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Full-Text Articles in Physical Sciences and Mathematics

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky Oct 2021

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …


Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg Jul 2021

Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg

Nursing Faculty Publications

The COVID-19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID-19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID-19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID-19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …


Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady Aug 2020

Near Simultaneous Laser Scanning Confocal And Atomic Force Microscopy (Conpokal) On Live Cells, Joree N. Sandin, Surya P. Aryal, Thomas E. Wilkop, Christopher I. Richards, Martha E. Grady

Physiology Faculty Publications

Techniques available for micro- and nano-scale mechanical characterization have exploded in the last few decades. From further development of the scanning and transmission electron microscope, to the invention of atomic force microscopy, and advances in fluorescent imaging, there have been substantial gains in technologies that enable the study of small materials. Conpokal is a portmanteau that combines confocal microscopy with atomic force microscopy (AFM), where a probe "pokes" the surface. Although each technique is extremely effective for the qualitative and/or quantitative image collection on their own, Conpokal provides the capability to test with blended fluorescence imaging and mechanical characterization. Designed …


Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki Dec 2019

Impact Of Motor Therapy With Dynamic Body-Weight Support On Functional Independence Measures In Traumatic Brain Injury: An Exploratory Study, Emily F. Anggelis, Elizabeth Salmon Powell, Philip M. Westgate, Amanda C. Glueck, Lumy Sawaki

Physical Medicine and Rehabilitation Faculty Publications

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments.

OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI.

METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = …


Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito Dec 2019

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …


Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha Nov 2019

Post-Acquisition Processing Confounds In Brain Volumetric Quantification Of White Matter Hyperintensities, Ahmed A. Bahrani, Omar M. Al-Janabi, Erin L. Abner, Shoshana H. Bardach, Richard J. Kryscio, Donna M. Wilcock, Charles D. Smith, Gregory A. Jicha

Neurology Faculty Publications

BACKGROUND: Disparate research sites using identical or near-identical magnetic resonance imaging (MRI) acquisition techniques often produce results that demonstrate significant variability regarding volumetric quantification of white matter hyperintensities (WMH) in the aging population. The sources of such variability have not previously been fully explored.

NEW METHOD: 3D FLAIR sequences from a group of randomly selected aged subjects were analyzed to identify sources-of-variability in post-acquisition processing that can be problematic when comparing WMH volumetric data across disparate sites. The methods developed focused on standardizing post-acquisition protocol processing methods to develop a protocol with less than 0.5% inter-rater variance.

RESULTS: A series …


Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru Oct 2019

Enhancing Timeliness Of Drug Overdose Mortality Surveillance: A Machine Learning Approach, Patrick J. Ward, Peter J. Rock, Svetla Slavova, April M. Young, Terry L. Bunn, Ramakanth Kavuluru

Kentucky Injury Prevention and Research Center Faculty Publications

BACKGROUND: Timely data is key to effective public health responses to epidemics. Drug overdose deaths are identified in surveillance systems through ICD-10 codes present on death certificates. ICD-10 coding takes time, but free-text information is available on death certificates prior to ICD-10 coding. The objective of this study was to develop a machine learning method to classify free-text death certificates as drug overdoses to provide faster drug overdose mortality surveillance.

METHODS: Using 2017–2018 Kentucky death certificate data, free-text fields were tokenized and features were created from these tokens using natural language processing (NLP). Word, bigram, and trigram features were created …


Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate Oct 2019

Socioemotional Selectivity And Psychological Health In Amyotrophic Lateral Sclerosis Patients And Caregivers: A Longitudinal, Dyadic Analysis, Suzanne C. Segerstrom, Edward J. Kasarskis, David W. Fardo, Philip M. Westgate

Psychology Faculty Publications

Objective: Socioemotional selectivity theory predicts that as the end of life approaches, goals and resources that provide immediate, hedonic reward become more important than those that provide delayed rewards. This study tested whether these goal domains differentially affected psychological health in the context of marital dyads in which one partner had been diagnosed with amyotrophic lateral sclerosis (ALS), a life-limiting disease.

Design: ALS patients (N = 102) being treated in three multidisciplinary clinics and their spouses (N = 100) reported their loneliness, financial worry and psychological health every 3 months for up to 18 months.

Main …


Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput Jun 2019

Tumor Heterogeneity As A Predictor Of Response To Neoadjuvant Chemotherapy In Locally Advanced Rectal Cancer, Alissa Greenbaum, David R. Martin, Therese J. Bocklage, Ji-Hyun Lee, Scott A. Ness, Ashwani Rajput

Pathology and Laboratory Medicine Faculty Publications

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) is the standard of care for locally advanced adenocarcinoma of the rectum, but it is currently unknown which patients have disease that will respond. This study tested the correlation between response to nCRT and intratumoral heterogeneity using next-generation sequencing assays.

PATIENTS AND METHODS: DNA was extracted from formalin-fixed, paraffin-embedded biopsy samples from a cohort of patients with locally advanced rectal adenocarcinoma (T3/4 or N1/2 disease) who received nCRT. High read-depth sequencing of > 400 cancer-relevant genes was performed. Tumor mutations and variant allele frequencies were used to calculate mutant-allele tumor heterogeneity (MATH) scores as measures of intratumoral …


Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo May 2019

Tdp-43 Proteinopathy In Aging: Associations With Risk-Associated Gene Variants And With Brain Parenchymal Thyroid Hormone Levels, Peter T. Nelson, Zsombor Gal, Wang-Xia Wang, Dana M. Niedowicz, Sergey C. Artiushin, Samuel Wycoff, Angela Wei, Gregory A. Jicha, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

TDP-43 proteinopathy is very prevalent among the elderly (affecting at least 25% of individuals over 85 years of age) and is associated with substantial cognitive impairment. Risk factors implicated in age-related TDP-43 proteinopathy include commonly inherited gene variants, comorbid Alzheimer's disease pathology, and thyroid hormone dysfunction. To test parameters that are associated with aging-related TDP-43 pathology, we performed exploratory analyses of pathologic, genetic, and biochemical data derived from research volunteers in the University of Kentucky Alzheimer's Disease Center autopsy cohort (n = 136 subjects). Digital pathologic methods were used to discriminate and quantify both neuritic and intracytoplasmic TDP-43 pathology …


Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang Apr 2019

Incorporating Pathway Information Into Feature Selection Towards Better Performed Gene Signatures, Suyan Tian, Chi Wang, Bing Wang

Biostatistics Faculty Publications

To analyze gene expression data with sophisticated grouping structures and to extract hidden patterns from such data, feature selection is of critical importance. It is well known that genes do not function in isolation but rather work together within various metabolic, regulatory, and signaling pathways. If the biological knowledge contained within these pathways is taken into account, the resulting method is a pathway-based algorithm. Studies have demonstrated that a pathway-based method usually outperforms its gene-based counterpart in which no biological knowledge is considered. In this article, a pathway-based feature selection is firstly divided into three major categories, namely, pathway-level selection, …


A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams Feb 2019

A Parent-Led Intervention To Promote Recovery Following Pediatric Injury: Study Protocol For A Randomized Controlled Trial, Meghan L. Marsac, Ginny Sprang, Leila Guller, Kristen L. Kohser, John M. Draus Jr., Nancy Kassam-Adams

Pediatrics Faculty Publications

Background: Injury is one of the most prevalent potentially emotionally traumatic events that children experience and can lead to persistent impaired physical and emotional health. There is a need for interventions that promote full physical and emotional recovery and that can be easily accessed by all injured children. Based on research evidence regarding post-injury recovery, we created the Cellie Coping Kit for Children with Injury intervention to target key mechanisms of action and refined the intervention based on feedback from children, families, and experts in the field. The Cellie Coping Kit intervention is parent-guided and includes a toy (for engagement), …


Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser Dec 2018

Large-Scale Genome-Wide Meta-Analysis Of Polycystic Ovary Syndrome Suggests Shared Genetic Architecture For Different Diagnosis Criteria, Felix Day, Tugce Karaderi, Michelle R. Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk, Margrit Urbanek, M. Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H. Mullin, Bronwyn G. A. Stuckey, Timothy D. Spector, Scott G. Wilson, Mark O. Goodarzi, Lea Davis, Barbara Obermayer-Pietsch, André G. Uitterlinden, Verneri Anttila, Benjamin M. Neale, Marjo-Riitta Jarvelin, Bart Fauser

Internal Medicine Faculty Publications

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related …


Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu Dec 2018

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …


Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh Nov 2018

Blood Transfusions In Preterm Infants: Changes On Perfusion Index And Intermittent Hypoxemia, Katrina T. Ibonia, Henrietta S. Bada, Philip M. Westgate, Enrique Gomez Pomar, Prasad Bhandary, Abhijit R. Patwardhan, Elie G. Abu Jawdeh

Pediatrics Faculty Publications

BACKGROUND

Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH.

STUDY DESIGN AND METHODS

We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO2) …


Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan Sep 2018

Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan

Applied Statistics Laboratory Faculty Publications

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes …


A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford Aug 2018

A Programme For Risk Assessment And Minimisation Of Progressive Multifocal Leukoencephalopathy Developed For Vedolizumab Clinical Trials, Asit Parikh, Kristin Stephens, Eugene Major, Irving Fox, Catherine Milch, Serap Sankoh, Michael H. Lev, James M. Provenzale, Jesse Shick, Mark Patti, Megan Mcauliffe, Joseph R. Berger, David B. Clifford

Neurology Faculty Publications

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory …


Absolute Configuration Of 2,2',3,3',6-Pentachlorinatedbiphenyl (Pcb 84) Atropisomers, Xueshu Li, Sean R. Parkin, Hans-Joachim Lehmler Jun 2018

Absolute Configuration Of 2,2',3,3',6-Pentachlorinatedbiphenyl (Pcb 84) Atropisomers, Xueshu Li, Sean R. Parkin, Hans-Joachim Lehmler

Chemistry Faculty Publications

Nineteen polychlorinated biphenyl (PCB) congeners, such as 2,2′,3,3′,6-pentachlorobiphenyl (PCB 84), display axial chirality because they form stable rotational isomers, or atropisomers, that are non-superimposable mirror images of each other. Although chiral PCBs undergo atropselective biotransformation and atropselectively alter biological processes, the absolute structure of only a few PCB atropisomers has been determined experimentally. To help close this knowledge gap, pure PCB 84 atropisomers were obtained by semi-preparative liquid chromatography with two serially connected Nucleodex β-PM columns. The absolute configuration of both atropisomers was determined by X-ray single-crystal diffraction. The PCB 84 atropisomer eluting first and second on the Nucleodex β-PM …


Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha Feb 2018

Motivators For Alzheimer's Disease Clinical Trial Participation, Shoshana H. Bardach, Sarah D. Holmes, Gregory A. Jicha

Graduate Center for Gerontology Faculty Publications

Background

Alzheimer’s disease (AD) research progress is impeded due to participant recruitment challenges. This study seeks to better understand, from the perspective of individuals engaged in clinical trials (CTs), research motivations.

Methods

Participants, or their caregivers, from AD treatment and prevention CTs were surveyed about research motivators.

Results

The 87 respondents had a mean age of 72.2, were predominantly Caucasian, 55.2% were male, and 56.3% had cognitive impairment. An overwhelming majority rated the potential to help themselves or a loved one and the potential to help others in the future as important motivators. Relatively few respondents were motivated by free …


Auditing Snomed Ct Hierarchical Relations Based On Lexical Features Of Concepts In Non-Lattice Subgraphs, Licong Cui, Olivier Bodenreider, Jay Shi, Guo-Qiang Zhang Feb 2018

Auditing Snomed Ct Hierarchical Relations Based On Lexical Features Of Concepts In Non-Lattice Subgraphs, Licong Cui, Olivier Bodenreider, Jay Shi, Guo-Qiang Zhang

Computer Science Faculty Publications

Objective—We introduce a structural-lexical approach for auditing SNOMED CT using a combination of non-lattice subgraphs of the underlying hierarchical relations and enriched lexical attributes of fully specified concept names. Our goal is to develop a scalable and effective approach that automatically identifies missing hierarchical IS-A relations.

Methods—Our approach involves 3 stages. In stage 1, all non-lattice subgraphs of SNOMED CT’s IS-A hierarchical relations are extracted. In stage 2, lexical attributes of fully-specified concept names in such non-lattice subgraphs are extracted. For each concept in a non-lattice subgraph, we enrich its set of attributes with attributes from its ancestor …


Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers Feb 2018

Neurotensin Receptor 3/Sortilin Contributes To Tumorigenesis Of Neuroendocrine Tumors Through Augmentation Of Cell Adhesion And Migration, Ji Tae Kim, Dana L. Napier, Heidi L. Weiss, Eun Y. Lee, Courtney M. Townsend, B. Mark Evers

Markey Cancer Center Faculty Publications

Neurotensin (NTS), a 13–amino acid peptide which is distributed predominantly along gastrointestinal tract, has multiple physiologic and pathologic functions, and its effects are mediated by three distinct NTS receptors (NTSRs). Overexpression and activation of NTS signaling components, especially NTS and/or NTSR1, are closely linked with cancer progression and metastasis in various types of cancers including neuroendocrine tumors (NETs). Although deregulation of NTSR3/sortilin has been implicated in a variety of human diseases, the expression and role of NTSR3/sortilin in NETs have not been elucidated. In this study, we investigated the expression and oncogenic effect of NTSR3/sortilin in NETs. Increased protein levels …


Microrna Expression Patterns In Human Anterior Cingulate And Motor Cortex: A Study Of Dementia With Lewy Bodies Cases And Controls, Peter T. Nelson, Wang-Xia Wang, Sarah A. Janse, Katherine L. Thompson Jan 2018

Microrna Expression Patterns In Human Anterior Cingulate And Motor Cortex: A Study Of Dementia With Lewy Bodies Cases And Controls, Peter T. Nelson, Wang-Xia Wang, Sarah A. Janse, Katherine L. Thompson

Sanders-Brown Center on Aging Faculty Publications

Overview

MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB).

Methods

RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals. RNA was profiled using Exiqon miRNA microarrays. Quantitative PCR for post-hoc replication was performed on separate cases (n=6 controls) and included RNA isolated from gray matter of MO, AC, primary somatosensory (BA 3), and dorsolateral prefrontal (BA 9) cortical regions.

Results

The miRNA expression patterns differed substantially according to …


Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks Dec 2017

Fluoroethoxy-1,4-Diphenethylpiperidine And Piperazine Derivatives: Potent And Selective Inhibitors Of [3H]Dopamine Uptake At The Vesicular Monoamine Transporter-2, Emily R. Hankosky, Shyam R. Joolakanti, Justin R. Nickell, Venumadhav Janganati, Linda P. Dwoskin, Peter A. Crooks

Pharmaceutical Sciences Faculty Publications

A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [3H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [3H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [3H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [3H]DA uptake at VMAT2, with Ki values in the nanomolar range (Ki = 0.014–0.073 μM). Compound 15d exhibited the highest affinity (Ki = 0.014 μM) at VMAT2, and had 160-, 5-, …


A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson Dec 2017

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …


Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah Nov 2017

Reducing Symptom Distress In Patients With Advanced Cancer Using An E-Alert System For Caregivers: Pooled Analysis Of Two Randomized Clinical Trials, David H. Gustafson, Lori L. Dubenske, Amy K. Atwood, Ming-Yuan Chih, Roberta A. Johnson, Fiona Mctavish, Andrew Quanbeck, Roger L. Brown, James F. Cleary, Dhavan Shah

Health and Clinical Sciences Faculty Publications

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could.

Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as …


Organic Solvent Exposure And Depressive Symptoms Among Licensed Pesticide Applicators In The Agricultural Health Study, Miriam Siegel, Sarah E. Starks, Wayne T. Sanderson, Freya Kamel, Jane A. Hoppin, Fred Gerr Nov 2017

Organic Solvent Exposure And Depressive Symptoms Among Licensed Pesticide Applicators In The Agricultural Health Study, Miriam Siegel, Sarah E. Starks, Wayne T. Sanderson, Freya Kamel, Jane A. Hoppin, Fred Gerr

Epidemiology and Environmental Health Faculty Publications

Purpose

Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among farmers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers.

Methods

Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0–60) …


Ordinal Convolutional Neural Networks For Predicting Rdoc Positive Valence Psychiatric Symptom Severity Scores, Anthony Rios, Ramakanth Kavuluru Nov 2017

Ordinal Convolutional Neural Networks For Predicting Rdoc Positive Valence Psychiatric Symptom Severity Scores, Anthony Rios, Ramakanth Kavuluru

Computer Science Faculty Publications

Background—The CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing (NLP) provided a set of 1000 neuropsychiatric notes to participants as part of a competition to predict psychiatric symptom severity scores. This paper summarizes our methods, results, and experiences based on our participation in the second track of the shared task.

Objective—Classical methods of text classification usually fall into one of three problem types: binary, multi-class, and multi-label classification. In this effort, we study ordinal regression problems with text data where misclassifications are penalized differently based on how far apart the ground truth and model predictions are …


Predicting Mental Conditions Based On "History Of Present Illness" In Psychiatric Notes With Deep Neural Networks, Tung Tran, Ramakanth Kavuluru Nov 2017

Predicting Mental Conditions Based On "History Of Present Illness" In Psychiatric Notes With Deep Neural Networks, Tung Tran, Ramakanth Kavuluru

Computer Science Faculty Publications

Background—Applications of natural language processing to mental health notes are not common given the sensitive nature of the associated narratives. The CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing (NLP) changed this scenario by providing the first set of neuropsychiatric notes to participants. This study summarizes our efforts and results in proposing a novel data use case for this dataset as part of the third track in this shared task.

Objective—We explore the feasibility and effectiveness of predicting a set of common mental conditions a patient has based on the short textual description of patient’s history …


Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane Oct 2017

Systems Biology Approach To Late-Onset Alzheimer's Disease Genome-Wide Association Study Identifies Novel Candidate Genes Validated Using Brain Expression Data And Caenorhabditis Elegans Experiments, Shubhabrata Mukherjee, Joshua C. Russell, Daniel T. Carr, Jeremy D. Burgess, Mariet Allen, Daniel J. Serie, Kevin L. Boehme, John S. K. Kauwe, Adam C. Naj, David W. Fardo, Dennis W. Dickson, Thomas J. Montine, Nilufer Ertekin-Taner, Matt R. Kaeberlein, Paul K. Crane

Biostatistics Faculty Publications

Introduction—We sought to determine whether a systems biology approach may identify novel late-onset Alzheimer's disease (LOAD) loci.

Methods—We performed gene-wide association analyses and integrated results with human protein-protein interaction data using network analyses. We performed functional validation on novel genes using a transgenic Caenorhabditis elegans Aβ proteotoxicity model and evaluated novel genes using brain expression data from people with LOAD and other neurodegenerative conditions.

Results—We identified 13 novel candidate LOAD genes outside chromosome 19. Of those, RNA interference knockdowns of the C. elegans orthologs of UBC, NDUFS3, EGR1, and ATP5H were associated with Aβ …


Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson Oct 2017

Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially …