Evaluation of an electronic prescription platform: Clinicians' feedback on three distinct services aiming to facilitate clinical decision and safer e-prescription.

BACKGROUND: Health Care Professionals (HCPs) are the main end-users of digital clinical tools such as electronic prescription systems. For this reason, it is of high importance to include HCPs throughout the design, development and evaluation of a newly introduced system to ensure its usefulness, as well as confirm that it tends to their needs and can be integrated in their everyday clinical practice. METHODS: In the context of the PrescIT project, an electronic prescription platform with three services was developed (i.e., Prescription Check, Prescription Suggestion, Therapeutic Prescription Monitoring). To allow an iterative process of discovery through user feedback, design and implementation, a two-phase evaluation was carried out, with the participation of HCPs from three hospitals in Northern Greece. The two-phase evaluation included presentations of the platform, followed by think-aloud sessions, individual platform testing and the collection of qualitative as well as quantitative feedback, through standard questionnaires (e.g., SUS, PSSUQ). RESULTS: Twenty one HCPs (8 in the first, 18 in the second phase, and five present in both) participated in the two-phase evaluation. HCPs comprised clinicians varying in their specialty and one pharmacist. Clinicians' feedback during the first evaluation phase already deemed usability as "excellent" (with SUS scores ranging from 75 to 95/100, showing a mean value of 86.6 and SD of 9.2) but also provided additional user requirements, which further shaped and improved the services. In the second evaluation phase, clinicians explored the system's usability, and identified the services' strengths and weaknesses. Clinicians perceived the platform as useful, as it provides information on potential adverse drug reactions, drug-to-drug interactions and suggests medications that are compatible with patients' comorbidities and current medication. CONCLUSIONS: The developed PrescIT platform aims to increase overall safety and effectiveness of healthcare services. Therefore, including clinicians in a two-phase evaluation confirmed that the introduced system is useful, tends to the users' needs, does not create fatigue and can be integrated in their everyday clinical practice to support clinical decision and e-prescribing.

Use of Real-World Data to Support Adverse Drug Reactions Prevention During ePrescription.

Adverse Drug Reactions (ADRs) are a crucial public health issue due to the significant health and monetary burden that they can impose. Real-World Data (RWD), e.g., Electronic Health Records, claims data, etc., can support the identification of potentially unknown ADRs and thus, they could provide raw data to mine ADR prevention rules. The PrescIT project aims to create a Clinical Decision Support System (CDSS) for ADR prevention during ePrescription and uses OMOP-CDM as the main data model to mine ADR prevention rules, based on the software stack provided by the OHDSI initiative. This paper presents the deployment of OMOP-CDM infrastructure using the MIMIC-III as a testbed.

The PrescIT Knowledge Graph: Supporting ePrescription to Prevent Adverse Drug Reactions.

Adverse Drug Reactions (ADRs) are an important public health issue as they can impose significant health and monetary burdens. This paper presents the engineering and use case of a Knowledge Graph, supporting the prevention of ADRs as part of a Clinical Decision Support System (CDSS) developed in the context of the PrescIT project. The presented PrescIT Knowledge Graph is built upon Semantic Web technologies namely the Resource Description Framework (RDF), and integrates widely relevant data sources and ontologies, i.e., DrugBank, SemMedDB, OpenPVSignal Knowledge Graph and DINTO, resulting in a lightweight and self-contained data source for evidence-based ADRs identification.

Early maladaptive schemas and symptoms of psychopathology in children in residential care.

According to schema theory, early maladaptive schemas (EMS) contribute to the onset and development of psychopathology. Given that research on EMS in children is limited, the contribution of the present study is that it investigates the role of EMS in psychopathology in children living in residential care. Participants of the present study were children who lived in residential care and were referred for assessment to the Day Center "The House of the Child" run by the Organisation "The Smile of the Child". The study sample comprised of 75 children (35 boys, 40 girls), mean age 12.7 years old. The Greek version of the Achenbach Child Behavior Checklist was completed by the child's caregiver, whereas the Greek version of the Schema Questionnaire for Children was administered to children. The research questions were explored by implementing both variable-focused (multiple regression) as well as person-focused (cluster analysis) techniques. The Confirmatory Factor Analysis conducted in the Schema Questionnaire for Children showed acceptable goodness of fit indices. The Vulnerability schema was found to be the highest scoring schema. Social isolation was a strong predictor for most indicators of psychopathology (internalizing and externalizing). Strong predictor for the Symptoms of Withdrawal, Anxiety/Depression, Social Problems and Thought Problems was the EMS of Failure. Hierarchical cluster analysis on schemas revealed two strong clusters, one with low scores and one with high scores in most EMS. In the cluster with high levels of EMS, Emotional deprivation, Failure, Defectiveness, Social isolation and Abandonment showed the highest scores. In this cluster, children presented statistically significant burdened indicators in externalizing psychopathology. Our hypotheses that EMS and, especially, schemas related to the domains of Disconnection/Rejection and Impaired Autonomy/Performance would be predictive indicators of psychopathology were confirmed. Cluster analysis confirmed the above findings and highlighted the role of schemas Emotional deprivation and Defectiveness in the emergence of psychopathology symptoms. The results of the current study highlight the importance of assessing EMS in children who live in residential care and could inform the development of appropriate intervention programs in this population to prevent the establishment of psychopathology.

ESCAPE: An Open-Label Trial of Personalized Immunotherapy in Critically lll COVID-19 Patients.

BACKGROUND: Macrophage activation-like syndrome (MALS) and complex immune dysregulation (CID) often underlie acute respiratory distress (ARDS) in COVID-19. We aimed to investigate the effect of personalized immunotherapy on clinical improvement of critical COVID-19. METHODS: In this open-label prospective trial, 102 patients with ARDS by SARS-CoV-2 were screened for MALS (ferritin >4,420 ng/mL) and CID (ferritin ≤4,420 ng/mL and low human leukocyte antigen (HLA)-DR expression on CD14-monocytes). Patients with MALS or CID with increased aminotransferases received intravenous anakinra; those with CID and normal aminotransferases received tocilizumab. The primary outcome was ≥25% decrease in the Sequential Organ Failure Assessment (SOFA) score and/or 50% increase in the respiratory ratio by day 8; 28-day mortality, change of SOFA score by day 28, serum biomarkers, and cytokine production by mononuclear cells were secondary endpoints. RESULTS: The primary study endpoint was met in 58.3% of anakinra-treated patients and in 33.3% of tocilizumab-treated patients (p: 0.01). Most patients in both groups received dexamethasone as standard of care. No differences were found in secondary outcomes, mortality, and SOFA score changes. Ferritin decreased among anakinra-treated patients; interleukin-6, soluble urokinase plasminogen activator receptor, and HLA-DR expression increased among tocilizumab-treated patients. Survivors by day 28 who received anakinra were distributed to lower severity levels of the WHO clinical progression scale. Greater incidence of secondary infections was found with tocilizumab treatment. CONCLUSION: Immune assessment resulted in favorable anakinra responses among critically ill patients with COVID-19 and features of MALS.

Priority of PET-CT vs CT Thorax for EBUS-TBNA 22G vs 19G: Mesothorax Lymphadenopathy.

Introduction: Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. Patients and Methods: We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. Results: There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. Conclusions: We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.

Effective early diagnosis for NSCLC: an algorithm.

INTRODUCTION: Lung cancer still remains undiagnosed for most patients until the disease is inoperable. AREAS COVERED: We performed search on PubMed with the keywords: EBUS, radial-EBUS, bronchoscopy, lung cancer, electromagnetic navigation, ct-biopsy, transthoracic biopsy. We present diagnostic equipment and imaging techniques such as positron emission tomography, endoscopical navigation systems, endobronchial ultrasound, radial-endobronchial ultrasound, transthoracic ultrasound biopsy, and computed tomography guided biopsies. EXPERT OPINION: However, lack of early disease symptoms remains the most important issue and therefore we should direct our efforts to screening and early disease diagnosis. An algorithm is proposed for biopsy upon initial disease diagnosis.

Using Business Process Management Notation to Model Therapeutic Prescription Protocols: The PrescIT Approach.

Clinical Decision Support Systems (CDSS) could play a prominent role in preventing Adverse Drug Reactions (ADRs) especially when integrated in larger healthcare systems (e.g. Electronic Health Record - EHR systems, Hospital Management Systems - HMS, e-Prescription systems etc.). This poster presents an approach to model Therapeutic Prescription Protocols (TPPs) via the Business Process Management Notation (BPMN), as part of the e-Prescription CDSS developed in the context of the PrescIT project.

A New Era in Engineering Plastics: Compatibility and Perspectives of Sustainable Alipharomatic Poly(ethylene terephthalate)/Poly(ethylene 2,5-furandicarboxylate) Blends.

The industrialisation of poly(ethylene 2,5-furandicarboxylate) for total replacement of poly(ethylene terephthalate) in the polyester market is under question. Preparation of high-performing polymer blends is a well-established strategy for tuning the properties of certain homopolymers and create tailor-made materials to meet the demands for a number of applications. In this work, the structure, thermal properties and the miscibility of a series of poly(ethylene terephthalate)/poly(ethylene 2,5-furandicarboxylate) (PET/PEF) blends have been studied. A number of thermal treatments were followed in order to examine the thermal transitions, their dynamic state and the miscibility characteristics for each blend composition. Based on their glass transition temperatures and melting behaviour the PET/PEF blends are miscible at high and low poly(ethylene terephthalate) (PET) contents, while partial miscibility was observed at intermediate compositions. The multiple melting was studied and their melting point depression was analysed with the Flory-Huggins theory. In an attempt to further improve miscibility, reactive blending was also investigated.

Factor structure and internal consistency of the ISPCAN Child Abuse Screening Tool Parent Version (ICAST-P) in a cross-country pooled data set in nine Balkan countries.

OBJECTIVE: Researchers are increasingly using parental report measures in population-based surveys of violence against children. No research thus far has examined the factor structure of the International Society for the Prevention of Child Abuse and Neglect (ISPCAN) Child Abuse Screening Tool Parent Version (ICAST-P), a non-commercialized measure for prevalence studies. METHODS: This paper uses secondary data from the Balkan Epidemiological Study on Child Abuse and Neglect (BECAN) which included 25,202 primary caregivers of school-going children in three grades (aged 11, 13 and 16). Primary caregivers completed the ICAST-P 2010-2011, which measures children's exposure to physical and psychological violence and neglect by caregivers and sexual violence by any perpetrator. Confirmatory factor analysis (CFA) was used to assess the reliability and the factor structure of the ICAST-P for a four-dimensional model and a bifactor model, with one general factor and four group factors representing the specific components of each set of items. Measurement invariance could not be tested. RESULTS: Lifetime prevalence for physical violence was 66.7 %, for psychological violence 66.6 %, for sexual violence 3.1 % and for neglect 9.1 %. CFA showed adequate fit for the hypothesized four-dimensional model, however, improved fit was shown for a bifactor model with abuse as the general factor. Internal consistency was good for physical and psychological violence, but not neglect and sexual violence. Hierarchical omega showed good internal consistency for the general factor. CONCLUSIONS: Parents report that their children experience high levels of violence. The factor structure of the ICAST-P is best captured using a bifactor modelling approach.

Towards High Molecular Weight Furan-Based Polyesters: Solid State Polymerization Study of Bio-Based Poly(Propylene Furanoate) and Poly(Butylene Furanoate).

In the era of polymers from renewable resources, polyesters derived from 2,5 furan dicarboxylic acid (FDCA) have received increasing attention due to their outstanding features. To commercialize them, it is necessary to synthesize high molecular weight polymers through efficient and simple methods. In this study, two furan-based polyesters, namely poly (propylene furanoate) (PPF) and poly(butylene furanoate) (PBF), were synthesized with the conventional two-step melt polycondensation, followed by solid-state polycondensation (SSP) conducted at different temperatures and reaction times. Molecular weight, structure and thermal properties were measured for all resultant polyesters. As expected, increasing SSP time and temperature results in polymers with increased intrinsic viscosity (IV), increased molecular weight and reduced carboxyl end-group content. Finally, those results were used to generate a simple mathematical model that prognosticates the time evolution of the materials' IV and end groups concentration during SSP.

Sustainable Plastics from Biomass: Blends of Polyesters Based on 2,5-Furandicarboxylic Acid.

Intending to expand the thermo-physical properties of bio-based polymers, furan-based thermoplastic polyesters were synthesized following the melt polycondensation method. The resulting polymers, namely, poly(ethylene 2,5-furandicarboxylate) (PEF), poly(propylene 2,5-furandicarboxylate) (PPF), poly(butylene 2,5-furandicarboxylate) (PBF) and poly(1,4-cyclohexanedimethylene 2,5-furandicarboxylate) (PCHDMF) are used in blends together with various polymers of industrial importance, including poly(ethylene terephthalate) (PET), poly(ethylene 2,6-naphthalate) (PEN), poly(L-lactic acid) (PLA) and polycarbonate (PC). The blends are studied concerning their miscibility, crystallization and solid-state characteristics by using wide-angle X-ray diffractometry (WAXD), differential scanning calorimetry (DSC) and polarized light microscopy (PLM). PEF blends show in general dual glass transitions in the DSC heating traces for the melt quenched samples. Only PPF-PEF blends show a single glass transition and a single melt phase in PLM. PPF forms immiscible blends except with PEF and PBF. PBF forms miscible blends with PCHDMF and PPF, whereas all other blends show dual glass transitions in DSC and phase separation in PLM. PCHDMF-PEF and PEN-PEF blends show two glass transition temperatures, but they shift to intermediate temperature values depending on the composition, indicating some partial miscibility of the polymer pairs.

Lifetime and past-year prevalence of children's exposure to violence in 9 Balkan countries: the BECAN study.

BACKGROUND: Children's exposure to violence is a major public health issue. The Balkan epidemiological study on Child Abuse and Neglect project aimed to collect internationally comparable data on violence exposures in childhood. METHODS: A three stage stratified random sample of 42,194 school-attending children (response rate: 66.7%) in three grades (aged 11, 13 and 16 years) was drawn from schools in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Former Yugoslavian Republic of Macedonia (FYROM), Greece, Romania, Serbia and Turkey. Children completed the ICAST-C questionnaire, which measures children's exposure to violence by any perpetrator. RESULTS: Exposure rates for psychological violence were between 64.6% (FYROM) and 83.2% (Greece) for lifetime and 59.62% (Serbia) and 70.0% (Greece) for past-year prevalence. Physical violence exposure varied between 50.6% (FYROM) and 76.3% (Greece) for lifetime and 42.5% (FYROM) and 51.0% (Bosnia) for past-year prevalence. Sexual violence figures were highest for lifetime prevalence in Bosnia (18.6%) and lowest in FYROM (7.6%). Lifetime contact sexual violence was highest in Bosnia (9.8%) and lowest in Romania (3.6%). Past-year sexual violence and contact sexual violence prevalence was lowest in Romania (5.0 and 2.1%) and highest in Bosnia (13.6 and 7.7% respectively). Self-reported neglect was highest for both past-year and lifetime prevalence in Bosnia (48.0 and 20.3%) and lowest in Romania (22.6 and 16.7%). Experiences of positive parental practices were reported by most participating children in all countries. CONCLUSIONS: Where significant differences in violence exposure by sex were observed, males reported higher exposure to past-year and lifetime sexual violence and females higher exposure to neglect. Children in Balkan countries experience a high burden of violence victimization and national-level programming and child protection policy making is urgently needed to address this.

USING THE PARENT-INFANT RELATIONSHIP GLOBAL ASSESSMENT SCALE TO IDENTIFY CAREGIVER-INFANT/TODDLER DYADS WITH ABUSIVE RELATIONSHIP PATTERNS IN SIX EUROPEAN COUNTRIES.

The study examined whether the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised Edition (DC: 0-3R; ZERO TO THREE, 2005) Parent-Infant Relationship Global Assessment Scale (PIR-GAS) is applicable to six European countries and contributes to the identification of caregiver-infant/toddler dyads with abusive relationship patterns. The sample consisted of 115 dyads with children's ages ranging from 1 to 47 months. Sixty-four dyads were recruited from community settings without known violence problems, and 51 dyads were recruited from clinical settings and already had been identified with violence problems or as being at risk for violence problems. To classify the dyads on the PIR-GAS categories, caregiver-child interactions were video-recorded and coded with observational scales appropriate for child age. To test whether the PIR-GAS allows for reliable identification of dyads with abusive relationship patterns, PIR-GAS ratings were compared with scores on the the International Society for the Prevention of Child Abuse and Neglect's (ISPCAN) Child Abuse Screening Tool-Parental Version (ICAST-P; D.K. Runyan et al., ), a questionnaire measuring abusive parental disciplinary practices. It was found that PIR-GAS ratings differentiated between the general and the clinical sample, and the dyads with abusive patterns of relationship were identified by both the PIR-GAS and the ICAST-P. Interrater reliability for the PIR-GAS ranged from moderate to excellent. The value of a broader use of tools such as the DC: 0-3R to promote early identification of families at risk for infant and toddler abuse and neglect is discussed.

Panacea, a semantic-enabled drug recommendations discovery framework.

BACKGROUND: Personalized drug prescription can be benefited from the use of intelligent information management and sharing. International standard classifications and terminologies have been developed in order to provide unique and unambiguous information representation. Such standards can be used as the basis of automated decision support systems for providing drug-drug and drug-disease interaction discovery. Additionally, Semantic Web technologies have been proposed in earlier works, in order to support such systems. RESULTS: The paper presents Panacea, a semantic framework capable of offering drug-drug and drug-diseases interaction discovery. For enabling this kind of service, medical information and terminology had to be translated to ontological terms and be appropriately coupled with medical knowledge of the field. International standard classifications and terminologies, provide the backbone of the common representation of medical data while the medical knowledge of drug interactions is represented by a rule base which makes use of the aforementioned standards. Representation is based on a lightweight ontology. A layered reasoning approach is implemented where at the first layer ontological inference is used in order to discover underlying knowledge, while at the second layer a two-step rule selection strategy is followed resulting in a computationally efficient reasoning approach. Details of the system architecture are presented while also giving an outline of the difficulties that had to be overcome. CONCLUSIONS: Panacea is evaluated both in terms of quality of recommendations against real clinical data and performance. The quality recommendation gave useful insights regarding requirements for real world deployment and revealed several parameters that affected the recommendation results. Performance-wise, Panacea is compared to a previous published work by the authors, a service for drug recommendations named GalenOWL, and presents their differences in modeling and approach to the problem, while also pinpointing the advantages of Panacea. Overall, the paper presents a framework for providing an efficient drug recommendations service where Semantic Web technologies are coupled with traditional business rule engines.

Indeterminacy of definitions and criteria in mental health: case study of emotional disorders.

RATIONALE, AIMS AND OBJECTIVES: The concept of emotions has gone through radical transformations during the last couple of centuries. Despite these severe re-specifications of its content, the concept of emotions (and especially some such as depression or anxiety) has acquired a central role in contemporary clinical Psychology and Psychiatry. This creates an apparent paradox, utilizing more and more concepts for which no clear conceptual understanding has been obtained. This paradox creates a challenge for researchers as well as clinicians, as on a daily basis, millions of people are currently ascribed with 'having' or 'being in' emotional states, which also entails certain interventions to be applied, without much clear insight into what exactly those states might really constitute. METHOD: Conceptual research in aetiological and historical transformation of theoretical accounts of emotions as well as an overview of relevant empirical research on fundamental emotions. Examining of critical respective questions such as: whether there are any universal 'typical' emotional reactions to be found in each and every known culture, indicating their intrinsic existence as being a part of the human condition; whether there are 'basic' and 'secondary' emotions; whether emotions are merely bodily events, patterns of behavioural reactions to given types of stimuli or whether they rely inevitably on their cognitive content; whether emotions are necessarily intentional (in Brentano's sense) viz. are inevitably about a real or an imaginary object or whether there can be objectless emotional states; whether emotions are in a significant sense rational or fundamentally irrational responses and so forth. Moreover, more recent experimental data advocating for one or the other response to the aforementioned fundamental questions are scrutinized. RESULTS: In both conceptual research (including the works of thinkers such as the highly influential contributions of Darwin, James, Cannon, Freud, Ryle and Sartre or contemporary attempts such as the ones of theorists like Solomon, Nash, Rey, Pugmire and Lyons) as well as in comprehensive theoretical schemes combining experimental data (such as the ones provided by the works of Schachter and Singer, Ekman and Friesen, Panksepp, Damasio and Griffiths), there seems to be a radical indeterminacy of conceptual content and fundamental features of emotions in general, as well as of particular emotional states. Furthermore, there is an apparent conceptual incapability to include each and every feature of emotional states within a single comprehensive definition without making reference to contingent particularities of their biological instantiation. CONCLUSIONS: At least in the crucial concept of emotional states, when examined carefully, it seems that (1) there are substantial barriers to the ambitious quest for a scientific grounding of taxonomies and definitions of phenomena like emotions, due to the inability to provide an independent verification of scientific propositions; (2) all major approaches in Psychology and Psychiatry seem to have serious shortcomings in defining emotions; (3) such shortcomings have to do with fundamental issues such as the nature of mental states; (4) most ordinary concepts of emotions utilized by clinicians and researchers tend to be circular and question begging when scrutinized theoretically; and (5) historically dominant beliefs, values and cultural systems tend to influence heavily both the acceptability of such representations of emotions as well as their very nature.

Molecular staging of surgical margins in oral squamous cell carcinoma using promoter methylation of p16(INK4A), cytoglobin, E-cadherin, and TMEFF2.

BACKGROUND: Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC. METHODS: Forty-eight consecutive OSCC cases were recruited and a 5 mm(3) tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin. RESULTS: Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival. CONCLUSIONS: The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.

GalenOWL: Ontology-based drug recommendations discovery.

BACKGROUND: Identification of drug-drug and drug-diseases interactions can pose a difficult problem to cope with, as the increasingly large number of available drugs coupled with the ongoing research activities in the pharmaceutical domain, make the task of discovering relevant information difficult. Although international standards, such as the ICD-10 classification and the UNII registration, have been developed in order to enable efficient knowledge sharing, medical staff needs to be constantly updated in order to effectively discover drug interactions before prescription. The use of Semantic Web technologies has been proposed in earlier works, in order to tackle this problem. RESULTS: This work presents a semantic-enabled online service, named GalenOWL, capable of offering real time drug-drug and drug-diseases interaction discovery. For enabling this kind of service, medical information and terminology had to be translated to ontological terms and be appropriately coupled with medical knowledge of the field. International standards such as the aforementioned ICD-10 and UNII, provide the backbone of the common representation of medical data, while the medical knowledge of drug interactions is represented by a rule base which makes use of the aforementioned standards. Details of the system architecture are presented while also giving an outline of the difficulties that had to be overcome. A comparison of the developed ontology-based system with a similar system developed using a traditional business logic rule engine is performed, giving insights on the advantages and drawbacks of both implementations. CONCLUSIONS: The use of Semantic Web technologies has been found to be a good match for developing drug recommendation systems. Ontologies can effectively encapsulate medical knowledge and rule-based reasoning can capture and encode the drug interactions knowledge.

UHRF1-mediated tumor suppressor gene inactivation in nonsmall cell lung cancer.

BACKGROUND: The UHRF1 gene possesses an essential role in DNA methylation maintenance, but its contribution to tumor suppressor gene hypermethylation in primary human cancers currently remains unclear. METHODS: mRNA expression levels of UHRF1, DNMT1, DNMT3A, DNMT3B, and E2F1 were evaluated in 105 primary nonsmall cell lung carcinomas by quantitative polymerase chain reaction. The methylation status of CDKN2A and RASSF1 promoters was examined by pyrosequencing. UHRF1 was knocked down by short hairpin RNA in A549 lung adenocarcinoma cells. RESULTS: All 4 genes were overexpressed in a coordinated manner in the lung tumor tissues, and their expression correlated with that of E2F1. Higher UHRF1 expression in tumor tissues correlated with the hypermethylation of CDKN2A (P = .005) and RASSF1 promoters (P = .034), and the relationship with a combined epigenotype was even stronger (P = 2.3 × 10(-4) ). When UHRF1 was knocked down in A549 lung adenocarcinoma cells, lower methylation levels of RASSF1, CYGB, and CDH13 promoters were observed. Also, UHRF1 knockdown clones demonstrated reduced proliferation and decreased cell migration properties. CONCLUSIONS: Our data demonstrate that UHRF1 is a key epigenetic switch, which controls cell cycle in nonsmall cell lung carcinoma through its ability to sustain the transcriptional silencing of tumor suppressor genes by maintaining their promoters in a hypermethylated status. Thus, UHRF1 should be considered, along with DNMTs, among the potential targets for cancer treatment and/or therapeutic stratification.

Trends of mortality rates during the last thirty years in Greece.

General mortality rates and specific mortality rates by major causes of death (coronary disease, cancer, tuberculosis, traffic accidents, suicide, vascular disorders of central neural system) in Greece have been studied throughout the 30-year period 1967--1996 and time trends have being calculated by nonlinear models of trend analysis. The results confirm the general pattern of decrease of mortality in Greece during the particular period of time as a result of the combination of the impact of two controversial trends: on one hand the decrease of infant mortality and mortality from infectious disorders and on the other the relatively slower and more gradual increase in mortality rates by disorders related to the western lifestyle culture, such as cardiovascular disorders and cancer. During the period under study in Greece the impact of the second trend seems to inflict less severe implication in the formulation of the pattern of general mortality especially as women are concerned. This statistically significant and gradually increasing difference in mortality between men and women in Greece has been confirmed in general mortality time trends as well as in the evaluation of the relatively better pattern of mortality trends of women from particular "western lifestyle" disorders.