Advances in the surgical and systemic therapeutic landscape of hepatocellular carcinoma have increased the complexity of patient management. A dynamic adaptation of the available staging-based ...algorithms is required to allow flexible therapeutic allocation. In particular, real-world hepatocellular carcinoma management increasingly relies on factors independent of oncological staging, including patients’ frailty, comorbid burden, critical tumour location, multiple liver functional parameters, and specific technical contraindications impacting the delivery of treatment and resource availability. In this Policy Review we critically appraise how treatment allocation strictly based on pretreatment staging features has shifted towards a more personalised treatment approach, in which expert tumour boards assume a central role. We propose an evidence-based framework for hepatocellular carcinoma treatment based on the novel concept of multiparametric therapeutic hierarchy, in which different therapeutic options are ordered according to their survival benefit (ie, from surgery to systemic therapy). Moreover, we introduce the concept of converse therapeutic hierarchy, in which therapies are ordered according to their conversion abilities or adjuvant abilities (ie, from systemic therapy to surgery).
Elevated anxiety levels degrade task performance, likely because of cognitive function reduction in the frontoparietal brain network. This study aimed to test whether anxiety could impact the frontal ...cortex anticipatory brain functions and to investigate the possible beneficial effect of response‐related feedback on task performance. The electroencephalographic activity was recorded while participants performed two Go/No‐go tasks: one with response‐related feedback on errors (feedback task) and one task without feedback (standard task). We first tested whether anxiety levels could be associated with pre‐stimulus ERP components such as the prefrontal negativity (pN), linked with top‐down attentional control, and the Bereitschaftspotential (BP), related to motor preparation. Then, we assessed whether feedback could affect anxious people's brain preparation, reducing the state of uncertainty and improving performance. Results showed that the pN was almost absent and the BP was lower during a standard task in the high anxiety than in the low anxiety group. In the feedback task, these components increased in the high anxious, becoming comparable to the low anxious. Behavioral results showed that false alarms in the high anxiety group were larger than in the low anxiety group during the standard task but became comparable in the feedback task. Similarly, response time in the high anxiety group was slower in the standard task than in the feedback task, and high anxious people were faster in the feedback task than in the standard one. This study contributes to clarifying neural correlates of anxiety, showing brain activity reductions related to action preparation in frontal areas. In addition, response‐related feedback tasks could be used to normalize task performance in high anxious people.
High levels of anxiety have been associated with degraded cognitive performance and recently with reduced task preparatory activity in the frontal cortex. Here, we tested the introduction of response‐related feedback in a sensory motor task, and we found in anxious people an immediate regularization of preparatory brain activity in the frontal cortex. Consequently, improvement in task performance was also found. Treatments based on response‐related feedback could represent a non‐pharmaceutical approach to anxiety disorders.
MicroRNAs are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular messenger RNAs. They are frequently ...dysregulated in cancer and have shown great potential as tissue-based markers for cancer classification and prognostication. microRNAs are also present in extracellular human body fluids such as serum, plasma, saliva, and urine. Most of circulating microRNAs are present in human plasma and serum cofractionate with the Argonaute2 (Ago2) protein. However, circulating microRNAs have been also found in membrane-bound vesicles such as exosomes. Since microRNAs circulate in the bloodstream in a highly stable, extracellular form, they may be used as blood-based biomarkers for cancer and other diseases. A knowledge base of extracellular circulating miRNAs is a fundamental tool for biomedical research. In this work, we present miRandola, a comprehensive manually curated classification of extracellular circulating miRNAs. miRandola is connected to miRò, the miRNA knowledge base, allowing users to infer the potential biological functions of circulating miRNAs and their connections with phenotypes. The miRandola database contains 2132 entries, with 581 unique mature miRNAs and 21 types of samples. miRNAs are classified into four categories, based on their extracellular form: miRNA-Ago2 (173 entries), miRNA-exosome (856 entries), miRNA-HDL (20 entries) and miRNA-circulating (1083 entries). miRandola is available online at: http://atlas.dmi.unict.it/mirandola/index.html.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Sport expertise affects cognitive brain processes and behavioral performance in speeded tasks outside of the sport context. • Neural proficiency may represent a brain mechanism ...responsible for skilled performance. • Sport-specific practice can modulate brain functions and performances in a decision-making task. • Competitive sport training enhances not only sport-specific but also sport-general cognitive skills. • Public health should encourage fencing practice because it improves strongly both physical and cognitive skills.
MT+ and V6 are key motion areas of the dorsal visual stream in both macaque and human brains. In the present study, we combined electrophysiological and neuroimaging methods (including retinotopic ...brain mapping) to find the electrophysiological correlates of V6 and to define its temporal relationship with the activity observed in MT+. We also determined the spatio-temporal profile of the motion coherency effect on visual evoked potentials (VEPs), and localized its neural generators. We found that area V6 participates in the very early phase of the coherent motion processing and that its electroencephalographic activity is almost simultaneous with that of MT+. We also found a late second activity in V6 that we interpret as a re-entrant feedback from extrastriate visual areas (e.g. area V3A). Three main cortical sources were differently modulated by the motion coherence: while V6 and MT+ showed a preference for the coherent motion, area V3A preferred the random condition. The response timing of these cortical sources indicates that motion signals flow in parallel from the occipital pole to the medial and lateral motion areas V6 and MT+, suggesting the view of a differential functional role.
► We used a combination of VEPs, fMRI and wide-field retinotopic mapping. ► Like MT+ area V6 participates in the early phase of the coherent motion processing. ► We found a second activity in V6 interpreted as a re-entrant feedback from V3A. ► V6 and MT+ preferred the coherent motion and V3A preferred the random condition. ► Motion signals flow in parallel to V6 and MT suggesting different functional roles.
A large literature indicated hypnosis as a useful tool to reduce pain perception, especially in high susceptible individuals. However, due to different methodological aspects, it was still not clear ...whether hypnosis modulates the early sensory processing of the stimuli or if it affects only the later stages of affective processing. In the present study, we measured the EEG activity of subjects with a medium level of hypnotizability while receiving electrical non-painful stimuli on the median nerve in the conditions of awake and hypnosis with suggestions of hypoesthesia. Subjective reports indicated that hypnosis reduced both the sensory and the affective perception of the stimuli. ERP data revealed that hypnosis reduced the activity of both the early (N20) and the late (P100, P150, P250) SEP components. Neuroelectric source imaging further confirmed the top-down hypnotic modulation of a network of brain areas including the SI (N20), SII (P100), right anterior insula (P150) and cingulate cortex (P150/P250). The present study provides neurophysiological evidence to the hypnotic regulation of somatosensory inputs outside of pain, that is since the earliest stage of thalamocortical processing. Also, because present subjects were selected regardless of the level of hypnotizability, inferences from the present study are more generalizable than investigations restricted to high-hypnotizable individuals.
•Hypnotic hypoesthesia reduces subjective perception of somatosensory stimuli.•Hypnotic hypoesthesia reduces the N20 ERP in the medium hypnotizable individuals.•Hypnotic hypoesthesia reduces the somatosensory P100, P150 and P250 ERPs.•Somatosensory cortex, anterior insula and cingulate cortex are involved in hypnosis.•Effects of hypnotic hypoesthesia are generalizable to medium susceptible subjects.
Event-Related Potentials (ERPs) occurring independently from any stimulus are purely endogenous (emitted potentials) and their neural generators can be unequivocally linked with cognitive processes. ...In the present study, the subjects performed two similar visual counting tasks: a standard two-stimulus oddball, and an omitted-target oddball task, characterized by the physical absence of the target stimulus. Our investigation aimed at localizing the neural sources of the scalp-recorded endogenous/emitted ERPs. To optimize the source localization, the high temporal resolution of electrophysiology was combined with the fine spatial information provided by the simultaneous recording of functional magnetic resonance (fMRI). Both tasks identified two endogenous ERP components in the 300 to 520 ms interval. An earlier component, pP2, showed a bilateral generator in the anterior Insula. A later P3 component (P3b) was generated bilaterally in the temporal-parietal junction, the premotor and motor area and the anterior intraparietal sulcus (this latter one only in the standard oddball). Anticipatory slow waves (beginning 900 to 500 ms pre-stimulus), also of endogenous nature, were produced by the inferior and middle frontal gyrus and the supplementary and cingulate motor areas. Our protocol disentangled pre- from post-stimulus fMRI activations and provided original clues to the psychophysiological interpretation of emitted/endogenous ERPs.
Natural compounds like flavonoids preserve intestinal mucosal integrity through their antioxidant, anti-inflammatory, and antimicrobial properties. Additionally, some flavonoids show prebiotic ...abilities, promoting the growth and activity of beneficial gut bacteria. This study investigates the protective impact of Lens culinaris extract (LE), which is abundant in flavonoids, on intestinal mucosal integrity during LPS-induced inflammation. Using Caco-2 cells as a model for the intestinal barrier, the study found that LE did not affect cell viability but played a cytoprotective role in the presence of LPS. LE improved transepithelial electrical resistance (TEER) and tight junction (TJ) protein levels, which are crucial for barrier integrity. It also countered the upregulation of pro-inflammatory genes TRPA1 and TRPV1 induced by LPS and reduced pro-inflammatory markers like TNF-α, NF-κB, IL-1β, and IL-8. Moreover, LE reversed the LPS-induced upregulation of AQP8 and TLR-4 expression. These findings emphasize the potential of natural compounds like LE to regulate the intestinal barrier and reduce inflammation's harmful effects on intestinal cells. More research is required to understand their mechanisms and explore therapeutic applications, especially for gastrointestinal inflammatory conditions.
Fatigue has been defined as an exercise-induced decline in force generation capacity because of changes at both the peripheral and central levels. Movement is preceded and accompanied by brain ...activities related to the preparation and execution of movement (movement related cortical potentials, MRCP), which have been correlated with the perception of effort (RPE). We combined force measurements, surface electromyography (sEMG), peripheral electrical stimulation (maximal twitch, MT) and MRCP analysis to further our understanding of the neural correlates of peripheral and central changes during a fatiguing task involving the lower limbs. Eighteen healthy volunteers performed 4 blocks of isometric knee extensions at 40% of the maximal voluntary contraction (MVC) for a total of 240 2-s contractions. At the baseline and after each block, we measured RPE, MT and MVC. We simultaneously recorded the force of the knee extensor muscles, root mean square (RMS) of the sEMG of the vastus lateralis muscle, and electroencephalography (EEG) from 64 channels. The MRCPs were extracted from the EEG recordings and averaged in the early (Block 1-2) and late (Block 3-4) blocks. Two cohorts were obtained by cluster analysis based on the RPE (i.e., perception of effort) and MT (i.e., peripheral fatigue). We observed a significant decline in both the MVC (-13%) and RMS (-25%) of the sEMG signal over the course of the task; thus, muscle fatigue had occurred in all of the participants regardless of the cohort. The MRCP amplitude was larger in the fatigued than the non-fatigued MT cohort in the supplementary and premotor areas, whereas the MRCP amplitude was larger in the fatigued than the non-fatigued RPE cohort in the aforementioned areas, and also in the primary motor and prefrontal cortices (PFC). The increase in the positive activity of the PFC, along with the perception of effort, represents a novel result, suggesting that it is modulated more by the perception of effort than peripheral fatigue.
Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle ...counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.
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