bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dalfampridine Effects Beyond Walking Speed in Multiple Sclerosis
Authors: Fjeldstad Cecilie , Suárez Gustavo , Klingler Michael , Henney Herbert R. , Rabinowicz Adrian L. , Pardo Gabriel 
Published: January 2015

Background: Dalfampridine extended release (ER) improves walking in people with multiple sclerosis (MS), as demonstrated by walking speed improvement. This exploratory study evaluated treatment effects of dalfampridine-ER on gait, balance, and walking through treatment withdrawal and reinitiation.
Methods: Dalfampridine-ER responders, based on Timed 25-Foot Walk (T25FW) assessment before study entry, were included in this open-label, three-period, single-center study. Period 1: on-drug evaluations performed at screening and 1 week after screening. Period 2: dalfampridine-ER withdrawal and off-drug evaluations (days 5 and 11). Period 3: dalfampridine-ER reinitiation/final on-drug evaluation (day 15). Primary outcome variables: NeuroCom composite scores for gait and balance; balance was evaluated if gait changes were significant. Secondary variables: individual NeuroCom scores, walking speed (T25FW) and distance (2-Minute Walk Test [2MWT]), and balance (Berg Balance Scale [BBS]).
Results: All 20 patients completed the study: mean age, 53.1 years; mean MS duration, 11.3 years; mean time taking dalfampridine-ER, 315.3 days. NeuroCom gait composite scores worsened during period 2 relative to period 1 and improved during period 3; the mean ± SD difference in gait composite scores on drug was 4.03 ± 1.51 points (P = .015). Balance composite scores did not change significantly. Improvements were observed for off-drug versus on-drug for T25FW (0.36 ft/sec, P &lt; .001), 2MWT (25.4 ft, P = .006), and BBS (1.7 points, P = .003). Safety profile was consistent with previous studies.
Conclusions: Significant improvements in gait, walking speed, distance, and balance were demonstrated by dalfampridine-ER reinitiation after a 10-day withdrawal period.
Preparation of Cells from Formalin‐Fixed, Paraffin‐Embedded Tissue for Use in Fluorescence In Situ Hybridization (FISH) Experiments
Authors: Weremowicz Stanislawa 
Published: January 2015

AbstractNumerical and structural chromosome abnormalities can be accurately detected in cells from archived tissues using fluorescence in situ hybridization (FISH). This unit describes two common approaches to performing FISH in formalin‐fixed, paraffin‐embedded tissue. The first approach utilizes 4 to 6 μm tissue sections in cases for which preserving tissue morphology is necessary, and the second involves extraction of intact nuclei from 50‐μm tissue sections. To interpret FISH results using 4 to 6 μm sections, an adequate number of nuclei must be evaluated to perform statistical analysis. Evaluation of 30 to 50 nuclei from the single‐cell suspension generally gives an interpretable result. © 2015 by John Wiley & Sons, Inc.
Unique latitudinal shape of ion upper transition height (HT) surface during deep solar minimum (2008–2009)
Authors: Tulasi Ram S. , Heelis R. , Gowtam V. Sai , Ajith K. K. , Su S.‐Y. 
Published: January 2015

AbstractThe ionospheric upper transition height (HT) is found to increase dramatically by ~100 km from 2008–2009 to 2010 only for a marginal increase in solar activity (F10.7) by 11.76 solar flux units. The latitudinal variation of HT surface during 2008–2009 period exhibits a local minimum at equatorial latitudes and increase at low latitudes. Further, the HT at equatorial latitudes exhibits slower rate of increase than at low latitudes. These interesting features are new and different from those reported in literature. A quick loss of O+ and increase in H+ ions are observed around ~550 to 650 km indicating that the charge exchange reaction is responsible for the slower rate of increase and lowered HT at equatorial latitudes. These new aspects of HT are more conspicuously observed during this deep solar minimum period where the resonant charge exchange reaction is taking place at altitudes as low as ~550 km.
Sensitivity of decomposition rates of soil organic matter with respect to simultaneous changes in temperature and moisture
Authors: Sierra Carlos A. , Trumbore Susan E. , Davidson Eric A. , Vicca Sara , Janssens I. 
Published: January 2015

AbstractThe sensitivity of soil organic matter decomposition to global environmental change is a topic of prominent relevance for the global carbon cycle. Decomposition depends on multiple factors that are being altered simultaneously as a result of global environmental change; therefore, it is important to study the sensitivity of the rates of soil organic matter decomposition with respect to multiple and interacting drivers. In this manuscript, we present an analysis of the potential response of decomposition rates to simultaneous changes in temperature and moisture. To address this problem, we first present a theoretical framework to study the sensitivity of soil organic matter decomposition when multiple driving factors change simultaneously. We then apply this framework to models and data at different levels of abstraction: (1) to a mechanistic model that addresses the limitation of enzyme activity by simultaneous effects of temperature and soil water content, the latter controlling substrate supply and oxygen concentration for microbial activity; (2) to different mathematical functions used to represent temperature and moisture effects on decomposition in biogeochemical models. To contrast model predictions at these two levels of organization, we compiled different data sets of observed responses in field and laboratory studies. Then we applied our conceptual framework to: (3) observations of heterotrophic respiration at the ecosystem level; (4) laboratory experiments looking at the response of heterotrophic respiration to independent changes in moisture and temperature; and (5) ecosystem‐level experiments manipulating soil temperature and water content simultaneously.
Evaluating a county‐based healthy nail salon recognition program
Authors: Garcia Erika , Sharma Swati , Pierce Michelle , Bhatia Sushma , Argao Sania Tong , Hoang Kim , Quach Thu 
Published: January 2015

ObjectivesThe City of San Francisco, California established a recognition program for nail salons that use safer nail products and receive worker safety training. This pilot study examined whether participating salons had reduced levels of toluene, methyl methacrylate (MMA), and total volatile organic compounds (TVOC), and improved knowledge and behavior compared to control salons.MethodsWe conducted personal air monitoring and administered surveys assessing knowledge and behaviors of two workers from each of six intervention salons and five control salons. We conducted assessments before and after the worker training.ResultsAlthough non‐significant, there was a reduction in toluene (−46% vs. 0%) and TVOC (−19% vs. +47%), but an increase in MMA (+113% and +72%) among intervention salons compared to control salons. Awareness of dibutyl phthalates in nail products increased (+55%) among intervention salons between surveys.ConclusionsA government‐administered nail salon recognition program may reduce chemical exposures and increase work‐related knowledge. Am. J. Ind. Med. 58:193–202, 2015. © 2015 Wiley Periodicals, Inc.
Working overtime and risk factors for coronary heart disease: A propensity score analysis based in the J‐SHINE (Japanese Study of Stratification, Health, Income, and Neighborhood) study
Authors: Tsuboya Toru , Aida Jun , Osaka Ken , Kawachi Ichiro 
Published: January 2015

BackgroundEvidence on the causal relationship between working overtime and the risk of coronary heart disease is limited.MethodsWe surveyed 2355 workers in Japan and conducted propensity‐matched logistic regression analysis, using propensity‐matched 438 pairs, to evaluate the associations between working overtime (more than 50 hr per week) and coronary risk factors: physical inactivity, cigarette smoking, sleep deprivation (<5 hr/day), psychological stress, overweight/obesity, and excessive alcohol consumption. The exposure and outcomes were self‐reported.ResultsAmong 2355 workers, 476 participants worked overtime. Propensity‐matched analysis revealed that the associations between working overtime and sleep deprivation (odds ratios (OR) and 95% confidence intervals: 2.33, 1.39–3.88) and high stress (2.13, 1.60–2.82). The associations between working overtime and physical inactivity, current smoking, and overweight/obesity were not statistically significant. Excessive alcohol consumption was inversely associated with working overtime.ConclusionsWorking overtime was positively associated with two coronary risk factors: sleep deprivation and increased psychological stress. Am. J. Ind. Med. 58:229–237, 2015. © 2015 Wiley Periodicals, Inc.
Films made from polyethylene‐co‐acrylic acid and soluble biopolymers sourced from agricultural and municipal biowaste
Authors: Franzoso Flavia , Causone Damiano , Tabasso Silvia , Antonioli Diego , Montoneri Enzo , Persico Paola , Laus Michele , Mendichi Raniero , Negre Michele 
Published: January 2015

ABSTRACTBlends were obtained from polyethylene‐co‐acrylic acid (PEAA) with 248 kDa molecular weight and two water soluble biopolymers isolated from the hydrolysate of postharvest tomato plant and urban biowaste compost. The two hydrolysates were constituted respectively from a polysaccharide (SP) with 27 kDa molecular weight and a lignin‐like polymer (LP) with 75 kDa molecular weight containing aliphatic and aromatic C moieties substituted by carboxyl, hydroxyl, and amino groups. Evidence was obtained for reactions occurring between the biopolymers and the synthetic polymer leading to new polymers with 151 to 1243 kDa molecular weights. The thermal and mechanical properties of the blends were studied. Compared with neat PEAA, the PEAA‐LP blends containing 5 to 10% LP exhibited 2 to 5× higher molecular weights, 10 to 50% lower crystallinity, 2 to 6× higher Young's modulus, over 3× higher stress at yield point and somewhat lower strain at break (55–280% vs. over 300%). On the contrary the PEAA‐SP blends exhibited 6 to 13% lower crystallinity and the same mechanical properties as neat PEAA. The results offer scope for investigating biopolymers sourced from other biowastes to understand more the reasons of the observed effects and exploit their full potential to modify or to replace synthetic polymers. Perspectives of economic and environmental benefits are discussed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2015,132, 41909.
Simple, convenient, low‐cost, and solventless greener way to pH‐responsive polymeric hydrogels: Synthesis and characterization
Authors: Franklin David S. , Guhanathan Selvam 
Published: January 2015

ABSTRACTUtilization of hydrogels in a simple, low‐cost, solventless. and greener approach toward the pH‐responsive hydrogels which comprise of citric acid (CA) with varying glycol unit viz., ethylene glycol (EG), diethylene glycol (DEG), and triethylene glycol (TEG) were prepared along with methacrylic acid (MAA). The formations of pre‐polymer and hydrogels were confirmed using 13C‐NMR and FT‐IR spectral techniques. Thermal studies (TGA, DTA, and DSC) and morphology (SEM) of various hydrogels have been investigated. Swelling studies of hydrogels at different pH ranging from 4.0 to 10.0 have also been performed. The results of swelling studies imply that the percentage of swelling is comparatively higher at neutral pH than acidic and alkaline pH. The reciprocal relationship was identified among thermal stability and swelling behavior of hydrogels while increasing the chain length from EG to TEG. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41921.
Examination of Autoantibody Status and Clinical Features Associated With Cancer Risk and Cancer‐Associated Scleroderma
Authors: Shah Ami A. , Hummers Laura K. , Casciola‐Rosen Livia , Visvanathan Kala , Rosen Antony , Wigley Fredrick M. 
Published: January 2015

ObjectiveWe previously reported a contemporaneous onset of cancer and scleroderma in patients with anti–RNA polymerase III antibodies, and we identified a biologic link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics are associated with cancer and a clustering of cancer with scleroderma onset.MethodsLogistic regression analysis was performed to assess the relationship of 2 outcomes, cancer (model 1) and a short (±2 years) cancer–scleroderma interval (model 2), with autoantibody status and scleroderma covariates.ResultsOf 1,044 scleroderma patients, 168 (16.1%) had cancer. In the adjusted model 1, only older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.02–1.05]) and white race (odds ratio 2.71 [95% confidence interval 1.22–6.04]) were significantly associated with an increased overall risk of cancer. In the adjusted model 2, only anti–RNA polymerase III positivity (odds ratio 5.08 [95% confidence interval 1.60–16.1]) and older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.00–1.08]) were significantly associated with a short cancer–scleroderma interval. While anti–RNA polymerase III positivity was associated with a short cancer–scleroderma interval independent of age at scleroderma onset, the cancer–scleroderma interval shortened with older age at scleroderma onset in other antibody groups (Spearman's correlation P < 0.05), particularly among patients with anti–topoisomerase I antibodies and patients who were negative for anticentromere, anti–topoisomerase I, and anti–RNA polymerase III antibodies.ConclusionIncreased age at scleroderma onset is strongly associated with cancer risk overall. While anti–RNA polymerase III status is an independent marker of coincident cancer and scleroderma at any age, a clustering of cancer with scleroderma is also seen in patients with anti–topoisomerase I and other autoantibody specificities who develop scleroderma at older ages.
Autophagy Activation and Protection From Mitochondrial Dysfunction in Human Chondrocytes
Authors: López de Figueroa Paloma , Lotz Martin K. , Blanco Francisco J. , Caramés Beatriz 
Published: January 2015

ObjectiveAutophagy is a key pathway of cellular homeostasis for removing damaged macromolecules and organelles, including mitochondria. Recent studies indicate that activation of autophagy is defective in aging and osteoarthritis (OA), contributing to cell death and tissue damage. In addition, there is increasing evidence that mitochondrial dysfunction plays an important role in OA pathogenesis. The objective of this study was to determine whether activation of autophagy protects against mitochondrial dysfunction in human chondrocytes.MethodsHuman chondrocytes were treated with oligomycin, an inhibitor of mitochondrial respiratory chain complex V. Autophagy activation was analyzed by determination of light chain 3 membrane‐bound form II (LC3‐II), a marker of autophagosome formation. To investigate whether autophagy protects from mitochondrial dysfunction, autophagy was induced by rapamycin, the selective inhibitor of mammalian target of rapamycin complex 1 (mTORC‐1), and by torin 1, the inhibitor of mTORC‐1 and mTORC‐2. Small interfering autophagy‐related 5 was used to evaluate the role of autophagy in mitochondrial dysfunction.ResultsMitochondrial dysfunction was induced by treatment with oligomycin, which significantly decreased mitochondrial membrane potential (ΔΨm). This was associated with increased production of reactive oxygen species and cell death. Autophagy activation, as reflected by LC3‐II, was decreased in a time‐dependent manner. To evaluate whether autophagy regulates mitochondrial function, chondrocytes were pretreated with rapamycin and torin 1 before oligomycin. Autophagy activation significantly protected against mitochondrial dysfunction. Conversely, genetic inhibition of autophagy induced significant mitochondrial function defects.ConclusionOur data highlight the role of autophagy as a critical protective mechanism against mitochondrial dysfunction. Pharmacologic interventions that enhance autophagy may have chondroprotective activity in cartilage degenerative processes such as OA.
Identification of a Prg4‐Expressing Articular Cartilage Progenitor Cell Population in Mice
Authors: Kozhemyakina Elena , Zhang Minjie , Ionescu Andreia , Ayturk Ugur M. , Ono Noriaki , Kobayashi Akio , Kronenberg Henry , Warman Matthew L. , Lassar Andrew B. 
Published: January 2015

ObjectiveTo generate knockin mice that express a tamoxifen‐inducible Cre recombinase from the Prg4 locus (Prg4GFPCreERt2 mice) and to use these animals to fate‐map the progeny of Prg4‐positive articular cartilage cells at various ages.MethodsWe crossed Prg4GFPCreERt2 mice with Rosa26floxlacZ or Rosa26mTmG reporter strains, admin‐istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre‐mediated recom‐bination by histochemistry and/or fluorescence microscopy.ResultsIn 1‐month‐old mice, the expression of the Prg4GFPCreERt2 allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin‐istered for 10 days, caused Cre‐mediated recombination in ∼70% of the superficial‐most chondrocytes. Prg4GFPCreERt2‐expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1‐month‐old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4GFPCreERt2‐expressing cells were largely restricted to the superficial‐most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage.ConclusionOur results suggest that Prg4‐expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4GFPCreERt2 is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4GFPCreERt2 allele should be a useful tool for inducing efficient Cre‐mediated recombination of loxP‐flanked alleles at sites of Prg4 expression.
Methotrexate Restores Regulatory T Cell Function Through Demethylation of the FoxP3 Upstream Enhancer in Patients With Rheumatoid Arthritis
Authors: Cribbs Adam P. , Kennedy Alan , Penn Henry , Amjadi Parisa , Green Patricia , Read Jordan E. , Brennan Fionula , Gregory Bernard , Williams Richard O. 
Published: January 2015

ObjectiveWe have previously shown, in a cohort of untreated rheumatoid arthritis (RA) patients, that the suppressive function of Treg cells is defective. However, other studies in cohorts of patients with established RA have shown that Treg cell function is normal. We hypothesized that treatment may restore Treg cell function and lead to reduced disease activity. The aim of this study was to investigate whether treatment with methotrexate (MTX) can result in epigenetic changes that lead to restoration of the Treg cell suppressive function in RA.MethodsPeripheral blood samples from RA patients were assessed using 3H‐thymidine incorporation to measure Treg cell suppression of T cell proliferation, and by enzyme‐linked immunosorbent assay to determine Treg cell suppression of interferon‐γ production. CTLA‐4 and FoxP3 expression was measured by flow cytometry and quantitative polymerase chain reaction (qPCR) in Treg cells from healthy individuals and RA patients. CD4+ T cells isolated from healthy individuals were cultured with interleukin‐2 (IL‐2), IL‐6, and tumor necrosis factor α in the presence or absence of MTX, and FoxP3 expression was determined using qPCR and flow cytometry. Methylation of the FOXP3 upstream enhancer was analyzed by bisulfite sequencing PCR.ResultsDefective Treg cell function was observed only in RA patients who had not been treated with MTX, whereas Treg cells from MTX‐exposed RA patients had restored suppressive function. This restored suppression was associated with increased expression of FoxP3 and CTLA‐4 in Treg cells. Bisulfite sequencing PCR of Treg cells cultured in MTX revealed a significant reduction in methylation of the FOXP3 upstream enhancer.ConclusionThis study identifies a novel mechanism of action of MTX, in which treatment of RA patients with MTX restores defective Treg cell function through demethylation of the FOXP3 locus, leading to a subsequent increase in FoxP3 and CTLA‐4 expression.
In vitro–in vivo extrapolations to evaluate the effect of concomitant drugs on tacrolimus (FK506) exposure
Authors: Oda Kazuo , Yamano Katsuhiro , Otsuka Yukio 
Published: January 2015

AbstractThe effect of concomitant drugs having a cytochrome P450 (CYP) 3A inhibitory potency on tacrolimus exposure was predicted from in vitro metabolism results. In this study, the IC50 values of concomitant drugs on the formation of M‐I, the major metabolite of tacrolimus, were determined, and the effect on oral exposure (AUCp.o.) of tacrolimus was assessed from static models. When an absorbed fraction (Fa) of 0.97, intestinal wall availability (Fg) of 0.27 and fraction metabolized by CYP3A (fm(CYP3A)) of 0.8 were used, the least bias was observed for the prediction of the AUCp.o. of tacrolimus. The relationship of the IC50 values of 11 inhibitors between tacrolimus and typical CYP3A substrates (midazolam and testosterone) was also analysed. A strong correlation was found between the IC50 values of tacrolimus and typical CYP3A substrates (r2 ≥ 0.85). The predictability of the effect of inhibitors on tacrolimus AUCp.o. was investigated based on the same static models with the use of published IC50 values for midazolam and testosterone. The bias for the prediction of tacrolimus AUCp.o. was minimal with the use of IC50 values determined using tacrolimus itself as a substrate. These results suggest that tacrolimus itself is still the best choice for predicting the AUCp.o. of tacrolimus, although our findings suggest that midazolam or testosterone may be used instead of tacrolimus to estimate roughly (predicted AUCp.o. within an approximately 2‐fold range of observed values) the effect of CYP3A inhibitors on the tacrolimus AUCp.o.. Copyright © 2015 John Wiley & Sons, Ltd.