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Alteration Of Iron Responsive Gene Expression In Arabidopsis Glutaredoxin S17 Loss Of Function Plants With Or Without Iron Stress, Ninghui Cheng, Han Yu, Xiaolan Rao, Sunghun Park, Erin L Connolly, Kendal D Hirschi, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Iron (Fe) is a mineral nutrient and a metal cofactor essential for plants. Iron limitation can have detrimental effects on plant growth and development, while excess iron inside plant cells leads to oxidative damage. As a result, plants have evolved complex regulatory networks to respond to fluctuations in cellular iron concentrations. The mechanisms that regulate these responses however, are not fully understood. Heterologous expression of an Arabidopsis thaliana monothiol glutaredoxin S17 (GRXS17) suppresses the over-accumulation of iron in the Saccharomyces cerevisiae Grx3/Grx4 mutant and disruption of GRXS17 causes plant sensitivity to exogenous oxidants and iron deficiency stress. GRXS17 may act …

Hericium Erinaceus: Erinacine A, Ventura Villanueva

Agricultural Education and Communication

Hericium erinaceus (Lion's Mane)

Erinacines - component found in Lion's Mane

A variety of mushroom that has been grabbing the attention of different pharmaceutical companies is the Hericium Erinaceus commonly known as Lion’s Mane. Lion’s Mane also known as, “Sheep’s head, Bear’s head, Bearded tooth carpophore, and Yamabushitmnnake” (Lion’s Mane (Hericium erinaceus)). Lion’s Mane in nature is found growing off the dry bark of trees (Kuo, 2016). Nowadays there are many products in the market that sell Lion’s Mane mushroom powder as a superfood. Lion’s Mane mushroom is known to have the component erinacines. Erinacines as of …

Reduced Expression Of The Pp2a Methylesterase, Pme-1, Or The Pp2a Methyltransferase, Lcmt-1, Alters Sensitivity To Beta-Amyloid-Induced Cognitive And Electrophysiological Impairments In Mice, Agnieszka Staniszewski, Hong Zhang, Kesava Asam, Rose Pitstick, Michael P. Kavanaugh, Ottavio Arancio, Russell E. Nicholls

Biomedical and Pharmaceutical Sciences Faculty Publications

Beta-amyloid (Ab) is thought to play a critical role in Alzheimer’s disease (AD), and application of soluble oligomeric forms of Ab produces AD-like impairments in cognition and synaptic plasticity in experimental systems. We found previously that transgenic overexpression of the PP2A methylesterase, PME-1, or the PP2A methyltransferase, LCMT-1, altered the sensitivity of mice to Ab-induced impairments, suggesting that PME-1 inhibition may be an effective approach for preventing or treating these impairments. To explore this possibility, we examined the behavioral and electrophysiological effects of acutely applied synthetic Ab oligomers in male and female mice heterozygous for either a PME-1 KO or …

Diffusion Dispersion Imaging: Mapping Oscillating Gradient Spin-Echo Frequency Dependence In The Human Brain., Aidin Arbabi, Jason Kai, Ali R Khan, Corey A Baron

Brain and Mind Institute Researchers' Publications

PURPOSE: Oscillating gradient spin-echo (OGSE) diffusion MRI provides information about the microstructure of biological tissues by means of the frequency dependence of the apparent diffusion coefficient (ADC). ADC dependence on OGSE frequency has been explored in numerous rodent studies, but applications in the human brain have been limited and have suffered from low contrast between different frequencies, long scan times, and a limited exploration of the nature of the ADC dependence on frequency.

THEORY AND METHODS: Multiple frequency OGSE acquisitions were acquired in healthy subjects at 7T to explore the power-law frequency dependence of ADC, the "diffusion dispersion." Furthermore, a …

Mechanisms Of Bak Activation In The Initiation Of Mitochondrial Apoptosis, Geetika Singh

Theses and Dissertations (ETD)

Mitochondrial apoptosis is crucial for normal mammalian development and adult homeostasis being regulated by B-Cell Lymphoma-2 (BCL-2) proteins. Deregulation of BCL-2 proteins form the basis for myriad of human pathologies including cancer and autoimmune diseases. Therefore, BCL-2 proteins are considered key therapeutic targets. BCL-2 homologous antagonist/killer (BAK) is an effector of outer mitochondrial membrane (OMM) pemeabilization or mitochondrial poration. Despite progress in understanding BAK-mediated mitochondrial poration, the underlying multi-step mechanism is not clearly defined. Here, we provide mechanistic details on the early steps in this process related to BAK activation, including transient direct activation and autoactivation. We demonstrate for the …

Evaluation Of Early Outcomes Of Modified Bentall Procedure As A Treatment Of Ascending Aortic Diseases, Ahmed S. Ali

Journal of Medicine in Scientific Research

Back ground Ascending aortic diseases are life-threatening conditions that have an increasing incidence. The modified Bentall procedure has become the technique of choice used to treat such diseases. Objectives This study evaluates early outcomes of patients who underwent modified Bentall procedure as a treatment of ascending aortic diseases. Patients and methods A total of 75 patients who underwent modified Bentall operation for ascending aortic diseases at the National Heart Institute during a 3-years period (July 2015 to August 2018) were studied prospectively. The included patients were divided according to the type of aortic disease into two groups: group A included …

Predictors Of Mortality In Valvular Infective Endocarditis: A Single-Center Study, Ahmed S. Ali

Journal of Medicine in Scientific Research

Background Valvular infective endocarditis (IE) may occur in association with either native or prosthetic valves, with great risk of mortality and morbidity. Surgical management is an essential part of the therapeutic process in these patients. Objectives This study aims at evaluation of early outcomes of surgically treated patients with native or prosthetic IE together with determining predictors of mortality. Patients and methods Outcomes of 60 patients who underwent surgery for native or prosthetic valve endocarditis at National Heart Institute during a 3-year period (April 2016 to March 2019) were studied prospectively. Preoperative, intraoperative, and postoperative data were tested as possible …

Fecal Lactoferrin As A Parameter In Determining Invasive Causes Of Acute Diarrhea, Abeer E. S. Hamed, Gehan F. Oreby, Mohamed F. Alsoda, Sahar H. Quashwa

Journal of Medicine in Scientific Research

Introduction Diarrhea may be acute, which subsides by 7–14 days and is related to infections (bacterial or viral) or reaction to medications, or chronic, which lasts more than 2 weeks and is mainly caused by inflammatory bowel disease, functional bowel disorder, food allergies, or parasitic infestations. The infective etiologies may be noninvasive or invasive pathogens that have the capacity to invade intestinal mucosa and stimulate local inflammatory response [by activated neutrophils that secrete lactoferrin (LF)] and sometimes cause ulceration, hemorrhage, and systemic inflammatory response. Stool culture is the standard method for the diagnosis of invasive diarrhea; however, it is laborious …

Interleukin 33 In Premenopausal Women With Rheumatoid Arthritis: Is It Related To Generalized Bone Loss?, Eman R. Amer, Hala A. E. Tabl, Sahar H. Quashwa, Taghreed F. M. Mostafa

Journal of Medicine in Scientific Research

Aim The aim was to study the role of interleukin (IL)-33 in rheumatoid arthritis (RA)-induced generalized bone loss in premenopausal women and its relation to general disease activity and various laboratory markers. Patients and methods A total of 60 premenopausal women with RA were enrolled in this work as a study group and 30 age-matched healthy women as a control group. The participants were subjected to full clinical, radiological, and laboratory assessments. The following were assessed in patients and controls by enzyme-linked immunosorbent assay technique: serum level of IL-33, 25-hydroxyvitamin D3 [25(OH) D3], and bone turnover markers, osteocalcin and C-terminal …

Renal And Cardiovascular Outcomes Associated With Cannabis Use In Veterans With Advanced Chronic Kidney Disease Transitioning To Dialysis, Praveen Kumar Potukuchi

Theses and Dissertations (ETD)

Background: Legalization of cannabis and its constituents may lead to increased exposure of a higher number of consumers to cannabis use, including those with chronic kidney disease (CKD). We expect increase in cannabis use, especially, in patients with compromised kidney function. However, there is sparse literature on the effects of cannabis use on cardiorenal and mortality outcomes among patients with advanced CKD. Objectives: The main goal of the current study was to examine the effect of cannabis use on renal and cerebrovascular outcomes as well as mortality in patients with advanced CKD. Using a nationwide cohort of US veterans with …

Acute Maltodextrin Supplementation During Resistance Exercise, Dylan T Wilburn, Steven B Machek, Thomas D Cardaci, Paul S Hwang, Darryn S Willoughby

Faculty, Staff and Students Publications

Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with …

Ipledge Must Abstain From Abstinence, Kami Lowery, Theodore Rosen, Janet Malek

Faculty, Staff and Students Publications

Isotretinoin has unmatched efficacy in the treatment of acne. However, because isotretinoin is a teratogen that can cause profound birth defects, the iPLEDGE program regulates the drug's distribution in the United States. To minimize fetal exposure to isotretinoin, the program requires that female patients capable of becoming pregnant use two forms of contraception or commit to abstinence while using this therapy. This manuscript argues that iPLEDGE should be revised to remove abstinence as an acceptable contraceptive option in the face of evidence that disputes its efficacy. All patients, regardless of reported sexual activity, should be required to use data-proven contraception. …

Selective Targeting Of Cyp3a5 Through Chemical And Genetic Approaches, William C. Wright

Theses and Dissertations (ETD)

Cytochrome P450 enzymes function to catalyze a wide range of reactions important for various biological processes. In humans, the CYP3A subfamily is particularly critical for drug response. Within this family are CYP3A4 and CYP3A5, which collectively metabolize greater than half of all currently prescribed drugs. These promiscuous enzymes can bind a broad and structurally diverse array of compounds, in turn leading to an increased risk of their modulation via small molecules. In the case of CYP3A5, which is over-expressed in some cancers, this leads to chemoresistance. Such aberrant expression and corresponding drug resistance merit a need to selectively target CYP3A5. …

Understanding Human Astrovirus From Pathogenesis To Treatment, Virginia Hargest

Theses and Dissertations (ETD)

While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. …

Scope Of Attention Variation As A Function Of Anxiety And Depression, Kathleen Anne O'Donnell

Electronic Theses, Projects, and Dissertations

As a social species, correct emotional perception is so vital, that the human brain has evolved a mechanism to control attentional choices by exerting a narrowed field of perception during danger, called the scope of attention (SoA). The SoA determines what information will be focused on or ignored by blocking the perception of non-relevant items and increasing selective focus on danger; even if danger is merely a sad-face. The emotional items blocked from perception cannot be remembered because they were never perceived. But, attention-control to emotional stimuli also varies with mood, as seen in mood-disorders. A mood-disorder’s effect upon the …

Pooled Crispr Screens With Imaging On Microraft Arrays Reveals Stress Granule-Regulatory Factors, Emily C Wheeler, Anthony Q Vu, Jaclyn M Einstein, Matthew Disalvo, Noorsher Ahmed, Eric L Van Nostrand, Alexander A Shishkin, Wenhao Jin, Nancy L Allbritton, Gene W Yeo

Faculty, Staff and Students Publications

Genetic screens using pooled CRISPR-based approaches are scalable and inexpensive, but restricted to standard readouts, including survival, proliferation and sortable markers. However, many biologically relevant cell states involve cellular and subcellular changes that are only accessible by microscopic visualization, and are currently impossible to screen with pooled methods. Here we combine pooled CRISPR-Cas9 screening with microraft array technology and high-content imaging to screen image-based phenotypes (CRaft-ID; CRISPR-based microRaft followed by guide RNA identification). By isolating microrafts that contain genetic clones harboring individual guide RNAs (gRNA), we identify RNA-binding proteins (RBPs) that influence the formation of stress granules, the punctate protein-RNA …

Rapid And Efficient Synthetic Assembly Of Multiplex Luciferase Reporter Plasmids For The Simultaneous Monitoring Of Up To Six Cellular Signaling Pathways, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Koen J T Venken

Faculty, Staff and Students Publications

High-throughput cell-based screening assays are valuable tools in the discovery of chemical probes and therapeutic agents. Such assays are designed to examine the effects of small compounds on targets, pathways, or phenotypes participating in normal and disease processes. While most cell-based assays measure single quantities, multiplexed assays seek to address these limitations by obtaining multiple simultaneous measurements. The signals from such measurements should be independently detectable and cover large dynamic ranges. Luciferases are good candidates for generation of such signals. They are genetically encoded, versatile, and cost-effective, and their output signals can be sensitively detected. We recently developed a multiplex …

Simultaneous Examination Of Cellular Pathways Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Multiplex experimentation that can assay multiple cellular signaling pathways in the same cells requires orthogonal genetically encoded reporters that report over large dynamic ranges. Luciferases are cost-effective, versatile candidates whose output signals can be sensitively detected in a multiplex fashion. Commonly used dual luciferase reporter assays detect one luciferase that is coupled to a single cellular pathway, and a second that is coupled to a control pathway for normalization purposes. We expanded this approach to multiplex hextuple luciferase assaying that can report on five cellular signaling pathways and one control, each of which is encoded by a unique luciferase. Light …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Clinical And Basic Research Investigations Into The Long‐Term Effects Of Prenatal Opioid Exposure On Brain Development, Taylor Boggess, W. Chris Risher

Biomedical Sciences

Coincident with the opioid epidemic in the United States has been a dramatic increase in the number of children born with neonatal abstinence syndrome (NAS), a form of withdrawal resulting from opioid exposure during pregnancy. Many research efforts on NAS have focused on short‐term care, including acute symptom treatment and weaning of the infants off their drug dependency prior to authorizing their release. However, investigations into the long‐term effects of prenatal opioid exposure (POE) on brain development, from the cellular to the behavioral level, have not been as frequent. Given the importance of the perinatal period for human brain development, …

The Trait Repertoire Enabling Cyanobacteria To Bloom Assessed Through Comparative Genomic Complexity And Metatranscriptomics, Huansheng Cao, Yohei Shimura, Morgan M. Steffen, Zhou Yang, Jingrang Lu, Allen Joel, Landon Jenkins, Masanobu Kawachi, Yanbin Yin, Ferran Garcia-Pichel

Food for Health: Publications

Water bloom development due to eutrophication constitutes a case of niche specialization among planktonic cyanobacteria, but the genomic repertoire allowing bloom formation in only some species has not been fully characterized. We posited that the habitat relevance of a trait begets its underlying genomic complexity, so that traits within the repertoire would be differentially more complex in species successfully thriving in that habitat than in close species that cannot. To test this for the case of bloom-forming cyanobacteria, we curated 17 potentially relevant query metabolic pathways and five core pathways selected according to existing ecophysiological literature. The available 113 genomes …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Regulation Of Myofilament Contractile Function In Human Donor And Failing Hearts, Kerry S. Mcdonald, Laurin M. Hanft, Joel C. Robinett, Maya Guglin, Kenneth S. Campbell

Internal Medicine Faculty Publications

Heart failure (HF) often includes changes in myocardial contractile function. This study addressed the myofibrillar basis for contractile dysfunction in failing human myocardium. Regulation of contractile properties was measured in cardiac myocyte preparations isolated from frozen, left ventricular mid-wall biopsies of donor (n = 7) and failing human hearts (n = 8). Permeabilized cardiac myocyte preparations were attached between a force transducer and a position motor, and both the Ca²⁺ dependence and sarcomere length (SL) dependence of force, rate of force, loaded shortening, and power output were measured at 15 ± 1°C. The myocyte preparation size was …

Determining The Genetic Control Of Neural Tube Malformation Through Genetic Interactions With Idgf3, Elli N. Fox

Honors Projects

Genetic mutations disrupting human neural tube formation can lead to birth defects such as spina bifida and anencephaly. Defects can result in lack of neural tube closure in either the caudal (spina bifida) or cranial (anencephaly) regions. Little is known about the genes that cause these malformations. Researchers have been using the model organism Drosophila melanogaster in an attempt to determine genes responsible for neural tube malformations. Recently, an ortholog of human chitin-like protein, imaginal disc growth factor 3 (Idgf3), has been identified as important in the proper formation of Drosophila egg dorsal appendages. However, the molecular mechanism responsible for …

Ire1Α And Igf Signaling Predict Resistance To An Endoplasmic Reticulum Stress-Inducing Drug In Glioblastoma Cells., Jeffrey J Rodvold, Su Xian, Julia Nussbacher, Brian Tsui, T Cameron Waller, Stephen C Searles, Alyssa Lew, Pengfei Jiang, Ivan Babic, Natsuko Nomura, Jonathan H Lin, Santosh Kesari, Hannah Carter, Maurizio Zanetti

Articles, Abstracts, and Reports

To date current therapies of glioblastoma multiforme (GBM) are largely ineffective. The induction of apoptosis by an unresolvable unfolded protein response (UPR) represents a potential new therapeutic strategy. Here we tested 12ADT, a sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor, on a panel of unselected patient-derived neurosphere-forming cells and found that GBM cells can be distinguished into "responder" and "non-responder". By RNASeq analysis we found that the non-responder phenotype is significantly linked with the expression of UPR genes, and in particular ERN1 (IRE1) and ATF4. We also identified two additional genes selectively overexpressed among non-responders, IGFBP3 and IGFBP5. CRISPR-mediated deletion of …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Intranasal Administration Of Pcrv Conjugated To A Tobacco Mosaic Virus Delivery Platform Protects Against P. Aeruginosa In A Murine Model Of Acute Pneumonia, Eman Barahim

NYMC Student Theses and Dissertations

Pseudomonas aeruginosa is a facultative anaerobic bacterium that is the most common type of Gram-negative bacteria causing nosocomial pneumonia in the United States. P. aeruginosa is an opportunistic pathogen ubiquitously found in the atmosphere that can colonize both plants and animals. It is known to cause a wide range of severe, persistent, and fatal infections ranging from acute and chronic pneumonia, skin and soft tissue infections to urinary tract infections, especially in immune-compromised individuals. Patients with cystic fibrosis are at high risk because of deficiencies in mucosal immunity and phagocytosis. Ultimately, Pseudomonas infections can be lethal. There is a very …

The Apicomplexan-Specific Fikk Kinase Is Crucial For Cyst Formation In Toxoplasma Gondii, Corey Gaylets

NYMC Student Theses and Dissertations

Toxoplasma gondii is an obligate intracellular pathogen. It is considered the second deadliest foodborne pathogen in the world with up to 1/3 of the human population estimated to be currently infected. The majority of immune competent people may exhibit mild symptoms following T gondii infection. The acute stage of infection is often well controlled by cellular immunity in healthy individuals. However sterilizing immunity does not occur as the tachyzoite stage of the parasite responsible for acute infection differentiates to a slow growing bradyzoite stage contained in tissues cysts that can persist for the life of the host. However, if the …

Cell Surface Regulatory Immune Targets In Anaplastic Thyroid Cancer, Sanjukta Chakraborty

NYMC Student Theses and Dissertations

Thyroid cancer incidence is increasing at an alarming rate almost trebling every decade. 52,070 new cases of thyroid cancer (14,260 in men and 37,810 in women) were diagnosed in 2019 with an estimated death toll of 2170. Although most thyroid tumors are treatable and has good prognosis, anaplastic thyroid cancer (ATC) is extremely aggressive with a grim poor prognosis of 6-9 months post diagnosis. ATC is completely refractory to mainstream therapies. In our study, immunohistochemical analyses of ATC tissues confirmed a T cell inflamed “hot” tumor immune microenvironment (TIME) as evidenced by presence of CD3+ and CD8+ T cells. This …