bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and function of CXCL16 in a novel model of gout
Authors: Ruth Jeffrey H. , Arendt Monica D. , Amin M. Asif , Ahmed Salahuddin , Marotte Hubert , Rabquer Bradley J. , Lesch Charles , Lee Solhee , Koch Alisa E. 
Published: April 2010

AbstractObjectiveTo better define the activity of soluble CXCL16 in the recruitment of polymorphonuclear neutrophils (PMNs) in vivo, utilizing a novel animal model of gout involving engraftment of SCID mice with normal human synovial tissue (ST) injected intragraft with gouty human synovial fluid (SF).MethodsFor in vitro studies, a modified Boyden chemotaxis system was used to identify CXCL16 as an active recruitment factor for PMNs in gouty SF. Migration of PMNs could be reduced by neutralization of CXCL16 activity in gouty SF. For in vivo analyses, fluorescent dye–tagged PMNs were injected intravenously into SCID mice while, simultaneously, diluted gouty SF containing CXCL16, or depleted of CXCL16 by antibody blocking, was administered intragraft. In addition, the receptor for CXCL16, CXCR6, was inhibited by incubating PMNs with a neutralizing anti‐CXCR6 antibody prior to injection into the mouse chimeras. Recruitment of PMNs to the gouty SF–injected normal human ST was then examined in this SCID mouse chimera system.ResultsCXCL16 concentrations were highly elevated in gouty SF, and PMNs were observed to migrate in response to CXCL16 in vitro. Normal human ST–SCID mouse chimeras injected intragraft with gouty SF that had been depleted of CXCL16 during PMN transfer showed a significant reduction of 50% in PMN recruitment to engrafted tissue as compared with that after administration of sham‐depleted gouty SF. Similar findings were achieved when PMNs were incubated with a neutralizing anti‐CXCR6 antibody before injection into chimeras.ConclusionOverall, the results of this study outline the effectiveness of the human–SCID mouse chimera system as a viable animal model of gout, serving to identify the primary function of CXCL16 as a significant mediator of in vivo recruitment of PMNs to gouty SF.
Modulation of the angiogenic phenotype of normal and systemic sclerosis endothelial cells by gain–loss of function of pentraxin 3 and matrix metalloproteinase 12
Authors: Margheri Francesca , Serratì Simona , Lapucci Andrea , Chillà Anastasia , Bazzichi Laura , Bombardieri Stefano , Kahaleh Bashar , Calorini Lido , Bianchini Francesca , Fibbi Gabriella , Del Rosso Mario 
Published: April 2010

AbstractObjectiveStudies have shown that in systemic sclerosis (SSc) endothelial cells, overproduction of matrix metalloproteinase 12 (MMP‐12) and pentraxin 3 (PTX3) is associated with defective angiogenesis. This study was undertaken to examine whether overexpression of the relevant molecules could inhibit angiogenesis of normal microvascular endothelial cells (MVECs), and whether silencing of these molecules in SSc MVECs could restore the lost angiogenic properties of the cells in vitro and in vivo.MethodsTransient transfection of MVECs with human MMP12 and PTX3 was performed by electroporation. Silencing of MMP12 and PTX3 was obtained by treatment with small interfering RNA, and treatment effects were validated by Western blotting with specific antibodies and a fluorimetric assay. In vitro cell migration and capillary morphogenesis were studied on Matrigel substrates. In vivo angiogenesis was studied using a Matrigel sponge assay in mice.ResultsTransfection of MMP12 and PTX3 in normal MVECs resulted in loss of proliferation, invasion, and capillary morphogenesis in vitro, attributed to truncation of the urokinase‐type plasminogen activator receptor by MMP12 and to the anti–fibroblast growth factor 2/anti–vascular endothelial growth factor activity of PTX3. These effects were particularly evident in mixed populations of transfected normal MVECs (50% transfected with MMP12 and 50% with PTX3). Silencing of the same molecules in SSc MVECs increased their invasion in Matrigel. Single‐gene silencing did not increase the capillary morphogenesis of SSc MVECs, whereas double‐gene–silenced cells showed a burst of capillary tube formation. Culture medium of silenced SSc MVECs stimulated angiogenesis in assays of Matrigel sponge invasion in mice.ConclusionOverexpression of either MMP12 or PTX3 in normal MVECs blunts their angiogenic properties. Loss of function of MMP12 and PTX3 in SSc MVECs restores the ability of the cells to produce capillaries in vitro and induces vascularization in vivo on a Matrigel sponge.
Intervertebral disc degeneration: New insights based on “skipped” level disc pathology
Authors: Cheung Kenneth M. C. , Samartzis Dino , Karppinen Jaro , Mok Florence P. S. , Ho Daniel W. H. , Fong Daniel Y. T. , Luk Keith D. K. 
Published: April 2010

AbstractObjectiveTypically, age and abnormal physical loading (“wear and tear”) have been associated with the development of intervertebral disc degeneration. In the past decade, various additional etiologic factors for disc degeneration have been sporadically reported in the literature; however, many investigators continue to place tremendous emphasis on the effects of age and biomechanics associated with disc degeneration. The aim of this study was to provide additional insight into the notion that age and biomechanics are key factors in the development of disc degeneration. To this end, we addressed the prevalence of and risk factors associated with a unique pattern of disc degeneration of the lumbar spine, “skipped” level (nonconsecutive) disc degeneration (SLDD).MethodsAs part of a large genetics‐based study in southern Chinese individuals (n = 1,989), a cross‐sectional analysis was performed in subjects exhibiting disc degeneration in ≥2 levels (n = 838) who were then categorized as having SLDD (n = 174) or non‐SLDD (contiguous, multilevel; n = 664). Various radiographic parameters were assessed based on T2‐weighted magnetic resonance imaging (MRI). Subject demographics were assessed, and univariate and multivariate logistic regression analyses were performed.ResultsOverall, 8.7% of the whole population (n = 1,989) had SLDD, while it was present in 20.8% of subjects with multilevel disc degeneration (n = 838). SLDD was more prevalent in male subjects (adjusted odds ratio [OR] 1.48, 95% confidence interval [95% CI] 1.04–2.10, P = 0.028). SLDD was significantly associated with the presence of Schmorl's nodes (adjusted OR 2.72, 95% CI 1.78–4.15, P < 0.001), which also presented in levels with no disc degeneration. A history of disc bulge/extrusion (P = 0.004) and/or a history of back injury (P = 0.010) was significantly associated with non‐SLDD, and a greater degree of overall severity of disc degeneration was also associated with non‐SLDD. Other demographic and MRI findings did not significantly differ between groups.ConclusionTo our knowledge, this report is the first to describe the prevalence and risk factors associated with SLDD. Our study challenges the paradigm that age and biomechanics are the key factors associated with the development of disc degeneration. Although age and biomechanical factors may play a role in the manifestation of disc degeneration, our novel findings of SLDD patterns provide further awareness of and support for the notion that additional etiologic factors may play a role in the development of disc degeneration. Such factors warrant further investigation to shed light on the cause of disc degeneration.
Ofatumumab, a human anti‐CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease‐modifying antirheumatic drugs: Results of a randomized, double‐blind, placebo‐controlled, phase I/II study
Authors: Østergaard Mikkel , Baslund Bo , Rigby William , Rojkovich Bernadette , Jorgensen Christian , Dawes Peter T. , Wiell Charlotte , Wallace Daniel J. , Tamer Søren C. , Kastberg Helle , Petersen Jørgen , Sierakowski Stanislaw 
Published: April 2010

AbstractObjectiveTo investigate the safety and efficacy of ofatumumab, a novel human anti‐CD20 monoclonal antibody (mAb), in patients with active rheumatoid arthritis (RA) whose disease did not respond to ≥1 disease‐modifying antirheumatic drug.MethodsThis combined phase I/II study investigated the safety and efficacy of 3 doses of ofatumumab. In part A (phase I), 39 patients received 2 intravenous (IV) infusions of ofatumumab (300 mg, 700 mg, or 1,000 mg) or placebo in a 4:1 ratio 2 weeks apart, using a specified premedication and infusion regimen. In part B (phase II), 225 patients received study treatment as per phase I in a 1:1:1:1 ratio. Safety was assessed by adverse events (AEs) and laboratory parameters. Efficacy was assessed by the American College of Rheumatology 20% criteria for improvement (ACR20), the Disease Activity Score in 28 joints, and the European League Against Rheumatism (EULAR) response criteria. B cell pharmacodynamics were also investigated.ResultsAEs were predominantly reported at the first infusion and were mostly mild to moderate in intensity. Rapid and sustained peripheral B cell depletion was observed in all dose groups. In phase II, patients in all ofatumumab dose groups had significantly higher ACR20 response rates (40%, 49%, and 44% for the 300 mg, 700 mg, and 1,000 mg doses, respectively) than did patients receiving placebo (11%) at week 24 (P < 0.001). Overall, 70% of patients receiving ofatumumab had a moderate or good response according to the EULAR criteria at week 24.ConclusionOur findings indicate that ofatumumab, administered as 2 IV infusions of doses up to 1,000 mg, is clinically effective in patients with active RA.
Mapping the geography of science: Distribution patterns and networks of relations among cities and institutes
Authors: Leydesdorff Loet , Persson Olle 
Published: April 2010

AbstractUsing Google Earth, Google Maps, and/or network visualization programs such as Pajek, one can overlay the network of relations among addresses in scientific publications onto the geographic map. The authors discuss the pros and cons of various options, and provide software (freeware) for bridging existing gaps between the Science Citation Indices (Thomson Reuters) and Scopus (Elsevier), on the one hand, and these various visualization tools on the other. At the level of city names, the global map can be drawn reliably on the basis of the available address information. At the level of the names of organizations and institutes, there are problems of unification both in the ISI databases and with Scopus. Pajek enables a combination of visualization and statistical analysis, whereas the Google Maps and its derivatives provide superior tools on the Internet.
Robust l2−l∞ state feedback control for uncertain discrete‐time switched systems with mode‐dependent time‐varying delays
Authors: Zong Guangdeng , Hou Linlin , Xu Shengyuan 
Published: April 2010

AbstractThis paper deals with the problem of robust l2−l∞ state feedback control for uncertain discrete‐time switched systems with mode‐dependent time‐varying delays. Attention is focused on the design of a switched state feedback controller, which guarantees the asymptotical stability of the closed‐loop system and reduces the effect of the disturbance input on the controlled output to a prescribed level for all admissible uncertainties. By resorting to a descriptor system approach, delay‐dependent sufficient conditions are presented in terms of linear matrix inequalities (LMIs). A numerical example is provided to demonstrate the effectiveness of the proposed algorithms. Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Diagnosis and treatment of small follicular thyroid carcinomas
Authors: Clerici T , Kolb W , Beutner U , Bareck E , Dotzenrath C , Kull C , Niederle B 
Published: April 2010

Abstract

Background
Follicular thyroid microcarcinomas (mFTCs) of 10 mm or less in size rarely manifest clinically and their clinical significance is controversial. This study assessed their characteristics and incidence, and analysed treatment modalities used for mFTC.

Methods
Members of the German Association of Endocrine Surgeons were asked to review patients with mFTC operated on between 1990 and 2005.

Results
Data for 90 patients from 26 institutions were reported. Histopathological slides were available for re-evaluation in 35 patients. Most initial diagnoses had to be revised because of incorrect size assessment or incorrect diagnosis (benign adenoma, papillary thyroid carcinoma (PTC), follicular variant of PTC). The diagnosis of mFTC was confirmed in only four patients. As a result of the incorrect histopathological diagnosis, unnecessary completion thyroidectomy and radioiodine ablation were performed in 17 and 20 patients respectively. The incidence of mFTC was calculated to be 0·12 per million population per year.

Conclusion
mFTC is exceptionally rare. Such tumours are overdiagnosed, resulting in unnecessary treatment associated with avoidable morbidity. Histopathological re-evaluation by an experienced pathologist is recommended before embarking on further treatments when a diagnosis of mFTC is made.
Patterns of recurrence in patients with acute diverticulitis
Authors: Eglinton T , Nguyen T , Raniga S , Dixon L , Dobbs B , Frizelle F A 
Published: April 2010

Abstract

Background
The natural history of acute diverticulitis remains unclear, with the role of prophylactic surgery following conservatively managed diverticulitis increasingly controversial. This study investigated recurrence rates, patterns and complications after conservatively managed diverticulitis.

Methods
This was a retrospective chart review of all patients admitted with diverticulitis between June 1997 and June 2002. Demographic data, management, recurrence rates, complications and subsequent surgery were recorded.

Results
Some 502 patients were identified, 337 with uncomplicated and 165 with complicated diverticulitis. Median follow-up was 101 (range 60–124) months. Of 320 patients with uncomplicated diverticulitis managed conservatively, 60 (18·8 per cent) had one episode of recurrence, whereas 15 (4·7 per cent) had two or more episodes. After an initial attack of uncomplicated diverticulitis, only 5·0 per cent developed complicated disease. Complicated disease recurred in 24 per cent, compared with a recurrence rate of 23·4 per cent in those with uncomplicated diverticulitis (P = 0·622). When recurrence occurred, it usually did so within 12 months of the initial episode.

Conclusion
Acute diverticulitis has a low recurrence rate and rarely progresses to complications. Any recurrence is usually early, in a pattern more consistent with failure of the index episode to settle. Subsequent elective surgery to prevent recurrence and the development of complications should be used sparingly.
A national propensity‐adjusted analysis of adjuvant radiotherapy in the treatment of resected pancreatic adenocarcinoma
Authors: McDade Theodore P. , Hill Joshua S. , Simons Jessica P. , Piperdi Bilal , Ng Sing Chau , Zhou Zheng , Kadish Sidney P. , Fitzgerald Thomas J. , Tseng Jennifer F. 
Published: April 2010

AbstractBACKGROUND:The benefit of adjuvant radiotherapy (RT) for resected pancreatic adenocarcinoma remains controversial after randomized clinical trials. In this national‐level US study, a propensity score (conditional probability of receiving RT) was used to adjust for potential confounding in nonrandomized designs from treatment group differences.METHODS:Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) registry (1988‐2005 dataset). Multivariate analyses to determine the effect of RT on overall survival were performed using propensity‐adjusted Cox proportional hazards and Kaplan‐Meier analyses.RESULTS:In total, 5676 patients with resected pancreatic adenocarcinoma were identified, and 40.8% of those patients had received adjuvant RT. Univariate predictors of survival included age, race, marital status, disease stage, tumor size, tumor extension, tumor grade, lymph node status, year of diagnosis, type of resection, and receipt of RT (all P < .002). In a Cox model, independent predictors of improved survival included white race, married status, earlier stage, smaller tumors, well differentiated tumors, negative lymph node (N0) status, recent diagnosis, and receipt of RT (all P < .05). In a propensity‐adjusted proportional hazards regression, the benefit of adjuvant treatment that included RT remained significant after adjusting for the likelihood of receiving RT (hazard ratio, 0.773; 95% confidence interval, 0.714‐0.836; P < .0001). Within all 5 propensity strata, Kaplan‐Meier survival differed significantly (P < .0001 [lowest and highest probability strata] and P = .0165 [middle stratum with a “pseudorandom” probability of RT]).CONCLUSIONS:Adjuvant RT for resected pancreatic adenocarcinoma was associated with a significant survival advantage in a large national database, even after using propensity score methods to adjust for differences between treatment groups. The authors concluded that adjuvant RT should be considered for all appropriate patients who have resected pancreatic adenocarcinoma. Cancer 2010. © 2010 American Cancer Society.
Signaling of ERBB receptor tyrosine kinases promotes neuroblastoma growth in vitro and in vivo
Authors: Richards Kristen N. , Zweidler‐McKay Patrick A. , Van Roy Nadine , Speleman Frank , Trevino Jesus , Zage Peter E. , Hughes Dennis P. M. 
Published: April 2010

AbstractBACKGROUND:ERBB receptor tyrosine kinases can mediate proliferation, migration, adhesion, differentiation, and survival in many types of cells and play critical roles in many malignancies. Recent reports suggest a role for EGFR signaling in proliferation and survival of neuroblastoma, a common form of pediatric cancer that often has an extremely poor outcome.METHODS:The authors examined ERBB family expression in neuroblastoma cell lines and patient samples by flow cytometry, western blot, and quantitative real time polymerase chain reaction (Q‐PCR). Response to ERBB inhibition was assessed in vitro by cell‐cycle analysis and western blot and in vivo by serial tumor‐size measurements.RESULTS:A panel of neuroblastoma cell lines and primary patient tumors expressed EGFR, HER‐3, and HER‐4, with HER‐2 in some tumors.HER‐4mRNA was expressed predominantly in cleavable isoforms. Whereas EGFR inhibition with erlotinib and pan‐ERBB inhibition with CI‐1033 inhibited EGF‐induced phosphorylation of EGFR, AKT, and ERK1/2, only CI‐1033 induced growth inhibition and dose‐dependent apoptosis in vitro. Both CI‐1033 and erlotinib treatment of neuroblastoma xenograft tumors resulted in decreased tumor growth in vivo, although CI‐1033 was more effective. In vivo expression of EGFR was observed predominantly in vascular endothelial cells.CONCLUSIONS:Pan‐ERBB inhibition is required for ERBB‐related neuroblastoma apoptosis in vitro, although EGFR contributes indirectly to tumor growth in vivo. Inhibition of EGFR in endothelial cells may be an important aspect of erlotinib's impact on neuroblastoma growth in vivo. Our results suggest that non‐EGFR ERBB family members contribute directly to neuroblastoma growth and survival, and pan‐ERBB inhibition represents a potential therapeutic target for treating neuroblastoma. Cancer 2010. © 2010 American Cancer Society.
Cloaking via change of variables for the Helmholtz equation
Authors: Kohn Robert V. , Onofrei Daniel , Vogelius Michael S. , Weinstein Michael I. 
Published: April 2010

AbstractThe transformation optics approach to cloaking uses a singular change of coordinates, which blows up a point to the region being cloaked. This paper examines a natural regularization, obtained by (1) blowing up a ball of radius ρ rather than a point, and (2) including a well‐chosen lossy layer at the inner edge of the cloak. We assess the performance of the resulting near‐cloak as the regularization parameter ρ tends to 0, in the context of (Dirichlet and Neumann) boundary measurements for the time‐harmonic Helmholtz equation. Since the goal is to achieve cloaking regardless of the content of the cloaked region, we focus on estimates that are uniform with respect to the physical properties of this region. In three space dimensions our regularized construction performs relatively well: the deviation from perfect cloaking is of order ρ. In two space dimensions it does much worse: the deviation is of order 1/|log ρ|. In addition to proving these estimates, we give numerical examples demonstrating their sharpness. Some authors have argued that perfect cloaking can be achieved without losses by using the singular change‐of‐variable‐based construction. In our regularized setting the analogous statement is false: without the lossy layer, there are certain resonant inclusions (depending in general on ρ) that have a huge effect on the boundary measurements. © 2010 Wiley Periodicals, Inc.
CD4+CD25+ regulatory T cells utilize FasL as a mechanism to restrict DC priming functions in cutaneous immune responses
Authors: Gorbachev Anton V. , Fairchild Robert L. 
Published: April 2010

AbstractRecent studies have suggested Fas‐mediated elimination of antigen‐presenting cells as an important mechanism down‐regulating the induction of autoimmune responses. It remains unknown whether this mechanism restricts the magnitude of immune responses to non‐self antigens. We used a mouse model of a cutaneous CD8+ T‐cell‐mediated immune response (contact hypersensitivity, CHS) to test if CD4+CD25+ T cells expressing FasL regulate hapten‐specific effector CD8+ T cell expansion through the elimination of Fas‐expressing hapten‐presenting DC. In WT mice, attenuation of CD4+CD25+ T regulatory cell activity by anti‐CD25 mAb increased hapten‐presenting DC numbers in skin‐draining LN, which led to increased effector CD8+ T‐cell priming for CHS responses. In contrast, CD4+CD25+ T cells did not regulate hapten‐specific CD8+ T‐cell priming and CHS responses initiated by Fas‐defective (lpr) DC. Thus, restricting DC priming functions through Fas–FasL interactions is a potent mechanism employed by CD4+CD25+ regulatory cells to restrict CD8+ T‐cell‐mediated allergic immune responses in the skin.
Steady‐state antigen‐expressing dendritic cells terminate CD4+ memory T‐cell responses
Authors: Nasreen Mariam , Waldie Tanya M. , Dixon Chantelle M. , Steptoe Raymond J. 
Published: April 2010

AbstractCD4+ T cells are important effectors of inflammation and tissue destruction in many diseases of immune dysregulation. As memory T cells develop early during the preclinical stages of autoimmune and inflammatory diseases, immunotherapeutic approaches to treatment of these diseases, once established, must include the means to terminate memory T‐cell responses. Traditionally, it has been considered that, due to their terminally differentiated nature, memory T cells are resistant to tolerance induction, although emerging evidence indicates that some immunotherapeutic approaches can terminate memory T‐cell responses. Here, we demonstrate that CD4+ memory T‐cell responses can be terminated when cognate antigen is transgenically expressed in steady‐state DC. Transfer of in‐vitro‐generated CD4+ memory T cells establishes, in nontransgenic recipients, a stable and readily recalled memory response to cognate antigen. In contrast, upon transfer to mice expressing cognate antigen targeted to DC, memory CD4+ T cells undergo a phase of limited proliferation followed by substantial deletion, and recall responses are effectively silenced. This finding is important in understanding how to effectively apply immunotherapy to ongoing T‐cell‐mediated autoimmune and inflammatory diseases.