Browsing by Issue Date, starting with "2022-03-04"
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- Contribution to the evaluation of clinical prognostic factors in canine lymphomaPublication . Henriques, Joaquim José Garcia Pereira; Pascoal, Maria Paula Guerreiro Chaves; Almeida, José Manuel Pereira de; Cabeçadas, José Manuel Valente SequeiraNon-Hodgkin Lymphoma (NHL) is the most common hematopoietic cancer in dogs, from which up to 50% of the cases are diffuse large B-cell lymphomas (DLBCL). The etiology, like in humans, is believed to be multifactorial. To the date, the best response rate and best survival times are offered by a combination therapy including cyclophosphamide, vincristine, doxorubicin and prednisolone, known by the acronym of CHOP. Infectious agents, namely vector-borne agents (VBA), can induce chronic B cell stimulation and immune deregulation permitting lymphomagenesis. Also, there are several reports in literature associating NHL with VBA, namely from the genus Borrelia and Leishmania mimicking or co-existing with hematopoietic malignancies either in humans or dogs. Vector-borne agents can induce haematological and clinical changes in hosts that, when existing in cancer patients, can either mislead the interpretation of clinical signs or interfere with recognized prognostic markers, namely blood cell populations. Prognosis, after quality of life, is determinant in veterinary oncology to further proceed with a treatment. Short survival times and therapy response rates determine the option for a non standard-of-care treatment or, lately, animal euthanasia without treatment. Consequently, easy to perform, “bench-to-bedside” widely available and cost-effective prognostic markers are fundamental to obtain client financial compliance and support treatment planning and disease outcome. Obtaining serological results on vector-borne agents or haematological information trough a total blood cell count and biochemical parameters are widely available and cost effective either by an “in-house” laboratory or trough commercial laboratories. Having in mind the existing published literature on human medicine regarding haematological parameters as prognostic indicators in lymphoma and the scarse information on the veterinary field, we aimed to: 1) investigate the prevalence of infection by four vector-borne agents (Leishmania infantum, Ehrlichia canis, Anaplasma phagocytophilum and Bartonella henselae), its potential role in lymphomagenesis and its possible association with the tumour subtype and with the haematological alterations present in dogs with lymphoma and, 2) determine the prognostic value of dogs’ sex, neutered status, clinical stage, presence of anaemia, presence of neutrophilia, presence of thrombocytopenia and the ratios lymphocyte-to-monocyte (LMR), neutrophil-tolymphocyte (NLR), platelet-to-lymphocyte (PLR) and platelet-to-neutrophil (PNR) in canine DLBCL that were naïve for treatment, fully staged and received chemotherapy with a 19 week-CHOP protocol. All dogs tested negative for B. henselae, A. phagocytophilum and E. canis by both serology and molecular detection. Regarding L. infantum, 8,2% of the dogs had a positive serologic result. Leishmania infantum DNA was detected in two samples of diffuse large B-cell lymphoma (DLBCL). These results show an increased, but not significant, seropositivity (8,2%, p=0,201) and molecular detection (3,3%, p=0,166), for L. infantum in dogs with lymphoma, when compared to matched historic controls in the same geographical area. In the second study, PNR showed to be an independent prognostic marker (p≤0,001) for TTPR at 180 and 365 days. Dogs with a PNR above 0,032 were more likely to progress before 180 days (sensitivity 46,5%, specificity 87,5%, p=0,004). On univariate analysis, NLR showed a prognostic significance for LSSR at 180 (p=0,006) and 365 days (p=0,009). A baseline NLR value below 7,45 was positively associated with survival at 180 days (sensitivity of 52%, specificity of 85.3%, p=0.025). The presence of substage b, was associated with early lymphoma progression and decreased survival at 180 days (p =0.031). Anaemia significantly reduced LSSR at 365 days (p=0,028). Although it was not possible to identify, in the first study, any significant association between canine lymphoma and the studied VBA, it was of extreme importance for the discussion of the second study on the possible effects on peripheral blood cell dynamics caused by the CBVD studied. Further studies, following dogs trough their CVBD disease evolution, are worthwhile and may help clarify a possible role of these agents in lymphomagenesis. This is the first study evaluating PLR and PNR in canine DLBCL and demonstrates that PNR could be a predictor of early lymphoma progression. Since peripheral blood cell composition can be affected by several non-oncological causes, the development of larger multicenter studies with homogeneous inclusion criteria could help to better determine the true predictive values of blood cell ratios in dogs suffering from DLBCL treated with CHOP chemotherapy.
- Getting decision support from context-specific online social networks: a case studyPublication . Freire, Manuela; Antunes, Francisco; Costa, João PauloThe combination between online social networks (OSN) and decision processes provides a favorable social data analysis paradigm for efficient decision support and business-processes integration. This paper presents a framework for handling OSN’s contents, providing a simpler and effective approach for information retrieval and processing. The objective is to address a decision-making problem, by using that framework to extract, process, structure and analyze the OSN’s data. The decision process is not only guided by OSN data, but also by social network analysis methodology and is entirely based on the communications among social media users. Our framework combines two different, though complementary, perspectives: the analysis of the interactions among users and the semantic analysis of their discourses. In addition, it aims to bridge technology and manual-based approaches, thus enhancing the possibilities for making a better use of an OSN, using free-available software. The case study, herein, aims to estimate customers’ requests, solely based on their Facebook posts, showing that the unstructured data of the web’s discourse can be used to support this kind of decision processes.
- Optimization of chitosan-based nanosystems to deliver plasmid DNA vaccinesPublication . Rodolfo, Carlos Afonso; Sousa, Ângela Maria Almeida de; Costa, Diana Rita Barata; Ferreira, Helena Isabel Fialho Florindo RoqueCancer is the second leading cause of death worldwide and it is estimated that soon it could become the first. Cervical cancer is the fourth most common cancer among women worldwide and in underdeveloped countries, it is the most common cancer among women. This cancer is most often caused by the Human Papilloma Virus (HPV). The incidence of this cancer has decreased in countries with good health systems due to a vaccination and prevention programme against this virus. Currently, vaccines are based on viruslike particles constructed from the recombinant expression of the L1 protein, which belongs to the HPV capsid. However, existing vaccines are only preventive and have no th erapeutic effect if the vaccine is administered to a person who has previously contracted the infection. Currently , DNA vaccines constitute an innovative tool with great potential to help in the battle against viral infections or from other pathogens , and against various types of cancer. To deliver the DNA to eukaryotic cells, a delivery system must be created to protect, transport and deliver the DNA to the target cells. DNA vaccines aim to encode genes, characteristic of pathogens or cancer cells, in orde r to activate and generate specific immune responses. In this context, the development of a DNA vaccine encoding the HPV E7 oncoprotein, responsible for interfering with the tumour suppressor retinoblastoma protein, which is responsible for regulating the cell cycle of eukaryotic cells, may be an effective tool against HPV potential and therapeuticinduced cervical cancer, due to its preventive effects. To maximise the efficiency of these vaccines, the development of an appropriate delivery system is critic al. Thus, the present work was based on the optimization of the formulation of delivery systems based on the chitosan polymer, and four types of chitosan with different molecular weights were explored: high molecular weight chitosan (HMW, 200500 kDa), low molecular weight (LMW, 50 to formulate the systems was the 190 kDa), 20 kDa and 5 kDa. The technique used ionotropic gelation, based on ionic crosslinking. The nanoparticle formulation resulted from the interaction positively charg ed chitosan polymers, and the established negatively charged between the crosslinker sodium tripolyphosphate (TPP) and the plasmid DNA (pADN), encoding mutated E7. The inclusion of TPP aims to compact the formed nanoparticles and increase their stability , thus favouring a more de fined round shape. To achieve the best delivery systems, a design of experiments (DoE) tool was used. This tool allowed combining several parameters/inputs simultaneously (chitosan and TPP concentrations) to obtain the optimal formulation conditions of the systems based on the chosen responses (size, polydispersity index (PDI) and zeta potential). After performing the proposed tests and characterizing the properties of the obtained formulations, the respective responses were introduced in the DoE program an d a statistical analysis was performed. The linear and quadratic models obtained were statistically significant (pvalue <0,05) and the "lack of al points for each chi fit" was not significant, with an adequate determination coefficient. The predicted optim tosan polymer were all successfully validated. Subsequently, further studies were conducted to evaluate the properties of the delivery systems formulated with the conditions defined at the optim al points. Scanning electron microscopy (SEM) analyses were performed to evaluate the morphology, Fourier transform infrared spectroscopy was used to evaluate the chemical properties and specific functional groups, while different stability tests were perfor med to evaluate the strength and DNA release, and finally cytotoxicity tests were performed to ensure the biocompatibility of the chitosan nanoparticles. The four delivery systems developed , presented satisfactory characteristics , such as spherical or oval stability and strength, DNA retention and good biocompatibility. nanoparticles, good In this sense, the DoE tool proved to be a powerful tool to explore and tailor the characteristics of chitosan/TPP/pADN nanosystems, allowing the development of a system suitable for the encapsulation, transport and delivery of pADN, thus providing the advancement of the DNA vaccine delivery research field.