Frontoparietal action-oriented codes support novel task set implementation

A key aspect of human cognitive flexibility concerns the ability to rapidly convert complex symbolic instructions into novel behaviors. Previous research proposes that this fast configuration is supported by two differentiated neurocognitive states, namely, an initial declarative maintenance of task knowledge, and a progressive transformation into a pragmatic, action-oriented state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this transformation. However, direct evidence for such frontoparietal formatting of novel task representations is still lacking. Here, we report the results of an fMRI experiment in which participants had to execute novel instructed stimulus-response associations. We then used a multivariate pattern-tracking procedure to quantify the degree of neural activation of instructions in declarative and procedural representational formats. This analysis revealed, for the first time, format-unique representations of relevant task sets in frontoparietal areas, prior to execution. Critically, the degree of procedural (but not declarative) activation predicted subsequent behavioral performance. Our results shed light on current debates on the architecture of cognitive control and working memory systems, suggesting a contribution of frontoparietal regions to output gating mechanisms that drive behavior

The neural bases of event monitoring across domains: a simultaneous ERP-fMRI study.

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, these transient processes rely on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts

Frontoparietal action-oriented codes support novel instruction implementation

A key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility

Ensuring sample quality for biomarker discovery studies - Use of ict tools to trace biosample life-cycle

The growing demand of personalized medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological material and its accompanying data are collected, handled and stored in accordance with standard operating procedures (SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research facilities and will represent the starting point of all future personalized medicine-based clinical trials

Fatal Huge Left Free Wall Ventricular Rupture after Acute Posterior Myocardial Infarction

A 77-year-old man, with a recent history of an acute inferior myocardial infarction, was referred to our hospital with echocardiographic and clinical signs of left ventricular free wall rupture (LVFWR). The intraoperative finding demonstrated a huge double LVFWR. The inferoposterior wall was dramatically destroyed without any possibility to repair

Effectiveness of Immunotherapy in Non-Small Cell Lung Cancer Patients with a Diagnosis of COPD: Is This a Hidden Prognosticator for Survival and a Risk Factor for Immune-Related Adverse Events?

simple summary the interaction between the immune system, chronic obstructive pulmonary disease (COPD), and non-small cell lung cancer (NSCLC) is complex and multifaceted and involves all cellular elements of the tumour microenvironment, together with the molecules expressed and secreted in the inflamed milieu. In patients with both diseases, considering that COPD is thought to impair the immune response against tumour cells, immune checkpoint inhibitors (ICIs) combined with chemotherapy appear to improve the pathological responses of NSCLC patients, showing promising improvements in survival. In the present review, we sought to understand the interaction between the two pathways and how the efficacy of immunotherapy in patients with NSCLC and COPD is affected in these patients. abstract the interplay between the immune system and chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is complex and multifaceted. In COPD, chronic inflammation and oxidative stress can lead to immune dysfunction that can exacerbate lung damage, further worsening the respiratory symptoms. In NSCLC, immune cells can recognise and attack the cancer cells, which, however, can evade or suppress the immune response by various mechanisms, such as expressing immune checkpoint proteins or secreting immunosuppressive cytokines, thus creating an immunosuppressive tumour microenvironment that promotes cancer progression and metastasis. The interaction between COPD and NSCLC further complicates the immune response. In patients with both diseases, COPD can impair the immune response against cancer cells by reducing or suppressing the activity of immune cells, or altering their cytokine profile. Moreover, anti-cancer treatments can also affect the immune system and worsen COPD symptoms by causing lung inflammation and fibrosis. Immunotherapy itself can also cause immune-related adverse events that could worsen the respiratory symptoms in patients with COPD-compromised lungs. In the present review, we tried to understand the interplay between the two pathologies and how the efficacy of immunotherapy in NSCLC patients with COPD is affected in these patients

Obesity and common pathways of cancer and cardiovascular disease

Abstract Obesity is constantly increasing worldwide due to the progressive globalization of sedentary lifestyle and diet rich in lipids and processed food. Cardiovascular complications and cancer are the two most fearsome long-term sequelae of obesity that justify the recent definition of this threaten as 'obesity epidemic'. Shared biological pathways can be recognized for obesity-induced cardiovascular and oncological complications that might prompt targeted interventions with potentially double beneficial effect. The present review aims at summarizing main common biological pathways linking obesity with cardiovascular diseases and cancer in order to provide a research framework within which therapeutic strategies might have at the same time cardiovascular-protective and cancer-preventive effects

Nutritional index for immune-checkpoint inhibitor in patients with metastatic gastro-esophageal junction/gastric cancer

Background: Nutritional status is strongly associated to prognosis in mGOJ/GC patients. The aim of the present study was to develop an ICI-specific nutritional index (NI).Methods: Ten serum and anthropometric nutritional markers derived from blood tests or CT scans were analyzed at baseline in patients treated with second-line ICI and correlated with overall survival (OS). An ICI-specific NI (the NUTRIICI) was developed with its specificity assessed in an independent group of patients treated with standard second-line chemotherapy.Results: From June 2014 to December 2018, 57 mGOJ/GC patients (14 females, 43 males) with a median(m) age of 61 years (range 29-85) received ICI as second-line therapy (Pembrolizumab n=26, Nivolumab n=1 6, Avelumab n=15). Among the 10 analyzed variables, Onodera's prognostic NI (PNI) <= 33 and waist-to-hip (WHR) <1 were independent predictors of OS and used to build the NUTRIICI. Patients with both favorable factors (i.e., PNI >33 and WHR >= 1, comparator group) had a mOS of 18.0 vs. 6.7 months of patients with one unfavorable factor (either PNI <= 33 or WHR <1, Hazard Ratio, HR 3.06), vs. 1.3 months of patients with both unfavorable factors (HR 17.56), overall P<0.0001. In the independent group of patients treated with standard chemotherapy NUTRIICI was not associated with prognosis (P=0.57).Conclusions: NUTRIICI is the first ICI-specific NI for mOGJ/GC patients receiving second-line ICI. A validation in larger cohorts is strongly encouraged