Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol\u27s anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol\u27s effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs

PROTEUS Study: A Prospective Randomised Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS/DESIGN PROTEUS is a randomised, multicentre, two-armed, non-inferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomised 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE

Representations of self and other in American Jewish history and social studies schoolbooks: An exploration of the changing shape of American Jewish identity

This dissertation explores the power of Jewish history and social studies textbooks as agents of socialization and identity formation in the United States. It examines the shaping of American Jewish identity, communal values, and orderings of experience through an analysis of the images in the texts. Central to the enterprise of identity formation is the erection of boundaries. By exploring the evolving nature of the binary construction of Self and Other in Jewish schoolbooks this dissertation provides a gauge of how American Jews have continually renegotiated their bifurcated identities.This study makes the following conclusions: (1) Unabashedly negative descriptions of Christians were more characteristic of the late nineteenth and early twentieth centuries than they were of the interwar years and beyond. (2) Textbook authors of German-Jewish extraction engaged in "othering" Eastern European Jews before 1924 due to the anti-immigration climate and Classical Reform Judaism's teleology. (3) During the interwar years, the definition of Self undergoes a marked change as American Jews increasingly conceive of themselves as a distinct ethnic group. Guided by cultural pluralist educators like Samson Benderly and Emanuel Gamoran, textbook authors provide readers with idealized and integrated archetypes meant to facilitate both acculturation and Jewish survival. (4) The increasing coloration of the Other in American tones and accents demonstrates the rapidity of American Jewish cultural integration. (5) As American Jews increasingly engaged in projection in their construction of both the "New Jew" and his Arab antagonist, they more and more used the canvas of Palestine to work out their own efforts to negotiate their way in American society.The final chapter examines the phenomenon of American Jewish syncretism and coalescence by documenting the erosion of traditional boundaries in the post-war period. Since 1945, liberal Jewish movements have struggled to define Jewish distinctiveness without resorting to crude stereotyping, which cuts against the grain of the dominant multicultural epistemological model.Thesis (Ph.D.)--Brandeis University, 2002.School code: 0021