bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor structure and measurement invariance of the Health Education Impact Questionnaire: Does the subjectivity of the response perspective threaten the contextual validity of inferences?
Authors: Elsworth Gerald R , Nolte Sandra , Osborne Richard H 
Published: May 2015

Objective: On-going evidence is required to support the validity of inferences about change and group differences in the evaluation of health programs, particularly when self-report scales requiring substantial subjectivity in response generation are used as outcome measures. Following this reasoning, the aim of this study was to replicate the factor structure and investigate the measurement invariance of the latest version of the Health Education Impact Questionnaire, a widely used health program evaluation measure. Methods: An archived dataset of responses to the most recent version of the English-language Health Education Impact Questionnaire that uses four rather than six response options (N = 3221) was analysed using exploratory structural equation modelling and confirmatory factor analysis appropriate for ordered categorical data. Metric and scalar invariance were studied following recent recommendations in the literature to apply fully invariant unconditional models with minimum constraints necessary for model identification. Results: The original eight-factor structure was replicated and all but one of the scales (Self Monitoring and Insight) was found to consist of unifactorial items with reliability of ⩾0.8 and satisfactory discriminant validity. Configural, metric and scalar invariance were established across pre-test to post-test and population sub-groups (sex, age, education, ethnic background). Conclusion: The results support the high level of interest in the Health Education Impact Questionnaire, particularly for use as a pre-test/post-test measure in experimental studies, other pre–post evaluation designs and system-level monitoring and evaluation.
MicroRNA-155–deficient dendritic cells cause less severe GVHD through reduced migration and defective inflammasome activation
Authors: Chen Sophia , Smith Benjamin A. H. , Iype Joseena , Prestipino Alessandro , Pfeifer Dietmar , Grundmann Sebastian , Schmitt-Graeff Annette , Idzko Marco , Beck Yvonne , Prinz Gabriele , Finke Jürgen , Duyster Justus , Zeiser Robert 
Published: May 2015

Key PointsGVHD induction is dependent on functional miR-155 in DCs of the allo-HCT recipient. MiR-155 deficiency reduces ATP-mediated cell migration, ERK and inflammasome activation, and IL-1β production of DCs.
Most partial domains in proteins are alignment and annotation artifacts
Authors: Triant Deborah A , Pearson William R 
Published: May 2015

Abstract
Background
Protein domains are commonly used to assess the functional roles and evolutionary relationships of proteins and protein families. Here, we use the Pfam protein family database to examine a set of candidate partial domains. Pfam protein domains are often thought of as evolutionarily indivisible, structurally compact, units from which larger functional proteins are assembled; however, almost 4% of Pfam27 PfamA domains are shorter than 50% of their family model length, suggesting that more than half of the domain is missing at those locations. To better understand the structural nature of partial domains in proteins, we examined 30,961 partial domain regions from 136 domain families contained in a representative subset of PfamA domains (RefProtDom2 or RPD2).

Results
We characterized three types of apparent partial domains: split domains, bounded partials, and unbounded partials. We find that bounded partial domains are over-represented in eukaryotes and in lower quality protein predictions, suggesting that they often result from inaccurate genome assemblies or gene models. We also find that a large percentage of unbounded partial domains produce long alignments, which suggests that their annotation as a partial is an alignment artifact; yet some can be found as partials in other sequence contexts.

Conclusions
Partial domains are largely the result of alignment and annotation artifacts and should be viewed with caution. The presence of partial domain annotations in proteins should raise the concern that the prediction of the protein’s gene may be incomplete. In general, protein domains can be considered the structural building blocks of proteins.
Widespread intron retention diversifies most cancer transcriptomes
Authors: Dvinge Heidi , Bradley Robert K. 
Published: May 2015

Abstract
Background
Somatic mutations affecting components of the RNA splicing machinery occur with high frequencies across many tumor types. These mutations give rise to distinct alterations in normal splice site and exon recognition, such as unusual 3′ splice site preferences, that likely contribute to tumorigenesis.

Methods
We analyzed genome-wide patterns of RNA splicing across 805 matched tumor and normal control samples from 16 distinct cancer types to identify signals of abnormal cancer-associated splicing.

Results
We found that abnormal RNA splicing, typified by widespread intron retention, is common across cancers even in the absence of mutations directly affecting the RNA splicing machinery. Almost all liquid and solid cancer types exhibited frequent retention of both alternative and constitutive introns relative to control normal tissues. The sole exception was breast cancer, where intron retention typified adjacent normal rather than cancer tissue. Different introns were preferentially retained in specific cancer types, although a small subset of introns enriched for genes encoding RNA splicing and export factors exhibited frequent retention across diverse cancers. The extent of intron retention correlated with the presence of IDH1 and IDH2 mutations in acute myeloid leukemia and across molecular subtypes in breast cancer. Many introns that were preferentially retained in primary cancers were present at high levels in the cytoplasmic mRNA pools of cancer cell lines.

Conclusions
Our data indicate that abnormal RNA splicing is a common characteristic of cancers even in the absence of mutational insults to the splicing machinery, and suggest that intron-containing mRNAs contribute to the transcriptional diversity of many cancers.
The association between antibody levels before and after 7-valent pneumococcal conjugate vaccine immunization and subsequent pneumococcal infection in chronic arthritis patients
Authors: Nagel Johanna , Geborek Pierre , Saxne Tore , Jönsson Göran , Englund Martin , Petersson Ingemar F , Nilsson Jan-Åke , Truedsson Lennart , Kapetanovic Meliha C 
Published: May 2015

Abstract
Introduction
The aim of present study is to inverstigate the association between antibody levels after vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) and subsequent serious pneumococcal infections in rheumatoid arthritis (RA) and spondylarthropathy (SpA) patients.

Methods
A cohort of 497 patients (RA = 248 and SpA = 249) received a single dose of PCV7. At vaccination, patients were treated with methotrexate (MTX; n = 85), anti-tumour necrosis factor (anti-TNF) + MTX (n = 169), anti-TNF monotherapy (n = 158) and non-steroidal anti-inflammatory drugs (NSAIDs)/analgesics (n = 85). Antibody levels of serotypes 6B and 23B were analyzed before and 4 to 6 weeks after vaccination using standard enzyme-linked immunosorbent assay (ELISA). Serious pneumococcal infections (pneumonia/lower respiratory tract infection, meningitis, sepsis, septic arthritis) occurring within 4.5 years after vaccination were identified in the Skåne Healthcare Register using the International Classification of Diseases, tenth revision (ICD-10) codes. The association between post-vaccination antibody levels and protection against infections and determination of protective cutoff levels was explored using receiver operating characteristic (ROC) curves. Predictors of infection were studied using regression analyses.

Results
Eighteen infections were registered in 15 patients before vaccination and 27 infections in 23 patients after vaccination. Patients with serious infections after vaccination had significantly lower post-vaccination antibody titres for both 6B (P = 0.04) and 23 F (P = 0.04). Post-vaccination antibody levels of at least 1.29 mg/L and 1.01 mg/L for 6B and 23, respectively, were associated with better protection from serious infections. Higher age, concomitant prednisolone but not MTX or anti-TNF were associated with such infections.

Conclusions
Patients with more robust antibody responses after vaccination with pneumococcal conjugate vaccine were less likely to suffer from serious infections. High age and prednisolone at vaccination were associated with putative serious pneumococcal infections in this cohort.

Trial registration number
EudraCT EU 2007-006539-29 and NCT00828997. Registered 23 January 2009.
Evidence for cadherin-11 cleavage in the synovium and partial characterization of its mechanism
Authors: Noss Erika H , Watts Gerald FM , Zocco Davide , Keller Tracy L , Whitman Malcolm , Blobel Carl P , Lee David M , Brenner Michael B 
Published: May 2015

Abstract
Introduction
Engagement of the homotypic cell-to-cell adhesion molecule cadherin-11 on rheumatoid arthritis (RA) synovial fibroblasts with a chimeric molecule containing the cadherin-11 extracellular binding domain stimulated cytokine, chemokine, and matrix metalloproteinases (MMP) release, implicating cadherin-11 signaling in RA pathogenesis. The objective of this study was to determine if cadherin-11 extracellular domain fragments are found inside the joint and if a physiologic synovial fibroblast cleavage pathway releases those fragments.

Methods
Cadherin-11 cleavage fragments were detected by western blot in cell media or lysates. Cleavage was interrupted using chemical inhibitors or short-interfering RNA (siRNA) gene silencing. The amount of cadherin-11 fragments in synovial fluid was measured by western blot and ELISA.

Results
Soluble cadherin-11 extracellular fragments were detected in human synovial fluid at significantly higher levels in RA samples compared to osteoarthritis (OA) samples. A cadherin-11 N-terminal extracellular binding domain fragment was shed from synovial fibroblasts after ionomycin stimulation, followed by presenilin 1 (PSN1)-dependent regulated intramembrane proteolysis of the retained membrane-bound C-terminal fragments. In addition to ionomycin-induced calcium flux, tumor necrosis factor (TNF)-α also stimulated cleavage in both two- and three-dimensional fibroblast cultures. Although cadherin-11 extracellular domains were shed by a disintegrin and metalloproteinase (ADAM) 10 in several cell types, a novel ADAM- and metalloproteinase-independent activity mediated shedding in primary human fibroblasts.

Conclusions
Cadherin-11 undergoes ectodomain shedding followed by regulated intramembrane proteolysis in synovial fibroblasts, triggered by a novel sheddase that generates extracelluar cadherin-11 fragments. Cadherin-11 fragments were enriched in RA synovial fluid, suggesting they may be a marker of synovial burden and may function to modify cadherin-11 interactions between synovial fibroblasts.
Borderline pulmonary pressures in scleroderma - a ‘pre-pulmonary arterial hypertension’ condition?
Authors: Kovacs Gabor , Olschewski Horst 
Published: May 2015

AbstractPatients with systemic sclerosis may develop borderline pulmonary arterial pressure. The clinical relevance of this condition is not always clear. Reported data support the evidence that this subgroup may represent an intermediate stage between normal pulmonary arterial pressure and manifest pulmonary arterial hypertension, a serious complication in scleroderma. Recognizing the clinical relevance of borderline pulmonary arterial pressure increase in scleroderma patients, future studies should aim for clear evidence for diagnostic and therapeutic algorithms for this population.
Very small embryonic-like stem cells are involved in pancreatic regeneration and their dysfunction with age may lead to diabetes and cancer
Authors: Bhartiya Deepa , Patel Hiren 
Published: May 2015

AbstractMouse pancreas has a remarkable ability to regenerate after partial pancreatectomy, and several investigators have studied the underlying mechanisms involved in this regeneration process; however, the field remains contentious. Elegant lineage-tracing studies undertaken over a decade have generated strong evidence against neogenesis from stem cells and in favor of reduplication of pre-existing islets. Ductal epithelium has also been implicated during regeneration. We recently provided direct evidence for the possible involvement of very small embryonic-like stem cells (VSELs) during regeneration after partial pancreatectomy in mice. VSELs were first reported in pancreas in 2008 and are mobilized in large numbers after treating mice with streptozotocin and in patients with pancreatic cancer. VSELs can be detected in mouse pancreas as small-sized LIN−/CD45−/SCA-1+ cells (3 to 5 μm), present in small numbers (0.6%), which express nuclear Oct-4 (octamer-binding transcription factor 4) and other pluripotent markers along with their immediate descendant ‘progenitors’, which are slightly bigger and co-express Oct-4 and PDX-1. VSELs and the progenitors get mobilized in large numbers after partial pancreatectomy and regenerate both pancreatic islets and acinar cells. In this review, we deliberate upon possible reasons why VSELs have eluded scientists so far. Because of their small size, VSELs are probably unknowingly and inadvertently discarded during processing. Similar to menopause and related loss of ovarian function, type 2 diabetes mellitus occurs because of a decline in beta-cell function possibly resulting from an age-related compromised niche which does not allow VSELs to maintain normal homeostasis. As suggested earlier for ovarian cancers, the presence of Oct-4 and other pluripotent markers in pancreatic cancers is suggestive of VSELs as the possible cancer-initiating stem cells. Several issues raised in the review require urgent confirmation and thus provide scope for further research before arriving at a consensus on the fundamental role played by VSELs in normal pancreas biology and during regeneration, aging, and cancer. In the future, such understanding may allow manipulation of endogenous VSELs to our advantage in patients with diabetes and also to treat cancer.
Autologous, allogeneic, induced pluripotent stem cell or a combination stem cell therapy? Where are we headed in cartilage repair and why: a concise review
Authors: Vonk Lucienne A. , de Windt Tommy S. , Slaper-Cortenbach Ineke C. M. , Saris Daniël B. F. 
Published: May 2015

AbstractThe evolution of articular cartilage repair procedures has resulted in a variety of cell-based therapies that use both autologous and allogeneic mesenchymal stromal cells (MSCs). As these cells are increasingly available and show promising results both in vitro and in vivo, cell-based strategies, which aim to improve ease of use and cost-effectiveness, are progressively explored. The use of MSCs in cartilage repair makes it possible to develop single-stage cell-based therapies. However, true single-stage procedures rely on one intervention, which will limit cell sources to fraction concentrates containing autologous MSCs or culture-expanded allogeneic MSCs. So far, it seems both autologous and allogeneic cells can safely be applied, but clinical studies are still ongoing and little information on clinical outcome is available. Further development of cell-based therapies may lead to clinical-grade, standardized, off-the-shelf products with easy handling for orthopedic surgeons. Although as of yet no preclinical or clinical studies are ongoing which explore the use of induced pluripotent stem cells for cartilage repair, a good manufacturing practice-grade induced pluripotent stem cell line might become the basis for such a product in the future, providing that cell fate can be controlled. The use of stem cells in clinical trials brings along new ethical issues, such as proper controls and selecting primary outcome measures. More clinical trials are needed to estimate detailed risk-benefit ratios and trials must be carefully designed to minimize risks and burdens for patients while choosing outcome measures that allow for adequate comparison with results from similar trials. In this review, we discuss the different aspects of new stem cell-based treatments, including safety and ethical issues, as well as provide an overview of current clinical trials exploring these approaches and future perspectives.
Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution
Authors: Lin Jen-Chieh , Hu Shing , Ho Pei-Hung , Hsu Hwei-Jan , Postlethwait John H. , Chung Bon-chu 
Published: May 2015

Abstract
HSD3B catalyzes the synthesis of δ4 steroids such as progesterone in the adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes. Our phylogenetic and conserved synteny analyses showed that the tandemly duplicated human HSD3B1 and HSD3B2 genes are coorthologs of zebrafish hsd3b1 on chromosome 9 (Dre9), whereas the gene called hsd3b2 resides on Dre20 in an ancestral chromosome segment, from which its ortholog was lost in the tetrapod lineage. Zebrafish hsd3b1(Dre 9) was expressed in adult gonads and headkidney, which contains interrenal glands, the zebrafish counterpart of the tetrapod adrenal. Knockdown of hsd3b1(Dre 9) caused the interrenal and anterior pituitary to expand and pigmentation to increase, resembling human HSD3B2 deficiency. The zebrafish hsd3b2(Dre 20) gene was expressed in zebrafish early embryos as maternal transcripts that disappeared 1 day after fertilization. Morpholino inactivation of hsd3b2(Dre 20) led to embryo elongation, which was rescued by the injection of hsd3b2 mRNA. Thus, zebrafish hsd3b2(Dre 20) evolved independently of hsd3b1(Dre 9) with a morphogenetic function during early embryogenesis. Zebrafish hsd3b1(Dre 9), on the contrary, functions like mammalian HSD3B2, whose deficiency leads to congenital adrenal hyperplasia.
Optical Properties of Three Differently Colored Crystal Modifications of a 2,3-Dicyanopyrazine Dye
Authors: Okada Naoya , Eto Ryohei , Horiguchi-Babamoto Emi , Kobayashi Takashi , Naito Hiroyoshi , Shiro Motoo , Takahashi Hiromi , Matsumoto Shinya 
Published: May 2015

Abstract
Optical properties of three crystal modifications of 5-t-butyl-2,3-dicyano-6-[4-(dimethylamino)styryl]pyrazine having different color appearances were measured and interpreted on the basis of crystal structure analysis. Two of the three modifications exhibited a bathochromic spectral shift both in absorption and fluorescence compared with those in a toluene solution of the dye. The crystal structure analysis revealed that a two-dimensional brick-wall structure is formed in both modifications. In contrast, the third modification showed a hypsochromic absorption shift with a large bathochromic fluorescence shift. The crystal structure of this modification was characterized by a one-dimensional stacked molecular column. The optical characteristics of the three modifications were qualitatively interpreted in terms of excitonic intermolecular interaction on the basis of their crystal structures.
Main Group Lewis Acids in Frustrated Lewis Pair Chemistry: Beyond Electrophilic Boranes
Authors: Weicker Sarah A , Stephan Douglas W 
Published: May 2015

Abstract
The advent of frustrated Lewis pair (FLP) chemistry almost a decade ago was based on the reactivity of sterically encumbered combinations of electrophilic boranes and phosphines with hydrogen. Since that time the chemistry has broadened dramatically in terms of reactivity and applications. Nonetheless, the majority of the work has continued to exploit the borane B(C6F5)3. In this review, we describe FLP chemistry that has developed by employing alternatives to this Lewis acid. Lewis acids derived from group 13, 14, and 15 based systems are described, thus demonstrating a growing area in the main group reactivity based on FLPs.
On Constructing the System of Elective Math Courses in Subject Oriented Education
Authors: Мардахаева  , Mardakhaeva Elena 
Published: May 2015

Тhe paper is aimed to help the inconsistency between the training of school graduates and requirements of universities for first-year students through
the creation of training courses in profession-oriented classes. A variant of construction of elective courses for subject oriented classes is exemplified
though the analysis of several topics from «Mathematics and Informatics». A sample program of elective course «Arithmetic and geometric progression
and introduction to the theory of limits» recommended for all profiles is displayed. On the basis of these principles it is possible to develop other programs
of elective courses for majoring classes on various subjects. The program contains all the necessary components, along with examples of tasks, materials
for practical classes and individual work.
Comprehensive Genetic Analysis of Paralogous Terminal Septin Subunits Shs1 and Cdc11 inSaccharomyces cerevisiae
Authors: Finnigan Gregory C , Takagi Julie , Cho Christina , Thorner Jeremy 
Published: May 2015

AbstractSeptins are a family of GTP-binding proteins considered to be cytoskeletal elements because they self-assemble into filaments and other higher-order structures in vivo. In budding yeast, septins establish a diffusion barrier at the bud neck between a mother and daughter cell, promote membrane curvature there, and serve as a scaffold to recruit other proteins to the site of cytokinesis. However, the mechanism by which any septin engages a partner protein has been unclear. The two most related and recently evolved subunits appear to be Cdc11 and Shs1, and the basic building blocks for assembling septin structures are hetero-octameric rods (Cdc11–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11 and Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Shs1). Loss of Cdc11 is not normally tolerated, whereas cells lacking Shs1 do not appear grossly abnormal. We established several different sensitized genetic backgrounds wherein Shs1 is indispensable, which allowed us to carry out the first comprehensive and detailed genetic analysis of Shs1 in vivo. Our analysis revealed several novel insights, including: (i) the sole portion of Shs1 essential for its function is a predicted coiled-coil-forming segment in its C-terminal extension (CTE); (ii) the CTE of Cdc11 shares this function; (iii) this role for the CTEs of Cdc11 and Shs1 is quite distinct from that of the CTEs of Cdc3 and Cdc12; and (iv) heterotypic Cdc11 and Shs1 junctions likely occur in vivo.Related article in GENETICS: Finnigan, G. C. et al., 2015 The Carboxy-Terminal Tails of Septins Cdc11 and Shs1 Recruit Myosin-II Binding Factor Bni5 to the Bud Neck in Saccharomyces cerevisiae. Genetics 200: 843–862.