Trait anxiety predicts amygdalar responses during direct processing of threat-related pictures

Previous studies on the associations between trait anxiety and amygdalar responses to threat stimuli have resulted in mixed findings, possibly due to sample characteristics, specific tasks, and analytical methods. The present functional magnetic resonance imaging (fMRI) study aimed to investigate linear or non-linear associations between trait anxiety and amygdalar responses in a sample of participants with low, medium, and high trait anxiety scores. During scanning, participants were presented with threat-related or neutral pictures and had either to solve an emotional task or an emotional-unrelated distraction task. Results showed that only during the explicit task trait anxiety was associated with right amygdalar responses to threat-related pictures as compared to neutral pictures. The best model was a cubic model with increased amygdala responses for very low and medium trait anxiety values but decreased amygdala activation for very high trait anxiety values. The findings imply a non-linear relation between trait anxiety and amygdala activation depending on task conditions

Acquisition and generalization of emotional and neural responses to faces associated with negative and positive feedback behaviours

Faces can acquire emotional meaning by learning to associate individuals with specific behaviors. Here, we investigated emotional evaluation and brain activations toward faces of persons who had given negative or positive evaluations to others. Furthermore, we investigated how emotional evaluations and brain activation generalize to perceptually similar faces. Valence ratings indicated learning and generalization effects for both positive and negative faces. Brain activation, measured with functional magnetic resonance imaging (fMRI), showed significantly increased activation in the fusiform gyrus (FG) to negatively associated faces but not positively associated ones. Remarkably, brain activation in FG to faces to which emotional meaning (negative and positive) was successfully generalized was decreased compared to neutral faces. This suggests that the emotional relevance of faces is not simply associated with increased brain activation in visual areas. While, at least for negative conditions, faces paired with negative feedback behavior are related to potentiated brain responses, the opposite is seen for perceptually very similar faces despite generalized emotional responses

An Integrated Magneto-Electrochemical Device for the Rapid Profiling of Tumour Extracellular Vesicles from Blood Plasma

Assays for cancer diagnosis via the analysis of biomarkers on circulating extracellular vesicles (EVs) typically have lengthy sample workups, limited throughput or insufficient sensitivity, or do not use clinically validated biomarkers. Here we report the development and performance of a 96-well assay that integrates the enrichment of EVs by antibody-coated magnetic beads and the electrochemical detection, in less than one hour of total assay time, of EV-bound proteins after enzymatic amplification. By using the assay with a combination of antibodies for clinically relevant tumour biomarkers (EGFR, EpCAM, CD24 and GPA33) of colorectal cancer (CRC), we classified plasma samples from 102 patients with CRC and 40 non-CRC controls with accuracies of more than 96%, prospectively assessed a cohort of 90 patients, for whom the burden of tumour EVs was predictive of five-year disease-free survival, and longitudinally analysed plasma from 11 patients, for whom the EV burden declined after surgery and increased on relapse. Rapid assays for the detection of combinations of tumour biomarkers in plasma EVs may aid cancer detection and patient monitoring

Effects of Badminton Expertise on Representational Momentum: A Combination of Cross-Sectional and Longitudinal Studies

Representational momentum (RM) has been found to be magnified in experts (e.g., sport players) with respect to both real and implied motion in expert-familiar domains. However, it remains unclear whether similar effects can be achieved in expert-unfamiliar domains, especially within the context of implied motion. To answer this question, we conducted two independent experiments using an implied motion paradigm and examined the expert effects of badminton training on RM in both adult and child players. In Experiment 1, we used a cross-sectional design and compared RM between adult professional badminton players and matched controls. The results revealed significantly enhanced RM for adult players, supporting the expert effect in expert-unfamiliar domains for implied motion. However, cross-sectional studies could not ascertain whether the observed expert effect was due to innate factors or expertise acquirement. Therefore, in Experiment 2, we used a longitudinal design and compared RM between two groups of child participants, naming child players who had enrolled professional badminton training program at a sports school and age-matched peer non-players who attended an ordinary primary school without sports training. Before training, there were no differences in RM among child players, their non-player peers, and adult non-players. However, after 4 years of badminton training, child players demonstrated significantly enhanced RM compared to themselves prior to training. The increased RM observed in both adult and child players suggests that badminton expertise modulates implied motion RM

QUBIQ: Uncertainty Quantification for Biomedical Image Segmentation Challenge

Uncertainty in medical image segmentation tasks, especially inter-rater variability, arising from differences in interpretations and annotations by various experts, presents a significant challenge in achieving consistent and reliable image segmentation. This variability not only reflects the inherent complexity and subjective nature of medical image interpretation but also directly impacts the development and evaluation of automated segmentation algorithms. Accurately modeling and quantifying this variability is essential for enhancing the robustness and clinical applicability of these algorithms. We report the set-up and summarize the benchmark results of the Quantification of Uncertainties in Biomedical Image Quantification Challenge (QUBIQ), which was organized in conjunction with International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020 and 2021. The challenge focuses on the uncertainty quantification of medical image segmentation which considers the omnipresence of inter-rater variability in imaging datasets. The large collection of images with multi-rater annotations features various modalities such as MRI and CT; various organs such as the brain, prostate, kidney, and pancreas; and different image dimensions 2D-vs-3D. A total of 24 teams submitted different solutions to the problem, combining various baseline models, Bayesian neural networks, and ensemble model techniques. The obtained results indicate the importance of the ensemble models, as well as the need for further research to develop efficient 3D methods for uncertainty quantification methods in 3D segmentation tasks.Comment: initial technical repor

Vascular permeability, vascular hyperpermeability and angiogenesis

The vascular system has the critical function of supplying tissues with nutrients and clearing waste products. To accomplish these goals, the vasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. Physiologists and many vascular biologists differ as to the definition of vascular permeability and the proper methodology for its measurement. We review these conflicting views, finding that both provide useful but complementary information. Vascular permeability by any measure is dramatically increased in acute and chronic inflammation, cancer, and wound healing. This hyperpermeability is mediated by acute or chronic exposure to vascular permeabilizing agents, particularly vascular permeability factor/vascular endothelial growth factor (VPF/VEGF, VEGF-A). We demonstrate that three distinctly different types of vascular permeability can be distinguished, based on the different types of microvessels involved, the composition of the extravasate, and the anatomic pathways by which molecules of different size cross-vascular endothelium. These are the basal vascular permeability (BVP) of normal tissues, the acute vascular hyperpermeability (AVH) that occurs in response to a single, brief exposure to VEGF-A or other vascular permeabilizing agents, and the chronic vascular hyperpermeability (CVH) that characterizes pathological angiogenesis. Finally, we list the numerous (at least 25) gene products that different authors have found to affect vascular permeability in variously engineered mice and classify them with respect to their participation, as far as possible, in BVP, AVH and CVH. Further work will be required to elucidate the signaling pathways by which each of these molecules, and others likely to be discovered, mediate the different types of vascular permeability

PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer

Abstract The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.