bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid Profile Changes in Patients With Chronic Inflammatory Arthritis Treated With Biologic Agents and Tofacitinib in Randomized Clinical Trials: A Systematic Review and Meta‐Analysis
Authors: Souto Alejandro , Salgado Eva , Maneiro José Ramón , Mera Antonio , Carmona Loreto , Gómez‐Reino Juan J. 
Published: October 2014

ObjectiveTo analyze lipid changes in patients with rheumatoid arthritis (RA) and patients with spondyloarthritis (SpA) treated with biologic agents or tofacitinib in randomized clinical trials (RCTs).MethodsA systematic literature search was performed, using the Medline, Embase, Cochrane Library, and Web of Knowledge databases. Meta‐analyses were performed using random‐effects models to assess changes in the percentage of patients with abnormal lipid values or in the mean percentage of increase in the cholesterol and triglycerides levels.ResultsTwenty‐five of 4,527 identified articles met the inclusion criteria. Compared with RA patients treated with placebo, those treated with tocilizumab were more likely to have hypercholesterolemia (odds ratio [OR] 4.64; 95% confidence interval [95% CI] 2.71, 7.95 [P < 0.001]), increased levels of high‐density lipoprotein (HDL) cholesterol (OR 2.25; 95% CI 1.14, 4.44 [P = 0.020]), and increased levels of low‐density lipoprotein (LDL) cholesterol (OR 4.80; 95% CI 3.27, 7.05 [P < 0.001]); this was not observed in patients treated with tumor necrosis factor (TNF) antagonists (OR 1.54; 95% CI 0.90, 2.66 [P = 0.119]) or tofacitinib (OR 3.4; 95% CI 0.62, 18.55 [P = 0.158]). Among patients receiving tofacitinib 5 mg twice daily, the mean percentage of increases in the HDL cholesterol level (weighted mean difference [WMD] 13.00 mg/dl; 95% CI 12.08, 13.93 [P < 0.001]) and the LDL cholesterol level (WMD 11.20 mg/dl; 95% CI 10.08, 12.32 [P < 0.001]) were higher than those in the comparator groups. Among patients treated with tofacitinib 10 mg twice daily, the mean percentage of increases in the HDL cholesterol level (WMD 15.21 mg/dl; 95% CI 13.28, 17.14 [P < 0.001]) and the LDL cholesterol level (WMD 15.42 mg/dl; 95% CI 11.77, 19.06 [P < 0.001]) were also higher than those in the comparator groups. No data were available for RA treated with other biologic agents or for SpA.ConclusionIn patients with RA treated with tocilizumab or tofacitinib but not with TNF antagonists, moderate changes in lipids are observed. Whether these changes pertain to the control of inflammation or to the mechanism of action of the biologic agents or tofacitinib remains undetermined.
Failed Degradation of JunB Contributes to Overproduction of Type I Collagen and Development of Dermal Fibrosis in Patients With Systemic Sclerosis
Authors: Ponticos Markella , Papaioannou Ioannis , Xu Shiwen , Holmes Alan M. , Khan Korsa , Denton Christopher P. , Bou‐Gharios George , Abraham David J. 
Published: October 2014

ObjectiveThe excessive deposition of extracellular matrix, including type I collagen, is a key aspect in the pathogenesis of connective tissue diseases such as systemic sclerosis (SSc; scleroderma). To further our understanding of the mechanisms governing the dysregulation of type I collagen production in SSc, we investigated the role of the activator protein 1 (AP‐1) family of transcription factors in regulating COL1A2 transcription.MethodsThe expression and nuclear localization of AP‐1 family members (c‐Jun, JunB, JunD, Fra‐1, Fra‐2, and c‐Fos) were examined by immunohistochemistry and Western blotting in dermal biopsy specimens and explanted skin fibroblasts from patients with diffuse cutaneous SSc and healthy controls. Gene activation was determined by assessing the interaction of transcription factors with the COL1A2 enhancer using transient transfection of reporter gene constructs, electrophoretic mobility shift assays, chromatin immunoprecipitation analysis, and RNA interference involving knockdown of individual AP‐1 family members. Inhibition of fibroblast mammalian target of rapamycin (mTOR), Akt, and glycogen synthase kinase 3β (GSK‐3β) signaling pathways was achieved using small‐molecule pharmacologic inhibitors.ResultsBinding of JunB to the COL1A2 enhancer was observed, with its coalescence directed by activation of gene transcription through the proximal promoter. Knockdown of JunB reduced enhancer activation and COL1A2 expression in response to transforming growth factor β. In SSc dermal fibroblasts, increased mTOR/Akt signaling was associated with inactivation of GSK‐3β, leading to blockade of JunB degradation and, thus, constitutively high expression of JunB.ConclusionIn patients with SSc, the accumulation of JunB resulting from altered mTOR/Akt signaling and a failure of proteolytic degradation underpins the aberrant overexpression of type I collagen. These findings identify JunB as a potential target for antifibrotic therapy in SSc.
Anti–Ribosomal P Protein Autoantibodies From Patients With Neuropsychiatric Lupus Impair Memory in Mice
Authors: Bravo‐Zehnder Marcela , Toledo Enrique M. , Segovia‐Miranda Fabián , Serrano Felipe G. , Benito María J. , Metz Claudia , Retamal Claudio , Álvarez Alejandra , Massardo Loreto , Inestrosa Nibaldo C. , González Alfonso 
Published: October 2014

ObjectiveTo define whether anti‐ribosomal P (anti‐P) autoantibodies from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) impair the function of hippocampal neurons that express the neuronal surface P antigen (NSPA) when accessing the brain via circulating blood.MethodsWe used anti‐P antibodies from patients with NPSLE and rabbit‐generated anti‐P and anti‐NSPA antibodies. Primary hippocampal neurons from mice were analyzed to determine antibody cell surface binding (double immunofluorescence), intracellular calcium variations (Fura 2 AM), and apoptosis (caspase 3 activation). Hippocampal‐dependent spatial flexible memory was assessed in mice subjected to a water maze test 24 hours after an intravenous injection of anti‐P or anti‐NSPA, using lipopolysaccharide (LPS) to permeate the blood–brain barrier. Presence of antibodies and apoptosis in the hippocampus was studied using immunohistochemistry and TUNEL assays.ResultsHippocampal neurons expressed NSPA on the cell surface, as revealed by anti‐P and anti‐NSPA staining colocalization, and responded to both anti‐P and anti‐NSPA by exhibiting increased intracellular calcium levels. Neuronal apoptosis was induced when anti‐P was directly injected by stereotaxis into the hippocampus or added to primary cultures. Upon LPS treatment, intravenously injected anti‐P impaired memory but did not elicit neuronal apoptosis in the hippocampus, where it was detectable in low amounts. Anti‐NSPA antibodies also impaired memory.ConclusionAnti‐P antibodies interact with NSPA on the surface of hippocampal neurons leading to apoptotic death or to functional perturbations, results that are likely dependent on the concentration of these antibodies. Circulating anti‐P can access the hippocampus and impair memory without requiring neuronal death when the blood–brain barrier is disrupted. NSPA can mediate antibody‐driven diffuse brain dysfunction, and anti‐P might contribute to the cognitive impairment that is frequently observed in SLE.
Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease
Authors: Chen Juan , Doyle Tracy J. , Liu Yongliang , Aggarwal Rohit , Wang Xiaoping , Shi Yonghong , Ge Sheng Xiang , Huang Heqing , Lin Qingyan , Liu Wen , Cai Yongjin , Koontz Diane , Fuhrman Carl R. , Golzarri Maria F. , Liu Yushi , Hatabu Hiroto , Nishino Mizuki , Araki Tetsuro , Dellaripa Paul F. , Oddis Chester V. , Rosas Ivan O. , Ascherman Dana P. 
Published: October 2014

ObjectiveInterstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA‐associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.MethodsPatients with RA who were enrolled in a well‐characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high‐resolution computed tomography scans of the chest. Multiplex enzyme‐linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute‐phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA‐ILD and biomarkers of interest.ResultsMMP‐7 and interferon‐γ–inducible protein 10 (IP‐10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA‐ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA‐ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid‐phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA‐ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.ConclusionLevels of MMP‐7 and IP‐10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
Enhanced Chondrogenesis of Induced Pluripotent Stem Cells From Patients With Neonatal‐Onset Multisystem Inflammatory Disease Occurs via the Caspase 1–Independent cAMP/Protein Kinase A/CREB Pathway
Authors: Yokoyama Koji , Ikeya Makoto , Umeda Katsutsugu , Oda Hirotsugu , Nodomi Seishiro , Nasu Akira , Matsumoto Yoshihisa , Izawa Kazushi , Horigome Kazuhiko , Kusaka Toshimasa , Tanaka Takayuki , Saito Megumu K. , Yasumi Takahiro , Nishikomori Ryuta , Ohara Osamu , Nakayama Naoki , Nakahata Tatsutoshi , Heike Toshio , Toguchida Junya 
Published: October 2014

ObjectiveNeonatal‐onset multisystem inflammatory disease (NOMID) is a dominantly inherited autoinflammatory disease caused by NLRP3 mutations. NOMID pathophysiology is explained by the NLRP3 inflammasome, which produces interleukin‐1β (IL‐1β). However, epiphyseal overgrowth in NOMID is resistant to anti–IL‐1 therapy and may therefore occur independently of the NLRP3 inflammasome. This study was undertaken to investigate the effect of mutated NLRP3 on chondrocytes using induced pluripotent stem cells (iPSCs) from patients with NOMID.MethodsWe established isogenic iPSCs with wild‐type or mutant NLRP3 from 2 NOMID patients with NLRP3 somatic mosaicism. The iPSCs were differentiated into chondrocytes in vitro and in vivo. The phenotypes of chondrocytes with wild‐type and mutant NLRP3 were compared, particularly the size of the chondrocyte tissue produced.ResultsMutant iPSCs produced larger chondrocyte masses than wild‐type iPSCs owing to glycosaminoglycan overproduction, which correlated with increased expression of the chondrocyte master regulator SOX9. In addition, in vivo transplantation of mutant cartilaginous pellets into immunodeficient mice caused disorganized endochondral ossification. Enhanced chondrogenesis was independent of caspase 1 and IL‐1, and thus the NLRP3 inflammasome. Investigation of the human SOX9 promoter in chondroprogenitor cells revealed that the CREB/ATF‐binding site was critical for SOX9 overexpression caused by mutated NLRP3. This was supported by increased levels of cAMP and phosphorylated CREB in mutant chondroprogenitor cells.ConclusionOur findings indicate that the intrinsic hyperplastic capacity of NOMID chondrocytes is dependent on the cAMP/PKA/CREB pathway, independent of the NLRP3 inflammasome.
The Mediating Effect of Leptin on the Relationship Between Body Weight and Knee Osteoarthritis in Older Adults
Authors: Fowler‐Brown Angela , Kim Dae Hyun , Shi Ling , Marcantonio Edward , Wee Christina C. , Shmerling Robert H. , Leveille Suzanne 
Published: October 2014

ObjectiveObesity is associated with an increased risk of osteoarthritis (OA) of the knee. Emerging evidence suggests that adipokines, substances produced by adipose tissue, may play a role in the development of knee OA. The aim of this study was to determine whether the inflammatory adipokine leptin partially mediates the relationship between body mass index (BMI) and knee OA.MethodsWe used baseline data from 653 participants who were 70 years of age or older in the population‐based Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly Boston Study. Height and weight were measured, and participants were assessed for knee OA using clinical criteria. Serum leptin was measured using a microsphere‐based assay.ResultsThe average BMI and the average serum leptin level were 27.5 kg/m2 and 589 pM, respectively; the prevalence of knee OA was 24.7%. In regression models adjusted for covariates, we found that a 5‐kg/m2 increase in BMI was associated with 32% increased odds of knee OA (odds ratio [OR] 1.32, 95% confidence interval [95% CI] 1.10, 1.58); a 200‐pM increase in serum leptin levels was associated with 11% increased odds of knee OA (OR 1.11, 95% CI 1.05, 1.17). The ratio of the standardized coefficients for the indirect:total effect calculated using the product‐of‐coefficients method was 0.49, suggesting that approximately half of the total effect of BMI on knee OA may be mediated by serum leptin. The estimated 95% CIs for the mediated effect suggest that this effect is statistically significant. Similarly, mediation analysis using a counterfactual approach suggested that the effect of leptin mediation was statistically significant.ConclusionWe found that almost half of the association between elevated BMI and knee OA could be explained by the inflammatory adipokine leptin.
Chemical Approach to a New Crystal Structure: Phase Control of Manganese Oxide on a Carbon Sphere Template
Authors: Nam Ki Min , Park Joon T. 
Published: October 2014

AbstractThe stabilization and growth of a non‐native structure, hexagonal wurtzite MnO (h‐MnO), is explored via kinetic control of manganese precursor on a carbon sphere template. MnO is most stable in the cubic rock‐salt structure (c‐MnO), and a number of studies have focused on the synthesis and properties of this rock‐salt phase. However, h‐MnO has not been fully characterized before our work. Prolonged heating at a relatively low temperature yields c‐MnO, whereas rapid heating of the reaction mixture at reflux produces h‐MnO in the presence of carbon spheres. The effect of benzyl amine concentration on the formation of two different oxidation states (c‐MnO and t‐Mn3O4) was examined as well. Moreover, the structural stability of the manganese oxides and phase transition of MnO in terms of the wurtzite to rock‐salt structural transformation have been investigated.
Multivariable Output Feedback Adaptive Terminal Sliding Mode Control for Underwater Vehicles
Authors: Wang Yaoyao , Gu Linyi , Gao Ming , Zhu Kangwu 
Published: October 2014

AbstractFor the four degrees of freedom (4‐DOF) trajectory tracking control problem of underwater vehicles in the presence of parametric uncertainties and external disturbances, a novel multivariable output feedback adaptive nonsingular terminal sliding mode control (ANTSMC) approach is proposed based on the equivalent output injection adaptive sliding mode observer (ASMO) and ANTSMC method. The ASMO is applied to reconstruct the full states in finite time and the ANTSMC method is designed to stabilize the trajectory tracking error to a small field in finite time. The proposed output feedback ANTSMC approach, using the adaptive technology, does not require the bound information of parametric uncertainties or external disturbances which successfully achieves the decrease of undesired chattering effectively. Corresponding stability analysis is presented. Comparative numerical simulation results are presented to validate the effectiveness of the proposed approach.
Congestion avoidance in city traffic
Authors: Kala Rahul , Warwick Kevin 
Published: October 2014

SummaryThe number of vehicles on the road (worldwide) is constantly increasing, causing traffic jams and congestion especially in city traffic. Anticipatory vehicle routing techniques have thus far been applied to fairly small networked traffic scenarios and uniform traffic. We note here a number of limitations of these techniques and present a routing strategy on the assumption of a city map that has a large number of nodes and connectivity and where the vehicles possess highly varying speed capabilities. A scenario of operation with such characteristics has not previously been sufficiently studied in the literature. Frequent short‐term planning is preferred as compared with infrequent planning of the complete map. Experimental results show an efficiency boost when single‐lane overtaking is allowed, traffic signals are accounted for and every vehicle prefers to avoid high traffic density on a road by taking an alternative route. Comparisons with optimistic routing, pessimistic routing and time message channel routing are given. Copyright © 2014 John Wiley & Sons, Ltd.
Interactions of amelogenin with phospholipids
Authors: Bekshe Lokappa Sowmya , Balakrishna Chandrababu Karthik , Dutta Kaushik , Perovic Iva , Spencer Evans John , Moradian‐Oldak Janet 
Published: October 2014

ABSTRACTAmelogenin protein has the potential to interact with other enamel matrix proteins, mineral, and cell surfaces. We investigated the interactions of recombinant amelogenin rP172 with small unilamellar vesicles as model membranes, toward the goal of understanding the mechanisms of amelogenin–cell interactions during amelogenesis. Dynamic light scattering (DLS), fluorescence spectroscopy, circular dichroism (CD), and nuclear magnetic resonance (NMR) were used. In the presence of phospholipid vesicles, a blue shift in the Trp fluorescence emission maxima of rP172 was observed (∼334 nm) and the Trp residues of rP172 were inaccessible to the aqueous quencher acrylamide. DLS studies indicated complexation of rP172 and phospholipids, although the possibility of fusion of phospholipids following amelogenin addition cannot be ruled out. NMR and CD studies revealed a disorder–order transition of rP172 in a model membrane environment. Strong fluorescence resonance energy transfer from Trp in rP172 to DNS‐bound‐phospholipid was observed, and fluorescence polarization studies indicated that rP172 interacted with the hydrophobic core region of model membranes. Our data suggest that amelogenin has ability to interact with phospholipids and that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities. © 2014 Wiley Periodicals, Inc. Biopolymers 103: 96–108, 2015.
Training situational awareness to reduce surgical errors in the operating room
Authors: Graafland M , Schraagen J M C , Boermeester M A , Bemelman W A , Schijven M P 
Published: October 2014

Abstract

Background
Surgical errors result from faulty decision-making, misperceptions and the application of suboptimal problem-solving strategies, just as often as they result from technical failure. To date, surgical training curricula have focused mainly on the acquisition of technical skills. The aim of this review was to assess the validity of methods for improving situational awareness in the surgical theatre.

Methods
A search was conducted in PubMed, Embase, the Cochrane Library and PsycINFO® using predefined inclusion criteria, up to June 2014. All study types were considered eligible. The primary endpoint was validity for improving situational awareness in the surgical theatre at individual or team level.

Results
Nine articles were considered eligible. These evaluated surgical team crisis training in simulated environments for minimally invasive surgery (4) and open surgery (3), and training courses focused at training non-technical skills (2). Two studies showed that simulation-based surgical team crisis training has construct validity for assessing situational awareness in surgical trainees in minimally invasive surgery. None of the studies showed effectiveness of surgical crisis training on situational awareness in open surgery, whereas one showed face validity of a 2-day non-technical skills training course.

Conclusion
To improve safety in the operating theatre, more attention to situational awareness is needed in surgical training. Few structured curricula have been developed and validation research remains limited. Strategies to improve situational awareness can be adopted from other industries.
A validated LC‐MS/MS assay for simultaneous quantification of methotrexate and tofacitinib in rat plasma: application to a pharmacokinetic study
Authors: Sharma Kuldeep , Giri Kalpeshkumar , Dhiman Vinay , Dixit Abhishek , Zainuddin Mohd , Mullangi Ramesh 
Published: October 2014

AbstractA highly sensitive, specific and rapid LC‐ESI‐MS/MS method has been developed and validated for simultaneous quantification of methotrexate (MTX) and tofacitinib (TFB) in rat plasma (50 μL) using phenacetin as an internal standard (IS), as per the US Food and Drug Administration guidelines. After a solid‐phase extraction procedure, the separation of the analytes and IS was performed on a Chromolith RP18e column using an isocratic mobile phase of 5 m m ammonium acetate (pH 5.0) and acetonitrile at a ratio of 25:75 (v/v) using flow‐gradient with a total run time of 3.5 min. The detection was performed in multiple reaction monitoring mode, using the transitions of m/z 455.2 → 308.3, m/z 313.2 → 149.2 and m/z 180.3 → 110.2 for MTX, TFB and IS, respectively. The calibration curves were linear over the range of 0.49–91.0 and 0.40–74.4 ng/mL for MTX and TFB, respectively. The intra‐ and interday accuracy and precision values for MTX and TFB were <15% at low quality control (QC), medium QC and high QC and <20% at lower limit of quantification. The validated assay was applied to derive the pharmacokinetic parameters for MTX and TFB post‐dosing of MTX and TFB orally and intravenously to rats. Copyright © 2014 John Wiley & Sons, Ltd.
Validation of HPLC‐UV method for determination of minor glycosides contained in Stevia rebaudiana Bertoni leaves
Authors: Aranda‐González Irma , Moguel‐Ordoñez Yolanda , Betancur‐Ancona David 
Published: October 2014

AbstractLeaves of Stevia rebaudiana contain glycosides with sweetness and biological activity. However besides the major glycosides, there are other glycosides within extracts that may contribute to its activity, and therefore it is important to quantify them. In this work, an isocratic HPLC method was validated for determination of dulcoside A, steviolbioside, rebaudioside C and rebaudioside B. An HPLC method was performed using a C18 column (250 × 4.6 mm, particle size 5 µm) and a UV detector set at 210 nm. The mobile phase consisted of a 32:68 (v/v) mixture of acetonitrile and sodium phosphate buffer (10 mmol/L, pH 2.6), set to a flow rate of 1.0 mL/min. The calculated parameters were: sensitivity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy and precision. The calibration curves were linear over the working range 25–150 µg/mL, with coefficient of correlation of ≥0.99 and coefficient of determination of ≥0.98. The LOD was 5.68–8.81 µg/mL, while the LOQ was 17.21–26.69 µg/mL. The percentage recoveries of fortified samples were 100 ± 10% and precision, relative standard deviation, was <10%. The method validation showed accuracy, linearity and precision; therefore this method can be applied for quantitative analysis of minor steviol glycosides in S. rebaudiana leaves. Copyright © 2014 John Wiley & Sons, Ltd.