Second primitive malignant tumour in patients with gynaecological cancer

OBJECTIVE: The purpose of this study was to characterise the occurrence of multiple primitive gynaecological malignant neoplasias, restricted to the genital tract and breast or associated with other organs, and to detect which types of association are most frequent concerning location, histology and staging. POPULATION AND METHODS: The records of patients with gynaecological cancer at the Portuguese Institute of Oncology--Lisbon Centre, between 1986 and 1993 were used in this study. RESULTS: Of the 10,746 women with gynaecological cancer, 91 (0.8%) were found to have a second primitive malignant neoplasia. Of these neoplasias, 64% (58 cases) were also located at a gynaecological site. The most frequent associations were endometrium/breast (13 cases), bilateral breast (12 cases) and ovary/endometrium (11 cases). The majority of primitive multiple gynaecological tumours were synchronous. Regarding gynaecological cancer and non-gynaecological cancer, in 28 cases (31%), the most common non-gynaecological location was the colon/rectum. Five patients had triple tumours. CONCLUSION: Although these situations are relatively rare the possibility of multiple primitive cancers should be considered with the presence of malignant tumours in two or more organs. This distinction between multiple primitive or metastatic cancers could be important for treatment as well as prognosis.     

Neural Network and Classification Approach in Identifying Customer Behavior in the Banking Sector: A Case Study of an International Bank

The customer relationship focus for banks is in development of main competencies and strategies of building strong profitable customer relationships through considering and managing the customer impression, influence on the culture of the bank, satisfactory treatment, and assessment of valued relationship building. Artificial neural networks (ANNs) are used after data segmentation and classification, where the designed model register records into two class sets, that is, the training and testing sets. ANN predicts new customer behavior from previously observed customer behavior after executing the process of learning from existing data. This article proposes an ANN model, which is developed using a six‐step procedure. The back‐propagation algorithm is used to train the ANN by adjusting its weights to minimize the difference between the current ANN output and the desired output. An evaluation process is conducted to determine whether the ANN has learned how to perform. The training process is halted periodically, and its performance is tested until an acceptable result is obtained. The principles underlying detection software are grounded in classical statistical decision theory.     

Fast computation of minimal elementary decompositions of metabolic flux vectors

The concept of elementary flux vector is valuable in a number of applications of metabolic engineering. For instance, in metabolic flux analysis, each admissible flux vector can be expressed as a non-negative linear combination of a small number of elementary flux vectors. However a critical issue concerns the total number of elementary flux vectors which may be huge because it combinatorially increases with the size of the metabolic network. In this paper we present a fast algorithm that randomly computes a decomposition of admissible flux vectors in a minimal number of elementary flux vectors without explicitly enumerating all of them.     

Exploring different technological platforms for supporting co-located collaborative games in the classroom

Computer Supported Collaborative Learning is a pedagogical approach that can be used for deploying educational games in the classroom. However, there is no clear understanding as to which technological platforms are better suited for deploying co-located collaborative games, nor the general affordances that are required. In this work we explore two different technological platforms for developing collaborative games in the classroom: one based on augmented reality technology and the other based on multiple-mice technology. In both cases, the same game was introduced to teach electrostatics and the results were compared experimentally using a real class.     

Insights into the Pharmacokinetics and In Vitro Cell-Based Studies of the Imidazoline I2 Receptor Ligand B06

The impact of neurodegenerative diseases (ND) is becoming unbearable for humankind due to their vast prevalence and the lack of efficacious treatments. In this scenario, we focused on imidazoline I₂ receptors (I₂-IR) that are widely distributed in the brain and are altered in patients with brain disorders. We took the challenge of modulating I₂-IR by developing structurally new molecules, in particular, a family of bicyclic α-iminophosphonates, endowed with high affinity and selectivity to these receptors. Treatment of two murine models, one for age-related cognitive decline and the other for Alzheimer’s disease (AD), with representative compound B06 ameliorated their cognitive impairment and improved their behavioural condition. Furthermore, B06 revealed beneficial in vitro ADME-Tox properties. The pharmacokinetics (PK) and metabolic profile are reported to de-risk B06 for progressing in the preclinical development. To further characterize the pharmacological properties of B06, we assessed its neuroprotective properties and beneficial effect in an in vitro model of Parkinson’s disease (PD). B06 rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine (6-OHDA) and showed a crucial anti-inflammatory effect in a cellular model of neuroinflammation. This research reveals B06 as a putative candidate for advancing in the difficult path of drug discovery and supports the modulation of I₂-IR as a fresh approach for the therapy of ND.     

The influence of Elfreda Chatman’s theories: a citation context analysis

The range of theoretical frameworks currently being used by researchers into information behaviour is abundant and diverse. We need to examine thoroughly the contribution of theories and models to further research, as this would help to improve future investigations in the field. This paper adopts this approach, by thoroughly examining the influence that Elfreda Chatman’s three middle-range theories have had on subsequent research. A citation context analysis was carried out on the basis of those received by Information poverty theory, life in the round theory and normative behaviour theory. Analysis covered the year of publication, the type of work and the subject-matter of the citing documents. The cites in context or theoretical incidents were analysed for frequency of citation in citing documents, the content of Chatman’s work being cited, the context co-citation analysis, the citation style and the citation location. The analysis of citation in context has allowed us to draw a distinction between the author and her work, while verifying that not all cites are the same. These differences reflect the unequal relevance of these theories to subsequent research.

     

Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib,Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation

Telomere shortening is the main molecular mechanism of aging, but not the only one. The adaptive immune system also ages, and older organisms tend to develop a chronic pro-inflammatory status with low-grade inflammation characterized by chronic activation of the innate immune system, called inflammaging. One of the main stimuli that fuels inflammaging is a high nutrient intake, triggering a metabolic inflammation process called metainflammation. In this study, we report the anti-inflammatory activity of several senolytic drugs in the context of chronic inflammation, by using two different zebrafish models: (i) a chronic skin inflammation model with a hypomorphic mutation in spint1a, the gene encoding the serine protease inhibitor, kunitz-type, 1a (also known as hai1a) and (ii) a non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) model with inflammation induced by a high-fat diet. Our results show that, although these models do not manifest premature aging, the senolytic drugs dasatinib, navitoclax, and venetoclax have an anti-inflammatory effect that results in the amelioration of chronic inflammation.     

Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB

Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm , whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC₉₉ values ranging from 0.4 to 2.0 μm . In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.