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PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex.

Coronary artery calcification (CAC) is a well-known cardiovascular risk factor. In the last year, the CAC score has been investigated in lung cancer (LC) screening, showing promising results in terms of mortality risk assessment. Nevertheless, its role in LC patients has still to be investigated. This study aims to evaluate the performance of a fully automated CAC scoring alone and combined with a prognostic index based on perioperative Routine Blood Tests (RBT) in predicting 5-year survival of patients with stage I LC.

The characteristics of formation waters play a crucial role in production development projects within Pre-Salt oil fields in the Santos Basin, offshore southeastern Brazil. This study investigated the compositional variations of brines of the Búzios Field (northeast of the Santos Basin), proposing for the first time an extensive hydrochemical mapping of the Pre-Salt aquifers and identifying nuances of connectivity. A comprehensive methodology was employed, including analysis of pressure gradients, cluster analysis, and hydrogeochemical modeling to classify different types of brine and understand their behavior under reservoir conditions. A hydrochemical classification routine was applied to 129 formation water samples, identifying seven distinct clusters using the unsupervised k-means algorithm. This clustering process efficiently differentiated representative, non-representative, and contaminated samples. The hydrochemical composition of the formation waters varied among the four hydraulic compartments identified in the field, with their boundaries defined by permeability barriers. Compared with the central portion of the field (regional aquifer), where salinities predominantly range from 155,000 to 185,000 mg/L of NaCl, enrichment of specific ions was observed at the field's extremities, such as boron (northeast), barium and lithium (north), and bicarbonate (west). These hydrochemical differences lead the brine salinities at the field's extremities to exceed 225,000 mg/L of NaCl. Hydrogeochemical modeling provided insights into the pH levels of each brine under reservoir conditions, showing a decrease of between 23 and 32% compared to surface pH values. The speciation analysis showed positive strontianite and barite saturation indices in certain types of formation water, indicating potential precipitation. These areas are considered critical for inorganic scaling in production equipment.

AbstractIt is known that adverse stimuli, such as altered diets during pregnancy and lactation,can result in deleterious effects on the progeny. The aim of this study was to evaluate the possible gastrointestinal repercussions in the offspring of Wistar rats exposed to high-fat diets. Pregnant rats were divided into three groups: normolipidic diet (3.5% lipids), a diet containing 28% lipids, and a diet with 40% lipids. Body weight and food, water, daily caloric, and macronutrient intake were evaluated in the pregnant rats. Structural and functional gastrointestinal parameters were assessed in 30-day-old male pups. Depending on the lipid content of the maternal diet, the pups may exhibit gastric mucosal thickening, an increase in the relative weight of the small intestine, a reduction in the jejunal and ileal mucosa, and a decrease in the total thickness of the ileum. Additionally, there may be a reduction in the number of villi per area in these organs and a thinning of the muscular layer in the large intestine. The structural changes induced by the maternal high-fat diet seem to reduce the stomach’s sensitivity to ethanol-induced ulcers, which is the only functional alteration observed. Therefore, the offspring of dams exposed to high-fat diets during pregnancy and lactation exhibits impaired gastrointestinal development, with alterations depending on dietary fat content and specific gastrointestinal regions. Structural changes did not always result in functional abnormalities and, in some cases, appeared protective. The long-term consequences of the observed morphological alterations require further investigation.

AbstractAccumulating evidence suggests that maternal overnutrition can result in a higher development risk of obesity and renal disease in the offspring’s adulthood. The present study tested different lipid levels in the maternal diet during pregnancy and lactation and its repercussions on the offspring of Wistar rats. Offspring of 1, 7, 30 and 90-d-old were divided into the following groups: Control (CNT) – offspring of dams that consumed a standard chow diet (3.5% of lipids); Experimental 1 (EXP1) – offspring of dams exposed to a high-fat diet (HFD) (28% of lipids); and Experimental 2 (EXP2) – offspring of dams exposed to a HFD (40% of lipids). Regarding maternal data, there was a decrease in the amount of diet ingested by EXP2. Daily caloric intake was higher in EXP1, while protein and carbohydrate intakes were lower in EXP2. While lipid intake was higher in the experimental groups, EXP1 consumed more lipids than EXP2, despite the body weight gain being higher in EXP2. Adult offspring from EXP1 presented higher blood glucose. Regarding morphometric analysis, in both experimental groups, there was an increase in the glomerular tuft and renal corpuscle areas, but an increase in the capsular space area only in EXP1. There was a decrease in the glomerular filtration rate (GFR) in EXP1, in contrast to an increase in GFR of EXP2, along with an increase in urinary protein excretion. In conclusion, the maternal HFDs caused significant kidney damage in offspring, but had different repercussions on the type and magnitude of recorded change.

A large number of research efforts have been made in trying to solve global decision problems with cellular automata by means of their cells reaching a distributed consensus via their local action. Among them, the determination of the most frequent state in configurations with arbitrary size, i.e., the density classification task, has been the most widely approached benchmark problem. The literature abounds with cases demonstrating that, depending on how it is formulated, a solution can be shown to exist or not. Here we address the problem in terms of deterministic, block-sequential asynchronous updates, over cyclic configurations, by which the possibility of a solution remains open. Our main results are negative in terms of the possibility of solving the problem with such formulation, encompassing the cases of any cellular automaton with any sequential update, and any elementary cellular automaton with any block-sequential update; furthermore, we uncover some properties that any potential solution with block-sequential update should have in order for it to be a candidate to solving the problem. Incidentally, we also give a new, very simple proof of the impossibility of solving the problem with any synchronous rule. • The solvability of the DCT by CAs under block-sequential updates is addressed • The DCT cannot be solved by any binary CA under a fully sequential update. • No elementary CA is capable of solving the DCT for any block-sequential update. • Conditions for a CA to solve the DCT under some block-sequential update are supplied. [ABSTRACT FROM AUTHOR]

Purpose: Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 17 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH). Methods: Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase(TPO)and Dual Oxidase 2(DUOX2)genes. A custom panel targeting 7 genes associated with TDH [(TPO), Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), DUOX2, Dual Oxidase Maturation Factor 2(DUOXA2), Solute Carrier Family 5 Member 5(SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants. Results: Four novel variants have been identified, two in TPO: c.2749-2 A > C and c.2752_2753delAG, [p.Ser918Cysfs*62] and two variants in DUOX2gene: c.425 C > G [p.Pro142Arg] and c.2695delC [p.Gln899Serfs*21]. Eighteen identified TPO, DUOX2and IYDvariants were previously described. We identified potentially pahogenic biallelic variants in TPOand DUOX2in 7 and 2 patients, respectively. We also detected a potentially pathogenic monoallelic variant in TPOand DUOX2in 7 and 1 patients respectively. Conclusions: 22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.

Background: To assess the prevalence of frailty by the Clinical Frailty Scale (CFS) and the 5-item FRAIL scale and their association with hospitalization in hemodialysis (HD) patients. Methods: This was a prospective observational study. We included patients of both genders ≥ 18 years old in HD treatment for at least 3 months. Demographic, clinical, and routine laboratory data were retrieved from the medical charts. Two different frailty assessment tools were used, the CFS and the FRAIL scale. Participants were followed up for 9 months and hospitalizations for all causes were evaluated. A Venn diagram was constructed to show the overlap of possible frailty and pre-frailty. Cox regression was used to identify the association between frailty and hospitalization. The significance level was 5%. Results: A total of 137 subjects were included in the analysis. The median age was 61 (52–67) years and 60% were male. The hospitalization rate and mortality in 9 months were 22.6% and 7.29%, respectively. Regarding frailty, the overall prevalence was 13.8% assessed by CFS and 36.5% according to the FRAIL scale. In the Cox regression, frailty by FRAIL scale was associated with a 2.8-fold increase in the risk of hospitalization (OR = 2.880; 95% CI = 1.361–6.096; p= 0.006), but frailty assessed by the CFS was not associated with the need for hospitalization. Conclusion: In HD patients, the FRAIL scale proved to be an easy-to-apply tool, identifying a high prevalence of frailty and being a predictor of hospital admission. Graphical abstract: