bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Information Theoretic Phase I–II Design for Molecularly Targeted Agents That Does Not Require an Assumption of Monotonicity
Authors: Mozgunov Pavel , Jaki Thomas 
Published: June 2018

SummaryFor many years phase I and phase II clinical trials have been conducted separately, but there has been a recent shift to combine these phases. Although a variety of phase I–II model-based designs for cytotoxic agents have been proposed in the literature, methods for molecularly targeted agents (TAs) are just starting to develop. The main challenge of the TA setting is the unknown dose–efficacy relationship that can have either an increasing, plateau or umbrella shape. To capture these, approaches with more parameters are needed or, alternatively, more orderings are required to account for the uncertainty in the dose–efficacy relationship. As a result, designs for more complex clinical trials, e.g. trials looking at schedules of a combination treatment involving TAs, have not been extensively studied yet. We propose a novel regimen finding design which is based on a derived efficacy–toxicity trade-off function. Because of its special properties, an accurate regimen selection can be achieved without any parametric or monotonicity assumptions. We illustrate how this design can be applied in the context of a complex combination–schedule clinical trial. We discuss practical and ethical issues such as coherence, delayed and missing efficacy responses, safety and futility constraints.
Evaluation of the WHO laboratory quality stepwise implementation tool
Authors: Datema T. A. M. , Roper K. G. , Cognat S. , Saad M. D. , Oskam L. , Dolmazon V. , Engelberts M. F. M. , Hessels P. , Klatser P. R. 
Published: June 2018

AbstractObjectivesTo introduce the Laboratory Quality Stepwise Implementation (LQSI) tool and provide data about its roll‐out, usage and effectiveness in assisting laboratories with quality improvement.MethodsThe LQSI tool, a freely available stepwise guide, was developed by WHO to assist laboratories with efficiently implementing a quality management system.ResultsSince the tool's launch in 2014, it has been accessed by 130 986 unique users from 195 of 206 listed states. Of 35 respondents to a survey, 12 (34%) indicated that their laboratory had been able to achieve accreditation/certification/licensing as a result of using the tool.ConclusionsThe LQSI tool, currently being used worldwide and available in English, French, Russian, Spanish, Arabic and Turkish, positively impacts the quality of services provided by clinical and public health laboratories, leading to improved clinical care and disease surveillance capacity as required by the IHR (2005) and envisioned by the Global Health Security Agenda.
Affinity and Distance. On the Newtonian Structure of Some Data Kernels
Authors: Aimar Hugo , Gómez Ivana 
Published: June 2018

Abstract
Let X be a set. Let K(x, y) > 0 be a measure of the affinity between the data points x and y. We prove that K has the structure of a Newtonian potential K(x, y) = φ(d(x, y)) with φ decreasing and d a quasi-metric on X under two mild conditions on K. The first is that the affinity of each x to itself is infinite and that for x ≠ y the affinity is positive and finite. The second is a quantitative transitivity; if the affinity between x and y is larger than λ > 0 and the affinity of y and z is also larger than λ, then the affinity between x and z is larger than ν(λ). The function ν is concave, increasing, continuous from R+ onto R+ with ν(λ) < λ for every λ > 0
Transglutaminase type 2 in the regulation of proteostasis
Authors: D’Eletto Manuela , Rossin Federica , Fedorova Olga , Farrace Maria Grazia , Piacentini Mauro 
Published: June 2018

Abstract
The maintenance of protein homeostasis (proteostasis) is a fundamental aspect of cell physiology that is essential for the survival of organisms under a variety of environmental and/or intracellular stress conditions. Acute and/or persistent stress exceeding the capacity of the intracellular homeostatic systems results in protein aggregation and/or damaged organelles that leads to pathological cellular states often resulting in cell death. These events are continuously suppressed by a complex macromolecular machinery that uses different intracellular pathways to maintain the proteome integrity in the various subcellular compartments ensuring a healthy cellular life span. Recent findings have highlighted the role of the multifunctional enzyme type 2 transglutaminase (TG2) as a key player in the regulation of intracellular pathways, such as autophagy/mitophagy, exosomes formation and chaperones function, which form the basis of proteostasis regulation under conditions of cellular stress. Here, we review the role of TG2 in these stress response pathways and how its various enzymatic activities might contributes to the proteostasis control.
»Und was macht nicht alles einen Namen!«
Authors: Affolter Hanspeter 
Published: June 2018

AbstractThe following article deals with the relationship between names and their symbolic capital as a theme in Theodor Fontane’s Poggenpuhls. While the eponymous poor but noble family relies on its notable surname, different names were being popularized through advertising as part of the social and economic upheavals at the end of the 19th century. This rivalry between a genealogical and a primarily economic way of publicizing and valorizing names is not only present in the novel’s dialogues, with noteworthy references to highly popular contemporary firms, but is also part of its spatial setting.
Civic Engagement Index (CEI) - the case of liberal arts universities from Romania
Authors: Hadad Shahrazad , Cantaragiu Ramona 
Published: June 2018

Abstract
We have arrived to a moment in history when the society we are living in is confronted with different sets of problems: hunger, crime, economic crises, natural disasters or cataclysms, and various human rights violations. At the moment the most appropriate way to solve these problems still lies with the organisms of the nation state. As such, the lack of civic sense and the increasing political apathy will only allow these problems to grow out of proportions. We are of the opinion that most of them can be counteracted if we try to educate the civic sense in people. By civic sense or engagement we understand a type of orientation towards being involved in social groups according to democratic principles. It is said the post-socialist countries are particularly threatened by the lack of civic engagement on behalf of their citizens that have reached the point where they take democracy for granted. This is why we explore the role played by universities in developing and shaping this civic attitude amongst young people. In order to do so, we resorted to questionnaires applied in liberal arts universities in Romania. These universities have a special relation to democratic principles, national pride and the perpetuation of the nation state as an ideal for its citizens and because of this we believe they represent a proper starting point for the current investigation. The areas that are targeted through the questionnaire are the following: the academic environment, the methods through which civic values are instilled in the hearts and minds of the students, and the institutional and personal factors that determine faculty to introduce civic values in their academic environments. Using the results we create the Civic Engagement Index (CEI) that can be used as a valuable benchmarking mechanism for those universities that are trying to enhance their civic engagement activities. Finally, we test the hypothesis that certain universities fail to create civic-oriented graduates and we propose ways in which the organizational culture could be transformed into a more supportive one: civic participation guides, civic responsibility classes, and service learning classes for faculty members to increase their openness towards the promotion of civic values.
Особливості структури туристичного ринку та взаємозв’язку між його суб’єктами
Authors: Zaychuk Kateryna 
Published: June 2018

У статті обґрунтовано поняття «туристичний ринок»; розглянуто структуру туристичного ринку; визначено суб’єктів туристичної діяльності; досліджено відносини між суб’єктами на туристичному ринку; окреслено перспективи подальшого розвитку туристичного ринку.
TBAI or KI‐Promoted Oxidative Coupling of Enamines and N‐Tosylhydrazine: An Unconventional Method toward 1,5‐ and 1,4,5‐Substituted 1,2,3‐Triazoles
Authors: Huang Wei , Zhu Chuanle , Li Minke , Yu Yue , Wu Wanqing , Tu Zhengchao , Jiang Huanfeng 
Published: June 2018

AbstractA novel method for the synthesis of 1,5‐ and 1,4,5‐substituted 1,2,3‐triazoles has been reported. This approach is promoted by iodine‐TBHP oxidation system using enamines and N‐tosylhydrazine as materials, which avoid the dependence of traditional methods on azides and transition metals. Through this approach, various 1,5‐ and 1,4,5‐substituted 1,2,3‐triazoles were delivered in moderate to high yields. The mechanistic study indicated that an amino exchange would be involved in the reaction process. Moreover, the product methyl 1‐(2‐methoxyphenyl)‐4‐methyl‐1H‐1,2,3‐triazole‐5‐carboxylate is a useful precursor to anti‐influenza A agent, and further application research was conducted.magnified image
Facile Fabrication of Fe2O3 Nanoparticles Anchored on Carbon Nanotubes as High‐Performance Anode for Lithium‐Ion Batteries
Authors: Fang Hua , Zou Wei , Yan Ji , Xing Yalan , Zhang Shichao 
Published: June 2018

AbstractFe2O3 nanoparticles (<10 nm) anchored on carbon nanotubes (denoted as Fe2O3‐NPs@CNT) are synthesized by a facile electrophoretic deposition strategy. In the composite, CNTs are utilized to construct a conductive matrix for uniformly dispersing Fe2O3‐NPs, building up a hierarchically porous architecture. The Fe2O3‐NPs anchored on CNTs can function as active sites for electrochemical reactions and facilitate fast electrochemical reaction kinetics, endowing the composite with improved electrochemical reversibility and desirable lithium storage capacity. The CNT framework can tightly hold Fe2O3‐NPs and thus provides fast electron transport to Fe2O3‐NPs, favouring high power performance in lithium‐ion batteries. The hierarchically porous structure can buffer the volume expansion/contraction caused by lithium insertion/extraction reactions. As expected, the composite delivers an ultrahigh reversible lithium storage capacity of 1231 mA h g−1 after 750 cycles at a high current rate of 1 A g−1. After tolerating the repeated volume fluctuation in the long cycle test, the composite still maintains its nanoporous architecture.
Management of Complete Talocrural Luxations by Selective Talocrural Arthrodesis using Hybrid Transarticular External Skeletal Fixation in Dogs
Authors: Önyay Taylan , İnal Kamil , Özbakır Deniz , Özak Ahmet , Yardımcı Cenk 
Published: June 2018

Objective This article presents a novel surgical technique in the management of open complete talocrural luxations and evaluates the results, and clinical benefits with its routine clinical utilization.
Study Design Retrospective study.
Animals Seventeen medium- or large-breed client-owned dogs of different breed, age and sex with complete talocrural luxations and radiographic follow-up of at least 24 weeks duration.
Method Selective talocrural arthrodesis was performed by using a hybrid transarticular external skeletal fixator frame. Clinical and radiographical evaluation was performed regarding the lesion, concomitant injury, duration of the surgery, time to first use of the limb, fixator removal time, complications and clinical outcomes.
Results Dogs started to use the injured limb between postoperative days 1 to 11. Pin or wire tract related complications were observed in all dogs. Time to fixator removal ranged from 57 to 90 days with a median of 73 days. All of the operated joints with an exception of one dog resulted in talocrural fusion. Mid-term clinical outcomes score was regarded as excellent in 13/17 dogs, good in 3/17 dogs and poor in 1/17 dogs subject to authors' evaluation.
Conclusion A transarticular hybrid external fixator may allow early use of postoperative limb with an excellent patient compliance and is well tolerated as well. The technique showed a promising opportunity of providing favourable limb use.
N,N’‐Bis(2‐mercaptoethyl)isophthalamide Binds Electrophilic Paracetamol Metabolites and Prevents Paracetamol‐Induced Liver Toxicity
Authors: Nilsson Johan L. Å. , Blomgren Anders , Nilsson Ulf J. , Högestätt Edward D. , Grundemar Lars 
Published: June 2018

AbstractParacetamol overdosing may cause liver injury including fulminant liver failure due to generation of the toxic metabolites, N‐acetyl‐p‐benzoquinone imine (NAPQI) and p‐benzoquinone (p‐BQ). Herein, the chelating agent, N,N’‐Bis(2‐mercaptoethyl)isophthalamide (NBMI), was examined for its potential ability to entrap NAPQI and p‐BQ and to prevent paracetamol‐induced liver injury. Both NBMI and the conventional paracetamol antidote N‐acetylcysteine (NAC) were investigated with regard to their abilities to scavenge the NAPQI and p‐BQ in a Transient Receptor Potential Ankyrin 1‐dependent screening assay. Stoichiometric evaluations indicated that NBMI was able to entrap these metabolites more efficiently than NAC. Furthermore, oral administration of either NBMI (680 mg/kg) or NAC (680 mg/kg) prevented the development of the characteristic liver necrosis and elevation of serum alanine aminotransferase in a mouse model for paracetamol‐induced liver injury. In summary, these results show that NBMI is able to entrap the toxic metabolites NAPQI and p‐BQ and to prevent paracetamol‐induced liver injury in mice.
Utilization and efficacy of elbasvir/grazoprevir for treating hepatitis C virus infection after liver transplantation
Authors: Miuma Satoshi , Miyaaki Hisamitsu , Soyama Akihiko , Hidaka Masaaki , Takatsuki Mitsuhisa , Shibata Hidetaka , Taura Naota , Eguchi Susumu , Nakao Kazuhiko 
Published: June 2018

AimRecently, elbasvir/grazoprevir combination therapy (EBR/GZR) was reported to have excellent antiviral effects for chronic genotype 1 hepatitis C virus (HCV) infection. However, it has not been recommended for patients with post‐liver transplant (LT) HCV re‐infections because of a lack of evidence for effectiveness and drug–drug interactions.MethodsWe report the usage of EBR/GZR in five post‐LT HCV re‐infected patients with the kinetics of renal function and tacrolimus trough levels during and after therapy. Furthermore, to evaluate the antiviral effects, we examined the HCV kinetics during and after therapy and compared this with other interferon‐free therapy in post‐LT patients (n = 19).ResultsAll patients treated with EBR/GZR therapy obtained rapid virologic response and sustained at 12 weeks post‐treatment. There was no evidence of worsening estimated glomerular filtration rates. Three patients were given tacrolimus as immunosuppressive therapy and its trough levels were controllable with dosage adjustments. One patient developed grade 1 diarrhea 3 days after therapy induction. To evaluate the antiviral effects of EBR/GZR therapy for these patients, we compared them to the effects of daclatasvir/asunaprevir combination therapy (n = 8) and sofosbuvir/ledipasvir combination therapy (n = 11). The EBR/GZR combination was not inferior to other therapies in its early phase and late‐phase antiviral effects.ConclusionsAlthough further studies with a larger number of patients are required, we suggest that EBR/GZR therapy is an alternative therapy for patients with post‐LT genotype 1 HCV re‐infection.
Use of fluoroquinolones in practice of veterinary medicine of Ukraine
Authors: Slobodyuk N. 
Published: June 2018

Antibacterial agents are one of the most important groups of medical preparations in the treatment of bacterial infection of different localization in humane and in veterinary medicine. The consequence of their rational use (the establishment of sensitivity of the pathogenic microflora, compliance with the course of treatment, etc.) have a high therapeutic effect and the minimum development of resistant strains of microorganisms. The widely used group of antimicrobial agents in veterinary medicine are second-generation fluorohinolone antibiotics that have good pharmacokinetic properties, a broad spectrum of bactericidal activity, and relatively low toxicity, although they have their own warnings and restrictions on the use of small animals during the formation of bone tissue. To achieve high therapeutic efficacy and minimizing of side effects, it is described the compatibility of some fluoroquinolones with other pharmacological groups. They found their application in the treatment of both productive animals, poultry, fur animals and petty domestic (dogs and cats) with a bacterial infection of the urinary tract, digestive and respiratory systems, infected wounds, etc. The article describes the detailed mechanism of action of the antibiotics of the fluoroquinolone group, which provides an opportunity for a deeper understanding of the manifestation of the bactericidal effect, as well as their classification by generation or generation. Particular attention deserves attention to the time of carrenia of fluoroquinolones in the context of their application to productive animals, because high quality livestock products minimize the development of resistant strains in humans and provide them with health. There is also a list of all registered medicinal products registered in Ukraine containing: ofloxacin, enrofloxacin, ciprofloxacin, marbofloxacin, denofloxacin, which carries important informative information for practicing doctors, pharmacists, etc.
Innovation and entrepreneurship for competitiveness in the EU: an empirical analysis
Authors: Herman Emilia 
Published: June 2018

Abstract
The nexus of innovation, entrepreneurship and competiveness represents a real challenge for the European economy, and not only, taking into account the important role of these determinants of inclusive and sustainable development in the context of the Fourth Industrial Revolution. The aim of this article is to explore the relation between innovation, entrepreneurship and national competitiveness, at the EU level, in order to highlight how innovation and entrepreneurship can influence the level of competitiveness and inclusive development in these countries. The results of the comparative analysis based on means-testing using independent samples t-test, at EU level, show that there are significant differences between low-medium innovation performance countries group and high and very high innovation countries performance group in terms of competitiveness, innovative entrepreneurship, productive entrepreneurship and economic and inclusive development, fact which emphasizes the need to take specific actions to improve EU innovation performance, especially in the EU countries included in the low-medium innovation performance countries group for improving national competitiveness and implicitly increasing the level of development. The correlation and regression analysis results suggest that the high level of national competitiveness in some EU countries can be mainly explained by high level of innovation performance, high level of innovative and productive entrepreneurship. The findings of the study can be useful for policymakers to formulate policies for improving national competitiveness within an inclusive development.
Using non-parametric technical data envelopment analysis - DEA, for measuring productive technical efficiency
Authors: Lita Iulian , Stamule Tănase 
Published: June 2018

Abstract
The following study is, in addition to a reassessment of literature and an analysis based on non-parametrical techniques based on linear programming. The analysis based on the Data Envelopment Analisys (DEA) technique will be used to see whether the model that we have used has a significant importance, if there are any substantial differences between the efficiency scores obtained or estimated through various methods. The theoretical part, based on the DEA technique will be analysed under the influence of both the works of Farell(1957), and also Charnes, Cooper, Rhodes(1978), Banker, Charnes, Cooper(1984) and other newer models. The dissolution of efficiency scores obtained through the CRS-DEA model has been studied for a long time into two different components: One is linked with the scale inefficiency and the other one represents the pure technical inefficiency. This dissolution can be done by using the CRS model with technology when not all the companies are operating at the optimum level, i.e. through the simultaneous application on the same set of data of the CRS and VRS models. In this study, the main non-parametrical Data Envelopment Analysis method is presented (Wu, Fan, Zhou, Zhou, 2012; Halkos, Tzeremes, 2009) and its application on a group of 42 companies (The headquarters of a top commercial bank in Romania - S.C. BRD GROUPE SOCIÉTÉ GÉNÉRALE ), based on the information gained in the years 2016-2017. This paper is original because it combines the already developed method with new techniques, in order to link together economic factors and operational research and leaves more room for future researches with the purpose of further assessing and changing the performance of every decisional unit under the influence of the environmental factors.
Методологічні основи формування соціоекономіко-екологічних обмежень власності на природні рекреаційно-туристичні ресурси
Authors: Martienko Antonina 
Published: June 2018

У статті визначено сутність соціоекономіко-екологічних обмежень форм та прав власності на природні рекреаційно-туристичні ресурси. Визначено передумови їх формування й основі напрями впровадження. Доведено, що обмеження повинні ґрунтуватися на інтересах загальнонародного привласнення природних ресурсів і залежно від специфічних особливостей природного рекреаційно-туристичного ресурсу та напрямів його використання формуються обмеження у формах і правах власності на нього.
Social-economic Responsibility Companies by use of Natural Resources
Authors: Strishenez Olena , Myhalchuk Maria 
Published: June 2018

The article examines the formal definition of the social and economic responsibility, which implies the duty of management to make decisions and take actions that improve the use of natural resources and the interests of both society and the organization. All companies are accountable to the state for compliance with current legislation regarding industrial activity. This primarily concerns ensuring that quality parameters of products with existing standards and certificates, pricing policy – the rules of competition titles and others.