bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of 15 novel risk loci for coronary artery disease and genetic risk of recurrent events, atrial fibrillation and heart failure
Authors: Verweij Niek , Eppinga Ruben N. , Hagemeijer Yanick , van der Harst Pim 
Published: May 2017

AbstractCoronary artery disease (CAD) is the major cause of morbidity and mortality in the world. Identification of novel genetic determinants may provide new opportunities for developing innovative strategies to predict, prevent and treat CAD. Therefore, we meta-analyzed independent genetic variants passing P <× 10−5 in CARDIoGRAMplusC4D with novel data made available by UK Biobank. Of the 161 genetic variants studied, 71 reached genome wide significance (p < 5 × 10−8) including 15 novel loci. These novel loci include multiple genes that are involved in angiogenesis (TGFB1, ITGB5, CDH13 and RHOA) and 2 independent variants in the TGFB1 locus. We also identified SGEF as a candidate gene in one of the novel CAD loci. SGEF was previously suggested as a therapeutic target based on mouse studies. The genetic risk score of CAD predicted recurrent CAD events and cardiovascular mortality. We also identified significant genetic correlations between CAD and other cardiovascular conditions, including heart failure and atrial fibrillation. In conclusion, we substantially increased the number of loci convincingly associated with CAD and provide additional biological and clinical insights.
Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection
Authors: Hulme Heather E. , Meikle Lynsey M. , Wessel Hannah , Strittmatter Nicole , Swales John , Thomson Carolyn , Nilsson Anna , Nibbs Robert J. B. , Milling Simon , Andren Per E. , Mackay C. Logan , Dexter Alex , Bunch Josephine , Goodwin Richard J. A. , Burchmore Richard , Wall Daniel M. 
Published: May 2017

AbstractSalmonellaTyphimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted duringS. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model ofS. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci ofS. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+sub capsular sinus macrophages was disrupted. MLN cells culturedex vivoand treated with PalC had reduced CD4+CD25+T cells and an increased number of B220+CD19+B cells. The reduction in CD4+CD25+T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome.
Solid Conical Cap-closing Hollow Tube Growth by Axial Screw Dislocations
Authors: Chu Yanhui , Li Jinjin , Chen Jikun 
Published: May 2017

AbstractExploration of the mechanisms for growth of the nanostructures is the key point to achieve nanomaterial syntheses with precisely controlled morphology and structure. Herein, we reported a new mechanism that realized the growth of solid conical cap-closing hollow tube by axial screw dislocations in the formation α-Al2O3 nanowires. A hollow tube was firstly grown by axial screw dislocations in the formation α-Al2O3 nanowires through vapor-phase synthesis. Afterwards, the hollow tube was closed up by generating a solid conical cap with axial screw dislocations based on the competition between the surface energy and the strain energy of screw dislocation controlled by the growth environment. The solid conical cap-closing hollow tube growth model based on the axial screw dislocations is expected to be a general growth mechanism for nanowires within low supersaturation. This study enriches the fundamental understanding with respective to the kinetics of nanostructured crystal growth and provides guidance to the precise structure control in nanosynthesis and manufacturing.
Oxygen atoms are critical in rendering THP-1 leukaemia cells susceptible to cold physical plasma-induced apoptosis
Authors: Bekeschus Sander , Wende Kristian , Hefny Mohamed Mokhtar , Rödder Katrin , Jablonowski Helena , Schmidt Anke , Woedtke Thomas von , Weltmann Klaus-Dieter , Benedikt Jan 
Published: May 2017

AbstractCold physical plasma has been suggested as a powerful new tool in oncology. However, some cancer cells such as THP-1 leukaemia cells have been shown to be resistant towards plasma-induced cell death, thereby serving as a good model for optimizing plasmas in order to foster pro-apoptotic anticancer effects. A helium/oxygen radio frequency driven atmospheric plasma profoundly induced apoptosis in THP-1 cells whereas helium, humidified helium, and humidified helium/oxygen plasmas were inefficient. Hydrogen peroxide – previously shown as central plasma-derived agent – did not participate in the killing reaction but our results suggest hypochlorous acid to be responsible for the effect observed. Proteomic analysis of THP-1 cells exposed to He/O2 plasma emphasized a prominent growth retardation, cell stress, apoptosis, and a pro-immunogenic profile. Altogether, a plasma setting that inactivates previously unresponsive leukaemia cells is presented. Crucial reactive species in the plasma and liquid environment were identified and discussed, deciphering the complexity of plasma from the gas phase into the liquid down to the cellular response mechanism. These results may help tailoring plasmas for clinical applications such as oxidation-insensitive types of cancer.
A New Solid Solution Approach for the Study of Self-Irradiating Damage in non-Radioactive Materials
Authors: Templeman Tzvi , Shandalov Michael , Schmidt Michael , Tal Amir , Sarusi Gabby , Yahel Eyal , Kelson Itzhak , Golan Yuval 
Published: May 2017

AbstractA new method to produce a model system for the study of radiation damage in non-radioactive materials is presented. The method is based on homogenously dissolving minute amounts of 228Th ions in thin films in a controllable manner using a small volume chemical bath deposition technique. This approach is demonstrated for PbS films. The properties of the PbS (228Th) solid solution film activity were investigated by monitoring the accompanying radioactive processes. Electrical resistivity studies were performed and decay-event damage accumulation was measured, followed by isochronal annealing which presented two annealing stages and another two sub-stages. This is the first report on self-irradiating damage studies in IV-VI semiconductors and the resulting films present a novel method for the analysis of dilute defect systems in semiconductor thin films.
Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
Authors: Lodi Alessia , Saha Achinto , Lu Xiyuan , Wang Bo , Sentandreu Enrique , Collins Meghan , Kolonin Mikhail G. , DiGiovanni John , Tiziani Stefano 
Published: May 2017

AbstractHigh-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions.
Functionalization of MoS2 with 1,2-dithiolanes: toward donor-acceptor nanohybrids for energy conversion
Authors: Canton-Vitoria Ruben , Sayed-Ahmad-Baraza Yuman , Pelaez-Fernandez Mario , Arenal Raul , Bittencourt Carla , Ewels Christopher P. , Tagmatarchis Nikos 
Published: May 2017

Abstract
The covalent functionalization of exfoliated semiconducting MoS2 by 1,2-dithiolanes bearing an ethylene glycol alkyl chain terminated to a butoxycarbonyl-protected amine and a photoactive pyrene moiety is accomplished. The MoS2-based nanohybrids were fully characterized by complementary spectroscopic, thermal, and microscopy techniques. Markedly, density functional theoretical studies combined with X-ray photoelectron spectroscopy analysis demonstrate preferential edge functionalization, primarily via sulfur addition along partially sulfur saturated zig-zag MoS2 molybdenum-edges, preserving intact the 2D basal structure of functionalized MoS2-based nanohybrids as confirmed by high-resolution transmission electron microscopy and electron energy loss spectroscopy. Furthermore, in the MoS2-pyrene hybrid, appreciable electronic interactions at the excited state between the photoactive pyrene and the semiconducting MoS2 were revealed as inferred by steady-state and time-resolved photoluminescence spectroscopy, implying its high potentiality to function in energy conversion schemes.
Blockade of interleukin-6 receptor in the periphery promotes rapid and sustained antidepressant actions: a possible role of gut–microbiota–brain axis
Authors: Zhang J-c , Yao W , Dong C , Yang C , Ren Q , Ma M , Hashimoto K 
Published: May 2017

AbstractDepression is a common, severe and chronic psychiatric disease. Although the currently available antidepressants have been used in the treatment of depression, their beneficial effects are limited. Accumulating evidence suggests that pro-inflammatory cytokines such as interleukin-6 (IL-6) have an important role in the pathogenesis of depression. This study was undertaken to examine whether anti-mouse IL-6 receptor antibody (MR16-1) induces antidepressant effects in a social defeat stress model. Intravenous injection of MR16-1 induced rapid-onset and long-lasting antidepressant effects in susceptible mice after social defeat stress through its anti-inflammatory actions. In contrast, intracerebroventricular injection of MR16-1 induced no antidepressant effects in susceptible mice. Furthermore, treatment with MR16-1 could significantly normalize alterations in the expression of synaptic proteins (postsynaptic density protein 95 and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor 1) and dendritic spine density in the brain regions of susceptible mice. Gut microbiota analysis using 16S ribosomal RNA gene sequencing showed that MR16-1 significantly improved decreased Firmicutes/Bacteroidetes ratio in susceptible mice. It also significantly improved decreased levels of Oscillospira in susceptible mice. These findings suggest that peripheral IL-6 has a key role in the pathogenesis of depression and that the blockade of IL-6 receptor in the periphery might have rapid-onset and long-lasting antidepressant effects by normalizing the altered composition of gut microbiota in susceptible mice after social defeat stress. Therefore, the blockade of IL-6 receptor in the periphery shows promise as a novel therapeutic approach for depressed patients with higher IL-6 blood levels.
Eine neue Berufsgruppe kommt in der Praxis an: Erste Erkenntnisse über Einsatzgebiete, Tätigkeiten und Gehalt von Physician Assistants/Arztassistenten in Deutschland
Authors: Marschall Tanja , Hoffmann Marcus 
Published: May 2017

Zusammenfassung
Hintergrund Seit 2010 wird an der Dualen Hochschule Baden-Württemberg (DHBW) Karlsruhe der Studiengang Physician Assistant/Arztassistenz (PA) angeboten. Tätigkeiten, Einsatzbereiche und gehaltliche Eingruppierungen der Absolventen im Anschluss sind bisher nur unzureichend bekannt. Ziel der vorliegenden Studie war es Informationen hierüber zu erhalten.
Methoden Alle Absolventen (2 Jahrgänge, n=27) sollten schriftlich befragt werden. Der hierfür entwickelte Erhebungsbogen umfasste 37 Fragen u. a. zur aktuellen Beschäftigungssituation, Tätigkeiten, Gehalt und zur Zufriedenheit mit Studium und Beruf. Es erfolgte eine deskriptive Analyse der Daten mittels SPSS.
Ergebnisse 25 Absolventen beteiligten sich an der Erhebung (96,1%); das Durchschnittsalter der Teilnehmer lag bei 32,2 Jahren (25–53 Jahre). 88% (n=22) waren als PA eingestellt, die meisten arbeiteten in der Inneren Medizin (n=11) oder der Chirurgie (n=9). Tätigkeiten, die häufig bzw. sehr häufig von den PA durchgeführt werden sind Vorbereitung von Entlassdokumenten, Übernahme einer Koordinationsfunktion im therapeutischen Team, aber auch die Mitwirkung bei Anamnese und körperlicher Untersuchung. Bei zwei Drittel der Befragten lag bei einer Vollzeittätigkeit das monatliche Bruttogrundgehalt über 3000 Euro. Insgesamt fanden 77,3% (n=17) der Absolventen ihre aktuelle Situation zufriedenstellend bzw. sehr zufriedenstellend.
Schlussfolgerung Die Absolventen der DHBW fügen sich offensichtlich hinsichtlich ihres Tätigkeitsspektrums und der Gehaltsstruktur gut in das Personalgefüge der Kliniken ein. Weitere Studien zur Akzeptanz dieser in Deutschland neuen Berufsgruppe sowie zur Abgrenzung zu etablierten Gesundheitsfachberufen folgen.
Der Gelenkinfekt ohne Implantat
Authors: Hückstädt Marc , Hofmann Gunter 
Published: May 2017

ZusammenfassungGelenkinfektionen können innerhalb kurzer Zeit zur irreversiblen Schädigung des Gelenkknorpels führen und bei septischen Verläufen lebensbedrohlich sein. Aus diesem Grund stellen sie einen Notfall dar und bedürfen der umgehenden Diagnostik und Therapie. Dieser Artikel soll einen Überblick über Grundlagen, Diagnostik und Therapie der septischen Arthritis geben und die Bedeutung der frühzeitigen adäquaten chirurgischen und antibiotischen Behandlung herausstellen. Die dargestellten Fallbeispiele sollen einen Eindruck von den Schwierigkeiten in Diagnostik und Therapie und schwerwiegenden Komplikationen bei verzögerter Behandlung vermitteln.
Die Kosten von Übergewicht und Adipositas in Deutschland – ein systematischer Literaturüberblick
Authors: Konnopka Alexander , Dobroschke Astrid , Lehnert Thomas , König Hans-Helmut 
Published: May 2017

Zusammenfassung
Ziel der Studie Ziel dieser Arbeit war eine systematische Übersicht über Krankheitskostenstudien zu Übergewicht und Adipositas für Deutschland zu erstellen.
Methodik Wir haben eine PubMed-Recherche durchgeführt. Um die Vergleichbarkeit zu erhöhen, haben wir alle Kostendaten auf das Jahr 2014 inflationiert. Bei Bottom-up Studien haben wir zusätzlich die relativen Kostenunterschiede zwischen Übergewicht bzw. Adipositas und Normalgewicht berechnet, meta-analytisch aggregiert und auf die Gesamtbevölkerung extrapoliert.
Ergebnisse Insgesamt konnten wir 15 Bottom-up Studien, 6 Top-down Studien und 2 Markov-Modellierungen identifizieren. Im Durchschnitt berichteten die Top-Down Studien direkte Kosten von 7,9 Mrd. Euro und indirekte Kosten von 3,6 Mrd. Euro. Die absoluten Ergebnisse der Bottom-up Studien waren aufgrund der Heterogenität der Studien nicht aggregierbar. Die gepoolten relativen Mittelwertdifferenzen in Studien mit Erwachsenen waren +22% für den Unterschied zwischen Übergewicht und Normalgewicht bzw. +53% für den Unterschied zwischen Adipositas und Normalgewicht. Die entsprechenden Effektstärken waren 0,07 (−0,05; 0,19), bzw. 0,15 (0,02; 0,28). Bei Kindern waren die relativen Mittelwertdifferenzen deutlich geringer und die dazugehörigen Effektstärken nahezu null. Die Extrapolation der Bottom-up Ergebnisse auf die Gesamtbevölkerung ergab direkte und indirekte Excess-Kosten von 22,2 Mrd. Euro für Übergewicht und 23,0 Mrd. Euro für Adipositas.
Schlussfolgerung Zusammenfassend zeigte sich sowohl bei den Top-down Studien als auch bei den Bottom-up Studien eine große Heterogenität der Ergebnisse, welche auf eine erhebliche Unsicherheit hindeutet und eindeutige Aussagen zu den Kosten von Übergewicht und Adipositas sehr erschwert. Insgesamt deuten die Ergebnisse darauf hin, dass die Gesamtkosten in Top-down Studien stark unterschätzt werden.
Nachweis und Bedeutung von Kidd-Antikörpern im Festphasensystem (Capture-R® Ready-Screen®, Immucor)
Authors: Flommersfeld Sabine , Ertl Birgit 
Published: May 2017

ZusammenfassungDer Nachweis von Kidd-Antikörpern gilt unter Immunhämatologen als besonders anspruchsvoll, da der Antikörper als transfusionsmedizinisch relevant eingestuft wird, aber nicht konsistent in allen Untersuchungsmethoden und oft nur passager nachweisbar ist. In Laboratorien, in denen der Capture-R® Ready-Screen®-Test zur Antikörpersuche eingeführt wurde, werden Kidd-Antikörper signifikant häufiger nachgewiesen als in der Röhrchen- oder Gelkartenzentrifugationsmethode im indirekten Antihumanglobulintest. Ob diese Antikörper, die nun vermehrt im Festphasensystem zu finden sind, klinisch auch eine Relevanz haben, ist insbesondere auch nach einer Publikation von Kay et al. in der Diskussion. Im Folgenden soll die Bedeutung des Nachweises der Kidd-Antikörper und deren klinischer Wertigkeit anhand der Literatur und den eigenen Daten dargestellt werden.
Leitlinien in der Praxis: Die neue S3-Leitlinie „Nicht erholsamer Schlaf/Schlafstörungen“ – Kapitel „Schlafbezogene Atmungsstörungen“
Authors: Gerlach M. , Sanner B. 
Published: May 2017

ZusammenfassungZu den schlafbezogenen Atmungsstörungen zählen die zentrale Schlafapnoe (ZSA), die obstruktive Schlafapnoe (OSA) und die schlafbezogene Hypoventilation bzw. Hypoxämie. Sie sind häufig und von zunehmender klinischer Relevanz. Das Kapitel zu dieser Krankheitsgruppe aus der S3-Leitlinie „Nicht erholsamer Schlaf/Schlafstörungen“ der Deutschen Gesellschaft für Schlafmedizin wurde am 29. November 2016 aktualisiert und bietet Neuerungen zu Epidemiologie, Diagnostik, Therapie und Systematik. Zur Epidemiologie wird die deutlich erhöhte Mortalität schwangerer Frauen mit OSA herausgestellt. In der Diagnostik der OSA wird betont, dass die Polygrafie unter bestimmten Voraussetzungen ausreichen kann. Änderungen der diagnostischen Empfehlungen zur ZSA erlauben nun die Diagnosestellung auch bei geringer Apnoerate unter der Voraussetzung einer typischen klinischen Situation. Entscheidende therapeutische Unterschiede haben sich bei der ZSA mit Herzinsuffizienz ergeben. Ferner wird differenziert zwischen schlafbezogener Hypoventilation und schlafbezogener Hypoxämie. Das Obesitas-Hypoventilations-Syndrom wird insgesamt breiter besprochen. Der vorliegende Artikel fasst die Änderungen zusammen und kommentiert sie.
Behandlung neu diagnostizierter Neuroblastome nach Ende der Klinischen Studien
Authors: Rößler Jochen 
Published: May 2017

Liebe Leserinnen und Leser,Anfang Dezember 2016 bedankte sich Herr Prof. Frank Berthold in einem Schreiben an die GPOH Neuroblastom-Studienzentren – ich zitiere – „…für 37 exzellente Jahre Kooperation für Patienten mit Neuroblastomen aller Ausprägungsgrade in Deutschland und einer Gesamt-Einschlussrate von 97% in 6 lückenlos aufeinander folgende Studien“. Anlass war das Ende der Rekrutierung für die Studie NB-2004 HR zum 31.12.2016. Auch die Studie NB-2004 endete zu diesem Zeitpunkt.
What is EU law about?
Authors: Arnull Anthony 
Published: May 2017

Abstract
The range of issues that the EU has been given the power to regulate has grown significantly since it was founded by just six Member States in 1951. The aim of the European Coal and Steel Community Treaty signed that year was to create a single market for those products. Its initial success prompted the Member States to embark on a much more ambitious venture: the European Economic Community (EEC), established by a treaty signed in Rome in 1957. At the heart of the EEC lay the free movement of goods, persons, services, and capital—the four freedoms that remain fundamental to the EU.
Secondary EU law
Authors: Arnull Anthony 
Published: May 2017

Abstract
A novel feature of the Treaties was that they created institutions distinct from the Member States with the capacity to make law. Such law is known as the secondary law of the EU. It is subordinate to the Treaties, which belong to the primary law of the EU. ‘Secondary EU Law’ explains the principles of conferral and competence, which play an important role in preserving a balance between the powers of the EU and those of the Member States. A leading role is played in the exercise of the EU’s competences by its four main political institutions: the European Parliament, the European Council, the Council, and the Commission.
EU law in the national courts
Authors: Arnull Anthony 
Published: May 2017

Abstract
‘EU law in the national courts’ explains the concepts of direct effect and primacy. The Court of Justice of the European Union has ruled that EU law may confer rights on individuals that may be enforced in the national courts of the Member States. Such rights enjoy primacy over conflicting national laws regardless of the constitutional status of those laws. Moreover, national law must where possible be interpreted consistently with overlapping rules of EU law. When a Member State breaches EU law, any individual who suffers loss as a result may claim damages in the national courts. How have national courts responded to these principles?
DeepSite: protein-binding site predictor using 3D-convolutional neural networks
Authors: Jiménez J , Doerr S , Martínez-Rosell G , Rose A S , De Fabritiis G 
Published: May 2017

Abstract

Motivation
An important step in structure-based drug design consists in the prediction of druggable binding sites. Several algorithms for detecting binding cavities, those likely to bind to a small drug compound, have been developed over the years by clever exploitation of geometric, chemical and evolutionary features of the protein.

Results
Here we present a novel knowledge-based approach that uses state-of-the-art convolutional neural networks, where the algorithm is learned by examples. In total, 7622 proteins from the scPDB database of binding sites have been evaluated using both a distance and a volumetric overlap approach. Our machine-learning based method demonstrates superior performance to two other competitive algorithmic strategies.

Availability and implementation
DeepSite is freely available at www.playmolecule.org. Users can submit either a PDB ID or PDB file for pocket detection to our NVIDIA GPU-equipped servers through a WebGL graphical interface.

Supplementary information
Supplementary data are available at Bioinformatics online.