RESUMO
MOTIVATION: Vaccines represent the most effective and cost-efficient weapons against a wide range of diseases. Nowadays new generation vaccines based on subunit antigens reduce adverse effects in high risk individuals. However, vaccine antigens are often poor immunogens when administered alone. Adjuvants represent a good strategy to overcome such hurdles, indeed they are able to: enhance the immune response; allow antigens sparing; accelerate the specific immune response; and increase vaccine efficacy in vulnerable groups such as newborns, elderly or immuno-compromised people. However, due to safety concerns and adverse reactions, there are only a few adjuvants approved for use in humans. Moreover, in practice current adjuvants sometimes fail to confer adequate stimulation. Hence, there is an imperative need to develop novel adjuvants that overcome the limitations of the currently available licensed adjuvants. RESULTS: We developed a computational framework that provides a complete pipeline capable of predicting the best citrus-derived adjuvants for enhancing the immune system response using, as a target disease model, influenza A infection. In silico simulations suggested a good immune efficacy of specific citrus-derived adjuvant (Beta Sitosterol) that was then confirmed in vivoAvailability: The model is available visiting the following URL: http://vaima.dmi.unict.it/AdjSim CONTACT: francesco.pappalardo@unict.it; fp@francescopappalardo.net.
Assuntos
Adjuvantes Imunológicos , Citrus , Sistema Imunitário , Vacinas contra Influenza , Idoso , Antígenos , Previsões , Humanos , Hospedeiro Imunocomprometido , Recém-Nascido , Modelagem Computacional Específica para o PacienteRESUMO
BACKGROUND: The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. METHODOLOGY: We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. RESULTS: The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). CONCLUSION: The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities.