bluuebunny/crossref_metadata_2025 huggingface dataset:
De lo tradicional a lo diverso: la investigación creación, un camino para investigar literatura. Apuntes desde la experiencia
Authors: Chávez Cervantes Ángela María
Published: June 2019

La Universidad Pedagógica y Tecnológica de Colombia (UPTC) ofrece, entre sus programas de formación posgradual, el programa de Maestría en Literatura; y este, a su vez, posee una línea de investigación denominada investigación creación. El presente artículo es el resultado de la reflexión que, como estudiante de dicha maestría, tuve en relación con esta metodología de investigación en literatura. Para ello, se hace un recorrido a través de la discusión y los pasos conceptuales que las diferentes instituciones, de validación de conocimiento y de Educación Superior en Colombia, han tomado para definir y legitimar la investigación creación en el ámbito académico. La práctica de la escritura creativa es el resultado de un proceso de investigación.
Del manifiesto a la internet: relaciones entre texto escrito, literatura y creación performática en Latinoamérica
Authors: Arenas Rodrigo
Published: June 2019

Este trabajo aborda el diálogo entre texto escrito y creación artística en performance, básicamente a partir de la praxis de esta última, centrándonos en las formas por medio de las cuales la performance se nutre del texto escrito. Se analiza al texto escrito como elemento en la construcción de las piezas; como registro; como paratexto; a la escritura sobre performance; a las peculiaridades de la relación entre texto escrito literario y performance, y las posibilidades que se presentan bajo el alero de las nuevas tecnologías. Se utiliza una metodología exploratoria, que además considera las experiencias del autor en el área. Todo, desde una perspectiva latinoamericana[1], por la que se intenta contribuir a la construcción de un cuerpo teórico desde y hacia nuestros territorios.
Construir la experiencia de la sed (aproximaciones pedagógicas y políticas a la escritura creativa)
Authors: Álvarez Juan , Cárdenas Juan
Published: June 2019

Pensar quizá sea mudarse de metáforas.

 Pensar con vocación creativa quizá sea escudriñar allí donde la sistematicidad de los conceptos metafóricos actúa para ocultar.
Leer para escribir, aporte de la escritura creativa (notas a mano alzada)
Authors: Jaramillo Morales Alejandra
Published: June 2019

Desde el año 2007, cuando se da inicio a la Maestría en Escrituras Creativas de la Universidad Nacional de Colombia, he trabajado como coordinadora de la línea de narrativa y he tenido a mi cargo, junto con otros colegas, la enseñanza en los talleres de primer y segundo semestre. Es decir, que en mi experiencia como profesora he desarrollado técnicas para el aprendizaje de las técnicas narrativas, especialmente en la forma en que nuestros estudiantes pueden encontrar la estructura de sus novelas y cuentos. He dado talleres de escritura en otras universidades como la Central en Bogotá y la Universidad Humboldt en Berlín, y con otras instituciones como el British Council, donde coordino el componente académico del programa Elipsis de formación de jóvenes escritores. Estas experiencias me han llevado a pensar los aportes que hace la escritura creativa al conocimiento académico contemporáneo en el área de la literatura, y por tanto quiero presentarles algunas reflexiones sobre los impactos que tiene en la lectura. La lectura para escribir alimenta, desde mi perspectiva, la lectura general de la literatura y eso es lo que quiero compartirles.
Las formas de lo real o ¿en cuáles circunstancias la palabra hace ver?
Authors: Ferreira de Almeida María Cándida
Published: June 2019

Este artículo regresa al problema de los procesos creativos involucrados en los pasajes de un arte a otro. Para el adelanto de esta reflexión, se eligió el problema de la configuración de lo real, tal como fue desarrollada en la pintura, en la fotografía o en el cine, para luego entender su apropiación por el lenguaje literario. El propósito del artículo será hacer comprender las operaciones que sustentan una representación realista, aquí pensada como un procedimiento retórico que se expresa bajo la evidencia, y que aun así interpela a una experiencia visual realista por medio exclusivo de la palabra escrita. Afrontando los límites de la palabra escrita, intentamos demostrar las tesis de este artículo, no solo en la prosa, locus tradicional del realismo, como también en la poesía.
A comparative study of concrete strength prediction using artificial neural network, multigene programming and model tree
Authors: Kulkarni Preeti , Londhe Shreenivas N. , Dixit Pradnya R.
Published: June 2019

In the current study 28 day strength of Recycled Aggregate Concrete (RAC) and Fly ash (class F) based concrete is predicted using Artificial Neural Network (ANN), Multigene Genetic Programming (MGGP) and Model Tree (MT). Four sets of models were designed for per cubic proportions of materials, Properties of materials and non-dimensional parameters as input parameters. The study shows that the predicted 28 day strength is in good agreement with the observed data and also generalize well to untrained data. ANN outperforms MGGP and MT in terms of model performance. Output of the developed models can be presented in terms of trained weights and biases in ANN, equations in MGGP and in the form of series of equations in MT. ANN, MGGP and MT can grasp the influence of input parameters which can be seen through Hinton diagrams in ANN, input frequency distribution in MGGP and coefficients of input parameters in MT. The study shows that these data driven techniques can be used for developing model/s to predict strength of concrete with an acceptable performance.
Arch effect in silos on discrete supports - Is it a myth or reality?
Authors: Zdravkov Lyubomir A.
Published: June 2019

Steel silos are interesting, complicated facilities. In order to assure its complete emptying by gravity they are often placed on supporting frame structure above the ground. Values of stresses in joints between thin walled shell and supporting frame elements are very high. It can cause the local buckling in the shell. The simplest way to design steel silos is to divide hypothetically the cylindrical shell into two parts - ring beam, supported in some points and shell above, uniformly supported. This conception is accepted by European Standard EN 1993-4-1. The particular moment is that the ring beam and cylindrical body above it are separated. Actually the two elements are jointed and work together in the same time. Considering the last results of Zeybek, Topkaya and Rotter from 2019, and as well as his own research, the author asks the question if it is true that the transferring of discrete base reactions to the cylindrical body is done by bending work of the ring beam, which is the conception in EN 1993-4-1? Or the vertical reaction forces are actually redistributed on the height based on the work of the cylindrical shell under compression as an arch. Using the contemporary capabilities of the programs for spatial analysis of building structures the author will try to find the answer of this question.
EFEKTIFITAS PELATIHAN MEDIA AUDIO-VISUAL TERKAIT ANEMIA IBU HAMIL DALAM PENINGKATAN KOMPETENSI PETUGAS PENYULUH KESEHATAN DI KABUPATEN BANYUMAS
Authors: Masfiah Siti , Gamelia Elviera , Ayu Maghfiroh Arrum Firda , Pramasatya Adhika
Published: June 2019

Pregnant suffers anemia can lead to infection and bleeding, which is a major factor in maternal mortality. In 2013 Central Java district recorded 3rd rank of 35 dictricts, at rate 126 per 100,000 live births. Cases of anemia in pregnant women in Banyumas accounted as 68.99%, higher than the national number. Banyumas did anemia counseling in pregnant mothers using leaflets, but did not effective. Health promotion media and materials based on local context are still limited. The ability of health workers are still based on extension activities with lectures, competency to make audio-visual health promotion is still limited. This study aimed to determine the effectiveness of audio-visual media training related anemia in pregnant women to increase the competence (knowledge and skills) of health workers in Banyumas.The study was quasy-experimental design with time series method. Population were 58 health educators in Banyumas and it was selected 33 sample by purposively. Data were collected by questionnaires for knowledge, and it was used checklist for observation the skills. For analyze the data�s normality I usedShapiro Wilk, and it used Wilcoxonto analyze the data�s difference.There was a significant difference of knowledge and skills at pretest and posttest I, but there was no significant difference on the posttest 1 and posttest II. Training of audio-visual media-related anemia in pregnant mothers increased the competence of health workers in Banyumas District.
UPAYA PENINGKATAN CAKUPAN ASI EKSKLUSIF DAN INISIASI MENYUSU DINI (IMD
Authors: Santi Mina Yumei
Published: June 2019

Infant mortality rate by Indonesia Demographic Health Survey in 2012 is still quite high at 32 per 1,000 live births and under five year mortality rates of 40 per 1,000 live births. An effort to prevent infant mortality is by breastfeeding soon after birth or so-called early initiation of breastfeeding and exclusive breastfeeding. Coverage of exclusive breastfeeding nationwide in 2014 amounted to 52.3% is still below the national target of 80%. The aim of this research was to find the efforts to improve the coverage of exclusive breastfeeding and the early initiation of breastfeeding. The Efforts that can do are empowering people through Mother Support Group, socialize the Government Regulation No. 33 of 2012 on exclusive breastfeeding and breastfeeding counselor provides power. The local government is advised to draw up local regulations that support the implementation of the early initiation of breastfeeding program and exclusive breastfeeding so as to have binding legal force for all parties involved as well as to conduct promotion, monitoring, evaluating and supervising the implementation and achievement of the program exclusive breastfeeding.
Authors: Khulsum Hanifah , Widiyanto Agnes Fitria , Suratman Suratman
Published: June 2019

Background : Consumed water must be free from hazardous and toxic chemicals. The preliminary test showed that Fe of well water was 5.25 mg/l. Fe-contained well water must be processed zeolite and activated charcoal to decrease Fe in water. The purpose of this research was to find out the effectiveness of the size variation of zeolite and activated charcoal to decrease Fe of the well water in Desa Kebasen..

Method : The type of this research was quasi experiment, pretest posttest control group designwith a completely randomized design (CRD). Samples was 56 samples of well water contained Fe > 1 mg/l which chosen by random sampling method. The intervention in this research used 80, 100, and 120 mesh of zeolite and activated charcoal with 4 times repetitions for each treatment. The data analysis used normality test with Shapiro Wilk, Krusskal Wallis test, and Mann Whitney test

Result : There was an average difference of Fe content before and after treatment used 80, 100, and 120 mesh of activated charcoal. There was an average difference of Fe content before and after treatment used 80, 100, and 120 mesh of zeolite.

Conclusions : The 100 mesh zeolite was most effective at lowered Fe of well water in Desa Kebasen by 93.86%.
Decision Support System Research on Forest Tending Problems Based on Process Management System
Authors: Jing Hui , Wang Wukui , Umutoni Aline
Published: June 2019

In this study, the decision-making process management of forest tending in the forestry business is decentralized, and forest tending decision-making activities at different points in time are integrated by decision makers at different geographical locations. The decision-making process was analyzed and optimized from a system perspective. Based on the optimized decision-making process, a forest tending business group decision support system (FTGDSS) was established. We first reviewed and discussed the characteristics and development of the forest tending business and forestry decision support system. Business Process Modeling Notation was used to draw a current state flow chart of the forest tending business, to identify and discover important decision points in the process of tending decision-making. We also analyzed the content and attributes of each decision point, and described the system structure, functional framework, knowledge base structure, and reasoning algorithm of FTGDSS in detail. Finally, FTGDSS was evaluated from the two dimensions of the technology adoption model. FTGDSS integrates different levels of time-space decision-making activities, historical tending data, business plans, decision-makers' management tendencies into the decision-making process and automatically extracts decision-making data from the forest business process management enterprise resource planning system (Smartforest) that improves the ease of use of the decision support system (DSS). It also improves the quality of forest tending decisions, and enables the DSS to better support multi-target management strategies.
Oxidative Stress as a Mediator of the Immunomodulation Exerted by Monoclonal Antibodies in the Treatment of Lung Cancer in Mice
Authors: Tang Jun , Ramis-Cabrer Daniel , Wang Xuejie , Barreiro Esther
Published: June 2019

Background: Lung cancer (LC) is a major leading cause of death worldwide. Immunomodulators that target several immune mechanisms have proven to reduce tumor burden in experimental models through induction of the immune microenvironment. We hypothesized that other biological mechanisms may also favor tumor burden reduction in lung cancer-bearing mice treated with immunomodulators. Methods: Tumor weight, area, and immune cells (T, B, macrophages, and TNF-alpha levels, immunohistochemistry) and tumor growth, oxidative stress, apoptosis, autophagy, and sirtuin-1 markers were analyzed (immunoblotting) in subcutaneous tumor of BALB/c mice injected with LP07 adenocarcinoma cells treated with monoclonal antibodies (CD-137, CTLA-4, PD-1, and CD-19, N=9/group) and non-treated control animals. Results: Compared to non-treated cancer mice, in tumors of monoclonal-treated animals, tumor area and weight and ki-67 significantly reduced, while T cell counts, oxidative stress, apoptosis, autophagy, and sirtuin-1 marker increased. Conclusion: Immunomodulators elicited a reduction in tumor burden (reduced tumor size and weight) through decreased tumor proliferation and increased oxidative stress, apoptosis, autophagy, and sirtuin-1 levels, which may have interfered with the immune profile of the tumor microenvironment. Future research should be devoted to the elucidation of the specific contribution of each biological mechanism to the reduced tumor burden.
Analysis of a Global Futures Trend-Following Strategy
Authors: Nokes Derek , Fulton Lawrence
Published: June 2019

Systematic traders employ algorithmic strategies to manage their investments. As a result of the deterministic nature of such strategies, it is possible to determine their exact responses to any conceivable set of market conditions. Consequently, sensitivity analysis can be conducted to systematically uncover undesirable strategy behavior and enhance strategy robustness by adding controls to reduce exposure during periods of poor performance / unfavorable market conditions or increase exposure during periods of strong performance / favorable market conditions. In this study, we formulate both a simple systematic trend-following strategy (i.e., trading model) to simulate investment decisions, and a market model to simulate the evolution of instrument prices. We then map the relationship between market model parameters under various conditions and strategy performance. We focus, in particular, on identifying the performance impact of changes in both serial dependence in price variability and changes in the trend. The long-range serial dependence of the true range worsens performance of the simple classic trend-following strategy. During periods of strong performance, the dispersion of trading outcomes increases significantly as long-range serial dependence increases.
Eficácia e efetividade do direito à liberdade
Authors: Barroso Luis Roberto
Published: June 2019

I - Breve introdução metajurídica. 1. A liberdade fora do Direito; 2. A aventura da liberdade. II - Eficácia e efetividade dos direitos constitucionais. 1. Constituição e supremacia constitucional; 2. As três grandes categorias de normas constitucionais; 3. Os direitos subjetivos constitucionais; 4. Efetividade da Constituição e garantias jurídicas dos direitos constitucionais. III - Eficácia e efetividade do direito à liberdade. 1. A caracterização jurídica do conceito de liberdade; 2. As liberdades públicas; 3. Algumas garantias constitucionais materiais do direito à liberdade; 4. Garantias constitucionais processuais do direito à liberdade. Habeas corpus e mandado de segurança. IV - Conclusão.
Crise do ato administrativo e a retomada de sua centralidade
Authors: Martins Ricardo Marcondes
Published: June 2019

Este estudo pretende examinar a suposta crise do ato administrativo. Para tanto, faz-se um contraponto com a crise do serviço público. Ademais, defende-se, a partir de uma percepção histórica dos estudos do Direito administrativo, a superação da crise. O estudo do ato administrativo, ainda hoje, por imposição científica, fornece a base teórica de todo Direito Administrativo. Defende-se a assunção de um conceito amplo, abrangente de todas as normas editadas no exercício da função administrativa. Fixado o conceito, apresenta-se um panorama da teoria do ato administrativo, com breve incursão sobre seus principais desdobramentos: a existência, a eficácia, a validade, a extinção, a modificação e os atributos.
Dever judicial de considerar as consequências práticas da decisão: interpretando o art. 20 da Lei de Introdução às Normas do Direito Brasileiro
Authors: Didier Fredie Souza , Oliveira Rafael Alexandria
Published: June 2019

O presente artigo analisa o conteúdo normativo e dogmático do art. 20 da Lei de Introdução às Normas do Direito Brasileiro, que impõe ao juiz o dever de considerar as consequências práticas da sua decisão quando baseada em valores jurídicos abstratos.
Legalidade é juridicidade: notas sobre a (i)legitimidade da aplicação de leis inconstitucionais pela Administração Pública
Authors: Madureira Claudio Penedo
Published: June 2019

Este artigo tem por objetivo demonstrar que os agentes estatais devem negar aplicação a leis inconstitucionais, mesmo quando a inconstitucionalidade desses atos legislativos ainda não tiver sido formalmente declarada pelos órgãos jurisdicionais competentes, pois o princípio administrativo da legalidade vincula o agir administrativo não apenas ao que prescrevem as leis (legalidade em sentido estrito), mas também às regras e princípios que sobressaem do texto constitucional (juridicidade ou legalidade em sentido amplo).Professor dos cursos de Graduação e Mestrado em Direito da Universidade Federal do Espírito Santo (Vitória-ES, Brasil). Doutor em Direito pela PUC/SP. Mestre em Direito Processual pela UFES. Procurador do Estado do Espírito Santo e advogado. E-mail: madureira.fmr@gmail.com
Engaging Foreign Law: Not So Liberally
Authors: Legrand Pierre
Published: June 2019

Taking its cue from a remarkable institutional initiative owing to the Georgetown University Law Center, this essay contests some of the key assumptions that have informed liberalism’s cosmopolitan turn. In particular, the argument addresses the way in which liberal legal thought has handled a doctrine widely known as “the rule of law”. The text challenges the universalizing drive having informed the dissemination of “the rule of law” and the attendant marginalization of culture in the form of the decredibilization of local knowledge. The paper suggests that “comparative law” can offer a valuable opportunity for the liberal self to revisit its uniformizing ideological commitments  — although not “comparative law” of the mainstream brand.
Os pressupostos epistemológicos e filosóficos da gestão de políticas públicas no Estado Democrático de Direito: uma perspectiva habermasiana
Authors: Leal Rogério Gesta
Published: June 2019

Pretende o presente ensaio: (a) identificar quais os pressupostos teóricos (filosóficos e políticos) que informam a vigente e tradicional concepção de gestão de políticas públicas no âmbito da Teoria do Estado Moderno de Direito; (b) demarcar os limites de esgotamento deste modelo; (c) avaliar como o contributo filosófico de Jürgen Habermas à Teoria da Democracia Procedimental pode auxiliar na constituição de um novo paradigma jurídico e político à gestão pública contemporânea dos interesses e demandas sociais.
Curriculum co-creation as a transformative strategy to address differential student outcomes: the example of Kingston University’s Student Curriculum Consultant Programme
Authors: Hughes Annie Livingstone , Mohamad Kamal , McDuff Nona , Michener Christina
Published: June 2019

This paper examines the role that curriculum co-creation can play in creating a more inclusive higher education and in so doing, address the complex challenge of differential student outcomes and attainment. It achieves this by exploring Kingston University’s Curriculum Consultant programme within this context of their Inclusive Curriculum Framework. Students who work as Curriculum Consultants use their own diverse lived experiences and Kingston University’s Inclusive Curriculum Framework (ICF) to collaborate with staff to create more accessible, diverse and globally relevant curricula at all levels of the institution. The consultants work with staff in a variety of ways, providing feedback on the Virtual Learning Environment (VLE) experience of individual modules, the inclusivity of teaching resources, and areas where the curriculum represents potential barriers to some groups of students. They also take leadership roles, participating in and facilitating staff development workshops focused on inclusive teaching and learning. This paper examines three instances of co-creation facilitated through the Curriculum Consultant programme. We argue that the Curriculum Consultant programme acts as a mechanism through which the institution can not only legitimate, but also actively endorse and encourage co-creation in order to create more inclusive curricula.
EL RÉGIMEN DE ALEGACIÓN Y PRUEBA DEL DERECHO EXTRANJERO EN ESPAÑA, A PROPÓSITO DE LA SENTENCIA DE LA AUDIENCIA PROVINCIAL DE MÁLAGA Nº 3/2019 DE 8 DE ENERO
Authors: Ortega Giménez Alfonso
Published: June 2019

El art. 281.2 LEC obliga a alegar y probar el derecho extranjero en su contenido y vigencia permitiendo al tribunal valerse de los medios de averiguación que estime necesarios para su aplicación. Es a la parte que lo invoque a quien corresponde demostrar el contenido y la vigencia, de modo que, una vez justificados esos dos extremos, dependerá del Juez la aplicación; así lo afirma la AP Málaga en su Sentencia 3/2019, de 8 de enero al señalar que, al no acreditarse el Derecho extranjero reclamado en una sucesión, procede resolver la cuestión debatida conforme a las normas del ordenamiento jurídico español.
Innovación sostenible para la cultura colombiana
Authors: Suárez Puerta Bianca Liliana
Published: June 2019

Las herramientas de reconocimiento del usuario, del entorno y de las situaciones del diseño estratégico hacen posible entregarle a la sociedad una mirada consciente del uso de los recursos necesarios para construir un futuro. De la misma manera, la visión de la innovación social busca el desarrollo de soluciones sostenibles desde el punto de vista económico, ambiental y social. Este artículo presenta algunas posturas de un proyecto de innovación social que busca la protección de la diversidad de expresiones culturales: Culturelab, ha motivado a estudiantes y agrupaciones culturales para pensar más allá de los muros de la universidad o la soledad de las ideas de los pequeños empresarios, para conocer y tener contacto con mercados y festivales internacionales. Con esta spin-off, se busca contribuir a la edad de oro del cine colombiano, mostrar que en Colombia hay mucho más que música exótica, un teatro independiente lleno de matices y, en general, un diverso escenario pluricultural. Este conocimiento muestra el proceso de gestión enfocado en crear empresas, que tiene un fuerte énfasis en la educación de los estudiantes de la carrera en Estudios y Gestión Cultural, y ofrece a los beneficiarios de la investigación experiencias artísticas de calidad que ayudan a aumentar el capital cultural de Colombia.
Demographic and socioeconomic characteristics of Canadian medical students: A cross-sectional study
Authors: Khan Rishad , Apramian Tavis , Kang Joel Hosung , Gustafson Jeffrey , Sibbald Shannon
Published: June 2019

Background: While the importance of medical students’ demographic characteristics in influencing the scope and location of their future practice is recognized, these data are not systematically collected in Canada. This study aimed to characterize and compare the demographics of Canadian medical students with the Canadian population.

Methods: Through an online survey, delivered in 2018, medical students at fourteen English-speaking Canadian medical schools provided their age, sex, gender identity, ethnicity, educational background, and rurality of the area they grew up in. Respondents also provided information on parental income, occupation, and education as markers of socioeconomic status. Data were compared to the 2016 Canadian Census.

Results: A total of 1388 students responded to the survey, representing a response rate of 16.6%. Most respondents identified as women (63.1%) and were born after 1989 (82.1%). Respondents were less likely, compared to the Canadian Census population, to identify as black (1.7% vs 6.4%) (P<0.001) or Aboriginal (3.5% vs. 7.4%) (P<0.001), and have grown up in a rural area (6.4% vs. 18.7%) (P<0.001). Respondents had higher socioeconomic status, indicated by parental education (29.0% of respondents’ parents had a master’s or doctoral degree, compared to 6.6% of Canadians aged 45-64), occupation (59.7% of respondents’ parents were high-level managers or professionals, compared to 19.2% of Canadians aged 45-64), and income (62.9% of respondents grew up in households with income >$100,000/year, compared to 32.4% of Canadians). Assessment of non-response bias showed that our sample was representative of all students at English-speaking Canadian medical schools with respect to age, though a higher proportion of respondents were female. Additionally, there were no differences between early and late respondents with respect to ethnicity, rurality, and parental income, occupation, and education.

Conclusions: Canadian medical students have different socioeconomic characteristics compared to the Canadian population. Collecting and analyzing these characteristics can inform evidence-based admissions policies.
Assessing the training needs of medical students in patient information gathering; a qualitative study
Authors: Gilligan Conor , Brubacher Sonja , Powell Martine
Published: June 2019

Background
Effective communication is at the heart of good medical practice but rates of error, patient complaints, and poor clinician job satisfaction are suggestive of room for improvement in this component of medical practice and education.
Methods
We conducted semi-structured interviews with experienced clinicians (n = 19) and medical students (n = 20) to explore their experiences associated with teaching and learning clinical communication skills and identify targets for improvements to addressing these skills in medical curricula.
Results
Interviews were thematically analysed and four key themes emerged; the importance of experience, the value of role-models, the structure of a consultation, and confidence.
Conclusions
The findings reinforce the need for improvement in teaching and learning communication skills in medicine, with particular opportunity to target approaches to teaching foundational skills which can establish a strong grounding before moving into more complex situations, thus preparing students for the flexibility required in medical interviewing. A second area of opportunity and need is in the engagement and training of clinicians as mentors and teachers, with the findings from both groups indicating that preparation for teaching and feedback is lacking. Medical programs can improve their teaching of communication skills and could learn from other fields s to identify applicable innovative approaches.
Genome Wide Search to Identify Reference Genes candidates for Gene Expression Analysis in Gossypium hirsutum
Authors: K Smitha P , K Vishnupriyan , Kar Ananya S. , M Anil Kumar , Bathula Christopher , N Chandrashekara K , Das Manjula , Dhar Sujan K
Published: June 2019

Background: With the advent of newer breeds and transgenic varieties of commercial crops, qPCR (quantitative polymerase chain reaction) experiments have become extremely popular for quick expression checks. Selection of appropriate reference genes plays a critical role in quantifying the expression of target gene. Most commonly used reference genes in expression studies are the “house-keeping genes”, involved in basic cellular processes. However, expression levels of such genes often vary in response to experimental conditions, forcing the researchers to validate the reference genes in every experiment. This study presents a data science driven unbiased genome-wide search results for selection of reference genes by assessing variation of >50,000 genes in a publicly available RNA-seq dataset of cotton species Gossypium hirsutum. Selected candidate genes were validated experimentally across 33 samples from normal and transgenic G. hirsutum plants, harvested from different areas of the plant at different time points under various developmental conditions. Experimental validation also includes commonly used genes from literature to suggest the most stable set of 5 genes to be used for assessment of quantitative expression in cotton plants (Fig.1). Result: Five genes (TMN5, TBL6, UTR5B, AT1g65240, CYP76B6) identified by data-driven analysis, along with two commonly used reference genes for cotton found in literature (GhPP2A1 and GhuBQ14) were validated using qPCR in a set of 33 experimental samples consisting of different tissues (leaves, square, stem and root), different stages of leaf (young and mature) and square development (small, medium and large) in both transgenic and non-transgenic plants. Expression stability of the genes was evaulated using four different algorithms - DeltaCT, Genorm, BestKeeper and Normfinder. GhPP2A1 and TMN5 were identified as the most stable genes, followed by GhuBQ14 across all the samples tested. Conclusion: This study, for the first time successfully displays a data science driven genome-wide search method followed by experimental validation as a method of choice for selection of stable reference genes for experiment with cotton species. Based on the results we recommend use of GhPP2A1, TMN5 and GhuBQ14 as the optimal candidate reference genes in qPCR experiments with normal or transgenic cotton plant tissues.
Qualitative research to inform hypothesis testing for fidelity-based sub-group analysis in clinical trials: Lessons learnt from the process evaluation of a multifaceted podiatry intervention for falls prevention
Authors: Scantlebury Arabella , Cockayne Sarah , Fairhurst Caroline , Rodgers Sara , Torgerson David , Hewitt Catherine , Adamson Joy
Published: June 2019

Background

Ensuring fidelity to complex interventions is a challenge when conducting pragmatic randomised controlled trials. We explore fidelity through a qualitative process evaluation, which was conducted alongside a pragmatic, multi-centred, two-arm cohort randomised controlled trial – the REFORM (Reducing Falls with Orthoses and a Multifaceted podiatry intervention) trial. The paper aims, through a qualitative process evaluation, to explore some of the factors that may have affected the delivery of the REFORM intervention and highlight how project specific fidelity can be assessed using a truly mixed methods approach when informed by qualitative insights.

Design

Semi-structured qualitative interviews carried out as part of a process evaluation. Interviews were analysed thematically.

Setting

7 NHS trusts in the UK and a University podiatry school in Ireland. Interviews were undertaken face-to-face or over the telephone.

Participants

21 REFORM trial participants and 14 podiatrists who delivered the REFORM intervention

Results

Factors affecting fidelity included: how similar the intervention was to routine practice, challenges of delivering a multifaceted intervention to a heterogeneous older population, and practical issues with delivery such as time and training. Trial participants’ views of the intervention, whether falls prevention is a personal priority, their experience of being part of a trial, and individual factors such as medical conditions also may have affected intervention fidelity.

Conclusions

Our process evaluation highlighted factors that were perceived to have affected the fidelity of the REFORM intervention and in doing so demonstrates the importance of considering fidelity when designing and evaluating pragmatic trials. We propose a number of recommendations of how important project specific insights from qualitative work can be incorporated into the design of fidelity measurement of future trials, which build on existing conceptual fidelity frameworks. In particular, we encourage adopting a mixed methods approach whereby qualitative insights can be used to suggest ways to enhance quantitative data collection facilitating integration through hypothesis generation, hypothesis testing and seeking explanation for trial findings. This will provide a framework of enabling measures of fidelity to be incorporated into the understanding of trial results which has been relatively neglected by existing literature.
Trial registration: ISRCTN68240461.
Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach
Authors: Jehl Frédéric , Désert Colette , Klopp Christophe , Brenet Marine , Rau Andrea , Leroux Sophie , Boutin Morgane , Muret Kévin , Blum Yuna , Esqu Diane , Gourichon David , Burlot Thierry , Collin Anne , Pitel Frédérique , Benani Alexandre , Zerjal Tatiana , Lagarrigue Sandrine
Published: June 2019

Background
Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection was undertaken. The aim of this study was to better understand the effect of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake.
Results
Chicken significantly increased their feed intake and decreased their abdominal adipose tissue weight in response to the low-energy diet, whereas their egg-production was unchanged. For each production trait, no significant interaction was observed between diet and line. Moreover, the low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) known to regulate feed intake, and to genes related to polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2) such as the arachidonic acid which is a precursor of anandamide, a key endocannabinoid. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It also upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area.
Conclusions
We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet.
Effects of Dexamethasone on Post-Operative Cognitive Dysfunction and Delirium in Adults Following General Anaesthesia: A Meta-Analysis of Randomised Controlled Trials
Authors: Li Li-Qin , Wang Cong , Fang Mei-Dan , Xu Hong-Yu , Lu Hong-Liu , Zhang Hou-Zhong
Published: June 2019

Background Several studies have investigated the effects of dexamethasone on postoperative cognitive dysfunction (POCD) or postoperative delirium (POD); however, their conclusions have not been consistent. So we conducted a meta-analysis to determine the effects of dexamethasone on POCD/POD in adults following general anesthesia. Methods Cochrane Central Register of Controlled Trials (CENTRAL, 2018, Issue 11 of 12) in the Cochrane Library (searched November 17, 2018); MEDLINE OvidSP (1946 to November 16, 2018); and Embase OvidSP (1974 to November 16, 2018) were searched for randomized controlled trials that evaluated the incidence of POCD/POD following dexamethasone administration, in adults (age ≥18 years) under general anesthesia. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework to assess the quality of evidence. Results Five studies were included (three studies/855 participants in dexamethasone group and 538 participants in placebo group for the incidence of POCD, and two studies/410 participants in dexamethasone group and 420 participants in placebo group for the incidence of POD). There was no significant difference between the dexamethasone group and the placebo group in terms of the incidence of POCD in 30 days after surgery (RR 1.00; 95% CI [0.51, 1.96], P = 1.00, I2 = 77%) or in the incidence of POD (RR 0.96; 95% CI [0.68, 1.35], P = 0.80, I2 = 0%). However, both analyses had some limitations since evidence remains limited and clinical heterogeneity, and we considered the quality of the evidence for the postoperative incidence of POCD and POD to be very low. Conclusions This meta-analysis revealed that prophylactic dexamethasone did not reduce the incidence of POCD and POD. Trials of alternative prevent strategies for POCD/POD, and a better understanding of the pathophysiology of those complex syndrome, are still needed to make progress of this field. Trial registration number: This study is registered with PROSPERO, 23 October 2018, number CRD42018114552.
Propofol attenuated the effect of TNF-α on occludin expression by inhibiting HIF-1α/VEGF/VEGFR-2/ERK signaling pathway in hCMEC/D3 cells
Authors: Zhang Yue , Ding Xiaowei , Miao Changhong , Chen Jiawei
Published: June 2019

Purpose: The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α(TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms.
Methods: The hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8.
Results: TNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGF, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression.
Conclusion: TNF-α could decrease the expression of occludin via activating Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, which was attenuated by propofol.
Multiplex qPCR Facilitates Identification of Betaherpesviruses in Patients With Acute Liver Failure of Unknown Etiology
Authors: Raposo Jéssica Vasques , Alves Arthur Daniel Rocha , Silva Alexandre Dos Santos Da , Santos Damião Carlos Dos , Melgaço Juliana Gil , Moreira Otacilio Cruz , Pinto Marcelo Alves , de Paula Vanessa
Published: June 2019

Background: The etiology of acute liver failure (ALF) is often unknown and reported to be associated with herpesviruses in a number of cases. In this study, we examined for betaherpesviruses infections in patients with ALF of unknown etiology using a multiplex qPCR to Betaherpesviruses subfamily.
Methods: Liver and serum samples from 27 patients with ALF of unknown etiology were analyzed with the aid of multiplex qPCR to identify betaherpesviruses. All positive samples were sequenced to confirm herpes infection and liver enzyme levels evaluated.
Results: Betaherpesviruses infection was effectively detected using multiplex qPCR. Seven (26%), two (7%) and three (11%) cases were positive for HHV-6, HHV-7 and HCMV, respectively. Two cases of dual infection (HHV-7/HHV-6 and HHV-7/HCMV) were additionally identified. Interestingly, HHV-7 was only detected in the presence of other betaherpesviruses. Sequencing information confirmed betaherpesviruses infection. High hepatic enzyme levels and INR values>1.4 were determined in all betaherpesvirus-positive patients.
Conclusions: Multiplex qPCR facilitated efficient quantification, indicating that differentiation between betaherpesviruses is possible with the sole use of real-time PCR. Liver and serum samples were positive for some betaherpesviruses, suggesting an association with ALF. Coinfection of HHV-7 with HHV-6 or HCMV was additionally detected, suggesting that the precursor betaherpesviruses infection can trigger HHV-7 infection. Based on these results, we propose that ALF patients should be screened for the presence of betaherpesviruses.
Preoperative hypoalbuminemia was associated with acute kidney injury in high-risk patients following non-cardiac surgery: a retrospective cohort study
Authors: Li Nan , Qiao Hong , Guo Jing-Fei , Yang Hong-Yun , Li Xue-Ying , Li Shuangling , Wang Dong-Xin , Yang Li
Published: June 2019

Background: Acute kidney injury (AKI) is a common complication following non-cardiac surgery with adverse short- and long- term morbidity and mortality. Evidence shows that hypoalbuminemia is associated with increased AKI risk in patients with infectious diseases and cancer and following cardiac surgery and transplant surgery. However, little evidence is available on non-cardiac surgery population. Thus, we investigated the association between preoperative hypoalbuminemia and AKI following non-cardiac surgery.
Methods: We retrospectively assessed perioperative risk factors and preoperative serum albumin concentration in 729 consecutive adult patients who underwent non-cardiac surgery from July 1, 2017, to June 30, 2018. Each patient was categorized according to maximal Kidney Disease Improving Global Outcomes criteria based on creatinine changes and urine output within the first week after surgery. Multivariate Logistic regression models were used to analyze the association between preoperative hypoalbuminemia and postoperative AKI.
Results: Of 729 patients, 188 (25.8%) developed AKI. AKI incidence was higher in patients with preoperative serum albumin <37.5 g/L than in those with preoperative serum albumin ≥37.5 g/L [35.9% (98/273) vs. 19.7% (90/456), P<0.001]. Multivariate logistic regression analysis showed that preoperative serum albumin <37.5 g/L (odds ratio 1.892; 95% confidence interval 1.238-2.891; P=0.003) was independently associated with postoperative AKI. Patients with preoperative serum albumin <37.5 g/L tended to have a higher but not significant ratio in AKI stage 2 (2.6% vs 1.1%, P=0.144) and much higher ratio in AKI stage 3 (4.8% vs 0.7%, P<0.001) than those with preoperative serum albumin ≥37.5 g/L. AKI patients had a higher in-hospital mortality rate [6.9% (13/188) vs. 0.2% (1/541), P<0.001]. Kaplan-Meier analysis revealed that the cumulative survival rate decreased with increasing AKI severity (P<0.001). Postoperative AKI was also associated with other worse outcomes, such as prolonged mechanical ventilation [53.4 (33.0, 73.8) vs 14.7 (11.1, 18.3) hours, P<0.001], intensive care unit stay [4.0 (3.1, 4.9) vs 2.0 (1.8, 2.3) days, P<0.001], postoperative hospital stay [17.8 (14.8, 20.9) vs 12.3 (11.3, 13.3) days, P<0.001], and higher total cost [13,453 (8,538, 20,228) vs 11,306 (6,277, 16,400) dollars, P<0.001].
Conclusions: Preoperative hypoalbuminemia was independently associated with AKI after non-cardiac surgery, and postoperative AKI was associated with poor outcomes.
Exploring the druggable space around the Fanconi anemia pathway using machine learning and mechanistic models
Authors: Esteban-Medina Marina , Peña-Chilet María , Loucera Carlos , Dopazo Joaquin
Published: June 2019

Background

In spite of the abundance of genomic data, predictive models that describe phenotypes as a function of gene expression or mutations are difficult to obtain because they are affected by the curse of dimensionality, given the disbalance between samples and candidate genes. And this is especially dramatic in scenarios in which the availability of samples is difficult, such as the case of rare diseases.

Results

The application of multi-output regression machine learning methodologies to predict the potential effect of external proteins over the signaling circuits that trigger Fanconi anemia related cell functionalities, inferred with a mechanistic model, allowed us to detect over 20 potential therapeutic targets.

Conclusions

The use of artificial intelligence methods for the prediction of potentially causal relationships between proteins of interest and cell activities related with disease-related phenotypes opens promising avenues for the systematic search of new targets in rare diseases.