bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between Metabolic Syndrome and Carotid Intima‐Media Thickness: Cross‐Sectional Comparison Between Psoriasis and Psoriatic Arthritis
Authors: Lin Yih Chang , Dalal Deepan , Churton Sarah , Brennan Danielle M. , Korman Neil J. , Kim Esther S. H. , Husni M. Elaine 
Published: August 2013

ObjectiveTo determine the differences in carotid intima‐media thickness (CIMT) between patients with psoriatic diseases with and without metabolic syndrome.MethodsEligible patients from the Cardiometabolic Outcome Measures in Psoriatic Arthritis Study database, which is comprised of both psoriasis and psoriatic arthritis (PsA) patients enrolled at 2 academic medical centers, were included. Detailed cardiovascular (CV) risk factors, including metabolic syndrome profiles, medication use, disease activity, and CIMT, were examined.ResultsA total of 343 patients with psoriatic disease were evaluated (42.28% with psoriasis and 57.72% with PsA). PsA patients were significantly older, with longer disease duration and higher blood pressure, body mass index, and C‐reactive protein (CRP) level. PsA patients took more disease‐modifying antirheumatic drugs (DMARDs) and corticosteroids and underwent more CV procedures. There were no differences in prior CV events, family history of CV risk, and Framingham/Adult Treatment Panel III Risk Score. PsA patients had a higher risk of metabolic syndrome (univariate odds ratio [OR] 1.78 [95% confidence interval (95% CI) 1.08–2.95], P = 0.025). Even after adjusting for age, CRP level, and diastolic blood pressure, PsA patients not taking DMARDs were twice as likely to have metabolic syndrome compared to psoriasis patients (adjusted OR 2.09 [95% CI 0.78–5.59], P = 0.049). PsA patients with metabolic syndrome had the thickest CIMT compared to any other group (P < 0.001).ConclusionPsA patients had an increased prevalence of metabolic syndrome with significantly greater CIMT measurements compared to patients with psoriasis. Furthermore, PsA patients with metabolic syndrome had the greatest CIMT measurements compared to PsA patients without metabolic syndrome and psoriasis patients with or without metabolic syndrome. Incremental increases in inflammatory pathways in PsA may contribute to a higher CV risk as compared to psoriasis patients.
Increased Frequency and Costs of Ambulatory Medical Care Utilization Prior to the Diagnosis of Rheumatoid Arthritis: A National Population‐Based Study
Authors: Lai Ning‐Sheng , Tsai Tzung‐Yi , Li Chung‐Yi , Koo Malcolm , Yu Chia‐Li , Lu Ming‐Chi 
Published: August 2013

ObjectiveTo investigate the frequency and costs associated with ambulatory medical care utilization over an 8‐year period in patients prior to the diagnosis of rheumatoid arthritis (RA).MethodsWe used Taiwan's National Health Insurance Research Database to identify 691 newly diagnosed RA cases between 2005 and 2010. We selected 1,382 controls without RA, frequency matched by sex, age, and the catastrophic illness certificate application year of the cases. The frequency and costs of ambulatory medical care utilization between the RA patients and controls were compared using the 2‐sample Kolmogorov‐Smirnov test.ResultsThe median frequency of ambulatory medical care utilization was significantly higher in RA patients compared with controls (29 versus 13; P < 0.001) in the year before diagnosis. The differences remained significant throughout all 8 annual periods before diagnosis. Similarly, the inflation‐adjusted costs of ambulatory medical care utilization in RA patients increased annually over the study period, from a median of $212 eight years preceding diagnosis to $798 one year preceding diagnosis. Frequency of ambulatory medical care utilization due to diseases of the musculoskeletal system and connective tissue (P < 0.001), acute respiratory infections (P < 0.001), diseases of the upper respiratory tract (P = 0.01), and diseases of the upper gastrointestinal tract (P = 0.04) were higher among RA patients in the 2‐year period preceding diagnosis.ConclusionWe found increased frequency and costs of ambulatory care utilization among RA patients in Taiwan preceding diagnosis of RA.
Transcutaneous Electrical Nerve Stimulation as an Adjunct to Education and Exercise for Knee Osteoarthritis: A Randomized Controlled Trial
Authors: Palmer Shea , Domaille Melissa , Cramp Fiona , Walsh Nicola , Pollock Jon , Kirwan John , Johnson Mark I. 
Published: August 2013

ObjectiveTo determine the additional effects of transcutaneous electrical nerve stimulation (TENS) for knee osteoarthritis (OA) when combined with a group education and exercise program (knee group).MethodsThe study was a randomized, sham‐controlled clinical trial. Patients referred for physiotherapy with suspected knee OA (confirmed using the American College of Rheumatology clinical criteria) were invited. Exclusion criteria included comorbidities preventing exercise, previous TENS experience, and TENS contraindications. Prospective sample size calculations required 67 participants in each trial arm. A total of 224 participants (mean age 61 years, 37% men) were randomized to 3 arms: TENS and knee group (n = 73), sham TENS and knee group (n = 74), and knee group (n = 77). All patients entered an evidence‐based 6‐week group education and exercise program (knee group). Active TENS produced a “strong but comfortable” paraesthesia within the painful area and was used as much as needed during the 6‐week period. Sham TENS used dummy devices with no electrical output. Blinded assessment took place at baseline and 3, 6, 12, and 24 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function subscale at 6 weeks. Secondary outcomes included WOMAC pain, stiffness, and total scores; extensor muscle torque; global assessment of change; exercise adherence; and exercise self‐efficacy. Data analysis was by intent to treat.ResultsAll outcomes improved over time (P < 0.05), but there were no differences between trial arms (P > 0.05). All improvements were maintained at 24‐week followup.ConclusionThere were no additional benefits of TENS, failing to support its use as a treatment adjunct within this context.
Carbon‐Based Anodes for Lithium Sulfur Full Cells with High Cycle Stability
Authors: Brückner Jan , Thieme Sören , Böttger‐Hiller Falko , Bauer Ingolf , Grossmann Hannah Tamara , Strubel Patrick , Althues Holger , Spange Stefan , Kaskel Stefan 
Published: August 2013

The lithium sulfur battery system has been studied since the late 1970s and has seen renewed interest in recent years. However, even after three decades of intensive research, prolonged cycling can only be achieved when a large excess of electrolyte and lithium is used. Here, for the first time, a balanced and stable lithium sulfur full cell is demonstrated with silicon–carbon as well as all‐carbon anodes. More than 1000 cycles, a specific capacity up to 1470 mAh g−1
sulfur (720 mAh g−1
cathode), and a high coulombic efficiency of over 99% even with a low amount of electrolyte are achieved. The alternative anodes do not suffer from electrolyte depletion, which is found to be the main cause of cell failure when using metallic lithium anodes.
The interconversion of the radial motional modes of an ion in a Penning trap mass spectrometer by 4n‐polar external radio frequency fields (n = 1,2,3,4)
Authors: Kretzschmar Martin 
Published: August 2013

In Penning trap mass spectrometry ion masses are determined by measuring the free cyclotron frequency via the resonant conversion of the magnetron into the cyclotron motional mode, induced by the interaction with an external radio‐frequency field. With octupolar rf‐fields of frequency the mass resolution has been improved by more than an order of magnitude as compared to conventional quadrupolar fields of frequency and with the same pulse duration. This result raises the question what one might expect from using 12‐polar rf‐fields with frequency or even 16‐polar rf‐fields with frequency .In this paper the theoretical model for the interconversion of the radial modes by quadrupolar and octupolar rf‐fields is generalized to general 4n‐polar fields. As in the earlier work the complex amplitudes of the cyclotron and magnetron oscillators are used as dynamical variables and the Hamiltonian equations of motion are reformulated in terms of Bloch vector components. The resulting non‐linear differential equations can be solved numerically.Results are presented on excitation functions (conversion at the exact resonance frequency) and on conversion line shapes (dependence of conversion on the detuning parameter). The most important observation is the decrease of the resonance width by a factor of 2 × 103 as one passes from quadrupolar () to 12‐polar () and 16‐polar () excitation.
Brief Report: Fibrosis Caused by Loss of PTEN Expression in Mouse Fibroblasts Is Crucially Dependent on CCN2
Authors: Liu Shangxi , Parapuram Sunil K. , Leask Andrew 
Published: August 2013

ObjectiveProtein phosphatase and tensin homolog (PTEN) expression is reduced in dermal fibroblasts isolated from patients with diffuse cutaneous systemic sclerosis, a fibrotic autoimmune disease. In support of this finding, deletion of the PTEN gene in the dermal fibroblasts of mice has been shown to result in skin fibrosis and in vivo overexpression of connective tissue growth factor (CTGF; CCN2), a proadhesive matricellular protein; however, whether CCN2 is required for the fibrosis caused by loss of PTEN is unclear. This study was undertaken to investigate the role of CCN2 in fibrosis caused by reduced PTEN expression.MethodsWe generated conditional knockout mice in which PTEN was deleted in fibroblasts, either alone or in combination with CCN2. Skin samples were collected for histologic examination, immunohistochemical analysis, and collagen assay.ResultsLoss of CCN2 resulted in resistance to the increases in collagen production and myofibroblast recruitment that are caused by loss of PTEN. CCN2 deficiency did not impair Akt phosphorylation or the increases in the intensity of proliferating cell nuclear antigen staining that were caused by loss of PTEN.ConclusionThese data are consistent with the notion that CCN2 is required for particular aspects of the fibroproliferative response; therapeutic strategies blocking CCN2 may be of clinical benefit in combating fibrotic disease.
Association of Bone Morphogenetic Protein 6 With Exocrine Gland Dysfunction in Patients With Sjögren's Syndrome and in Mice
Authors: Yin Hongen , Cabrera‐Perez Javier , Lai Zhenan , Michael Drew , Weller Melodie , Swaim William D. , Liu Xibao , Catalán Marcelo A. , Rocha Eduardo M. , Ismail Nevien , Afione Sandra , Rana Noreen A. , Di Pasquale Giovanni , Alevizos Ilias , Ambudkar Indu , Illei Gabor G. , Chiorini John A. 
Published: August 2013

ObjectivePrimary Sjögren's syndrome (SS) is characterized by autoimmune activation and loss of function in secretory epithelia. The present study was undertaken to investigate and characterize changes in the epithelia associated with the loss of gland function in primary SS.MethodsTo identify changes in epithelial gene expression, custom microarrays were probed with complementary RNA (cRNA) isolated from minor salivary glands (MSGs) of female patients with primary SS who had low focus scores and low salivary flow rates, and the results were compared with those obtained using cRNA from the MSGs of sex‐matched healthy volunteers. The effect of bone morphogenetic protein 6 (BMP‐6) on salivary gland function was tested using adeno‐associated virus–mediated gene transfer to the salivary glands of C57BL/6 mice.ResultsA significant increase in expression of BMP‐6 was observed in RNA isolated from SS patients compared with healthy volunteers. Overexpression of BMP‐6 locally in the salivary or lacrimal glands of mice resulted in the loss of fluid secretion as well as changes in the connective tissue of the salivary gland. Assessment of the fluid movement in either isolated acinar cells from mice overexpressing BMP‐6 or a human salivary gland cell line cultured with BMP‐6 revealed a loss in volume regulation in these cells. Lymphocytic infiltration in the submandibular gland of BMP‐6 vector–treated mice was increased. No significant changes in the production of proinflammatory cytokines or autoantibodies associated with SS (anti‐Ro/SSA and anti‐La/SSB) were found after BMP‐6 overexpression.ConclusionIn addition to identifying BMP‐6 expression in association with xerostomia and xerophthalmia in primary SS, the present results suggest that BMP‐6–induced salivary and lacrimal gland dysfunction in primary SS is independent of the autoantibodies and immune activation associated with the disease.
Lipopolysaccharide Increases the Incidence of Collagen‐Induced Arthritis in Mice Through Induction of Protease HTRA‐1 Expression
Authors: Hou Yuzhu , Lin Haijiang , Zhu Linnan , Liu Zhaoting , Hu Fanlei , Shi Jianfeng , Yang Tao , Shi Xiaoyun , Zhu Mingzhao , Godley Bernard F. , Wang Qiang , Li Zhanguo , Zhao Yong 
Published: August 2013

ObjectiveThe protease HTRA‐1 is closely associated with rheumatoid arthritis (RA). The molecular mechanisms that control HTRA‐1 expression are currently unknown. This study was undertaken to determine the regulatory role of Toll‐like receptors (TLRs) on HTRA‐1 expression in mice with collagen‐induced arthritis (CIA) and in synovial cells from RA patients.MethodsHTRA‐1 messenger RNA and protein production in mouse fibroblasts, mouse macrophages, and freshly isolated RA patient synovial cells treated with TLR ligands were detected by real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. Arthritis incidence and severity were determined using clinical scores and histopathologic analysis. Involvement of HTRA‐1 in lipopolysaccharide (LPS)–increased arthritis incidence and severity in mice was determined using anti–HTRA‐1 monoclonal antibody. The signal pathways involved in HTRA‐1 expression were accessed by specific inhibitors, RNA interference, dual‐luciferase reporter, and chromatin immunoprecipitation methods.ResultsLPS and tenascin‐C, but not the other TLR ligands tested, strongly induced HTRA‐1 expression. LPS significantly increased HTRA‐1 expression in the joint tissue as well as arthritis incidence and severity in mice with CIA. Blocking HTRA‐1 by antibody significantly decreased LPS‐promoted CIA severity. Inhibiting NF‐κB significantly decreased LPS‐induced HTRA‐1 expression in mouse and human cells. Dual‐luciferase reporter assay and ChIP analysis showed that p65 directly binds to HTRA‐1 promoter (amino acid 347).ConclusionOur findings indicate that TLR‐4 activation increases HTRA‐1 expression through the NF‐κB pathway in fibroblasts and macrophages. HTRA‐1 expression is involved in the enhancing effects of LPS on CIA. This study offers new insights into the regulation of HTRA‐1 expression via LPS/TLR‐4 and the role of HTRA‐1 in RA pathogenesis.
Genome‐Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders
Authors: Miller Frederick W. , Cooper Robert G. , Vencovský Jiří , Rider Lisa G. , Danko Katalin , Wedderburn Lucy R. , Lundberg Ingrid E. , Pachman Lauren M. , Reed Ann M. , Ytterberg Steven R. , Padyukov Leonid , Selva‐O'Callaghan Albert , Radstake Timothy R. D. J. , Isenberg David A. , Chinoy Hector , Ollier William E. R. , O'Hanlon Terrance P. , Peng Bo , Lee Annette , Lamb Janine A. , Chen Wei , Amos Christopher I. , Gregersen Peter K. ,   with the Myositis Genetics Consortium
Published: August 2013

ObjectiveTo identify new genetic associations with juvenile and adult dermatomyositis (DM).MethodsWe performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.ResultsCompared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.ConclusionOur findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.
Progressing Toward, and Recovering From, Knee Replacement Surgery: A Five‐Year Cohort Study
Authors: Riddle Daniel L. , Perera Robert A. , Stratford Paul W. , Jiranek William A. , Dumenci Levent 
Published: August 2013

ObjectiveTo determine the trajectories of preoperative worsening and postoperative recovery for both the index knee and the contralateral knee of patients undergoing knee replacement surgery.MethodsOf the 4,796 subjects in the Osteoarthritis Initiative cohort study database, we examined 5‐year data from 177 patients who underwent isolated unilateral knee replacement surgery and no other joint replacement surgery. Patient‐reported outcomes captured domains defined by the International Classification of Functioning, Disability, and Health. Domains of knee structure and function, activity limitation, and participation restriction were examined using growth‐curve modeling over 5‐year periods prior to and following surgery.ResultsPreoperative worsening of the index knee was substantial in all domains of knee impairment, activity limitation, and societal participation. Pain intensity worsened only slightly from 5 years to 2.5 years prior to surgery, but worsened by ∼2 points (0–10‐point scale) during the 2.5 years prior to surgery. Trajectories of improvement following surgery varied depending on the outcome measure. The contralateral knee also changed over time, such that by ∼2 years following surgery, pain was worse and by 3 years, activity limitation was worse in the contralateral knee as compared to the index knee.ConclusionPatients who elect to undergo knee replacement surgery demonstrate perioperative trajectories of change that influence most health domains for both the index knee and the contralateral knee. After a period of no change, escalation of pain and worsening functioning in the index knee begins ∼2.5 years prior to surgery, which may be a key trigger for surgery.
Automated docking studies provide insights into molecular determinants of ligand recognition by N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB)
Authors: Huang Xinyi , Hernick Marcy 
Published: August 2013

ABSTRACTThe metal‐dependent deacetylase N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside deacetylase (MshB) catalyzes the deacetylation of N‐acetyl‐1‐d‐myo‐inosityl‐2‐amino‐2‐deoxy‐α‐d‐glucopyranoside (GlcNAc‐Ins), the committed step in mycothiol (MSH) biosynthesis. MSH is the thiol redox buffer used by mycobacteria to protect against oxidative damage and is involved in the detoxification of xenobiotics. As such, MshB is a target for the discovery of new drugs to treat tuberculosis (TB). While MshB substrate specificity and inhibitor activity have been probed extensively using enzyme kinetics, information regarding the molecular basis for the observed differences in substrate specificity and inhibitor activity is lacking. Herein we begin to examine the molecular determinants of MshB substrate specificity using automated docking studies with a set of known MshB substrates. Results from these studies offer insights into molecular recognition by MshB via identification of side chains and dynamic loops that may play roles in ligand binding. Additionally, results from these studies suggest that a hydrophobic cavity adjacent to the active site may be one important determinant of MshB substrate specificity. Importantly, this hydrophobic cavity may be advantageous for the design of MshB inhibitors with high affinity and specificity as potential TB drugs. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 406–417, 2014.
Effect of substituting arginine and lysine with alanine on antimicrobial activity and the mechanism of action of a cationic dodecapeptide (CL(14‐25)), a partial sequence of cyanate lyase from rice
Authors: Taniguchi Masayuki , Takahashi Nobuteru , Takayanagi Tomohiro , Ikeda Atsuo , Ishiyama Yohei , Saitoh Eiichi , Kato Tetsuo , Ochiai Akihito , Tanaka Takaaki 
Published: August 2013

ABSTRACTThe antimicrobial activity of analogs obtained by substituting arginine and lysine in CL(14‐25), a cationic α‐helical dodecapeptide, with alanine against Porphyromonas gingivalis, a periodontal pathogen, varied significantly depending on the number and position of cationic amino acids. The alanine‐substituted analogs had no hemolytic activity, even at a concentration of 1 mM. The antimicrobial activities of CL(K20A) and CL(K20A, K25A) were 3.8‐fold and 9.1‐fold higher, respectively, than that of CL(14‐25). The antimicrobial activity of CL(R15A) was slightly lower than that of CL(14‐25), suggesting that arginine at position 15 is not essential but is important for the antimicrobial activity. The experiments in which the alanine‐substituted analogs bearing the replacement of arginine at position 24 and/or lysine at position 25 were used showed that arginine at position 24 was crucial for the antimicrobial activity whenever lysine at position 25 was substituted with alanine. Helical wheel projections of the alanine‐substituted analogs indicate that the hydrophobicity in the vicinity of leucine at position 16 and alanines at positions 18 and/or 21 increased by substituting lysine at positions 20 and 25 with alanine, respectively. The degrees of diSC3‐5 release from P. gingivalis cells and disruption of GUVs induced by the alanine‐substituted analogs with different positive charges were not closely related to their antimicrobial activities. The enhanced antimicrobial activities of the alanine‐substituted analogs appear to be mainly attributable to the changes in properties such as hydrophobicity and amphipathic propensity due to alanine substitution and not to their extents of positive charge (cationicity). © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 58–68, 2014.