bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infliximab Versus Conventional Combination Treatment and Seven‐Year Work Loss in Early Rheumatoid Arthritis: Results of a Randomized Swedish Trial
Authors: Eriksson Jonas K. , Wallman Johan K. , Miller Heather , Petersson Ingemar F. , Ernestam Sofia , Vivar Nancy , van Vollenhoven Ronald F. , Neovius Martin 
Published: March 2016

ObjectiveTo compare long‐term work loss in methotrexate‐refractory early rheumatoid arthritis (RA) patients randomized to the addition of infliximab or conventional combination treatment.MethodsThis study was a multicenter, 2‐arm, parallel, randomized, active‐controlled, open‐label trial. RA patients with <1‐year symptom duration were recruited from 15 rheumatology clinics in Sweden between 2002–2005. Patients who did not achieve low disease activity after 3–4 months of methotrexate therapy were randomized to the addition of infliximab or conventional combination treatment with sulfasalazine plus hydroxychloroquine. Yearly sick leave and disability pension days >7 years after randomization were retrieved from nationwide registers kept by the Swedish Social Insurance Agency.ResultsOf 210 working‐age patients, 109 were randomized to infliximab (mean age 48.4 years, 73% women) and 101 to conventional treatment (mean age 48.7 years, 77% women). The year before randomization, the mean number of annual work days lost was 127 in the infliximab arm and 118 in the conventional treatment group (mean difference 9 [95% confidence interval (95% CI) −23, 39]). Compared to the year before randomization, the mean changes at 7 years were −25 days in the infliximab and −26 days in the conventional treatment group (adjusted mean difference 10 [95% CI −25, 46]). The cumulative mean for work‐loss days was 846 in the infliximab group and 701 in the conventional treatment group (adjusted mean difference 104 [95% CI −56, 284]).ConclusionLong‐term work loss improved significantly in early RA patients randomized to infliximab plus methotrexate or conventional combination therapy. No difference was detected between strategies, and the level of work‐loss days remained twice that observed in the general population.
Prevalence of Post‐Chikungunya Infection Chronic Inflammatory Arthritis: A Systematic Review and Meta‐Analysis
Authors: Rodríguez‐Morales Alfonso J. , Cardona‐Ospina Jaime A. , Fernanda Urbano‐Garzón Sivia , Sebastian Hurtado‐Zapata Juan 
Published: March 2016

ObjectiveTo determine the percentage of patients who would develop chronic inflammatory rheumatism (CIR) following chikungunya (CHIK) virus disease.MethodsWe conducted a systematic review of the literature in 3 databases (PubMed, Science Citation Index, and Scopus) to identify studies assessing the proportion of patients who progress to CHIK‐CIR. We performed a random‐effects model meta‐analysis to calculate the pooled prevalence and 95% confidence intervals (95% CIs). A 2‐tailed alpha level of 5% was used for hypothesis testing. Measures of heterogeneity, including Cochran's Q statistic, the I2 index, and the tau‐squared test, were calculated and reported. Subgroup analyses were conducted by type of study and country, by studies evaluating chronic arthritis, and by studies with ≥200 patients and followup ≥18 months. Publication bias was assessed using a funnel‐plot.ResultsUp to June 15, 2015, our literature search yielded 578 citations. The pooled prevalence of CHIK‐CIR in 18 selected studies among 5,702 patients was 40.22% (95% CI 31.11–49.34; τ2 = 0.0838). From studies derived from India, prevalence was 27.27% (95% CI 15.66–38.88; τ2 = 0.0411), while from France, prevalence was 50.25% (95% CI 25.38–75.12; τ2 = 0.1797). The prevalence of CHIK chronic arthritis was 13.66% (95% CI 9.31–18.00; τ2 = 0.0060). Considering just those studies with ≥200 patients assessed, prevalence was 34.14% (95% CI 23.99–44.29; τ2 = 0.0525). In studies with a followup ≥18 months, prevalence was 32.13% (95% CI 22.21–42.04; τ2 = 0.0453).ConclusionAccording to our results in the most conservative scenario, approximately 25% of CHIK cases would develop CHIK‐CIR (34% if we just consider the most representative studies), and 14% would develop chronic arthritis.
Autologous stem cell transplantation in first complete remission may not extend progression‐free survival in patients with peripheral T cell lymphomas
Authors: Yam Clinton , Landsburg Daniel J. , Nead Kevin T. , Lin Xinyi , Mato Anthony R. , Svoboda Jakub , Loren Alison W. , Frey Noelle V. , Stadtmauer Edward A. , Porter David L. , Schuster Stephen J. , Nasta Sunita D. 
Published: March 2016

Patients with peripheral T cell lymphomas (PTCL) generally have a poor prognosis when treated with conventional chemotherapy. Consolidation with autologous stem cell transplantation (ASCT) has been reported to improve progression‐free survival. However, these studies have not compared consolidative ASCT with active observation in patients with PTCL achieving first complete remission (CR1) following induction chemotherapy. We conducted a retrospective analysis of PTCL patients treated at the University of Pennsylvania between 1/1/2007 and 12/31/2014. Patients with cutaneous T cell lymphoma, concurrent B cell lymphomas, and anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma (ALK‐positive ALCL) were excluded from the study. We compared progression‐free survival for patients who underwent ASCT in CR1 following CHOP‐like induction regimens and patients who underwent active observation during CR1. 48 patients met all inclusion and exclusion criteria and underwent either active observation (28 patients) or consolidative ASCT (20 patients) in CR1. The 1‐year cumulative incidence of relapse in the observation and ASCT groups was 50% (95% confidence interval [CI]: 30–67%) and 46% (95% CI: 23–67%), respectively (P = 0.55). Median progression‐free survival in the observation and ASCT groups was 15.8 and 12.8 months, respectively (log rank, P = 0.79). Estimated 3‐year progression‐free survival in the observation and ASCT groups was 37 and 41%, respectively. In conclusion, for PTCL patients achieving CR1 following CHOP‐like induction chemotherapy, ASCT does not appear to improve progression‐free survival compared to active observation. This finding should be confirmed in a larger, prospective study. Am. J. Hematol. 91:672–676, 2016. © 2016 Wiley Periodicals, Inc.
Expression of ADAM17 and ADAM10 in nasal polyps
Authors: Bae Woo Yong , Park Seong Kook , Kim Do Hun , Koh Tae Kyung , Hur Dae Young , Chueh Hee Won 
Published: March 2016

BackgroundThe “a disintegrin and metalloproteases” (ADAMs) are a multifunctional gene family that contribute to the homeostasis of the extracellular matrix, transduction of specific intracellular signals, organogenesis, inflammation, tissue remodeling, adhesion, and cell migration. ADAM17 is the best‐characterized of the “sheddases,” and its putative substrates are widespread, including various inflammatory modulators. ADAM10 is the most similar to ADAM17 in terms of protein sequence and the structural properties of their catalytic domains. The objective of this work was to assess the roles of ADAM17 and ADAM10 in nasal polyps (NPs) by measuring their expression.MethodsThe expression of ADAM10 and 17 was investigated in NPs at endonasal sinus surgery (n = 15) and compared with that in inferior turbinate mucosa samples obtained from nonallergic hypertrophic rhinitis patients (n = 15). Tissue samples were analyzed by real‐time polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining.ResultsThe ADAM17 messenger RNA (mRNA) and protein levels were significantly higher in the inferior turbinate than in NPs (p < 0.05). The ADAM10 mRNA and protein levels did not differ significantly between NPs and inferior turbinates (p > 0.05). ADAM10 and ADAM17 were expressed primarily in inflammatory cells, submucosal glandular cells, and lining epithelial cells.ConclusionADAM17 may contribute to the development of NPs in contrast to ADAM10, based on their expression patterns. It may be important to discover the role of ADAM17 in the development of NP and helpful to examine the specific mechanism of the development of NPs.
T regulatory and Th17 cells in chronic rhinosinusitis with polyps
Authors: Miljkovic Dijana , Psaltis Alkis , Wormald Peter‐John , Vreugde Sarah 
Published: March 2016

BackgroundChronic rhinosinusitis (CRS) is categorized into 2 types based on the absence (CRSsNP) and presence of nasal polyps (CRSwNP). Although CRSsNP patients lack nasal polyps, the mucosa may show variable degrees of polypoid change. This raises the question of whether or not the classification system is an over simplification and that CRSsNP and CRSwNP only represent 2 phenotypic extremes along a broader spectrum of immunologically different disease processes. To investigate this, adaptive and innate immune cells were compared in the different tissue types within CRSsNP and CRSwNP patients.MethodsTissue from 15 CRSwNP, 6 CRSsNP, and 8 healthy control patients was obtained prospectively. Nonpolypoid mucosa, polypoid tissues, and polyps were obtained at the time of endoscopic sinus surgery and analyzed using flow cytometry for various adaptive and innate immune cell subsets.ResultsIn the polyps from CRSwNP patients there were significantly more T regulatory (Treg) cells (12.86 ± 12.60 vs 2.83 ± 4.68) and Th17 cells (16.12 ± 11.75 vs 2.31 ± 2.13) compared to the polypoid tissue from CRSsNP patients. Cellular infiltrates in the nonpolypoid or polypoid mucosa of the different patient categories showed no difference in CRSwNP, CRSsNP and control groups.ConclusionThis observational study identified an increase in Treg and Th17 cells in CRSwNP patients implying that these cells may be implicated in polyp development. Importantly it also identified a similar inflammatory infiltrate in nonpolyp or polypoid mucosa across control, CRSsNP, and CRSwNP groups inferring that polyps should be sampled when studying CRSwNP.
Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis
Authors: van der Heijde Désirée , Landewé Robert B. , Mease Philip J. , McInnes Iain B. , Conaghan Philip G. , Pricop Luminita , Ligozio Greg , Richards Hanno B. , Mpofu Shephard 
Published: March 2016

ObjectiveTo assess whether secukinumab treatment in patients with active psoriatic arthritis (PsA) is associated with sustained inhibition of radiographic progression.MethodsIn this phase III, double‐blind, placebo‐controlled study, 606 patients with PsA were randomized to receive intravenous (IV) secukinumab at a dose of 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab at a dose of 150 mg or 75 mg (the IV→150 mg and IV→75 mg groups, respectively) or placebo. Patients were stratified according to prior anti–tumor necrosis factor (anti‐TNF) exposure (71% were anti‐TNF naive). At week 16, placebo‐treated patients who had at least a 20% reduction in the tender and swollen joint counts (responders) continued to receive placebo until week 24; nonresponders were re‐randomized to receive secukinumab at a dose of 150 mg or 75 mg. The modified total Sharp/van der Heijde score (SHS) was determined at baseline, week 16 or 24, and week 52.ResultsIn the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed that secukinumab reduced radiographic progression at week 24, regardless of previous anti‐TNF treatment. Among anti‐TNF–naive patients, the mean changes from baseline to week 24 in the modified total SHS were 0.05 in the pooled secukinumab group and 0.57 in the placebo group; among patients with an inadequate response or intolerance to anti‐TNF treatment, the mean changes were 0.16 and 0.58, respectively. Anti‐TNF–naive patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52 irrespective of concomitant methotrexate use. A high proportion of patients receiving secukinumab showed no progression (change in SHS of ≤ 0.5) from baseline to week 24 (82.3% of the IV→150 mg group and 92.3% of the IV→75 mg group) and from week 24 to week 52 (85.7% of the IV→150 mg group and 85.8% of the IV→75 mg group).ConclusionSecukinumab inhibited radiographic progression over 52 weeks of treatment in patients with active PsA.
Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial
Authors: Poddubnyy Denis , Listing Joachim , Sieper Joachim 
Published: March 2016

ObjectiveTo investigate the course of active inflammatory and fatty lesions seen on magnetic resonance imaging (MRI) in patients with early axial spondyloarthritis (SpA) treated with the tumor necrosis factor (TNF) inhibitor infliximab added to naproxen as compared to those treated with naproxen alone.MethodsA total of 158 patients with active axial SpA were randomized (2:1) to receive 28 weeks of treatment with either infliximab 5 mg/kg plus naproxen 1,000 mg/day or placebo plus naproxen 1,000 mg/day. MRI of the sacroiliac (SI) joints and of the spine was performed at baseline and week 28. Images were scored for active inflammation and for fatty lesions.ResultsAfter 28 weeks, there was a significant reduction of inflammation in the spine and in the SI joints in both treatment groups, which was, however, more prominent in the infliximab plus naproxen group (mean ± SD spine osteitis change score −2.9 ± 5.1, versus −2.0 ± 4.2 in the placebo plus naproxen group [P < 0.001]; SI joint osteitis change score −4.3 ± 5.2 in the infliximab plus naproxen group versus −3.9 ± 3.7 in the placebo plus naproxen group [P = 0.003]). Similarly, there was a significant increase in the fatty lesion score after 28 weeks in both groups; this change did not, however, differ significantly between groups (spine fatty lesion change score 0.8 ± 1.7 in the infliximab plus naproxen group versus 1.0 ± 1.8 in the placebo plus naproxen group [P = 0.72]; SI joint fatty lesion change score 1.7 ± 2.7 in the infliximab plus naproxen group versus 1.4 ± 2.6 in the placebo plus naproxen group [P = 0.86]).ConclusionThese findings indicate that effective antiinflammatory treatment of axial SpA is associated with an increase in fatty lesion scores, independent of concomitant treatment with or without anti‐TNF.
The Effect of Comedication With a Conventional Synthetic Disease‐Modifying Antirheumatic Drug on Drug Retention and Clinical Effectiveness of Anti–Tumor Necrosis Factor Therapy in Patients With Axial Spondyloarthritis
Authors: Nissen Michael J. , Ciurea Adrian , Bernhard Jürg , Tamborrini Giorgio , Mueller Ruediger , Weiss Bettina , Toniolo Martin , Exer Pascale , Gabay Cem , Finckh Axel ,   for the physicians of the Swiss Clinical Quality Management Cohort
Published: March 2016

ObjectiveTo explore the effect of comedication with conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) on drug retention and clinical effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (SpA).MethodsThe study included all patients starting treatment with a TNFi in a large prospective cohort of axial SpA patients (Swiss Clinical Quality Management in axial SpA). Crude drug retention was analyzed using the Kaplan‐Meier method, and in adjusted analyses, Cox proportional hazards regression was used to model TNFi discontinuation. We evaluated multiple disease activity measures and validated clinical response criteria over time.ResultsA total of 2,765 TNFi treatment courses were included from 1,914 patients with axial SpA, 20.4% in combination with a conventional synthetic DMARD. In unadjusted analyses, the monotherapy group had significantly shorter median TNFi retention time (32.7 months) compared to the cotherapy group (39.1 months) (P = 0.04). In multivariate adjusted analyses, the monotherapy group had significantly lower TNFi retention, with a hazard ratio (HR) of 1.17 (95% confidence interval [95% CI] 1.01–1.35). This effect was even larger when only infliximab‐treated patients were considered, with an HR for monotherapy of 1.36 (95% CI 1.06–1.74). Clinical response rates were almost identical at 1 year, with a change in the Bath Ankylosing Spondylitis Disease Activity Index of −2.02 and −2.00 (P = 0.83) and a change in the Ankylosing Spondylitis Disease Activity Score using C‐reactive protein of −1.14 and −1.12 (P = 0.45) in the monotherapy and cotherapy groups, respectively.ConclusionWe demonstrate an association between the combination of a TNFi with conventional synthetic DMARDs and improved drug retention in patients with axial SpA, particularly in the subgroup of patients with infliximab.
Rapid screening and identification of lycodine‐type alkaloids in Lycopodiaceae and Huperziaceae plants by ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry
Authors: Shan Si‐Ming , Luo Jian‐Guang , Pan Ke , Zou Hong‐yan , Kong Ling‐Yi 
Published: March 2016

AbstractLycodine‐type alkaloids have gained significant interest owing to their unique skeletal characteristics and acetylcholinesterase activity. This study established a rapid and reliable method using ultra‐performance liquid chromatography coupled with electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐ESI‐Q/TOF‐MS/MS) for comprehensive characterization of lycodine‐type alkaloids for the first time. The lycodine‐type alkaloids were detected successfully from Lycopodiastrum casuarinoides, Huperzia serrata and Phlegmarirus carinatus in seven plants of the Lycopodiaceae and Huperziaceae families, based on the established characteristic MS fragmentation of five known alkaloids. Furthermore, a total of 13 lycodine‐type alkaloids were identified, of which three pairs of isomers were structurally characterized and differentiated. This study further improves mass analysis of lycodine‐type alkaloids and demonstrates the superiority of UPLC with a high‐resolution mass spectrometer for the rapid and sensitive structural elucidation of other trace active compounds. Copyright © 2016 John Wiley & Sons, Ltd.
Development and validation of a sensitive LC–MS/MS assay for quantification of bruceine D in rat plasma
Authors: Zhang Yining , Zhen Yong , Zhang Ying , Liu Shouyue 
Published: March 2016

AbstractA sensitive LC–MS/MS method for the determination of bruceine D in rat plasma was developed. The analyte and IS were separated on a Luna C18 column (2.1 × 50 mm, 1.7 μm) using a mobile phase of acetonitrile and 0.1% formic acid in water (40:60, v/v) at a flow rate of 0.25 mL/min. The selected reaction monitoring mode was chosen to monitor the precursor‐to‐product ion transitions of m/z 409.2 → 373.2 for bruceine D and m/z 469.2 → 229.3 for IS using a negative ESI mode. The method was validated over a concentration range of 0.5–2000 ng/mL for bruceine D. Total chromatography time for each run was 3.5 min. The method was successfully applied to a pharmacokinetic study of bruceine D in rats. Copyright © 2016 John Wiley & Sons, Ltd.
A self‐contrast approach to evaluate the inhibitory effect of chrysosplenetin, in the absence and presence of artemisinin, on the in vivo P‐glycoprotein‐mediated digoxin transport activity
Authors: Yang Bei , Ma Li‐Ping , Ma Wei , Wei Shi‐Jie , Ji Hong‐Yan , Li Hou‐Gang , Dang Hong‐Wan , Liu Cheng , Wu Xiu‐Li , Chen Jing 
Published: March 2016

AbstractIn this study, we used a self‐contrast method, which excluded the individual difference, to evaluate the inhibitory effect of chrysosplentin (CHR) in the presence or absence of artemisinin (ART) on the P‐glycoprotein (P‐gp) transport activity. A sensitive and rapid UHPLC–MS/MS method was applied for quantification of digoxin, a P‐gp‐specific substrate, in rat plasma. A pharmacokinetic study was carried out: first after an oral administration of digoxin at a dose of 0.09 mg/kg (first period), followed by a 20‐day wash‐out, then after another administration of digoxin (second period). During the second period, test compounds were orally given three times per day for seven consecutive days. Results showed that the t1/2 of digoxin in all the groups had no significant difference between the first and second periods. The AUC0–24, Cmax, tmax, and Clz/F of the negative control and ART alone groups showed no difference. However, the AUC0–24 and Cmax in the CHR alone, CHR–ART (1:2) and verapamil (positive control) groups showed 2.34‐, 3.04‐, 1.79‐, and 1.81‐, 1.99‐, 2.06‐fold increases along with 3.50‐, 3.84‐ and 4.76‐fold decreases for CLz/F, respectively. The tmax in the CHR–ART (1:2) group increased 3.73‐fold. In conclusion, our self‐contrast study suggested that CHR, especially when combined with ART in a ratio of 1:2, inhibited P‐gp activity while ART alone has no effect. Copyright © 2016 John Wiley & Sons, Ltd.
Frankincense Revisited, Part II: Volatiles in Rare Boswellia Species and Hybrids
Authors: Niebler Johannes , Eslamieh Jason , Buettner Andrea 
Published: March 2016

In this second part of the investigation of volatiles and semivolatiles in Boswellia gum resins, an additional five less common species were analyzed by (SPME‐)GC/MS, namely B. ameero, B. elongata, B. neglecta, B. popoviana, and B. rivae. Moreover, the results of hybridization experiments are reported in combination with the volatile composition of their gum resins. Our study shows that B. sacra benefits from an intraspecific cross‐pollination, as the resulting hybrid B. sacra var. supersacra has a far higher seed germination rate and viability.
Pump and pipeline performance when pumping slurries with different particle gradings
Authors: Sellgren Anders , Visintainer Robert , Furlan John , Matoušek Václav 
Published: March 2016

AbstractA pipeline slurry friction loss model consisting of three regimes was initially proposed by Wilson then extended to four components consisting of fluid, pseudo‐homogeneous, heterogeneous, and fully stratified regimes. The weighting technique using up to four regime‐related components often works well for friction loss estimations based on simple input data and model parameters. This also holds for the Hydraulic Institute's pump performance derating procedure for settling slurries. The comparisons and discussion focus on coarse particle slurries and some cases where the modelling estimations for pipeline and pump performance were not particularly accurate.
Flow of non‐Newtonian fluids in pipes with large roughness
Authors: Graham Lachlan J. W. , Pullum Lionel , Wu Jie 
Published: March 2016

AbstractPipes with large roughnesses can occur due to erosion, corrosion, and scale. These roughnesses can be much larger than are accounted for in the Moody diagram. Experimental tests have shown that laminar flow of non‐Newtonian fluids in pipes with large roughnesses can be accurately predicted by using a constricted diameter, where the diameter measurement is taken as the typical minimum of the rough pipe. Turbulent flows of non‐Newtonian fluids are less accurately predicted by available methods and it is suggested that test work be performed if it is required to account for large pipe roughness.