bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel
Authors: Creutzig Ursula , van den Heuvel-Eibrink Marry M. , Gibson Brenda , Dworzak Michael N. , Adachi Souichi , de Bont Eveline , Harbott Jochen , Hasle Henrik , Johnston Donna , Kinoshita Akitoshi , Lehrnbecher Thomas , Leverger Guy , Mejstrikova Ester , Meshinchi Soheil , Pession Andrea , Raimondi Susana C. , Sung Lillian , Stary Jan , Zwaan Christian M. , Kaspers Gertjan J. L. , Reinhardt Dirk 
Published: August 2012

AbstractDespite major improvements in outcome over the past decades, acute myeloid leukemia (AML) remains a life-threatening malignancy in children, with current survival rates of ∼ 70%. State-of-the-art recommendations in adult AML have recently been published in this journal by Döhner et al. The primary goal of an international expert panel of the International BFM Study Group AML Committee was to set standards for the management, diagnosis, response assessment, and treatment in childhood AML. This paper aims to discuss differences between childhood and adult AML, and to highlight recommendations that are specific to children. The particular relevance of new diagnostic and prognostic molecular markers in pediatric AML is presented. The general management of pediatric AML, the management of specific pediatric AML cohorts (such as infants) or subtypes of the disease occurring in children (such as Down syndrome related AML), as well as new therapeutic approaches, and the role of supportive care are discussed.
High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses
Authors: Haroche Julien , Charlotte Frédéric , Arnaud Laurent , von Deimling Andreas , Hélias-Rodzewicz Zofia , Hervier Baptiste , Cohen-Aubart Fleur , Launay David , Lesot Annette , Mokhtari Karima , Canioni Danielle , Galmiche Louise , Rose Christian , Schmalzing Marc , Croockewit Sandra , Kambouchner Marianne , Copin Marie-Christine , Fraitag Sylvie , Sahm Felix , Brousse Nicole , Amoura Zahir , Donadieu Jean , Emile Jean-François 
Published: August 2012

Abstract
Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF mutations have been observed in Langerhans cell histiocytosis (LCH). We investigated the frequency of BRAF mutations in several types of histiocytoses. Histology from 127 patients with histiocytoses were reviewed. Detection of BRAFV600 mutations was performed by pyrosequencing of DNA extracted from paraffin embedded samples. Diagnoses of Erdheim-Chester disease (ECD), LCH, Rosai-Dorfman disease, juvenile xanthogranuloma, histiocytic sarcoma, xanthoma disseminatum, interdigitating dendritic cell sarcoma, and necrobiotic xanthogranuloma were performed in 46, 39, 23, 12, 3, 2, 1, and 1 patients, respectively. BRAF status was obtained in 93 cases. BRAFV600E mutations were detected in 13 of 24 (54%) ECD, 11 of 29 (38%) LCH, and none of the other histiocytoses. Four patients with ECD died of disease. The high frequency of BRAFV600E in LCH and ECD suggests a common origin of these diseases. Treatment with vemurafenib should be investigated in patients with malignant BRAFV600E histiocytosis.
sRNAdb: A small non-coding RNA database for gram-positive bacteria
Authors: Pischimarov Jordan , Kuenne Carsten , Billion André , Hemberger Jüergen , Cemič Franz , Chakraborty Trinad , Hain Torsten 
Published: August 2012

Abstract

Background
The class of small non-coding RNA molecules (sRNA) regulates gene expression by different mechanisms and enables bacteria to mount a physiological response due to adaptation to the environment or infection. Over the last decades the number of sRNAs has been increasing rapidly. Several databases like Rfam or fRNAdb were extended to include sRNAs as a class of its own. Furthermore new specialized databases like sRNAMap (gram-negative bacteria only) and sRNATarBase (target prediction) were established. To the best of the authors’ knowledge no database focusing on sRNAs from gram-positive bacteria is publicly available so far.

Description
In order to understand sRNA’s functional and phylogenetic relationships we have developed sRNAdb and provide tools for data analysis and visualization. The data compiled in our database is assembled from experiments as well as from bioinformatics analyses. The software enables comparison and visualization of gene loci surrounding the sRNAs of interest. To accomplish this, we use a client–server based approach. Offline versions of the database including analyses and visualization tools can easily be installed locally on the user’s computer. This feature facilitates customized local addition of unpublished sRNA candidates and related information such as promoters or terminators using tab-delimited files.

Conclusion
sRNAdb allows a user-friendly and comprehensive comparative analysis of sRNAs from available sequenced gram-positive prokaryotic replicons. Offline versions including analysis and visualization tools facilitate complex user specific bioinformatics analyses.
Genetic changes during a laboratory adaptive evolution process that allowed fast growth in glucose to an Escherichia coli strain lacking the major glucose transport system
Authors: Aguilar César , Escalante Adelfo , Flores Noemí , de Anda Ramón , Riveros-McKay Fernando , Gosset Guillermo , Morett Enrique , Bolívar Francisco 
Published: August 2012

Abstract

Background

Escherichia coli strains lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system (PTS), which is the major bacterial component involved in glucose transport and its phosphorylation, accumulate high amounts of phosphoenolpyruvate that can be diverted to the synthesis of commercially relevant products. However, these strains grow slowly in glucose as sole carbon source due to its inefficient transport and metabolism. Strain PB12, with 400% increased growth rate, was isolated after a 120 hours adaptive laboratory evolution process for the selection of faster growing derivatives in glucose. Analysis of the genetic changes that occurred in the PB12 strain that lacks PTS will allow a better understanding of the basis of its growth adaptation and, therefore, in the design of improved metabolic engineering strategies for enhancing carbon diversion into the aromatic pathways.

Results
Whole genome analyses using two different sequencing methodologies: the Roche NimbleGen Inc. comparative genome sequencing technique, and high throughput sequencing with Illumina Inc. GAIIx, allowed the identification of the genetic changes that occurred in the PB12 strain. Both methods detected 23 non-synonymous and 22 synonymous point mutations. Several non-synonymous mutations mapped in regulatory genes (arcB, barA, rpoD, rna) and in other putative regulatory loci (yjjU, rssA and ypdA). In addition, a chromosomal deletion of 10,328 bp was detected that removed 12 genes, among them, the rppH, mutH and galR genes. Characterization of some of these mutated and deleted genes with their functions and possible functions, are presented.

Conclusions
The deletion of the contiguous rppH, mutH and galR genes that occurred simultaneously, is apparently the main reason for the faster growth of the evolved PB12 strain. In support of this interpretation is the fact that inactivation of the rppH gene in the parental PB11 strain substantially increased its growth rate, very likely by increasing glycolytic mRNA genes stability. Furthermore, galR inactivation allowed glucose transport by GalP into the cell. The deletion of mutH in an already stressed strain that lacks PTS is apparently responsible for the very high mutation rate observed.
Effects of patient factors on noninvasive liver stiffness measurement using acoustic radiation force impulse elastography in patients with chronic hepatitis C
Authors: Chen Sheng-Hung , Li Yu-Fen , Lai Hsueh-Chou , Kao Jung-Ta , Peng Cheng-Yuan , Chuang Po-Heng , Su Wen-Pang , Chiang I-Ping 
Published: August 2012

Abstract

Background
Previous research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology.

Methods
A cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM.

Results
To classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R2 = 0.661, adjusted R2 = 0.629), ActiTest A scores (R2 = 0.662, adjusted R2 = 0.636), and METAVIR activity (A) grades (R2 = 0.651, adjusted R2 = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM.

Conclusions
The degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.
Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study
Authors: Sjöwall Johanna , Ledel Anna , Ernerudh Jan , Ekerfelt Christina , Forsberg Pia 
Published: August 2012

AbstractBackgroundPersistent symptoms after treatment of neuroborreliosis (NB) are well-documented, although the causative mechanisms are mainly unknown. The effect of repeated antibiotic treatment has not been studied in detail. The aim of this study was to determine whether: (1) persistent symptoms improve with doxycycline treatment; (2) doxycycline has an influence on systemic cytokine responses, and; (3) improvement of symptoms could be due to doxycycline-mediated immunomodulation.Methods/Design15 NB patients with persistent symptoms ≥6 months post-treatment were double-blindly randomized to receive 200 mg of doxycycline or a placebo for three weeks. After a six-week wash-out period, a cross-over with a three-week course of a placebo or doxycycline was conducted. The primary outcome measures were improvement of persistent symptoms assessed by neurological examinations, a symptom severity score and estimation of the quality of life. The secondary outcome measure was changes in systemic cytokine responses.ResultsAll 15 patients finished the study. No doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events.DiscussionNo doxycycline-mediated improvement of post-treatment symptoms or quality of life was observed. Nor could any doxycycline-mediated changes in systemic cytokine responses be detected. The study was completed without any serious adverse events. To conclude, in this pilot study, doxycycline-treatment did not lead to any improvement of either the persistent symptoms or quality of life in post-NB patients. Accordingly, doxycycline does not seem to be the optimal treatment of diverse persistent symptoms post-NB. However, the results need to be confirmed in larger studies.Trial registrationNCT01205464 (clinicaltrials.gov)
High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among Indians
Authors: Rani Deepa Selvi , Nallari Pratibha , Priyamvada Singh , Narasimhan Calambur , Singh Lalji , Thangaraj Kumarasamy 
Published: August 2012

Abstract

Background
Troponin I (TNNI3) is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in hypertrophic cardiomyopathy patients (HCM). However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study.

Methods
We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls, inhabited in the same geographical region of southern India.

Results
Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E) mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85%) with a rare codon (GAA: 14%). Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T) exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing.

Conclusion
Our study has provided valuable information regarding the prevalence of TNNI3 mutations in Indian HCM patients and its risk assessment, these will help in genetic counseling and to adopt appropriate treatment strategies.
Study protocol: Brief intervention for medication overuse headache - A double-blinded cluster randomised parallel controlled trial in primary care
Authors: Kristoffersen Espen Saxhaug , Straand Jørund , Benth Jūratė Saltytė , Russell Michael Bjørn , Lundqvist Christofer 
Published: August 2012

Abstract

Background
Chronic headache (headache ≥ 15 days/month for at least 3 months) affects 2–5% of the general population. Medication overuse contributes to the problem. Medication-overuse headache (MOH) can be identified by using the Severity of Dependence Scale (SDS). A “brief intervention” scheme (BI) has previously been used for detoxification from drug and alcohol overuse in other settings. Short, unstructured, individualised simple information may also be enough to detoxify a large portion of those with MOH. We have adapted the structured (BI) scheme to be used for MOH in primary care.

Methods/Design
A double-blinded cluster randomised parallel controlled trial (RCT) of BI vs. business as usual. Intervention will be performed in primary care by GPs trained in BI. Patients with MOH will be identified through a simple screening questionnaire sent to patients on the GPs lists. The BI method involves an approach for identifying patients with high likelihood of MOH using simple questions about headache frequency and the SDS score. Feedback is given to the individual patient on his/her score and consequences this might have regarding the individual risk of medication overuse contributing to their headache. Finally, advice is given regarding measures to be taken, how the patient should proceed and the possible gains for the patient. The participating patients complete a headache diary and receive a clinical interview and neurological examination by a GP experienced in headache diagnostics three months after the intervention. Primary outcomes are number of headache days and number of medication days per month at 3 months. Secondary outcomes include proportions with 25 and 50% improvement at 3 months and maintenance of improvement and quality of life after 12 months.

Discussion
There is a need for evidence-based and cost-effective strategies for treatment of MOH but so far no consensus has been reached regarding an optimal medication withdrawal method. To our knowledge this is the first RCT of structured non-pharmacological MOH treatment in primary care. Results may hold the potential of offering an instrument for treating MOH patients in the general population by GPs.

Trial registration
ClinicalTrials.gov identifier: NCT01314768
Diagnostic and economic evaluation of new biomarkers for Alzheimer’s disease: the research protocol of a prospective cohort study
Authors: Handels Ron LH , Aalten Pauline , Wolfs Claire AG , OldeRikkert Marcel , Scheltens Philip , Visser Pieter Jelle , Joore Manuela A , Severens Johan L , Verhey Frans RJ 
Published: August 2012

AbstractBackgroundNew research criteria for the diagnosis of Alzheimer’s disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy of current clinical diagnostic work-up and emerging biomarkers in MRI, PET and CSF, 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.Methods/designIn a cohort design 241 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life, costs and emerging biomarkers are gathered.Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to a reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.A decision analytic model is built combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.DiscussionSeveral other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.Trial registrationNCT01450891
Relationship between blood lipid profiles and pancreatic islet β cell function in Chinese men and women with normal glucose tolerance: a cross-sectional study
Authors: Zheng Tianpeng , Gao Yun , Tian Haoming 
Published: August 2012

Abstract

Background
Dyslipidemia is present in people with diabetes as well as subjects with normal glucose tolerance (NGT). The purpose of this study was to investigate the relationship between lipid profiles and β cell function in Chinese individuals with NGT but without history of diabetes or prediabetes.

Methods
A total of 893 men and 1454 women aged 18–76 years living in Sichuan, China, who were not being treated with lipid-lowering drugs were enrolled in this study. Insulin sensitivity (IR) was evaluated using the homeostasis model assessment –IR (HOMA-IR), β-cell function was calculated by the following equation: ΔI30/ΔG30/ HOMA-IR (ΔI30/ΔG30: the ratio of incremental glucose and insulin 30 min after glucose intake). Multivariate linear regression analyses were performed to estimate the relationship between blood lipid and β cell function as standardized coefficients (β).

Results
β cell function decreased in men and women with increasing age. We found inverse relationships between β cell function and total cholesterol (TC) in men and women (β = −0.157 and −0.113, respectively, both p < 0.001), low-density lipoprotein–cholesterol (LDL-C; β = −0.130 and −0.068, respectively, both p < 0.001), TC/high-density lipoprotein–cholesterol (HDL-C) ratio (β = −0.084, p < 0.01 and −0.096, p < 0.001), and triglycerides (TG) (women only; β = −0.053, p < 0.05). However, β cell function was not associated with HDL-C in men or women (β = −0.034 and 0.000, respectively, both p > 0.05) or the TG/HDL-C ratio (β = −0.035 and −0.013, respectively, both p > 0.05). β cell function was significantly worse in males than in females in all age groups, except in subjects aged > 70 years.

Conclusions
Dyslipidemia is associated with dysfunction of pancreatic β cells in subjects with NGT and this is particularly evident in people with elevated TC and LDL-C levels, especially males.

Trial Registration Number
#TR-CCH-Chi CTR-CCH-00000361
Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors
Authors: Wang Cheng-Li , Lu Chiu-Ying , Pi Chia-Chen , Zhuang Yu-Jing , Chu Ching-Liang , Liu Wen-Hsiung , Chen Chun-Jen 
Published: August 2012

AbstractBackgroundThe fungus ofGanodermais a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture ofG. formosanumand shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2.ResultsPS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3), laminarin, or piceatannol (a spleen tyrosine kinase inhibitor), suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4). PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression.ConclusionsOur results indicate that the extracellular polysaccharides produced byG. formosanumstimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.