Digital Commons Network^™

Scalable Open Science Approach For Mutation Calling Of Tumor Exomes Using Multiple Genomic Pipelines, Kyle Ellrott, Matthew H Bailey, Gordon Saksena, Kyle R Covington, Cyriac Kandoth, Chip Stewart, Julian Hess, Singer Ma, Kami E Chiotti, Michael Mclellan, Heidi J Sofia, Carolyn Hutter, Gad Getz, David Wheeler, Li Ding, Mc3 Working Group, The Cancer Genome Atlas Research Network

Open Access Publications

The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. …

Interleukin-7 Restores Lymphocytes In Septic Shock: The Iris-7 Randomized Clinical Trial, Bruno Francois, Andrew H Walton, Jacqueline Unsinger, Teresa Blood, Jane Blood, Richard S Hotchkiss, Et Al

Open Access Publications

BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity.

METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 …

Physiological Mechanisms Of Sustained Fumagillin-Induced Weight Loss, Jie An, Michael L Patnode, Vanessa K Ridaura, Jeffrey I Gordon, Et Al

Open Access Publications

Current obesity interventions suffer from lack of durable effects and undesirable complications. Fumagillin, an inhibitor of methionine aminopeptidase-2, causes weight loss by reducing food intake, but with effects on weight that are superior to pair-feeding. Here, we show that feeding of rats on a high-fat diet supplemented with fumagillin (HF/FG) suppresses the aggressive feeding observed in pair-fed controls (HF/PF) and alters expression of circadian genes relative to the HF/PF group. Multiple indices of reduced energy expenditure are observed in HF/FG but not HF/PF rats. HF/FG rats also exhibit changes in gut hormones linked to food intake, increased energy harvest by …

Largest Gwas Of Ptsd (N=20 070) Yields Genetic Overlap With Schizophrenia And Sex Differences In Heritability., L E Duncan, A Ratanatharathorn, A E Aiello, L M Almli, A B Amstadter, A E Ashley-Koch, D G Baker, J C Beckham, L J Bierut, J Bisson, B Bradley, C-Y Chen, S Dalvie, L A Farrer, S Galea, M E Garrett, J E Gelernter, G Guffanti, M A Hauser, E O Johnson, R C Kessler, N A Kimbrel, A King, N Koen, H R Kranzler, M W Logue, A X Maihofer, A R Martin, M W Miller, R A Morey, N R Nugent, J P Rice, S Ripke, A L Roberts, N L Saccone, J W Smoller, D J Stein, M B Stein, J A Sumner, M Uddin, R J Ursano, D E Wildman, R Yehuda, H Zhao, M J Daly, I Liberzon, K J Ressler, C M Nievergelt, K C Koenen

Open Access Publications

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h

Phase 1b/2a Trial Of The Superoxide Dismutase Mimetic Gc4419 To Reduce Chemoradiotherapy-Induced Oral Mucositis In Patients With Oral Cavity Or Oropharyngeal Carcinoma, Carryn M Anderson, Stephen T Sonis, Christopher M Lee, Douglas Adkins, Bryan G Allen, Wenqing Sun, Sanjiv S Agarwala, Madhavi L Venigalla, Yuhchyau Chen, Weining Zhen, Diane R Mould, Jon T Holmlund, Jeffrey M Brill, John M Buatti

Open Access Publications

PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM).

PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending <60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT.

RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in …

Dural Tears In Adult Deformity Surgery: Incidence, Risk Factors, And Outcomes, Sravisht Iyer, Eric O Klineberg, Lukas P Zebala, Michael P Kelly, Robert A Hart, Munish C Gupta, D Kojo Hamilton, Gregory M Mundis, Daniel Sciubba, Christopher P Ames, Justin S Smith, Virginie Lafage, Douglas Burton, Han Jo Kim, International Spine Study Group (Issg)

Open Access Publications

Study Design: Retrospective cohort study.

Objectives: Describe the rate of dural tears (DTs) in adult spinal deformity (ASD) surgery. Describe the risk factors for DT and the impact of this complication on clinical outcomes.

Methods: Patients with ASD undergoing surgery between 2008 and 2014 were separated into DT and non-DT cohorts; demographics, operative details, radiographic, and clinical outcomes were compared. Statistical analysis included

Results: A total of 564 patients were identified. The rate of DT was 10.8% (n = 61). Patients with DT were older (61.1 vs 56.5 years,

Conclusions: The rate of DT was 10.8% in an ASD cohort. …

Successful Surgical Repair And Perioperative Management Of 6-Month-Old With Total Anomalous Pulmonary Venous Return In A Developing Country: Considerations For The Treatment Of Pulmonary Hypertension, Lakshmi Gokanapudy, Kenneth Remy, Sathappan Karuppiah, Eneida Melgar Humala, Ibrahim Abdullah, Michael Ruppe, William Schechter, Robert Michler, Joseph Tobias

Open Access Publications

Total anomalous pulmonary venous return (TAPVR) is a rare congenital cardiac defect, accounting for 1.5-3% of cases of congenital heart disease. With prenatal ultrasonography, the majority of these patients are diagnosed in utero with definitive surgery performed during the neonatal period. However, as prenatal screening may not be available in developing countries, patients may present in later infancy. We present successful surgical repair of a 6-month-old infant with TAPVR who presented for medical care at 5 months of age in Lima, Peru. The late presentation of such infants and the limited resources available for the treatment of elevated pulmonary vascular …

A Systematic, Intensive Statistical Investigation Of Data From The Comprehensive Analysis Of Reported Drugs (Card) For Compliance And Illicit Opioid Abstinence In Substance Addiction Treatment With Buprenorphine/Naloxone, Kenneth Blum, David Han, Edward J Modestino, Scott Saunders, A Kennison Roy 3rd, W Jacobs, Darryl S Inaba, David Baron, Marlene Oscar-Berman, Mary Hauser, Rajendra D Badgaiyan, David E Smith, John Femino, Mark S Gold

Open Access Publications

BACKGROUND: Buprenorphine and naloxone (bup/nal), a combination partial mu receptor agonist and low-dose delta mu antagonist, is presently recommended and used to treat opioid-use disorder. However, a literature review revealed a paucity of research involving data from urine drug tests that looked at compliance and abstinence in one sample.

METHOD: Statistical analysis of data from the Comprehensive Analysis of Reported Drugs (CARD) was used to assess compliance and abstinence during treatment in a large cohort of bup/nal patients attending chemical-dependency programs from eastern USA in 2010 and 2011.

RESULTS: Part 1: Bup/nal was present in 93.4% of first (n = …

Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu

Open Access Publications

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 …

Deletion Of Tsc2 In Nociceptors Reduces Target Innervation, Ion Channel Expression, And Sensitivity To Heat, Dan Carlin, Judith P. Golden, Amit Mogha, Vijay K. Samineni, Kelly R. Monk, Robert W. Gereau, Valeria Cavalli

Open Access Publications

No abstract provided.

Trpv1 Agonist, Capsaicin, Induces Axon Outgrowth After Injury Via Ca2+/Pka Signaling, Erin Frey, Scott Karney-Grobe, Trevor Krolak, Jeff Milbrandt, Aaron Diantonio

Open Access Publications

No abstract provided.

Cardiovascular Disease Risk Factor Responses To A Type 2 Diabetes Care Model Including Nutritional Ketosis Induced By Sustained Carbohydrate Restriction At 1 Year: An Open Label, Non-Randomized, Controlled Study, Nasir H. Bhanpuri, Sarah J. Hallberg, Paul T. Williams, Amy L. Mckenzie, Kevin D. Ballard, Wayne W. Campbell, James P. Mccarter, Stephen D. Phinney, Jeff S. Volek

Open Access Publications

No abstract provided.

Study Protocol For The Anesthesiology Control Tower—Feedback Alerts To Supplement Treatments (Actfast-3) Trial: A Pilot Randomized Controlled Trial In Intraoperative Telemedicine [Version 1; Referees: 2 Approved], Stephen Gregory, Teresa M. Murray-Torres, Bradley A. Fritz, Arbi Ben Abdallah, Daniel L. Helsten, Troy S. Wildes, Anshuman Sharma, Michael S. Avidan, Actfast Study Group

Open Access Publications

No abstract provided.

The Genetic Underpinnings Of Variation In Ages At Menarche And Natural Menopause Among Women From The Multi-Ethnic Population Architecture Using Genomics And Epidemiology (Page) Study: A Trans-Ethnic Meta-Analysis, D. C. Rao, Karen Schwander, Et Al.

Open Access Publications

No abstract provided.

Diagnostic Performance Of Multiplex Nucleic Acid Testing Of Bronchoalveolar Lavage And Bronchial Wash Specimens For Respiratory Viral Pathogens, Satish Munigala, Carey-Ann D. Burnham, Neil W. Anderson, Stephen Y. Liang, Steven J. Lawrence, David K. Warren

Open Access Publications

No abstract provided.

Amphiregulin Modifies The Minnesota Acute Graft-Versus-Host Disease Risk Score: Results From Bmt Ctn 0302/0802, Iskra Pusic

Open Access Publications

No abstract provided.

A Brain Electrical Activity Electroencephalographic-Based Biomarker Of Functional Impairment In Traumatic Brain Injury: A Multi-Site Validation Trial, Daniel Hanley, Leslie S. Prichep, Neeraj Badjatia, Jeffrey Bazarian, Richard Chiacchierini, Kenneth C. Curley, John Garrett, Elizabeth Jones, Rosanne Naunheim, Brian O'Neil, John O'Neill, David W. Wright, J. Stephen Huff

Open Access Publications

No abstract provided.

Feasibility Of Co-Registered Ultrasound And Acoustic-Resolution Photoacoustic Imaging Of Human Colorectal Cancer, Xiandong Leng, William Chapman, Bin Rao, Sreyankar Nandy, Ruimin Chen, Rehan Rais, Ivan Gonzalez, Qifa Zhou, Deyali Chatterjee, Matthew Mutch, Quing Zhu

Open Access Publications

No abstract provided.

Developing An Evidence-Based Program Sustainability Training Curriculum: A Group Randomized, Multi-Phase Approach, Rebecca Vitale, Timothy Blaine, Elizabeth Zofkie, Sarah Moreland-Russell, Todd Combs, Ross C. Brownson, Doug A. Luke

Open Access Publications

No abstract provided.

Fat Composition In Infant Formula Contributes To The Severity Of Necrotising Enterocolitis, Chhinder P. Sodhi, William B. Fulton, Misty Good, Mustafa Vurma, Tapas Das, Chron-Si Lai, Hongpeng Jia, Yukihiro Yamaguchi, Peng Lu, Thomas Prindle Jr, John A. Ozolek, David J. Hackam

Open Access Publications

No abstract provided.

Sustained Efficacy And Detailed Clinical Follow-Up Of First-Line Ibrutinib Treatment In Older Patients With Chronic Lymphocytic Leukemia: Extended Phase 3 Results From Resonate-2, Nancy L. Bartlett, Et Al.

Open Access Publications

No abstract provided.

Mycobacterium Tuberculosis Type Vii Secretion System Effectors Differentially Impact The Escrt Endomembrane Damage Response, Ekansh Mittal, Michael L. Skowyra, Grace Uwase, Emir Tinaztepe, Alka Mehra, Stefan Köster, Phyllis I. Hanson, Jennifer A. Philips

Open Access Publications

No abstract provided.

Phase I Studies Of Azd1208, A Proviral Integration Moloney Virus Kinase Inhibitor In Solid And Haematological Cancers, Geoffrey L. Uy, Et Al

Open Access Publications

No abstract provided.

Combining Immunotherapy With Radiation Therapy In Thoracic Oncology, Shahed N. Badiyan, Michael C. Roach, Michael D. Chuong, Stephanie R. Rice, Nasarachi E. Onyeuku, Jill Remick, Srinivas Chilukuri, Erica Glass, Pranshu Mohindra, Charles B. Simone Ii

Open Access Publications

No abstract provided.

Gpr56/Adgrg1 Regulates Development And Maintenance Of Peripheral Myelin, Sarah D. Ackerman, Amit Mogha, Breanne L. Harty, Mitchell D'Rozario, Nicholas E. Sanchez, Paul Gamble, Matthew R. Macewan, Wilson Zachary Ray, Kelly R. Monk, Et Al

Open Access Publications

No abstract provided.

Multilevel Correlates Of Household Anthropometric Typologies In Colombian Mothers And Their Infants, D. C. Parra, L. F. Gomez, L. Iannotti, D. Haire-Joshu, A. K. Sebert Kuhlmann, R. C. Brownson

Open Access Publications

No abstract provided.

Construction, Expression, And Characterization Of Rsea-Egf And In Vitro Evaluation Of Its Antitumor Activity Against Nasopharyngeal Cancer, Xueting Liu, Liping Zeng, Zhongqiu Zhou, Yang Xie, Shan Wang, Junyan Zhang, Ying He, Zehong Zou, Jianguo Zhang, Ailin Tao

Open Access Publications

No abstract provided.

Synthesis And Evaluation Of Troponoids As A New Class Of Antibiotics, Feng Cao, Cari Orth, Maureen J. Donlin, Patrick Adegboyega, Marvin J. Meyers, Ryan P. Murelli, Mohamed Elagawany, Bahaa Elgendy, John E. Tavis

Open Access Publications

No abstract provided.

Risk Of Surgical Site Infection (Ssi) Following Colorectal Resection Is Higher In Patients With Disseminated Cancer: An Nccn Member Cohort Study, Bruce Hall, Et Al

Open Access Publications

No abstract provided.

Pleiotropic Effects Of Variants In Dementia Genes In Parkinson Disease, Laura Ibanez, Umber Dube, Albert A. David, Maria V. Fernandez, John Budde, Breanna Cooper, Monica Diez-Fairen, Sara Ortega-Cubero, Pau Pastor, Joel S. Perlmutter, Carlos Cruchaga, Bruno A. Benitez

Open Access Publications

No abstract provided.