An Efficient Edge Computing-Enabled Network for Used Cooking Oil Collection.

In Portugal, more than 98% of domestic cooking oil is disposed of improperly every day. This avoids recycling/reconverting into another energy. Is also may become a potential harmful contaminant of soil and water. Driven by the utility of recycled cooking oil, and leveraging the exponential growth of ubiquitous computing approaches, we propose an IoT smart solution for domestic used cooking oil (UCO) collection bins. We call this approach SWAN, which stands for Smart Waste Accumulation Network. It is deployed and evaluated in Portugal. It consists of a countrywide network of collection bin units, available in public areas. Two metrics are considered to evaluate the system's success: (i) user engagement, and (ii) used cooking oil collection efficiency. The presented system should (i) perform under scenarios of temporary communication network failures, and (ii) be scalable to accommodate an ever-growing number of installed collection units. Thus, we choose a disruptive approach from the traditional cloud computing paradigm. It relies on edge node infrastructure to process, store, and act upon the locally collected data. The communication appears as a delay-tolerant task, i.e., an edge computing solution. We conduct a comparative analysis revealing the benefits of the edge computing enabled collection bin vs. a cloud computing solution. The studied period considers four years of collected data. An exponential increase in the amount of used cooking oil collected is identified, with the developed solution being responsible for surpassing the national collection totals of previous years. During the same period, we also improved the collection process as we were able to more accurately estimate the optimal collection and system's maintenance intervals.

Tumor beta2-microglobulin and HLA-A expression is increased by immunotherapy and can predict response to CIT in association with other biomarkers.

Background: Downregulation of MHC class I expression and/or defects in the antigen presentation pathways are commonly reported in human cancers. Numerous studies previously have explored extensively the molecular mechanisms that underlie HLA-class I and Beta2-Microglobulin (B2M) downregulation. However, the techniques presently available to detect expression of MHC class I proteins lack the robustness, specificity and sensitivity needed for systematic integration and analysis in clinical trials. Furthermore, the dynamics of HLA-class I and B2M expression have not been comprehensively studied as a potential biomarker for immunotherapy. Methods: Using novel, validated, immunohistochemistry (IHC)-based methods for quantifying B2M and HLA-A in tumor samples from diverse cancer types, we have determined loss of B2M and HLA-A proteins in 336 archived, primary specimens and 329 biopsies from metastatic patients collected during Roche-sponsored Phase 1 clinical trials investigating novel immunotherapy candidates as monotherapy or in combination with CPI. Results: Up to 56% of cases with B2M or HLA-A loss were noted in the investigated tumor types. The frequency of loss was dependent on indication and stage of disease and revealed heterogeneous expression patterns across patients. B2M and HLA-A loss was increased in metastatic lesions compared to primary tumors, indicating selection of MHC class I low clones in metastatic and refractory tumor cells. High on-treatment B2M expression correlated with successful clinical outcome (RECIST), while high baseline B2M did not. A treatment-induced increase of B2M expression was noted in most of the patients with low B2M levels at baseline. The triple biomarker combination of B2M, CD8 and PDL1 strongly improved response prediction to cancer immunotherapy. Conclusion: Our results indicate that B2M and HLA-A loss occurs frequently in tumors and is reversed in most instances following immunotherapy which supports the conclusion that MHC class I loss is not the dominant resistance mechanism to CPI treatment. This investigation reveals a highly dynamic expression of HLA-A and B2M in tumors affected by indication, metastatic status, immunophenotype and immunotherapy treatment. Baseline expression levels of B2M on tumors may be of utility as a constituent of a biomarker panel used for selecting patients for immunotherapy clinical trials.

Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques.

BACKGROUND: Naturally occurring colorectal cancers (CRC) in rhesus macaques share many features with their human counterparts and are useful models for cancer immunotherapy; but mechanistic data are lacking regarding the comparative molecular pathogenesis of these cancers. METHODS: We conducted state-of-the-art imaging including CT and PET, clinical assessments, and pathological review of 24 rhesus macaques with naturally occurring CRC. Additionally, we molecularly characterized these tumors utilizing immunohistochemistry (IHC), microsatellite instability assays, DNAseq, transcriptomics, and developed a DNA methylation-specific qPCR assay for MLH1, CACNA1G, CDKN2A, CRABP1, and NEUROG1, human markers for CpG island methylator phenotype (CIMP). We furthermore employed Monte-Carlo simulations to in-silico model alterations in DNA topology in transcription-factor binding site-rich promoter regions upon experimentally demonstrated DNA methylation. RESULTS: Similar cancer histology, progression patterns, and co-morbidities could be observed in rhesus as reported for human CRC patients. IHC identified loss of MLH1 and PMS2 in all cases, with functional microsatellite instability. DNA sequencing revealed the close genetic relatedness to human CRCs, including a similar mutational signature, chromosomal instability, and functionally-relevant mutations affecting KRAS (G12D), TP53 (R175H, R273*), APC, AMER1, ALK, and ARID1A. Interestingly, MLH1 mutations were rarely identified on a somatic or germline level. Transcriptomics not only corroborated the similarities of rhesus and human CRCs, but also demonstrated the significant downregulation of MLH1 but not MSH2, MSH6, or PMS2 in rhesus CRCs. Methylation-specific qPCR suggested CIMP-positivity in 9/16 rhesus CRCs, but all 16/16 exhibited significant MLH1 promoter hypermethylation. DNA hypermethylation was modelled to affect DNA topology, particularly propeller twist and roll profiles. Modelling the DNA topology of a transcription factor binding motif (TFAP2A) in the MLH1 promoter that overlapped with a methylation-specific probe, we observed significant differences in DNA topology upon experimentally shown DNA methylation. This suggests a role of transcription factor binding interference in epigenetic silencing of MLH1 in rhesus CRCs. CONCLUSIONS: These data indicate that epigenetic silencing suppresses MLH1 transcription, induces the loss of MLH1 protein, abrogates mismatch repair, and drives genomic instability in naturally occurring CRC in rhesus macaques. We consider this spontaneous, uninduced CRC in immunocompetent, treatment-naïve rhesus macaques to be a uniquely informative model for human CRC.

From imaging to precision: low cost and accurate determination of stereotactic coordinates for brain surgery Sapajus apella using MRI.

The capuchin monkey (Sapajus apella), a New World monkey species, exhibits prominent characteristics that make it an ideal model for neuroscience research. These characteristics include its phylogenetic traits, telencephalization coefficient, anatomical structures and pathways, genetic profile, immune responses, cognitive abilities, and complex behavioral repertoires. Traditionally, methodologies for stereotactic neurosurgery in research models have relied on the use of brain atlases. However, this approach can lead to errors due to the considerable variation in brain size and shape among individual monkeys. To address this issue, we developed a protocol for deriving individual coordinates for each monkey using a straightforward and relatively inexpensive method involving MRI imaging. Our protocol utilizes a specially designed, 3D-printed stereotactic head-holder that is safe to use with an MR magnet, non-invasive placement of fiducial markers, and post-processing with open-source software. This approach enhances MRI data visualization, improves anatomical targeting, and refines the design of neurosurgical experiments. Our technique could also prove beneficial in other areas of neuroscience research that require accurate calculation of stereotaxic coordinates. Furthermore, it could be useful for other nonhuman primate species for which brain atlases are typically unavailable.

Facts and Hopes on Biomarkers for Successful Early Clinical Immunotherapy Trials: Innovative Patient Enrichment Strategies.

Despite the clinical validation and unequivocal benefit to patients, the development of cancer immunotherapies is facing some key challenges and the attrition rate in early phases of development remains high. Identifying the appropriate patient population that would benefit most from the drug is on the critical path for successful clinical development. We believe that a systematic implementation of patient enrichment strategies early in the drug development process and trial design, is the basis for an innovative, more efficient, and leaner clinical development to achieve earlier a clear proof of concept or proof of failure. In this position article, we will describe and propose key considerations for the implementation of patient enrichment strategies as an opportunity to provide decision-enabling data earlier in the drug development process. We introduce an innovative multidimensional tool for immuno-oncology drug development that focuses on facilitating the identification and prioritization of enrichment-relevant biomarkers, based on the drug mechanism of action. To illustrate its utility, we discuss patient enrichment examples and use a case in the field of cancer immunotherapy, together with technical and regulatory considerations. Overall, we propose to implement fit for purpose enrichment strategies for all investigational drugs as early as possible in the development process. We believe that this will increase the success rate of immuno-oncology clinical trials, and eventually bring new and better medicines to patients faster.

A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials.

PURPOSE: To examine whether CD8+ T-cell numbers in paired tumor biopsies in early-stage clinical trials can be used as an early indicator of clinical benefit for cancer immunotherapies. EXPERIMENTAL DESIGN: Paraffin sections of tumor biopsies were stained immunohistochemically for CD8+ T cells, which were digitally enumerated. The tumor biopsies were from cancer patients in early-phase trials testing novel immunotherapeutic agents. Paired biopsies taken before the start of treatment and on-treatment were compared. A total of 155 patients were used as the training set and an additional 221 patients were used as the validation set. RESULTS: Using the Cox proportional hazard model, a ≥0.9- increase in fold change (FC) on a ln scale in CD8+ T cells (corresponding to a 2.5-fold increase on the linear scale), from baseline, demonstrated a greater association with prolonged progression-free survival and allowed improved differentiation between groups above and below the threshold. Similarly, a ≥6.2 threshold in geometric mean of the on-treatment density (OTD) of T cells, which approximately corresponds to 500 cells/mm2, correlated with longer PFS. The combination of both criteria (FC and OTD) provided the best discrimination between clinically nonactive and active compounds. CONCLUSIONS: We propose that a composite score of CD8+ T-cell density in paired biopsies taken before and on-treatment may be a new biomarker to inform on clinical outcomes in early immunotherapy clinical trials.

Predictive Model of All-Cause Death in Patients with Heart Failure using Heart Rate Variability. / Modelo Preditivo de Mortalidade por Todas as Causas em Pacientes com Insuficiência Cardíaca Usando a Variabilidade da Frequência Cardíaca.

BACKGROUND: Central Illustration : Predictive Model of All-Cause Death in Patients with Heart Failure using Heart Rate Variability. BACKGROUND: Short and long-duration heart rate variability (HRV) data from Holter monitoring could identify predictors of all-cause death in heart failure (HF) patients. OBJECTIVES: To build a predictive model of all-cause death in patients with HF using HRV. METHODS: Retrospective study including patients with suspected or confirmed HF who were admitted for decompensated HF or syncope that underwent Holter monitoring. In analysis of augmented sympathetic tonus, we evaluated the lowest HRV in nonoverlapping 10-minutes periods throughout 24h continuous electrocardiographic signal recording (short HRV variables). Variables with p<0.01 were included in a multivariate Cox regression model to determine the occurrence of the all-cause death. Variables with statistical significance in Cox regression were chosen to build the predictive model. P<0.05 was considered significant. RESULTS: A total of 116 patients were included, mean age of 71.9±16.3 years, 45.7% men, mean follow-up of 2.83±1.27 years. Thirty-nine deaths occurred (33.6%). By comparing survivors vs. non-survivors, the variables that showed statistical significance were lowest SDNN, lowest rMSSD, age and left ventricular ejection fraction (LVEF). In Cox regression, independent predictors of all-cause death were: age>69 years (HR 3.95, 95%CI 1.64-9.52); LVEF≤57% (HR 4.70, 95%CI 2.38-9.28) and lowest rMSSD≤12ms (HR 5.54, 95%CI 2.04-15.08). An integer value was assigned to each variable. Score<3 showed AUC=0.802 (95%CI 0.72-0.87). CONCLUSION: In HF patients hospitalized for decompensated HF or syncope, independent long-term predictors of all-cause death were age, LVEF, and 10-minutes rMSSD. These findings indicate that even brief moments of high sympathetic tone can impact survival, specifically in the elderly and patients with HF with reduced ejection fraction.

Association between hospitalizations for sensitive conditions and quality of primary care.

OBJECTIVE: To analyze the association between municipal rates of ambulatory care sensitive conditions (ACSC) hospitalization and the quality of primary health care (PHC), socioeconomic, and demographic variables and those related to local characteristics of the health system from 2010 to 2019. METHOD: Ecological time series study in Brazilian municipalities analyzing the correlation of ACSC hospitalization rates with PHC quality measured by the three cycles of the Primary Care Access and Program for improving primary care access and quality (PMAQ-AB). The study included municipalities whose teams participated in 80% or more of at least two PMAQ-AB cycles. The correlation between standardized ACSC hospitalization rates and PHC quality and other variables was analyzed. Spearman's test was used between the response variable and numerical explanatory variables. Generalized equations estimation was used as a multivariate model associating ACSC hospitalization rates with the other variables over the years. RESULTS: A total of 3,500 municipalities were included in the models. The quality of PHC (PMAQ-AB score) showed an inverse association with the variation in ACSC hospitalization rates. Hospitalization rates fell by -2% per year every ten-point increase in the PMAQ-AB score, adjusted by the remaining variables. A one-unit increase in the beds per 1,000 inhabitants variable had an impact of approximately +6.4% on ACSC hospitalization rates. Regarding population size, larger municipalities had lower ACSC hospitalization rates. Increased PHC coverage and lower socioeconomic inequality were also associated with the reduction in hospitalizations. CONCLUSIONS: The reduction in ACSC hospitalization rates over time was associated with an increase in the quality of PHC. It was also associated with a reduction in the number of hospital beds and municipalities with better socioeconomic indicators.

Assessment of Wood Bio-Concrete Properties Modified with Silane-Siloxane.

Bio-based materials, such as wood bio-concrete (WBC), hold promise in reducing energy consumption and carbon footprint of the construction industry. However, the durability of these materials is not well understood and can be negatively affected by the high water absorption capacity of wood bio-aggregates. In the field of cement composites, for example, silane-siloxane-based water repellent has been used to protect such materials from natural environmental attack. Nevertheless, there is still a limited understanding of various aspects related to this type of treatment, including its performance when applied to the bio-concrete substrate. This research aimed to investigate the influence of silane-siloxane on the rheology and hydration of cementitious paste through isothermal calorimetry and thermogravimetric analysis. Additionally, the impact of silane-siloxane on the physical and mechanical properties of WBCs was examined by conducting tests at fresh state (flow table and entrained air content) and hardened state (compressive strength and capillary water absorption). The composites were produced with a volumetric fraction of 45% of wood shavings while the cement matrix consisted of a combination of cement, rice husk ash, and fly ash. Silane-siloxane was applied in three ways: as coating, incorporated as an admixture, and in a combination of both methods. The results indicated that by incorporating silane in the cementitious pastethe viscosity increased by 40% and the hydration was delayed by approximately 6 h when compared to the reference. In addition, silane improved the compressive strength of WBCs by 24% when incorporated into the mixture, expressively reduced the water sorptivity of WBCs (93%), and was more effective if used as coating.

Differential Expression of miRNAs in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, muscle atrophy and in later stages, death. Diagnosis has an average delay of 1 year after symptoms onset, which impairs early management. The identification of a specific disease biomarker could help decrease the diagnostic delay. MicroRNA (miRNA) expression levels have been proposed as ALS biomarkers, and altered function has been reported in ALS pathogenesis. The aim of this study was to assess the differential expression of plasma miRNAs in ALS patients and two control populations (healthy controls and ALS-mimic disorders). For that, 16 samples from each group were pooled, and then 1008 miRNAs were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). From these, ten candidate miRNAs were selected and validated in 35 ALS patients, 16 ALS-mimic disorders controls and 15 healthy controls. We also assessed the same miRNAs in two different time points of disease progression. Although we were unable to determine a miRNA signature to use as disease or condition marker, we found that miR-7-2-3p, miR-26a-1-3p, miR-224-5p and miR-206 are good study candidates to understand the pathophysiology of ALS.

Late Mortality After Myocardial Injury in Critical Care Non-Cardiac Surgery Patients Using Machine Learning Analysis.

Myocardial injury after noncardiac surgery (MINS) increases mortality within 30 days. We aimed to evaluate the long-term impact of myocardial injury in a large cohort of patients admitted to intensive care after noncardiac surgery. All patients who stayed, at least, overnight with measurement of high-sensitive cardiac troponin were included. Clinical characteristics and occurrence of MINS were assessed between patients who died and survivors using chi-square test and Student t test. Variables with p <0.01 in the univariate model were included in the Cox regression model to identify predictor variables. Survival decision tree (SDT), a machine learning model, was also used to find the predictors and their correlations. We included 2,230 patients with mean age of 63.8±16.3 years, with most (55.6%) being women. The prevalence of MINS was 9.4% (209 patients) and there were 556 deaths (24.9%) in a median follow-up of 6.7 years. Univariate analysis showed variables associated with late mortality, namely: MINS, arterial hypertension, previous myocardial infarction, atrial fibrillation, dementia, urgent surgery, peripheral artery disease (PAD), chronic health status, and age. These variables were included in the Cox regression model and SDT. The predictor variables of all-cause death were MINS (hazard ratio [HR] 2.21; 95% confidence interval [CI] 1.77 to 2.76), previous myocardial infarction (HR 1.47; 95% CI 1.14 to 1.89); urgent surgery (HR 1.24; 95% CI 1.01 to 1.52), PAD (HR 1.83; 95% CI 1.23 to 2.73), dementia (HR 2.54; 95% CI 1.86 to 3.46) and age (HR 1.05; 95% CI 1.04 to 1.06). SDT had the same predictors, except PAD. In conclusion, increased high-sensitive troponin levels in patients who underwent noncardiac surgery raised the risk of short and late mortality.

New Evidence Suggests a Much Complex Classification for the Genetic Pattern of Inheritance in Primary Brain Calcification.

Primary familial brain calcification (PFBC), often called Fahr's disease, is a condition in which calcium phosphate accumulates in the brain, mainly in the basal ganglia, thalamus, and cerebellum, and without the association of any metabolic or infectious cause. Patients present a variety of neurological and psychiatric disorders, usually during adulthood. The disease is caused by autosomal dominant pathogenic variants in genes such as SLC20A2, PDGFRB, PDGFB, and XPR1. MYORG and JAM2 are the other genes linked to homozygous patterns of inheritance. Here, we briefly discuss the recent cases reported by Ceylan et al. (2022) and Al-Kasbi et al. (2022), which challenge the current association with two previous genes and a clear pattern of inheritance. Ceylan et al. report a new biallelic variant related to a pathogenic variant in the SLC20A2 gene, which is typically associated with a heterozygous mutation pattern. The affected siblings displayed a severe and early onset of the disease, revealing a phenotype similar to that seen in CMV infections, often named as pseudo-TORCH. Furthermore, a study of genes related to intellectual disability conducted by Al-Kasbi et al. demonstrated that the biallelic manifestation of the XPR1 gene was associated with early symptoms, leading to the belief that the homozygous pattern of genes responsible for causing PFBC with an autosomal dominant pattern may also be linked to early-onset manifestations of PFBC. Further studies might explore the variety of clinical presentations linked to PFBC genes, especially if we pay attention to complex patterns of inheritance, reinforcing the need for a more detailed bioinformatic analysis.

Unraveling molecular characteristic of fluoride neurotoxicity on U87 glial-like cells: insights from transcriptomic and proteomic approach.

The potential of fluoride (F) as a neurotoxicant in humans is still controversial in the literature. However, recent studies have raised the debate by showing different mechanism of F-induced neurotoxicity, as oxidative stress, energy metabolism and inflammation in the central nervous system (CNS). In the present study, we investigated the mechanistic action of two F concentration (0.095 and 0.22 µg/ml) on gene and protein profile network using a human glial cell in vitro model over 10 days of exposure. A total of 823 genes and 2,084 genes were modulated after exposure to 0.095 and 0.22 µg/ml F, respectively. Among them, 168 were found to be modulated by both concentrations. The number of changes in protein expression induced by F were 20 and 10, respectively. Gene ontology annotations showed that the main terms were related to cellular metabolism, protein modification and cell death regulation pathways, such as the MAP kinase (MAPK) cascade, in a concentration independent manner. Proteomics confirmed the changes in energy metabolism and also provided evidence of F-induced changes in cytoskeleton components of glial cells. Our results not only reveal that F has the potential to modulate gene and protein profiles in human U87 glial-like cells overexposed to F, but also identify a possible role of this ion in cytoskeleton disorganization.

Neuroprotective effects of açaí (Euterpe oleracea Mart.) against diabetic retinopathy.

Introduction: Diabetes mellitus describes a metabolic disorder of multiple etiologies, characterized by chronic hyperglycemia, which induces a series of molecular events capable of leading to microvascular damage, affecting the blood vessels of the retina, causing diabetic retinopathy. Studies indicate that oxidative stress plays a central role in complications involving diabetes. Açaí (Euterpe oleracea) has attracted much attention given its antioxidant capacity and potential associated health benefits in preventing oxidative stress, one of the causes of diabetic retinopathy. The objective of this work was to evaluate the possible protective effect of açaí (E. oleracea) on the retinal function of mice with induced diabetes, based on full field electroretinogram (ffERG). Methods: We opted for mouse models with induced diabetes by administration of a 2% alloxan aqueous solution and treatment with feed enriched with açaí pulp. The animals were divided into 4 groups: CTR (received commercial ration), DM (received commercial ration), DM + açaí (E. oleracea-enriched ration) and CTR + açaí (E. oleracea-enriched ration). The ffERG was recorded three times, 30, 45 and 60 days after diabetes induction, under scotopic and photopic conditions to access rod, mixed and cone responses, in addition to monitoring the weight and blood glucose of the animals during the study period. Statistical analysis was performed using the two-way ANOVA test with Tukey's post-test. Results: Our work obtained satisfactory results with the ffERG responses in diabetic animals treated with açaí, where it was observed that there was no significant decrease in the b wave ffERG amplitude of this group over time when compared to the results of the Diabetic group not treated with açaí, which showed a significant reduction of this ffERG component. Discussion: The results of the present study show, for the first time, that treatment with an açaí-enriched diet is effective against the decrease in the amplitude of visual electrophysiological responses in animals with induced diabetes, which opens a new horizon for the prevention of retinal damage in diabetic individuals from treatment with açaí base. However, it is worth mentioning that our findings consist of a preliminary study and further researches and clinical trials are needed to examine açaí potential as an alternative therapy for diabetic retinopathy.

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites.

Stimulus representations in visual cortex shaped by spatial attention and microsaccades.

Microsaccades (MSs) are commonly associated with spatially directed attention, but how they affect visual processing is still not clear. We studied MSs in a task in which the animal was randomly cued to attend to a target stimulus and ignore distractors, and it was rewarded for detecting a color change in the target. We found that the enhancement of firing rates normally found with attention to a cued stimulus was delayed until the first MS directed towards that stimulus. Once that MS occurred, attention to the target was engaged and there were persistent effects of attention on firing rates for the remainder of the trial. These effects were found in the superficial and deep layers of V4 as well as the lateral pulvinar and IT cortex. Although the tuning curves of V4 cells do not change depending on the locus of spatial attention, we found pronounced effects of MS direction on stimulus representations that persisted for the length of the trial in V4. In intervals following a MS towards the target in the RF, stimulus decoding from population activity was substantially better than in intervals following a MS away from the target. Likewise, turning curves of cells were substantially sharper following a MS towards the target in the RF. This sharpening appeared to result from both a "refreshing" of the initial transient sensory response to stimulus onset, and a magnification of the effects of attention in this condition. MSs to the target also enhanced the neuronal response to the behaviorally relevant target color change and led to faster reaction times. These results thus reveal a major link between spatial attention, object processing and its coordination with eye movements.

Should orthognathic surgery be performed in growing patients? A scoping review.

The aim of this study was to determine whether the benefits of orthognathic surgery in a growing individual outweigh its risks. A scoping review was performed according to the PRISMA-ScR guideline. A bibliographic search from MEDLINE, Cochrane Library and LILACS was conducted until February 1, 2022. Scientific publications which reported orthognathic surgery in individuals under 18 years of age were considered. Inclusion criteria were performed according to PICOS model: do individuals with dentofacial deformity submitted to orthognathic surgery with an immature skeleton other than waiting growth cessation have overall benefits over any possible pos-operative consequences? Predictor of interest was growth status and outcome variables were positive benefits or negative consequences related to orthognathic surgery. Two reviewers screened records independently, and any disagreement between them was resolved by a third reviewer. Eligible studies were compiled into an extraction data form and were verified for validity and reliability. Risk of bias between studies was carried out using Review Manager. A total of 15 articles were included in this scoping review, comprising retrospective studies (9), case reports (3), and surveys (3). The topics covered varied from assessment of the functional needs, role, quality of life after orthognathic surgery, impact on growth, relation with temporomandibular joint surgical treatments, minimal referral age for surgery by orthodontists and complex cranio-maxillofacial deformities. Due to the heterogeneity of the articles, it was not possible to perform a meta-analysis. Within the limitations of the study it seems that the existing evidence seems favorable towards the intervention, improving quality of life in growing individuals, even at the risk of a second surgery.