bluuebunny/crossref_metadata_2025_split huggingface dataset:
R723, a selective JAK2 inhibitor, effectively treats JAK2V617F-induced murine myeloproliferative neoplasm
Authors: Shide Kotaro , Kameda Takuro , Markovtsov Vadim , Shimoda Haruko K. , Tonkin Elizabeth , Fang Shuling , Liu Chian , Gelman Marina , Lang Wayne , Romero Jason , McLaughlin John , Bhamidipati Somasekhar , Clough Jeffrey , Low Caroline , Reitsma Andrea , Siu Stacey , Pine Polly , Park Gary , Torneros Allan , Duan Matt , Singh Rajinder , Payan Donald G. , Matsunaga Takuya , Hitoshi Yasumichi , Shimoda Kazuya 
Published: April 2011

Abstract
The activating mutations in JAK2 (including JAK2V617F) that have been described in patients with myeloproliferative neoplasms (MPNs) are linked directly to MPN pathogenesis. We developed R723, an orally bioavailable small molecule that inhibits JAK2 activity in vitro by 50% at a concentration of 2nM, while having minimal effects on JAK3, TYK2, and JAK1 activity. R723 inhibited cytokine-independent CFU-E growth and constitutive activation of STAT5 in primary hematopoietic cells expressing JAK2V617F. In an anemia mouse model induced by phenylhydrazine, R723 inhibited erythropoiesis. In a leukemia mouse model using Ba/F3 cells expressing JAK2V617F, R723 treatment prolonged survival and decreased tumor burden. In V617F-transgenic mice that closely mimic human primary myelofibrosis, R723 treatment improved survival, hepatosplenomegaly, leukocytosis, and thrombocytosis. R723 preferentially targeted the JAK2-dependent pathway rather than the JAK1- and JAK3-dependent pathways in vivo, and its effects on T and B lymphocytes were mild compared with its effects on myeloid cells. Our preclinical data indicate that R723 has a favorable safety profile and the potential to become an efficacious treatment for patients with JAK2V617F-positive MPNs.
Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years
Authors: Taylor Kristin , Gurney Kate , Han Jenny , Pencek Richard , Walsh Brandon , Trautmann Michael 
Published: April 2011

AbstractBackgroundThe once-weekly (QW) formulation of the glucagon-like peptide-1 receptor agonist exenatide has been demonstrated to improve A1C, fasting plasma glucose (FPG), body weight, serum lipid profiles, and blood pressure in patients with type 2 diabetes through 52 weeks of treatment. In this report, we describe the 2-year results of the open-label, open-ended extension to the DURATION-1 trial of exenatide QW for type 2 diabetes.MethodsA 2-stage protocol was used: patients received either exenatide QW (2 mg) or exenatide twice daily for 30 weeks (5 μg for the first 4 weeks and 10 μg thereafter), followed by 1.5 years of treatment with exenatide QW (2 mg), for a total of 2 years (104 weeks) of exenatide treatment. Of the 295 (intent-to-treat [ITT]) patients who entered the trial, 73% (n = 216) completed 2 years of treatment (completer population). Baseline characteristics (mean ± SE) for these patients were: A1C, 8.2 ± 0.1%; FPG, 168.4 ± 43.0 mg/dL; body weight, 101.1 ± 18.7 kg; and diabetes duration, 7 ± 5 years.ResultsIn the completer population, significant improvements (LS mean ± SE [95% CI]) were maintained after 2 years of treatment in A1C (-1.71 ± 0.08% [-1.86 to -1.55%]), FPG (-40.1 ± 2.9 mg/dL [-45.7 to -34.5 mg/dL]), and body weight (-2.61 ± 0.52 kg [-3.64 to -1.58 kg]) compared with baseline. The percentages of patients who achieved an A1C of <7.0% and ≤6.5% at 2 years were 60% and 39%, respectively. A significant reduction in systolic blood pressure (SBP; -3.0 ± 1.0 mmHg [-4.9 to -1.1 mmHg]) was maintained through 2 years of treatment. Serum lipid profiles were also significantly improved, including triglycerides (geometric LS mean change from baseline, -15 ± 2.7% [-21% to -10%]), total cholesterol (-8.6 ± 2.8 mg/dL [-14.0 to -3.1 mg/dL]), and low-density lipoproteins (-4.5 ± 2.2 mg/dL [-8.9 to -0.01 mg/dL]). Changes in A1C, body weight, FPG, SBP, and lipids in the ITT population were similar to those seen in the completer population. Nausea (predominantly mild in intensity) was the most common adverse event, although the frequency and intensity of nausea decreased over time. No severe hypoglycemia was observed.ConclusionsExenatide QW was well tolerated during the 2-year treatment period. This study demonstrated sustained glucose control and weight loss throughout 2 years of treatment with exenatide QW.Trial RegistrationClinicalTrials.govNCT00308139
Polytetrafluorethylene-Au as a substrate for surface-enhanced Raman spectroscopy
Authors: Žvátora Pavel , Řezanka Pavel , Prokopec Vadym , Siegel Jakub , Švorčík Václav , Král Vladimír 
Published: April 2011

Abstract
This study deals with preparation of substrates suitable for surface-enhanced Raman spectroscopy (SERS) applications by sputtering deposition of gold layer on the polytetrafluorethylene (PTFE) foil. Time of sputtering was investigated with respect to the surface properties. The ability of PTFE-Au substrates to enhance Raman signals was investigated by immobilization of biphenyl-4,4'-dithiol (BFD) from the solutions with various concentrations. BFD was also used for preparation of sandwich structures with Au or Ag nanoparticles by two different procedures. Results showed that PTFE can be used for fabrication of SERS active substrate with easy handle properties at low cost. This substrate was sufficient for the measurement of SERS spectrum of BFD even at 10-8 mol/l concentration.
Comparison of user groups' perspectives of barriers and facilitators to implementing electronic health records: a systematic review
Authors: McGinn Carrie Anna , Grenier Sonya , Duplantie Julie , Shaw Nicola , Sicotte Claude , Mathieu Luc , Leduc Yvan , Légaré France , Gagnon Marie-Pierre 
Published: April 2011

Abstract

Background
Electronic health record (EHR) implementation is currently underway in Canada, as in many other countries. These ambitious projects involve many stakeholders with unique perceptions of the implementation process. EHR users have an important role to play as they must integrate the EHR system into their work environments and use it in their everyday activities. Users hold valuable, first-hand knowledge of what can limit or contribute to the success of EHR implementation projects. A comprehensive synthesis of EHR users' perceptions is key to successful future implementation. This systematic literature review was aimed to synthesize current knowledge of the barriers and facilitators influencing shared EHR implementation among its various users.

Methods
Covering a period from 1999 to 2009, a literature search was conducted on nine electronic databases. Studies were included if they reported on users' perceived barriers and facilitators to shared EHR implementation, in healthcare settings comparable to Canada. Studies in all languages with an empirical study design were included. Quality and relevance of the studies were assessed. Four EHR user groups were targeted: physicians, other health care professionals, managers, and patients/public. Content analysis was performed independently by two authors using a validated extraction grid with pre-established categorization of barriers and facilitators for each group of EHR users.

Results
Of a total of 5,695 potentially relevant publications identified, 117 full text publications were obtained after screening titles and abstracts. After review of the full articles, 60 publications, corresponding to 52 studies, met the inclusion criteria. The most frequent adoption factors common to all user groups were design and technical concerns, ease of use, interoperability, privacy and security, costs, productivity, familiarity and ability with EHR, motivation to use EHR, patient and health professional interaction, and lack of time and workload. Each user group also identified factors specific to their professional and individual priorities.

Conclusions
This systematic review presents innovative research on the barriers and facilitators to EHR implementation. While important similarities between user groups are highlighted, differences between them demonstrate that each user group also has a unique perspective of the implementation process that should be taken into account.
Selective regulation of nerve growth factor expression in developing cutaneous tissue by early sensory innervation
Authors: Wyatt Sean L , Spori Bodo , Vizard Tom N , Davies Alun M 
Published: April 2011

Abstract

Background
In the developing vertebrate peripheral nervous system, the survival of sympathetic neurons and the majority of sensory neurons depends on a supply of nerve growth factor (NGF) from tissues they innervate. Although neurotrophic theory presupposes, and the available evidence suggests, that the level of NGF expression is completely independent of innervation, the possibility that innervation may regulate the timing or level of NGF expression has not been rigorously investigated in a sufficiently well-characterized developing system.

Results
To address this important question, we studied the influence of innervation on the regulation of NGF mRNA expression in the embryonic mouse maxillary process in vitro and in vivo. The maxillary process receives its innervation from predominantly NGF-dependent sensory neurons of the trigeminal ganglion and is the most densely innervated cutaneous territory with the highest levels of NGF in the embryo. When early, uninnervated maxillary processes were cultured alone, the level of NGF mRNA rose more slowly than in maxillary processes cultured with attached trigeminal ganglia. In contrast to the positive influence of early innervation on NGF mRNA expression, the levels of brain-derived neurotrophic factor (BDNF) mRNA and neurotrophin-3 (NT3) mRNA rose to the same extent in early maxillary processes grown with and without trigeminal ganglia. The level of NGF mRNA, but not BDNF mRNA or NT3 mRNA, was also significantly lower in the maxillary processes of erbB3
-/- mice, which have substantially fewer trigeminal neurons than wild-type mice.

Conclusions
This selective effect of initial innervation on target field NGF mRNA expression provokes a re-evaluation of a key assertion of neurotrophic theory that the level of NGF expression is independent of innervation.
EBF factors drive expression of multiple classes of target genes governing neuronal development
Authors: Green Yangsook S , Vetter Monica L 
Published: April 2011

Abstract

Background
Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors.

Results
We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity.

Conclusions
The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.
Unexpected complexity of the Reef-Building Coral Acropora millepora transcription factor network
Authors: Ryu Taewoo , Mavromatis Charalampos Harris , Bayer Till , Voolstra Christian R , Ravasi Timothy 
Published: April 2011

Abstract

Background
Coral reefs are disturbed on a global scale by environmental changes including rising sea surface temperatures and ocean acidification. Little is known about how corals respond or adapt to these environmental changes especially at the molecular level. This is mostly because of the paucity of genome-wide studies on corals and the application of systems approaches that incorporate the latter. Like in any other organism, the response of corals to stress is tightly controlled by the coordinated interplay of many transcription factors.

Results
Here, we develop and apply a new system-wide approach in order to infer combinatorial transcription factor networks of the reef-building coral Acropora millepora. By integrating sequencing-derived transcriptome measurements, a network of physically interacting transcription factors, and phylogenetic network footprinting we were able to infer such a network. Analysis of the network across a phylogenetically broad sample of five species, including human, reveals that despite the apparent simplicity of corals, their transcription factors repertoire and interaction networks seem to be largely conserved. In addition, we were able to identify interactions among transcription factors that appear to be species-specific lending strength to the novel concept of "Taxonomically Restricted Interactions".

Conclusions
This study provides the first look at transcription factor networks in corals. We identified a transcription factor repertoire encoded by the coral genome and found consistencies of the domain architectures of transcription factors and conserved regulatory subnetworks across eumetazoan species, providing insight into how regulatory networks have evolved.
The dectin-1/inflammasome pathway is responsible for the induction of protective T-helper 17 responses that discriminate between yeasts and hyphae ofCandida albicans
Authors: Cheng Shih-Chin , van de Veerdonk Frank L , Lenardon Megan , Stoffels Monique , Plantinga Theo , Smeekens Sanne , Rizzetto Lisa , Mukaremera Liliane , Preechasuth Kanya , Cavalieri Duccio , Kanneganti Thirumala Devi , van der Meer Jos W M , Kullberg Bart Jan , Joosten Leo A B , Gow Neil A R , Netea Mihai G 
Published: April 2011

ABSTRACTIn the mucosa, the immune pathways discriminating between colonizing and invasive Candida, thus inducing tolerance or inflammation, are poorly understood. Th17 responses induced by Candida albicans hyphae are central for the activation of mucosal antifungal immunity. An essential step for the discrimination between yeasts and hyphae and induction of Th17 responses is the activation of the inflammasome by C. albicans hyphae and the subsequent release of active IL-1β in macrophages. Inflammasome activation in macrophages results from differences in cell-wall architecture between yeasts and hyphae and is partly mediated by the dectin-1/Syk pathway. These results define the dectin-1/inflammasome pathway as the mechanism that enables the host immune system to mount a protective Th17 response and distinguish between colonization and tissue invasion by C. albicans.
Treatment of personality disorder: skills-based therapies
Authors: Evershed Sue 
Published: April 2011

SummaryA variety of therapies have been developed or adapted to treat personality disorder over recent years. This article will review skills-based treatments (as opposed to insight-based treatments). Two approaches are outlined: cognitive-behavioural therapy and dialectical behaviour therapy. The article details the underpinning theory and the model of personality disorder utilised by the two approaches, and describes how the therapy is applied. Evidence of therapeutic efficacy is presented along with information about accessing training and therapy materials.
Ethical perspectives on suicide and suicide prevention
Authors: Kelly Chris , Dale Eric 
Published: April 2011

SummaryPhilosophy both influences and is influenced by clinical and legal practice relating to suicide. This article begins with a brief history of attitudes in the UK and Europe towards those who attempt suicide. It describes the main philosophical positions regarding suicide, including the principle of respect for life, the utilitarian position, the theological principle, and the principles of autonomy and duty to others. It concludes that short-term interventions are justified in most cases, for example when the suicide attempt is a ‘cry for help’ and/or the individual is ambivalent in their attempt or likely to have a mental illness.
Sensorimotor approaches to trauma treatment
Authors: Fisher Janina 
Published: April 2011

SummaryResearch has consistently demonstrated a connection between affect dysregulation and experiences of early childhood neglect, trauma and attachment failure. Without adequate regulation of the infant's distress states, the nervous system and affect-regulating brain structures fail to develop optimally. Affect dysregulation is a component of all mood, anxiety and borderline personality disorders as well as a contributor to addictive and suicidal behaviour. Methods to increase self-regulation are crucial to the effectiveness of any treatment for these problems. Traditional therapeutic modalities that address distorted cognitions or focus on emotional expression attempt to address affect regulation but fail to modify its underlying basis in the nervous system. Sensorimotor psychotherapy, as a somatically oriented therapy, approaches affect dysregulation as a subcortical issue. Its interventions directly address the underlying causes of dysregulation in the body and nervous system.
Working with offenders: challenges to the recovery agenda
Authors: Dorkins Eluned , Adshead Gwen 
Published: April 2011

SummaryRecovery approaches are now being developed in forensic as well as general mental health services. These are welcome developments that offer new ways of working with a socially excluded group of patients. However, the theoretical basis of recovery, with its individual humanistic ethos, may struggle to articulate the unique problems of forensic service users. In this article, we describe those problems and propose a ‘third way’ of thinking that bridges the recovery agenda (which looks for the best in people) and the forensic agenda (which must consider the worst in people). We propose using a ‘narrative approach’, which sees the forensic service user's offence and cruelty as part of their human story. We link this explicitly with the work of Dan McAdams and his concept of the redemption narrative.
Hope in psychiatry
Authors: Schrank Beate , Hayward Mark , Stanghellini Giovanni , Davidson Larry 
Published: April 2011

SummaryHope has long been considered a relevant variable in medical disciplines, but little attention has been paid to the concept, and its clinical and research implications, in psychiatry. This article illuminates the topic of hope from four different perspectives relevant to psychiatric research and practice. The four authors discuss hope from the viewpoint of their specific area of expertise, providing an overview of philosophical, conceptual, research and recovery-related reflections concerning hope in psychiatry.
Medical leadership: competencies in action
Authors: Garg Shruti , van Niekerk Jon , Campbell Margaret 
Published: April 2011

SummaryThe engagement of the medical profession in management and leadership activities has become a priority for the UK's National Health Service (NHS). It makes sense to develop these leadership competencies as early as possible, inculcating leadership skills in junior doctors. The recent core and specialist curriculum competencies address this and, together with the Medical Leadership Competency Framework developed by the Academy of Medical Royal Colleges and the NHS, sets out a blueprint for personal development plans for junior doctors. A culture shift is called for, such that doctors in training prioritise their leadership development alongside their medical training. This article is of particular relevance to educational supervisors, as it describes how they can support junior doctors in achieving the leadership and management competencies outlined in the 2009 core and specialty psychiatry curriculum.
‘Forensic service user’: transitional identity or life sentence?
Authors: Roberts Glenn 
Published: April 2011

SummaryIt has been suggested that a recovery-focused approach and treatment under the Mental Health Act are mutually exclusive, hence the limited applicability of ‘recovery’ in forensic psychiatry. This is heightened if recovery is seen as a ‘model’ that does or does not fit, and lessened if seen as ‘values-in-action’ that need reinterpretation in context.
Service user involvement in mental health research: a user's perspective
Authors: Syrett Michel 
Published: April 2011

SummaryThis article focuses on service user involvement in supporting and undertaking mental health research. It is written from the author's perspective as a service user with bipolar disorder who has built on previous experience as an academic researcher in business and management studies by active involvement in a number of mental health research projects in a service user capacity. The article highlights contrasting approaches taken by different projects in how they involve service users and provides learning points based on the author's and other service users' experiences.
The zone of parental control and decision-making in young people: legal derivation and influences
Authors: Hawkins Tim , Player Ben , Curtice Martin 
Published: April 2011

SummaryThe 2007 amendments to the Mental Health Act 1983 and their accompanying Code of Practice produced new guidance on the limits of parental influence over young people's ability to consent. Previously, professional practice on decision-making and consent was guided by a combination of the Mental Health Act 1983 Code of Practice, the Family Law Reform Act 1969 and evolving English and Welsh case law. The 2007 amendments to the 1983 Act take heed of such influences and the Code of Practice specifically includes reference to European case law. What was previously left open to balanced professional interpretation has now been formalised into statute law. A central facet of this is the introduction of the concept of the zone of parental control, which derives largely from European case law. This article considers the derivation from case law of this novel concept and in particular its relationship with the European Convention on Human Rights.
What makes a medical leader?
Authors: Bhugra Dinesh 
Published: April 2011

SummaryMedical leadership is important and must be a part of training. It requires qualities at three levels: the personal, the interpersonal (working with and through others) and the organisational (in political and cultural contexts). Some of the traits of good leadership can be taught and learnt, whereas others are inherent. The roles of individual leaders depend on the organisations in which they are involved. Different contexts require different leadership styles.
Mechanochromic and Color-change Properties of 2,6-Di(2-pyridyl)benzo[1,2-b:4,5-b′]difuran in the Solid and Solution
Authors: Tsuji Hayato , Favier Guillaume Marcel Olivier , Mitsui Chikahiko , Lee Sunri , Hashizume Daisuke , Nakamura Eiichi 
Published: April 2011

Abstract
2,6-Di(2-pyridyl)benzo[1,2-b:4,5-b′]difuran (2-PyBDF) shows a π–π-stacking packing structure in a single crystal and some intriguing properties: mechanochromism in the solid state, and solvent and concentration dependence of absorption and emission spectra.