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Abstract Background Perceval-S has become a reliable and commonly used option in surgical aortic valve replacement (AVR) since its first implantation in humans 15 years ago. Despite the fact that this aortic valve has been proven efficient enough in the short and mid-term period, there is still lack of evidence for the long-term outcomes. Materials and methods This is an observational retrospective study in a high-volume cardiovascular center. Pertinent data were collected for all the patients in whom Perceval-S was implanted from 2013 to 2020. Results The total number of patients was 205 with a mean age 76.4 years. Mean survival time was 5.5 years (SE = 0.26). The overall survival probability of patients undergoing aortic valve replacement with Perceval-S at 6 months was 91.0% (Standard Error SE = 2.0%), at one year 88.4% (SE = 2.3%) and at 5-years 64.8% (SE = 4.4%). A detrimental cardiac event leading to death was the probable cause of death in 35 patients (55.6%). The initiation of Transcatheter Aortic Valve Replacement (TAVR) program in our center in 2017 was associated with a decline in the number of very high-risk patients treated with sutureless bioprosthesis. This fact is demonstrated by the significant shift towards lower surgical risk cases, as median Euroscore II was reduced from 5,550 in 2016 to 3,390 in 2020. Mini sternotomy was implemented in 79,5% of cases favoring less invasive approach. Low incidence of reinterventions, patient prosthesis mismatch and structural valve degeneration was detected. Conclusions The survival rate after aortic valve replacement with implantation of Perceval-S is satisfactory in the long-term follow-up. Cases of bioprosthesis dysfunction were limited. Mini sternotomy was used in the majority of cases. TAVR initiation program impacted on the proportion of patients treated with Perceval-S with reduction of high-risk patients submitted to surgery.

Introduction: The evidence concerning Moral Distress (MD) among physicians is limited, while such data are absent for physicians working in the Greek National Health System (GNHS). The purpose of this study is the investigation of MD among physicians in Greece and the validation Moral Distress Scale-Revised (MDS-R) as a reliable method for the measurement of MD in the Greek language. Methods: This is a multicenter study in which 200 physicians of all specialties and degrees participated. A self-reporting questionnaire was used. The MDS-R questionnaire is constituted of 21 items that describe conditions met in clinical practice, aiming to investigate the frequency and intensity of such cases. The questionnaire was translated and validated in the Greek language. Results: The test-retest procedure was undergone in a sample of 18 physicians and it was found significant and high agreement in all of the MD scale items. Therefore, all 21 items of the MDS-R questionnaire were found suitable for inclusion in the Greek version of MDS-R. A model of four main factors emerged after the analysis of the results with a total variance of 46,8% and all these factors were correlated with each other. MD was detected to a significant degree in more than half participants. The incidence and intensity of MD were higher in physicians who worked in general hospitals compared to those working in cancer hospitals, which is reported for the first time. Conclusions: The Greek version of MDS-R is a valid and reliable instrument for the investigation of MD among Greek physicians. Moral distress impacts the Greek physicians but the degree depends on the working position. Moral distress is also associated with leaving a working position among Greek physicians.

Background: This study is a pioneer systematic review and meta-analysis aimed at comparing the influence of Class II and Class III skeletal malocclusions on pharyngeal airway dimensions. It stands as the inaugural comprehensive assessment to collate and analyze the disparate findings from previously published articles on this topic. The objective of this study was to identify published articles that compare the effects of class II and class III skeletal malocclusion on the pharyngeal airway dimensions. Methods: An all-inclusive search for existing published studies was done to identify peer-reviewed scholarly articles that compared the influence of class II and class III skeletal malocclusion on pharyngeal airway dimensions. The search was done via five electronic databases: Cochrane Library, EMBASE, Scopus, Web of Science, and PubMed. Screening of the articles was done and the eligible studies were critically assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Results: The initial search yielded 476 potential articles of which, nine were finally included in this study for a total of 866 patients. Three studies were of cross-sectional design and six were of retrospective study design. Following a critical analysis and review of the studies, class III skeletal malocclusion had significantly larger volume and area measurements compared to class II skeletal malocclusion. Conclusion: Research in the field of literature has established that variations in skeletal classifications have a discernible effect on the size of the pharyngeal airways. With the advancement of skeletal malocclusions to a class III, there is an observed increase in both the volume and cross-sectional area of the airways.

Abstract Disease-causing mutations in genes encoding transcription factors (TFs) can affect TF interactions with their cognate DNA-binding motifs. Whether and how TF mutations impact upon the binding to TF composite elements (CE) and the interaction with other TFs is unclear. Here, we report a distinct mechanism of TF alteration in human lymphomas with perturbed B cell identity, in particular classic Hodgkin lymphoma. It is caused by a recurrent somatic missense mutation c.295 T > C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cells. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF CEs. IRF4-C99R thoroughly modifies IRF4 function by blocking IRF4-dependent plasma cell induction, and up-regulates disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single mutation causes a complex switch of TF specificity and gene regulation and open the perspective to specifically block the neomorphic DNA-binding activities of a mutant TF.

Operating centrifugal pumps under two-phase flow conditions presents challenges such as phase separation, cavitation, and flow instabilities, compromising reliability and performance. A specialized design is crucial to mitigate these issues. This study utilized computational fluid dynamics (CFDs) to understand two-phase flow behavior and assess the impact of different blade geometries on pump performance under such conditions. For this purpose, the inhomogeneous multiphase model was employed, wherein the momentum and continuity flow equations were individually solved for each phase across three different impellers with varying blade angle distributions. The computational results indicated higher gas concentrations on the pressure side of the blade, with gas pocket size correlating with flow rate and inlet gas concentration. The blade angle distribution’s effect was more pronounced with increased gas concentrations, while a tendency of gas bubbles to coalesce towards the impeller shroud was also observed. The presence of gas promoted flow recirculation and separation, substantially reducing impeller performance. Blade angle distribution critically influenced the flow field, affecting flow separation, stability, efficiency, and overall performance, highlighting the importance of optimized blade design for enhanced centrifugal pump performance in liquid–gas two-phase flow conditions.

Active reconnaissance is the primary source of information gathering about the infrastructure of a target network for intruders. Its main functions are host discovery and port scanning, the basic techniques of which are thoroughly analyzed in the present paper. The main contribution of the paper is the definition of a modeling approach regarding (a) all possible intruder actions, (b) full or partial knowledge of the intruder’s preferred methodology, and (c) the topology of the target network. The result of the modeling approach, which is based on state diagrams, is the extraction of a set of all probable paths that the intruder may follow. On top of this, a number of relevant metrics are calculated to enable the dynamic assessment of the risk to specific network assets according to the point on the paths at which the intruder is detected. The proposed methodology aims to provide a robust model that can enable the efficient and automated application of deception techniques to protect a given network. A series of experiments has also been performed to assess the required resources for the modeling approach when applied in real-world applications and provide the required results with bearable overhead to enable the online application of deception measures.

The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.

Diagnosing any of the more than 30 types of T-cell lymphomas is considered a challenging task for many pathologists and currently requires morphological expertise as well as the integration of clinical data, immunophenotype, flow cytometry and clonality analyses. Even considering all available information, some margin of doubt might remain using the current diagnostic procedures. In recent times, the genetic landscape of most T-cell lymphomas has been elucidated, showing a number of diagnostically relevant mutations. In addition, recent data indicate that some of these genetic alterations might bear prognostic and predictive value. Extensive genetic analyses, such as whole exome or large panel sequencing are still expensive and time consuming, therefore limiting their application in routine diagnostic. We therefore devoted our effort to develop a lean approach for genetic analysis of T-cell lymphomas, focusing on maximum efficiency rather than exhaustively covering all possible targets. Here we report the results generated with our small amplicon-based panel that could be used routinely on paraffin-embedded and even decalcified samples, on a single sample basis in parallel with other NGS-panels used in our routine diagnostic lab, in a relatively short time and with limited costs. We tested 128 available samples from two German reference centers as part of our routine work up (among which 116 T-cell lymphomas), which is the largest routine diagnostic series reported to date. Our results showed that this assay had a very high rate of technical success (97%) and could detect mutations in the majority (79%) of tested T-cell lymphoma samples.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma often with poor prognosis. To identify genes defining ALCL cell state and dependencies, the authors here characterize ALCL-specific super-enhancers and describe the BATF3/IL-2R−module as a therapeutic opportunity for ALCL.

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3’untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.

Plasmablastic lymphoma (PBL) is an aggressive lymphoma subtype characterized by poor prognosis but the molecular knowledge of the disease is limited. Here, the authors perform whole exome sequencing and copy number determination of primary samples highlighting IRF4 and JAK-STAT pathways as therapeutic targets for PBL.

The adipokine leptin modulates intestinal inflammation in mice. Here the authors describe a patient with inflammatory bowel disease and lipodystrophy, providing evidence that leptin aggravates intestinal inflammation with proinflammatory effects on leukocytes that are reversible by TNFα blockade.

In acute myeloid leukemia, there is an ongoing debate on the prognostic value of the early bone marrow assessment in patients receiving intensive therapy. In this retrospective study, we analyzed the prognostic impact of the early response in 1,008 patients with newly diagnosed acute myeloid leukemia, who were treated at our institution with intensive chemotherapy followed by consolidation chemotherapy and/or allogeneic hematopoietic stem cell transplantation (HSCT). We found that early blast persistence has an independent negative prognostic impact on overall survival, eventfree survival and relapse-free survival. This negative prognostic impact may only be overcome in patients showing at least a partial remission at the early bone marrow assessment and who subsequently achieve blast clearance by additional induction chemotherapy prior to consolidation therapy with allogeneic HSCT. In accordance, we propose that the time slope of remission is an additional leukemia-related dynamic parameter that reflects chemosensitivity and thus may inform post-induction therapy decision-making. In addition to patient-related factors, European LeukemiaNet risk group, measurable residual disease monitoring and donor availability, this may particularly apply to European LeukemiaNet intermediate-risk patients, for whom a decision between consolidation chemotherapy and allogeneic HSCT remains challenging in many cases.

In our era of big data and information overload, content consumers utilise a variety of sources to meet their data and informational needs for the purpose of acquiring an in-depth perspective on a subject, as each source is focused on specific aspects. The same principle applies to the online social networks (OSNs), as usually, the end-users maintain accounts in multiple OSNs so as to acquire a complete social networking experience, since each OSN has a different philosophy in terms of its services, content, and interaction. Contrary to the current literature, we examine the users’ behavioural and disseminated content patterns under the assumption that accounts maintained by users in multiple OSNs are not regarded as distinct accounts, but rather as the same individual with multiple social instances. Our social analysis, enriched with information about the users’ social influences, revealed behavioural patterns depending on the examined OSN, its social entities, and the users’ exerted influence. Finally, we ranked the examined OSNs based on three types of social characteristics, revealing correlations between the users’ behavioural and content patterns, social influences, social entities, and the OSNs themselves.

BackgroundWithin the bone marrow (BM), mature T cells are maintained under homeostatic conditions to facilitate proper hematopoietic development. This homeostasis depends upon a peculiar elevated frequency of regulatory T cells (Tregs) and immune regulatory activities from BM-mesenchymal stem cells (BM-MSCs). In response to BM transplantation (BMT), the conditioning regimen exposes the BM to a dramatic induction of inflammatory cytokines and causes an unbalanced T-effector (Teff) and Treg ratio. This imbalance negatively impacts hematopoiesis, particularly in regard to B-cell lymphopoiesis that requires an intact cross-talk between BM-MSCs and Tregs. The mechanisms underlying the ability of BM-MSCs to restore Treg homeostasis and proper B-cell development are currently unknown.MethodsWe studied the role of host radio-resistant cell-derived CD40 in restoring Teff/Treg homeostasis and proper B-cell development in a murine model of BMT. We characterized the host cellular source of CD40 and performed radiation chimera analyses by transplanting WT or Cd40-KO with WT BM in the presence of T-reg and co-infusing WT or - Cd40-KO BM-MSCs. Residual host and donor T cell expansion and activation (cytokine production) and also the expression of Treg fitness markers and conversion to Th17 were analyzed. The presence of Cd40+ BM-MSCs was analyzed in a human setting in correlation with the frequency of B-cell precursors in patients who underwent HSCT and variably developed acute graft-versus-host (aGVDH) disease.ResultsCD40 expression is nearly undetectable in the BM, yet a Cd40-KO recipient of WT donor chimera exhibited impaired B-cell lymphopoiesis and Treg development. Lethal irradiation promotes CD40 and OX40L expression in radio-resistant BM-MSCs through the induction of pro-inflammatory cytokines. OX40L favors Teff expansion and activation at the expense of Tregs; however, the expression of CD40 dampens OX40L expression and restores Treg homeostasis, thus facilitating proper B-cell development. Indeed, in contrast to dendritic cells in secondary lymphoid organs that require CD40 triggers to express OX40L, BM-MSCs require CD40 to inhibit OX40L expression.ConclusionsCD40+ BM-MSCs are immune regulatory elements within BM. Loss of CD40 results in uncontrolled T cell activation due to a reduced number of Tregs, and B-cell development is consequently impaired. GVHD provides an example of how a loss of CD40+ BM-MSCs and a reduction in B-cell precursors may occur in a human setting.

The descriptive concepts of “semantic” taxonomies are assigned to content items of the publishing domain for supporting a plethora of operations, mostly regarding the organization and discoverability of the content, as well as for recommendation tasks. However, either not all publishers rely on such structures, or in many cases employ their own proprietary taxonomies, thus the content is either difficult to be retrieved by the end users or stored in publisher-specific fragmented “data-silos”, respectively. To address these issues, the modular and scalable “Dominance Metric” methodology is proposed for rating the dominance and importance of concepts in semantic taxonomies. Our proposed metric is applied both on the vast multidisciplinary Microsoft Academic Graph Fields of Study taxonomy and the MeSH controlled vocabulary in order for their enhanced and refined versions to be produced. Moreover, we describe the cleansing process of the resulting taxonomy from Microsoft’s structure by deduplicating concepts and refining the hierarchical relations towards the increase of its representation quality. Our evaluation procedure provided valuable insights by showcasing that high volume, namely the number of publications a concept is assigned to, does not necessarily imply high influence, but the latter is also affected by the structural and topological properties of the individual entities.

Alcohol consumption is a known, modifiable risk factor for incident atrial fibrillation (AF). However, it remains unclear whether the protective effect of moderate alcohol consumption-that has been reported for various cardiovascular diseases also applies to the risk for new-onset AF. The purpose of this meta-analysis was to evaluate the role of different drinking patterns (low: 168 grams/week) on the risk for incident AF. Major electronic databases were searched for observational cohorts examining the role of different drinking behaviors on the risk for incident AF. We analyzed 16 studies (13,044,007 patients). Incident AF rate was 2.3%. Moderate alcohol consumption significantly reduced the risk for new-onset AF when compared to both abstainers (logOR: −0.20; 95%CI: −0.28–−0.12; I2: 96.71%) and heavy drinkers (logOR: −0.28; 95%CI: −0.37–−0.18; I2: 95.18%). Heavy-drinking pattern compared to low also increased the risk for incident AF (logOR: 0.14; 95%CI: 0.01–0.2; I2: 98.13%). Substantial heterogeneity was noted, with more homogeneous results documented in cohorts with follow-up shorter than five years. Our findings suggest a J-shaped relationship between alcohol consumption and incident AF. Up to 14 drinks per week seem to decrease the risk for developing AF. Because of the substantial heterogeneity observed, no robust conclusion can be drawn. In any case, our results suggest that the association between alcohol consumption and incident AF is far from being a straightforward dose-response effect.

The appearance of images in social messages is continuously increasing, along with user engagement with that type of content. Analysis of social images can provide valuable latent information, often not present in the social posts. In that direction, a framework is proposed exploiting latent information from Twitter images, by leveraging the Google Cloud Vision API platform, aiming at enriching social analytics with semantics and hidden textual information. As validated by our experiments, social analytics can be further enriched by considering the combination of user-generated content, latent concepts, and textual data extracted from social images, along with linked data. Moreover, we employed word embedding techniques for investigating the usage of latent semantic information towards the identification of similar Twitter images, thereby showcasing that hidden textual information can improve such information retrieval tasks. Finally, we offer an open enhanced version of the annotated dataset described in this study with the aim of further adoption by the research community.

Sentiment analysis usually refers to the analysis of human-generated content via a polarity filter. Affective computing deals with the exact emotions conveyed through information. Emotional information most frequently cannot be accurately described by a single emotion class. Multilabel classifiers can categorize human-generated content in multiple emotional classes. Ensemble learning can improve the statistical, computational and representation aspects of such classifiers. We present a baseline stacked ensemble and propose a weighted ensemble. Our proposed weighted ensemble can use multiple classifiers to improve classification results without hyperparameter tuning or data overfitting. We evaluate our ensemble models with two datasets. The first dataset is from Semeval2018-Task 1 and contains almost 7000 Tweets, labeled with 11 sentiment classes. The second dataset is the Toxic Comment Dataset with more than 150,000 comments, labeled with six different levels of abuse or harassment. Our results suggest that ensemble learning improves classification results by 1.5 % to 5.4 % .

Epstein–Barr virus (EBV)-associated posttransplant lymphoproliferative disease (PTLD) with central nervous system (CNS) involvement is a severe complication after solid organ transplantation. Standard treatment with reduction of immunosuppression and anti-CD20 antibody application often fails leading to poor outcome. Here, we report the case of an 11-year-old boy with multilocular EBV-positive CNS PTLD 10 years after liver transplantation. Complete remission was achieved by repeated intravenous and intrathecal anti-CD20 antibody rituximab administration combined with intrathecal chemotherapy (methotrexate, cytarabine, prednisone) over a time period of 3 months. Due to the poor prognosis of CNS PTLD and lack of EBV-specific T-cells (EBV-CTLs) in patient’s blood, we decided to perform EBV-directed T-cell immunotherapy as a consolidating treatment. The patient received five infusions of allogeneic EBV-CTLs from a 5/10 HLA-matched unrelated third-party donor. No relevant acute toxicity was observed. EBV-CTLs became detectable after first injection and increased during the treatment course. Next-generation sequencing (NGS) TCR-profiling verified the persistence and expansion of donor-derived EBV-specific clones. After two transfers, epitope spreading to unrelated EBV antigens occurred suggesting onset of endogenous T-cell production, which was supported by detection of recipient-derived clones in NGS TCR-profiling. Continuous complete remission was confirmed 27 months after initial diagnosis.

Whipple’s disease (WD) is a rare chronic systemic infection with a wide range of clinical symptoms, routinely diagnosed in biopsies from the small intestine and other tissues by periodic acid–Schiff (PAS) diastase staining and immunohistological analysis with specific antibodies. The aim of our study was to improve the pathological diagnosis of WD. Therefore, we analyzed the potential of fluorescence in situ hybridization (FISH) for diagnosing WD, using a Tropheryma (T.) whipplei-specific probe. 19 formalin-fixed paraffin-embedded (FFPE) duodenal biopsy specimens of 12 patients with treated (6/12) and untreated (6/12) WD were retrospectively examined using PAS diastase staining, immunohistochemistry, and FISH. 20 biopsy specimens with normal intestinal mucosa, Helicobacter pylori, or mycobacterial infection, respectively, served as controls. We successfully detected T. whipplei in tissue biopsies with a sensitivity of 83% in untreated (5/6) and 40% in treated (4/10) cases of WD. In our study, we show that FISH-based diagnosis of individual vital T. whipplei in FFPE specimens is feasible and can be considered as ancillary diagnostic tool for the diagnosis of WD in FFPE material. We show that FISH not only detect active WD but also be helpful as an indicator for the efficiency of antibiotic treatment and for detection of recurrence of disease when the signal of PAS diastase and immunohistochemistry lags behind the recurrence of disease, especially if the clinical course of the patient and antimicrobial treatment is considered.

Recently there has been an exponential growth of the number of publicly available legal resources. Portals allowing users to search legal documents, through keyword queries, are now widespread. However, legal documents are mainly stored and offered in different sources and formats that do not facilitate semantic machine-readable techniques, thus making difficult for legal stakeholders to acquire, modify or interlink legal knowledge. In this paper, we describe Solon, a legal document management platform. It offers advanced modelling, managing and mining functions over legal sources, so as to facilitate access to legal knowledge. It utilizes a novel method for extracting semantic representations of legal sources from unstructured formats, such as PDF and HTML text files, interlinking and enhancing them with classification features. At the same time, utilizing the structure and specific features of legal sources, it provides refined search results. Finally, it allows users to connect and explore legal resources according to their individual needs. To demonstrate the applicability and usefulness of our approach, Solon has been successfully deployed in a public sector production environment, making Greek tax legislation easily accessible to the public. Opening up legislation in this way will help increase transparency and make governments more accountable to citizens.

Nowadays, social networks incessantly influence the lives of young people. Apart from entertainment and informational purposes, social networks have penetrated many fields of educational practices and processes. This review tries to highlight the use of social networks in higher education, as well as points out some factors involved. Moreover, through a literature review of related articles, we aim at providing insights into social network influences with regard to (a) the learning processes (support, educational processes, communication and collaboration enhancement, academic performance) from the side of students and educators; (b) the users’ personality profile and learning style; (c) the social networks as online learning platforms (LMS—learning management system); and (d) their use in higher education. The conclusions reveal positive impacts in all of the above dimensions, thus indicating that the wider future use of online social networks (OSNs) in higher education is quite promising. However, teachers and higher education institutions have not yet been highly activated towards faster online social networks’ (OSN) exploitation in their activities.

Background: The application of Health Information Technologies (HITs) can be an effective way to advance medical research and health services provision. The two-fold objective of this work is to: (i) identify and review state-of-the-art HITs that facilitate the aims of evidence-based medicine and (ii) propose a methodology for HIT assessment. Methods: The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Furthermore, we consolidated existing knowledge in the field and proposed a Synthesis Framework for the Assessment of Health Information Technology (SF/HIT) in order to evaluate the joint use of Randomized Controlled Trials (RCTs) along with HITs in the field of evidence-based medicine. Results: 55 articles met the inclusion criteria and refer to 51 (RCTs) published between 2008 and 2016. Significant improvements in healthcare through the use of HITs were observed in the findings of 31 out of 51 trials—60.8%. We also confirmed that RCTs are valuable tools for assessing the effectiveness, acceptability, safety, privacy, appropriateness, satisfaction, performance, usefulness and adherence. Conclusions: To improve health service delivery, RCTs apply and exhibit formalization by providing measurable outputs. Towards this direction, we propose the SF/HIT as a framework which may help researchers to carry out appropriate evaluations and extend their studies.

We retrospectively analyzed the p.V158F polymorphism of Fcγ-receptor IIIA (FCGR3A, CD16) in patients with PTLD treated with rituximab monotherapy. Previous reports had indicated that the lower affinity F allele affects rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and is linked to inferior outcome of rituximab monotherapy in B cell malignancies. 25 patients with PTLD after solid organ transplantation were included in this analysis. They had received 4 weekly doses of rituximab as part of two clinical trials, which had a rituximab monotherapy induction regimen in common. 16/25 patients received further treatment with CHOP-21 after rituximab monotherapy (PTLD-1, NCT01458548). The FCGR3A status was correlated to the response after 4 cycles of rituximab monotherapy. Response to rituximab monotherapy was not affected by F carrier status. This is in contrast to previous findings in B cell malignancies where investigators found a predictive impact of FCGR3A status on outcome to rituximab monotherapy. One explanation for this finding could be that ADCC is impaired in transplant recipients receiving immunosuppression. These results suggest that carrying a FCRG3A F allele does not negatively affect rituximab therapy in immunosuppressed patients.

Post-transplantation lymphoproliferative disorder (PTLD) with plasmacellular differentiation has been reported as a rare subtype of monomorphic B-cell post-transplant lympho-proliferation with histological and immunophenotypical features of plasmacytoma in the non-transplant population. Here we present clinical, laboratory and histopathological features, treatment and outcome of 8 patients from the German prospective PTLD registry. Clinically, extranodal manifestations were common while osteolytic lesions were rare and none of the patients had bone marrow involvement. Immunohistochemistry showed light chain restriction and expression of CD138 without CD20 expression in all samples. An association with Epstein-Barr virus was found in 3 out of 8 cases. We suggest that the Ann Arbor classification is most useful for this disease entity and report a generally good response to treatment including reduction of immuno-suppression, surgery and irradiation in localized disease and systemic chemotherapy analogous to plasmacell myeloma in advanced disease.

Background The hierarchical organization of hematopoiesis with unidirectional lineage determination has become a questionable tenet in view of the experimental evidence of reprogramming and transdifferentiation of lineage-determined cells. Clinical examples of hematopoietic lineage plasticity are rare. Here we report on a patient who presented with an acute B-lymphoblastic leukemia and developed a Langerhans’ cell sarcoma 9 years later. We provide evidence that the second neoplasm is the result of transdifferentiation.Design and Methods B-cell acute lymphoblastic leukemia was diagnosed in an 11-year old boy in 1996. Treatment according to the ALL-BFM-1995 protocol resulted in a complete remission. Nine years later, in 2005, Langerhans’ cell sarcoma was diagnosed in a supraclavicular lymph node. Despite treatment with different chemotherapy protocols the patient had progressive disease. Finally, he received an allogeneic peripheral blood stem cell transplant and achieved a continuous remission. Molecular studies of IGH- and TCRG-gene rearrangements were performed with DNA from the Langerhans’ cell sarcoma and the cryopreserved cells from the acute B-lymphoblastic leukemia. The expression of PAX5 and ID2 was analyzed with real-time reverse transcriptase polymerase chain reaction.Results Identical IGH-rearrangements were demonstrated in the acute B-lymphoblastic leukemia and the Langerhans’ cell sarcoma. The key factors required for B-cell and dendritic cell development, PAX5 and ID2, were differentially expressed, with a strong PAX5 signal in the acute B-lymphoblastic leukemia and only a weak expression in the Langerhans’ cell sarcoma, whereas ID2 showed an opposite pattern.Conclusions The identical IGH-rearrangement in both neoplasms indicates transdifferentiation of the acute B-lymphoblastic leukemia into a Langerhans’ cell sarcoma. Loss of PAX5 and the acquisition of ID2 suggest that these key factors are involved in the transdifferentiation from a B-cell phenotype into a Langerhans’/dendritic cell phenotype. (Clinical trial registration at: Deutsches KrebsStudienRegister, http://www.studien.de, study-ID:8)