bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of genotype and age on cerebral [18F]FDG uptake varies between transgenic APPSwe-PS1dE9 and Tg2576 mouse models of Alzheimer’s disease
Authors: Snellman Anniina , Takkinen Jatta S. , López-Picón Francisco R. , Eskola Olli , Solin Olof , Rinne Juha O. , Haaparanta-Solin Merja 
Published: April 2019

AbstractBack-translation of clinical imaging biomarkers of Alzheimer’s disease (AD), such as alterations in cerebral glucose metabolism detected by [18F]FDG positron emission tomography (PET), would be valuable for preclinical studies evaluating new disease-modifying drugs for AD. However, previous confounding results have been difficult to interpret due to differences in mouse models and imaging protocols between studies. We used an equivalent study design and [18F]FDG µPET imaging protocol to compare changes in cerebral glucose metabolism in commercial transgenic APPSwe-PS1dE9 (n = 12), Tg2576 (n = 15), and wild-type mice (n = 15 and 9). Dynamic [18F]FDG scans were performed in young (6 months) and aged (12 or 17 months) mice and the results verified by ex vivo methods (i.e., tissue counting, digital autoradiography, and beta-amyloid and Iba-1 immunohistochemistry). [18F]FDG uptake exhibited significant regional differences between genotypes (TG < WT) and ages (6 months <12 months) in the APPSwe-PS1dE9 model, whereas similar differences were not present in Tg2576 mice. In both models, only weak correlations were detected between regional beta-amyloid deposition or microgliosis and [18F]FDG uptake. By using equivalent methodology, this study demonstrated differences in cerebral glucose metabolism dysfunction detected with [18F]FDG PET between two widely used commercial AD mouse models.
Air pollution during New Year’s fireworks and daily mortality in the Netherlands
Authors: Greven Frans E. , Vonk Judith M. , Fischer Paul , Duijm Frans , Vink Nienke M. , Brunekreef Bert 
Published: April 2019

AbstractShort-term exposure to air pollution has been associated with cardiovascular and respiratory mortality and morbidity. Little is known about associations between air pollution caused by firework events and daily mortality. We investigated whether particulate matter from fireworks during New Year’s celebrations was associated with daily mortality. We analyzed the celebrations of the years 1995–2012. PM10 concentrations increased dramatically during the firework events. Countrywide, the daily average PM10 concentrations from 27–30 December was 29 μg/m3 and increased during the first hour of the New Year by 277 μg/m3. In the more densely populated areas of the Netherlands the increase was even steeper, 598 μg/m3 in the first hour of the New Year. No consistent associations were found using linear regression models between PM10 concentrations during the first six hours of 1 January and daily mortality in the general population. Yet, using a case-crossover analysis firework-days and PM10 concentrations were associated with daily mortality. Therefore, in light of the contradictory results obtained with the different statistical analyses, we recommend further epidemiological research on the health effects of exposure to firework emissions.
Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies
Authors: Montigaud Yoann , Périnel Sophie , Dubus Jean-Christophe , Leclerc Lara , Suau Marie , Goy Clémence , Clotagatide Anthony , Prévôt Nathalie , Pourchez Jérémie 
Published: April 2019

AbstractEthical restrictions are limitations of in vivo inhalation studies, on humans and animal models. Thus, in vitro or ex vivo anatomical models offer an interesting alternative if limitations are clearly identified and if extrapolation to human is made with caution. This work aimed to develop an ex vivo infant-like respiratory model of bronchopulmonary dysplasia easy to use, reliable and relevant compared to in vivo infant data. This model is composed of a 3D-printed head connected to a sealed enclosure containing a leporine thorax. Physiological data and pleural-mimicking depressions were measured for chosen respiratory rates. Homogeneity of ventilation was assessed by 81mkrypton scintigraphies. Regional radioaerosol deposition was quantified with 99mtechnetium-diethylene triamine pentaacetic acid after jet nebulization. Tidal volumes values are ranged from 33.16 ± 7.37 to 37.44 ± 7.43 mL and compliance values from 1.78 ± 0.65 to 1.85 ± 0.99 mL/cmH2O. Ventilation scintigraphies showed a homogenous ventilation with asymmetric repartition: 56.94% ± 9.4% in right lung and 42.83% ± 9.36 in left lung. Regional aerosol deposition in lungs exerted 2.60% ± 2.24% of initial load of radioactivity. To conclude the anatomical model satisfactorily mimic a 3-months old BPD-suffering bronchopulmonary dysplasia and can be an interesting tool for aerosol regional deposition studies.
The Transition to Paschen’s Law for Microscale Gas Breakdown at Subatmospheric Pressure
Authors: Loveless Amanda M. , Meng Guodong , Ying Qi , Wu Feihong , Wang Kejing , Cheng Yonghong , Garner Allen L. 
Published: April 2019

AbstractThe decrease in electronic device size necessitates greater understanding of gas breakdown and electron emission at microscale to optimize performance. While traditional breakdown theory using Paschen’s law (PL), driven by Townsend avalanche, fails for gap distance d $$\lesssim $$
≲
15 μm, recent studies have derived analytic equations for breakdown voltage when field emission and Townsend avalanche drive breakdown. This study derives a new analytic equation that predicts breakdown voltage VB within 4% of the exact numerical results of a previously derived theory and new experimental results at subatmospheric pressure for gap distances from 1–25 μm. At atmospheric pressure, VB transitions to PL near the product of pressure and gap distance, pd, corresponding to the Paschen minimum; at lower pressures, the transition to PL occurs to the left of the minimum. We further show that the work function plays a major role in determining which side of the Paschen minimum VB transitions to PL as pressure approaches atmospheric pressure while field enhancement and the secondary emission coefficient play smaller roles. These results indicate that appropriate combinations of these parameters cause VB to transition to PL to the left of the Paschen minimum, which would yield an extended plateau similar to some microscale gas breakdown experimental observations.
Impact of novel NS5A resistance-associated substitutions of hepatitis C virus detected in treatment-experienced patients
Authors: Nitta Sayuri , Asahina Yasuhiro , Kato Takanobu , Tsuchiya Jun , Inoue-Shinomiya Emi , Sato Ayako , Tsunoda Tomoyuki , Miyoshi Masato , Kawai-Kitahata Fukiko , Murakawa Miyako , Itsui Yasuhiro , Nakagawa Mina , Azuma Seishin , Kakinuma Sei , Hikita Hayato , Takehara Tetsuo , Watanabe Mamoru 
Published: April 2019

AbstractResistance-associated substitutions (RASs) of hepatitis C virus (HCV) in the NS5A region impair the efficacy of NS5A inhibitors. In this study, we evaluated the characteristics of the novel RASs observed in treatment-failure patients, A92K and a deletion at P32 (P32del), and the susceptibility of viruses with these RASs to various anti-HCV reagents by using JFH-1 based recombinant HCV with NS5A from a genotype 1b Con1 strain (JFH1/5ACon1). We introduced A92K or P32del solely or in combination with Q24K, L28M, R30Q or L31F into the NS5A of JFH1/5ACon1. Viruses harboring R30Q/A92K showed high extracellular core antigens and infectivity titers, whereas the other viruses with RASs showed low replication levels and infectivity titers. All the viruses with A92K or P32del were markedly resistant to ledipasvir, velpatasvir and elbasvir. Interestingly, viruses with R30Q/A92K were more susceptible to grazoprevir than viruses without RAS. All the viruses had a similar susceptibility to ribavirin and sofosbuvir. In conclusion, combination RASs R30Q/A92K enhanced virus production whereas other RASs impaired virus replication. Both A92K and P32del conferred severe resistance even to second generation NS5A inhibitors. However, these viruses were susceptible to grazoprevir, ribavirin and sofosbuvir. Thus, combination regimens with these reagents may eradicate viruses harboring A92K or P32del.
High Skp2 expression is associated with a mesenchymal phenotype and increased tumorigenic potential of prostate cancer cells
Authors: Šimečková Šárka , Kahounová Zuzana , Fedr Radek , Remšík Ján , Slabáková Eva , Suchánková Tereza , Procházková Jiřina , Bouchal Jan , Kharaishvili Gvantsa , Král Milan , Beneš Petr , Souček Karel 
Published: April 2019

AbstractSkp2 is a crucial component of SCFSkp2 E3 ubiquitin ligase and is often overexpressed in various types of cancer, including prostate cancer (PCa). The epithelial-to-mesenchymal transition (EMT) is involved in PCa progression. The acquisition of a mesenchymal phenotype that results in a cancer stem cell (CSC) phenotype in PCa was described. Therefore, we aimed to investigate the expression and localization of Skp2 in clinical samples from patients with PCa, the association of Skp2 with EMT status, and the role of Skp2 in prostate CSC. We found that nuclear expression of Skp2 was increased in patients with PCa compared to those with benign hyperplasia, and correlated with high Gleason score in PCa patients. Increased Skp2 expression was observed in PCa cell lines with mesenchymal and CSC-like phenotype compared to their epithelial counterparts. Conversely, the CSC-like phenotype was diminished in cells in which SKP2 expression was silenced. Furthermore, we observed that Skp2 downregulation led to the decrease in subpopulation of CD44+CD24− cancer stem-like cells. Finally, we showed that high expression levels of both CD24 and CD44 were associated with favorable recurrence-free survival for PCa patients. This study uncovered the Skp2-mediated CSC-like phenotype with oncogenic functions in PCa.
Genome-wide analysis in Hevea brasiliensis laticifers revealed species-specific post-transcriptional regulations of several redox-related genes
Authors: Zhang Yi , Leclercq Julie , Wu Shuangyang , Ortega-Abboud Enrique , Pointet Stéphanie , Tang Chaorong , Hu Songnian , Montoro Pascal 
Published: April 2019

AbstractMicroRNA-mediated post-transcriptional regulation has been reported on ROS production and scavenging systems. Although microRNAs first appeared highly conserved among plant species, several aspects of biogenesis, function and evolution of microRNAs were shown to differ. High throughput transcriptome and degradome analyses enable to identify small RNAs and their mRNA targets. A non-photosynthetic tissue particularly prone to redox reactions, laticifers from Hevea brasiliensis, revealed species-specific post-transcriptional regulations. This paper sets out to identify the 407 genes of the thirty main redox-related gene families harboured by the Hevea genome. There are 161 redox-related genes expressed in latex. Thirteen of these redox-related genes were targeted by 11 microRNAs. To our knowledge, this is the first report on a mutation in the miR398 binding site of the cytosolic CuZnSOD. A working model was proposed for transcriptional and post-transcriptional regulation with respect to the predicted subcellular localization of deduced proteins.
An ecological measure to screen executive functioning in MS: the Picture Interpretation Test (PIT) 360°
Authors: Realdon Olivia , Serino Silvia , Savazzi Federica , Rossetto Federica , Cipresso Pietro , Parsons Thomas D. , Cappellini Giacomo , Mantovani Fabrizia , Mendozzi Laura , Nemni Raffaello , Riva Giuseppe , Baglio Francesca 
Published: April 2019

AbstractExecutive functions are crucial for performance of everyday activities. In Multiple Sclerosis (MS), executive dysfunctions can be apparent from the early onset of the disease. Technology-based time-efficient and resource-saving tools for early evaluation of executive functions using an ecological approach are needed to assess functional performance in real-life. The aim was to compare the efficiency of the Picture Interpretation Test 360° (PIT 360°) with traditional measures on executive dysfunction in Persons with Multiple Sclerosis (PwMS) and Healthy Controls (HC). Participants were 31 patients with Relapsing-Remitting MS (mean age = 44.323 ± 13.149; mean Expanded Disability Status Scale = 2) and 39 HC (mean age = 39.538 ± 15.728). All were tested with standard neuropsychological tests of executive functions, PIT 360°, and measures of user experience. While standard neuropsychological tests failed to differentiate between PwMS and HC group, the PIT 360° was successful in detecting executive dysfunction in PwMS. All participants reported the PIT 360° to be an engaging tool and endorsed positive reactions to their experience. Overall, the PIT 360° is a quick, sensitive, and ecological tool that captures real-world executive dysfunction in PwMS. This engaging measure is sensitive for the detection of executive deficits since the early phases of the disease.
Effect of ranolazine on plasma arginine derivatives and urinary isoprostane 8-iso-PGF2α in patients with myocardial infarction in the randomized RIMINI-Trial
Authors: Schwemer Tjark F. , Deutscher Navina , Diermann Nadine , Böger Rainer , Schwedhelm Edzard , Blankenberg Stefan , Friedrich Felix W. 
Published: April 2019

AbstractThe purpose of the present study was to assess whether 6-week ranolazine application on top of guideline-based treatment impacts on the arginine/NO pathway and urinary isoprostane 8-iso-PGF2α as marker of oxidative stress in patients directly after a myocardial infarction. 20 patients with unstable angina pectoris and proof of acute cardiac ischemia entered the study. 10 subjects received the study drug ranolazine in addition to standard treatment, the others received only standard treatment. Urine and venous blood were collected before and after treatment. At the end of the study and compared to baseline, homoarginine levels had increased in the control group. This was not the case in ranolazine-patients. Interestingly, in ranolazine-treated-patients arginine plasma levels were significantly higher at the end of the study than at baseline (difference +26 µmol/L, 95% CI 8.6 to 44 µmol/L). ADMA and SDMA levels were not different. Urine levels of the oxidative stress marker 8-iso-PGF2α tended to be lower in ranolazine-treated patients (−144 pmol/mg creatinine). Findings of this hypothesis-driven study give evidence that ranolazine treatment enhances arginine plasma levels and lowers oxidative stress.
PCC0208027, a novel tyrosine kinase inhibitor, inhibits tumor growth of NSCLC by targeting EGFR and HER2 aberrations
Authors: Dong Qiuju , Yu Pengfei , Ye Liang , Zhang Jianzhao , Wang Hongbo , Zou Fangxia , Tian Jingwei , Kurihara Hiroshi 
Published: April 2019

AbstractPCC-0208027 is a novel tyrosine kinase inhibitor that has a strong inhibitory effect on epidermal growth factor receptor (EGFR)- or HER2-driven cancers. The aim is to assess the anti-tumor activity of PCC0208027 and related mechanisms in non-small cell lung cancer (NSCLC). We examined the activity of PCC0208027 on various mutated EGFRs, HER2, and HER4. MTT assays, flow cytometry, and Western blotting were used to examine the effects of PCC0208027 on NSCLC cells with different genetic characteristics and relevant molecular mechanisms. Nude mouse xenograft models with HCC827, NCI-H1975, and Calu-3 cells were used to evaluate the in vivo anti-tumor activity of PCC0208027. Results showed that PCC0208027 effectively inhibited the enzyme activity of EGFR family members, including drug-sensitive EGFR mutations, acquired drug-resistant EGFR T790M and EGFR C797S mutations, and wild-type (WT) HER2. PCC0208027 blocked EGFR phosphorylation, thereby downregulating downstream PI3K/AKT and MAPK/ERK signaling pathways and inducing G0/G1 arrest in NSCLC cells. PCC0208027 inhibited tumor growth in mouse xenograft models of HCC827, NCI-H1975, and Calu-3 cells. In summary, our findings suggest that PCC0208027 has the potential to become an oral antineoplastic drug for NSCLC treatment and is worthy of further development.
Imaging cell morphology and physiology using X-rays
Authors: Weinhardt Venera , Chen Jian-Hua , Ekman Axel , McDermott Gerry , Le Gros Mark A. , Larabell Carolyn 
Published: April 2019

Abstract
Morphometric measurements, such as quantifying cell shape, characterizing sub-cellular organization, and probing cell–cell interactions, are fundamental in cell biology and clinical medicine. Until quite recently, the main source of morphometric data on cells has been light- and electron-based microscope images. However, many technological advances have propelled X-ray microscopy into becoming another source of high-quality morphometric information. Here, we review the status of X-ray microscopy as a quantitative biological imaging modality. We also describe the combination of X-ray microscopy data with information from other modalities to generate polychromatic views of biological systems. For example, the amalgamation of molecular localization data, from fluorescence microscopy or spectromicroscopy, with structural information from X-ray tomography. This combination of data from the same specimen generates a more complete picture of the system than that can be obtained by a single microscopy method. Such multimodal combinations greatly enhance our understanding of biology by combining physiological and morphological data to create models that more accurately reflect the complexities of life.
Apoptotic cell-derived extracellular vesicles: structure–function relationships
Authors: Grant Lois R. , Milic Ivana , Devitt Andrew 
Published: April 2019

AbstractApoptosis is an essential process for normal physiology and plays a key role in the resolution of inflammation. Clearance of apoptotic cells (ACs) involves complex signalling between phagocytic cells, ACs, and the extracellular vesicles (EVs) they produce. Here, we discuss apoptotic cell-derived extracellular vesicles (ACdEVs) and how their structure relates to their function in AC clearance and the control of inflammation, focussing on the ACdEV proteome. We review the current knowledge, ongoing work and future directions for research in this field.
Packaging development: how chromatin controls transcription in zebrafish embryogenesis
Authors: Horsfield Julia A. 
Published: April 2019

AbstractHow developmental gene expression is activated, co-ordinated and maintained is one of the biggest questions in developmental biology. While transcription factors lead the way in directing developmental gene expression, their accessibility to the correct repertoire of genes can depend on other factors such as DNA methylation, the presence of particular histone variants and post-translational modifications of histones. Collectively, factors that modify DNA or affect its packaging and accessibility contribute to a chromatin landscape that helps to control the timely expression of developmental genes. Zebrafish, perhaps better known for their strength as a model of embryology and organogenesis during development, are coming to the fore as a powerful model for interpreting the role played by chromatin in gene expression. Several recent advances have shown that zebrafish exhibit both similarities and differences to other models (and humans) in the way that they employ chromatin mechanisms of gene regulation. Here, I review how chromatin influences developmental transcriptional programmes during early zebrafish development, patterning and organogenesis. Lastly, I briefly highlight the importance of zebrafish chromatin research towards the understanding of human disease and transgenerational inheritance.
Gesundheitssicherung als staatliche Aufgabe. Der öffentliche Gesundheitsdienst im Rahmen „völkischer Staatspolitik“
Authors: Schleiermacher Sabine 
Published: April 2019

ZusammenfassungGegenstand des Beitrags sind Tätigkeitsbereiche der mit dem Gesetz über die Vereinheitlichung des öffentlichen Gesundheitswesens (GVG) vom 3. Juli 1934 etablierten Gesundheitsämter und deren Funktionsträger während des Nationalsozialismus und in der frühen Nachkriegszeit in Thüringen und Württemberg. Untersucht werden die Umsetzung des vom Reichsministerium des Innern vorgegebenen neuen Paradigmas der «Erb- und Rassenpflege» in den Gesundheitsämtern, Funktionsbereiche der Gesundheitsämter, die Rolle der Amtsärzte und ihre Ermessensspielräume, die Auswirkungen des Krieges auf die konkreten Tätigkeiten der Amtsärzte sowie die regionalen Besonderheiten im Ländervergleich und schließlich Aspekte struktureller, programmatischer und personeller Kontinuität im Öffentlichen Gesundheitsdienst nach der Befreiung 1945.
DNVF-Memorandum III – Methoden für die Versorgungsforschung, Teil 4 – Konzept und Methoden der organisationsbezogenen Versorgungsforschung: Kurzfassung
Authors: Ansmann Lena , Albert Ute-Susann , Auer Ramona , Baumann Walter , Bitzer Eva , Bögel Martina , Ernstmann Nicole , Gostomzyk Johannes , Götz Katja , Hahn Ursula , Hammer Antje , Hollederer Alfons , Hower Kira , Kostuj Tanja , Kowalski Christoph , Nöst Stefan , Nowak Marina , Pfaff Holger , Rölker-Denker Lars , Vollmar Horst , Wirtz Markus 
Published: April 2019

ZusammenfassungDas Forschungsfeld der organisationsbezogenen Versorgungforschung ist von zunehmender Bedeutung. Ausgehend von der Vertiefung zu Methoden der organisationsbezogenen Versorgungsforschung des Memorandums III, Teil 1 aus dem Jahr 2009 werden die weiterentwickelten Standards und Grundlagen zusammengefasst. Das Memorandum behandelt die theoretische Rahmung, grundlegende Methodenansätze und Methoden zur Konzeption, Evaluation und Implementierung komplexer Interventionen in Versorgungsorganisationen.
Unveiling the Insular Lobe of Reil: Neurophysiological and Anatomical Features
Authors: Damiani Daniel , Nascimento Ana Maria , Pires Vanessa Gonçalves 
Published: April 2019

AbstractThe insular lobe has long been investigated, from its anatomical descriptions to its neurophysiological activity. Located in a central location, the insular lobe participates in several afferent and efferent pathways, forming part of the eloquent and fundamental structures that make up the central core of the brain. The lobe of the insula has participation in language function, such as speech, sensory (e.g., taste), limbic, autonomic (visceral), also forming part of complex associative circuits, including part of the circuits of mirror neurons. Several functional descriptions attributed to the insular lobe have been made in patients suffering from cerebrovascular diseases, as well as in those with epilepsy. Much progress and many descriptions have also been made in patients with tumors. Despite much information already available about the insular lobe, it is likely that much will be discovered in the coming years.
Light–heat conversion dynamics in highly diversified water-dispersed hydrophobic nanocrystal assemblies
Authors: Mazzanti Andrea , Yang Zhijie , Silva Mychel G. , Yang Nailiang , Rizza Giancarlo , Coulon Pierre-Eugène , Manzoni Cristian , de Paula Ana Maria , Cerullo Giulio , Della Valle Giuseppe , Pileni Marie-Paule 
Published: April 2019

Significance
Metal and semiconductor nanoparticles have been widely exploited in research, because of their striking capability to concentrate light energy at the nanoscale and convert it to heat at ultrahigh speed. However, most nanoparticles are made of homogeneous materials, which limits the possibility to engineer their photothermal properties. Additional degrees of freedom are provided by nanoassemblies: periodically arranged nanocrystals of few nanometers in size embedded into an organic matrix. Here we display a specific mechanism presiding over the light–heat ultrafast conversion in a highly diversified family of nanoassemblies, which is intimately related to their hybrid composition at the nanoscale. The exceptional photothermal properties of nanocrystal assemblies open prospects in nanomedicine (photothermal therapy) and energy harvesting.