bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semantic Validation of Standard-based Electronic Health Record Documents with W3C XML Schema
Authors: Janzek-Hawlat S. , Sibinovic S. , Duftschmid G. , Rinner C. 
Published: April 2010

Summary
Objectives: The goal of this article is to examine whether W3C XML Schema provides a practicable solution for the semantic validation of standard-based electronic health record (EHR) documents. With semantic validation we mean that the EHR documents are checked for conformance with the underlying archetypes and reference model.
Methods: We describe an approach that allows XML Schemas to be derived from archetypes based on a specific naming convention. The archetype constraints are augmented with additional components of the reference model within the XML Schema representation. A copy of the EHR document that is transformed according to the before-mentioned naming convention is used for the actual validation against the XML Schema.
Results: We tested our approach by semantically validating EHR documents conformant to three different ISO/EN 13606 archetypes respective to three sections of the CDA implementation guide “Continuity of Care Document (CCD)” and an implementation guide for diabetes therapy data. We further developed a tool to automate the different steps of our semantic validation approach.
Conclusions: For two particular kinds of archetype prescriptions, individual transformations are required for the corresponding EHR documents. Otherwise, a fully generic validation is possible. In general, we consider W3C XML Schema as a practicable solution for the semantic validation of standard-based EHR documents.
Use of Diagnostic Decision Support Systems in Medical Education
Authors: McGowan J. J. , Berner E. S. 
Published: April 2010

Summary
Background: Diagnostic decision support systems are designed to assist physicians with making diagnoses. This article illustrates some of the issues that will be faced as diagnostic decision support systems become used in medical education.
Objectives: The objectives of this article are to examine 1) the skills that are needed to properly use these programs as part of the students’ clinical experiences; 2) the changes that will be necessary in our curricula once these programs are more extensively utilized, including the implications of using these systems as an educational resource or simulation tool, and 3) the research issues that arise when these systems become an established part of our educational programs.
Methods: This is a critical analysis of the literature on diagnostic decision support systems and medical education.
Results: To optimally use diagnostic decision support programs, students will need grounding in the basic knowledge and skills that have always been necessary to become a physician, such as the ability to accurately gather and interpret clinical information from the patient. In addition, students will need specific skills in 1) selecting appropriate system vocabulary and functions, and 2) applying the diagnostic system’s suggestions to their particular patient.
Conclusions: When computer-based decision support systems are incorporated in medical education, they will likely lead to changes in the traditional medical curriculum. Research will be needed on how use of these programs changes the students’ knowledge, problem-solving and information-seeking skills.
Automating Individualized Coaching and Authentic Role-play Practice for Brief Intervention Training
Authors: Saker R. , Amano K. , Hayes-Roth B. 
Published: April 2010

Summary
Objectives: Brief intervention helps to reduce alcohol abuse, but there is a need for accessible, cost-effective training of clinicians. This study evaluated STAR Workshop, a web-based training system that automates efficacious techniques for individualized coaching and authentic role-play practice.
Methods: We compared STAR Workshop to a web-based, self-guided e-book and a no-treatment control, for training the Engage for Change (E4C) brief intervention protocol. Subjects were medical and nursing students. Brief written skill probes tested subjects’ performance of individual protocol steps, in different clinical scenarios, at three test times: pre-training, post-training, and post-delay (two weeks). Subjects also did live phone interviews with a standardized patient, post-delay.
Results: STAR subjects performed significantly better than both other groups. They showed significantly greater improvement from pre-training probes to post-training and post-delay probes. They scored significantly higher on post-delay phone interviews.
Conclusion: STAR Workshop appears to be an accessible, cost-effective approach for training students to use the E4C protocol for brief intervention in alcohol abuse. It may also be useful for training other clinical interviewing protocols.
MedSkills: a Learning Environment for Evidence-based Medical Skills
Authors: Nyssen M. , Buyl R. 
Published: April 2010

Summary
Objectives: EBP (evidence-based practice) is becoming the standard paradigm in modern healthcare. Therefore different healthcare providers have the need for easily accessible evidence-based information. The Internet creates new opportunities to fill the gaps in education that are experienced by healthcare workers. Contributing to solutions and filling in the needs in the above-mentioned scope, the University of Brussels initiated a European project called MedSkills in 2004.
Methods: MedSkills’ main goal was to create a copyright-free reference work containing valuable evidence-based information on medical skills for all levels of healthcare professionals (paramedics, nurses and physicians, teachers of medical skills and students).
Results: We succeeded in designing and creating a framework to suit the requirements of different users, in ‘cellular’, ‘organ’, ‘body’ and ‘best treatment’ content maps. A wiki tool was installed to allow the project to be built and in order to maintain itself.
Conclusions: This multi-professional and international initiative, unique in its kind aims at contributing to a gold standard for European healthcare, via the creation of a freely available, consistent and updatable evidence-based teaching environment.
CCR2 Plays a Critical Role in Dendritic Cell Maturation: Possible Role of CCL2 and NF-κB
Authors: Jimenez Fabio , Quinones Marlon P. , Martinez Hernan G. , Estrada Carlos A. , Clark Kassandra , Garavito Edgar , Ibarra Jessica , Melby Peter C. , Ahuja Seema S. 
Published: April 2010

AbstractWe postulated that CCR2-driven activation of the transcription factor NF-κB plays a critical role in dendritic cell (DC) maturation (e.g., migration, costimulation, and IL-12p70 production), necessary for the generation of protective immune responses against the intracellular pathogen Leishmania major. Supporting this notion, we found that CCR2, its ligand CCL2, and NF-κB were required for CCL19 production and adequate Langerhans cell (LC) migration both ex vivo and in vivo. Furthermore, a role for CCR2 in upregulating costimulatory molecules was indicated by the reduced expression of CD80, CD86, and CD40 in Ccr2−/− bone marrow-derived dendritic cells (BMDCs) compared with wild-type (WT) BMDCs. Four lines of evidence suggested that CCR2 plays a critical role in the induction of protective immunity against L. major by regulating IL-12p70 production and migration of DC populations such as LCs. First, compared with WT, Ccr2−/− lymph node cells, splenocytes, BMDCs, and LCs produced lower levels of IL-12p70 following stimulation with LPS/IFN-γ or L. major. Second, a reduced number of LCs carried L. major from the skin to the draining lymph nodes in Ccr2−/− mice compared with WT mice. Third, early treatment with exogenous IL-12 reversed the susceptibility to L. major infection in Ccr2−/− mice. Finally, disruption of IL-12p70 in radioresistant cells, such as LCs, but not in BMDCs resulted in the inability to mount a fully protective immune response in bone marrow chimeric mice. Collectively, our data point to an important role for CCR2-driven activation of NF-κB in the regulation of DC/LC maturation processes that regulate protective immunity against intracellular pathogens.
Persistent Chronic Inflammation and Infection by Chikungunya Arthritogenic Alphavirus in Spite of a Robust Host Immune Response
Authors: Hoarau Jean-Jacques , Jaffar Bandjee Marie-Christine , Krejbich Trotot Pascale , Das Trina , Li-Pat-Yuen Ghislaine , Dassa Bérengère , Denizot Mélanie , Guichard Elsa , Ribera Anne , Henni Tawfiq , Tallet Frank , Moiton Marie Pierre , Gauzère Bernard Alex , Bruniquet Sandrine , Jaffar Bandjee Zaïnoul , Morbidelli Philippe , Martigny Gérard , Jolivet Michel , Gay Frederick , Grandadam Marc , Tolou Hugues , Vieillard Vincent , Debré Patrice , Autran Brigitte , Gasque Philippe 
Published: April 2010

Abstract
Alphaviruses, including Chikungunya virus (CHIKV), produce a transient illness in humans, but severe forms leading to chronic incapacitating arthralgia/arthritis have been reported by mechanisms largely ill-characterized. The pathogenesis of CHIKV was addressed in a prospective cohort study of 49 hospitalized patients from Reunion Island subsequently categorized into two distinct groups at 12 mo postinfection. Comprehensive analyses of the clinical and immunological parameters throughout the disease course were analyzed in either the “recovered” or the “chronic” groups to identify prognostic markers of arthritis-like pathology after CHIKV disease. We found that the chronic group consisted mainly of more elderly patients (&gt;60 y) and with much higher viral loads (up to 1010 viruses per milliliter of blood) during the acute phase. Remarkably, a rapid innate immune antiviral response was demonstrated by robust dendritic/NK/CD4/CD8 cell activation and accompanied by a rather weak Th1/Th2 cytokine response in both groups. Interestingly, the antiviral immune response witnessed by high levels of IFN-α mRNA in PBMCs and circulating IL-12 persisted for months only in the chronic group. CHIKV (RNA and proteins) was found in perivascular synovial macrophages in one chronic patient 18 mo postinfection surrounded by infiltrating NK and T cells (CD4++ but rare cytotoxic CD8). Fibroblast hyperplasia, strong angiogenesis, tissue lesions given the high levels of matrix metalloproteinase 2, and acute cell death [high cleaved poly(ADP-ribose) polymerase staining] were observed in the injured synovial tissue. These observed cellular and molecular events may contribute to chronic arthralgia/arthritis targeted by methotrexate used empirically for effective treatment but with immunosuppressive function in a context of viral persistence.
Targeting Activation-Induced Cytidine Deaminase Overcome Tumor Evasion of Immunotherapy by CTLs
Authors: Liu Jin-Qing , Joshi Pramod S. , Wang Chuansong , El-Omrani Hani Y. , Xiao Yi , Liu Xiuping , Hagan John P. , Liu Chang-Gong , Wu Lai-Chu , Bai Xue-Feng 
Published: April 2010

Abstract
Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. AID silencing did not decrease the mutation frequencies of tumor Ag gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID-positive tumors.
A Novel Promiscuous Class of Camelid Single-Domain Antibody Contributes to the Antigen-Binding Repertoire
Authors: Deschacht Nick , De Groeve Kurt , Vincke Cécile , Raes Geert , De Baetselier Patrick , Muyldermans Serge 
Published: April 2010

Abstract
It is well established that, in addition to conventional Abs, camelids (such as Camelus dromedarius and Lama glama) possess unique homodimeric H chain Abs (HCAbs) devoid of L chains. The Ag-binding site of these HCAbs consists of a single variable domain, referred to as VHH. It is widely accepted that these VHHs, with distinct framework-2 imprints evolved within the V(H) clan III-family 3, are exclusively present on HCAbs. In this study, we report the finding of a distinct leader signal sequence linked to variable genes displaying a high degree of homology to the clan II, human VH(4) family that contributes to the HCAb Ag-binding diversity. Although the VHH framework-2 imprints are clearly absent, their VH(4)-D-JH recombination products can be rearranged to the H chains of both classical and HCAbs. This suggests that for these V domains the presence of a L chain to constitute the Ag-binding site is entirely optional. As such, the capacity of this promiscuous VH(4) family to participate in two distinct Ab formats significantly contributes to the breadth of the camelid Ag-binding repertoire. This was illustrated by the isolation of stable, dendritic cell-specific VH(4) single domains from a VH(4)-HCAb phage display library. The high degree of homology with human VH(4) sequences is promising in that it may circumvent the need for “humanization” of such single-domain Abs in therapeutic applications.
Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response
Authors: Her Zhisheng , Malleret Benoit , Chan Monica , Ong Edward K. S. , Wong Siew-Cheng , Kwek Dyan J. C. , Tolou Hugues , Lin Raymond T. P. , Tambyah Paul Anantharajah , Rénia Laurent , Ng Lisa F. P. 
Published: April 2010

Abstract
Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-α were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.
CD8 Locus Nuclear Dynamics during Thymocyte Development
Authors: Ktistaki Eleni , Garefalaki Anna , Williams Adam , Andrews Simon R. , Bell Donald M. , Foster Katie E. , Spilianakis Charalampos G. , Flavell Richard A. , Kosyakova Nadezda , Trifonov Vladmir , Liehr Thomas , Kioussis Dimitris 
Published: April 2010

Abstract
Nuclear architecture and chromatin reorganization have recently been shown to orchestrate gene expression and act as key players in developmental pathways. To investigate how regulatory elements in the mouse CD8 gene locus are arranged in space and in relation to each other, three-dimensional fluorescence in situ hybridization and chromosome conformation capture techniques were employed to monitor the repositioning of the locus in relation to its subchromosomal territory and to identify long-range interactions between the different elements during development. Our data demonstrate that CD8 gene expression in murine lymphocytes is accompanied by the relocation of the locus outside its subchromosomal territory. Similar observations in the CD4 locus point to a rather general phenomenon during T cell development. Furthermore, we show that this relocation of the CD8 gene locus is associated with a clustering of regulatory elements forming a tight active chromatin hub in CD8-expressing cells. In contrast, in nonexpressing cells, the gene remains close to the main body of its chromosomal domain and the regulatory elements appear not to interact with each other.
The effectiveness of various predictors of criminal careers
Authors: Osborn S.G. , West D.J. 
Published: April 2010

Data accumulated from a long term follow up of a sample of normal boys is utilised to test the value of social background factors as predictors of a delinquency career extending into adult life. Classroom behaviour and criminality in the family are found to be effective predictors.A search was made for factors that might distinguish between persisting recidivists and those whose conviction careers terminate after the 19th birthday. Apart from having fewer juvenile convictions, “temporary” recidivists were less likely to have come from criminal families or, at age 18, to display the social habits and attitudes typical of the delinquent section of the population.Assessments of “antisociality”, based upon interview assessments at age 18, proved as predictive of reconvictions as official conviction history or self‐reported delinquency scores. It was concluded that youths' reported social habits are important indicators in the prognosis of a criminal career.Latecomers to crime, convicted for the first time for offences after the 19th birthday, did not share the early background adversities found among other delinquents, but behavioural deviations were evident among them from an early age.
An analytic approach to work with families
Authors: Box Sally 
Published: April 2010

SummaryI have attempted in this paper to explore some of the main elements in this approach to work with families, particularly in terms of how the therapists view the sessions with the family and try to respond to what the family brings to them. I have suggested that the therapist pair and the family represent two systems and that it is the task of the therapists to understand and interpret the way the different members of the family are feeling, the underlying preoccupations they share and their characteristic ways of coping with these. For this, they attempt to use their experience of the interactions within the clearly defined boundaries of a session.I have tried to indicate a little of how the therapists draw upon their own immediate reactions as evidence in the process; and also to convey the importance we attach, in this way of working, to offering the family a way of thinking about difficulties and of approaching them—an approach to life in general, one might say.
EuGène-maize: a web site for maize gene prediction
Authors: Montalent Pierre , Joets Johann 
Published: April 2010

Abstract
Motivation:A large part of the maize B73 genome sequence is now available and emerging sequencing technologies will offer cheap and easy ways to sequence areas of interest from many other maize genotypes. One of the steps required to turn these sequences into valuable information is gene content prediction. To date, there is no publicly available gene predictor specifically trained for maize sequences. To this end, we have chosen to train the EuGène software that can combine several sources of evidence into a consolidated gene model prediction.
Availability: http://genome.jouy.inra.fr/eugene/cgi-bin/eugene_form.pl
Contact: joets@moulon.inra.fr
Supplementary information: Supplementary data are available at Bioinformatics online.
Novel statistical framework to identify differentially expressed genes allowing transcriptomic background differences
Authors: Ling Zhi-Qiang , Wang Yi , Mukaisho Kenichi , Hattori Takanori , Tatsuta Takeshi , Ge Ming-Hua , Jin Li , Mao Wei-Min , Sugihara Hiroyuki 
Published: April 2010

AbstractMotivation: Tests of differentially expressed genes (DEGs) from microarray experiments are based on the null hypothesis that genes that are irrelevant to the phenotype/stimulus are expressed equally in the target and control samples. However, this strict hypothesis is not always true, as there can be several transcriptomic background differences between target and control samples, including different cell/tissue types, different cell cycle stages and different biological donors. These differences lead to increased false positives, which have little biological/medical significance.Result: In this article, we propose a statistical framework to identify DEGs between target and control samples from expression microarray data allowing transcriptomic background differences between these samples by introducing a modified null hypothesis that the gene expression background difference is normally distributed. We use an iterative procedure to perform robust estimation of the null hypothesis and identify DEGs as outliers. We evaluated our method using our own triplicate microarray experiment, followed by validations with reverse transcription–polymerase chain reaction (RT–PCR) and on the MicroArray Quality Control dataset. The evaluations suggest that our technique (i) results in less false positive and false negative results, as measured by the degree of agreement with RT–PCR of the same samples, (ii) can be applied to different microarray platforms and results in better reproducibility as measured by the degree of DEG identification concordance both intra- and inter-platforms and (iii) can be applied efficiently with only a few microarray replicates. Based on these evaluations, we propose that this method not only identifies more reliable and biologically/medically significant DEG, but also reduces the power-cost tradeoff problem in the microarray field.Availability: Source code and binaries freely available for download at http://comonca.org.cn/fdca/resources/softwares/deg.zipContact: sugihara@belle.shiga-med.ac.jpSupplementary information: Supplementary data are available at Bioinformatics online.
Integrated change: creating synergy between leader and organizational development
Authors: Guidroz Ashley M. , Luce Karen W. , Denison Daniel R. 
Published: April 2010

PurposeThe purpose of this paper is to share with organizations a method for integrating organizational culture change and leadership development within one balanced corporate initiative.Design/methodology/approachThis paper describes the benefits of organizational culture and leadership development, the steps taken to design such a program within a large, global manufacturing organization, and the benefits of the integrated program.FindingsIntegrating organizational culture with leadership development can help create a clear “line of sight” between the individual and the organization and builds broader accountability for the success of organizational change initiatives.Practical implicationsIntegrated culture and leadership programs can be designed within any environment. This case study serves as an example to provide readers with ideas for how to create and implement similar programs in other organizations.Originality/valueKotter stresses the need for leadership in organizational change, however, few case studies have been published in this area that articulate how leadership and organizational development can be successfully integrated.