bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthropometric factors have significant influence on the outcome of the GHRH–arginine test: establishment of normative data for an automated immunoassay specifically measuring 22 kDa human growth hormone
Authors: Deutschbein Timo , Bidlingmaier Martin , Schopohl Jochen , Strasburger Christian J , Petersenn Stephan 
Published: December 2016

Context
Adult growth hormone (GH) deficiency (GHD) is diagnosed by provocative testing of GH secretion.

Objective
To improve the diagnostic accuracy of GH-releasing hormone (GHRH) plus arginine (GARG) testing, we evaluated the influence of age, BMI and sex and established normative data for an automatic immunoassay specifically measuring 22 kDa human GH.

Design/setting
Prospective multicenter study.

Participants
Eighty-seven patients with hypothalamic–pituitary disease and 200 healthy controls. Patients were classified according to the number of pituitary hormone deficiencies (PHD). GHD was assumed when ≥2 PHD (in addition to GH) were present (n = 51); 36 patients with <2 PHD were considered GH sufficient (GHS). ROC analysis identified cutoffs with ≥95% specificity for GHD. Controls were prospectively stratified for sex, age and BMI.

Interventions
All participants received GHRH and l-arginine.

Main outcome measures
GH was measured by immunoassay (iSYS, IDS).

Results
In controls, multiple stepwise regression analysis showed that BMI (21%, P < 0.0001), sex (20%, P < 0.0001) and age (5%, P < 0.001), accounted for 46% of GH peak level variability during GARG. Comparison of peak GH during GARG (GHD vs GHS + controls) revealed an overall cutoff of 3.9 ng/mL (sensitivity 86%, specificity 95%). After adjustment for BMI and sex, optimal cutoffs (male vs female) were 6.5 vs 9.7 ng/mL in lean, 3.5 vs 8.5 ng/mL in overweight and 2.2 vs 4.4 ng/mL in obese subjects respectively.

Conclusion
BMI and sex account for most of the variability of peak GH levels during GARG. Consequently, diagnostic accuracy of the GARG test is significantly improved by use of adjusted cutoffs.
MOD-4023, a long-acting carboxy-terminal peptide-modified human growth hormone: results of a Phase 2 study in growth hormone-deficient adults
Authors: Strasburger Christian J , Vanuga Peter , Payer Juraj , Pfeifer Marija , Popovic Vera , Bajnok László , Góth Miklós , Olšovská Veˇra , Trejbalová L‘udmila , Vadasz Janos , Fima Eyal , Koren Ronit , Amitzi Leanne , Bidlingmaier Martin , Hershkovitz Oren , Hart Gili , Biller Beverly M K 
Published: December 2016

Objective
Growth hormone (GH) replacement therapy currently requires daily injections, which may cause distress and low compliance. C-terminal peptide (CTP)-modified growth hormone (MOD-4023) is being developed as a once-weekly dosing regimen in patients with GH deficiency (GHD). This study’s objective is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of MOD-4023 administered once-weekly in GHD adults.

Design
54 adults with GHD currently treated with daily GH were normalized and randomized into 4 weekly dosing cohorts of MOD-4023 at 18.5%, 37%, 55.5% or 123.4% of individual cumulative weekly molar hGH dose. The study included 2 stages: Stage A assessed the effectiveness and PK/PD profiles of the 4 dosing regimens of MOD-4023. Stage B was an extension period of once-weekly MOD-4023 administration (61.7% molar hGH content) to collect further safety data and confirm the results from Stage A.

Results
Dose-dependent response was observed for both PK and PD data of weekly MOD-4023 treatment. Insulin-like growth factor I (IGF-I) SDS levels were maintained within normal range. The 18.5% cohort was discontinued due to low efficacy. MOD-4023 was well tolerated and exhibited favorable safety profile in all dose cohorts. The reported adverse events were consistent with known GH-related side effects.

Conclusions
Once-weekly MOD-4023 administration in GHD adults was found to be clinically effective while maintaining a favorable safety profile and may obviate the need for daily injections. Weekly GH injections may improve compliance and overall outcome. The promising results achieved in this Phase 2 study led to a pivotal Phase 3 trial, which is currently ongoing.
Affective alterations in patients with Cushing’s syndrome in remission are associated with decreased BDNF and cortisone levels
Authors: Valassi E , Crespo I , Keevil B G , Aulinas A , Urgell E , Santos A , Trainer P J , Webb S M 
Published: December 2016

ObjectiveAffective alterations and poorer quality of life often persist in patients with Cushing’s syndrome (CS) in remission. Brain-derived neurotrophic factor (BDNF) regulates the hypothalamic–pituitary–adrenal axis (HPA) and is highly expressed in brain areas controlling mood and response to stress. Our aims were to assess affective alterations after long-term remission of CS and evaluate whether they are associated with serum BDNF, salivary cortisol (SalF) and/or cortisone (SalE) concentrations.Subjects and methodsThirty-six CS patients in remission (32 females/4 males; mean age (±s.d.), 48.8 ± 11.8 years; median duration of remission, 72 months) and 36 gender-, age- and BMI-matched controls were included. Beck Depression Inventory-II (BDI-II), Center for Epidemiological Studies Depression Scale (CES-D), Positive Affect Negative Affect Scale (PANAS), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and EuroQoL and CushingQoL questionnaires were completed and measured to evaluate anxiety, depression, stress perception and quality of life (QoL) respectively. Salivary cortisol was measured using liquid chromatography/tandem mass spectrometry (LC/TMS). BDNF was measured in serum using an ELISA.ResultsRemitted CS patients showed worse scores in all questionnaires than controls: STAI (P< 0.001), BDI (P< 0.001), CES-D (P< 0.001), PANAS (P< 0.01), PSS (P< 0.01) and EuroQoL (P< 0.01). A decrease in BDNF was observed in CS vs controls (P= 0.038), and low BDNF was associated with more anxiety (r= −0.247,P= 0.037), depression (r= −0.249,P= 0.035), stress (r= −0.277,P= 0.019) and affective balance (r= 0.243,P= 0.04). Morning salivary cortisone was inversely associated with trait anxiety (r= −0.377,P= 0.040) and depressed affect (r= −0.392,P= 0.032) in CS patients. Delay to diagnosis was associated with depressive symptoms (BDI-II:r= 0.398,P= 0.036 and CES-D:r= 0.449,P= 0.017) and CushingQoL scoring (r= −0.460,P< 0.01).ConclusionsLow BDNF levels are associated with affective alterations in ‘cured’ CS patients, including depression, anxiety and impaired stress perception. Elevated levels of SalE might also be related to poor affective status in these patients.
Population Genomics of Daphnia pulex
Authors: Lynch Michael , Gutenkunst Ryan , Ackerman Matthew , Spitze Ken , Ye Zhiqiang , Maruki Takahiro , Jia Zhiyuan 
Published: December 2016

Abstract
Using data from 83 isolates from a single population, the population genomics of the microcrustacean Daphnia pulex are described and compared to current knowledge for the only other well-studied invertebrate, Drosophila melanogaster. These two species are quite similar with respect to effective population sizes and mutation rates, although some features of recombination appear to be different, with linkage disequilibrium being elevated at short (&lt;100 bp) distances in D. melanogaster and at long distances in D. pulex. The study population adheres closely to the expectations under Hardy–Weinberg equilibrium, and reflects a past population history of no more than a twofold range of variation in effective population size. Fourfold redundant silent sites and a restricted region of intronic sites appear to evolve in a nearly neutral fashion, providing a powerful tool for population genetic analyses. Amino acid replacement sites are predominantly under strong purifying selection, as are a large fraction of sites in UTRs and intergenic regions, but the majority of SNPs at such sites that rise to frequencies &gt;0.05 appear to evolve in a nearly neutral fashion. All forms of genomic sites (including replacement sites within codons, and intergenic and UTR regions) appear to be experiencing an ∼2× higher level of selection scaled to the power of drift in D. melanogaster, but this may in part be a consequence of recent demographic changes. These results establish D. pulex as an excellent system for future work on the evolutionary genomics of natural populations.
Zinc Cluster Transcription Factors Alter Virulence in Candida albicans
Authors: Issi Luca , Farrer Rhys A , Pastor Kelly , Landry Benjamin , Delorey Toni , Bell George W , Thompson Dawn A , Cuomo Christina A , Rao Reeta P 
Published: December 2016

Abstract
Almost all humans are colonized with Candida albicans. However, in immunocompromised individuals, this benign commensal organism becomes a serious, life-threatening pathogen. Here, we describe and analyze the regulatory networks that modulate innate responses in the host niches. We identified Zcf15 and Zcf29, two Zinc Cluster transcription Factors (ZCF) that are required for C. albicans virulence. Previous sequence analysis of clinical C. albicans isolates from immunocompromised patients indicates that both ZCF genes diverged during clonal evolution. Using in vivo animal models, ex vivo cell culture methods, and in vitro sensitivity assays, we demonstrate that knockout mutants of both ZCF15 and ZCF29 are hypersensitive to reactive oxygen species (ROS), suggesting they help neutralize the host-derived ROS produced by phagocytes, as well as establish a sustained infection in vivo. Transcriptomic analysis of mutants under resting conditions where cells were not experiencing oxidative stress revealed a large network that control macro and micronutrient homeostasis, which likely contributes to overall pathogen fitness in host niches. Under oxidative stress, both transcription factors regulate a separate set of genes involved in detoxification of ROS and down-regulating ribosome biogenesis. ChIP-seq analysis, which reveals vastly different binding partners for each transcription factor (TF) before and after oxidative stress, further confirms these results. Furthermore, the absence of a dominant binding motif likely facilitates their mobility, and supports the notion that they represent a recent expansion of the ZCF family in the pathogenic Candida species. Our analyses provide a framework for understanding new aspects of the interface between C. albicans and host defense response, and extends our understanding of how complex cell behaviors are linked to the evolution of TFs.
“O mal de Alzheimer nacional”: (in)justiça, história e literatura
Authors: Da Cruz Lua Gill 
Published: December 2016

Cinquenta anos depois do golpe militar brasileiro, as artes ainda procuram refletir e representar o período. Um dos grandes exemplos da literatura brasileira contemporânea, e sobre o qual este texto pretende versar, é o livro K. (2011), de Bernardo Kucinski. A trama centra-se na busca de um pai, K., por sua filha, A., desaparecida política no período do regime militar, e para a qual exige justiça, através da construção de uma narrativa. A leitura da obra proposta buscará contrastar diferentes áreas do conhecimento, como História, Psicanálise, Política e Direito, em especial com o texto de Shoshana Felman, O inconsciente jurídico (2002). A perspectiva levantada pela autora é a de que os julgamentos e a lei, de maneira geral, reproduzem e repetem os traumas sociais e políticos, a partir do seu inconsciente jurídico (dotada dos conceitos de trauma e de inconsciente de Freud). Os julgamentos históricos são marcados pela sua impossibilidade de escuta da voz do testemunho, enquanto a literatura seria o espaço no qual a hipocrisia da violência é colocada à prova, garantindo a escuta daqueles que não tem voz garantida no ambiente jurídico.
O caráter dialogal da língua por uma perspectiva instrucional da significação
Authors: Freitas Mara Rubia Rodrigues 
Published: December 2016

Segundo Ducrot (1987), a significação da frase (na língua) permite construir instruções que o interlocutor deve seguir para atribuir sentido aos enunciados (no discurso). Considerando que o sentido é uma representação da enunciação, e que a encenação enunciativa prevê um eu que se dirige a um tu, é evidente o caráter dialogal do discurso. Embora a língua, na qualidade de sistema de formas abstratas, não seja generosa em evidenciar esse caráter, acreditamos que ela traga, inscrito no sistema, o substrato do diálogo, devido à natureza instrucional da significação. Nossa proposta é investigar como se configuram as instruções que permitem ao interlocutor recuperar sentidos construídos pelo locutor, tomando como marco a Teoria da Argumentação na Língua (ANL), abordagem que parte do discurso para explicar a língua. Nossa metodologia prevê a análise de uma peça publicitária à luz de conceitos da ANL, objetivando evidenciar a potencialidade dialogal da língua.
O jardim sem limites, de Lídia Jorge – ou, por outras palavras, a situação do Portugal pós-25 de abril
Authors: Minuzzi Luara Pinto 
Published: December 2016

Este trabalho tem por objetivo pensar o livro O jardim sem limites, da escritora Lídia Jorge, como uma alegoria da situação de Portugal após a Revolução dos Cravos: o microcosmo Casa da Arara, onde os personagens do romance habitam, representaria o macrocosmo Portugal, assim como os habitantes do primeiro e do segundo andar e a tensão entre esses dois níveis, corresponderiam às diferentes gerações que compõem o povo português. Dessa forma, o cotidiano conflituoso em que convivem os moradores mais jovens do segundo piso e os mais velhos do primeiro seria a representação do distanciamento entre uma geração que viveu o salazarismo e que combateu o regime e outra que nasceu após o fim do totalitarismo e que não compreende os sacrifícios realizados pelos primeiros a fim de que todos pudessem usufruir da liberdade. Para tal análise, foram utilizados, como fundamentação teórica, estudos de filósofos que pensam a nação lusa, sua identidade e história, como Eduardo Lourenço, Boaventura de Sousa Santos e Jorge Babo.
A intolerância religiosa na literatura de Jorge Amado
Authors: Sperb Paula 
Published: December 2016

A partir da proposta do eixo temático “Expressão de Conflitos”, do evento Duo VII – Dialogue Under Ocuupation, nos dispomos a fazer uma reflexão sobre a intolerância religiosa enquanto temática da literatura de Jorge Amado. A intolerância religiosa aparece especialmente na obra Tenda dos Milagres (1968), em cenas de perseguição aos pais-de-santo e terreiros de candomblé. Entendemos o fenômeno da intolerância racial como uma consequência das teorias raciais que vigoraram no Brasil como paradigma científico no final do século XIX e início do século XX. Essas teorias viam a raça como explicação para o primitivismo/atraso ou civilização/avanço. O candomblé, segundo essa perspectiva científica, por estar ligado à cultura africana (ou seja, negra), representava o suposto atraso do Brasil, que precisava ser combatido e solucionado. Quando foi deputado federal pelo partido comunista, Jorge Amado criou e aprovou a emenda que estabelecia a liberdade religiosa e de culto no Brasil, em 1946. Para realizar este trabalho utilizamos principalmente o suporte teórico de Leite (1976), Schwarcz (2001) e Skidmore (1989).
A leitura do hipertexto sob a perspectiva da Teoria da Enunciação
Authors: Rossa Juliana 
Published: December 2016

Este artigo tem como objetivo realizar o cruzamento interdisciplinar das teorias da enunciação e do hipertexto. O estudo, de natureza teórica, caracteriza-se por ser uma análise que interliga as contribuições da teoria da enunciação de Émile Benveniste com teorias sobre hipertexto, pela ótica de autores como Lúcia Santaella, Pierre Lévy, Alex Primo e George Landow. Observamos que as categorias de pessoa, tempo e espaço – as quais Benveniste debita a subjetividade da linguagem – potencializam-se no hipertexto. Essa potencialização, que é uma das características do ciberespaço pela infinidade de elos multiconectados, induz a uma forma especial de leitura desses hipertextos. Dessa forma, propomos o termo hipersubjetividade da linguagem para tratar do discurso no ambiente virtual, o qual possui um leitor diferenciado e imersivo no complexo cenário do ambiente virtual.
Las competencias digitales en las grandes empresas del sector empresarial español. (Digital skills in big companies of the Spanish business sector)
Authors: Infante Moro Alfonso , Infante Moro Juan Carlos , Martínez López Francisco José , García Ordaz Mercedes 
Published: December 2016

<p><strong><em> </em>Resumen</strong></p><p>Este estudio surge a partir de otra investigación realizada sobre la evolución de las competencias digitales en el sector empresarial español, “Currícula en SI/TI en las empresas españolas: Estudio longitudinal (2001-2011)” (Infante, Infante, Martínez y García, 2015). Por tal motivo, se pretende situar la evolución de dichas competencias, habilidades digitales en las grandes empresas españolas, en un marco comparativo para cotejarlas con las del sector empresarial español en general, definiendo la importancia de estas habilidades y su evolución. Además, se busca encuadrarlas en el funcionamiento de estas empresas a través de las herramientas utilizadas y sus funciones dentro estas, con el fin de que los futuros trabajadores estén formados en las habilidades demandadas por dichas empresas. La investigación fue realizada a través de encuesta a 190 empresas, con una clara conclusión: el grado de conocimientos en competencias digitales es mayor para los futuros trabajadores de las grandes empresas que para los trabajadores de las empresas españolas en general.</p><p> </p><p><strong>Abstract</strong></p><p>This study stems from another research about the evolution of digital skills in the Spanish business sector, “Curricula in IS/IT in Spanish companies: Longitudinal study (2001- 2011)” (Infante, Infante, Martínez y García, 2015). Therefore, it is intended to place the development of these abilities, digital skills in big Spanish companies, in a comparative frame to the Spanish business sector in general, defining the importance of them and their evolution. In addition, these skills were framed in the operation of these companies through the tools used and their functions within them, in order that future workers are trained in the skills demanded by these companies.</p><p>The research has been conducted through a survey to 190 companies, with a clear conclusion: the extent of the knowledge in digital skills more important for future workers in big companies that for workers in Spanish companies in general.</p>
Las escuelas de pensamiento del emprendimiento social. Schools of Thought in Social Entrepreneurship
Authors: Bravo Monge Cris 
Published: December 2016

<p><strong>Resumen</strong></p><p>El emprendimiento social propone ser una promesa para el alivio de los problemas sociales del mundo. Al ser un concepto relativamente nuevo, la definición es sumamente amplia, lo cual resulta contraproducente para su construcción y diseminación. El propósito del estudio es identificar las diferentes propuestas de emprendimiento social llevadas a cabo por las cuatro principales organizaciones a nivel mundial que actualmente promueven el concepto de emprendimiento social: Fundación Ashoka, Fundación Skoll, Fundación Schwab y el Centro Yunus; así como de otras organizaciones practicantes y relacionadas con la enseñanza del concepto en educación superior. El estudio cualitativo utilizó el análisis de documentos de estas organizaciones, así como entrevistas a tres académicos expertos y practicantes del emprendimiento social. El estudio identificó tres escuelas de pensamiento claramente diferenciadas con base en su visión de cómo el ingreso, la escalabilidad y la replicabilidad de los proyectos afectan el emprendimiento social. El estudio provee evidencia de las diferencias importantes en la definición del concepto de emprendimiento social por parte de fundaciones más conocidas en el campo. La distinción de las escuelas de pensamiento es particularmente importante para la enseñanza y la definición de políticas públicas de emprendimiento social.</p><p> </p><p><strong>Abstract</strong></p><p>Social Entrepreneurship is a new and exciting topic that holds a great promise in helping alleviate the social problems in the world. As a new subject, the meaning of the term is too broad which interferes with the construction and understanding of the concept. The purpose of this study is to identify the elements of the different proposals of what social entrepreneurship looks like, from the perspective of four organizations leading social entrepreneurship projects: Ashoka Foundation, Skoll Foundation, Schwab Foundation and Yunus Center; as well as from three other field and academic related institutions fostering and practicing social entrepreneurship. The study used document analysis from Skoll Foundation, Schwab Foundation, Yunus Center and Ashoka Foundation, and an open ended interview applied to experts from practitioner institutions. The study identified three clearly differentiated schools of thought, based on their views on revenue, scalability, replicability and geographic location. The definition of the different schools of thoughts is particularly important for the teaching of social entrepreneurship, and for the promotion of more adequate and accurate social policies to foster the development of social entrepreneurship.</p>
Remuneración a la fuerza de ventas: variables que determinan su éxito o fracaso. Remuneration of sales force: Variables that determine your success or failure.
Authors: Torres Carballo Federico , Tiffer Sotomayor Haydeé , Sandoval Sánchez Yarima 
Published: December 2016

<p><strong>Resumen</strong></p><p>La remuneración a la fuerza de ventas es un tema fundamental en las organizaciones comerciales. ¿Qué tipo de incentivos incrementan el esfuerzo del vendedor para lograr las metas de la organización? ¿Si se combinan diferentes esquemas de incentivos se incrementa la dedicación del vendedor? Este es el primer estudio realizado en Costa Rica con técnicas experimentales para abordar tales cuestiones. Se realizan un conjunto de sesiones con más de doscientos estudiantes de carreras afines a la administración de negocios, a fin de estudiar, específicamente, los concursos de ventas cuyo esquema de remuneración consiste en un primer premio seguido de varios premios menores asignados según el logro de ventas por parte del vendedor. Se encontró que no siempre más es mejor y que algunas combinaciones en ambientes en los que los sujetos se comunican continuamente pueden hasta reducir el esfuerzo por lograr los objetivos organizacionales.</p><p> </p><p><strong>Abstract</strong></p><p>The remuneration to the sales force is a major issue in commercial organizations. What kind of incentives increase the selling effort to achieve the goals of the organization? With the combination of different incentive schemes it is possible to increase seller’s dedication? This is the first study applied in Costa Rica, using experimental techniques to address such issues. A set of sessions are conducted with more than 200 students, from careers related to business administration, to study sales contests with a compensation scheme, in which there is a first prize followed by several smaller prizes assigned to the achieved sales made by the seller. It was found that it is possible to reduce the effort to achieve organizational objectives when the subjects can communicate constantly.</p>
A Seldinger approach to nasotracheal positioning of a subglottic jet ventilation catheter in the awake patient
Authors: Langford Roger 
Published: December 2016

SummaryWe describe use of the Seldinger technique to safely secure the airway of an awake adult patient with partial laryngeal obstruction. A similar technique has previously been described for the placement of tracheal tubes in spontaneously ventilating anaesthetised paediatric patients. However, we believe that this is the first report of successful placement of a subglottic jet‐ventilation catheter in an awake patient.