tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field</i>: Counterfeit Percocet–Related Overdose Cluster — Georgia, June 2017
Authors: Laura Edison, Amber Erickson, Sasha Smith, Gaylord Lopez, Stephanie Hon, Alexandra King, Nancy Nydam, J. Patrick O’Neal, Cherie Drenzek
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

multiagency press conferences on June 6 to notify the public about the presence of the dangerous counterfeit pills.A counterfeit Percocet cluster case was defined as 1) an opioid toxidrome (i.e., with central nervous system depression, respiratory depression, and pupillary miosis) requiring resuscitation, ventilation, naloxone, or all three; 2) a history of purchasing street pills; and 3) ingestion of as few as one or two pills, resulting in disproportionately severe central nervous system, respiratory, or cardiovascular depression occurring in a person evaluated by EMS or at an ED since June 1, 2017 (1).During June 6-13, EMS providers and EDs reported possible cases daily, and district epidemiologists reviewed medical records to determine whether patients met the case definition.Concomitant syndromic surveillance was conducted by reviewing Georgia statewide ED admission data received daily, using a text-search for drug overdose syndrome.This surveillance was used to determine whether the cluster extended beyond the initially identified area.Local law enforcement personnel delivered pills obtained from one patient to the Georgia Bureau of Investigation crime laboratory for chemical analysis.Syndromic surveillance demonstrated a sharp increase in overdoses reported by EDs on June 5 (Figure).Chemical analysis of obtained pills identified cyclopropyl fentanyl and U-47700, two rare and potent illicit synthetic opioids.The source of the pill was not identified.* The figure depicts all emergency department visits that met the overdose syndrome definition.Syndromic surveillance data cannot be used to determine whether these visits met the counterfeit Percocet cluster case definition, but they can monitor trends in overdoses.The North-Central Health District consists of 13 counties in central Georgia (http://northcentralhealthdistrict.org/).
Prognostic Value of Serial ST2 Measurements in Patients With Acute Heart Failure
Authors: Laura C. van Vark, Ivonne Lesman-Leegte, Sara J. Baart, Douwe Postmus, Yigal M. Pinto, Joke G. Orsel, B. Daan Westenbrink, Hans P. Brunner-la Rocca, Addy J.M. van Miltenburg, Eric Boersma, Hans L. Hillege, K. Martijn Akkerhuis
Journal: Journal of the American College of Cardiology (2017)
Incorporation of a Ligand Peptide for Immune Inhibitory Receptor LAIR‐1 on Biomaterial Surfaces Inhibits Macrophage Inflammatory Responses
Authors: Yoon Kyung Kim, Shu‐Hui Chu, Jessica Y. Hsieh, Cody M. Kamoku, Andrea J. Tenner, Wendy F. Liu, Szu‐Wen Wang
Journal: Advanced Healthcare Materials (2017)

Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory receptor broadly expressed on immune cells, with its ligands residing within the extracellular matrix protein collagen. In this study, surfaces are modified with a LAIR-1 ligand peptide (LP), and it is observed that macrophages cultured on LAIR-1 LP-conjugated surfaces exhibit significantly reduced secretion of inflammatory cytokines in response to proinflammatory stimuli that reflect an injured environment. These downregulated mediators include TNF-α, MIP-1α, MIP-1β, MIP-2, RANTES, and MIG. Knockdown of LAIR-1 using siRNA abrogates this inhibition of cytokine secretion, supporting the specificity of the inhibitory effect to this receptor. These results are the first to demonstrate that integration of LAIR-1 ligands with biomaterials could suppress inflammatory responses.
AIDS-Related Central Nervous System Toxoplasmosis With Increased 18F-Fluoroethyl-l-Tyrosine Amino Acid PET Uptake Due to LAT1/2 Expression of Inflammatory Cells
Authors: Markus Hutterer, Elisabeth Bumes, Markus J. Riemenschneider, Jirka Grosse, Dirk Hellwig, Norbert Galldiks, Karl-Josef Langen, Peter Hau
Journal: Clinical Nuclear Medicine (2017)

We report the case of a 40-year-old woman with a progressive right-sided hemiparesis. Standard MRI revealed a contrast-enhancing brain lesion within the left basal ganglia. Ffluoroethyl-L-tyrosine (F-FET) PET showed a distinct tracer uptake (lesion-to-brain ratio [LBR]: LBRmax = 2.03, LBRmean = 1.68) with a significant larger metabolic lesion volume than contrast-enhancement in MRI, indicating cerebral glioma. Surprisingly, histopathologic analysis demonstrated central nervous system toxoplasmosis with pronounced inflammatory reaction (reactive astrogliosis, microglia activation, macrophage, and T-lymphocyte infiltration), which was associated with strong LAT1/LAT2/CD98 expression. In conclusion, inflammatory brain lesions, such as cerebral toxoplasmosis, represent a potential pitfall of F-FET PET mimicking a brain tumor.
<i>Notes from the Field:</i> High Volume of Lyme Disease Laboratory Reporting in a Low-Incidence State — Arkansas, 2015–2016
Authors: Natalie A. Kwit, Elizabeth A. Dietrich, Christina Nelson, Richard Taffner, Jeannine Petersen, Martin Schriefer, Paul Mead, Susan Weinstein, Dirk Haselow
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Investigación transfronteriza de un brote epidémico de Shigella sonnei en un grupo de turistas noruegos tras un viaje a Rusia
Authors: B Schimmer, H Meldal, N G Perederij, L Vold, M A Petukhova, D Grahek-Ogden, K Nygård
Journal: Eurosurveillance (2007)

A principios de septiembre de 2006, se alerto al Instituto Noruego de Salud Publica de un brote de infecciones por Shigella sonnei (shigelosis) en 23 pasajeros noruegos que habian viajado en un autobus turistico desde Kirkenes, Noruega hasta Murmansk, Rusia.
Re: Maud Rijnders, Ronald de Wit, Joost L. Boormans, Martijn P.J. Lolkema, Astrid A.M. van der Veldt. Systematic Review of Immune Checkpoint Inhibition in Urological Cancers. Eur Urol. 2017;72:411–23
Authors: Nelson Martinez Merizalde Balarezo, Mark Monroe Rivera, Romina A. Tejada
Journal: European Urology (2017)
Abstract 16442: Reprogramming of p66Shc and JunD Improves Age-Related Dysfunction of Angiogenic Early Outgrowth Cells
Authors: Francesco Paneni, Sarah Costantino, Nicolle Kränkel, Francesco Cosentino, Thomas Lüscher
Journal: Circulation (2013)

Introduction:  Early outgrowth cells (EOCs) are important modulators of the vascular repair process, favouring myocardial neovascularization. Impairment of EOCs functionality in human aging is mostly driven by reactive oxygen species (ROS), but the molecular mechanisms remain largely unknown. We previously reported that transcription factor JunD and mitochondrial adaptor p66Shc are critically involved in ROS-induced vascular aging.   Hypothesis:  The present study investigates the role of JunD and p66Shc in age-related EOCs dysfunction.   Methods:  EOCs were isolated and cultured from peripheral blood mononuclear cells of young (25±3 years; n=7) and old (65±6 years; n=7) healthy volunteers enrolled via the Blood Donation Service of the University Hospital Zurich, Switzerland. Gene silencing of p66Shc was performed with siRNA technology (Microsynth®), while JunD overexpression was obtained with a predesigned vector (Origene®). Scrambled siRNA or empty vector were used as negative controls for p66Shc and JunD, respectively. Three days after transfection young and old EOCs were harvested for measurement of O2- levels by ESR spectroscopy, migration assay and real-time PCR. Written informed consent was obtained from all subjects.   Results:  EOCs isolated form old individuals showed increased p66Shc expression and JunD downregulation as compared with young subjects. p66Shc and JunD dysregulation in old EOCs was associated with increased O2- generation, blunted migration, upregulation of the NADPH subunit Nox2 as well as reduced expression of the scavenger enzymes manganese superoxide dismutase (MnSOD) and aldehyde dehydrogenase-2 (ALDH2). Interestingly, either p66Shc knockdown or JunD overexpression significantly suppressed age-related O2- production, improved EOCs migration and restored the balance between oxidant and antioxidant enzymes.   Conclusions:  p66Shc and JunD are critically involved in age-dependent EOCs dysfunction by altering their redox state. Modulation of aging and longevity genes may improve the clinical efficacy of stem cell therapy in elderly cardiovascular patients.
Injecting drug use continues in older drug users too
Authors: Peter Higgs, Paul Dietze
Journal: BMJ (2017)

Rao and Roche note that the number of people aged over 50 who have substance misuse problems is rising globally across a range of settings.1 This rise also applies to people who inject drugs, at least in the developed world.2

Australian surveillance data from 2016 indicate a large, ageing cohort of (predominantly) opioid injectors.3 Similarly, national data show that 22% of over …
TCT-75 Impact of the Timing of P2Y12 Inhibitor Discontinuation Prior to CABG in Patients with Left Main Disease: Results from the EXCEL Trial
Authors: Christopher Kelly, A. Pieter Kappetein, Joseph Sabik, William Brown, Piet Willem Boonstra, Yiran Zhang, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2017)
Integrin Î±6 variants and colorectal cancer
Authors: Jean-François Beaulieu
Journal: Gut (2017)

I read with interest the study by De Archangelis et al 1 on the protective role of hemidesmosomes against colitis and colorectal cancer using genetically modified mouse integrin α6 subunit mutant models. I was however surprised to read that, based on their observations with these α6 mutant mice, the authors concluded that the α6β4 integrin can be classified as a tumour suppressor in the colon. Indeed, earlier studies have reported that in carcinomas, α6β4 can be released from hemidesmosomes to become associated with microfilament-associated cell motility adhesomes and, consequently, engage in various signal transduction pathways that contribute to tumour progression.2 3 While it is recognised that the roles of α6β4 may …
Closed-loop interaction with the cerebral cortex using a novel micro-ECoG-based implant: the impact of beta vs. gamma stimulation frequencies on cortico-cortical spectral responses
Authors: C. Alexis Gkogkidis, Xi Wang, Tobias Schubert, Mortimer Gierthmühlen, Fabian Kohler, Andreas Schulze-Bonhage, Wolfram Burgard, Jörn Rickert, Jörg Haberstroh, Martin Schüttler, Thomas Stieglitz, Tonio Ball
Journal: Brain-Computer Interfaces (2017)

Medical brain implants for closed-loop interaction with the cerebral cortex promise new treatment options for brain disorders, and thus great efforts are being made to develop devices for long-term application. Closed-loop interaction can be implemented using electrophysiological recording techniques, and can be used to modulate local cortical activity or long-range functional connectivity. In a case study performed in sheep chronically implanted with a novel micro-electrocorticography-based device, we show that (1) open-loop single-pulse electrical stimulation (SPES) elicited the well-known cortico-cortical evoked potentials (CCEPs), and (2) closed-loop repetitive-pulse electrical stimulation (RPES) elicited specific cortico-cortical spectral responses (CCSRs). CCSRs were spatially focalized in the gamma band, compared with beta band independent of RPES frequency. The topography of CCSRs was different compared with CCEPs, suggesting that CCEPs and CCSRs capture different aspects of cortico-cortical connectivity. We propose that CCSRs provide new useful measures of functional connectivity, and that in particular gamma-band CCSRs may be an optimal choice if spatially precise closed-loop interaction is desired. However, the parameter space of micro-electrocorticography stimulation patterns and associated changes in μECoG frequency bands needs to be further explored and many questions remain before closed-loop brain implants can be used in clinical applications.
Bioethics Panels Open Door Slightly to Germline Gene Editing
Authors: Jeff Lyon
Journal: JAMA (2017)

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Long-term proton pump inhibitors and risk of gastric cancer development after treatment for <i>Helicobacter pylori</i>: a population-based study
Authors: Ka Shing Cheung, Esther W Chan, Angel Y S Wong, Lijia Chen, Ian C K Wong, Wai Keung Leung
Journal: Gut (2017)

Objective Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy. Designs This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure. Result Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years. Conclusion Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.
Abstract 18359: Long Term Follow-up of Aortic Coarctation Repair Using Leg-arm Blood Pressure Difference to Assess Hemodynamic Profiles
Authors: Daniel F Labuz, James A Berry, Lee A Pyles
Journal: Circulation (2015)

Introduction: Patients with successfully repaired coarctation (CoA) need long term follow up due to the risk of abnormal arterial elasticity and complications of hypertension. We hypothesize that even subtle hemodynamic abnormalities are marked by lack of a blood pressure standing wave effect to the lower extremities (arm ≥ leg systolic BP: ARM Group) and is associated with elevated aortic flow velocities, increased left ventricular posterior wall thickness (LVPWd), higher arm BP and a greater requirement for interventions compared to subjects with the normal standing wave effect (leg &gt; arm SBP: LEG Group). Methods: CoAs repaired between 1990 and 2008 with at least two documented right arm and leg SBPs at clinic visits along with M-mode, 2D and Doppler echocardiography were selected. The largest recorded peak instantaneous (PeakV) and mean velocities (MeanV) in the descending aorta were reviewed, as were measures of the proximal transverse arch (TA) and LVPWd. Measurements were indexed by Z-score. Patient records were also reviewed for reintervention and antihypertensive medical therapy. Results: Eighty patients met our criteria with 29 ARM (median age 12 years) and 51 LEG (median 13 years) Group members. Compared to LEG, ARM had significantly increased arm SBP Z-score (p &lt;0.001), PeakV (p &lt;10 -4 ), MeanV (p &lt;10 -6 ), and LVPWd (p &lt;0.01) (Figure). There was no difference in arm diastolic BP (p =0.7) or TA diameter (p =0.3). Even without overt markers such as hypertension or medication, otherwise healthy ARM subjects were still found to have the same relationships. Furthermore, 11/29 (38%) ARM compared to 39/51 (76%) LEG were normotensive with no previous intervention and no BP medicine (Fisher’s p &lt;0.001). Conclusions: Higher leg SBP after CoA repair is a marker for salutary hemodynamic and echo parameters as well as freedom from interventions post repair. Follow-up tailored by recognizing good outcome in LEG Group could be accomplished with less expense and obtrusive testing.
Somatic mutations and clonal hematopoiesis in congenital neutropenia
Authors: Jun Xia, Christopher A. Miller, Jack Baty, Amrita Ramesh, Matthew R. M. Jotte, Robert S. Fulton, Tiphanie P. Vogel, Megan A. Cooper, Kelly J. Walkovich, Vahagn Makaryan, Audrey A. Bolyard, Mary C. Dinauer, David B. Wilson, Adrianna Vlachos, Kasiani C. Myers, Robert J. Rothbaum, Alison A. Bertuch, David C. Dale, Akiko Shimamura, Laurence A. Boxer, Daniel C. Link
Journal: Blood (2017)
TCT-446 Trends in trans-catheter aortic valve replacement in patients with bicuspid aortic valve stenosis: insights from National Inpatient Sample database
Authors: Bhaskar Bhardwaj, Siva Taduru, Harsh Golwala, Varun Kumar, Nileshkumar Patel, Nish Patel, Shilpkumar Arora, Mauricio Cohen, Sudarshan Balla
Journal: Journal of the American College of Cardiology (2017)
Funcionamiento de la red Enter-net en la vigilancia internacional
Authors: I. S.T. Fisher
Journal: Eurosurveillance (1999)

Enter-net es una red internacional para la vigilancia de infecciones gastrointestinales en el hombre que monitoriza la salmonelosis y la Escherichia coli O157 productora de verotoxinas (VTEC), asi como sus resistencias antimicrobianas. Desde su creacion, participaron en la red los 15 paises de la Union Europea (UE), ademas de Suiza y Noruega (mapa). La red esta financiada por la Comision Europea (CE) y es continuacion de la red de vigilancia Salm-Net (1994-97), cuyo objetivo principal era armonizar los procedimientos de fagotipia de salmonellas y establecer una base de datos internacional de salmonellas de actualizacion periodica. A traves de la deteccion e investigacion de brotes, Salm-Net mostro que un intercambio de informacion oportuno entre expertos de distintos paises de la UE podia dar lugar a la adopcion de medidas sanitarias eficaces, tanto dentro como fuera de Europa. Enter-net sigue en la misma linea y amplia estas ventajas mediante la inclusion de la prevencion de infecciones por E. coli O157.
A Synthetic CD8α:MyD88 Coreceptor Enhances CD8+ T-cell Responses to Weakly Immunogenic and Lowly Expressed Tumor Antigens
Authors: Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzales, Eduardo Davila
Journal: Cancer Research (2017)

Abstract T cell–based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T-cell efficacy, including suboptimal T-cell receptor (TCR) activation and an immunosuppressive tumor environment. Here, we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T-cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88–engineered T cells exhibited increased proliferation and expression of effector and costimulatory molecules in a tumor antigen–dependent manner. These effects were accompanied by elevated activation of TCR and Toll-like receptor signaling-related proteins. CD8α:MyD88–expressing T cells improved antitumor responses in mice. Enhanced antitumor activity was associated with a unique tumor cytokine/chemokine signature, improved T-cell infiltration, reduced markers of T-cell exhaustion, elevated levels of proteins associated with antigen presentation, and fewer macrophages with an immunosuppressive phenotype in tumors. Given these observations, CD8α:MyD88 represents a unique and versatile approach to help overcome immunosuppression and enhance T-cell responses to tumor antigens. Cancer Res; 77(24); 7049–58. ©2017 AACR.
PS06.03 INSIGHT Study Interim Analysis: Impact of VeriStrat Results on Patient Management in Early and Locally Advanced NSCLC
Authors: P.R. Walker, E. Schaefer, P. Thompson Rich, J. Dubay, N. Ikhlaque, D. Oubre, E. Pauli, J. Orsini, E. Santos, A. Veatch Rose, C. Jordan, R. Page, A. Arnaud, B. Mitchell
Journal: Journal of Thoracic Oncology (2017)
Nouveau variant de la maladie de Creutzfeldt Jakob : quoi de neuf ?
Authors: O N Gill
Journal: Eurosurveillance (2000)

Le 17 juillet 2000, un communique a officiellement annonce que l’augmentation au Royaume-Uni de l’incidence du nouveau variant de la maladie de Creutzfeldt Jakob (nvMCJ) avait atteint le seuil de signification statistique. Ce numero d’Eurosurveillance est donc au cœur de l’actualite (1). Un cluster de cinq cas, dont un cas probable, identifie dans une zone localisee est en cours d’investigation (2). Depuis le deces, en 1995, du premier patient atteint de la maladie, 76 cas confirmes et probables de nvMCJ ont ete denombres et l’incidence augmente d’environ 20 a 30 % par an. Cependant, le Comite consultatif sur les encephalopathies spongiformes (Spongiform Encephalopathy Advisory Committee) du Royaume-Uni a conclu qu’il est encore trop tot pour savoir si cette tendance a la hausse se maintiendra ou pour faire des previsions sur la taille definitive de l’epidemie de nvMCJ (1).
Comparative untargeted proteomic analysis of ADME proteins and tumor antigens for tumor cell lines
Authors: Xiaomei Gu, Qing Xiao, Qian Ruan, Yuezhong Shu, Ashok Dongre, Ramaswamy Iyer, W. Griffith Humphreys, Yurong Lai
Journal: Acta Pharmaceutica Sinica B (2017)

In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3B2, H226, Ovcar3 and N87 were extracted and digested with γLysC and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the MaxQuant and the protein abundances were estimated using total peak area (TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption, metabolism, disposition and elimination (ADME) proteins including UDP-glucuronosyltransferase, cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.