Researchers’ opinions about ethically sound dissemination of BCI research to the public media

BCI research and (future) applications raise ethical questions. A websurvey among 144 BCI researchers identified disseminating BCI research to the public media as a central topic. Most researchers felt that BCI scientists must responsibly communicate with the media and that general ethical guidelines on BCI research and application are needed within the next 5 years. We recommend further debate on ethical aspects related to BCI and the development of guidelines

BNCI systems as a potential assistive technology: ethical issues and participatory research in the BrainAble project

This paper highlights aspects related to current research and thinking about ethical issues in relation to Brain Computer Interface (BCI) and Brain-Neuronal Computer Interfaces (BNCI) research through the experience of one particular project, BrainAble, which is exploring and developing the potential of these technologies to enable people with complex disabilities to control computers. It describes how ethical practice has been developed both within the multidisciplinary research team and with participants. Results: The paper presents findings in which participants shared their views of the project prototypes, of the potential of BCI/BNCI systems as an assistive technology, and of their other possible applications. This draws attention to the importance of ethical practice in projects where high expectations of technologies, and representations of “ideal types” of disabled users may reinforce stereotypes or drown out participant “voices”. Conclusions: Ethical frameworks for research and development in emergent areas such as BCI/BNCI systems should be based on broad notions of a “duty of care” while being sufficiently flexible that researchers can adapt project procedures according to participant needs. They need to be frequently revisited, not only in the light of experience, but also to ensure they reflect new research findings and ever more complex and powerful technologies

JAK‐STAT signaling shapes the NF‐κB response in CLL towards venetoclax sensitivity or resistance via Bcl‐XL

Preventing or overcoming resistance to the Bcl-2 inhibitor venetoclax is an emerging unmet clinical need in patients with chronic lymphocytic leukemia (CLL). The upregulation of anti-apoptotic Bcl-2 members through signaling pathways within the tumor microenvironment appears as a major factor leading to resistance to venetoclax. Previously, we reported that T cells can drive resistance through CD40 and non-canonical NF-κB activation and subsequent Bcl-XL induction. Moreover, the T cell-derived cytokines IL-21 and IL-4 differentially affect Bcl-XL expression and sensitivity to venetoclax via unknown mechanisms. Here, we mechanistically dissected how Bcl-XL is regulated in the context of JAK-STAT signaling in primary CLL. First, we demonstrated a clear antagonistic role of IL-21/STAT3 signaling in the NF-κB-mediated expression of Bcl-XL, whereas IL-4/STAT6 further promoted the expression of Bcl-XL. In comparison, Bfl-1, another NF-κB target, was not differentially affected by either cytokine. Second, STAT3 and STAT6 affected Bcl-XL transcription by binding to its promoter without disrupting the DNA-binding activity of NF-κB. Third, in situ proximity ligation assays (isPLAs) indicated crosstalk between JAK-STAT signaling and NF-κB, in which STAT3 inhibited canonical NF-κB by accelerating nuclear export, and STAT6 promoted non-canonical NF-κB. Finally, NF-κB inducing kinase (NIK) inhibition interrupted the NF-κB/STAT crosstalk and re-sensitized CLL cells to venetoclax. In conclusion, we uncovered distinct crosstalk mechanisms that shape the NF-κB response in CLL towards venetoclax sensitivity or resistance via Bcl-XL, thereby revealing new potential therapeutic targets

Stability in Bullying and Victimization and its Association with Social Adjustment in Childhood and Adolescence

This study examined the concurrent and longitudinal associations between stability in bullying and victimization, and social adjustment in childhood and adolescence. Participants were 189 girls and 328 boys who were studied in primary school and in secondary school. The mean age of the participants was 11.1 years in primary school and 14.1 years in secondary school. The measures consisted of peer reported social and personal characteristics. Children who bullied in childhood and adolescence were less liked and more disliked in childhood, and more aggressive and disruptive both in childhood and adolescence, than children who bullied only in childhood or adolescence. Children who bullied or who were victimized only in childhood did not differ largely in adolescence from the children that were never bullies or victims. Children who were victimized in adolescence closely resembled those who were victimized in childhood and adolescence in terms of being liked or disliked, being nominated as a friend, and shyness. The study stresses the need to distinguish between stable and transient bullies and victims

BRIEF COMMUNICATION “The Neuroscience of Responsibility”—Workshop Report

“The Neuroscience of Responsibility ” that was hel

Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?

Chronic lymphocytic leukemia (CLL) cells cycle between lymphoid tissue sites where they actively proliferate, and the peripheral blood (PB) where they become quiescent. Strong evidence exists for a crucial role of B cell receptor (BCR) triggering, either by (self-)antigen or by receptor auto-engagement in the lymph node (LN) to drive CLL proliferation and provide adhesion. The clinical success of Bruton’s tyrosine kinase (BTK) inhibitors is widely accepted to be based on blockade of the BCR signal. Additional signals in the LN that support CLL survival derive from surrounding cells, such as CD40L-presenting T helper cells, myeloid and stromal cells. It is not quite clear if and to what extent these non-BCR signals contribute to proliferation in situ. In vitro BCR triggering, in contrast, leads to low-level activation and does not result in cell division. Various combinations of non-BCR signals delivered via co-stimulatory receptors, Toll-like receptors (TLRs), and/or soluble cytokines are applied, leading to comparatively modest and short-lived CLL proliferation in vitro. Thus, an unresolved gap exists between the condition in the patient as we now understand it and applicable knowledge that can be harnessed in the laboratory for future therapeutic applications. Even in this era of targeted drugs, CLL remains largely incurable with frequent relapses and emergence of resistance. Therefore, we require better insight into all aspects of CLL growth and potential rewiring of signaling pathways. We aim here to provide an overview of in vivo versus in vitro signals involved in CLL proliferation, point out areas of missing knowledge and suggest future directions for research