bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connective tissue growth factor promoter activity in normal and wounded skin
Authors: Kapoor Mohit , Liu Shangxi , Huh Kun , Parapuram Sunil , Kennedy Laura , Leask Andrew 
Published: October 2008

Abstract
In skin, connective tissue growth factor (CTGF/CCN2) is induced during tissue repair. However, what the exact cell types are that express CTGF in normal and wounded skin remain controversial. In this report, we use transgenic knock-in mice in which the Pacific jellyfish Aequorea victoria enhanced green fluorescent protein (E-GFP) gene has been inserted between the endogenous CTGF promoter and gene. Unwounded (day 0) and wounded (days 3 and 7) skin was examined for GFP to detect cells in which the CTGF promoter was active, α-smooth muscle actin (α-SMA) to detect myofibroblasts, and NG2 expression to detect pericytes. In unwounded mice, CTGF expression was absent in epidermis and was present in a few cells in the dermis. Upon wounding, CTGF expression was induced in the dermis. Double immunolabeling revealed that CTGF-expressing cells also expressed α-SMA, indicating the CTGF was expressed in myofibroblasts. A subset (~30%) of myofibroblasts were also NG2 positive, indicating that pericytes significantly contributed to the number of myofibroblasts in the wound. Pericytes also expressed CTGF. Collectively, these results indicate that CTGF expression in skin correlates with myofibroblast induction, and that CTGF-expressing pericytes are significant contributors to myofibroblast activity during cutaneous tissue repair.
Redox mechanisms in hepatic chronic wound healing and fibrogenesis
Authors: Novo Erica , Parola Maurizio 
Published: October 2008

AbstractReactive oxygen species (ROS) generated within cells or, more generally, in a tissue environment, may easily turn into a source of cell and tissue injury. Aerobic organisms have developed evolutionarily conserved mechanisms and strategies to carefully control the generation of ROS and other oxidative stress-related radical or non-radical reactive intermediates (that is, to maintain redox homeostasis), as well as to 'make use' of these molecules under physiological conditions as tools to modulate signal transduction, gene expression and cellular functional responses (that is, redox signalling). However, a derangement in redox homeostasis, resulting in sustained levels of oxidative stress and related mediators, can play a significant role in the pathogenesis of major human diseases characterized by chronic inflammation, chronic activation of wound healing and tissue fibrogenesis. This review has been designed to first offer a critical introduction to current knowledge in the field of redox research in order to introduce readers to the complexity of redox signalling and redox homeostasis. This will include ready-to-use key information and concepts on ROS, free radicals and oxidative stress-related reactive intermediates and reactions, sources of ROS in mammalian cells and tissues, antioxidant defences, redox sensors and, more generally, the major principles of redox signalling and redox-dependent transcriptional regulation of mammalian cells. This information will serve as a basis of knowledge to introduce the role of ROS and other oxidative stress-related intermediates in contributing to essential events, such as the induction of cell death, the perpetuation of chronic inflammatory responses, fibrogenesis and much more, with a major focus on hepatic chronic wound healing and liver fibrogenesis.
Identification of CDK2 substrates in human cell lysates
Authors: Chi Yong , Welcker Markus , Hizli Asli A , Posakony Jeffrey J , Aebersold Ruedi , Clurman Bruce E 
Published: October 2008

Abstract
Background
Protein phosphorylation regulates a multitude of biological processes. However, the large number of protein kinases and their substrates generates an enormously complex phosphoproteome. The cyclin-dependent kinases - the CDKs - comprise a class of enzymes that regulate cell cycle progression and play important roles in tumorigenesis. However, despite intense study, only a limited number of mammalian CDK substrates are known. A comprehensive understanding of CDK function requires the identification of their substrate network.

Results
We describe a simple and efficient approach to identify potential cyclin A-CDK2 targets in complex cell lysates. Using a kinase engineering strategy combined with chemical enrichment and mass spectrometry, we identified 180 potential cyclin A-CDK2 substrates and more than 200 phosphorylation sites. About 10% of these candidates function within pathways related to cell division, and the vast majority are involved in other fundamental cellular processes. We have validated several candidates as direct cyclin A-CDK2 substrates that are phosphorylated on the same sites that we identified by mass spectrometry, and we also found that one novel substrate, the ribosomal protein RL12, exhibits site-specific CDK2-dependent phosphorylation in vivo.

Conclusions
We used methods entailing engineered kinases and thiophosphate enrichment to identify a large number of candidate CDK2 substrates in cell lysates. These results are consistent with other recent proteomic studies, and suggest that CDKs regulate cell division via large networks of cellular substrates. These methods are general and can be easily adapted to identify direct substrates of many other protein kinases.
Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas
Authors: Westermann Frank , Muth Daniel , Benner Axel , Bauer Tobias , Henrich Kai-Oliver , Oberthuer André , Brors Benedikt , Beissbarth Tim , Vandesompele Jo , Pattyn Filip , Hero Barbara , König Rainer , Fischer Matthias , Schwab Manfred 
Published: October 2008

Abstract
Background
Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes.

Results
We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and chromatin immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MYC. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-non-amplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-non-amplified but not in stage 4s-non-amplified neuroblastomas. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis.

Conclusions
High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression, which is predominantly driven by c-MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression.
Improved genome assembly and evidence-based global gene model set for the chordate Ciona intestinalis: new insight into intron and operon populations
Authors: Satou Yutaka , Mineta Katsuhiko , Ogasawara Michio , Sasakura Yasunori , Shoguchi Eiichi , Ueno Keisuke , Yamada Lixy , Matsumoto Jun , Wasserscheid Jessica , Dewar Ken , Wiley Graham B , Macmil Simone L , Roe Bruce A , Zeller Robert W , Hastings Kenneth EM , Lemaire Patrick , Lindquist Erika , Endo Toshinori , Hotta Kohji , Inaba Kazuo 
Published: October 2008

Abstract
Background
The draft genome sequence of the ascidian Ciona intestinalis, along with associated gene models, has been a valuable research resource. However, recently accumulated expressed sequence tag (EST)/cDNA data have revealed numerous inconsistencies with the gene models due in part to intrinsic limitations in gene prediction programs and in part to the fragmented nature of the assembly.

Results
We have prepared a less-fragmented assembly on the basis of scaffold-joining guided by paired-end EST and bacterial artificial chromosome (BAC) sequences, and BAC chromosomal in situ hybridization data. The new assembly (115.2 Mb) is similar in length to the initial assembly (116.7 Mb) but contains 1,272 (approximately 50%) fewer scaffolds. The largest scaffold in the new assembly incorporates 95 initial-assembly scaffolds. In conjunction with the new assembly, we have prepared a greatly improved global gene model set strictly correlated with the extensive currently available EST data. The total gene number (15,254) is similar to that of the initial set (15,582), but the new set includes 3,330 models at genomic sites where none were present in the initial set, and 1,779 models that represent fusions of multiple previously incomplete models. In approximately half, 5'-ends were precisely mapped using 5'-full-length ESTs, an important refinement even in otherwise unchanged models.

Conclusion
Using these new resources, we identify a population of non-canonical (non-GT-AG) introns and also find that approximately 20% of Ciona genes reside in operons and that operons contain a high proportion of single-exon genes. Thus, the present dataset provides an opportunity to analyze the Ciona genome much more precisely than ever.
Recruiting patients for drug trials: a difficult task
Authors: Skerritt U. , Pitt B. , Armstrong S. , O'Brien A. 
Published: October 2008

In successfully recruiting patients for drug trials in dementia the Therapeutic Research Unit for the Elderly (TRUE) had referrals from various sources. The local Memory Clinic (MC) provided 38 patients for screening of which 31 (81%) were recruited, 75% of the overall number recruited. This number was small (n=41) despite various efforts and does not reflect the time invested and amount of contact work with GPs, out-patient departments and other psychiatric services.The memory clinic provides a source of recruitment of patients for drug trials as well as services for those who do not qualify for such trials. But recruiting without the aid of a memory clinic is difficult and time-consuming and new approaches must be found.
Special Interest Group for Neuroscience in Psychiatry
Authors: Goodwin Guy M. 
Published: October 2008

The inaugural meeting of a Special Interest Group for Neuroscience in Psychiatry was held at the meeting of the College in Glasgow in 1995, chaired by Professor Stuart Checkley.The following statement has been prepared for the group to announce its existence and stimulate discussion of its aims.
The mission of the group will be to promote the application of neuroscience to the core problems of aetiology and treatment in psychiatry. The term neuroscience encapsulates those aspects of anatomy, physiology, pharmacology, genetics and psychology which contribute mutually to an improved understanding of how the brain functions in health and disease.
‘The Reading model’: an integrated psychotherapy service
Authors: Knowles Jane 
Published: October 2008

This article describes the principles and structure, staffing and training of an integrated psychotherapy service for the people of West Berkshire and South Oxfordshire (Reading, Henley, Wokingham, Newbury and Didcot) a population of 530 000.The service is integrated internally as a joint outpatient and therapeutic community service that can provide psychodynamic psychotherapy across a wide range of length, intensity and styles. Externally it is integrated with the general adult psychiatry service, referrers, social services and community mental health teams.
Staff attitudes to a psychiatric hospital closure
Authors: Ardagh-Walter Nick , Naik Prakash , Tombs David 
Published: October 2008

Many psychiatric hospitals in the UK have closed. Factors influencing staff morale around the time of a hospital closure will affect the functioning of that institution. This study surveyed staff anxieties, attitudes and expectations in a major psychiatric hospital three weeks prior to its closure. We found evidence of widespread denial despite energetic dissemination of information. There were also significant differences between staff groups. Our findings will have implications for the management of future hospital closures.“We have to get it into our heads that a hospital is like a shell, a framework to contain certain processes, and when the processes are superseded, the shell must, most probably, be scrapped and the framework dismantled” (Enoch Powell, 1961).
Nursery observation in the training of child psychiatry registrars
Authors: Etchegoyen Alicia , Stubley Joanne 
Published: October 2008

This paper discusses a training opportunity based on an adaptation of the Infant Observation method. This is a much shorter module, of ten weekly visits.We describe three training components: (a) an opportunity to learn directly about child development and to become familiar with children's verbal and nonverbal communications; (b) a direct experience of the emotional impact and strength of primitive feelings, both in the children and in the trainees themselves, and (c) learning to be a ‘non-participant’ observer. We believe that the ability to observe without intervention is extremely important in the development of clinical skids. We suggest that this is the cornerstone of the method and that it may have a wider application to the training of those in the caring professions, including psychiatrists, nurses and social workers.
The role of the speciality tutor in the training of junior doctors in psychiatry
Authors: Hughes Patricia 
Published: October 2008

“The Speciality Tutor is a psychiatrist working in the fields of child and adolescent psychiatry, psychotherapy, forensic psychiatry, learning disability, psycho-geriatrics, or the dependencies (drugs and alcohol), who is regarded as the tutor for the organisation of training in that speciality in the Region. There is one tutor for each Region.” (Royal College of Psychiatrists, 1996)The speciality tutor is recognised but not appointed by the College. He or she may be appointed by the University, the Regional Post graduate Education Committee, or by a local committee, for example, the local Division of Psychiatry. The appointment, however, must have the agreement of colleagues (Royal College of Psychiatrists, 1996).
Antipsychotic medication in learning disability Impact of audit and evidence-based medicine on quality of prescribing in a community assessment treatment unit
Authors: Cooray Sherva E. , Tolmac Jovanka 
Published: October 2008

Aims and methodAntipsychotic medication, an effective treatment modality in the management of psychiatric/behaviour disorders in people with learning disability, is often criticised because of poor clinical practice. Rational and judicious use, subject to evidence-based guidelines and systematic monitoring, is mandatory. A five-year clinical audit programme on the quality of prescribing for this clientele was undertaken.ResultsSignificant quality improvement with minimal resource consumption was demonstrated.Clinical implicationsClinical audit facilitates high-quality prescribing: pragmatic and economic, it can easily be integrated into routine clinical practice.
Investigation of depot neuroleptic injection site reactions
Authors: Jones Julie C. , Day Jennifer C. , Taylor John R. , Thomas Christopher S. 
Published: October 2008

Aims and methodA cross-sectional survey was performed on 318 patients receiving depot medication. The presence or absence of a depot site reaction was recorded by psychiatric nursing staff on a standardised form.ResultsSeventeen per cent of patients were found to have clinically significant depot site reactions. Such reactions were associated with increased frequency of injection and increased total volume of depot administered in the previous 12 months. The severity of a depot site reaction was unrelated to the concentration of depot preparation administered.Clinical implicationsDepot site reactions may be reduced by maximising the interval between injections and using low volume (highly concentrated) preparations of depot neuroleptic medication.
Old age psychiatrists' views on continuing in-patient care
Authors: Wattis John , Macdonald Andrew , Newton Paul 
Published: October 2008

Aims and methodsThe aim of this study was to elicit views from UK consultants in old age psychiatry concerning changes that were taking place in long-term care for older people with mental illness (especially dementia) and their views on a draft consensus statement produced by the Faculty for Psychiatry of Old Age on behalf of the College. A postal questionnaire was circulated as part of a wider survey of 472 consultants and a single postal reminder was sent to non-responders.ResultsTwo hundred and forty-two (51%) consultants responded. Nearly nine out of 10 respondents were in favour of continuing NHS consultant-supervised long-stay beds and three-quarters of them preferred a return to national numerical guidelines for bed numbers, though at a level approximately half of previous guidelines and provision. This was accompanied by a view that such beds should no longer be ‘for life’ with over three-quarters of respondents supporting discharge if, for example, behaviour problems resolved. If Government policy continued to support ‘eligibility criteria’ rather than guidelines, 60% were in favour of national rather than local criteria. There was very strong support for the draft consensus statement (now published in modified form as College Policy) and the ‘eligibility criteria’ it contained. Agreed criteria for waiting times in acute beds for continuing NHS, nursing home or residential care were not widely used.Clinical implicationsConsultants want to continue to be responsible for some longer-term care and efforts should be made to develop the role of NHS longer-term care within the 'spectrum of services' provided for older people with psychiatric disorder, perhaps by acting as local ‘centres of excellence’ in dementia care as well as by providing services for patients with the more difficult behavioural problems. The more widespread use of ‘agreed waiting times' for patients in acute beds requiring longer-term care should be explored.
Practical training in the administration of ECT
Authors: Barnes Richard , Kingsley David 
Published: October 2008

Aims and methodElectroconvulsive therapy (ECT) Is widely used In Britain and in most cases is administered by junior doctors. Many are inexperienced in its administration and the variety of machines available makes acquiring experience difficult. This report discusses a unique training programme involving a specially constructed ‘dummy patient’.ResultsThis allows trainees to experience the practical administration of ECT and also learn in detail about the working of the ECT machine and the interpretation of electroencephalograms prior to giving treatment to patients.Clinical implicationsWe believe this training device will have a significant positive effect on the way junior doctors are trained in ECT.
Psychiatric training and the Caiman reforms Survey of third year senior house officers
Authors: McCallum Seonaid , McGilvray Lisa , Bennie Peter , Whyte Sue 
Published: October 2008

Aims and methodAll third year senior house officers (SHOs) training in psychiatry in Scotland were canvassed by a postal questionnaire. They were asked about their views on training and the impact of the Caiman reforms in psychiatry.ResultsResults showed that 33% of trainees were not receiving one hour of consultant supervision per week. The quality of teaching in day release programmes was rated as average or poor by 75%. Three-quarters had not seen a copy of A Guide to Specialist Registrar Training, but had a good knowledge of the changes it proposed. Most were satisfied with their clinical training but expressed concerns about the Caiman reforms.Clinical implicationsThe loss of the registrar grade has extended the time trainees spend as SHOs and there was concern that there would be a loss of breadth of training. We intend to repeat the survey in mid–1999, by which time the Caiman changes should be fully operational in psychiatry.
Hidden high-dose antipsychotic prescribing: effects of p.r.n. doses
Authors: Milton John , Lawton John , Smith Mark , Buckley Ann 
Published: October 2008

Aims and methodThe Royal College of Psychiatrists' Consensus Statement on “The use of high-dose antipsychotic medication’ suggests only fully qualified psychiatrists (MRCPsych) should recommend the prescribing of high-dose antipsychotic treatment. We observed changes in anti-psychotic prescribing in two surveys of psychiatric in-patients conducted eight and 32 months after publication of the Consensus Statement.ResultsOverall mean chlorpromazine equivalent doses of antipsychotic drugs reduced between the surveys. When p.r.n. (as required) prescribing (usually done by junior doctors) is included, mean potential doses and numbers of patients who might receive ‘high-doses' increases substantially, although the reduction between surveys in total mean dose and proportion of patients on high-dose antipsychotic medication is preserved, and the actual use of p.r.n. medication was low (4–5% of p.r.n. prescriptions).Clinical implicationsWe recommend the development of local guidelines for junior staff concerning antipsychotic drug prescribing, regular monitoring of p.r.n. medication by consultants, and pharmacists' involvement in reviews of patients prescribed high-dose antipsychotic medication.
Prescriptions, licences and evidence
Authors: Healy David , Nutt David 
Published: October 2008

Aims and methodThere is considerable confusion at present among clinicians as regards the appropriateness of prescribing off-licence. Because of the nature of the registration process it is likely that a considerable proportion of prescribing will always be off-licence. This paper seeks to clarify when it is appropriate to prescribe off-licence. We convened a workshop on behalf of the British Association for Psychopharmacology involving clinicians and regulators from a variety of countries to explore this issue both generally and for specific childhood and learning disability clinical situations. Recent statements from the defence unions and consumer groups were also scrutinised.ResultsAcross senior clinicians and regulators from a number of European countries and North America there is a consensus that prescribing off-licence is a necessary part of the art of medicine.Clinical implicationsCurrent advice to clinicians on the issue of off-licence prescribing can sometimes overemphasise the hazards and neglect the benefits that may stem from appropriate off-licence prescribing. Good prescribing involves specifying treatment goals and monitoring outcomes and it is more important to share this with the patient than it is to communicate the licensed status of the drug being prescribed.