bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Health Costs of Inflammatory Polyarthritis 10 Years after Disease Onset: Results from the Norfolk Arthritis Register
Authors: Nikiphorou Elena , Davies Charlotte , Mugford Miranda , Cooper Nicola , Brooksby Alan , Bunn Diane K. , Young Adam , Verstappen Suzanne M.M. , Symmons Deborah P.M. , MacGregor Alex J. 
Published: April 2015

Objectives.To explore the change in direct medical costs associated with inflammatory polyarthritis (IP) 10 to 15 years after its onset.Methods.Patients from the Norfolk Arthritis Register who had previously participated in a health economic study in 1999 were traced 10 years later and invited to participate in a further prospective questionnaire-based study. The study was designed to identify direct medical costs and changes in health status over a 6-month period using previously validated questionnaires as the primary source of data.Results.A representative sample of 101 patients with IP from the 1999 cohort provided complete data over the 6-month period. The mean disease duration was 14 years (SD 2.1, median 13.6, interquartile range 12.6–15.4). The mean direct medical cost per patient over the 6-month period was £1496 for IP (inflated for 2013 prices). This compared with £582 (95% CI £355–£964) inflated to 2013 prices per patient with IP 10 years earlier in their disease. The increased cost was largely associated with the use of biologics in the rheumatoid arthritis subgroup of patients (51% of total costs incurred). Other direct cost components included primary care costs (11%), hospital outpatient (19%), day care (12%), and inpatient stay (4%).Conclusion.The direct healthcare costs associated with IP have more than doubled with increasing disease duration, largely as a result of the use of biologics. The results showed a shift in the direct health costs from inpatient to outpatient service use.
The Effect of Disease Severity and Comorbidity on Length of Stay for Orthopedic Surgery in Rheumatoid Arthritis: Results from 2 UK Inception Cohorts, 1986–2012
Authors: Nikiphorou Elena , Morris Stephen , Dixey Josh , Williams Peter L. , Kiely Patrick , Walsh David A. , MacGregor Alex , Young Adam 
Published: April 2015

Objective.To examine factors predicting length of stay (LoS) for orthopedic intervention in rheumatoid arthritis (RA).Methods.LoS for orthopedic intervention was examined in 2 consecutive, multicenter inception cohorts: the Early RA Study (n = 1465, 9 centers) and the Early RA Network (n = 1236, 23 centers). Date, type of orthopedic procedure, and LoS were recorded and validated against national data, the UK National Joint Registry, and the UK Hospital Episode Statistics database. Clinical, laboratory, and radiographic measures and comorbidity recorded at baseline and annually were examined for their predictive power on LoS using regression analysis.Results.A total of 770 of 2701 patients (28.5%) had 1602 orthopedic interventions: 40% major (mainly total hip/knee replacements), 24% intermediate (mainly hand/wrist and ankle/foot surgery), and 16% minor (mainly soft tissue surgery). Median (interquartile range) LoS was 8 (5–13), 3 (1–5), and 1 (0–2) days for major, intermediate, and minor interventions, respectively. Older age predicted longer LoS (p < 0.001) whereas a more recent operation year predicted shorter LoS (p < 0.001). Markers of active disease, namely low hemoglobin, high Health Assessment Questionnaire, and high Disease Activity Scores in the first year all predicted longer LoS for all types of surgery (p = 0.001, p < 0.001, p = 0.05, respectively). Presence of 1 or more major comorbidities predicted longer LoS (p < 0.001).Conclusion.Comorbidity and standard clinical and laboratory markers of disease activity affect the LoS for orthopedic surgery in RA, which has important clinical and economic implications, providing a target for improving patient outcomes.
Yoga in Sedentary Adults with Arthritis: Effects of a Randomized Controlled Pragmatic Trial
Authors: Moonaz Steffany Haaz , Bingham Clifton O. , Wissow Lawrence , Bartlett Susan J. 
Published: April 2015

Objective.To evaluate the effect of Integral-based hatha yoga in sedentary people with arthritis.Methods.There were 75 sedentary adults aged 18+ years with rheumatoid arthritis (RA) or knee osteoarthritis randomly assigned to 8 weeks of yoga (two 60-min classes and 1 home practice/wk) or waitlist. Poses were modified for individual needs. The primary endpoint was physical health [Medical Outcomes Study Short Form-36 (SF-36) physical component summary (PCS)] adjusted for baseline; exploratory adjusted outcomes included fitness, mood, stress, self-efficacy, SF-36 health-related quality of life (HRQOL), and RA disease activity. In everyone completing yoga, we explored longterm effects at 9 months.Results.Participants were mostly female (96%), white (55%), and college-educated (51%), with a mean (SD) age of 52 years (12 yrs). Average disease duration was 9 years and 49% had RA. At 8 weeks, yoga was associated with significantly higher PCS (6.5, 95% CI 2.0–10.7), walking capacity (125 m, 95% CI 15–235), positive affect (5.2, 95% CI 1.4–8.9), and lower Center for Epidemiologic Studies Depression Scale (−3.0, 95% CI −4.8 – −1.3). Significant improvements (p < 0.05) were evident in SF-36 role physical, pain, general health, vitality, and mental health scales. Balance, grip strength, and flexibility were similar between groups. Twenty-two out of 28 in the waitlist group completed yoga. Among all yoga participants, significant (p < 0.05) improvements were observed in mean PCS, flexibility, 6-min walk, and all psychological and most HRQOL domains at 8 weeks with most still evident 9 months later. Of 7 adverse events, none were associated with yoga.Conclusion.Preliminary evidence suggests yoga may help sedentary individuals with arthritis safely increase physical activity, and improve physical and psychological health and HRQOL. Clinical Trials NCT00349869.
Outcome Domains and Measures in Total Joint Replacement Clinical Trials: Can We Harmonize Them? An OMERACT Collaborative Initiative
Authors: Singh Jasvinder A. , Dohm Michael , Sprowson Andrew P. , Wall Peter D. , Richards Bethan L. , Gossec Laure , Hawker Gillian A. , Riddle Daniel L. , Buchbinder Rachelle 
Published: April 2015

Objective.To develop a plan for harmonizing outcomes for people undergoing total joint replacement (TJR), to achieve consensus regarding TJR outcome research.Methods.The TJR working group met during the 2014 Outcome Measures in Rheumatology (OMERACT) 12 meeting in Budapest, Hungary. Multiple conference calls preceded the face-to-face meeting. Brief presentations were made during a 1.5-h meeting, which included an overview of published systematic reviews of TJR trials and the results of a recent systematic review of TJR clinical trial outcome domains and measures. This was followed by discussion of potential core set areas/domains for TJR clinical trials (as per OMERACT Filter 2.0) as well as the challenges associated with the measurement of these domains.Results.Working group participants discussed which TJR clinical trial outcome domains/areas map to the inner versus outer core for core domain set. Several challenges were identified with TJR outcomes including how to best measure function after TJR, elucidating the source of the pre- and post-TJR joint pain being measured, joint-specific versus generic quality of life instruments and the importance of patient satisfaction and revision surgery as outcomes. A preliminary core domain set for TJR clinical trials was proposed and included pain, function, patient satisfaction, revision, adverse events, and death. This core domain set will be further vetted with a broader audience.Conclusion.An international effort with active collaboration with the orthopedic community to standardize key outcome domains and measures is under way with the TJR working group. This effort will be further developed with new collaborations.
L’Europe, combien de divisions ?
Authors: Martinache Igor 
Published: April 2015

L’Europe cristallise aujourd’hui bien des tensions. Mais, de même qu’elle représente une construction institutionnelle sans précédent, les débats qu’elle suscite ne suivent pas les lignes de clivage habituelles, obligeant à sortir des alternatives simplistes et à réinterroger des notions que l’on croyait familières : marché, démocratie, intégration, solidarité sociale et bien d’autres. Une seule chose est sûre : si elle divise aujourd’hui, il ne faudrait pas oublier en ces temps agités que l’Union fait la force.
La construction européenne : un refus originel de la démocratie
Authors: Salais Robert 
Published: April 2015

Nombre d’économistes (et, plus largement, d’Européens) s’étonnent que si peu soit fait, pour transformer en profondeur les règles du marché et de la finance à l’échelle mondiale et sortir de la crise économique. En fait, l’issue recherchée par les tenants de l’ordre mondial marchand financiarisé est avant tout politique. Pour paraphraser le Guépard dans le livre de Giuseppe Tomasi di Lampedusa, comment tout bouger sans que rien ne change ? La conjecture [1] est que la construction européenne constitue une sorte de laboratoire grandeur nature de certaines des solutions politiques envisagées pour sauvegarder cet ordre mondial. L’un des principaux enjeux réside dans le contrôle des aspirations des peuples. Pour éviter cela, comment continuer à les impliquer dans l’existant sans pour autant céder à ces aspirations 1 ?
Les métamorphoses de l’intégration
Authors: Favell Adrian 
Published: April 2015

La pensée progressiste envisage généralement l’« intégration » comme la finalité ultime du processus d’immigration. Néanmoins, face à la montée de sentiments anti-immigrés en Europe – ces derniers ciblant désormais tout autant des citoyens européens de l’Est et du Sud que les Musulmans ou les Africains sans-papiers – la pertinence de ce concept nécessite d’être remis en question.
Survival of Effector CD8+ T Cells during Influenza Infection Is Dependent on Autophagy
Authors: Schlie Katrin , Westerback Ashley , DeVorkin Lindsay , Hughson Luke R. , Brandon Jillian M. , MacPherson Sarah , Gadawski Izabelle , Townsend Katelin N. , Poon Vincent I. , Elrick Mary A. , Côté Helene C. F. , Abraham Ninan , Wherry E. John , Mizushima Noboru , Lum Julian J. 
Published: April 2015

Abstract
The activation and expansion of effector CD8+ T cells are essential for controlling viral infections and tumor surveillance. During an immune response, T cells encounter extrinsic and intrinsic factors, including oxidative stress, nutrient availability, and inflammation, that can modulate their capacity to activate, proliferate, and survive. The dependency of T cells on autophagy for in vitro and in vivo activation, expansion, and memory remains unclear. Moreover, the specific signals and mechanisms that activate autophagy in T effector cells and their survival are not known. In this study, we generated a novel inducible autophagy knockout mouse to study T cell effector responses during the course of a virus infection. In response to influenza infection, Atg5−/− CD8+ T cells had a decreased capacity to reach the peak effector response and were unable to maintain cell viability during the effector phase. As a consequence of Atg5 deletion and the impairment in effector-to-memory cell survival, mice fail to mount a memory response following a secondary challenge. We found that Atg5−/− effector CD8+ T cells upregulated p53, a transcriptional state that was concomitant with widespread hypoxia in lymphoid tissues of infected mice. The onset of p53 activation was concurrent with higher levels of reactive oxygen species (ROS) that resulted in ROS-dependent apoptotic cell death, a fate that could be rescued by treating with the ROS scavenger N-acetylcysteine. Collectively, these results demonstrate that effector CD8+ T cells require autophagy to suppress cell death and maintain survival in response to a viral infection.
Global Broadband Benchmarking 2013: Best Practice Lessons for Governments
Authors: Roetter Martyn F. 
Published: April 2015

Abstract
Is there a “one size fits all” set of international best practices for broadband policy? No, argues Martyn Roetter, because local circumstances are far too diverse. However, he says that there are many useful lessons to be drawn from experiences in different parts of the world. He reviews successful broadband projects in fifteen countries from five regions: Latin America, Africa, Asia, Europe, and North America. Based on these examples, and acknowledging their differences, Mr. Roetter distills common characteristics of successful (and unsuccessful) broadband policies in the areas of public-private partnerships, public funding of broadband, effectively competitive markets, spectrum management, and the role of government intervention. Ultimately, he concludes that the roles of government and the private sector must be complementary.
Human Pluripotent Stem Cell-Derived Radial Glia Recapitulate Developmental Events and Provide Real-Time Access to Cortical Neurons and Astrocytes
Authors: Duan Lishu , Peng Chian-Yu , Pan Liuliu , Kessler John A. 
Published: April 2015

Abstract

Studies of human cerebral cortex development are limited by difficulties in accessing and manipulating human neural tissue at specific development stages. We have derived human radial glia (hRG), which are responsible for most cerebral cortex neurogenesis, from human pluripotent stem cells. These hRG display the hallmark morphological, cellular, and molecular features of radial glia in vitro. They can be passaged and generate layer-specific subtypes of cortical neurons in a temporal and passage-dependent fashion. In later passages, they adopt a distinct progenitor phenotype that gives rise to cortical astrocytes and GABAergic interneurons. These hRG are also capable of following developmental cues to engraft, differentiate, migrate, and integrate into the embryonic mouse cortex when injected into E14 lateral ventricles. Moreover, hRG-derived cells can be cryopreserved at specific stages and retain their stage-specific phenotypes and competence when revived. Our study demonstrates that cultured hRG maintain a cell-intrinsic clock that regulates the progressive generation of stage-specific neuronal and glial subtypes. It also describes an easily accessible cell source for studying hRG lineage specification and progression and an on-demand supply of specific cortical neuron subtypes and astrocytes.

Significance
This study describes a protocol that uses human pluripotent stem cells to differentiate into radial glia and, in turn, generate a large number of cortical pyramidal neurons, interneurons, and astrocytes that are important for both mechanistic studies and use in cellular replacement therapy.
Inhibition of an NAD+ Salvage Pathway Provides Efficient and Selective Toxicity to Human Pluripotent Stem Cells
Authors: Kropp Erin M. , Oleson Bryndon J. , Broniowska Katarzyna A. , Bhattacharya Subarna , Chadwick Alexandra C. , Diers Anne R. , Hu Qinghui , Sahoo Daisy , Hogg Neil , Boheler Kenneth R. , Corbett John A. , Gundry Rebekah L. 
Published: April 2015

Abstract

The tumorigenic potential of human pluripotent stem cells (hPSCs) is a major limitation to the widespread use of hPSC derivatives in the clinic. Here, we demonstrate that the small molecule STF-31 is effective at eliminating undifferentiated hPSCs across a broad range of cell culture conditions with important advantages over previously described methods that target metabolic processes. Although STF-31 was originally described as an inhibitor of glucose transporter 1, these data support the reclassification of STF-31 as a specific NAD+ salvage pathway inhibitor through the inhibition of nicotinamide phosphoribosyltransferase (NAMPT). These findings demonstrate the importance of an NAD+ salvage pathway in hPSC biology and describe how inhibition of NAMPT can effectively eliminate hPSCs from culture. These results will advance and accelerate the development of safe, clinically relevant hPSC-derived cell-based therapies.

Significance
The tumorigenic potential of human pluripotent stem cells (hPSCs) is a major limitation to the widespread use of hPSC derivatives in the clinic. This study provides detailed analyses of cellular metabolic flux to define an efficient strategy for selective hPSC elimination that is effective across many culture conditions and does not have cytotoxic effects on hPSC-derived progeny. Of broad significance to the stem cell and regenerative medicine fields, this study also highlights the importance of examining the effect of in vitro culturing parameters when evaluating the efficacy of hPSC-elimination strategies, especially those that target metabolic processes.
Selective Proteomic Proximity Labeling Assay Using Tyramide (SPPLAT): A Quantitative Method for the Proteomic Analysis of Localized Membrane‐Bound Protein Clusters
Authors: Rees Johanna Susan , Li Xue‐Wen , Perrett Sarah , Lilley Kathryn Susan , Jackson Antony Philip 
Published: April 2015

AbstractThis manuscript describes a new and general method to identify proteins localized into spatially restricted membrane microenvironments. Horseradish peroxidase (HRP) is brought into contact with a target protein by being covalently linked to a primary or secondary antibody, an antigen or substrate, a drug, or a toxin. A biotinylated tyramide‐based reagent is then added. In the presence of HRP and hydrogen peroxide, the reagent is converted into a free radical that only diffuses a short distance before covalently labeling proteins within a few tens to hundreds of nanometers from the target. The biotinylated proteins can then be isolated by standard affinity chromatography and identified by liquid chromatography (LC) and mass spectrometry (MS). The assay can be made quantitative by using stable isotope labeling with amino acids in cell culture (SILAC) or isobaric tagging at the peptide level. © 2015 by John Wiley & Sons, Inc.
Mapping 3′ mRNA Isoforms on a Genomic Scale
Authors: Jin Yi , Geisberg Joseph V. , Moqtaderi Zarmik , Ji Zhe , Hoque Mainul , Tian Bin , Struhl Kevin 
Published: April 2015

AbstractMost eukaryotic genes are transcribed into mRNAs with alternative poly(A) sites. Emerging evidence suggests that mRNA isoforms with alternative poly(A) sites can perform critical regulatory functions in numerous biological processes. In recent years, a number of strategies utilizing high‐throughput sequencing technologies have been developed to aid in the identification of genome‐wide poly(A) sites. This unit describes a modified protocol for a recently published 3′READS (3′ region extraction and deep sequencing) method that accurately identifies genome‐wide poly(A) sites and that can be used to quantify the relative abundance of the resulting 3′ mRNA isoforms. This approach minimizes nonspecific sequence reads due to internal priming and typically yields a high percentage of sequence reads that are ideally suited for accurate poly(A) identification. © 2015 by John Wiley & Sons, Inc.
Tools and Procedures for Visualization of Proteins and Other Biomolecules
Authors: Pan Lurong , Aller Stephen G. 
Published: April 2015

AbstractProtein, peptides, and nucleic acids are biomolecules that drive biological processes in living organisms. An enormous amount of structural data for a large number of these biomolecules has been described with atomic precision in the form of structural “snapshots” that are freely available in public repositories. These snapshots can help explain how the biomolecules function, the nature of interactions between multi‐molecular complexes, and even how small‐molecule drugs can modulate the biomolecules for clinical benefits. Furthermore, these structural snapshots serve as inputs for sophisticated computer simulations to turn the biomolecules into moving, “breathing” molecular machines for understanding their dynamic properties in real‐time computer simulations. In order for the researcher to take advantage of such a wealth of structural data, it is necessary to gain competency in the use of computer molecular visualization tools for exploring the structures and visualizing three‐dimensional spatial representations. Here, we present protocols for using two common visualization tools—the Web‐based Jmol and the stand‐alone PyMOL package—as well as a few examples of other popular tools. © 2015 by John Wiley & Sons, Inc.
Heymann Nephritis in Lewis Rats
Authors: Wang Yuan Min , Lee Vincent W.S. , Wu Huiling , Harris David C.H. , Alexander Stephen I. 
Published: April 2015

AbstractHuman membranous nephritis is a major cause of end‐stage kidney disease. Active Heymann nephritis (HN) is an auto‐immune model of membranous nephritis induced in Lewis rats by immunization with a crude renal tubular antigen (Fx1A) or megalin (gp330). The pathogenesis of HN is through the binding of anti‐Fx1A autoantibodies to the auto‐antigen expressed on glomerular epithelial cells, resulting in severe glomerular injury and proteinuria. The pathological features of HN include immune deposits in glomeruli and infiltration of glomeruli and the tubulointerstitium by macrophages and T cells. This unit describes the method of the preparation of Fx1A and the induction of HN in Lewis rats by immunization with Fx1A. © 2015 by John Wiley & Sons, Inc.
Neural Stem Cell‐Mediated Delivery of Oncolytic Adenovirus
Authors: Kim Julius W. , Kane J. Robert , Young Jacob S. , Chang Alan L. , Kanojia Deepak , Qian Shuo , Spencer Drew A. , Ahmed Atique U. , Lesniak Maciej S. 
Published: April 2015

AbstractThe use of stem cells (SCs) as carriers for therapeutic agents has now progressed to early clinical trials. These clinical trials exploring SC‐mediated delivery of oncolytic adenoviruses will commence in the near future, hopefully yielding meritorious results that can provoke further scientific inquiry. Preclinical animal studies have demonstrated that SCs can be successfully loaded with conditionally‐replicative adenoviruses and delivered to the tumor, whereupon they may evoke pronounced therapeutic efficacy. In this protocol, we describe the maintenance of SCs, provide an analysis of optimal adenoviral titers for SC loading, and evaluate the optimized viral loading on SCs. © 2015 by John Wiley & Sons, Inc.
Uncompensated Polychromatic Analysis of Mitochondrial Membrane Potential Using JC‐1 and Multilaser Excitation
Authors: De Biasi Sara , Gibellini Lara , Cossarizza Andrea 
Published: April 2015

AbstractThe lipophilic cation JC‐1 (5,5′,6,6′‐tetrachloro‐1,1′,3,3′‐tetraethyl‐benzimidazolyl carbocyanine iodide) has been used for more than 20 years as a specific dye for measuring mitochondrial membrane potential (ΔΨm). In this unit, we revise our original protocol (that made use of a single 488 nm laser for the detection of monomers and aggregates, and where compensation was an important step) to use dual‐laser excitation. Moreover, thanks to recently developed multilaser instruments and novel probes for surface and intracellular markers, JC‐1 can be utilized by polychromatic flow cytometry to simultaneously detect, without any compensation between fluorescences, ΔΨm along with other biological parameters, such as apoptosis and the production of reactive oxygen species. © 2015 by John Wiley & Sons, Inc.