranes (PPROM) compared to that of healthy pregnant women.

STUDY DESIGN: This was a pilot study with case-control design in pregnant patients enrolled between January 2017 and June 2019. Patients with healthy pregnancies and those affected by PPROM between 20- and 33+6 weeks of gestation were matched by gestational age and selected for inclusion to the study. Patients were excluded for multiple gestation and presence of a major obstetrical complication such as preeclampsia, diabetes, fetal growth restriction and stillbirth. A …

Sexual Dysfunction And Sexual Distress In Lymphoma Patients: A Mixed Methods Pilot Study, Dorothie S. Durosier Mertilus

USF Tampa Graduate Theses and Dissertations

Lymphoma, especially non-Hodgkin lymphoma (NHL), is among the most common categories of cancer in the United States (National Cancer Institute [NCI], 2019). The survival rate for lymphoma has significantly improved over the last few decades due to advances in therapy. However, despite these advances, lymphoma patients experience many negative consequences of cancer treatment, including sexual dysfunction (NCI, 2021b). The purpose of this mixed methods pilot study was to explore the presence and experiences of sexual dysfunction and related sexual distress in both male and female lymphoma patients during cancer treatment. A concurrent triangulated design was used to: 1) evaluate the …

A Comprehensive Review On Nutraceuticals: Therapy Support And Formulation Challenges, Vivek Puri, Manju Nagpal, Inderbir Singh, Manjinder Singh, Gitika Arora Dhingra, Kampanart Huanbutta, Divya Dheer, Ameya Sharma, Tanikan Sangnim

Faculty, Staff and Student Publications

Nutraceuticals are the nourishing components (hybrid of nutrition and pharmaceuticals) that are biologically active and possess capability for maintaining optimal health and benefits. These products play a significant role in human health care and its endurance, most importantly for the future therapeutic development. Nutraceuticals have received recognition due to their nutritional benefits along with therapeutic effects and safety profile. Nutraceuticals are globally growing in the field of services such as health care promotion, disease reduction, etc. Various drug nutraceutical interactions have also been elaborated with various examples in this review. Several patents on nutraceuticals in agricultural applications and in various …

Dll3 As An Emerging Target For The Treatment Of Neuroendocrine Neoplasms, James Yao, Emily Bergsland, Rahul Aggarwal, Ana Aparicio, Himisha Beltran, Judy S Crabtree, Christine L Hann, Toni Ibrahim, Lauren A Byers, Hironobu Sasano, John Umejiego, Marianne Pavel

Faculty, Staff and Student Publications

INTRODUCTION: Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis.

METHODS: This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the …

Evaluation Of Mrna-1273 Vaccine In Children 6 Months To 5 Years Of Age, Evan J Anderson, C Buddy Creech, Vladimir Berthaud, Arin Piramzadian, Kimball A Johnson, Marcus Zervos, Fredric Garner, Carl Griffin, Khozema Palanpurwala, Mark Turner, Jeffrey Gerber, Richard L Bennett, Kashif Ali, Madhavi Ampajwala, Gary Berman, Jennifer Nayak, Carey Chronis, Barbara Rizzardi, William J Muller, Christopher A Smith, George Fuchs, Daniel Hsia, Joanne E Tomassini, Dianne Delucia, Caroline Reuter, Barbara Kuter, Xiaoping Zhao, Weiping Deng, Honghong Zhou, Daniela Ramirez Schrempp, Kelly Hautzinger, Bethany Girard, Karen Slobod, Roderick Mcphee, Rolando Pajon, Anne Aunins, Rituparna Das, Jacqueline M Miller, Sabine Schnyder Ghamloush, Kidcove Study Group

Faculty, Staff and Student Publications

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown.

METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-μg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these …

Epacadostat Plus Pembrolizumab And Chemotherapy For Advanced Solid Tumors: Results From The Phase I/Ii Echo-207/Keynote-723 Study, John D Powderly, Samuel J Klempner, Aung Naing, Johanna Bendell, Ignacio Garrido-Laguna, Daniel V T Catenacci, Matthew H Taylor, James J Lee, Fred Zheng, Feng Zhou, Xiaohua Gong, Hema Gowda, Gregory L Beatty

Faculty, Staff and Student Publications

Background: Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy.

Methods: Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab …

The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahi, Md Amran Gazi, Ali Faisal Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere

Department of Paediatrics and Child Health

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach.
Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and …

Developing A Patient Satisfaction Measure For Imaging-Based Patient Information During Clinical Consultations, Hindrik J.J. Pinkster, Anne M.L. Meesters, Frank F.A. Ijpma, Erik Taal, Joep Kraeima, Peter M. Ten Klooster

Patient Experience Journal

Different types of medical imaging are increasingly being used to explain specific aspects of injuries to patients during consultations. However, there are no validated questionnaires available yet that specifically measure patients’ satisfaction with the use of such images. The objective of this study was to develop and evaluate a patient-centred measure of satisfaction with the use of medical imaging modalities in clinical treatment. A preliminary 22-item version of the Questionnaire for Patient Satisfaction with Imaging (QPSI) was developed based on extant literature and interviews with trauma patients. Final item selection and psychometric evaluations were conducted amongst a sample of 106 …

Patients’ Perceptions And Knowledge Of Source Isolation For Multi-Resistant Organisms In An Australian Metropolitan Hospital: A Bedside Interview With Questionnaire Study, Alison Smith, Gillian Ray-Barruel

Patient Experience Journal

The aim of this study was to explore perceptions and knowledge of source isolation among hospitalised patients colonised or infected with multi-resistant organisms, to identify if information provided and delivery method are helpful and appropriate, and to identify areas for practice improvements. Purposive sampling was conducted. Between November 2019 and January 2020, bedside interviews with structured questionnaires (combining multiple-choice and free-text questions) were conducted with adult in-patients requiring isolation for multi-resistant organisms in a 180-bed metropolitan hospital in Brisbane, Australia. Data analysis included quantifying multiple-choice responses and thematic analysis of free-text responses. Thirty participants completed the interview questionnaire. Lack of …

Going From An Academic Medical Center To A Community Hospital: Patient Experiences With Transfers, Alexander Kazberouk, Nicole Boyd, Sandra Oreper, Michael Chang, James D. Harrison, Priya A. Prasad, Ari Hoffman

Patient Experience Journal

Academic medical centers (AMCs) often operate at or near full capacity, which leads to delays in care while smaller community hospitals may have excess capacity. To address this issue and to match patient needs to care acuity, patients may be transferred from an AMC emergency department for direct admission to a community hospital. We aimed to explore the experiences and perspectives of patients who were transferred. We randomly selected patients transferred between February 2019 and February 2020. We conducted structured thirty-minute interviews containing fixed response and open-ended questions focusing on the transfer rationale and experience, care quality, and patient financial …

Improving The Accuracy Of Interactive Voice Response (Ivr) Technology For Pediatric Experience Scores, Elizabeth Spaargaren Ms, Mph, Cpxp, Abigail Kozak Mba, Cpxp, Cara Herbener Cpxp, Barbara Lawlor Burke Ma, Cpxp

Patient Experience Journal

The increased use of interactive voice response (IVR) in assessing patient and family experience should be paired with evidence-based practices on how to obtain the most accurate information via this survey mode. We added a brief clarification sentence of the survey scale at the start of the IVR call to improve our experience data both qualitatively and quantitatively. Our setting was an urban pediatric hospital. We gathered lived experiences from our patients, families, and providers to understand and design a change to the IVR survey mode that would reduce survey inaccuracies. Outcome measures were assessed by baseline measurement and post-intervention …

The Impact Of Follow-Up Calls After A Pediatric Emergency Department Visit, Joseph R. Mijares Iii, Sephora Morrison

Patient Experience Journal

Pediatric emergency department (ED) visits can be a stressful time for patients and their caregivers. This high stress environment can lead to questions and needed clarifications post-discharge. We implemented a post-discharge callback system to resolve these concerns for a focused subset of patients who historically have provided the most negative comment feedback on ED patient experience surveys. We hypothesized that comment types would shift to more positive than negative and the themes of the comments received would change. We developed a discharge callback process that focused on patients who were triaged as ESI level 4 during their emergency department visit. …

Children’S Experiences Of Hospitalization Over Time: An Evaluation Of Using Poetry And Creative Writing By Children To Assess Their Experiences Of Hospitalization, David Wood

Patient Experience Journal

This article explores children’s experiences of hospital admissions through their poetry and creative writing and assesses the validity of this medium compared to other methods of evaluation. Pediatric patient experiences of hospital and their effects on children have been studied in various ways and there have been stepwise changes throughout the past century, matching the overall changes of medical care from paternalistic to patient centered. 17 poems were analyzed from children aged 6-13 years old (median 10) for recurrent themes whilst admitted to a large tertiary hospital in the north of England. Children frequently wrote about attacks on their senses, …

Living With Brain Cancer: From Researcher To Patient, Stephen P. Chelko, Daniel L. Fay Ph.D.

Patient Experience Journal

As an academic researcher, my work-life revolves around testing the efficaciousness of pharmaceutical drugs on the prevention of cardiac dysfunction, arrhythmias, and sudden cardiac death in animal models of heart disease. I never thought I would go from someone studying a life-threatening disease to a patient living with one in twenty-four hours. Yet, that transformation occurred October 8, 2019. I was just appointed to Assistant Professor at Johns Hopkins University School of Medicine (JHUSOM), yet after sitting for my professional headshot I had a grand mal seizure. I cannot recall this event, but I bit the tip of my tongue …

Hormonal Therapies Up-Regulate Manf And Overcome Female Susceptibility To Immune Checkpoint Inhibitor Myocarditis, Yaohua Zhang, Chengcao Sun, Yajuan Li, Juan Qin, Kaushik Amancherla, Ying Jing, Qingsong Hu, Ke Liang, Zhao Zhang, Youqiong Ye, Lisa A Huang, Tina K Nguyen, Sergey D Egranov, Zilong Zhao, Andrew Wu, Yutao Xi, Jun Yao, Mien-Chie Hung, George A Calin, Jie Cheng, Bora Lim, Lorenz H Lehmann, Joe-Elie Salem, Douglas B Johnson, Michael A Curran, Dihua Yu, Leng Han, Radbod Darabi, Liuqing Yang, Javid J Moslehi, Chunru Lin

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis …

The Single-Cell Immunogenomic Landscape Of B And Plasma Cells In Early-Stage Lung Adenocarcinoma, Dapeng Hao, Guangchun Han, Ansam Sinjab, Lorena Isabel Gomez-Bolanos, Rossana Lazcano, Alejandra Serrano, Sharia D Hernandez, Enyu Dai, Xuanye Cao, Jian Hu, Minghao Dang, Ruiping Wang, Yanshuo Chu, Xingzhi Song, Jianhua Zhang, Edwin R Parra, Jennifer A Wargo, Stephen G Swisher, Tina Cascone, Boris Sepesi, Andrew P Futreal, Mingyao Li, Steven M Dubinett, Junya Fujimoto, Luisa M Solis Soto, Ignacio I Wistuba, Christopher S Stevenson, Avrum Spira, Shabnam Shalapour, Humam Kadara, Linghua Wang

Faculty, Staff and Student Publications

Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they are poorly characterized. We performed paired single-cell RNA and B-cell receptor (BCR) sequencing of 16 early-stage LUADs and 47 matching multiregion normal tissues. By integrative analysis of ∼50,000 TIBs, we define 12 TIB subsets in the LUAD and adjacent normal ecosystems and demonstrate extensive remodeling of TIBs in LUADs. Memory B cells and plasma cells (PC) were highly enriched in tumor tissues with more differentiated states and increased frequencies of somatic hypermutation. Smokers exhibited markedly elevated PCs and PCs with distinct differentiation trajectories. BCR clonotype diversity …

Targeting The Eif2ak1 Signaling Pathway Rescues Red Blood Cell Production In Sf3b1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts, Vera Adema, Feiyang Ma, Rashmi Kanagal-Shamanna, Natthakan Thongon, Guillermo Montalban-Bravo, Hui Yang, Scott A Peslak, Feng Wang, Pamela Acha, Francesc Sole, Pamela Lockyer, Margherita Cassari, Jaroslaw P Maciejewski, Valeria Visconte, Irene Gañán-Gómez, Yuanbin Song, Carlos Bueso-Ramos, Matteo Pellegrini, Tuyet M Tan, Rafael Bejar, Jennifer S Carew, Stephanie Halene, Valeria Santini, Gheath Al-Atrash, Karen Clise-Dwyer, Guillermo Garcia-Manero, Gerd A Blobel, Simona Colla

Faculty, Staff and Student Publications

SF3B1 mutations, which occur in 20% of patients with myelodysplastic syndromes (MDS), are the hallmarks of a specific MDS subtype, MDS with ringed sideroblasts (MDS-RS), which is characterized by the accumulation of erythroid precursors in the bone marrow and primarily affects the elderly population. Here, using single-cell technologies and functional validation studies of primary SF3B1-mutant MDS-RS samples, we show that SF3B1 mutations lead to the activation of the EIF2AK1 pathway in response to heme deficiency and that targeting this pathway rescues aberrant erythroid differentiation and enables the red blood cell maturation of MDS-RS erythroblasts. These data support the development of …

Secreted Fas Decoys Enhance The Antitumor Activity Of Engineered And Bystander T Cells In Fas Ligand-Expressing Solid Tumors, Pradip Bajgain, Alejandro G Torres Chavez, Kishore Balasubramanian, Lindsey Fleckenstein, Premal Lulla, Helen E Heslop, Juan Vera, Ann M Leen

Faculty, Staff and Students Publications

T-cell immunotherapy has demonstrated remarkable clinical outcomes in certain hematologic malignancies. However, efficacy in solid tumors has been suboptimal, partially due to the hostile tumor microenvironment composed of immune-inhibitory molecules. One such suppressive agent abundantly expressed in solid tumors is Fas ligand (FasL), which can trigger apoptosis of Fas-expressing effector cells such as T cells and natural killer (NK) cells. To alleviate this FasL-induced suppression of tumor-specific immune cells in solid tumors, we describe here the development of a Fas decoy that is secreted by engineered cells upon activation and sequesters the ligand, preventing it from engaging with Fas on …