bluuebunny/crossref_metadata_2025 huggingface dataset:
Landscape structure and the genetic effects of a population collapse
Authors: Caplins Serena A. , Gilbert Kimberly J. , Ciotir Claudia , Roland Jens , Matter Stephen F. , Keyghobadi Nusha
Published: October 2014

Both landscape structure and population size fluctuations influence population genetics. While independent effects of these factors on genetic patterns and processes are well studied, a key challenge is to understand their interaction, as populations are simultaneously exposed to habitat fragmentation and climatic changes that increase variability in population size. In a population network of an alpine butterfly, abundance declined 60–100% in 2003 because of low over-winter survival. Across the network, mean microsatellite genetic diversity did not change. However, patch connectivity and local severity of the collapse interacted to determine allelic richness change within populations, indicating that patch connectivity can mediate genetic response to a demographic collapse. The collapse strongly affected spatial genetic structure, leading to a breakdown of isolation-by-distance and loss of landscape genetic pattern. Our study reveals important interactions between landscape structure and temporal demographic variability on the genetic diversity and genetic differentiation of populations. Projected future changes to both landscape and climate may lead to loss of genetic variability from the studied populations, and selection acting on adaptive variation will likely occur within the context of an increasing influence of genetic drift.
Structural and mechanistic insights into Mcm2–7 double-hexamer assembly and function
Authors: Sun Jingchuan , Fernandez-Cid Alejandra , Riera Alberto , Tognetti Silvia , Yuan Zuanning , Stillman Bruce , Speck Christian , Li Huilin
Published: October 2014

Eukaryotic cells license each DNA replication origin during G1 phase by assembling a prereplication complex that contains a Mcm2–7 (minichromosome maintenance proteins 2–7) double hexamer. During S phase, each Mcm2–7 hexamer forms the core of a replicative DNA helicase. However, the mechanisms of origin licensing and helicase activation are poorly understood. The helicase loaders ORC–Cdc6 function to recruit a single Cdt1–Mcm2–7 heptamer to replication origins prior to Cdt1 release and ORC–Cdc6–Mcm2–7 complex formation, but how the second Mcm2–7 hexamer is recruited to promote double-hexamer formation is not well understood. Here, structural evidence for intermediates consisting of an ORC–Cdc6–Mcm2–7 complex and an ORC–Cdc6–Mcm2–7–Mcm2–7 complex are reported, which together provide new insights into DNA licensing. Detailed structural analysis of the loaded Mcm2–7 double-hexamer complex demonstrates that the two hexamers are interlocked and misaligned along the DNA axis and lack ATP hydrolysis activity that is essential for DNA helicase activity. Moreover, we show that the head-to-head juxtaposition of the Mcm2–7 double hexamer generates a new protein interaction surface that creates a multisubunit-binding site for an S-phase protein kinase that is known to activate DNA replication. The data suggest how the double hexamer is assembled and how helicase activity is regulated during DNA licensing, with implications for cell cycle control of DNA replication and genome stability.
Swi/Snf dynamics on stress-responsive genes is governed by competitive bromodomain interactions
Authors: Dutta Arnob , Gogol Madelaine , Kim Jeong-Hoon , Smolle Michaela , Venkatesh Swaminathan , Gilmore Joshua , Florens Laurence , Washburn Michael P. , Workman Jerry L.
Published: October 2014

The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why such mechanisms are required to enhance Swi/Snf activity on nucleosomes. Snf2, the catalytic subunit of the Swi/Snf remodeling complex, has been shown to be a target of the Gcn5 acetyltransferase. Our study found that acetylation of Snf2 regulates both recruitment and release of Swi/Snf from stress-responsive genes. Also, the intramolecular interaction of the Snf2 bromodomain with the acetylated lysine residues on Snf2 negatively regulates binding and remodeling of acetylated nucleosomes by Swi/Snf. Interestingly, the presence of transcription activators mitigates the effects of the reduced affinity of acetylated Snf2 for acetylated nucleosomes. Supporting our in vitro results, we found that activator-bound genes regulating metabolic processes showed greater retention of the Swi/Snf complex even when Snf2 was acetylated. Our studies demonstrate that competing effects of (1) Swi/Snf retention by activators or high levels of histone acetylation and (2) Snf2 acetylation-mediated release regulate dynamics of Swi/Snf occupancy at target genes.
Arid3a is essential to execution of the first cell fate decision via direct embryonic and extraembryonic transcriptional regulation
Authors: Rhee Catherine , Lee Bum-Kyu , Beck Samuel , Anjum Azeen , Cook Kendra R. , Popowski Melissa , Tucker Haley O. , Kim Jonghwan
Published: October 2014

Despite their origin from the inner cell mass, embryonic stem (ES) cells undergo differentiation to the trophectoderm (TE) lineage by repression of the ES cell master regulator Oct4 or activation of the TE master regulator Caudal-type homeobox 2 (Cdx2). In contrast to the in-depth studies of ES cell self-renewal and pluripotency, few TE-specific regulators have been identified, thereby limiting our understanding of mechanisms underlying the first cell fate decision. Here we show that up-regulation and nuclear entry of AT-rich interactive domain 3a (Arid3a) drives TE-like transcriptional programs in ES cells, maintains trophoblast stem (TS) cell self-renewal, and promotes further trophoblastic differentiation both upstream and independent of Cdx2. Accordingly,Arid3a−/−mouse post-implantation placental development is severely impaired, resulting in early embryonic death. We provide evidence that Arid3a directly activates TE-specific and trophoblast lineage-specific genes while directly repressing pluripotency genes via differential regulation of epigenetic acetylation or deacetylation. Our results identify Arid3a as a critical regulator of TE and placental development through execution of the commitment and differentiation phases of the first cell fate decision.
Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming
Authors: Choi Jang Hyun , Choi Sun-Sil , Kim Eun Sun , Jedrychowski Mark P. , Yang Yong Ryoul , Jang Hyun-Jun , Suh Pann-Ghill , Banks Alexander S. , Gygi Steven P. , Spiegelman Bruce M.
Published: October 2014

Phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) at Ser273 by cyclin-dependent kinase 5 (CDK5) in adipose tissue stimulates insulin resistance, but the underlying molecular mechanisms are unclear. We show here that Thrap3 (thyroid hormone receptor-associated protein 3) can directly interact with PPARγ when it is phosphorylated at Ser273, and this interaction controls the diabetic gene programming mediated by the phosphorylation of PPARγ. Knockdown of Thrap3 restores most of the genes dysregulated by CDK5 action on PPARγ in cultured adipocytes. Importantly, reduced expression of Thrap3 in fat tissue by antisense oligonucleotides (ASOs) regulates a specific set of genes, including the key adipokines adiponectin and adipsin, and effectively improves hyperglycemia and insulin resistance in high-fat-fed mice without affecting body weight. These data indicate that Thrap3 plays a crucial role in controlling diabetic gene programming and may provide opportunities for the development of new therapeutics for obesity and type 2 diabetes.
Structures of K42N and K42Y sperm whale myoglobins point to an inhibitory role of distal water in peroxidase activity
Authors: Wang Chunxue , Lovelace Leslie L. , Sun Shengfang , Dawson John H. , Lebioda Lukasz
Published: October 2014

Sperm whale myoglobin (Mb) functions as an oxygen-storage protein, but in the ferric state it possesses a weak peroxidase activity which enables it to carry out H2O2-dependent dehalogenation reactions. Hemoglobin/dehaloperoxidase fromAmphitrite ornata(DHP) is a dual-function protein represented by two isoproteins DHP A and DHP B; its peroxidase activity is at least ten times stronger than that of Mb and plays a physiological role. The `DHP A-like' K42Y Mb mutant (K42Y) and the `DHP B-like' K42N mutant (K42N) were engineered in sperm whale Mb to mimic the extended heme environments of DHP A and DHP B, respectively. The peroxidase reaction rates increased ∼3.5-fold and ∼5.5-fold in K42Y and K42NversusMb, respectively. The crystal structures of the K42Y and K42N mutants revealed that the substitutions at position 42 slightly elongate not only the distances between the distal His55 and the heme iron but also the hydrogen-bonding distances between His55 and the Fe-coordinated water. The enhanced peroxidase activity of K42Y and K42N thus might be attributed in part to the weaker binding of the axial water molecule that competes with hydrogen peroxide for the binding site at the heme in the ferric state. This is likely to be the mechanism by which the relationship `longer distal histidine to Fe distance – better peroxidase activity', which was previously proposed for heme proteins by Matsuiet al.(1999) (J. Biol. Chem.274, 2838–2844), works. Furthermore, positive cooperativity in K42N was observed when its dehaloperoxidase activity was measured as a function of the concentration of the substrate trichlorophenol. This serendipitously engineered cooperativity was rationalized by K42N dimerization through the formation of a dityrosine bond induced by excess H2O2.
The structural basis of urea-induced protein unfolding in β-catenin
Authors: Wang Chao , Chen Zhongzhou , Hong Xia , Ning Fangkun , Liu Haolin , Zang Jianye , Yan Xiaoxue , Kemp Jennifer , Musselman Catherine A. , Kutateladze Tatinna G. , Zhao Rui , Jiang Chengyu , Zhang Gongyi
Published: October 2014

Although urea and guanidine hydrochloride are commonly used to denature proteins, the molecular underpinnings of this process have remained unclear for a century. To address this question, crystal structures of β-catenin were determined at various urea concentrations. These structures contained at least 105 unique positions that were occupied by urea molecules, each of which interacted with the protein primarilyviahydrogen bonds. Hydrogen-bond competition experiments showed that the denaturing effects of urea were neutralized when polyethylene glycol was added to the solution. These data suggest that urea primarily causes proteins to unfold by competing and disrupting hydrogen bonds in proteins. Moreover, circular-dichroism spectra and nuclear magnetic resonance (NMR) analysis revealed that a similar mechanism caused protein denaturation in the absence of urea at pH levels greater than 12. Taken together, the results led to the conclusion that the disruption of hydrogen bonds is a general mechanism of unfolding induced by urea, high pH and potentially other denaturing agents such as guanidine hydrochloride. Traditionally, the disruption of hydrophobic interactions instead of hydrogen bonds has been thought to be the most important cause of protein denaturation.
Enzyme–substrate complex structures of CYP154C5 shed light on its mode of highly selective steroid hydroxylation
Authors: Herzog Konrad , Bracco Paula , Onoda Akira , Hayashi Takashi , Hoffmann Kurt , Schallmey Anett
Published: October 2014

CYP154C5 fromNocardia farcinicais a bacterial cytochrome P450 monooxygenase active on steroid molecules. The enzyme has recently been shown to exhibit exclusive regioselectivity and stereoselectivity in the conversion of various pregnans and androstans, yielding 16α-hydroxylated steroid products. This makes the enzyme an attractive candidate for industrial application in steroid hormone synthesis. Here, crystal structures of CYP154C5 in complex with four different steroid molecules were solved at resolutions of up to 1.9 Å. These are the first reported P450 structures from the CYP154 family in complex with a substrate. The active site of CYP154C5 forms a flattened hydrophobic channel with two opposing polar regions, perfectly resembling the size and polarity distribution of the steroids and thus resulting in highly specific steroid binding withKdvalues in the range 10–100 nM. Key enzyme–substrate interactions were identified that accounted for the exclusive regioselectivity and stereoselectivity of the enzyme. Additionally, comparison of the four CYP154C5–steroid structures revealed distinct structural differences, explaining the observed variations in kinetic data obtained for this P450 with the steroids pregnenolone, dehydroepiandrosterone, progesterone, androstenedione, testosterone and nandrolone. This will facilitate the generation of variants with improved activity or altered selectivity in the future by means of protein engineering.
Coping with career boundaries and boundary-crossing in the graduate labour market
Authors: Okay-Somerville Belgin , Scholarios Dora
Published: October 2014

Purpose

– The purpose of this paper is to explore the nature and role of career boundaries for enabling/constraining career self-management (CSM) for occupational boundary-crossing in the UK graduate labour market (GLM).

Design/methodology/approach

– The data are provided by career history interviews with 36 UK graduates. The analysis contrasts transitions for those who started careers in low-, intermediate-, and high-skilled segments of the labour market.

Findings

– Availability of development and progression opportunities were the most prominent career boundary experienced. Ease of boundary-crossing differed by career stage and educational background. Boundaries enabled CSM by acting as psychological/external push factors, but push factors only aided progression to high-skilled segments for a third of graduates who started careers in underemployment. For the rest, an adaptation of expectations to labour market realities was observed.

Research limitations/implications

– Although career history interviews limit generalisability, they contextualise boundaries and deepen understanding of career actors’ subjective experiences and responses.

Practical implications

– The study highlights the role of labour market and demand-side constraints for career transitions as well as proactive career behaviours. This has implications for career counsellors, employers, and individuals.

Originality/value

– This paper provides a distinctive “boundary-focused” analysis of emerging career boundaries in the GLM. The findings point to the intricate interplay between structure and agency for career development.
Continuous training, job satisfaction and gender
Authors: Burgard Claudia , Görlitz Katja
Published: October 2014

Purpose

– The purpose of this paper is to analyze the relationship between participation in further training courses and job satisfaction, focussing in particular on gender differences.

Design/methodology/approach

– Using data from the German Socio-Economic Panel (SOEP), a Probit-adapted OLS (POLS) model is employed which allows to account for individual fixed effects. The analysis controls for a variety of socio-demographic, job and firm characteristics.

Findings

– The authors find a difference between males and females in the correlation between training and job satisfaction which is positive for males but insignificant for females. This difference becomes even more pronounced when applying individual fixed effects. To gain insights into the reasons for this difference, the authors further investigate training characteristics by gender. The authors find that financial support and career-orientation of courses only seems to matter for the job satisfaction of men but not for the satisfaction of women.

Practical implications

– In Germany, financial support and career-orientation of training courses only seem to matter for the job satisfaction of men but not for the satisfaction of women. This has important implications for the investment in and outcomes of these training endeavors from both, a participant and an employer perspective.

Originality/value

– This paper extends the existing literature in several ways. The authors use job satisfaction as an outcome of training which comprises non-pecuniary returns in addition to monetary returns. In addition, the authors point out gender differences and examine the heterogeneity of training courses by gender. This seems important since job satisfaction processes differ to a large extent by gender and since it is well-known that training participation also differs by gender. The panel structure of the data enables a methodological advancement in terms of accounting for time-invariant unobserved heterogeneity which is likely to matter for the results.
Evaluating brief cognitive behavioural therapy within primary care
Authors: McHugh Patrick , Gordon Michael , Byrne Michael
Published: October 2014

Purpose

– The purpose of this paper is to evaluate the clinical effectiveness of a brief CBT intervention within a primary care adult mental health service.

Design/methodology/approach

– In total, 92 participants with mild to moderate mental health difficulties were provided with five sessions of brief CBT. Clinical improvement was measured using the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) at pre-treatment, mid-treatment and post-treatment, and on the Beck Depression Inventory-II (BDI-II) at pre-treatment and post-treatment.

Findings

– The planned five sessions of CBT were completed by 48.9 percent (n=45) of participants. Treatment completers with full clinical data (n=31) showed large statistically significant improvements on the CORE-OM and BDI-II from pre-therapy to post-therapy. Of treatment completers and non-completers with post-therapy and mid-therapy CORE-OM data, respectively (n=34), 61.8 percent showed reliable and clinically significant change. No statistically significant differences were found between treatment completers (n=45) and non-completers (n=47) in their pre-therapy clinical scores or socio-demographic characteristics.

Practical implications

– Brief CBT can be a clinically effective primary care intervention but needs to be implemented in a way that ensures high treatment engagement across a range of service users.

Originality/value

– This paper contributes to the evidence base of a primary care psychological intervention and demonstrates the importance of assessing treatment completion when evaluating clinical effectiveness.
Reorientation of three‐component borehole magnetic data
Authors: Virgil C. , Ehmann S. , Hördt A. , Leven M. , Steveling E.
Published: October 2014

Three‐component borehole magnetics provide important additional information compared to total field or horizontal and vertical measurements. These data can be used for several tasks such as the localization of ferromagnetic objects, the determination of apparent polar wander curves and the computation of the magnetization of rock units. However, the crucial point in three‐component borehole magnetics is the reorientation of the measured data from the tool's frame to the geographic reference frame North, East and Downwards. For this purpose, our tool, the Göttinger Borehole Magnetometer, comprises three orthogonally aligned fibre optic gyros along with three fluxgate sensors. With these sensors, the vector of the magnetic field along with the tool rotation can be recorded continuously during the measurement. Using the high–precision gyro data, we can compute the vector of the magnetic anomaly with respect to the Earth's reference frame. Based on the comparison of several logs measured in the Outokumpu Deep Drill Hole (OKU R2500, Finland), the repeatability of the magnetic field vector is 0.8° in azimuthal direction, 0.08° in inclination and 71 nT in magnitude.
Contrasting effects of phylogenetic relatedness on plant invader success in experimental grassland communities
Authors: Li Shao‐peng , Guo Tao , Cadotte Marc W. , Chen Yong‐jian , Kuang Jia‐liang , Hua Zheng‐shuang , Zeng Yi , Song Ying , Liu Zheng , Shu Wen‐sheng , Li Jin‐tian
Published: October 2014

Identifying the factors determining the success of invasive species is critical for management of biological invasions. Darwin's naturalization conundrum states that exotic species closely related to natives should be successful because of a shared affinity for local environmental conditions, but at the same time close relatives often compete more intensively, limiting ‘niche’ opportunities for the invaders. Previous studies have generally considered these two ‘opposing’ hypotheses as mutually exclusive, yet evidence for both of them abounds, indicating a practical dilemma for management of biological invasions.

In this study, we sowed the seeds of the invasive exotic Ambrosia artemisiifolia L. into 369 experimental plant communities to mimic an introduction of the exotics into a series of new habitats. We further linked the establishment and growth performance of the invader in these experimental communities to the phylogenetic relatedness between the invader and the community residents where it was introduced.

We found that the probability of invader establishment declined with increasing phylogenetic distance between the invader and residents, whereas the average size of surviving invader individuals increased with the phylogenetic distance.

These results can be at least partly explained by the observations that close relatives tend to create similar soil microhabitat through harbouring similar soil enzymes (e.g. alkaline and acid phosphatases) benefiting invader establishment and that intense competitive interactions between the invader and its close relatives suppressed exotic growth.

Synthesis and applications. This study presents the first experimental evidence that phylogenetic relatedness has contrasting effects on different aspects of invader success, thus shedding light on the long‐standing Darwin's naturalization conundrum. Moreover, our findings also have important implications for management of plant invasions: for controlling invasive species characterized by high establishment probability, native species distantly related to the invasive species can be planted in sites surrounding the invasion foci, whereas the opposite seems to be true for controlling those characterized by large individual size.
Dispensing of potentially teratogenic drugs before conception and during pregnancy: a population‐based study
Authors: Zomerdijk IM , Ruiter R , Houweling LMA , Herings RMC , Straus SMJM , Stricker BH
Published: October 2014

Objective

To study the dispensing of potentially teratogenic drugs in the 12‐month period before as well as during pregnancy in the Netherlands.

Design

Population‐based study.

Setting

A cohort was constructed using a linkage between the PHARMO Database Network and the Netherlands Perinatal Registry (PRN).

Population

A total of 203 962 Dutch pregnancies reported between 1999 and 2007

Methods

Drug‐dispensing information was identified from the PHARMO Database Network for the 12‐month period before conception and during pregnancy. Drugs with either a Swedish FASS ‘D’ classification, an Australian ADEC or American FDA ‘D’ or ‘X’ classification were considered potentially teratogenic (n = 202).

Mean outcome measures

Proportion of pregnancies that received potentially teratogenic drugs in the 12‐month period before and during pregnancy and specific for the risk category X drugs and newly initiated drugs.

Results

Sixteen percent of the pregnancies received a potentially teratogenic drug in the 12‐month period before and 5.07% during pregnancy. Doxycycline and paroxetine were most frequently received during pregnancy by 1.01% and 0.85% of women, respectively; 0.66% of the women received a risk category X drug during pregnancy which most frequently consisted of triptorelin (0.25%), norethisterone (0.22%) and simvastatin (0.03%). Fifty‐three percent of the women who received a potentially teratogenic drug during pregnancy received this for the first time during the study period. These percentages were heterogeneous between therapeutic drug classes.

Conclusions

Five percent of the pregnancies received a potentially teratogenic drug during pregnancy and 0.66% received a drug from the risk category X. It may be possible to reduce these proportions when reasons for prescription have been explored.
Psychological distress, burnout level and job satisfaction in emergency medicine: A cross‐sectional study of physicians in China
Authors: Xiao Yunbei , Wang Jinguo , Chen Si , Wu Zhigang , Cai Jian , Weng Zhiliang , Li Chengdi , Zhang Xiaowei
Published: October 2014

Background

Chinese physicians are not only facing heavy work overloads, but also abuse and injury because of patient mistrust of physicians. The primary objective of the present study was to measure psychological distress, burnout levels and job satisfaction among Chinese emergency physicians.

Methods

All the physicians from the EDs of three large general hospitals were recruited to undertake a questionnaire‐based survey from March to April 2012. The Hospital Anxiety and Depression Scale (HADS), Maslach Burnout Inventory‐General Survey and Minnesota Satisfaction Questionnaire were used. Correlations between job satisfaction and psychological distress and burnout were calculated using the Pearson correlation. An outcome was considered statistically significant if P < 0.05.

Results

Completed questionnaires were received from 205 (82.0%) physicians. The mean HADS anxiety subscale scores for the ED physicians and general population were 7.8 ± 3.4 and 4.7 ± 3.5, respectively (t = 1.526, P < 0.05). Additionally, the mean HADS depression subscale scores were 7.9 ± 3.6 and 4.7 ± 3.9, respectively (t = 1.567, P < 0.05). Fifty‐two (25.4%) exhibited high levels of career burnout. All aspects of job satisfaction were significantly lower in the ED physicians compared with a previous report (P < 0.05). Burnout was significantly negatively correlated with intrinsic and extrinsic job satisfaction in the sampled population.

Conclusion

Psychological distress is prevalent in this group of ED physicians, and it deserves attention from the whole society. Burnout and job satisfaction among ED physicians are at a ‘moderate’ level. Burnout is negatively associated with higher job satisfaction.
Coherences of Instrumental and Sensory Characteristics: Case Study on Cherry Tomatoes
Authors: Csambalik László , Divéky‐Ertsey Anna , Pap Zoltán , Orbán Csaba , Stégerné Máté Mónika , Gere Attila , Stefanovits‐Bányai Éva , Sipos László
Published: October 2014

The aim of this study was to investigate 6 cherry tomato varieties in terms of morphological, instrumental, and sensory attributes. Hungarian cherry tomato landraces have not been investigated in comparison with new commercial varieties for these traits. Parameters investigated were water‐soluble antioxidant capacity (FRAP, DPPH, and TEAC), and total polyphenol, vitamin C, β‐carotene, lycopene, total soluble solids, and acid contents. Colorimetric measurements as well as sensory analyses were conducted. It was concluded that varied antioxidant assays should be used in parallel to overcome the selectivity of any 1 method. Total phenolic content significantly contributed to results of antioxidant assays for the investigated varieties. The sensory profiles of the 6 cherry tomato varieties have been created. The differences between the products based on the 18 attributes were analyzed by Tukey post hoc test. The biplot of the principal component analysis showed that the sensory panel could discriminate the samples along the principal components. No correlation was found between colorimetric data a* and b* measured from pulp and lycopene, but a negative connection of β‐carotene and hue was noted. Total polyphenol content showed correlations with colorimetric results, except for b*. The influence of tomato skin color on color perception is significant as in the present study instrumental data measured from pulp did not match that of the panelists evaluating intact fruit. Instrumental results of sugar content were supported by the ratings of the sensory panel.
Effect of Nicorandil in Patients with Heart Failure: A Systematic Review and Meta‐Analysis
Authors: Zhao Fujie , Chaugai Sandip , Chen Peng , Wang Yan , Wang Dao Wen
Published: October 2014

Background and purpose

It is unclear whether nicorandil, a metabolic therapeutic drug, can be applied clinically to therapy of heart failure (HF). This meta‐analysis evaluated therapeutic effects of nicorandil on HF patients.

Experimental approach

We performed a systematic review and meta‐analysis of published studies evaluating effect of nicorandil on HF patients. Studies were stratified according to controlled versus uncontrolled designs and analyzed using random‐effects meta‐analysis models.

Key results

We identified a total of 20 studies with a total of 1222 patients. In five randomized controlled studies, nicorandil treatment resulted in reduction in all‐cause mortality and hospitalization for cardiac causes (HR: 0.35, P < 0.001) and improved cardiac pump function (SMD: 0.31, P = 0.02). In 15 observational studies, nicorandil therapy increases cardiac pump function (SMD: 0.75, P < 0.001), improves NYHA functional class (WMD: −1.33, P < 0.001), decreases PCWP (WMD: −6.86 mm Hg, P < 0.001), and pulmonary arterial pressure (SMD: −0.84, P < 0.001).

Conclusions and implications

The use of nicorandil in HF patients exerts substantial beneficial effects, suggesting that it may be an additional therapeutic agent for HF.
Rosuvastatin May Reduce the Incidence of Cardiovascular Events in Patients with Acute Coronary Syndromes Receiving Percutaneous Coronary Intervention by Suppressing miR‐155/SHIP‐1 Signaling Pathway
Authors: Xie Wenchao , Li Ping , Wang Zhengdong , Chen Jian , Lin Zhihai , Liang Xiangwen , Mo Yingxi
Published: October 2014

Purpose

The beneficial effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied.

Methods

Patients with ACS receiving PCI (n = 159) were randomized to control group (placebo treatment) or to rosuvastatin group (20 mg 12 h before PCI, and a further 20 mg 2 h preprocedure dose). Levels of INF‐γ, TNF‐α, IL‐6, miR‐155/SHIP‐1, and CD4+FoxP3+Treg in peripheral blood were detected before PCI and 24 h after PCI. Clinical data of these patients were also collected in this prospective study.

Results

Compared with placebo, rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infarction (PMI) and levels of cardiac troponin I (cTnI) associated with decreased relative expression of serum miR‐155, levels of inflammatory cytokines (INF‐γ, TNF‐α, and IL‐6), increased SHIP‐1 expression and CD4+FoxP3+Treg percentage values (P < 0.05). In addition, patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events (MACE) compared to the patients with placebo treatment (16 patients vs. 28 patients, P = 0.038).

Conclusions

Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI, which may be explained at least in part, by mechanism involving suppression of miR‐155/SHIP‐1 signaling pathway.
Comparison of osteotomy versus non‐osteotomy approach for congenital scoliosis: a retrospective study of three surgical techniques
Authors: Li Shenghua , Ou Yunsheng , Liu Bo , Zhu Yong , Quan Zhengxue , Jiang Dianming
Published: October 2014

Background

Currently, there are many reports about congenital scoliosis (CS) treatment, but there are still controversies existing with respect to selecting its surgical methods.

Methods

Retrospective analyses were conducted on 31 CS patients. The surgical treatments included the following: posterior instrumentation (10 patients; group 1), pedicle subtraction osteotomy (11 patients; group 2) and vertebral column resection (10 patients; group 3).

Results

All patients had remarkable improvements in morphology, image findings, visual analogue scale and American Spinal Injury Association classification. Groups 2 and 3 had greater preoperative sagittal Cobb's angle (25.0, 62.2 and 9.2°, respectively), greater intra‐operative blood loss (604.5, 620.0 and 460.0 mL, respectively) and fewer fused segments (5.8, 6.3 and 9.2, respectively) than group 1. As compared with group 1, groups 2 and 3 had greater correction rate of coronal Cobb's angle (79.6 ± 12.8, 78.2 ± 10.1% versus 56.1 ± 11.1%), and coronal trunk inclination (77.6 ± 14.2, 85.2 ± 11.0% versus 45.0 ± 42.5%). The sagittal Cobb's angle correction rates of three groups were 67.7 ± 42.9, 79.3 ± 27.6, 84.3 ± 12.1%, respectively, which showed no significant difference (P = 0.461). With an average follow‐up of 3.5, 3.2 and 4.0 years, the correction loss rate of coronal Cobb's angle in group 1 was higher than those of groups 2 and 3.

Conclusion

For CS patients, osteotomy procedure had less fused segments, along with a greater correction rate and lower correction loss, which were more advantageous for those with severe deformity in sagittal plane or nerve decompression requirements.
Quantitative efficacy of soy isoflavones on menopausal hot flashes
Authors: Li Lujin , Lv Yinghua , Xu Ling , Zheng Qingshan
Published: October 2014

Aim

This study aimed to quantitate the efficacy of soy isoflavones in the treatment of menopausal hot flashes.

Methods

Model based meta‐analysis (MBMA) was used to quantitate the efficacy of soy isoflavones. We conducted a systemic literature search to build a time–effect model for placebo and soy isoflavones in treating menopausal hot flashes. Studies were identified, subjected to inclusion and exclusion criteria, and reviewed.

Results

From 55 articles, 16 studies of soy isoflavones met the inclusion criteria, and contained 65 and 66 mean effect values in placebo and soy isoflavone groups, respectively, from about 1710 subjects. Interestingly, the developed model was found to describe adequately the time course of hot flashes reduction after administration of placebo and soy isoflavones. Using this model, we found that the maximal percentage change of hot flashes reduction by soy isoflavones was 25.2% after elimination of the placebo effect, accounting for 57% of the maximum effects of estradiol (Emax‐estradiol = 44.9%). However, a time interval of 13.4 weeks was needed for soy isoflavones to achieve half of its maximal effects, much longer than estradiol, which only required 3.09 weeks. These results suggest that treatment intervals of 12 weeks are too short for soy isoflavones, which require at least 48 weeks to achieve 80% of their maximum effects.

Conclusions

Soy isoflavones show slight and slow effects in attenuating menopausal hot flashes compared with estradiol.
A Joint Model for Multistate Disease Processes and Random Informative Observation Times, with Applications to Electronic Medical Records Data
Authors: Lange Jane M. , Hubbard Rebecca A. , Inoue Lurdes Y. T. , Minin Vladimir N.
Published: October 2014

Multistate models are used to characterize individuals’ natural histories through diseases with discrete states. Observational data resources based on electronic medical records pose new opportunities for studying such diseases. However, these data consist of observations of the process at discrete sampling times, which may either be pre-scheduled and non-informative, or symptom-driven and informative about an individual's underlying disease status. We have developed a novel joint observation and disease transition model for this setting. The disease process is modeled according to a latent continuous-time Markov chain; and the observation process, according to a Markov-modulated Poisson process with observation rates that depend on the individual's underlying disease status. The disease process is observed at a combination of informative and non-informative sampling times, with possible misclassification error. We demonstrate that the model is computationally tractable and devise an expectation-maximization algorithm for parameter estimation. Using simulated data, we show how estimates from our joint observation and disease transition model lead to less biased and more precise estimates of the disease rate parameters. We apply the model to a study of secondary breast cancer events, utilizing mammography and biopsy records from a sample of women with a history of primary breast cancer.
Papier‐mach(in)e: Thinking with “sticky”paper in the cloud
Authors: Enriquez‐Gibson Judith
Published: October 2014

There is nothing less about paper and its use when it comes to academic study as we experience increasingly converging media spaces and functionalities of online applications within the screens of our laptops, mobile phones and tablet devices. The paper persists, and the paperless office, classroom and pedagogy become nothing but pure rhetoric. Hence, it is most pertinent to focus on paper and its “stickiness” in maintaining educational structures and practices. Usually hidden from view or neglected in educational technology studies is a consideration on how we think and interact not only with our mind but also with our heads and limbs. This paper will argue that paper has a composite place or bearing, a kind of stickiness to our technologised bodies, digital mobilities and hybrid practices in what I have coined here aspapier‐mach(in)e. This claim will be supported by evidence that demonstrates how we simply think both practically and pathically and that our mobilities in media and physical spaces are in one form or another meshed with paper. In fact, a drive towards a paperless classroom or pedagogy is without much foundation when it comes to mobilising a sustainable agenda for technology‐enhanced learning.
Increasing performance by differentiated teaching? Experimental evidence of the student benefits of digital differentiation
Authors: Haelermans Carla , Ghysels Joris , Prince Fernao
Published: October 2014

This paper explores the effect of digital differentiation on student performance using a randomized experiment. The experiment is conducted in a second year biology class among 115 prevocational students in the Netherlands. Differentiation allowed students in the treatment group to work at three different levels. The results show that there is a significant effect of digital differentiation on the posttest score. This effect is robust to adding covariates such as students' ability, grade repetition, age, gender, class and average neighborhood income. There are no differential effects when dividing students in three groups, by ability. The results imply that differentiation in large classrooms is possible and beneficial for all students, once done digitally.
The scale for the self‐efficacy and perceptions in the safe use of the Internet for teachers: The validity and reliability studies
Authors: Cavus Nadire , Ercag Erinc
Published: October 2014

There has been an increase in the vulnerability in Internet security, and the unconscious usage of the Internet is a very important issue throughout the world as it is in Cyprus today. The best way to solve such an issue would be to make people aware of this situation. Based on this idea, teachers should firstly be trained to use the Internet in a safe and conscious manner so to be able to aid their students and the student's parents in the correct and safe usage of the Internet. The aim of this study is to determine teachers' self‐efficacy and perceptions in safer use of the Internet so to be able to identify and develop a multidimensional tool, which is both valid and reliable, and can be therefore used in other scientific studies as well. Through a confirmatory factor analysis, the “Scale for the Self‐Efficacy and Perceptions in the Safe Use of the Internet for Teachers” was validated in four dimensions: “Security in Social Networking Sites,” “Malicious Software,” “Web Security & Social Engineering” and “Computer Security,” The scale developed has the characteristics of being the first of its kind in a developing country such as Cyprus. According to the results of the study, the scale in terms of validity and reliability was found to be appropriate in all aspects of the necessary criteria. As a result, the developed scale could help or be used by teachers, in Cyprus and in other countries, to be able to access the Internet safely and aid them in other scientific areas of study in determining teachers' self‐efficacy.
Internal structure of virtual communications in communities of inquiry in higher education: Phases, evolution and participants' satisfaction
Authors: Gutierrez‐Santiuste Elba , Gallego‐Arrufat Maria‐Jesus
Published: October 2014

This study investigates the phases of development of synchronous and asynchronous virtual communication produced in a community of inquiry (CoI) by analyzing the internal structure of each intervention in the forum and each chat session to determine the evolution of their social, cognitive and teaching character. It also analyzes the participating higher education students' satisfaction with the activities, with the professors' actions, and with themselves. We use a mixed methodology that includes content analysis of the virtual communications by crossing two categorization systems: (1) type of communication according to the model adopted from Garrison, Anderson and Archer (social, cognitive and teaching presence) and (2) phases in the evolution of the communication (initiation, proposal, development, opinion/closing and good‐byes). The data are relevant to the students' satisfaction and grades earned. The results suggest differences in the quantity and content of the communication in each phase and an evolution from social to cognitive elements, ending with social contributions. The students are satisfied with the virtual communications related to both the activities and the professors and evaluate themselves positively.
Barriers to blended digital distance vocational learning for non‐traditional students
Authors: Safford Kimberly , Stinton Julia
Published: October 2014

This research identifies and examines the challenges of blending digital distance and vocational learning for non‐traditional and low‐socio‐economic status students who are new to university education. A survey of students in vocational primary education and early years qualifications in a distance university is illuminated by interviews with individual students and video diaries recorded by them during module study. Barriers to study include where and when to go online, finding support for digital study, navigating virtual learning environments and knowing what is relevant, variable or no technologies in the workplace, making connections between workplace technologies and ICT for study, and storing and organising digital information. As university education goes increasingly online, the research aims to improve institutional awareness and provision for widening participation. The research findings suggest practical changes to ameliorate experiences of digital distance vocational learning and by these means to improve student retention, progression and completion.
Sjögren Syndrome‐associated lymphomas: an update on pathogenesis and management
Authors: Nocturne Gaetane , Mariette Xavier
Published: October 2014

Primary Sjögren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low‐grade B cell non‐Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa‐associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)‐like structures, high TNFSF13B (BAFF) and Flt3‐ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto‐immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto‐antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF‐kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen‐driven B‐cell lymphoma. The control of disease activity by a well‐targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.
Defining greed
Authors: Seuntjens Terri G. , Zeelenberg Marcel , Breugelmans Seger M. , van de Ven Niels
Published: October 2014

Although greed is both hailed as the motor of economic growth and blamed as the cause of economic crises, very little is known about its psychological underpinnings. Five studies explored lay conceptualizations of greed among US and Dutch participants using a prototype analysis. Study 1 identified features related to greed. Study 2 determined the importance of these features; the most important features were classified as central (e.g., self‐interested, never satisfied), whereas less important features were classified as peripheral (e.g., ambition, addiction). Subsequently, we found that, compared to peripheral features, participants recalled central features better (Study 3), faster (Study 4), and these central features were more present in real‐life episodes of greed (Study 5). These findings provide a better understanding of the elements that make up the experience of greed and provide insights into how greed can be manipulated and measured in future research.
Optimal prosthesis sizing in transcatheter aortic valve implantation by exclusive use of three‐dimensional transoesophageal echocardiography
Authors: Kretzschmar Daniel , Lauten Alexander , Goebel Bjoern , Doenst Torsten , Poerner Tudor C. , Ferrari Markus , Figulla Hans R. , Hamadanchi Ali
Published: October 2014

Purpose

The assessment of aortic annular size is critical, and inappropriate sizing is thought to be a main reason of paravalvular aortic regurgitation. Multidetector computed tomograph is associated with the risk of contrast nephropathy. For optimal evaluation of the complex structure of the aortic annulus, three‐dimensional (3D)‐methods should be used. We therefore sought to determine the value of 3D‐transoesophageal echocardiography (3D‐TEE) for appropriate sizing.

Methods

Hundred and one patients (mean age 81·4 years) with symptomatic aortic valve stenosis (AS) and high surgical risk profile (mean log. EuroScore 28·8%) being scheduled for transcatheter aortic valve implantation (TAVI) were included. 2D‐ and 3D‐TEE were performed before the procedure to evaluate the aortic annulus diameter.

Results

Maximum, minimum and mean (max diameter + min diameter/2) annulus diameters were 24·7, 23·1 and 23. 9 mm in 3D‐TEE and compared to 22·6 mm in 2D‐TEE (P<0·001; 0·07; <0·001). The interobserver variability for 3D‐TEE was low with a mean difference of 0·18 mm compared to 2D‐TEE with 0·59 mm. The application of 3D‐TEE caused a change of prosthesis size selection in 40% of patients compared to 2D‐TEE. In this study, we implanted three different types of catheter‐mounted valves (Edwards‐SAPIEN™ XT valve, CoreValve™ and JenaValve™). Final angiography confirmed valve competence (mild insufficiency) in 91%, and there was no aortic regurgitation greater than moderate in the follow‐up echocardiographic evaluation.

Conclusion

Assessment of aortic annulus dimensions for TAVI size selection can safely be performed with 3D‐TEE only. Based on our results with significantly higher annulus diameter compared to 2D‐TEE, we recommend 3D‐TEE to reduce prosthesis undersizing.