Modeling AI Trust for 2050

The study explores the future of AI-driven media and info-communication as envisioned by experts from all world regions, defining relevant terminology and expectations for 2050. Participants engaged in a 4-week series of surveys, questioning their definitions and projections about AI for the field of media and communication. Their expectations predict universal access to democratically available, automated, personalized and unbiased information determined by trusted narratives, recolonization of information technology and the demystification of the media process. These experts, as technology ambassadors, advocate AI-to-AI solutions to mitigate technology-driven misuse and misinformation. The optimistic scenarios shift responsibility to future generations, relying on AI-driven solutions and finding inspiration in nature. Their present-based forecasts could be construed as being indicative of professional near-sightedness and cognitive dissonance. Visualizing our findings into a Glasses Model of AI Trust, the study contributes to key debates regarding AI policy, developmental trajectories, and academic research in media and info-communication fields

Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

Importance: The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. Objective: To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. Design, Setting, and Participants: This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. Main Measures and Outcomes: Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. Results: A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had not. Of the individuals at CHR reinterviewed with the GAF, 39 (30.0%) showed good overall functioning (GAF score, ≥65), whereas 91 (70.0%) had poor overall functioning (GAF score, <65). Within the CHR sample, better anger recognition at baseline was associated with worse functional outcome (odds ratio [OR], 0.88; 95% CI, 0.78-0.99; P =.03). In individuals at CHR with a good functional outcome, positive associations were found between anger recognition and hippocampal volume (ze = 3.91; familywise error [FWE] P =.02) and between fear recognition and medial prefrontal cortex volume (z = 3.60; FWE P =.02), compared with participants with a poor outcome. The onset of psychosis was not associated with baseline emotion recognition performance (neutral OR, 0.93; 95% CI, 0.79-1.09; P =.37; happy OR, 1.03; 95% CI, 0.84-1.25; P =.81; fear OR, 0.98; 95% CI, 0.85-1.13; P =.77; anger OR, 1.00; 95% CI, 0.89-1.12; P =.96). No difference was observed in the association between performance and regional gray matter volumes in individuals at CHR who developed or did not develop psychosis (FWE P <.05). Conclusions and Relevance: In this study, poor functional outcome in individuals at CHR was found to be associated with baseline abnormalities in recognizing negative emotion. This finding has potential implications for the stratification of individuals at CHR and suggests that interventions that target socioemotional processing may improve functional outcomes.

“Others-in-Law”: Legalism in the Economy of Religious Differences

Religious legalism encompasses a wide range of attitudes that assign religious meaning to legal content or to legal compliance. The phenomenology of religious legalism is assuming a significant role in various contemporary debates about legal pluralism, accommodation of religious minorities, religious freedom, and so forth. This article revises this conception and the commonplace equation of Judaism and legalism. It suggests that we ought to regard both as part of the economy of religious differences by which religious identities are expressed and defined as alternatives. The common ascription of religious legalism to Judaism (and Islam) is criticized here through a historical analysis of the law-religion-identity matrix in three cultural settings: late ancient Judeo-Hellenic, medieval Judeo–Arabic, and post-Reformation Europe

BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (Pten BRF1 ) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In Pten BRF1 tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis

Cancer-associated fibroblasts produce matrix-bound vesicles that influence endothelial cell function

Intercellular communication between different cell types in solid tumors contributes to tumor growth and metastatic dissemination. The secretome of cancer-associated fibroblasts (CAFs) plays major roles in these processes. Using human mammary CAFs, we showed that CAFs with a myofibroblast phenotype released extracellular vesicles that transferred proteins to endothelial cells (ECs) that affected their interaction with immune cells. Mass spectrometry–based proteomics identified proteins transferred from CAFs to ECs, which included plasma membrane receptors. Using THY1 as an example of a transferred plasma membrane–bound protein, we showed that CAF-derived proteins increased the adhesion of a monocyte cell line to ECs. CAFs produced high amounts of matrix-bound EVs, which were the primary vehicles of protein transfer. Hence, our work paves the way for future studies that investigate how CAF-derived matrix-bound EVs influence tumor pathology by regulating the function of neighboring cancer, stromal, and immune cells

Transcriptional Landscape of the Prenatal Human Brain

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development