bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthopedic communication about osteoarthritis treatment: Does patient race matter?
Authors: Hausmann Leslie R. M. , Hanusa Barbara H. , Kresevic Denise M. , Zickmund Susan , Ling Bruce S. , Gordon Howard S. , Kwoh C. Kent , Mor Maria K. , Hannon Michael J. , Cohen Peter Z. , Grant Richard , Ibrahim Said A.
Published: January 2011

Objective

To understand racial disparities in the use of total joint replacement, we examined whether there were racial differences in patient‐provider communication about treatment of chronic knee and hip osteoarthritis in a sample of African American and white patients referred to Veterans Affairs orthopedic clinics.

Methods

Audio recorded visits between patients and orthopedic surgeons were coded using the Roter Interaction Analysis System and the Informed Decision‐Making model. Racial differences in communication outcomes were assessed using linear regression models adjusted for study design, patient characteristics, and clustering by provider.

Results

The sample (n = 402) included 296 white and 106 African American patients. Most patients were men (95%) and ages 50–64 years (68%). Almost half (41%) reported an income <$20,000. African American patients were younger and reported lower incomes than white patients. Visits with African American patients contained less discussion of biomedical topics (β = −9.14; 95% confidence interval [95% CI] −16.73, −1.54) and more rapport‐building statements (β = 7.84; 95% CI 1.85, 13.82) than visits with white patients. However, no racial differences were observed with regard to length of visit, overall amount of dialogue, discussion of psychosocial issues, patient activation/engagement statements, physician verbal dominance, display of positive affect by patients or providers, or discussion related to informed decision making.

Conclusion

In this sample, communication between orthopedic surgeons and patients regarding the management of chronic knee and hip osteoarthritis did not, for the most part, vary by patient race. These findings diminish the potential role of communication in Veterans Affairs orthopedic settings as an explanation for well‐documented racial disparities in the use of total joint replacement.
Impulse control disorders in parkinson disease: A multicenter case–control study
Authors: Voon Valerie , Sohr Mandy , Lang Anthony E. , Potenza Marc N. , Siderowf Andrew D. , Whetteckey Jacqueline , Weintraub Daniel , Wunderlich Glen R. , Stacy Mark
Published: January 2011

Objective:

To assess factors associated with impulse control disorders (ICDs) in Parkinson disease (PD) using a multicenter case–control design.

Methods:

Patients enrolled in the DOMINION study, a multicenter study assessing the cross‐sectional frequency of ICDs in PD, were eligible to participate in the case–control study. PD patients with and without an ICD (n = 282 each) (compulsive gambling, buying, sexual behavior, and eating) were matched individually on age, gender, and dopamine agonist treatment. Subjects were assessed with a comprehensive neurological, psychiatric, and cognitive assessment battery.

Results:

ICD patients reported more functional impairment (p < 0.001); greater depressive (p < 0.0001), state (p < 0.0001), and trait (p < 0.0001) anxiety; greater obsessive–compulsive symptoms (p < 0.0001); higher novelty‐seeking (p < 0.001) and impulsivity (p < 0.001); and differences in reward preference reflecting greater choice impulsivity (p < 0.05). Patients with multiple ICDs had greater dyskinesia scores compared to those with single ICDs.

Interpretation:

ICDs in PD are associated with multiple psychiatric and cognitive impairments, including affective and anxiety symptoms, as well as elevated obsessionality, novelty seeking, and impulsivity. These results highlight the importance of assessing multiple mental health domains in individuals with PD and ICDs, and suggest possible pathophysiological mechanisms and risk indicators for these disorders. ANN NEUROL 2011
Methodology for the solutions of some reduced Fokker‐Planck equations in high dimensions
Authors: Er G.K.
Published: January 2011

In this paper, a new methodology is formulated for solving the reduced Fokker‐Planck (FP) equations in high dimensions based on the idea that the state space of large‐scale nonlinear stochastic dynamic system is split into two subspaces. The FP equation relevant to the nonlinear stochastic dynamic system is then integrated over one of the subspaces. The FP equation for the joint probability density function of the state variables in another subspace is formulated with some techniques. Therefore, the FP equation in high‐dimensional state space is reduced to some FP equations in low‐dimensional state spaces, which are solvable with exponential polynomial closure method. Numerical results are presented and compared with the results from Monte Carlo simulation and those from equivalent linearization to show the effectiveness of the presented solution procedure. It attempts to provide an analytical tool for the probabilistic solutions of the nonlinear stochastic dynamics systems arising from statistical mechanics and other areas of science and engineering.
Nanopartikel in biologischen Systemen
Authors: Stark Wendelin J.
Published: January 2011

Das Verhalten von Nanopartikeln in biologischen Systemen dient als Grundlage zur Erforschung neuer medizinischer Behandlungsmethoden und ermöglicht die Entwicklung “sicherer” Nanotechnologie. Dieser Aufsatz diskutiert Moleküle und kleinste Partikel im Kontakt mit einzelnen Zellen oder ganzen Organismen mit Fokus auf anorganischen Materialien. Dabei treffen wir auf unerwartete, nicht‐klassische Verhaltensweisen solcher Partikel: veränderte Verteilungsmuster, chemisch aktive Grenzflächen und Festkörper mit dynamischem Verhalten. Die extern gesteuerte Platzierung von Medikamenten mithilfe von funktionalisierten Nanomagneten bringt Aspekte der Mechanik in die Arzneimittelforschung ein. In weiteren Abschnitten wird auf Persistenz und Bioakkumulation von Nanopartikeln mit Hinblick auf Langzeiteffekte eingegangen.
Measuring of coalescence in polymer melt blends flowing through converging channels
Authors: Miroshnikov Yuri P. , Egorov Alexey K. , Egorova Mariya V.
Published: January 2011

Droplets of polymer blends flowing through convergent channels undergo collisions and coalescence because of the appropriate wineglass‐shaped flow paths with essential flow constriction at the entrance zone. Therefore, an attempt has been undertaken to use capillary flow for studying coalescence phenomena in polymer blends. When the initial drop diameters in a barrel (before extrusion), db, and in the extrudate, de, are measured, coalescence efficiency can be easily calculated as Ec = d/d, provided that no breakup of elongated domains occurs. Compared with methods employing simple shear flow, it has several advantages. For example, the convergent flow pattern combining both shear and extensional flows is directly related to industrial processing operations like extrusion, injection molding, blowing, etc. The method imposes minor limitations on processing parameters and materials used. Applicability of the technique proposed was verified by systematic studies of coalescence in PMMA/PS binary melts blends during capillary extrusion and by comparing these results to theoretical predictions and experimental data from literature. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Biocidal polymers: Synthesis, antimicrobial activity, and possible toxicity of poly (hydroxystyrene‐co‐methylmethacrylate) derivatives
Authors: Kenawy El‐Refaie , El‐Shanshoury Abd El‐Raheem R. , Omar Shaker Nihal , El‐Sadek Baheya Mohamed , Khattab Abeer H. B. , Ismail Badr Badr
Published: January 2011

Functionalized polymers have gained much interest in the last decades. This is due to their functional group and their polymer nature that give them unique properties and more advantages than the corresponding small molecules. In this trend, polyhydroxystyrene‐co‐MMA was modified to introduce amino group in the side chain of the polymer. The amine modified polymer was reacted with two classes of active compounds. The first class is aldehydes such as vanilline, p‐hydroxybenzaldehyde, p‐chlorobenzaldehyde, and anisaldehyde. The second class is phenolic esters such as p‐hydroxymethylbenzoate, 2,4‐dihydroxymethyl benzoate, and methyl salicylate. The antimicrobial activities of the polymer and modified polymer with these two classes were explored with Gram‐negative bacteria (Escherichia coli), Gram‐positive bacteria (Bacillus subtilus), fugus like yeast (Candida albicans SC5314), and pathogenic molds (Aspergillus flavus, Trycophyton rubrum, and F. oxysporium). In vitro studies indicated that the start polymer did not affect on the test microorganisms, in contrary to its derivatives. The diameter of inhibition zone varied according to the active group in the modified polymer, polymer microstructure, and the test microorganism. Derivatives I, II, and III were selected among the most effective antimicrobial compounds. Their inhibitory effects on the ratio of surviving cell number (M/C) increased by increasing derivatives concentrations. Derivatives I and II were inhibitorier to C. albicans and molds than to bacteria while derivative III was only antibacterial. These derivatives seemed toxic to Brine shrimp by increasing their concentrations above 10 ppm, with derivative III being the less toxic, compared to others. To clarify this toxic effect and to decrease the toxicity of these derivatives, more detailed studies are necessary, and this will be focused in the nearest future. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Preparation and characterizations of organic fluorine–silicon and polytetrafluoroethylene modified polyester
Authors: Jin Jian , Wang Xue , Xiao Chang‐fa
Published: January 2011

Hydrophobically modified polyester was synthesized via copolymerization between hydroxy‐fluorosilicone polymer (FGX) and bis(2‐hydroxyethyl) terephthalate (BHET), which was named as CMPET. The relations between surface properties of CMPET and FGX viscosity and dosage were studied by contact angle measurements. An optimized synthesis route was determined. b‐CMPET with better hydrophobic property was obtained by adding polytetrafluoroethylene (PTFE) into CMPET. A full characterization were given to both CMPET and b‐CMPET, including 1H‐NMR, ESCA, mechanical properties, water absorption, contact angle and surface energy analysis. It was found that chemical bondings were formed between FGX and BHET in c‐CMPET via copolymerization. The addition of 12% FGX with viscosity of 2000CP after the system pressure reached the low pressure for 20 min is an optimum condition. The modified polyester (CMPET‐12) shows the best hydrophobic effect. Blending a certain amount of PTFE powder with low‐surface energy can further enhance the hydrophobic properties of CMPET, due to a strong tendency of PTFE migrate to the sample surface together with organic fluorine–silicon segments. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis of high molecular weight poly(L‐lactic acid) via melt/solid polycondensation: Intensification of dehydration and oligomerization during melt polycondensation
Authors: Song Fangchao , Wu Linbo
Published: January 2011

Melt/solid state polycondensation (MP/SSP) is a cost‐effective route for synthesis of high molecular weight poly(L‐lactic acid) (PLLA). However, the reaction rates in its four stages need to be enhanced greatly and the reaction times to be shortened largely before the MP/SSP technology can be industrialized. In this study, a new catalyst addition policy, i.e., adding TSA at the dehydration stage and SnCl2·2H2O at the MP stage, and more appropriate temperature and pressure programs were presented and applied in the MP process of LLA. The presence of TSA from dehydration appeared very effective for speeding up the dehydration and oligomerization stages as well as depressing racemization in the whole MP process. The polymerization degree (Xn) of oligomer was clearly increased, and the reaction time was shortened to a great extent. Direct using reduced pressure was also very helpful for intensifying the dehydration stage, only leading to LLA loss as little as 2%. A PLLA with Mw of 44,000 and optical purity of 96.8% suitable for subsequent SSP was produced after dehydration for 2 h, oligomerization for 2 h and MP for 4 h under appropriate conditions. And an interesting strong dependence of the Mw of final PLLA product on the Xn of the oligomer was observed. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Oligomer ethylene glycol based electrolytes for dye‐sensitized solar cell
Authors: Lan Zhang , Wu Jihuai , Lin Jianming , Huang Miaoliang
Published: January 2011

Oligomer ethylene glycol (O‐EG) based electrolytes without volatile components were prepared and used in dye‐sensitized solar cell (DSSC). The characteristics such as viscosity, ionic conductivity, and ionic activation energy of O‐EG based electrolytes including liquid, gel and solid states were investigated and compared. It is found that the gel and solid O‐EG electrolytes have two Ea values with the changed phase state by going with the increased temperature, and they can increase the onset of applied voltage for generating dark current in DSSCs as from 0.222 V with liquid O‐EG electrolyte to 0.420 V with gel and solid O‐EG electrolytes, which results in the enhanced light‐to‐electricity conversion efficiency from 1.4% with liquid to 1.82% with gel and 1.86% with solid electrolytes. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Synthesis and thermal properties of poly(n‐butyl acrylate)/n‐hexadecane microcapsules using different cross‐linkers and their application to textile fabrics
Authors: Alay Sennur , Göde Fethiye , Alkan Cemil
Published: January 2011

This study focused on the preparation, characterization, and determination of thermal properties of microencapsulated n‐hexadecane with poly(butyl acrylate) (PBA) to be used in textiles with heat storage property. Microcapsules were synthesized by emulsion polymerization method, and the particle size, particle size distribution, shape, and thermal storage/release properties of the synthesized microcapsules were analyzed using Fourier‐transform infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry techniques. Allyl methacrylate, ethylene glycol dimethacrylate, and glycidyl methacrylate were used as cross‐linkers to produce unimodal particle size distribution. MicroPBA microcapsules produced using allyl methacrylate cross‐linker were applied to 100% cotton and 50/50% cotton/polyester blend fabrics by pad‐cure method. The mean particle size of microcapsules ranges from 0.47 to 4.25 μm. Differential scanning calorimetry analysis indicated that hexadecane in the microcapsules melts at nearly 17°C and crystallizes at around 15°C. The contents of n‐hexadecane of different PBA microcapsules were in the range of 27.7–50.7%, and the melting enthalpies for these ratios were between 65.67 and 120.16 J/g, respectively. The particle size and thermal properties of microcapsules changed depending on the cross‐linker type. The cotton and 50/50% cotton/polyester blend fabrics stored 6.56 and 28.59 J/g thermal energy, respectively. The results indicated that PBA microcapsules have the potential to be used as a solid‐state thermal energy storage material in fabrics. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Quantification of thermal material degradation during the processing of biomedical thermoplastics
Authors: Ragaert Kim , Dekeyser Arne , Cardon Ludwig , Degrieck Joris
Published: January 2011

Three‐dimensional plotting, a melt‐based technique that involves the guided deposition of extruded filaments, is a promising method for the manufacture of thermoplastic scaffolds for tissue engineering. However, the polymer degrades during processing because of a prolonged residence time at an elevated temperature in the dispensing head before actual extrusion. This thermal degradation has been attributed to random chain scission; in this research, it has been quantified as a function of the residence time for a selection of polylactide‐based polymers. The utilized techniques include thermogravimetric analysis (overall mass loss), differential scanning calorimetry (glass‐transition, melting, and recrystallization temperatures), gel permeation chromatography (molecular mass), and inherent viscosity measurements. Experiments have shown that a static heating interval greater than 6 h is sufficient to destroy the molecular chain integrity of poly(l‐lactide) and poly(d,l‐lactide). Copolymers with poly(ε‐caprolactone) and poly(glycolic acid) are more resilient to thermal loading but are still severely affected. Overall, the differential scanning calorimetry results have been judged to be a good source of complementary data for the quantification of the degradation phenomenon, whereas inherent viscosity measurements have been confirmed to be related to the gel permeation chromatography results, which indicate shortening of the polymer chain. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Surface, tribological, and mechanical characterization of synthetic skins for tribological applications in cosmetic science
Authors: Bhushan Bharat , Tang Wei
Published: January 2011

Synthetic skin as an ideal human‐tissue substitute is needed for the research and assessment of hair‐ and skin‐care products. In this study, a systematic study was carried out of the surface, tribological, and mechanical properties of two synthetic skins and rat skin with and without skin‐cream treatment with scanning electron microscopy, atomic force microscopy, and a nanoindenter. The film thickness, adhesive force, coefficient of friction, surface roughness, and contact angle of the two synthetic skins and rat skin were comparable. The hardness of one synthetic skin was more similar to rat skin. After treatment with skin cream, the trends of the properties of the two synthetic skins and rat skin were similar. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Surface attachment of horseradish peroxidase to nylon modified by plasma‐immersion ion implantation
Authors: Kondyurin Alexey , Nosworthy Neil J. , Bilek Marcela M. M. , Jones Robert , Pigram Paul J.
Published: January 2011

The surface of polyamide (nylon 6) was modified by plasma‐immersion ion implantation (PIII) with nitrogen ions. Structural changes associated with carbonization, oxidation, and depolymerization were observed in the modified surface layer with Fourier transform infrared/attenuated total reflection (FTIR–ATR) spectroscopy, surface energy measurements, and X‐ray photoelectron spectroscopy (XPS). The enzyme activity of surface‐attached horseradish peroxidase was studied with a tetramethylbenzidine colorimetric activity assay. Compared to untreated controls, the PIII‐treated surface showed a higher level of the attached protein with increased longevity of bioactivity. Detection of the immobilized protein layer was made difficult by the presence of amide groups in nylon. Here we demonstrate the potential of combining FTIR–ATR spectroscopy with XPS measurements for this purpose. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120:2891–2903, 2011
Role of interleukin‐6 in a patient with tumor necrosis factor receptor–associated periodic syndrome: Assessment of outcomes following treatment with the anti–interleukin‐6 receptor monoclonal antibody tocilizumab
Authors: Vaitla Prashantha M. , Radford Paul M. , Tighe Patrick J. , Powell Richard J. , McDermott Elizabeth M. , Todd Ian , Drewe Elizabeth
Published: January 2011

In this report, we describe treatment outcomes in the first case of a patient with tumor necrosis factor receptor–associated periodic syndrome (TRAPS) treated with the anti–interleukin‐6 (anti–IL‐6) receptor monoclonal antibody tocilizumab. Since IL‐6 levels are elevated in TRAPS, we hypothesized that tocilizumab might be effective. The patient, a 52‐year‐old man with lifelong TRAPS in whom treatment with etanercept and anakinra had failed, was administered tocilizumab for 6 months, and the therapeutic response was assessed by measurement of monocyte CD16 expression and cytokine levels. Following treatment, the evolving acute attack was aborted and further attacks of TRAPS were prevented. The patient did not require corticosteroids and showed significant clinical improvement in scores for pain, stiffness, and well‐being. Moreover, the acute‐phase response diminished significantly with treatment. Monocyte CD16 expression was reduced and the numbers of circulating CD14+CD16+ and CD14++CD16− monocytes were transiently decreased. However, cytokine levels were not reduced. This case supports the notion of a prominent role for IL‐6 in mediating the inflammatory attacks in TRAPS, but blockade of IL‐6 did not affect the underlying pathogenesis. These preliminary findings require confirmation.
Tumor necrosis factor blocking therapy alters joint inflammation and hypoxia
Authors: Kennedy Aisling , Ng Chin Teck , Chang Ting Cheng , Biniecka Monika , O'Sullivan Jacintha N. , Heffernan Eric , Fearon Ursula , Veale Douglas J.
Published: January 2011

Objective

To examine the effect of tumor necrosis factor (TNF) blocking therapy on hypoxia in vivo, macroscopic and microscopic inflammation, and magnetic resonance imaging (MRI) results in patients with inflammatory arthritis.

Methods

Patients with inflammatory arthritis (n = 20) underwent full clinical assessment, arthroscopy, synovial biopsy, and MRI before and after initiation of biologic therapy. Macroscopic synovitis/vascularity was assessed with a visual analog scale, and tissue PO2 (tPO2) was measured at arthroscopy using a Licox probe. Cell‐specific markers (CD4, CD8, CD68, CD20, and CD19) and blood vessel maturity were quantified by immunohistologic analysis and dual‐immunofluorescence factor VIII/α‐smooth muscle actin staining, respectively. Contiguous gadoteric acid–enhanced MRI of the target knee was used to assess synovial enhancement.

Results

Biologic therapy responders showed a significant increase of tPO2 in vivo (P < 0.05). This response was associated with significant reductions in 28‐joint Disease Activity Score using the C‐reactive protein level (DAS28‐CRP) (P = 0.012), macroscopic synovitis (P = 0.017), macroscopic vascularity (P = 0.05), CD4+ T cells (P < 0.041), and CD68+ macrophages (P < 0.011). Blood vessel numbers were also reduced in responders; however, this did not reach statistical significance. Strong inverse correlations were demonstrated between changes in tPo2 levels and changes in DAS28‐CRP (r = −0.53, P < 0.001), CD4 (r = −0.44, P < 0.026), CD68 (r = −0.46, P < 0.003), and macroscopic vascularity (r = −0.314, P = 0.049) after therapy. Furthermore, changes in inflammation as measured by MRI showed a strong inverse correlation with tPO2 levels (r = −0.688, P < 0.002) and positive correlations with CRP levels (r = 0.707, P = 0.001), macroscopic synovitis (r = 0.457, P = 0.056), macroscopic vascularity (r = 0.528, P= 0.017), CD4 (r = 0.553, P < 0.032), and CD68 (r = 0.670, P < 0.002) after therapy.

Conclusion

This is the first study to show that successful biologic therapy significantly improves in vivo synovial hypoxia. Changes are strongly associated with changes in macroscopic and microscopic measures of joint inflammation and MRI improvement. These data further strengthen the concept that hypoxia is an important event driving synovial inflammation.
Type I interferon–dependent CD86high marginal zone precursor B cells are potent T cell costimulators in mice
Authors: Wang John H. , Wu Qi , Yang PingAr , Li Hao , Li Jun , Mountz John D. , Hsu Hui‐Chen
Published: January 2011

Objective

To investigate the role of CD86high marginal zone (MZ) precursor B cells in type I interferon (IFN)–induced T cell–dependent responses in autoimmune BXD2 mice.

Methods

Confocal microscopic imaging was used to determine the location of plasmacytoid dendritic cells (DCs), MZ precursor B cells, and CD4 T cells in the spleens of BXD2 and BXD2‐Ifnar−/− mice. Immunohistochemical staining was used to determine IgGbright cells in the spleens of BXD2 and BXD2‐Ifnar−/− mice. Enzyme‐linked immunosorbent assay was used to determine serum levels of IFNα and autoantibodies, and 4‐hydroxy‐3‐nitrophenylacetyl hapten (NP)–chicken γ‐globulin (CGG) (NP‐CGG)– or NP‐Ficoll–induced anti‐NP2 antibody titers. Real‐time quantitative polymerase chain reaction was used to determine the levels of type I IFN transcripts. T cell proliferation was measured using 3H‐thymidine. The expression of CD86 and CD80 was determined by fluorescence‐activated cell sorting analysis.

Results

The deletion of type I IFN receptor abrogated the development of IgGbright cells and suppressed a T cell–dependent antibody response. Type I IFN signaling was associated with the expression of CD86, but not CD80, on follicular, MZ, and MZ precursor B cells. However, MZ precursor B cells demonstrated the highest expression of CD86 and the highest capacity for T cell costimulation with intact type I IFN receptor. This effect was blocked by an antibody that neutralizes CD86. In IFN receptor–intact BXD2 mouse spleens, MZ precursor B cells clustered at the T cell–B cell border. CD86 deletion suppressed germinal center formation, autoantibody production, and development of autoimmune diseases in BXD2 mice.

Conclusion

Type I IFN can promote autoimmune responses in BXD2 mice through up‐regulation of CD86high expression on MZ precursor B cells and trafficking of MZ precursor B cells to the T cell–B cell border to provide costimulation of CD4 T cells.
Genome‐wide association study of rheumatoid arthritis in Koreans: Population‐specific loci as well as overlap with European susceptibility loci
Authors: Freudenberg Jan , Lee Hye‐Soon , Han Bok‐Ghee , Shin Hyoung Do , Kang Young Mo , Sung Yoon‐Kyoung , Shim Seung‐Cheol , Choi Chan‐Bum , Lee Annette T. , Gregersen Peter K. , Bae Sang‐Cheol
Published: January 2011

Objective

To perform a genome‐wide association study (GWAS) in Koreans in order to identify susceptibility loci for rheumatoid arthritis (RA).

Methods

We generated high‐quality genotypes for 441,398 single‐nucleotide polymorphisms (SNPs) in 801 RA cases and 757 controls. We then tested 79 markers from 46 loci for replication in an independent sample of 718 RA cases and 719 controls.

Results

Genome‐wide significance (P < 5 × 10–08) was attained by markers from the major histocompatibility complex region and from the PADI4 gene. The replication data showed nominal association signals (P < 5 × 10–02) for markers from 11 of the 46 replicated loci, greatly exceeding random expectation. Genes that were most significant in the replication stage and in the combined analysis include the known European RA loci BLK, AFF3, and CCL21. Thus, in addition to the previously associated STAT4 alleles, variants at these three loci may contribute to RA not only among Europeans, but also among Asians. In addition, we observed replication signals near the genes PTPN2, FLI1, ARHGEF3, LCP2, GPR137B, TRHDE, and CGA1. Based on the excess of small P values in the replication stage study, we estimate that more than half of these loci are genuine RA susceptibility genes. Finally, we systematically analyzed the presence of association signals in Koreans at established European RA loci, which showed a significant enrichment of European RA loci among the Korean RA loci.

Conclusion

Genetic risk for RA involves both population‐specific loci as well as many shared genetic susceptibility loci in comparisons of Asian and European populations.
Enhanced molecular chaperone activity of the small heat‐shock protein αB‐crystallin following covalent immobilization onto a solid‐phase support
Authors: Garvey Megan , Griesser Stefani S. , Griesser Hans J. , Thierry Benjamin , Nussio Matthew R. , Shapter Joseph G. , Ecroyd Heath , Giorgetti Sofia , Bellotti Vittorio , Gerrard Juliet A. , Carver John A.
Published: January 2011

The well‐characterized small heat‐shock protein, αB‐crystallin, acts as a molecular chaperone by interacting with unfolding proteins to prevent their aggregation and precipitation. Structural perturbation (e.g., partial unfolding) enhances the in vitro chaperone activity of αB‐crystallin. Proteins often undergo structural perturbations at the surface of a synthetic material, which may alter their biological activity. This study investigated the activity of αB‐crystallin when covalently bound to a support surface; αB‐crystallin was immobilized onto a range of solid material surfaces, and its characteristics and chaperone activity were assessed. Immobilization was achieved via a plasma‐deposited thin polymeric interlayer containing aldehyde surface groups and reductive amination, leading to the covalent binding of αB‐crystallin lysine residues to the surface aldehyde groups via Schiff‐base linkages. Immobilized αB‐crystallin was characterized by X‐ray photoelectron spectroscopy, atomic force microscopy, and quartz crystal microgravimetry, which showed that ∼300 ng cm−2 (dry mass) of oligomeric αB‐crystallin was bound to the surface. Immobilized αB‐crystallin exhibited a significant enhancement (up to 5000‐fold, when compared with the equivalent activity of αB‐crystallin in solution) of its chaperone activity against various proteins undergoing both amorphous and amyloid fibril forms of aggregation. The enhanced molecular chaperone activity of immobilized αB‐crystallin has potential applications in preventing protein misfolding, including against amyloid disease processes, such as dialysis‐related amyloidosis, and for biodiagnostic detection of misfolded proteins. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 376–389, 2011
Oxidation of Polycyclic Aromatic Hydrocarbons with Hydrogen Peroxide in the Presence of Transition Metal Mono‐Substituted Keggin‐Type Polyoxometalates
Authors: Estrada Ana C. , Simões Mário M. Q. , Santos Isabel C. M. S. , Neves M. Graça P. M. S. , Cavaleiro José A. S. , Cavaleiro Ana M. V.
Published: January 2011

The oxidation of anthracene, naphthalene, 1‐ethylnaphthalene, and 2‐ethylnaphthalene with environmentally benign hydrogen peroxide has been studied in the presence of the tetrabutylammonium salts of iron and manganese mono‐substituted Keggin‐type polyoxometalates [XW11M(H2O)O39]n− (X=P, Si, or B, M=MnIII or FeIII). The reactions were performed under homogeneous conditions at 80 °C, using acetonitrile as the solvent. For all the catalysts studied, anthracene was selectively oxidized to 9,10‐anthraquinone at 100 % conversion in the presence of [BW11Mn(H2O)O39]6−. The oxidation of 1‐ethylnaphthalene and 2‐ethylnaphthalene occurs mainly at the alkyl substituent, along with the formation of phthalic anhydrides, which resulted from aromatic ring oxidation, with iron substituted anions. Naphthalene could not be oxidized with the conditions used. To understand the reaction pathways, the oxidation of several products was performed in the presence of [PW11Fe(H2O)O39]4−. Under the conditions used, the oxidation of vinylnaphthalene derivatives gave rise to mainly carbon–carbon double‐bond cleavage, affording the corresponding naphthaldehydes in high yields (>67 %). Possible reaction pathways are presented and the role of different catalysts is discussed.
Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher‐risk myelodysplastic syndromes
Authors: Silverman Lewis R. , Fenaux Pierre , Mufti Ghulam J. , Santini Valeria , Hellström‐Lindberg Eva , Gattermann Norbert , Sanz Guillermo , List Alan F. , Gore Steven D. , Seymour John F.
Published: January 2011

BACKGROUND:

In the AZA‐001 trial, azacitidine (75 mg/m2/d subcutaneously for Days 1‐7 of every 28‐day cycle) demonstrated improved survival compared with conventional care regimens in patients with International Prognostic Scoring System‐defined intermediate‐2‐ or high‐risk myelodysplastic syndrome and World Health Organization‐defined acute myeloid leukemia with 20% to 30% bone marrow blasts.

METHODS:

This secondary analysis of the AZA‐001 phase 3 study evaluated the time to first response and the potential benefit of continued azacitidine treatment beyond first response in responders.

RESULTS:

Overall, 91 of 179 patients achieved a response to azacitidine; responding patients received a median of 14 treatment cycles (range, 2‐30). Median time to first response was 2 cycles (range, 1‐16). Although 91% of first responses occurred by 6 cycles, continued azacitidine improved response category in 48% of patients. Best response was achieved by 92% of responders by 12 cycles. Median time from first response to best response was 3.5 cycles (95% confidence interval [CI], 3.0‐6.0) in 30 patients who ultimately achieved a complete response, and 3.0 cycles (95% CI, 1.0‐3.0) in 21 patients who achieved a partial response.

CONCLUSIONS:

Continued azacitidine therapy in responders was associated with a quantitative increase in response to a higher response category in 48% of patients, and therefore may enhance clinical benefit in patients with higher‐risk MDS. Cancer 2011. © 2011 American Cancer Society.
Patient‐reported receipt of and interest in smoking‐cessation interventions after a diagnosis of cancer
Authors: Cooley Mary E. , Emmons Karen M. , Haddad Robert , Wang Qian , Posner Marshall , Bueno Raphael , Cohen Tiffany‐Jen , Johnson Bruce E.
Published: January 2011

BACKGROUND:

Smoking cessation is essential after the diagnosis of cancer to enhance clinical outcomes. Although effective smoking‐cessation treatments are available, <50% of smokers with cancer report receiving treatment. Reasons for the low dissemination of such treatment are unclear.

METHODS:

Data were collected from questionnaires and medical record reviews from 160 smokers or recent quitters with lung or head and neck cancer. Descriptive statistics, Cronbach alpha coefficients, and logistic regression were used in the analyses. The median age of participants was 57 years, 63% (n = 101) were men, 93% (n = 149) were white, and 57% (n = 91) had lung cancer.

RESULTS:

Eight‐six percent (n = 44) of smokers and 75% (n = 82) of recent quitters reported that healthcare providers gave advice to quit smoking. Sixty‐five percent (n = 33) of smokers and 47% (n = 51) of recent quitters reported that they were offered assistance from their healthcare providers to quit smoking. Fifty‐one percent (n = 26) of smokers and 20% (n = 22) of recent quitters expressed an interest in a smoking‐cessation program. An individualized smoking‐cessation program was the preferred type of program. Among smokers, younger patients with early stage disease and those with partners who were smokers were more interested in programs.

CONCLUSIONS:

Although the majority of patients received advice and were offered assistance to quit smoking, approximately 50% of smokers were interested in cessation programs. Innovative approaches to increase interest in cessation programs need to be developed and tested in this population. Cancer 2011. © 2011 American Cancer Society.
A clustered ground‐glass hepatocyte pattern represents a new prognostic marker for the recurrence of hepatocellular carcinoma after surgery
Authors: Tsai Hung‐Wen , Lin Yih‐Jyh , Lin Pin‐Wen , Wu Han‐Chieh , Hsu Kai‐Hsi , Yen Chia‐Jui , Chan Shih‐Huang , Huang Wenya , Su Ih‐Jen
Published: January 2011

BACKGROUND:

The recurrence of hepatocellular carcinoma (HCC) after hepatectomy is a serious event. It has been demonstrated that different ground‐glass hepatocyte (GGH) patterns harbor specific hepatitis B virus (HBV) pre‐S deletion mutants and represent preneoplastic lesions in chronic HBV infection. In the current study, the authors investigated whether a specific GGH pattern in nontumorous liver tissues was associated with the recurrence of HBV‐related HCC after surgery.

METHODS:

Clinicopathologic data from 82 patients with HBV‐related HCC were reviewed. GGH patterns were assessed on hematoxylin and eosin‐stained sections. Tissue hepatitis B surface antigen (HBsAg) expression was evaluated by immunohistochemical staining. Serum profiles of pre‐S status, viral load, and HBV genotype were determined and correlated with clinical recurrence and survival after surgery.

RESULTS:

The results indicated that the clustered pattern of GGHs or HBsAg expression was associated significantly with decreased local recurrence‐free survival (LRFS) during a mean follow‐up of 46.4 months (P<.001). This biomarker was comparable to or better than the prognostic value of other parameters, such as multifocal tumors (P = .022), satellite nodules (P = .005), small cell dysplasia (P = .045), or elevated viral load (P = .027), to predict recurrent HCC. Multivariate analysis also revealed that type II GGHs, which expressed marginal HBsAg and consistently clustered in nodules, were independent variables associated with LRFS (P<.001) and overall survival (P = .003).

CONCLUSIONS:

The current results indicated that the assessment of GGH patterns or HBsAg expression in nontumorous liver tissues provides an easily recognized, new risk marker for the recurrence of HBV‐related HCC after hepatic resection. Cancer 2011. © 2011 American Cancer Society.
Do patients consider preoperative chemoradiation for primary rectal cancer worthwhile?
Authors: Kennedy Erin D. , Schmocker Selina , Victor Charles , Baxter Nancy N. , Kim John , Brierley James , McLeod Robin S.
Published: January 2011

BACKGROUND:

The objective of this study was to elicit future patients' preferences for preoperative chemoradiation (pre‐CRT) for rectal cancer to determine whether patients' preferences are consistent with current treatment guidelines.

METHODS:

During a standardized interview, the treatment protocol, risks, benefits, and long‐term outcomes associated with 1) surgery alone (SA) and 2) pre‐CRT followed by surgery (CR + S) were described to healthy individuals, and a threshold task was performed. Each participant was asked which treatment option they would prefer when the risk of local recurrence was set initially at 15% for both options. If the participant indicated SA (which was expected), then the risk of local recurrence for CR + S was lowered systematically until the participant's preference changed from SA to CR + S. This threshold point represented the risk of local recurrence for pre‐CRT that the participant would require before they would choose treatment with pre‐CRT.

RESULTS:

Fifty individuals participated in the study, and the majority were well educated. Twenty‐seven of 50 participants (54%) required a risk of local recurrence with CR + S of ≤5% (ie, equivalent to an absolute risk reduction ≥10%) before they would choose treatment with pre‐CRT. Regression analysis did not identify any variables that were predictive of the participants' preferences.

CONCLUSIONS:

Participants seemed to highly value functional outcomes and seemed willing to accept a higher risk of local recurrence to achieve this. Therefore, developers of future guidelines may need to downgrade the use of pre‐CRT for all patients with stage II/III tumors from a guideline to an option. Cancer 2011. © 2011 American Cancer Society.
A novel KIF5B‐ALK variant in nonsmall cell lung cancer
Authors: Wong Daisy Wing‐Sze , Leung Elaine Lai‐Han , Wong Sunny Kit‐Man , Tin Vicky Pui‐Chi , Sihoe Alan Dart‐Loon , Cheng Lik‐Cheung , Au Joseph Siu‐Kie , Chung Lap‐Ping , Wong Maria Pik
Published: January 2011

BACKGROUND:

The anaplastic lymphoma kinase (ALK) gene is involved frequently in chromosomal translocations, resulting in fusion genes with different partners found in various lymphoproliferative conditions. It was recently reported in nonsmall cell lung cancer (NSCLC) that the fusion protein encoded by echinoderm microtubule‐associated protein‐like 4‐ALK (EML4‐ALK) fusion gene conferred oncogenic properties. The objective of the current study was to identify other possible ALK fusion genes in NSCLC.

METHODS:

Immunohistochemical analysis was used to screen for aberrant ALK expression in primary NSCLC. The authors used 5′ rapid amplification of complementary DNA ends to screen for potential, novel 5′ fusion partners of ALK other than EML4‐ALK. Reverse transcriptase‐polymerase chain reaction and fluorescence in situ hybridization analyses were used to confirm the identity of 5′ fusion partners. The genomic breakpoint was verified using genomic sequencing. Overexpression of the novel ALK fusion gene and variants 3a and 3b of EML4‐ALK was performed to assess downstream signaling and functional effects.

RESULTS:

The authors identified a novel gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 15 to ALK exon 20 in a primary lung adenocarcinoma. Western blot analysis of clinical tumor tissues revealed the expression of a protein whose size correlated with that of the predicted KIF5B‐ALK. Overexpression of KIF5B‐ALK in mammalian cells led to the activation of signal transducer and activator of transcription 3 and protein kinase B and to enhanced cell proliferation, migration, and invasion.

CONCLUSIONS:

The discovery of the novel KIF5B‐ALK variant further consolidated the role of aberrant ALK signaling in lung carcinogenesis. Cancer 2011. © 2011 American Cancer Society.
Modeling the mortality reduction due to computed tomography screening for lung cancer
Authors: Foy Millennia , Yip Rowena , Chen Xing , Kimmel Marek , Gorlova Olga Y. , Henschke Claudia I.
Published: January 2011

BACKGROUND:

The efficacy of computed tomography (CT) screening for lung cancer remains controversial because results from the National Lung Screening Trial are not yet available. In this study, the authors used data from a single‐arm CT screening trial to estimate the mortality reduction using a modeling‐based approach to construct a control comparison arm.

METHODS:

To estimate the potential lung cancer mortality reduction because of CT screening, a previously developed and validated model was applied to the screening trial to predict the number of lung cancer deaths in the absence of screening. By using age, gender, and smoking characteristics matching those of the trial participants, the model was used to simulate 5000 trials in the absence of CT screening to produce the expected number of lung cancer deaths along with 95% confidence intervals (95% CIs), while adjusting for healthy volunteer bias.

RESULTS:

There were 64 observed lung cancer deaths in the screening cohort (n = 7995), whereas the model predicted 117.7 deaths (95% CI, 98 deaths‐139 deaths), indicating a mortality reduction of 45.6% (P < .001). When a more conservative healthy volunteer adjustment was applied, 111.3 lung cancer deaths were predicted (95% CI, 91 deaths‐132 deaths), for a lung cancer‐specific mortality reduction of 42.5% (P < .001).

CONCLUSIONS:

The results of the current study indicate that CT screening along with early stage treatment can reduce lung cancer‐specific mortality. This mortality reduction is greatly influenced by the protocol of nodule follow‐up and treatment, and the length of follow‐up. Cancer 2011. © 2011 American Cancer Society.
Tristetraprolin regulates interleukin‐6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma
Authors: Van Tubergen Elizabeth , Vander Broek Robert , Lee Julia , Wolf Gregory , Carey Thomas , Bradford Carol , Prince Mark , Kirkwood Keith L. , D'Silva Nisha J.
Published: January 2011

BACKGROUND:

Tumor‐derived cytokines play a significant role in the progression of head and neck squamous cell carcinoma (HNSCC). Targeting proteins, such as tristetraprolin (TTP), that regulate multiple inflammatory cytokines may inhibit the progression of HNSCC. However, TTP's role in cancer is poorly understood. The goal of the current study was to determine whether TTP regulates inflammatory cytokines in patients with HNSCC.

METHODS:

TTP messenger RNA (mRNA) and protein expression were determined by quantitative real‐time–polymerase chain reaction (Q‐RT‐PCR) and Western blot analysis, respectively. mRNA stability and cytokine secretion were evaluated by quantitative RT‐PCR and enzyme‐linked immunoadsorbent assay, respectively, after overexpression or knockdown of TTP in HNSCC. HNSCC tissue microarrays were immunostained for interleukin‐6 (IL‐6) and TTP.

RESULTS:

TTP expression in HNSCC cell lines was found to be inversely correlated with the secretion of IL‐6, vascular endothelial growth factor (VEGF), and prostaglandin E2 (PGE2). Knockdown of TTP increased mRNA stability and the secretion of cytokines. Conversely, overexpression of TTP in HNSCC cells led to decreased secretion of IL‐6, VEGF, and PGE2. Immunohistochemical staining of tissue microarrays for IL‐6 demonstrated that staining intensity is prognostic for poor disease‐specific survival (P = .023), tumor recurrence and development of second primary tumors (P = .014), and poor overall survival (P = .019).

CONCLUSIONS:

The results of the current study demonstrated that down‐regulation of TTP in HNSCC enhances mRNA stability and promotes secretion of IL‐6, VEGF, and PGE2. Furthermore, high IL‐6 secretion in HNSCC tissue is a biomarker for poor prognosis. In as much as enhanced cytokine secretion is associated with poor prognosis, TTP may be a therapeutic target to reduce multiple cytokines concurrently in patients with HNSCC. Cancer 2011. © 2011 American Cancer Society.
Higher population‐based incidence rates of triple‐negative breast cancer among young African‐American women
Authors: Amirikia Kathryn C. , Mills Paul , Bush Jason , Newman Lisa A
Published: January 2011

BACKGROUND:

Differences in the breast cancer burden of African‐American women compared with white American women are well documented. Recent controversies have emerged regarding age‐appropriate mammographic screening guidelines, and these surveillance recommendations may influence future breast cancer disparities. The objective of the current study was to evaluate age‐specific breast cancer stage distributions and incidence rates of triple‐negative breast cancer (TNBC) in a population‐based tumor registry.

METHODS:

The authors analyzed breast cancers from the California Cancer Registry (CCR) that were diagnosed between 1988 and 2006. The results were stratified by age and race/ethnicity, with white Americans identified as non‐Hispanic whites (NHWs) and African Americans identified as non‐Hispanic blacks (NHBs). Breast cancer stage distributions and TNBC incidence rates also were analyzed.

RESULTS:

In total, 375,761 invasive breast cancers were evaluated (including 276,938 in NHWs and 21,681 in NHBs). NHBs and Hispanics tended to be younger than NHWs (median ages 57 years, 54 years, and 64 years, respectively). Lifetime incidence rates were higher for NHWs compared with NHBs and Hispanics; however, for women aged <44 years, incidence was highest among NHBs. NHBs also had higher incidence rates of stage III and IV disease and a higher incidence of TNBC in all age categories.

CONCLUSIONS:

Population‐based data demonstrated that African‐American women had a more advanced stage distribution for breast cancer compared with white American women and higher incidence rates for TNBC. These patterns were observed for women ages 40 to 49 years and for older women, and they suggest that mammographic screening for the early detection of breast cancer will be particularly relevant for younger African‐American women. Cancer 2011. © 2011 American Cancer Society.