Medical Specialties Commons^™

Development Of A Novel Biomarker Platform For Profiling Key Protein-Protein Interactions To Predict The Efficacy Of Bh3-Mimetic Drugs, Andrew J Kinloch, Faiyaz Rahman, Bahriye Karakas, Muhammad Shahid, Bora Lim, Stephanie J Bouley, James A Walker, Erinna F Lee, Walter D Fairlie, Kevin R Kelly, Michael H Cardone

Faculty, Staff and Student Publications

One of the hallmarks of cancer cells is their failure to respond to the cellular mechanism of apoptosis. The B-cell lymphoma 2 (BCL-2) family of proteins regulate apoptosis. Their ability to do so can be measured using several methods that in turn anticipate the fate of the cancer cell in response to apoptosis-inducing treatment. These assays ultimately identify the readiness of the cancer cell to undergo apoptosis, which is referred to as the mitochondrial priming state. These metrics, however, have been challenging to implement in the clinic.

Anti-Viral Cd8 Central Memory Veto Cells As A New Platform For Car T Cell Therapy, Wei-Hsin Liu, Anat Globerson Levin, Assaf Lask, Galit Horn, Tova Waks, Bar Nathansohn Levi, Irit Milman Krentsis, Einav Shoshan, Xiaohua Su, Maksim Mamonkin, Richard E Champlin, Yair Reisner, Esther Bachar Lustig

Faculty, Staff and Student Publications

Central memory CD8 T cells exhibit marked veto activity enhancing engraftment in several mouse models of T cell-depleted bone marrow (TDBM) allografting. Graft-versus-host disease (GVHD) can be prevented by stimulation of mouse or human memory CD8 T cells against their cognate antigens under cytokine deprivation, in the early phase of culture followed by further expansion with IL21, IL15, and IL7. Thus, human anti-viral CD8 central memory veto T cells generated from CMV and EBV-positive donors are currently evaluated in a clinical trial at MD Anderson Cancer Centre (MDACC). Results in 15 patients indicate a low risk of GVHD. Considering that …

Multicenter Evaluation Of A New Strip-Based Blood Glucose System For Point-Of-Care Testing In Critical And Non-Critical Care Settings, Michael Goodman, Sven Bercker, Nancy Breitenbeck, Cristina Canada-Vilalta, Daisy D Canepa, William A Clarke, Christopher W Farnsworth, Edward O Ganser, Nienke Geerts, Barbara Goldsmith, Gary Headden, Debra Hoppensteadt, Birgit Klapperich, Ryan Matika, Gabrielle Miles, Sagori Mukhopadhyay, James H Nichols, Rebecca M O'Dell, Zubaid Rafique, Andre Schuetzenmeister, Robbert Slingerland, Ann F Stankiewicz, Jonathan R Swanson, Nam K Tran, Alan H B Wu, Brad S Karon

Faculty, Staff and Students Publications

Background: Evaluation of the performance of Cobas® Pulse (Roche Diagnostics GmbH, Mannheim, Germany), a new blood glucose (BG) monitoring system (BGMS; referred to here as BGMSA) intended for point-of-care testing using samples from patients in diverse clinical settings by intended point-of-care test operators.

Methods: Arterial, capillary, venous, or heel stick whole blood (WB) samples from patients in non-critical and critical care settings were collected and analyzed using BGMSA and the Nova StatStrip® BGMS (Nova Biomedical, Waltham, MA; referred to here as BGMSB), and a hexokinase comparator (Cobas 6000 Analyzer Series; Roche Diagnostics GmbH). The blood glucose measurement accuracy was assessed …

The Tweak/Fn14 Signaling Mediates Skeletal Muscle Wasting During Cancer Cachexia, Meiricris Tomaz Da Silva, Anirban Roy, Anh Tuan Vuong, Aniket S Joshi, Cristeena Josphien, Meghana V Trivedi, Sajedah M Hindi, Vihang A Narkar, Ashok Kumar

Faculty, Staff and Student Publications

Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting. The TWEAK-Fn14 system regulates muscle mass in diverse conditions. However, its role in the regulation of muscle mass during cancer cachexia remains less understood. Here, we demonstrate that the levels of Fn14 are induced in skeletal muscle of multiple mouse models of cancer cachexia. Muscle-specific deletion of Fn14 reduces myofiber atrophy in mouse models of pancreatic and lung cancer cachexia. Silencing of Fn14 in KPC pancreatic cancer cells prior to their implantation in mice attenuates tumor growth without affecting myofiber size. Muscle-specific deletion of Fn14 reduces the gene …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Secreted Phosphoprotein 1 In Lung Diseases, Hongli Liu, Cristian Coarfa, Arzoo N Charania, Jennifer L Larson-Casey, Ivan O Rosas, Chao He

Faculty, Staff and Students Publications

Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN) or early T lymphocyte activation protein 1 (ETA-1), is a multifunctional protein involved in numerous biological processes, including immune modulation, stress response, and tissue remodeling. The role of SPP1 in interstitial lung diseases (ILDs) has become an area of increasing interest, given its elevated expression in various ILDs such as idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD), and pneumoconiosis, especially with recent data derived from single-cell RNA sequencing. In addition to ILDs, SPP1 has been implicated in infectious granulomatous lung diseases, lung and pleural malignancies, airway diseases, and COVID-19. …

Biallelic Loss-Of-Function Variant In Minpp1 Causes Pontocerebellar Hypoplasia With Characteristic Severe Neurodevelopmental Disorder, Aljazi Al-Maraghi, Rulan Shaath, Katherine Ford, Waleed Aamer, Jehan Alrayahi, Sura Hussein, Elbay Aliyev, Nourhen Agrebi, Muhammad Kohailan, Satanay Z Hubrack, Sasirekha Palaniswamy, Adam D Kennedy, Karen L Debalsi, Sarah H Elsea, Ruba Benini, Tawfeg Ben-Omran, Bernice Lo, Ammira S A Akil, Khalid A Fakhro

Faculty, Staff and Students Publications

Pontocerebellar hypoplasia (PCH) encompasses a group of autosomal recessive neurodegenerative disorders marked by cerebellar and pontine atrophy. Multiple subtypes of PCH have been identified, among which the rare subtype PCH type 16 is caused by MINPP1 genetic variants. MINPPI encodes an enzyme essential for inositol polyphosphate dephosphorylation, regulating calcium and iron homeostasis. We conducted genome sequencing on a proband from the consanguineous family, who presented with a severe neurodegenerative disorder, to identify the underlying cause of disease. A comprehensive clinical assessment in addition to neuroradiological findings are described. We performed the functional validation of the identified variant and conducted untargeted …

Circulating Tumor Dna Monitoring And Blood Tumor Mutational Burden In Patients With Metastatic Solid Tumors Treated With Atezolizumab, Charles Swanton, Russell W Madison, Candice Francheska B Tambaoan, Funda Meric-Bernstam, Christopher J Sweeney, Razelle Kurzrock, Howard A Burris, David R Spigel, Hanna Tukachinsky, Jason Hughes, Julia Malato, Bongin Yoo, Tania Szado, Cheryl Schwab, Lincoln W Pasquina, Amaya Gasco, Katja Schulze, Claire F Friedman

Faculty, Staff and Student Publications

Immune checkpoint inhibitors are important for treatment across tumor types but are not universally effective in controlling disease. Early understanding of tumor response, or lack thereof, can inform treatment decisions. This study evaluates changes in circulating tumor DNA (ctDNA) and blood tumor mutational burden (bTMB) for associations with response to programmed cell death 1 ligand 1 (PD-L1) blockade. We sequenced cell-free DNA collected at the start of therapy, on treatment, and at the end of therapy for 153 patients treated with atezolizumab as part of the pan-tumor MyPathway study (NCT02091141). ctDNA tumor fraction (TF) and bTMB were assessed …

Comparison Of Thrombectomy Alone Versus Bridging Thrombolysis In A Us Population Using Regression Discontinuity Analysis, Youngran Kim, Sergio Salazar-Marioni, Rania Abdelkhaleq, Ananya Iyyangar, Diogo Haussen, Jonathan Grossberg, Jaydevsinh Dolia, Aqueel Pabaney, Mahmoud Mohammaden, Ameer Hassan, Wondwossen Tekle, Hamzah Saei, Mohamad Abdalkader, Piers Klein, Taha Nisar, Adeel Saleemi, Shahram Majidi, Johanna Fifi, Gabrielle Valestin, Guillermo Linares, Kara Christopher, David S Liebeskind, Mouhammad Jumaa, Syed Zaidi, Raul Nogueira, Brijesh Mehta, Joy Sessa, Juan Vivanco-Suarez, Aaron Rodriguez-Calienes, Milagros Galecio-Castillo, Santiago Ortega-Gutierrez, James Siegler, Mary Penckofer, Italo Linfante, Sunil A Sheth, Svin Registry Consortium

Faculty, Staff and Student Publications

The role of intravenous thrombolysis (IVT) in combination with endovascular thrombectomy (EVT) for the treatment of large vessel occlusion acute ischemic stroke has been evaluated exclusively outside the US, in randomized clinical trials which failed to demonstrate non-inferiority of skipping IVT. Because practice patterns and IVT dosing differ within the US, and prior observational US-based cohorts suggested improved clinical outcomes in patients who received IVT before EVT, a US-based evaluation is needed. This is a quasi-experimental study of a large US cohort using a regression discontinuity design (RDD) that enables the estimation of causal effects when randomization is not feasible. …

Advanced Age Worsens Phenotypes Of Ocular Hypertension In Mice, Priyamvada M Pitale, Solomon E Gibson, Caroline C Keehn, Arman T Yazdian, Guofu Shen, Benjamin J Frankfort

Faculty, Staff and Students Publications

Glaucoma is a neurodegenerative disorder of the optic nerve and retinal ganglion cells (RGCs) and a major cause of blindness. The two most important risk factors for glaucoma are ocular hypertension (OHT) and advanced age. In this study, we explored the combined impact of aging and OHT on retinal neuronal and microvasculature health. We induced OHT using the bead-injection model in 12 week old (young) and 1.5 year old (old) mice and monitored intraocular pressure (IOP) for 2 weeks. We then explored vascular phenotypes, blood retinal barrier components, RGC counts, and electroretinogram (ERG) changes. Aged mice displayed reduced retinal microvasculature …

The Effect Of Bilateral Inferior Oblique Myectomy Surgery On The Astigmatism, Ayman M Elghonemy

Journal of Medicine in Scientific Research

INTRODUCTION: The function of the inferior oblique (IO) muscle is to externally rotate, elevate, and abducts the eye. Inferior oblique myectomy (IOM) is one of the most commonly used techniques for correction of inferior oblique overactions (IOOA). Surgical strabismus procedures have been known to cause refractive changes. The change in ocular torsion is known to cause changes to the axis of astigmatism. AIM: To study the effect of bilateral inferior oblique myectomy on the axis and power of astigmatism. METHODS AND MATERIAL: Medical records of 40 patients (80 eyes) who underwent bilateral IOM have been reviewed. Both eyes spherical equivalent, …

Cytogenetic Annotation Automation In Myelodysplastic Syndrome Research Databases, Samuel Urrutia, Kelly S Chien, Ziyi Li, Alexandre Bazinet, Guilin Tang, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

No abstract provided.

The Impact Of Breast Radiotherapy On The Tumor Genome And Immune Ecosystem, Aislyn Schalck, Tuan Tran, Jianzhuo Li, Emi Sei, Shanshan Bai, Min Hu, Jerome Lin, Scott J Bright, Samuel Reddick, Fei Yang, Harsh Batra, Alejandro Contreras, Maria Gabriela Raso, Michael C Stauder, Karen E Hoffman, Jay P Reddy, Kevin T Nead, Benjamin D Smith, Gabriel O Sawakuchi, Wendy A Woodward, Stephanie S Watowich, Jennifer K Litton, Isabelle Bedrosian, Elizabeth A Mittendorf, Huong Le-Petross, Nicholas E Navin, Simona F Shaitelman

Faculty, Staff and Student Publications

Radiotherapy is a pillar of breast cancer treatment; however, it remains unclear how radiotherapy modulates the tumor microenvironment. We investigated this question in a cohort of 20 patients with estrogen-receptor positive (ER+) breast tumors who received neoadjuvant radiotherapy. Tumor biopsies were collected before and 7 days postradiation. Single-cell DNA sequencing (scDNA-seq) and scRNA-seq were conducted on 8 and 11 patients, respectively, at these two time points. The scRNA data showed increased infiltration of naive-like CD4 T cells and an early, activated CD8 T cell population following radiotherapy. Radiotherapy also eliminated existing cytotoxic T cells and resulted in myeloid cell increases. …

Heterozygous Kmt2d Loss Diminishes Enhancers To Render Medulloblastoma Cells Vulnerable To Combinatory Inhibition Of Lsd1 And Oxphos, Shilpa S Dhar, Calena Brown, Ali Rizvi, Lauren Reed, Sivareddy Kotla, Constantin Zod, Janak Abraham, Jun-Ichi Abe, Veena Rajaram, Kaifu Chen, Min Gyu Lee

Faculty, Staff and Student Publications

The histone H3 lysine 4 (H3K4) methyltransferase KMT2D (also called MLL4) is one of the most frequently mutated epigenetic modifiers in many cancers, including medulloblastoma (MB). Notably, heterozygous KMT2D loss frequently occurs in MB and other cancers. However, its oncogenic role remains largely uncharacterized. Here, we show that heterozygous Kmt2d loss in murine cerebellar regions promotes MB genesis driven by heterozygous loss of the MB-suppressor gene Ptch via the upregulation of tumor-promoting programs (e.g., oxidative phosphorylation [OXPHOS]). Downregulation of the transcription-repressive tumor suppressor NCOR2 by heterozygous Kmt2d loss, along with Ptch

Overcoming Nk-Mediated Rejection By Anti-3rd-Party Central Memory Veto Cd8 T Cells Through Downregulation Of Dnam-1 On Alloreactive Nk Cells, Wei-Hsin Liu, Aloukick Kumar Singh, Christa Blagdon, Sandeep Kumar Yadav, Einav Shoshan, Esther Bachar-Lustig, Yair Reisner

Faculty, Staff and Student Publications

Anti-3rd-party central memory veto CD8 T (veto Tcm) cells can overcome T cell-mediated graft rejection under mild conditioning without causing significant graft versus host disease (GVHD). We previously demonstrated that these veto Tcm cells can effectively delete anti-donor T cell clones through a Fas-FasL mechanism, whereas their ability to neutralize alloreactive natural killer (NK) cells and the mechanism of such potential activity remained unknown. Using “nude” mice as recipients of allogeneic T cell-depleted hematopoietic stem cell transplantation (HSCT), we demonstrate effective inhibition of NK-mediated rejection by Tcm cells. Ex vivo studies revealed that Tcm cells express high levels of CD155, …

Antibiofilm Properties Of 4-Hydroxy-3-Methyl-2-Alkenylquinoline, A Novel Burkholderia-Derived Alkaloid, Mckinley D Williams, Taylor R Sweeney, Sabrina Trieu, Ravi Orugunty, Abdelahhad Barbour, Fereshteh Younesi, Michael Glogauer, Nopakorn Hansanant, Ronald Shin, Shi-En Lu, Kevin Cao, Abraham Tenorio, Sigmund J Haidacher, Anthony M Haag, Thomas D Horvath, Leif Smith

Faculty, Staff and Students Publications

Biofilms are an important colonization mechanism employed by several microbial species to better establish themselves and monopolize the acquisition of resources across different environs. Some bacteria have evolved specialized metabolites that, when secreted, disrupt the formation and stability of biofilms generated by competing heterospecies, providing the producing organism with an ecological advantage. Soil-derived species are probable candidates for the identification of such compounds, given the intense level of competition that occurs within the terrestrial ecosystem. The MS14 strain of Burkholderia contaminans isolated from soil in Mississippi has previously been shown to produce antimicrobial compounds like occidiofungin and ornibactin. In this …

Seroprevalence Of Hepatitis C Among Inpatients Who Underwent Different Otorhinolaryngology Surgeries In A Tertiary Referral Institute., Anwar Moawad Elbatawy, Mohammad Mostafa Gaballah

Journal of Medicine in Scientific Research

Background Hepatitis C viral infection is endemic among Egyptian patients due to the higher prevalence among these populations. About 3% of the world’s population (170 million patients) are infected with viral C. The prevalence of HCV antibodies is 14.7% among the age group 15-59. This study is concerned with assessing the prevalence of viral C antibodies among different age groups and variable otorhinolaryngology surgical procedures for these patients. Material and Methods All patients admitted for any operative procedure should be investigated for viral C antibodies in the blood among the national survey in Egypt to control the prevention and active …

Outcome Of Multiple Organ Dysfunction In Older Major Trauma Critical Care Patients In The Intensive Care Unit, Talal Ibrahim Mostafa Hagag, Salwa Mohamed Ahmed Dahesh, Shimaa Mohamed Kalama

Journal of Medicine in Scientific Research

Background: Elderly trauma patients in the ICU often face the critical complication of Multiple Organ Dysfunction Score (MODS). Age-related physiological changes, comorbidities, and impaired recovery mechanisms contribute to poorer outcomes. Recognizing how MODS affects this population's ability to survive is essential for enhancing critical care strategies. Objective: To evaluate the incidence, predictors, and outcomes of MODS in trauma patients aged 70 years and older, focusing on survival rates and key influencing factors. Methods: This prospective observational study focused on ICU patients aged 70 and older who underwent surgery between January 1 and June 1, 2024. The study tracked various factors …

A Study On The Cognitive Functions In Adolescents And Children With Type-1-Diabetes Mellitus, Randa Mohamed Fathi Darwish, Jihan Raafat Seif Sourial, Samar Mohamed Samir Mohamed

Journal of Medicine in Scientific Research

Background: Type one Diabetes Mellitus-(T1DM) can be accompanied with cognitive impairments due to dysglycemic states including hyperglycemia, hypoglycemic states, and diabetic ketoacidosis (DKA). This study evaluates cognitive functions in children with T1DM and examines the impact of factors associated with diabetes. Methods: This cross-sectional study included 100 children with T1DM (6–14 years) and 100 agematched non-diabetic controls at the National Institute for Diabetes and Endocrinology, Cairo. Cognitive function was assessed using the Arabic Stanford–Binet Intelligence Scale. Glycemic control (HbA1C ≥ 7%) and DKA history were analyzed. Results: Children with T1DM had significantly lower IQ scores (84.15 ± 17.61) than controls …

The Impact Of Narratives And Active Video Games Among Black And Hispanic Children With Overweight And Obesity: A Randomized Controlled Trial, Amy S Lu, Tom Baranowski, Tiago V Barreira, Amy Fleischman, Melanie C Green, Shirley Y Huang, I-Min Lee, Lynne L Levitsky, Farzad Noubary, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: Overweight and obesity disproportionately affect Black and Hispanic children who also play more video games. Narratives, coupled with home-based active video games (AVGs), may enhance PA and mitigate these disparities. This study tested the effect of narrative-enhanced home-based AVGs among predominantly Black and Hispanic children with overweight and obesity.

Methods: This 6-month three-group RCT recruited 135 children aged 7-14 from pediatric clinics in Boston, MA (January 2020 - May 2022) during the COVID-19 pandemic. Participants were randomized into: [Narrative + AVG], receiving an Xbox/Kinect with six AVGs interspersed with a narrative animation Ataraxia (72 episodes over six months), which …

Correction: Complement Activity And Autophagy Are Dysregulated In The Lungs Of Patients With Nonresolvable Covid-19 Requiring Lung Transplantation, Pooja Shivshankar, Stacey L Mueller-Ortiz, Aleksey Y Domozhirov, Weizhen Bi, Scott D Collum, Marie-Francoise Doursout, Manish Patel, Isabella N Lefebvre, Bindu Akkanti, Simon Yau, Howard J Huang, Rahat Hussain, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

No abstract provided.

Time To Treatment In Pediatric Patients With Repeated Episodes Of Status Epilepticus, Jennifer V Gettings, Iván Sánchez Fernández, Anne Anderson, J Nicholas Brenton, Afra Can, Justice Clark, Raquel Farias Moeller, Howard P Goodkin, Yi-Chen Lai, Mohamad A Mikati, Lindsey A Morgan, Edward Novotny, Adam P Ostendorf, Juan Piantino, James J Riviello, Kumar Sannagowdara, Robert C Tasker, Dmitry Tchapyjnikov, Mark S Wainwright, Angus Wilfong, Korwyn Williams, Bo Zhang, Tobias Loddenkemper, Marina Gaínza-Lein, Pediatric Status Epilepticus Research Group (Pserg)

Duncan NRI Faculty and Staff Publications

Objective: To compare pediatric patients who presented with repeated status epilepticus episodes to patients with a single episode of status epilepticus and identify distinguishing clinical factors.

Methods: Retrospective analysis of a multicenter, prospective observational cohort of pediatric patients with status epilepticus between 2011 and 2019.

Results: Out of 504 status epilepticus episodes in 420 patients, 50 patients (10.3%) had repeated episodes of status epilepticus. The only predictor of repeated status epilepticus was a prior diagnosis of epilepsy. There was no difference in time to treatment with the first benzodiazepine in patients presenting with their first status epilepticus episode compared to …

Extracorporeal Membrane Oxygenation For Systemic Lupus Erythematosus: An Elso Registry Analysis, Maria Pereira, Danielle Guffey, Katherine Doane, Eyal Muscal, Carla Levin, Peter Rycus, Marc Anders, Andrea Ontaneda

Faculty, Staff and Students Publications

The success of extracorporeal membrane oxygenation (ECMO) in treating Systemic Lupus Erythematosus (SLE) and the risk factors associated with mortality remain uncertain. Methods: We describe the survival outcomes at discharge of the largest SLE cohort on ECMO support. We performed a retrospective cohort study of the Extracorporeal Life Support Organization registry database from 2012 to 2022. Pediatric and adult survivor groups were analyzed using descriptive statistics for the primary study outcome of survival to hospital discharge. Risk predictors for survival were determined by logistic regression.Results: We included 48 children and 368 adults with SLE. Overall, 198 patients (54%) survived …

Hand Hygiene Roles, Challenges, And Intervention Feedback From School Staff: A Qualitative Analysis, Belize, 2022-2023, Anh N Ly, Christina Craig, Dian Maheia, Yolanda Gongora, Vickie Romero, Rosalva Blanco, Allison Lino, Kelsey Mcdavid, Allison Stewart, Victoria Trinies, Alexandra Medley, Francis Morey, Russell Manzanero, Matthew Lozier, Kristy O Murray

Faculty, Staff and Students Publications

Hand hygiene (HH) in school settings can reduce the spread of infectious diseases and student absenteeism due to illness. During the COVID-19 pandemic, the World Health Organization recommended HH as a public health measure to prevent disease transmission. Understanding school staff's experiences with school-based programs is important for future program development and improvement. As part of a mixed-methods study, we conducted in-depth interviews in March 2022 with school administrators and teachers at 12 primary schools in Belize, selected based on high gaps in HH resources, to understand HH responsibilities, supplies, and challenges. An intervention was implemented to increase HH knowledge …

Low Cd25 In Alk+ Anaplastic Large Cell Lymphoma Is Associated With Older Age, Thrombocytopenia, And Increased Expression Of Surface Cd3 And Cd8, Shuyu E, L Jeffrey Medeiros, Hong Fang, Shaoying Li, Guilin Tang, Sa A Wang, Wei Wang, C Cameron Yin, M James You, Swaminathan P Iyer, Luis Malpica, Lianqun Qiu, Zhenya Tang, Qing Wei, Pei Lin, Jie Xu

Faculty, Staff and Student Publications

Background/objectives: Anaplastic lymphoma kinase (ALK)-positive (+) anaplastic large cell lymphoma (ALCL) is known to express CD25, but its significance has not been well studied.

Methods: In the present study, we identified 54 ALK+ ALCL patients with CD25 results available and investigated the significance of CD25 expression levels.

Results: Forty-two (78%) cases had high CD25 expressions, whereas low CD25 expressions were found in 12 (22%) cases. Compared with ALK+ ALCL patients with CD25-high neoplasms, patients with CD25-low neoplasms were older (median: 40 years vs. 29 years, p = 0.01) and more often had thrombocytopenia (40% vs. 0%, p = 0.02). Between …

The Cgas/Sting Pathway: Friend Or Foe In Regulating Cardiomyopathy, Weiyue Wang, Yuanxu Gao, Hyun Kyoung Lee, Albert Cheung-Hoi Yu, Markus Kipp, Hannes Kaddatz, Jiangshan Zhan

Duncan NRI Faculty and Staff Publications

Inflammation is a central hallmark of cardiomyopathy, where misdirected immune responses contribute to chronic myocardial dysfunction. Among the emerging molecular mechanisms implicated in this process, the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway has garnered increasing attention. Acting as a key cytosolic DNA sensor, the cGAS/STING pathway orchestrates inflammatory responses triggered by microbial infections or endogenous cellular stressors such as autophagy and apoptosis. Despite its pivotal role, the precise molecular mechanisms regulating this pathway and its role in cardiomyopathy-associated inflammation remain poorly understood and subject to ongoing debate. To address this scientific gap, we first reviewed key …

Steps Toward Clinical Validation Of Exhaled Volatile Organic Compound Biomarkers For Hypoglycemia In Persons With Type 1 Diabetes., Mark Woollam, Paula Angarita-Rivera, Sanskar Thakur, Ali Daneshkhah, Amanda P Siegel, Dana S Hardin, Mangilal Agarwal

Ambulatory and Primary Care Articles

Persons with type 1 diabetes (T1D) must track/control their blood glucose (BG) levels to avoid hypoglycemic events (BG <  70 mg/dL), which in the most severe cases can lead to seizures or even death. Canines may lead the way toward innovative testing solutions, as they can be trained to identify hypoglycemia simply and noninvasively by smelling exhaled volatile organic compounds (VOCs). To identify breath-based biomarkers of hypoglycemia, samples were collected during two consecutive summers at a diabetes camp (Cohort 1 and Cohort 2), and VOCs were analyzed by gas chromatography-mass spectrometry. Conserved VOCs between the two cohorts were identified, but individual VOCs alone had low accuracies for detection. Therefore, supervised multivariate statistical analysis was undertaken to identify a biosignature in the training data set (Cohort 1) that could detect hypoglycemia with higher accuracy (sensitivity = 94.8%/specificity = 95.0%). When this model was blindly tested on Cohort 2, hypoglycemia was classified with sensitivity = 90.0%/specificity = 89.9%. Ultimately, this study makes strides toward clinical validation through verifying biomarkers of hypoglycemia in hundreds of breath samples. These results may be translated to design a sensor array that could be integrated into a portable breathalyzer to increase glycemic control in persons with T1D.

Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang

Pharmacy Faculty Articles and Research

Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …

Implementation Of A Health Care Transition Pathway For Children And Adults With Inborn Errors Of Metabolism: A Pilot Project, Brittany M. Murray

Doctor of Nursing Practice Scholarly Projects

Background: Children with medically complex diseases require highly specialized care by a highly specialized team. Those with rare disease, including inborn errors of metabolism (IEMs), are a medically complex population and face significant challenges undergoing the health care transition from a child/family-centered model to an adult/patient-centered model of care. The project site follows patients with IEMs in the Metabolism Program, but previously did not have a coordinated process and had insufficient resources for patients/families for the health care transition.

Methods: The Plan-Do-Study-Act (PDSA) method was utilized as the model for improvement. Due to the complexity of the population and time …

“Non-Markovian” And “Directional” Errors Inhibit Scientific Self-Correction And Can Lead Fields Of Study Astray: An Illustration Using Gardening And Obesity-Related Outcomes, Jon Agley, Sarah E Deemer, David B Allison

Children’s Nutrition Research Center Staff Publications

Herein we coin the terms non-Markovian error and biased Markovian error to describe categories of scientific errors for which general progress within a field of study may be unlikely to result in scientific self-correction. We provide examples of such errors and show their impact on studies about gardening and obesity.