bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary conservation of sequence and secondary structures in CRISPR repeats
Authors: Kunin Victor , Sorek Rotem , Hugenholtz Philip 
Published: April 2007

Abstract
Background
Clustered regularly interspaced short palindromic repeats (CRISPRs) are a novel class of direct repeats, separated by unique spacer sequences of similar length, that are present in approximately 40% of bacterial and most archaeal genomes analyzed to date. More than 40 gene families, called CRISPR-associated sequences (CASs), appear in conjunction with these repeats and are thought to be involved in the propagation and functioning of CRISPRs. It has been recently shown that CRISPR provides acquired resistance against viruses in prokaryotes.

Results
Here we analyze CRISPR repeats identified in 195 microbial genomes and show that they can be organized into multiple clusters based on sequence similarity. Some of the clusters present stable, highly conserved RNA secondary structures, while others lack detectable structures. Stable secondary structures exhibit multiple compensatory base changes in the stem region, indicating evolutionary and functional conservation.

Conclusion
We show that the repeat-based classification corresponds to, and expands upon, a previously reported CAS gene-based classification, including specific relationships between CRISPR and CAS subtypes.
Discovery of tissue-specific exons using comprehensive human exon microarrays
Authors: Clark Tyson A , Schweitzer Anthony C , Chen Tina X , Staples Michelle K , Lu Gang , Wang Hui , Williams Alan , Blume John E 
Published: April 2007

Abstract
Background
Higher eukaryotes express a diverse population of messenger RNAs generated by alternative splicing. Large-scale methods for monitoring gene expression must adapt in order to accurately detect the transcript variation generated by this splicing.

Results
We have designed a high-density oligonucleotide microarray with probesets for more than one million annotated and predicted exons in the human genome. Using these arrays and a simple algorithm that normalizes exon signal to signal from the gene as a whole, we have identified tissue-specific exons from a panel of 16 different normal adult tissues. RT-PCR validation confirms approximately 86% of the predicted tissue-enriched probesets. Pair-wise comparisons between the tissues suggest that as many as 73% of detected genes are differentially alternatively spliced. We also demonstrate how an inclusive exon microarray can be used to discover novel alternative splicing events. As examples, 17 new tissue-specific exons from 11 genes were validated by RT-PCR and sequencing.

Conclusion
In conjunction with a conceptually simple algorithm, comprehensive exon microarrays can detect tissue-specific alternative splicing events. Our data suggest significant expression outside of known exons and well annotated genes and a high frequency of alternative splicing events. In addition, we identified and validated a number of novel exons with tissue-specific splicing patterns. The tissue map data will likely serve as a valuable source of information on the regulation of alternative splicing.
Growth control of the eukaryote cell: a systems biology study in yeast
Authors: Castrillo Juan I , Zeef Leo A , Hoyle David C , Zhang Nianshu , Hayes Andrew , Gardner David CJ , Cornell Michael J , Petty June , Hakes Luke , Wardleworth Leanne , Rash Bharat , Brown Marie , Dunn Warwick B , Broadhurst David , O'Donoghue Kerry , Hester Svenja S , Dunkley Tom PJ , Hart Sarah R , Swainston Neil , Li Peter , Gaskell Simon J , Paton Norman W , Lilley Kathryn S , Kell Douglas B , Oliver Stephen G 
Published: April 2007

Abstract
Background
Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking.

Results
Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth.

Conclusion
This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.
Persistent violent offending: what do we know?
Authors: Hodgins Sheilagh 
Published: April 2007

SummaryA great deal is known about men who display a stable pattern of antisocial behaviour since childhood. However, more research is needed to identify subtypes within this population so as to further understanding of the causal processes that initiate and maintain violent behaviours and to identify interventions that specifically target the deficits presented by each subtype. Evidence-based practice means not only using treatments proven to be effective but also basing conceptualisations of disorders on scientific evidence.
Precision of actuarial risk assessment instruments
Authors: Hart Stephen D. , Michie Christine , Cooke David J. 
Published: April 2007

BackgroundActuarial risk assessment instruments (ARAIs) estimate the probability that individuals will engage in future violence.AimsTo evaluate the ‘margins of error’ at the group and individual level for risk estimates made using ARAIs.MethodAn established statistical method was used to construct 95% CI for group and individual risk estimates made using two popular ARAIs.ResultsThe 95% CI were large for risk estimates at the group level; at the individual level, they were so high as to render risk estimates virtually meaningless.ConclusionsThe ARAIs cannot be used to estimate an individual's risk for future violence with any reasonable degree of certainty and should be used with great caution or not at all. In theory, reasonably precise group estimates could be made using ARAIs if developers used very large construction samples and if the tests included few score categories with extreme risk estimates.
Collecting service use data for economic evaluation in DSPD populations
Authors: Barrett Barbara , Byford Sarah 
Published: April 2007

BackgroundEconomic evaluation of the Dangerous and Severe Personality Disorder Programme is essential to ensure value for money. The collection of individual-level service use information is crucial to any such evaluation, but the best way to collect these data in secure facilities is unclear.AimsTo develop a method for the collection of individual-level service use information for prisoners/patients in secure facilities.MethodsServices provided within secure facilities were identified through examination of facility and policy literature, and discussions with managerial and clinical staff. Appropriate methods of measuring the quantities of services used were then explored and a new research tool capable of capturing all relevant services was developed and pilot tested.ResultsThe Secure Facilities Service Use Schedule (SF–SUS) records service use information from records and is capable of capturing data on the use of all individual-level services provided within a secure facility plus external services commonly accessed by occupants.DiscussionThe SF–SUS is able to collect meaningful individual-level service use information for the economic evaluation of services provided within secure facilities.
Personality disorder and impaired functioning from adolescence to adulthood
Authors: Skodol Andrew E. , Johnson Jeffrey G. , Cohen Patricia , Sneed Joel R. , Crawford Thomas N. 
Published: April 2007

BackgroundLittle is currently known about functioning and impairment during adulthood associated with the course of personality disorders.AimsTo investigate the association of personality disorder stability from adolescence through middle adulthood with measures of global functioning and impairment, using prospective epidemiological data.MethodA community-based sample of 658 individuals was interviewed at mean ages 14, 16, 22 and 33 years.ResultsIndividuals with persistent personality disorder had markedly poorer functioning and greater impairment at mean age 33 years than did those who had never been identified as having such disorder or who had a personality disorder that was in remission, after co-occurring Axis I disorders at age 33 years were taken into account. Remitted disorder was associated with mild long-term impairment. Adult-onset personality disorders, however, were also associated with significant impairment.ConclusionsPersistent and adult-onset personality disorders are associated with functional impairment among adults in the community. These effects are independent of co-occurring Axis 1 disorders.
Cognitive remediation therapy in schizophrenia
Authors: Wykes Til , Reeder Clare , Landau Sabine , Everitt Brian , Knapp Martin , Patel Anita , Romeo Renee 
Published: April 2007

BackgroundCognitive difficulties are prevalent in people with a diagnosis of schizophrenia and are associated with poor long-term functioning.AimsTo evaluate the effectiveness of cognitive remediation therapy on cognitive difficulties experienced by people with schizophrenia.MethodParticipants with a diagnosis of schizophrenia, a social behaviour problem and a cognitive difficulty (n=85) were randomised to 40 sessions of cognitive remediation or treatment as usual in a single-blind randomised controlled trial. Working memory, cognitive flexibility and planning, were measured at weeks 0, 14 and 40.ResultsThere were durable improvements in working memory (advantage 1.33 points, 95% CI 0.43–2.16, standardised effect size 0.34) as well as an indication of improvement in cognitive flexibility. Memory improvement predicted improvement in social functioning. Costs were lower in the cognitive remediation group following therapy but rose at follow-up. However, cost-effectiveness analyses showed that improvements in memory were achieved at little additional cost.ConclusionsCognitive remediation therapy is associated with durable improvements in memory, which in turn are associated with social functioning improvements in people with severe mental illness.
Chinese herbal medicine for schizophrenia
Authors: Rathbone John , Zhang Lan , Zhang Mingming , Xia Jun , Liu Xiehe , Yang Yanchun , Adams Clive Elliott 
Published: April 2007

BackgroundChinese herbal medicine has been used to treat millions of people with schizophrenia for thousands of years.AimsTo evaluate Chinese herbal medicine as a treatment for schizophrenia.MethodA systematic review of randomised controlled trials (RCTs).ResultsSeven trials were included. Most studies evaluated Chinese herbal medicine in combination with Western antipsychotic drugs; in these trials results tended to favour combination treatment compared with antipsychotic alone (Clinical Global Impression ‘not improved/worse’ n= 123, RR=0.19, 95% CI 0.1-0.6, NNT=6,95% CI 5–11; n=109, Brief Psychiatric Rating Scale ‘not improved/worse’ RR=0.78,95% CI 0.5-1.2; n=109, Scale for the Assessment of Negative Symptoms ‘not improved/worse’ RR=0.87,95% CI 0.7-1.2; n= 109, Scale for the Assessment of Positive Symptoms ‘not improved/worse’ RR=0.69,95% CI 0.5-1.0, NNT=6 95% CI 4-162). Medium-term study attrition was significantly less for people allocated the herbal/antipsychotic mix (n=897, four RCTs, RR=0.34,95% CI 0.2–0.7, NNT=23,95% CI 18-43).ConclusionsResults suggest that combining Chinese herbal medicine with antipsychotics is beneficial.
Prison mental health inreach services
Authors: Steel Julie , Thornicroft Graham , Birmingham Luke , Brooker Charlie , Mills Alice , Harty Mari , Shaw Jenny 
Published: April 2007

SummaryPrison mental health inreach teams have been established nationwide in England and Wales over the past 3 years to identify and treat mental disorders among prisoners. This paper summarises the policy content and what has been achieved thus far, and poses challenges that these teams face if they are to become a clear and effective component in the overall system of forensic mental healthcare.
Acute in-patient psychiatry: how patients spend their time on acute psychiatric wards
Authors: Radcliffe Jonathan , Smith Roger 
Published: April 2007

Aims and MethodWe observed levels of social interaction and activity among in-patients on 16 acute psychiatric wards in 6 hospitals in a large mental health trust. Each ward was observed for 1 week and attendance at organised activities was audited over 3-week periods.ResultsAt any time during the day 84% of in-patients were socially disengaged and mainly inactive. On average only 4% of in-patients' time was spent in an organised group activity, with many in-patients opting out altogether. Provision and take-up of group activity programmes varied widely between wards.Clinical ImplicationsProvision of organised activity needs to be a higher priority in acute services, and there should be national and local standards for what should be provided. Concerted organisational strategies and assertive approaches by staff are needed to engage in-patients in group activity programmes.
Basic competency testing to meet Clinical Negligence Scheme for Trusts standards
Authors: Kloer Mary , Mynors-Wallis Laurence , Cope Denise 
Published: April 2007

Aims and MethodIn order to meet revised (2005) Clinical Negligence Scheme for Trusts standards, tests of competency in key clinical skills were set for psychiatric senior house officers (SHOs) at the start of their posts.ResultsThe assessment of basic competencies demonstrated that 9 out of 14 SHOs met the required standards in tests of key clinical skills (overall competency rate of 64%). Senior house officers were generally in agreement with the principles behind the assessments.Clinical ImplicationsCompetency testing is becoming important at all stages of training and within all medical specialties. The recommended methods combine assessment of both knowledge-based competencies and clinical performance in the workplace.
Effects of a crisis resolution and home treatment team on in-patient admissions
Authors: Jethwa Krishma , Galappathie Nuwan , Hewson Paul 
Published: April 2007

Aims and MethodTo evaluate the effects of a crisis resolution and home-based treatment team upon in-patient admission rates. We collected data for 2 years prior and 1 year post-implementation of such a service in Leeds. The chosen time frame allowed the new service to settle in and controlled for seasonal variations.ResultsThere were 4353 admissions during the period of the study, with 3325 in the 2 years prior to the service and 1028 in the year after. Generalised linear analysis found a 37.5% reduction in monthly admissions after the introduction of the team (P < 0.0001).Clinical ImplicationsThis study shows that in everyday clinical practice crisis resolution and home treatment teams lead to a sustained reduction in in-patient admission rates.
Correlation of Computed Tomography and Positron Emission Tomography in Patients With Metastatic Gastrointestinal Stromal Tumor Treated at a Single Institution With Imatinib Mesylate: Proposal of New Computed Tomography Response Criteria
Authors: Choi Haesun , Charnsangavej Chuslip , Faria Silvana C. , Macapinlac Homer A. , Burgess Michael A. , Patel Shreyaskumar R. , Chen Lei L. , Podoloff Donald A. , Benjamin Robert S. 
Published: April 2007

Purpose Response Evaluation Criteria in Solid Tumors (RECIST) are insensitive in evaluating gastrointestinal stromal tumors (GISTs) treated with imatinib. This study evaluates whether computed tomography (CT) findings of GIST after imatinib treatment correlate with tumor responses by [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) and develops reliable, quantitative, CT response criteria. Patients and Methods A total of 172 lesions selected by RECIST were evaluated in 40 patients with metastatic GISTs treated with imatinib. All patients had pretreatment and 2-month follow-up CTs and FDG-PETs. Multivariate analysis was performed using tumor size and density (Hounsfield unit [HU]) on CT and maximum standardized uptake value (SUVmax) on FDG-PET. Patients were observed up to 28 months. Results Mean baseline tumor size and density on CT were 5.3 cm and 72.8 HU, respectively, and mean baseline SUVmax on FDG-PET was 5.8. Thirty-three patients had good response on FDG-PET. A decrease in tumor size of more than 10% or a decrease in tumor density of more than 15% on CT had a sensitivity of 97% and a specificity of 100% in identifying PET responders versus 52% and 100% by RECIST. Good responders on CT at 2 months had significantly longer time to progression than those who did not respond (P = .01). Conclusion Small changes in tumor size or density on CT are sensitive and specific methods of assessing the response of GISTs. If the prognostic value of our proposed CT response criteria can be confirmed prospectively, the criteria should be employed in future studies of patients with GIST.
Death in Patients With Recurrent Prostate Cancer After Radical Prostatectomy: Prostate-Specific Antigen Doubling Time Subgroups and Their Associated Contributions to All-Cause Mortality
Authors: Freedland Stephen J. , Humphreys Elizabeth B. , Mangold Leslie A. , Eisenberger Mario , Dorey Frederick J. , Walsh Patrick C. , Partin Alan W. 
Published: April 2007

Purpose Among patients with biochemical recurrence after radical prostatectomy, we found previously that postoperative prostate-specific antigen doubling time (PSADT) was associated with risk of prostate cancer death. However, given the small number of patients in the highest risk PSADT subgroup, it is unclear which PSADT subgroups contribute the greatest to prostate cancer–specific death and how this influences all-cause mortality. Patients and Methods This study was a retrospective analysis of 379 patients treated with radical prostatectomy between 1982 and 2000 who had a biochemical recurrence and PSADT data available. Mean and median follow-up after surgery was 11.4 (standard deviation, 5.4) and 11.0 years, respectively (range, 1.6 to 23.0 years). Results Shorter PSADT was significantly associated with prostate cancer–specific and all-cause mortality (P < .001). Although patients with a PSADT less than 3 months were at the greatest risk of death, because of the limited number of patients in this group, they accounted for only 13% of prostate cancer deaths at 15 years after biochemical recurrence, whereas patients with an intermediate PSADT (3.0 to 8.9 months) accounted for 58% of all prostate cancer deaths. Among patients with a PSADT less than 15 months, prostate cancer accounted for 90% of all deaths. Only patients in the slowest PSADT subgroup (≥ 15 months) had a greater risk of competing-causes mortality compared with that from prostate cancer. Conclusion Among a select cohort of young, healthy patients with PSA recurrence after radical prostatectomy and a PSADT less than 15 months, prostate cancer accounted for an estimated 90% of all deaths by 15 years after recurrence. The majority of prostate cancer deaths occurred among patients with an intermediate PSADT (3.0 to 8.9 months).
Phase I Trial of Imexon in Patients With Advanced Malignancy
Authors: Dragovich Tomislav , Gordon Michael , Mendelson David , Wong Lucas , Modiano Manuel , Chow H.-H. Sherry , Samulitis Betty , O'Day Steven , Grenier Kathryn , Hersh Evan , Dorr Robert 
Published: April 2007

Purpose Imexon, a pro-oxidant small molecule, has antitumor activity in preclinical models. The drug induces apoptosis through accumulation of reactive oxygen species. The purpose of this trial was to define the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and pharmacodynamics of imexon in patients with advanced cancers. Patients and Methods Forty-nine patients with metastatic cancer received intravenous imexon over 30 to 45 minutes for 5 consecutive days (one course) every other week (days 1 through 5 and 15 through 19) monthly. Doses were initially escalated using an accelerated trial design and then a modified Fibonacci method. Plasma imexon levels and six different thiols were measured by high-performance liquid chromatography assays. Results There were 13 dose levels evaluated, from 20 mg/m2/d to 1,000 mg/m2/d. The MTD recommended for phase II studies was 875 mg/m2/d for 5 days every 2 weeks (n = 9 patients). The two dose-limiting toxicities at 1,000 mg/m2/d involved grade 3 abdominal pain and fatigue and grade 4 neutropenia, which occurred in one patient each. Other common toxicities included nausea and vomiting (58%) and constipation (63%); both were managed well with prophylactic medications. One partial response was obtained in a heavily pretreated patient with non-Hodgkin's lymphoma. Pharmacokinetic studies showed dose-independent clearance, with a 95-minute mean half-life. Plasma thiol studies showed a dose- and area under the curve–dependent decrease in cystine levels 8 hours after dosing at ≥ 750 mg/m2/d. Conclusion The phase II recommended dose of imexon is 875 mg/m2/d for 5 days every other week. A decrease in plasma thiols did correlate with imexon exposure.