bluuebunny/crossref_metadata_2025_split huggingface dataset:
INTREPID—INformation-theoretic TREe traversal for Protein functional site IDentification
Authors: Sankararaman Sriram , Sjölander Kimmen 
Published: September 2008

Abstract
Motivation: Identification of functionally important residues in proteins plays a significant role in biological discovery. Here, we present INTREPID—an information–theoretic approach for functional site identification that exploits the information in large diverse multiple sequence alignments (MSAs). INTREPID uses a traversal of the phylogeny in combination with a positional conservation score, based on Jensen–Shannon divergence, to rank positions in an MSA. While knowledge of protein 3D structure can significantly improve the accuracy of functional site identification, since structural information is not available for a majority of proteins, INTREPID relies solely on sequence information. We evaluated INTREPID on two tasks: predicting catalytic residues and predicting specificity determinants.
Results: In catalytic residue prediction, INTREPID provides significant improvements over Evolutionary Trace, ConSurf as well as over a baseline global conservation method on a set of 100 manually curated enzymes from the Catalytic Site Atlas. In particular, INTREPID is able to better predict catalytic positions that are not globally conserved and hence, attains improved sensitivity at high values of specificity. We also investigated the performance of INTREPID as a function of the evolutionary divergence of the protein family. We found that INTREPID is better able to exploit the diversity in such families and that accuracy improves when homologs with very low sequence identity are included in an alignment. In specificity determinant prediction, when subtype information is known, INTREPID-SPEC, a variant of INTREPID, attains accuracies that are competitive with other approaches for this task.
Availability: INTREPID is available for 16919 families in the PhyloFacts resource (http://phylogenomics.berkeley.edu/phylofacts).
Contact: sriram_s@cs.berkeley.edu
Supplementary information: Relevant online supplementary material is available at http://phylogenomics.berkeley.edu/INTREPID.
varDB: a pathogen-specific sequence database of protein families involved in antigenic variation
Authors: Hayes C. Nelson , Diez Diego , Joannin Nicolas , Honda Wataru , Kanehisa Minoru , Wahlgren Mats , Wheelock Craig E. , Goto Susumu 
Published: September 2008

Abstract
Summary: Infectious diseases are a major threat to global public health and prosperity. The causative agents consist of a suite of pathogens, ranging from bacteria to viruses, including fungi, helminthes and protozoa. Although these organisms are extremely varied in their biological structure and interactions with the host, they share similar methods of evading the host immune system. Antigenic variation and drift are mechanisms by which pathogens change their exposed epitopes while maintaining protein function. Accordingly, these traits enable pathogens to establish chronic infections in the host. The varDB database was developed to serve as a central repository of protein and nucleotide sequences as well as associated features (e.g. field isolate data, clinical parameters, etc.) involved in antigenic variation. The data currently contained in varDB were mined from GenBank as well as multiple specialized data repositories (e.g. PlasmoDB, GiardiaDB). Family members and ortholog groups were identified using a hierarchical search strategy, including literature/author-based searches and HMM profiles. Included in the current release are&gt;29 000 sequences from 39 gene families from 25 different pathogens. This resource will enable researchers to compare antigenic variation within and across taxa with the goal of identifying common mechanisms of pathogenicity to assist in the fight against a range of devastating diseases.
Availability: varDB is freely accessible at http://www.vardb.org/
Contact: nelson@kuicr.kyoto-u.ac.jp; goto@kuicr.kyoto-u.ac.jp
Supplementary information: Supplementary data are available at Bioinformatics online.
Genetic and environmental contributions to the diversity of substances used in adolescent twins: a longitudinal study of age and sex effects
Authors: Derringer Jaime , Krueger Robert F. , McGue Matt , Iacono William G. 
Published: September 2008

ABSTRACTAims  To determine how genetic and environmental contributions affecting the number of psychoactive substances used varies with age and gender over the course of adolescence.Design  Estimates of genetic, shared environmental and non‐shared environmental contributions to total variance in diversity of substances used at ages 11, 14 and 17 years were obtained by fitting a multivariate behavior genetic (Cholesky) model.Participants  A total of 711 male and 675 female twins.Measurements  Participants reported whether they had used each of 11 substances.Findings  The average diversity of substances used increased over time for both males and females, and males generally reported a wider diversity of substances used than females. Influences of genetic factors increased with age and were greater for males than for females at ages 14 and 17 years. Genetic factors remained consistent (i.e. highly correlated) across ages for both males and females, as did shared environmental influences for males. Non‐shared environmental factors for both sexes and females' shared environmental factors were age‐specific.Conclusions  Regardless of sex, the proportion of variance in substances used attributable to genetic factors increases during adolescence, although it is greater for males than females at later ages. These findings indicate that prevention interventions may be most effective if they target early adolescence when environmental factors account for the majority of variance in substance use. The high correlation of genetic factors across ages suggests that early use may sometimes signal an early expression of a developmentally stable genetic predisposition.
Overdose training and take‐home naloxone for opiate users: prospective cohort study of impact on knowledge and attitudes and subsequent management of overdoses
Authors: Strang John , Manning Victoria , Mayet Soraya , Best David , Titherington Emily , Santana Laura , Offor Elizabeth , Semmler Claudia 
Published: September 2008

ABSTRACTAim  To examine the impact of training in overdose management and naloxone provision on the knowledge and confidence of current opiate users; and to record subsequent management of overdoses that occur during a 3‐month follow‐up period.Design  Repeated‐measures design to examine changes in knowledge and confidence immediately after overdose management training; retention of knowledge and confidence at 3 months; and prospective cohort study design to document actual interventions applied at post‐training overdose situations.Method  A total of 239 opiate users in treatment completed a pre‐training questionnaire on overdose management and naloxone administration and were re‐assessed immediately post‐training, at which point they were provided with the take‐home emergency supply of naloxone. Three months later they were re‐interviewed.Results  Significant improvements were seen in knowledge of risks of overdose, characteristics of overdose and appropriate actions to be taken; and in confidence in the administration of naloxone. A 78% follow‐up rate was achieved (186 of 239) among whom knowledge of both the risks and physical/behavioural characteristics of overdose and also of recommended management actions was well retained. Eighteen overdoses (either experienced or witnessed) had occurred during the 3 months between the training and the follow‐up. Naloxone was used on 12 occasions (a trained client's own supply on 10 occasions). One death occurred in one of the six overdoses where naloxone was not used. Where naloxone was used, all 12 resulted in successful reversal.Conclusions  With overdose management training, opiate users can be trained to execute appropriate actions to assist the successful reversal of potentially fatal overdose. Wider provision may reduce drug‐related deaths further. Future studies should examine whether public policy of wider overdose management training and naloxone provision could reduce the extent of opiate overdose fatalities, particularly at times of recognized increased risk.
No reason for optimism: the expected impact of commitments in the European Commission's Alcohol and Health Forum
Authors: De Bruijn Avalon 
Published: September 2008

ABSTRACTBackground Europe is the heaviest‐drinking region in the world, more than 2.5 times the rest of the world's average.The Commission's conclusion The cornerstone for the European Commission's action to decrease the alcohol‐related harm of this consumption and the main emphasis for its work is the Alcohol and Health Forum, with its Task Forces on Marketing Communication and Youth‐Specific Aspects of Alcohol. The Forum, which was launched in June 2007, aims to provide a common platform for all interested stakeholders. Forum members are invited to make commitments to reduce alcohol‐related harm, in the form of a monitored and evaluated action plan. By 29 February 2008, 79 commitments have been provided by the members of the Forum.Appraisal of the initiative Taking into account the limited information available, the proposed commitments indicate few evidence‐based approaches. A large majority of the summaries do not, or only slightly, address the relevance of their commitment and give no evidence of why their proposed action is important in reducing alcohol‐related harm. Even fewer commitments mention indicators of effectiveness of the proposed actions or propose to evaluate the effectiveness of the proposed actions.Conclusion While most economic operators in the Forum have resources to undertake actions which could be highly effective, they commit principally to educational programmes which have been found to be mainly ineffective. This, and the neglect of existing legislation, do not give reason for optimism on the impact of the proposed commitments.
High dependency care in an obstetric setting in the UK
Authors: Saravanakumar K. , Davies L. , Lewis M. , Cooper G. M. 
Published: September 2008

SummaryOur objective was to establish the utilisation and pattern of high dependency care in a tertiary referral obstetric unit. Data of pregnant or recently pregnant women admitted to the obstetric high dependency unit from 1984 to 2007 were included to evaluate the admission rate. Four years’ information of an ongoing prospective audit was collated to identify the indications for admission, maternal monitoring, transfers to intensive care unit, and location of the baby. The overall high dependency unit admission rate is 2.67%, but increased to 5.01% in the most recent 4 years. Massive obstetric haemorrhage is now the most common reason for admission. Invasive monitoring was undertaken in 30% of women. Two‐thirds of neonates (66.3%) stayed with their critically ill mothers in the high dependency unit. Transfer to the intensive care unit was needed in 1.4 per 1000 deliveries conducted. We conclude that obstetric high dependency care provides holistic care from midwives, obstetricians and anaesthetists while retaining the opportunity of early bonding with babies for critically ill mothers.
The role of T‐regulatory cells and Toll‐like receptors in the pathogenesis of human inflammatory bowel disease
Authors: Himmel Megan E. , Hardenberg Gijs , Piccirillo Ciriaco A. , Steiner Theodore S. , Levings Megan K. 
Published: September 2008

SummaryTwo related chronic inflammatory diseases, Crohn’s disease and ulcerative colitis, are together often referred to as inflammatory bowel disease (IBD). Current treatment options are not curative, and patients face lifelong therapy and debilitation. IBD is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4+ T‐regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4+ T cells express Toll‐like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T‐cell responses in the gut. In this review, we focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, we discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T‐cell‐dependent responses to bacterial proteins, such as flagellin, are central to the aetiology of this disease.
Nurses’ responses to ethical dilemmas in nursing practice: meta‐analysis
Authors: De Casterlé Bernadette Dierckx , Izumi Shigeko , Godfrey Nelda S. , Denhaerynck Kris 
Published: September 2008

AbstractTitle.  Nurses’ responses to ethical dilemmas in nursing practice: meta‐analysis. Aim.  This paper is a report of a study to explore nurses’ responses to ethical dilemmas in daily nursing practice.Background.  Concern about nurses’ ethical competence is growing. Most nurses perceived that there were barriers in their work environment to ethical practice, compromising their ability to perform ethically. Since most research focuses on contextual barriers to nurses’ ethical practice, little is known about how nurses involve themselves in ethical decision‐making and action in daily care.Method.  A meta‐analysis of nurses’ ethical behaviour was conducted using data from nine studies in four countries (n = 1592 registered nurses). In all studies, the Ethical Behaviour Test was used to measure nurses’ ethical responses, based on an adapted version of Kohlberg’s theory of moral development. Data were analysed using random‐intercept regression analysis.Findings.  All groups, except the expert group, displayed a uniform pattern of conventional ethical reasoning and practice. When nurses were faced with ethical dilemmas, they tended to use conventions as their predominant decision‐guiding criteria rather than patients’ personal needs and well‐being.Conclusion.  Conformist practice (following conventions rather than pursuing good for the patient) constitutes a major barrier for nurses to take the appropriate ethical actions, as creativity and critical reflection are absent. There is an urgent need to find ways to promote nurses’ ethical development from conventional to postconventional ethical practice. More research is needed to strengthen existing empirical evidence.
The immediate lived experience of the 2004 tsunami disaster by Swedish tourists
Authors: Råholm Maj‐Britt , Arman Maria , Rehnsfeldt Arne 
Published: September 2008

AbstractTitle.  The immediate lived experience of the 2004 tsunami disaster by Swedish tourists. Aim.  This paper is a report of a study of the immediate lived experiences of victims and relatives of the 2004 tsunami disaster.Background.  Disasters serve to remind us of our frailty and vulnerability and raise existential questions. From the perspective of caring sciences, suffering is regarded as a natural source for change in patients’ understanding of the world and the meaningfulness of their lives.Method.  A phenomenological hermeneutic study was conducted, using in‐depth interviews with a convenience sample of 19 informants in 2006–2007. Ricoeur’s theory of interpretation served as a guiding principle for interpreting the interview texts.Findings.  The immediate lived experiences of the tsunami survivors and their relatives revealed a comprehensive picture, described as different acts of the drama. These acts were: ‘experiencing the very core of existence’, ‘a changed understanding of life’ and ‘the power of communion’. Confronting our frailty and vulnerability makes us more authentic to ourselves, to our relatives and to life itself. The first step towards progression involves an act where the suffering is seen and validated by another person. Reshaping the suffering together with the family adds a valuable dimension to life. Availability and presence by the family opened up for communion.Conclusion.  The immediate lived experiences of the tsunami disaster from an existential and ontological perspective constitute an important aspect of understanding the whole phenomenon. Concepts such as communion, understanding life and progression of suffering can help us construct an image of this previously unresearched dimension.
Making patients safer: nurses’ responses to patient safety alerts
Authors: Lankshear Annette , Lowson Karen , Harden Jane , Lowson Paula , Saxby Ruth C 
Published: September 2008

AbstractTitle.  Making patients safer: nurses’ responses to patient safety alerts. Aim.  This paper is a report of a study to determine whether action required by patient safety alerts was effectively taken.Background.  Over the last 10 years, there has been a growing awareness of the number of patients unintentionally harmed in the course of their treatment. Safety alerts are designed to reduce the incidence of adverse events by removing these predisposing factors.Method.  A multi‐method study was carried out in 20 acute, two mental health, four ambulance and 15 primary care provider organizations in the United Kingdom in 2006–2007 using surveys, interviews with senior managers and front‐line staff, collection of documentary evidence and equipment audit. The implementation of three safety alerts for nursing action is reported.Findings.  Most staff were aware of the dangers posed by gloves to staff with latex allergy, but only 20% were aware of the types of common equipment that posed a danger to sensitive patients. Almost 40% of nurses were unable to give a correct acidity value to allow nasogastric feeding to commence. One alert, on needle‐free intravascular connectors, was distributed in only a few organizations as the term used was unfamiliar at all levels of the organization.Conclusion.  Healthcare providers have succeeded in setting up successful systems to disseminate alerts to middle management level, but there is evidence that implementation of recommendations by nurses is sub‐optimal.
Adherence: a concept analysis
Authors: Bissonnette Janice M. 
Published: September 2008

AbstractTitle. Adherence: a concept analysis.Aim. This paper is a report of an analysis of the concept of adherence.Background. The transition in terminology from compliance to adherence, and more recently to concordance, requires re‐clarification of ‘adherence’ as a concept in nursing practice. Differences exist in the use of the term adherence and how or if it differs from compliance or concordance.Data sources. Using the Medical Subject Headings terms adherence, non‐adherence and treatment refusal, the Cumulative Index to Nursing and Allied Health Literature, Medline, PsychINFO and Cochrane library databases were searched for publications between 1970 and 2007.Method. The evolutionary analytic method was used to identify and explore transitions in the concept of adherence over time and across healthcare disciplines. A representative sample of papers was identified from the disciplines of nursing, medicine, psychology and pharmacy.Results. We identified 114 papers: 27 from nursing, 39 from psychology, 33 from general medicine and 15 from pharmacology sources. The final sample included eight from pharmacy and 15 from mental health, medicine and nursing. We found no distinct differentiation between adherence and compliance. The surrogate terms serving as manifestations of adherence are concordance, agreement, cooperation and partnership. The most common definition found was as follows: ‘Adherence can be defined as the extent to which patients follow the instructions they are given for prescribed treatments’. No definition of adherence exists that reflects a patient‐centred approach, the dynamic nature of adherence behaviour and the power imbalance implied by these terms.Conclusion. This concept analysis of adherence is a preliminary step towards broadening nurses’ appreciation of the complexity of patient adherence behaviour.
Triptolide Inhibits the Differentiation of Th17 cells and Suppresses Collagen‐induced Arthritis
Authors: Wang Y. , Jia L. , Wu C.‐y. 
Published: September 2008

AbstractTriptolide, a diterpenoid isolated from the Chinese herbTripterygium wilfordiiHook F, has been demonstrated to be effective in the treatment of a variety of autoimmune diseases. T helper type 17 (Th17) cells represent a novel subset of CD4+T cells involved in the immunopathogenesis of autoimmune diseases. Currently, the effects of triptolide on the differentiation of Th17 cells remain unclear. Here, we found that triptolide significantly inhibited the generation of Th17 cells from murine splenocytes and purified CD4+T cells in a dose‐dependent manner. The suppressive effects of triptolide were persistent even after it had been removed from cell cultures. Importantly, triptolide inhibited the transcription of interleukin‐17 (IL‐17) mRNA and IL‐6‐induced phosphorylation of STAT3, a key signalling molecule involved in the development of Th17 cells. Moreover, these suppressive effects of triptolide on Th17 differentiation were not due to cytotoxicity of triptolide because the numbers of viable cells had no significant difference between triptolide‐treated and non‐triptolide‐treated cells.In vivostudies demonstrated that the treatment of collagen‐induced arthritis (CIA) mice with triptolide reduced arthritis scores and swollen degree of joints. At the same time, the levels of collagen type II (CII)‐specific IL‐17 production and the percentages of CII‐specific IL‐17+CD4+T cells in the cells from draining lymph nodes and spleens were significantly reduced in CIA mice treated with triptolide. These results suggested that triptolide displayed an immunosuppressive effect on CIA by down‐regulating CII‐specific Th17 cells. Taken together, our results may provide a new light on the potential mechanism of the immunosuppressive and anti‐inflammatory effects of triptolid.
Autoinhibition of IL‐15 Expression in KC Cells is ERK1/2 and PI3K Dependent
Authors: Zhang S.‐Q. , Luo X. , Yang S. , Liu J.‐L. , Yang C.‐J. , Yin X.‐Y. , Huang H.‐L. , Zhang X.‐J. 
Published: September 2008

AbstractInterleukin (IL)‐15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL‐15 on expression of IL‐15, IL‐6 and TNF‐α in KC are unknown. We have investigated the effects of IL‐15 on the expression of the three genes in primary culture of KC by the real‐time PCR, Western blot and ELISA. We observed that exogenous IL‐15 suppressed the endogenous expression of IL‐15, decreased the expression of IL‐6 at mRNA and protein levels in KC. The inhibition was blocked by anti‐IL‐15 monoclonal antibody and by inactive IL‐15, I50D mutant IL‐15. In contrast, IL‐15 increased TNF‐α transcription in these cells. Mechanistic studies demonstrated that the auto‐regulation of IL‐15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto‐inhibitory mechanism controlling cellular IL‐15 levels.