bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transferrin-a modulates hepcidin expression in zebrafish embryos
Authors: Fraenkel Paula G. , Gibert Yann , Holzheimer Jason L. , Lattanzi Victoria J. , Burnett Sarah F. , Dooley Kimberly A. , Wingert Rebecca A. , Zon Leonard I. 
Published: December 2008

AbstractThe iron regulatory hormone hepcidin is transcriptionally up-regulated in response to iron loading, but the mechanisms by which iron levels are sensed are not well understood. Large-scale genetic screens in the zebrafish have resulted in the identification of hypochromic anemia mutants with a range of mutations affecting conserved pathways in iron metabolism and heme synthesis. We hypothesized that transferrin plays a critical role both in iron transport and in regulating hepcidin expression in zebrafish embryos. Here we report the identification and characterization of the zebrafish hypochromic anemia mutant, gavi, which exhibits transferrin deficiency due to mutations in transferrin-a. Morpholino knockdown of transferrin-a in wild-type embryos reproduced the anemia phenotype and decreased somite and terminal gut iron staining, while coinjection of transferrin-a cRNA partially restored these defects. Embryos with transferrin-a or transferrin receptor 2 (TfR2) deficiency exhibited low levels of hepcidin expression, however anemia, in the absence of a defect in the transferrin pathway, failed to impair hepcidin expression. These data indicate that transferrin-a transports iron and that hepcidin expression is regulated by a transferrin-a–dependent pathway in the zebrafish embryo.
Epithelial neutrophil-activating peptide-78 recruits neutrophils into pleural effusion
Authors: Liu G-N. , Shi H-Z. , Xie Z-H. , Shen H-H. , Huang H-Q. , Deng J-M. , Liang Q-L. , Wu Y-B. 
Published: December 2008

The aim of this study was to investigate the presence of epithelial neutrophil-activating peptide (ENA)-78 in pleural effusions, as well as the chemoattractant activity of pleural ENA-78 on neutrophils.Pleural effusion and serum samples were collected from 75 patients who presented to the respiratory institute (19 with malignant pleural effusion, 21 with tuberculous pleural effusion, 18 with infectious pleural effusion and 17 with transudative pleural effusion). The concentrations of ENA-78, myeloperoxidase and neutrophil elastase were determined, and the chemoattractant activity of ENA-78 for neutrophils bothin vitroandin vivowas also observed.The concentrations of ENA-78, myeloperoxidase and neutrophil elastase in infectious pleural effusion were significantly higher than those in malignant, tuberculous and transudative groups, respectively (all p<0.01). Infectious pleural fluid was chemotactic for neutrophilsin vitroand anti-ENA-78 antibody could partly inhibit these chemotactic effects. Intrapleural administration of ENA-78 produced a marked progressive influx of neutrophils into pleural space.Compared with noninfectious pleural effusion, ENA-78 appeared to be increased in infectious pleural effusion. Our data suggested that ENA-78 was able to induce neutrophil infiltration into pleural space and might be responsible for pleural neutrophil degranulation.
Assessment of the feasibility of exon 45–55 multiexon skipping for duchenne muscular dystrophy
Authors: van Vliet Laura , de Winter Christa L , van Deutekom Judith CT , van Ommen Gert-Jan B , Aartsma-Rus Annemieke 
Published: December 2008

Abstract

Background
The specific skipping of an exon, induced by antisense oligonucleotides (AON) during splicing, has shown to be a promising therapeutic approach for Duchenne muscular dystrophy (DMD) patients. As different mutations require skipping of different exons, this approach is mutation dependent. The skipping of an entire stretch of exons (e.g. exons 45 to 55) has recently been suggested as an approach applicable to larger groups of patients. However, this multiexon skipping approach is technically challenging. The levels of intended multiexon skips are typically low and highly variable, and may be dependent on the order of intron removal. We hypothesized that the splicing order might favor the induction of multiexon 45–55 skipping.

Methods
We here tested the feasibility of inducing multiexon 45–55 in control and patient muscle cell cultures using various AON cocktails.

Results
In all experiments, the exon 45–55 skip frequencies were minimal and comparable to those observed in untreated cells.

Conclusion
We conclude that current state of the art does not sufficiently support clinical development of multiexon skipping for DMD.
Association of the germline TP53R337H mutation with breast cancer in southern Brazil
Authors: Assumpção Juliana G , Seidinger Ana Luíza , Mastellaro Maria José , Ribeiro Raul C , Zambetti Gerard P , Ganti Ramapriya , Srivastava Kumar , Shurtleff Sheila , Pei Deqing , Zeferino Luiz Carlos , Dufloth Rozany M , Brandalise Silvia Regina , Yunes José Andres 
Published: December 2008

Abstract

Background
The germline TP53-R337H mutation is strongly associated with pediatric adrenocortical tumors (ACT) in southern Brazil; it has low penetrance and limited tissue specificity in most families and therefore is not associated with Li-Fraumeni syndrome. However, other tumor types, mainly breast cancer, have been observed in carriers of several unrelated kindreds, raising the possibility that the R337H mutation may also contribute to breast tumorigenesis in a genetic background-specific context.

Methods
We conducted a case-control study to determine the prevalence of the R337H mutation by sequencing TP53 exon 10 in 123 women with breast cancer and 223 age- and sex-matched control subjects from southern Brazil. Fisher's test was used to compare the prevalence of the R337H.

Results
The R337H mutation was found in three patients but in none of the controls (p = 0.0442). Among the carriers, two had familial history of cancer meeting the Li-Fraumeni-like criteria. Remarkably, tumors in each of these three cases underwent loss of heterozygosity by eliminating the mutant TP53 allele rather than the wild-type allele. Polymorphisms were identified within the TP53 (R72P and Ins16) and MDM2 (SNP309) genes that may further diminish TP53 tumor suppressor activity.

Conclusion
These results demonstrate that the R337H mutation can significantly increase the risk of breast cancer in carriers, which likely depends on additional cooperating genetic factors. These findings are also important for understanding how low-penetrant mutant TP53 alleles can differentially influence tumor susceptibility.
Long-Term Smoking Cessation Outcomes Among Childhood Cancer Survivors in the Partnership for Health Study
Authors: Emmons Karen M. , Puleo Elaine , Mertens Ann , Gritz Ellen R. , Diller Lisa , Li Frederick P. 
Published: December 2008

PurposePartnership for Health (PFH) was found to increase smoking cessation among smokers in the Childhood Cancer Survivors Study (CCSS) at the 8- and 12-month postbaseline follow-up. This report provides outcomes at 2 to 6 years postbaseline; the primary outcome is a four-category smoking status variable (quit at all follow-ups, quit at final follow-up only, smoker at all follow-ups, and smoker at final follow-up only); quit attempts among those who reported smoking at the final follow-up is a secondary outcome.MethodsPFH was a randomized control trial with two conditions, peer phone counseling (PC) and self-help (SH), that involved smokers (n = 796) enrolled in the CCSS cohort.ResultsLong-term quit rates were higher in PC versus SH participants. Long-term smoking cessation outcomes were lower among those who were nicotine dependent, of lower educational levels, and among men, and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy. There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers.ConclusionCessation rates continue to be significantly higher among participants in the PC condition versus SH, although the differences were not large. This article highlights differences in long-term engagement with smoking cessation among those who received the intervention.
Role of Androgen Deprivation Therapy for Node-Positive Prostate Cancer
Authors: Wong Yu-Ning , Freedland Stephen , Egleston Brian , Hudes Gary , Schwartz J. Sanford , Armstrong Katrina 
Published: December 2008

Purpose To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era. Patients and Methods We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT. Results A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition. Conclusion Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.
The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report
Authors: Monclair Tom , Brodeur Garrett M. , Ambros Peter F. , Brisse Hervé J. , Cecchetto Giovanni , Holmes Keith , Kaneko Michio , London Wendy B. , Matthay Katherine K. , Nuchtern Jed G. , von Schweinitz Dietrich , Simon Thorsten , Cohn Susan L. , Pearson Andrew D.J. 
Published: December 2008

Purpose The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. Methods To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. Results In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% ± 4% v 90% ± 3%; P = .0010). Conclusion Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.
Prophylactic Cranial Irradiation in Extensive Disease Small-Cell Lung Cancer: Short-Term Health-Related Quality of Life and Patient Reported Symptoms—Results of an International Phase III Randomized Controlled Trial by the EORTC Radiation Oncology and Lung Cancer Groups
Authors: Slotman Berend J. , Mauer Murielle E. , Bottomley Andrew , Faivre-Finn Corinne , Kramer Gijs W.P.M. , Rankin Elaine M. , Snee Michael , Hatton Matthew , Postmus Pieter E. , Collette Laurence , Senan Suresh 
Published: December 2008

Purpose Prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) leads to significantly fewer symptomatic brain metastases and improved survival. Detailed effects of PCI on health-related quality of life (HRQOL) are reported here. Patients and Methods Patients (age, 18 to 75 years; WHO ≤ 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter. Results Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055). Conclusion PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.
Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer
Authors: Wolpin Brian M. , Hezel Aram F. , Abrams Thomas , Blaszkowsky Lawrence S. , Meyerhardt Jeffrey A. , Chan Jennifer A. , Enzinger Peter C. , Allen Brittany , Clark Jeffrey W. , Ryan David P. , Fuchs Charles S. 
Published: December 2008

Purpose The PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine. Patients and Methods Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival. Results Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9. Conclusion Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.
Analytical and numerical investigation of the optimum pressure distribution along a low-pressure axial fan blade
Authors: Pascu M , Miclea M , Epple P , Delgado A , Durst F 
Published: December 2008

In the field of axial flow turbomachines, the two-dimensional cascade model is often used experimentally or numerically to investigate fundamental flow characteristics and overall performance of the impeller. The core of the present work is a design method for axial fan cascades aiming to derive inversely the optimum blade shape based on the requirements of the impeller and not using any predefined aerofoil profiles. While most design strategies based on the aerofoil theory assume constant total pressure at all streamlines, i.e. free-vortex flow, this paper investigates the possibility of varying the total pressure along the blade and based on that, an analytical expression of the outlet blade angle is determined. When computing the blade profile at a specified radius, critical parameters reflecting on the flow characteristics are observed and adjusted (i.e. sufficient lift and controlled deceleration of the flow on the contour) so that the resulting profile is derived for minimum losses. The validation of this design strategy is given by the numerical results obtained when employed as an optimization tool for an industrial fan: 10–20 per cent absolute increase in the static efficiency of the optimized impeller.
A disc to air heat flux error and uncertainty analysis applied to a turbomachinery test rig design
Authors: Cooke A , Childs P , Sayma N , Long C A 
Published: December 2008

This article describes a Monte Carlo simulation-based error and an uncertainty analysis for values of disc to air heat fluxes as part of the design of an experimental axial turbine test rig. This work is of interest for those who study heat transfer and measurement or the design and use of experimental test rigs. An inverse analysis of theoretical disc surface temperatures was performed for different thermocouple configurations to compare the errors and uncertainties resulting from each to establish whether there was any configuration that would return the lowest magnitudes of error and uncertainty and hence influence the location of the proposed instrumentation. It is shown that great care needs to be taken when using an analysis of this kind together with temperature measurements having realistic and typical uncertainty values. This is because such an analysis is purely analytical, and any small fluctuations in the inputs, such as typical thermocouple uncertainties and noise, result in the process of an inverse analysis becoming unstable. This instability has two effects: (a) the returned values of heat flux have an inbuilt bias error and (b) the magnitudes of uncertainty can exceed>100 per cent.
Newtonian mechanics in scale of minutia
Authors: Teodorescu M , Rahnejat H 
Published: December 2008

This article commemorates Newton's contributions to mechanics in small scale. In particular, it deals with Newtonian slow viscous action of fluids in narrow conjunctions leading to hydrodynamics. It is shown that the Newtonian continuum relies on some bulk properties of fluids as opposed to their molecular interactions. When the latter and surface energy effects become dominant, the interaction potentials deviate from the Newtonian continuum. A plethora of largely empirically based force laws are used to describe conjunctional behaviours in nanoscale, usually lightly loaded. Some of these force laws are described, and their applicability to nanoconjunctions of very small devices and some biological systems is noted. In general, a thorough understanding of all the involved kinetics is required. Representative problems in soft nanoscale contacts in normal (humid) atmosphere are highlighted in the article. It is shown that contact load/adhesion depends on several key parameters including surface roughness, surface free energy, atmospheric moisture, and normal approach velocity.
The teacher's role in promoting collaborative dialogue in the classroom
Authors: Webb Noreen M. 
Published: December 2008

BackgroundResearch on student‐led small‐group learning in schools going back nearly four decades has documented many types of student participation that promote learning. Less is known about how the teacher can foster effective groupwork behaviours.AimsThis paper reviews research that explores the role of the teacher in promoting learning in small groups. The focus is on how students can learn from their peers during small‐group work, how teachers can prepare students for collaborative group work, and the role of teacher discourse and classroom norms in small‐group dialogue.MethodStudies selected for review focused on student‐led small‐group contexts for learning in which students were expected to collaborate, reported data from systematic observations of group work, and linked observational data to teacher practices and student learning outcomes.Results and conclusionsThis review uncovered multiple dimensions of the teacher's role in fostering beneficial group dialogue, including preparing students for collaborative work, forming groups, structuring the group‐work task, and influencing student interaction through teachers' discourse with small groups and with the class. Common threads through the research are the importance of students explaining their thinking, and teacher strategies and practices that may promote student elaboration of ideas.
Understanding attributional biases, emotions and self‐esteem in poor me paranoia: Findings from an early psychosis sample
Authors: Fornells‐Ambrojo M. , Garety P. A. 
Published: December 2008

ObjectivesTrower and Chadwick's (1995) theory of two types of paranoia (‘poor me’ and ‘bad me’) provides a framework for understanding the seemingly contradictory evidence on persecutory delusions. Paranoia has been argued to defend against low self‐esteem, but people with persecutory delusions report high levels of emotional distress and, in some instances, low self‐worth. The current study investigates attributions and emotions in a sample of people with early psychosis who have persecutory delusions. ‘Poor me’ paranoia has been found to be more frequent than ‘bad me’ paranoia in the early stages of psychosis. Anger and a tendency to blame other people are hypothesized to characterize ‘poor me’ paranoia.Design and methodsThe study had a cross‐sectional design. Twenty individuals with early psychosis, 21 clinical controls with depression and 32 healthy volunteers completed a thorough assessment of emotions and attributions.ResultsThe ‘poor me’ paranoia group showed higher levels of anger, anxiety and depression than the non‐clinical control group. Self‐esteem and guilt were however preserved. A tendency to blame others but not themselves was characteristic of the ‘poor me’ paranoia group whereas people in the clinical control group tended to self‐blame for failures. Anger, but not self‐esteem, was associated with an attributional bias characterized by blaming other people instead of oneself.ConclusionsIn conclusion, anger, a previously overlooked emotion in the study of persecutory delusions, warrants further attention. The other‐directed nature of this emotion highlights the potential role of interpersonal schemas in understanding paranoia.