Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab

Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.Agência financiadora Merck Sharp and Dohme, Lda, Portugal MK8259-22info:eu-repo/semantics/publishedVersio

Pharmacokinetics of Carboplatin in Combination with Low-Dose Cyclophosphamide in Female Dogs with Mammary Carcinoma

This prospective study aimed to evaluate the effect of metronomic cyclophosphamide on carboplatin’s tolerability, efficacy, and pharmacokinetics in dogs with mammary carcinoma. Sixteen female dogs with mammary carcinoma were divided into groups: 300 mg/m2 intravenous (i.v.) carboplatin therapy (G1 = 8) or 300 mg/m2 i.v. carboplatin which was associated with 12.5 mg/m2 oral cyclophosphamide in a metronomic regimen (G2 = 8). The investigated animals underwent a clinical evaluation, a mastectomy, a carboplatin chemotherapy, and serial blood sampling for the pharmacokinetic analysis. The adverse events and survival rates were monitored. A non-compartmental analysis was applied to calculate the pharmacokinetic parameters of carboplatin in the 2nd and 4th chemotherapy cycles. Carboplatin PK showed high interindividual variability with a 10-fold variation in the area under the plasma concentration–time curve (AUC) in G1. The systemic plasma exposure to carboplatin was equivalent in both of the treatments considering the AUC and maximum plasma concentration (Cmax) values. Although the red blood cells (p < 0.0001), platelets (p = 0.0005), total leukocytes (p = 0.0002), and segmented neutrophils (p = 0.0007) were reduced in G2, the survival rate increased (p = 0.0044) when it was compared to G1. In conclusion, adding low daily doses of cyclophosphamide to a carboplatin therapy showed promising outcomes in female dogs with mammary tumors

Extracellular vesicles from pancreatic cancer stem cells lead an intratumor communication network (EVNet) to fuel tumour progression

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Objective: Intratumor heterogeneity drives cancer progression and therapy resistance. However, it has yet to be determined whether and how subpopulations of cancer cells interact and how this interaction affects the tumour. Design: We have studied the spontaneous flow of extracellular vesicles (EVs) between subpopulations of cancer cells: cancer stem cells (CSC) and non-stem cancer cells (NSCC). To determine the biological significance of the most frequent communication route, we used pancreatic ductal adenocarcinoma (PDAC) orthotopic models, patient-derived xenografts (PDXs) and genetically engineered mouse models (GEMMs). Results: We demonstrate that PDAC tumours establish an organised communication network between subpopulations of cancer cells using EVs called the EVNet). The EVNet is plastic and reshapes in response to its environment. Communication within the EVNet occurs preferentially from CSC to NSCC. Inhibition of this communication route by impairing Rab27a function in orthotopic xenographs, GEMMs and PDXs is sufficient to hamper tumour growth and phenocopies the inhibition of communication in the whole tumour. Mechanistically, we provide evidence that CSC EVs use agrin protein to promote Yes1 associated transcriptional regulator (YAP) activation via LDL receptor related protein 4 (LRP-4). Ex vivo treatment of PDXs with antiagrin significantly impairs proliferation and decreases the levels of activated YAP.Patients with high levels of agrin and low inactive YAP show worse disease-free survival. In addition, patients with a higher number of circulating agrin+ EVs show a significant increased risk of disease progression. Conclusion: PDAC tumours establish a cooperation network mediated by EVs that is led by CSC and agrin, which allows tumours to adapt and thrive. Targeting agrin could make targeted therapy possible for patients with PDAC and has a significant impact on CSC that feeds the tumour and is at the centre of therapy resistance.The work was supported by NORTE-01–0145-FEDER-000029, Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund and national funds through FCT—Foundation for Science and Technology POCI-01–0145-FEDER-32189. Programa Operacional Regional do Norte and co-financed by European Regional Development Fund under the project "The Porto Comprehensive Cancer Center" with the reference NORTE-01-0145-FEDER-072678 - Consórcio PORTO.CCC – Porto.Comprehensive Cancer Center. CFR is supported by FCT (SFRH/BD/131461/2017), NB by (SFRH/BD/130801/2017), IB by FCT (SFRH/BD/144854/2019), and BA by FCT (PD/BD/135546/2018). DG’s contribution was supported by the NCI (R21 CA179907). We acknowledge the support of the i3S Scientific Platforms: Translational Cytometry, Animal Facility, Bioimaging and Histology and Electron Microscopy are members of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01–0145-FEDER-022122). Proteomics was performed at the Proteomics Facility of The Spanish National Center for Biotechnology (CNB-CSIC), ProteoRed, PRB3-ISCIII, supported by grant PT17/0019.info:eu-repo/semantics/publishedVersio

Resíduos de serviços de saúde – RSS, o caso da região norte / Waste from health services - RSS, the case of the northern region

Na atualidade, o manejo deficiente dos RSS é um problema de saúde pública, acarretando complicações tanto para a saúde ambiental como para a saúde da população. Neste contexto elaborou-se esta pesquisa na Região Norte, com objetivo de diagnosticar os índices de produção e descarte de RSS e verificar a influência político ambiental entre os anos de 2014 a 2018 na gestão/gerenciamento desses resíduos. A coleta dos dados secundários foi efetuada a partir de acesso a plataforma de dados livres do Panorama dos Resíduos Sólidos no Brasil publicado pela Associação Brasileira de Empresas de Limpeza Pública e Resíduos Especiais – ABRELPE. Foi efetuada uma análise quantiqualitativa dos RSS e da geração per capta na região norte entre os anos de 2014 a 2018, além de analisar os tipos de disposição final dada a estes resíduos. Os dados obtidos também indicaram que 2015 e 2017 foram os anos que corresponderam a maiores produções de RSS e em 2018 esse valor foi o menor dos cinco anos em questão. Além disso, a média da produção destes resíduos foi decrescente desde 2014 até 2018 de 2014 e 2018, todos os Estado objetos desta pesquisa apresentaram queda na produção percapta destes resíduos, com destaque para Roraima (-0,100 kg). A destinação ou disposição final do RSS ainda continua sendo um desafio na Região Norte, uma vez que entre 2014 e 2018 a maior proporção desses resíduos receberam outras formas de disposição final além de Incineração e Autoclave, o que induz ainda a práticas irregulares deste processo. Dessa forma, é necessária a mobilização dos gestores públicos municipais de saúde juntamente com os gestores dos serviços e demais profissionais atuantes em órgãos ambientais para que seja efetivada políticas públicas voltadas a sensibilização dos profissionais na prática eficiente nos planos de gerenciamento desses resíduos

A lógica fuzzy no estudo da qualidade da água do rio Uraim Paragominas-PA / The fuzzy logic in the study of water quality in the Uraim Paragominas- PA

A preservação da qualidade das águas é um fator importante para o equilíbrio aquático e para o abastecimento da população que utiliza o corpo hídrico. Esta pesquisa justifica-se pela influência do regime pluviométrico sobre os corpos hídricos com alterações dos parâmetros físico-químicos destes, que interferem diretamente na qualidade da água dos rios e podem ser ocasionadas por diferentes fatores, como o aumento ou diminuição do índice de chuvas de uma região. Nesse sentido o objetivo deste trabalho é fazer um estudo da influência do índice pluviométrico do município de Paragominas-PA nos parâmetros pH, Turbidez, Cor e DBO das águas do rio Uraim utilizando para isso, o software MATrix LABoratory - MATLAB. Quanto ao método, ele foi hipotético-dedutivo, com isso a pesquisa torna-se observativa, sistemática, direta, com caráter exploratório. Os dados obtidos indicaram forte relação entre as variáveis analisadas, que entre os parâmetros hídricos o pH sofre interferências de parâmetros como a turbidez, cor, DBO, especialmente no período chuvoso. Além disso, devido a decomposição do material orgânico e a alta produtividade de algas presentes na água, influencia no aumento de microrganismos fotossintetizantes no recurso hídrico elevando as taxas de gás carbônico (CO2). Com uma base de dados consistente no que tange os índices pluviométricos do município de Paragominas e alguns parâmetros relacionados com a qualidade da agua do rio Uraim, observou-se a importância do uso de ferramentas computacionais para avaliação e verificação dos parâmetros da qualidade da agua. 

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

A motion tracking solution for indoor localization using smartphones

As sensor-rich mobile devices became a commodity, more opportunities appeared for the creation of location-aware services. While GPS is a well established solution for outdoor localization, there is still no standard solution for localization indoors. This paper presents a novel accurate indoor positioning mechanism that is meant to run in common smartphones to be a readily and widely available solution. The system is based on multiple gait-model based filtering techniques for accurate movement quantification in combination with an advanced fused positioning mechanism that leverages sequences of opportunistic observations towards an accurate localization process. Magnetic field fluctuations, Wi-Fi readings and movement data are incrementally matched with a feature spot map containing multi-dimensional spatially-related features that characterize the building. A novel and convenient way of mapping the architectural and environmental properties of buildings is also introduced, which avoids the burden normally associated with the process. The system has been evaluated by multiple users in open and crowded spaces where overall median localization errors between 1.11 m and 1.68 m were obtained. While the reported errors are already satisfactory in the context of indoor localization, improvements may be readily achieved through the inclusion of additional reference features. High accuracy performance coupled with an opportunistic and infrastructure-free approach creates a very desirable solution for the indoor localization market doge