bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct acting anti-hepatitis C virus drugs: Clinical pharmacology and future direction
Authors: Geddawy Ayman , Ibrahim Yasmine F. , Elbahie Nabil M. , Ibrahim Mohammad A. 
Published: April 2017

Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.
Methanogenesis inhibition by phosphorus in anaerobic liquid waste treatment
Authors: Mancipe-Jiménez D. C. , Costa C. , Márquez M. C. 
Published: April 2017

Abstract The effect of a sudden influent phosphorus concentration increase on a completely mixed reactor of an anaerobic liquid waste treatment process was evaluated. Chemical oxygen demand (COD), volatile fatty acids (VFA), suspended solids, pH and gas production were measured for process monitoring. Optical and scanning electron microscopic observations were also performed. Kinetic parameters were estimated from substrate and microorganisms concentrations, mass balances and experimental data. After phosphorus concentration increase, VFA concentration enhanced by 500% approximately and COD removal, gas production, bacterial growth coefficient (Y) and maximum bacterial growth rate (μmax) decreased 20%, 18%, 54% and 35% respectively. An excessive growth of filamentous microorganisms was also observed. The equilibrium established between acidogenic and methanogenic microorganisms was visibly affected causing a decrease of methanogenic activity. The experimental results showed that phosphorous arises as a methanogenesis inhibitor and a growth factor for filamentous microorganism under anaerobic conditions.
Singularly perturbed hyperbolic problems on metric graphs: asymptotics of solutions
Authors: Golovaty Yuriy , Flyud Volodymyr 
Published: April 2017

Abstract
We are interested in the evolution phenomena on star-like networks composed of several branches which vary considerably in physical properties. The initial boundary value problem for singularly perturbed hyperbolic differential equation on a metric graph is studied. The hyperbolic equation becomes degenerate on a part of the graph as a small parameter goes to zero. In addition, the rates of degeneration may differ in different edges of the graph. Using the boundary layer method the complete asymptotic expansions of solutions are constructed and justified.
Transurethral resection of the prostate, bladder explosion and hyponatremic encephalopathy: a rare case report of malpractice
Authors: Vacchiano Giuseppe , Rocca Aldo , Compagna Rita , Zamboli Anna Ginevra Immacolata , Cirillo Vera , Di Domenico Lorenza , Di Nardo Veronica , Servillo Giuseppe , Amato Bruno 
Published: April 2017

AbstractWe present an original case report of a bladder explosion during a TURP intervention for benign prostatic hypertrophy, that was brought on by the absorption of about 5 liters of glycine 1.5% and then onset of a severe hyponatremia. The quick and inappropriate correction of this electrolyte imbalance led the onset of encephalopathy and the death of the patient. The authors discuss the pathogenesis of these uncommon diseases and, considering the most recent Italian Legislation, they highlight the importance to respect good clinical practice standards and guidelines to ensure the most appropriate treatments for the patient and remove any assumptions of medical liability.
Guidelines for balancing the flow in extrusion dies: the influence of the material rheology
Authors: Rajkumar A. , Ferrás L.L. , Fernandes C. , Carneiro Olga S. , Nóbrega J. Miguel 
Published: April 2017

Abstract
In this work we present improved design guidelines to support the die designer activity, when searching for the flow channel geometry that allows the achievement of a balanced flow distribution, in complex profile extrusion dies. The proposed methodology relies on surrogate models, obtained through a detailed and extensive numerical study, carried out with the open source computational library OpenFOAM®, in which an appropriate numerical solver for the problems under study was implemented. The main contribution of this work is to further enlarge the applicability of the simplified design methodology (Rajkumar A, Ferrás LL, Fernandes C, Carneiro OS, Becker M, Nóbrega JM. Int. Polym. Proc. 2017, 32, 58–71.) previously proposed by this group for similar purposes, by considering the effect of processing parameters and material rheology. The sensitivity analyses performed showed that, among the studied parameters, the power-law exponent was the only one that affected the system behavior. Thus, the previous proposed surrogate models were modified to include the effect of this parameter. Verification studies performed for three geometries and different rheological and process parameters evidenced the effectiveness of the proposed simplified design methodology.
Read! – On the intonational properties of short imperatives in Spanish
Authors: Robles-Puente Sergio 
Published: April 2017

AbstractIn this study, the intonation of one-word imperatives is compared with that of one-word declaratives in Peninsular Spanish in order to establish differences and similarities between them. The analysis of 373 utterances produced by 8 speakers (117 in a declarative context and 256 in an imperative context) demonstrates that the intonational link between declaratives and imperatives is irrefutable since L+H* L% configurations are found in both pragmatic contexts. Nevertheless, imperatives can also show tonal movements not found in declaratives: L+H* LH%, L+H* HL%, L+H* H%, L* H%. Finally, the study demonstrates that due to the limitations short imperative utterances involve, speakers implement tonal movements rarely attested in imperatives with multiple pitch accents.
Clinical outcomes of 130 patients with primary and secondary lung tumors treated with Cyberknife robotic stereotactic body radiotherapy
Authors: Janvary Zsolt Levente , Jansen Nicolas , Baart Veronique , Devillers Magali , Dechambre David , Lenaerts Eric , Seidel Laurence , Barthelemy Nicole , Berkovic Patrick , Gulyban Akos , Lakosi Ferenc , Horvath Zsolt , Coucke Philippe A. 
Published: April 2017

Abstract

Background
Authors report clinical outcomes of patients treated with robotic stereotactic body radiotherapy (SBRT) for primary, recurrent and metastatic lung lesions.

Patients and methods
130 patients with 160 lesions were treated with Cyberknife SBRT, including T1-3 primary lung cancers (54%), recurrent tumors (22%) and pulmonary metastases (24%). The mean biologically equivalent dose (BED10Gy) was 151 Gy (72–180 Gy). Median prescribed dose for peripheral and central lesions was 3×20 Gy and 3×15 Gy, respectively. Local control (LC), overall survival (OS), and cause-specific survival (CSS) rates, early and late toxicities are reported. Statistical analysis was performed to identify factors influencing local tumor control.

Results
Median follow-up time was 21 months. In univariate analysis, higher dose was associated with better LC and a cut-off value was detected at BED10Gy ≤ 112.5 Gy, resulting in 1-, 2-, and 3-year actuarial LC rates of 93%, vs 73%, 80% vs 61%, and 63% vs 54%, for the high and low dose groups, respectively (p = 0.0061, HR = 0.384). In multivariate analysis, metastatic origin, histological confirmation and larger Planning Target Volume (PTV) were associated with higher risk of local failure. Actuarial OS and CSS rates at 1, 2, and 3 years were 85%, 74% and 62%, and 93%, 89% and 80%, respectively. Acute and late toxicities ≥ Gr 3 were observed in 3 (2%) and 6 patients (5%), respectively.

Conclusions
Our favorable LC and survival rates after robotic SBRT, with low rates of severe toxicities, are coherent with the literature data in this mixed, non-selected study population.
Evaluation of brain edema formation defined by MRI after LINAC-based stereotactic radiosurgery
Authors: Harat Maciej , Lebioda Andrzej , Lasota Judyta , Makarewicz Roman 
Published: April 2017

Abstract

Background
Peri-lesional edema is a serious and well-known complication of stereotactic radiosurgery (SRS). Here we evaluated edema risk after SRS and assessed its formation and resolution dynamics.

Patients and methods
107 patients underwent SRS for heterogeneous diagnoses: 34 (29%) with arteriovenous malformations, 38 (35%) with meningiomas, 16 (15%) with metastatic tumors, 16 (15%) with acoustic neuromas, 3 with (3%) cavernomas, and 2 (2%) each with anaplastic astrocytomas and anaplastic oligoastrocytomas. Edema area was delineated in MRI T2-FLAIR sequences 0, 6, 12, 18, 24, 30, and 38 months after treatment. Lesion location was defined as either above (n = 80) or below (n = 32) the “Frankfurt modified line” (FML).

Results
17% of patients developed or had worsening post-treatment edema. Edema volume was maximal at 6 months (mean 7.2, SD 1.2) post radiosurgery. Post-SRS edema was 5.1 (1.06 – 24.53) times more likely in patients with lesions above the FML. There was no association between edema development and age, PTV size, number of beams, and diagnosis (p = 0.07).

Conclusions
Radiosurgery-associated edema develops within 6 months of treatment and decreases over time. Edema occurrence is strongly related to lesion location, and its presence is much more likely when the treated lesions are situated above the Frankfurt line.
Critical time point for apoptotic cell death in an experimental ischemia/reperfusion model and the effect of N-acetylcystein
Authors: Ozsarlak-Sozer Gonen , Emre Mustafa , Demirkol Serhat , Açıkalın Arbil , Çetiner Salih , Topçu Zeki , Demir-Dora Devrim 
Published: April 2017

Abstract

Objective
Kidney transplantation is an important treatment option in end stage renal failure. Tissue death may be an important problem when a kidney is removed from a cadaver and transported to a donor a long distance away. The purpose of this study is to determine the critical time point for apoptotic cell death in a renal ischemia/reperfusion model and determine the effects of N-acetylcystein on apoptosis induced by ischemia injury.

Methods
Apoptotic cell death after induced renal ischemia followed by reperfusion, was estimated in a group of Wistar albino rats by immunoflourescence and ELISA techniques. N-acetylcystein, an antioxidant agent, was given to the rats to study the effect on apoptosis. Tissues were examined immunohistochemically at 0, 1 h, 24 h, 5 days and 10 days for detection of apoptotic cells.

Results
Our results showed that an ischemia for 60 min followed by reperfusion for 60 min triggered apoptosis. Moreover, N-acetylcystein significantly diminished both the ischemia/reperfusion damage and apoptosis.

Conclusion
We anticipate our results would be important for kidney transplantation in estimating the critical time point for apoptosis and administration of N-acetylcystein prior to removal of the organ may be important in delaying the onset of apoptosis.
PDF Simulations of the Ignition of Hydrogen/Air, Ethylene/Air and Propane/Air Mixtures by Hot Transient Jets
Authors: Fischer Simon , Markus Detlev , Ghorbani Asghar , Maas Ulrich 
Published: April 2017

Abstract
A numerical investigation is carried out to study ignition events of different premixed stoichiometric fuel/air mixtures by hot exhaust gas jets. The simulations are performed for premixed, stoichiometric hydrogen/air, ethylene/air and propane/air mixtures in configurations relevant to safety applications. The ignition events of the different fuel/air mixtures by their corresponding exhaust gas jet are examined qualitatively analyzing processes and conditions leading to ignition. A stand-alone probability density function (PDF) method in connection with a projection method (PM) to calculate the mean pressure is used to model the turbulent flow. The transport equation for the joint velocity – turbulent frequency – scalar PDF is solved by a Monto Carlo/particle method. In order to reduce the computational costs concerning the chemical kinetics the reaction diffusion manifolds (REDIM) technique is used to get an appropriate reduced kinetic scheme.
Anisotropic Nature of Raw, Radially Strained, and Radially Strained and Aged Steel Tubes
Authors: Strickland J. N. , Ohl B. , Chitwood G. , Krishnan K. , Kohn G. , Young M. L. 
Published: April 2017

Abstract
Because of the difficulty of measuring anisotropy in steel tubes, industries often rate overall tube strength based on tensile properties of the raw steel, or of the steel in a single direction (along the axis of the tube). This paper discusses the use of mini-tensile testing to develop a much more accurate way of assessing the anisotropic strength of these steel tubes, which is typically unobtainable through conventional tensile testing. In this study, the amount of anisotropy is determined within the tube by measuring the yield strength of the steel in three conditions (raw, strained, and strained and aged), three orientations (radial, transverse (hoop), axial (longitudinal), and locations (inner diameter, neutral axis, and outer diameter) within the tube. The data shows that the strength is approximately 10 % greater for the strained and strained and aged steels in the transverse direction than in the axial direction because of work hardening during the upsetting process. Microstructural examination using optical microscopy and scanning electron microscopy was used to explain the mini-tensile test results and to support the observation that the steel tubes are more likely to fail in axial tension than in burst (internal pressure radially outward) and collapse (external pressure radially inward).
Unusual semi‐extractability as a hallmark of nuclear body‐associated architectural noncoding RNAs
Authors: Chujo Takeshi , Yamazaki Tomohiro , Kawaguchi Tetsuya , Kurosaka Satoshi , Takumi Toru , Nakagawa Shinichi , Hirose Tetsuro 
Published: April 2017

AbstractNEAT1_2 long noncoding RNA (lncRNA) is the molecular scaffold of paraspeckle nuclear bodies. Here, we report an improved RNA extraction method: extensive needle shearing or heating of cell lysate in RNA extraction reagent improved NEAT1_2 extraction by 20‐fold (a property we term “semi‐extractability”), whereas using a conventional method NEAT1_2 was trapped in the protein phase. The improved extraction method enabled us to estimate that approximately 50 NEAT1_2 molecules are present in a single paraspeckle. Another architectural lncRNA, IGS16, also exhibited similar semi‐extractability. A comparison of RNA‐seq data from needle‐sheared and control samples revealed the existence of multiple semi‐extractable RNAs, many of which were localized in subnuclear granule‐like structures. The semi‐extractability of NEAT1_2 correlated with its association with paraspeckle proteins and required the prion‐like domain of the RNA‐binding protein FUS. This observation suggests that tenacious RNA–protein and protein–protein interactions, which drive nuclear body formation, are responsible for semi‐extractability. Our findings provide a foundation for the discovery of the architectural RNAs that constitute nuclear bodies.
Quantitative Assessment of Fat Levels inCaenorhabditis elegansUsing Dark Field Microscopy
Authors: Fouad Anthony D , Pu Shelley H , Teng Shelly , Mark Julian R , Fu Moyu , Zhang Kevin , Huang Jonathan , Raizen David M , Fang-Yen Christopher 
Published: April 2017

AbstractThe roundworm Caenorhabditis elegans is widely used as a model for studying conserved pathways for fat storage, aging, and metabolism. The most broadly used methods for imaging fat in C. elegans require fixing and staining the animal. Here, we show that dark field images acquired through an ordinary light microscope can be used to estimate fat levels in worms. We define a metric based on the amount of light scattered per area, and show that this light scattering metric is strongly correlated with worm fat levels as measured by Oil Red O (ORO) staining across a wide variety of genetic backgrounds and feeding conditions. Dark field imaging requires no exogenous agents or chemical fixation, making it compatible with live worm imaging. Using our method, we track fat storage with high temporal resolution in developing larvae, and show that fat storage in the intestine increases in at least one burst during development.
Proteomics Analysis Identifies Orthologs of Human Chitinase-Like Proteins as Inducers of Tube Morphogenesis Defects inDrosophila melanogaster
Authors: Zimmerman Sandra G , Merrihew Gennifer E , MacCoss Michael J , Berg Celeste A 
Published: April 2017

AbstractTwo papers in this issue demonstrate novel proteomic approaches that enhance genetic analysis. Matsuoka et al. investigated how diet-regulated........Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing and, when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation. We implemented a novel approach that uses magnetic beads to isolate a small population of specialized ovarian cells, cells that nonautonomously regulate morphogenesis of epithelial tubes that form and secrete eggshell structures called dorsal appendages (DAs). Differential mass spectrometry analysis of these cells detected elevated levels of four of the six Idgf family members (Idgf1, Idgf2, Idgf4, and Idgf6) in flies mutant for bullwinkle (bwk), which encodes a transcription factor and is a known regulator of DA-tube morphogenesis. We show that, during oogenesis, dysregulation of Idgfs (either gain or loss of function) disrupts the formation of the DA tubes. Previous studies demonstrate roles for Drosophila Idgfs in innate immunity, wound healing, and cell proliferation and motility in cell culture. Here, we identify a novel role for Idgfs in both normal and aberrant tubulogenesis processes.
Systemkrisenbewältigung durch Bankenabwicklung? Aktuelle Bemerkungen zu unrealistischen Erwartungen
Authors: Binder Jens-Hinrich 
Published: April 2017

Zusammenfassung
Mit der Krise des italienischen Kreditinstituts Monte dei Paschi di Siena ist der in Reaktion auf die Finanzkrise neu geschaffene Rechtsrahmen für die Sanierung und Abwicklung von Kreditinstituten und Wertpapierfirmen einer ersten Feuertaufe unterworfen worden. Dass der italienische Staat das Institut durch Rettungsmaßnahmen stützen will, wirft die Frage auf, ob das neue Recht versagt hat – oder ob dagegen verstoßen wird. Der Beitrag nimmt dies zum Anlass, die Tauglichkeit des durch die Bankenabwicklungsrichtlinie von 2014 und die SRM-Verordnung eingeführten Rechtsrahmens für die Anwendung in systemischen Krisen zu untersuchen. Er plädiert für mehr Realitätsnähe bei der Einschätzung der Leistungsfähigkeit dieses Rechtsrahmens und analysiert vor diesem Hintergrund die nach beiden Rechtsakten verbleibenden Spielräume für Stützungsmaßnahmen zu Gunsten insolvenzgefährdeter Banken.
Doch keine Generalamnestie im Kapitalmarktstrafrecht
Authors: Kudlich Hans 
Published: April 2017

Zusammenfassung
Kurz nach dem Inkrafttreten der Änderungen des WpHG durch das Erste Finanzmarktnovellierungsgesetz vom 30. 6. 2016 (BGBl I, 1514) ist die Frage aufgeworfen worden, ob eine unglückliche Regelung über das Inkrafttreten der Änderungen aufgrund einer fehlerhaften Harmonisierung mit dem Inkrafttreten der in Bezug genommenen Marktmissbrauchsverordnung (VO (EU) Nr. 596/2014 des Europäischen Parlaments und des Rates vom 16. 4. 2014, ABl Nr. L 173 v. 12. 6. 2014, S. 1) nicht nur zu einer Strafbarkeitslücke für einen Tag, sondern – wegen des Günstigkeitsprinzips des § 2 Abs. 3 StGB – zu einer unbeabsichtigten Generalamnestie für alle früheren und noch nicht abgeurteilten Straftaten (und Ordnungswidrigkeiten) nach dem WpHG geführt hat. Der 5. Strafsenat hat diese verneint und keine Ahndungslücke angenommen.
Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers
Authors: Gheldiu Ana-Maria , Vlase Laurian , Popa Adina , Briciu Corina , Muntean Dana , Bocsan Corina , Buzoianu Anca , Achim Marcela , Tomuta Ioan , Todor Ioana , Neag Maria 
Published: April 2017

Purpose: To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. Methods: This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. Results: Fluvoxamine pretreatment increased Cmax and AUC0-∞ of nebivolol (Cmax: 1.67 ± 0.690 vs 2.20 ± 0.970 ng/mL; AUC0-∞: 12.1 ± 11.0 vs 19.3 ± 19.5 ng*h/mL ) and of its active metabolite (Cmax: 0.680 ± 0.220 vs 0.960 ± 0.290 ng/mL; AUC0-∞: 17.6 ±20.1 vs 25.5 ± 29.9 ng*h/mL). Apart from Cmax,AUC0-t and AUC0-∞, the other pharmacokinetic parameters (tmax, kel and t½) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. Conclusions: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.