Anti-inflammatory actions of aspirin-triggered resolvin D1 (AT-RvD1) in bronchial epithelial cells stimulated by cigarette smoke extract.

Smoking causes several diseases such as chronic obstructive pulmonary disease (COPD). Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. Here we evaluated the role of AT-RvD1 (100 nM) in bronchial epithelial cells (BEAS-2B) stimulated by cigarette smoke extract (CSE; 1%; 1 cigarette) for 24 h. CSE induced the productions of IL-1ß, TNF-α, IL-10, IL-4 and IFN-γ as well as the activations of NF-κB and STAT3 and the expression of ALX/FPR2 receptor. AT-RvD1 reduced the IL-1ß and TNF-α production and increased the production of IFN-γ. These effects were reversed BOC2, an antagonist of ALX/FPR2 receptor for AT-RvD1. The production of IL-4 and IL-10 were not altered by AT-RvD1. In addition, AT-RvD1 reduced the phosphorylation of NF-κB and STAT3 when compared to CSE-stimulated BEAS-2B cells. No alteration of ALX/FPR2 expression was observed by AT-RvD1 when compared to CSE group. In the human monocytic leukemia cell line, the relative number of copies of IL-1ß and IL-4 was significantly higher in CSE + AT-RvD1 group compared CSE group, however, the expression of M1 cytokine was more pronounced than M2 profile. AT-RvD1 could be an important target for the reduction of inflammation in the airways associated with smoking.

Profile analysis of emerging respiratory virus in children.

Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus, metapneumovirus, influenza, parainfluenza, rhinovirus, and, more recently, Sars-CoV-2, which has been responsible for the COVID-19 pandemic. The objective of our study was to evaluate clinical data from a viral panel performed in children hospitalized with SARS or COVID-19 in the infirmary or ICU of 5 pediatric hospitals in the city of Goiânia, Goiás, Brazil. Demographic, clinical, and laboratory data were collected for analysis, and data on the outcomes underwent statistical treatment. A total of 128 patients were selected for the study, 54% of whom were male and 46% female. The viral panel included rhinovirus, COVID-19, metapneumovirus, adenovirus, and parainfluenza. Descriptive analyses of age profile showed differences in the involvement of particular viruses. The percentage of patients who required hospitalization in the ICU, infirmary, as well as individuals who were discharged after therapy or who died, were described. Our work shows that epidemiological surveillance measures are indispensable, especially if used in the continued analysis of viral panels in all pediatric patients with SARS.

Women and working in healthcare during the Covid-19 pandemic in Brazil: bullying of colleagues.

BACKGROUND: Based on a feminist approach, we analyzed the experiences of workplace bullying suffered by women front-line healthcare professionals dealing with the Covid-19 pandemic. We start from studies that show that women make up 70% of the global health workforce, 85% in the area of nursing, and 90% in the case of social care workers. An unequivocal need thus exists to address gender issues regarding the composition of the labor force in the health area. The pandemic has aggravated recurring problems involving healthcare professionals at the various caregiving levels, such as mental harassment (bullying) and its effects on mental health. METHODS: Data were gathered from an online survey of a convenience (non-probability) sample composed of 1,430 volunteer respondents, all women that work in the public health system in Brazil. The analyses and discussions involved the responses to a questionnaire containing 12 closed-ended questions and one open-ended question. RESULTS: The results revealed a context of workplace bullying aggravated by precarious material, institutional and organizational conditions in the area of health services against the backdrop of the Covid-19 pandemic in Brazil. This context has variously led to aggression, isolation, heavy workloads, and invasion of privacy, humiliation, persecution and fear as it was possible to see, mainly, in the answers to the study's open-ended question. This situation degrades both work relations and the integrity of the healthcare professionals who work on the front line to treat Covid-19 cases. CONCLUSION: We conclude that bullying is a psychosocial phenomenon that heightens the oppression and subordination still experienced by women in the contemporary context, but with new hues in a scenario of frontline response to Covid-19.

Development of solid dispersions based on 3- (2,6-difluorobenzyl) -5- (5-bromo-1H-indol-3-ylmethylene) thiazolidine-2,4-dione for schistosomicidal treatment.

Schistosomiasis is an endemic disease in Brazil. It is important to broaden the treatment options to control and containment of the disease. Thiazolidine derivatives appear as important alternatives to treatment. In vitro studies have demonstrated excellent schistosomiasis activity for LPSF/GQ-238. The molecule, however, has poorly water-soluble. This study focused on increasing the aqueous solubility of LPSF/GQ-238 by obtaining solid dispersions. Were prepared by the solvent techniques, using Soluplus®, Polyethylene glycol (PEG), and Polyvinylpyrrolidone (PVP-K30) as carriers. Solubility tests, Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Exploratory Differential Calorimetry (DSC), and Raman Spectroscopy characterized these new intermediate products. The solubility tests showed that the higher the proportion of polymer used in the preparation of the dispersion, the greater the solubility presented. The observation of the morphology by SEM analysis, elucidated, that the new chemical entity (NCE) has a characteristic crystalline structure. The folding of this structure by the polymer was observed in all analyzed dispersions, thus demonstrating the amorphous state of the product. The scales observed in the structures of the dispersions demonstrate the successive wrinkles that occurred. The greater the proportion of the polymer, the greater the number of folds that occurred, which may explain the greater solubility observed in these preparations. The X-ray diffraction profile of the NCE reveals the presence of intense peaks, presenting a crystalline pattern. The polymer, on the other hand, shows amorphous nature, evidenced by the absence of peaks. All the analyzed dispersions did not present the characteristic peaks of the NCE, evidencing the amorphous behavior of the products. The thermal degradation profile of the NCE presents a characteristic crystalline structure endothermic peak. This peak was not observed in any of the obtained dispersions, evidencing the obtaining of a new solid state. Raman spectroscopy showed that peaks in the range 200-400 (cm-1) by NCE were lost when compared to all analyzed dispersions, showing a slight change in the structure of the molecule when dispersed, probably due to the formation of hydrogen bonds with the polymer. The in vitro study showed a significant improvement in the activity of the NCE against the adult worm and to the schistosomulae. It was possible to observe that the obtained solid dispersions were physicochemically and biologically viable for schistosomicidal treatment due to the increase of solubility of the molecule.

Cellular dormancy: A widespread phenomenon that perpetuates infectious diseases.

Under adverse environmental conditions, microorganisms are able to enter a state of cellular dormancy which consists of cell cycle arrest and interruption of multiplication. This process ensures their perpetuation in the infected host organism and enables the spread of disease. Throughout biological evolution, dormancy allowed microorganisms to persist in a harsh niche until favorable conditions for their reactivation were re-established. Here, we propose to discuss the dormancy of bacteria and protozoa pathogens focusing on the potential mechanisms and components associated with dormancy.

Management of Digitaria insularis in soybean pre-sowing desiccation by ACCase alternative herbicides and its impact on soybean carryover.

The objective of this study was to evaluate the use of alternative herbicides to ACCase inhibitors to control Digitaria insularis (sourgrass) during pre-sowing soybean desiccation. Two field experiments were conducted with two temporal replicates under different climatic conditions, with the following treatments: imazethapyr + glyphosate, clethodim + fluroxypyr, chlorimuron + glyphosate, imazapic + imazapyr, mesotrione + atrazine + glyphosate, tembotrione + atrazine + glyphosate, nicosulfuron + atrazine and imazamox + glyphosate, all of which were composed of a sequential application of glufosinate ammonium. The water stress conditions in experiment 1 compromised the efficacy of acetolactate synthase enzyme (ALS) inhibitor herbicides in the control of sourgrass. Even under water restriction conditions, the treatments containing mesotrione + atrazine + glyphosate and tembotrione + atrazine + glyphosate provided control greater than 80%. In experiment 2, the combination of ALS inhibitors with glyphosate proved to be a great alternative for the management of sourgrass control. All treatments showed no significant phytotoxicity in soybean for either experiment.

Artificial neural networks and adaptive neuro-fuzzy inference systems for prediction of soil respiration in forested areas southern Brazil.

The purpose of this study was to estimate the temporal variability of CO2 emission (FCO2) from O2 influx into the soil (FO2) in a reforested area with native vegetation in the Brazilian Cerrado, as well as to understand the dynamics of soil respiration in this ecosystem. The database is composed of soil respiration data, agroclimatic variables, improved vegetation index (EVI), and soil attributes used to train machine learning algorithms: artificial neural network (ANN) and an adaptive neuro-fuzzy inference system (ANFIS). The predictive performance was evaluated based on the mean absolute error (MEA), root mean square error (RMSE), mean absolute percentage error (MAPE), agreement index (d), confidence coefficient (c), and coefficient of determination (R2). The best estimation results for validation were FCO2 with multilayer perceptron neural network (MLP) (R2 = 0.53, RMSE = 0.967 µmol m-2 s-1) and radial basis function neural network (RBF) (R2 = 0.54, RMSE = 0.884 µmol m-2 s-1) and FO2 with MLP (R2 = 0.45, RMSE = 0.093 mg m-2 s-1) and RBF (R2 = 0.74, 0.079 mg m-2 s-1). Soil temperature and macroporosity are important predictors of FCO2 and FO2. The best combination of variables for training the ANFIS was selected based on trial and error. The results were as follows: FCO2 (R2 = 16) and FO2 (R2 = 29). In all models, FCO2 outperformed FO2. A primary factor analysis was performed, and FCO2 and FO2 correlated best with the weather and soil attributes, respectively.

Psychometric properties of the Brazilian version of the fear of COVID-19 scale (FCV-19S).

COVID-19 can bring several psychological problems to patients and non-patients, which highlights the need for a better understanding of outcomes that can emerge due the occurrence of the virus. One of these variables is fear, present in situations of continuous uncertainty. Fear is a key variable for mental health and tracking it and its correlates might help to develop proper education and prevention programs. Currently, Brazil is one of the epicentres of the COVID-19 pandemic, with its public health system scrapped and not being able to contain the amount of infected people. Therefore, a proper measure to screen the fear of COVID-19 will help to provide improvements in mental health in such contexts. For that, two studies were performed. In Study 1 (N = 230) we assessed the factorial structure of the measure through exploratory factor analysis, and item parameters using item response theory. In Study 2 (N = 302), we assessed whether the structure would replicate in an independent sample and through confirmatory factor analysis, besides assessing convergent validity using Structural Equation Modelling and proposing a shorter version of the measure. Both long and short versions presented a reliable unidimensional structure and similar patterns of correlations with depression, anxiety, and stress. Overall, our results showed that the FCV-19S and its short version are useful measures to the assessment of fear of COVID-19 in Brazil.

Colloidal stability of milk: reinterpretation of alcohol test results by digital microscopy.

In this research communication we propose a new approach by portable digital microscopy with a 200× objective to improve the visualization of microparticles of pasteurized milk submitted to the alcohol test. Not only did the method reduce the subjectivity of the readings, but also generated high resolution images of the microparticles, which allows the creation of a specific image pattern for each type of final product. In comparison to a control pasteurized milk treatment, the results confirmed the effect and the specificity of added salts (sodium citrate, disodium phosphate or their combination) on the stability of the milk to the alcohol test. Finally, the mixture of stabilizing salts of citrate/phosphate provided the highest degree of stability to pasteurized milk among the treatments studied.

Psychometric properties of the Coronavirus Anxiety Scale (CAS) in Brazil.

We aimed to adapt the Coronavirus Anxiety Scale (CAS) in Brazil, using a range of statistical techniques (e.g., factor analysis, item response theory). Two studies were conducted (Ntotal = 512). The unidimensional structure presented a good model fit and reliability, significant convergent validity, and all items presenting very high discrimination levels, adequately assessing medium and high anxiety levels. We also gathered evidence on cutoff points for detecting anxiety symptoms, reinforcing the diagnostic feasibility (for screening) of the CAS. Our findings emphasize the CAS as useful for rapid assessment and research involving COVID-19 and mental health markers.

Visible Light Photoelectrochemical Sensor for Dopamine: Determination Using Iron Vanadate Modified Electrode.

This study reports a facile approach for constructing low-cost and remarkable electroactivity iron vanadate (Fe-V-O) semiconductor material to be used as a photoelectrochemical sensor for dopamine detection. The structure and morphology of the iron vanadate obtained by the Successive Ionic Adsorption and Reaction process were critically characterized, and the photoelectrochemical characterization showed a high photoelectroactivity of the photoanode in visible light irradiation. Under best conditions, dopamine was detected by chronoamperometry at +0.35 V vs. Ag/AgCl, achieving two linear response ranges (between 1.21 and 30.32 µmol L-1, and between 30.32 and 72.77 µmol L-1). The limits of detection and quantification were 0.34 and 1.12 µmol L-1, respectively. Besides, the accuracy of the proposed electrode was assessed by determining dopamine in artificial cerebrospinal fluid, obtaining recovery values ranging from 98.7 to 102.4%. The selectivity was also evaluated by dopamine detection against several interferent species, demonstrating good precision and promising application for the proposed method. Furthermore, DFT-based electronic structure calculations were also conducted to help the interpretation. The dominant dopamine species were determined according to the experimental conditions, and their interaction with the iron vanadate photoanode was proposed. The improved light-induced DOP detection was likewise evaluated regarding the charge transfer process.

Chemokines and the extracellular matrix: Set of targets for tumor development and treatment.

The extracellular matrix (ECM) consists of various molecules that support tissue cells, including proteins, fibronectin, laminin, collagen IV, and glycosaminoglycans. In addition to interactions between the ECM and cells, the ECM also interacts with chemokines, and growth factors, and these interactions ensure cell survival, development, differentiation, and migration of both immune system cells and tumor cells. This review provides an overview of the mechanisms of interaction between the ECM and chemokines, focusing on the tumor microenvironment and the modulation of these elements as a target for therapies in several types of cancer.

Nutrient density and affordability of foods in Brazil by food group and degree of processing.

OBJECTIVE: Affordable nutrition refers to the relation between nutrient density of foods and their monetary cost. There are limited data on affordable nutrition in low- and middle-income countries. The present study aimed to develop a nutrient density score and nutrient affordability metrics for 377 most consumed foods in Brazil. DESIGN: The foods were aggregated into seven major food groups and four NOVA food categories. Nutrient composition data were obtained from the Brazilian Institute of Geography and Statistics. Food prices were obtained from retailer websites and were converted to prices per 100 g and 418 kJ. The Nutrient Rich Food (NRF8.2) score was based on protein, fiber, vitamins A, C and E, Ca, Fe and K. Nutrients to limit were sugar and Na. Affordability was measured as kcal/R$ and nutrients/R$. RESULTS: Grains, fats and sweets were more energy dense and had lower NRF8.2 scores than dairy, vegetables and fruits. Grains, fats and sweets were the lowest cost sources of energy. Vegetables and fruits, beans, nuts and seeds and eggs and dairy were the lowest cost sources of multiple nutrients. Ultra-processed foods (48 % of total) had higher energy density and lower NRF8.2 scores than did unprocessed foods. In Brazil, fruits, vegetables and dairy products offered the most nutrients per real. CONCLUSIONS: Analysis of the relationship between nutrient density of foods and their cost can help identify locally available foods that are nutrient rich, affordable and culturally acceptable. Achieving high nutrient density at an affordable cost should be the goal of Brazil's food systems.

Does admission time matter in a paediatric intensive care unit? A prospective cohort study.

AIM: Studies assessing the association between admission time to paediatric intensive care unit (PICU) and mortality are sparse with conflicting results. We aimed to evaluate the impact of time of admission on PICU mortality within 48 h after admission. METHODS: This was a single-centre prospective cohort. We collected data from all consecutive children aged 1 month to 16 years over 10 years. RESULTS: We included a total of 1368 admissions, with a PICU mortality of 6.6%. Compared with daytime admissions, the overall mortality rate (5.3% vs. 8.5%, P = 0.026) and the mortality within 48 h after admission were higher for those admitted during night-time (2% vs. 4.2%, P = 0.021). There were no differences between mortality rates and the day of admission (weekend admissions vs. weekday admissions). The adjusted odds of death within 48 h after admission was 2.5 (95% confidence interval = 1.22-5.24, P = 0.012) for patients admitted at night-time. A secondary analysis assessing trends in mortality rates during admission showed that the last 5 years of study were more responsible for the chances of death within 48 h (odds ratio = 7.6, 95% confidence interval = 1.91-30.17, P = 0.0039). CONCLUSION: Admission to the PICU during night shifts was strongly associated with death compared to daytime admissions. A time analysis of the moment of admission is necessary as a metric of quality of care to identify the interruption or improvement in the continuity of care. Further studies are needed to assess the modified contributing factors.

Critical Frequency of Self-Heating in a Superelastic Ni-Ti Belleville Spring: Experimental Characterization and Numerical Simulation.

The mechanical loading frequency affects the functional properties of shape memory alloys (SMA). Thus, it is crucial to study its effect for the successful use of these materials in dynamic applications. Based on the superelastic cyclic behavior, this work presents an experimental methodology for the determination of the critical frequency of the self-heating of a NiTi Belleville conical spring. For this, cyclic compressive tests were carried out using a universal testing machine with loading frequencies ranging from 0.5 Hz to 10 Hz. The temperature variation during the cyclic tests was monitored using a micro thermocouple glued to the NiTi Belleville spring. Numerical simulations of the spring under quasi-static loadings were performed to assist the analysis. From the experimental methodology applied to the Belleville spring, a self-heating frequency of 1.7 Hz was identified. The self-heating is caused by the latent heat accumulation generated by successive cycles of stress-induced phase transformation in the material. At 2.0 Hz, an increase of 1.2 °C in the average temperature of the SMA device was verified between 1st and 128th superelastic cycles. At 10 Hz, the average temperature increase reached 7.9 °C and caused a 10% increase in the stiffness and 25% decrease in the viscous damping factor. Finally, predicted results of the force as a function of the loading frequency were obtained.

Backside-illuminated scientific CMOS detector for soft X-ray resonant scattering and ptychography.

The impressive progress in the performance of synchrotron radiation sources is nowadays driven by the so-called `ultimate storage ring' projects which promise an unprecedented improvement in brightness. Progress on the detector side has not always been at the same pace, especially as far as soft X-ray 2D detectors are concerned. While the most commonly used detectors are still based on microchannel plates or CCD technology, recent developments of CMOS (complementary metal oxide semiconductor)-type detectors will play an ever more important role as 2D detectors in the soft X-ray range. This paper describes the capabilities and performance of a camera equipped with a newly commercialized backside-illuminated scientific CMOS (sCMOS-BSI) sensor, integrated in a vacuum environment, for soft X-ray experiments at synchrotron sources. The 4 Mpixel sensor reaches a frame rate of up to 48 frames s-1 while matching the requirements for X-ray experiments in terms of high-intensity linearity (>98%), good spatial homogeneity (<1%), high charge capacity (up to 80 ke-), and low readout noise (down to 2 e- r.m.s.) and dark current (3 e- per second per pixel). Performance evaluations in the soft X-ray range have been carried out at the METROLOGIE beamline of the SOLEIL synchrotron. The quantum efficiency, spatial resolution (24 line-pairs mm-1), energy resolution (<100 eV) and radiation damage versus the X-ray dose (<600 Gy) have been measured in the energy range from 40 to 2000 eV. In order to illustrate the capabilities of this new sCMOS-BSI sensor, several experiments have been performed at the SEXTANTS and HERMES soft X-ray beamlines of the SOLEIL synchrotron: acquisition of a coherent diffraction pattern from a pinhole at 186 eV, a scattering experiment from a nanostructured Co/Cu multilayer at 767 eV and ptychographic imaging in transmission at 706 eV.

Arboviruses (chikungunya, dengue, and Zika) associated with ophthalmic changes: a focus on aqueous fluid and vitreous humor.

The aim of this study was to conduct a bibliographic survey and correlates the presence of arboviroses in the eyeball with the main eye changes presented by the population under study. This study is a systematic review of journals and indexed articles, carried out between January 2019 and June 2019, in which there was a query in the Pubmed/Medline and Scielo databases without temporal restriction. In addition to the aforementioned databases, the Brazilian Association of Organ Transplantation Association database, which provides epidemiological data on organ and tissue transplants in Brazil, was used as a research source. The Midwest region contributed to the increase in the number of organ transplants in Brazil. The number of corneal transplants in Brazil surpassed the number of organ transplants by four times. Several ophthalmic changes associated with Chikungunya, Dengue, and Zika virus infections have been diagnosed; however, few studies have identified the presence of the virus in the eyeball. Arboviruses are of great relevance to public health due to a number of factors, ranging from the diversity of infectious agents involved and the plurality of clinical manifestations because the absence of efficient laboratory support, leading to delayed disease confirmation due to lack of differential diagnostics available. Added to these difficulties is the lack of specific therapy, leaving only the symptomatic control of clinical manifestations as the only treatment option. However, the manifestations are directly associated with the decreased quality of vision and consequently the quality of life of patients.

Dermatophagoides pteronyssinus-induced pro-inflammatory responses mediated via STAT3 and NF-kappaB signaling pathways in human bronchial epithelial cells - Inhibitory effects of Lafoensia pacari and ellagic acid.

The house dust mite allergen Dermatophagoides pteronyssinus (Der p) is a major driver of allergic asthma. Studies from our group demonstrated anti-eosinophilic effects of ethanolic extract of Lafoensia pacari stem bark (and ellagic acid, isolated from L. pacari extract), used as traditional medicine in Brazil to naturally treat inflammatory conditions. Here, we extended these results through performing phytochemical analysis of the constituents of L. pacari using liquid chromatography-mass spectrometry and evaluating the anti-inflammatory effects of both L. pacari and ellagic acid in the human BEAS-2B bronchial epithelial cell line stimulated with Der p. Ellagic acid (major constituent), gallic acid, ferulic acid, chlorogenic acid and rosmarinic acid, but not flavonoids (rutin, kaempferol, luteolin and quercetin), were found in the L. pacari. Pro-inflammatory mediators, IL-6, IL-8 and CCL-2 production were increased in BEAS-2B stimulated with Der p (10 µg/mL, 24 h) compared to control. L. pacari (250 µg/mL) and ellagic acid (100 µM) significantly reduced the concentration of these mediators. L. pacari increased the production of the anti-inflammatory cytokine, IL-10. These results were associated with the downregulation of NF-κB and STAT3 pathways. These findings indicate a novel anti-inflammatory action for L. pacari and ellagic acid in the airways allergic inflammatory response.

Factors Associated With Unplanned Extubation in Children: A Case-Control Study.

PURPOSE: Although several studies assess unplanned extubation (UE) in children, few have addressed determinants of UE and factors associated with reintubation in a case-controlled manner. We aimed to identify the risk factors and outcomes associated with UE in a pediatric intensive care unit. METHODS: Cases of UE were randomly matched with control patients at a ratio of 1:4 for age, severity of illness, and admission diagnosis. For cases and controls, we also collected data associated with UE events, reintubation, and outcomes. RESULTS: We analyzed 94 UE patients (0.75 UE per 100 intubation days) and found no differences in demographics between the 2 groups. Logistic regression revealed that patient agitation (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.28-4.65), continuous sedation infusion (OR: 3.27; 95% CI: 1.70-6.29), night shifts (OR: 9.16; 95% CI: 4.25-19.72), in-charge nurse experience <2 years (OR: 2.38; 95% CI: 1.13-4.99), and oxygenation index (OI) >5 (OR: 76.9; 95% CI: 16.79-352.47) were associated with UE. Risk factors for reintubation after UE included prior level of sedation (COMFORT score < 27; OR: 7.93; 95% CI: 2.30-27.29), copious secretion (OR: 11.88; 95% CI: 2.20-64.05), and OI > 5 (OR: 9.32; 95% CI: 2.45-35.48). CONCLUSIONS: This case-control study showed that both patient- and nurse-associated risk factors were related to UE. Risk factors associated with reintubation included lower levels of consciousness, copious secretions, and higher OI. Further evidence-based studies, including a larger sample size, are warranted to identify predisposing factors in UEs.

Effective Connectivity Study Guiding the Neuromodulation Intervention in Figurative Language Comprehension Using Optical Neuroimaging.

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.