bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial
Authors: Manders Sofie HM , Kievit Wietske , Adang Eddy , Brus Herman L , Moens Hein J Bernelot , Hartkamp Andre , Hendriks Lidy , Brouwer Elisabeth , Visser Henk , Vonkeman Harald E , Hendrikx Jos , Jansen Tim L , Westhovens Rene , van de Laar Mart AFJ , van Riel Piet LCM 
Published: May 2015

Abstract
Introduction
For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.

Methods
We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.

Results
Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.

Conclusions
All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.

Trial registration
Netherlands Trial Register number NTR1605. Registered 24 December 2008.
Association of large intergenic noncoding RNA expression with disease activity and organ damage in systemic lupus erythematosus
Authors: Wu Yanfang , Zhang Feifei , Ma Jianyang , Zhang Xiaoyan , Wu Lingling , Qu Bo , Xia Shiwei , Chen Shunle , Tang Yuanjia , Shen Nan 
Published: May 2015

Abstract
Introduction
Despite growing evidence that large intergenic noncoding RNAs (lincRNAs) can regulate gene expression and widely take part in normal physiological and disease conditions, our knowledge of systemic lupus erythematosus (SLE)-related lincRNAs remains limited. The aim of this study was to detect the levels of four lincRNAs (ENST00000500949: linc0949, ENST00000500597: linc0597, ENST00000501992: linc1992, and ENST00000523995: linc3995) involved in innate immunity in the peripheral blood mononuclear cells (PBMCs) of patients with SLE and correlate these lincRNA levels with disease activity, organ damage, clinical features and medical therapies.

Methods
PBMCs were obtained from 102 patients with SLE, 54 patients with rheumatoid arthritis (RA) and 76 healthy donors. lincRNA expression levels were measured by real-time quantitative polymerase chain reaction. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, and organ damage was evaluated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index.

Results
linc0949 and linc0597 were significantly decreased in patients with SLE compared with patients with RA and healthy control subjects. linc0949 was correlated with SLEDAI-2K score (r = −0.329, P = 0.0007), as well as with complement component C3 level (r = 0.348, P = 0.0003). The level of linc0949 was also reduced in patients with SLE who had the presence of cumulative organ damage. In addition, decreasing expression of linc0949 was associated with lupus nephritis. linc0949 expression significantly increased after treatment, whereas neither disease activity nor organ damage correlated with linc0597 expression.

Conclusions
Our results provide novel empirical evidence that linc0949 could be a potential biomarker for diagnosis, disease activity and therapeutic response in SLE.
Migration towards SDF-1 selects angiogenin-expressing bone marrow monocytes endowed with cardiac reparative activity in patients with previous myocardial infarction
Authors: Ascione Raimondo , Rowlinson Jonathan , Avolio Elisa , Katare Rajesh , Meloni Marco , Spencer Helen L , Mangialardi Giuseppe , Norris Caroline , Kränkel Nicolle , Spinetti Gaia , Emanueli Costanza , Madeddu Paolo 
Published: May 2015

Abstract
Introduction
Chemokine-directed migration is crucial for homing of regenerative cells to the infarcted heart and correlates with outcomes of cell therapy trials. Hence, transplantation of chemokine-responsive bone marrow cells may be ideal for treatment of myocardial ischemia. To verify the therapeutic activity of bone marrow mononuclear cells (BM-MNCs) selected by in vitro migration towards the chemokine stromal cell-derived factor-1 (SDF-1) in a mouse model of myocardial infarction (MI), we used BM-MNCs from patients with previous large MI recruited in the TransACT-1&2 cell therapy trials.

Methods
Unfractioned BM-MNCs, SDF-1-responsive, and SDF-1-nonresponsive BM-MNCs isolated by patients recruited in the TransACT-1&2 cell therapy trials were tested in Matrigel assay to evaluate angiogenic potential. Secretome and antigenic profile were characterized by flow cytometry. Angiogenin expression was measured by RT-PCR. Cells groups were also intramyocardially injected in an in vivo model of MI (8-week-old immune deficient CD1-FOXN1nu/nu mice). Echocardiography and hemodynamic measurements were performed before and at 14 days post-MI. Arterioles and capillaries density, infiltration of inflammatory cells, interstitial fibrosis, and cardiomyocyte proliferation and apoptosis were assessed by immunohistochemistry.

Results
In vitro migration enriched for monocytes, while CD34+ and CD133+ cells and T lymphocytes remained mainly confined in the non-migrated fraction. Unfractioned total BM-MNCs promoted angiogenesis on Matrigel more efficiently than migrated or non-migrated cells. In mice with induced MI, intramyocardial injection of unfractionated or migrated BM-MNCs was more effective in preserving cardiac contractility and pressure indexes than vehicle or non-migrated BM-MNCs. Moreover, unfractioned BM-MNCs enhanced neovascularization, whereas the migrated fraction was unique in reducing the infarct size and interstitial fibrosis. In vitro studies on isolated cardiomyocytes suggest participation of angiogenin, a secreted ribonuclease that inhibits protein translation under stress conditions, in promotion of cardiomyocyte survival by migrated BM-MNCs.

Conclusions
Transplantation of bone marrow cells helps post-MI healing through distinct actions on vascular cells and cardiomyocytes. In addition, the SDF-1-responsive fraction is enriched with angiogenin-expressing monocytes, which may improve cardiac recovery through activation of cardiomyocyte response to stress. Identification of factors linking migratory and therapeutic outcomes could help refine regenerative approaches.
In vitro culture and production of syringin and rutin in Saussurea involucrata (Kar. et Kir.) – an endangered medicinal plant
Authors: Kuo Chao-Lin , Agrawal Dinesh-Chandra , Chang Hung-Chi , Chiu Ya-Ting , Huang Chu-Peng , Chen Yi-Lin , Huang Shih-Hung , Tsay Hsin-Sheng 
Published: May 2015

Abstract

Background

Saussurea involucrata (Kar. et Kir.) commonly known as ‘snow lotus’ or ‘Xue Lian’ is an important plant in the traditional Chinese system of medicine. The plant contains flavonoids such as syringin and rutin. These compounds have been reported to be anti-rheumatic, anti-inflammatory and dilate blood vessels, lower blood pressure, prevent cardiovascular diseases, enhance immunity, and act as anti-aging, anti-cancer, and anti-fatigue agents. The species has become endangered due to the excessive collection of S. involucrata plants in the wild, slower plant growth and ecological destruction of natural habitats. There is a severe shortage of plant material, while the market demand is ever increasing. Hence, it is very important to apply tissue culture technique for plant propagation and production of the bioactive compounds of this species.

Results
Multiple shoot induction and proliferation in shoot base explants derived from in vitro raised seedlings of S. involucrata was achieved on 3/4 strength of Murashige and Skoog’s (MS) basal medium (MSBM) supplemented with 1.0 mg/L−1 BA and 1.5 mg/L−1 NAA. Rooting was induced in 100 % shoots cultured on 1/2X MSBM supplemented with 1.0 mg/L−1 IBA for one week and then transfer to auxin free medium. The plantlets could be acclimatized successfully by sachet technique and established in the greenhouse. Maximum callus induction and proliferation in leaf segments was achieved on 1/2X MSBM supplemented with 0.5 mg/L−1 BA, 0.5 mg/L−1 NAA, 0.4 % gelrite and on incubation at 20 °C. Container closures had an influence on the quality and quantity of callus and production of the active compounds. The HPLC analysis showed much higher syringin content in in vitro shoots and callus as compared to commercially available market crude drug.

Conclusion
The present study describes an in vitro culture protocol of Saussurea involucrata. The bioactive compounds, syringin and rutin could be produced through tissue culture technique without sacrificing the endangered Saussurea involucrata plants in the wild.
Inflammatory environment and oxidized LDL convert circulating human proangiogenic cells into functional antigen-presenting cells
Authors: Vinci Maria Cristina , Piacentini Luca , Chiesa Mattia , Saporiti Federica , Colombo Gualtiero I , Pesce Maurizio 
Published: May 2015

Abstract
The function of human circulating PACs has been described extensively. However, little focus has been placed on understanding how these cells differ in their functions in the presence of microenvironments mimicking vascular inflammation. We hypothesized that exposure to proinflammatory cytokines or the oxLDL, an autoantigen abundant in advanced atherosclerotic plaques, converts PACs into immune-modulating/proinflammatory cells. Hence, we examined the effect of oxLDL and inflammatory stimuli on their phenotype by use of a functional genomics model based on secretome and whole genome transcriptome profiling. PACs obtained from culturing a PBMC fraction in angiogenic medium were primed with DC differentiation cytokines and then exposed to proinflammatory cytokines or oxLDL. Under these conditions, PACs converted into APCs, expressed maturation markers CD80 and CD83, and showed an increased up-regulation of CD86. APCcy and APCox induced a robust T cell BrdU incorporation. Despite a similar ability to induce lymphocyte proliferation, APCcy and APCox differed for the secretory pathway and mRNA expression. Analysis of the differentially expressed genes identified 4 gene “clusters,” showing reciprocal modulation in APCcy vs. APCox, justifying, according to functional genomics analyses, a different putative function of the cells in antigen processing. Together, these data show that treatment with inflammatory cytokines or oxLDL converts human PAC phenotypes and functions into that of APCs with similar lymphocyte-activating ability but distinct maturation degree and paracrine functions.
Association of Exposure to Di-2-Ethylhexylphthalate Replacements With Increased Insulin Resistance in Adolescents From NHANES 2009–2012
Authors: Attina Teresa M. , Trasande Leonardo 
Published: May 2015

Context:
Di-isononyl phthalate (DINP) and di-isodecyl phthalate (DIDP) are environmental chemicals increasingly used to replace di-2-ethylhexylphthalate (DEHP) and commonly found in processed foods. Phthalate exposures, in particular DEHP, have been associated with insulin resistance in adolescents, but there are no data regarding the two substitutes, DINP and DIDP.

Objective:
This study aimed to examine associations of DINP, DIDP, and DEHP with insulin resistance outcomes.

Design, Setting, and Participants:
This was a cross-sectional analysis of 2009–2012 National Health and Nutrition Examination Surveys (NHANES) composed of 356 fasting 12–19-year-olds.

Main Outcome Measures:
Insulin resistance as a categorical outcome expressed as homeostatic model assessment of insulin resistance (HOMA-IR), using a cut point of 4.39 to define insulin resistance. We also examined continuous HOMA-IR as an outcome in secondary analyses.

Results:
Controlling for demographic and behavioral factors, diet, age, body mass index, and urinary creatinine, for each log increase in DINP metabolite, a 0.08 (P = .001) increase in HOMA-IR was identified. Compared with the first tertile of DINP (23.4% adjusted prevalence), the third tertile was associated with a 34.4% prevalence (95% confidence interval [CI], 27.3–41.6%; P = .033) of insulin resistance. Similarly, compared with the first tertile of DEHP (20.5% adjusted prevalence), the third tertile had 37.7% prevalence (95% CI 29.8–45.6%; P = .003).

Conclusions:
Urinary DINP concentrations were associated with increased insulin resistance in this cross-sectional study of adolescents. The previously identified association of DEHP with insulin resistance was also confirmed. Further, longitudinal studies are needed to confirm these associations, with the possibility to assess opportunities for intervention.
A Brn2–Zic1 axis specifies the neuronal fate of retinoic-acid-treated embryonic stem cells
Authors: Urban Sylvia , Kobi Dominique , Ennen Marie , Langer Diana , Le Gras Stéphanie , Ye Tao , Davidson Irwin 
Published: May 2015

ABSTRACT
Mouse embryonic stem cells (ESCs) treated with all-trans retinoic acid differentiate into a homogenous population of glutamatergic neurons. Although differentiation is initiated through activation of target genes by the retinoic acid receptors, the downstream transcription factors specifying neuronal fate are less well characterised. Here, we show that the transcription factor Brn2 (also known as Pou3f2) is essential for the neuronal differentiation programme. By integrating results from RNA-seq following Brn2 silencing with results from Brn2 ChIP-seq, we identify a set of Brn2 target genes required for the neurogenic programme. Further integration of Brn2 ChIP-seq data from retinoic-acid-treated ESCs and P19 cells with data from ESCs differentiated into neuronal precursors by Fgf2 treatment and that from fibroblasts trans-differentiated into neurons by ectopic Brn2 expression showed that Brn2 occupied a distinct but overlapping set of genomic loci in these differing conditions. However, a set of common binding sites and target genes defined the core of the Brn2-regulated neuronal programme, among which was that encoding the transcription factor Zic1. Small hairpin RNA (shRNA)-mediated silencing of Zic1 prevented ESCs from differentiating into neuronal precursors, thus defining a hierarchical Brn2–Zic1 axis that is essential to specify neural fate in retinoic-acid-treated ESCs.
Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides
Authors: Ramirez M. Desmond , Oakley Todd H. 
Published: May 2015

ABSTRACT
Cephalopods are renowned for changing the color and pattern of their skin for both camouflage and communication. Yet, we do not fully understand how cephalopods control the pigmented chromatophore organs in their skin and change their body pattern. Although these changes primarily rely on eyesight, we found that light causes chromatophores to expand in excised pieces of Octopus bimaculoides skin. We call this behavior light-activated chromatophore expansion (or LACE). To uncover how octopus skin senses light, we used antibodies against r-opsin phototransduction proteins to identify sensory neurons that express r-opsin in the skin. We hypothesized that octopus LACE relies on the same r-opsin phototransduction cascade found in octopus eyes. By creating an action spectrum for the latency to LACE, we found that LACE occurred most quickly in response to blue light. We fit our action spectrum data to a standard opsin curve template and estimated the λmax of LACE to be 480 nm. Consistent with our hypothesis, the maximum sensitivity of the light sensors underlying LACE closely matches the known spectral sensitivity of opsin from octopus eyes. LACE in isolated preparations suggests that octopus skin is intrinsically light sensitive and that this dispersed light sense might contribute to their unique and novel patterning abilities. Finally, our data suggest that a common molecular mechanism for light detection in eyes may have been co-opted for light sensing in octopus skin and then used for LACE.
Characterization of the target of ivermectin, the glutamate-gated chloride channel, fromAnopheles gambiae
Authors: Meyers Jacob I. , Gray Meg , Kuklinski Wojtek , Johnson Lucas B. , Snow Christopher D. , Black William C. , Partin Kathryn M. , Foy Brian D. 
Published: May 2015

ABSTRACTThe use of insecticide-treated nets and indoor residual insecticides targeting adult mosquito vectors is a key element in malaria control programs. However, mosquito resistance to the insecticides used in these applications threatens malaria control efforts. Recently, the mass drug administration of ivermectin (IVM) has been shown to kill Anopheles gambiae mosquitoes and disrupt Plasmodium falciparum transmission in the field. We cloned the molecular target of IVM from A. gambiae, the glutamate-gated chloride channel (AgGluCl), and characterized its transcriptional patterns, protein expression and functional responses to glutamate and IVM. AgGluCl cloning revealed an unpredicted fourth splice isoform as well as a novel exon and splice site. The predicted gene products contained heterogeneity in the N-terminal extracellular domain and the intracellular loop region. Responses to glutamate and IVM were measured using two-electrode voltage clamp on Xenopus laevis oocytes expressing AgGluCl. IVM induced non-persistent currents in AgGluCl-a1 and did not potentiate glutamate responses. In contrast, AgGluCl-b was insensitive to IVM, suggesting that the AgGluCl gene could produce IVM-sensitive and -insensitive homomultimers from alternative splicing. AgGluCl isoform-specific transcripts were measured across tissues, ages, blood feeding status and sex, and were found to be differentially transcribed across these physiological variables. Lastly, we stained adult, female A. gambiae for GluCl expression. The channel was expressed in the antenna, Johnston's organ, supraesophageal ganglion and thoracic ganglia. In summary, we have characterized the first GluCl from a mosquito, A. gambiae, and described its unique activity and expression with respect to it as the target of the insecticide IVM.
Can parents be effective screeners in identifying developmental dysplasia of the hip? Review of a self-check guide
Authors: Lee Angela , Doherty Nina , Dodds Richard , Davies Neville 
Published: May 2015

Background: Infants have been screened for developmental dysplasia of the hip (DDH) since the 1960s. However, changes to the national screening programme in 2008 have reduced the surveillance of DDH following the removal of the 8-month infant hip check, leaving only the 6–8 week hip check as standard. Aim: The study was to ascertain if parents/carers could be effective screeners in the detection of infant DDH using a self-check guide. Design and setting: A self-check guide for DDH was developed to enlist parents as screeners. The guide highlights common signs used to alert to the possibility of DDH or hip dislocation. It was disseminated during 2008–13 by the Royal Berkshire NHS Foundation Trust in West Berkshire, through maternity services and health centres. Results: Of those infants referred to our clinic as a result of parental screening, 73% were ‘abnormal’; of these, 33% went on to treatment with splintage. The mean age of infants was 5.36 months, and 20% of positive findings were in infants aged 7 months or over at the time seen. None went on to have open surgery. These patients represented 5–10% of the overall group of DDH-positive patients. If left undiagnosed, they may have gone on to late presentation requiring surgery as a child, or undiagnosed acetabular dysplasia and possible surgical treatment in relatively early adulthood. Conclusion: Given the right guidance, parents could assist in detecting DDH in their infant.
Primary care in Caribbean Small Island Developing States
Authors: Kranenburg J.D. , Essink D.R. 
Published: May 2015

Abstract
Caribbean Small Island Developing States (SIDS) made good process on improving the health of their populations; but concerns exist when it comes to meeting changing health needs. Due to remoteness and limited resources it is difficult to respond to high rates of non-communicable diseases (NCDs). Furthermore, little is known about how primary care (PC) is organised and how this responds to current health issues. This study focused on gaining insights in the organisation of PC of Caribbean SIDS based on currently available literature. This literature review was an explorative multiple case study, where structure of PC and health status of 16 Caribbean SIDS were reviewed using available scientific and grey literature between the years 1997 and 2014. Thirty documents were used to analyse 20 indicators for the dimensions “Structure of Primary Care” and “Health Status”. Results were mapped in order to identify if there is a possible relation between structures of PC to the health of the populations. When reviewing the structure of PC, the majority of information was available for “Economic conditions of PC” (78%) and the least information was available for “Governance of PC” (40%). With regards to health status, all islands show improvements on “Life expectancy at birth” since 2007. In contrast, on average, the mortality due to NCDs did not improve. Saint Lucia performs best on “Structure of PC”. The British Virgin Islands have the best health status. When both dimensions were analysed, Saint Lucia performs best. There is still little known on the responsiveness of PC of Caribbean SIDS to NCDs. There is a need for elaborate research on: (1) If and how the functioning of these health systems relate to the health status; (2) What islands can learn from an analysis over time and what they can learn from cross-island analysis; and (3) Filling the gaps of knowledge which currently exist within this field of research.
General solution and generalized Ulam-Hyers stability of a generalized n- type additive quadratic functional equation in Banach space and Banach algebra: direct and fixed point methods
Authors: Murthy S. , Arunkumar M. , Govindan V. 
Published: May 2015

<p>In this paper, the authors introduce and investigate the general solution and generalized Ulam-Hyers stability of a generalized <em>n</em>-type additive-quadratic functional equation.</p><p><br />g(x + 2y; u + 2v) + g(x 􀀀 2y; u 􀀀 2v) = 4[g(x + y; u + v) + g(x 􀀀 y; u 􀀀 v)] 􀀀 6g(x; u)<br />+ g(2y; 2v) + g(􀀀2y;􀀀2v) 􀀀 4g(y; v) 􀀀 4g(􀀀y;􀀀v)</p><p>Where is a positive integer with , in Banach Space and Banach Algebras using direct and fixed point methods.</p>