Mapping the landscape of histomorphological cancer phenotypes using self-supervised learning on unannotated pathology slides.

Cancer diagnosis and management depend upon the extraction of complex information from microscopy images by pathologists, which requires time-consuming expert interpretation prone to human bias. Supervised deep learning approaches have proven powerful, but are inherently limited by the cost and quality of annotations used for training. Therefore, we present Histomorphological Phenotype Learning, a self-supervised methodology requiring no labels and operating via the automatic discovery of discriminatory features in image tiles. Tiles are grouped into morphologically similar clusters which constitute an atlas of histomorphological phenotypes (HP-Atlas), revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. These properties are maintained in a multi-cancer study.

Distribution and Endemism Areas of Bonamia Thouars (Convolvulacea) in Brazil.

Brazil harbors the highest richness of Convolvulaceae with 424 species recognized mainly distributed in the Amazon, Atlantic Forest, Caatinga and Cerrado phytogeographic domains. Seventeen of these species are representatives of Bonamia, with ten endemic to the country. The aim of the study was to map the distribution of this group to understand its richness, its sampling and detecting areas of endemism, valuable information for conservation. We collected data gathered from herbaria and from the online database. The data were refined (1) excluding of records not at the species level; (2) records with no identification of collection site or with only the identification of the state of collection. There was calculated the richness, the number of records and an estimate of richness per cell. We conducted a parsimony analysis of endemism for distribution analysis. Finally, the knowledge of richness for the species was analyzed. There were gathered 420 occurrence records, in 87 grid cells. Most grid cells observed in the study presented one species. Two endemic areas were found for the genus. The results contribute to the understanding of the distribution of the group in Brazil, highlighting shortfalls in collections.

The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN). Telomere shortening, a crucial genomic alteration linked to CIN, emerged at precancer stage. Moreover, later-stage lesions demonstrated increasing cancer stemness and decreasing alveolar identity, suggesting epithelial de-differentiation during early LUAD carcinogenesis. The innate immune cells progressively diminished from precancer to invasive LUAD, concomitant with a gradual recruitment of adaptive immune cells (except CD8+ and gamma-delta T cells that decreased in later stages) and upregulation of numerous immune checkpoints, suggesting LUAD precancer evolution is associated with a shift from innate to adaptive immune response and immune evasion mediated by various mechanisms.

Invasion and Grading of Pulmonary Non-Mucinous Adenocarcinoma.

Lung adenocarcinoma staging and grading were recently updated to reflect the link between histologic growth patterns and outcomes. The lepidic growth pattern is regarded as "in-situ," whereas all other patterns are regarded as invasive, though with stratification. Solid, micropapillary, and complex glandular patterns are associated with worse prognosis than papillary and acinar patterns. These recent changes have improved prognostic stratification. However, multiple pitfalls exist in measuring invasive size and in classifying lung adenocarcinoma growth patterns. Awareness of these limitations and recommended practices will help the pathology community achieve consistent prognostic performance and potentially contribute to improved patient management.

First occurrence of feline sporotrichosis in a metropolitan area of Central-West Brazil.

Sporotrichosis is a neglected mycosis that affects human and animal hosts, including domestic cats. In Brazil, its most frequently diagnosed etiological agent is Sporothrix brasiliensis. Zoonotic transmission of S. brasiliensis occurs via direct contact between an infected cat and a susceptible human host. Notification of confirmed cases of feline sporotrichosis is not mandatory in Brazil. The metropolitan area of Goiania city can be considered a silent area for the occurrence of feline sporotrichosis. In this context, voluntary reporting of feline sporotrichosis cases is recommended for all healthcare professionals. This study aimed to report the first occurrence of S. brasiliensis in a cat from the metropolitan area of Goiania city. Cytopathology, mycology, thermal dimorphism and calmodulin gene amplification tests were performed. The mycological and molecular biological diagnoses corresponded to S. brasiliensis. The etiological agent of zoonotic sporotrichosis was detected in the metropolitan area of Goiania city, and therefore there is a risk of the emergence of new cases of cats infected with S. brasiliensis and the occurrence of zoonotic transmission of this fungus.

The Grading System for Lung Adenocarcinoma: Brief Review of its Prognostic Performance and Future Directions.

Histologic grading of tumors is associated with prognosis in many organs. In the lung, the most recent grading system proposed by International association for the Study of Lung Cancer (IASLC) and adopted by the World Health Organization (WHO) incorporates the predominant histologic pattern, as well as the presence of high-grade architectural patterns (solid, micropapillary, and complex glandular pattern) in proportions >20% of the tumor surface. This system has shown improved prognostic ability when compared with the prior grading system based on the predominant pattern alone, across different patient populations. Interobserver agreement is moderate to excellent, depending on the study. IASLC/WHO grading system has been shown to correlate with molecular alterations and PD-L1 expression in tumor cells. Recent studies interrogating gene expression has shown correlation with tumor grade and molecular alterations in the tumor microenvironment that can further stratify risk of recurrence. The use of machine learning algorithms to grade nonmucinous adenocarcinoma under this system has shown accuracy comparable to that of expert pulmonary pathologists. Future directions include evaluation of tumor grade in the context of adjuvant and neoadjuvant therapies, as well as the development of better prognostic indicators for mucinous adenocarcinoma.

Association between Urinary Sodium Excretion and Body Fat in School-Aged Children: Insights from the ARIA Study.

Childhood obesity has been associated with increased sodium intake. Nonetheless, evidence linking sodium intake to Body Mass Index (BMI) and Body Fat Mass Percentage (%BF) remains limited, especially in the pediatric age group. Therefore, this study aims to investigate whether there is an association between 24 h urinary sodium excretion with BMI and %BF in a sample group of children from the ARIA study. This cross-sectional analysis included 303 children aged 7 to 12 from across 20 public schools in Porto, Portugal. Weight and %BF were assessed using the Tanita™ BC-418 Segmental Body Analyzer. Children's Total Energy Intake (TEI) was estimated through a single 24 h Recall Questionnaire, and urinary sodium and potassium excretion was estimated by a 24 h urine collection. The association of %BF and BMI with 24 h sodium excretion was estimated by a binary logistic regression adjusted for sex, age, physical activity, total energy intake, parental education, and 24 h urinary excreted potassium. There was a significant positive association between higher levels of urinary sodium excretion and higher %BF values, even after adjusting for confounders. However, the same was not observed for BMI. Our findings suggest that higher sodium intake is associated with higher values of %BF among children, regardless of TEI and potassium intake.

Red blood cell membrane-camouflaged gold-core silica shell nanorods for cancer drug delivery and photothermal therapy.

Gold core mesoporous silica shell (AuMSS) nanorods are multifunctional nanomedicines that can act simultaneously as photothermal, drug delivery, and bioimaging agents. Nevertheless, it is reported that once administrated, nanoparticles can be coated with blood proteins, forming a protein corona, that directly impacts on nanomedicines' circulation time, biodistribution, and therapeutic performance. Therefore, it become crucial to develop novel alternatives to improve nanoparticles' half-life in the bloodstream. In this work, Polyethylenimine (PEI) and Red blood cells (RBC)-derived membranes were combined for the first time to functionalize AuMSS nanorods and simultaneously load acridine orange (AO). The obtained results revealed that the RBC-derived membranes promoted the neutralization of the AuMSS' surface charge and consequently improved the colloidal stability and biocompatibility of the nanocarriers. Indeed, the in vitro data revealed that PEI/RBC-derived membranes' functionalization also improved the nanoparticles' cellular internalization and was capable of mitigating the hemolytic effects of AuMSS and AuMSS/PEI nanorods. In turn, the combinatorial chemo-photothermal therapy mediated by AuMSS/PEI/RBC_AO nanorods was able to completely eliminate HeLa cells, contrasting with the less efficient standalone therapies. Such data reinforce the potential of AuMSS nanomaterials to act simultaneously as photothermal and chemotherapeutic agents.

Limosilactobacillus reuteri as an Adjuvant in the Treatment of Peri-implant Mucositis in Total Rehabilitation: An Exploratory Study.

OBJECTIVES: Mechanical debridement is the traditional method for the treatment of peri-implant mucositis (P-im) and its success depends on the patient's correct oral hygiene. It is believed that probiotics may help by their ability to modulate the oral biofilm, resulting in anti-inflammatory and antibacterial plaque action. The aim of this study was to evaluate the adjuvant effect of the probiotic Limosilactobacillus reuteri (LR) in the mechanical treatment of P-im. MATERIALS AND METHODS: This exploratory study included 29 subjects with implant-supported total rehabilitation and P-im, divided into test (TG) and control (CG) groups, equally subjected to professional mechanical debridement, with the administration of a daily GUM PerioBalance lozenge for 30 days added to the TG. The modified Plaque Index (mPlI) modified Sulcus Bleeding Index (mBI) and pocket depth (PD) were evaluated before the intervention (baseline) and 6 and 10 weeks later. STATISTICAL ANALYSIS: Parametric and nonparametric tests with 5% significance level were used in the statistical analysis, using IBM SPSS Statistics 27.0 software. RESULTS: Both treatments resulted in reduced mPlI, mBI, and PD at 6 weeks; while from 6 to 10 weeks there was an increase in mPlI and mBI and maintenance of PD. Compared with baseline, differences were close to statistical significance in the reduction in PD at 10 weeks in the CG (p = 0.018), after Bonferroni correction, and statistically significant in the mPlI at 6 weeks in the CG (p = 0.004) and in the TG (p = 0.002) as well as at 10 weeks in the TG (p = 0.016). Comparing the groups in the postintervention assessments, no statistically significant differences were found. CONCLUSION: LR adjuvant mechanical treatment of P-im does not show a clear benefit compared with mechanical treatment alone, with both interventions achieving similar clinical results. Further prospective and long-term studies are needed.

Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer.

KRASG12C inhibitors (adagrasib and sotorasib) have shown clinical promise in targeting KRASG12C-mutated lung cancers; however, most patients eventually develop resistance. In lung patients with adenocarcinoma with KRASG12C and STK11/LKB1 co-mutations, we find an enrichment of the squamous cell carcinoma gene signature in pre-treatment biopsies correlates with a poor response to adagrasib. Studies of Lkb1-deficient KRASG12C and KrasG12D lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.

International reproducibility study of thymic epithelial tumors staging: pT stage is an issue. proposals for improvement. A RYTHMIC/ITMIG study.

INTRODUCTION: Pathologists are staging thymic epithelial tumors (TET) according to the 8th UICC/AJCC TNM system. Within the French RYTHMIC network, dedicated to TET, agreement on pathologic tumor stage (pT) among the pathology panelists was difficult. The aim of our study was to determine the interobserver reproducibility of pT at an international level, to explore the source of discrepancies and potential interventions to address these. METHODS: An international panel of pathologists was recruited through the International Thymic Malignancy Interest Group (ITMIG). The study focused on invasion of mediastinal pleura, pericardium, and lung. From a cohort of cases identified as challenging within the RYTHMIC network, we chose a series of test and validation cases (n = 5 and 10, respectively). RESULTS: Reproducibility of the pT stage was also challenging at an international level as none of the 15 cases was classified as the same pT stage by all ITMIG pathologists. The agreement rose from slight (κ = 0.13) to moderate (κ = 0.48) between test and validation series. Discussion among the expert pathologists pinpointed two major reasons underlying discrepancies: 1) Thymomas growing with their "capsule" and adhering to the pleurae, pericardium, or lung were often misinterpreted as invading these structures. 2) Recognition of the mediastinal pleura was identified as challenging. CONCLUSION: Our study underlines that the evaluation of the pT stage of TET is problematic and needs to be addressed in more detail in an upcoming TNM classification. The publication of histopathologic images of landmarks, including ancillary tests could improve reproducibility for future TNM classifications.

Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren's Syndrome.

Objectives: Sjögren's Disease (SjD) is an autoimmune disorder characterized by progressive dysfunction, inflammation and destruction of salivary and lacrimal glands, and by extraglandular manifestations. Its etiology and pathophysiology remain incompletely understood, though a role for autoreactive B cells has been considered key. Here, we investigated the role of effector and regulatory T cells in the pathogenesis of SjD. Methods: Histological analysis, RNA-sequencing and flow cytometry were conducted on glands, lungs, eyes and lymphoid tissues of mice with regulatory T cell-specific deletion of stromal interaction proteins (STIM) 1 and 2 ( Stim1/2 Foxp3 ), which play key roles in calcium signaling and T cell function. The pathogenicity of T cells from Stim1/2 Foxp3 mice was investigated through adoptively transfer into lymphopenic host mice. Additionally, single-cell transcriptomic analysis was performed on peripheral blood mononuclear cells (PBMCs) of patients with SjD and control subjects. Results: Stim1/2 Foxp3 mice develop a severe SjD-like disorder including salivary gland (SG) and lacrimal gland (LG) inflammation and dysfunction, autoantibodies and extraglandular symptoms. SG inflammation in Stim1/2 Foxp3 mice is characterized by T and B cell infiltration, and transcriptionally by a Th1 immune response that correlates strongly with the dysregulation observed in patients with SjD. Adoptive transfer of effector T cells from Stim1/2 Foxp3 mice demonstrates that the SjD-like disease is driven by interferon (IFN)-γ producing autoreactive CD4 + T cells independently of B cells and autoantiboodies. scRNA-seq analysis identifies increased Th1 responses and attenuated memory Treg function in PBMCs of patients with SjD. Conclusions: We report a more accurate mouse model of SjD while providing evidence for a critical role of Treg cells and IFN-γ producing Th1 cells in the pathogenesis of SjD, which may be effective targets for therapy.

Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

Atopic dermatitis in early life and pain at 10 years of age: An exploratory study.

Pain is a distinctive burden in atopic dermatitis and recognized as an important and highly prevalent symptom. It is unknown if the presence of atopic disease may sensitize children to adverse pain profiles in the long term. We aimed to assess the impact of early-life atopic dermatitis-like symptoms on pain at 10 years of age. We used data from 1302 and 874 participants of the Generation XXI birth cohort evaluated at 6 and 15 months, respectively, and 10 years. Atopy-like symptoms since birth, including atopic dermatitis, were collected at ages 6 and 15 months by interviewing parents. Pain history in the last 3 months at age 10 was collected from parents and children using structured questionnaires. We computed relative risks (RR) and respective 95% confidence intervals of pain features at age 10 according to each atopic-like symptom at 6 and 15 months. Children whose parents reported atopic dermatitis-like symptoms at 6 months and at 15 months had higher risk of reporting any pain (RR 1.75 [1.15-2.66]) and multisite pain, respectively (RR 1.67 [1.18-2.37]) at 10 years of age.  Conclusion: Atopic dermatitis symptoms in early life were associated with a higher risk of pain at age 10, suggesting that potential for sensitization during the first decade of life and highlighting the importance of improving the health care of children with atopic dermatitis is worth investigating. What is Known: • Atopic disorders have been associated with many non-atopic comorbidities, including chronic pain. • Pain and atopic dermatitis share common inflammatory pathways. Inflammation, injury to the skin from scratching, fissures, and intolerance to irritants related to atopic dermatitis can cause pain. What is New: • Atopic dermatitis in early life is linked to an increased likelihood of experiencing pain at the age of 10, which suggests that exploring the potential for sensitization is a worthwhile area of investigation. • Our proof-of-concept study highlights the potential benefit of studying management targets and improving itching and relieving skin pain as quickly as possible, avoiding potential long-term consequences of the sensitization process.

Reduced graphene oxide-reinforced tricalcium phosphate/gelatin/chitosan light-responsive scaffolds for application in bone regeneration.

Bone is a mineralized tissue with the intrinsic capacity for constant remodeling. Rapid prototyping techniques, using biomaterials that mimic the bone native matrix, have been used to develop osteoinductive and osteogenic personalized 3D structures, which can be further combined with drug delivery and phototherapy. Herein, a Fab@Home 3D Plotter printer was used to promote the layer-by-layer deposition of a composite mixture of gelatin, chitosan, tricalcium phosphate, and reduced graphene oxide (rGO). The phototherapeutic potential of the new NIR-responsive 3D_rGO scaffolds was assessed by comparing scaffolds with different rGO concentrations (1, 2, and 4 mg/mL). The data obtained show that the rGO incorporation confers to the scaffolds the capacity to interact with NIR light and induce a hyperthermy effect, with a maximum temperature increase of 16.7 °C after under NIR irradiation (10 min). Also, the increase in the rGO content improved the hydrophilicity and mechanical resistance of the scaffolds, particularly in the 3D_rGO4. Furthermore, the rGO could confer an NIR-triggered antibacterial effect to the 3D scaffolds, without compromising the osteoblasts' proliferation and viability. In general, the obtained data support the development of 3D_rGO for being applied as temporary scaffolds supporting the new bone tissue formation and avoiding the establishment of bacterial infections.

In situ formation of alginic acid-gold nanohybrids for application in cancer photothermal therapy.

Gold-based nanoparticles present excellent optical properties that propelled their widespread application in biomedicine, from bioimaging to photothermal applications. Nevertheless, commonly employed manufacturing methods for gold-based nanoparticles require long periods and laborious protocols that reduce cost-effectiveness and scalability. Herein, a novel methodology was used for producing gold-alginic acid nanohybrids (Au-Alg-NH) with photothermal capabilities. This was accomplished by promoting the in situ reduction and nucleation of gold ions throughout a matrix of alginic acid by using ascorbic acid. The results obtained reveal that the Au-Alg-NHs present a uniform size distribution and a spike-like shape. Moreover, the nanomaterials were capable to mediate a temperature increase of ≈11°C in response to the irradiation with a near-infrared region (NIR) laser (808 nm, 1.7 W cm-2 ). The in vitro assays showed that Au-Alg-NHs were able to perform a NIR light-triggered ablation of cancer cells (MCF-7), being observed a reduction in the cell viability to ≈27%. Therefore, the results demonstrate that this novel methodology holds the potential for producing Au-Alg-NH with photothermal capacity and higher translatability to the clinical practice, namely for cancer therapy.

Updates on lung adenocarcinoma: invasive size, grading and STAS.

Advancements in the classification of lung adenocarcinoma have resulted in significant changes in pathological reporting. The eighth edition of the tumour-node-metastasis (TNM) staging guidelines calls for the use of invasive size in staging in place of total tumour size. This shift improves prognostic stratification and requires a more nuanced approach to tumour measurements in challenging situations. Similarly, the adoption of new grading criteria based on the predominant and highest-grade pattern proposed by the International Association for the Study of Lung Cancer (IASLC) shows improved prognostication, and therefore clinical utility, relative to previous grading systems. Spread through airspaces (STAS) is a form of tumour invasion involving tumour cells spreading through the airspaces, which has been highly researched in recent years. This review discusses updates in pathological T staging, adenocarcinoma grading and STAS and illustrates the utility and limitations of current concepts in lung adenocarcinoma.

Component-resolved diagnosis in childhood and prediction of asthma in early adolescence: A birth cohort study.

INTRODUCTION: Component-resolved diagnosis (CRD) has been decisive in exploring the mechanisms of IgE sensitization, but the predictive ability to detect asthma has not been addressed. We aim to develop and evaluate the performance of a personalized predictive algorithm for asthma that integrates information on allergic sensitization using CRD. METHODS: One thousand one hundred one twenty-five children from the Generation XXI birth cohort were randomly selected to perform a screening test for allergic sensitization and a subsample was characterized using CRD against 112 allergen components. Allergen components were analyzed using volcano plots and partial least squares (PLS) analysis. Logistic regression was performed to assess the associations between the obtained latent components (LC) and allergic outcomes (asthma, rhinitis, eczema) including other potential predictors used in previous asthma risk scores. The accuracy of the model in predicting asthma was assessed using Receiver Operating Characteristic (ROC) curve statistics. RESULTS: In the PLS, the first LC was positively associated with asthma, rhinitis, and eczema. This LC was mainly driven by positive weights for Der p 1/2/23, Der f 1/2, and Fel d 1. The main components in the second LC were pollen and food allergens. History of early wheezing and parental allergy were included in the predictive model and the area under the curve improved to 0.82. CONCLUSIONS: This is the first approach to improve the clinical applicability of CRD by combining CRD and clinical data to predict asthma at 13 years. Sensitization to distinct allergen molecules seems relevant to improve the accuracy of asthma prediction models.

BRIEF-A: Factor structure and measurement invariance across self-report and informant forms.

OBJECTIVE: This study analyzes the psychometric properties of the two forms (self-report and informant) of the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) in a sample of healthy Portuguese adults. METHOD: The participants were 608 adults, 304 of whom answered the self-report form (ages 18-59; 137 male and 167 female) and 304 who answered the informant form (ages 18-70; 110 male and 194 female). RESULTS: The internal consistency for the indexes and the Global Executive Composite was very good (≥.90), whereas for the scales they were either acceptable (between .70 and .80) or good (≥.80), except for the Inhibit scale in both forms. Confirmatory factor analysis was used to test seven competing factor models for each of the forms. The original two-factor model (Behavioral Regulation and Metacognition Indexes) showed a slightly better model fit than the three-factor model (Behavioral Regulation, Emotional Regulation, and Metacognition Indexes) in both forms. The multiple-group analysis of the two-correlated-factor model across forms was supported (configural, metric, and partial scalar invariance). CONCLUSIONS: Overall, the BRIEF-A showed adequate psychometric properties, suggesting that it is a useful instrument to assess everyday executive functioning in healthy Portuguese adults.