Translational Medical Research Commons^™

The Guide To Community Preventive Services Review Of Interventions To Promote Health Equity In The United States, Robert Hahn, Jonathan E. Fielding, M.D., M.P.H., M.A., M.B.A, Robert L. Johnson, M.D., Carles Muntaner, M.D., Ph.D., M.H.S., Benedict I. Truman, M.D., M.P.H., Tracy Orleans

Journal of Health Disparities Research and Practice

The optimal approach to eliminating health inequities is through evidence-based interventions. In 2009, the non-federal Community Preventive Services Task Force launched a series of systematic reviews of interventions to promote health equity. Topics to be considered include education, employment, housing, and transportation. Thus far, reviews have focused on educational interventions: center-based early childhood education, full-day kindergarten programs, out-of-school time academic programs, high school completion programs, and school-based health centers. These reviews demonstrate the benefits of diverse educational interventions in advancing health equity. Here, we summarize the strategy of Community Guide health equity reviews, first findings and challenges.

Improving Access And Utilization Of Data To Support Research And Programs Intended To Eliminate Disparities And Promote Health Equity, Rosaly Correa-De-Araujo

Journal of Health Disparities Research and Practice

Numerous Federal initiatives are addressing health and health care disparities. The ultimate goal is to achieve “a nation free of disparities in health and health care.” Social determinants of health remain mostly responsible for health/health care disparities among population groups within and between countries. In the United States, there is little evidence that disparities associated with such determinants are decreasing, with only 10% of those associated with race/ethnicity and income having demonstrated improvement in recent years. A variety of data sources are available from the Federal and private sectors to support research on disparities, but no single national survey seems …

Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

Dissertations and Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of histone …

Motor Learning And Adaptation In People With Knee Osteoarthritis And Chronic Pain, Heather Turcotte, Katherine S. Rudolph

Osteopathic Medicine Student Research Posters

Osteoarthritis (OA) affects an estimated 50 million people in the US, and approximately 43% have limitations in daily function due to arthritis pain.3 Individuals with knee osteoarthritis (OA) have heightened sensitization to pain2,5 as well as reduced strength, diminished function and quality of life1 that prompts them to seek care from health care providers. Physical therapists commonly work with patients to improve function and quality of life by helping them learn to move without pain. Unfortunately, chronic pain causes changes to the nervous system that may impact the ability to learn new ways but the extent to which chronic pain …

Ixazomib Enhances Parathyroid Hormone-Induced Β-Catenin/T-Cell Factor Signaling By Dissociating Β-Catenin From The Parathyroid Hormone Receptor., Yanmei Yang, Hong Lei, Ya-Wei Qiang, Bin Wang

Center for Translational Medicine Faculty Papers

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that …

The Community-Acquired Pneumonia Organization (Capo) Cloud-Based Research Platform (The Capo-Cloud): Facilitating Data Sharing In Clinical Research, William A. Mattingly, Timothy L. Wiemken, Stephen P. Furmanek, Paula Peyrani, Robert R. Kelley, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Pneumonia is a costly and deadly respiratory disease that afflicts millions every year. Advances in pneumonia care require significant research investment and collaboration among pneumonia investigators. Despite the importance of data sharing for clinical research it remains difficult to share datasets with old and new investigators. We present CAPOCloud, a web-based pneumonia research platform intended to facilitate data sharing and make data more accessible to new investigators.

Methods: We establish the first two use cases for CAPOCloud to be the automatic subsetting and constraining of the CAPO database and the automatic summarization of the database in aggregate. We use …

Pneumonia Research And The Omics Revolution: It Is Time For Pneumomics, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

A New Journal Section: Patient Management, Forest W. Arnold, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Impact Of Obesity On Mortality In Hospitalized Patients With Pneumonia Due To 2009 H1n1 Influenza A Virus Versus Other Etiologies, Martin A. Espinosa-Ginic, Ryan T. Hurt, Stephen P. Furmanek, Paula Peyrani, Julio A. Ramirez, Timothy Lee Wiemken, The Capo Investigators

The University of Louisville Journal of Respiratory Infections

Background: Reports from the 2009 H1N1 influenza A virus (2009 H1N1) pandemic indicate increased mortality in obese patients hospitalized with pneumonia. However, articles published prior to the pandemic have suggested that obesity may be a protective factor for mortality in these patients. The objective of this study was to compare the impact of obesity on mortality in hospitalized patients with pneumonia due to the 2009 H1N1 versus pneumonia due to other etiologies.

Methods: This was a secondary analysis of the CAPO international cohort study. Study groups were defined as follows: Group One, pneumonia due to 2009 H1N1: Patients hospitalized with …

Short Duration Of Antibiotic Therapy In Hospitalized Patients With Community-Acquired Pneumonia: Results From The Capo International Cohort Study, Alejandro Chirino Navarta, Paula Peyrani, Timothy L. Wiemken, Marcos I. Restrepo, James D. Chalmers, Carlos M. Luna, Francesco Blasi, Julio A. Ramirez, Stefano Aliberti

The University of Louisville Journal of Respiratory Infections

Introduction: Experts suggest a short duration of antibiotic therapy (DOT) in responding patients with community-acquired pneumonia (CAP). The aim of this study was to evaluate clinical outcomes after hospital discharge among patients treated with short-course antibiotic therapy (SCT) vs. long-course antibiotic therapy (LCT) for CAP.

Methods: A secondary analysis of the Community-Acquired Pneumonia Organization (CAPO) database from January 2007 to June 2013 was performed, including hospitalized CAP patients who reached clinical stability within 5 days. Two groups were identified: patients who were treated with antibiotic therapy for a total duration of 5 days or less (SCT Group) vs. …

Analysis Of The Local And Systemic Cytokine Response Profiles In Patients With Community-Acquired Pneumonia. Relationship With Disease Severity And Outcomes., Rafael Fernandez-Botran, Timothy Lee Wiemken, Robert R. Kelley, Paula Peyrani, Jose Bordon, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

The goals of this study were to investigate the relationship of systemic and local cytokine responses with time to clinical stability (TCS) in patients with community-acquired pneumonia (CAP) and to develop a model to integrate multiple cytokine data into “cytokine response profiles” based on local vs. systemic and pro- vs. anti-inflammatory cytokine patterns in order to better understand their relationships with measures of CAP severity and outcomes. Forty hospitalized patients enrolled through the Community Acquired Pneumonia Inflammatory Study Group (CAPISG) were analyzed. Based on the ranked distribution of the levels of eight different pro-inflammatory cytokines and chemokines (IL-1b, IL-6, IL-8, …

Impact Of Temperature Relative Humidity And Absolute Humidity On The Incidence Of Hospitalizations For Lower Respiratory Tract Infections Due To Influenza, Rhinovirus, And Respiratory Syncytial Virus: Results From Community-Acquired Pneumonia Organization (Capo) International Cohort Study, Timothy L. Wiemken, William A. Mattingly, Stephen P. Furmanek, Brian E. Guinn, Connor L. English, Ruth Carrico, Paula Peyrani, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Abstract

Background: Transmissibility of several etiologies of lower respiratory tract infections (LRTI) may vary based on outdoor climate factors. The objective of this study was to evaluate the impact of outdoor temperature, relative humidity, and absolute humidity on the incidence of hospitalizations for lower respiratory tract infections due to influenza, rhinovirus, and respiratory syncytial virus (RSV).

Methods: This was a secondary analysis of an ancillary study of the Community Acquired Pneumonia Organization (CAPO) database. Respiratory viruses were detected using the Luminex xTAG respiratory viral panel. Climate factors were obtained from the National Weather Service. Adjusted Poisson regression models with robust …

Predicting 30-Day Mortality In Hospitalized Patients With Community-Acquired Pneumonia Using Statistical And Machine Learning Approaches, Timothy L. Wiemken, Stephen P. Furmanek, William A. Mattingly, Brian E. Guinn, Rodrigo Cavallazzi, Rafael Fernandez-Botran, Leslie A Wolf, Connor L. English, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Predicting if a hospitalized patient with community-acquired pneumonia (CAP) will or will not survive after admission to the hospital is important for research purposes as well as for institution of early patient management interventions. Although population-level mortality prediction scores for these patients have been around for many years, novel patient-level algorithms are needed. The objective of this study was to assess several statistical and machine learning models for their ability to predict 30-day mortality in hospitalized patients with CAP.

Methods: This was a secondary analysis of the University of Louisville (UofL) Pneumonia Study database. Six different statistical and/or machine …

A 49-Year-Old Woman With Chronic Skin Lesions, Acute Mental Status Changes And New Pulmonary Infiltrate: Case Discussion From The University Of Louisville Hospital, Bhavani Puskur, Youssef Khafateh, Srikant Ramachandruni, Veronica Corcino, Mark Burns, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Clinical Research: Educational Videos - The Process Of Clinical Research: Step-By-Step From Idea To Publication, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Clinical research can be defined as the creation and dissemination of new knowledge with the goal to improve outcomes in patients with a particular health problem. In this short video, Dr. Julio Ramirez, from the University of Louisville, offers an overview of the process of clinical research and describe how an investigator moves from the generation of an idea to the publication of study findings.

Timelines Of Translational Science: From Technology Initiation To Fda Approval, Laura M. Mcnamee, Michael Jay Walsh, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

While timelines for clinical development have been extensively studied, there is little data on the broader path from initiation of research on novel drug targets, to approval of drugs based on this research. We examined timelines of translational science for 138 drugs and biologicals approved by the FDA from 2010±2014 using an analytical model of technology maturation. Research on targets for 102 products exhibited a characteristic (S-curve) maturation pattern with exponential growth between statistically defined technology initiation and established points. The median initiation was 1974, with a median of 25 years to the established point, 28 years to first clinical …

Cyclin B1 Mediates The Effect Of Uchl1 In Promoting Cell Cycle Progression In Uterine Papillary Serous Carcinoma, Suet Ying Kwan

Dissertations and Theses (Open Access)

Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer with poor survival rates and a high risk of recurrence. The rarity of UPSC poses challenges to the discovery of novel targeted therapies. Therefore, the purpose of this dissertation was to identify novel therapeutic targets that could aid in the management of UPSC. To do so, we began with the relatively large cohort of UPSC cases in the TCGA data set, which was used to identify differentially expressed genes between UPSC and low-grade endometrioid endometrial carcinoma (EEC) and normal tissue.

We identified Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1 …

Molecular Determinants Of Residual Disease In Ovarian Cancer, Kshipra M. Gharpure

Dissertations and Theses (Open Access)

The standard treatment for high grade serous ovarian cancer is primary cytoreductive surgery followed by adjuvant chemotherapy. Residual disease followed by surgery is associated with adverse overall and progression-free survival as well as poor response to adjuvant chemotherapy. Accurate identification of patients at high risk of residual disease will help avoid unnecessary surgeries and help in triaging these patients to neoadjuvant chemotherapy prior to interval surgical debulking. In this study, we address this clinical issue by identifying and validating molecular biomarkers that can predict the likelihood of residual disease in ovarian cancer patients. Using publically available databases and microarray datasets, …

Integrative Analysis Of Omics Data In Adult Glioma And Other Tcga Cancers To Guide Precision Medicine, Xin Hu, Xin Hu

Dissertations and Theses (Open Access)

Transcriptomic profiling and gene expression signatures have been widely applied as effective approaches for enhancing the molecular classification, diagnosis, prognosis or prediction of therapeutic response towards personalized therapy for cancer patients. Thanks to modern genome-wide profiling technology, scientists are able to build engines leveraging massive genomic variations and integrating with clinical data to identify “at risk” individuals for the sake of prevention, diagnosis and therapeutic interventions. In my graduate work for my Ph.D. thesis, I have investigated genomic sequencing data mining to comprehensively characterise molecular classifications and aberrant genomic events associated with clinical prognosis and treatment response, through applying high-dimensional …