bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the SLCO1B3 Gene on Sulfonylurea Failure in Patients with Type 2 Diabetes in China
Authors: Ren Qian , Han Xueyao , Ren Jin , Liu Xinyu , Ji Linong 
Published: April 2017

Abstract
Sulfonylureas are widely used class of drugs for the treatment of type 2 diabetes (T2DM). Recent research has demonstrated that SLCO1B3 functions as a determinant of the insulinotropic effect of glibenclamide at the tissue level. However, whether this gene can influence the efficacy of glibenclamide in type 2 diabetic patients is not currently well-understood.
All of our study subjects were enrolled from the Xiaoke Pills Clinical Trial. The subjects were treated with glibenclamide, and followed for 48 weeks. The rs4149117 genotype (T334G) in the SLCO1B3 gene was identified by direct sequencing. Relationships between genotype and efficacy and safety outcomes were evaluated by logistic or linear regression models as appropriate.
A total of 374 subjects were enrolled in this study. The average age was 54.4±8.9 years, the percentage of males was 52.9%, and 91% of participants finished the genotype analysis successfully. Logistic regression analysis demonstrated that there was no significant difference between genotype and treatment failure of glibenclamide under an additive genetic model after adjusting for age, sex, renal function and diabetes duration (OR=1.009, 95% CI 0.692–1.473, P=0.961). The linear regression model demonstrated that the rs4149117 mutation in SLCO1B3 was significantly associated with a reduction in FPG after 48 weeks of treatment, independent of age, sex, renal function and diabetes duration (P=0.017, beta=0.130). In safety outcome analysis, we observed that rs4149117 had no association with hypoglycaemia.
The rs4149117 mutation in the SLCO1B3 gene is not associated with sulfonylurea efficacy.
Brain networks for confidence weighting and hierarchical inference during probabilistic learning
Authors: Meyniel Florent , Dehaene Stanislas 
Published: April 2017

Significance
What has been learned must sometimes be unlearned in a changing world. Yet knowledge updating is difficult since our world is also inherently uncertain. For instance, a heatwave in winter is surprising and ambiguous: does it denote an infrequent fluctuation in normal weather or a profound change? Should I trust my current knowledge, or revise it? We propose that humans possess an accurate sense of confidence that allows them to evaluate the reliability of their knowledge, and use this information to strike the balance between prior knowledge and current evidence. Our functional MRI data suggest that a frontoparietal network implements this confidence-weighted learning algorithm, acting as a statistician that uses probabilistic information to estimate a hierarchical model of the world.
BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia
Authors: Ohlen Sarah B. , Russell Magdalena L. , Brownstein Michael J. , Lefcort Frances 
Published: April 2017

Significance
Familial dysautonomia (FD) is a fatal genetic disorder that disrupts development of the peripheral nervous system (PNS) and causes progressive degeneration of the PNS and retina, ultimately leading to blindness. The underlying cellular mechanisms responsible for neuronal death in FD have been elusive. Using a mouse model that recapitulates impaired PNS development, we report here that developing peripheral neurons die in FD as the result of disruptions in mitochondrial and actin function. Cell death can be prevented in vivo by the small molecule BGP-15. Given that disrupted mitochondrial function appears to be a hallmark of neurodegenerative diseases, future studies on the efficacy of BGP-15 for mitigating neuronal loss in other disorders is warranted.
Structure of a protective epitope of group BStreptococcustype III capsular polysaccharide
Authors: Carboni Filippo , Adamo Roberto , Fabbrini Monica , De Ricco Riccardo , Cattaneo Vittorio , Brogioni Barbara , Veggi Daniele , Pinto Vittoria , Passalacqua Irene , Oldrini Davide , Rappuoli Rino , Malito Enrico , Margarit Immaculada y Ros , Berti Francesco 
Published: April 2017

SignificanceThis article describes the characterization of the antigenic determinant of the capsular polysaccharide from the clinically relevant serotype III of group BStreptococcus(GBS). NMR and X-ray crystallography have been applied to elucidate the interaction of type III GBS oligosaccharides obtained by synthetic and depolymerization procedures of the bacterial polysaccharide with a functional monoclonal antibody. A Fab–GBS oligosaccharide complex structure has been solved at high resolution (2.7 Å). The results demonstrate the existence of a sialic acid-dependent functional epitope of GBS that is fully contained within four consecutive sugars deriving from the type III GBS polysaccharide backbone and one branched disaccharide present in this sequence. This finding has implications for the development of vaccines against GBS infection.
Speeding up or reaching out?
Authors: Sayers Dave , Harding Jamie , Barchas-Lichtenstein Jena , Coffey Michael , Rock Frances 
Published: April 2017

Abstract
The Welsh Assembly, a devolved legislature in the UK, and its executive the Welsh Government, have a distinctly intensive commitment to equality – emphasising universality with weighty obligations on public services. This article uses the ‘discourse-historical approach’ (DHA) to critically review an eleven-year social service reform strategy (produced in 2007), and to weigh up its emphasis on fiscal efficiency and universal equality. We refer to these competing priorities as ‘speeding up’ and ‘reaching out’, respectively. Our findings show an imbalance towards the former, largely sidelining the possible value of services to those currently under-served. The article discusses this mismatch in respect of the dominant policymaking framework of ‘New Public Management’ and its emphases on productivity, efficiency, and quantifiable accountability. We also show the value of DHA in analysing ‘fights for dominance’ – in this case between competing discourses within a flagship policy document.
Hardballs and softballs
Authors: Clayman Steven E. , Fox Matthew P. 
Published: April 2017

AbstractThe design of questions in news interviews and news conferences has proven to be an illuminating window into the tenor of press-state relations. Quantitative studies have charted aggregate variations in adversarial questioning, but less is known about variations in the intensity of adversarialness within any particular question. Such variation is captured by the vernacular distinction between “hardball” versus “softball” questions. Hardballs advance an oppositional viewpoint vigorously, while softballs do so at most mildly. In this paper we investigate recurrent language practices through which journalists modulate the oppositionality of a question, thereby either hindering or facilitating response. The objective is to better understand how adversarialness is enacted in direct encounters between politicians and journalists.
modSaRa: a computationally efficient R package for CNV identification
Authors: Xiao Feifei , Niu Yue , Hao Ning , Xu Yanxun , Jin Zhilin , Zhang Heping 
Published: April 2017

Abstract

Summary
Chromosomal copy number variation (CNV) refers to a polymorphism that a DNA segment presents deletion or duplication in the population. The computational algorithms developed to identify this type of variation are usually of high computational complexity. Here we present a user-friendly R package, modSaRa, designed to perform copy number variants identification. The package is developed based on a change-point based method with optimal computational complexity and desirable accuracy. The current version of modSaRa package is a comprehensive tool with integration of preprocessing steps and main CNV calling steps.

Availability and Implementation
modSaRa is an R package written in R, C ++ and Rcpp and is now freely available for download at http://c2s2.yale.edu/software/modSaRa.

Supplementary information
Supplementary data are available at Bioinformatics online.
A UV cross-linking method combined with infrared imaging to analyse RNA–protein interactions
Authors: Malmqvist Tony , Spickett Carl , Gallo Jean-Marc , Anthony Karen 
Published: April 2017

Abstract
Photo cross-linking of proteins with short RNA oligomers is a classical method to study RNA–protein interactions that are implicated in many aspects of RNA metabolism and function. Most commonly, this involves the use of [γ-32P]-labeled RNA probes. Although very sensitive, these procedures are complicated by the safety issues associated with the use of radioisotopes. Here, we describe a modified UV cross-linking method using oligonucleotide probes end labelled with the infrared dye IRDye®800. After UV cross-linking, proteins are separated by SDS-PAGE and cross-linked products are visualized with the Odyssey® Infrared Imaging system. This end labelling approach provides a streamlined alternative to random labelling which reduces the efficiency of in-vitro transcription. End labelling is also independent of the length of the probe, thus facilitating quantitative comparisons. To validate the method, we have confirmed the binding of HuD to the 3′-UTR of the mRNA for the microtubule-associated protein tau, implicated in the pathogenesis of Alzheimer’s disease. UV cross-linking of HuD with a labeled 21-mer probe was successfully performed using a recombinant purified glutathione-S-transferase–HuD fusion protein as well as with lysates from CHO cells transfected with HuD cDNA. UV cross-linking combined with infrared imaging offers a convenient and robust strategy to analyse RNA–protein interactions and their emerging importance in disease.
Integrated modelling to support decision-making for marine social–ecological systems in Australia
Authors: Melbourne-Thomas Jessica , Constable Andrew J , Fulton Elizabeth A , Corney Stuart P , Trebilco Rowan , Hobday Alistair J , Blanchard Julia L , Boschetti Fabio , Bustamante Rodrigo H , Cropp Roger , Everett Jason D , Fleming Aysha , Galton-Fenzi Ben , Goldsworthy Simon D , Lenton Andrew , Lara-Lopez Ana , Little Rich , Marzloff Martin P , Matear Richard , Mongin Mathieu , Plagányi Eva , Proctor Roger , Risbey James S , Robson Barbara J , Smith David C , Sumner Michael D , van Putten E Ingrid 
Published: April 2017

AbstractPolicy- and decision-makers require assessments of status and trends for marine species, habitats, and ecosystems to understand if human activities in the marine environment are sustainable, particularly in the face of global change. Central to many assessments are statistical and dynamical models of populations, communities, ecosystems, and their socioeconomic systems and management frameworks. The establishment of a national system that could facilitate the development of such model-based assessments has been identified as a priority for addressing management challenges for Australia’s marine environment. Given that most assessments require cross-scale information, individual models cannot capture all of the spatial, temporal, biological, and socioeconomic scales that are typically needed. Coupling or integrating models across scales and domains can expand the scope for developing comprehensive and internally consistent, system-level assessments, including higher-level feedbacks in social–ecological systems. In this article, we summarize: (i) integrated modelling for marine systems currently being undertaken in Australia, (ii) methods used for integration and comparison of models, and (iii) improvements to facilitate further integration, particularly with respect to standards and specifications. We consider future needs for integrated modelling of marine social–ecological systems in Australia and provide a set of recommendations for priority focus areas in the development of a national approach to integrated modelling. These recommendations draw on—and have broader relevance for—international efforts around integrated modelling to inform decision-making for marine systems.
Getting More Than You Bargained for? Rethinking the Meaning of ‘Work’ in Employment Law
Authors: Davies A C L 
Published: April 2017

Abstract
There are many different situations in which the law requires a determination of whether an individual can be said to be ‘working’: to determine his or her status as an ‘employee’ or ‘worker’, to decide his or her entitlement to contractual pay, to assess his or her entitlement to the National Minimum Wage and to distinguish working time from ‘rest periods’ for the purposes of working time legislation. Where the individual is engaged in core work tasks at the workplace, it is straightforward to say that he or she is ‘working’. However, it will be argued in this article that there is a significant problem of ‘availability’: where workers are not actively engaged in core work tasks at the workplace, but are not fully at liberty either. This might be because they are waiting to be offered work or ‘on call’ in case of emergencies, for example. This ‘available’ time is often not recognised by the law as ‘work’, with the result that the workers in question may miss out on pay, employment rights and proper rest breaks. The article maps the problem of ‘availability’, arguing that it strikes at the heart of how labour lawyers think about employment relationships, and suggests an alternative analysis.
DynOmics: dynamics of structural proteome and beyond
Authors: Li Hongchun , Chang Yuan-Yu , Lee Ji Young , Bahar Ivet , Yang Lee-Wei 
Published: April 2017

Abstract
DynOmics (dynomics.pitt.edu) is a portal developed to leverage rapidly growing structural proteomics data by efficiently and accurately evaluating the dynamics of structurally resolved systems, from individual molecules to large complexes and assemblies, in the context of their physiological environment. At the core of the portal is a newly developed server, ENM 1.0, which permits users to efficiently generate information on the collective dynamics of any structure in PDB format, user-uploaded or database-retrieved. ENM 1.0 integrates two widely used elastic network models (ENMs)—the Gaussian Network Model (GNM) and the Anisotropic Network Model (ANM), extended to take account of molecular environment. It enables users to assess potentially functional sites, signal transduction or allosteric communication mechanisms, and protein–protein and protein–DNA interaction poses, in addition to delivering ensembles of accessible conformers reconstructed at atomic details based on the global modes of motions predicted by the ANM. The ‘environment’ is defined in a flexible manner, from lipid bilayer and crystal contacts, to substrate or ligands bound to a protein, or surrounding subunits in a multimeric structure or assembly. User-friendly interactive features permit users to easily visualize how the environment alter the intrinsic dynamics of the query systems. ENM 1.0 can be accessed at http://enm.pitt.edu/ or http://dyn.life.nthu.edu.tw/oENM/.
Optical observations of the Phoenicid meteor shower in 2014 and activity of comet 289P/Blanpain in the early 20th century
Authors: Fujiwara Yasunori , Nakamura Takuji , Uehara Satoshi , Sagayama Toru , Toda Hiroyuki ,   the NHK Cosmic Front TV Crew
Published: April 2017

Abstract
Optical observations of the Phoenicid meteor shower were made in North Carolina, USA, with seven video cameras and two digital cameras over a period of about 5 hr between 22:30 UT on 2014 December 1 and 04:00 UT on December 2. Activity of the Phoenicids was confirmed during this period, including the predicted maximum around 00 h UT on December 2. The activity level was not high, considering that 29 Phoenicid meteors and 109 non-Phoenicid meteors were detected. A gentle peak in the activity was recognized between 01:00 UT and 03:00 UT on December 2. The compact radiant of the Phoenicids agreed well with what was predicted. A comparison of the observed and predicted peak times, radiant position, bright meteors’ dominance, and radiants’ spread revealed that the observed meteors originated from the dust trails formed by comet 289P/Blanpain at the perihelion passage in the early 20th century. This indicates that the parent body of the Phoenicids, comet 289P/Blanpain, was still active as a comet in the early 20th century and provided meteoroids, although its activity level was significantly weaker than that at the beginning of the 19th century.
Uridine Diphosphate-Glucuronosyltransferase (UGT) 2B Subfamily Interspecies Differences in Carnivores
Authors: Kondo Mitsuki , Ikenaka Yoshinori , Nakayama Shouta M. M. , Kawai Yusuke K. , Mizukawa Hazuki , Mitani Yoko , Nomiyama Kei , Tanabe Shinsuke , Ishizuka Mayumi 
Published: April 2017

Abstract
UDP-glucuronosyltransferases (UGTs) are among the most important xenobiotic metabolizing enzymes that conjugate a wide range of chemicals. Previous studies showed that Felidae and Pinnipedia species have very low UGT activities toward some phenolic compounds because of the UGT1A6 pseudogene and small numbers of UGT1A isozymes. In addition to the UGT1As, UGT2Bs isozymes also conjugate various endogenous (eg, estrogens, androgens, and bile acids) and exogenous compounds (opioids, non-steroidal anti-inflammatory drugs, and environmental pollutants). However UGT2B activity and genetic background are unknown in carnivore species. Therefore, this study was performed to elucidate the species differences of UGT2Bs. Using typical substrates for UGT2Bs, UGT activity was measured in vitro. In addition, UGT2B genetic features are analyzed in silico. Results of UGT activity measurement indicate marked species differences between dogs and other carnivores (cats, Northern fur seals, Steller sea lions, Harbor seals, and Caspian seals). Dogs have very high Vmax/Km toward estradiol (17-glucuronide), estrone, lorazepam, oxazepam, and temazepam. Conversely, cats and pinniped species (especially Caspian seals and Harbor seals) have very low activities toward these substrates. The results of genetic synteny analysis indicate that Felidae and pinniped species have very small numbers of UGT2B isozymes (one or none) compared with dogs, rodents, and humans. Furthermore, Felidae species have the same nonsense mutation in UGT2B, which suggests that Felidae UGT2B31-like is also a pseudogene in addition to UGT1A6. These findings of lower activity of UGT2B suggest that Felidae and some pinniped species have very low UGT activity toward a wide range of chemicals. These results are important for Felidae and Pinnipedia species that are frequently exposed to drugs and environmental pollutants.
Patient factors in decision-making for orthopaedic surgery: a prospective analysis
Authors: Jasinski Matthew J. , Lumley Mark A. , Mandel Shlomo 
Published: April 2017

Background:
Previous research on surgical decision-making is inconsistent regarding the relative importance of patient and surgeon preferences for treatment. Few studies have related clinical indicators and patients’ inherent attitudes to subsequent physician recommendations and treatment decisions. In this study we evaluated the influence of a patient’s baseline attitudes and clinical factors on the patient’s intention for surgery, the physician’s recommendation about surgery, and ultimate surgical decision-making.

Methods:
Patients with musculoskeletal pain (N=202) were assessed for clinical indicators of surgery and attitudinal variables before their initial surgical consultation. Logistic regressions analyzed how baseline variables subsequently predicted surgeon’s recommendations and whether or not the patient had surgery, and compared the relative importance of the predictors. We also examined which variables predicted adherence to surgeon’s recommendations.

Results:
Higher baseline pain, disability, knowledge of risks, and family encouragement for surgery positively predicted the patient’s intention to have surgery, which, in turn, was the strongest predictor of the surgeon’s recommendation. Both surgeon’s recommendation and patient’s baseline intention for surgery jointly predicted final treatment decisions. In addition, patient’s intention for surgery was the only predictor of whether or not patients adhered to their surgeon’s recommendation.

Conclusions:
Patients may form strong opinions about surgery before consulting a surgeon, and these opinions impact the physician’s recommendation and ultimate treatment decisions, sometimes leading patients to act inconsistently with their surgeon’s recommendation. These findings help clarify the influence that patients have in treatment decision-making and highlight the importance of recognizing the critical role of patients’ backgrounds in elective surgery.
An anatomic and histologic study of the origin and terminal points in the anterior and posterior cruciate ligaments in rats
Authors: Yan Denglu , Feng Zhenhua , Wang Zhaojie , Zhang Zhi 
Published: April 2017

Background:It remains unclear why the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL) are most commonly torn at their proximal and distal attachments, respectively. This animal study was designed to evaluate the difference in tissue structure between the origins and terminal attachments of the ACL and PCL.Methods:Knee samples from 30 rats were assessed anatomically, histologically, and morphologically to determine differences in tissue structure.Results:The ACL and PCL originate in the epiphyseal plates of the distal femur and proximal tibia, respectively, and they terminate as fibrous tissue into the tibial and femoral bones, respectively. The cruciate ligaments are constructed mostly of collagen, but at their origins the collagen is directly connected to the epiphyseal plate and less so to the bone. At the terminal attachments, the collagen is more fibrous and grows directly into bone tissue. The morphology of the cells at the origins show heterogeneity whereas homogeneity is seen at the terminal attachments. The terminal attachment of the cruciate ligament has more fibrous bundles that contains more fibroblasts than the origin structure that has less fibrous tissue and contains more chondrocytes (P<0.01).Conclusions:At the ACL and PCL origins, the collagen fibers are directly connected to the epiphyseal plate and less so to bone. In contrast, at the terminal attachments, the collagen is directly connected to bone and actually becomes bone tissue, thereby providing secure adherence. This might explain why ACL and PCL cruciate ligament tears more often occur closer to their sites of origin.