Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Framing an NFL legend: a comparative analysis framing and structural pluralism in regional vs. national newspaper coverage of Brett Favre's retirement(s)

Department Head: Greg Luft.2010 Spring.Includes bibliographical references (pages 135-140).When legendary quarterback Brett Favre retired from the Green Bay Packers, not even he knew what the coming year had in store. Favre's subsequent un-retirement, additional season with the New York Jets, and re-retirement attracted immense media attention unparalleled by another athlete. Framing theory was used to compare regional (Green Bay Press Gazette) and national (New York Times and USA Today) newspaper coverage during the tumultuous yearlong period. Qualitative content analysis revealed differences and similarities between the publications' framing of the storyline. Structural pluralism theory proposed further differences between the two classes of publication. This phenomenon suggests smaller, less varied communities' media report less conflict than news reports covering larger, more complex areas. Additionally, the study provided evidence of a ritualistic, religious treatment of sports in modern society and its print media

Improvement of variant reclassification in genetic neurodevelopmental conditions

Purpose: Limited knowledge about disease mechanisms, few published cases, and the lack of functional assessment of variants for neurodevelopmental genetic disorders challenge diagnostic classification for variants and increase the frequency of variants of uncertain significance (VUS). Because inheritance patterns aid in variant interpretation for neurodevelopmental conditions, genetic testing including only the proband leads to larger numbers of VUS than testing strategies that include the parents. Methods: We reinterpreted genetic variants submitted to the Simons Searchlight research registry using American College of Medical Genetics and Genomics variant interpretation guidelines, familial cascade testing, and literature curation with annual VUS reevaluation. Results: Simons Searchlight has independently evaluated 2834 genetic laboratory reports; 20.4% of variants (1.7% copy-number variants and 18.7% monogenic variants) were reclassified with 230 upgrades and 173 downgrades in pathogenicity. Of 351 monogenic VUS on the original clinical test report, 25.4% were reclassified as likely pathogenic or pathogenic. VUS in SCN2A, SLC6A1, or STXBP1 were more likely to have VUS reclassified compared with variants in other genes. Conclusion: Regular reevaluation of neurodevelopmental genetic variants can be helpful because relevant variant reclassifications occur frequently and may affect clinical care. Simons Searchlight contributes to the international neurodevelopmental community by systematically reviewing uncertain variants annually and providing reclassified variants to participants, researchers, and ClinVar