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Summary Background Cutaneous immune-related adverse events (irAEs) represent the most frequent toxicities induced by immune checkpoint inhibitors (ICIs). Objectives To investigate clinical associations of cutaneous toxicities induced by different ICI therapies. Methods This was a multicentre retrospective international cohort study of patients with cancer who developed cutaneous irAEs under ICI therapy. Analysis was performed of the rates and basic characteristics of all cutaneous toxicities, and identification of any associations was performed using univariate and multivariate models. Results In total, 762 patients were included, who developed 993 cutaneous toxicities. Forty different types of skin toxicities were identified. Psoriasis (175 patients, 23·0%) and pruritus (171 patients, 22·4%) were the most common toxicities, followed by macular rash (161 patients, 21·1%) and eczematous-type reactions (150 patients, 19·7%). Multivariate analysis showed that among patients with macular rash, vitiligo or multiple toxicities, patients received ICIs more frequently for melanoma than for NSCLC. Moreover, anti-CTLA4 was less frequent than anti-programmed death 1 treatment in patients with macular rash [odds ratio (OR) 0·11, 95% confidence interval (CI) 0·01–0·76] and vitiligo (OR 0·07, 95% CI 0·006–0·78). A significant association was also seen in patients treated with a combination of ICI and chemotherapy vs. ICI monotherapy. They less frequently developed psoriasis (OR 0·08, 95% CI 0·02–0·31), lichenoid reactions (OR 0·15, 95% CI 0·03–0·77) and eczematous reactions (OR 0·24, 95% CI 0·07–0·78), all compared with pruritic rash. Conclusions Our study showed that skin-oriented toxicities do not share a single pattern and are related to several factors, including the specific agent administered and the underlying malignancy treated. Follow-up plans should be individualized in order to minimize the risk for severe reactions that could compromise optimum therapeutic outcome. What is already known about this topic? Patients with cancer treated with different immune checkpoint inhibitors (ICIs) carry an increased risk of developing various types of skin toxicities. What are the clinical implications of this work? In this multicentre cohort study we showed that ICI-related skin toxicities do not share a single pattern and may depend on several factors, including the specific agent administered and the underlying malignancy.Among patients with macular rash, vitiligo or multiple skin toxicities, patients received ICIs more frequently for melanoma than for non-small cell lung cancer.The combination of ICI and chemotherapy compared with ICI monotherapy occurred to a lesser extent in patients with psoriatic rash lichenoid and eczematous reactions, compared with patients with pruritus.Clinical awareness and specialized dermatological consultation should be advocated.

To assess the real-world clinical treatment outcomes with brodalumab in patients with moderate-to-severe plaque psoriasis in Greece.This was a longitudinal, retrospective, real-world analysis of data from medical records of 106 patients with moderate-to-severe plaque psoriasis, treated with brodalumab for up to 24 months at four University Dermatology Centers in Greece. Efficacy assessments of psoriasis severity [Psoriasis Area and Severity Index (PASI) and Body Surface Area affected (BSA) scores] and its impact on patients' quality of life (QoL) [Dermatology Life Quality Index (DLQI) score] were evaluated at different timepoints up to 24 months.Treatment with brodalumab reduced both mean PASI (14.0-1.5,Brodalumab is effective long term, improving disease severity and health-related QoL in patients with moderate-to-severe plaque psoriasis in a real-world setting.

This document is one of the deliverables of the ACCEPT project, under WP2 – Foundations, and in particular, task T2.4-Security Access Control (SEAC) framework design & guidelines for technical solution developers. The purpose of this deliverable is to give a detailed description of the final cybersecurity framework as it has been designed in agreement with the system architecture. A lot of attention has been given to the protection of the personal data of the users throughout the whole platform. All mechanisms and principles followed are designed with respect to General Data Protection Regulation. All data that are being processed inside the ACCEPT platform have been anonymized, while security mechanisms have been implemented in all components of the platform, to protect the end user’s privacy. A risk assessment has been completed by relevant partners to achieve a clear view of the potential risks and threats, and to plan the proper countermeasures to eliminate them. Finally, this deliverable describes the specific security mechanisms that were finally chosen and incorporated in the ACCEPT platform, following the previous version the Deliverable D2.5-Report on cybersecurity framework design & specifications for data protection & privacy v1.

Crowdsourcing aims to deliver services and content by aggregating contributions from a large user population. For mobile networks and IoT systems, crowdsourcing is used to gather and process sensor data from mobile devices (crowdsensing), in order to deliver real-time, context-aware services and possibly support user collaboration in extended geographic areas. In applications like geonsensitive navigation, location-based activity sharing and recommendations, the challenge of adequate service quality and user experience may be at stake, as the services are provided securely to an ever-growing user population. This happens due to the inherent trade-off between security and real-time performance that ultimately sets in doubt any scalability prospect beyond a certain user-interaction load. This work introduces a publish-subscribe architecture for mobile crowdsensing systems, which can be transparently scaled up to higher usage load, while retaining adequate performance and security by load balancing into multiple MQTT brokers. The security support combines a lightweight TLS implementation with an integrated mechanism for two-level access control: user-device interactions and message topics. We provide proof-of-concept measurements that show how our solution scales to increasing interaction loads through load-balancing the processing cost that includes the overhead of the security mechanisms applied. The system architecture was implemented in a vehicular crowdsensing navigation network that allows to exchange navigation information at real-time, for improved routing of vehicles to their destination.

Nipple pain and discomfort during or after breastfeeding remains one of the most common reasons for premature cessation of lactation among the affected women. The belief that yeasts, and especially

// Anastasia E. Kottorou 1 , Anna G. Antonacopoulou 1 , Foteinos-Ioannis D. Dimitrakopoulos 1, 3 , Georgia Diamantopoulou 2 , Chaido Sirinian 1 , Melpomeni Kalofonou 1, 6 , Theodoros Theodorakopoulos 2 , Chrysa Oikonomou 3 , Evangelos C. Katsakoulis 2 , Angelos Koutras 1, 3 , Thomas Makatsoris 1, 3 , Nikos Demopoulos 4 , Georgia Stephanou 4 , Michalis Stavropoulos 5 , Konstantinos C. Thomopoulos 2 and Haralabos P. Kalofonos 1, 3 1 Clinical and Molecular Oncology Laboratory, Division of Oncology, Medical School, University of Patras, Patras, Greece 2 Division of Gastroenterology, University Hospital of Patras, Patras, Greece 3 Division of Oncology, University Hospital of Patras, Patras, Greece 4 Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, Patras, Greece 5 Department of Surgery, Medical School, University of Patras, Patras, Greece 6 Institute of Biomedical Engineering, Imperial College London, London, UK Correspondence to: Haralabos P. Kalofonos, email: kalofonos@upatras.gr Keywords: transcribed-ultra conserved regions; colorectal cancer and adenomas; tissue and plasma methylation; screening biomarker; expression levels Received: January 12, 2017 Accepted: March 02, 2018 Published: April 20, 2018 ABSTRACT Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, Uc283 and Uc346 were lower in neoplastic tissues from 64 CRC patients (statistically significant for Uc160, p

e15130 Background: Expression of Transcribed Ultra Conserved Regions (T-UCRs) is often deregulated in cancer. We investigated the role of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal adenocarcinomas and their prognostic and diagnostic value. Methods: Expression and methylation levels of the T-UCRs were assessed in neoplastic and paired non-malignant fresh frozen (FF) tissue specimens from 64 colorectal cancer (CRC) patients, as well as in 6 FF adenoma tissue specimens. In addition, T-UCR methylation levels were assessed in FFPE tumor tissues from 80 CRC patients and in plasma from 161 patients (50 CRC, 59 adenoma patients, 40 healthy subjects and 12 patients with colon inflammation or diverticulosis). Results: Expression levels of all three T-UCRs were lower in neoplastic, compared to non-malignant tissues, although at a statistically significant level only for Uc160 ( p< 0.001). Also, methylation levels of Uc160, Uc283 and Uc346 were higher in tumors compared to non-malignant tissues ( p< 0.001, p= 0.001 and p= 0.004 respectively). Tissue methylation levels of Uc160 were associated with TTP ( p= 0.017). The combination of Uc283 and Uc346 methylation levels was related to OS, however without reaching statistical significance ( p= 0.066). Methylation status of Uc160 and Uc346 in plasma differed significantly among the four patient groups with CRC patients exhibiting the higher levels. Moreover, a strong correlation was found between Uc160 plasma methylation levels and adenoma or adenocarcinoma size and lymph node infiltration ( p< 0.001 and p= 0.024 respectively). When methylation status was used to predict if a subject has CRC, sensitivity and specificity were 35% and 89% respectively, while the values changed to 45% and 74.3% respectively when we combined the sum of the three T-UCR plasma methylation levels. For adenomas, the combination of Uc160 and Uc346 plasma methylation displayed 30.2% (sensitivity) and 80.7% (specificity). Conclusions: T-UCR expression and methylation is deregulated in CRC while their methylation has prognostic value and appears a promising non-invasive screening test for CRC and adenomas, provided that the sensitivity of the assay is improved.