bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Objectively Assessed Physical Activity and Fatigue in Patients With Rheumatoid Arthritis: Inverse Correlation of Activity and Fatigue
Authors: Rongen‐van Dartel S. A. A. , Repping‐Wuts H. , van Hoogmoed D. , Knoop H. , Bleijenberg G. , van Riel P. L. C. M. , Fransen J. 
Published: December 2013

ObjectiveFatigue is generally associated with low physical activity in patients with various chronic medical conditions. However, such an association has not been reported among patients with rheumatoid arthritis (RA). The objectives of this study were to investigate whether daily activity level is associated with fatigue in patients with RA, and whether pain, disability, coping, and/or cognition are associated with the level of daily activity.MethodsPatients with RA who visited our outpatient clinic were recruited consecutively. Fatigue severity was measured using the Checklist Individual Strength (CIS20). Physical activity was measured for 14 consecutive days using an ankle‐worn actometer. The daily activity level of each patient was calculated, and each patient was classified as having a low or high activity level with respect to the group average. Data were analyzed by linear regression.ResultsA total of 167 patients were included in the analysis; 25% had a low activity level and 75% had a high activity level. A regression analysis revealed that higher activity levels were associated with reduced fatigue (P = 0.008). The mean ± SD CIS fatigue score was 30.9 ± 12.3 among the patients with a high activity level and 35.7 ± 12.8 among the patients with a low activity level (P = 0.03). Pain, disability, coping, and cognition were not associated significantly with daily activity level.ConclusionAmong patients with RA, a higher level of daily physical activity was associated with reduced levels of fatigue. This relationship was not explained by differences in sex, age, disease duration, pain, disability, or other fatigue‐related factors.
Understanding Presenteeism in Patients With Ankylosing Spondylitis: Contributing Factors and Association With Sick Leave
Authors: Gordeev Vladimir S. , Maksymowych Walter P. , Schachna Lionel , Boonen Annelies 
Published: December 2013

ObjectiveTo understand the impact of ankylosing spondylitis (AS) on presenteeism and to explore its relationship to sick leave.MethodsAS patients completed a questionnaire consisting of sociodemographics, disease characteristics, and work outcomes, including sick leave and presenteeism, assessed by the Work Limitations Questionnaire (WLQ). Associations between a broad range of explanatory variables with the WLQ and AS‐related sick leave were assessed by zero‐inflated negative binomial and zero‐inflated Poisson regressions.ResultsOf 311 employed patients (204 men [65.6%]), 18% had sick leave in the past month. Limitations in meeting time management demands (33.7%), physical demands (30.2%), mental–interpersonal demands (20.2%), and output (19.0%) were noted. With the mean ± SD WLQ index score of 6.7 ± 5.9, the average decrease in work productivity attributable to health was 6.3%; an extra 7.1% of work hours would be needed to compensate for lost productivity. Helplessness, female sex, and impaired health‐related quality of life (Ankylosing Spondylitis Quality of Life instrument [ASQoL]) were major contributors to the level of presenteeism (P < 0.01). At‐work limitations (WLQ) and lower quality of life (ASQoL) were significantly associated with probability of sick leave, while the length of sick leave was strongly associated with lower educational level and helplessness (P < 0.01), and in some models, also with disease duration and country of residence (P < 0.05).ConclusionAS hinders patients' work, mainly in time management and physical demand domains. The WLQ and ASQoL are able to identify patients who incur sick leave. Helplessness contributes independently to the level of presenteeism and the length of sick leave.
Analysis of Trial Data for Infliximab and Golimumab: Baseline C‐Reactive Protein Level and Prediction of Therapeutic Response in Patients With Psoriatic Arthritis
Authors: Au Shiu‐Chung , Ramirez‐Fort Marigdalia K. , Gottlieb Alice B. 
Published: December 2013

ObjectiveAnti–tumor necrosis factor medications have demonstrated good efficacy in treating psoriatic arthritis (PsA). Clinical responses at the primary end point in recent clinical trials of golimumab in PsA subjects yielded lower American College of Rheumatology 20% criteria for improvement (ACR20) responses than those seen in the Infliximab Multinational Psoriatic Arthritis Controlled Trial 2 infliximab study. However, baseline C‐reactive protein (CRP) levels of PsA subjects enrolled in these trials differed significantly. We hypothesized that baseline CRP levels predict the observed differing clinical response rates at the primary end point.MethodsCombining the data from the infliximab and golimumab trials, we stratified the data by baseline CRP levels and then correlated these cohorts with response to treatment, specifically the Psoriasis Area and Severity Index and the ACR20, ACR50, and ACR70 responses.ResultsThe mean baseline CRP level in the infliximab trial was 1.9 mg/dl versus 1.4 mg/dl in the golimumab trial. Only 23% of golimumab subjects had a CRP level ≥1.7 mg/dl versus 35% of infliximab subjects (P = 0.0023). All subjects with a CRP level ≥1.7 mg/dl at baseline achieved higher ACR20, ACR50, ACR70 response rates (56%, 36%, and 18%, respectively) at the primary end point of 14 weeks in the infliximab and golimumab clinical trials than any subjects with a CRP level <1.7 mg/dl (48%, 28%, and 13%, respectively [P = 0.045, P = 0.027, and P = 0.089, respectively]).ConclusionThese results demonstrate that an increased baseline CRP level predicted improved therapeutic response at the primary end point for subjects treated with both golimumab and infliximab. To allow for comparison between future drug development studies and meta‐analyses, baseline CRP levels should be factored into the multivariate analysis.
2D:4D Ratio in children at familial high‐risk for eating disorders: The role of prenatal testosterone exposure
Authors: Kothari Radha , Gafton Joseph , Treasure Janet , Micali Nadia 
Published: December 2013

ABSTRACTObjectivesMarkers of prenatal hormone exposure have been associated with the development of eating disorder (ED) behaviors. Our aim was to determine whether 2D:4D ratio, a marker for in utero testosterone exposure, is associated with risk for ED in a large population‐based cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: This is the first study to investigate prenatal testosterone exposure in children at high‐risk for ED, using 2D:4D as a marker. We compared children whose mothers reported a lifetime ED (anorexia, bulimia, or both; N = 446) to children whose mothers did not (n = 5,367). Results: Daughters of women with lifetime bulimia nervosa (BN) had lower 2D:4D ratio (B: −0.01, 95% CI: −0.02 to −0.002, P = 0.02), indicating higher prenatal testosterone exposure, than daughters of mothers unaffected by ED. No differences were observed in the male children of women with an ED. Conclusions: Findings suggest that children at high‐risk for BN may be exposed to higher levels of testosterone in utero. Fetal exposure to androgen excess is thought to be causal in the development of polycystic ovary syndrome (PCOS), a disorder which is highly comorbid with binge eating and BN. Future research should investigate the potential role of testosterone exposure in utero as a risk factor for BN and binge eating. Am. J. Hum. Biol. 26:176–182, 2014. © 2013 The Authors. American Journal of Human Biology Published by Wiley Periodicals, Inc.
FGFR1 signaling is associated with the magnitude of morphological integration in human head shape
Authors: Hünemeier Tábita , Gómez‐Valdés Jorge , De Azevedo Soledad , Quinto‐Sánchez Mirsha , Passaglia Luciane , Salzano Francisco M. , Sánchez‐Mejorada Gabriela , Alonzo Víctor Acuña , Martínez‐Abadías Neus , Bortolini Maria‐Cátira , González‐José Rolando 
Published: December 2013

ABSTRACTObjectivesThe head can be used as a model to study complex phenotypes controlled simultaneously by morphological integration (MI) due to common factors, and modular patterns caused by local factors affecting the development and functional demands of specific structures. The fibroblast growth factor and receptor system (FGF/FGFR) participates in cell communication and pattern formation in osseous tissues, among others, and there is compelling evidence from mouse model studies suggesting a role of the FGF/FGFR pathway as a covariance‐generating signaling process in head development. Here we use human data to test if specific genetic variants of another gene of this pathway, the FGFR1 gene, can be associated with differences in the integration of the head.MethodsWe explored whether and how three specific variants on FGFR1, previously associated with human cephalic index, influence the pattern and level of head integration of one Native American and one admixed group from Mexico. MI, measured as the intensity of covariation among head traits, was assessed using data from three‐dimensional head landmark coordinates taken on 176 individuals.ResultsIndividuals carrying the derived allele of the rs4647905:G>C polymorphism present significantly greater levels of head MI, especially in facial structures and on the shape space where the modular portion of the covariation is explicitly removed.ConclusionsSince FGFR genes present nonconservative and tissue‐specific splicing sites, they may have some effect on protein structure and performance likely involved in developmental processes responsible for the magnitude and pattern of MI in the human head. Am. J. Hum. Biol. 26:164–175, 2014. © 2013 Wiley Periodicals, Inc.
Unraveling the complex maternal history of Southern African Khoisan populations
Authors: Barbieri Chiara , Güldemann Tom , Naumann Christfried , Gerlach Linda , Berthold Falko , Nakagawa Hirosi , Mpoloka Sununguko W. , Stoneking Mark , Pakendorf Brigitte 
Published: December 2013

ABSTRACTThe Khoisan populations of southern Africa are known to harbor some of the deepest‐rooting lineages of human mtDNA; however, their relationships are as yet poorly understood. Here, we report the results of analyses of complete mtDNA genome sequences from nearly 700 individuals representing 26 populations of southern Africa who speak diverse Khoisan and Bantu languages. Our data reveal a multilayered history of the indigenous populations of southern Africa, who are likely to be the result of admixture of different genetic substrates, such as resident forager populations and pre‐Bantu pastoralists from East Africa. We find high levels of genetic differentiation of the Khoisan populations, which can be explained by the effect of drift together with a partial uxorilocal/multilocal residence pattern. Furthermore, there is evidence of extensive contact, not only between geographically proximate groups, but also across wider areas. The results of this contact, which may have played a role in the diffusion of common cultural and linguistic features, are especially evident in the Khoisan populations of the central Kalahari. Am J Phys Anthropol 153:435–448, 2014. © 2013 Wiley Periodicals, Inc.
Fish biodiversity sampling in stream ecosystems: a process for evaluating the appropriate types and amount of gear
Authors: Smith Joseph M. , Wells Sarah P. , Mather Martha E. , Muth Robert M. 
Published: December 2013

ABSTRACTBecause human impacts and climate change threaten aquatic ecosystems, a need exists to quantify catchment‐scale biodiversity patterns and identify conservation actions that can mitigate adverse human impacts on aquatic biota.Whereas many traditional aquatic resource questions can be answered by repeatedly sampling a few target species with limited types of gear in the same habitats, sampling fish biodiversity patterns at larger scales requires a different approach. Researchers and managers need to determine the types of sampling gear and amount of effort that provide a representative estimate of biodiversity in a range of habitats across a catchment.Using a randomized block design within a 90‐m stream reach that contained the same habitats as the scientific study area, fish assemblages were compared using three different types of gear (minnow traps, backpack electrofishing, and hoop nets) at three levels of effort (one, two, and three mixed‐gear units) over four replicate days.A mixture of gear types best quantified fish assemblages. A combination of 10 minnow traps, 20‐m of backpack electrofishing, and two hoop nets caught the most species. Additional gear added few new species. Resampling confirmed these results.When researchers and managers initiate sampling on a new stream or river system, they do not know how effective each gear type is and whether their sampling effort is adequate. Although the types and amount of gear may be different for other studies, systems, and research questions, the five‐step process described here for making sampling decisions and evaluating sampling efficiency can be applied widely to any system to restore, manage, and conserve aquatic ecosystems. It is believed that incorporating this gear‐evaluation process into a wide variety of studies and ecosystems will increase rigour within and across aquatic biodiversity studies. Copyright © 2013 John Wiley & Sons, Ltd.
Epicutaneous Application of Toll‐like Receptor 7 Agonists Leads to Systemic Autoimmunity in Wild‐Type Mice: A New Model of Systemic Lupus Erythematosus
Authors: Yokogawa Maki , Takaishi Mikiro , Nakajima Kimiko , Kamijima Reiko , Fujimoto Chisa , Kataoka Sayo , Terada Yoshio , Sano Shigetoshi 
Published: December 2013

ObjectiveTo examine whether topical treatment of wild‐type mice with Toll‐like receptor 7 (TLR‐7) agonists leads to lupus‐like autoimmunity.MethodsWild‐type FVB/N, BALB/c, and C57BL/6 mice were treated with the topical TLR‐7 agonist imiquimod or R848 administered to the ear 3 times weekly. During treatment, the mice were monitored for serum autoantibody and creatinine levels as well as histopathology of the kidneys, spleens, livers, hearts, and skin. Immunologic abnormalities were analyzed by immunohistochemistry, quantitative reverse transcription–polymerase chain reaction, and fluorescence‐activated cell sorting. The role of plasmacytoid dendritic cells (PDCs) in the development of autoimmune disease was validated by in vivo treatment with an anti‐PDC antibody. Diseased mice underwent ultraviolet B irradiation, to evaluate skin photosensitivity. The disease‐causing effect of topical application of imiquimod was compared with that of systemic (intraperitoneal) administration. TLR‐7– and TLR‐9–deficient mice were used to validate the role of TLR‐7.ResultsWild‐type mice of different genetic backgrounds developed systemic autoimmune disease following 4 weeks of topical treatment with imiquimod or R848, with elevated levels of autoantibodies to double‐stranded DNA and multiple organ involvement, including glomerulonephritis, hepatitis, carditis, and photosensitivity. Expression of Ifna and Mx1, the interferon‐α–stimulated gene, was up‐regulated in the organs of imiquimod‐treated mice. However, disease caused by intraperitoneal injection of imiquimod was less severe than that induced by topical application. In vivo depletion of PDCs by a specific antibody protected mice against the autoimmunity induced by topical administration of imiquimod, suggesting a role of PDCs. Furthermore, TLR‐7–deficient mice, but not TLR‐9–deficient mice, were protected against autoimmunity.ConclusionThis protocol provides a novel model of inducible systemic lupus erythematosus in wild‐type mice and underscores the skin as the primary organ that allows TLR‐7 agonists to induce SLE.
Development of Vision‐Based Navigation System for Wheeled Agent
Authors: Su Kuo‐Ho , Lian Feng‐Li , Yang Chan‐Yun 
Published: December 2013

AbstractIn this paper, a vision‐based navigation system including support vector machine (SVM) path planner and fuzzy sliding‐mode controlled (SMC) path follower is developed for a wheeled agent. The developed system, comprising image acquisition, map formatting, path planning, label assignment, and path tracking inference mechanisms, aims to gracefully follow a planned smooth path. To obtain accurate coordinate values, the captured images are first adjusted by calibration processing. As a roadmap method for path generation, theVoronoi diagram is employed as a preprocessor and theGaussian kernelSVMpostprocessor is applied consecutively. To deal with the uncertainties, a path follower based on fuzzySMCis embedded to track the planned path on line. In this study, a practical framework is implemented to assess the performance. With the real devised system, a series of experiments are carried out and analyzed to confirm the expected performance. The experiments show a robust capability of the system for both path planning and path tracking under various obstacle layouts.
Advances in lanthanide‐based luminescent peptide probes for monitoring the activity of kinase and phosphatase
Authors: Pazos Elena , Vázquez M. Eugenio 
Published: December 2013

AbstractSignaling pathways based on protein phosphorylation and dephosphorylation play critical roles in the orchestration of complex biochemical events and form the core of most signaling pathways in cells (i.e. cell cycle regulation, cell motility, apoptosis, etc.). The understanding of these complex signaling networks is based largely on the biochemical study of their components, i.e. kinases and phosphatases. The development of luminescent sensors for monitoring kinase and phosphatase activity is therefore an active field of research. Examples in the literature usually rely on the modulation of the fluorescence emission of organic fluorophores. However, given the exceptional photophysical properties of lanthanide ions, there is an increased interest in their application as emissive species for monitoring kinase and phosphatase activity. This review summarizes the advances in the development of lanthanide‐based luminescent peptide sensors as tools for the study of kinases and phosphatases and provides a critical description of current examples and synthetic approaches to understand these lanthanide‐based luminescent peptide sensors.
In Pichia pastoris, growth rate regulates protein synthesis and secretion, mating and stress response
Authors: Rebnegger Corinna , Graf Alexandra B. , Valli Minoska , Steiger Matthias G. , Gasser Brigitte , Maurer Michael , Mattanovich Diethard 
Published: December 2013

AbstractProtein production in yeasts is related to the specific growth rate μ. To elucidate on this correlation, we studied the transcriptome of Pichia pastoris at different specific growth rates by cultivating a strain secreting human serum albumin at μ = 0.015 to 0.15 h–1 in glucose‐limited chemostats. Genome‐wide regulation revealed that translation‐related as well as mitochondrial genes were upregulated with increasing μ, while autophagy and other proteolytic processes, carbon source‐responsive genes and other targets of the TOR pathway as well as many transcriptional regulators were downregulated at higher μ. Mating and sporulation genes were most active at intermediate μ of 0.05 and 0.075 h–1. At very slow growth (μ = 0.015 h–1) gene regulation differs significantly, affecting many transporters and glucose sensing. Analysis of a subset of genes related to protein folding and secretion reveals that unfolded protein response targets such as translocation, endoplasmic reticulum genes, and cytosolic chaperones are upregulated with increasing growth rate while proteolytic degradation of secretory proteins is downregulated. We conclude that a high μ positively affects specific protein secretion rates by acting on multiple cellular processes.
Scale‐down models to optimize a filter train for the downstream purification of recombinant pharmaceutical proteins produced in tobacco leaves
Authors: Buyel Johannes F. , Fischer Rainer 
Published: December 2013

AbstractThe extraction of biopharmaceutical proteins from intact leaves involves the release of abundant particulate contaminants that must be removed economically from the process stream before chromatography, for example, using disposable filters that comply with good manufacturing practice. We therefore scaled down an existing 200‐kg process for the purification of two target proteins from tobacco leaves (the monoclonal antibody 2G12 and the fluorescent protein DsRed, as monitored by surface plasmon resonance spectroscopy and fluorescence imaging, respectively) and screened different materials on the 2‐kg scale to reduce the number of depth filtration steps from three to one. We assessed filter cost and capacity, filtrate turbidity, and protein recovery when the filter materials were challenged with extracts from different tobacco varieties and related species grown in soil or rockwool. PDF4 was consistently the most suitable depth filter because it was the least expensive, it did not interact significantly with the target proteins, and it had the greatest overall capacity. The filter capacity was generally reduced when plants were grown in rockwool, but this substrate has a low bioburden, thus improving process safety. Our data concerning the clarification of plant extracts will help in the design of more cost‐effective downstream processes and accelerate their development.
A rapid flow cytometry assay for the relative quantification of protein encapsulation into bacterial microcompartments
Authors: Kim Edward Y. , Tullman‐Ercek Danielle 
Published: December 2013

AbstractBacterial microcompartments (MCPs) are protein‐based organelles that have been suggested as scaffolds for creating in vivo nanobioreactors. One of the key steps towards engineering MCPs is to understand and maximize the encapsulation of enzymes into the lumen of the MCP. However, there are currently no high‐throughput methods for investigating protein encapsulation. Here, we describe the development of a rapid in vivo assay for quantifying the relative amount of protein encapsulated within MCPs based on fluorescence. In this assay, we fuse a degradation peptide to a MCP‐targeted fluorescence reporter and use flow cytometry to measure overall fluorescence from the encapsulated, protected reporter protein. Using this assay, we characterized various MCP‐targeting signal sequence mutants for their ability to encapsulate proteins and identified mutants that encapsulate a greater amount of protein than the wild type signal sequence. This assay is a powerful tool for reporting protein encapsulation and is an important step towards encapsulating metabolic enzymes into MCPs for synthetic biochemical pathways.