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2020

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Full-Text Articles in Medicine and Health Sciences

Malignant Eccrine Adenoma With Sarcomatous (Heterologous) Components: Report Of A Rare Skin Adnexal Neoplasm With Literature Review, Hira Ishtiaq, Muhammad Abdulwaasey, Muhammad Usman Tariq, Saira Fatima Dec 2020

Malignant Eccrine Adenoma With Sarcomatous (Heterologous) Components: Report Of A Rare Skin Adnexal Neoplasm With Literature Review, Hira Ishtiaq, Muhammad Abdulwaasey, Muhammad Usman Tariq, Saira Fatima

Department of Pathology and Laboratory Medicine

Malignant eccrine spiradenoma (MES) is an exceedingly rare skin adnexal tumor that arises from pre-existing benign eccrine spiradenoma (BES). MES tumors show a wide spectrum of morphological features, posing a diagnostic challenge to the pathologist. Sarcomatous (heterologous) elements are seen in a few of these tumors, further complicating the morphological picture. We herein describe a case of a 66-year-old male who presented with a recently enlarging, ulcerated, nodular skin lesion over the right leg that had been present for the last 25 years. The patient underwent wide local excision of the tumor. Microscopic examination revealed a neoplastic lesion comprising benign …


Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon Dec 2020

Genetic Variants In Immune Related Genes As Predictors Of Responsiveness To Bcg Immunotherapy In Metastatic Melanoma Patients., Romela Irene Ramos, Misa A Shaw, Leland Foshag, Stacey L Stern, Negin Rahimzadeh, David Elashoff, Dave Hoon

Articles, Abstracts, and Reports

Adjuvant immunotherapy in melanoma patients improves clinical outcomes. However, success is unpredictable due to inherited heterogeneity of immune responses. Inherent immune genes associated with single nucleotide polymorphisms (SNPs) may influence anti-tumor immune responses. We assessed the predictive ability of 26 immune-gene SNPs genomic panels for a clinical response to adjuvant BCG (Bacillus Calmette-Guérin) immunotherapy, using melanoma patient cohorts derived from three phase III multicenter clinical trials: AJCC (American Joint Committee on Cancer) stage IV patients given adjuvant BCG (pilot cohort; n = 92), AJCC stage III patients given adjuvant BCG (verification cohort; n = 269), and …


Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk Dec 2020

Epidemiology Of Non-Alcoholic Fatty Liver Disease And Risk Of Hepatocellular Carcinoma Progression, Krishna Chaitanya Thandra, Adam Barsouk, Kalyan Saginala, John Sukumar Aluru, Prashanth Rawla, Alexander Barsouk

Kimmel Cancer Center Faculty Papers

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Its incidence has grown alongside the increasing global prevalence of type 2 diabetes, obesity, and metabolic syndrome. The risk of progression to hepatocellular carcinoma for nonalcoholic steatohepatitis patients over 5 years is 8%, and despite targeted and immunotherapy treatment advances, HCC maintains a bleak 5-year survival of 19%. NAFLD’s primary risk factors are components of metabolic syndrome as well as possible sleep disturbances. NAFLD is most common among men 50-60 years of age, though incidence in women catches up after menopause. In the US, Hispanics are …


When Working Out Makes You Sick To Your Stomach: What To Know About Exercise-Induced Nausea, Anne R. Crecelius Dec 2020

When Working Out Makes You Sick To Your Stomach: What To Know About Exercise-Induced Nausea, Anne R. Crecelius

Health and Sport Science Faculty Publications

You’re doing it! You’re working out, reaping all those benefits of exercise that have been drilled into your head.

So you’re pedaling your heart out or running like you’re escaping a zombie horde. You’re feeling accomplished, on cloud nine, until … your stomach starts to churn. You may even feel dizzy. Your feelings of accomplishment have turned to agony as you deal with a bout of nausea.

Exercise-induced nausea is quite common, as are exercise-induced gastrointestinal (GI) problems in general, affecting perhaps up to 90% of endurance athletes.

So why does this happen and, more important, how can you prevent …


Differential Effects Of Rasa3 Mutations On Hematopoiesis Are Profoundly Influenced By Genetic Background And Molecular Variant., Ray F. Robledo, Steven L. Ciciotte, Joel H Graber, Yue Zhao, Amy J Lambert, Babette Gwynn, Nathaniel J Maki, Elena C Brindley, Emily Hartman, Lionel Blanc, Luanne L. Peters Dec 2020

Differential Effects Of Rasa3 Mutations On Hematopoiesis Are Profoundly Influenced By Genetic Background And Molecular Variant., Ray F. Robledo, Steven L. Ciciotte, Joel H Graber, Yue Zhao, Amy J Lambert, Babette Gwynn, Nathaniel J Maki, Elena C Brindley, Emily Hartman, Lionel Blanc, Luanne L. Peters

Faculty Research 2020

Studies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage. Here, conditional deletion in hematopoietic stem and progenitor cells (HSPCs) using Vav-iCre recapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, …


Mouse Mutant Phenotyping At Scale Reveals Novel Genes Controlling Bone Mineral Density., Anna L Swan, Christine Schütt, Jan Rozman, Maria Del Mar Muñiz Moreno, Stefan Brandmaier, Michelle Simon, Stefanie Leuchtenberger, Mark Griffiths, Robert Brommage, Piia Keskivali-Bond, Harald Grallert, Thomas Werner, Raffaele Teperino, Lore Becker, Gregor Miller, Ala Moshiri, John R Seavitt, Derek D Cissell, Terrence F Meehan, Elif F Acar, Christopher J Lelliott, Ann M Flenniken, Marie-France Champy, Tania Sorg, Abdel Ayadi, Robert E Braun, Heather Cater, Mary E Dickinson, Paul Flicek, Juan Gallegos, Elena J Ghirardello, Jason D Heaney, Sylvie Jacquot, Connor Lally, John G Logan, Lydia Teboul, Jeremy Mason, Nadine Spielmann, Colin Mckerlie, Stephen A. Murray, Lauryl M J Nutter, Kristian F Odfalk, Helen Parkinson, Jan Prochazka, Corey L Reynolds, Mohammed Selloum, Frantisek Spoutil, Karen L. Svenson, Taylor S Vales, Sara E Wells, Jacqueline K White, Radislav Sedlacek, Wolfgang Wurst, Kent K C Lloyd, Peter I Croucher, Helmut Fuchs, Graham R Williams, Duncan Bassett, Valerie Gailus-Durner, Yann Herault, Ann-Marie Mallon, Steve D M Brown, Philipp Mayer-Kuckuk, Martin Hrabe De Angelis, Impc Consortium Dec 2020

Mouse Mutant Phenotyping At Scale Reveals Novel Genes Controlling Bone Mineral Density., Anna L Swan, Christine Schütt, Jan Rozman, Maria Del Mar Muñiz Moreno, Stefan Brandmaier, Michelle Simon, Stefanie Leuchtenberger, Mark Griffiths, Robert Brommage, Piia Keskivali-Bond, Harald Grallert, Thomas Werner, Raffaele Teperino, Lore Becker, Gregor Miller, Ala Moshiri, John R Seavitt, Derek D Cissell, Terrence F Meehan, Elif F Acar, Christopher J Lelliott, Ann M Flenniken, Marie-France Champy, Tania Sorg, Abdel Ayadi, Robert E Braun, Heather Cater, Mary E Dickinson, Paul Flicek, Juan Gallegos, Elena J Ghirardello, Jason D Heaney, Sylvie Jacquot, Connor Lally, John G Logan, Lydia Teboul, Jeremy Mason, Nadine Spielmann, Colin Mckerlie, Stephen A. Murray, Lauryl M J Nutter, Kristian F Odfalk, Helen Parkinson, Jan Prochazka, Corey L Reynolds, Mohammed Selloum, Frantisek Spoutil, Karen L. Svenson, Taylor S Vales, Sara E Wells, Jacqueline K White, Radislav Sedlacek, Wolfgang Wurst, Kent K C Lloyd, Peter I Croucher, Helmut Fuchs, Graham R Williams, Duncan Bassett, Valerie Gailus-Durner, Yann Herault, Ann-Marie Mallon, Steve D M Brown, Philipp Mayer-Kuckuk, Martin Hrabe De Angelis, Impc Consortium

Faculty Research 2020

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored …


A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti Dec 2020

A Conformation Variant Of P53 Combined With Machine Learning Identifies Alzheimer Disease In Preclinical And Prodromal Stages, Giulia Abate, Marika Vezzoli, Letizia Polito, Antonio Guaita, Diego Albani, Moira Marizzoni, Emirena Garrafa, Alessandra Marengoni, Gianluigi Forloni, Giovanni B. Frisoni, Jeffrey L. Cummings, Maurizio Memo, Daniela Uberti

School of Medicine Faculty Publications

© 2020 by the authors. Li-censee MDPI, Basel, Switzerland. Early diagnosis of Alzheimer’s disease (AD) is a crucial starting point in disease man-agement. Blood-based biomarkers could represent a considerable advantage in providing AD-risk information in primary care settings. Here, we report new data for a relatively unknown blood-based biomarker that holds promise for AD diagnosis. We evaluate a p53-misfolding conformation rec-ognized by the antibody 2D3A8, also named Unfolded p53 (U-p532D3A8+), in 375 plasma samples derived from InveCe.Ab and PharmaCog/E-ADNI longitudinal studies. A machine learning approach is used to combine U-p532D3A8+ plasma levels with Mini-Mental State Examination (MMSE) and apolipoprotein E …


“We’Re, Like, The Most Unhealthy People In The Country”: Employing An Equity Lens To Reduce Barriers To Healthy Food Access In Rural Appalachia, Kathryn Cardarelli, Emily M. Dewitt, Rachel Gillespie, Heather Norman-Burgdolf, Natalie Jones, Janet Tietyen Mullins Dec 2020

“We’Re, Like, The Most Unhealthy People In The Country”: Employing An Equity Lens To Reduce Barriers To Healthy Food Access In Rural Appalachia, Kathryn Cardarelli, Emily M. Dewitt, Rachel Gillespie, Heather Norman-Burgdolf, Natalie Jones, Janet Tietyen Mullins

Dietetics and Human Nutrition Faculty Publications

Introduction

Obesity disproportionately affects rural communities, and Appalachia has some of the highest obesity rates in the nation. Successful policy, systems, and environmental (PSE) interventions to reduce obesity must reflect the circumstances of the population. We used a health equity lens to identify barriers and facilitators for healthy food access in Martin County, Kentucky, to design interventions responsive to social, cultural, and historical contexts.

Methods

We conducted 5 focus groups in Martin County, Kentucky, in fall 2019 to obtain perspectives on the local food system and gauge acceptability of PSE interventions. We used grounded theory to identify perceived barriers and …


Modeling Action Potential Reversals In Tunicate Hearts, John W. Cain, Luran He, Lindsay D. Waldrop Dec 2020

Modeling Action Potential Reversals In Tunicate Hearts, John W. Cain, Luran He, Lindsay D. Waldrop

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Tunicates are small invertebrates which possess a unique ability to reverse flow in their hearts. Scientists have debated various theories regarding how and why flow reversals occur. Here we explore the electrophysiological basis for reversals by simulating action potential propagation in an idealized model of the tubelike tunicate heart. Using asymptotic formulas for action potential duration and conduction velocity, we propose tunicate-specific parameters for a two-current ionic model of the action potential. Then, using a kinematic model, we derive analytical criteria for reversals to occur. These criteria inform subsequent numerical simulations of action potential propagation in a fiber paced at …


Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells Dec 2020

Quantifying Anticancer Drug Doxorubicin Binding To Dna Using Optical Tweezers, Zachary Ells

Honors Program Theses and Projects

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. …


Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett Dec 2020

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of …


Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu Dec 2020

Epigenetic Regulation Of Wnt Signaling By Carboxamide-Substituted Benzhydryl Amines That Function As Histone Demethylase Inhibitors, Wen Zhang, Vitaliy M. Sviripa, Yanqi Xie, Tianxin Yu, Meghan G. Haney, Jessica S. Blackburn, Charles A. Adeniran, Chang-Guo Zhan, David S. Watt, Chunming Liu

Molecular and Cellular Biochemistry Faculty Publications

Aberrant activation of Wnt signaling triggered by mutations in either Adenomatous Polyposis Coli (APC) or CTNNB1 (β-catenin) is a hallmark of colorectal cancers (CRC). As part of a program to develop epigenetic regulators for cancer therapy, we developed carboxamide-substituted benzhydryl amines (CBAs) bearing either aryl or heteroaryl groups that selectively targeted histone lysine demethylases (KDMs) and functioned as inhibitors of the Wnt pathway. A biotinylated variant of N-((5-chloro-8-hydroxyquinolin-7-yl) (4-(diethylamino)phenyl)-methyl)butyramide (CBA-1) identified KDM3A as a binding partner. KDM3A is a Jumonji (JmjC) domain-containing demethylase that is significantly upregulated in CRC. KDM3A regulates the demethylation of histone H3's lysine …


Core Commitments For Field Trials Of Gene Drive Organisms, Kanya C. Long, Luke Alphey, George J. Annas, Cinnamon S. Bloss, Karl J. Campbell, Jackson Champer, Chun-Hong Chen, Amit Choudhary, George M. Church, James P. Collins, Kimberly L. Cooper, Jason A. Delborne, Owain R. Edwards, Claudia I. Emerson, Kevin Esvelt, Sam Weiss Evans, Robert M. Friedman, Valentino M. Gantz, Fred Gould, Sarah Hartley, Elizabeth Heitman, Janet Hemingway, Hirotaka Kanuka, Jennifer Kuzma, James V. Lavery, Yoosook Lee, Marce Lorenzen, Jeantine E. Lunshof, John M. Marshall, Philipp W. Messer, Craig Montell, Kenneth A. Oye, Megan J. Palmer, Philippos Aris Papathanos, Prasad N. Paradkar, Antoinette J. Piaggio, Jason L. Rasgon, Gordana Rašić, Larisa Rudenko, J. Royden Saah, Maxwell J. Scott, Jolene T. Sutton, Adam E, Vorsino, Omar S. Akbari Dec 2020

Core Commitments For Field Trials Of Gene Drive Organisms, Kanya C. Long, Luke Alphey, George J. Annas, Cinnamon S. Bloss, Karl J. Campbell, Jackson Champer, Chun-Hong Chen, Amit Choudhary, George M. Church, James P. Collins, Kimberly L. Cooper, Jason A. Delborne, Owain R. Edwards, Claudia I. Emerson, Kevin Esvelt, Sam Weiss Evans, Robert M. Friedman, Valentino M. Gantz, Fred Gould, Sarah Hartley, Elizabeth Heitman, Janet Hemingway, Hirotaka Kanuka, Jennifer Kuzma, James V. Lavery, Yoosook Lee, Marce Lorenzen, Jeantine E. Lunshof, John M. Marshall, Philipp W. Messer, Craig Montell, Kenneth A. Oye, Megan J. Palmer, Philippos Aris Papathanos, Prasad N. Paradkar, Antoinette J. Piaggio, Jason L. Rasgon, Gordana Rašić, Larisa Rudenko, J. Royden Saah, Maxwell J. Scott, Jolene T. Sutton, Adam E, Vorsino, Omar S. Akbari

USDA Wildlife Services: Staff Publications

We must ensure that trials are scientifically, politically, and socially robust, publicly accountable, and widely transparent.

Gene drive organisms (GDOs), whose genomes have been genetically engineered to spread a desired allele through a population, have the potential to transform the way societies address a wide range of daunting public health and environmental challenges. The development, testing, and release of GDOs, however, are complex and often controversial. A key challenge is to clarify the appropriate roles of developers and others actively engaged in work with GDOs in decision-making processes, and, in particular, how to establish partnerships with relevant authorities and other …


Efficacy Of Pulmonary Ultrasound Compared To N-Terminal Prohormone Brain Natriuretic Peptide As A Diagnostic Tool For Congestive Heart Failure In Patients Presenting With Acute Dyspnea In The Emergency Setting, Leah Krohn, Michael Burns Dec 2020

Efficacy Of Pulmonary Ultrasound Compared To N-Terminal Prohormone Brain Natriuretic Peptide As A Diagnostic Tool For Congestive Heart Failure In Patients Presenting With Acute Dyspnea In The Emergency Setting, Leah Krohn, Michael Burns

Physician Assistant Capstones, 2020-current

Objective: To determine the efficacy of using pulmonary ultrasound as a diagnostic tool in acute dyspnea of undetermined cause compared to the use of serum N-Terminal prohormone Brain Natriuretic Peptide (NT-proBNP) in the diagnosis of heart failure.

Design: Systematic literature review

Methods: Searches were conducted in PubMed and Scopus using the terms pulmonary ultrasound and congestive heart failure and studies within the last 10 years. Studies that used pulmonary ultrasound compared to BNP as a marker for the diagnosis of heart failure were included.

Results: All three studies found that the use of pulmonary ultrasound was a more specific …


Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya Dec 2020

Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya

Publications

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed …


Let-Dependent Low Dose And Synergistic Inhibition Of Human Angiogenesis By Charged Particles: Validation Of Mirnas That Drive Inhibition, Amber M. Paul, Yen-Ruh Wuu, Burong Hu, Hazeem Okunola, Elizabeth A. Blaber, Margareth Cheng-Campbell, Afshin Beheshti, Peter Grabham Dec 2020

Let-Dependent Low Dose And Synergistic Inhibition Of Human Angiogenesis By Charged Particles: Validation Of Mirnas That Drive Inhibition, Amber M. Paul, Yen-Ruh Wuu, Burong Hu, Hazeem Okunola, Elizabeth A. Blaber, Margareth Cheng-Campbell, Afshin Beheshti, Peter Grabham

Publications

Space radiation inhibits angiogenesis by two mechanisms depending on the linear energy transfer (LET). Using human 3D micro-vessel models, blockage of the early motile stage of angiogenesis was determined to occur after exposure to low LET ions (/AMU), whereas inhibition of the later stages occurs after exposure to high LET ions (>8 KeV/AMU). Strikingly, the combined effect is synergistic, detectible as low as 0.06 Gy making mixed ion space radiation more potent. Candidates for bystander transmission are microRNAs (miRNAs), and analysis on miRNA-seq data from irradiated mice shows that angiogenesis would in theory be downregulated. Further analysis of three …


Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis Dec 2020

Correction: Moxley, R.A., Et Al. Intimate Attachment Of Escherichia Coli O157:H7 To Urinary Bladder Epithelium In The Gnotobiotic Piglet Model. Microorganisms 2020, 8, 263, Rodney A. Moxley, Tom W. Bargar, Stephen D. Kachman, Diane R. Baker, David Francis

School of Veterinary and Biomedical Sciences: Faculty Publications

The authors wish to make the following corrections to this paper [1]: On page 2, the sentence that reads, “Hence, EHEC is a rare but established cause of HUS in children and adults.” should read, “Hence, EHEC is a rare but established cause of UTI-associated HUS in children and adults.” On page 4, the sentence that reads, “As noted previously, 14 of 126 (13.3%) piglets orally inoculated with EHEC O157:H7 strains developed mild to moderate purulent cystitis within 8 d PI [25] (Table 1).” should read, “As noted previously, 14 of 105 (13.3%) piglets orally inoculated with EHEC O157:H7 strains …


Missing Lateral Relationships In Top‑Level Concepts Of An Ontology, Ling Zheng, Yan Chen, Hua Min, P. Lloyd Hildebrand, Hao Liu, Michael Halper, James Geller, Sherri De Coronado, Yehoshua Perl Dec 2020

Missing Lateral Relationships In Top‑Level Concepts Of An Ontology, Ling Zheng, Yan Chen, Hua Min, P. Lloyd Hildebrand, Hao Liu, Michael Halper, James Geller, Sherri De Coronado, Yehoshua Perl

Publications and Research

Background: Ontologies house various kinds of domain knowledge in formal structures, primarily in the form of concepts and the associative relationships between them. Ontologies have become integral components of many health information processing environments. Hence, quality assurance of the conceptual content of any ontology is critical. Relationships are foundational to the definition of concepts. Missing relationship errors (i.e., unintended omissions of important definitional relationships) can have a deleterious effect on the quality of an ontology. An abstraction network is a structure that overlays an ontology and provides an alternate, summarization view of its contents. One kind of abstraction network is …


Inaction On Lead Despite The Relevant Knowledge: Predictors, Covariates, And Outreach Implications, Alessandra Rossi, Bernabas Wolde, Pankaj Lal, Melissa Harclerode Dec 2020

Inaction On Lead Despite The Relevant Knowledge: Predictors, Covariates, And Outreach Implications, Alessandra Rossi, Bernabas Wolde, Pankaj Lal, Melissa Harclerode

Department of Biology Faculty Scholarship and Creative Works

Testing residential soil and paint for lead provides actionable information. By showing where and how much lead exists on the residence, it allows one to quantify risk and determine the best ways to reduce exposure along with the corresponding health and financial costs. For these reasons, several federal and state programs offer outreach to audiences on the benefits of testing residential soil and paint for lead. Not all individuals who know about lead’s adverse health effects, however, test their residence for lead, potentially limiting the actionable information that could have helped to reduce their exposure. Such individuals represent a challenge …


Outlier Concepts Auditing Methodology For A Large Family Of Biomedical Ontologies, Ling Zheng, Hua Min, Yan Chen, Vipina Keloth, James Geller, Yehoshua Perl, George Hripcsak Dec 2020

Outlier Concepts Auditing Methodology For A Large Family Of Biomedical Ontologies, Ling Zheng, Hua Min, Yan Chen, Vipina Keloth, James Geller, Yehoshua Perl, George Hripcsak

Publications and Research

Background: Summarization networks are compact summaries of ontologies. The “Big Picture” view offered by summarization networks enables to identify sets of concepts that are more likely to have errors than control concepts. For ontologies that have outgoing lateral relationships, we have developed the "partial-area taxonomy" summarization network. Prior research has identified one kind of outlier concepts, concepts of small partials-areas within partial-area taxonomies. Previously we have shown that the small partial-area technique works successfully for four ontologies (or their hierarchies).

Methods: To improve the Quality Assurance (QA) scalability, a family-based QA framework, where one QA technique is potentially applicable to …


A Drosophila Screen Identifies Nkcc1 As A Modifier Of Ngly1 Deficiency, Dana M Talsness, Katie G Owings, Emily Coelho, Gaelle Mercenne, John M Pleinis, Raghavendran Partha, Kevin A Hope, Aamir Zuberi, Nathan L Clark, Cathleen Lutz, Aylin R Rodan, Clement Y Chow Dec 2020

A Drosophila Screen Identifies Nkcc1 As A Modifier Of Ngly1 Deficiency, Dana M Talsness, Katie G Owings, Emily Coelho, Gaelle Mercenne, John M Pleinis, Raghavendran Partha, Kevin A Hope, Aamir Zuberi, Nathan L Clark, Cathleen Lutz, Aylin R Rodan, Clement Y Chow

Faculty Research 2020

N-Glycanase 1 (NGLY1) is a cytoplasmic deglycosylating enzyme. Loss-of-function mutations in the NGLY1 gene cause NGLY1 deficiency, which is characterized by developmental delay, seizures, and a lack of sweat and tears. To model the phenotypic variability observed among patients, we crossed a Drosophila model of NGLY1 deficiency onto a panel of genetically diverse strains. The resulting progeny showed a phenotypic spectrum from 0 to 100% lethality. Association analysis on the lethality phenotype, as well as an evolutionary rate covariation analysis, generated lists of modifying genes, providing insight into NGLY1 function and disease. The top association hit was Ncc69 (human NKCC1/2 …


Toll-Like Receptor 7 Is Required For Lacrimal Gland Autoimmunity And Type 1 Diabetes Development In Male Nonobese Diabetic Mice., Ivy L Debreceni, Michael S Chimenti, David V. Serreze, Aron M Geurts, Yi-Guang Chen, Scott M Lieberman Dec 2020

Toll-Like Receptor 7 Is Required For Lacrimal Gland Autoimmunity And Type 1 Diabetes Development In Male Nonobese Diabetic Mice., Ivy L Debreceni, Michael S Chimenti, David V. Serreze, Aron M Geurts, Yi-Guang Chen, Scott M Lieberman

Faculty Research 2020

Sjögren syndrome (SS) is an immunologically complex, chronic autoimmune disease targeting lacrimal and salivary glands. Nonobese diabetic (NOD) mice spontaneously develop inflammation of lacrimal and salivary glands with histopathological features similar to SS in humans including focal lymphocytic infiltrates in the affected glands. The innate immune signals driving lymphocytic infiltration of these glands are not well-defined. Here we evaluate the role of Toll-like receptor (TLR) 7 in the development of SS-like manifestations in NOD mice. We created a Tlr7 knockout NOD mouse strain and performed histological and gene expression studies to characterize the effects of TLR7 on autoimmunity development. TLR7 …


Mass Cytometry Defines Virus-Specific Cd4 + T Cells In Influenza Vaccination, Priyanka B Subrahmanyam, Tyson H Holmes, Dongxia Lin, Laura F Su, Gerlinde Obermoser, Jacques Banchereau, Virginia Pascual, Adolfo García-Sastre, Randy A Albrecht, Karolina Palucka, Mark M Davis, Holden T Maecker Dec 2020

Mass Cytometry Defines Virus-Specific Cd4 + T Cells In Influenza Vaccination, Priyanka B Subrahmanyam, Tyson H Holmes, Dongxia Lin, Laura F Su, Gerlinde Obermoser, Jacques Banchereau, Virginia Pascual, Adolfo García-Sastre, Randy A Albrecht, Karolina Palucka, Mark M Davis, Holden T Maecker

Faculty Research 2020

The antiviral response to influenza virus is complex and multifaceted, involving many immune cell subsets. There is an urgent need to understand the role of CD4+ T cells, which orchestrate an effective antiviral response, to improve vaccine design strategies. In this study, we analyzed PBMCs from human participants immunized with influenza vaccine, using high-dimensional single-cell proteomic immune profiling by mass cytometry. Data were analyzed using a novel clustering algorithm, denoised ragged pruning, to define possible influenza virus-specific clusters of CD4+ T cells. Denoised ragged pruning identified six clusters of cells. Among these, one cluster (Cluster 3) was found to increase …


Deep Learning-Based Cross-Classifications Reveal Conserved Spatial Behaviors Within Tumor Histological Images., Javad Noorbakhsh, Saman Farahmand, Ali Foroughi Pour, Sandeep Namburi, Dennis Caruana, David Rimm, Mohammad Soltanieh-Ha, Kourosh Zarringhalam, Jeffrey Chuang Dec 2020

Deep Learning-Based Cross-Classifications Reveal Conserved Spatial Behaviors Within Tumor Histological Images., Javad Noorbakhsh, Saman Farahmand, Ali Foroughi Pour, Sandeep Namburi, Dennis Caruana, David Rimm, Mohammad Soltanieh-Ha, Kourosh Zarringhalam, Jeffrey Chuang

Faculty Research 2020

Histopathological images are a rich but incompletely explored data type for studying cancer. Manual inspection is time consuming, making it challenging to use for image data mining. Here we show that convolutional neural networks (CNNs) can be systematically applied across cancer types, enabling comparisons to reveal shared spatial behaviors. We develop CNN architectures to analyze 27,815 hematoxylin and eosin scanned images from The Cancer Genome Atlas for tumor/normal, cancer subtype, and mutation classification. Our CNNs are able to classify TCGA pathologist-annotated tumor/normal status of whole slide images (WSIs) in 19 cancer types with consistently high AUCs (0.995 ± 0.008), as …


Maternal Prenatal Cortisol Programs The Infant Hypothalamic–Pituitary–Adrenal Axis, Jessica L. Irwin, Amy L. Meyering, Gage Peterson, Laura M. Glynn, Curt A. Sandman, Laurel M. Hicks, Elysia Poggi Davis Dec 2020

Maternal Prenatal Cortisol Programs The Infant Hypothalamic–Pituitary–Adrenal Axis, Jessica L. Irwin, Amy L. Meyering, Gage Peterson, Laura M. Glynn, Curt A. Sandman, Laurel M. Hicks, Elysia Poggi Davis

Psychology Faculty Articles and Research

One of the key proposed agents of fetal programming is exposure to maternal glucocorticoids. Experimental animal studies provide evidence that prenatal exposure to elevated maternal glucocorticoids has consequences for hypothalamic–pituitary–adrenal (HPA) axis functioning in the offspring. There are very few direct tests of maternal glucocorticoids, such as cortisol, during human pregnancy and associations with infant cortisol reactivity. The current study examined the link between maternal prenatal cortisol trajectories and infant cortisol reactivity to the pain of inoculation in a sample of 152 mother-infant (47.4% girls) pairs. The results from the current study provide insight into fetal programming of the infant …


Knowledge, Attitudes, And Practices Against The Growing Threat Of Covid-19 Among Medical Students Of Pakistan, Khola Noreen, Zil-E Rubab, Muhammad Umar, Rehana Rehman, Mukhtiar Baig, Fizzah Baig Dec 2020

Knowledge, Attitudes, And Practices Against The Growing Threat Of Covid-19 Among Medical Students Of Pakistan, Khola Noreen, Zil-E Rubab, Muhammad Umar, Rehana Rehman, Mukhtiar Baig, Fizzah Baig

Department of Biological & Biomedical Sciences

Background: On account of the COVID-19 pandemic, many changes have been implicated in university medical students. We are cognizant that pandemic can be controlled with dedicated contributions from all involved in the healthcare profession. Therefore, it is important to know the pandemic and application of knowledge by the medical students to formulate a further line of management in Pakistan.
Objective: We aimed toinvestigate the knowledge, attitudes, and practices (KAP) regarding COVID-19 and its impact on medical students of Pakistan.
Methods: A cross-sectional survey was conducted in June 2020 by a validated self-administered questionnaire. The survey instrument was tailored from a …


Translating Evidence-Based Guidelines Into Practice—Are We Getting It Right? A Multi-Centre Prospective International Audit Of Nutrition Care In Patients With Foregut Tumors (Inform), Merran Findlay, Judith D. Bauer, Rupinder Dhaliwal, Marian De Van Der Schueren, Alessandro Laviano, Adrianne Widaman, Lisa Martin, Andrew G. Day, Leah M. Gramlich Dec 2020

Translating Evidence-Based Guidelines Into Practice—Are We Getting It Right? A Multi-Centre Prospective International Audit Of Nutrition Care In Patients With Foregut Tumors (Inform), Merran Findlay, Judith D. Bauer, Rupinder Dhaliwal, Marian De Van Der Schueren, Alessandro Laviano, Adrianne Widaman, Lisa Martin, Andrew G. Day, Leah M. Gramlich

Faculty Research, Scholarly, and Creative Activity

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC (n = 119) or EC (n = 51) in 11 cancer …


Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan Dec 2020

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs predicted responses in …


The Involvement Of Neuroimmune Cells In Adipose Innervation., Magdalena Blaszkiewicz, Elizabeth Wood, Sigi Koizar, Jake Willows, Ryan Anderson, Yu-Hua Tseng, James W Godwin, Kristy L Townsend Dec 2020

The Involvement Of Neuroimmune Cells In Adipose Innervation., Magdalena Blaszkiewicz, Elizabeth Wood, Sigi Koizar, Jake Willows, Ryan Anderson, Yu-Hua Tseng, James W Godwin, Kristy L Townsend

Faculty Research 2020

BACKGROUND: Innervation of adipose tissue is essential for the proper function of this critical metabolic organ. Numerous surgical and chemical denervation studies have demonstrated how maintenance of brain-adipose communication through both sympathetic efferent and sensory afferent nerves helps regulate adipocyte size, cell number, lipolysis, and 'browning' of white adipose tissue. Neurotrophic factors are growth factors that promote neuron survival, regeneration, and plasticity, including neurite outgrowth and synapse formation. Peripheral immune cells have been shown to be a source of neurotrophic factors in humans and mice. Although a number of immune cells reside in the adipose stromal vascular fraction (SVF), it …


Prd-2 Directly Regulates Casein Kinase I And Counteracts Nonsense-Mediated Decay In The Neurospora Circadian Clock., Christina M Kelliher, Randy Lambreghts, Qijun Xiang, Christopher L. Baker, Jennifer J Loros, Jay C Dunlap Dec 2020

Prd-2 Directly Regulates Casein Kinase I And Counteracts Nonsense-Mediated Decay In The Neurospora Circadian Clock., Christina M Kelliher, Randy Lambreghts, Qijun Xiang, Christopher L. Baker, Jennifer J Loros, Jay C Dunlap

Faculty Research 2020

No abstract provided.