Digital Commons Network^™

Dnmt3a Deficiency In The Skin Causes Focal, Canonical Dna Hypomethylation And A Cellular Proliferation Phenotype, David Y. Chen, Ian M. Ferguson, Krista A. Braun, Leslie A. Sutton, Nichole M. Helton, Sai Mukund Ramakrishnan, Amanda M. Smith, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Single-Cell Analyses Of Crohn’S Disease Tissues Reveal Intestinal Intraepithelial T Cells Heterogeneity And Altered Subset Distributions, Natalia Jaeger, Ramya Gamini, Marina Cella, Jorge L. Schettini, Mattia Bugatti, Shanrong Zhao, Charles V. Rosadini, Ekaterina Esaulova, Blanda Di Luccia, Baylee Kinnett, William Vermi, Maxim N. Artyomov, Thomas A. Wynn, Ramnik J. Xavier, Scott A. Jelinsky, Marco Colonna

Open Access Publications

No abstract provided.

Monocyte Progenitors Give Rise To Multinucleated Giant Cells, Anne Kathrin Lösslein, Micah D. Dunlap, Shabaana A. Khader, Et Al.

Open Access Publications

No abstract provided.

Old Vaccines For New Infections: Exploiting Innate Immunity To Control Covid-19 And Prevent Future Pandemics, Konstantin Chumakov, Michael S. Avidan, Christine S. Benn, Stefano M. Bertozzi, Lawrence Blatt, Angela Y. Chang, Dean T. Jamison, Shabaana A. Khader, Shyam Kottilil, Mihai G. Netea, Annie Sparrow, Robert C. Gallo

Open Access Publications

No abstract provided.

The Sars-Cov-2 Nucleocapsid Protein Is Dynamic, Disordered, And Phase Separates With Rna, Jasmine Cubuk, Jhullian J. Alston, J. Jeremías Incicco, Sukrit Singh, Melissa D. Stuchell-Brereton, Michael D. Ward, Maxwell I. Zimmerman, Neha Vithani, Daniel Griffith, Jason A. Wagoner, Gregory R. Bowman, Kathleen B. Hall, Andrea Soranno, Alex S. Holehouse

Open Access Publications

No abstract provided.

Chromosome Xq23 Is Associated With Lower Atherogenic Lipid Concentrations And Favorable Cardiometabolic Indices, Pradeep Natarajan, Lucinda Antonacci-Fulton, Susan K. Dutcher, D.C. Rao, C. Charles Gu, Karen Schwander, Yun Ju Sung, Et Al.

Open Access Publications

No abstract provided.

Pushing The Needle Of Entrepreneurship And Innovation: Where Do Plastic And Reconstructive Surgeons Stand?, Sumun Khetpal, Alvaro Reátegui, Joseph Lopez, Justin M. Sacks, Adnan Prsic

Open Access Publications

No abstract provided.

Role Of Sirt1 In Isoflurane Conditioning-Induced Neurovascular Protection Against Delayed Cerebral Ischemia Secondary To Subarachnoid Hemorrhage, Meizi Liu, Keshav Jayaraman, Tusar Giri, Gregory J Zipfel, Umeshkumar Athiraman

Open Access Publications

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, …

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 …

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 …

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 …

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

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 …

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.

Functional Interaction Between Wnt And Bmp Signaling In Periosteal Bone Growth, Deye Song, Guangxu He, Yu Shi, Jiangdong Ni, Fanxin Long

Open Access Publications

No abstract provided.

Multitarget Stool Rna Test For Noninvasive Detection Of Colorectal Neoplasia In A Multicenter, Prospective, And Retrospective Cohort, Erica K. Barnell, Yiming Kang, Andrew R. Barnell, Kimberly R. Kruse, Jared Fiske, Zachary R. Pittz, Adnan R. Khan, Thomas A. Huebner, Faith L. Holmes, Malachi Griffith, Obi L. Griffith, Aadel A. Chaudhuri, Elizabeth M. Wurtzler

Open Access Publications

No abstract provided.

Impact Of Intrauterine Fetal Resuscitation With Oxygen On Oxidative Stress In The Developing Rat Brain, Jia Jiang, Tusar Giri, Nandini Raghuraman, Alison G. Cahill, Arvind Palanisamy

Open Access Publications

No abstract provided.

Acetylated Tau Inhibits Chaperone-Mediated Autophagy And Promotes Tau Pathology Propagation In Mice, Benjamin Caballero, Celeste M. Karch, Et Al.

Open Access Publications

No abstract provided.

Pathogenesis And Current Treatment Of Osteosarcoma: Perspectives For Future Therapies, Richa Rathore, Brian A Van Tine

Open Access Publications

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. The standard-of-care curative treatment for osteosarcoma utilizes doxorubicin, cisplatin, and high-dose methotrexate, a standard that has not changed in more than 40 years. The development of patient-specific therapies requires an in-depth understanding of the unique genetics and biology of the tumor. Here, we discuss the role of normal bone biology in osteosarcomagenesis, highlighting the factors that drive normal osteoblast production, as well as abnormal osteosarcoma development. We then describe the pathology and current standard of care of osteosarcoma. Given the complex heterogeneity of osteosarcoma tumors, we …

Identification Of A Novel Genetic Marker For Risk Of Degenerative Rotator Cuff Disease Surgery In The Uk Biobank, Elizabeth L Yanik, Jay D Keener, Shiow J Lin, Graham A Colditz, Rick W Wright, Bradley A Evanoff, Nitin B Jain, Nancy L Saccone

Open Access Publications

BACKGROUND: While evidence indicates that familial predisposition influences the risk of developing degenerative rotator cuff disease (RCD), knowledge of specific genetic markers is limited. We conducted a genome-wide association study of RCD surgery using the UK Biobank, a prospective cohort of 500,000 people (40 to 69 years of age at enrollment) with genotype data.

METHODS: Cases with surgery for degenerative RCD were identified using linked hospital records. The cases were defined as an International Classification of Diseases, Tenth Revision (ICD-10) code of M75.1 determined by a trauma/orthopaedic specialist and surgery consistent with RCD treatment. Cases were excluded if a diagnosis …

Postnatal Expression Profiles Of Atypical Cadherin Fat1 Suggest Its Role In Autism, Jeannine A Frei, Cheryl J Brandenburg, Jonathan E Nestor, Didier M Hodzic, Celine Plachez, Helen Mcneill, Derek M Dykxhoorn, Michael W Nestor, Gene J Blatt, Yu-Chih Lin

Open Access Publications

Genetic studies have linked FAT1 (FAT atypical cadherin 1) with autism spectrum disorder (ASD); however, the role that FAT1 plays in ASD remains unknown. In mice, the function of Fat1 has been primarily implicated in embryonic nervous system development with less known about its role in postnatal development. We show for the first time that FAT1 protein is expressed in mouse postnatal brains and is enriched in the cerebellum, where it localizes to granule neurons and Golgi cells in the granule layer, as well as inhibitory neurons in the molecular layer. Furthermore, subcellular characterization revealed FAT1 localization in neurites and …

Telomere Erosion In Human Pluripotent Stem Cells Leads To Atr-Mediated Mitotic Catastrophe, Alexandre T. Vessoni, Tianpeng Zhang, Annabel Quinet, Ho-Chang Jeong, Michael Munroe, Matthew Wood, Enzo Tedone, Alessandro Vindigni, Jerry W. Shay, Roger A. Greenberg, Luis F.Z. Batista

Open Access Publications

It is well established that short telomeres activate an ATM-driven DNA damage response that leads to senescence in terminally differentiated cells. However, technical limitations have hampered our understanding of how telomere shortening is signaled in human stem cells. Here, we show that telomere attrition induces ssDNA accumulation (G-strand) at telomeres in human pluripotent stem cells (hPSCs), but not in their differentiated progeny. This led to a unique role for ATR in the response of hPSCs to telomere shortening that culminated in an extended S/G2 cell cycle phase and a longer period of mitosis, which was associated with aneuploidy and mitotic …

Endothelial Ether Lipids Link The Vasculature To Blood Pressure, Behavior, And Neurodegeneration, Larry D. Spears, Sangeeta Adak, Guifang Dong, Xiaochao Wei, George Spyropoulos, Qiang Zhang, Li Yin, Chu Feng, Donghua Hu, Irfan J. Lodhi, Fong-Fu Hsu, Rithwick Rajagopal, Kevin K. Noguchi, Carmen M. Halabi, Lindsey Brier, Annie R. Bice, Brian V. Lananna, Erik S. Musiek, Oshri Avraham, Valeria Cavalli, Jerrah K. Holth, David M. Holtzman, David F. Wozniak, Joseph P. Culver, Clay F. Semenkovich

Open Access Publications

No abstract provided.

Acitretin Mitigates Uroporphyrin‑Induced Bone Defects In Congenital Erythropoietic Porphyria Models, Juliana Bragazzi Cunha, Jared S. Elenbaas, Dhiman Maitra, Ning Kuo, Rodrigo Azuero-Dajud, Allison C. Ferguson, Megan S. Griffin, Stephen I. Lentz, Jordan A. Shavit, M. Bishr Omary

Open Access Publications

No abstract provided.

Informative Regions In Viral Genomes, Jaime Leonardo Moreno-Gallego, Alejandro Reyes

Open Access Publications

Viruses, far from being just parasites affecting hosts' fitness, are major players in any microbial ecosystem. In spite of their broad abundance, viruses, in particular bacteriophages, remain largely unknown since only about 20% of sequences obtained from viral community DNA surveys could be annotated by comparison with public databases. In order to shed some light into this genetic dark matter we expanded the search of orthologous groups as potential markers to viral taxonomy from bacteriophages and included eukaryotic viruses, establishing a set of 31,150 ViPhOGs (Eukaryotic Viruses and Phages Orthologous Groups). To do this, we examine the non-redundant viral diversity …

Acceleration Of Small Intestine Development And Remodeling Of The Microbiome Following Hyaluronan 35 Kda Treatment In Neonatal Mice, Hala Chaaban, Kathryn Burge, Jeffrey Eckert, Majoi Trammell, David Dyer, Ravi S Keshari, Robert Silasi, Girija Regmi, Cristina Lupu, Misty Good, Steven J Mcelroy, Florea Lupu

Open Access Publications

The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 …

Prospective Spect-Ct Organ Dosimetry-Driven Radiation-Absorbed Dose Escalation Using The In-111 (111in)/Yttrium 90 (90y) Ibritumomab Tiuxetan (Zevalin ®) Theranostic Pair In Patients With Lymphoma At Myeloablative Dose Levels, Richard L Wahl, Eric C Frey, Heather A Jacene, Brad S Kahl, Steven Piantadosi, Jesus A Bianco, Richard J Hammes, Miah Jung, Wayne Kasecamp, Bin He, George Sgouros, Ian W Flinn, Lode J Swinnen

Open Access Publications

PURPOSE: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin's lymphoma using the theranostic pair of

METHODS: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts > 75,000/mm

RESULTS: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of

CONCLUSIONS: Patient-specific outpatient

Single Cell Transcriptional And Chromatin Accessibility Profiling Redefine Cellular Heterogeneity In The Adult Human Kidney, Yoshiharu Muto, Parker C. Wilson, Nicolas Ledru, Haojia Wu, Henrik Dimke, Sushrut S. Waikar, Benjamin D. Humphreys

Open Access Publications

No abstract provided.