bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-invasive markers of cardiovascular risk in patients with subclinical hypothyroidism: A systematic review and meta-analysis of 27 case control studies
Authors: Yao Kecheng , Zhao Tianming , Zeng Linghai , Yang Jianming , Liu Yanqun , He Qian , Zou Xiulan 
Published: March 2018

AbstractIt has been reported that subclinical hypothyroidism (SCH) is closely related to subclinical atherosclerosis. According to the impact of SCH on noninvasive markers of cardiovascular risk, we fulfilled a meta-analysis of included studies to provide an integrated overview. We searched electronic databases and included all relevant studies involving SCH and epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), pulse wave velocity (PWV), flow-mediated dilation (FMD) and glyceryl trinitrate-induced dilation (GNT- induced dilation). The result was calculated in a meta-analysis to assess the impact of SCH on these markers. A total of 27 studies were entered in the final analysis. Compared with euthyroid subjects, SCH patients exhibited a significantly increased CIMT (SMD: 0.369 mm; 95%CI: 0.038, 0.700; P = 0.029) and EAT (SMD: 1.167 mm; 95%CI: 0.869, 1.466; P = 0.000) and increased PWV (SMD: 3.574 m/s; 95%CI: 0.935, 6.213, P = 0.008). We also found significantly lower FMD (SMD: −1.525%, 95%CI: −2.156, −0.894, P = 0.000) and lower GNT-induced dilation (SMD: −0.384%, 95%CI: −0.625, −0.142, P = 0.002). Sensitivity analysis and subgroup analysis confirmed the above results. Our meta-analysis confirmed a significant association of SCH and cardiovascular risk with arterial wall thickening and stiffening and endothelial dysfunction. These findings will help to establish detailed cardiovascular prevention strategies for SCH patients.
Evaluation of the selective toxic effect of the charge switchable diethyldithiocarbamate-loaded nanoparticles between hepatic normal and cancerous cells
Authors: Abu-Serie Marwa M. 
Published: March 2018

AbstractLiver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival. The charge switchable of coated DDC-loaded NPs in neutral and acidic pH (−19 and +28.5 mv, respectively) was illustrated. This special privilege of coated NPs mediated DDC releasing in a slightly acidic pH (tumor microenvironment) rather than a neutral pH (microenvironment of normal cells). Thence, these coated NPs showed the highest selective apoptosis-mediated toxicity only in murine hepatoma cells (Hepa) that may attribute to suppression of NF-κB expression and ALDH1A1 activity, subsequently collapsing 89.7% CD133+CSCs. These new findings declare that coated NPs could be promising safe selective anticancer drug for targeting hepatic CSCs and that requires additional future investigations using animal models of liver cancer.
Stimulation of alpha2-adrenergic receptors impairs influenza virus infection
Authors: Matsui Ken , Ozawa Makoto , Kiso Maki , Yamashita Makoto , Maekawa Toshihiko , Kubota Minoru , Sugano Sumio , Kawaoka Yoshihiro 
Published: March 2018

AbstractInfluenza A viruses cause seasonal epidemics and occasional pandemics. The emergence of viruses resistant to neuraminidase (NA) inhibitors and M2 ion channel inhibitors underlines the need for alternate anti-influenza drugs with novel mechanisms of action. Here, we report the discovery of a host factor as a potential target of anti-influenza drugs. By using cell-based virus replication screening of a chemical library and several additional assays, we identified clonidine as a new anti-influenza agent in vitro. We found that clonidine, which is an agonist of the alpha2-adrenergic receptor (α2-AR), has an inhibitory effect on the replication of various influenza virus strains. α2-AR is a Gi-type G protein-coupled receptor that reduces intracellular cyclic AMP (cAMP) levels. In-depth analysis showed that stimulation of α2-ARs leads to impairment of influenza virus replication and that α2-AR agonists inhibit the virus assembly step, likely via a cAMP-mediated pathway. Although clonidine administration did not reduce lung virus titers or prevent body weight loss, it did suppress lung edema and improve survival in a murine lethal infection model. Clonidine may thus protect against lung damage caused by influenza virus infection. Our results identify α2-AR-mediated signaling as a key pathway to exploit in the development of anti-influenza agents.
On-target action of anti-tropomyosin drugs regulates glucose metabolism
Authors: Kee Anthony J. , Chagan Jayshan , Chan Jeng Yie , Bryce Nicole S. , Lucas Christine A. , Zeng Jun , Hook Jeff , Treutlein Herbert , Laybutt D. Ross , Stehn Justine R. , Gunning Peter W. , Hardeman Edna C. 
Published: March 2018

AbstractThe development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets. The impact of the drugs on GSIS was significantly less in Tpm3.1 knock out (KO) mice indicating that the drug action is on-target. Experiments in MIN6 β-cells indicated that the inhibition of GSIS by the drugs was due to disruption to the cortical actin cytoskeleton. The impact of the drugs on insulin-stimulated glucose uptake (ISGU) was also examined in skeletal muscle ex vivo. In the absence of drug, ISGU was decreased in KO compared to WT muscle, confirming a role of Tpm3.1 in glucose uptake. Both compounds suppressed ISGU in WT muscle, but in the KO muscle there was little impact of the drugs. Collectively, this data indicates that the ATM drugs affect glucose metabolism in vivo by inhibiting Tpm3.1’s function with few off-target effects.
Discrete shear band plasticity through dislocation activities in body-centered cubic tungsten nanowires
Authors: Wang Jiangwei , Wang Yanming , Cai Wei , Li Jixue , Zhang Ze , Mao Scott X. 
Published: March 2018

AbstractShear band in metallic crystals is localized deformation with high dislocation density, which is often observed in nanopillar deformation experiments. The shear band dynamics coupled with dislocation activities, however, remains unclear. Here, we investigate the dynamic processes of dislocation and shear band in body-centered cubic (BCC) tungsten nanowires via an integrated approach of in situ nanomechanical testing and atomistic simulation. We find a strong effect of surface orientation on dislocation nucleation in tungsten nanowires, in which {111} surfaces act as favorite sites under high strain. While dislocation activities in a localized region give rise to an initially thin shear band, self-catalyzed stress concentration and dislocation nucleation at shear band interfaces cause a discrete thickening of shear band. Our findings not only advance the current understanding of defect activities and deformation morphology of BCC nanowires, but also shed light on the deformation dynamics in other microscopic crystals where jerky motion of deformation band is observed.
Lagrangian coherent structure assisted path planning for transoceanic autonomous underwater vehicle missions
Authors: Ramos A. G. , García-Garrido V. J. , Mancho A. M. , Wiggins S. , Coca J. , Glenn S. , Schofield O. , Kohut J. , Aragon D. , Kerfoot J. , Haskins T. , Miles T. , Haldeman C. , Strandskov N. , Allsup B. , Jones C. , Shapiro J. 
Published: March 2018

AbstractTransoceanic Gliders are Autonomous Underwater Vehicles (AUVs) for which there is a developing and expanding range of applications in open-seas research, technology and underwater clean transport. Mature glider autonomy, operating depth (0–1000 meters) and low energy consumption without a CO2 footprint enable evolutionary access across ocean basins. Pursuant to the first successful transatlantic glider crossing in December 2009, the Challenger Mission has opened the door to long-term, long-distance routine transoceanic AUV missions. These vehicles, which glide through the water column between 0 and 1000 meters depth, are highly sensitive to the ocean current field. Consequently, it is essential to exploit the complex space-time structure of the ocean current field in order to plan a path that optimizes scientific payoff and navigation efficiency. This letter demonstrates the capability of dynamical system theory for achieving this goal by realizing the real-time navigation strategy for the transoceanic AUV named Silbo, which is a Slocum deep-glider (0–1000 m), that crossed the North Atlantic from April 2016 to March 2017. Path planning in real time based on this approach has facilitated an impressive speed up of the AUV to unprecedented velocities resulting in major battery savings on the mission, offering the potential for routine transoceanic long duration missions.
Subcellular localisation modulates ubiquitylation and degradation of Ascl1
Authors: Gillotin Sébastien , Davies John D. , Philpott Anna 
Published: March 2018

AbstractThe proneural transcription factor Ascl1 is a master regulator of neurogenesis, coordinating proliferation and differentiation in the central nervous system. While its expression is well characterised, post-translational regulation is much less well understood. Here we demonstrate that a population of chromatin-bound Ascl1 can be found associated with short chains of ubiquitin while cytoplasmic Ascl1 harbours much longer ubiquitin chains. Only cytoplasmic ubiquitylation targets Ascl1 for destruction, which occurs by conjugation of ubiquitin to lysines in the basic helix-loop-helix domain of Ascl1 and requires the E3 ligase Huwe1. In contrast, chromatin-bound Ascl1 associated with short ubiquitin-chains, which can occur on lysines within the N-terminal region or the bHLH domain and is not mediated by Huwe1, is not targeted for ubiquitin-mediated destruction. We therefore offer further insights into post-translational regulation of Ascl1, highlighting complex regulation of ubiquitylation and degradation in the cytoplasm and on chromatin.
RETRACTED ARTICLE: In vitro evaluation of the toxic effects of MgO nanostructure in Hela cell line
Authors: Akram M. Waseem , Fakhar-e-Alam Muhammad , Atif M. , Butt Alvina Rafique , Asghar Ali , Jamil Yasir , Alimgeer K. S. , Wang Zhiming M. 
Published: March 2018

AbstractMgO is an attractive choice for carcinogenic cell destruction in photodynamic therapy, as confirmed by manifold analysis. The prime focus of the presented research is to investigate the toxicity caused by morphologically different MgO nanostructures obtained by annealing at various annealing temperatures. Smart (stimuli-responsive) MgO nanomaterials are a very promising class of nanomaterials, and their properties can be controlled by altering their size, morphology, or other relevant characteristics. The samples investigated here were grown by the co-precipitation technique. Toxicity-dependent parameters were assessed in a HeLa cell model after annealing the grown samples at 350 °C, 450 °C, and 550 °C. After the overall characterization, an analysis of toxicity caused by changes in the MgO nanostructure morphology was tested in a HeLa cell model using a neutral red assay and microscopy. The feasibility of using MgO for PDT was assessed. Empirical modelling was applied to corroborate the experimental results obtained from assessing cell viability losses and reactive oxygen species. The results indicate that MgO is an excellent candidate material for medical applications and could be utilized for its potential ability to upgrade conventionally used techniques.
Cancer Vaccine Therapy Using Carcinoembryonic Antigen - expressing Dendritic Cells generated from Induced Pluripotent Stem Cells
Authors: Kitadani Junya , Ojima Toshiyasu , Iwamoto Hiromitsu , Tabata Hirotaka , Nakamori Mikihito , Nakamura Masaki , Hayata Keiji , Katsuda Masahiro , Miyajima Masayasu , Yamaue Hiroki 
Published: March 2018

AbstractClinical application of dendritic cell (DC) vaccine therapy is hindered by the need for a large quantity of DCs generated from peripheral blood monocytes of the patient. We investigated whether genetically modified human induced pluripotent stem cell (iPSC)-derived dendritic cells (hiPSDCs) expressing carcinoembryonic antigen (CEA) could induce CEA-specific cytotoxic T cells in a human model and whether genetically modified mouse iPSDCs (miPSDCs) expressing CEA showed an actual antitumor effect using a CEA transgenic mouse model. We differentiated hiPSDCs from iPSCs of three healthy donors and transduced CEA cDNA into the hiPSDCs. The surface marker expression, cytokine secretion and migratory capacity of the hiPSDCs were equivalent to those of human monocyte-derived DCs (hMoDCs). Cytotoxic T cells activated by hiPSDCs-CEA exhibited CEA-specific cytotoxic activity against the target cells expressing CEA. Furthermore, in the CEA transgenic mouse model, cytotoxic T cells activated in mice immunized with miPSDCs-CEA displayed CEA-specific cytotoxic activity against MC38-CEA. In the subcutaneous tumour model, vaccination with miPSDCs-CEA achieved a significant growth inhibitory effect on MC38-CEA. No adverse events caused by the administration of miPSDCs were observed. Genetic modification of iPSDCs, inducing the expression of CEA, is a promising tool for clinical applications of vaccine therapy for treating gastrointestinal cancer patients.
Double‐layer suspended stripline resonator with high quality factor for base‐station diplexer application
Authors: Xia Lei , Song Lei , Wu Bian , Bo Xiaodong , Chen Jianzhong 
Published: March 2018

A novel double‐layer suspended stripline (DSSL) resonator with high unloaded quality factor is proposed. The DSSL resonator consists of a thin substrate with metal strips on both sides connected by a metallic via hole suspended in the centre of an air‐filled cavity, which leads to a much higher unloaded quality factor than the conventional single‐layer suspended stripline resonator with an identical resonant frequency. The resonance characteristics of the DSSL resonator are parametric analysed. For demonstration, a compact diplexer for base‐station application with channel centre frequencies at 1.95 and 2.14 GHz and absolute bandwidths of 60 MHz is designed, fabricated and measured. The synthesised, simulated and measured results show a good agreement.
Improved visible light communication positioning algorithm based on image sensor tilting at room corners
Authors: Fu Minglei , Zhu Weijun , Le Zichun , Manko Dmytro 
Published: March 2018

We developed an improved algorithm for an indoor positioning system based on an image sensor. By using the algorithm that tilts the image sensor when it is placed at room corners, the authors reduced the positioning error at the corners and increased the effective positioning area. When in room corners, the image sensor is placed at an appropriate angle that allows the reception of light from all three light‐emitting diodes (LEDs). The unknown sensor position is calculated from the geometrical relations among the LED images created on the tilted image sensor plane. According to the obtained experimental results, signal–to‐noise ratio of the received signal can be improved when the image sensor tilts at certain angle at the corner. It was found that the effective range of the tilt angle of the image sensor is estimated to be within the range of 30°–60° at the corners. The root mean‐square of the positioning error obtained with the developed algorithm is 0.6 mm when the image sensor is located within the effective positioning area. The effective positioning area was increased by 15.3% at the corner areas when the image sensor was tilted by the optimal angle.
All‐optical NOT and XOR logic gates using photonic crystal nano‐resonator and based on an interference effect
Authors: Mohebzadeh‐Bahabady Ahmad , Olyaee Saeed 
Published: March 2018

In this study, a small size, low power, simple and high contrast ratio (CR) structure was designed and simulated to use in photonic crystal‐based all‐optical logic gates. This structure can be used for both all‐optical logic NOT and XOR gates. The suggested structure is composed of three waveguides and a nano‐resonator. The nano‐resonator was designed by removing two dielectric rods. For use as an optical NOT logic gate, one of the input ports enters the control signal. In this case, the CR between logic levels ‘0’ and ‘1’ is 20.53 dB, which is higher than that of the provided gates based on structures published recently. The CR for the XOR gate is 19.95 dB. The response time to the input signal of the designed gate is 0.466 ps. The simplicity of the structure, small size, and high CR are the advantages of this structure compared to previously provided logic gates. The results have proven a superior prospect for the proposed structure to use in all optical integrated circuits.
Die Wertigkeit des gemeinsamen Faches Orthopädie-Unfallchirurgie im 2. Staatsexamen – Vergleich der schriftlichen 2. Staatsexamina mit dem Nationalen Kompetenzbasierten Lernzielkatalog Chirurgie
Authors: Sterz Jasmina , Britz Vanessa , Münzberg Matthias , Kadmon Martina , Schleicher Iris , Meder Adrian , Kamp Rainer , Janko Maren , Marzi Ingo , Rüsseler Miriam 
Published: March 2018

Zusammenfassung
Hintergrund Der Nationale Kompetenzbasierte Lernzielkatalog Chirurgie (NKLC) definiert für jedes seiner 230 Lernziele eine Kompetenzebene von „Kompetenzebene 1: Faktenwissen“ bis zu „Kompetenzebene 3: selbstständiges Handeln“. Trotz des erwiesenen Einflusses von summativen Prüfungen auf das Lernverhalten von Studierenden bilden diese Lernziele nicht die Grundlage für das 2. Staatsexamen. Die vorliegende Studie untersucht, inwiefern die Prüfungsfragen des 2. Staatsexamens bereits die orthopädisch-unfallchirurgischen Lernziele des NKLC adressieren und welche thematische Schwerpunktsetzung hierbei erfolgt.
Material und Methoden Es erfolgte eine retrospektive Analyse basierend auf den Examensfragen von Herbst (H) 2009 bis Herbst 2014 (n = 11). Zunächst wurden im NKLC durch 5 Ober- und Fachärzte die Lernziele aus den Bereichen Orthopädie und Unfallchirurgie identifiziert. Nachfolgend wurden aus den 11 untersuchten Staatsexamina die Fragen definiert, die sich auf die orthopädisch-unfallchirurgischen Lernziele bezogen. Analysiert wurden die Gesamtzahl der Fragen, die Anzahl der Fragen pro Examen sowie pro Lernziel und Kompetenzebene.
Ergebnisse Insgesamt konnten 113 Lernziele des NKLC (entspricht 49,1% aller Lernziele des NKLC) dem Fach Orthopädie und Unfallchirurgie zugeordnet werden. Im Studienzeitraum adressierten 543 Fragen diese 113 Lernziele (entspricht 15,6% aller 3480 Fragen). Pro Examen konnten durchschnittlich 49,36 ± 14,1 (Min. 30; Max. 80) Fragen mit Bezug zu Orthopädie und Unfallchirurgie identifiziert werden. Insgesamt wurden 13,45 ± 6,39 (Min. 6; Max. 24) Fragen zu Lernzielen (LZ) der Kompetenzebene 3a und b, 21,45 ± 9,94 (Min. 9; Max. 39) Fragen zu LZ der Kompetenzebene 2 und 14,45 ± 6,36 (Min. 6; Max. 25) Fragen zu LZ der Kompetenzebene 1 gestellt. Die Mehrheit der Fragen adressierten „Erkrankungen des rheumatischen Formenkreises“ (n = 16 im Herbst 2009).
Schlussfolgerung Die Anzahl der Fragen mit unfallchirurgisch-orthopädischem Schwerpunkt im 2. Staatsexamen erscheint in Relation zur Gesamtzahl aller gestellten Fragen ausreichend hoch. Allerdings liegt eine thematische Imbalance vor, und gerade klinisch wichtige Lernziele mit hoher Kompetenzebene werden nicht ausreichend häufig geprüft. Eine bessere Abstimmung der Staatsprüfung mit den Lernzielkatalogen ist erforderlich.
Incidence of Diabetic Ketoacidosis of New-Onset Type 1 Diabetes in Children and Adolescents in Different Countries Correlates with Human Development Index (HDI): An Updated Systematic Review, Meta-Analysis, and Meta-Regression
Authors: Große Johann , Hornstein Henriette , Manuwald Ulf , Kugler Joachim , Glauche Ingmar , Rothe Ulrike 
Published: March 2018

AbstractType 1 diabetes mellitus (T1DM) is usually diagnosed by insulin deficiency at a young age. Diabetic ketoacidosis (DKA) represents a severe complication occurring before the first diagnosis of T1DM. Actually, the data situation is still unsettled in assessing the current state of diagnosis. This study summarizes the latest rates of DKA of new-onset T1DM in children and adolescents in different countries available over the last five years. Different T1DM-related, geographical and socioeconomic moderators are suitable to explain the heterogeneity of observed DKA rates. A systematic literature search using PubMed, EMBASE*, and MedLine* (*via OVID) was conducted to extract worldwide DKA rates covering publications from April 2011 to May 2016. We define DKA consistently by pH<7.3 or bicarbonate<15 mmol/l. We identified 34 suitable studies covering DKA rates in 25 countries. Overall DKA rates were compared to earlier studies to identify a temporal trend. We further applied a random effects meta-analysis and used meta-regression to reveal moderators of DKA rate heterogeneity. This review evaluating 34 studies includes 47 000 children and adolescents in total. DKA rates varied from 14.7% (Denmark) to 79.8% (Saudi Arabia). DKA rates are still high but a decline can also be recognized. The meta-regression shows that latitude (p<0.000) and human development index (HDI) (p<0.000) are moderators of DKA rates. The frequency of DKA rates occurrence varies widely for different countries. Both latitude and HDI partially explain the observed heterogeneity, while other moderators such as density of physicians showed no obvious correlation.