bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determining the Minimally Important Difference in the Clinical Disease Activity Index for Improvement and Worsening in Early Rheumatoid Arthritis Patients
Authors: Curtis J. R. , Yang S. , Chen L. , Pope J. E. , Keystone E. C. , Haraoui B. , Boire G. , Thorne J. C. , Tin D. , Hitchon C. A. , Bingham C. O. , Bykerk V. P. 
Published: May 2015

ObjectiveSimplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well‐defined in real‐world clinic settings, especially for early RA patients with low/moderate disease activity.MethodsData from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self‐reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self‐reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity.ResultsA total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10–22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units.ConclusionThese minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.
Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry
Authors: Foeldvari Ivan , Becker Ingrid , Horneff Gerd 
Published: May 2015

ObjectiveUveitis is a major extraarticular quality of life–restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).MethodsPatients’ characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated.ResultsUveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58–2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient‐years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient‐years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient‐years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3–3.8) while taking etanercept and 1.8 years (IQR 1.8–2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3–10.0) in the etanercept cohort and 4.8 years (IQR 1.0–5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis.ConclusionPatients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept.
Relationship Between Medial Meniscal Extrusion and Cartilage Loss in Specific Femorotibial Subregions: Data From the Osteoarthritis Initiative
Authors: Bloecker K. , Wirth W. , Guermazi A. , Hunter D. J. , Resch H. , Hochreiter J. , Eckstein F. 
Published: May 2015

ObjectiveMedial meniscal extrusion is known to be related to structural progression of knee osteoarthritis. However, it is unclear whether medial meniscal extrusion is more strongly associated with cartilage loss in certain medial femorotibial subregions than in others.MethodsSegmentation of the medial tibial and femoral cartilage (baseline; 1‐year followup) and the medial meniscus (baseline) was performed in 60 participants with frequent knee pain (mean ± SD ages 61.3 ± 9.2 years, body mass index 31.3 ± 3.9 kg/m2) and with unilateral medial radiographic joint space narrowing (JSN) grades 1–3, using double‐echo steady‐state magnetic resonance images. Medial meniscal extrusion distance and extrusion area (percentage) between the external meniscal and tibial margin at baseline, and longitudinal medial cartilage loss in 8 anatomic subregions were determined.ResultsA significant association (Pearson's correlation coefficient) was seen between medial meniscal extrusion area in JSN knees and cartilage loss over 1 year throughout the entire medial femorotibial compartment. The strongest correlation was with cartilage loss in the external medial tibia (r =−0.34, P < 0.01 in JSN; r =−0.30, P = 0.02 in knees without JSN).ConclusionMedial meniscal extrusion was associated with subsequent medial cartilage loss. The external medial tibial cartilage may be particularly vulnerable to thinning once the meniscus extrudes and its surface is exposed to direct, nonphysiological, cartilage‐to‐cartilage contact.
Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials
Authors: Graudal Niels , Hubeck‐Graudal Thorbjørn , Faurschou Mikkel , Baslund Bo , Jürgens Gesche 
Published: May 2015

ObjectiveThe costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease‐modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA.MethodsEight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta‐analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel‐Haenszel method (dichotomous data) using a random‐effects model.ResultsThe primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (−0.09 units [−0.61, 0.44]) of treatment or during the first 2 years (0.66 units [−0.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids.ConclusionThe difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.
Symptoms of Depression and Risk of New Episodes of Low Back Pain: A Systematic Review and Meta‐Analysis
Authors: Pinheiro Marina B. , Ferreira Manuela L. , Refshauge Kathryn , Ordoñana Juan R. , Machado Gustavo C. , Prado Lucas R. , Maher Christopher G. , Ferreira Paulo H. 
Published: May 2015

ObjectiveTo investigate the contribution of symptoms of depression to future episodes of low back pain (LBP).MethodsA search was conducted of AMED, CINAHL, Embase, Health and Society (H&S), LILACS, MEDLINE, PsycINFO, Scopus, and Web of Science databases. We included cohort studies investigating the effect of symptoms of depression on the development of new episodes of LBP, either lifetime incidence or a recurrent episode, in a population free of LBP at baseline. We accepted the original study's definition for a new episode of LBP, and for classifying patients as LBP‐free at study entry. Two independent investigators extracted data and assessed methodological quality. Meta‐analyses with random effects were used to pool risk estimates.ResultsWe included 19 studies, with 11 incorporated in the meta‐analyses. Overall pooled results showed that symptoms of depression increased the risk of developing LBP (odds ratio [OR] 1.59, 95% confidence interval [95% CI] 1.26–2.01). The risk was similar in studies that used the diagnostic interview method (OR 1.66, 95% CI 1.14–2.42) and in studies using self‐report screening questionnaires (OR 1.68, 95% CI 1.05–2.70). No statistically significant relationship was observed when we pooled studies that employed nonspecific screening questionnaires (OR 1.17, 95% CI 0.48–2.87). Three studies provided results in incremental categories of symptoms of depression and the pooled OR for the most severe level of depression (OR 2.51, 95% CI 1.58–3.99) was higher than for the lowest level (OR 1.51, 95% CI 0.89–2.56).ConclusionIndividuals with symptoms of depression have an increased risk of developing an episode of LBP in the future, with the risk being higher in patients with more severe levels of depression.
Vitamin D Supplementation in Adolescents and Young Adults With Juvenile Systemic Lupus Erythematosus for Improvement in Disease Activity and Fatigue Scores: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Lima Glauce L. , Paupitz Juliane , Aikawa Nadia E. , Takayama Liliam , Bonfa Eloisa , Pereira Rosa M. R. 
Published: May 2015

ObjectiveVitamin D has an important immunomodulatory effect, but there are no trials that directly address the boosting of serum levels of 25‐hydroxyvitamin D (25[OH]D) in juvenile‐onset systemic lupus erythematosus (SLE). The aim of this study was to evaluate the effect of vitamin D supplementation on disease activity and fatigue in juvenile‐onset SLE.MethodsThis study was a randomized, double‐blind, placebo‐controlled, 24‐week trial. Forty juvenile‐onset SLE patients were randomized (1:1) to receive oral cholecalciferol 50,000 IU/week (juvenile‐onset SLE‐VitD) or placebo (juvenile‐onset SLE‐PL). Medications remained stable throughout the study. Serum levels of 25(OH)D were measured using radioimmunoassay. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measurement (ECLAM). Fatigue was assessed using the Kids Fatigue Severity Scale (K‐FSS).ResultsAt baseline, groups were similar regarding age, body mass index, organ involvement, glucocorticoid dose, use of immunosuppressive drugs, SLEDAI, ECLAM, K‐FSS, and levels of 25(OH)D. After 24 weeks, the mean level of 25(OH)D was higher in the juvenile‐onset SLE‐VitD group than in the juvenile‐onset SLE‐PL group (P < 0.001). At the end of the intervention, a significant improvement in SLEDAI (P = 0.010) and in ECLAM (P = 0.006) was observed in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group. Regarding fatigue evaluation, a reduction of fatigue related to social life score was found in the juvenile‐onset SLE‐VitD group compared to the juvenile‐onset SLE‐PL group (P = 0.008). Cholecalciferol was well tolerated with no serious adverse events.ConclusionThis study suggests that cholecalciferol supplementation for 24 weeks is effective in decreasing disease activity and improving fatigue in juvenile‐onset SLE patients.
L‐Rhamnulose‐1‐phosphate Aldolase from Thermotoga maritima in Organic Synthesis: One‐Pot Multistep Reactions for the Preparation of Imino‐ and Nitrocyclitols
Authors: Oroz‐Guinea Isabel , Hernández Karel , Camps Bres Flora , Guérard‐Hélaine Christine , Lemaire Marielle , Clapés Pere , García‐Junceda Eduardo 
Published: May 2015

AbstractRhamnulose‐1‐phosphate aldolase from Thermotoga maritima (Rhu1PATm) has been recently cloned and characterised. This hyperthermophilic enzyme offers intriguing possibilities for practical catalysis. This is due to its high stability under extreme reaction conditions, such as high temperature or the presence of organic co‐solvents. The Rhu1PATm potentiality in organic synthesis has been explored focusing on (i) the reaction stereocontrol, (ii) the possibility of combining it with other mesophilic enzymes in multienzyme systems and (iii) its application to the synthesis of imino‐ and nitrocyclitols. In our study, the diastereoselectivity of Rhu1PATm was similar to the one reported for Rhu1PA from Escherichia coli (Rhu1PAEc). However, we observed significant differences for some aldehyde acceptors. Indeed, the diastereoselectivity control was not complete, since mixtures of L‐threo (2R,3S; natural stereopreference) and D‐erythro (2R,3R) diastereoisomers were obtained as described for Rhu1PAEc. Rhu1PATm was able to catalyse aldol reactions using nitroaldehydes and N‐Cbz‐aminoaldehydes. Conversion of the selected nitroaldehydes was complete, leading to mixtures of L‐threo and D‐erythro diastereoisomers, in 95:5 and 75:25 ratios. When N‐Cbz‐aminoaldehydes were used, aldol reaction yields were lower and the stereoselectivity L‐threo:D‐erythro ranged between 32:68 to>95:5.magnified image
Multistep Synthesis of (S)‐3‐Hydroxyisobutyric Acid from Glucose usingPseudomonas taiwanensisVLB120 B83 T7 Catalytic Biofilms
Authors: Lang Karsten , Buehler Katja , Schmid Andreas 
Published: May 2015

AbstractThe chiral building block (S)‐3‐hydroxyisobutyric acid [(S)‐3‐HIBA] was produced either by conversion of isobutyric acid or directly from glucose utilizing cells ofPseudomonas taiwanensisVLB120 B83 T7 as catalysts. This strain carries a point mutation in the gene encoding 3‐hydroxyisobutyrate dehydrogenase (mmsB), leading to its inactivation. The maximal specific activity in resting‐cell biotransformations using isobutyric acid as substrate was 4.9±0.4 U gcdw−1. Overexpression of the 2‐ketoisovalerate pathway genesalsS, ilvC,andilvD, and the introduction ofkivdencoding 2‐ketoacid decarboxylase resulted in the efficient fermentative synthesis of (S)‐3‐HIBA directly from glucose. Up to 22 mM (2.3 g L−1) (S)‐3‐HIBA were produced at 3.7±0.3 U gcdw−1in repeated batch experiments without observable product degradation. Utilizing a biofilm reactor it was possible to continuously produce up to 6 mM (0.63 g L−1) of (S)‐3‐hydroxyisobutyric acid with a volumetric productivity of 1.32 mmol(S)‐3‐HIBA h−1 L−1. Overall, the conversion of isobutyric acid to (S)‐3‐HIBA was found to be the rate‐limiting step, leading to the accumulation of a mixture of (S)‐3‐hydroxyisobutyric acid and isobutyric acid. This study demonstrates for the first time the production of (S)‐3‐HIBA from renewable carbon in shake flasks and biofilm reactors and sets the stage for further optimizations towards the efficient production of 3‐HIBA and its derivatives in continuous fermentations.magnified image
Biography of Nobel laureate Shuji Nakamura
Authors: Nakamura Shuji 
Published: May 2015

Shuji Nakamura discovered p‐type doping in Gallium Nitride (GaN) and developed blue, green, and white “InGaN‐based” light emitting diodes (LEDs) and blue laser diodes (LDs). His inventions made possible energy efficient, solid‐state lighting systems and enabled the next generation of optical storage. In this biography, Shuji Nakamura tells the story of his personal life and his scientific career.
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Ability of Interleukin‐33– and Immune Complex–Triggered Activation of Human Mast Cells to Down‐Regulate Monocyte‐Mediated Immune Responses
Authors: Rivellese Felice , Suurmond Jolien , Habets Kim , Dorjée Annemarie L. , Ramamoorthi Nandhini , Townsend Michael J. , de Paulis Amato , Marone Gianni , Huizinga Tom W. J. , Pitzalis Costantino , Toes René E. M. 
Published: May 2015

ObjectiveMast cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). In particular, their activation by interleukin‐33 (IL‐33) has been linked to the development of arthritis in animal models. The aim of this study was to evaluate the functional responses of human mast cells to IL‐33 in the context of RA.MethodsHuman mast cells were stimulated with IL‐33 combined with plate‐bound IgG or IgG anti–citrullinated protein antibodies (ACPAs), and their effects on monocyte activation were evaluated. Cellular interactions of mast cells in RA synovium were assessed by immunofluorescence analysis, and the expression of messenger RNA (mRNA) for mast cell–specific genes was evaluated in synovial biopsy tissue from patients with early RA who were naive to treatment with disease‐modifying antirheumatic drugs.ResultsIL‐33 induced the up‐regulation of Fcγ receptor type IIa and enhanced the activation of mast cells by IgG, including IgG ACPAs, as indicated by the production of CXCL8/IL‐8. Intriguingly, mast cell activation triggered with IL‐33 and IgG led to the release of mediators such as histamine and IL‐10, which inhibited monocyte activation. Synovial mast cells were found in contact with CD14+ monocyte/macrophages. Finally, mRNA levels of mast cell–specific genes were inversely associated with disease severity, and IL‐33 mRNA levels showed an inverse correlation with the levels of proinflammatory markers.ConclusionWhen human mast cells are activated by IL‐33, an immunomodulatory phenotype develops, with human mast cells gaining the ability to suppress monocyte activation via the release of IL‐10 and histamine. These findings, together with the presence of synovial mast cell–monocyte interactions and the inverse association between the expression of mast cell genes at the synovial level and disease activity, suggest that these newly described mast cell–mediated inhibitory pathways might have a functional relevance in the pathogenesis of RA.
Core information set for oesophageal cancer surgery
Authors: Blazeby J M , Macefield R , Blencowe N S , Jacobs M , McNair A G K , Sprangers M , Brookes S T , Avery K N L , Blazeby J M , Blencowe N S , Brookes S T , Elliot J , Jacobs M , Korfage I , Macefield R , Mackichan F , Nicklin J , Smets E M A , Sprangers M A G , Strong S , Titcomb D R , van Berge Henegouwen M I , Whistance R , Witherstone J , Berrisford R , Blazeby J M , Byrne J , Dwerryhouse S , Galloway S , Griffin S M , Hassn A , Hewin D , Higgs S , Lamb P , Manson J , Moxon R , Osbourn S , Pursnani K , Shackcloth M , Underwood T , Whiting J , Williamson P 
Published: May 2015

Abstract

Background
Surgeons provide patients with information before surgery, although standards of information are lacking and practice varies. The development and use of a ‘core information set’ as baseline information before surgery may improve understanding. A core set is a minimum set of information to use in all consultations before a specific procedure. This study developed a core information set for oesophageal cancer surgery.

Methods
Information was identified from the literature, observations of clinical consultations and patient interviews. This was integrated to create a questionnaire survey. Stakeholders (patients and professionals) were surveyed twice to assess views on importance of information from ‘not essential’ to ‘absolutely essential’ using Delphi methods. Items not meeting predefined criteria were discarded after each survey and the final retained items were voted on, in separate patient and professional stakeholder meetings, to agree the core set.

Results
Some 67 information items were identified initially from multiple sources. Survey response rates were 76·5 per cent (185 of 242) and 54·8 per cent (126 of 230) for patients and professionals respectively (first round), and over 83 per cent in both groups thereafter. Health professionals rated short-term clinical outcomes most highly (technical complications), whereas patients prioritized information related to long-term benefits. The consensus meetings agreed the final set, which consisted of: in-hospital milestones to recovery, rates of open-and-close surgery, in-hospital mortality, major complications (reoperation), milestones in recovery after discharge, longer-term eating and drinking and overall quality of life, and chances of survival.

Conclusion
This study has established a core information set for surgery for oesophageal cancer.
Paradoxical increase in blood pressure following bilateral native nephrectomy
Authors: Ajlan Balgees A. , Safdar Osama Y. , Shalabi Mohammed , Kari Jameela A. 
Published: May 2015

Key Clinical MessageHypertension with Chronic kidney disease is often difficult to control medically. In such patients, nephrectomy can help to control blood pressure (BP). We describe a case of a 6‐year‐old boy with autosomal recessive polycystic kidney disease who showed a paradoxical increase in BP following bilateral nephrectomy.
Type‐driven data layouts for improved vectorisation
Authors: Šinkarovs Artjoms , Scholz Sven‐Bodo 
Published: May 2015

SummaryVector instructions of modern CPUs are crucially important for the performance of compute‐intensive algorithms. Auto‐vectorisation often fails because of an unfortunate choice of data layout by the programmer. This paper proposes a data layout inference for auto‐vectorisation that identifies layout transformations that convert single instruction, multiple data‐unfavourable layouts of data structures into favourable ones. We present a type system for layout transformations, and we sketch an inference algorithm for it. Finally, we present some initial performance figures for the impact of the inferred layout transformations. They show that non‐intuitive layouts that are inferred through our system can have a vast performance impact on compute intensive programs. Copyright © 2015 John Wiley & Sons, Ltd.