Translational Medical Research Commons^™

Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian

Surgery Faculty Publications

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …

A Research Framework For Evaluating Next Generation Sequencing In Community-Acquired Pneumonia, Ashley M. Wilde, Elena Swingler, Sarah E. Moore Pharmd, Brian C. Bohn Pharmd, Matthew Song Pharmd, Bcidp, Ruth Carrico, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Conference Proceedings: Select Abstracts Presented At 2021 Advocate Aurora Health Scientific Day

Journal of Patient-Centered Research and Reviews

Abstracts published within this supplement were presented at the 47th annual Advocate Aurora Health Scientific Day, held virtually on May 26, 2021. This research symposium provides a forum for disseminating results from studies conducted by faculty, fellows, residents, and other allied health professionals associated with Midwest-based health system Advocate Aurora Health, which publishes the Journal of Patient-Centered Research and Reviews.

Covid-19-Associated Pulmonary Aspergillosis: A Case Report From The Covid-19 Surveillance Program., Mohamad Belal Aldaas, Dylan Goldsmith, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

A 72-year-old male was brought to the hospital following a motorcycle crash and was admitted for multiple trauma management. His initial course of hospitalization was complicated by mild hypoxemia and altered mental status. Respiratory workup and imaging were consistent with SARS-CoV-2 pneumonia. He completed a five-day course of remdesivir and a ten-day course of dexamethasone. Twenty days later, he developed a low-grade fever. His chest computerized tomography (CT) showed gas and fluid containing parenchymal collection in the anteromedial right middle lobe measuring up to 4.8 cm, most consistent with a pulmonary abscess. Antimicrobial treatment was started.

The patient became hypoxic …

A Light In The Dark: End-Of-Life Conversations In Advanced Cancer Patients Improve Caregiver Grief, Nicole Meeks

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Wright AA, Zhang B, Ray A, Mack JW, Trice E, Balboni T, Mitchell SL, Jackson VA, Block SD, Maciejewski PK, & Prigerson HG. Associations between end-of-life discussions, patient mental health, medical care near death, and caregiver bereavement adjustment. JAMA. 2008;300(14):1665-1673. https://doi.org/10.1001/jama.300.14.1665

for a patient with end stage cancer and an anxious caregiver.

Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

del Amo J, Polo R, Moreno S, et al. “Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.” Annals of Internal Medicine. 2020;173(7):536-541. doi.org/10.7326/m20-3689

for a patient with HIV and concerns about COVID-19 for immunocompromised individuals.

University Of Louisville International Travel Clinic: Pivoting During The Covid-19 Pandemic, Dawn Balcom, Subathra Marimuthu, Leslie A Wolf, Luanne Didelot, Sarah Tan, Daniel Hall, Ruth Carrico

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Association Of Lung Cancer With Pneumonia And Chlamydia Pneumoniae Infection, Johnny Zakhour Md, Daniel Muller, Alex Glynn, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Introduction: The degree of association and type of causal versus non-causal relationship between pneumonia and lung cancer (LC) are evolving discussions. We reviewed English publications on the degree of association between pneumonia and subsequent LC.

Methods: We searched the PubMed database using key words for pneumonia, LC, and chlamydia infection. We selected peer-reviewed studies of patients with pneumonia and LC. Case reports and other literature reviews were excluded from this review.

Results: Five studies examined the incidence and/or risk of LC for a total of 415,750 patients, and four studies examined cases with Chlamydia pneumoniae chronic infection at the time …

The Contribution Of Patient Reported Outcome Measures To Shared Decision-Making In Radiation Oncology At A Midwestern Comprehensive Cancer Center, Kellie Bodeker

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Chronic diseases, such as lung cancer, require a provider-patient relationship developed over time. This relationship fosters shared decision-making (SDM), a collaborative, dynamic information exchange and analysis between provider and patient regarding treatment and desired outcomes. Established benefits to SDM include an improved quality of life and decreased anxiety and depression. Despite established benefits, recent research suggests radiation oncologists are not engaging in SDM. A decision-aid tool utilizing patient reported outcome measures may increase SDM between radiation oncologists and patients with lung cancer. Patient-reported outcome measures, wherein the patient provides direct assessment of their health and quality of life, …

Barriers And Benefits Experienced In Qualitative Geriatric Emergency Care Research During The Covid-19 Era, James D. Van Oppen, Emma Regen, Kay Phelps, Timothy J. Coats, Jose M. Valderas, Simon P. Conroy, Nicola Mackintosh

Journal of Geriatric Emergency Medicine

No abstract provided.

Pulmonary Inflammation And Injury Triggered By Spine Surgery In Recovered Covid-19 Patients Demand Consideration, Luciano Rodrigo Lopes, Silvana Kertzer Kasinski

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Why Should People Use Face Masks In The Time Of Covid? The Jri Position, Jose Bordon, Alex Glynn, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

No Difference In Clinical Outcomes For African American And White Patients Hospitalized With Sars-Cov-2 Pneumonia In Louisville, Kentucky, Julio A. Ramirez, Stephen P. Furmanek, Thomas Chandler, Stephen S. Hanson, Dawn Balcom, Subathra Marimuthu, Sathya Krishnasamy, Jose Bordon, Rodrigo Cavallazzi, Amr Aboelnasr, Mahder A. Tella, William A. Mattingly, Ashley M. Wilde, Daisy Sangroula, Demetra Antimisiaris, Donghoon Chung, Guillermo Cabral, Gabino R Fernandez-Botran, Jiapeng Huang, Martin Gnoni, Ozan Akca, Paul Schulz, Phillip F. Bressoud, Priya Krishnan, Sally Suliman, William P. Mckinney, Bryan Moffett, Leslie A Wolf, Mark Burns, Alex Glynn, Ruth Carrico, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

Introduction: Current literature indicates that African American individuals are at increased risk of becoming infected with the SARS-CoV-2 virus and suffer higher SARS-CoV-2-related mortality rates. However, there is a lack of consensus as to how the clinical outcomes of African American patients differ from those of other groups. The objective of this study was to define the clinical outcomes of African American and White hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) in Louisville, Kentucky.

Methods: This was a retrospective cohort study of hospitalized patients with SARS-CoV-2 CAP at eight hospitals in Louisville, Kentucky. Severity of CAP at time of hospitalization …

A Moral Dilemma: The Use Of Zinc In Patients Hospitalized With Covid Pneumonia, Ebony M. Manigault, Laura Donohue, Elizabeth Moore, Yara Abuaita

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Yao JS, Paguio JA, Dee EC, Tan HC, Moulick A, Milazzo C, Jurado J, Della Penna N, Celi LA. The minimal effect of zinc on the survival of hospitalized patients with COVID-19: an observational study. Chest. 2021 Jan;159(1):108-111. https://doi.org/10.1016/j.chest.2020.06.082

for a patient hospitalized with COVID pneumonia requiring high flow oxygen.

Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

It has become increasingly evident that a high percentage of patients that recover from acute COVID-19 infection continue to suffer from a variety of persistent symptoms even months after viral clearance, the most common ones being fatigue, dyspnea, anosmia, dysgeusia, cognitive dysfunction, and psychological problems, including anxiety and depression. This syndrome, known as Post-acute sequelae of COVID-19 (PASC), can severely affect the life quality and represents an important health care concern. The exact causes for the symptoms observed in patients with PASC remain to be adequately characterized, but are likely to be associated with multiple factors, including residual disease and/or …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

A Novel In Vitro Method For Pelvic Floor Dysfunction In Pcos Women, Ruben Vila

University Honors Theses

Background:

Poly Cystic Ovary Syndrome and Pelvic Floor Dysfunction are reproductive diseases with comorbidities whose novel relationship deserves further investigation.

Methods:

Levator Ani Muscle/Paravaginal Attachment was dissected from female Rhesus Macaque and subjected to tissue dissociation. Cells were treated with serum level hormones E2, T, and DHT. PCR, ICC, and IHC were used, followed by statistical analysis.

Results:

RNA analysis show differences in relative expression for endpoints ER, PR, AR, Ki-67, Col1A, and Vimentin. IHC along with ICC showed expression and localization in vivo.

Conclusions:

A novel in vitro model was created from macaque Levator Ani Muscle/Paravaginal Attachment for Pelvic …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations and Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Interventional Treatment With The Transjugular Intrahepatic Portosystemic Shunt (Tips) Procedure May Offer A Preferable Alternative To Systemic Anticoagulation In Patients With Cirrhosis And Portal Vein Thrombosis, Molly N. Pantelic

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Wang Z, Jiang MS, Zhang HL, et al. Is post-tips anticoagulation therapy necessary in patients with cirrhosis and portal vein thrombosis? A randomized controlled trial. Radiology. 2016;279(3):943-951. https://doi.org/10.1148/radiol.2015150369

for a patient with cryptogenic cirrhosis, gastroesophageal varices, pancreatic cancer, and portal vein thrombosis.

Luspatercept Diminishes The Need For Red Blood Cell Replacement In Transfusion-Dependent Β-Thalassemia Patients, Joudeh B. Freij

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231. https://doi.org/10.1056/NEJMoa1910182

for a patient with transfusion-dependent beta-thalassemia.

Sleeve Gastrectomy Improves Metabolic Syndrome In Psychologically Stable Patients With Schizophrenia, Irene Chen

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Archid R, Archid N, Meile T, Hoffman J, Wulff D, Teufel M, Muthig M, Quante M, Konigsrainer A, Lange J. Patients with schizophrenia do not demonstrate worse outcome after sleeve gastrectomy: a short-term cohort study. Obesity Surgery. 2019;29:506-510. https://doi.org/10.1007/s11695-018-3578-0

for a patient with schizophrenia and obesity.

External Beam Radiation Therapy Carries Lower Risk Of Sexual Dysfunction As Compared To Radical Prostatectomy In Treatment Of Patients With Localized Prostate Cancer, Aamod S. Dekhne

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report appraising:

Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016;375(15):1425-1437. https://doi.org/10.1056/NEJMoa1606221

for a patient with localized prostate cancer and concerns regarding future sexual dysfunction.

The Driving Simulator Visual Field In Glaucoma – A Novel Task To Test Available Field Of View, Deepta Ghate

Theses & Dissertations

Glaucoma causes peripheral vision loss and impaired driving performance. We developed a novel driving simulator visual field task (DSVF) in a panoramic driving simulator to map the available field of view under different perceptual task loads in naturalistic settings. Our hypothesis is that “available field of view” will decrease with increasing task load in both glaucoma subjects and controls. This is a cross-sectional study with 28 glaucoma subjects and 19 controls. DSVF (60̊ x 20̊ visual field at 2.5 m) was tested in a high-fidelity interactive driving simulator in 4 different scenarios: a) no distractions b) no driving condition with …

A Fully-Automated, Deep Learning-Based Framework For Ct-Based Localization, Segmentation, Verification And Planning Of Metastatic Vertebrae, Tucker Netherton, Tucker James Netherton

Dissertations and Theses (Open Access)

Palliative radiotherapy is an effective treatment for the palliation of symptoms caused by vertebral metastases. Visible evidence of disease is localized on medical images as part of the treatment planning process. However, complicating factors such as time pressures, anatomic variants in the spine, and similarities in adjacent vertebrae are associated with wrong level treatments of the spine. In addition, erroneous manual contouring of anatomic structures is a major failure mode in radiotherapy treatment planning.

The purpose of this study is to mitigate the challenges associated with treatment planning of the spine by automating the treatment planning process for three-dimensional conformal …

Streptococcus Anginosus Lung Infection And Empyema: A Case Report And Review Of The Literature, Nishita Tripathi, Kuldeep Ghosh, Anupama Raghuram

The University of Louisville Journal of Respiratory Infections

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for …

Pvn Activity In Cardiac Sympathetic Afferent Reflex (Csar) Control And Cardiovascular Function, Shane H. Boomer

Honors Thesis

Regulation of blood pressure is essential in bodily health. Hypertension and hypotension can be associated with varying diseases that could potentiate further disease. From this, understanding the mechanisms that regulate blood pressure is important within medicine. In my study, I will be focusing on a cardiovascular reflex that is less well understood, the cardiac sympathetic afferent reflex (CSAR). In particular, this work will examine sex differences in this reflex in overall function and in the involvement of an area of the brain called the paraventricular nucleus (PVN). We will test the hypothesis that there will be a significant difference between …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Chloroquine: Autophagy Inhibitor, Antimalarial, Bitter Taste Receptor Agonist In Fight Against Covid-19, A Reality Check?, Pawan Sharma, Kielan D. Mcalinden, Saeid Ghavami, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate …