Digital Commons Network^™

Association Of Blood Concentrations Of Complement Split Product Ic3b And Serum C3 With Systemic Lupus Erythematosus Disease Activity, Alfred H J Kim, Vibeke Strand, Deepali P Sen, Qiang Fu, Nancy L Mathis, Martin J Schmidt, Robin R Bruchas, Nick R Staten, Paul K Olson, Chad M Stiening, John P Atkinson

Open Access Publications

OBJECTIVE: To examine correlations between blood levels of complement split product iC3b and serum component C3 with clinically meaningful changes in disease activity in patients with systemic lupus erythematosus (SLE).

METHODS: A total of 159 consecutive patients with SLE, diagnosed according to the American College of Rheumatology or Systemic Lupus International Collaborating Clinics classification criteria, were enrolled in CASTLE (Complement Activation Signatures in Systemic Lupus Erythematosus), a prospective observational study. Patients with 1-7 study visits were included in this longitudinal analysis. In addition, 48 healthy volunteers were enrolled to establish a normal reference value for the ratio of blood iC3b …

Insulin Resistance And Chronic Kidney Disease Progression, Cardiovascular Events, And Death: Findings From The Chronic Renal Insufficiency Cohort Study, Sarah J Schrauben, Patricia Kao, Et Al

Open Access Publications

BACKGROUND: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD.

METHODS: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without …

Plaidoh: A Novel Method For Functional Prediction Of Long Non-Coding Rnas Identifies Cancer-Specific Lncrna Activities, Sarah C Pyfrom, Hong Luo, Jacqueline E Payton

Open Access Publications

BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments.

RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods. PLAIDOH integrates transcriptome, subcellular localization, enhancer landscape, genome architecture, chromatin interaction, …

Comprehensive Gene Expression Meta-Analysis Identifies Signature Genes That Distinguish Microglia From Peripheral Monocytes/Macrophages In Health And Glioma, Verena Haage, Marcus Semtner, Ramon Oliveira Vidal, Daniel Perez Hernandez, Winnie W Pong, Zhihong Chen, Dolores Hambardzumyan, Vincent Magrini, Amy Ly, Jason Walker, Elaine Mardis, Philipp Mertins, Sascha Sauer, Helmut Kettenmann, David H Gutmann

Open Access Publications

Monocytes/macrophages have begun to emerge as key cellular modulators of brain homeostasis and central nervous system (CNS) disease. In the healthy brain, resident microglia are the predominant macrophage cell population; however, under conditions of blood-brain barrier leakage, peripheral monocytes/macrophages can infiltrate the brain and participate in CNS disease pathogenesis. Distinguishing these two populations is often challenging, owing to a paucity of universally accepted and reliable markers. To identify discriminatory marker sets for microglia and peripheral monocytes/macrophages, we employed a large meta-analytic approach using five published murine transcriptional datasets. Following hierarchical clustering, we filtered the top differentially expressed genes (DEGs) through …

An Observational Study Of End-Tidal Carbon Dioxide Trends In General Anesthesia, Annemarie Akkermans, Judith A R Van Waes, Aleda Thompson, Amy Shanks, Linda M Peelen, Michael F Aziz, Daniel A Biggs, William C Paganelli, Jonathan P Wanderer, Daniel L Helsten, Sachin Kheterpal, Wilton A Van Klei, Leif Saager

Open Access Publications

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO

METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO

RESULTS: Both TWA-AUC and median ETCO

CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO

Mitochondrial Fusion Supports Increased Oxidative Phosphorylation During Cell Proliferation, Cong-Hui Yao, Rencheng Wang, Yahui Wang, Che-Pei Kung, Jason D. Weber, Gary J. Patti

Open Access Publications

Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting …

Multiancestry Genome-Wide Association Study Of Lipid Levels Incorporating Gene-Alcohol Interactions, Paul S. De Vries, Yun J. Sung, Karen Schwander, Aldi T. Kraja, Mary F. Feitosa, Lisa De Las Fuentes, Renee De Mutsert, C Charles Gu, Yize Li, Treva K. Rice, Lihua Wang, Christine Williams, Mary K. Wojczynski, Michael A. Province, Dabeeru C. Rao, Et Al

Open Access Publications

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test …

A Randomized, Placebo-Controlled Trial Of Fidaxomicin For Prophylaxis Of Clostridium Difficile-Associated Diarrhea In Adults Undergoing Hematopoietic Stem Cell Transplantation, Kathleen M. Mullane, Erik R. Dubberke, Et Al

Open Access Publications

Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients.

Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin (200 mg) or a matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically-indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. …

Association Between 5-Year Clinical Outcome In Patients With Nonmedically Evacuated Mild Blast Traumatic Brain Injury And Clinical Measures Collected Within 7 Days Postinjury In Combat, Christine L. Mac Donald, Jason Barber, Jana Patterson, Ann M. Johnson, Sureyya Dikmen, Jesse R. Fann, Nancy Temkin

Open Access Publications

Importance: Although previous work has examined clinical outcomes in combat-deployed veterans, questions remain regarding how symptoms evolve or resolve following mild blast traumatic brain injury (TBI) treated in theater and their association with long-term outcomes.

Objective: To characterize 5-year outcome in patients with nonmedically evacuated blast concussion compared with combat-deployed controls and understand what clinical measures collected acutely in theater are associated with 5-year outcome.

Design, Setting, and Participants: A prospective, longitudinal cohort study including 45 service members with mild blast TBI within 7 days of injury (mean 4 days) and 45 combat deployed nonconcussed controls was carried out. Enrollment …

Voltage-Independent Sk-Channel Dysfunction Causes Neuronal Hyperexcitability In The Hippocampus Of Fmr1 Knock-Out Mice, Pan-Yue Deng, Dan Carlin, Young Mi Oh, Leila K. Myrick, Stephen T. Warren, Valeria Cavalli, Vitaly A. Klyachko

Open Access Publications

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K

A Hox-Tale Regulatory Circuit For Neural Crest Patterning Is Conserved Across Vertebrates, Hugo J. Parker, Bony De Kumar, Stephen A. Green, Karin D. Prummel, Christopher Hess, Charles K. Kaufman, Christian Mosimann, Leanne M. Wiedemann, Marianne E. Bronner, Robb Krumlauf

Open Access Publications

No abstract provided.

Effect Of Tdcs On Aberrant Functional Network Connectivity In Refractory Hallucinatory Schizophrenia: A Pilot Study, Youngwoo Bryan Yoon, Minah Kim, Junhee Lee, Kang Ik K. Cho, Seoyeon Kwak, Tae Young Lee, Jun Soo Kwon

Open Access Publications

No abstract provided.

Aav-Mediated Taz Gene Replacement Restores Mitochondrial And Cardioskeletal Function In Barth Syndrome, Silveli Suzuki-Hatano, Madhurima Saha, Skylar A. Rizzo, Rachael L. Witko, Bennett J. Gosiker, Manashwi Ramanathan, Meghan S. Soustek, Michael D. Jones, Peter B. Kang, Barry J. Byrne, W. Todd Cade, Christina A. Pacak

Open Access Publications

No abstract provided.

Imaging Of Her2 With [89zr]Pertuzumab In Response To T-Dm1 Therapy, Adriana V.F. Massicano, Supum Lee, Bryant K. Crenshaw, Tolulope A. Aweda, Retta El Sayed, Ian Super, Ron Bose, Bernadette V. Marquez-Nostra, Suzanne E. Lapi

Open Access Publications

No abstract provided.

Clinical Trials In Multiple Sclerosis: Potential Future Trial Designs, Navid Manouchehri, Yinan Zhang, Amber Salter, Rehana Z Hussain, Hans-Peter Hartung, Bernhard Hemmer, Ralf Linker, Benjamin M Segal, Gary Cutter, Olaf Stüve

Open Access Publications

Clinical trials of new treatments in multiple sclerosis (MS) currently require large sample sizes and long durations in order to yield reliable results. The differential responses of an already heterogeneous population of MS patients to individual disease-modifying therapies (DMTs) will further complicate future trials. MS trials with smaller samples and faster outcomes are conceivable through the substitution of current clinical and MRI outcomes with objectively measureable genomic and proteomic biomarkers. Currently, biomarkers that could be utilized for diagnosis and monitoring of MS disease activity are in the early validation phase. The power of single biomarkers or multiple correlated biomarkers to …

Mild Chronic Perturbation Of Inhibition Severely Alters Hippocampal Function, Min-Yu Sun, Luke Ziolkowski, Peter Lambert, Hong-Jin Shu, Micah Keiser, Nicholas Rensing, Natasha Warikoo, Monika Martinek, Carson Platnick, Ann Benz, John Bracamontes, Gustav Akk, Joe Henry Steinbach, Charles F. Zorumski, Michael Wong, Steven Mennerick

Open Access Publications

No abstract provided.

A Short Translational Ramp Determines The Efficiency Of Protein Synthesis, Manasvi Verma, Junhong Choi, Kyle A. Cottrell, Zeno Lavagnino, Erica N. Thomas, Slavica Pavlovic-Djuranovic, Pawel Szczesny, David W. Piston, Hani S. Zaher, Joseph D. Puglisi, Sergej Djuranovic

Open Access Publications

No abstract provided.

The Single-Cell Transcriptomic Landscape Of Early Human Diabetic Nephropathy, Parker C. Wilson, Haojia Wu, Yuhei Kirita, Kohei Uchimura, Nicolas Ledru, Helmut G. Rennke, Paul A. Welling, Sushrut S. Waikar, Benjamin D. Humphreys

Open Access Publications

No abstract provided.

The Architecture Of Functional Lateralisation And Its Relationship To Callosal Connectivity In The Human Brain, Vyacheslav R. Karolis, Maurizio Corbetta, Michel Thiebaut De Schotten

Open Access Publications

No abstract provided.

Effectiveness Of Postoperative Radiotherapy After Radical Cystectomy For Locally Advanced Bladder Cancer, Benjamin W. Fischer-Valuck, Jeff M. Michalski, Todd A. Dewees, Eric Kim, Zachary L. Smith, Gerald L. Andriole, Vivek Arora, Arnold Bullock, Robert S. Figenshau, Robert L. Grubb, Eric M. Knoche, Russell K. Pachynski, Bruce J. Roth, Hiram A. Gay, Brian C. Baumann, Et Al

Open Access Publications

No abstract provided.

Monthly Extended-Release Risperidone (Rbp-7000) In The Treatment Of Schizophrenia, Anne Andorn, Jay Graham, John Csernansky, John W. Newcomer, Sunita Shinde, Gilbert Muma, Christian Heidbreder, Maurizio Fava

Open Access Publications

No abstract provided.

Palatine Tonsillar Metastasis Of Lung Adenocarcinoma: An Unusual Immunohistochemical Phenotype And A Potential Diagnostic Pitfall, Ying Tian, Yunan Han, Jiang Du, Yao Zhang, Nan Liu, Xin Du, Bo Li

Open Access Publications

Metastasis rarely occurs to the palatine tonsils. Herein, we present an exceedingly rare case of palatine tonsillar metastasis from poorly differentiated lung adenocarcinoma with anaplastic lymphoma kinase (ALK) mutation in a 51-year-old woman. The patient manifested clinically as pharyngalgia without obvious respiratory symptoms, with swelling tonsil histomorphologically resembling lymphoma and partially expressing the markers of epithelial and squamous cell carcinoma (CK5/6, P63, and P40). Due to the non-specific immunohistochemical expression, it is easily misdiagnosed as a primary poorly differentiated squamous cell carcinoma of the tonsil. This case highlights the importance of a comprehensive assessment of suspicious tonsillar lesions, that may …

Comparison Of Voxel-Wise And Histogram Analyses Of Glioma Adc Maps For Prediction Of Early Therapeutic Change, Thomas L. Chenevert, Dariya I. Malyarenko, Craig J. Galban, Diana M. Gomez-Hassan, Pia C. Sundgren, Christina I. Tsien, Brian D. Ross

Open Access Publications

No abstract provided.

Toward A Comprehensive View Of Cancer Immune Responsiveness: A Synopsis From The Sitc Workshop, Davide Bedognetti, David G. Denardo, Et Al

Open Access Publications

No abstract provided.

Multiplatform Urinary Metabolomics Profiling To Discriminate Cachectic From Non-Cachectic Colorectal Cancer Patients: Pilot Results From The Colocare Study, Jennifer Ose, Adetunji T Toriola, Et Al

Open Access Publications

Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary metabolic profiles in newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (

Transcriptomic Analysis Of Enteropathy In Zambian Children With Severe Acute Malnutrition, Mubanga Chama, Beatrice C. Amadi, Kanta Chandwe, Kanekwa Zyambo, Ellen Besa, Nurmohammad Shaikh, I. Malick Ndao, Phillip I. Tarr, Chad Storer, Richard Head, Paul Kelly

Open Access Publications

No abstract provided.

A Mixture Of U.S. Food And Drug Administration–Approved Monoaminergic Drugs Protects The Retina From Light Damage In Diverse Models Of Night Blindness, Henri Leinonen, Elliot H. Choi, Anthony Gardella, Vladimir J. Kefalov, Krzysztof Palczewski

Open Access Publications

No abstract provided.

Lung Transplant Referral For Individuals With Cystic Fibrosis: Cystic Fibrosis Foundation Consensus Guidelines, Kathleen J. Ramos, Patrick J. Smith, Edward F. Mckone, Joseph M. Pilewski, Amy Lucy, Sarah E. Hempstead, Erin Tallarico, Albert Faro, Daniel B. Rosenbluth, Alice L. Gray, Jordan M. Dunitz, Cf Lung Transplant Referral Guidelines Committee

Open Access Publications

No abstract provided.

Computational Search For Uv Radiation Resistance Strategies In Deinococcus Swuensis Isolated From Paramo Ecosystems, Jorge Díaz-Riaño, Leonardo Posada, Iván Camilo Acosta, Carlos Ruíz-Pérez, Catalina García-Castillo, Alejandro Reyes, María Mercedes Zambrano

Open Access Publications

Ultraviolet radiation (UVR) is widely known as deleterious for many organisms since it can cause damage to biomolecules either directly or indirectly via the formation of reactive oxygen species. The goal of this study was to analyze the capacity of high-mountain Espeletia hartwegiana plant phyllosphere microorganisms to survive UVR and to identify genes related to resistance strategies. A strain of Deinococcus swuensis showed a high survival rate of up to 60% after UVR treatment at 800J/m2 and was used for differential expression analysis using RNA-seq after exposing cells to 400J/m2 of UVR (with >95% survival rate). Differentially expressed genes were …

The Upper-Airway Microbiota And Loss Of Asthma Control Among Asthmatic Children, Yanjiao Zhou, Leonard B. Bacharier, Mario Castro, Gregory A. Storch, Kristine Wylie, Avraham Beigelman, Et Al.

Open Access Publications

No abstract provided.