bluuebunny/crossref_metadata_2025 huggingface dataset:
RFC1 80G>A Is a Genetic Determinant of Methotrexate Efficacy in Rheumatoid Arthritis: A Human Genome Epidemiologic Review and Meta‐Analysis of Observational Studies
Authors: Kung Tabitha N. , Dennis Jessica , Ma YiQing , Xie Gang , Bykerk Vivian , Pope Janet , Thorne Carter , Keystone Edward , Siminovitch Katherine A. , Gagnon France
Published: December 2013

Objective

Associations have been reported between candidate genes and the response to methotrexate (MTX) in rheumatoid arthritis (RA) patients, but most of the studies have been small and have yielded conflicting results. This study was undertaken to provide a systematic review of all genetic variant associations with MTX efficacy and toxicity, and to conduct a meta‐analysis evaluating the most commonly studied single‐nucleotide polymorphism for which prior cumulative analysis has been lacking.

Methods

A systematic review and meta‐analysis were performed to identify genetic variant associations with MTX efficacy and toxicity. Studies were identified from the Medline, EMBase, HuGENet Navigator, and Cochrane Library databases through December 2012, and from the 2009–2011 abstracts of the American College of Rheumatology and the European League Against Rheumatism annual meeting proceedings. Additional unpublished genotype data from a Canadian cohort of patients with early RA were also included.

Results

Among the 87 identified studies examining genetic associations with MTX efficacy and toxicity, the reduced folate carrier 1 gene (RFC1) variant 80G>A (Arg27His, rs1051266) was selected for random‐effects meta‐analysis. RFC1 80G>A was associated with MTX efficacy in both the recessive model (odds ratio [OR] 1.42, 95% confidence interval [95% CI] 1.04–1.93) and the additive model (OR 1.28, 95% CI 1.10–1.49). Restriction of the sensitivity analyses to studies that involved Caucasian subjects only and that used similar outcome measures (MTX failure versus nonfailure) maintained and improved the associations in both models. No significant association between RFC1 80G>A and MTX toxicity was detected.

Conclusion

In these analyses of available data from observational studies, RFC1 80G>A was found to be associated with MTX efficacy, but not toxicity, in RA patients. This variant merits further prospective analysis as a potential predictor of MTX efficacy. Variability in the definitions of response in pharmacogenetic studies is a source of data heterogeneity that should be addressed.
Antibodies to IgG4 Hinge Can Be Found in Rheumatoid Arthritis Patients During All Stages of Disease and May Exacerbate Chronic Antibody‐Mediated Inflammation
Authors: van de Stadt Lotte A. , de Vrieze Henk , Derksen Ninotska I. L. , Brouwer Mieke , Wouters Diana , van Schaardenburg Dirkjan , Wolbink Gertjan , Rispens Theo
Published: December 2013

Objective

In rheumatoid arthritis (RA), autoantibodies such as anti–citrullinated protein antibodies (ACPAs) develop in response to neoepitopes that are formed under conditions of chronic inflammation. These autoantibodies may subsequently be fragmented by inflammation‐associated proteases, leading to the formation of F(ab′)2 fragments. The hinge of F(ab′)2 fragments can serve as a neoepitope, and so‐called antihinge antibodies (AHAs) can be found in RA patients, which might modulate the function of (fragmented) autoantibodies. We undertook this study to investigate the presence and specificities of AHAs in different stages of RA and to study their function.

Methods

The presence of AHAs was assessed by radioimmunoassay in healthy controls, blood donors who later developed RA, patients with arthralgia, patients with early RA, and patients with established RA. Specificity of the AHAs was analyzed with inhibition assays, and complement‐activating ability was studied with a C4b deposition assay.

Results

Antibodies to IgG1 hinge, IgG2 hinge, and IgG4 hinge were detected in patients with established RA, with anti–IgG4 hinge antibodies being most specific (appearing in 1% of healthy controls, 3.8% of blood donors who later developed RA, 13% of arthralgia patients, 19% of early RA patients, and 16% of established RA patients). Anti–IgG4 hinge antibodies were subclass specific and were able to restore C4b deposition by IgG4 F(ab′)2 fragments. In patients with arthralgia and patients with early RA, anti–IgG4 hinge antibodies were associated with rheumatoid factors and ACPAs.

Conclusion

Anti–IgG4 hinge antibodies are present in RA patients and have low sensitivity but high specificity for RA. Since a significant proportion of ACPAs can be of the IgG4 subclass, the formation of anti–IgG4 hinge antibodies may represent one mechanism of ACPA‐mediated inflammation.
The Role of Transforming Growth Factor β Signaling in Fibroblast‐like Synoviocytes From Patients With Oligoarticular Juvenile Idiopathic Arthritis: Dysregulation of Transforming Growth Factor β Signaling, Including Overexpression of Bone Morphogenetic Protein 4, May Lead to a Chondrocyte Phenotype and May Contribute to Bony Hypertrophy
Authors: Brescia AnneMarie C. , Simonds Megan M. , McCahan Suzanne M. , Fawcett Paul T. , Rose Carlos D.
Published: December 2013

Objective

This study was designed to investigate the pathogenic contributions of fibroblast‐like synoviocytes (FLS) to juvenile idiopathic arthritis (JIA) by identifying pathways with dysregulated gene expression in FLS from patients with oligoarticular JIA.

Methods

FLS were derived from synovial fluid obtained by arthrocentesis from patients with JIA undergoing intraarticular steroid injections and from orthopedic control patients. Gene expression profiles of the JIA and control FLS were obtained using the Affymetrix platform, with application of Ingenuity Pathway Analysis and Gene Set Enrichment Analysis software to define gene sets in dysregulated pathways and networks of potential pathologic relevance in this disease. Biologically relevant differentially expressed genes were confirmed by RNA and protein analysis.

Results

Exploration of global gene expression profiles of the JIA FLS revealed important dysregulated pathways, including the transforming growth factor β (TGFβ) signaling, as well as endochondral bone formation, cartilage formation, and β‐catenin networks. Importantly, bone morphogenetic protein 4 (BMP‐4) was significantly overexpressed in the JIA FLS. FLS from patients with oligoarticular JIA exhibit a chondrocyte phenotype, as evidenced by expression of type II collagen and aggrecan.

Conclusion

Dysregulation of the pathways involved in the pathogenesis of oligoarticular JIA were revealed through gene expression profiling. JIA FLS displayed dysregulated TGFβ signaling and exhibited a hypertrophic chondrocyte phenotype. These characteristics, along with contributions from the β‐catenin network may have implications for endochondral bone formation and local growth disturbances in oligoarticular JIA. Overexpression of BMP‐4 in FLS from patients with oligoarticular JIA in particular may play an important role in disease pathogenesis, with a direct effect on functional outcome and with implications for future treatment.
Significant expression of a Chinese scorpion peptide, BmK1, in Escherichia coli through promoter engineering and gene dosage strategy
Authors: Wang Jianfeng , Xiong Zhiqiang , Yang Yingying , Zhao Na , Wang Yong
Published: December 2013

Heterologous expression is an efficient alternative to conventional extraction to produce a specific Buthus martensii Karsch (BmK) peptide. In this work, BmK1 was successfully expressed in Escherichia coli after genetic codon optimization, but BmK1 content was <6% of total cellular protein. To improve BmK1 expression, a trc promoter library with a wide relative strength was constructed, and three promoters, PpJF136 (0.55), PpJF325 (1.29), and PpJF288 (2.31), were selected to control BmK1 expression. A higher BmK1 expression (>13.9% of total protein) was obtained using a stronger promoter, PpJF325. Furthermore, a maximum BmK1 content (>21.7% of total protein) was obtained by combining promoter PpJF325 and three copies of the BmK1 gene. The yield of the purified BmK1 achieved 196.74 mg L−1 in E. coli BL21(DE3) pJF431, which was improved 2.09‐fold compared with the control. This was the highest reported production of scorpion peptides in E. coli.
Peculiarities of metabolism of anthracene and pyrene by laccase‐producing fungus Pycnoporus sanguineusH1
Authors: Li Xuanzhen , Wang Yan , Wu Shijin , Qiu Lequan , Gu Li , Li Jingjing , Zhang Bao , Zhong Weihong
Published: December 2013

The metabolic peculiarities of anthracene and pyrene by Pycnoporus sanguineus H1 were investigated. The fungus H1 could grow on potato dextrose agar plates with anthracene and anthraquinone as carbon sources. In liquid medium, the strain degraded 8.5% of anthracene as the sole carbon source, with no ligninolytic enzymes detected, indicating that intracellular catabolic enzymes might be responsible for the initial oxidation of anthracene. When bran was added to the medium, the degradation rate of anthracene and pyrene increased to 71.3% and 30.2%, respectively, and the laccase activities increased to a maximal value of 501.2 and 587.6 U/L, respectively. By gas chromatography–mass spectrometry analysis, anthraquinone was detected as the unique intermediate product of anthracene oxidation, with a yield molar ratio of 0.3. In vitro experiments showed that the extracellular culture fluid containing laccase transformed anthracene to anthraquinone with a yield molar ratio of 1.0, which was less than that of the in vivo experiment, indicating that anthraquinone could be further metabolized by the strain. Pyrene could not be oxidized by culture fluid. These results showed that both extracellular laccase and intracellular catabolic enzymes might play an important role in the initial oxidation of anthracene, whereas pyrene could be only oxidized by intracellular catabolic enzymes through cometabolism.
In vitro differentiation of mesenchymal stem cells into mesangial cells when co‐cultured with injured mesangial cells
Authors: Wong Chee‐Yin , Tan Eng‐Lai , Cheong Soon‐Keng
Published: December 2013

Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co‐cultured with oxidant‐injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co‐cultured with injured mesangial cells had a mesangial cell‐like morphology and contracted in response to angiotensin II. They expressed CD54− CD62E+ in direct contrast to the CD54+ CD62E− of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co‐cultured with injured mesangial cells.
Pax3 isoforms in sensory neurogenesis: Expression and function in the ophthalmic trigeminal placode
Authors: Adams Jason S. , Sudweeks Sterling N. , Stark Michael R.
Published: December 2013

Background: In the trigeminal placode, Pax3 is classified as necessary but not sufficient for sensory neuron differentiation. One hypothesis is that different Pax3 isoforms regulate cellular differentiation uniquely. Pax3 is known to sometimes activate and sometimes repress gene transcription, and its activity can be dependent on the isoforms present. Pax3 isoforms had not previously been characterized in chick sensory neurogenesis. Results: Reverse transcriptase‐polymerase chain reaction (PCR) analysis revealed three well‐expressed Pax3 splice variants: full‐length (flPax3), Pax3V1, and Pax3V2. Each was characterized for its effect on neurogenesis by misexpression in placodal ectoderm. The differences observed were more apparent under conditions of enhanced neurogenesis (by means of Notch inhibition), where flPax3 and Pax3V1 caused failed differentiation, while Pax3V2 misexpression resembled the neuronal differentiation seen in controls. Quantitative PCR analysis revealed a progressive increase in Pax3 expression, but no significant change in relative isoform expression. Of interest, Notch inhibition led to a significant increase in Pax3 expression. Conclusions: We can conclude that: (1) flPax3 and Pax3V1 inhibit neuronal differentiation; (2) Pax3V2 is permissive for neuronal differentiation; (3) while absolute levels change over time, relative splice form expression levels are largely maintained in the trigeminal placode domain; and (4) Pax3 expression generally increases in response to Notch inhibition. Developmental Dynamics 243:1249–1261, 2014. © 2013 Wiley Periodicals, Inc.
Characteristics of the lipid and fatty acid compositions of the Humboldt squid, Dosidicus gigas: The trophic relationship between the squid and its prey
Authors: Saito Hiroaki , Sakai Mitsuo , Wakabayashi Toshie
Published: December 2013

The lipids and fatty acids of the Humboldt squid (Dosidicus gigas) were examined to assess its lipid physiology and the relationship between the squid and its prey. Similar to highly migratory fishes, D. gigas has high levels of 22:6n‐3 (DHA) in its TAGs (21.9–29.0% for mantles and 21.8–23.9% for arms), different from stomach content lipids (1.9–16.5%), which fluctuated or were at very low levels in some samples. The major PUFA in the tissue (mantle, arm, integument, and gonad) phospholipids were 20:5n‐3 (icosapentaenoic acid, EPA), and DHA. Markedly high levels of both EPA and DHA with noticeable levels of 20:4n‐6 (arachidonic acid; ARA) were observed in phosphatidylethanolamine (17.2–28.8% for EPA, 8.8–22.6% for DHA, and 2.4–11.8% for ARA), while DHA was found as a major component in phosphatidylcholine (30.6–47.8% for DHA). These findings imply a concentration of these PUFA from the storage lipids in the tissues of D. gigas, and that the squid actively concentrates EPA and in particular DHA as a top predator, similar to highly migratory fishes. D. gigas is a healthful marine food containing high levels of EPA and DHA with noticeable levels of ARA.
Comparison of the antioxidant capacity of lipid‐soluble compounds in selected cold‐pressed oils using photochemiluminescence assay (PCL) and DPPH method
Authors: Sielicka Maria , Małecka Maria , Purłan Małgorzata
Published: December 2013

The paper describes the use of photochemiluminescence assay (PCL) and DPPH method for the measurement of lipid‐soluble antioxidants capacity (ACL) of six commercially available cold‐pressed, non‐refined flaxseed, walnut, rapeseed, pumpkin seed, evening primrose and black cumin oils. The cold‐pressed plant oils are rich in various valuable bioactive compounds, e.g., tocopherols, tocotrienols, carotenoids, sterols, phospholipids and may reveal the antioxidant properties. The photochemiluminescence analysis (PCL) and free radical scavenging activity toward DPPH. were fully applicable for the evaluation of the antioxidant capacity of lipophilic fraction of samples and the outcomes correlated (r = 0.91). The highest ACL exhibited black cumin oil in case of both methods.

Practical applications: Photochemiluminescence analysis and radical scavenging activity toward DPPH. were fully applicable for the evaluation of the antioxidant capacity of lipophilic fraction of oil samples. However, providing a simple and reliable analytical method to detect the antioxidant capacities at very low concentrations of antioxidants in the sample is of major interest. Photochemiluminescence analysis shows many advantages over the other methodologies as it is fully automatic, sensitive, quick and does not require any time‐consuming or complicated sample preparation steps that is needed in case of, e.g., DPPH method.
Application of direct HPTLC‐MALDI for the qualitative and quantitative profiling of neutral and acidic glycosphingolipids: The case of NEU3 overexpressing C2C12 murine myoblasts
Authors: Torretta Enrica , Vasso Michele , Fania Chiara , Capitanio Daniele , Bergante Sonia , Piccoli Marco , Tettamanti Guido , Anastasia Luigi , Gelfi Cecilia
Published: December 2013

Glycosphingolipids (GSLs) are a class of ubiquitous lipids characterized by a wide structural repertoire and a variety of functional implications. Importantly, altered levels have been correlated with different diseases, suggesting their crucial role in health. Conventional methods for the characterization and quantification are based on high‐performance TLC (HPTLC) separation and comparison with the migration distance of standard samples or on MS. We set up and herein report the application of an ImagePrep method for glycosphingolipids qualitative and quantitative profiling through direct HPTLC‐MALDI with particular application to wild‐type and NEU3 sialidase‐overexpressing C2C12 myoblasts. Lipids were analyzed by HPTLC, coupled with MALDI‐TOF, and the resulting GSLs profiles were compared to the [3H]sphingolipids HPTLC patterns obtained after metabolic radiolabeling. GSLs detection by HPTLC‐MALDI was optimized by testing different methods for matrix delivery and by performing quantitative analyses using serial dilutions of GSLs standards. Through this approach an accurate analysis of each variant of neutral and acidic GSLs, including the detection of different fatty‐acid chain variants for each GSL, was provided and these results demonstrated that HPTLC‐MALDI is an easy and high‐throughput analytical method for GSLs profiling, suggesting its use for an early detection of markers in different diseases, including cancer and heart ischemia.
Rapid screening of the heterogeneity of DNA methylation by single‐strand conformation polymorphism and CE‐LIF in the presence of electro‐osmotic flow
Authors: Yu Meng‐Hsuan , Huang Ya‐Chi , Chang Po‐Ling
Published: December 2013

DNA methylation is a complex event in epigenetic studies because of both the large CpG islands present upstream of the promoter region and the different distribution of DNA methylation despite similar methylation levels. For this reason, we proposed a fast, cost‐effective method for the screening of DNA methylation based on SSCP and CE‐LIF. In this study, the PCR products that were amplified from bisulfite‐treated genomic DNA were denatured at 94°C, followed by immediate chilling in ice water to form the ssDNA. The ssDNA were separated by 1.5% poly(ethylene oxide) (Mavg 8 000 000 Da) in the presence of EOF according to the different conformations represented by their unique methylation states. This result demonstrated that four hepatocellular carcinoma cell lines represented a different heterogeneity of DNA methylation and could be distinguished by SSCP‐CE. The results obtained from SSCP‐CE also corresponded with those obtained from combined bisulfide restriction analysis and methylation‐sensitive high‐resolution melting analysis. Therefore, the proposed SSCP‐CE method may potentially be used for rapid screening for determination of the heterogeneity of DNA methylation in further epigenetic studies and clinical diagnosis.
Deposition flux of aerosol particles and 15 polycyclic aromatic hydrocarbons in the North China Plain
Authors: Wang Xilong , Liu Shuzhen , Zhao Jingyu , Zuo Qian , Liu Wenxin , Li Bengang , Tao Shu
Published: December 2013

The present study examined deposition fluxes of aerosol particles and 15 polycyclic aromatic hydrocarbons (PAHs) associated with the particles in the North China Plain. The annual mean deposition fluxes of aerosol particles and 15 PAHs were 0.69 ± 0.46 g/(m2 × d) and 8.5 ± 6.2 μg/(m2 × d), respectively. Phenanthrene, fluoranthene, pyrene, chrysene, benzo[b]fluoranthene, and benzo[k]fluoranthene were the dominant PAHs bound to deposited aerosol particles throughout the year. The total concentration of 15 PAHs in the deposited aerosol particles was the highest in winter but lowest in spring. The highest PAH concentration in the deposited aerosol particles in winter was because the heating processes highly increased the concentration in atmospheric aerosol particles. Low temperature and weak sunshine in winter reduced the degradation rate of deposited aerosol particle-bound PAHs, especially for those with low molecular weight. The lowest PAH concentration in deposited aerosol particles in spring resulted from the frequently occurring dust storms, which diluted PAH concentrations. The mean deposition flux of PAHs with aerosol particles in winter (16 μg/[m2 × d]) reached 3 times to 5 times that in other seasons (3.5–5.0 μg/[m2 × d]). The spatial variation of the deposition flux of PAHs with high molecular weight (e.g., benzo[a]pyrene) was consistent with their concentrations in the atmospheric aerosol particles, whereas such a phenomenon was not observed for those with low molecular weight (e.g., phenanthrene) because of their distinct hydrophobicity, Henry's law constant, and the spatially heterogeneous meteorological conditions. Environ Toxicol Chem 2014;33:753–760. © 2013 SETAC
Competition matters: Species interactions prolong the long-term effects of pulsed toxicant stress on populations
Authors: Kattwinkel Mira , Liess Matthias
Published: December 2013

Recent empirical studies have revealed the importance of species competition for the effects of toxicants on populations. In the present study, the authors applied a generic individual-based simulation model of 2 competing species to analyze the consequences of interspecific competition for population dynamics under pulsed contamination. The results indicated that competition that causes a density-dependent decrease in reproduction can substantially prolong the long-term effects of the toxicant. In the example investigated, population recovery time increased from approximately 1 generation time without competition to more than 3 generation times under competition. In particular, species with low reproductive capacity exhibited a strongly prolonged recovery time when interspecific competition was included in the model. The authors conclude that toxicant concentrations derived from risk assessments for pesticides that do not consider competition might be under-protective for populations in real-world systems. The consideration of competition is especially relevant for species with low reproductive capacities to enable a realistic estimation of recovery pace. Environ Toxicol Chem 2014;33:1458–1465. © 2013 SETAC
A simulation study on effects of exposure to a combination of pesticides used in an orchard and tuber crop on the recovery time of a vulnerable aquatic invertebrate
Authors: Focks Andreas , Luttik Robert , Zorn Mathilde , Brock Theo , Roex Erwin , Van der Linden Ton , Brink Paul J. Van den
Published: December 2013

The aim of the present study was to assess whether population effects and recovery times increase when a population of a vulnerable aquatic invertebrate is exposed to concentrations of 1 or multiple pesticides. The 2 sets of pesticide combinations tested are typical for orchard and tuber crops in The Netherlands. Exposure concentrations were predicted using the FOCUS step 3 modeling framework and the Dutch drainage ditch scenario. Recovery times were assessed using the MASTEP population model. We simulated the population dynamics and pesticide effects in a Monte Carlo style by using median effective concentration values drawn from an arthropod species sensitivity distribution. In the tuber scenario, exposure to λ-cyhalothrin resulted in long-term effects, whereas exposure to the co-occurring compound fluazinam hardly resulted in (additional) effects. In the orchard scenario, 3 pesticides resulted in large effects just after exposure, but pulse exposures to these compounds did not coincide. The probabilities of effects for the single compounds added up for the combination; in contrast, the recovery times were not higher for the combination compared to those associated with exposure to the individual compounds. The conclusion from the present study's simulations is that exposure to the evaluated pesticide packages may lead to increased mortality probabilities and effect sizes of the combination, but does not lead to longer recovery times for populations with synchronized reproduction than when exposed to the individual compounds. Environ Toxicol Chem 2014;33:1489–1498. © 2013 SETAC
Iodine‐Promoted Synthesis of 1‐Alkyl‐3‐aroylindolizines from N‐(Aroylmethyl)pyridinium Salts and Aliphatic Aldehydes
Authors: Tan Chen , Yan Peiyun , Ye Weijian , Yao Juan , Wu Weiming , Wang Cunde
Published: December 2013

An effective and practical method has been developed for the diversity‐oriented synthesis of 1‐alkyl‐3‐aroylindolizines via the 1,3‐dipolar cycloaddition of pyridinium ylides and aliphatic aldehydes in the presence of molecular iodine and a catalytic amount of MnO2. The synthesis proceeds by tandem reactions involving [3+2] cycloaddition, dehydration of the cycloadduct, and dehydroaromatization. Molecular iodine served both as a catalyst and a dehydroaromatization reagent in the reaction.
Transtracheal approach to repair of a tracheo‐colonic fistula 44 years after colonic interposition
Authors: Mehra Saral , Scherl Sophie , Lazarus Cathy , Dewey Eliza , Urken Mark L.
Published: December 2013

Background

We present a case report of a trachea‐colonic fistula and demonstrate our unique approach to repair, which was efficient and effective.

Methods

The patient was a 50‐year‐old man who had a congenital tracheoesophageal fistula repair with colonic interposition as a child who now developed a fistula between his colon and trachea.

Results

We performed a transtracheal approach, with primary closure of redundant colon mucosa as well as direct repair of the trachea. An inferiorly based sternocleidomastoid muscle flap was interposed between these 2 layers to augment the repair. The patient had an uneventful recovery with an effective reconstitution of the alimentary tract and the airway.

Conclusion

Tracheo‐colonic fistula is an extremely rare pathology, and the scarring that develops after a prior esophagectomy makes a traditional lateral approach very difficult. The transtracheal approach is an effective method to obtain needed exposure in order to carry out the repair. © 2014 Wiley Periodicals, Inc. Head Neck 36: E117–E120, 2014
Angioembolization of a leaking radial artery pseudoaneurysm in a radial forearm free flap
Authors: Senchenkov Alex
Published: December 2013

Background

A radial forearm free flap (RFFF) is used frequently in oral and pharyngeal reconstruction. Pseudoaneurysms within RFFFs and their management have not been previously reported.

Methods and Results

In the present case, a patient with chemoradiation failure of the right base of the tongue clear cell carcinoma underwent salvage resection and failed reconstruction with pectoralis major muscle flap. He subsequently underwent RFFF reconstruction with delayed development of a radial artery pseudoaneurysm at the site of a previous arterial line within the RFFF, which was not present perioperatively. A rupture of this pseudoaneurysm manifested with recurrent bleeding. Angiography with embolization successfully arrested the bleeding without compromising the flap.

Conclusion

Ruptured pseudoaneurysm of the radial artery within the RFFF is a rare and life‐threatening complication, which in the posterior oral cavity and pharynx can be effectively managed with angioembolization. © 2014 Wiley Periodicals, Inc. Head Neck 37: E12‐E14, 2015
Unexpected thrombus migration obstructing the right coronary ostium after thoracic aorta graft replacement
Authors: Shim Jae‐Kwang , Song Young , Lee Taek‐Yeon , Kim Yoon‐Jae , Kwak Young‐Lan
Published: December 2013

Unexpected and reversible causes of ventricular dysfunction requiring a prompt second surgical procedure to restore the cardiac function should always be sought before the initiation of positive inotropic support. We report a case of obstruction of the right coronary ostium by an organized thrombus that had migrated retrogradely from the false lumen of a dissected aortic aneurysm. The resultant ventricular dysfunction hindered separation from cardiopulmonary bypass. Prompt recognition was done by transesophageal echocardiography and a second surgical procedure was immediately performed to remove the thrombus before irreversible ventricular dysfunction occurred. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound 42:318–320, 2014
Neuronal and nonneuronal COX‐2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge
Authors: An Ying , Belevych Natalya , Wang Yufen , Zhang Hao , Herschman Harvey , Chen Qun , Quan Ning
Published: December 2013

Treating acute brain injuries with COX‐2 inhibitors can produce both neuroprotective and neurotoxic effects. This study investigated the role of COX‐2 in modulating acute brain injury induced by excitotoxic neural damage. Intrastriatal injection of excitotoxin (RS)‐(tetrazole‐5yl) glycine elicited COX‐2 expression in two distinct groups of cells. cortical neurons surrounding the lesion and vascular cells in the lesion core. The vascular COX‐2 was expressed in two cell types, endothelial cells and monocytes. Selective deletion of COX‐2 in vascular cells in Tie2Cre Cox‐2flox/flox mice did not affect the induction of COX‐2 in neurons after the excitotoxin injection but resulted in increased lesion volume, indicating a neuroprotective role for the COX‐2 expressed in the vascular cells. Selective deletion of monocyte COX‐2 in LysMCre Cox‐2flox/flox mice did not reduce COX‐2‐dependent neuroprotection, suggesting that endothelial COX‐2 is sufficient to confer neuroprotection. Pharmacological inhibition of COX‐2 activity in Tie2Cre Cox‐2flox/flox mice reduced lesion volume, indicating a neurotoxic role for the COX‐2 expressed in neurons. Furthermore, COX‐2‐dependent neurotoxicity was mediated, at least in part, via the activation of the EP1 receptor. These results show that Cox‐2 expression induced in different cell types can confer opposite effects. © 2013 Wiley Periodicals, Inc.
Evidence that the LRRK2 ROC domain Parkinson's disease‐associated mutants A1442P and R1441C exhibit increased intracellular degradation
Authors: Greene Izabella D. , Mastaglia Francis , Meloni Bruno P. , West Kristin A. , Chieng Joanne , Mitchell Chris J. , Gai Wei‐Ping , Boulos Sherif
Published: December 2013

Mutations in the leucine‐rich repeat kinase 2 (lrrk2) gene are the leading genetic cause of Parkinson's disease (PD). In characterizing the novel ROC domain mutant A1442P, we compared its steady‐state protein levels, propensity to aggregate, and toxicity with the pathogenic R1441C mutant and wild‐type (WT) LRRK2. Mutant (R1441C and A1442P) and WT LRRK2 fused to green fluorescent protein (GFP) and FLAG were transiently expressed in HEK293 cells using plasmid constructs. Western analysis and fluorescence microscopy consistently demonstrated lower mutant LRRK2 protein levels compared with WT. A time‐course expression study using flow cytometry showed that WT LRRK2 expression increased initially but then plateaued by 72 hr. Conversely, R1441C and A1442P mutant expression attained 85% and 74% of WT levels at 24 hr but fell to 68% and 55% of WT levels by 72 hr, respectively. We found that proteasome inhibition markedly increased mutant LRRK2 to levels approaching those of WT. Taken together, our findings reveal increased intracellular degradation for both mutants. Furthermore, the impact of mutant and WT LRRK2 expression on HEK293 cell viability was assessed under normative and oxidative (hydrogen peroxide) conditions and found not to differ. Expression of WT and mutant LRRK2 protein gave rise to intracellular aggregates of similar appearance and cellular localization. In summary, we provide evidence that the novel A1442P mutant and the previously investigated R1441C pathogenic mutant exhibit increased intracellular degradation, a property reportedly demonstrated for the pathogenic LRRK2 kinase domain mutant I2020T. © 2013 Wiley Periodicals, Inc.
Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: A phase II TCOG study
Authors: Wang Ling‐Wei , Hsiao Chin‐Fu , Chen William Tzu‐Liang , Lee Hao‐Hsien , Lin Tzu‐Chen , Chen Hung‐Chang , Chen Hong‐Hwa , Chien Chun‐Ru , Lin Tze‐Yi , Liu Tsang‐Wu
Published: December 2013

Background

To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer.

Patients and Methods

Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur‐uracil and folinate on days 1–30 and 38–65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX‐2) in tumor tissues was evaluated microscopically as a prognostic factor.

Results

From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low‐positioned tumors. Patients with tumors expressing high‐level COX‐2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease‐free survival (P = 0.04), and overall survival (P = 0.03) than those with low‐level expression.

Conclusions

Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high‐level COX‐2 after CRT and surgery. J. Surg. Oncol. 2014 109:580–585. © 2013 Wiley Periodicals, Inc.
MRI surveillance following treatment of extremity soft tissue sarcoma
Authors: Cheney Matthew D. , Giraud Christine , Goldberg Saveli I. , Rosenthal Daniel I. , Hornicek Francis J. , Choy Edwin , Mullen John T. , Chen Yen‐Lin , DeLaney Thomas F.
Published: December 2013

Background and Objectives

Local recurrence (LR) following limb‐sparing surgery and radiation therapy (RT) for extremity soft tissue sarcoma (STS) is rare. The current study investigates the utility of surveillance nuclear magnetic resonance imaging (MRI) for detection of asymptomatic LRs.

Methods

The study cohort consisted of 168 adult patients with extremity STS treated with limb‐sparing surgery and RT with curative intent between October 2001 and January 2011. Follow‐up surveillance MRIs and history and physical examinations were performed per the NCCN guidelines with additional MRIs as clinically indicated. The method of LR detection and MRI number and indication were determined.

Results

After a median follow‐up of 4.7 years (range: 0.6–10.5) 11 (6.5%; 11/168) patients developed LRs. Five hundred two MRIs were obtained, 429 (85.5%; 429/502) for surveillance and 73 (14.5%; 73/502) as clinically indicated. One hundred fourteen patients underwent ≥1 surveillance MRI. The median surveillance MRI interval was 6.4 months (range 1.4–68.9). Surveillance MRI detected an asymptomatic LR in 1 (0.9%; 1/114) patient with a complex reconstruction.

Conclusions

Surveillance MRI infrequently detects asymptomatic LRs following limb‐sparing surgery and RT for extremity STS and should be limited to patients whose primary tumor sites are not easily assessed by history and physical examination. J. Surg. Oncol. 2014 109:593–596. © 2013 Wiley Periodicals, Inc.
Making the case for cost‐effectiveness research
Authors: Abbott Daniel E. , Sutton Jeffrey M. , Edwards Michael J.
Published: December 2013

Cost‐effectiveness research is a component of clinical outcomes that addresses both cost and outcomes simultaneously, providing an understanding of what incremental costs, if any, are required for better clinical outcomes. In the current health care climate, these analyses are increasingly performed, and critical, as practitioners must optimize patient care at lower costs. This review discusses cost effectiveness research, its utilization in surgical oncology, and future opportunities provided by its methodologies. J. Surg. Oncol. 2014 109:509–515. © 2013 Wiley Periodicals, Inc.
Modal expansion approach for accurately computing resonant modes in a high‐Q optical resonator
Authors: Kang Young Mo , Xue Mingfeng , Arbabi Amir , Jin Jian‐Ming , Goddard Lynford L.
Published: December 2013

We present a method based on the modal expansion approach for computing resonant modes of a high‐Q optical resonator. We reconstruct both the complex eigenfrequencies and the spatial modal profiles by solving an inhomogeneous linear system excited by a current source in the resonator. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:278–284, 2014
Frequency selective surface filters with polarized band pass/band reject performances
Authors: D'Assunção A. G. , Fontgalland G. , Neto A. Gomes , Baudrand Henri
Published: December 2013

This work presents a wave concept iterative procedure design of a frequency selective surface (FSS) structure, which elements are composed by integration of square ring and cross dipole conducting patch elements. The proposed FSS geometry allows the development of a band pass or band reject filter, depending of the incident wave polarization. Simulated and measured results for the transmission coefficient are compared and a good agreement is observed. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:483–487, 2014
Precise measurement of fiber dispersion based on phase‐modulated signal fading
Authors: Zhang Shangjian , Zou Xinhai , Zhang Yali , Zhang Xiaoxia , Liu Yong
Published: December 2013

We propose a novel method for accurately measuring the chromatic dispersion based on the fading effect of the phase‐modulated signal. The fiber dispersion, acting as an optical phase filter, causes the periodical fading of the phase‐modulated signal, and the polynomial fitting of the fading curve enables the precise determination of the characteristic notch frequency and the fiber dispersion. Our method can be used for the chromatic dispersion measurement at different operating wavelengths and dispersive fibers by using a vector network analyzer. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:427–430, 2014
Optical fiber humidity sensor based on a tapered fiber with hydroxyethylcellulose/polyvinylidenefluoride composite
Authors: Lokman Asiah , Nodehi Somayeh , Batumalay M. , Arof H. , Ahmad H. , Harun Sulaiman Wadi
Published: December 2013

A simple relative humidity (RH) sensor is demonstrated using a tapered fiber with an hydrogel coating. Hydroxyethylcellulose/polyvinylidenefluoride polymers are used to form the hydrogel coating of the tapered fiber as they are sensitive to moisture and thus the humidity of the atmosphere. Changes in humidity level alter the refractive index of the fiber coating and this condition leads to variation in optical output power. A difference of up to 0.89 dB of the transmitted optical power is observed when RH changes from 50 to 80%. The proposed sensor has a sensitivity of about 0.0228 dB/%RH with a slope linearity of more than 99.91%. In summary, the hydrogel coating acts as an inner cladding whose refractive index decreases with the rise in humidity and thus allows more light to be transmitted in humid state. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:380–382, 2014
Circularly polarized meshed patch antenna using coplanar Y‐shaped coupling feed
Authors: Yasin Tursunjan , Baktur Reyhan
Published: December 2013

This article describes a circularly polarized optically transparent meshed patch antenna designed for small satellite applications. The antenna consists of a nearly square meshed patch that is fed with a coplanar Y‐shaped feed. The configuration of the antenna and feed network has the advantage of being integrable with solar panels of small satellites to resolve the limited surface area issue. The results for a prototyped left‐handed circularly polarized antenna operating at 2.34 GHz are presented. The axial ratio is 2 dB, and the gain is 4.7 dB at the center frequency. The 10‐dB impedance bandwidth is close to 2% and the 3‐dB axial ratio bandwidth is 7 MHz. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:487–489, 2014
A wide‐locking ÷3 BiCMOS injection‐locked frequency divider using internal feedback
Authors: Jang Sheng‐Lyang , Hsieh Jen‐Hsiang , Juang Miin‐Horng
Published: December 2013

A wide locking range divide‐by‐3 injection‐locked frequency divider (ILFD) using a standard 0.18‐μm SiGe 3P6M BiCMOS process is presented. The ÷3 ILFD circuit is realized with an n‐core MOS LC‐tank oscillator. The ILFD uses a push‐push signal circuit and two linear mixers with one radio‐frequency injection input port and one push‐push signal input port. An HBT is used to amplify the push‐push signal and extend locking range. The core power consumption of the ILFD core is 13.2 mW at the drain‐source voltage of 0.8 V. The divider's free‐running frequency is tunable from 3.079 to 3.163 GHz and at the incident power of 0 dBm, the locking range is 19.28%, from 8.9 to 10.8 GHz. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:493–497, 2014
Improved band‐notch techniques for miniature UWB CPW‐fed slot antenna
Authors: Naser‐Moghadasi Mohammad , Asadpor Loghman
Published: December 2013

This article describes a compact ultrawideband (UWB) antenna that exhibits desirable band‐notch and gain characteristics. The antenna consists of a rectangular aperture etched on a printed circuit board's ground plane that is excited by a rectangular‐shaped patch. It uses a novel technique comprising of open‐end stubs at the periphery of the ground in the vicinity of the feed‐line to improve its voltage standing wave ratio (VSWR) performance across the UWB. The proposed antenna uses three techniques to provide band‐notch function necessary to eliminate the wireless local‐area network interfering signals between 5 and 6 GHz. The frequency of the band‐notch characteristic can be tuned by varying the parameters defining the notch structure. The antenna was fabricated and its performance measured to validate its feasibility including the band‐notch techniques. A compact 19 × 19 mm2 antenna with aperture area of 9 × 18 mm2 was realized that exhibits an excellent VSWR performance and stable radiation patterns across the UWB spectrum. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:408–415, 2014
Millimeter‐wave coplanar waveguide series stubs on BCB and low resistivity silicon
Authors: Islam Rownak , Henderson Rashaunda
Published: December 2013

30–225 GHz coplanar waveguide (CPW) series stubs are studied in a benzocylobutene and 10‐Ω‐cm silicon stack. Truncated side grounds improve the rejection of a 230 GHz CPW band pass filter (BPF). Silicon shielding using a grounded CPW line provides 1.79 dB insertion loss for a 215 GHz BPF. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:375–380, 2014
Effect of montmorillonite and shear stress on the orientation of single walled carbon nanotubes in polypopylene composite fiber
Authors: Jeong Du Sik , Choi Won Seok , Lee Yong Taek , Ryu Sung Hun
Published: December 2013

The effect of montmorillonite and shear stress on the orientation of single walled carbon nanotubes and properties of SWCNT/MMT/polypropylene composite was investigated. The effect of functionalization of SWCNT on the orientation was also investigated. Polarized Raman spectroscopy was used to analyze the orientation of the SWCNTs. Orientation of SWCNTs was dependent on the experienced shear stress and functionalization of SWCNTs. The addition of MMT also improved the orientation of functionalized SWCNTs, while its effect was not significant for pristine SWCNTs. The existence of critical shear stress was observed for the orientation of the SWCNTs and the orientation of SWCNTs was found to occur more efficiently above this critical shear stress. Melt viscosity and heat of fusion data also confirmed that the addition of MMT‐induced improved orientation and dispersion of SWCNTs, especially for functionalized SWCNTs. POLYM. ENG. SCI., 54:2455–2459, 2014. © 2013 Society of Plastics Engineers
An interpenetrating network biohydrogel of gelatin and gellan gum by using a combination of enzymatic and ionic crosslinking approaches
Authors: Wen Cai , Lu Lingling , Li Xinsong
Published: December 2013

Gelatin is a popular substrate for cell culture applications due to its biocompatibility and biodegradability. However, the mechanical property of gelatin is not satisfactory in certain tissue engineering areas where tunable and higher mechanical strengths are required. To achieve this purpose without exposure of materials to cytotoxic chemicals or procedures, a new biohydrogel of gelatin and gellan gum with an interpenetrating network (IPN) structure was prepared using a combination of enzymatic and ionic crosslinking approaches. The gelation procedure and thermal stability of theIPNstructure were demonstrated in detail by a rheological study. The resultingIPNbiohydrogel exhibited significantly increased and tunable mechanical strength, decreased swelling ratios and lower degradation rate compared with pure gelatin gel. The composite biohydrogels supported the attachment and proliferation ofL929fibroblasts as shownin vitro. These results indicate that this mechanically robust biohydrogel has the promising potential for serving as a cell support in the field of tissue engineering. © 2013 Society of Chemical Industry
Proteomic analysis ofSP600125‐controlledTrkA‐dependent targets inSK‐N‐MCneuroblastoma cells:Inhibition ofTrkAactivity bySP600125
Authors: Jung Eun Joo , Park Hyung Chul , Chung Ky Hyun , Kim Choong Won
Published: December 2013

The c‐JunN‐terminal kinase (JNK) is well known to play an important role in cell death signaling of the p75 neurotrophin receptor. However, little has been studied about a role ofJNKin the signaling pathways of the tropomyosin‐related kinaseA(TrkA) neurotrophin receptor. In this study, we investigatedJNKinhibitorSP600125‐controlledTrkA‐dependent targets by proteomic analysis to better understand an involvement ofJNKinTrkA‐mediated signaling pathways.PDQuest image analysis and protein identification results showed that hnRNP C1/C2, α‐tubulin, β‐tubulin homolog, actin homolog, and eIF‐5A‐1 protein spots were upregulated by ectopic expression ofTrkA, whereas α‐enolase, peroxiredoxin‐6,PROS‐27,HSP70,PP1‐gamma, andPDH E1‐alpha were downregulated byTrkA, and theseTrkA‐dependent upregulation and downregulation were significantly suppressed bySP600125. Notably,TrkAlargely affected certainPTM(s) but not total protein amounts of theSP600125‐controlledTrkA‐dependent targets. Moreover,SP600125 strongly suppressedTrkA‐mediated tyrosine phosphorylation signaling pathways as well asJNKsignaling, indicating thatSP600125 could function as aTrkAinhibitor. Taken together, our results suggest thatTrkAcould play an important role in the cytoskeleton, cell death, cellular processing, and glucose metabolism through activation or inactivation of theSP600125‐controlledTrkA‐dependent targets.