bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Toronto Psoriatic Arthritis Screen Version 2 (ToPAS 2)
Authors: Tom Brian D.M. , Chandran Vinod , Farewell Vernon T. , Rosen Cheryl F. , Gladman Dafna D. 
Published: April 2015

Objective.We previously developed and performed an initial validation of a screening questionnaire, the Toronto Psoriatic Arthritis Screen (ToPAS), for psoriatic arthritis (PsA). In our original analysis, we found that the index constructed appeared to discriminate well between those with a confirmed diagnosis of PsA and those without PsA in various clinical settings. However, it was suggested that ToPAS would benefit from additional refinement to the questions and the scoring system, because items pertaining to axial involvement were not included in our original index. Subsequently, a second version of ToPAS was developed, ToPAS 2, which incorporated the suggested refinements. We aimed to validate ToPAS 2 as a screening instrument for PsA.Methods.ToPAS 2 was administered to 3 “diagnostic” groups of individuals — patients with PsA, patients with psoriasis, and healthy controls, and the data collected were analyzed.Results.It was found that the new version of ToPAS, ToPAS 2, again performed well, with the axial domain now featuring in the new scoring system. The constructed index, ToPAS2_cap, had an overall area under the receiver-operation curve of 0.910, with overall values of sensitivity and specificity, at a cutpoint of 8 (or 7), of 87.2% (92.0%) and 82.7% (77.2%), respectively.Conclusion.ToPAS 2 shows much promise as a screening instrument for identifying PsA both in people with psoriasis and in individuals from the general population. Its performance against other proposed screening instruments for PsA should be evaluated in other clinics and for other study designs.
Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing
Authors: Rao Deepak A. , Wei Kevin , Merola Joseph F. , O’Brien William R. , Takvorian Samuel U. , Dellaripa Paul F. , Schur Peter H. 
Published: April 2015

Objective.Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution.Methods.We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period.Results.Of the 2345 samples tested over 2 years, 1998 were IF-negative. Among these IF-negative samples, 49 samples (2.5%) derived from 38 patients tested positive for MPO-ANCA or PR3-ANCA. Only 1 IF-negative, MPO/PR3-positive patient was subsequently diagnosed with ANCA-associated vasculitis (AAV). Eleven IF-negative, MPO/PR3-positive patients (29%) had been previously diagnosed and treated for AAV, all with positive IF and antibody tests prior to treatment. Four patients had evidence of cutaneous vasculitis not attributed to AAV, while several of the remaining IF-negative, MPO/PR3-positive patients had other immunologic disorders, including systemic lupus erythematosus (5 patients) and inflammatory bowel disease (3 patients).Conclusion.In this real-life cohort assayed simultaneously by IF and multiplexed bead assays, the detection of MPO-ANCA or PR3-ANCA without a positive IF rarely led to a new diagnosis of systemic vasculitis, and was more likely to occur in the context of a non-vasculitic inflammatory condition. Our results suggest that concurrent IF and MPO/PR3 testing may be of limited use in preventing a missed diagnosis of new-onset AAV.
Counting Costs under Severe Financial Constraints: A Cost-of-Illness Analysis of Spondyloarthropathies in a Tertiary Hospital in Greece
Authors: Tsifetaki Niki , Migkos Michail P. , Papagoras Charalampos , Voulgari Paraskevi V. , Athanasakis Kostas , Drosos Alexandros A. 
Published: April 2015

Objective.To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece.Methods.Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros.Results.The mean ± SD annual direct cost for the patients with SpA reached €8680 ± 6627. For the patients with PsA and AS, the cost was estimated to be €8097 ± 6802 and €9531 ± 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA.Conclusion.SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments.
Longterm Efficacy and Safety of Abatacept in Patients with Rheumatoid Arthritis Treated in Routine Clinical Practice: Effect of Concomitant Methotrexate after 24 Weeks
Authors: Takahashi Nobunori , Kojima Toshihisa , Kaneko Atsushi , Kida Daihei , Hirano Yuji , Fujibayashi Takayoshi , Yabe Yuichiro , Takagi Hideki , Oguchi Takeshi , Miyake Hiroyuki , Kato Takefumi , Watanabe Tsuyoshi , Hayashi Masatoshi , Kanayama Yasuhide , Funahashi Koji , Asai Shuji , Yoshioka Yutaka , Takemoto Toki , Terabe Kenya , Asai Nobuyuki , Ishiguro Naoki 
Published: April 2015

Objective.Our study aimed to evaluate the longterm efficacy and safety of abatacept (ABA), and to explore factors that increase its longterm efficacy in patients with rheumatoid arthritis (RA) treated in routine clinical practice.Methods.There were 231 participants with RA treated with ABA who were prospectively registered in a Japanese multicenter registry. They were followed up for at least 52 weeks.Results.Mean age of the patients was 64.3 years, mean disease duration was 12.1 years, mean 28-joint Disease Activity Score (DAS28)-C-reactive protein was 4.49, and 48.5% of patients were concomitantly treated with methotrexate (MTX). Overall retention rate of ABA was 77.1% at 52 weeks; 14.8% of patients discontinued because of inadequate response and 3.5% because of adverse events. The proportion of patients achieving DAS28-defined low disease activity (LDA) significantly increased from baseline to 52 weeks (7.3% to 43.8%, p < 0.01); 40.9% of patients who did not achieve LDA at 24 weeks had more than 1 categorical improvement in DAS28-defined disease activity at 52 weeks. Multivariate logistic regression revealed concomitant MTX use to be an independent predictor of the categorical improvement in DAS28-defined disease activity from 24 to 52 weeks (adjusted OR 3.124, p = 0.010).Conclusion.In routine clinical practice, ABA demonstrated satisfactory clinical efficacy and safety in patients with established RA for 52 weeks. The clinical efficacy of ABA increased with time even after 24 weeks, and this was strongly influenced by concomitant MTX use. Our study provides valuable real-world findings on the longterm management of RA with ABA.
Prediction of shear‐wave velocity from CPT data at Eskisehir (Turkey), using a polynomial model
Authors: Mola‐Abasi H. , Dikmen U. , Shooshpasha I. 
Published: April 2015

ABSTRACTIt is widely known that seismic shear‐wave velocity is one of the most important parameters in site characterization studies. In some instances, it is necessary to determine shear‐wave velocity indirectly from common in situ tests, such as the cone penetration test. There are numerous earlier studies showing this possibility. In this study, the relation between shear‐wave velocity and subsoil geotechnical properties, e.g., cone‐tip resistance and sleeve friction from cone penetration test is reinvestigated in a study area located in Eskisehir, Turkey. New polynomial models are proposed for the correlation. A total of 437 samples extracted from 37 sites made of clay, sand, sand‐clay mixture, and miscellaneous soil types have been used. We compare our results involving polynomial fitting with earlier results of statistical correlation using power‐law or logarithmic relations between shear‐wave velocity and cone‐tip resistance or sleeve friction. The predicted values using our model are checked against the measured ones to evaluate the performance of the polynomial model. The results suggest that the newly proposed approach provides a means for recognizing more efficiently the patterns in the data and reliably predicting the shear‐wave velocity. Additionally, the sensitivity analysis reveals the influence of parameters and the contribution of each coefficient in the polynomial model. Cone penetration test cone‐tip resistance relates more strongly than sleeve friction to shear‐wave velocity. The intercept term in the polynomial is of primary importance in such correlation, for all soil types.
PLZF Regulates CCR6 and Is Critical for the Acquisition and Maintenance of the Th17 Phenotype in Human Cells
Authors: Singh Satya P. , Zhang Hongwei H. , Tsang Hsinyi , Gardina Paul J. , Myers Timothy G. , Nagarajan Vijayaraj , Lee Chang Hoon , Farber Joshua M. 
Published: April 2015

Abstract
Th17 cells, which express the chemokine receptor CCR6, are implicated in many immune-mediated disorders, such as psoriasis and multiple sclerosis. We found that expression levels of CCR6 on human effector/memory CD4+ T cells reflect a continuum of Th17 differentiation. By evaluating the transcriptome in cells with increasing CCR6, we detected progressive upregulation of ZBTB16, which encodes the broad complex, tramtrack, bric-à-brac–zinc finger transcription factor promyelocytic leukemia zinc finger protein (PLZF). Using chromatin immunoprecipitation for modified histones, p300, and PLZF, we identified enhancer-like sites at −9/−10 and −13/−14 kb from the upstream transcription start site of CCR6 that bind PLZF in CCR6+ cells. For Th cells from adult blood, both in the CCR6+ memory population and in naive cells activated ex vivo, knockdown of ZBTB16 downregulated CCR6 and other Th17-associated genes. ZBTB16 and RORC (which encodes the “master regulator” RORγt) cross-regulate each other, and PLZF binds at the RORC promoter in CCR6+ cells. In naive Th cells from cord blood, ZBTB16 expression was confined to CD161+ cells, which are Th17 cell precursors. ZBTB16 was not expressed in mouse Th17 cells, and Th17 cells could be made from luxoid mice, which harbor an inactivating mutation in Zbtb16. These studies demonstrate a role for PLZF as an activator of transcription important both for Th17 differentiation and the maintenance of the Th17 phenotype in human cells, expand the role of PLZF as a critical regulator in the human adaptive immune system, and identify a novel, essential element in a regulatory network that is of significant therapeutic interest.
Internal Medicine Residents' Perspectives on Receiving Feedback in Milestone Format
Authors: Angus Steven , Moriarty John , Nardino Robert J. , Chmielewski Amy , Rosenblum Michael J. 
Published: April 2015

Abstract

Background
In contrast to historical feedback, which was vague or provided residents' numerical scores without clear meaning, milestone-based feedback is focused on specific knowledge, skills, and behaviors that define developmental trajectory. It was anticipated that residents would welcome the more specific and actionable feedback provided by the milestone framework, but this has not been studied.

Objective
We assessed internal medicine (IM) residents' perceptions of receiving feedback in the milestone framework, particularly assessing perception of the utility of milestone-based feedback compared to non–milestone-based feedback.

Methods
We surveyed a total of 510 IM residents from 7 institutions. Survey questions assessed resident perception of milestone feedback in identifying strengths, weaknesses, and trajectory of professional development. Postgraduate years 2 and 3 (PGY-2 and PGY-3) residents were asked to compare milestones with prior methods of feedback.

Results
Of 510 residents, 356 (69.8%) responded. Slightly less than half of the residents found milestone-based feedback “extremely useful” or “very useful” in identifying strengths (44%), weaknesses (43%), specific areas for improvement (45%), and appropriate education progress (48%). Few residents found such feedback “not very useful” or “not at all useful” in these domains. A total of 51% of PGY-2 and PGY-3 residents agreed that receiving milestone-based feedback was more helpful than previous forms of feedback.

Conclusions
IM residents are aware of the concepts of milestones, and half of the residents surveyed found milestone feedback more helpful than previous forms of feedback. More work needs to be done to understand how milestone-based feedback could be delivered more effectively to enhance resident development.
Mastery of Status Epilepticus Management via Simulation-Based Learning for Pediatrics Residents
Authors: Malakooti Marcelo R. , McBride Mary E. , Mobley Bonnie , Goldstein Joshua L. , Adler Mark D. , McGaghie William C. 
Published: April 2015

Abstract

Background
Management of status epilepticus (SE) in the pediatric population is highly time-sensitive. Failure to follow a standard management algorithm may be due to ineffective provider education, and can lead to unfavorable outcomes.

Objective
To design a learning module using high-fidelity simulation technology to teach mastery achievement of a hospital algorithm for managing SE.

Methods
Thirty pediatrics interns were enrolled. Using the Angoff method, an expert panel developed the minimal passing score, which defined mastery. Scoring of simulated performance was done by 2 observers. Sessions were digitally recorded. After the pretest, participants were debriefed on the algorithm and required to repeat the simulation. If mastery (minimal passing score) was not achieved, debriefing and the simulation were repeated until mastery was met. Once mastery was met, participants graded their comfort level in managing SE.

Results
No participants achieved mastery at pretest. After debriefing and deliberate simulator training, all (n = 30) achieved mastery of the algorithm: 30% achieved mastery after 1 posttest, 63% after a second, and 6.7% after a third. The Krippendorff α was 0.94, indicating strong interrater agreement. Participants reported more self-efficacy in managing SE, a preference for simulation-based education for learning practice-based algorithms of critical conditions, and highly rated the educational intervention.

Conclusions
A simulation-based mastery learning program using deliberate practice dramatically improves pediatrics residents' execution of a SE management protocol. Participants enjoyed and benefited from simulation education. Future applications include improving adherence to other hospital protocols.
Tracking Neuronal Migration in Adult Brain Slices
Authors: Bakhshetyan Karen , Saghatelyan Armen 
Published: April 2015

AbstractNeuronal migration is one of the fundamental processes underlying the proper assembly and function of neural circuitry. The majority of neuronal precursors are generated far away from their sites of integration and need to migrate substantial distances to reach their final destination. Neuronal migration occurs not only in the embryonic brain but also in a few regions of the adult brain such as the olfactory bulb (OB). The mechanisms orchestrating cell migration in the adult brain are, however, poorly understood, despite their clinical relevance. Here we describe a method for time‐lapse imaging of cell migration in acute brain slices. This method, combined with genetic and/or pharmacological manipulations of different molecular pathways, makes it possible to determine the dynamics and molecular mechanisms of cell migration in the adult brain. In addition, time‐lapse imaging in acute brain slices makes it possible to monitor cell movement in a microenvironment that closely resembles in vivo conditions and to study neuroblast displacement along with other cellular elements such as astrocytes and blood vessels. © 2015 by John Wiley & Sons, Inc.
Mapping Regulatory Factors by Immunoprecipitation from Native Chromatin
Authors: Orsi Guillermo A. , Kasinathan Sivakanthan , Zentner Gabriel E. , Henikoff Steven , Ahmad Kami 
Published: April 2015

AbstractOccupied Regions of Genomes from Affinity‐purified Naturally Isolated Chromatin (ORGANIC) is a high‐resolution method that can be used to quantitatively map protein‐DNA interactions with high specificity and sensitivity. This method uses micrococcal nuclease (MNase) digestion of chromatin and low‐salt solubilization to preserve protein‐DNA complexes, followed by immunoprecipitation and paired‐end sequencing for genome‐wide mapping of binding sites. In this unit, we describe methods for isolation of nuclei and MNase digestion of unfixed chromatin, immunoprecipitation of protein‐DNA complexes, and high‐throughput sequencing to map sites of bound factors. © 2015 by John Wiley & Sons, Inc.
Toll‐Like Receptors
Authors: Takeda Kiyoshi , Akira Shizuo 
Published: April 2015

AbstractThe mammalian Toll‐like receptor (TLR) family consists of 13 members, and recognizes specific patterns of microbial components, called pathogen‐associated molecular patterns (PAMPs). TLR‐dependent recognition of PAMPs leads to activation of the innate immune system, which subsequently leads to activation of antigen‐specific adaptive immunity. The TLR‐mediated signaling pathways consist of the MyD88‐dependent pathway and TRIF‐dependent pathway, both of which induce gene expression. This unit discusses mammalian TLRs (TLR1 to 13) that have an essential role in the innate immune recognition of microorganisms. Also discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs. © 2015 by John Wiley & Sons, Inc.
Effects of injected ice particles in the lower stratosphere on the Antarctic ozone hole
Authors: Nagase H. , Kinnison D. E. , Petersen A. K. , Vitt F. , Brasseur G. P. 
Published: March 2015

AbstractThe Antarctic ozone hole will continue to be observed in the next 35–50 years, although the emissions of chlorofluorocarbons (CFCs) have gradually been phased out during the last two decades. In this paper, we suggest a geo‐engineering approach that will remove substantial amounts of hydrogen chloride (HCl) from the lower stratosphere in fall, and hence limit the formation of the Antarctic ozone hole in late winter and early spring. HCl will be removed by ice from the atmosphere at temperatures higher than the threshold under which polar stratospheric clouds (PSCs) are formed if sufficiently large amounts of ice are supplied to produce water saturation. A detailed chemical‐climate numerical model is used to assess the expected efficiency of the proposed geo‐engineering method, and specifically to calculate the removal of HCl by ice particles. The size of ice particles appears to be a key parameter: larger particles (with a radius between 10 and 100 µm) appear to be most efficient for removing HCl. Sensitivity studies lead to the conclusions that the ozone recovery is effective when ice particles are supplied during May and June in the latitude band ranging from 70°S to 90°S and in the altitude layer ranging from 10 to 26 km. It appears, therefore, that supplying ice particles to the Antarctic lower stratosphere could be effective in reducing the depth of the ozone hole. In addition, photodegradation of CFCs might be accelerated when ice is supplied due to enhanced vertical transport of this efficient greenhouse gas.
Parameters controlling dynamically self‐consistent plate tectonics and single‐sided subduction in global models of mantle convection
Authors: Crameri Fabio , Tackley Paul J. 
Published: March 2015

AbstractRecent advances in numerical modeling allow global models of mantle convection to more realistically reproduce the behavior at convergent plate boundaries; in particular, the inclusion of a free surface at the outer boundary has been shown to facilitate self‐consistent development of single‐sided subduction. This allows for a more extensive study of subduction in the context of global mantle convection, as opposed to commonly used regional models. Our first study already indicated important differences between mantle convection with single‐sided subduction and mantle convection with double‐sided subduction. Here we further investigate the effect of various physical parameters and complexities on inducing Earth‐like plate tectonics and its evolution in time. Results reinforce the previous finding that using a free surface instead of a free‐slip outer boundary dramatically changes subduction style, with free surface cases displaying many episodes of single‐sided subduction, which leads to more realistic slab dip, stress state, trench retreat rate, and slab‐induced mantle flow. Longevity of single‐sided subduction is promoted by a layer of hydrated crust with a low yield strength to lubricate the subduction channel, a low‐viscosity asthenosphere, and a high strength of the slab (determined by a combination of high‐diffusion creep viscosity and intermediate friction coefficient), although its effective viscosity is in the observationally constrained range in the bending region. The time evolution displays interesting events including subduction polarity reversals, subduction shut‐off, and slab break‐off.
Impact of Shanghai urban land surface forcing on downstream city ozone chemistry
Authors: Zhu Bin , Kang Hanqing , Zhu Tong , Su Jifeng , Hou Xuewei , Gao Jinhui 
Published: March 2015

AbstractThe urban land surface has a significant impact on local urban heat island effects and air quality. In addition, it influences the atmospheric conditions and air quality in the downwind cities. In this study, the impact of Shanghai urban land surface forcing on weather conditions and air quality over Kunshan was investigated using the Weather Research and Forecasting model coupled with a multilayer urban canopy model and the Community Multiscale Air Quality model. Two simulations were conducted to identify the impact of upstream effects with and without upstream urban land surfaces in control and sensitivity experiments. The results show that the near‐surface temperature and boundary layer height over Kunshan increased significantly with the appearance of the upstream urban land surface. Horizontal transport of O3 and its precursors, from Shanghai to Kunshan, are suppressed in the lower boundary layer but are strengthened in the upper boundary layer because of strong urban heat island circulation. As a result, O3 chemical production is decreased in the lower boundary layer of Kunshan but is increased in the upper boundary layer. On average, daytime O3 concentrations over Kunshan are decreased by approximately 2 ppbv in the lower boundary layer but are increased by as much as 40 ppbv in the upper air.