1,720,961 research outputs found
Exoscopic vs. microscopic transsphenoidal surgery for Cushing’s disease: a retrospective single-center study on 388 patients
No full textMicroscopic and endoscopic transsphenoidal surgeries represent the standard treatment for Cushing’s disease (CD). At our institution a new exoscopic approach was implemented. After proof of the general use for transsphenoidal pituitary surgery, the aim of this study was to compare the exoscopic 4K3D video microscope with the microscopic transsphenoidal surgery for patients with CD. We conducted a retrospective analysis on 388 patients with CD treated in our medical center via microscopic transsphenoidal surgery (MTS) between January 2008 and July 2019 or via exoscopic transsphenoidal surgery (ExTS) between May 2019 and May 2021. Parameters investigated included histology, pre- and postoperative MRI with tumor size, pre- and postoperative ACTH and cortisol levels, duration of surgery, perioperative and postoperative complications as well as clinical outcome. Patients who underwent ExTS in CD experienced a lower incidence of SIADH/diabetes insipidus (p = 0.0164), a higher rate of remission (p = 0.0422), and a shorter duration of surgery (p < 0.0001), compared to MTS. However, there was no significant difference regarding new postoperative pituitary insufficiency and intraoperative CSF space opening. We found that ExTS had multiple benefits compared to MTS for tumor resection in case of CD. These results are in line with our previous publication on the general applicability of an exoscope in pituitary surgery. To our knowledge, this is the first clinical study proving the superiority of ExTS in CD. These results are promising, nevertheless further studies comparing exoscopic with the endoscopic approach are necessary to finally evaluate the utility of the new technique
Der Ephrin-B2-EphB4-Signalweg als therapeutisches Ziel in der Entstehung spinaler Metastasen
No full textIntroduction
The development of spinal metastases is a common and complex problem in the management of cancer patients, with the spine being one of the main sites to where metastases will spread. If untreated, spinal metastases rapidly lead to progressive myelopathy with extensive effects on ambulatory status, quality of life and survival rates of affected patients. Although major developments in the field of surgical and oncological procedures have led to improved therapeutic options, the molecular steps of spinal metastasis formation still remain inadequately understood. EphB4 and Ephrin-B2 have repeatedly been identified as key regulators in metastatic cell dissemination, tumor cell – endothelial cell interaction and tumor growth. We investigated the effects of a therapeutic alteration of this molecular interaction on long- term metastasis formation.
Methods
Bioluminescent B16 melanoma cells were injected retrogradely into the carotid artery of Ephrin-B2-knockout (efnb2iΔEC) and control (efnb2lox/lox) mice in a pre- and post- metastatic setting (“pre-“ and “post-tumor”). Potential therapeutic effects were evaluated after applying soluble Ephrin-B2-Fc, as well as NVP-BHG 712, a small molecular inhibitor of the EphB4 receptor tyrosine kinase. Tumor growth and dissemination were surveyed utilizing in-vivo bioluminescent imaging procedures and compressive spinal loci were identified using magnetic resonance imaging. Immunohistochemical evaluation of tumor cell proliferation and vasculature were performed and the organ specific tumor load was examined using a luciferase detection assay.
Results
In pre-tumor treated efnb2lox/lox mice the application of Ephrin-B2-Fc (median: 20.5 days, n=7, p=0.0048) and NVP-BHG 712 (median: 21 days, n=14, p=0.0002) induced significantly earlier neurologic deficits when compared to the placebo-treated group (median: 24.5 days, n=11), by increasing the number and volume of spinal metastases. In post-tumor treated efnb2lox/lox mice there was no significant difference in survival
times or number of spinal metastases in the MRI. The earlier appearance of neurological deficits in efnb2iΔEC-knockout mice (median efnb2i∆EC placebo: 18 days, n=7, p=<0.0001) could be significantly delayed by pre-tumor treatment with Ephrin-B2- Fc. (median: 23 days, n=8).
Conclusion
The molecular interaction between EphB4 and Ephrin-B2 significantly affected the formation of spinal metastases. The physiological EphrinB2-EphB4 interaction in efnb2lox/lox control mice showed tumor suppressive effects by increasing tumor cell repulsion from the endothelium. The therapeutic disruption of these repulsive effects decreased neurological survival through an increased number and volume of metastases. Under the effects of the prometastatic endothelial Ephrin-B2 knockout (efnb2i∆EC), these physiologically inert repulsive functions could be partially reestablished through Ephrin-B2-Fc.Einführung
Die Entstehung spinaler Metastasen ist eine häufige und schwerwiegende Komplikation in der Behandlung von Krebspatienten. Die Wirbelsäule stellt hierbei eine der häufigsten Lokalisationen ossärer Metastasierung dar. Ohne adäquate Therapie führen spinale Metastasen binnen kürzester Zeit zu einer zunehmenden Myelopathie und Destruktion der neuralen Elemente, mit weitreichenden Auswirkungen auf das Überleben und die Lebensqualität der betroffenen Patienten. Trotz stetiger Entwicklungen in der onkologischen und neurochirurgischen Therapie dieses komplexen Krankheitsbildes bleiben die grundlegenden Entstehungsmechanismen weiterhin weitestgehend unverstanden. EphB4 und Ephrin-B2 wurden wiederholt als wichtige Regulatoren in der Metastasenentstehung, sowie in der Interaktion zwischen Tumor- und Endothelzellen identifiziert. Wir haben die Auswirkungen dieser molekularen Interaktion, sowie mögliche therapeutische Beeinflussungen der Entstehung spinaler Metastasen untersucht.
Methodik
BIolumineszierende B16-Melanomzellen wurden jeweils in einem prä- und postmetastatischen Ansatz retrograd in die A. carotis communis von Ephrin-B2- Knockout- (efnb2iΔEC) und Kontrollmäusen (efnb2lox/lox) injiziert. Potenzielle therapeutische Effekte des löslichen Antikörpers Ephrin-B2-Fc, sowie des spezifischen EphB4 Tyrosinkinaseinhibitors NVP-BHG 712 wurden evaluiert. Tumorwachstum und Verteilungsmuster wurden durch Biolumineszenz-Bildgebungsverfahren in vivo überwacht und Tumorwachstum und Myelonkompression mittels spinalem MRT dargestellt. Immunhistochemische Färbungen wurden hinsichtlich Proliferation und Angiogenese ausgewertet, sowie die Anzahl der metastatischen Tumorzellen pro Organ mittels eines Luziferase-Assays.
Ergebnisse
In prä-tumor vorbehandelten efnb2lox/lox Mäusen zeigten sowohl die mittels Ephrin-B2- Fc (Mittelwert: 20.5 Tage, n=7, p=0.0048) als auch die mit NVP-BHG 712 (Mittelwert: 21 Tage, n=14, p=0.0002) therapierte Gruppe signifikant frühere neurologische Defizite durch vermehrte spinale Metastasen als die Placebo-behandelten Tiere (Mittelwert: 24,5 Tage, n=11). In den post-tumor behandelten efnb2lox/lox Tieren zeigte sich kein Unterschied im Überleben oder der spinalen Tumorlast. Das signifikant frühere Auftreten neurologischer Defizite in Ephrin-B2-knockout (efnb2iΔEC ) Mäusen (Mittelwert efnb2i∆EC Placebo: 18 Tage, n=7, p=<0.0001) konnte durch die prämetastatische Gabe von Ephrin-B2-Fc deutlich verzögert werden (Mittelwert: 23 Tage, n=8).
Schlussfolgerung
Die molekulare Interaktion zwischen EphB4 und Ephrin-B2 beeinflusst die Entstehung spinaler Metastasen. Der physiologische Zustand inhibiert das Tumorwachstum durch vermehrte Abstoßung der zirkulierenden Tumorzellen. Die therapeutische Unterbrechung dieses protektiven Effektes führte zu einem signifikant früheren neurologischen Defizit durch vermehrtes Wachstum spinaler Metastasen. Unter dem prometastatischen endothelialen Ephrin-B2-knockout konnte durch prämetastatische Applikation des Ephrin-B2-Fc Antikörpers die physiologisch bestehende Abstoßungsreaktion partiell wiederhergestellt werden, sodass eine signifikante Verlängerung des neurologischen Überlebens erreicht wurde
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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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