bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Detailed Protocol for Formaldehyde‐Assisted Isolation of Regulatory Elements (FAIRE)
Authors: Simon Jeremy M. , Giresi Paul G. , Davis Ian J. , Lieb Jason D. 
Published: April 2013

AbstractNucleosome displacement is a key event in the regulation of gene expression in the eukaryotic genome. This unit details an approach called Formaldehyde‐Assisted Isolation of Regulatory Elements (FAIRE) for isolating nucleosome‐depleted regions. FAIRE does not rely on the use of antibodies or enzymes, and has proven successful in most eukaryotic cells and tissues. The set of regulatory elements enriched by FAIRE is similar to those identified through DNase hypersensitivity. The enriched fragments can be detected by quantitative PCR, tiling DNA microarrays, or next‐generation sequencing. Although the signal‐to‐noise ratio is typically lower than that observed for DNase assays, FAIRE has high sample‐to‐sample reproducibility, requires very low amounts of input material, is inexpensive, is amenable to high‐throughput adaptations, and is a relatively simple procedure with a high rate of success, even for those without extensive experience in molecular biology protocols. Curr. Protoc. Mol. Biol. 102:21.26.1–21.26.15. © 2013 by John Wiley & Sons, Inc.
Assessment of Cell Viability
Authors: Johnson Simon , Nguyen Vy , Coder David 
Published: April 2013

AbstractCell viability may be judged by morphological changes or by changes in membrane permeability and/or physiological state inferred from the exclusion of certain dyes or the uptake and retention of others. This unit presents methods based on dye exclusion, esterase activity, and mitochondrial membrane potential, as well as protocols for determining the pre‐fixation viability of fixed cells either before or after fixation with amine‐reactive dyes suitable for a range of excitation wavelengths. Membrane‐impermeable dead cell and live cell dyes as well as dye‐exclusion procedures for microscopy are also included. Curr. Protoc. Cytom. 64:9.2.1‐9.2.26. © 2013 by John Wiley & Sons, Inc.
Levels of Serum Anti–Müllerian Hormone, a Marker for Ovarian Reserve, in Women With Rheumatoid Arthritis
Authors: Brouwer Jenny , Laven Joop S. E. , Hazes Johanna M. W. , Schipper Izaäk , Dolhain Radboud J. E. M. 
Published: April 2013

ObjectiveFertility is reduced in women with rheumatoid arthritis (RA), even before diagnosis. This may be due to a diminished ovarian reserve. The current study examined serum levels of anti–Müllerian hormone (AMH), the most reliable endocrine marker for ovarian reserve, in early RA patients and the influence of disease activity and methotrexate (MTX) use on AMH concentrations.MethodsSerum AMH levels were measured in 72 women with recent‐onset RA ages 18–42 years and compared to 509 healthy women. The association between AMH and rheumatoid factor (RF), anti–cyclic citrullinated peptide (anti‐CCP), erosions, C‐reactive protein (CRP) level, disease activity (Disease Activity Score in 28 joints [DAS28]), and use of MTX was assessed.ResultsAt diagnosis, age‐adjusted serum AMH levels did not differ significantly between patients and controls (P = 0.254). AMH levels were not related to the presence of RF (P = 0.487), anti‐CCP (P = 0.686), or erosions (P = 0.350), and showed no significant correlation with CRP levels (r = −0.207, P = 0.083) or disease activity scores (DAS28; r = 0.007, P = 0.955). After 6 months of treatment, AMH levels in patients (n = 53) were lower than at the time of diagnosis (P < 0.001), but did not differ from controls (P = 0.741). There was no significant difference in AMH values after 6 months of treatment between patients who did (n = 31) or did not (n = 22) receive MTX (P = 0.287).ConclusionAMH levels in women with early RA are comparable to those of healthy controls, indicating that the reduced fertility in this patient group is not caused by diminished ovarian reserve. AMH levels are not affected either by disease activity or by short‐term MTX use.
Biomechanical Deviations During Level Walking Associated With Knee Osteoarthritis: A Systematic Review and Meta‐Analysis
Authors: Mills Kathryn , Hunt Michael A. , Ferber Reed 
Published: April 2013

ObjectiveTo identify which gait deviations are consistently associated with knee osteoarthritis (KOA) and how these are influenced by disease severity, the involved compartment, and sex.MethodsFive electronic databases and reference lists of publications were searched. Cross‐sectional, observational studies comparing temporospatial variables, joint kinematics, and joint moments between individuals with KOA and healthy controls or between KOA subgroups were considered for review. Only publications scoring ≥50% on a modified methodology quality index were included. Because of the number of gait deviations examined, only biomechanical variables reported by ≥4 publications were further analyzed. Where possible, a meta‐analysis was performed using effect sizes (ES) calculated from discrete variables.ResultsIn total, 41 publications examining 20 variables were included. The majority of consistent gait deviations associated with KOA were exhibited by those with severe disease in the temporospatial domain. Individuals with severe KOA exhibited greater stride duration than controls (ES 1.35 [95% confidence interval (95% CI) 1.03, 1.67]) and a decrease in cadence (ES −0.75 [95% CI −1.12, −0.39]) compared with controls. The evidence for kinematic and joint moment change was primarily limited or conflicting. There was a lack of evidence for alterations in the external knee adduction moment.ConclusionIndividuals with KOA exhibit a range of gait deviations compared with controls. Despite its common usage in KOA gait studies, we did not find consistent evidence that knee adduction moment differs between those with and without KOA or between disease severity levels. Further research examining the reasons for a lack of difference in many gait variables in those with knee OA is needed.
Association of Frequent Knee Bending Activity With Focal Knee Lesions Detected With 3T Magnetic Resonance Imaging: Data From the Osteoarthritis Initiative
Authors: Virayavanich Warapat , Alizai Hamza , Baum Thomas , Nardo Lorenzo , Nevitt Michael C. , Lynch John A. , McCulloch Charles E. , Link Thomas M. 
Published: April 2013

ObjectiveTo evaluate the association of baseline frequent knee bending activities with the prevalence and progression of cartilage and meniscal abnormalities over 3 years and to assess the effect of frequent knee bending on the different knee compartments with 3T magnetic resonance imaging (MRI).MethodsWe studied 115 subjects without radiographic knee osteoarthritis (OA) but with risk factors for OA from the Osteoarthritis Initiative database. The inclusion criteria at baseline were age 45–55 years, body mass index of 19–27 kg/m2, Western Ontario and McMaster Universities Osteoarthritis Index pain score of 0, and Kellgren/Lawrence grade <2. Knee bending activities (kneeling, squatting, stair climbing, and weight lifting) were assessed by questionnaire at the baseline clinic visit. Cartilage and meniscal abnormalities were graded using the Whole‐Organ MRI Score. Logistic regression was used to determine the association of frequent knee bending with cartilage and meniscal abnormalities.ResultsFrequent knee bending activities were associated with an increased risk of prevalent cartilage lesions (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.39–9.52), in particular in the patellofemoral compartment (OR 3.09, 95% CI 1.22–7.79). The increase in risk was higher in subjects involved in ≥2 knee bending activities. At 3‐year followup, individuals reporting frequent knee bending were more likely to show progression of cartilage damage (OR 4.12, 95% CI 1.27–13.36) and meniscal abnormalities (OR 4.34, 95% CI 1.16–16.32).ConclusionFrequent knee bending activities were associated with a higher prevalence of knee cartilage lesions (particularly in the patellofemoral compartment) and with an increased risk of progression of cartilage and meniscal lesions in asymptomatic middle‐aged subjects.
Creatine Supplementation in Fibromyalgia: A Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Alves Christiano R. R. , Santiago Bianca M. , Lima Fernanda R. , Otaduy Maria C. G. , Calich Ana Luisa , Tritto Aline C. C. , de Sá Pinto Ana Lúcia , Roschel Hamilton , Leite Cláudia C. , Benatti Fabiana B. , Bonfá Eloisa , Gualano Bruno 
Published: April 2013

ObjectiveTo investigate the efficacy and safety of creatine supplementation in fibromyalgia patients.MethodsA 16‐week, randomized, double‐blind, placebo‐controlled, parallel‐group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double‐blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through 31P magnetic resonance spectroscopy.ResultsAfter the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus −2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus −0.5% and −7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus −3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported.ConclusionCreatine supplementation increased intramuscular phosphorylcreatine content and improved lower‐ and upper‐body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.
Brief Report: Rheumatoid Arthritis Is Associated With Left Ventricular Concentric Remodeling: Results of a Population‐Based Cross‐Sectional Study
Authors: Myasoedova Elena , Davis John M. , Crowson Cynthia S. , Roger Véronique L. , Karon Barry L. , Borgeson Daniel D. , Therneau Terry M. , Matteson Eric L. , Rodeheffer Richard J. , Gabriel Sherine E. 
Published: April 2013

ObjectiveTo study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling.MethodsA cross‐sectional, community‐based study was conducted among adult (age ≥50 years) patients with RA and age‐ and sex‐matched subjects with neither RA nor a history of heart failure. All participants underwent standard 2‐dimensional Doppler echocardiography. LV geometry was classified into the following 4 categories based on relative wall thickness and sex‐specific cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry.ResultsAmong 200 patients with RA and 600 age‐ and sex‐matched subjects without RA, the mean age was 65 years, and 74% of the individuals in both cohorts were female. Compared with subjects without RA, patients with RA were significantly more likely to have abnormal LV geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03–2.00), even after adjusting for cardiovascular risk factors and comorbidities. Among subjects with abnormal LV geometry, the odds of concentric LV remodeling were significantly increased in patients with RA (OR 4.73, 95% CI 2.85–7.83). In linear regression analyses, the LV mass index appeared to be lower in patients with RA who were currently receiving corticosteroids (β ± SE −0.082 ± 0.027, P = 0.002), even after adjusting for cardiovascular risk factors and comorbidities.ConclusionRA was strongly associated with abnormal LV remodeling (particularly concentric LV remodeling) among RA patients without heart failure. This association remained significant after adjustment for cardiovascular risk factors and comorbidities. RA disease–related factors may promote changes in LV geometry. The biologic mechanisms underlying LV remodeling warrant further investigation.
Vitamin D in Systemic Lupus Erythematosus: Modest Association With Disease Activity and the Urine Protein‐to‐Creatinine Ratio
Authors: Petri Michelle , Bello Kayode J. , Fang Hong , Magder Laurence S. 
Published: April 2013

ObjectiveTo investigate whether an increase in vitamin D levels in patients with systemic lupus erythematosus (SLE) was associated with improvement in disease activity.MethodsA total of 1,006 SLE patients were monitored over 128 weeks. SLE patients with low levels of 25‐hydroxyvitamin D (25[OH]D; <40 ng/ml) were given supplements of 50,000 units of vitamin D2 weekly plus 200 units of calcium/vitamin D3 twice daily. Longitudinal regression models were used to estimate the association between levels of 25(OH)D and various measures of disease activity.ResultsThe SLE patients had the following characteristics: 91% were female, their mean age was 49.6 years, and their ethnicity was 54% Caucasian, 37% African American, and 8% other. For those with levels of 25(OH)D <40 ng/ml, a 20‐unit increase in the 25(OH)D level was associated with a mean decrease of 0.22 (95% confidence interval [95% CI] −0.41, −0.02) (P = 0.032) in the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This corresponded to a 21% decrease in the odds of having a SELENA–SLEDAI ≥5 (95% CI 1, 37). The mean urine protein‐to‐creatinine ratio decreased by 2% (95% CI −0.03, −0.01) (P = 0.0001), corresponding to a 15% decrease in the odds of having a ratio >0.5 (95% CI 2, 27).ConclusionWe found that a 20‐ng/ml increase in the 25(OH)D level was associated with a 21% decrease in the odds of having a high disease activity score and a 15% decrease in the odds of having clinically important proteinuria. Although these associations were statistically significant, the clinical importance is relatively modest. There was no evidence of additional benefit of 25(OH)D beyond a level of 40 ng/ml.
Relevance of Grade 1 Gray‐Scale Ultrasound Findings in Wrists and Small Joints to the Assessment of Subclinical Synovitis in Rheumatoid Arthritis
Authors: Witt Matthias , Mueller Felix , Nigg Axel , Reindl Christiane , Leipe Jan , Proft Fabian , Stein Nicola , Hammitzsch Ariane , Mayer Stefan , Dechant Claudia , Schulze‐Koops Hendrik , Grunke Mathias 
Published: April 2013

ObjectiveTo investigate the clinical relevance of grade 1 findings on gray‐scale ultrasound (GSUS) of the joints in patients with rheumatoid arthritis (RA).MethodsWe examined the wrists and small joints of 100 patients with early or established RA and 30 healthy controls, using GSUS and power Doppler ultrasound (PDUS). Independent clinical assessment of all joints for tenderness and swelling according to the European League Against Rheumatism examination technique was performed. Joints with grade 1 findings on GSUS were identified, and associations with swelling, pain, and findings on PDUS were assessed. Grade 1 findings on GSUS in patients with early RA were reassessed after 6 months of antirheumatic treatment.ResultsGrade 1 results represented the majority of all GSUS findings in patients with RA and were also frequently recorded in healthy controls. Grade 1 GSUS findings were not associated with tenderness, swelling, or positive results on PDUS. In comparison to joints with grade 2 and grade 3 findings on GSUS, joints with grade 1 findings were less likely to respond to treatment.ConclusionThe present results indicate that grade 1 findings on GSUS have limited clinical relevance.
Soluble Receptor for Advanced Glycation End Products Alleviates Nephritis in (NZB/NZW)F1 Mice
Authors: Lee Sang‐Won , Park Kyu‐Hyung , Park Sungha , Kim Ji‐Hye , Hong Sung‐Yu , Lee Soo‐Kon , Choi Donghoon , Park Yong‐Beom 
Published: April 2013

ObjectiveTo investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus‐prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone.MethodsTwenty‐eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF‐κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti–double‐stranded DNA (anti‐dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence‐activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining.ResultsIn comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti‐dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF‐κB in the kidney, resulting in reduction in the expression of downstream genes of NF‐κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations.ConclusionTreatment with sRAGE significantly improved nephritis in lupus‐prone mice, with efficacy comparable to that of standard induction treatment for lupus nephritis. These data suggest that sRAGE has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.
Interferon‐γ Mediates Anemia but Is Dispensable for Fulminant Toll‐like Receptor 9–Induced Macrophage Activation Syndrome and Hemophagocytosis in Mice
Authors: Canna Scott W. , Wrobel Julia , Chu Niansheng , Kreiger Portia A. , Paessler Michele , Behrens Edward M. 
Published: April 2013

ObjectiveMacrophage activation syndrome (MAS) is a devastating cytokine storm syndrome complicating many inflammatory diseases and characterized by fever, pancytopenia, and systemic inflammation. It is clinically similar to hemophagocytic lymphohistiocytosis (HLH), which is caused by viral infection of a host with impaired cellular cytotoxicity. Murine models of MAS and HLH illustrate that interferon‐γ (IFNγ) is the driving stimulus for hemophagocytosis and immunopathology. This study was undertaken to investigate the inflammatory contributors to a murine model of Toll‐like receptor 9 (TLR‐9)–induced fulminant MAS.MethodsWild‐type, transgenic, and cytokine‐inhibited mice were treated with an IL‐10 receptor blocking antibody and a TLR‐9 agonist, and parameters of MAS were evaluated.ResultsFulminant MAS was characterized by dramatic elevations in IFNγ, IL‐12, and IL‐6 levels. Increased serum IFNγ levels were associated with enhanced IFNγ production within some hepatic cell populations but also with decreased numbers of IFNγ‐positive cells. Surprisingly, IFNγ‐knockout mice developed immunopathology and hemophagocytosis comparable to that seen in wild‐type mice. However, IFNγ‐knockout mice did not become anemic and had greater numbers of splenic erythroid precursors. IL‐12 neutralization phenocopied disease in IFNγ‐knockout mice. Interestingly, type I IFNs contributed to the severity of hypercytokinemia and weight loss, but their absence did not otherwise affect MAS manifestations.ConclusionThese data demonstrate that both fulminant MAS and hemophagocytosis can arise independently of IFNγ, IL‐12, or type I IFNs. They also suggest that IFNγ‐mediated dyserythropoiesis, not hemophagocytosis, is the dominant cause of anemia in fulminant TLR‐9–induced MAS. Thus, our data establish a novel mechanism for the acute anemia of inflammation, but suggest that a variety of triggers can result in hemophagocytic disease.
Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Have Defective Treg Cell Function Exacerbated by the Presence of a Suppression‐Resistant Effector Cell Population
Authors: Free Meghan E. , Bunch Donna O'Dell , McGregor Julie Anne , Jones Britta E. , Berg Elisabeth A. , Hogan Susan L. , Hu Yichun , Preston Gloria A. , Jennette J. Charles , Falk Ronald J. , Su Maureen A. 
Published: April 2013

ObjectiveThe development of pathogenic antineutrophil cytoplasmic antibodies (ANCAs) can result in systemic small vessel vasculitis. However, the breakdown in immune tolerance that results in the induction and persistence of ANCAs is not well understood. We undertook this study to test our hypothesis that abnormal T cell regulation is central to disease pathogenesis in patients with ANCA‐associated vasculitis (AAV).MethodsPeripheral blood samples were obtained from 62 patients with AAV and 19 healthy controls for flow cytometric analysis of CD4+ T cell populations. Functional T cell studies were performed with fluorescence‐activated cell sorted CD4+ T cell populations stimulated with anti‐CD3/anti‐CD28.ResultsWe demonstrated two separate abnormalities in T cell regulation in patients with AAV. First, we showed that the Treg cell frequency was increased in the peripheral blood of patients with active disease, but Treg cells from patients with AAV had decreased suppressive function. Treg cells from patients with active disease disproportionately used a FoxP3 isoform lacking exon 2, which might alter Treg cell function. Second, we identified a CD4+ T cell population with increased frequency that was resistant to Treg cell suppression, produced proinflammatory cytokines, and was antigen experienced.ConclusionAAV is associated with disruption of the suppressive Treg cell network and with increased frequency of a distinct proinflammatory effector T cell subset that comprises the majority of peripheral CD4+ T cells.