Funzioni speciali e applicazioni

In questa tesi viene presentato uno studio dell'equazione ipergeometrica, dell'equazione di Legendre e delle proprietà delle loro soluzioni. Infine vengono presentate alcune tra le possibili applicazioni di tali equazioni.

Long Non-Coding RNAs as Molecular Signatures for Canine B-Cell Lymphoma Characterization

Background: Diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) and follicular lymphoma (FL) are the most common B-cell lymphomas (BCL) in dogs. Recent investigations have demonstrated overlaps of these histotypes with the human counterparts, including clinical presentation, biologic behavior, tumor genetics, and treatment response. The molecular mechanisms that underlie canine BCL are still unknown and new studies to improve diagnosis, therapy, and the utilization of canine species as spontaneous animal tumor models are undeniably needed. Recent work using human DLBCL transcriptomes has suggested that long non-coding RNAs (lncRNAs) play a key role in lymphoma pathogenesis and pinpointed a restricted number of lncRNAs as potential targets for further studies. Results: To expand the knowledge of non-coding molecules involved in canine BCL, we used transcriptomes obtained from a cohort of 62 dogs with newly-diagnosed multicentric DLBCL, MZL and FL that had undergone complete staging work-up and were treated with chemotherapy or chemo-immunotherapy. We developed a customized R pipeline performing a transcriptome assembly by multiple algorithms to uncover novel lncRNAs, and delineate genome-wide expression of unannotated and annotated lncRNAs. Our pipeline also included a new package for high performance system biology analysis, which detects high-scoring network biological neighborhoods to identify functional modules. Moreover, our customized pipeline quantified the expression of novel and annotated lncRNAs, allowing us to subtype DLBCLs into two main groups. The DLBCL subtypes showed statistically different survivals, indicating the potential use of lncRNAs as prognostic biomarkers in future studies. Conclusions: In this manuscript, we describe the methodology used to identify lncRNAs that differentiate B-cell lymphoma subtypes and we interpreted the biological and clinical values of the results. We inferred the potential functions of lncRNAs to obtain a comprehensive and integrative insight that highlights their impact in this neoplasm

New molecular and therapeutic insights into canine diffuse large B cell lymphoma elucidates the role of the dog as a model for human disease

open21siopenAresu, Luca; Ferraresso, Serena; Marconato, Laura; Cascione, Luciano; Napoli, Sara; Gaudio, Eugenio; Kwee, Ivo; Tarantelli, Chiara; Testa, Andrea; Maniaci, Chiara; Ciulli, Alessio; Hillmann, Petra; Bohnacker, Thomas; Wymann, Matthias P; Comazzi, Stefano; Milan, Massimo; Riondato, Fulvio; Dalla Rovere, Giulia; Giantin, Mery; Giannuzzi, Diana; Bertoni, FrancescoAresu, Luca; Ferraresso, Serena; Marconato, Laura; Cascione, Luciano; Napoli, Sara; Gaudio, Eugenio; Kwee, Ivo; Tarantelli, Chiara; Testa, Andrea; Maniaci, Chiara; Ciulli, Alessio; Hillmann, Petra; Bohnacker, Thomas; Wymann, Matthias P; Comazzi, Stefano; Milan, Massimo; Riondato, Fulvio; Dalla Rovere, Giulia; Giantin, Mery; Giannuzzi, Diana; Bertoni, Francesc

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

The Sex-Specific Detrimental Effect of Diabetes and Gender-Related Factors on Pre-admission Medication Adherence Among Patients Hospitalized for Ischemic Heart Disease: Insights From EVA Study

Background: Sex and gender-related factors have been under-investigated as relevant determinants of health outcomes across non-communicable chronic diseases. Poor medication adherence results in adverse clinical outcomes and sex differences have been reported among patients at high cardiovascular risk, such as diabetics. The effect of diabetes and gender-related factors on medication adherence among women and men at high risk for ischemic heart disease (IHD) has not yet been fully investigated.Aim: To explore the role of sex, gender-related factors, and diabetes in pre-admission medication adherence among patients hospitalized for IHD.Materials and Methods: Data were obtained from the Endocrine Vascular disease Approach (EVA) (ClinicalTrials.gov Identifier: NCT02737982), a prospective cohort of patients admitted for IHD. We selected patients with baseline information regarding the presence of diabetes, cardiovascular risk factors, and gender-related variables (i.e., gender identity, gender role, gender relations, institutionalized gender). Our primary outcome was the proportion of pre-admission medication adherence defined through a self-reported questionnaire. We performed a sex-stratified analysis of clinical and gender-related factors associated with pre-admission medication adherence.Results: Two-hundred eighty patients admitted for IHD (35% women, mean age 70), were included. Around one-fourth of the patients were low-adherent to therapy before hospitalization, regardless of sex. Low-adherent patients were more likely diabetic (40%) and employed (40%). Sex-stratified analysis showed that low-adherent men were more likely to be employed (58 vs. 33%) and not primary earners (73 vs. 54%), with more masculine traits of personality, as compared with medium-high adherent men. Interestingly, women reporting medication low-adherence were similar for clinical and gender-related factors to those with medium-high adherence, except for diabetes (42 vs. 20%, p = 0.004). In a multivariate adjusted model only employed status was associated with poor medication adherence (OR 0.55, 95%CI 0.31–0.97). However, in the sex-stratified analysis, diabetes was independently associated with medication adherence only in women (OR 0.36; 95%CI 0.13–0.96), whereas a higher masculine BSRI was the only factor associated with medication adherence in men (OR 0.59, 95%CI 0.35–0.99).Conclusion: Pre-admission medication adherence is common in patients hospitalized for IHD, regardless of sex. However, patient-related factors such as diabetes, employment, and personality traits are associated with adherence in a sex-specific manner

Equazione di Smoluchowski a coefficienti variabili e applicazioni

In questo lavoro viene presentato un modello matematico per l'aggregazione e la diffusione della beta-amiloide nel cervello umano affetto dalla malattia di Alzheimer, con la particolarità di considerare coefficienti di diffusione variabili e non costanti. Il modello è basato sull'equazione di Smoluchowski discreta per l'aggregazione, modificata in modo opportuno per considerare anche il fenomeno di diffusione

Natural and synthetic sweeteners: applications and toxicological aspects

Los edulcorantes que, en general, aportan bajo contenido calórico, son principalmente destinados a diabéticos y obesos que deben restringir fuertemente su ingesta de carbohidratos. Sin embargo, resultan ser utilizados por un amplio espectro de la población. Los edulcorantes sintéticos más conocidos han sido la sacarina y el ciclamato, cuyo uso ha generado una fuerte controversia a nivel internacional que perdura hasta la fecha, dado que algunos estudios vinculan su empleo en altas dosis con la producción de cáncer de vejiga en animales de laboratorio, mientras que otros estudios lo niegan. El aspartamo, menos tóxico que los anteriores dado que ningún estudio lo clasificó como carcinógeno, presenta sin embargo efectos secundarios neuropsíquicos así como ciertos efectos paradojales que pueden provocar inhibición del supresor del apetito cuando son consumidos en dosis elevadas. En los últimos tiempos han surgido los edulcorantes obtenidos a partir de productos naturales como taumatina, monelina y miraculina, entre otros, los que parecen presentar menores efectos tóxicos. Un análisis de la perspectiva actual esbozando la situación argentina en materia de edulcorantes es discutida en el presente trabajo.Lower calory intake sweeteners have been principally aimed to diabetics and obeses who must strongly restrain their carbohidrates intake. Nowadays, the use of these sweeteners is also extended to a large population espectrum. Saccarin and cyclamate are well known synthetic sweeteners that have produced strong controversy at intemational level. Some studies relate the use of artificial sweetners in large dosis with bladder cancer occurrence in laboratory animals, while others presented negative results. Aspartame is less toxic than those mentioned above; howewer, it presents secundary neuropsychiatric effects and certain paradoxal effect that could facilitate the inhibition of an appetite suppresor. Natural sweeteners recently isolated, as thaumatins, monellin, and miraculin showed lower toxic effect. An outline of the Argentine situation in sweetners application is discussed in the present work.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Natural and synthetic sweeteners: applications and toxicological aspects

Los edulcorantes que, en general, aportan bajo contenido calórico, son principalmente destinados a diabéticos y obesos que deben restringir fuertemente su ingesta de carbohidratos. Sin embargo, resultan ser utilizados por un amplio espectro de la población. Los edulcorantes sintéticos más conocidos han sido la sacarina y el ciclamato, cuyo uso ha generado una fuerte controversia a nivel internacional que perdura hasta la fecha, dado que algunos estudios vinculan su empleo en altas dosis con la producción de cáncer de vejiga en animales de laboratorio, mientras que otros estudios lo niegan. El aspartamo, menos tóxico que los anteriores dado que ningún estudio lo clasificó como carcinógeno, presenta sin embargo efectos secundarios neuropsíquicos así como ciertos efectos paradojales que pueden provocar inhibición del supresor del apetito cuando son consumidos en dosis elevadas. En los últimos tiempos han surgido los edulcorantes obtenidos a partir de productos naturales como taumatina, monelina y miraculina, entre otros, los que parecen presentar menores efectos tóxicos. Un análisis de la perspectiva actual esbozando la situación argentina en materia de edulcorantes es discutida en el presente trabajo.Lower calory intake sweeteners have been principally aimed to diabetics and obeses who must strongly restrain their carbohidrates intake. Nowadays, the use of these sweeteners is also extended to a large population espectrum. Saccarin and cyclamate are well known synthetic sweeteners that have produced strong controversy at intemational level. Some studies relate the use of artificial sweetners in large dosis with bladder cancer occurrence in laboratory animals, while others presented negative results. Aspartame is less toxic than those mentioned above; howewer, it presents secundary neuropsychiatric effects and certain paradoxal effect that could facilitate the inhibition of an appetite suppresor. Natural sweeteners recently isolated, as thaumatins, monellin, and miraculin showed lower toxic effect. An outline of the Argentine situation in sweetners application is discussed in the present work.Colegio de Farmacéuticos de la Provincia de Buenos Aire