bluuebunny/crossref_metadata_2025_split huggingface dataset:
Properties and osteoblast cytocompatibility of self-curing acrylic cements modified by glass fillers
Authors: Lopes PP , Garcia MP , Fernandes MH , Fernandes MHV 
Published: August 2012

Materials filled with a silicate glass (MSi) and a borate glass (MB) were developed and compared in terms of their in vitro behavior. The effect of filler composition and concentration (0, 30, 40 and 50 wt%) on the curing parameters, residual monomer, water uptake, weight loss, bioactivity, mechanical properties (bending and compression) and osteoblast cytocompatibility was evaluated. The addition of bioactive glass filler significantly improved the cements curing parameters and the mechanical properties. The most relevant results were obtained for the lower filler concentration (30 wt%) a maximum flexural strength of 40.4 MPa for MB3 and a maximum compressive strength of 95.7 MPa for MSi3. In vitro bioactivity in acellular media was enhanced by the higher glass contents in the cements. Regarding the biological assessment, the incorporation of the silicate glass significantly improved osteoblast cytocompatibility, whereas the presence of the borate glass resulted in a poor cell response. Nevertheless it was shown that the surviving cells on the MB surface were in a more differentiated stage compared to those growing over non-filled poly(methyl methacrylate). Results suggest that the developed formulations offer a high range of properties that might be interesting for their use as self-curing cements.
Mean Platelet Volume and Related Factors in Patients at Different Stages of Diabetic Nephropathy
Authors: Turgutalp Kenan , Özhan Onur , Akbay Esen , Tombak Anıl , Tiftik Naci , Ozcan Turkay , Yılmaz Sercan , Helvacı İlter , Kiykim Ahmet 
Published: August 2012

Introduction: Mean platelet volume (MPV) is an independent cardiovascular disease predictor, and characteristics of MPV in patients with diabetic nephropathy (DN) are not well known. Aim: To determine the MPV levels in patients at different stages of DN. Patients and Methods: The MPV levels were investigated in healthy participants (group 1, n = 157), patients with type 2 diabetes mellitus without complication (group 2, n = 160), diabetic patients with clinical proteinuria (group 3, n = 144), and in patients with chronic kidney disease due to DN (group 4, n = 160). Findings: The MPV level was higher in all diabetic patients than that in normal participants ( P < .05). The MPV values had a positive correlation with the serum creatinine and proteinuria, and a negative correlation with the glomerular filtration rate ([GFR] P < .001 for all, r values; .72, and .82, and −.92, respectively). Conclusion: The MPV values were higher in diabetic groups than that in normal participants. Both GFR and proteinuria were the most powerful determinants of MPV.
Bivalirudin Utilization in Rats Undergoing Cardiopulmonary Bypass
Authors: Zhang Ruidong , Huang Yue , Zhang Mazhong , Liu Jinfen 
Published: August 2012

Objective: To investigate the impact of bivalirudin alternative treatment on antiheparin/platelet factor 4 antibody levels perioperatively in rats undergoing cardiopulmonary bypass (CPB). Methods: Two groups of rats received heparin pretreatment and two groups of rats not, and during CPB all the four groups received either bivalirudin or heparin. Pre-CPB and post-CPB day 7 venous blood samples were used to determine the levels of antiheparin/PF4 antibody immunoglobulin (Ig) G with enzyme-linked immunosorbent assay. Results: Preoperative heparin pretreatment increased the antiheparin/PF4 antibody IgG levels ( P < .01), while the administration of heparin further increased this levels ( P < .01). The use of bivalirudin prevented further increase in antiheparin/PF4 antibody IgG levels. Conclusion: Bivalirudin, as a direct thrombin inhibitor, could circumvent the increased antiheparin/PF4 antibody level in circulation due to the heparin administration.
Cerebral coenurosis in a cat caused by Taenia serialis: neurological, magnetic resonance imaging and pathological features
Authors: Jull Philip , Browne Elizabeth , Boufana Belgees S , Schöniger Sandra , Davies Emma 
Published: August 2012

Clinical summary: A 4-year-old Birman cat was presented with marked obtundation and non-ambulatory tetraparesis. Two well-demarcated, intra-axial T2-hyperintense, T1-hypointense structures, which did not contrast enhance, were evident on magnetic resonance imaging (MRI). Histopathology of the structures revealed metacestodes that were morphologically indicative of larval stages of Taenia species. Polymerase chain reaction amplification of a fragment within the 12S rRNA gene confirmed the subspecies as Taenia serialis. Practical significance: This is the first report of MRI findings of cerebral coenurosis caused by T serialis in a cat. Early MRI should be considered an important part of the diagnostic work-up for this rare clinical disease, as it will help guide subsequent treatment and may improve the prognosis.
Inhibition of hedgehog signaling for the treatment of murine sclerodermatous chronic graft-versus-host disease
Authors: Zerr Pawel , Palumbo-Zerr Katrin , Distler Alfiya , Tomcik Michal , Vollath Stefan , Munoz Luis E. , Beyer Christian , Dees Clara , Egberts Friederike , Tinazzi Ilaria , Del Galdo Francesco , Distler Oliver , Schett Georg , Spriewald Bernd M. , Distler Jörg H. W. 
Published: August 2012

AbstractChronic graft-versus-host disease (cGVHD) is a prognosis limiting complication of allogeneic stem cell transplantation. The molecular mechanisms underlying cGVHD are incompletely understood, and targeted therapies are not yet established for clinical use. Here we examined the role of the hedgehog pathway in sclerodermatous cGVHD. Hedgehog signaling was activated in human and murine cGVHD with increased expression of sonic hedgehog and accumulation of the transcription factors Gli-1 and Gli-2. Treatment with LDE223, a highly selective small-molecule antagonist of the hedgehog coreceptor Smoothened (Smo), abrogated the activation of hedgehog signaling and protected against experimental cGVHD. Preventive therapy with LDE223 almost completely impeded the development of clinical and histologic features of sclerodermatous cGVHD. Treatment with LDE223 was also effective, when initiated after the onset of clinical manifestations of cGVHD. Hedgehog signaling stimulated the release of collagen from cultured fibroblasts but did not affect leukocyte influx in murine cGVHD, suggesting direct, leukocyte-independent stimulatory effects on fibroblasts as the pathomechanism of hedgehog signaling in cGVHD. Considering the high morbidity of cGVHD, the current lack of efficient molecular therapies for clinical use, and the availability of well-tolerated inhibitors of Smo, targeting hedgehog signaling might be a novel strategy for clinical trials in cGVHD.
Microfluidic kit-on-a-lid: a versatile platform for neutrophil chemotaxis assays
Authors: Sackmann Eric K. , Berthier Erwin , Young Edmond W.K. , Shelef Miriam A. , Wernimont Sarah A. , Huttenlocher Anna , Beebe David J. 
Published: August 2012

AbstractImprovements in neutrophil chemotaxis assays have advanced our understanding of the mechanisms of neutrophil recruitment; however, traditional methods limit biologic inquiry in important areas. We report a microfluidic technology that enables neutrophil purification and chemotaxis on-chip within minutes, using nanoliters of whole blood, and only requires a micropipette to operate. The low sample volume requirements and novel lid-based method for initiating the gradient of chemoattractant enabled the measurement of human neutrophil migration on a cell monolayer to probe the adherent and migratory states of neutrophils under inflammatory conditions; mouse neutrophil chemotaxis without sacrificing the animal; and both 2D and 3D neutrophil chemotaxis. First, the neutrophil chemotaxis on endothelial cells revealed 2 distinct neutrophil phenotypes, showing that endothelial cell-neutrophil interactions influence neutrophil chemotactic behavior. Second, we validated the mouse neutrophil chemotaxis assay by comparing the adhesion and chemotaxis of neutrophils from chronically inflamed and wild-type mice; we observed significantly higher neutrophil adhesion in blood obtained from chronically inflamed mice. Third, we show that 2D and 3D neutrophil chemotaxis can be directly compared using our technique. These methods allow for new avenues of research while reducing the complexity, time, and sample volume requirements to perform neutrophil chemotaxis assays.
Impact of hydroxyurea on clinical events in the BABY HUG trial
Authors: Thornburg Courtney D. , Files Beatrice A. , Luo Zhaoyu , Miller Scott T. , Kalpatthi Ram , Iyer Rathi , Seaman Phillip , Lebensburger Jeffrey , Alvarez Ofelia , Thompson Bruce , Ware Russell E. , Wang Winfred C. 
Published: August 2012

AbstractThe Pediatric Hydroxyurea Phase 3 Clinical Trial (BABY HUG) was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia. An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninety-three subjects were randomized to hydroxyurea (20 mg/kg/d) or placebo; there were 374 patient-years of on-study observation. Hydroxyurea was associated with statistically significantly lower rates of initial and recurrent episodes of pain, dactylitis, acute chest syndrome, and hospitalization; even infants who were asymptomatic at enrollment had less dactylitis as well as fewer hospitalizations and transfusions if treated with hydroxyurea. Despite expected mild myelosuppression, hydroxyurea was not associated with an increased risk of bacteremia or serious infection. These data provide important safety and efficacy information for clinicians considering hydroxyurea therapy for very young children with sickle cell anemia. This clinical trial is registered with the National Institutes of Health (NCT00006400, www.clinicaltrials.gov).
Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns
Authors: Schuh Anna , Becq Jennifer , Humphray Sean , Alexa Adrian , Burns Adam , Clifford Ruth , Feller Stephan M. , Grocock Russell , Henderson Shirley , Khrebtukova Irina , Kingsbury Zoya , Luo Shujun , McBride David , Murray Lisa , Menju Toshi , Timbs Adele , Ross Mark , Taylor Jenny , Bentley David 
Published: August 2012

Abstract
Chronic lymphocytic leukemia is characterized by relapse after treatment and chemotherapy resistance. Similarly, in other malignancies leukemia cells accumulate mutations during growth, forming heterogeneous cell populations that are subject to Darwinian selection and may respond differentially to treatment. There is therefore a clinical need to monitor changes in the subclonal composition of cancers during disease progression. Here, we use whole-genome sequencing to track subclonal heterogeneity in 3 chronic lymphocytic leukemia patients subjected to repeated cycles of therapy. We reveal different somatic mutation profiles in each patient and use these to establish probable hierarchical patterns of subclonal evolution, to identify subclones that decline or expand over time, and to detect founder mutations. We show that clonal evolution patterns are heterogeneous in individual patients. We conclude that genome sequencing is a powerful and sensitive approach to monitor disease progression repeatedly at the molecular level. If applied to future clinical trials, this approach might eventually influence treatment strategies as a tool to individualize and direct cancer treatment.
Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes
Authors: Sekeres Mikkael A. , Tiu Ramon V. , Komrokji Rami , Lancet Jeffrey , Advani Anjali S. , Afable Manuel , Englehaupt Ricki , Juersivich Joyce , Cuthbertson David , Paleveda Jennifer , Tabarroki Ali , Visconte Valeria , Makishima Hideki , Jerez Andres , Paquette Ronald , List Alan F. , Maciejewski Jaroslaw P. 
Published: August 2012

Abstract
Lenalidomide and azacitidine each have activity in myelodysplastic syndromes (MDS) patients, where both microenvironment and cell-regulatory mechanisms contribute to disease pathogenesis. The objective of this multicenter, phase 2 expansion trial was to determine the efficacy and safety of combination therapy with azacitidine (75 mg/m2/d for 5 days) and lenalidomide (10 mg/d for 21 days; 28-day cycle) in patients with higher-risk MDS. Among 36 patients enrolled (18 phase 1, 18 phase 2), median age was 68 years (range, 47-78 years) and follow-up was 12 months (range, 3-55 years). IPSS categories included intermediate-1 (n = 5 patients with excess blasts), intermediate-2 (20), and high (11). Common grade 3/4 nonhematologic adverse events included febrile neutropenia (22% of patients), other infection (11%), pulmonary (11%), cardiac (11%), constitutional (11%), and dermatologic (11%). The overall response rate (per modified MDS International Working Group criteria) was 72%: 16 patients (44%) achieved a complete response (CR), and 10 (28%) had hematologic improvement. Median CR duration was 17+ months (range, 3-39+); median overall survival was 37+ months (range, 7-55+) for CR patients, and 13.6 months for the entire cohort (range, 3-55). TET2/DNMT3A/IDH1/2 mutational status was associated with response in a limited number of patients. The lenalidomide/azacitidine combination is well-tolerated and highly active in treating greater-risk MDS. This study is registered at http://www.clinicaltrials.gov as NCT00352001.
Melanoma incidence trends in Limburg after screening and prevention campaigns
Authors: Vanstraelen D , Deleu H , Van Robays J , Dhollander D , Cloes E , Lousberg D , Kuipers G , Adriaens B , Mebis J , Mathei C , Buntinx F 
Published: August 2012

Abstract

Background
Malignant melanoma is a skin cancer of which the incidence is said to be raising in recent years. Prevention may result in decrease of the incidence. Early detection may result in the detection of earlier stages of the disease. In Limburg a combined campaign of prevention and screening has been performed in recent years and its effects should be evaluated.

Objectives
To study time trends of malignant melanoma incidence and the evolution of stages of detected melanomas and to relate them to interventions in previous years.

Methods
An ongoing multi-faceted intervention, including information as well as screening invitations (Euromelanoma project) was implemented in 1999. Time trends of malignant melanoma were studied on the basis of data from the Limburg Cancer Registry (LIKAR) of 1996-2005. Stages were studied on the basis of an additional clinical registration completed by pathologists and dermatologists.

Results
Over the years 1996-2005, the crude incidence rate of malignant melanoma was 6.8/100,000 patient-years in males and 11.6 in females, with a European standardized incidence rate (ESR) of 6.4 in males and 10.5 in females. The incidence progressively increased with age.
In males, the ESR initially decreased, followed by a significant increase from 3.0 in 1998 to 7.6 in 2005. On average this is a yearly increase of 0.5 per 100,000 persons (p= 0.04). In females the curve fluctuates, resulting in almost similar rates in 1996 and 2004 (p = 0.85), but with a sudden increase from 9.2 to 15.8 between 2004 and 2005.
Neither the Breslow nor the Clarck classification showed any significant change over the registration period. The proportion of lymph node invasion, metastasis and ulcerations did not change.

Discussion
With the exception of a small and clinically irrelevant increase in ESR in males, no changes over time were detected in incidence or stage distribution. The effect of the intervention seems limited.
Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation
Authors: Dall’Olio Giovanni Marco , Laayouni Hafid , Luisi Pierre , Sikora Martin , Montanucci Ludovica , Bertranpetit Jaume 
Published: August 2012

Abstract

Background
Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints.

Results
Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1.

Conclusions
These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show lower population differentiation, while genes involved in traits related to the environment should show higher variability. Taken together, this work broadens our knowledge on how events of population differentiation and of positive selection are distributed among different parts of a metabolic pathway.
Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study
Authors: Coentrão Luis , Santos-Araújo Carla , Dias Claudia , Neto Ricardo , Pestana Manuel 
Published: August 2012

Abstract

Background
Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation.

Methods
A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC.

Results
Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024).

Conclusion
Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.
Elevated levels of serum amyloid A indicate poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Wang Jun-Ye , Zheng Yu-Zhen , Yang Juan , Lin Yue-Hao , Dai Shu-Qin , Zhang Ge , Liu Wan-Li 
Published: August 2012

Abstract

Background
Increase of Serum amyloid A (SAA) level has been observed in patients with a variety of cancers. The objective of this study was to determined whether SAA level could be used as a prognostic parameter in patients with esophageal squamous cell carcinoma (ESCC).

Methods
SAA levels were measured by rate nephelometry immunoassay in 167 healthy controls and 167 ESCC patients prior to surgical resection. Statistical associations between clinicopathological observations and SAA levels were determined using the Mann–Whitney U test. The clinical value of SAA level as a prognostic parameter was evaluated using the Cox’s proportional hazards model.

Results
SAA levels were significantly higher in patients with ESCC compared to levels in healthy controls (13.88 ± 15.19 mg/L vs. 2.26 ± 1.66 mg/L, P < 0.001). Elevation of SAA levels (≥ 8.0 mg/L) was observed in 54.5% (91/167) of patients with ESCC but not in healthy controls. SAA levels were associated with tumor size (P < 0.001), histological differentiation (P = 0.015), T classification (P < 0.001), clinical stage (P < 0.001), lymph node metastasis (P < 0.001) and distant metastasis (P < 0.001), but not with the age and gender of the patients or tumor location. Multivariate analysis revealed that patients with an elevated level of SAA (≥ 8.0 mg/L) had significantly lower 5-year survival rate than those with non-elevated SAA (< 8.0 mg/L, log-rank P < 0.0001).

Conclusions
An elevated level of preoperative SAA was found to associate with tumor progression and poor survival in patients with ESCC.