STAMINA: Bioinformatics Platform for Monitoring and Mitigating Pandemic Outbreaks

Data Availability Statement: All data driven applications used the our world in data COVID-19 datasets, complimented by proprietary datasets share by the STAMINA consortium.Copyright © 2022 by the authors. This paper presents the components and integrated outcome of a system that aims to achieve early detection, monitoring and mitigation of pandemic outbreaks. The architecture of the platform aims at providing a number of pandemic-response-related services, on a modular basis, that allows for the easy customization of the platform to address user’s needs per case. This customization is achieved through its ability to deploy only the necessary, loosely coupled services and tools for each case, and by providing a common authentication, data storage and data exchange infrastructure. This way, the platform can provide the necessary services without the burden of additional services that are not of use in the current deployment (e.g., predictive models for pathogens that are not endemic to the deployment area). All the decisions taken for the communication and integration of the tools that compose the platform adhere to this basic principle. The tools presented here as well as their integration is part of the project STAMINA.The paper presented is based on research undertaken as part of the European Commission-funded project STAMINA (Grant Agreement 883441)

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Design and development of personal activity organiser application in iOS

115 σ.Οι «έξυπνες» συσκευές και συγκεκριμένα τα «έξυπνα» τηλέφωνα (smartphones), αποτελούν πλέον αναπόσπαστο κομμάτι της καθημερινότητας μας. Σε αυτά, προσφέρεται μια πληθώρα εφαρμογών, που μας βοηθούν σε πολλέςπτυχές της ζωής μας. Ο σκοπός της διπλωματικής εργασίας είναι η σχεδίαση και η ανάπτυξη μίας εφαρμογής, η οποία θα λειτουργεί σαν προσωπικός βοηθός για το χρήστη της, βοηθώντας τον να καταγράψει και να εκτελέσει το πρόγραμμα της καθημερινότητας του. Η εφαρμογή προορίζεται για τις συσκευές που χρησιμοποιούν το λειτουργικό σύστημα iOS, οι οποίες είναι το iPhone,το iPod και το iPad. Η εφαρμογή θα παρέχει στο χρήστη τη δυνατότητα να δημιουργεί δραστηριότητες και να τις οργανώνει σε ένα πρόγραμμα. Για κάθε δραστηριότητα ο χρήστης θα μπορεί να θέτει μία τοποθεσία για τη πραγματοποίηση της. Οι δραστηριότητες θα χωρίζονται σε δύο κατηγορίες, τις προγραμματισμένες και τις μη προγραμματισμένες. Για τις προγραμματισμένες ο χρήστης θα λαμβάνει ειδοποιήσεις χρονικά, κάποια στιγμή πριν από τη δραστηριότητα και τη στιγμή της έναρξης της. Για τις μη προγραμματισμένες θα χρησιμοποιηθούν υπηρεσίες τοποθεσίας και ο χρήστης θα ειδοποιείται όταν βρίσκεται σε κοντινή απόσταση από την επιθυμητή τοποθεσία. Η χρήστης θα μπορεί να προσθέτει νέες τοποθεσίες από τον χάρτη αλλά θα μπορεί να χρησιμοποιεί και το λογαριασμό του στο Facebook για να αναζητά κοντινές τοποθεσίες. Αυτές τις τοποθεσίες θα είναι δυνατό να τις διαθέτει και στους άλλους χρήστες της εφαρμογής μέσω ενός server. Η ανάπτυξη της εφαρμογής έγινε με τη βοήθεια δύο υπολογιστών της Apple, ενός Macmini και ενός MacbookPro, σε περιβάλλον MacOSX 10.8.4. Επίσης για τη δοκιμή της εφαρμογής χρησιμοποιήθηκαν δύο iOS συσκευές, ένα iPhone 5 και ένα iPodtouch τέταρτης γενιάς, τα οποία χρησιμοποιούν της έκτη έκδοση του λειτουργικού συστήματος, το iOS 6. Τέλος, για την ανάπτυξη της εφαρμογής, χρειάστηκε να εγγραφούμε ως μέλη στο πρόγραμμα ανάπτυξης εφαρμογών για iOS της Apple (iOS Developer Program).Smart devices and especially smartphones, are an integral part of our everyday lives. They offer a huge amount of applications, that could help us in almost every aspect of our lives. The purpose of this thesis is to design and develop an application, which works as a personal assistant for the user, helping him to record and perform the program of his everyday life. The application is intended for devices that use the operating system iOS, which are iPhone, iPod and iPad. The application will provide the user the ability to create activities and to organize them in a program. For each activity, the user may specify a location for itsaccomplishment. Activities will be divided into two categories, scheduled and not scheduled. For the scheduled activities, the user will receive notifications, sometime prior to the activity and at the time of accomplishment. For the not scheduled ones,location based services will be used and the user will be notified when he is within walking distance from the desired location. The user will not only be able to add new locations on the map, but also use his account on Facebook to search for nearby locations. These locations will be possible to be disposed to other users of the application via a server. The development of the application was performed using two computers of Apple, a Mac mini and a Macbook Pro, in an environment of Mac OS X 10.8.4. Also, for testing the application we used two iOS devices, an iPhone 5 and an iPod touch fourth generation, which use iOS 6. Finally, for the application development, we had to register as members of application development program for iOS of Apple (iOS Developer Program).Εμμανουήλ Γ. ΚαραμανήςΠέτρος-Φλώριος Ν. Μπάκαλο

Evidence of Association Between Methylenetetrahydrofolate Reductase Gene and Susceptibility to Breast Cancer: A Candidate-Gene Association Study in a South-Eastern European Population

The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a candidate gene for breast cancer (BC). However, the specific role of MTHFR polymorphisms and haplotypes has not been fully clarified and replicated. We examined the association of two common MTHFR polymorphisms (C677T and A1298C) and their haplotypes in a candidate-gene association study, involving 300 female patients with BC and 283 healthy women. The single locus analysis for the two polymorphisms revealed an association only for the C677T polymorphism [odds ratio (95% confidence interval), OR=2.05 (1.21-3.48)], but adjustment for age diminished this association [OR=1.76 (0.92-3.42)]. The menopausal status showed no significant effect in the association between the MTHFR polymorphisms and BC. The analysis of haplotypes showed an association for the C677-A1298 haplotypes (p=0.04). The available evidence from our study may support a contributory role of MTHFR polymorphisms in BC development. Future larger studies may help in elucidating the genetics of BC further

On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients

Background & AimsWe assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. MethodsNinety-five HBeAg-negative patients received peginterferonalfa-2a for 48weeks and were followed-up for 48weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA 10% at 24weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074

On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients

Background &amp; AimsWe assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. MethodsNinety-five HBeAg-negative patients received peginterferonalfa-2a for 48weeks and were followed-up for 48weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA &lt;2000IU/ml at study week 96. ResultsTwenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline 10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P=0.001]. The PARC rule (no decrease in HBsAg and &lt;2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of 10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of &lt;10% (1 achieved SR; negative predictive value: 93%). ConclusionsIn HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline &gt;10% at 24weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074