bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases
Authors: Al-Bari Md. Abdul Alim 
Published: February 2015

Abstract
Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases.
A Phase I study to assess the safety, tolerability and pharmacokinetic profile of boceprevir and sildenafil when dosed separately and together, in healthy male volunteers
Authors: Mora-Peris Borja , Else Laura , Goldmeier David , Mears Alison , Weston Rosy , Cooke Graham , Khoo Saye , Back David , Winston Alan 
Published: February 2015

Abstract

Objectives
Boceprevir is a first-generation direct-acting antiviral licensed for the treatment of hepatitis C infection. Sildenafil is an oral therapy for erectile dysfunction. As boceprevir is a potent inhibitor of CYP3A4, potential pharmacokinetic interactions may occur when it is coadministered with sildenafil. The aim of this study was to assess the pharmacokinetic profile of sildenafil and boceprevir when dosed separately and together in healthy volunteers.

Methods
Thirteen male subjects completed the following study procedures: phase 1 (Day 0), a single dose of 25 mg of sildenafil was administered; washout period (Days 1–9); phase 2 (Days 10–15), 800 mg of boceprevir three times a day was administered; and phase 3 (Day 16), 800 mg of boceprevir and 25 mg of sildenafil were administered. All drugs were administered in the fed state. Intensive pharmacokinetic sampling was undertaken on Days 0, 15 and 16. Differences in the pharmacokinetic parameters of sildenafil, N-desmethyl-sildenafil and boceprevir between phase 3 and the earlier phases were evaluated by changes in the geometric mean ratios (GMRs).

Results
All the drugs were well tolerated with no safety concerns arising. In the presence of boceprevir (phase 3 versus phase 1), the GMR for the plasma Cmax and the AUC24 for sildenafil increased by 1.9-fold (95% CI 1.5–2.4) and 2.7-fold (95% CI 2.1–3.4), respectively, whereas a reduction in the Cmax of N-desmethyl-sildenafil was observed (GMR 0.5, 95% CI 0.4–0.7). No significant changes in boceprevir exposure were observed between phases 3 and 2.

Conclusions
Exposure of sildenafil is increased in the presence of boceprevir. A dose adjustment of sildenafil is therefore necessary. An initial dose of 25 mg of sildenafil is suggested.
CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism
Authors: Rammohan Jayan , Ruiz Manzano Ana , Garner Ashley L. , Stallings Christina L. , Galburt Eric A. 
Published: February 2015

Abstract
CarD is an essential and global transcriptional regulator in mycobacteria. While its biological role is unclear, CarD functions by interacting directly with RNA polymerase (RNAP) holoenzyme promoter complexes. Here, using a fluorescent reporter of open complex, we quantitate RPo formation in real time and show that Mycobacterium tuberculosis CarD has a dramatic effect on the energetics of RNAP bound complexes on the M. tuberculosis rrnAP3 ribosomal RNA promoter. The data reveal that Mycobacterium bovis RNAP exhibits an unstable RPo that is stabilized by CarD and suggest that CarD uses a two-tiered, concentration-dependent mechanism by associating with open and closed complexes with different affinities. Specifically, the kinetics of open-complex formation can be explained by a model where, at saturating concentrations of CarD, the rate of bubble collapse is slowed and the rate of opening is accelerated. The kinetics and open-complex stabilities of CarD mutants further clarify the roles played by the key residues W85, K90 and R25 previously shown to affect CarD-dependent gene regulation in vivo. In contrast to M. bovis RNAP, Escherichia coli RNAP efficiently forms RPo on rrnAP3, suggesting an important difference between the polymerases themselves and highlighting how transcriptional machinery can vary across bacterial genera.
Comparison Between Acrylic Cage and Polyetheretherketone (PEEK) Cage in Single-level Anterior Cervical Discectomy and Fusion
Authors: Farrokhi Majid R. , Nikoo Zahra , Gholami Mehrnaz , Hosseini Khadijeh 
Published: February 2015

Study Design:
Prospective, single-blind randomized-controlled clinical study.

Objective:
To compare polyetheretherketone (PEEK) cage with a novel Acrylic cage to find out which fusion cage yielded better clinical outcomes following single-level anterior cervical discectomy and fusion (ACDF).

Summary of Background Data:
ACDF is considered a standard neurosurgical treatment for degenerative diseases of cervical intervertebral disks. There are many options, including bone grafts, bone cement, and spacers made of titanium, carbon fiber, and synthetic materials, used to restore physiological disk height and enhance spinal fusion, but the ideal device, which would provide immediate structural support and subsequent osteointegration and stability, has not been identified yet. To overcome this, we designed a new, inexpensive Acrylic cage.

Materials and Methods:
A total of 64 patients were eligible to participate and were randomly allocated to undergo ACDF either with Acrylic interbody fusion cage filled with bone substitute (n=32) or PEEK cage (n=32). Nurick’s grading was used for quantifying the neurological deficit. Clinical and radiologic outcome was assessed preoperatively, immediately after surgery, and subsequently at 2, 6, and 12 months of follow-up using Odom’s criteria and dynamic radiographs (flexion-extension) and computed tomography scans, respectively.

Results:
There was a statistically significant improvement in the clinical outcomes of the Acrylic cage group compared with the PEEK cage group (mean difference: −0.438; 95% confidence interval, −0.807 to −0.068; P=0.016). There was a statistically significant difference in disk space height increase between the 2 groups at the 6- and 12-month follow-up. The Acrylic cage achieved higher fusion rate (good fusion) than the PEEK cage (96.9% vs. 93.8%). Intervertebral angle demonstrated a significant difference among the 2 treated groups throughout the follow-up period.

Conclusion:
This study suggests that the use of Acrylic cage is associated with good clinical and radiologic outcomes and it can be therefore a good substitute for bone graft and other cages in ACDF.
Efficacy of Dietary Treatment for Inducing Disease Remission in Eosinophilic Gastroenteritis
Authors: Lucendo Alfredo J. , Serrano‐Montalbán Beatriz , Arias Ángel , Redondo Olga , Tenias José M. 
Published: February 2015

ABSTRACTObjectives:Various dietary interventions have been used to treat patients with eosinophilic gastroenteritis (EGE). Concrete evidence as to the effectiveness of such treatments in inducing disease remission is, however, lacking. The aim of the study was to systematically review the efficacy of dietary therapies in inducing EGE remission.Methods:We performed a systematic search for the MEDLINE, EMBASE, and SCOPUS libraries for studies investigating the efficacy of dietary interventions (in both histological and symptomatic remission) for children and adults with EGE and colitis.Results:The search yielded 490 references; 30 were included in the review, with most of these references being “low‐quality” individual cases or short case series. No significant publication bias was found. Elemental diets in children were linked to 75.8% of clinical improvement, but few of these patients underwent a histological evaluation. Allergy‐testing results have been used scarcely in EGE. Empiric elimination of allergy‐associated foods was the most commonly used option. The variable results in terms of symptom relief, however, were scarcely accompanied by histological confirmation. Clinical and methodological heterogeneity hindered the performance of quantitative summaries for the efficacy of dietary therapies in inducing disease remission.Conclusions:Symptomatic improvements reported for dietary treatment in EGE by most of the available literature are questionable because of the lack of objective evaluation of clinical changes and the very limited assessment of histological remission. Because of the relative lack of well‐designed, high‐quality studies, the unequivocal use of dietary treatment for patients with EGE and colitis cannot be supported. Further research should be undertaken.
Flexible expressed region analysis for RNA-seq withderfinder
Authors: Collado-Torres Leonardo , Nellore Abhinav , Frazee Alyssa C. , Wilks Christopher , Love Michael I. , Langmead Ben , Irizarry Rafael A. , Leek Jeffrey T. , Jaffe Andrew E. 
Published: February 2015

AbstractBackgroundDifferential expression analysis of RNA sequencing (RNA-seq) data typically relies on reconstructing transcripts or counting reads that overlap known gene structures. We previously introduced an intermediate statistical approach called differentially expressed region (DER) finder that seeks to identify contiguous regions of the genome showing differential expression signal at single base resolution without relying on existing annotation or potentially inaccurate transcript assembly.ResultsWe present thederfindersoftware that improves our annotation-agnostic approach to RNA-seq analysis by: (1) implementing a computationally efficient bump-hunting approach to identify DERs which permits genome-scale analyses in a large number of samples, (2) introducing a flexible statistical modeling framework, including multi-group and time-course analyses and (3) introducing a new set of data visualizations for expressed region analysis. We apply this approach to public RNA-seq data from the Genotype-Tissue Expression (GTEx) project and BrainSpan project to show thatderfinderpermits the analysis of hundreds of samples at base resolution in R, identifies expression outside of known gene boundaries and can be used to visualize expressed regions at base-resolution. In simulations our base resolution approaches enable discovery in the presence of incomplete annotation and is nearly as powerful as feature-level methods when the annotation is complete.Conclusionsderfinderanalysis using expressed region-level and single base-level approaches provides a compromise between full transcript reconstruction and feature-level analysis.The package is available fromBioconductoratwww.bioconductor.org/packages/derfinder.
Where the elements go when it rains: carbon and nutrient stocks of soil amended with stabilised organic matter
Authors: Ng E-L , Schefe C.R. , Cavagnaro T.R. , Patti A.F 
Published: February 2015

AbstractThe addition of compost to the soil can increase C and nutrient levels, but how these are affected by different rainfall regimes remain unknown. This study determines the carbon (C), nitrogen (N) and phosphorus (P) stocks after drying and rewetting events in a compost-amended grassland ecosystem at 3 depths (0-5, 5-10, 10-30cm). Compost addition consistently increased C, N and P stocks despite altered rainfall but these improvements can only be detected by careful consideration of soil depths.
Market orientation and business results among small‐scale service firms
Authors: Polo Peña Ana Isabel , Frías Jamilena Dolores María , Castañeda García José Alberto 
Published: February 2015

PurposeThe purpose of this paper is to validate market orientation (MO) and business results scales in an area of significant interest for the literature: namely, service firms of a small and micro‐scale in a market sharing many similarities with Latin America (cultural, social and economic), specifically the Spanish rural tourism market.Design/methodology/approachOn the basis of a literature review covering works specializing in MO and its impact on the service sector, and in the characteristics of small‐ and micro‐sized service firms (SMSF), a qualitative and a quantitative study are carried out in Spain, at a national level.FindingsThe results validate the scales and identify that MO comprises the following dimensions: information‐gathering, dissemination of information, and response to the market. The validated business results scale includes economic/financial results and others of a more personal nature linked to the entrepreneur business owner.Practical implicationsThe work provides knowledge regarding the activities undertaken by SMSF in the area of MO. Professionals from the small‐ and micro‐sized service sector can use this knowledge to plan and design market‐focussed actions that will lead to improved business performance.Originality/valueThe work validates MO and business results scales that have been widely studied throughout the literature but that leave a significant gap in the case of SMSF operating in Latin American countries. The business base in these countries comprises a large percentage of such small‐scale operations.
Heterogeneous research networks in Latin American schools of business management
Authors: Orozco Luis Antonio , Luis Villaveces José 
Published: February 2015

PurposeThe purpose of this paper is to empirically evaluate the effect of heterogeneity in inter‐organizational collaboration networks on international high‐quality scientific performance of the most reputed business management schools in Latin America according toAméricaEconomíaranking.Design/methodology/approachStarting from the debate between advantages and disadvantages of heterogeneity in scientific performance framed in the debate between organizational population ecology and organizational institutionalism theories, this research explores the relationship between heterogeneity, reputation and the most important features for doing research. Using a binomial negative regression, the paper evaluates the partial effect of those variables in the count of scientific production.FindingsThere is an isomorphical tendency from the most reputed schools to establish heterogeneous networks, showing empirical evidence to normative proposals from Latin America, specially formulated in the light of Sabato triangle. Also there are differentiations between schools in aspects like human capital, double‐degree agreements, and schools’ trajectories.Research limitations/implicationsIt is necessary to choose a wider sample of schools and to include Latin American journals. The study of diversity (between researchers) and its relationship with heterogeneity (between organizations) is also needed.Practical implicationsThe research shows that elite business management schools in Latin America that present better performance also present high levels of heterogeneity in their inter‐organizational collaboration. Therefore, the promotion of heterogeneity could enhance scientific performance and improve techno‐economical networks.Social implicationsThis research hopes to aim the research policy design to be able to steer and promote heterogeneity that could improve the relationship between producers and users of knowledge.Originality/valueThe relationships between reputation, heterogeneity, and scientific performance in administration in Latin America had not been addressed empirically. The worth of this research is the empirical confirmation to the advantages of heterogeneity, rather than intellectual capital features of schools, in research collaboration that contribute to the debate about heterogeneity and performance.
Characteristics and effectiveness of university spin‐off support programmes
Authors: Beraza‐Garmendia José María , Rodríguez‐Castellanos Arturo 
Published: February 2015

PurposeThe purpose of this paper is to identify different program models supporting the creation of spin‐offs at universities, analyzes the characteristics that differentiate them, and identifies the factors that determine their effectiveness.Design/methodology/approachThe analysis was performed using data collected through a survey targeting the heads of spin‐off support programs at universities in the UK and Spain. The authors then applied factorial and cluster analysis techniques and a logistic regression analysis to the data to confirm the results.FindingsThe analysis identified three types of spin‐off support programs in these universities. Among these, the authors found one that appears to be the most effective model. The authors also found a certain “country effect” on the characteristics of the most effective model. Finally, the authors noted the importance the literature places on university R&D activity and the existence of a favorable environment for the performance of spin‐off programs.Research limitations/implicationsThis research is limited by the use of number of spin‐offs and survival rate as performance indicators for support programs. Future research should consider the effective contributions to economic growth and the extent to which such effects are related to university‐level policies.Practical implicationsThe typology of the spin‐off support programs identified here provides insight for recommendations to improve less‐effective models.Originality/valueThis study contributes to the understanding of the role of university policy measures in spin‐off support program effectiveness, and of how the environment influences these policies.
Assessing value co-creation and value capture potential in services: a management framework
Authors: Töytäri Pekka 
Published: February 2015

Purpose
– The purpose of this paper is to investigate the managerial practices to assess value creation and value capture potential in longitudinal buyer-seller relationships, and proposes a framework for evaluating such potential for maximizing sales function efficiency.

Design/methodology/approach
– The research is based on an exploratory multi-case study with seven internationally operating companies from a variety of industries, with the aim of building the framework for sales opportunity management. The framework is then refined in eight workshops with 21 companies.

Findings
– The findings suggest that industrial companies need to develop new capabilities to efficiently manage value selling opportunities at different stages of the opportunity lifecycle.

Research limitations/implications
– The underlying sales approach of the research is proactive value selling in a service business context. The findings may not be generalizable into other sales contexts.

Practical implications
– The paper provides practicing managers with an actionable sales opportunity management framework for an effective management of sales quality.

Originality/value
– The research contributes to a previously unexplored area of sales management, and suggests a managerial practice linking strategy to implementation at the customer interface.
Strategic roles of service sites: application of Ferdows’s model
Authors: Hallavo Ville , Kuula Markku , Putkiranta Antero 
Published: February 2015

Purpose– The purpose of this paper is to examine the applicability to the service business of general models used in the manufacturing environment. This is done by applying Ferdows’s model, “the strategic role of the plant”, in two cases.Design/methodology/approach– This study uses the case approach. One case (IBM Nordic) is based on an interview, while the other case (Google) relies on secondary data. In each case the operations are mapped on Ferdows’s model.Findings– The cases indicate that the same kind of roles can be found in the service business as in traditional manufacturing environments, and that these roles are widely used. However, for communicative purposes, the model was terminologically slightly modified.Research limitations/implications– Although this study presents the findings of only two cases, the knowledge of material available from public sources leads us to believe that these findings are universal. The model is easy to communicate in the service sector and is thus a very valuable tool.Originality/value– Models used in the traditional manufacturing and operations management environment have not yet been fully discovered by, nor sufficiently applied in, the service sector. Academics and practitioners are busy trying to create new models in this sector, without noticing that the “old” tools are still usable. Benchmarking against the models used in other sectors might be a worthwhile exercise.
“Expect the unexpected”
Authors: Ellert Guido , Schafmeister Guido , Wawrzinek David , Gassner Heike 
Published: February 2015

Purpose– The purpose of this paper is to analyse event management by using three value creation logics, value chain, value network and value shop. In event management, value is generated through intermediation where the dominant creation logic is a value network. However, the complexity of events and danger of unexpected problems is increasing, which, in the worst case, leads to event failure. This fact makes it necessary to change the general attitude towards this topic from risk management to uncertainty management and use the value shop in order to solve problems efficiently.Design/methodology/approach– This paper is based on the methodology of phenomenological hermeneutics which analyzes the object of study by interpreting the facticity and provides basics to generate a conceptual model.Findings– The dominant value creation logic must be changed to prevent the value network from failure in generating value, since only the value shop provides high quality problem solving. Trust not only in planning but also in the own problem-solving competence and available tools is a major part of the value shop. As a practical example of high quality problem solving, the performance of high reliability organisations can be used by event managers.Research limitations/implications– Using these hermeneutical gained logic, additional empirical research projects in event management, leadership and problem-solving competence of top managers, are promptly intended. Additionally, studies concerning competences and structures of the uncertainty management team have to be determined and developed as well as education and coaching has to be generated in order to achieve best results in problem solving.Practical implications– Practical implications of this paper are: considering the value shop as the dominant value creation logic in uncertainty management; establishing a specially trained Complex Problem-Solving Team; and considering trust to be an essential element of the value shop.Social implications– The basic job requirements a successful value net (event-) manager has to provide in such a complex system are: acting as integrator, mediator and problem solver simultaneously. Additionally event managers need to be trained to rethink the value creation logic and use the value shop within the value net to stay flexible and work successfully during their events.Originality/value– Derived from this new perspective the necessity of enhancing the implemented value creation logic according to uncertainties allows event managers to solve unexpected problems faster and more efficiently.