bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy
Authors: Owen Carolyn J. , Toze Cynthia L. , Koochin Anna , Forrest Donna L. , Smith Clayton A. , Stevens Jane M. , Jackson Shannon C. , Poon Man-Chiu , Sinclair Gary D. , Leber Brian , Johnson Peter R. E. , Macheta Anthony , Yin John A. L. , Barnett Michael J. , Lister T. Andrew , Fitzgibbon Jude 
Published: August 2008

Abstract
Familial platelet disorder with propensity to myeloid malignancy (FPD/AML) is an autosomal dominant syndrome characterized by platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML). The disorder, caused by inherited mutations in RUNX1, is uncommon with only 14 pedigrees reported. We screened 10 families with a history of more than one first degree relative with MDS/AML for inherited mutations in RUNX1. Germ- line RUNX1 mutations were identified in 5 pedigrees with a 3:2 predominance of N-terminal mutations. Several affected members had normal platelet counts or platelet function, features not previously reported in FPD/AML. The median incidence of MDS/AML among carriers of RUNX1 mutation was 35%. Individual treatments varied but included hematopoietic stem cell transplantation from siblings before recognition of the inherited leukemogenic mutation. Transplantation was associated with a high incidence of complications including early relapse, failure of engraftment, and posttransplantation lymphoproliferative disorder. Given the small size of modern families and the clinical heterogeneity of this syndrome, the diagnosis of FPD/AML could be easily overlooked and may be more prevalent than previously recognized. Therefore, it would appear prudent to screen young patients with MDS/AML for RUNX1 mutation, before consideration of sibling hematopoietic stem cell transplantation.
Nuclear survivin in pN2 nonsmall cell lung cancer: prognostic and clinical implications
Authors: Mohamed S. , Yasufuku K. , Nakajima T. , Hiroshima K. , Chiyo M. , Yoshida S. , Suzuki M. , Sekine Y. , Shibuya K. , Agamy G. , El-Shahhat H. , Fujisawa T. , Yoshino I. 
Published: August 2008

Patients with N2 nonsmall cell lung cancer (N2-NSCLC) represent heterogeneous groups. Survivin is a member of the inhibitor of apoptosis family. If N2-NSCLC patients could be stratified, based on survivin expression and/or its relation to cell cycle proteins, into homogeneous subgroups, certain therapies could be selected for those patients.Survivin expression in 78 surgically resected primary pathological N2-NSCLC tumours was evaluated using immunohistochemistry. Relationships of survivin expression to overall survival, clinical features and expression of six cell cycle-related proteins (pRb, cyclin D1, p16INK4A, p53, p21Waf1and Ki-67) were analysed.Nuclear survivin and the number of mediastinal lymph node (LN) stations were independent prognostic factors. The patient group with combined negative survivin/single mediastinal LN station were the most favourable prognostic group, and was related to the clinical nodal factor. Indeed, patients with negative survivin/low Ki-67 labelling indices had the best survival, especially in nonsquamous histopathology.The current authors conclude that nuclear survivin is strongly related to lymph node metastasis and proliferative potentials in pathological N2 nonsmall cell lung cancer patients. Pre-operative N2 nonsmall cell lung cancer patients with combined negative nuclear survivin and a single mediastinal lymph node station, or low proliferative indices, particularly in clinical N0-1 disease and nonsquamous histopathology, respectively, are expected to have a favourable post-operative prognosis and may be candidates for primary resection.
Pseudomonas aeruginosatransmission is infrequent in New Zealand cystic fibrosis clinics
Authors: Schmid J. , Ling L. J. , Leung J. L. S. , Zhang N. , Kolbe J. , Wesley A. W. , Mills G. D. , Brown P. J. , Jones D. T. , Laing R. T. R. , Pattemore P. K. , Taylor D. R. , Grimwood K. 
Published: August 2008

Pseudomonas aeruginosais an important pathogen in cystic fibrosis (CF). Although most patients harbour uniqueP. aeruginosaisolates, some clinics report patients sharing common strains. The overall importance of person-to-person transmission inP. aeruginosaacquisition and whether routine patient segregation is necessary remains uncertain. The present authors therefore investigated the extent ofP. aeruginosatransmission in New Zealand CF clinics.New Zealand’s seven major CF centres were assessed, combining epidemiological data with computer-assistedSalI DNA fingerprinting of 496 isolates from 102 patients.One cluster of related isolates was significantly more prevalent in the largest clinic than expected by chance. The seven patients with isolates belonging to this cluster had more contact with each other than the remaining patients attending this centre. No other convincing evidence of transmission was found in any of the other smaller clinics. ThreeP. aeruginosastrains believed to be transmissible between patients in Australian and British CF clinics are present in New Zealand, but there was no definite evidence they had spread.Pseudomonas aeruginosatransmission is currently infrequent in New Zealand cystic fibrosis clinics. This situation could change rapidly and ongoing surveillance is required. The current results confirm that computer-assistedSalI DNA fingerprinting is ideally suited for such surveillance.
Transcriptome analysis reveals response regulator SO2426-mediated gene expression in Shewanella oneidensis MR-1 under chromate challenge
Authors: Chourey Karuna , Wei Wei , Wan Xiu-Feng , Thompson Dorothea K 
Published: August 2008

Abstract

Background

Shewanella oneidensis MR-1 exhibits diverse metal ion-reducing capabilities and thus is of potential utility as a bioremediation agent. Knowledge of the molecular components and regulatory mechanisms dictating cellular responses to heavy metal stress, however, remains incomplete. In a previous work, the S. oneidensis so2426 gene, annotated as a DNA-binding response regulator, was demonstrated to be specifically responsive at both the transcript and protein levels to acute chromate [Cr(VI)] challenge. To delineate the cellular function of SO2426 and its contribution to metal stress response, we integrated genetic and physiological approaches with a genome-wide screen for target gene candidates comprising the SO2426 regulon.

Results
Inactivation of so2426 by an in-frame deletion resulted in enhanced chromate sensitivity and a reduced capacity to remove extracellular Cr(VI) relative to the parental strain. Time-resolved microarray analysis was used to compare transcriptomic profiles of wild-type and SO2426-deficient mutant S. oneidensis under conditions of chromate exposure. In total, 841 genes (18% of the arrayed genome) were up- or downregulated at least twofold in the Δso2426 mutant for at least one of six time-point conditions. Hierarchical cluster analysis of temporal transcriptional profiles identified a distinct cluster (n = 46) comprised of co-ordinately regulated genes exhibiting significant downregulated expression (p < 0.05) over time. Thirteen of these genes encoded proteins associated with transport and binding functions, particularly those involved in Fe transport and homeostasis (e.g., siderophore biosynthetic enzymes, TonB-dependent receptors, and the iron-storage protein ferritin). A conserved hypothetical operon (so1188-so1189-so1190), previously identified as a potential target of Fur-mediated repression, as well as a putative bicyclomycin resistance gene (so2280) and cation efflux family protein gene (so2045) also were repressed in the so2426 deletion mutant. Furthermore, the temporal expression profiles of four regulatory genes including a cpxR homolog were perturbed in the chromate-challenged mutant.

Conclusion
Our findings suggest a previously unrecognized functional role for the response regulator SO2426 in the activation of genes required for siderophore-mediated Fe acquisition, Fe storage, and other cation transport mechanisms. SO2426 regulatory function is involved at a fundamental molecular level in the linkage between Fe homeostasis and the cellular response to chromate-induced stress in S. oneidensis.
Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus
Authors: Genç Yeliz , Özkanca Reşit , Bekdemir Yunus 
Published: August 2008

Abstract

Background

Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance.

Methods
Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested.

Results
The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl)-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl)-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl)-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably.

Conclusion
This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.
Development of a health care utilisation data-based index for rheumatoid arthritis severity: a preliminary study
Authors: Ting Gladys , Schneeweiss Sebastian , Scranton Richard , Katz Jeffrey N , Weinblatt Michael E , Young Melissa , Avorn Jerry , Solomon Daniel H 
Published: August 2008

Abstract
Introduction
Health care utilisation ('claims') databases contain information about millions of patients and are an important source of information for a variety of study types. However, they typically do not contain information about disease severity. The goal of the present study was to develop a health care claims index for rheumatoid arthritis (RA) severity using a previously developed medical records-based index for RA severity (RA medical records-based index of severity [RARBIS]).

Methods
The study population consisted of 120 patients from the Veteran's Administration (VA) Health System. We previously demonstrated the construct validity of the RARBIS and established its convergent validity with the Disease Activity Score (DAS28). Potential claims-based indicators were entered into a linear regression model as independent variables and the RARBIS as the dependent variable. The claims-based index for RA severity (CIRAS) was created using the coefficients from models with the highest coefficient of determination (R2) values selected by automated modelling procedures. To compare our claims-based index with our medical records-based index, we examined the correlation between the CIRAS and the RARBIS using Spearman non-parametric tests.

Results
The forward selection models yielded the highest model R2 for both the RARBIS with medications (R2 = 0.31) and the RARBIS without medications (R2 = 0.26). Components of the CIRAS included tests for inflammatory markers, number of chemistry panels and platelet counts ordered, rheumatoid factor, the number of rehabilitation and rheumatology visits, and Felty's syndrome diagnosis. The CIRAS demonstrated moderate correlations with the RARBIS with medication and the RARBIS without medication sub-scales.

Conclusion
We developed the CIRAS that showed moderate correlations with a previously validated records-based index of severity. The CIRAS may serve as a potentially important tool in adjusting for RA severity in pharmacoepidemiology studies of RA treatment and complications using health care utilisation data.
Disruption of the thrombospondin-2 gene alters the lamellar morphology but does not permit vascularization of the adult mouse lumbar disc
Authors: Gruber Helen E , Bornstein Paul , Sage E Helene , Ingram Jane A , Zinchenko Natalia , Norton H James , Hanley Edward N 
Published: August 2008

Abstract
Introduction
The biological basis for the avascular state of the intervertebral disc is not well understood. Previous work has suggested that the presence of thrombospondin-1 (TSP-1), a matricellular protein, in the outer annulus reflects a role for this protein in conferring an avascular status to the disc. In the present study we have examined thrombospondin-2 (TSP-2), a matricellular protein with recognized anti-angiogenic activity in vivo and in vitro.

Methods
We examined both the location and expression of TSP-2 in the human disc, and its location in the disc and bordering soft tissues of 5-month-old normal wild-type (WT) mice and of mice with a targeted disruption of the TSP-2 gene. Immunohistochemistry and quantitative histology were utilized in this study.

Results
TSP-2 was found to be present in some, but not all, annulus cells of the human annulus and the mouse annulus. Although there was no difference in the number of disc cells in the annulus of TSP-2-null mice compared with that of WT animals, polarized light microscopy revealed a more irregular lamellar collagen structure in null mouse discs compared with WT mouse discs. Additionally, vascular beds at the margins of discs of TSP-2-null mice were substantially more irregular than those of WT animals. Counts of platelet endothelial cell adhesion molecule-1-positive blood vessels in the tissue margin bordering the ventral annulus showed a significantly larger vascular bed in the tissue bordering the disc of TSP-2-null mice compared with that of WT mice (P = 0.0002). There was, however, no vascular ingrowth into discs of the TSP-2-null mice.

Conclusion
These data confirm a role for TSP-2 in the morphology of the disc and suggest the presence of other inhibitors of angiogenesis in the disc. We have shown that although an increase in vasculature was present in the TSP-2-null tissue in the margin of the disc, vascular ingrowth into the body of the disc did not occur. Our results point to the need for future research to understand the transition from the well-vascularized status of the fetal and young discs to the avascular state of the adult human disc or the small mammalian disc.
Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells
Authors: Radestock Yvonne , Hoang-Vu Cuong , Hombach-Klonisch Sabine 
Published: August 2008

Abstract
Introduction
Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast cancer cells are not fully understood. The aim of this study was to investigate short-term and long-term effects of relaxin on cancer cell motility and S100A4 expression and to determine the long-term effects of relaxin on in vivo tumour growth in an oestrogen-independent context.

Method
We have established stable transfectants of highly invasive oestrogen-receptor alpha-negative MDA-MB-231 human breast cancer cells with constitutive expression of bioactive H2-relaxin (MDA/RLN2). RLN2 secretion was determined by ELISA. Relaxin receptor RXFP1 (Relaxin-family-peptide) was detected by reverse transcription (RT) PCR and its activation was assessed by induction of cyclic adenosine monophosphate (cAMP). Stable MDA/RLN2 clones and RLN2 treated MDA-MB-231 cells were subjected to motility and in vitro-invasion assays. Proliferation was assessed in bromodeoxyuridine (BrdU) and MTT assays. S100A4 expression was determined by RT-PCR and Western blot. Specific small interfering RNA was employed to down-regulate relaxin receptor and S100A4. MDA/EGFP vector control and two MDA/RLN2 clones were injected subcutaneously in nude mice to determine tumour growth and cancer cell invasiveness in vivo. Xenograft tumour tissues were assessed by histology and immunohistochemistry and frozen tissues were used for the detection of S100A4 and RLN2.

Results
Short-term exposure to relaxin for 24 hours increased cell motility in a relaxin receptor-dependent manner. This increase in cell motility was mediated by S100A4. Long-term exposure to relaxin secreted from stable transfectants reduced cell motility and in vitro invasiveness. Relaxin decreased cell proliferation and down-regulated cellular S100A4 levels in MDA-MB-231 and T47D breast cancer cells. Stable MDA/RLN2 transfectants produced smaller xenograft tumours containing reduced S100A4 protein levels in vivo.

Conclusion
Our results indicate that long-term exposure to relaxin confers growth inhibitory and anti-invasive properties in oestrogen-independent tumours in vivo, which may in part be mediated through a down-regulation of S100A4.
Decision‐making about pregnancy for women with cystic fibrosis
Authors: Simcox Angela M. , Hewison Jenny , Duff Alistair J. A. , Morton Alison M. , Conway Steven P. 
Published: August 2008

ObjectivesThis study aims to generate experiential data about the decision‐making process encountered by 12 women with cystic fibrosis (CF) considering pregnancy.DesignThis study uses a qualitative grounded theory methodology to analyse the data and develop a conceptual hierarchical model of salient issues.MethodsTwelve women completed a semi‐structured interview accompanied by quantitative self‐report measures of quality of life and psychological well‐being, and indicators of health and treatment status were used.ResultsDescriptive data demonstrated that the sample did not differ significantly from other published samples. Four core categories emerged: (1) impact of the decision; (2) preparation for making and living with the decision; (3) owning the decision; and (4) personal dilemmas. Each comprised a number of overlapping conceptual and subcategories. Influencing factors included the impact of pregnancy on participants' health, and upon their ability to care for the child, the pregnancy experiences of other women with CF, the moral implications of having a child and the support and beliefs of family members.DiscussionThe findings extend the current knowledge in this area. We recommend development of guidelines for supporting and advising chronically ill young women about the psychosocial and emotional issues.
Multidisciplinary allocation of chronic pain treatment: Effects and cognitive‐behavioural predictors of outcome
Authors: Samwel Han J. A. , Kraaimaat Floris W. , Crul Ben J. P. , van Dongen Robert D. , Evers Andrea W. M. 
Published: August 2008

Objectives. Multidisciplinary treatment approaches have been found to be effective for chronic pain patients although there are large individual differences in outcomes. To increase overall treatment effects, tools are needed to identify patients most likely to benefit from tailored, comprehensive modular treatment schemes.Design. The present study evaluates the effects of a multidisciplinary pain treatment allocation protocol in chronic pain patients and seeks to identify cognitive‐behavioural predictors of outcome. Pain intensity, functional disability, depression, and use of medication in an intervention group of 110 chronic pain patients were compared to the outcomes of a 110 strong control group.Results. Paired pre‐ and post‐treatmentttests showed that all primary outcomes had significantly decreased in the intervention group with ANCOVAs revealing a main group effect for post‐treatment pain intensity levels and functional disability. Pairedttests demonstrated both variables to have significantly reduced after treatment relative to the levels reported by the control group. Predictor analyses further showed higher levels of acceptance to significantly predict larger reductions in pain intensity in the intervention but not in the control group.Conclusion. The tested multidisciplinary allocation scheme for out‐patient treatment of chronic pain complaints was effective in reducing pain intensity and functional disability. Findings also showed that especially those patients that are able to accept their condition are likely to profit most from the treatment in terms of pain reduction.
Finding a pathway: Information and uncertainty along the prostate cancer patient journey
Authors: Nanton V. , Docherty A. , Meystre C. , Dale J. 
Published: August 2008

Objectives. To investigate the role of information in mediating the potential negative effects of uncertainty in prostate cancer in relation to the individual patient journey, conceptualized as the individual's response to his disease over time.Design. A qualitative methodology was adopted to investigate men's constructions of their experience of information and its changing role in the management of uncertainty along the pathway of care. A cross‐sectional design allowed comparison of the responses of men at similar stages and along different time points in the cancer pathway. Data collection was undertaken via focus group discussions and individual interviews.Method. Men from 4 weeks post‐diagnosis to palliative care were recruited from hospital out‐patient clinic registers and a local support group. Seven focus groups and 22 semi‐structured interviews were held involving a total of 22 participants. Transcripts were analysed through a process of theme comparison.Results. Findings suggest that uncertainty is both multifaceted and changing. Its impact is affected by a range of personal, disease related, and social factors. For some men it may bring about positive readjustment rather than a negative response. Effective communication of information by health professionals provides reassurance, knowledge, and understanding the balance of which varies over time and between individuals.Conclusion. Health professionals may contribute to the reduction of the negative effects of uncertainty through communication of information regarding process of care as well as medical issues. Strategies tailored to individual differences in information requirements and to changing needs may facilitate positive adjustment.