25 research outputs found
MobiDB 3.0: more annotations for intrinsic disorder, conformational diversity and interactions in proteins
The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics. Predictions have been expanded to provide new types of annotation on backbone rigidity, secondary structure preference and disordered binding regions. MobiDB 3.0 contains information for the complete UniProt protein set and synchronization has been improved by covering all UniParc sequences. An advanced search function allows the creation of a wide array of custom-made datasets for download and further analysis. A large amount of information and cross-links to more specialized databases are intended to make MobiDB the central resource for the scientific community working on protein intrinsic disorder and mobility
An Exploratory Study of Field Failures
Field failures, that is, failures caused by faults that escape the testing
phase leading to failures in the field, are unavoidable. Improving verification
and validation activities before deployment can identify and timely remove many
but not all faults, and users may still experience a number of annoying
problems while using their software systems. This paper investigates the nature
of field failures, to understand to what extent further improving in-house
verification and validation activities can reduce the number of failures in the
field, and frames the need of new approaches that operate in the field. We
report the results of the analysis of the bug reports of five applications
belonging to three different ecosystems, propose a taxonomy of field failures,
and discuss the reasons why failures belonging to the identified classes cannot
be detected at design time but shall be addressed at runtime. We observe that
many faults (70%) are intrinsically hard to detect at design-time
MobiDB 3.0: More annotations for intrinsic disorder, conformational diversity and interactions in proteins
The MobiDB (URL: mobidb.bio.unipd.it) database of protein disorder and mobility annotations has been significantly updated and upgraded since its last major renewal in 2014. Several curated datasets for intrinsic disorder and folding upon binding have been integrated from specialized databases. The indirect evidence has also been expanded to better capture information available in the PDB, such as high temperature residues in X-ray structures and overall conformational diversity. Novel nuclear magnetic resonance chemical shift data provides an additional experimental information layer on conformational dynamics. Predictions have been expanded to provide new types of annotation on backbone rigidity, secondary structure preference and disordered binding regions. MobiDB 3.0 contains information for the complete UniProt protein set and synchronization has been improved by covering all UniParc sequences. An advanced search function allows the creation of a wide array of custom-made datasets for download and further analysis. A large amount of information and cross-links to more specialized databases are intended to make MobiDB the central resource for the scientific community working on protein intrinsic disorder and mobility.Fil: Piovesan, Damiano. UniversitĂ di Padova; ItaliaFil: Tabaro, Francesco. UniversitĂ di Padova; ItaliaFil: Paladin, Lisanna. UniversitĂ di Padova; ItaliaFil: Necci, Marco. UniversitĂ di Padova; Italia. Instituto Agrario San Michele all'Adige Fondazione Edmund Mach; ItaliaFil: Micetić, Ivan. UniversitĂ di Padova; ItaliaFil: Camilloni, Carlo. UniversitĂ degli Studi di Milano; ItaliaFil: Davey, Norman. Universidad de Dublin; IrlandaFil: Dosztányi, Zsuzsanna. Eötvös Loránd University; HungrĂaFil: MĂ©száros, Bálint. Eötvös Loránd University; HungrĂaFil: MonzĂłn, Alexander. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Parisi, Gustavo Daniel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y TecnologĂa; ArgentinaFil: Schad, Eva. Hungarian Academy Of Sciences; HungrĂaFil: Sormanni, Pietro. University of Cambridge; Reino UnidoFil: Tompa, Peter. Vrije Unviversiteit Brussel; BĂ©lgicaFil: Vendruscolo, Michele. University of Cambridge; Reino UnidoFil: Vranken, Wim F.. Vrije Unviversiteit Brussel; BĂ©lgicaFil: Tosatto, Silvio C. E.. UniversitĂ di Padova; Itali
Effectiveness of perampanel as the only add-on: Retrospective, multicenter, observational real-life study on epilepsy patients
Objective: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment. Methods: We performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency, and adverse events were recorded at 3, 6, and 12 months after PER introduction. Subanalyses by early or late use of PER and by concomitant ASM were also conducted. Results: Five hundred and three patients were included (age 36.5 ± 19.9 years). Eighty-one percent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the subanalyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3-month follow-up (66% vs 53%, P =.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials. Significance: This study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs
Perampanel effectiveness and tolerability in patients with epilepsy at long-term follow-up
Introduction: The main of the present study was to assess the effectiveness and tolerability of perampanel (PER) in association with 1 or 2 concomitant antiseizure medications (ASMs) in patients with epilepsy throughout a follow-up period of 24 months or longer in a real-world setting.Methods: This retrospective, observational, multi-center study collected data from both underage (<18 years old) and adult patients who had started PER in association with 1 or 2 ASMs. Only patients who had started PER and were followed up for at least 24 months were included. Response to treatment was analyzed at the 24-, 36-, and 48-month visits by considering the last visit undergone by patients. Subgroup analyses were performed according to age, gender, and epilepsy type and patients were categorized following PER treatment in concomitance with 1 or 2 ASMs to evaluate the factors affecting the achievement of seizure freedom (SF) at the 24-month FU.Results: Ninety-four patients were included (mean age 36.89 years; 51.1% female). At the 24-month follow-up visit, 90 (95.74%) patients were still receiving PER concomitantly with 1 or 2 ASMs. The mean PER dose was 6.02 mg/day and SF was achieved by 33 (35.1%) patients. A significantly higher SF rate was found in patients who had started PER with only 1 ASM when compared to those who had started PER with 2 concomitant ASMs. Effectiveness was maintained also in the subgroups of patients with a 36-or 48-month follow-up visit. Adult patients had a higher final daily dosage of PER than underage patients. Logistic regression found that the lowest number of previously failed ASMs was associated with a higher SF rate (p = 0.036).Conclusion: Perampanel demonstrated a good effectiveness in association with 1 or 2 ASMs in both pediatric and adult patients, without having to use a high dose of the drug. The possibility to present SF was higher when PER was added early. Finally, the maintenance of effectiveness was observed also in the subgroups of patients with a follow-up of 36 and 48 months. (C) 2021 Elsevier Inc. All rights reserved
Effectiveness of Perampanel as the Only Add-on: Retrospective, Multicenter, Observational Real Life Study on epilepsy patients.
Objective: Perampanel (PER) is indicated as adjunctive antiseizure medication (ASM) in adolescents and adults with epilepsy. Data from clinical trials show good efficacy and tolerability, while limited information is available on the routine clinical use of PER, especially when used as only add-on treatment.
Methods: we performed an observational, retrospective, multicenter study on people with focal or generalized epilepsy aged >12 years, consecutively recruited from 52 Italian epilepsy centers. All patients received PER as the only add-on treatment to a background ASM according to standard clinical practice. Retention rate, seizure frequency and adverse events were recorded at 3, 6 and 12 months after PER introduction. Sub-analyses by early or late use of PER and by concomitant ASM were also conducted.
Results: 503 patients were included (age 36.5±19.9 years). Eighty-one per cent had focal epilepsy. Overall, the retention rate was very high in the whole group (89% at 12 months) according with efficacy measures. No major differences were observed in the sub-analyses, although patients who used PER as early add-on, as compared with late add-on, more often reached early seizure freedom at 3 months follow-up (66% vs. 53%, p=0.05). Treatment-emergent adverse events occurred in 25%, far less commonly than in PER randomized trials.
Significance: this study confirms the good efficacy and safety of PER for focal or generalized epilepsy in real-life conditions. We provide robust data about its effectiveness as only add-on treatment even in patients with a long-standing history of epilepsy and previously treated with many ASMs