40 results on '"Ruberto, S"'
Search Results
2. Direct numerical simulation of sublimating ice particles
- Author
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Reitzle, M., Ruberto, S., Stierle, R., Gross, J., Janzen, T., and Weigand, B.
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- 2019
- Full Text
- View/download PDF
3. A systematic experimental study on the evaporation rate of supercooled water droplets at subzero temperatures and varying relative humidity
- Author
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Ruberto, S., Reutzsch, J., Roth, N., and Weigand, B.
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- 2017
- Full Text
- View/download PDF
4. Computational Intelligence for Life Sciences
- Author
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Besozzi, D, Manzoni, L, Nobile, M, Spolaor, S, Castelli, M, Vanneschi, L, Cazzaniga, P, Ruberto, S, Rundo, L, Tangherloni, A, Besozzi D., Manzoni L., Nobile M. S., Spolaor S., Castelli M., Vanneschi L., Cazzaniga P., Ruberto S., Rundo L., Tangherloni A., Besozzi, D, Manzoni, L, Nobile, M, Spolaor, S, Castelli, M, Vanneschi, L, Cazzaniga, P, Ruberto, S, Rundo, L, Tangherloni, A, Besozzi D., Manzoni L., Nobile M. S., Spolaor S., Castelli M., Vanneschi L., Cazzaniga P., Ruberto S., Rundo L., and Tangherloni A.
- Abstract
Computational Intelligence (CI) is a computer science discipline encompassing the theory, design, development and application of biologically and linguistically derived computational paradigms. Traditionally, the main elements of CI are Evolutionary Computation, Swarm Intelligence, Fuzzy Logic, and Neural Networks. CI aims at proposing new algorithms able to solve complex computational problems by taking inspiration from natural phenomena. In an intriguing turn of events, these nature-inspired methods have been widely adopted to investigate a plethora of problems related to nature itself. In this paper we present a variety of CI methods applied to three problems in life sciences, highlighting their effectiveness: we describe how protein folding can be faced by exploiting Genetic Programming, the inference of haplotypes can be tackled using Genetic Algorithms, and the estimation of biochemical kinetic parameters can be performed by means of Swarm Intelligence. We show that CI methods can generate very high quality solutions, providing a sound methodology to solve complex optimization problems in life sciences.
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- 2019
5. Prevalence and correlates of QTc prolongation in Italian psychiatric care: cross-sectional multicentre study
- Author
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Nosè, M., Bighelli, I., Castellazzi, M., Martinotti, G., Carrà, G., Lucii, C., Ostuzzi, G., Sozzi, F., Barbui, C., Acciavatti, T., Adamo, A., Aguglia, A., Albanese, C., Baccaglini, S., Bardicchia, F., Barone, R., Barone, Y., Bartoli, F., Bergamini, C., Bertolini, F., Bolognesi, S., Bordone, A., Bortolaso, P., Bugliani, M., Calandra, C., Calò, S., Cardamone, G., Caroleo, M., Carra, E., Carretta, D., Chiocchi, L., Clerici, M., Corbo, M., Corsi, E., Costanzo, R., Costoloni, G., D'Arienzo, F., Debolini, S., De Capua, A., Di Napoli, W. A., Dinelli, M., Facchi, E., Fargnoli, F., Fiori, F., Franchi, A., Gardellin, F., Gazzoletti, E., Ghio, L., Giacomin, M., Gregis, M., Iovieno, N., Koukouna, D., Lax, A., Lintas, C., Luca, A., Luca, M., Lussetti, M., Madrucci, M., Magnani, N., Magni, L., Manca, E., Martorelli, C., Mattafirri, R., Percudani, M., Perini, G., Petrosemolo, P., Pezzullo, M., Piantanida, S., Pinna, F., Prato, K., Prestia, D., Quattrone, D., Reggianini, C., Restaino, F., Ribolsi, M., Rinosi, G., Rizzo, C., Rizzo, R., Roggi, M., Rossi, G., Rossi, S., Ruberto, S., Santoro, R., Santi, M., Signorelli, M. S., Soscia, F., Staffa, P., Stilo, M., Strizzolo, S., Suraniti, F., Tavian, N., Tortelli, L., Tosoni, F., Valdagno, M., Zanobini, V., Nosè, M, Bighelli, I, Castellazzi, M, Martinotti, G, Carra', G, Lucii, C, Ostuzzi, G, Sozzi, F, Barbui, C, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santoro, R, Santi, M, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, and Zanobini, V
- Subjects
Adult ,Male ,medicine.medical_specialty ,Psychotropic drugs ,Epidemiology ,medicine.medical_treatment ,Long QT syndrome ,Antidepressant ,Drug overdose ,Adverse effect ,QT interval ,Antipsychotic ,03 medical and health sciences ,Electrocardiography ,0302 clinical medicine ,Risk Factors ,Psychotropic drug ,medicine ,Prevalence ,Humans ,cardiovascular diseases ,Psychiatry ,Settore MED/25 - Psichiatria ,Polypharmacy ,business.industry ,Environmental and Occupational Health ,Public Health, Environmental and Occupational Health ,Public Health ,Psychiatry and Mental Health ,Original Articles ,medicine.disease ,030227 psychiatry ,Substance abuse ,Long QT Syndrome ,Cross-Sectional Studies ,Italy ,Aripiprazole ,Female ,business ,adverse effect ,antipsychotic ,psychotropic drugs ,Antipsychotic Agents ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Aims.In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach.Method.The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded.Results.During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation.Conclusions.The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.
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- 2016
6. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval
- Author
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Barbui, Corrado, Bighelli, Irene, Carrà, Giuseppe, Castellazzi, Mariasole, Lucii, Claudio, Martinotti, Giovanni, Nosè, Michela, Ostuzzi, Giovanni, Acciavatti, T., Adamo, A., Aguglia, A., Albanese, C., Baccaglini, S., Bardicchia, F., Barone, R., Barone, Y., Bartoli, F., Bergamini, C., Bertolini, F., Bolognesi, S., Bordone, A., Bortolaso, P., Bugliani, M., Calandra, C., Calò, S., Cardamone, G., Caroleo, M., Carra, E., Car-Retta, D., Chiocchi, L., Cinosi, E., Clerici, M., Corbo, M., Corsi, E., Costanzo, R., Costoloni, G., D'Arienzo, F., Debolini, S., De Capua, A., Di Napoli, W. A., Dinelli, M., Facchi, E., Fargnoli, F., Fiori, F., Franchi, A., Gardellin, F., Gastaldon, C., Gazzoletti, E., Ghio, L., Giacomin, M., Gregis, M., Iovieno, N., Koukouna, D., Lax, A., Lintas, C., Luca, A., Luca, M., Lussetti, M., Madrucci, M., Magnani, N., Magni, L., Manca, E., Martorelli, C., Mattafirri, R., Paladini, C., Papola, D., Percudani, M., Perini, G., Petrosemolo, P., Pezzullo, M., Piantanida, S., Pinna, F., Prato, K., Prestia, D., Quattrone, D., Reggianini, C., Restaino, F., Ribolsi, M., Rinosi, G., Rizzo, C., Rizzo, R., Roggi, M., Rossi, G., Rossi, S., Ruberto, S., Santi, M., Santoro, R., Sepede, G., Signorelli, M. S., Soscia, F., Sozzi, F., Staffa, P., Stilo, M., Strizzolo, S., Suraniti, F., Tavian, N., Tortelli, L., Tosoni, F., Valdagno, M., Zanobini, V., Barbui, C, Bighelli, I, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, and Zanobini, V
- Subjects
Male ,Genetics and Molecular Biology (all) ,medicine.medical_treatment ,Aripiprazole ,lcsh:Medicine ,Pharmacology ,Cardiovascular Medicine ,dose-dependent risk ,Biochemistry ,Electrocardiography ,0302 clinical medicine ,Heart Rate ,Medicine and Health Sciences ,80 and over ,Antipsychotics ,lcsh:Science ,Aged, 80 and over ,Multidisciplinary ,Pharmaceutics ,Medicine (all) ,Mental Disorders ,Confounding ,Drug Information ,Drugs ,Middle Aged ,Long QT Syndrome ,Bioassays and Physiological Analysis ,Italy ,Cardiovascular Diseases ,Cardiology ,Female ,QT interval corrected for heart rate ,Adult ,Aged ,Antipsychotic Agents ,Cross-Sectional Studies ,Dose-Response Relationship ,Drug ,Haloperidol ,Humans ,Young Adult ,Polypharmacy ,Agricultural and Biological Sciences (all) ,medicine.drug ,Research Article ,medicine.medical_specialty ,Patients ,QTc lenghtening ,therapy risk ,Long QT syndrome ,antipsychotic drugs ,Research and Analysis Methods ,polypharmacy ,QT interval ,03 medical and health sciences ,Dose Prediction Methods ,Drug Therapy ,Internal medicine ,Dose-Response Relationship, Drug ,Biochemistry, Genetics and Molecular Biology (all) ,Heart rate ,medicine ,Antipsychotic ,Inpatients ,business.industry ,lcsh:R ,Electrophysiological Techniques ,medicine.disease ,030227 psychiatry ,Health Care ,Defined daily dose ,Settore MED/25 ,lcsh:Q ,Cardiac Electrophysiology ,business ,030217 neurology & neurosurgery - Abstract
Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.
- Published
- 2016
7. Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature
- Author
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Meid, A, Bighelli, I, Mächler, S, Mikus, G, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D’Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, Haefeli, W, A. D. Meid, I. Bighelli, S. Mächler, G. Mikus, G. Carrà, M. Castellazzi, C. Lucii, G. Martinotti, M. Nosè, G. Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, D. Carretta, L. Chiocchi, E. Cinosi, M. Clerici, M. Corbo, E. Corsi, R. Costanzo, G. Costoloni, F. D’Arienzo, S. Debolini, A. De Capua, W. A. Di Napoli, M. Dinelli, E. Facchi, F. Fargnoli, F. Fiori, A. Franchi, F. Gardellin, C. Gastaldon, E. Gazzoletti, L. Ghio, M. Giacomin, M. Gregis, N. Iovieno, D. Koukouna, A. Lax, C. Lintas, A. Luca, M. Luca, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, C. Martorelli, R. Mattafirri, C. Paladini, D. Papola, M. Percudani, G. Perini, P. Petrosemolo, M. Pezzullo, S. Piantanida, F. Pinna, K. Prato, D. Prestia, D. Quattrone, C. Reggianini, F. Restaino, M. Ribolsi, G. Rinosi, C. Rizzo, R. Rizzo, M. Roggi, G. Rossi, S. Rossi, S. Ruberto, M. Santi, R. Santoro, G. Sepede, M. S. Signorelli, F. Soscia, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini, C. Barbui, W. E. Haefeli, Meid, A, Bighelli, I, Mächler, S, Mikus, G, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D’Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, Haefeli, W, A. D. Meid, I. Bighelli, S. Mächler, G. Mikus, G. Carrà, M. Castellazzi, C. Lucii, G. Martinotti, M. Nosè, G. Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, D. Carretta, L. Chiocchi, E. Cinosi, M. Clerici, M. Corbo, E. Corsi, R. Costanzo, G. Costoloni, F. D’Arienzo, S. Debolini, A. De Capua, W. A. Di Napoli, M. Dinelli, E. Facchi, F. Fargnoli, F. Fiori, A. Franchi, F. Gardellin, C. Gastaldon, E. Gazzoletti, L. Ghio, M. Giacomin, M. Gregis, N. Iovieno, D. Koukouna, A. Lax, C. Lintas, A. Luca, M. Luca, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, C. Martorelli, R. Mattafirri, C. Paladini, D. Papola, M. Percudani, G. Perini, P. Petrosemolo, M. Pezzullo, S. Piantanida, F. Pinna, K. Prato, D. Prestia, D. Quattrone, C. Reggianini, F. Restaino, M. Ribolsi, G. Rinosi, C. Rizzo, R. Rizzo, M. Roggi, G. Rossi, S. Rossi, S. Ruberto, M. Santi, R. Santoro, G. Sepede, M. S. Signorelli, F. Soscia, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini, C. Barbui, and W. E. Haefeli
- Abstract
Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and co-administration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure.
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- 2017
8. First-generation antipsychotics and QTc: any role for mediating variables?
- Author
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Carrà, G., Crocamo, Cristina, Bartoli, F., Lax, A., Tremolada, Martina, Lucii, C., Martinotti, G., Nosè, M., Bighelli, I., Ostuzzi, G., Castellazzi, M., Clerici, M., Barbui, C., Acciavatti, T., Adamo, A., Aguglia, A., Albanese, C., Baccaglini, S., Bardicchia, F., Barone, R., Barone, Y., Bergamini, C., Bertolini, F., Bolognesi, S., Bordone, A., Bortolaso, P., Bugliani, M., Calandra, C., Calò, S., Cardamone, G., Caroleo, M., Carra, E., Carretta, D., Chiocchi, L., Cinosi, E., Corbo, M., Corsi, E., Costanzo, R., Costoloni, G., D’Arienzo, F., Debolini, S., De Capua, A., Di Napoli, W. A., Dinelli, M., Facchi, E., Fargnoli, F., Fiori, F., Franchi, A., Gardellin, F., Gastaldon, C., Gazzoletti, E., Ghio, L., Giacomin, M., Gregis, M., Iovieno, N., Koukouna, D., Lintas, C., Luca, A., Luca, M., Lussetti, M., Madrucci, M., Magnani, N., Magni, L., Manca, E., Martorelli, C., Mattafirri, R., Paladini, C., Papola, D., Percudani, M., Perini, G., Petrosemolo, P., Pezzullo, M., Piantanida, S., Pinna, F., Prato, K., Prestia, D., Quattrone, D., Reggianini, C., Restaino, F., Ribolsi, M., Rinosi, G., Rizzo, C., Rizzo, R., Roggi, M., Rossi, G., Rossi, S., Ruberto, S., Santi, M., Santoro, R., Sepede, G., Signorelli, M. S., Soscia, F., Sozzi, F., Staffa, P., Stilo, M., Strizzolo, S., Suraniti, F., Tavian, N., Tortelli, L., Tosoni, F., Valdagno, M., Zanobini, V., Carra', G, Crocamo, C, Bartoli, F, Lax, A, Tremolada, M, Lucii, C, Martinotti, G, Nosè, M, Bighelli, I, Ostuzzi, G, Castellazzi, M, Clerici, M, and Barbui, C
- Subjects
Adult ,Male ,QT prolongation ,alcohol ,antipsychotic agents ,drug therapy combination ,risk factors ,Antipsychotic Agents ,Cross-Sectional Studies ,Electrocardiography ,Female ,Heart Rate ,Humans ,Italy ,Long QT Syndrome ,Mental Disorders ,Middle Aged ,Pharmacology (medical) ,Settore MED/25 - Psichiatria ,Neurology ,Neurology (clinical) ,Psychiatry and Mental Health ,antipsychotic agent ,risk factor - Abstract
Objective: Corrected QT (QTc) interval prolongation is often associated with use of first-generation antipsychotics (FGAs). However, other factors require appropriate consideration, including age and gender, the role of other known medications associated with QTc prolongation, and severe comorbid conditions, such as co-occurring alcohol abuse/dependence. We aimed to study potential mediating roles of different, related, candidate variables on QTc. Methods: We capitalized on data from a large (N = 2366), cross-sectional, national survey, the STAR Network QTc study, using a representative sample of people taking FGAs, and recruited from mental health services across Italy. Results: About one-third of the sample was treated with FGAs, and almost one-tenth of the subjects took a different, additional, drug known to cause QTc prolongation. Our findings confirmed that there is an impact from FGAs, age, gender, alcohol misuse, and concurrent risky drugs on QTc. However, comorbid alcohol abuse/dependence and concurrent risky drugs did not mediate the effect of FGAs on QTc. Conclusions: Our findings showed that FGAs, concurrent risky drugs, and alcohol use disorders prolonged QTc. FGAs had a direct effect on QTc, confirming the need for clinicians to monitor a risk that could lead to sudden unexplained death. Copyright © 2016 John Wiley & Sons, Ltd.
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- 2016
9. Role of Co-occurring Alcohol and Substances Abuse on QTc Interval Prolongation Among Psychiatric Patients: A Cross-sectional National Survey
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Corbo, M., primary, Acciavatti, T., additional, Fiori, F., additional, Santacroce, R., additional, Aguglia, A., additional, Bartoli, F., additional, Calò, S., additional, Ribolsi, M., additional, Barone, Y., additional, Pinna, F., additional, Stilo, M., additional, Staffa, P., additional, Caroleo, M., additional, Ruberto, S., additional, Signorelli, M.S., additional, Suraniti, F., additional, Quattrone, D., additional, Reggianini, C., additional, Carra, E., additional, Gazzoletti, E., additional, Campese, O., additional, Castellazzi, M., additional, Ostuzzi, G., additional, Bighelli, I., additional, Nosè, M., additional, Barbui, C., additional, and Martinotti, G., additional
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- 2017
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10. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval
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Barbui, C, Bighelli, I, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, Bighelli, I, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, and Zanobini, V
- Abstract
Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.
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- 2016
11. Prevalence and correlates of QTc prolongation in Italian psychiatric care: Cross-sectional multicentre study
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Nosè, M, Bighelli, I, Castellazzi, M, Martinotti, G, Carra', G, Lucii, C, Ostuzzi, G, Sozzi, F, Barbui, C, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santoro, R, Santi, M, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, CARRA', GIUSEPPE, Barbui, C., Di Napoli, WA, Signorelli, MS, Nosè, M, Bighelli, I, Castellazzi, M, Martinotti, G, Carra', G, Lucii, C, Ostuzzi, G, Sozzi, F, Barbui, C, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santoro, R, Santi, M, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, CARRA', GIUSEPPE, Barbui, C., Di Napoli, WA, and Signorelli, MS
- Abstract
Aims. In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach. Method. The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded. Results. During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation. Conclusions. The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that re
- Published
- 2016
12. Influenza del tipo di ramo sull'andamento della fioritura e sulla crescita dei frutti di cultivar di albicocco allevate in areale vesuviano
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RUBERTO S., BARRA S., GIACCONE M., HERNANDEZ, GUSTAVO, BASILE, BORIS, FORLANI, MARCELLO, CIRILLO, CHIARA, Ruberto, S., Barra, S., Hernandez, Gustavo, Giaccone, M., Basile, Bori, Forlani, Marcello, and Cirillo, Chiara
- Published
- 2008
13. Caratterizzazione morfologica, molecolare, agronomica ed olearia della varietà di olivo Pennulara
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Ruberto S., FORLANI, MARCELLO, CIRILLO, CHIARA, Ruberto, S., Forlani, Marcello, and Cirillo, Chiara
- Published
- 2007
14. Experimental investigation of the evaporation rate of supercooled water droplets at constant temperature and varying relative humidity
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Ruberto, S., primary, Reutzsch, J., additional, and Weigand, B., additional
- Published
- 2016
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15. Psychosomatic approach to patients with headache: alternative or integrated diagnoses?
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DE GIORGIO, Giuseppina, Ruberto, S, Firenze, Caterina, and Quartesan, Roberto
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psychosomatic ,alexithymia - Published
- 2010
16. ESAGP – A semantic GP framework based on alignment in the error space
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Nicolau, M, Krawiec, K, Heywood, MI, Castelli, M, Garci-Sanchez, P, Merelo, JJ, Santos, MR, Sim, K, Ruberto, S, Vanneschi, L, Silva, S, VANNESCHI, LEONARDO, CASTELLI, MAURO, Silva, S., Nicolau, M, Krawiec, K, Heywood, MI, Castelli, M, Garci-Sanchez, P, Merelo, JJ, Santos, MR, Sim, K, Ruberto, S, Vanneschi, L, Silva, S, VANNESCHI, LEONARDO, CASTELLI, MAURO, and Silva, S.
- Abstract
This paper introduces the concepts of error vector and error space, directly bound to semantics, one of the hottest topics in genetic programming. Based on these concepts, we introduce the notions of optimally aligned individuals and optimally coplanar individuals. We show that, given optimally aligned, or optimally coplanar, individuals, it is possible to construct a globally optimal solution analytically. Thus, we introduce a genetic programming framework for symbolic regression called Error Space Alignment GP (ESAGP) and two of its instances: ESAGP-1, whose objective is to find optimally aligned individuals, and ESAGP-2, whose objective is to find optimally coplanar individuals. We also discuss how to generalize the approach to any number of dimensions. Using two complex real-life applications, we provide experimental evidence that ESAGP-2 outperforms ESAGP-1, which in turn outperforms both standard GP and geometric semantic GP. This suggests that “adding dimensions” is beneficial and encourages us to pursue the study in many different directions, that we summarize in the final part of the manuscript
- Published
- 2014
17. Computational Intelligence for Life Sciences
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Stefano Ruberto, Simone Spolaor, Leonardo Rundo, Paolo Cazzaniga, Andrea Tangherloni, Leonardo Vanneschi, Daniela Besozzi, Mauro Castelli, Luca Manzoni, Marco S. Nobile, Rundo, Leonardo [0000-0003-3341-5483], Apollo - University of Cambridge Repository, Besozzi, D, Manzoni, L, Nobile, M, Spolaor, S, Castelli, M, Vanneschi, L, Cazzaniga, P, Ruberto, S, Rundo, L, Tangherloni, A, Besozzi, Daniela, Manzoni, Luca, Nobile, Marco S., Spolaor, Simone, Castelli, Mauro, Vanneschi, Leonardo, Cazzaniga, Paolo, Ruberto, Stefano, Rundo, Leonardo, Tangherloni, Andrea, Information Systems IE&IS, NOVA Information Management School (NOVA IMS), NOVA IMS Research and Development Center (MagIC), and Information Management Research Center (MagIC) - NOVA Information Management School
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Computational Intelligence ,Evolutionary Computation ,Genetic Algorithm ,Genetic Programming ,Haplotype Assembly ,Parameter Estimation ,Particle Swarm Optimization ,Protein Folding ,Swarm Intelligence ,Optimization problem ,Computer science ,Computational intelligence ,Genetic programming ,0102 computer and information sciences ,01 natural sciences ,Swarm intelligence ,Evolutionary computation ,Theoretical Computer Science ,SDG 3 - Good Health and Well-being ,Genetic algorithm ,Algebra and Number Theory ,Settore INF/01 - Informatica ,business.industry ,Particle swarm optimization ,Computational Theory and Mathematics ,010201 computation theory & mathematics ,Artificial intelligence ,Computational problem ,business ,Information Systems - Abstract
Besozzi, D., Manzoni, L., Nobile, M. S., Spolaor, S., Castelli, M., Vanneschi, L., ... Tangherloni, A. (2020). Computational Intelligence for Life Sciences. Fundamenta Informaticae, 171(1-4), 57-80. https://doi.org/10.3233/FI-2020-1872 Computational Intelligence (CI) is a computer science discipline encompassing the theory, design, development and application of biologically and linguistically derived computational paradigms. Traditionally, the main elements of CI are Evolutionary Computation, Swarm Intelligence, Fuzzy Logic, and Neural Networks. CI aims at proposing new algorithms able to solve complex computational problems by taking inspiration from natural phenomena. In an intriguing turn of events, these nature-inspired methods have been widely adopted to investigate a plethora of problems related to nature itself. In this paper we present a variety of CI methods applied to three problems in life sciences, highlighting their effectiveness: we describe how protein folding can be faced by exploiting Genetic Programming, the inference of haplotypes can be tackled using Genetic Algorithms, and the estimation of biochemical kinetic parameters can be performed by means of Swarm Intelligence. We show that CI methods can generate very high quality solutions, providing a sound methodology to solve complex optimization problems in life sciences. authorsversion published
- Published
- 2020
18. Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature
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A. D. Meid, I. Bighelli, S. Mächler, G. Mikus, G. Carrà, M. Castellazzi, C. Lucii, G. Martinotti, M. Nosè, G. Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, D. Carretta, L. Chiocchi, E. Cinosi, M. Clerici, M. Corbo, E. Corsi, R. Costanzo, G. Costoloni, F. D’Arienzo, S. Debolini, A. De Capua, W. A. Di Napoli, M. Dinelli, E. Facchi, F. Fargnoli, F. Fiori, A. Franchi, F. Gardellin, C. Gastaldon, E. Gazzoletti, L. Ghio, M. Giacomin, M. Gregis, N. Iovieno, D. Koukouna, A. Lax, C. Lintas, A. Luca, M. Luca, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, C. Martorelli, R. Mattafirri, C. Paladini, D. Papola, M. Percudani, G. Perini, P. Petrosemolo, M. Pezzullo, S. Piantanida, F. Pinna, K. Prato, D. Prestia, D. Quattrone, C. Reggianini, F. Restaino, M. Ribolsi, G. Rinosi, C. Rizzo, R. Rizzo, M. Roggi, G. Rossi, S. Rossi, S. Ruberto, M. Santi, R. Santoro, G. Sepede, M. S. Signorelli, F. Soscia, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini, C. Barbui, W. E. Haefeli, Meid, A, Bighelli, I, Mächler, S, Mikus, G, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D’Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, and Haefeli, W
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QT interval ,medicine.medical_specialty ,electrocardiography ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,cohort study ,030212 general & internal medicine ,drug–drug interaction ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Original Research ,drug–drug interactions ,psychiatry ,medicine.diagnostic_test ,business.industry ,Pharmacodynamics ,Cardiology ,Psychology (miscellaneous) ,business ,Electrocardiography ,cohort study, drug–drug interactions, electrocardiography, psychiatry, QT interval ,Cohort study - Abstract
Background:Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions.Methods:In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses.Results:Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and co-administration of a ‘known’ risk drug as a further risk factor.Conclusions:These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs.
- Published
- 2017
19. ESAGP – A semantic GP framework based on alignment in the error space
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Stefano Ruberto, Sara Silva, Mauro Castelli, Leonardo Vanneschi, Nicolau, M, Krawiec, K, Heywood, MI, Castelli, M, Garci-Sanchez, P, Merelo, JJ, Santos, MR, Sim, K, Ruberto, S, Vanneschi, L, and Silva, S
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Mean squared error ,business.industry ,Computer science ,Semantic space ,Genetic programming ,Construct (python library) ,Space (commercial competition) ,Semantics ,law.invention ,law ,Cartesian coordinate system ,genetic programming ,Artificial intelligence ,business ,Symbolic regression - Abstract
This paper introduces the concepts of error vector and error space, directly bound to semantics, one of the hottest topics in genetic programming. Based on these concepts, we introduce the notions of optimally aligned individuals and optimally coplanar individuals. We show that, given optimally aligned, or optimally coplanar, individuals, it is possible to construct a globally optimal solution analytically. Thus, we introduce a genetic programming framework for symbolic regression called Error Space Alignment GP (ESAGP) and two of its instances: ESAGP-1, whose objective is to find optimally aligned individuals, and ESAGP-2, whose objective is to find optimally coplanar individuals. We also discuss how to generalize the approach to any number of dimensions. Using two complex real-life applications, we provide experimental evidence that ESAGP-2 outperforms ESAGP-1, which in turn outperforms both standard GP and geometric semantic GP. This suggests that “adding dimensions” is beneficial and encourages us to pursue the study in many different directions, that we summarize in the final part of the manuscript
20. A Systematic Review: Early Simultaneous Vomer Flap with Primary Cleft Lip Repair, Does it Bring More Benefits?
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Putri IL, Widiono ES, Liana S, Ruberto S, and Dyah Kencono Wungu C
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- Humans, Plastic Surgery Procedures methods, Infant, Cleft Lip surgery, Surgical Flaps, Cleft Palate surgery, Vomer surgery
- Abstract
Introduction: Vomer flap is a technique to close cleft lip and palate. This technique is a simple procedure that has many benefits. However, the vomer flap's application together with primary lip closure is still questionable., Objective: To find out whether the vomer flap's application in primary cleft lip repair can provide significant benefits., Design: A systematic review was conducted using the PRISMA methodology has been licensed in PROSPERO databases (CRD42023399487)., Setting: A comprehensive search was set out, utilizing eight data sources up to March 2023., Participants: Both cohort studies and randomized control trials regarding the use of vomer flaps performed concurrently with cleft lip repair in children up to six months old., Results: This article involved 8 studies involving 542 patients who met the inclusion criteria, consisting of 6 retrospective cohort studies, 1 RCT study, and 1 prospective cohort study. Vomer flaps provide a reduction in palatal cleft distance of 3-5 mm, a relatively small number of fistulas (0-4%), improvement of velopharyngeal function (nasal tone and nasal emission), maximal development of the maxilla although it is still controversial., Conclusion: The vomer flap's application in primary cleft lip repair provides many advantages, such as reduced palatal and alveolar clefts, decreased risk of oronasal fistula, increased velopharyngeal function, and increased maxillary growth. It is reliable for the management of cleft lip and palate., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
- Full Text
- View/download PDF
21. Correlation between antibodies against the pathogenic pHERV-W envelope protein and the inflammatory phase of multiple sclerosis.
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Ruberto S, Cossu D, and Sechi LA
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- Humans, Gene Products, env genetics, Gene Products, env metabolism, Antibodies, Multiple Sclerosis, Pregnancy Proteins metabolism, Endogenous Retroviruses metabolism
- Abstract
The role of retroviral envelope proteins belonging to the Human Endogenous Retroviral family 'W' (HERV-W), specifically syncytin-1 and pathogenic HERV-W (pHERV-W), as potential risk factors in multiple sclerosis (MS) has been established. This study aimed to investigate the humoral response to syncytin-1 and pHERV-W-derived peptides in a group of relapsing remitting MS patients categorized as having acute or stable disease. Furthermore, an inhibition assay was conducted to assess the extent of cross-reactivity between the two epitopes. The findings revealed that MS patients in the acute phase exhibited a higher specific antibody response to the pHERV-W env epitope compared to syncytin-1. This suggests a potential pathogenic role for pHERV-W env during the inflammatory stages of central nervous system involvement, and these antibody responses could serve as useful biomarkers for monitoring the progression of the disease., (© 2023 The Authors. Immunology published by John Wiley & Sons Ltd.)
- Published
- 2024
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22. A Multigene-Panel Study Identifies Single Nucleotide Polymorphisms Associated with Prostate Cancer Risk.
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Manca MA, Scarpa F, Cossu D, Simula ER, Sanna D, Ruberto S, Noli M, Ashraf H, Solinas T, Madonia M, Cusano R, and Sechi LA
- Subjects
- Male, Humans, Genotype, Inflammation genetics, Prostate, Genetic Predisposition to Disease, Case-Control Studies, Polymorphism, Single Nucleotide, Prostatic Neoplasms genetics
- Abstract
The immune system plays a critical role in modulating cancer development and progression. Polymorphisms in key genes involved in immune responses are known to affect susceptibility to cancer. Here, we analyzed 35 genes to evaluate the association between variants of genes involved in immune responses and prostate cancer risk. Thirty-five genes were analyzed in 47 patients with prostate cancer and 43 healthy controls using next-generation sequencing. Allelic and genotype frequencies were calculated in both cohorts, and a generalized linear mixed model was applied to test the relationship between prostate cancer risk and nucleotide substitution. Odds ratios were calculated to describe the association between each single nucleotide polymorphism (SNP) and prostate cancer risk. Significant changes in allelic and genotypic distributions were observed for IL4R , IL12RB1 , IL12RB2 , IL6 , TMPRSS2 , and ACE2 . Furthermore, a generalized linear mixed model identified statistically significant associations between prostate cancer risk and SNPs in IL12RB2 , IL13 , IL17A , IL4R , MAPT , and TFNRS1B . Finally, a statistically significant association was observed between IL2RA and TNFRSF1B and Gleason scores, and between SLC11A1 , TNFRSF1B and PSA values. We identified SNPs in inflammation and two prostate cancer-associated genes. Our results provide new insights into the immunogenetic landscape of prostate cancer and the impact that SNPs on immune genes may have on affecting the susceptibility to prostate cancer.
- Published
- 2023
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23. Latent Potential of Multifunctional Selenium Nanoparticles in Neurological Diseases and Altered Gut Microbiota.
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Ashraf H, Cossu D, Ruberto S, Noli M, Jasemi S, Simula ER, and Sechi LA
- Abstract
Neurological diseases remain a major concern due to the high world mortality rate and the absence of appropriate therapies to cross the blood-brain barrier (BBB). Therefore, the major focus is on the development of such strategies that not only enhance the efficacy of drugs but also increase their permeability in the BBB. Currently, nano-scale materials seem to be an appropriate approach to treating neurological diseases based on their drug-loading capacity, reduced toxicity, targeted delivery, and enhanced therapeutic effect. Selenium (Se) is an essential micronutrient and has been of remarkable interest owing to its essential role in the physiological activity of the nervous system, i.e., signal transmission, memory, coordination, and locomotor activity. A deficiency of Se leads to various neurological diseases such as Parkinson's disease, epilepsy, and Alzheimer's disease. Therefore, owing to the neuroprotective role of Se (selenium) nanoparticles (SeNPs) are of particular interest to treat neurological diseases. To date, many studies investigate the role of altered microbiota with neurological diseases; thus, the current review focused not only on the recent advancement in the field of nanotechnology, considering SeNPs to cure neurological diseases, but also on investigating the potential role of SeNPs in altered microbiota.
- Published
- 2023
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24. Antibodies against HSV-1 and Curli Show the Highest Correlation in Parkinson's Disease Patients in Comparison to Healthy Controls.
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Jasemi S, Paulus K, Noli M, Simula ER, Ruberto S, and Sechi LA
- Subjects
- Animals, Humans, alpha-Synuclein metabolism, Amyloid metabolism, Antibodies, Herpesvirus 4, Human, Peptides, Viral Proteins, Epstein-Barr Virus Infections, Herpesvirus 1, Human metabolism, Mycobacterium avium subsp. paratuberculosis, Parkinson Disease metabolism
- Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder involving the accumulation of alpha-synuclein (α-syn)/Lewy bodies in the brain and -enteric nervous system. The etiology of the disease is not well understood, but bacterial and viral infections may contribute to the pathogenesis of PD. It has been suggested that the gastrointestinal (GI) complications observed in PD patients may arise from bacterial dysbiosis, leading to curli/α-syn deposits in the enteric nervous system. Enteric bacteria secrete curli, a functional amyloid peptide involved in adhesion to surfaces, cell invasion, and biofilm formation. However, these bacterial amyloids can initiate additional α-syn deposits through immune system activation and cross-seeding. In this study, we investigate the humoral response against α-syn, curli peptides, and various bacterial and viral immunogen peptides in PD patients, and compare them with those in healthy controls (HCs). Polyclonal IgG antibodies (Abs) were detected against peptides derived from α-syn (α-syn100−114), curli (Curli133−141), Porphyromonas gingivalis Pg (RgpA800−812, Kpg328−339), Aggregatibacter actinomycetemcomitans (LtxA1429−445, LtxA264−80), Mycobacterium avium subsp. paratuberculosis (MAP3865c125−133, MAP1,4-a-gbp157−173 and MAP_402718−32), Epstein−Barr virus (EBNA1400−413, BOLF1305−320), and Herpes Simplex virus 1 (UI4222−36), as investigated by indirect ELISA of 51 serum samples from PD and 58 sex and age-matched HCs. Significant differences in OD (optical density) values and Abs positivity between PD patients and HCs were observed for Kpg (82.3% vs. 10.3%), followed by RgpA (60.7% vs. 24.1%), curli (51% vs. 22.4%), and UI42 (43.1% vs. 25.8%) in PD, compared to HCs sera (p < 0.001). No significant difference was found in the ODs obtained from other tested peptides in PD patients, compared to HCs. Significant positive correlations between OD values obtained by ELISA were observed for UI42 and curli (r = 0.811, p < 0.0001), Kpg and RgpA (r = 0.659, p < 0.0001), followed by LtxA1 and LtxA2 (r = 0.653, p < 0.0001). The correlation between the HY scale (Hoehn and Yahr Scale) and LtxA1 (r = 0.306, p < 0.028) and HY and Kpg (r = 0.290, p < 0.038) were significantly positive. This study reports a significantly increased humoral response against curli, Pg, and HSV-1 in PD patients, implying that they could be important factors in the pathogenesis of the disease. In addition, the high positive correlation between UI42 and curli may suggest the involvement of HSV-1 in GI dysbiosis. Therefore, the role of each individual pathogen and curli in PD needs to be further investigated.
- Published
- 2022
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25. HERV-K Envelope Protein Induces Long-Lasting Production of Autoantibodies in T1DM Patients at Onset in Comparison to ZNT8 Autoantibodies.
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Noli M, Meloni G, Ruberto S, Jasemi S, Simula ER, Cossu D, Bo M, Palermo M, and Sechi LA
- Abstract
Human endogenous retroviruses (HERVs) have been thought of as silent passengers within our genomes, but their reactivation has been linked with several autoimmune diseases, including type 1 diabetes (T1DM). In order to evaluate the potential role of HERVs, in addition to the recognized role of HERV-W, we focused on the debated role of the HERV-K family in T1DM. Therefore, we performed a serological evaluation of IgG antibodies against HERV-K Env epitope (HERV-K Env19−37) in comparison to an important β-cellular autoimmunity biomarker, ZnT8, from plasma samples of Sardinian children at the onset of T1DM, different T1DM groups (1−5 and 6−12 years since diagnosis), and healthy controls (HCs), by an indirect enzyme-linked immunosorbent assay (ELISA). A significant antibody response was observed against HERV-K Env19−37 (p < 0.0001) in T1DM patients compared to HCs, and significantly higher IgG responses were detected in the group at the onset compared to the other T1DM groups and HCs. Unlike the trend of the β-cellular autoimmunity autoantibodies, for HERV-K Env antibodies we observed positive values that persist over time up to 5 years since the onset of T1DM. Our results add new evidence about the presence of antibodies against HERV-K in T1DM, but further investigations are necessary to relate these results with the established role of HERVs, considering the contrasting results for HERV-K.
- Published
- 2022
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26. Increased Presence of Antibodies against Type I Interferons and Human Endogenous Retrovirus W in Intensive Care Unit COVID-19 Patients.
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Simula ER, Manca MA, Noli M, Jasemi S, Ruberto S, Uzzau S, Rubino S, Manca P, and Sechi LA
- Subjects
- Autoantibodies, Female, Humans, Intensive Care Units, Male, COVID-19, Endogenous Retroviruses, Interferon Type I
- Abstract
In this work, we observed an increased presence of antibodies (Abs) against type I interferon (IFN-I) in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care unit (ICU) compared to non-ICU COVID-19 patients and healthy control (HC) subjects. Human endogenous retrovirus W (HERV-W) can reactivate after viral infection; therefore, we also investigated the presence of antibodies against HERV-W envelope (HERV-W-env)-derived epitopes. A total of 113 subjects (41 female and 72 male subjects) were analyzed. A significant difference in autoantibodies against IFN-α, IFN-ω, and HERV-W was observed between HCs and ICU patients; indeed, the latter have higher levels of autoantibodies against IFN-α, IFN-ω, and HERV-W than subjects with mild COVID-19 and HCs. Neutralizing anti-IFN-I autoantibodies may affect the ability of IFN-I to bind to the type I interferon receptor (IFNAR), blocking the activation of the antiviral response. IMPORTANCE In this work, we report the increased presence of IFN autoantibodies in correlation with HERV-W-env autoantibodies in ICU COVID-19 patients. The novelty of the results is in the association of these IFN autoantibodies with autoantibodies against HERV-W-env, a protein recently discovered to be overexpressed in lymphocytes of COVID-19 patients and correlated with severe disease and pneumonia. Type I IFNs are part of a complex cross-regulatory network; however, in a small percentage of cases, the increase in autoantibodies against these proteins may lead to damage to the host instead of protection against infectious diseases.
- Published
- 2022
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27. Bisphenols induce human genomic damage and modulate HERVs/env expression.
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Ruberto S, Santovito A, Simula ER, Noli M, Manca MA, and Sechi LA
- Subjects
- Benzhydryl Compounds toxicity, Genomics, Humans, Leukocytes, Mononuclear, Phenols, Sulfones, Endogenous Retroviruses
- Abstract
Bisphenol A (BPA), a recognized endocrine-disrupting chemical, is used in the production of epoxy and polycarbonate resins. Since human exposure to BPA has been associated with increased cancer susceptibility, the market has shifted to products often labeled as "BPA free" containing BPA analogs such as bisphenol F (BPF) and bisphenol S (BPS). However, the European legislation on BPF and BPS is still unclear. This study analyzed the effects of BPA, BPF, and BPS exposure on human peripheral blood mononuclear cells by using in vitro micronucleus assay. Furthermore, it investigated the impact of bisphenols exposure on human endogenous retroviruses (HERVs) expression, which is implicated with the pathogenesis of several human diseases. The micronucleus assay revealed a significant genotoxic effect in peripheral blood cells after exposure to BPA and BPF at concentrations of 0.1, 0.05, and 0.025 μg/ml, and to BPS at 0.1 and 0.05 μg/ml. In addition, BPA exposure seems to upregulate the expression of HERVs, while a downregulation was observed after BPF and BPS treatments. Overall, our data showed the toxic effect of BPA and its analogs on circulating cells in the blood and demonstrated that they could modulate the HERVs expression., (© 2022 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagen Society.)
- Published
- 2022
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28. Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism.
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Carta A, Manca MA, Scoppola C, Simula ER, Noli M, Ruberto S, Conti M, Zarbo IR, Antonucci R, Sechi LA, and Sotgiu S
- Abstract
ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.
- Published
- 2022
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29. Automating the Calibration of Visible Light Positioning Systems.
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Amsters R, Ruberto S, Demeester E, Stevens N, and Slaets P
- Subjects
- Calibration, Humans, Light
- Abstract
Visible light positioning is one of the most popular technologies used for indoor positioning research. Like many other technologies, a calibration procedure is required before the system can be used. More specifically, the location and identity of each light source need to be determined. These parameters are often measured manually, which can be a labour-intensive and error-prone process. Previous work proposed the use of a mobile robot for data collection. However, this robot still needed to be steered by a human operator. In this work, we significantly improve the efficiency of calibration by proposing two novel methods that allow the robot to autonomously collect the required calibration data. In postprocessing, the necessary system parameters can be calculated from these data. The first novel method will be referred to as semi-autonomous calibration, and requires some prior knowledge of the LED locations and a map of the environment. The second, fully-autonomous calibration procedure requires no prior knowledge. Simulation results show that the two novel methods are both more accurate than manual steering. Fully autonomous calibration requires approximately the same amount of time to complete, whereas semi-autonomous calibration is significantly faster.
- Published
- 2022
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30. Efficacy of BCG vaccine in animal models of neurological disorders.
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Cossu D, Ruberto S, Yokoyama K, Hattori N, and Sechi LA
- Subjects
- Animals, BCG Vaccine, Disease Models, Animal, Vaccination, Mycobacterium bovis, Nervous System Diseases prevention & control
- Abstract
The Bacillus Calmette-Guerin (BCG) vaccine can modulate the immune response via antigen-specific immune response, but also it can confer nonspecific protection and therapeutic benefits in several neurological conditions through different heterologous effects of vaccination. However, the precise mechanism of action of BCG remains unclear. In this review, different mechanisms underlying BCG-mediated immunity will be explained in animal models that reflects characteristic feature of neuroinflammatory and neurodegenerative disorders such as multiple sclerosis, Alzheimer's and Parkinson's diseases. Furthermore, evidence for a beneficial effect of the BCG on neuropsychiatric disorders, will be also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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31. HERV-K and HERV-H Env Proteins Induce a Humoral Response in Prostate Cancer Patients.
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Manca MA, Solinas T, Simula ER, Noli M, Ruberto S, Madonia M, and Sechi LA
- Abstract
A higher expression of human endogenous retroviruses (HERVs) has been associated with several malignancies, including prostate cancer, implying a possible use as a diagnostic or prognostic cancer biomarker. For this reason, we examined the humoral response against different epitopes obtained from the envelope protein of HERV-K (HERV-K env-su
19-37 , HERV-K env-su109-126 ), HERV-H (HERV-H env-su229-241 , HERV-H env387-399 ) and HERV-W (HERV-W env-su93-108 , HERV-W env-su248-262 ) in the plasma of patients affected by prostate cancer (PCa), and compared to that of benign prostate hyperplasia (BPH) and a borderline group of patients with atypical small acinar proliferation (ASAP) and prostate intraepithelial neoplasia (PIN) and healthy controls. A significant antibody response was observed against HERV-K env-su109-126 ( p = 0.004) and HERV-H env-su229-241 ( p < 0.0001) in PCa patients compared to HCs, BPH and borderline cohorts, whilst no significance difference was found in the antibodies against HERV-W env-su93-108 and HERV-W env-su248-262 in patients with PCa. Our results provided further proof of the association between HERV-K and PCa and added new evidence about the possible involvement of HERV-H in PCa pathogenesis, highlighting their possibility of being used as biomarkers of the disease.- Published
- 2022
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32. GSTT1 , GSTP1 and XPC genes are associated with longevity in an Italian cohort.
- Author
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Scarfò M, Sciandra C, Ruberto S, and Santovito A
- Subjects
- Adolescent, Case-Control Studies, DNA-Binding Proteins genetics, Genotype, Glutathione S-Transferase pi genetics, Glutathione Transferase genetics, Humans, Polymorphism, Genetic, Risk Factors, X-ray Repair Cross Complementing Protein 1, Genetic Predisposition to Disease, Longevity genetics
- Abstract
Longevity is a complex process controlled by environmental and genetic factors. We evaluated the association of seven drug metabolising and DNA-repair gene polymorphisms with longevity in an Italian cohort. A sample of 756 subjects aged 18-98 was genotyped for CYP1A1 (rs1048943, A>G), GSTM1 (rs 1183423000, presence/absence), GSTT1 (rs1601993659, presence/absence), GSTP1 (rs1695, A>G), XRCC1 (rs1799782, C>T), XRCC1 (rs25489, A>G) and XPC (rs2228001, A>C) gene polymorphisms. The association between the studied gene polymorphisms and longevity was evaluated by dividing the sample into three age groups: 18-50, 51-85, and 86-98. We observed a significant decrease in the frequency of the GSTT1 null, GSTP1 G and XPC C alleles in the oldest group with respect to the youngest one. We also obtained the same results when dividing the sample into 18-85 and 86-98 age groups. The general linear model analyses confirmed a significant decreasing trend with age of the above mentioned alleles. We hypothesised that these minor alleles, being important in the sensitivity against the development of different types of cancer, may reflect a reduced life-expectancy in carrier subjects and may explain their significantly lower frequency observed among subjects belonging to the oldest age group.
- Published
- 2021
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33. Association of TGFβ1 codon 10 (T>C) and IL-10 (G>C) cytokine gene polymorphisms with longevity in a cohort of Italian population.
- Author
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Ruberto S and Santovito A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Codon, Cohort Studies, Female, Humans, Interleukin-10 metabolism, Italy, Male, Middle Aged, Transforming Growth Factor beta1 metabolism, Young Adult, Interleukin-10 genetics, Longevity genetics, Polymorphism, Single Nucleotide, Transforming Growth Factor beta1 genetics
- Abstract
Longevity is a complex process controlled by both environmental and genetic factors. We evaluated the association of four cytokine gene polymorphisms with longevity in an Italian cohort. A sample of 1019 subjects aged 10 to 100 and belonging to the North-Italian population was genotyped for IL-6 (G>C, rs1800796), IL-10-1082 (G>A, rs1800896), TNF-α-308 (G>A, rs1800629), and TGFβ1 codon 10 (T>C, rs1800471) gene polymorphisms. The association between cytokine gene polymorphisms and longevity was evaluated by dividing the sample into four age groups: 10 to 24, 25 to 49, 50 to 85, and 86 to 100. We observed a significant decrease in the frequency of IL-10 A allele in the 25 to 49 (P = 1.1 × 10
-3 ), 50 to 85 (P < 1 × 10-4 ), and 86 to 100 (P = 2 × 10-3 ) age groups compared to that in the youngest age group. Similarly, we found a significant decrease (P < 1 × 10-4 ) in the frequency of TGFβ1 C allele in the 50 to 85 and 86 to 100 age groups compared to that in the 10 to 24 and 25 to 49 age groups. Previously, high levels of TGFβ1 were detected in elderly subjects, suggesting that this cytokine could counterbalance the harmful effects of inflammation. Similarly, IL-10 has strong anti-inflammatory properties and can inhibit the production of proinflammatory cytokines. In the literature, the lowest levels of functional cytokines were found to be associated with TGFβ1 (T>C) and IL-10 (G>A) gene polymorphisms, with consequent increase in the duration of inflammation and cancer risk. For these reasons, it is plausible to observe low rates of these mutations in elderly subjects, as found in our study., (© 2020 Wiley Periodicals LLC.)- Published
- 2021
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34. Embedding covariate adjustments in tree-based automated machine learning for biomedical big data analyses.
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Manduchi E, Fu W, Romano JD, Ruberto S, and Moore JH
- Subjects
- Algorithms, Automation, Humans, Big Data, Data Analysis, Machine Learning
- Abstract
Background: A typical task in bioinformatics consists of identifying which features are associated with a target outcome of interest and building a predictive model. Automated machine learning (AutoML) systems such as the Tree-based Pipeline Optimization Tool (TPOT) constitute an appealing approach to this end. However, in biomedical data, there are often baseline characteristics of the subjects in a study or batch effects that need to be adjusted for in order to better isolate the effects of the features of interest on the target. Thus, the ability to perform covariate adjustments becomes particularly important for applications of AutoML to biomedical big data analysis., Results: We developed an approach to adjust for covariates affecting features and/or target in TPOT. Our approach is based on regressing out the covariates in a manner that avoids 'leakage' during the cross-validation training procedure. We describe applications of this approach to toxicogenomics and schizophrenia gene expression data sets. The TPOT extensions discussed in this work are available at https://github.com/EpistasisLab/tpot/tree/v0.11.1-resAdj ., Conclusions: In this work, we address an important need in the context of AutoML, which is particularly crucial for applications to bioinformatics and medical informatics, namely covariate adjustments. To this end we present a substantial extension of TPOT, a genetic programming based AutoML approach. We show the utility of this extension by applications to large toxicogenomics and differential gene expression data. The method is generally applicable in many other scenarios from the biomedical field.
- Published
- 2020
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35. Evaluation of the possible association of body mass index and four metabolic gene polymorphisms with longevity in an Italian cohort: a role for APOE , eNOS and FTO gene polymorphisms.
- Author
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Santovito A, Galli G, and Ruberto S
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Cohort Studies, Female, Gene Frequency, Humans, Italy, Male, Middle Aged, Peptidyl-Dipeptidase A genetics, Young Adult, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Apolipoproteins E genetics, Body Mass Index, Longevity genetics, Nitric Oxide Synthase Type III genetics, Polymorphism, Genetic
- Abstract
Background: Longevity is considered the result of interactions between environmental and genetic factors. Aim: To investigate the possible association of body mass index and the frequencies of APOE , ACE , eNOS and FTO gene polymorphisms with longevity. Subjects and methods: In total, 1100 healthy volunteers aged 10-100 were recruited. Subjects were genotyped for APOE , ACE , eNOS and FTO gene polymorphisms. Data about height and weight were also collected. The sample was split into four age groups: 1-24, 25-49, 50-85 and 86-100 years. Results: Significant differences were found in BMI values between age groups. A significant decrease of the APOE4 , eNOS 393 and FTO A and allele frequencies was observed in the 86-100 age group compared to the younger groups. For ACE gene, no significant differences were found in the allele frequencies between groups. A similar trend was also observed when the sample was subdivided into two main age groups: 1-85 and 86-100 years. Conclusion: This study provides evidence for a role of APOE , eNOS and FTO gene polymorphisms in longevity. It has been estimated that the number of centenarians worldwide will double each decade until 2100, making population data about gene polymorphisms relevant for further studies about longevity.
- Published
- 2019
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36. Induction of chromosomal aberrations and micronuclei by 2-hydroxy-4-methoxybenzophenone (oxybenzone) in human lymphocytes.
- Author
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Santovito A, Ruberto S, Galli G, Menghi C, Girotti M, and Cervella P
- Subjects
- Adult, Cells, Cultured, Cytokinesis drug effects, Dose-Response Relationship, Drug, Female, Humans, Lymphocytes pathology, Male, Micronuclei, Chromosome-Defective chemically induced, Micronucleus Tests, Mitotic Index, Benzophenones toxicity, Chromosome Aberrations chemically induced, Endocrine Disruptors toxicity, Lymphocytes drug effects, Sunscreening Agents toxicity
- Abstract
Oxybenzone or benzophenone-3 (2-hydroxy-4-methoxybenzophenone; BP-3) is a filter used in a variety of personal care products for protection of human skin and hair from damage by ultraviolet radiation. BP-3 is suspected to exhibit endocrine disruptive properties. Indeed, it was found to be able to interact with the endocrine system causing alteration of its homeostasis, with consequent adverse health effects. Moreover, it is ubiquitously present in the environment, mostly in aquatic ecosystems, with consequent risks to the health of aquatic organisms and humans. In the present study, we analyzed the cytogenetic effects of BP-3 on human lymphocytes using in vitro chromosomal aberrations and micronuclei assays. Blood samples were obtained from five healthy Italian subjects. Lymphocyte cultures were exposed to five concentrations of BP-3 (0.20, 0.10, 0.05, 0.025, and 0.0125 μg/mL) for 24 and 48 h (for chromosomal aberrations and micronuclei tests, respectively). The concentration of 0.10 µg/mL represents the acceptable/tolerable daily intake reference dose established by European Union, whereas 0.20, 0.05, 0.025, and 0.0125 µg/mL represent multiple and sub-multiple of this concentration value. Our results reported cytogenetic effects of BP-3 on cultured human lymphocytes in terms of increased micronuclei and chromosomal aberrations' frequencies at all tested concentrations, including concentrations lower than those established by European Union. Vice versa, after 48-h exposure, a significant reduction of the cytokinesis-block proliferation index value in cultures treated with BP-3 was not observed, indicating that BP-3 does not seem to produce effects on the proliferation/mitotic index when its concentration is equal to or less than 0.20 μg/mL.
- Published
- 2019
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37. In vitro evaluation of genomic damage induced by glyphosate on human lymphocytes.
- Author
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Santovito A, Ruberto S, Gendusa C, and Cervella P
- Subjects
- Cell Nucleus drug effects, Chromosome Aberrations, Cytokinesis drug effects, Cytokinesis genetics, Glycine administration & dosage, Glycine toxicity, Herbicides administration & dosage, Humans, Micronucleus Tests, Mitotic Index, Mutagenicity Tests methods, Mutagens administration & dosage, Mutagens toxicity, Glyphosate, DNA Damage drug effects, Glycine analogs & derivatives, Herbicides toxicity, Lymphocytes drug effects
- Abstract
Glyphosate is an important broad-spectrum herbicide used in agriculture and residential areas for weed and vegetation control, respectively. In our study, we analyzed the in vitro clastogenic and/or aneugenic effects of glyphosate by chromosomal aberrations and micronuclei assays. Human lymphocytes were exposed to five glyphosate concentrations: 0.500, 0.100, 0.050, 0.025, and 0.0125 μg/mL, where 0.500 μg/mL represents the established acceptable daily intake value, and the other concentrations were tested in order to establish the genotoxicity threshold for this compound. We observed that chromosomal aberration (CA) and micronuclei (MNi) frequencies significantly increased at all tested concentrations, with exception of 0.0125 μg/mL. Vice versa, no effect has been observed on the frequencies of nuclear buds and nucleoplasmic bridges, with the only exception of 0.500 μg/mL of glyphosate that was found to increase in a significant manner the frequency of nucleoplasmic bridges. Finally, the cytokinesis-block proliferation index and the mitotic index were not significantly reduced, indicating that glyphosate does not produce effects on the proliferation/mitotic index at the tested concentrations.
- Published
- 2018
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38. Genomic damage induced by the widely used fungicide chlorothalonil in peripheral human lymphocytes.
- Author
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Santovito A, Gendusa C, Ferraro F, Musso I, Costanzo M, Ruberto S, and Cervella P
- Subjects
- Adult, Cells, Cultured, Cytokinesis drug effects, Cytokinesis genetics, Dose-Response Relationship, Drug, Female, Humans, Lymphocytes pathology, Male, Micronuclei, Chromosome-Defective chemically induced, Mitotic Index, Chromosome Aberrations chemically induced, Environmental Pollutants toxicity, Fungicides, Industrial toxicity, Lymphocytes drug effects, Nitriles toxicity
- Abstract
Chlorothalonil is an important broad spectrum fungicide widely used in agriculture, silviculture, and urban settings. As a result of its massive use, chlorothalonil was found in all environmental matrices, with consequent risks to the health of terrestrial and aquatic organisms, as well as for humans. We analyzed the effects of chlorothalonil on human lymphocytes using in vitro chromosomal aberrations (CAs) and micronuclei (MNi) assays. Lymphocytes were exposed to five concentrations of chlorothalonil: 0.600 µg/mL, 0.060 µg/mL, 0.030 µg/mL, 0.020 µg/mL, and 0.015 µg/mL, where 0.020 and 0.600 µg/mL represent the ADI and the ARfD concentration values, respectively, established by FAO/WHO for this compound; 0.030 and 0.060 μg/mL represent intermediate values of these concentrations and 0.015 μg/mL represents the ADI value established by the Canadian health and welfare agency. We observed cytogenetic effects of chlorothalonil on cultured human lymphocytes in terms of increased CAs and MNi frequencies at all tested concentrations, including the FAO/WHO ADI and ARfD values of 0.020 and 0.600 μg/mL, respectively, but with exception of the Canadian ADI value of 0.015 μg/mL. Finally, no sexes differences were found in the levels of CAs and MNi induced by different chlorothalonil concentrations. Similarly, the mitotic index and the cytokinesis-block proliferation index did not show any significant effect on the proliferative capacity of the cells, although at the chlorothalonil concentration of 0.600 μg/mL the P-values of both indices were borderline., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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39. Hospitalization and other risk factors for depressive and anxious symptoms in oncological and non-oncological patients.
- Author
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De Fazio P, Cerminara G, Ruberto S, Caroleo M, Puca M, Rania O, Suffredini E, Procopio L, and Segura-Garcìa C
- Subjects
- Adult, Anxiety Disorders psychology, Depressive Disorder psychology, Female, Hospitalization, Humans, Inpatients statistics & numerical data, Male, Middle Aged, Prevalence, Risk Factors, Surveys and Questionnaires, Anxiety Disorders diagnosis, Cancer Survivors psychology, Depressive Disorder diagnosis, Inpatients psychology, Neoplasms psychology
- Abstract
Objective: Depression and anxiety are common in hospitalized patients. In particular, oncological patients might be vulnerable to depression and anxiety. The aim of this study is to assess and compare different variables and the prevalence of anxiety and depression symptoms between oncological and medically ill inpatients and to identify variables that can influence depressive and anxious symptoms during hospitalization of patients., Methods: A total of 360 consecutive hospitalized patients completed the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Patients Health Questionnaire-9, General Health Questionnaire (GHQ-12), 12-Item Short-Form Survey: physical component summary (PCS), and mental component summary (MCS). Patients were divided into oncological patients and non-oncological patients: groups 1 and 2., Results: Only two significant differences were evident between the groups: the PCS of 12-item Short-form Survey was higher in non-oncological patient (p < 0.000), and the GHQ total score was higher in oncological patients. Variables significantly associated with HADS-D ≥ 8 were lower MCS, higher GHQ-12 score, lower PCS, more numerous previous hospitalizations, longer duration of hospitalization, and positive psychiatric family history. Variables significantly associated with HADS-A ≥ 8 were lower MCS, higher GHQ-12 score, positive psychiatric family history, longer duration of hospitalization, and younger age., Conclusions: Anxiety and depression symptoms in concurrent general medical conditions were associated with a specific sociodemographic profile, and this association has implications for clinical care. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
40. [Psychosomatic approach to patients with headache: alternative or integrated diagnoses?].
- Author
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De Giorgio G, Ruberto S, Firenze C, and Quartesan R
- Subjects
- Adult, Female, Humans, Middle Aged, Headache diagnosis, Headache etiology, Psychophysiologic Disorders diagnosis, Psychophysiologic Disorders etiology
- Abstract
Each person has an inseparable body-mind unity, with psychic factors that can also manifest themselves through changes in the functions of the body, and with changing somatic states that contribute to mental experience. This explains why somatic symptoms fall within psychiatry. When a patient complains about physical symptoms, it is essentially an integrated, multidisciplinary diagnosis which is used to identify the various factors (biological and psychological) which worsen the disorder, and a psychiatric dimensional approach is used to integrate the descriptive symptomatic diagnosis with the psychostructural diagnosis. The same symptoms, in fact, may underlie different psychological dynamics that direct the treatment and determine the prognosis, as explained in three clinical cases that we described. The literature on headaches reports a high rate of co-morbidity between migraines and psychiatric disorders, but doesn't take into account the fact that often the symptom of headache is part of the disorder, even when it presents on its own. In conclusion, a holistic approach is needed for the patient to be diagnosed as having a "psychiatric" form of headache. A medical examination of the illness leading to a diagnoses is essential, according to the criteria of the International Classification of Headache Disease (ICHD-II). In clinical practice, we have integrated the descriptive diagnosis (ICHD-II mini-Plus) with the psychological (Diagnostic Criteria of Psychosomatic Research - DCPR) and psycho-structural (Kenberg's interview, Minnesota Multiphasic Personality Inventory - MMPI) diagnoses. The clarification of the dynamics underlying the definition of symptoms and the role played by psychological factors has influenced the identification of therapeutic objectives and in the identification of the most appropriate strategies.
- Published
- 2010
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