Medical Specialties Commons^™

Biliverdin Reductase Bridges Focal Adhesion Kinase To Src To Modulate Synaptic Signaling, Chirag Vasavda, Evan R Semenza, Jason Liew, Ruchita Kothari, Ryan S Dhindsa, Shruthi Shanmukha, Anthony Lin, Robert Tokhunts, Cristina Ricco, Adele M Snowman, Lauren Albacarys, Francesco Pastore, Cristian Ripoli, Claudio Grassi, Eugenio Barone, Michael D Kornberg, Xinzhong Dong, Bindu D Paul, Solomon H Snyder

Duncan NRI Faculty and Staff Publications

Synapses connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. Synaptic function and plasticity—the neuronal process of adapting to diverse and variable inputs—depend on the dynamic nature of synaptic molecular components, which is mediated in part by cell adhesion signaling pathways. Here, we found that the enzyme biliverdin reductase (BVR) physically links together key focal adhesion signaling molecules at the synapse. BVR-null (BVR−/−) mice exhibited substantial deficits in learning and memory on neurocognitive tests, and hippocampal slices in which BVR was postsynaptically depleted showed deficits in electrophysiological responses to stimuli. …

Evaluation Of Heat Inactivation Of Human Norovirus In Freshwater Clams Using Human Intestinal Enteroids, Tsuyoshi Hayashi, Yoko Yamaoka, Atsushi Ito, Takashi Kamaishi, Ryuichi Sugiyama, Mary K Estes, Masamichi Muramatsu, Kosuke Murakami

Faculty, Staff and Students Publications

Foodborne disease attributed to the consumption of shellfish contaminated with human norovirus (HuNoV) is one of many global health concerns. Our study aimed to determine the conditions of the heat-inactivation of HuNoV in freshwater clams (Corbicula japonica) using a recently developed HuNoV cultivation system employing stem-cell derived human intestinal enteroids (HIEs). We first measured the internal temperature of the clam tissue in a water bath during boiling at 90 °C and found that approximately 2 min are required for the tissue to reach 90 °C. Next, GII.4 HuNoV was spiked into the center of the clam tissue, followed …

Concerted Type I Interferon Signaling In Microglia And Neural Cells Promotes Memory Impairment Associated With Amyloid Β Plaques, Ethan R Roy, Gabriel Chiu, Sanming Li, Nicholas E Propson, Rupa Kanchi, Baiping Wang, Cristian Coarfa, Hui Zheng, Wei Cao

Faculty, Staff and Students Publications

The principal signals that drive memory and cognitive impairment in Alzheimer's disease (AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon (IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Using a fate-mapping reporter system to track cellular responses to IFN-I, we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits and resulted in reduced microgliosis, inflammation, and neuritic pathology. Microglia-specific Ifnar1 deletion attenuated …

Factors Affecting Emergency Department Mental Health Visits, Logan Daul

Honors Thesis

Research has shown that current quantities of emergency department visits for mental health and substance use are increasing at a startling rate. These increases are acknowledged in quantitative studies and some important information can be gathered from qualitative studies however determining specific causes for these emergent visits are difficult. The purpose of this study is to derive findings from statistical analyses focusing on quantities of emergency department visits for mental health and substance use disorders. Comparisons will be drawn at the state level between the per capita quantity of emergency department visits and poverty rate, climate, psychiatric healthcare infrastructure, urban …

Comparison Of Hemodynamic Responses Between Conventional And Virtual Reality Therapies In Patients With Heart Failure Admitted To An Emergency Room, Angélica Bologna Raposo, Alice Haniuda Moliterno, João Pedro Lucas Neves Silva, Rafael Varago Favri, Ana Paula Coelho Figueira Freire, Francis Lopes Pacagnelli

All Faculty Scholarship for the College of Education and Professional Studies

This study aimed to evaluate and to compare the acute response, due to semi-immersive virtual reality (VR) and conventional therapies (CT), of hemodynamic parameters in hospitalized individuals admitted to an emergency unity for heart failure (HF). This is a viability study with 11 individuals subjected to sessions with and without VR. At CT, stretching, active or active-assisted exercises, and fractional inspiration were performed. In VR therapy (VRT), VR box glasses were used to promote VR relaxation associated with CT. The hemodynamic parameters evaluated were heart rate, systolic and diastolic blood pressure, oxygen saturation, and double product. To analyze them, Student’s …

Racial And Ethnic Differences In Genomic Profiling Of Early Onset Colorectal Cancer, David M Hein, Weiye Deng, Marylena Bleile, Syed Ali Kazmi, Brooke Rhead, Francisco M De La Vega, Amy L Jones, Radhika Kainthla, Wen Jiang, Brandi Cantarel, Nina N Sanford

Faculty, Staff and Student Publications

The incidence and mortality of early onset colorectal cancer (EOCRC) is rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, White Hispanic) using data from the American Association for Cancer Research Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1752 EOCRC patients, non-Hispanic Black patients had higher rates of KRAS mutations (60.9%; P = .001, q = 0.015), and non-Hispanic White and non-Hispanic Black …

Eight Tips For The Implementation Of The First Licenced Peanut Allergy Oral Immunotherapy Into Clinical Practice., Jay M. Portnoy, Christina E. Ciaccio, Janet Beausoleil, George Du Toit, Stanley Fineman, Stephen A. Tilles, June Zhang, Claire Lawrence, Mohamed Yassine, S Shahzad Mustafa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Shared learnings from the early use of novel therapies can aid in their optimization. The recent introduction of peanut oral immunotherapy (peanut OIT; Palforzia [Peanut (Arachis hypogaea) Allergen Powder-dnfp]) for peanut allergy addresses a significant unmet need but also highlights the requirement for consideration of several factors by both prescribers and patients.

OBJECTIVE: To provide guidance for prescribers of licenced peanut OIT to facilitate treatment delivery and improve outcomes.

METHODS: Clinicians with experience of licenced peanut OIT (United States n = 6, United Kingdom n = 1) participated in a series of interviews and group discussions designed to elicit …

Pattern Differentiation And Tuning Shift In Human Sensory Cortex Underlie Long-Term Threat Memory, Yuqi You, Lucas R Novak, Kevin J Clancy, Wen Li

Faculty, Staff and Student Publications

The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system 1, but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit 2-4. Through non-human research, the sensory cortex has emerged as a critical substrate for long-term threat memory 5-9, underpinned by sensory cortical pattern separation/completion 10,11 and tuning shift 12,13. In humans, research has begun to associate the human sensory cortex with long-term threat memory 14,15, but the lack of mechanistic insights obscures a direct linkage. Towards that end, …

Characterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson's Diseasecharacterization Of Retinal Function And Structure In The Mptp Murine Model Of Parkinson’S Disease, Katie K N Tran, Vickie H Y Wong, Jeremiah K H Lim, Ali Shahandeh, Anh Hoang, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

In addition to well characterized motor symptoms, visual disturbances are increasingly recognized as an early manifestation in Parkinson's disease (PD). A better understanding of the mechanisms underlying these changes would facilitate the development of vision tests which can be used as preclinical biomarkers to support the development of novel therapeutics for PD. This study aims to characterize the retinal phenotype of a mouse model of dopaminergic dysfunction and to examine whether these changes are reversible with levodopa treatment. We use a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD to characterize the neurotoxic effects of MPTP on in vivo retinal function (electroretinography, …

Bi-Order Multimodal Integration Of Single-Cell Data, Jinzhuang Dou, Shaoheng Liang, Vakul Mohanty, Qi Miao, Yuefan Huang, Qingnan Liang, Xuesen Cheng, Sangbae Kim, Jongsu Choi, Yumei Li, Li Li, May Daher, Rafet Basar, Katayoun Rezvani, Rui Chen, Ken Chen

Faculty, Staff and Student Publications

Integration of single-cell multiomics profiles generated by different single-cell technologies from the same biological sample is still challenging. Previous approaches based on shared features have only provided approximate solutions. Here, we present a novel mathematical solution named bi-order canonical correlation analysis (bi-CCA), which extends the widely used CCA approach to iteratively align the rows and the columns between data matrices. Bi-CCA is generally applicable to combinations of any two single-cell modalities. Validations using co-assayed ground truth data and application to a CAR-NK study and a fetal muscle atlas demonstrate its capability in generating accurate multimodal co-embeddings and discovering cellular identity.

Central Nervous System Immune Interactome Is A Function Of Cancer Lineage, Tumor Microenvironment, And Stat3 Expression, Hinda Najem, Martina Ott, Cynthia Kassab, Arvind Rao, Ganesh Rao, Anantha Marisetty, Adam M Sonabend, Craig Horbinski, Roel Verhaak, Anand Shankar, Santhoshi N Krishnan, Frederick S Varn, Víctor A Arrieta, Pravesh Gupta, Sherise D Ferguson, Jason T Huse, Gregory N Fuller, James P Long, Daniel E Winkowski, Ben A Freiberg, Charles David James, Leonidas C Platanias, Maciej S Lesniak, Jared K Burks, Amy B Heimberger

Faculty, Staff and Student Publications

BACKGROUND

Immune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.

METHODS

En bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.

RESULTS

Within gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163⁺ macrophages were evident throughout the TME of metastatic …

The Efficacy Of Tailored Text Messages To Improve Medication Adherence And Lifestyle Changes For Patients With Type 2 Diabetes Mellitus, Vanessa B. Silverio

Evidence-Based Practice Project Reports

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by increased amounts of glucose in the blood, and is the seventh leading cause of death in the United States (United Health Foundation [UHF]), 2021). T2DM can be effectively treated with medication and behavioral lifestyle modifications. Even small improvements in glycemic control can reduce the risk for debilitating complications such as heart disease, stroke, kidney disease, sepsis, and retinopathy (Wang et al., 2021, Haider et al., 2019). The purpose of this evidence-based practice (EBP) project was to identify the most effective intervention for improving medication adherence, lifestyle changes, and hemoglobin …

Intensive, Interprofessional Therapy: A Case Approach, Emma C. Schrotenboer

Honors Theses

This research looks at the impacts of intensive, interprofessional therapy for children with disabilities. There is very little literature currently published on this topic, although what is available generally finds that more intense therapy is more beneficial. The child who was studied was a camper at Adam’s Camp therapy camp, a week-long program that involves six hours of therapy each day with therapists from five different fields. Her progress over the week, as well as her retention of skills several weeks later, were determined by pre- and post-camp surveys sent to the mother and the therapists’ notes from during the …

Sex Differences In The Association Between Cardiovascular Diseases And Dementia Subtypes: A Prospective Analysis Of 464,616 Uk Biobank Participants, Caiyun Dong, Chunmiao Zhou, Chunying Fu, Wenting Hao, Akihiko Ozaki, Nipun Shrestha, Salim S. Virani, Shiva Raj Mishra, Dongshan Zhu

Office of the Provost

Background: Whether the association of cardiovascular diseases (CVDs) with dementia differs by sex remains unclear, and the role of socioeconomic, lifestyle, genetic, and medical factors in their association is unknown.
Methods: We used data from the UK Biobank, a population-based cohort study of 502,649 individuals. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between CVD (coronary heart diseases (CHD), stroke, and heart failure) and incident dementia (all-cause dementia, Alzheimer's Disease (AD), and vascular dementia (VD)). The moderator roles of socioeconomic (education, income), …

Reno-Protective And Immune Effects Of Growth Differentiation Factor 15 In Obesity-Related Kidney Disease, Jessie T. Sullivan

Honors Thesis

According to the World Health Organization, worldwide obesity has tripled since 1975 and is still on the rise, putting people at a higher risk of some cardiovascular diseases and kidney disease. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied recently for its role in multiple biological processes and diseases. The member of the transforming growth factor beta (TGF-b) family has been investigated as a therapeutic agent and biomarker for obesity and associated cardiovascular diseases, stroke, diabetes, osteoarthritis, cancer, and kidney disease. Studies have shown the anti-inflammation, anti-obesity, and anti-diabetic effects of GDF15, but few have …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Dexmedetomidine To Reduce Ponv, Amanda Johnson Srna, Joshua Lawrence Srna, Staci Martinez Srna, Taylor Mayberry Srna, Dwayne Accardo Dnp, Crna, Aprn

Doctor of Nursing Practice Projects

Purpose/Background Postoperative nausea and vomiting (PONV) contribute to patient dissatisfaction, discomfort, adverse outcomes, and increased healthcare costs. Despite current protocols that aim to reduce PONV by prevention/antiemetic administration, PONV continues to be a common manifestation in many postoperative patients (Elvir-Lazo et al., 2020). This scoping review aimed to analyze available research on the efficacy of dexmedetomidine to reduce perioperative opioid requirements and PONV.

Methods Synthesis of this scoping review began with a systematic approach to search databases and identify eligibility criteria articles. Of the 21 articles that met criteria, a synthesis table was formed to visualize the qualitative (smoking status, …

Feasibility And Efficacy Of Bisphosphonate Use For The Prevention Of Bone And Muscle Loss, Laura E. Flores

Theses & Dissertations

Loss of bone and muscle mass often occurs in tandem, increasing the risk of fragility fractures. Whereas many drugs are approved for the treatment of bone loss, there are few treatments available for the concomitant loss of bone and muscle. Identification of a treatment to mitigate pathologic bone and muscle atrophy has the potential to impact countless populations and influence approaches for healthy aging. Bisphosphonates have emerged as a potential treatment for both bone and muscle loss in cellular, murine, and observational human studies. Our findings of modest weight maintenance in postmenopausal women treated with 12-months of risedronate, relative to …

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du

Theses & Dissertations

The prevalence of nonalcoholic fatty liver disease (NAFLD) among Chinese young adults (CYA) aged 18-25 years ranges from 4.7% to 15.1% and has kept increasing in recent years. Previous studies reported limited awareness and knowledge of NALFD among middle-aged and older Chinese populations, however, they have not investigated awareness in CYA, for which there is no well-validated questionnaire. There is currently no efficacious educational intervention on NAFLD for CYA.

The objectives were 1) to develop and validate a questionnaire which can be used to assess the awareness and knowledge of NAFLD among CYA; 2) to assess the awareness and knowledge …

Variation In Thiopurine Metabolism In Hispanic Children, Kayeleigh Higgerson Do

Research Days

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Overall survival rate is > 90% in the United States. However, ethnic and racial disparities remain. Hispanic patients have an inferior overall survival compared to non-Hispanics. The reasons for these differences remain unclear. Mercaptopurine (6MP) is a crucial drug in ALL treatment. Variations in the TMPT and NUDT15 genes lead to altered 6MP metabolism and accumulation of toxic metabolites (6TGN or 6MMPN). Each metabolite is associated with specific dose-limiting toxicities. The accumulation of 6TGN causes myelosuppression, and increased 6MMPN causes GI toxicity. While variants in these genes have been identified …

Potassium Status In Pediatric Chronic Kidney Disease, Katherine L. Kurzinski

Research Days

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Background: Potassium trends are well described in adult chronic kidney disease (CKD) and hyperkalemia is known to be associated with increased disease progression, morbidity, and mortality. Large scale studies assessing potassium trends and the prevalence of hyperkalemia in pediatric CKD have not been performed.

Objectives/Goal: We aimed to characterize median serum potassium levels and the prevalence of hyperkalemia for each CKD stage using the CKiD cohort. The relationship of serum potassium and hyperkalemia with patient demographics, CKD etiology (glomerular or non-glomerular), presence of acidosis, and degree of proteinuria was also evaluated.

Methods/Design: Median serum potassium …

Association Of Rare Variants In Kidney Developmental Genes With Hypertension And Ckd: A Uk Biobank Study, Benjamin L. Spector

Research Days

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Background: Prior studies show chronic kidney disease (CKD) is heritable but only a few common variants have been associated with CKD and kidney dysfunction. Much of CKD heritability remains unknown and limited studies have explored the role of rare genetic variants in this missing heritability.

Objectives/Goal: Identify rare genetic variants in renal developmental genes associated with hypertension and CKD.

Methods/Design: We examined the association between rare variants in 58 candidate genes from five renal developmental compartments and presence of CKD and elevated blood pressure (BP) in 49,989 individuals using whole exome sequencing and phenotypic data …

Type 2 Diabetes Mellitus During The Covid-19 Pandemic, Erica Wee

Research Days

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Background The prevalence of type 2 diabetes mellitus (T2D) in youth has increased significantly over the past decades secondary to the increased prevalence of obesity. Epidemiologic data estimates that the incidence of youth-onset T2D increased 5% per year between 2002 and 2012. Recent studies have shown that childhood obesity increased with the COVID-19 pandemic. However, if this resulted in increased incidence of T2D has not been well-reported.

Objectives: This study seeks to evaluate new-onset T2D in youth during the COVID-19 pandemic (March 2020 to February 2021). We examined the frequency of new-onset T2D and proportion …

Treatment Of Recurrent Wilms Tumor With Irinotecan/Temozolomide, Meagan Vacek

Research Days

Background: Despite improvement in relapse free survival (RFS) in recurrent Wilms tumor, the 4- year RFS rate for patients treated with vincristine/dactinomycin/doxorubicin is approximately 40%. Ifosfamide, carboplatin and etoposide are commonly used in relapsed solid tumors but have significant toxicities and require hospital admission for administration. Our patient focused on quality of life, and this led to exploration of other treatment options.

Objectives/Goal: Describe a case of multiply relapsed Wilms tumor with management on oral chemotherapy for improved quality of life and remission for almost 1 year.

Methods/Design: Case Report

Results: The patient is an 11-year-old female diagnosed with Wilms …

Increasing Incentive Spirometry Use In Patients With Sickle Cell Disease Admitted To Children’S Mercy Hospital, Thomas Cochran, Alexandra Prosser

Research Days

Background: Acute chest syndrome is one of the leading causes of morbidity and mortality in patients with sickle cell disease. The National Heart, Lung, and Blood Institute (NHLBI) provides specific recommendations for providing ten breaths of incentive spirometry (IS) every two hours while awake for patients with sickle cell disease to help prevent development of acute chest syndrome.

Problem Statement: We reviewed provision of incentive spirometry at Children’s Mercy between 08/01/2021 and 11/01/2021. Data was collected and the target population was identified via a report generated from the electronic medical records with specific criteria. Of those patients admitted with sickle …

Wilms Tumor Presenting With Spontaneous Necrosis And Clostridium Perfringens Co-Infection, Ronald Palmen, Abbey Elsbernd, Kristin Palmen

Research Days

Background: Wilm’s Tumor (WT) is the most common renal malignancy of childhood. The initial presentation of WT may mimic infection or other malignancies with nonspecific symptoms including fever, abdominal/flank pain, or hematuria. This poses a diagnostic challenge for providers, particularly when both infection and malignancy are observed. We describe a case of WT with spontaneous necrosis initially obscured by overlying Clostridium perfringens infection, making diagnosis of the cancer difficult.

Case Description: A previously healthy 5-year-old girl presented to the emergency department with a two-day history of left flank pain and fevers. In the emergency department, she was tachycardic (130 bpm), …

Acute Complications In Pediatric Patients With Diabetes Admitted With Isolated Diabetic Ketoacidosis, Isolated Hyperglycemic Hyperosmolar State, And Mixed Hyperosmolar Diabetic Ketoacidosis, Erica Zarse

Research Days

Background: Diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), and mixed DKA and HHS (hyperosmolar DKA) are hyperglycemic emergencies for which children with diabetes mellitus (DM) are admitted to the hospital. To date, there is little evidence to guide the management of pediatric diabetic patients with hyperosmolarity.

Objectives: The objective of this study is to compare the in-hospital complications at our institution in patients who have isolated DKA to those with a component of hyperosmolarity.

Methods: We reviewed medical records of patients from 01/2019 through 12/2020 admitted with DKA (serum bicarbonate ≤16 mEq/L) and/or HHS (blood glucose ≥600 mg/dL and osmolality …

Case Series: Bone Marrow Failure In Teen Siblings With Unique Rps19 Variant, Alexandra Prosser

Research Days

Background: Upon diagnosis of aplastic anemia, inherited bone marrow failure syndromes and acquired etiologies must be considered. Investigating causality is particularly important when multiple family members are affected. It is also essential to identify novel causative genetic variants of bone marrow failure to direct treatment in these patients.

Objectives: To describe the diagnosis and management of siblings who presented two weeks apart with severe pancytopenia and were diagnosed with severe aplastic anemia.

Methods: The first patient is a 13-year-old non-binary female who presented with severe pancytopenia on routine labs. Bone marrow biopsy revealed marked hypocellularity (0-10%) with hypoplasia. The second …

Memory T Cell Populations In Human Leukemia, Sara Mcelroy

Research Days

Background: Incorporating the immune system into cancer management is an area of robust research. Treatment modalities aimed at activating cytotoxic T cells against malignancies include immune checkpoint inhibitors, bispecific T-cell engagers, and chimeric antigen receptor (CAR) tumor-specific T cells. Most anti-cancer T cell research is narrowly focused, but knowledge about the nature of diverse sub-populations of T cells in cancer, particularly memory T cells, is vital prior to potential incorporation into therapies. T memory stem cells (Tscm) are of interest due to their longevity and powerful abilities of self-renewal and creating the full spectrum of memory CD8+ T cells, including …