Response to trametinib, hydroxychloroquine, and bevacizumab in a young woman with NRAS-mutated metastatic intrahepatic cholangiocarcinoma: a case report.

Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with NRAS-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in RAS-mutated tumors.

First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors.

Aspergillus fungi constitute a pivotal element within ecosystems, serving as both contributors of biologically active compounds and harboring the potential to cause various diseases across living organisms. The organism's proteolytic enzyme complex, termed the degradome, acts as an intermediary in its dynamic interaction with the surrounding environment. Using techniques such as genome and transcriptome sequencing, alongside protein prediction methodologies, we identified putative extracellular peptidases within Aspergillus ochraceus VKM-F4104D. Following manual annotation procedures, a total of 11 aspartic, 2 cysteine, 2 glutamic, 21 serine, 1 threonine, and 21 metallopeptidases were attributed to the extracellular degradome of A. ochraceus VKM-F4104D. Among them are enzymes with promising applications in biotechnology, potential targets and agents for antifungal therapy, and microbial antagonism factors. Thus, additional functionalities of the extracellular degradome, extending beyond mere protein substrate digestion for nutritional purposes, were demonstrated.

Comparing experience- and description-based economic preferences across 11 countries.

Recent evidence indicates that reward value encoding in humans is highly context dependent, leading to suboptimal decisions in some cases, but whether this computational constraint on valuation is a shared feature of human cognition remains unknown. Here we studied the behaviour of n = 561 individuals from 11 countries of markedly different socioeconomic and cultural makeup. Our findings show that context sensitivity was present in all 11 countries. Suboptimal decisions generated by context manipulation were not explained by risk aversion, as estimated through a separate description-based choice task (that is, lotteries) consisting of matched decision offers. Conversely, risk aversion significantly differed across countries. Overall, our findings suggest that context-dependent reward value encoding is a feature of human cognition that remains consistently present across different countries, as opposed to description-based decision-making, which is more permeable to cultural factors.

The relationship between charitable giving and emotional facial expressions: Results from affective computing.

This study investigated the relationship between emotional states (valence, arousal, and six basic emotions) and donation size in pet charities, and it compared the effectiveness of affective computing and emotion self-report methods in assessing attractiveness. Using FaceReader software and self-report, we measured the emotional states of participants (N = 45) during the donation task. The results showed that sadness, happiness, and anger were significantly related to donation size. Sadness and anger increased donations, whereas happiness decreased them. Arousal was not significantly correlated with the willingness to donate. These results are supported by both methods, whereas the self-reported data regarding the association of surprise, fear, and disgust with donation size are inconclusive. Thus, unpleasant emotions increase donation size, and combining affective computing with self-reported data improves the prediction of the effectiveness of a charity appeal. This study contributes to the understanding of the relationship between emotions and charitable behavior toward pet charities and evaluates the effectiveness of marketing mix elements using affective computing. The limitations include the laboratory setting for this experiment and the lack of measurement of prolonged and repeated exposure to unpleasant charity appeals.

Evaluating the Influence of Musical and Monetary Rewards on Decision Making through Computational Modelling.

A central question in behavioural neuroscience is how different rewards modulate learning. While the role of monetary rewards is well-studied in decision-making research, the influence of abstract rewards like music remains poorly understood. This study investigated the dissociable effects of these two reward types on decision making. Forty participants completed two decision-making tasks, each characterised by probabilistic associations between stimuli and rewards, with probabilities changing over time to reflect environmental volatility. In each task, choices were reinforced either by monetary outcomes (win/lose) or by the endings of musical melodies (consonant/dissonant). We applied the Hierarchical Gaussian Filter, a validated hierarchical Bayesian framework, to model learning under these two conditions. Bayesian statistics provided evidence for similar learning patterns across both reward types, suggesting individuals' similar adaptability. However, within the musical task, individual preferences for consonance over dissonance explained some aspects of learning. Specifically, correlation analyses indicated that participants more tolerant of dissonance behaved more stochastically in their belief-to-response mappings and were less likely to choose the response associated with the current prediction for a consonant ending, driven by higher volatility estimates. By contrast, participants averse to dissonance showed increased tonic volatility, leading to larger updates in reward tendency beliefs.

Regionally specific cortical lateralization of abstract and concrete verb processing: Magnetic mismatch negativity study.

The neural underpinnings of processing concrete and abstract semantics remain poorly understood. Previous fMRI studies have shown that multimodal and amodal neural networks respond differentially to different semantic types; importantly, abstract semantics activates more left-lateralized networks, as opposed to more bilateral activity for concrete words. Due to the lack of temporal resolution, these fMRI results do not allow to easily separate language- and task-specific brain responses and to disentangle early processing stages from later post-comprehension phenomena. To tackle this, we used magnetoencephalography (MEG), a time-resolved neuroimaging technique, in combination with a task-free oddball mismatch negativity (MMN) paradigm, an established approach to tracking early automatic activation of word-specific memory traces in the brain. We recorded the magnetic MMN responses in 30 healthy adults to auditorily presented abstract and concrete action verbs to assess lateralization of word-specific lexico-semantic processing in a set of neocortical areas. We found that MMN responses to these stimuli showed different lateralization patterns of activity in the upper limb motor area (BA4) and parts of Broca's area (BA45/BA47) within ∼100-350 ms after the word disambiguation point. Importantly, the greater leftward response lateralization for abstract semantics was due to the lesser involvement of the right-hemispheric homologues, not increased left-hemispheric activity. These findings suggest differential region-specific involvement of bilateral sensorimotor systems already in the early automatic stages of processing abstract and concrete action semantics.

Transspinal Direct Current Electrical Stimulation Selectively Affects the Excitability of the Corticospinal System, Depending on the Intensity but Not Motor Skills.

Transspinal direct current stimulation (tsDCS) is a non-invasive technique used to modulate spinal cord activity. However, the effects and mechanisms of this stimulation are currently not comprehensively known. This study aimed to estimate the effect of different intensities of tsDCS applied at the level of cervical enlargement of the spinal cord (C7-Th1 segments) on the excitability of the corticospinal system (CSS) and the correction of motor skills in healthy subjects. The effect of tsDCS was estimated by the motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) in the primary motor cortex (M1). The study involved 54 healthy adults aged 22 ± 4 years. The application of 11 min anodal tsDCS at the level of the cervical spine C7-Th1 with a current intensity of 2.5 mA did not change the MEP amplitude of the upper limb muscles, in contrast to the data that we previously obtained with a current intensity of 1.5 mA. We also found no difference in the effect of 2.5 mA stimulation on motor skill correction in healthy subjects in the nine-hole peg test (9-HPT) and the serial reaction time task (SRT) as with 1.5 mA stimulation. Our data show that an increase in the intensity of stimulation does not lead to an increase in the effects but rather reduces the effects of stimulation. These results provide information about the optimally appropriate stimulation current intensities to induce CSS excitability and the ability of tsDCS to influence motor skills in healthy adults.

Correction: The Prediction of Market-level Food Choices by the Neural Valuation Signal.

[This corrects the article DOI: 10.1371/journal.pone.0286648.].

Neuromodulation of choice-induced preference changes: the tDCS study of cognitive dissonance.

Introduction: Difficult choices between two equally attractive options result in a cognitive discrepancy between dissonant cognitions such as preferences and actions often followed by a sense of psychological discomfort known as cognitive dissonance. It can lead to changes in the desirability of options: the chosen option becomes more desirable, whereas the rejected option is devalued. Despite the ample experimental evidence to show this effect, the neural mechanisms and timing of such choice-induced preference changes are not fully understood. Methods: In this study, we used transcranial direct current stimulation (tDCS) to modulate the activity of the posterior medial frontal cortex (pMFC), which has been associated with conflict monitoring and choice-induced preference changes in neuroimaging studies. Prior to a revised version of Brehm's free-choice paradigm, participants in two experiments underwent cathodal (inhibitory) or anodal (excitatory) tDCS of the pMFC compared to sham (placebo) stimulation prior to the choice phase. Results: Our results showed that cathodal tDCS significantly decreased the choice-induced preference change relative to a sham, but only in direct comparisons of rejected options. No significant effect of anodal tDCS in comparison with sham was observed. Discussion: This study replicates the general behavioral effect of cognitive dissonance and provide partial support for the theory of the pMFC contribution to choice-related cognitive dissonance and subsequent preference changes, with possible limitations of an under-sampling for the obtained effect size and an asymmetry in the inhibitory-excitatory effects of non-invasive tDCS.