bluuebunny/crossref_metadata_2025_split huggingface dataset:
Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus
Authors: Zhang Yan , Wang Yong-Fei , Yang Jing , Zhang Jing , Sun Liangdan , Hirankarn Nattiya , Pan Hai-Feng , Lau Chak Sing , Chan Tak Mao , Lee Tsz Leung , Leung Alexander Moon Ho , Mok Chi Chiu , Zhang Lu , Shen Jiangshan Jane , Wong Sik Nin , Lee Ka Wing , Ho Marco Hok Kung , Lee Pamela Pui Wah , Chung Brian Hon-Yin , Chong Chun Yin , Wong Raymond Woon Sing , Mok Mo Yin , Wong Wilfred Hing Sang , Tong Kwok Lung , Tse Niko Kei Chiu , Li Xiang-Pei , Avihingsanon Yingyos , Rianthavorn Pornpimol , Deekajorndej Thavatchai , Suphapeetiporn Kanya , Shotelersuk Vorasuk , Ying Shirley King Yee , Fung Samuel Ka Shun , Lai Wai Ming , Wong Chun-Ming , Ng Irene Oi Lin , Garcia-Barcelo Maria-Merce , Cherny Stacey S , Tam Paul Kwong-Hang , Sham Pak Chung , Yang Sen , Ye Dong Qing , Cui Yong , Zhang Xue-Jun , Yang Wanling , Lau Yu Lung 
Published: March 2015

Abstract
Introduction
Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking.

Methods
Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry.

Results
All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, and supportive evidence of association with SLE was found (meta-analysis: P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta =2.70E-09). It showed independent effects through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in patients with SLE.

Conclusions
Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.
Detecting cathepsin activity in human osteoarthritis via activity-based probes
Authors: Ben-Aderet Louisa , Merquiol Emmanuelle , Fahham Duha , Kumar Ashok , Reich Eli , Ben-Nun Yael , Kandel Leonid , Haze Amir , Liebergall Meir , Kosińska Marta K , Steinmeyer Juergen , Turk Boris , Blum Galia , Dvir-Ginzberg Mona 
Published: March 2015

Abstract
Introduction
Lysosomal cathepsins have been reported to contribute to Osteoarthritis (OA) pathophysiology due to their increase in pro-inflammatory conditions. Given the causal role of cathepsins in OA, monitoring their specific activity could provide means for assessing OA severity. To this end, we herein sought to assess a cathepsin activity-based probe (ABP), GB123, in vitro and in vivo.

Methods
Protein levels and activity of cathepsins B and S were monitored by immunoblot analysis and GB123 labeling in cultured primary chondrocytes and conditioned media, following stimuli with tumor necrosis factor alpha (TNFα) and/or Interleukin 1 beta (IL-1β). Similarly, cathepsin activity was examined in sections of intact cartilage (IC) and degraded cartilage (DC) regions of OA. Finally, synovial fluid (SF) and serum from donors with no signs of diseases, early OA, late OA and rheumatoid arthritis (RA) patients were analyzed with GB123 to detect distinct activity levels of cathepsin B and S.

Results
Cathepsin activity in cell lysates, conditioned media explants and DC sections showed enhanced enzymatic activity of cathepsins B and S. Further histological analysis revealed that cathepsin activity was found higher in superficial zones of DC than in IC. Examining serum and SF revealed that cathepsin B is significantly elevated with OA severity in serum and SF, yet levels of cathepsin S are more correlated with synovitis and RA.

Conclusions
Based on our data, cathepsin activity monitored by ABPs correlated well with OA severity and joint inflammation, directing towards a novel etiological target for OA, which possesses significant translational potential in developing means for non-invasive detection of early signs of OA.
Prolonged efficacy of the 300IR 5‐grass pollen tablet up to 2 years after treatment cessation, as measured by a recommended daily combined score
Authors: Didier Alain , Malling Hans‐Jørgen , Worm Margitta , Horak Friedrich , Sussman Gordon L 
Published: March 2015

AbstractBackgroundThe 300IR (index of reactivity) 5‐grass pollen tablet has favorable short‐term and sustained clinical efficacy in patients with grass pollen‐induced allergic rhinoconjunctivitis (ARC). Here, we report maintenance of efficacy and safety over 2 years following treatment discontinuation.MethodsRandomized, double‐blind, placebo‐controlled, parallel‐group, multicenter Phase 3 trial in patients aged 18–50 years with ARC. During study years 1–3, patients received a daily sublingual tablet containing either 300IR 5‐grass pollen extract or placebo, according to a discontinuous pre‐ and coseasonal protocol. Study years 4 and 5 were treatment‐free. In response to health authorities’ recommendations, the daily combined score (DCS) was assessed in a post‐hoc analysis as the efficacy endpoint. Components of the DCS were daily rhinoconjunctivitis total symptom score (DRTSS) and daily rescue medication score (DRMS).Results633 patients with ARC were randomized to placebo (n = 219) or 300IR 5‐grass pollen tablet, beginning 4 months (4 M, n = 207) or 2 months (2 M, n = 207) prior to the estimated start of the grass pollen season and continuing until season's end. During the first post‐treatment year, a statistically significant difference versus placebo in least squares (LS) mean DCS was noted in patients previously receiving active treatment (300IR (2 M) point estimate: −0.16, 95% confidence interval (CI95%): [−0.26, −0.06], p = 0.0019; −31.1%; 300IR (4 M) point estimate: −0.13, CI95%: [−0.23, −0.03], p = 0.0103, −25.3%). During the second post‐treatment year, patients in the 300IR (4 M) group, but not the 300IR (2 M) group, showed a statistically significant difference in LS mean DCS versus placebo (point estimate: −0.11, CI95%: [−0.21; 0.00], p = 0.0478, −28.1%). This significant efficacy seen during the post‐treatment years in patients previously treated with 5‐grass pollen tablet compared favorably with that during the 3 prior years of active treatment. A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post‐treatment years (except for DRTSS in year 5). In the absence of any active treatment, the safety profile was similar in the active groups versus placebo group during either post‐treatment year.ConclusionsIn adults with grass pollen‐associated ARC, 5‐grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season's end demonstrated efficacy across all variables during active treatment, and this effect was prolonged for up to 2 years post‐treatment.Trial registrationClinicalTrials.gov identifier: NCT00418379.
Activation of Transient Receptor Potential Vanilloid 3 Channel Suppresses Adipogenesis
Authors: Cheung Sin Ying , Huang Yu , Kwan Hiu Yee , Chung Hau Yin , Yao Xiaoqiang 
Published: March 2015

Abstract
The present study shows that activation of the transient receptor potential vanilloid 3 channel (TRPV3) suppresses adipocyte differentiation. We also found that a major functional catechin compound in green tea and cocoa, (−)-epicatechin, exerts antiadipogenic effects in the adipocytes through direct activation of TRPV3. TRPV3 was detected in the 3T3-L1 adipocytes using immunohistochemistry and semiquantitative PCR. TRPV3 activation by activators (−)-epicatechin and diphenylborinic anhydride was determined using live cell fluorescent Ca2+ imaging and patch-clamp electrophysiology. Using RNA interference, immunoblotting, and Oil red O staining, we found that the TRPV3 agonists prevented adipogenesis by inhibiting the phosphorylation of insulin receptor substrate 1, the downstream phosphoinositide 3-kinase/Akt/forkhead box protein O1 axis, and the expression of the adipogenic genes peroxisome proliferator–activated receptor γ and CCAAT/enhancer-binding protein α. TRPV3 overexpression hindered adipogenesis in the 3T3-L1 cells. In vivo studies showed that chronic treatment with the TRPV3 activators prevented adipogenesis and weight gain in the mice fed on high-fat diets. Moreover, TRPV3 expression was reduced in the visceral adipose tissue from mice fed on high-fat diets and obese (ob/ob) and diabetic (db/m+) mice. In conclusion, our study illustrates the antiadipogenic role of TRPV3 in the adipocytes.
FSP-1 Impairs the Function of Endothelium Leading to Failure of Arteriovenous Grafts in Diabetic Mice
Authors: Luo Jinlong , Liang Ming , Mitch William E. , Danesh Farhad R. , Yu Michael , Cheng Jizhong 
Published: March 2015

Abstract
To understand how endothelial cell (EC) dysfunction contributes to the failure of arteriovenous graft (AVG), we investigated the role of fibroblast-specific protein 1 (FSP-1) in cultured ECs and a mouse AVG model. In vitro, we uncovered a new FSP-1-dependent pathway that activates rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) in ECs, leading to phosphorylation of myosin light chain 2 resulting in EC dysfunction. In cultured ECs, high glucose stimulated FSP-1 expression and increased permeability of an EC monolayer. The increase in permeability by the high glucose concentration was mediated by FSP-1 expression. Treatment of cultured ECs with FSP-1 caused leakage of the endothelial barrier plus increased expression of adhesion molecules and decreased expression of junction molecules. These responses were initiated by binding of FSP-1 to receptor for advanced glycation end products, which resulted in ROCK1 activation. In vivo, diabetes increased infiltration of inflammatory cells into AVGs and stimulated neointima formation. Increased FSP-1 expression and ROCK1 activation were found in AVGs of diabetic mice. Blocking FSP-1 suppressed diabetes-induced ROCK1 activation in AVGs. In mice with FSP-1 knockout or with ROCK1 knockout, accumulation of inflammatory cells and neointima formation in AVG were attenuated despite diabetes. Thus, mechanisms of inhibiting FSP-1 in ECs could improve AVG function.
The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates Hepatic Metabolism in Rats Fed a High-Fat Diet
Authors: Jiang Baoping , Le Liang , Wan Wenting , Zhai Wei , Hu Keping , Xu Lijia , Xiao Peigen 
Published: March 2015

AbstractAn infusion of Coreopsis tinctoria (CT) flowering tops is traditionally used in Portugal to control hyperglycemia; however, the effects of CT protection against high-fat diet (HFD)-induced hepatic insulin resistance have not been systematically studied and the precise mechanism of action is not clear. The metabolomic profiles of insulin-resistant rats fed a HFD and a CT-supplemented diet (HFD supplemented with CT drinking) for 8 weeks were investigated. Serum samples for clinical biochemistry and liver samples for histopathology and liquid chromatography-mass spectrometry-based metabolomic research were collected. Western blot and quantitative real-time PCR analyses were further used to measure the expression of several relevant enzymes together with perturbed metabolic pathways. Using analysis software, the CT treatment was found to significantly ameliorate the disturbance in 10 metabolic pathways. Combined metabolomic, Western blot, and quantitative real-time PCR analyses revealed that CT treatment significantly improved the glucose homeostasis by, on the one hand, through inhibiting the expression of gluconeogenic pathway key proteins glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and, on the other hand, via regulating the mRNA or protein levels of the Krebs cycle critical enzymes (citrate synthase, succinate dehydrogenase complex, subunit A, flavoprotein, and dihydrolipoamide S-succinyltransferase). These results provide metabolic evidence of the complex pathogenic mechanism involved in hepatic insulin resistance and that the supplementation with CT improves insulin resistance at a global scale. Liquid chromatography-mass spectrometry-based metabolomics approaches are helpful to further understand diabetes-related mechanisms.
Entertainment TV and Social Nature of Communication
Authors: Березин  , Berezin V. 
Published: March 2015

The article explores the trends in TV broadcasting of recent decades. Special
attention is given to the latest period starting December 2013. The conclusion
is made that TV producers and authors are set to pull audience with
content spilling aggression and violence while talk shows and personals
serve as an alternative to the dark side of life. The author investigates the
telecommunication on the basis of academic views of national (M. Bakhtin,
S. Bulgakov, J. Lotman) and foreign researchers (N. Luhmann, J. Habermas).
Western thinkers from a new angle articulated ideas generated by the
Russian philosophers and scholars who preached consensus in considerations
and debates on the human spirit. The linguistic performance of the
spirit should not develop by the way of surface formalization, just for show
but should go along augmentation of spiritual significance of being. Much
attention is given to analyzing the shift of attitude towards social and political
journalism as a tramline in journalism. This is due to the fact that the
value criteria in reflecting the objective reality are being lowered in TV media
products both at home and overseas.
Compact Bid Languages and Core Pricing in Large Multi-item Auctions
Authors: Goetzendorff Andor , Bichler Martin , Shabalin Pasha , Day Robert W. 
Published: March 2015

We introduce an auction design framework for large markets with hundreds of items and complex bidder preferences. Such markets typically lead to computationally hard allocation problems. Our new framework consists of compact bid languages for sealed-bid auctions and methods to compute second-price rules such as the Vickrey–Clarke–Groves or bidder-optimal, core-selecting payment rules when the optimality of the allocation problem cannot be guaranteed. To demonstrate the efficacy of the approach for a specific, complex market, we introduce a compact bidding language for TV advertising markets and investigate the resulting winner-determination problem and the computation of core payments. For realistic instances of the respective winner-determination problems, very good solutions with a small integrality gap can be found quickly, although closing the integrality gap to find marginally better solutions or prove optimality can take a prohibitively large amount of time. Our subsequent adaptation of a constraint-generation technique for the computation of bidder-optimal core payments to this environment is a practically viable paradigm by which core-selecting auction designs can be applied to large markets with potentially hundreds of items. Such auction designs allow bidders to express their preferences with a low number of parameters, while at the same time providing incentives for truthful bidding. We complement our computational experiments in the context of TV advertising markets with additional results for volume discount auctions in procurement to illustrate the applicability of the approach in different types of large markets. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2014.2076 . This paper was accepted by Lorin Hitt, information systems.
Follow-up Outcomes in a Large Cohort of Patients With HPV-Negative LSIL Cervical Screening Test Results
Authors: Barron Stacey , Austin R. Marshall , Li Zaibo , Zhao Chengquan 
Published: March 2015

Abstract

Objectives:
Cervical screening guidelines now recommend repeat cotesting of patients aged 30 years and older having a human papillomavirus (HPV)–negative low-grade squamous intraepithelial lesion (LSIL) in 1 year as preferred management. Only limited follow-up data on patients with HPV-negative LSILs are available from routine US clinical practice settings.

Methods:
In total, 680 patients with Hybrid Capture 2 (Qiagen, Hinden, Germany) high-risk HPV-negative LSIL ThinPrep (Hologic, Marlborough, MA) results were identified. Patients’ ages and histopathologic, cytologic, and HPV follow-up results were identified.

Results:
Among 680 patients with HPV-negative LSILs, 468 had follow-up within 1 year. During the study period, 14 (3.0%) of 468 had follow-up high-grade squamous intraepithelial lesion (HSIL) and 184 (39.3%) LSIL findings. No diagnoses of cervical carcinoma were documented. There were no significant follow-up differences between age groups. Of the 321 patients who had follow-up HPV testing, 271 (84.4%) had negative and 50 (15.6%) had positive HPV results.

Conclusions:
This is the largest study documenting follow-up results for patients with HPV-negative LSIL results based on prevalent US FDA–approved cotesting methods from one collection vial. These data document that risk for follow-up HSILs in these patients is low and also that no cervical cancers were diagnosed. These findings support recent recommendations for repeat cotesting after 1 year as an appropriate option for patients with HPV-negative LSIL results.
Effect of Blood Sampling, Processing, and Storage on the Measurement of Complement Activation Biomarkers
Authors: Yang Shangbin , McGookey Michael , Wang Yi , Cataland Spero R. , Wu Haifeng M. 
Published: March 2015

Abstract

Objectives:
Recent studies have shown that complement hyperactivation contributes to development of thrombotic microangiopathy. The evaluation of complement biomarkers is known to be influenced by inappropriate specimen handling. However, there has been no study fully addressing this topic.

Methods:
Blood from each donor was subjected to 62 different handling conditions prior to complement assays.

Results:
Complement biomarkers (C4d/C3a/factor Bb/C5a/C5b-9) are stable at room temperature (RT) for up to 4 hours in whole blood containing citrate or EDTA. However, under similar conditions, levels of C4d and C3a were significantly higher in serum than those in plasma. Thawing of the samples on ice or at RT had no significant effect on complement levels. In contrast, thawing at 37°C resulted in striking increases in levels of the complement system in serum and citrated plasma but not in EDTA plasma. Up to four freeze/thaw cycles on ice or RT did not substantially increase the levels of C3a, factor Bb, C5a, and C5b-9 but had a significant effect on C4d. Long-term storage of citrated plasma at −80°C for up to 6 years had no significant effect on levels of complement factors.

Conclusions:
The results from this study thus provide crucial guidelines for future investigations using complement biomarkers to define the role of complement system in disease.
Comparison of the bead-based simultaneous analysis of specific platelet antibodies assay (SASPA) and Pak Lx Luminex technology with the monoclonal antibody immobilization of platelet antigens assay (MAIPA) to detect platelet alloantibodies
Authors: Rockenbauer Lisa , Eichelberger Beate , Panzer Simon 
Published: March 2015

AbstractThe identification of platelet alloantibodies is indispensible for the diagnoses of fetal/neonatal alloimmune thrombocytopenia and refractoriness to platelet transfusions.We compared the results obtained with the gold-standard assay for the detection and specification of platelet antibodies, the monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA), with those from two bead-based assays, simultaneous analysis of specific platelet antibodies assay (SASPA), and the recently commercialized bead-based assay Pak Lx.For the detection of alloantibodies by SASPA, the sensitivity was 94.6%, the specificity was 99.5% The respective results for Pak Lx were 98% and 99.8%. Some antibody specificities were revealed by SASPA or Pak Lx but not by MAIPA. However, there were also antibodies detected by MAIPA that were not seen by SASPA or Pak Lx. Antibody dilution experiments suggest that SASPA or Pak Lx are more sensitive than MAIPA.All three assays have limitations, but Pak Lx is suited for screening. However, other assays are necessary if results are not conclusive or for evaluations beyond the commercial assay’s design.
Measurement of the inflammatory response in the early postoperative period after hip and knee arthroplasty
Authors: Wasko Marcin Krzysztof , Bobecka-Wesołowska Konstancja , Tomasiuk Ryszard , Kowalczewski Jacek 
Published: March 2015

AbstractThe aim of this study was to identify an inflammatory marker with fast and predictable kinetics to enable future discrimination between normal postoperative inflammation and potential infection after total hip and knee arthroplasty cases.Changes in serum levels of C-reactive protein (CRP), interleukins (IL) 1β, 6 and 8 and NT-proCNP peptide were measured before and during first 5 postoperative days in 100 patients undergoing total hip or knee arthroplasty. We also compared two methods to describe the magnitude of inflammation – applying separate two sample tests at each time point, and summary measures – area under the curve (AUC).IL-6 showed a similar kinetics pattern to the CRP in response to surgical trauma. Significantly greater level changes in all markers but NT-proCNP were observed in knee patients. Persisting high levels of CRP, but not other markers, were observed in obese hip patients. IL-6 was found to be an adjunct to routine CRP use.IL-6 has faster kinetics and is less influenced by patient weight, therefore it seems to be more useful in clinical practice. Summary measures describe the inflammatory response well and are easier to analyze than multiple analyses of single time points.
QKD-Based Secured Burst Integrity Design for Optical Burst Switched Networks
Authors: Balamurugan A. M. , Sivasubramanian A. , Parvathavarthini B. 
Published: March 2015

AbstractThe field of optical transmission has undergone numerous advancements and is still being researched mainly due to the fact that optical data transmission can be done at enormous speeds. It is quite evident that people prefer optical communication when it comes to large amount of data involving its transmission. The concept of switching in networks has matured enormously with several researches, architecture to implement and methods starting with Optical circuit switching to Optical Burst Switching. Optical burst switching is regarded as viable solution for switching bursts over networks but has several security vulnerabilities. However, this work exploited the security issues associated with Optical Burst Switching with respect to integrity of burst. This proposed Quantum Key based Secure Hash Algorithm (QKBSHA-512) with enhanced compression function design provides better avalanche effect over the conventional integrity algorithms.