1,720,957 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Mechanical phenotyping of cancer stemness in colorectal cancer
Get PDFPrograma de Doctorat en Medicina i Recerca Translacional / Tesi realitzada a l'Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)[eng] In this thesis work, I explored the link between cancer stemness and the mechanical properties of colorectal cancer (CRC) cells. In the last decades, the cancer stem cell (CSC) model underwent an important paradigm shift, from a static and intrinsic concept of CSCs to a more dynamic and plastic notion, integrating the influence of the microenvironment. Similarly, during the last five years, my experimental approach had to shift, from assuming that cancer stem cells are static and thus won’t change in response to different culture conditions, to the realization that their stemness is largely affected by the microenvironment, and thus I had to establish the experimental conditions that would maintain the desired cellular phenotypes. This effort is not reflected in the present work, but it constitutes its foundation.
CRC tumors are composed of heterogeneous cell populations including a pool of cancer stem cells (CSCs) that express LGR5. The link between cancer cell differentiation states and their metastatic potential has been the focus of extensive investigation, with some studies pointing to microenvironmentally defined plasticity as a mechanism indispensable for metastasis formation. In this highly heterogeneous and plastic context, differences in mechanical phenotypes may favor or impair the ability of specific cell populations to progress through the metastatic cascade. However, whether distinct cell populations in CRC tumors display different mechanical properties, and how these properties might contribute to metastasis is unknown.
In the present study I performed a broad biophysical characterization of CRC patient derived organoids (PDOs) engineered to fluorescently label cells expressing LGR5. I found that LGR5+ and LGR5- cells display distinct mechanical phenotypes. Compared to LGR5- cells, LGR5+ cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, and show a higher survival rate in response to mechanical confinement. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, I show that this downregulation is a robust signature of colorectal tumors. Finally, I also show that LGR5+ cells adhere better to the endothelial surface and form transendothelial gaps with higher efficiency than LGR5- cells. Together, these results show that LGR5- cells display a mechanically dynamic phenotype that favors dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype that promotes extravasation and metastatic growth. The observed coupling between mechanical states and cancer cell heterogeneity may be an indispensable adaptive mechanism for metastatic progression.[spa] En esta tesis, he explorado la relación entre las células madre cancerosas y las propiedades mecánicas de las células del cáncer de colon. En las últimas décadas, el modelo de células madre de cancerosas ha experimentado un importante cambio de paradigma, pasando de un concepto estático e intrínseco de células madre cancerosas a una noción más dinámica y plástica, que integra la influencia del microambiente. Del mismo modo, durante los últimos cinco años, mi enfoque experimental tuvo que cambiar, pasando de suponer que las células madre cancerosas son estáticas y, por tanto, no cambiarán en respuesta a diferentes condiciones de cultivo, a la constatación de que su carácter de células madre se ve afectado en gran medida por el microambiente, por lo que tuve que establecer las condiciones experimentales que mantuvieran los fenotipos celulares deseados. Este esfuerzo no se refleja en el presente trabajo, pero constituye su fundamento.
Los tumores de cáncer colorrectal están compuestos por poblaciones celulares heterogéneas que incluyen un conjunto de células madre cancerosas, marcadas por la expresión de LGR5. La relación entre los estados de diferenciación de las células cancerosas y su potencial metastásico ha sido objeto de una amplia investigación, y algunos estudios apuntan a la plasticidad definida por el microambiente como mecanismo indispensable para la formación de metástasis. En este contexto altamente heterogéneo y plástico, las diferencias en los fenotipos mecánicos pueden favorecer o perjudicar el potencial metastático de las células cancerosas. Sin embargo, se desconoce si las distintas poblaciones celulares de los tumores de colon presentan diferentes propiedades mecánicas y cómo estas propiedades podrían contribuir a las metástasis.
En este estudio llevé a cabo una amplia caracterización biofísica de organoides derivados de pacientes de cáncer de colon diseñados para etiquetar con fluorescencia células que expresan LGR5. Descubrí que las células LGR5+ y LGR5- muestran fenotipos mecánicos distintos. En comparación con las células LGR5-, las células LGR5+ son más rígidas, se adhieren mejor a la matriz extracelular, se mueven más lentamente tanto como células individualmente que en grupo, muestran mas YAP nuclear y una mayor tasa de supervivencia en respuesta al confinamiento mecánico. Estas diferencias se explican en gran medida por la regulación a la baja de las proteínas de unión de la membrana a la corteza Ezrin/Radixina/Moesina en las células LGR5+. Mediante el análisis de los patrones de expresión scRNA-seq de una cohorte de pacientes, demuestro que esta regulación a la baja es una firma robusta de los tumores colorrectales. Por último, también demuestro que las células LGR5+ se adhieren mejor a la superficie endotelial y forman brechas transendoteliales con mayor eficacia que las células LGR5-. En conjunto, estos resultados muestran que las células LGR5- presentan un fenotipo mecánicamente dinámico que favorece la diseminación desde el tumor
primario, mientras que las células LGR5+ presentan un fenotipo mecánicamente estable y resistente que favorece la extravasación y el crecimiento metastásico. El acoplamiento observado entre los estados mecánicos y la heterogeneidad de las células cancerosas puede ser un mecanismo adaptativo indispensable para la progresión metastásica
Mechanical phenotyping of cancer stemness in colorectal cancer
Get PDF[eng] In this thesis work, I explored the link between cancer stemness and the mechanical properties of colorectal cancer (CRC) cells. In the last decades, the cancer stem cell (CSC) model underwent an important paradigm shift, from a static and intrinsic concept of CSCs to a more dynamic and plastic notion, integrating the influence of the microenvironment. Similarly, during the last five years, my experimental approach had to shift, from assuming that cancer stem cells are static and thus won’t change in response to different culture conditions, to the realization that their stemness is largely affected by the microenvironment, and thus I had to establish the experimental conditions that would maintain the desired cellular phenotypes. This effort is not reflected in the present work, but it constitutes its foundation.
CRC tumors are composed of heterogeneous cell populations including a pool of cancer stem cells (CSCs) that express LGR5. The link between cancer cell differentiation states and their metastatic potential has been the focus of extensive investigation, with some studies pointing to microenvironmentally defined plasticity as a mechanism indispensable for metastasis formation. In this highly heterogeneous and plastic context, differences in mechanical phenotypes may favor or impair the ability of specific cell populations to progress through the metastatic cascade. However, whether distinct cell populations in CRC tumors display different mechanical properties, and how these properties might contribute to metastasis is unknown.
In the present study I performed a broad biophysical characterization of CRC patient derived organoids (PDOs) engineered to fluorescently label cells expressing LGR5. I found that LGR5+ and LGR5- cells display distinct mechanical phenotypes. Compared to LGR5- cells, LGR5+ cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, and show a higher survival rate in response to mechanical confinement. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing scRNA-seq expression patterns from a patient cohort, I show that this downregulation is a robust signature of colorectal tumors. Finally, I also show that LGR5+ cells adhere better to the endothelial surface and form transendothelial gaps with higher efficiency than LGR5- cells. Together, these results show that LGR5- cells display a mechanically dynamic phenotype that favors dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype that promotes extravasation and metastatic growth. The observed coupling between mechanical states and cancer cell heterogeneity may be an indispensable adaptive mechanism for metastatic progression.[spa] En esta tesis, he explorado la relación entre las células madre cancerosas y las propiedades mecánicas de las células del cáncer de colon. En las últimas décadas, el modelo de células madre de cancerosas ha experimentado un importante cambio de paradigma, pasando de un concepto estático e intrínseco de células madre cancerosas a una noción más dinámica y plástica, que integra la influencia del microambiente. Del mismo modo, durante los últimos cinco años, mi enfoque experimental tuvo que cambiar, pasando de suponer que las células madre cancerosas son estáticas y, por tanto, no cambiarán en respuesta a diferentes condiciones de cultivo, a la constatación de que su carácter de células madre se ve afectado en gran medida por el microambiente, por lo que tuve que establecer las condiciones experimentales que mantuvieran los fenotipos celulares deseados. Este esfuerzo no se refleja en el presente trabajo, pero constituye su fundamento.
Los tumores de cáncer colorrectal están compuestos por poblaciones celulares heterogéneas que incluyen un conjunto de células madre cancerosas, marcadas por la expresión de LGR5. La relación entre los estados de diferenciación de las células cancerosas y su potencial metastásico ha sido objeto de una amplia investigación, y algunos estudios apuntan a la plasticidad definida por el microambiente como mecanismo indispensable para la formación de metástasis. En este contexto altamente heterogéneo y plástico, las diferencias en los fenotipos mecánicos pueden favorecer o perjudicar el potencial metastático de las células cancerosas. Sin embargo, se desconoce si las distintas poblaciones celulares de los tumores de colon presentan diferentes propiedades mecánicas y cómo estas propiedades podrían contribuir a las metástasis.
En este estudio llevé a cabo una amplia caracterización biofísica de organoides derivados de pacientes de cáncer de colon diseñados para etiquetar con fluorescencia células que expresan LGR5. Descubrí que las células LGR5+ y LGR5- muestran fenotipos mecánicos distintos. En comparación con las células LGR5-, las células LGR5+ son más rígidas, se adhieren mejor a la matriz extracelular, se mueven más lentamente tanto como células individualmente que en grupo, muestran mas YAP nuclear y una mayor tasa de supervivencia en respuesta al confinamiento mecánico. Estas diferencias se explican en gran medida por la regulación a la baja de las proteínas de unión de la membrana a la corteza Ezrin/Radixina/Moesina en las células LGR5+. Mediante el análisis de los patrones de expresión scRNA-seq de una cohorte de pacientes, demuestro que esta regulación a la baja es una firma robusta de los tumores colorrectales. Por último, también demuestro que las células LGR5+ se adhieren mejor a la superficie endotelial y forman brechas transendoteliales con mayor eficacia que las células LGR5-. En conjunto, estos resultados muestran que las células LGR5- presentan un fenotipo mecánicamente dinámico que favorece la diseminación desde el tumor
primario, mientras que las células LGR5+ presentan un fenotipo mecánicamente estable y resistente que favorece la extravasación y el crecimiento metastásico. El acoplamiento observado entre los estados mecánicos y la heterogeneidad de las células cancerosas puede ser un mecanismo adaptativo indispensable para la progresión metastásica
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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