Adjuvant Immunotherapy in High-Risk Muscle-Invasive Urothelial Cancer: An Updated Meta-Analysis of Randomized Controlled Trials.

Introduction: Neoadjuvant cisplatin-based chemotherapy followed by radical surgery is the standard treatment for muscle-invasive urothelial carcinoma (MIUC). The Checkmate-274 and AMBASSADOR trials have demonstrated improvements in disease-free survival (DFS) with adjuvant immunotherapy. Consequently, this meta-analysis aimed to assess the effectiveness of strategies involving checkpoint inhibitors in managing high-risk MIUC.

Portuguese Lipid Study (e_LIPID).

: Incidence of cardiovascular disease (CVD) is increasing in low- and middle-income countries because of changing lifestyles. Since dyslipidaemia is a major independent cardiovascular risk factor, its correct identification is critical to implement specific interventions for CVD prevention. This study aimed to characterise the lipid profile of the Portuguese population.

Structure of tetrameric forms of the serotonin-gated 5-HT3 receptor ion channel.

Multimeric membrane proteins are produced in the endoplasmic reticulum and transported to their target membranes which, for ion channels, is typically the plasma membrane. Despite the availability of many fully assembled channel structures, our understanding of assembly intermediates, multimer assembly mechanisms, and potential functions of non-standard assemblies is limited. We demonstrate that the pentameric ligand-gated serotonin 5-HT3A receptor (5-HT3AR) can assemble to tetrameric forms and report the structures of the tetramers in plasma membranes of cell-derived microvesicles and in membrane memetics using cryo-electron microscopy and tomography.

Immunotherapy Plus Chemotherapy Versus Chemotherapy Alone as First-Line Treatment for Advanced Urothelial Cancer: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Platinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC.

Generation and validation of a classification model to diagnose familial hypercholesterolaemia in adults.

Background And Aims: The early diagnosis of familial hypercholesterolaemia is associated with a significant reduction in cardiovascular disease (CVD) risk. While the recent use of statistical and machine learning algorithms has shown promising results in comparison with traditional clinical criteria, when applied to screening of potential FH cases in large cohorts, most studies in this field are developed using a single cohort of patients, which may hamper the application of such algorithms to other populations. In the current study, a logistic regression (LR) based algorithm was developed combining observations from three different national FH cohorts, from Portugal, Brazil and Sweden.

High-Throughput Microscopy Characterization of Rare Variants.

Familial hypercholesterolemia (FH) is the most common inherited life-threatening disorder of lipid metabolism. Early diagnosis and treatment are the key to reduce the cumulative life-long cardiovascular burden of patients with FH. The high number of variants described as variants of unknown significance is the largest obstacle to achieve a definitive FH diagnosis.

The Hypocholesterolemic Potential of the Edible Algae : Proteomic and Quantitative PCR Analysis.

A brown seaweed consumed worldwide, , has been used to prevent atherosclerosis and hypercholesterolemia, among other uses. However, the mechanisms of action that lead to these effects are not yet fully understood. This work aims to study the in vitro effect of an aqueous extract of , previously characterized as rich in phlorotannins and peptides, on the expression of different proteins involved in the synthesis and transport of cholesterol.

Comparative study on the performance of different classification algorithms, combined with pre- and post-processing techniques to handle imbalanced data, in the diagnosis of adult patients with familial hypercholesterolemia.

Familial Hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism. Current criteria for FH diagnosis, like Simon Broome (SB) criteria, lead to high false positive rates. The aim of this work was to explore alternative classification procedures for FH diagnosis, based on different biological and biochemical indicators.

Disparities in Stroke Patient-Reported Outcomes Measurement Between Healthcare Systems in Brazil.

Introduction: Acute stroke interventions, such as stroke units and reperfusion therapy, have the potential to improve outcomes. However, there are many disparities in patient characteristics and access to the best stroke care. Thus, we aim to compare patient-reported outcome measures (PROMs) after stroke in two stroke centers representing the public and private healthcare systems in Brazil.

Functional profiling of LDLR variants: Important evidence for variant classification: Functional profiling of LDLR variants.

Background: Familial Hypercholesterolemia (FH) is a semidominant disorder of the lipid metabolism associated with premature atherosclerosis and coronary heart disease. So far, about 3,000 unique LDLR variants have been described, most of which lack functional evidence proving their effect on LDLR function, despite the important role that functional studies play in variant classification.

Objective: In this work, we aimed to functionally characterize 13 rare missense variants, identified worldwide and in Portugal, in clinical FH patients.

Performance comparison of different classification algorithms applied to the diagnosis of familial hypercholesterolemia in paediatric subjects.

Familial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, characterized by increased low density lipoprotein cholesterol (LDLc) levels. The main purpose of the current work was to explore alternative classification methods to traditional clinical criteria for FH diagnosis, based on several biochemical and biological indicators. Logistic regression (LR), decision tree (DT), random forest (RF) and naive Bayes (NB) algorithms were developed for this purpose, and thresholds were optimized by maximization of Youden index (YI).

Klebsiella-induced infections in domestic species: a case-series study in 697 animals (1997-2019).

Klebsiella species, particularly K. pneumoniae, are well-known opportunistic enterobacteria related to complexity of clinical infections in humans and animals, commonly refractory to conventional therapy. The domestic animals may represent a source of the pathogenic and multidrug-resistant Klebsiella species to humans.

Applicability of Martin-Hopkins formula and comparison with Friedewald formula for estimated low-density lipoprotein cholesterol in e_COR study population.

Introduction: Low-density lipoprotein cholesterol (LDL) is essential in managing cardiovascular disease risk. Since 1972, the Friedewald formula has been used to estimate LDL concentration, although with some limitations. In 2013, Martin et al.

Characterization of Two Variants at Met 1 of the Human Gene Encoding the Same Amino Acid but Causing Different Functional Phenotypes.

Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, characterized by increased levels of total and LDL plasma cholesterol, which leads to premature atherosclerosis and coronary heart disease. FH phenotype has considerable genetic heterogeneity and phenotypic variability, depending on LDL receptor activity and lifestyle. To improve diagnosis and patient management, here, we characterized two single nucleotide missense substitutions at Methionine 1 of the human gene (c.

Applicability of Martin-Hopkins formula and comparison with Friedewald formula for estimated low-density lipoprotein cholesterol in e_COR study population.

Introduction: Low-density lipoprotein cholesterol (LDL) is essential in managing cardiovascular disease risk. Since 1972, the Friedewald formula has been used to estimate LDL concentration, although with some limitations. In 2013, Martin et al.

LDLR variants functional characterization: Contribution to variant classification.

Background And Aims: Familial hypercholesterolaemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. LDLR mutations are the cause of disease in 90% of the cases but functional studies have only been performed for about 15% of all LDLR variants. In the Portuguese Familial Hypercholesterolemia Study (PFHS), 142 unique LDLR alterations were identified and 44 (30%) lack functional characterization.

Metabolic Dysfunction and Asthma: Current Perspectives.

The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed.

Phenotypical, Clinical, and Molecular Aspects of Adults and Children With Homozygous Familial Hypercholesterolemia in Iberoamerica.

Objective: Characterize homozygous familial hypercholesterolemia (HoFH) individuals from Iberoamerica. Approach and Results: In a cross-sectional retrospective evaluation 134 individuals with a HoFH phenotype, 71 adults (age 39.3±15.

Compliance of indoor air quality during sleep with legislation and guidelines - A case study of Lisbon dwellings.

This study aimed to provide a comprehensive characterisation of the indoor air quality during the sleeping period of 10 couples at Lisbon dwellings, using a multi-pollutant approach, and to understand how the compliance with legislation and guidelines was to assure a good indoor air quality. The assessment of indoor air quality was conducted in the cold season using real time monitors during the sleeping period for comfort parameters (temperature and relative humidity) and air pollutants (carbon dioxide - CO, carbon monoxide - CO, formaldehyde - CHO, total volatile organic compounds - VOCs, and particulate matter - PM and PM), together with active sampling of bioaerosols (fungi and bacteria) before and after the sleeping period. Lower compliance (less than 50% of the cases) with the Portuguese legislation was found for temperature, CO (3440 ± 1610 mg m), VOCs (1.

Prevalence and risk factors of fatty liver in Portuguese adults.

Background: Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period.

Materials And Methods: A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years).