bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis
Authors: Makishima Hideki , Visconte Valeria , Sakaguchi Hirotoshi , Jankowska Anna M. , Abu Kar Sarah , Jerez Andres , Przychodzen Bartlomiej , Bupathi Manoj , Guinta Kathryn , Afable Manuel G. , Sekeres Mikkael A. , Padgett Richard A. , Tiu Ramon V. , Maciejewski Jaroslaw P. 
Published: February 2012

Abstract
Myelodysplastic syndromes (MDSs) are chronic and often progressive myeloid neoplasms associated with remarkable heterogeneity in the histomorphology and clinical course. Various somatic mutations are involved in the pathogenesis of MDS. Recently, mutations in a gene encoding a spliceosomal protein, SF3B1, were discovered in a distinct form of MDS with ring sideroblasts. Whole exome sequencing of 15 patients with myeloid neoplasms was performed, and somatic mutations in spliceosomal genes were identified. Sanger sequencing of 310 patients was performed to assess phenotype/genotype associations. To determine the functional effect of spliceosomal mutations, we evaluated pre-mRNA splicing profiles by RNA deep sequencing. We identified additional somatic mutations in spliceosomal genes, including SF3B1, U2AF1, and SRSF2. These mutations alter pre-mRNA splicing patterns. SF3B1 mutations are prevalent in low-risk MDS with ring sideroblasts, whereas U2AF1 and SRSF2 mutations are frequent in chronic myelomonocytic leukemia and advanced forms of MDS. SF3B1 mutations are associated with a favorable prognosis, whereas U2AF1 and SRSF2 mutations are predictive for shorter survival. Mutations affecting spliceosomal genes that result in defective splicing are a new leukemogenic pathway. Spliceosomal genes are probably tumor suppressors, and their mutations may constitute diagnostic biomarkers that could potentially serve as therapeutic targets.
Age- and gender-specific population attributable risks of metabolic disorders on all-cause and cardiovascular mortality in Taiwan
Authors: Wang Wuan-Szu , Wahlqvist Mark L , Hsu Chih-Cheng , Chang Hsing-Yi , Chang Wan-Chi , Chen Chu-Chih 
Published: February 2012

Abstract

Background
The extent of attributable risks of metabolic syndrome (MetS) and its components on mortality remains unclear, especially with respect to age and gender. We aimed to assess the age- and gender-specific population attributable risks (PARs) for cardiovascular disease (CVD)-related mortality and all-cause mortality for public health planning.

Methods
A total of 2,092 men and 2,197 women 30 years of age and older, who were included in the 2002 Taiwan Survey of Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), were linked to national death certificates acquired through December 31, 2009. Cox proportional hazard models were used to calculate adjusted hazard ratios and PARs for mortality, with a median follow-up of 7.7 years.

Results
The respective PAR percentages of MetS for all-cause and CVD-related mortality were 11.6 and 39.2 in men, respectively, and 18.6 and 44.4 in women, respectively. Central obesity had the highest PAR for CVD mortality in women (57.5%), whereas arterial hypertension had the highest PAR in men (57.5%). For all-cause mortality, younger men and post-menopausal women had higher PARs related to Mets and its components; for CVD mortality, post-menopausal women had higher overall PARs than their pre-menopausal counterparts.

Conclusions
MetS has a limited application to the PAR for all-cause mortality, especially in men; its PAR for CVD mortality is more evident. For CVD mortality, MetS components have higher PARs than MetS itself, especially hypertension in men and waist circumference in post-menopausal women. In addition, PARs for diabetes mellitus and low HDL-cholesterol may exceed 20%. We suggest differential control of risk factors in different subpopulation as a strategy to prevent CVD-related mortality.
Cocoa intake and arterial stiffness in subjects with cardiovascular risk factors
Authors: Recio-Rodríguez José Ignacio , Gómez-Marcos Manuel A , Patino-Alonso María C , Agudo-Conde Cristina , Rodríguez-Sánchez Emiliano , García-Ortiz Luis ,   Vaso-Risk group
Published: February 2012

Abstract

Background
To analyze the relationship of cocoa intake to central and peripheral blood pressure, arterial stiffness, and carotid intima-media thickness in subjects with some cardiovascular risk factor.

Findings
Design: A cross-sectional study of 351 subjects (mean age 54.76 years, 62.4% males). Measurements: Intake of cocoa and other foods using a food frequency questionnaire, central and peripheral (ambulatory and office) blood pressure, central and peripheral augmentation index, pulse wave velocity, ambulatory arterial stiffness index, carotid intima-media thickness, and ankle-brachial index.
Results: Higher pulse wave velocity and greater cardiovascular risk were found in non-cocoa consumers as compared to high consumers (p < 0.05). In a multivariate analysis, these differences disappeared after adjusting for age, gender, the presence of diabetes, systolic blood pressure and antihypertensive and lipid-lowering drug use. All other arterial stiffness measures (central and peripheral augmentation index, ambulatory arterial stiffness index, ankle-brachial index, and carotid intima-media thickness) showed no differences between the different consumption groups.

Conclusions
In subjects with some cardiovascular risk factors, cocoa consumption does not imply improvement in the arterial stiffness values.

Trial Registration
Clinical Trials.gov Identifier: NCT01325064.
An assessment of the construct validity of the ASCOT measure of social care-related quality of life with older people
Authors: Malley Juliette N , Towers Ann-Marie , Netten Ann P , Brazier John E , Forder Julien E , Flynn Terry 
Published: February 2012

Abstract

Background
The adult social care outcomes toolkit (ASCOT) includes a preference-weighted measure of social care-related quality of life for use in economic evaluations. ASCOT has eight attributes: personal cleanliness and comfort, food and drink, control over daily life, personal safety, accommodation cleanliness and comfort, social participation and involvement, occupation and dignity. This paper aims to demonstrate the construct validity of the ASCOT attributes.

Methods
A survey of older people receiving publicly-funded home care services was conducted by face-to-face interview in several sites across England. Additional data on variables hypothesised to be related and unrelated to each of the attributes were also collected. Relationships between these variables and the attributes were analysed through chi-squared tests and analysis of variance, as appropriate, to test the construct validity of each attribute.

Results
301 people were interviewed and approximately 10% of responses were given by a proxy respondent. Results suggest that each attribute captured the extent to which respondents exercised choice in how their outcomes were met. There was also evidence for the validity of the control over daily life, occupation, personal cleanliness and comfort, personal safety, accommodation cleanliness and comfort, and social participation and involvement attributes. There was less evidence regarding the validity of the food and drink and dignity attributes, but this may be a consequence of problems finding good data against which to validate these attributes, as well as problems with the distribution of the food and drink item.

Conclusions
This study provides some evidence for the construct validity of the ASCOT attributes and therefore support for ASCOT's use in economic evaluation. It also demonstrated the feasibility of its use among older people, although the need for proxy respondents in some situations suggests that developing a version that is suitable for proxies would be a useful future direction for this work. Validation of the instrument on a sample of younger social care users would also be useful.
Nodal solutions of second-order two-point boundary value problems
Authors: Ma Ruyun , Yang Bianxia , Dai Guowei 
Published: February 2012

Abstract
We shall study the existence and multiplicity of nodal solutions of the nonlinear second-order two-point boundary value problems,

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The proof of our main results is based upon bifurcation techniques.

Mathematics Subject Classifications: 34B07; 34C10; 34C23.
Mitochondrial myopathy presenting as fibromyalgia: a case report
Authors: Abdullah Mishal , Vishwanath Sahana , Elbalkhi Amro , Ambrus Julian L 
Published: February 2012

Abstract

Introduction
To the best of our knowledge, we describe for the first time the case of a woman who met the diagnostic criteria for fibromyalgia, did not respond to therapy for that disorder, and was subsequently diagnosed by biochemical and genetic studies with a mitochondrial myopathy. Treatment of the mitochondrial myopathy resulted in resolution of symptoms. This case demonstrates that mitochondrial myopathy may present in an adult with a symptom complex consistent with fibromyalgia.

Case presentation
Our patient was a 41-year-old Caucasian woman with symptoms of fatigue, exercise intolerance, headache, and multiple trigger points. Treatment for fibromyalgia with a wide spectrum of medications including non-steroidal anti-inflammatory drugs, antidepressants, gabapentin and pregabalin had no impact on her symptoms. A six-minute walk study demonstrated an elevated lactic acid level (5 mmol/L; normal < 2 mmol/L). Biochemical and genetic studies from a muscle biopsy revealed a mitochondrial myopathy. Our patient was started on a compound of coenzyme Q10 (ubiquinone) 200 mg, creatine 1000 mg, carnitine 200 mg and folic acid 1 mg to be taken four times a day. She gradually showed significant improvement in her symptoms over a course of several months.

Conclusions
This case demonstrates that adults diagnosed with fibromyalgia may have their symptom complex related to an adult onset mitochondrial myopathy. This is an important finding since treatment of mitochondrial myopathy resulted in resolution of symptoms.
Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type 1 and type 2
Authors: Yang Xi , Wada Taizo , Imadome Ken-Ichi , Nishida Naonori , Mukai Takeo , Fujiwara Mitsuhiro , Kawashima Haruka , Kato Fumiyo , Fujiwara Shigeyoshi , Yachie Akihiro , Zhao Xiaodong , Miyawaki Toshio , Kanegane Hirokazu 
Published: February 2012

Abstract

Background
X-linked lymphoproliferative syndrome (XLP) is a rare inherited immunodeficiency by an extreme vulnerability to Epstein-Barr virus (EBV) infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP are now divided into type 1 (XLP-1) and type 2 (XLP-2), which are caused by mutations of SH2D1A/SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) genes, respectively. The diagnosis of XLP in individuals with EBV-associated HLH (EBV-HLH) is generally difficult because they show basically similar symptoms to sporadic EBV-HLH. Although EBV-infected cells in sporadic EBV-HLH are known to be mainly in CD8+ T cells, the cell-type of EBV-infected cells in EBV-HLH seen in XLP patients remains undetermined.

Methods
EBV-infected cells in two patients (XLP-1 and XLP-2) presenting EBV-HLH were evaluated by in EBER-1 in situ hybridization or quantitative PCR methods.

Results
Both XLP patients showed that the dominant population of EBV-infected cells was CD19+ B cells, whereas EBV-infected CD8+ T cells were very few.

Conclusions
In XLP-related EBV-HLH, EBV-infected cells appear to be predominantly B cells. B cell directed therapy such as rituximab may be a valuable option in the treatment of EBV-HLH in XLP patients.
Brief eclectic psychotherapy v. eye movement desensitisation and reprocessing therapy for post-traumatic stress disorder: randomised controlled trial
Authors: Nijdam Mirjam J. , Gersons Berthold P. R. , Reitsma Johannes B. , de Jongh Ad , Olff Miranda 
Published: February 2012

BackgroundTrauma-focused cognitive–behavioural therapy (CBT) and eye movement desensitisation and reprocessing therapy (EMDR) are efficacious treatments for post-traumatic stress disorder (PTSD), but few studies have directly compared them using well-powered designs and few have investigated response patterns.AimsTo compare the efficacy and response pattern of a trauma-focused CBT modality, brief eclectic psychotherapy for PTSD, with EMDR (trial registration: ISRCTN64872147).MethodOut-patients with PTSD were randomly assigned to brief eclectic psychotherapy (n = 70) or EMDR (n = 70) and assessed at all sessions on self-reported PTSD (Impact of Event Scale – Revised). Other outcomes were clinician-rated PTSD, anxiety and depression.ResultsBoth treatments were equally effective in reducing PTSD symptom severity, but the response pattern indicated that EMDR led to a significantly sharper decline in PTSD symptoms than brief eclectic psychotherapy, with similar drop-out rates (EMDR: n = 20 (29%), brief eclectic psychotherapy: n = 25 (36%)). Other outcome measures confirmed this pattern of results.ConclusionsAlthough both treatments are effective, EMDR results in a faster recovery compared with the more gradual improvement with brief eclectic psychotherapy.
Prenatal exposure to tobacco and future nicotine dependence: population-based cohort study
Authors: Rydell Mina , Cnattingius Sven , Granath Fredrik , Magnusson Cecilia , Galanti Maria Rosaria 
Published: February 2012

BackgroundMaternal smoking during pregnancy may increase the risk of nicotine dependence, especially in girls, but data are conflicting and confounding by other familial factors cannot be ruled out.AimsTo clarify the relationship between prenatal tobacco exposure and adolescent tobacco uptake and dependence in boys and girls respectively, while taking confounding factors into close consideration.MethodWe conducted a prospective longitudinal study, comprising 3020 Swedish youths followed from 11 to 18 years of age. Exposure and outcome information was elicited via self-administered parental and repeated youth questionnaires. Hazard ratios (HRs), odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated as measures of associations.ResultsGirls prenatally exposed to maternal tobacco use had a two-to threefold increased odds of experiencing a high number of withdrawal symptoms (OR = 2.83, 95% CI 1.68–4.87), craving for tobacco (OR = 2.04, 95% CI 1.28–3.32) and heavy tobacco use (five or more cigarettes orsnusdips per day) (OR = 1.93, 95% CI 1.30–2.86). These associations were weaker among boys, and did not reach formal statistical significance. Associations between prenatal tobacco exposure and onset of regular tobacco use in both genders appeared to be mostly explained by parents' social position and postnatal smoking behaviour.ConclusionsPrenatal exposure to tobacco is linked to an increased risk of nicotine dependence among adolescent girls.
Research Resource: The Pdx1 Cistrome of Pancreatic Islets
Authors: Khoo Cynthia , Yang Juxiang , Weinrott Samuel A. , Kaestner Klaus H. , Naji Ali , Schug Jonathan , Stoffers Doris A. 
Published: February 2012

AbstractThe homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mutations in Pdx1 cause early and late onset forms of diabetes in humans. Despite these central roles in development and adult β-cell function, we have only rudimentary knowledge of the transcriptome targets of Pdx1 that mediate these phenotypes. Therefore, we performed global location analysis of Pdx1 occupancy in pancreatic islets. We used evolutionary conservation of target genes to identify the most relevant Pdx1 targets by performing chromatin immunoprecipitation sequencing on both human and mouse islets. Remarkably, the conserved target set is highly enriched for genes annotated to function in endocrine system and metabolic disorders, various signaling pathways, and cell survival, providing a molecular explanation for many of the phenotypes resulting from Pdx1 deficiency.
An Examination of the Indentation Size Effect and Bi-Linear Behavior of FCC Metals
Authors: Stegall D.E. , Crawford B. , Elmustafa A.A. 
Published: February 2012

AbstractWe investigated pure FCC metals including Aluminum, Nickel, Silver, and 70/30 Copper Zinc (alpha-brass) alloy for the indentation size effect (ISE) and the bilinear behavior using a single Berkovich indenter tip in a single test machine. The results were consistent with those reported by Elmustafa and Stone, 2003 of the ISE and the bilinear behavior using two separate indenter tips (Berkovich and Vickers) from two separate machines. This behavior is mechanistic in nature and is observed regardless of the type of the self similar indenter tip employed. Furthermore, the research presented in this paper would seem to also validate the conclusions that Elmustafa et al (2004) articulate that the Strain Gradient Plasticity collapses at small scales and that the bilinear behavior of these FCC metals is attributed to the presence of long range shear stresses induced by geometrically necessary dislocations. Also, we observed what has been defined as a “tapping” issue for materials with high E/H ratios when using the CSM. The CSM protocol results in erroneous hardness results at very shallow depths for high E/H ratio soft metals due to the so called “tapping” of the stylus as articulated by Pharr et al. (2009). This method should only be used as a secondary technique to the load control protocol when examining the ISE effect.
Cyclooxygenase‐2 Expression in Gingival Biopsies From Periodontal Patients Is Correlated With Connective Tissue Loss
Authors: Mesa Francisco , Aguilar Mariano , Galindo‐Moreno Pablo , Bravo Manuel , O'Valle Francisco 
Published: February 2012

Background: The objective of this study is to compare cyclooxygenase‐2 (COX‐2) protein expression in gingival biopsies from patients with chronic periodontitis (CP), patients with gingivitis (GV), and individuals with no periodontal disease (control group) and to establish its relationship with clinical variables and connective tissue loss in the lamina propria.Methods: A cross‐sectional and analytic study was conducted in 108 gingival biopsies from 52 patients with CP, 39 with GV, and 17 controls. All biopsies were processed for conventional histopathologic study, immunohistochemical determination of COX‐2 protein expression, and automatic quantification of connective tissue by image analysis.Results: The protein expression of COX‐2, mainly produced by plasma cells and monocytes, was significantly related to the presence of periodontal disease, bleeding index, intensity of inflammatory infiltrate, and loss of connective tissue in the lamina propria of gingival biopsies (P <0.01, Spearman test). COX‐2 expression was also directly correlated with attachment loss (P <0.05, Spearman test).Conclusions: COX‐2 protein expression is higher in patients with GV and CP than in individuals without periodontal disease and is inversely correlated with the amount of connective tissue in the lamina propria as determined by image analysis. This finding suggests that COX‐2 participates in mechanisms and pathway signaling related to the destruction of fibrillar support structures of the periodontium.
Partial versus Productive Immunoglobulin Heavy Locus Rearrangements in Chronic Lymphocytic Leukemia: Implications for B-Cell Receptor Stereotypy
Authors: Tsakou Eugenia , Agathagelidis Andreas , Boudjoghra Myriam , Raff Thorsten , Dagklis Antonis , Chatzouli Maria , Smilevska Tatjana , Bourikas George , Merle-Beral Helene , Manioudaki-Kavallieratou Eleni , Anagnostopoulos Achilles , Brüggemann Monika , Davi Frederic , Stamatopoulos Kostas , Belessi Chrysoula 
Published: February 2012

AbstractThe frequent occurrence of stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences among unrelated cases with chronic lymphocytic leukemia (CLL) is widely taken as evidence for antigen selection. Stereotyped VH CDR3 sequences are often defined by the selective association of certain immunoglobulin heavy diversity (IGHD) genes in specific reading frames with certain immunoglobulin heavy joining (IGHJ) genes. To gain insight into the mechanisms underlying VH CDR3 restrictions and also determine the developmental stage when restrictions in VH CDR3 are imposed, we analyzed partial IGHD-IGHJ rearrangements (D-J) in 829 CLL cases and compared the productively rearranged D-J joints (that is, in-frame junctions without junctional stop codons) to (a) the productive immunoglobulin heavy variable (IGHV)-IGHD-IGHJ rearrangements (V-D-J) from the same cases and (b) 174 D-J rearrangements from 160 precursor B-cell acute lymphoblastic leukemia cases (pre-B acute lymphoblastic leukemia (ALL)). Partial D-J rearrangements were detected in 272/829 CLL cases (32.8%). Sequence analysis was feasible in 238 of 272 D-J rearrangements; 198 of 238 (83.2%) were productively rearranged. The D-J joints in CLL did not differ significantly from those in pre-B ALL, except for higher frequency of the IGHD7-27 and IGHJ6 genes in the latter. Among CLL carrying productively rearranged D-J, comparison of the IGHD gene repertoire in productive V-D-J versus D-J revealed the following: (a) overuse of IGHD reading frames encoding hydrophilic peptides among V-D-J and (b) selection of the IGHD3-3 and IGHD6-19 genes in V-D-J junctions. These results document that the IGHD and IGHJ gene biases in the CLL expressed VH CDR3 repertoire are not stochastic but are directed by selection operating at the immunoglobulin protein level.
Influence of the nature of an electric field applied during the solution heat treatment of the Al-Mg-Si-Cu Alloy AA6111 on subsequent natural aging
Authors: Conrad Hans , Wang Jun 
Published: February 2012

Abstract
The effect of a “non-contacting” electric field (Method A) applied during the solution heat treatment of the Al – Mg – Si – Cu alloy AA6111 on subsequent natural aging measured by resistivity was determined and compared with that without field and with a field in which the specimen is connected to the positive terminal of the power supply (Method B(+)). Method A gave an increase in the level of the aging curve compared to that without field, but the increase was less than that with Method B(+). Neither field method had an effect on the general form of the aging curve, which was in accord with the Avrami equation with n = 0.49 and k = 0.02. The maximum resistivity for natural aging increased linearly with the as-quenched resistivity for the range in solutionizing temperatures (475 – 550 °C) without and with an electric field (0.2 and 2.5 kV cm−1) considered. This relationship gave: (a) the magnitude of the contribution of the insoluble constituents to the resistivity and (b) the ratio of the resistivity due to clusters of solutes formed during natural aging to that due to the as-quenched solute distribution. An electric charge on vacancy – solute atom clusters appears to be an important factor in the influence of an applied electric field on solubility.