bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of ten F8 splicing mutations in RNA isolated from patient's leucocytes: assessment of in silico prediction tools accuracy
Authors: Martorell L. , Corrales I. , Ramirez L. , Parra R. , Raya A. , Barquinero J. , Vidal F. 
Published: February 2015

SummaryAlthough 8% of reported FVIII gene (F8) mutations responsible for haemophilia A (HA) affect mRNA processing, very few have been fully characterized at the mRNA level and/or systematically predicted their biological consequences by in silico analysis. This study is aimed to elucidate the effect of potential splice site mutations (PSSM) on the F8 mRNA processing, investigate its correlation with disease severity, and assess their concordance with in silico predictions. We studied the F8 mRNA from 10 HA patient's leucocytes with PSSM by RT‐PCR and compared the experimental results with those predicted in silico. The mRNA analysis could explain all the phenotypes observed and demonstrated exon skipping in six cases (c.222G>A, c.601+1delG, c.602‐11T>G, c.671‐3C>G, c.6115+9C>G and c.6116‐1G>A) and activation of cryptic splicing sites, both donor (c.1009+1G>A and c.1009+3A>C) and acceptor sites (c.266‐3delC and c.5587‐1G>A). In contrast, the in silico analysis was able to predict the score variation of most of the affected splice site, but the precise mechanism could only be correctly determined in two of the 10 mutations analysed. In addition, we have detected aberrant F8 transcripts, even in healthy controls, so this must be taken into account as they could mask the actual contribution of some PSSM. We conclude that F8 mRNA analysis using leucocytes still constitutes an excellent approach to investigate the transcriptional effects of the PSSM in HA, whereas prediction in silico is not always reliable for diagnostic decision‐making.
miR‐486 regulates metastasis and chemosensitivity in hepatocellular carcinoma by targeting CLDN10 and CITRON
Authors: Sun Huiyan , Cui Chunping , Xiao Fengjun , Wang Hua , Xu Jun , Shi Xuefeng , Yang Yuefeng , Zhang Qunwei , Zheng Xiaofei , Yang Xiaoming , Wu Chutse , Wang Lisheng 
Published: February 2015

AimmiRNA‐486 (miR‐486) was first identified from the human fetal liver cDNA library and considered to be associated with hepatocellular carcinoma (HCC) development. Its roles in regulation of HCC metastasis and chemosensitivity have not been explored yet.MethodsmiR‐486 expression in HCC tissues, cell lines and serum was evaluated by real‐time polymerase chain reaction. miR‐486 overexpression or downregulation in the cell lines SMMC‐7721/LM3 was conducted by lentivirus transfection. Cell proliferation, migration and apoptosis were quantitated using commercial assays. Matrix metalloproteinase activity was quantitated by gelatin zymography. The target genes of miR‐486 were screened by 3′‐untranslated region luciferase report assays and their function was validated by small RNA interference.ResultsWe show here that miR‐486 is frequently down‐expressed in HCC tissues and cell lines. Lentivirus‐mediated restoration of miR‐486 in HCC cell lines resulted in significant reduction in the ability of cell growth, colony formation and migration. However, miR‐486 inhibition enhances proliferation and invasion of HCC cells. Two genes, CITRON and CLDN10 which regulate cell proliferation and invasion, respectively, were identified as the direct targets of miR‐486 in HCC cells. CITRON and CLDN10 knockdown by siRNA results in similar phenotypes of miR‐486 restoration in HCC cell lines. In addition, miR‐486 enhances the chemosensitivity of HCC cells to sorafenib.ConclusionOur data indicated that miR‐486 may function as a novel tumor suppressor in HCC.
Serum miRNA‐122 in acute liver injury induced by kidney injury and sepsis in CD‐1 mouse models
Authors: Leelahavanichkul Asada , Somparn Poorichaya , Panich Thanaporn , Chancharoenthana Wiwat , Wongphom Jutamas , Pisitkun Trairak , Hirankarn Nattiya , Eiam‐Ong Somchai 
Published: February 2015

AbstractAimmiRNA‐122 (miR‐122) is a new, interesting liver injury biomarker but little is known about its effects when there is an indirect acute liver injury.MethodsWe investigated this by using indirect liver injury mice models with bilateral ureter obstruction (BUO), bilateral nephrectomy (BiNx) and cecal ligation and puncture (CLP). A direct liver injury model, liver ischemia/reperfusion injury (liver I/R), was performed in parallel. Liver injury (i.e. liver histology, alanine transaminase [ALT]), kidney damage (i.e. serum creatinine) and cytokines (i.e. tumor necrosis factor‐α, interleukin [IL]‐6, IL‐1β, IL‐10) were assessed.ResultsSix hours after BUO/BiNx/CLP, the ALT and serum cytokines were approximately 1.5‐fold higher than the baseline whereas miR‐122 did not change. After 6 h of BiNx, there were prominent hepatocyte vacuolization but no elevations of miR‐122. However, after 24 h of BUO/BiNx/CLP, ALT, hepatocyte vacuolization and miR‐122 increased. The cytokines at 6 h might have induced the production of miR‐122 at 24 h. The results from the in vitro study with HepG2 cells and each of the cytokines resulted in increased miR‐122. On the other hand, when the direct liver injury model was used, there was a fivefold and 22‐fold increase in the ALT at 0.5 and 1 h after surgery, respectively, and high serum miR‐122 which corroborated the results from the liver histopathology.ConclusionWe demonstrated that prior serum cytokine accumulation increased serum miR‐122 in indirect liver injury induced by BUO/BiNx and less severe sepsis mouse models. Cytokine accumulation may be responsible for miR‐122 expression in these models. The clinical importance of liver injury demonstrated by the discordance between serum miR‐122 and ALT was an interesting issue.
Phase II, randomized, open, controlled study of AS03‐adjuvanted H5N1 pre‐pandemic influenza vaccine in children aged 3 to 9 years: follow‐up of safety and immunogenicity persistence at 24 months post‐vaccination
Authors: Díez‐Domingo Javier , Baldó José‐María , Planelles‐Catarino Maria Victoria , Garcés‐Sánchez María , Ubeda Isabel , Jubert–Rosich Angels , Marès Josep , Garcia‐Corbeira Pilar , Moris Philippe , Teko Maurice , Vanden Abeele Carline , Gillard Paul 
Published: February 2015

BackgroundAn AS03‐adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3–9 years.MethodsIn this follow‐up of the Phase II study, we report immunogenicity persistence and safety at 24 months post‐vaccination in children aged 3–9 years. The randomized, open‐label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune‐mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination‐inhibition assay 12 and 24 months after vaccination; cross‐reactivity and cell‐mediated responses were also assessed. (NCT00502593).ResultsThe safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine‐related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell‐mediated immunity was strong, and CD4+ T cells with a TH1 profile were observed.ConclusionsTwo doses of an AS03‐adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell‐mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination.
Evidence of regenerative ability inMyxicola infundibulum(Annelida, Sabellida): evolutionary and systematic implications
Authors: Licciano Margherita , Watson Gordon James , Murray Joanna Michelle , Giangrande Adriana 
Published: February 2015

AbstractMembers of only a few species of annelids are reported as being incapable of regeneration; of these,Myxicola infundibulumis the only example in the family Sabellidae. Interestingly, its congenerMyxicola aestheticaexhibits noteworthy regenerative ability. Unambiguously identifying non‐regenerating species is critical to reconstructing how regenerative abilities evolved within the phylum. However, studies designed specifically to assess the regenerative potential ofM. infundibulumhave never been performed. In this study, we aimed to confirm the lack of regeneration ability ofM. infundibulum, reported previously for Atlantic specimens, or to determine the extent to which regeneration occurs. Our results showed that individuals from the Mediterranean Sea (Adriatic Sea) do undergo regeneration of lost body parts, although to a lesser extent than do other sabellids. Therefore,M. infundibulumshould no longer be considered a non‐regenerating species. At present, uncertainties regarding phylogenetic relationships of Sabellidae prevent inferences about the polarity of change inM. infundibulum. Since our findings are counter to those of previous studies which describe Atlantic specimens as non‐regenerating, more extensive analysis is required to ascertain if they could actually belong to a different species than MediterraneanM. infundibulum, accounting for these differences in reported regenerative capacity.
Wireless Smartphone ECG Enables Large‐Scale Screening in Diverse Populations
Authors: HABERMAN ZACHARY C. , JAHN RYAN T. , BOSE RUPAN , TUN HAN , SHINBANE JEROLD S. , DOSHI RAHUL N. , CHANG PHILIP M. , SAXON LESLIE A. 
Published: February 2015

Twelve‐Lead ECG as a Cardiovascular Screening ToolBackgroundThe ubiquitous presence of internet‐connected phones and tablets presents a new opportunity for cost‐effective and efficient electrocardiogram (ECG) screening and on‐demand diagnosis. Wireless, single‐lead real‐time ECG monitoring supported by iOS and android devices can be obtained quickly and on‐demand. ECGs can be immediately downloaded and reviewed using any internet browser.ObjectiveWe compared the standard 12‐lead ECG to the smartphone ECG in healthy young adults, elite athletes, and cardiology clinic patients. Accuracy for determining baseline ECG intervals and rate and rhythm was assessed.MethodsIn 381 participants, 30‐second lead I ECG waveforms were obtained using an iPhone case or iPad. Standard 12‐lead ECGs were acquired immediately after the smartphone tracing was obtained. De‐identified ECGs were interpreted by automated algorithms and adjudicated by two board‐certified electrophysiologists.ResultsBoth smartphone and standard ECGs detected atrial rate and rhythm, AV block, and QRS delay with equal accuracy. Sensitivities ranged from 72% (QRS delay) to 94% (atrial fibrillation). Specificities were all above 94% for both modalities.ConclusionSmartphone ECG accurately detects baseline intervals, atrial rate, and rhythm and enables screening in diverse populations. Efficient ECG analysis using automated discrimination and an enhanced smartphone application with notification capabilities are features that can be easily incorporated into the acquisition process.
Early childhood behavioral inhibition, adult psychopathology and the buffering effects of adolescent social networks: a twenty‐year prospective study
Authors: Frenkel Tahl I. , Fox Nathan A. , Pine Daniel S. , Walker Olga L. , Degnan Kathryn A. , Chronis‐Tuscano Andrea 
Published: February 2015

BackgroundWe examined whether the temperament of behavioral inhibition is a significant marker for psychopathology in early adulthood and whether such risk is buffered by peer social networks.MethodsParticipants (N = 165) were from a prospective study spanning the first two decades of life. Temperament was characterized during infancy and early childhood. Extent of involvement in peer social networks was measured during adolescence, and psychopathology was assessed in early adulthood. Latent Class Analyses generated comprehensive variables at each of three study time‐points. Regressions assessed (a) the direct effect of early behavioral inhibition on adult psychopathology (b) the moderating effect of adolescent involvement in social peer networks on the link between temperamental risk and adult psychopathology.ResultsStable behavioral inhibition in early childhood was negatively associated with adult mental health (R2 = .07, p = .005, β = −.26), specifically increasing risk for adult anxiety disorders (R2 = .04, p = .037, β = .19). These temperament‐pathology relations were significantly moderated by adolescent peer group social involvement and network size (Total R2 = .13, p = .027, β = −.22). Temperament predicted heightened risk for adult anxiety when adolescent social involvement was low (p = .002, β = .43), but not when adolescent social involvement was high.ConclusionsStable behavioral inhibition throughout early childhood is a risk factor for adult anxiety disorders and interacts with adolescent social involvement to moderate risk. This is the first study to demonstrate the critical role of adolescent involvement in socially active networks in moderating long‐lasting temperamental risk over the course of two decades, thus informing prevention/intervention approaches.
Maternal thermal effect on diapause inTrichogrammaspecies (Hymenoptera: Trichogrammatidae)
Authors: Voinovich N. D. , Reznik S. Y. , Vaghina N. P. 
Published: February 2015

AbstractBoth direct thermal and maternal photoperiodic effects on diapause induction have been thoroughly investigated in many insect species, while maternal thermal effects have been infrequently studied. We studied the effect of temperature during development of maternal generation on the proportion of diapausing progeny in four species of the genusTrichogrammaWestw., minute egg parasitoids, widely used for biological control of lepidopteran pests. The maternal generations were reared at day lengths of 12 and 18 h and temperatures of 17, 20, 25 and 30°C, and their progeny developed under day length of 12 h and temperatures of 13 and 14°C. InT. evanescensandT. piceum, the proportion of diapausing progeny decreased with increasing temperature under all tested photoperiods and thermal regimes of progeny development; the high temperature of 30°C totally averted diapause of progeny. InT. buesiandT. principium,low temperatures of 17 and 20°C resulted in relatively high proportion of diapausing progeny only when the maternal generation developed under short‐day conditions. The threshold of the maternal thermal response varied from 17–18 to 22–23°C. Under field conditions,Trichogrammafemales are exposed to such high temperatures only during summer, when diapause in their progeny is in any case prevented by the maternal photoperiodic response and by the thermal response of the larvae. We conclude that the maternal thermal effect on diapause induction, although to a different extent, is inherent toTrichogrammaspecies but, at least as suggested by laboratory experiments, it does not play any role in the regulation of seasonal development under natural conditions. However, during mass rearing ofTrichogrammawasps, it should be taken into account that high temperature, even when combined with short photoperiod, can avert diapause in the next generation.
CEOs' Leadership Styles and Managers' Innovative Behaviour: Investigation of Intervening Effects in an Entrepreneurial Context
Authors: Kang Jae Hyeung , Solomon George T. , Choi David Y. 
Published: February 2015

ABSTRACTWe examine the relationships and intervening mechanisms between founding CEOs' transformational/transactional leadership and the innovative behaviour of managers. We develop and test our hypotheses on a sample of 39 participating CEOs and 105 managers with the use of a multilevel structural equation model. The results show that both transformational and transactional leadership on the part of the CEO relate positively to managers' innovative behaviour. We also discover that firm's innovative climate mediates the relationship between transformational leadership and innovative behaviour. However, we fail to find the mediating effect of innovative climate between transactional leadership and innovative behaviour. Our findings contribute to an improved understanding of how founding CEOs' different leadership styles affect employees' innovative behaviour in start‐ups and to what extent the innovative climate influences the relationship.
“Liking” and “Take Away” Preferences for Mexican Consumers: Cross‐Cultural Comparison with Thais for Psychological Style
Authors: Calderón Eduardo , Angulo Ofelia , O'Mahony Michael , Wichchukit Sukanya 
Published: February 2015

AbstractThere are reports in the literature that for paired preference tests with a “No Preference” option, Mexican consumers have a lower frequency of “No Preference” responses than Thais. For a more exact comparison of these differences in psychophysical style, Mexican consumers performed preference tests using, as closely as possible, the experimental method used in the Thai experiments. Comparison between this study and the Thai studies confirmed the differences in “No Preference” frequencies, suggesting a systematic cross‐cultural effect of psychophysical style. Mexican consumers also performed “take away” preferences for the first time and their results corresponded more with the regular paired preference tests than was the case with Thais.Practical ApplicationsPaired preference tests are a subset of measures available for consumer acceptance. Considering the importance of efforts to predict consumer acceptance, it is essential to understand the variables and biases associated with such tests. Because cross‐cultural measurement is becoming more critical in a globalized world, any systematic cross‐cultural differences should not be ignored. The present study investigated a possible stable cross‐cultural difference with the use of paired preference tests between two potential markets. For companies that sell their products in a variety of countries, such differences will need to be taken into account when interpreting paired preference data and accordingly are worthy of investigation.
Are ‘informative presuppositions’ presuppositions?
Authors: Tonhauser Judith 
Published: February 2015

AbstractPresuppositions are contents of utterances that must be mutually known by the interlocutors, i.e. the speaker and the addressees, in order for an utterance of a sentence with the presupposition trigger to be judged to be acceptable. However, a substantial subset of contents traditionally taken to be presuppositions does not exhibit this property and can instead be used to inform the addressee about the supposedly presuppositional content. Classical analyses of these so‐called ‘informative presuppositions’ nevertheless assume that they are associated with a common ground requirement but one that can be accommodated. According to an alternative characterization, ‘informative presuppositions’ are not associated with a common ground requirement but are informative like Potts' conventional implicatures; such a characterization does not need to make reference to accommodation. The debate about the characterization of ‘informative presuppositions’ has been based almost exclusively on judgments about English provided by native speaker researchers. This paper explores how results from research with theoretically untrained speakers (including one‐on‐one elicitation and experiments) as well as corpus studies can bear on this debate. I argue that such results, though tenuous, support the alternative characterization at least for some ‘informative presuppositions’ and emphasize the merit of bringing data collected through a wide range of methodologies to bear on theoretical research on meaning.
Demonstrating mood repair with a situation‐based measure of self‐compassion and self‐criticism
Authors: Falconer Caroline J. , King John A. , Brewin Chris R. 
Published: February 2015

ObjectivesThe clinical significance of self‐criticism and self‐compassion has prompted the development of questionnaires assessing these constructs. However, there is a lack of measures assessing their interaction within specific contexts and potential involvement in mood repair processes.DesignTo rectify this, we developed the Self‐Compassion and Self‐Criticism Scales (SCCS), based on responses to specific scenarios, and examined its psychometric properties in an online survey and an experimental situation.MethodIn study 1, standard psychometric procedures were used to investigate the reliability and validity of the SCCS. In study 2, an experimental challenge involving a difficult language task was used to test its sensitivity to change.ResultsIn study 1, exploratory factor analysis (n = 413) showed a clear two‐factor structure of the SCCS denoting two orthogonal scales, with high internal validity (α ≥ .87). Correlations between the SCCS and existing measures also demonstrated appropriate convergent validity. Study 2 (n = 90) provided preliminary evidence that the SCCS can detect changes in self‐appraisals. Participants receiving no performance feedback from the challenge task showed reduced state self‐criticism and increased state self‐compassion, demonstrating mood repair.ConclusionsThe SCCS has promise as a situational measure of self‐compassion and self‐criticism.Practitioner points

In the context of specific problem situations, clients' levels of self‐criticism and self‐compassion may well be orthogonal and can be assessed with the SCCS.

In setting treatment goals and assessing treatment outcome, it may be helpful to target both self‐compassion and self‐criticism separately.
Uniform Ergodicity of the Particle Gibbs Sampler
Authors: Lindsten Fredrik , Douc Randal , Moulines Eric 
Published: February 2015

AbstractThe particle Gibbs sampler is a systematic way of using a particle filter within Markov chain Monte Carlo. This results in an off‐the‐shelf Markov kernel on the space of state trajectories, which can be used to simulate from the full joint smoothing distribution for a state space model in a Markov chain Monte Carlo scheme. We show that the particle Gibbs Markov kernel is uniformly ergodic under rather general assumptions, which we will carefully review and discuss. In particular, we provide an explicit rate of convergence, which reveals that (i) for fixed number of data points, the convergence rate can be made arbitrarily good by increasing the number of particles and (ii) under general mixing assumptions, the convergence rate can be kept constant by increasing the number of particles superlinearly with the number of observations. We illustrate the applicability of our result by studying in detail a common stochastic volatility model with a non‐compact state space.