Medical Specialties Commons^™

Aberrant Dna Hydroxymethylation Reshapes Transcription Factor Binding In Myeloid Neoplasms, Jia Li, Tingting Hong, Yue Wei, Lei Guo, Minjung Lee, Hui Yang, Caleb Class, Yaling Yang, Xiaoqiong Wang, Hua He, Stefan Siwko, M James You, Yubin Zhou, Guillermo Garcia-Manero, Yun Huang

Faculty, Staff and Student Publications

Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been detected in patients with myeloid neoplasms, suggesting that 5hmC might act as a valuable epigenetic mark to reflect the disease status of myeloid neoplasms. Here, we report systematic genome-wide mapping of the DNA hydroxymethylomes in over 70 patients with myeloid neoplasms. Our integrative analysis leads to the identification of distinct 5hmC signatures that can sensitively discriminate patients from healthy individuals. At the molecular level, we unveiled dynamic 5hmC changes within key transcription factor (e.g., the CEBP family) binding motifs that are essential for hematopoiesis and myeloid lineage specification. 5hmC redistribution was found …

Gut Microbiome Alterations Associated With Diabetes In Mexican Americans In South Texas, Suet-Ying Kwan, Caroline M Sabotta, Aron Joon, Peng Wei, Lauren E Petty, Jennifer E Below, Xiaogang Wu, Jianhua Zhang, Robert R Jenq, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans have a high prevalence of diabetes and burden of diabetes-related complications, highlighting the need for novel preventive strategies and noninvasive predictors of diabetes risk tailored to this population. Changes in the gut microbiome have the potential to predict diabetes. Here, we aimed to identify alterations in the gut microbiome associated with diabetes in the high-risk population of Mexican Americans in South Texas. Stool samples were collected from 216 subjects from the population-based Cameron County Hispanic Cohort. Among them, 75 had type 2 diabetes. Taxonomic and functional profiling of the stool samples were assessed by 16S and shotgun metagenomic …

Nf-Kb (P50/P65)-Mediated Pro-Inflammatory Microrna (Mirna) Signaling In Alzheimer's Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

No abstract provided.

Expanding Anti-Cd38 Immunotherapy For Lymphoid Malignancies, Xu Wang, Xinfang Yu, Wei Li, Praveen Neeli, Ming Liu, Ling Li, Mingzhi Zhang, Xiaosheng Fang, Ken H Young, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Lymphoid neoplasms, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and NK/T cell neoplasms, are a major cause of blood cancer morbidity and mortality. CD38 (cyclic ADP ribose hydrolase) is a transmembrane glycoprotein expressed on the surface of plasma cells and MM cells. The high expression of CD38 across MM and other lymphoid malignancies and its restricted expression in normal tissues make CD38 an attractive target for immunotherapy. CD38-targeting antibodies, like daratumumab, have been approved for the treatment of MM and tested against lymphoma and leukemia in multiple clinical trials.

METHODS: We generated chimeric antigen receptor (CAR) T cells targeting …

Mycn-Driven Fatty Acid Uptake Is A Metabolic Vulnerability In Neuroblastoma, Ling Tao, Mahmoud A Mohammad, Giorgio Milazzo, Myrthala Moreno-Smith, Tajhal D Patel, Barry Zorman, Andrew Badachhape, Blanca E Hernandez, Amber B Wolf, Zihua Zeng, Jennifer H Foster, Sara Aloisi, Pavel Sumazin, Youli Zu, John Hicks, Ketan B Ghaghada, Nagireddy Putluri, Giovanni Perini, Cristian Coarfa, Eveline Barbieri

Faculty, Staff and Students Publications

Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and …

Gain-Of-Signal Assays For Probing Inhibition Of Sars-Cov-2 Mpro/3clpro In Living Cells, Seyed Arad Moghadasi, Morgan A Esler, Yuka Otsuka, Jordan T Becker, Sofia N Moraes, Constance B Anderson, Srinivas Chamakuri, Christopher Belica, Chloe Wick, Daniel A Harki, Damian W Young, Louis Scampavia, Timothy P Spicer, Ke Shi, Hideki Aihara, William L Brown, Reuben S Harris

Faculty, Staff and Students Publications

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that …

Podium Presentation: Racial Inequities And Breastfeeding In A Nicu: A Quality Improvement Project, Emilia C. Garcia

2022 Providence Nurse Research Conference

No abstract provided.

Podium Persentation: Trauma-Informed Care In Palliative Care, Amber Piranio

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Spontaneous Intraventricular Empyema In A Patient With Bacterial Sinusitis, Rachel Freedberg, Brian J. Carlson, Cynthia Murphy, Teresa Bigand

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Sleep-Associated Impairment In Hospital Nurses Working 12-Hour Day Or Night Shifts During The Covid-19 Pandemic: A Large Health System Multisite Pilot Study, Jamie Roney, Teresa Bigand, Ross Bindler, Trisha Saul, Rebecca Penders, Douglas L Weeks, Lois James, Marian Wilson

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Identifying Barriers To Quality Mother-Infant Interactions In The Nicu Through Naturalistic Systematic Observations, Christine Neugebauer, Miranda Cox, Melissa Deckert, Ann M. Mastergeorge

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Continuous Labor Epidural Placement Trends Among Parturients: An Evidence-Based Practice Project, Aleksandr A. Lyakhov, Teresa Bigand, Amanda Affleck, Kenn Daratha, Kris Daratha

2022 Providence Nurse Research Conference

Background:

Childbirth is very painful, and unmanaged pain may reduce patient satisfaction or lead to other complications. Evidence indicates that pain severity is lower among parturient women administered analgesia via a continuous labor epidural (CLE) and that maternal request is sufficient indication for CLE placement to manage labor pain. In some cases, a medical induction of labor may be scheduled, offering an opportunity for proactive pain management from hospital staff. Yet, trends on timing of CLE placement among parturient women with scheduled labor induction versus spontaneous labor in hospitals in Eastern Washington at one health system are unclear.

Purpose:

The …

Podium Presentation: Pediatric Immunizations: Improving Hedis Measures And Vaccination Rates, Brianna Baublitz, Brenda Senger, Denise Ogorek, Teresa Bigand, Devorah Overbay

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Registered Nurses' Diet Quality And Overall Health During The Sars-Cov-2 Pandemic, Teresa Bigand, Ross Bindler, Lois James, Rachel Faulkner, Rebecca Penders, Trisha Saul, Marietta Sperry, Marian Wilson

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Covid And Antidepressants: Ongoing Use Of Ssris And The Hospital Course Of Covid-19 Patients: A Retrospective Outcome Analysis, Sherri Mendelson

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Opioid Use Among Total Knee Arthroplasty Patients, Kelsie Welle, Karen Colorafi, Kenn Daratha

2022 Providence Nurse Research Conference

No abstract provided.

T Wave Inversions In An Asymptomatic Patient: What Do You Expect And What Is The Next Step?, Ravi Choxi

Transformative Medicine

A 55-year-old male of Asian descent presents for a first time appointment to a primary care office for an annual physical examination. He has no known medical history and is in his usual state of health. He denies any chest pain, dyspnea, syncope, lightheadedness, exercise intolerance, lower extremity edema or orthopnea. Vital signs are notable for a blood pressure of 142/92 mmHg and a heart rate of 86 beats per minute. Physical exam findings are notable for a soft 1/6 systolic murmur heard best in the bilateral upper sternal borders. Electrocardiogram is performed (Figure 1).
Questions:
• Describe the ECG? …

Sinus Pauses And Asystole As A Rare Presentation Of Thyrotoxic Crisis: A Case Report, Christian Akem Dimala, Charnjeet Sandhu, Oreoluwa Oladiran, Agnieszka Mochon, William Finneran Iii

Transformative Medicine

Introduction

Thyroid crisis is a rare and life-threatening endocrine emergency characterized by exaggerated clinical manifestations of hyperthyroidism with cardiovascular manifestations being the most severe. Rhythm disturbances, sinus tachycardia and atrial fibrillation, are the commonest cardiac manifestations of severe thyrotoxicosis; however, asystole remains a very atypical and uncommon presentation. We present a case of thyrotoxicosis due to Grave’s disease complicated by multiple episodes of asystole.

Case Presentation

A 65-year-old female recently diagnosed with Grave’s disease presented to the hospital with recurrent episodes of syncope. Her hospital course was significant for atrial fibrillation with subsequent progression to sinus pauses and asystole spontaneously …

The Modified Rankin Scale Can Accurately Be Derived From The Electronic Medical Record, Derek Isenberg, Nelson Prus, Frederick Ramsey, Nina T. Gentile

Transformative Medicine

Abstract

Introduction

The modified Rankin Scale (mRS) is used to assess functional outcomes after a stroke and is the primary outcome in many stroke trials. For retrospective stroke research or stroke research in which patients are lost to study follow up, review of the electronic medical record (EMR) may be the sole way to estimate a patient’s functional outcome. The purpose of this study is to determine if a mRS can be accurately derived from the electronic medical record EMR.

Methods

This study used data from completed stroke studies in which in-person 90-day mRS were collected as part of the …

Brain Functional Topology Differs By Sex In Cognitively Normal Older Adults, Zhengshi Yang, Filippo Cieri, Jefferson W. Kinney, Jeffrey L. Cummings, Dietmar Cordes, Jessica Z K Caldwell

Brain Health Faculty Research

Introduction: Late onset Alzheimer’s disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer’s Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of …

Reflections On Beam Configuration Optimization For Intensity-Modulated Proton Therapy, Wenhua Cao, Humberto Rocha, Radhe Mohan, Gino Lim, Hadis M Goudarzi, Brígida C Ferreira, Joana M Dias

Faculty, Staff and Student Publications

Presumably, intensity-modulated proton radiotherapy (IMPT) is the most powerful form of proton radiotherapy. In the current state of the art, IMPT beam configurations (i.e. the number of beams and their directions) are, in general, chosen subjectively based on prior experience and practicality. Beam configuration optimization (BCO) for IMPT could, in theory, significantly enhance IMPT's therapeutic potential. However, BCO is complex and highly computer resource-intensive. Some algorithms for BCO have been developed for intensity-modulated photon therapy (IMRT). They are rarely used clinically mainly because the large number of beams typically employed in IMRT renders BCO essentially unnecessary. Moreover, in the newer …

Role Of Lipid-Lowering Therapy In Peripheral Artery Disease, Agastya Deepak Belur, Aangi J. Shah, Salim S. Virani, Mounica Vorla, Dinesh K. Kalra

Office of the Provost

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant …

Occult Polyclonality Of Preclinical Pancreatic Cancer Models Drives In Vitro Evolution, Maria E Monberg, Heather Geiger, Jaewon J Lee, Roshan Sharma, Alexander Semaan, Vincent Bernard, Justin Wong, Fang Wang, Shaoheng Liang, Daniel B Swartzlander, Bret M Stephens, Matthew H G Katz, Ken Chen, Nicolas Robine, Paola A Guerrero, Anirban Maitra

Faculty, Staff and Student Publications

Heterogeneity is a hallmark of cancer. The advent of single-cell technologies has helped uncover heterogeneity in a high-throughput manner in different cancers across varied contexts. Here we apply single-cell sequencing technologies to reveal inherent heterogeneity in assumptively monoclonal pancreatic cancer (PDAC) cell lines and patient-derived organoids (PDOs). Our findings reveal a high degree of both genomic and transcriptomic polyclonality in monolayer PDAC cell lines, custodial variation induced by growing apparently identical cell lines in different laboratories, and transcriptomic shifts in transitioning from 2D to 3D spheroid growth models. Our findings also call into question the validity of widely available immortalized, …

Transmission, Strain Diversity, And Zoonotic Potential Of Chronic Wasting Disease, Sandra Pritzkow

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting several species of captive and free-ranging cervids. In the past few decades, CWD has been spreading uncontrollably, mostly in North America, resulting in a high increase of CWD incidence but also a substantially higher number of geographical regions affected. The massive increase in CWD poses risks at several levels, including contamination of the environment, transmission to animals cohabiting with cervids, and more importantly, a putative transmission to humans. In this review, I will describe the mechanisms and routes responsible for the efficient transmission of CWD, the strain diversity of natural CWD, …

Podium Presentation: Mindfulness Bundle Impact On Nurse Burnout Study, Gisele Nicole Bazan, Tiffany Patterson, Kelsey Sawyer, Deborah Wambui Kamau, Jamie Roney, Michelle Bradberry, Cynthia Louise Grissman, Sahar Mihandoust, Randall Stennett, Joann Long

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Nursing And Emotional Health Before And During The Covid-19 Hospital Surges, Marietta Sperry, Ellen Romesburg, Teresa Bigand, Marian Wilson, Lois James

2022 Providence Nurse Research Conference

Background:

Occupational burnout, a symptom of chronic work-related stress, can lead to negative health outcomes such as anxiety, depression, diabetes, insomnia, and increased risk for cardiovascular disease. Burnout also augments negative occupational risks such as increased sick days, decreased productivity, disability claims, and turnover. Nurses working in the hospital setting report high levels of work-related stress and burnout related to patient acuity levels and short staffing, and rates have further worsened in the context of the COVID-19 pandemic. The emergence of the virus brought multiple hospital surges, greatly increasing nursing workload as patient acuity climbed and simultaneously, national nurse …

Podium Presentation: Relationships Between Nursing Stress And Perceived Importance Of Access To Chaplains During The Covid-19 Pandemic, Teresa Bigand, Adam Gaines, Sheila Doucette, Danell Stengem, Rachel Freedberg, Jamie Roney, Rosemary Timmerman

2022 Providence Nurse Research Conference

Background:

Hospital chaplains are trained to provide spiritual support to inpatients, family members, and support persons across the continuum of care. Patients receiving a chaplain visit during their hospital stay report higher satisfaction, quality of life, and spiritual well-being. Chaplain consultation during hospitalization is related to higher rates of hospice enrollment and lower rates of in-hospital deaths. Additionally, evidence suggests nurses who are employed in hospitals with staff chaplains report lower stress and compassion fatigue based on frequency of interactions with chaplains during worked shifts. Since the COVID-19 pandemic, hospital nurses providing front-line care report higher stress levels compared to …

Podium Presentation: Levels Of Compassion Satisfaction Among Prescribers, Nursing Staff, And Chaplains, Teresa Bigand, Adam Gaines, Dawn Bock, Jamie Roney, Rachel Freedberg, Rosemary Timmerman, Danell Stengem

2022 Providence Nurse Research Conference

Background:

Patient care delivered in hospitals is fast-paced, complex, and ever-changing. During the COVID-19 pandemic, nurses, prescribers, and chaplains provided front-line, whole-person care in hospital settings to patients who had decreased or no access to visitors without the use of technology while facing acute illness and difficult prognoses. During the pandemic, nurses and physicians reported increased fatigue and stress in scientific literature. Poor emotional well-being may lead to decreased compassion satisfaction. Increased compassion satisfaction may mitigate adverse occupational and patient-centered outcomes, support fewer missed days at work, lead to higher staff satisfaction, and raise patient satisfaction scores. Literature reports that …

Podium Presentation: Entangled: Nurses With Mental Health Problems Who Died By Suicide, Adriana Barnes

2022 Providence Nurse Research Conference

No abstract provided.

Podium Presentation: Promoting Holistic Health: Impact Of Vocati On The Spiritual And Moral Development In Youth, Joann Long, Jeremy Smith

2022 Providence Nurse Research Conference

Background: Approximately one out of every six individuals are adolescents between the ages of 10 to 19. Promoting health and reducing risks for this age group has life-long health and societal consequences. Evidence suggests positive and negative risk-taking behaviors cluster in this population. Models for the promotion of positive youth development have shifted in focus from avoidance of risk-taking behaviors to emphasis on psychosocial competence and holistic well-being. Evidence suggests spiritual wellbeing, regardless of conceptual definition, is more often than not associated with positive health outcomes and development in youth. However, few studies have included spiritual and moral constructs in …