bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic value of depressive symptoms, fear-avoidance, and self-efficacy for duration of lost-time benefits in workers with musculoskeletal disorders
Authors: Lötters F , Franche R-L , Hogg-Johnson S , Burdorf A , Pole J D 
Published: April 2006

Background:The psychological factors of depressive symptoms, fear-avoidance, and self-efficacy are deemed to be important in the work disability process. However, the prognostic value of these factors for time on benefit is not well understood.Aims:To analyse the prognostic value of psychological factors for the number of days on total compensation benefit over a 12 month period.Methods:In a longitudinal study of 187 workers receiving total compensation benefits due to musculoskeletal disorders, the prognostic value of psychological factors measured 4–5 weeks post-injury for duration on total compensation benefit over 12 months was analysed. Cox proportional hazard regression analyses were conducted. Special emphasis was given to variable selection and to the analysis of confounding effects of potential prognostic variables.Results:The final model indicated that increased depressive symptoms and poorer physical health significantly increase the number of days on total benefit. Confounders included in the final model were pain and fear of income loss. In the final model the impact of fear-avoidance ceased to be significant when work related variables were included in the fully adjusted model. This illustrates that interrelationships between variables must be taken into account when building multivariate prognostic models. The addition of work related variables to the model did not result in any major changes in the adjusted model, which suggests that when measured 4–5 weeks post-injury, psychological and physical health factors are strong predictors of time on benefits, while work conditions are less important.Conclusion:Results suggest that the presence of depressive symptoms and poor physical health in workers on benefit due to musculoskeletal disorders increases the number of days on total compensation benefits significantly, when controlling for confounding variables.
C/EBPα directs monocytic commitment of primary myeloid progenitors
Authors: Wang Dehua , D'Costa Jenice , Civin Curt I. , Friedman Alan D. 
Published: April 2006

AbstractC/EBPα is required for generation of granulocyte-monocyte progenitors, but the subsequent role of C/EBPα in myeloid lineage commitment remains uncertain. We transduced murine marrow cells with C/EBPα-estradiol receptor (ER) or empty vector and subjected these to lineage depletion just prior to culture in estradiol with myeloid cytokines. This protocol limits biases due to lineage-specific effects on developmental kinetics, proliferation, and apoptosis. Also, lowering the dose of estradiol reduced activated C/EBPα-ER to near the physiologic range. C/EBPα-ER increased Mac1+/Gr1–/MPO–/low monocytes 1.9-fold while reducing Mac1+/Gr1+/MPOhi granulocytes 2.5-fold at 48 hours, even in 0.01 μM estradiol. This pattern was confirmed morphologically and by quantitative polymerase chain reaction (PCR) assay of lineage markers. To directly assess effects on immature progenitors, transduced cells were cultured for 1 day with and then in methylcellulose without estradiol. A 2-fold increase in monocytic compared with granulocytic colonies was observed in IL-3/IL-6/SCF or GM-CSF, but not G-CSF, even in 0.01 μM estradiol. C/EBPα-ER induced PU.1 mRNA, and PU.1-ER stimulated monocytic development, suggesting that transcriptional induction of PU.1 by C/EBPα contributes to monopoiesis. A C/EBPα variant incapable of zippering with c-Jun did not induce monopoiesis, and a variant unable to bind NF-κB p50 stimulated granulopoiesis, suggesting their cooperation with C/EBPα during monocytic commitment.
PDA: Pooled DNA analyzer
Authors: Yang Hsin-Chou , Pan Chia-Ching , Lin Chin-Yu , Fann Cathy SJ 
Published: April 2006

Abstract

Background
Association mapping using abundant single nucleotide polymorphisms is a powerful tool for identifying disease susceptibility genes for complex traits and exploring possible genetic diversity. Genotyping large numbers of SNPs individually is performed routinely but is cost prohibitive for large-scale genetic studies. DNA pooling is a reliable and cost-saving alternative genotyping method. However, no software has been developed for complete pooled-DNA analyses, including data standardization, allele frequency estimation, and single/multipoint DNA pooling association tests. This motivated the development of the software, 'PDA' (Pooled DNA Analyzer), to analyze pooled DNA data.

Results
We develop the software, PDA, for the analysis of pooled-DNA data. PDA is originally implemented with the MATLAB® language, but it can also be executed on a Windows system without installing the MATLAB®. PDA provides estimates of the coefficient of preferential amplification and allele frequency. PDA considers an extended single-point association test, which can compare allele frequencies between two DNA pools constructed under different experimental conditions. Moreover, PDA also provides novel chromosome-wide multipoint association tests based on p-value combinations and a sliding-window concept. This new multipoint testing procedure overcomes a computational bottleneck of conventional haplotype-oriented multipoint methods in DNA pooling analyses and can handle data sets having a large pool size and/or large numbers of polymorphic markers. All of the PDA functions are illustrated in the four bona fide examples.

Conclusion
PDA is simple to operate and does not require that users have a strong statistical background. The software is available at http://www.ibms.sinica.edu.tw/%7Ecsjfann/first%20flow/pda.htm.
The relationship between organisational characteristics and the effects of clinical guidelines on medical performance in hospitals, a meta-analysis
Authors: Dijkstra Rob , Wensing Michel , Thomas Ruth , Akkermans Reinier , Braspenning Joze , Grimshaw Jeremy , Grol Richard 
Published: April 2006

AbstractObjectiveTo measure the effectiveness of strategies to implement clinical guidelines andthe influence of organisational characteristics on hospital care.MethodsSystematic review and meta regression analysis including randomisedcontrolled trials, controlled clinical trials and controlled before-and-after studies.Results53 studies were identified, including 81 comparisons. The total effect of allintervention strategies appeared to be Odds ratio 2.13 (SD 1.72-2.65). Interventionstrategies (such as educational material, reminders, feedback) and other professionalinterventions that mostly comprised revisions of professional roles were found to berelatively strong components of multi faceted interventions. Outcomes of organisationaleffect modifiers were better in a learning environment in inpatient studies than inoutpatient studies. Interventions developed outside hospitals yielded better outcomes; OR4.62 (SD 2.82-7.57) versus OR 1.78 (SD 1.36-2.23).ConclusionBoth single and multifaceted interventions seemed to be effective in hospitalsettings. Evidence for the effects of organisational determinants remained limited.
Folate-targeted immunotherapy effectively treats established adjuvant and collagen-induced arthritis
Authors: Paulos Chrystal M , Varghese Bindu , Widmer William R , Breur Gert J , Vlashi Erina , Low Philip S 
Published: April 2006

AbstractActivated macrophages express a cell surface receptor for the vitamin folic acid. Because this receptor is inaccessible or not measurably expressed on other normal cells, folic acid has been recently exploited to selectively deliver attached radio-emitters to sites of activated macrophage accumulation, allowing scintigraphic imaging of inflamed joints and organs of arthritic rats. We demonstrate here that folate-linked haptens can also be targeted to activated macrophages, decorating their cell surfaces with highly immunogenic molecules. Under conditions in which the rodent has already been immunized against keyhole limpet hemocyanine-(fluorescein isothiocyanate) FITC, activated macrophages are eliminated. Administration of folate-FITC conjugates to rodents with experimental arthritis attenuates (a) systemic and peri-articular inflammation, (b) bone and cartilage degradation, and (c) arthritis-related body weight loss. Treatment with folate-hapten conjugates is comparable to methotrexate, etanercept, anakinra, and celecoxib at alleviating the symptoms of arthritis. We conclude that reduction of activated macrophages by folate-targeted immunotherapy can ameliorate the symptoms of arthritis in two rodent models of the disease.
Cyclooxygenases and prostaglandin E2 receptors in growth plate chondrocytes in vitro and in situ – prostaglandin E2dependent proliferation of growth plate chondrocytes
Authors: Brochhausen Christoph , Neuland Pia , Kirkpatrick C James , Nüsing Rolf M , Klaus Günter 
Published: April 2006

AbstractProstaglandin E2 (PGE2) plays an important role in bone development and metabolism. To interfere therapeutically in the PGE2 pathway, however, knowledge about the involved enzymes (cyclooxygenases) and receptors (PGE2 receptors) is essential. We therefore examined the production of PGE2 in cultured growth plate chondrocytes in vitro and the effects of exogenously added PGE2 on cell proliferation. Furthermore, we analysed the expression and spatial distribution of cyclooxygenase (COX)-1 and COX-2 and PGE2 receptor types EP1, EP2, EP3 and EP4 in the growth plate in situ and in vitro. PGE2 synthesis was determined by mass spectrometry, cell proliferation by DNA [3H]-thymidine incorporation, mRNA expression of cyclooxygenases and EP receptors by RT-PCR on cultured cells and in homogenized growth plates. To determine cellular expression, frozen sections of rat tibial growth plate and primary chondrocyte cultures were stained using immunohistochemistry with polyclonal antibodies directed towards COX-1, COX-2, EP1, EP2, EP3, and EP4. Cultured growth plate chondrocytes transiently secreted PGE2 into the culture medium. Although both enzymes were expressed in chondrocytes in vitro and in vivo, it appears that mainly COX-2 contributed to PGE2-dependent proliferation. Exogenously added PGE2 stimulated DNA synthesis in a dose-dependent fashion and gave a bell-shaped curve with a maximum at 10-8 M. The EP1/EP3 specific agonist sulprostone and the EP1-selective agonist ONO-D1-004 increased DNA synthesis. The effect of PGE2 was suppressed by ONO-8711. The expression of EP1, EP2, EP3, and EP4 receptors in situ and in vitro was observed; EP2 was homogenously expressed in all zones of the growth plate in situ, whereas EP1 expression was inhomogenous, with spared cells in the reserve zone. In cultured cells these four receptors were expressed in a subset of cells only. The most intense staining for the EP1 receptor was found in polygonal cells surrounded by matrix. Expression of receptor protein for EP3 and EP4 was observed also in rat growth plates. In cultured chrondrocytes, however, only weak expression of EP3 and EP4 receptor was detected. We suggest that in growth plate chondrocytes, COX-2 is responsible for PGE2 release, which stimulates cell proliferation via the EP1 receptor.
Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis
Authors: Michou Laëtitia , Croiseau Pascal , Petit-Teixeira Elisabeth , du Montcel Sophie Tezenas , Lemaire Isabelle , Pierlot Céline , Osorio José , Frigui Wafa , Lasbleiz Sandra , Quillet Patrick , Bardin Thomas , Prum Bernard , Clerget-Darpoux Françoise , Cornélis François ,   the European Consortium on Rheumatoid Arthritis Families
Published: April 2006

AbstractRecently, we proposed a classification of HLA-DRB1 alleles that reshapes the shared epitope hypothesis in rheumatoid arthritis (RA); according to this model, RA is associated with the RAA shared epitope sequence (72–74 positions) and the association is modulated by the amino acids at positions 70 and 71, resulting in six genotypes with different RA risks. This was the first model to take into account the association between the HLA-DRB1 gene and RA, and linkage data for that gene. In the present study we tested this classification for validity in an independent sample. A new sample of the same size and population (100 RA French Caucasian families) was genotyped for the HLA-DRB1 gene. The alleles were grouped as proposed in the new classification: S1 alleles for the sequences A-RAA or E-RAA; S2 for Q or D-K-RAA; S3D for D-R-RAA; S3P for Q or R-R-RAA; and X alleles for no RAA sequence. Transmission of the alleles was investigated. Genotype odds ratio (OR) calculations were performed through conditional logistic regression, and we tested the homogeneity of these ORs with those of the 100 first trio families (one case and both parents) previously reported. As previously observed, the S2 and S3P alleles were significantly over-transmitted and the S1, S3D and X alleles were under-transmitted. The latter were grouped as L alleles, resulting in the same three-allele classification. The risk hierarchy of the six derived genotypes was the same: (by decreasing OR and with L/L being the reference genotype) S2/S3P, S2/S2, S3P/S3P, S2/L and S3P/L. The homogeneity test between the ORs of the initial and the replication samples revealed no significant differences. The new classification was therefore considered validated, and both samples were pooled to provide improved estimates of RA risk genotypes from the highest (S2/S3P [OR 22.2, 95% confidence interval 9.9–49.7]) to the lowest (S3P/L [OR 4.4, 95% confidence interval 2.3–8.4]).
Activation of transforming growth factor-β1and early atherosclerosis in systemic lupus erythematosus
Authors: Jackson Michelle , Ahmad Yasmeen , Bruce Ian N , Coupes Beatrice , Brenchley Paul EC 
Published: April 2006

AbstractThe efficiency of activating latent transforming growth factor (TGF)-β1 in systemic lupus erythematosus (SLE) may control the balance between inflammation and fibrosis, modulating the disease phenotype. To test this hypothesis we studied the ability to activate TGF-β1 in SLE patients and control individuals within the context of inflammatory disease activity, cumulative organ damage and early atherosclerosis. An Activation Index (AI) for TGF-β1 was determined for 32 patients with SLE and 33 age-matched and sex-matched control individuals by quantifying the increase in active TGF-β1 under controlled standard conditions. Apoptosis in peripheral blood mononuclear cells was determined by fluorescence-activated cell sorting. Carotid artery intima-media thickness was measured using standard Doppler ultrasound. These measures were compared between patients and control individuals. In an analysis conducted in patients, we assessed the associations of these measures with SLE phenotype, including early atherosclerosis. Both intima-media thickness and TGF-β1 AI for SLE patients were within the normal range. There was a significant inverse association between TGF-β1 AI and levels of apoptosis in peripheral blood mononuclear cells after 24 hours in culture for both SLE patients and control individuals. Only in SLE patients was there a significant negative correlation between TGF-β1 AI and low-density lipoprotein cholesterol (r = -0.404; P = 0.022) and between TGF-β1 AI and carotid artery intima-media thickness (r = -0.587; P = 0.0004). A low AI was associated with irreversible damage (SLICC [Systemic Lupus International Collaborating Clinics] Damage Index ≥1) and was inversely correlated with disease duration. Intima-media thickness was significantly linked to total cholesterol (r = 0.371; P = 0.037). To conclude, in SLE low normal TGF-β1 activation was linked with increased lymphocyte apoptosis, irreversible organ damage, disease duration, calculated low-density lipoprotein levels and increased carotid IMT, and may contribute to the development of early atherosclerosis.
Solute removal during continuous renal replacement therapy in critically ill patients: convection versus diffusion
Authors: Ricci Zaccaria , Ronco Claudio , Bachetoni Alessandra , D'amico Giuseppe , Rossi Stefano , Alessandri Elisa , Rocco Monica , Pietropaoli Paolo 
Published: April 2006

Abstract
Introduction
The best modality, for continuous renal replacement therapy (CRRT) is currently uncertain and it is poorly understood how transport of different solutes, whether convective or diffusive, changes over time.

Methods
We conducted a prospective cross over study in a cohort of critically ill patients, comparing small (urea and creatinine) and middle (β2 microglobulin) molecular weight solute clearance, filter lifespan and membrane performance over a period of 72 hours, during 15 continuous veno-venous dialysis (CVVHD) and 15 continuous veno-venous hemofiltration (CVVH)sessions. Both modalities were administered based on a prescription of 35 ml/kg/h and using polyacrylonitrile filters.

Results
Median filter lifespan was significantly longer during CVVHD (37 hours, interquartile range (IQR) 19.5 to 72.5) than CVVH (19 hours, IQR 12.5 to 28) (p = 0.03). Median urea time weighted average (TWA) clearances were not significantly different during CVVH (31.6 ml/minute, IQR 23.2 to 38.9) and CVVHD (35.7 ml/minute, IQR 30.1 to 41.5) (p = 0.213). Similar results were found for creatinine: 38.1 ml/minute, IQR 28.5 to 39, and 35.6 ml/minute, IQR 26 to 43 (p = 0.917), respectively. Median β2m TWA clearance was higher during convective (16.3 ml/minute, IQR 10.9 to 23) than diffusive (6.27 ml/minute, IQR 1.6 to 14.9) therapy; nonetheless this difference did not reach statistical significance (p = 0.055). Median TWA adsorptive clearance of β2m appeared to have scarce impact on overall solute removal (0.012 ml/minute, IQR -0.09 to 0.1, during hemofiltration versus -0.016 ml/minute, IQR -0.08 to 0.1 during dialysis; p = 0.79). Analysis of clearance modification over time did not show significant modifications of urea, creatinine and β2m clearance in the first 48 hours during both treatments. In the CVVHD group, the only significant difference was found for β2m between 72 hours and baseline clearance.

Conclusion
Polyacrylonitrile filters during continuous hemofiltration and continuous hemodialysis delivered at 35 ml/kg/h are comparable in little and middle size solute removal. CVVHD appears to warrant longer CRRT sessions. The capacity of both modalities for removing such molecules is maintained up to 48 hours.
Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?
Authors: Santos Wilson JQ , Zanetta Dirce MT , Pires Antonio C , Lobo Suzana MA , Lima Emerson Q , Burdmann Emmanuel A 
Published: April 2006

Abstract
Introduction
Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group.

Method
We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000.

Results
Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]).

Conclusion
The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The three forms of ATN exhibited different clinical characteristics. Mortality was strikingly higher in ischaemic and mixed ATN than in nephrotoxic ATN. Although the type of ATN was not an independent predictor of death, the independent factors related to mortality were different for ischaemic, mixed and all patients combined. These data indicate that the three types of ATN represent different patient populations, which should be taken into consideration in future studies.
Relationship between stress and relapse in multiple sclerosis: part I. Important features
Authors: Brown R F , Tennant C C , Sharrock M , Hodgkinson S , Dunn S M , Pollard J D 
Published: April 2006

Objective The aim of this two-year prospective study was to examine the relationship between multiple aspects of life-event stress and relapse in multiple sclerosis (MS) patients. Background Few studies have defined the critical features of this life-event stress; for example, stressor duration, frequency, severity, disease-dependency, valency, or stressor constructs, such as the propensity to cause emotional distress/threat or the frustration of life goals. Methods 101 consecutive participants with MS were recruited from two MS clinics in Sydney, Australia. Stressful life events were assessed at study-entry and at three-monthly intervals for two years. Patient-reported relapses were recorded and corroborated by neurologists or evaluated against accepted relapse criteria. Results Acute events, but not chronic difficulties (CDs), predicted relapse occurrence: acute stressor frequency counts predicted greater relapse risk, along with low disability score (EDSS) and being male. We also confirmed the bi-directional stress-illness hypothesis: stressors predicted relapse, and relapse separately predicted stressors. Conclusions Life-event stress impacts to a small degree on MS relapse. The number and not the severity of acute stressors are most important; chronic stressors do not predict later relapse. Males and those with early stage disease are also at greater risk of relapse. MS patients should be encouraged to reduce acute stressors during times of high stress, and feel reassured that disease-related chronic stressors do not increase their relapse risk.