Digital Commons Network^™

Gut Microbiome Contributions To Altered Metabolism In A Pig Model Of Undernutrition, Hao-Wei Chang, Nathan P. Mcnulty, Matthew C. Hibberd, David O'Donnell, Jiye Cheng, Vincent Lombard, Bernard Henrissat, Olga Ilkayeva, Michael J. Muehlbauer, Christopher B. Newgard, Michael J. Barratt, Xi Lin, Jack Odle, Jeffrey I. Gordon

Open Access Publications

No abstract provided.

A Domestic Cat Whole Exome Sequencing Resource For Trait Discovery, Alana R. Rodney, Rueben M. Buckley, Robert S. Fulton, Catrina Fronick, Todd Richmond, Christopher R. Helps, Peter Pantke, Dianne J. Trent, Karen M. Vernau, John S. Munday, Andrew C. Lewin, Rondo Middleton, Leslie A. Lyons, Wesley C. Warren

Open Access Publications

No abstract provided.

Advantages Of 18f-Fdg Pet/Ct Imaging Over Modified Duke Criteria And Clinical Presumption In Patients With Challenging Suspicion Of Infective Endocarditis, Valentin Pretet, Cyrille Blondet, Yvon Ruch, Matias Martinez, Soraya El Ghannudi, Olivier Morel, Yves Hansmann, Thomas H Schindler, Alessio Imperiale

Open Access Publications

According to European Society of Cardiology guidelines (ESC2015) for infective endocarditis (IE) management, modified Duke criteria (mDC) are implemented with a degree of clinical suspicion degree, leading to grades such as "possible" or "rejected" IE despite a persisting high level of clinical suspicion. Herein, we evaluate the

African Americans Have Differences In Csf Soluble Trem2 And Associated Genetic Variants, Suzanne E. Schindler, Carlos Cruchaga, Amulya Jospeh, Lena Mccue, Fabiana H.G. Farias, Consuelo H. Wilkins, Yuetiva Deming, Rachel L. Henson, Robert J. Mikesell, Laura Piccio, Jorge J. Llibre-Guerra, Krista L. Moulder, Anne M. Fagan, Beau M. Ances, Tammie L.S. Benzinger, Chengjie Xiong, David M. Holtzman, John C. Morris

Open Access Publications

No abstract provided.

Cohort Study Protocol To Characterize The Incidence And Severity Of Neuropathic Pain In Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Chioma U. Odozor, Kristen Roles, Carrie Burk, Thomas Kannampallil, David B. Clifford, Jay F. Piccirillo, Simon Haroutounian

Open Access Publications

No abstract provided.

Kcnk3 Mutation Causes Altered Immune Function In Pulmonary Arterial Hypertension Patients And Mouse Models, James D West, Eric D Austin, Elise M Rizzi, Ling Yan, Harikrishna Tanjore, Amber L Crabtree, Christy S Moore, Gladson Muthian, Erica J Carrier, David A Jacobson, Rizwan Hamid, Peggy L Kendall, Susan Majka, Anandharajan Rathinasabapathy

Open Access Publications

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed

Genetics Of Substance Use Disorders: A Review, Joseph D Deak, Emma C Johnson

Open Access Publications

Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by …

Canonical And Interior Circular Rnas Function As Competing Endogenous Rnas In Psoriatic Skin, Xiaoxin Liu, Jacqueline Frost, Anne Bowcock, Weixiong Zhang

Open Access Publications

(1) Background: Understanding the function of circular RNAs (circRNAs), a class of noncoding RNA, in psoriatic skin can provide important insights into the complex regulation of genes contributing to the pathogenesis of psoriasis. (2) Methods: A novel method was applied to RNA-seq datasets from 93 skin biopsy samples to comprehensively identify circRNAs of all types, i.e., canonical circRNAs from the intron-exon junctions of mRNAs and interior circRNAs (i-circRNAs) from the interior regions of exons, introns, and intergenic regions. Selected circRNAs were experimentally validated by qRT-PCR and Sanger sequencing. CircRNAs with abundant and differential expression were identified and their putative function …

Lysophospholipid Acylation Modulates Plasma Membrane Lipid Organization And Insulin Sensitivity In Skeletal Muscle, Patrick J Ferrara, Haowei Song, John Turk, Et Al

Open Access Publications

Aberrant lipid metabolism promotes the development of skeletal muscle insulin resistance, but the exact identity of lipid-mediated mechanisms relevant to human obesity remains unclear. A comprehensive lipidomic analysis of primary myocytes from individuals who were insulin-sensitive and lean (LN) or insulin-resistant with obesity (OB) revealed several species of lysophospholipids (lyso-PLs) that were differentially abundant. These changes coincided with greater expression of lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme involved in phospholipid transacylation (Lands cycle). Strikingly, mice with skeletal muscle-specific knockout of LPCAT3 (LPCAT3-MKO) exhibited greater muscle lysophosphatidylcholine/phosphatidylcholine, concomitant with improved skeletal muscle insulin sensitivity. Conversely, skeletal muscle-specific overexpression of LPCAT3 (LPCAT3-MKI) …

Phase Ii Study Of Pazopanib With Oral Topotecan In Patients With Metastatic And Non-Resectable Soft Tissue And Bone Sarcomas, Brian Schulte, Nisha Mohindra, Mohammed Milhem, Steven Attia, Steven Robinson, Varun Monga, Angela C Hirbe, Peter Oppelt, John Charlson, Irene Helenowski, Susan Abbinanti, Rasima Cehic, Scott Okuno, Brian A Van Tine, Mark Agulnik

Open Access Publications

BACKGROUND: Pazopanib is active in refractory soft-tissue sarcoma (STS) and significantly prolongs PFS. Prior studies of combinations of metronomic topotecan with pazopanib have indicated preclinical evidence of response in patients with sarcoma.

METHODS: This prospective, single arm, phase II study evaluated the efficacy of the combination of pazopanib with topotecan in patients with metastatic or unresectable non-adipocytic STS. Furthermore, it incorporated exploratory arms for osteosarcoma and liposarcoma. The primary endpoint was progression-free rate at 12 weeks in the non-adipocytic STS cohort.

RESULTS: 57.5% of patients in the non-adipocytic STS cohort were progression free at 12 weeks, which did not meet …

Association Of Circulating Sex Hormones With Inflammation And Disease Severity In Patients With Covid-19, Sandeep Dhindsa, Nan Zhang, Michael J. Mcphaul, Zengru Wu, Amit K. Ghoshal, Emma C. Erlich, Kartik Mani, Gwendalyn J. Randolph, John R. Edwards, Philip A. Mudd, Abhinav Diwan

Open Access Publications

Importance: Male sex is a risk factor for developing severe COVID-19 illness. It is not known whether sex hormones contribute to this predisposition.

Objective: To investigate the association of concentrations of serum testosterone, estradiol, and insulinlike growth factor 1 (IGF-1, concentrations of which are regulated by sex hormone signaling) with COVID-19 severity.

Design, Setting, and Participants: This prospective cohort study was conducted using serum samples collected from consecutive patients who presented from March through May 2020 to the Barnes Jewish Hospital in St Louis, Missouri, with COVID-19 (diagnosed using nasopharyngeal swabs).

Exposures: Testosterone, estradiol, and IGF-1 concentrations were measured at …

Characteristics And Outcomes Among Us Patients Hospitalized For Ischemic Stroke Before Vs During The Covid-19 Pandemic, Adam De Havenon, John P. Ney, Brian Callaghan, Samuel Hohmann, Ernie Shippey, Shadi Yaghi, Mohammad Anadani, Jennifer J. Majersik

Open Access Publications

Importance: After the emergence of COVID-19, studies reported a decrease in hospitalizations of patients with ischemic stroke (IS), but there are little to no data regarding hospitalizations for the remainder of 2020, including outcome data from a large cohort of patients with IS and comorbid COVID-19.

Objective: To assess hospital discharge rates, demographic factors, and outcomes of hospitalization associated with the COVID-19 pandemic among US patients with IS before vs during the COVID-19 pandemic.

Design, Setting, and Participants: This retrospective cohort study used data from the Vizient Clinical Data Base on 324 013 patients with IS at 478 nonfederal hospitals …

Left Ventricle Phenotyping Utilizing Tissue Doppler Imaging In Premature Infants With Varying Severity Of Bronchopulmonary Dysplasia, Eunice Torres, Philip T Levy, Afif El-Khuffash, Hongjie Gu, Aaron Hamvas, Gautam K Singh

Open Access Publications

Bronchopulmonary dysplasia (BPD) is characterized by alveolar-capillary simplification and is associated with pulmonary hypertension (PH) in preterm infants. The contribution of left ventricle (LV) disease towards this severe BPD-PH phenotype is not well established. We aimed to describe the longitudinal trajectory of the LV function as measured by tissue Doppler imaging (TDI) and its association with BPD-PH. We retrospectively assessed prospectively acquired clinical and echocardiographic data from 77 preterm infants born between 2011 and 2013. We characterized the LV function by measuring systolic and diastolic myocardial velocities (s', e', a'), isovolumetric relaxation time (IVRT), and myocardial performance index with TDI …

Tdp-43 And Pink1 Mediate Chchd10s59l Mutation–Induced Defects In Drosophila And In Vitro, Minwoo Baek, Yun-Jeong Choe, Sylvie Bannwarth, Jihye Kim, Swati Maitra, Gerald W. Dorn Ii, J. Paul Taylor, Veronique Paquis-Flucklinger, Nam Chul Kim

Open Access Publications

No abstract provided.

Long-Term Intake Of Gluten And Cognitive Function Among Us Women, Yiqing Wang, Benjamin Lebwohl, Raaj Mehta, Yin Cao, Peter H.R. Green, Francine Grodstein, Manol Jovani, Paul Lochhead, Olivia I. Okereke, Laura Sampson, Walter C. Willett, Qi Sun, Andrew T. Chan

Open Access Publications

Importance: Gluten avoidance has been suggested as having a benefit to cognitive health among the general population, given the link between gluten and cognitive impairment in patients with celiac disease. However, data are lacking in individuals without celiac disease.

Objective: To examine whether gluten intake is associated with cognitive function in women without celiac disease.

Design, Setting, and Participants: This cohort study included US women who participated in the longitudinal, population-based Nurses' Health Study II and had not previously or subsequently been diagnosed with celiac disease. Dietary data were collected from 1991 to 2015, and data on cognitive function were …

Experimental Methods To Study The Pathogenesis Of Human Enteric Rna Viruses, Somya Aggarwal, Ebrahim Hassan, Megan T Baldridge

Open Access Publications

Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different …

Prognostic Assessment In High-Grade Soft-Tissue Sarcoma Patients: A Comparison Of Semantic Image Analysis And Radiomics, Jan C Peeken, Matthew B Spraker, Et Al

Open Access Publications

BACKGROUND: In patients with soft-tissue sarcomas of the extremities, the treatment decision is currently regularly based on tumor grading and size. The imaging-based analysis may pose an alternative way to stratify patients' risk. In this work, we compared the value of MRI-based radiomics with expert-derived semantic imaging features for the prediction of overall survival (OS).

METHODS: Fat-saturated T2-weighted sequences (T2FS) and contrast-enhanced T1-weighted fat-saturated (T1FSGd) sequences were collected from two independent retrospective cohorts (training: 108 patients; testing: 71 patients). After preprocessing, 105 radiomic features were extracted. Semantic imaging features were determined by three independent radiologists. Three machine learning techniques (elastic …

Procaspase-Activating Compound-1 Synergizes With Trail To Induce Apoptosis In Established Granulosa Cell Tumor Cell Line (Kgn) And Explanted Patient Granulosa Cell Tumor Cells In Vitro, Powel Crosley, Anniina Farkkila, Adrianne L Jenner, Chloé Burlot, Olivia Cardinal, Kyle G Potts, Kate Agopsowicz, Marjut Pihlajoki, Markku Heikinheimo, Morgan Craig, Yangxin Fu, Mary M Hitt

Open Access Publications

Granulosa cell tumors (GCT) constitute only ~5% of ovarian neoplasms yet have significant consequences, as up to 80% of women with recurrent GCT will die of the disease. This study investigated the effectiveness of procaspase-activating compound 1 (PAC-1), an activator of procaspase-3, in treating adult GCT (AGCT) in combination with selected apoptosis-inducing agents. Sensitivity of the AGCT cell line KGN to these drugs, alone or in combination with PAC-1, was tested using a viability assay. Our results show a wide range in cytotoxic activity among the agents tested. Synergy with PAC-1 was most pronounced, both empirically and by mathematical modelling, …

Analysis Of Delayed Surgical Treatment And Oncologic Outcomes In Clinical Stage I Non-Small Cell Lung Cancer, Brendan T. Heiden, Daniel B. Eaton, Kathryn E. Engelhardt, Su-Hsin Chang, Yan Yan, Mayank R. Patel, Daniel Kreisel, Ruben G. Nava, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri

Open Access Publications

Importance: The association between delayed surgical treatment and oncologic outcomes in patients with non-small cell lung cancer (NSCLC) is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis.

Objective: To use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes.

Design, Setting, and Participants: This retrospective cohort study was conducted using a novel data set from the Veterans Health Administration (VHA) system. Included patients had clinical stage I NSCLC and were undergoing resection from 2006 to 2016 within the VHA system. Time to surgical treatment …

Requirement Of Fc-Fc Gamma Receptor Interaction For Antibody-Based Protection Against Emerging Virus Infections, Shamus P Keeler, Julie M Fox

Open Access Publications

Identification of therapeutics against emerging and re-emerging viruses remains a continued priority that is only reinforced by the recent SARS-CoV-2 pandemic. Advances in monoclonal antibody (mAb) isolation, characterization, and production make it a viable option for rapid treatment development. While mAbs are traditionally screened and selected based on potency of neutralization in vitro, it is clear that additional factors contribute to the in vivo efficacy of a mAb beyond viral neutralization. These factors include interactions with Fc receptors (FcRs) and complement that can enhance neutralization, clearance of infected cells, opsonization of virions, and modulation of the innate and adaptive immune …

Current And Prospective Methods For Assessing Anti-Tumor Immunity In Colorectal Cancer, Yulia I Nussbaum, Yariswamy Manjunath, Kanve N Suvilesh, Wesley C Warren, Chi-Ren Shyu, Jussuf T Kaifi, Matthew A Ciorba, Jonathan B Mitchem

Open Access Publications

Colorectal cancer (CRC) remains one of the deadliest malignancies worldwide despite recent progress in treatment strategies. Though immune checkpoint inhibition has proven effective for a number of other tumors, it offers benefits in only a small group of CRC patients with high microsatellite instability. In general, heterogenous cell groups in the tumor microenvironment are considered as the major barrier for unveiling the causes of low immune response. Therefore, deconvolution of cellular components in highly heterogeneous microenvironments is crucial for understanding the immune contexture of cancer. In this review, we assimilate current knowledge and recent studies examining anti-tumor immunity in CRC. …

Braf-Mek Inhibitors As Steroid-Sparing Bridge Prior To Checkpoint Blockade Therapy In Symptomatic Intracranial Melanoma, Karam Khaddour, Tanner M. Johanns, George Ansstas

Open Access Publications

The introduction of immune checkpoint blockade (ICB) and BRAF-MEK inhibitors has substantially improved outcomes in patients with metastatic melanoma. However, several challenging factors may hinder the efficacy of ICB in patients with symptomatic intracranial metastatic melanoma who are immunosuppressed due to the use of steroids prior to the administration of ICB. This has resulted in the exclusion of patients treated with high dose steroid at baseline from the majority of ICB clinical trials. In addition, despite the high efficacy of BRAF-MEK inhibitors in

Computerized Tumor Multinucleation Index (Muni) Is Prognostic In P16+ Oropharyngeal Carcinoma, Can F Koyuncu, Wade L Thorstad, R D Chernock, Jingqin Luo, Et Al

Open Access Publications

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from …

Diagnostic Accuracy Of Health Care Administrative Diagnosis Codes To Identify Nontuberculous Mycobacteria Disease: A Systematic Review, Carlos Mejia-Chew, Lauren Yaeger, Kevin Montes, Thomas C. Bailey, Margaret A. Olsen

Open Access Publications

Background: Health care administrative database research frequently uses standard medical codes to identify diagnoses or procedures. The aim of this review was to establish the diagnostic accuracy of codes used in administrative data research to identify nontuberculous mycobacterial (NTM) disease, including lung disease (NTMLD).

Methods: We searched Ovid Medline, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to April 2019. We included studies assessing the diagnostic accuracy of

Results: We identified 5549 unique citations. Of the 96 full-text articles reviewed, 7 eligible studies of moderate quality (3730 participants) were included in …

Physical Activity, Weight, And Outcomes In Patients Receiving Chemotherapy For Metastatic Breast Cancer (C40502/Alliance), Jennifer A. Ligibel, Luke Huebner, Hope S. Rugo, Harold J. Burstein, Debra L. Toppmeyer, Carey K. Anders, Cynthia Ma, William T. Barry, Vera Suman, Lisa A. Carey, Ann H. Partridge, Clifford A. Hudis, Eric P. Winer

Open Access Publications

Background: Obesity and inactivity are associated with increased risk of cancer-related and overall mortality in breast cancer, but there are few data in metastatic disease.

Methods: Cancer and Leukemia Group B 40502 was a randomized trial of first-line taxane-based chemotherapy for patients with metastatic breast cancer. Height and weight were collected at enrollment. After 299 patients enrolled, the study was amended to assess recreational physical activity (PA) at enrollment using the Nurses' Health Study Exercise Questionnaire. Associations with progression-free survival (PFS) and overall survival (OS) were evaluated using stratified Cox modeling (strata included hormone receptor status, prior taxane, bevacizumab use, …

Molecular, Cellular And Functional Changes In The Retinas Of Young Adult Mice Lacking The Voltage-Gated K+ Channel Subunits Kv8.2 And K2.1, Xiaotian Jiang, Rabab Rashwan, Valentina Voigt, Jeanne Nerbonne, David M Hunt, Livia S Carvalho

Open Access Publications

Cone Dystrophy with Supernormal Rod Response (CDSRR) is a rare autosomal recessive disorder leading to severe visual impairment in humans, but little is known about its unique pathophysiology. We have previously shown that CDSRR is caused by mutations in the

Evaluation Of Perirenal Anatomic Landmarks On Computed Tomography To Reduce The Risk Of Thoracic Complications During Supracostal Percutaneous Nephrolithotomy, Alexander K. Chow, Shellee Ogawa, Cary Seigel, Kenneth G. Sands, Joel Vetter, Alana Desai, Ramakrishna Venkatesh

Open Access Publications

No abstract provided.

Tim4 Expression By Dendritic Cells Mediates Uptake Of Tumor-Associated Antigens And Anti-Tumor Responses, Nicoletta Caronni, William Vermi, Et Al.

Open Access Publications

No abstract provided.

Surgical Infection Society 2020 Updated Guidelines On The Management Of Complicated Skin And Soft Tissue Infections, Therese M. Duane, Jared M. Huston, Morgan Collom, Adam Beyer, Sara Parli, Sara Buckman, Mark Shapiro, Amy Mcdonald, Jose Diaz, Jeffrey M. Tessier, James Sanders

Open Access Publications

No abstract provided.

Longitudinal Growth Differentiation Factor 15 (Gdf15) And Long-Term Intraocular Pressure Fluctuation In Glaucoma: A Pilot Study, Jonathan B. Lin, Arsham Sheybani, Andrea Santeford, Rajendra S. Apte

Open Access Publications

No abstract provided.