Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop

Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field

Beyond the Global Brain Differences:Intraindividual Variability Differences in 1q21.1 Distal and 15q11.2 BP1-BP2 Deletion Carriers

BACKGROUND: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and globalbrain differences compared with noncarriers. However, interpreting regional differences is challenging if a globaldifference drives the regional brain differences. Intraindividual variability measures can be used to test for regionaldifferences beyond global differences in brain structure.METHODS: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n =30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matchednoncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual’sregional difference and global difference, were used to test for regional differences that diverge from the globaldifference.RESULTS: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differedmore than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thicknessin regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal andsomatosensory cortex differed more than the global difference in cortical thickness.CONCLUSIONS: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distaland 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanismsinvolved in altered neurodevelopment

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

Opinion and Special Article: The Need for Specialized Training in Womens Neurology.

Womens Neurology is an emerging subspecialty that focuses on neurologic disorders across a womans lifetime. This new domain recognizes that both health and disease are directly affected by hormonal and reproductive changes throughout the life span. This field includes neurologic diseases with a higher prevalence in women and diseases that require specialized management during pregnancy, postpartum period, lactation, and menopause. A survey was sent to US neurology residency program directors to understand the state of training in the area. Their responses highlighted an urgent need for additional education in this field for neurology residents. In this study, we discuss the educational gaps in this area, the clinical benefits of a womens neurology discipline, and the instructional gaps in this area and provide practical recommendations for training programs in womens neurology using 2 innovative fellowship programs

Toward the Integration of Technology-Based Interventions in the Care Pathway for People with Dementia: A Cross-National Study

Background: The integration of technology-based interventions into health and care provision in our aging society is still a challenge especially in the care pathway for people with dementia. Objective: The study aims to: (1) identify which socio-demographic characteristics are independently associated with the use of the embodied conversational agent among subjects with dementia, (2) uncover patient cluster profiles based on these characteristics, and (3) discuss technology-based interventions challenges. Methods: A virtual agent was used for four weeks by 55 persons with dementia living in their home environment. Results: Participants evaluated the agent as easy-to-use and quickly learnable. They felt confident while using the system and expressed the willingness to use it frequently. Moreover, 21/55 of the patients perceived the virtual agent as a friend and assistant who they could feel close to and who would remind them of important things. Conclusions: Technology-based interventions require a significant effort, such as personalized features and patient-centered care pathways, to be effective. Therefore, this study enriches the open discussion on how such virtual agents must be evidence-based related and designed by multidisciplinary teams, following patient-centered care as well as user-centered design approaches

The illusion of control drives bet size and reward anticipation in pathological and recreational gamblers

Disordered gambling is the first-ever disorder classified as a behavioural addiction, offering a unique model to study addiction mechanisms in the absence of neurotoxic effects from substances. Previous research suggests that maladaptive reward processing and altered perceptions of control may be key drivers in the development and persistence of gambling behaviour. However, the mechanisms that underlie this association of reward processing and perception of control with gambling are not well understood. In this study, we tested 45 pathological and 45 recreational gamblers using a naturalistic slot machine task, which manipulated reward magnitude and illusion of control in a 2x2 factorial design. We also used a computational reinforcement learning model to examine differences in reward and control processing between addicted and recreational gamblers. Our findings suggest that reward and control have distinct effects on gambling behaviour, with reward magnitude primarily influencing bet behaviour, while illusions of control additionally influence the anticipation of winning. This distortion of expected odds due to an illusion of control may drive continued gambling despite unfavourable outcomes and enhanced risk-taking. Moreover, the illusion of control differentially affected pathological and recreational gamblers and may thus provide a window into the nature of risk-taking across gamblers