bluuebunny/crossref_metadata_2025_split huggingface dataset:
The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts
Authors:   Experts in Chronic Myeloid Leukemia
Published: April 2013

Abstract
As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.
Childhood respiratory cohort studies: do they generate useful outcomes?
Authors: Turner S. 
Published: April 2013

Educational aimsTo describe the strengths and limitations of cohort studies.To give insight into the likely magnitude of effect of exposures on asthma causation.To summarise the relative weight of predictors of asthma prognosis.To describe results from cohort studies where interventions were made.SummaryCohort studies give insight into the evolution of respiratory disease over time and provide a low level of evidence for causation. The initial pioneering cohort studies in which symptoms and/or exposures were captured in early life and related to respiratory outcome in later life are now part of a large family which is diverse in age and exposures; however, asthma remains a fairly constant outcome.This article aims to first describe the strengths and weaknesses of the various asthma cohort studies. Thereafter, the article aims to describe the insight that cohort studies have given into asthma causation, with a focus on relative magnitude of effect, and also to describe the relative weight of factors identified in cohort studies as predictors of persisting asthma symptoms. It is clear that many factors are implicated in asthma causation; in isolation, each exerts a rather modest positive of negative effect on causation, but are likely to be acting in combination and modifying each other's relative risk. There is no single “good” predictor of asthma outcome, but the coexistence of parental asthma/atopy in a child with at least three episodes of wheeze by their third birthday indicates a high relative risk for asthma at 11–13 years of age. There remains no cure for asthma and the next step needs to apply what cohort studies have taught us to intervention studies where several exposures are modified in at risk individuals during the first year of life.
Measurement of exhaled breath temperature in science and clinical practice
Authors: Popov T.A. , Kralimarkova T.Z. , Dimitrov V.D. 
Published: April 2013

Educational aimsTo review the link between inflammation and increased vascularity and blood flow of the airways, and exhaled breath temperature.To position exhaled breath temperature (EBT) as a physiological characteristic differing from core temperature measured at other body sites.To review the existing experience about measuring EBT in different disease states of the respiratory system.To emphasise the influence of airway remodeling/destruction in modulating EBT.SummaryEvaluation of the exhaled breath temperature (EBT) has been suggested as a new method to detect and monitor pathological processes in the respiratory system. The putative mechanism of this approach is based upon changes in the blood flow in the conducting airways that are characteristic of different disease states, which influence the temperature of the exhaled gases. The first attempts to prove this concept were made in conjunction with measurement of exhaled nitric oxide fraction (FeNO) about a decade ago. They made use of an open-circuit, single-breath method in a closed indoor environment, and demonstrated associations between EBT on the one hand, and bronchial blood flow,FeNOand sputum cellular content on the other.These findings have been further extended to practical applicability with the introduction of multiple-breath, portable hand-held devices. Measurement of EBT using these is less dependent on the ambient environment and easier to perform. Studies have been conducted to explore the relationship between EBT and different physiological characteristics, and to assess possible confounding influences in the process of measurement. The value of the method has been explored in the diagnosis and monitoring of asthma, chronic obstructive pulmonary disease and other respiratory diseases. While initially, emphasis focused on airway inflammation as the primary process to be captured by this method, it was subsequently realised that destructive and other remodelling processes reducing the integral contact surface of the conducting airways and/or damaging their vasculature would also affect the end result by shifting EBT downwards. As obstructive airway disease is, in most cases, a combination of airway inflammation and remodelling/destruction, EBT should be viewed as an individual characteristic indicating fluctuating changes in the balance of these processes. Hence, an important potential application of the method is in monitoring airway diseases.EBT measurement has emerged as an attractive noninvasive new approach in respiratory and, possibly, other diseases. Systematic research will determine its place in clinical practice.
S-iteration process for quasi-contractive mappings
Authors: Kumar Vivek , Latif Abdul , Rafiq Arif , Hussain Nawab 
Published: April 2013

Abstract
In this note, we show that the S-iteration process due to Sahu and Petrusel (Nonlinear Anal. TMA 74(17):6012-6023, 2011) is faster than the Picard, Mann, Ishikawa and Noor iteration processes for Zamfirescu operators. Also, using computer programs in

C
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, we present some examples to compare the convergence rate of iterative processes due to Picard, Mann, Ishikawa, Noor, Agarwal et al. and Sahu and Petrusel.
Transcriptional regulation of flavonoid biosynthesis in nectarine (Prunus persica) by a set of R2R3 MYB transcription factors
Authors: Ravaglia Daniela , Espley Richard V , Henry-Kirk Rebecca A , Andreotti Carlo , Ziosi Vanina , Hellens Roger P , Costa Guglielmo , Allan Andrew C 
Published: April 2013

Abstract

Background
Flavonoids such as anthocyanins, flavonols and proanthocyanidins, play a central role in fruit colour, flavour and health attributes. In peach and nectarine (Prunus persica) these compounds vary during fruit growth and ripening. Flavonoids are produced by a well studied pathway which is transcriptionally regulated by members of the MYB and bHLH transcription factor families. We have isolated nectarine flavonoid regulating genes and examined their expression patterns, which suggests a critical role in the regulation of flavonoid biosynthesis.

Results
In nectarine, expression of the genes encoding enzymes of the flavonoid pathway correlated with the concentration of proanthocyanidins, which strongly increases at mid-development. In contrast, the only gene which showed a similar pattern to anthocyanin concentration was UDP-glucose-flavonoid-3-O-glucosyltransferase (UFGT), which was high at the beginning and end of fruit growth, remaining low during the other developmental stages. Expression of flavonol synthase (FLS1) correlated with flavonol levels, both temporally and in a tissue specific manner. The pattern of UFGT gene expression may be explained by the involvement of different transcription factors, which up-regulate flavonoid biosynthesis (MYB10, MYB123, and bHLH3), or repress (MYB111 and MYB16) the transcription of the biosynthetic genes. The expression of a potential proanthocyanidin-regulating transcription factor, MYBPA1, corresponded with proanthocyanidin levels. Functional assays of these transcription factors were used to test the specificity for flavonoid regulation.

Conclusions
MYB10 positively regulates the promoters of UFGT and dihydroflavonol 4-reductase (DFR) but not leucoanthocyanidin reductase (LAR). In contrast, MYBPA1 trans-activates the promoters of DFR and LAR, but not UFGT. This suggests exclusive roles of anthocyanin regulation by MYB10 and proanthocyanidin regulation by MYBPA1. Further, these transcription factors appeared to be responsive to both developmental and environmental stimuli.
Social determinants of health and seasonal influenza vaccination in adults ≥65 years: a systematic review of qualitative and quantitative data
Authors: Nagata Jason M , Hernández-Ramos Isabel , Kurup Anand Sivasankara , Albrecht Daniel , Vivas-Torrealba Claudia , Franco-Paredes Carlos 
Published: April 2013

Abstract

Background
Vaccination against influenza is considered the most important public health intervention to prevent unnecessary hospitalizations and premature deaths related to influenza in the elderly, though there are significant inequities among global influenza vaccine resources, capacities, and policies. The objective of this study was to assess the social determinants of health preventing adults ≥65 years old from accessing and accepting seasonal influenza vaccination.

Methods
A systematic search was performed in January 2011 using MEDLINE, ISI – Web of Science, PsycINFO, and CINAHL (1980–2011). Reference lists of articles were also examined. Selection criteria included qualitative and quantitative studies written in English that examined social determinants of and barriers against seasonal influenza vaccination among adults≥65 years. Two authors performed the quality assessment and data extraction. Thematic analysis was the main approach for joint synthesis, using identification and juxtaposition of themes associated with vaccination.

Results
Overall, 58 studies were analyzed. Structural social determinants such as age, gender, marital status, education, ethnicity, socio-economic status, social and cultural values, as well as intermediary determinants including housing-place of residence, behavioral beliefs, social influences, previous vaccine experiences, perceived susceptibility, sources of information, and perceived health status influenced seasonal influenza vaccination. Healthcare system related factors including accessibility, affordability, knowledge and attitudes about vaccination, and physicians’ advice were also important determinants of vaccination.

Conclusions
Our results demonstrate that the ability of adults ≥65 years to receive seasonal influenza vaccine is influenced by structural, intermediate, and healthcare-related social determinants which have an impact at the health system, provider, and individual levels.
BMI mediates the association between low educational level and higher blood pressure during pregnancy in Japan
Authors: Jwa Seung Chik , Fujiwara Takeo , Hata Akira , Arata Naoko , Sago Haruhiko , Ohya Yukihiro 
Published: April 2013

Abstract

Background
Research investigating the association between socioeconomic status (SES) and blood pressure (BP) during pregnancy is limited and its underlying pathway is unknown. The aim of this study was to investigate the mediators of the association between educational level as an indicator of the SES and BP in early and mid-pregnancy among Japanese women.

Methods
Nine hundred and twenty-three pregnant women in whom BP was measured before 16 weeks and at 20 weeks of gestation were enrolled in this study. Maternal educational levels were categorized into three groups: high (university or higher), mid (junior college), and low (junior high school, high school, or vocational training school).

Results
The low educational group had higher systolic (low vs. high, difference = 2.39 mmHg, 95% confidence interval [CI]: 0.59 to 4.19) and diastolic BP levels (low vs. high, difference = 0.74 mmHg, 95% CI: –0.52 to 1.99) in early pregnancy. However, the same associations were not found after adjustment for pre-pregnancy body mass index (BMI). BP reduction was observed in mid-pregnancy in all three educational groups and there was no association between educational level and pregnancy-induced hypertension.

Conclusion
In Japanese women, the low educational group showed higher BP during pregnancy than the mid or high educational groups. Pre-pregnancy BMI mediates the association between educational level and BP.
A prospective comparative study to assess the contribution of radioisotope tracer method to dye-only method in the detection of sentinel lymph node in breast cancer
Authors: Eser Mehmet , Kement Metin , Kaptanoglu Levent , Gecer Melin , Abamor Evrim , Tutal Firat , Balin Salim , Kurt Necmi , Uzun Huseyin 
Published: April 2013

Abstract

Background
Metastasis in the axillary lymph nodes is the most important known prognostic factor for breast cancer. We aimed to investigate the contribution of the radioisotope tracer method to the dye-only method by performing sentinel lymph node biopsy on the same patient group during a single surgical session.

Methods
Forty-two patients who underwent operations in our clinic from February 2010 to October 2011 and with masses of <5 cm and clinically and radiologicallly negative axilla (T1-2 N0) were prospectively included in this study. After paraffin examination results were obtained, the numbers and metastatic states of the lymph nodes that were unidentifiable during surgery (although they were stained) but were detected by a gamma probe, lymph nodes that were only stained, lymph nodes that were only radioactive (hot), and lymph nodes that were both stained and radioactive (stained-hot) were determined in all patients. In patients who underwent axillary lymph node dissection, the total numbers of lymph nodes removed and their metastatic states were determined separately.

Results
At least one blue-stained sentinel lymph node was identified in all patients during the blue-stained lymph node detection stage. The average number of sentinel nodes removed at this stage was 2.1 ± 1.1. In the second surgical stage (the stage in which nodes with axillary counts were investigated with the gamma probe) in these 41 patients, at least one additional hot node was removed, or at least one of the nodes that was removed because it was blue was also hot. In addition to the lymph nodes removed in the dye stage, 34 hot lymph nodes were excised from 21 patients. Overall, the average number of hot lymph nodes removed was 2.9 ± 1.5. In all patients, subsequent frozen sections and histopathological examinations were 100% concordant with the sentinel lymph nodes that were removed; the stained sentinel lymph nodes that were removed first did not affect the decision to perform axillary dissection.

Conclusion
The results of our study indicate that performing sentinel lymph node biopsy with dye only is sufficient and as effective as the combined method.
Structural and functional studies of S-adenosyl-L-methionine binding proteins: a ligand-centric approach
Authors: Gana Rajaram , Rao Shruti , Huang Hongzhan , Wu Cathy , Vasudevan Sona 
Published: April 2013

Abstract

Background
The post-genomic era poses several challenges. The biggest is the identification of biochemical function for protein sequences and structures resulting from genomic initiatives. Most sequences lack a characterized function and are annotated as hypothetical or uncharacterized. While homology-based methods are useful, and work well for sequences with sequence identities above 50%, they fail for sequences in the twilight zone (<30%) of sequence identity. For cases where sequence methods fail, structural approaches are often used, based on the premise that structure preserves function for longer evolutionary time-frames than sequence alone. It is now clear that no single method can be used successfully for functional inference. Given the growing need for functional assignments, we describe here a systematic new approach, designated ligand-centric, which is primarily based on analysis of ligand-bound/unbound structures in the PDB. Results of applying our approach to S-adenosyl-L-methionine (SAM) binding proteins are presented.

Results
Our analysis included 1,224 structures that belong to 172 unique families of the Protein Information Resource Superfamily system. Our ligand-centric approach was divided into four levels: residue, protein/domain, ligand, and family levels. The residue level included the identification of conserved binding site residues based on structure-guided sequence alignments of representative members of a family, and the identification of conserved structural motifs. The protein/domain level included structural classification of proteins, Pfam domains, domain architectures, and protein topologies. The ligand level included ligand conformations, ribose sugar puckering, and the identification of conserved ligand-atom interactions. The family level included phylogenetic analysis.

Conclusion
We found that SAM bound to a total of 18 different fold types (I-XVIII). We identified 4 new fold types and 11 additional topological arrangements of strands within the well-studied Rossmann fold Methyltransferases (MTases). This extends the existing structural classification of SAM binding proteins. A striking correlation between fold type and the conformation of the bound SAM (classified as types) was found across the 18 fold types. Several site-specific rules were created for the assignment of functional residues to families and proteins that do not have a bound SAM or a solved structure.
Genetic connectivity between land and sea: the case of the beachflea Orchestia montagui (Crustacea, Amphipoda, Talitridae) in the Mediterranean Sea
Authors: Pavesi Laura , Tiedemann Ralph , De Matthaeis Elvira , Ketmaier Valerio 
Published: April 2013

Abstract

Introduction
We examined patterns of genetic divergence in 26 Mediterranean populations of the semi-terrestrial beachflea Orchestia montagui using mitochondrial (cytochrome oxidase subunit I), microsatellite (eight loci) and allozymic data. The species typically forms large populations within heaps of dead seagrass leaves stranded on beaches at the waterfront. We adopted a hierarchical geographic sampling to unravel population structure in a species living at the sea-land transition and, hence, likely subjected to dramatically contrasting forces.

Results
Mitochondrial DNA showed historical phylogeographic breaks among Adriatic, Ionian and the remaining basins (Tyrrhenian, Western and Eastern Mediterranean Sea) likely caused by the geological and climatic changes of the Pleistocene. Microsatellites (and to a lesser extent allozymes) detected a further subdivision between and within the Western Mediterranean and the Tyrrhenian Sea due to present-day processes. A pattern of isolation by distance was not detected in any of the analyzed data set.

Conclusions
We conclude that the population structure of O. montagui is the result of the interplay of two contrasting forces that act on the species population genetic structure. On one hand, the species semi-terrestrial life style would tend to determine the onset of local differences. On the other hand, these differences are partially counter-balanced by passive movements of migrants via rafting on heaps of dead seagrass leaves across sites by sea surface currents. Approximate Bayesian Computations support dispersal at sea as prevalent over terrestrial regionalism.
Use of immuno-dominant epitope derived from genotype 4 as a diagnostic reagent for detecting the antibodies against Hepatitis E Virus
Authors: Bing-shui Xiu , Xiao-yan Feng , Jing He , Kun Chen , Jing Liu , Zhen-hua Dai , Xi-Qin Yang , Guo-hua Wang , You-chun Wang , He-qiu Zhang , Xiao-guo Song , Cui-xia Zhu 
Published: April 2013

Abstract

Background
Despite the genotype 4 has become the dominant cause of hepatitis E disease in China, none antigen derived from genotype 4 of hepatitis E virus (HEV) was used in current commercial anti-HEV immunoassay, and the serological reactivity of antigen derive from genotype 4 is not well-charactered.

Methods
We expressed and purified the 4 main immuno-dominant epitopes derived from genotype 1 and 4 including ORF2 (410-621aa) of genotype 4, ORF3 (47-114aa) of genotype 4, ORF2 (396-606aa) of genotype 1 and ORF3 (56-123aa) of genotype 4.

Results
The ORF2 of genotype 4 displayed good diagnostics performance according to ROC analysis using in-house panel, and the immunoassays based the ORF2 of genotype 4 was then developed to detect the anti-HEV IgG antibodies and evaluated further in 530 anti-HEV IgG positive specimens and 380 negative specimens. The sensitivity and the specificity is 98.1% (520/530) and 94.7% (360/380) for immunoassay based on ORF2 of genotype 4, 96.6% (512/530) and 92.6% (352/380) for commercial immunoassay based on genotype 1. It is noted that all of the positive samples will be detected by combing two assays together. The anti-HEV immunoassays based on genotype 4 are in accordance with Chinese anti-HEV national standard,and show an good agreement of 95.8% with commercial assay (kappa=0.913, P=0.014).

Conclusions
The immunoassay based on ORF2G4 displays good performance, and combining assay based on genotype 1 together with genotype 4 will benefit the HEV diagnosis in large scale samples.
Concurrent bevacizumab and temozolomide alter the patterns of failure in radiation treatment of glioblastoma multiforme
Authors: Shields Lisa BE , Kadner Robert , Vitaz Todd W , Spalding Aaron C 
Published: April 2013

Abstract

Background
We investigated the pattern of failure in glioblastoma multiforma (GBM) patients treated with concurrent radiation, bevacizumab (BEV), and temozolomide (TMZ). Previous studies demonstrated a predominantly in-field pattern of failure for GBM patients not treated with concurrent BEV.

Methods
We reviewed the treatment of 23 patients with GBM who received 30 fractions of simultaneous integrated boost IMRT. PTV60 received 2 Gy daily to the tumor bed or residual tumor while PTV54 received 1.8 Gy daily to the surrounding edema. Concurrent TMZ (75 mg/m^2) daily and BEV (10 mg/kg every 2 weeks) were given during radiation therapy. One month after RT completion, adjuvant TMZ (150 mg/m^2 × 5 days) and BEV were delivered monthly until progression or 12 months total.

Results
With a median follow-up of 12 months, the median disease-free and overall survival were not reached. Four patients discontinued therapy due to toxicity for the following reasons: bone marrow suppression (2), craniotomy wound infection (1), and pulmonary embolus (1). Five patients had grade 2 or 3 hypertension managed by oral medications. Of the 12 patients with tumor recurrence, 7 suffered distant failure with either subependymal (5/12; 41%) or deep white matter (2/12; 17%) spread detected on T2 FLAIR sequences. Five of 12 patients (41%) with a recurrence demonstrated evidence of GAD enhancement. The patterns of failure did not correlate with extent of resection or number of adjuvant cycles.

Conclusions
Treatment of GBM patients with concurrent radiation, BEV, and TMZ was well tolerated in the current study. The majority of patients experienced an out-of-field pattern of failure with radiation, BEV, and TMZ which has not been previously reported. Further investigation is warranted to determine whether BEV alters the underlying tumor biology to improve survival. These data may indicate that the currently used clinical target volume thought to represent microscopic disease for radiation may not be appropriate in combination with TMZ and BEV.