bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Effectiveness and Safety of Treatment With Anti–Tumor Necrosis Factor α Drugs in a Cohort of Colombian Patients With Rheumatoid Arthritis
Authors: Santos-Moreno Pedro , Sánchez-Vanegas Guillermo
Published: May 2019

Objective

To compare the clinical response at 24 months and evaluate the adverse events (AEs) of patients with rheumatoid arthritis (RA) treated with etanercept 50 (injectable solution 50 mg prefilled syringe), etanercept 25 (lyophilized 25 mg), infliximab, adalimumab, or golimumab.

Methods

A cohort study was carried out in patients with RA, in treatment with etanercept (injectable solution 50 mg prefilled syringe or lyophilized 25 mg), infliximab, adalimumab, or golimumab. Duration of study: follow-up was carried out for 24 months. The difference of initial and final 28-joint Disease Activity Score, remission incidence, difference of initial and final Health Assessment Questionnaire score, disability recovery, and AE rate were evaluated.

Results

The study enrolled 435 patients (108 adalimumab, 107 infliximab, 92 etanercept 25 mg, 81 etanercept 50 mg, and 47 golimumab). For etanercept 50, the median difference between basal and at the end of follow-up 28-joint Disease Activity Score was 1.7. For golimumab, it was 1.4; for adalimumab, it was 1.1; for etanercept 25, it was 1.02; and for infliximab, it was 0.96 (p = 0.001). The median difference between basal and final Health Assessment Questionnaire ranged was 1.66 for etanercept 50, 1.34 for etanercept 25, 1.3 for golimumab, 1.24 for adalimumab, and 1.07 for infliximab (p = 0.0005). Comparatively, etanercept 50 presented the highest cumulative incidence (77%; 95% confidence interval [CI], 67%–86%) and remission incidence (64 cases per 100 person-months; 95% CI, 4.9–8.1 cases per 100 person-months) and the lowest AE rate (8.6 per 100 person-years; 95% CI, 5.3–15 per 100 person-years).

Conclusions

In patients with RA treated with anti–tumor necrosis factor α drugs, the highest incidence of remission and the lowest rate of AEs were documented for the cohort exposed to etanercept 50 mg.
Efficient differentiation and polarization of primary cultured neurons on poly(lactic acid) scaffolds with microgrooved structures
Authors: Otomo Asako , Ueda Mahoko Takahashi , Fujie Toshinori , Hasebe Arihiro , Okamura Yosuke , Takeoka Shinji , Hadano Shinji , Nakagawa So
Published: May 2019

Synthetic biodegradable polymers including poly(lactic acid) (PLA) are attractive cell culture substrates because their surfaces can be micropatterned to support cell adhesion. The cell adhesion properties of a scaffold mainly depend on its surface chemical and structural features; however, it remains unclear how these characteristics affect the growth and differentiation of cultured cells or their gene expression. In this study, we fabricated two differently structured PLA nanosheets: flat and microgrooved. We assessed the growth and differentiation of mouse primary cultured cortical neurons on these two types of nanosheets after pre-coating with poly-D-lysine and vitronectin. Interestingly, prominent neurite bundles were formed along the grooves on the microgrooved nanosheets, whereas thin and randomly extended neurites were only observed on the flat nanosheets. Comparative RNA sequencing analyses revealed that the expression of genes related to postsynaptic density, dendritic shafts, and asymmetric synapses was significantly and consistently up-regulated in cells cultured on the microgrooved nanosheets when compared with those cultured on the flat nanosheets. These results indicate that microgrooved PLA nanosheets can provide a powerful means of establishing a culture system for the efficient and reproducible differentiation of neurons, which will facilitate future investigations of the molecular mechanisms underlying the pathogenesis of neurological disorders.
Chromatin-enriched RNAs mark active and repressive cis-regulation: an analysis of nuclear RNA-seq
Authors: Sun Xiangying , Wang Zhezhen , Perez-Cervantes Carlos , Ruthenburg Alex , Moskowitz Ivan , Gribskov Michael , Yang Xinan Holly
Published: May 2019

Long noncoding RNAs (lncRNAs) localize in the cell nucleus and influence gene expression through a variety of molecular mechanisms. RNA sequencing of two biochemical fractions of nuclei reveals a unique class of lncRNAs, termed chromatin-enriched nuclear RNAs (cheRNAs) that are tightly bound to chromatin and putatively function to cis-activate gene expression. Until now, a rigorous analytic pipeline for nuclear RNA-seq has been lacking. In this study, we survey four computational strategies for nuclear RNA-seq data analysis and show that a new pipeline, Tuxedo, outperforms other approaches. Tuxedo not only assembles a more complete transcriptome, but also identifies cheRNA with higher accuracy. We have used Tuxedo to analyze gold-standard K562 cell datasets and further characterize the genomic features of intergenic cheRNA (icheRNA) and their similarity to those of enhancer RNA (eRNA). Moreover, we quantify the transcriptional correlation of icheRNA and adjacent genes, and suggest that icheRNA may be the cis-acting transcriptional regulator that is more positively associated with neighboring gene expression than eRNA predicted by state-of-art method or CAGE signal. We also explore two novel genomic associations, suggesting cheRNA may have diverse functions. A possible new role of H3K9me3 modification coincident with icheRNA may be associated with active enhancer derived from ancient mobile elements, while a potential cis-repressive function of antisense cheRNA (as-cheRNA) is likely to be involved in transiently modulating cell type-specific cis-regulation.

Author Summary

Chromatin-enriched nuclear RNA (cheRNA) is a class of gene regulatory non-coding RNAs. CheRNA provides a powerful way to profile the nuclear transcriptional landscape, especially to profile the noncoding transcriptome. The computational framework presented here provides a reliable approach to identifying cheRNA, and for studying cell-type specific gene regulation. We found that intergenic cheRNA, including intergenic cheRNA with high levels of H3K9me3 (a mark associated with closed/repressed chromatin), may act as a transcriptional activator. In contrast, antisense cheRNA, which originates from the complementary strand of the protein-coding gene, may interact with diverse chromatin modulators to repress local transcription. With our new pipeline, one future challenge will be refining the functional mechanisms of these noncoding RNA classes through exploring their regulatory roles, which are involved in diverse molecular and cellular processes in human and other organisms.
TheSynchytrium endobioticumAvrSen1 triggers a Hypersensitive Response in Sen1 potatoes while natural variants evade detection
Authors: van de Vossenberg Bart T.L.H. , Prodhomme Charlotte , van Arkel Gert , van Gent-Pelzer Marga P.E. , Bergervoet Marjan , Brankovics Balázs , Przetakiewicz Jarosław , Visser Richard G.F , van der Lee Theo A.J. , Vossen Jack H.
Published: May 2019

Synchytrium endobioticumis an obligate biotrophic fungus of the phylum Chytridiomycota. It causes potato wart disease, has a world-wide quarantine status and is included on the HHS and USDA Select Agent list.S. endobioticumisolates are grouped in pathotypes based on their ability to evade host-resistance in a set of differential potato varieties. So far, thirty-nine pathotypes are reported. A single dominant gene (Sen1) governs pathotype 1 resistance and we anticipated that the underlying molecular model would involve a pathogen effector (AvrSen1) that is recognized by the host. TheS. endobioticumspecific secretome of fourteen isolates representing six different pathotypes was screened for effectors specifically present in pathotype 1(D1) isolates but absent in others. We identified a singleAvrSen1candidate. Expression of this candidate in potatoSen1plants showed a specific hypersensitive response, which co-segregated with theSen1resistance in potato populations. No HR was obtained with truncated genes found in pathotypes that evaded recognition bySen1. These findings established that our candidate gene was indeedAvrsen1.TheS. endobioticum AvrSen1is a single copy gene and encodes a 376 amino acid protein without predicted function or functional domains, and is the first effector gene identified in Chytridiomycota, an extremely diverse yet underrepresented basal lineage of fungi.

Author Summary

Plant pathogens can have a great social and economic impact, and are a continuous threat to food security. A clear example isSynchytrium endobioticum, the fungus causing potato wart disease. The impact of the pathogen, lack of effective chemical control agents and the longevity of resting spores produced by the pathogen led to a world-wide quarantine status forS. endobioticum. Strict phytosanitary measures and the use of resistance potato varieties are currently the only way to prevent the spread of the disease. The emergence of new pathotypes that overcome resistance urged to study the underlying molecular mechanisms ofS. endobioticumrecognition by the plant. Here we describe the identification of the first effector (AvrSen1) ofS. endobioticumthat is recognized by theSen1resistance gene product. Also, we report the loss ofAvrSen1in other pathotypes thus avoiding recognition by the plant and triggering immune responses. AvrSen1 represents the first effector to be identified in the basal fungal lineage Chytridiomycota. The discovery of AvrSen1 provides an important tool to manage potato wart disease. Moreover, knowledge about Chytridiomycota effectors will shed light on other (pathogenic) interactions and the co-evolution of Chytridiomycota species with their hosts.
Pressure-induced phase transitions in Na2B12H12, structural investigation on a candidate for solid-state electrolyte
Authors: Moury Romain , Łodziana Zbigniew , Remhof Arndt , Duchêne Léo , Roedern Elsa , Gigante Angelina , Hagemann Hans
Published: May 2019

closo-Borates, such as Na2B12H12, are an emerging class of ionic conductors that show promising chemical, electrochemical and mechanical properties as electrolytes in all-solid-state batteries. Motivated by theoretical predictions, high-pressurein situpowder X-ray diffraction on Na2B12H12was performed and two high-pressure phases are discovered. The first phase transition occurs at 0.5 GPa and it is persistent to ambient pressure, whereas the second transition takes place between 5.7 and 8.1 GPa and it is fully reversible. The mechanisms of the transitions by means of group theoretical analysis are unveiled. The primary-order parameters are identified and the stability at ambient pressure of the first polymorph is explained by density functional theory calculations. Finally, the parameters relevant to engineer and build an all-solid-state battery, namely, the bulk modulus and the coefficient of the thermal expansion are reported. The relatively low value of the bulk modulus for the first polymorph (14 GPa) indicates a soft material which allows accommodation of the volume change of the cathode during cycling.
The effects of soft skill integration on quality of college life of diploma business students
Authors: Tan Cheng_Yoke , Kanesan Abdullah Abdul Ghani , Ali Abdul Jalil
Published: May 2019

Purpose

The purpose of this study was to examine the effects of soft skill integration in the curriculum on quality of college life of diploma business students in Malaysian private higher educational institutions.

Design/methodology/approach

Descriptive quantitative survey research was used to assess the views and relationship between variables from 429 business students in Peninsular Malaysia. The adapted self-administered questionnaires were distributed through stratified random sampling method. Descriptive analysis, correlation and regression analysis were used in the findings.

Findings

The results advocated significant influence from soft skill integration on quality of college life. Soft skill integration in critical thinking and problem solving especially has significant positive influence on quality of college life in all the aspects from academic, social and also facilities.

Research limitations/implications

Generalizability of the research as it was conducted in the northern region of Peninsular Malaysia only. It was also limited by subjectivity bias of the students who responded to the questionnaire.

Practical implications

The implication of this study was that it serves as an evidence-based information of soft skill integration and effects on college quality. In this way, it provides an empirical reference to the authorities for better guidelines, evaluation, control and development in the curriculum, delivery approaches, co-curriculum, campus environment or facilities.

Social implications

Local education in particular is closely linked to the neighboring community and also dependent on the socio-economic needs of the state or region. According to Kayrooz and Parker (2010), greater engagement with local issues and higher local autonomy for spending could lead to greater effectiveness and efficiencies.

Originality/value

The study was a pioneering research in the context of Malaysian private higher education, guided by Devadasonet al.’s (2010) soft skill integration study in Malaysian public higher education, plus Sirgyet al.’s (2007) study on quality of college life.
Transition management in individual organizational career planning
Authors: Laser Jan
Published: May 2019

Purpose

The purpose of this paper is to introduce the subjective perspective via the transition approach to organizational career planning so that employees’ individual transition phases can be evaluated, planned and guided.

Design/methodology/approach

A theoretical–conceptual analysis is conducted in this paper.

Findings

The individual perspective can be included in career planning via the transition approach. By dividing the transition into individual phases, the different requirements of employees over the course of time can be analysed individually and corresponding measures (for example coaching) can be derived.

Originality/value

The added value of this paper is that organizational career planning can individually analyse employees’ transitions, using a transition approach, increasing the likelihood of a successful transition.
The Use of Roche, Wainer, and Thissen's Skeletal Maturity of the Knee
Authors: Konigsberg Lyle W. , Sgheiza Valerie
Published: May 2019

The Roche, Wainer, and Thissen (RWT) knee method was designed to assess maturity in living individuals, but is infrequently cited in studies of skeletal measures for legal age thresholds or estimation of age‐at‐death for forensic cases. We implement the RWT method using R scripts and analyze its utility in establishing an age threshold of 18 years. We fit the RWT model and verify its accuracy in estimating skeletal age against results and known age data provided by RWT. We also found the transition distribution for full skeletal maturity. Agreement between the RWT method and our implementation was good, with a maximum deviation of 0.03 years. The modes of transition to full skeletal maturity are 18.37 and 17.16 years for males and females. The corresponding Bayes factors are 5.73 and 1.77, indicating that complete skeletal maturity of the knee does not provide conclusive evidence of attainment of 18 years of age.
Fluorescence of a Natural Fluorophore as a Key to Improve Fingerprint Contrast Image
Authors: Oliveira Ana Celeste Ximenes , Leão Alexandre , Balzuweit Karla , Siman Livia , Mesquita Oscar Nassif , Ladeira Luiz Orlando , Cury Luiz Alberto
Published: May 2019

The optical and morphological properties of resveratrol were investigated. This nontoxic fluorescent natural material, emitting in the visible blue light, was used as an optical marker, enabling the enhancement of the image contrast coming from relief pictures marked on challenging surfaces. By applying appropriated imaging softwares, this marker was verified to be very useful in the latent fingerprint recognition deposited on different wood surface types, mainly those with high level of roughness, where conventional forensic materials do not allow effective fingerprint image visualization.
Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris
Authors: Liao Sha , Han Liwen , Zheng Xiaopu , Wang Xin , Zhang Peng , Wu Jingni , Liu Ruimin , Fu Youlan , Sun Jiaxin , Kang Ximeng , Liu Kechun , Fan Tai‐ping , Li Shao , Zheng Xiaohui
Published: May 2019

Background and Purpose

Tanshinol borneol ester (DBZ) is a novel synthetic compound derived from Dantonic®, a botanical drug approved in 26 countries outside the United States for angina pectoris and currently undergoing FDA Phase III clinical trial. Here, we investigated the angiogenic effects of (S)‐DBZ and (R)‐DBZ isomers in vitro and in vivo.

Experimental Approach

A network pharmacology approach was used to predict molecular targets of DBZ. The effects of DBZ isomers on proliferation, migration, and tube formation of human endothelial cells were assessed. For in vivo approaches, the transgenic Tg (vegfr2:GFP) zebrafish and C57BL/6 mouse Matrigel plug models were used. ELISA and western blots were used to quantitate the release and expression of relevant target molecules and signalling pathways.

Key Results

DBZ produced a biphasic modulation on proliferation and migration of three types of human endothelial cells. Both DBZ isomers induced tube formation in Matrigel assay and a 12‐day co‐culture model in vitro. Moreover, DBZ promoted Matrigel neovascularization in mice and partially reversed the vascular disruption in zebrafish induced by PTK787. Mechanistically, DBZ enhanced the cellular levels of VEGF, VEGFR2, and MMP‐9, as well as activating Akt and MAPK signalling in endothelial cells. Selective inhibition of PI3K and MEK significantly attenuated its angiogenic effects.

Conclusions and Implications

These data reveal, for the first time, that DBZ promotes multiple key steps of angiogenesis, at least in part through Akt and MAPK signalling pathways, and suggest it may be potentially developed further for treating myocardial infarction and other cardiovascular diseases.
Interactions among threats affect conservation management outcomes: Livestock grazing removes the benefits of fire management for small mammals in Australian tropical savannas
Authors: Legge Sarah , Smith James G. , James Alex , Tuft Katherine D. , Webb Terry , Woinarski John C. Z.
Published: May 2019

Conservation scientists and practitioners usually focus on understanding and managing individual threats to biodiversity. However, threats may interact, making management outcomes unpredictable. Here, we investigated whether interactions between fire regimes and introduced livestock affect the conservation goal of population recovery for small mammals in Australia's tropical savannas, using a long‐term and landscape‐scale study. Mammal richness and abundance increased as management reduced the average annual fire extent and frequency at large and medium scales. However, these relationships between fire and richness and abundance were only evident in areas where introduced livestock were removed. This interaction may arise because predation by feral cats is amplified in areas with reduced vegetation ground cover, and cover is reduced over longer periods when livestock have access to burnt areas, because they selectively graze regenerating grass. Fire management for conservation receives substantial investment across northern Australia, and in savannas worldwide; this study shows that without appropriate management of other factors, this investment may be ineffective. More broadly, managing single threats to biodiversity may be compromised if interactions between threats are not explicitly considered. This study provides an example of how such interactions can be evaluated for improved biodiversity conservation.
In ST‐segment elevation myocardial infarction, the echocardiographic parameters of microvascular obstruction are not associated with left ventricular remodeling at five years of follow‐up
Authors: Dregoesc Mihaela Ioana , Iancu Adrian Corneliu , Ober Camelia Diana , Homorodean Cãlin , Bãlãnescu Şerban , Bolboacã Sorana
Published: May 2019

Objective

The correlation between the echocardiographic Doppler flow parameters of microvascular obstruction (MVO) and coronary wedge pressure (CWP) measured as a marker of severe compressive microvascular dysfunction and a predictor of adverse left ventricular remodeling was evaluated in a group of high‐risk acute anterior myocardial infarction survivors.

Methods

Twenty‐four patients with mechanically reperfused anterior STEMI were divided into two groups based on the 38 mm Hg CWP cutoff for adverse left ventricular remodeling. Diastolic deceleration time (DDT), coronary flow reserve (CFR), systolic retrograde flow, peak systolic and peak diastolic velocities in the infarct‐related artery were determined 3–5 days after revascularization. An echocardiographic 20% increase in left ventricular volumes defined adverse remodeling.

Results

No significant differences were recorded between groups with regard to the echocardiographic parameters of MVO. No significant correlation was identified between CWP on one side and DDT (P = 0.30) and CFR (P = 0.39) on the other, irrespective of total ischemic time and extracted thrombus length. No difference in 5 years of follow‐up left ventricular remodeling was detected in patients with DDT<900 msec as compared to those with DDT≥900 msec. The medium increase in left ventricular end‐systolic volume in patients with low CWP was 24.78%, while it reached 127.27% (P = 0.03) in patients with CWP>38 mm Hg.

Conclusions

Coronary wedge pressure did not correlate with the surrogate parameters for MVO, but it was a predictor of left ventricular remodeling. None of the echocardiographic MVO parameters was associated with adverse remodeling at 5 years of follow‐up.
Investigating the association between callous‐unemotional traits with relational bullying and victimization: A cross‐national study
Authors: Fanti Kostas A. , Kokkinos Costantinos M. , Voulgaridou Ioanna , Hadjicharalambous Maria‐Zoe
Published: May 2019

Prior research supports an association between callous‐unemotional (CU) traits with relational bullying, but evidence associating CU traits with relational victimization is limited. Further, the relationship between CU traits with relational “bully,” “bully‐victim,” and “victim” classifications has been largely neglected. The current study addresses these critical gaps in the literature using a cross‐national study design. The sample comprised of 1887 (51.5% of girls) Greek and Cypriot children (MAge = 11.17) who completed a battery of self‐report measures. Group differences suggested that children in the relational bully and bully‐victim groups scored higher on CU traits compared to children in the victim and low‐risk groups. Although these associations were similar across countries, boys in Greece were more likely to be identified in the bullying only group. In contrast, boys in Cyprus represented the higher percentage identified as bully‐victims and girls in Cyprus represented the higher percentage identified as victim‐only. Regression analysis results indicated that CU traits predicted relational bullying but not victimization. Notwithstanding, other important unexamined factors known to contribute to relational bullying and victimization, our findings suggest that prevention efforts should consider CU traits in order to protect youth from relational bullying. However, differences between countries and gender should also be taken into account.
Effects of fibrinogen supplementation on clot formation in blood samples from cardiac surgery patients before and after tranexamic acid administration
Authors: Waldén K. , Shams Hakimi C. , Jeppsson A. , Karlsson M.
Published: May 2019

Objectives

To investigate if supplementation with fibrinogen concentrate to blood samples collected after tranexamic acid administration improve clot formation more than what can be achieved with fibrinogen in the absence of tranexamic acid.

Background

It is not known if the combination of fibrinogen and tranexamic acid has additional effects than what can be achieved individually.

Methods

Four blood samples were collected from 15 coronary artery bypass patients. Two samples were collected before surgery, before and after 2 g tranexamic acid was administered. The preoperative samples were diluted to haematocrit 21%. Two samples were collected after surgery, before and after a second dose of 2 g tranexamic acid. Fibrinogen concentrate corresponding to a dose of 3 g in a 70‐kg patient was added to the samples. Platelet‐independent clotting time and maximum clot firmness assessed by thromboelastometry (ROTEM‐FIBTEM®) were compared between the samples.

Results

Administration of tranexamic acid shortened clotting time marginally (−6%) before surgery, P = 0·029) but did not influence clot firmness. Fibrinogen concentrate shortened clotting time (−14% before and −12% after surgery, both P = 0·003) and increased clot firmness (+51 and +39%, both P < 0·001). The effects of fibrinogen did not differ before and after tranexamic acid administration. Fibrinolysis was not detected in any sample.

Conclusions

The results of this in vitro study suggest that the enhancing effects of fibrinogen on clot firmness in blood samples from cardiac surgery patients are not further increased in the presence of tranexamic acid. Further studies on patients with ongoing bleeding and/or hyperfibrinolysis are necessary to validate the results.
Integrating water‐saving schemes in the design of sanitary sewers
Authors: Basupi Innocent
Published: May 2019

Urbanisation and climate change worsen the ever‐increasing gap between demand and the supply of water. Closing the gap between water demand and supply remains a global challenge that influences the growing uptake of water‐saving schemes (WSSs) to reduce the threat to water security. This study proposes a method for simultaneous design of sanitary sewers (SSs) and the selection of WSSs. An integrated design approach (or problem) that matches SSs with WSSs was formulated and solved as a multi‐objective optimisation problem. The two objectives considered are: (1) minimisation of the total cost and (2) maximisation of the cost benefits of interventions. The main constraints considered include the sanitary sewer technical and hydraulic performances. The problem was solved using the well‐known NSGA2 optimisation technique. The proposed method was demonstrated using a subsystem of the Tsholofelo Extension sanitary sewer in Gaborone. The results obtained from the integrated approach suggest that WSSs influence designs of the sanitary sewer (SS) and the other way round.
Comparison of Quadriceps Q-Angle Values of Soccer Players and Wrestlers
Authors: Şen Murat , Çetin Semra , Ece Cuma , Aydogan Alaeddin , Çetin H.Nedim
Published: May 2019

The aim of this study is to compare according to different positions the mean right and left knee Q angle of footballers and wrestlers. In this study, found the female soccer and wrestlers mean age 20.51 ± 3.47 years, height 165.43 ± 4.82 cm, weight 58.23 ± 5.18 kg. Male soccer and wrestlers has with mean age 21.30 ± 3.45 years, height 173.28 ± 5.45 cm, weight 65.66 ± 5.73 kg. One-way ANOVA, Student t, and Duncan post hoc test were used for statistical analysis. In this study, found that the mean right and left knee Q angles of male athletes were 15.08 ± 1.79° and 14.49 ± 1.82° for the standing position, 14.26 ± 1.84° and 13.29 ± 1.82° for the supine position.The mean right and left knee Q angles of Female athletes were 18.11 ± 1.32° and 17.90 ± 1.35° for the standing position, 17.52 ± 1.36°and 16.82 ± 1.29° for the supine position. In this study, were found abnormal results. The difference between the Q angle values of footballers and wrestlers was found to be statistically significant (p <0.001). The Q angle values for male soccer players were found 15.35 for standing right Q angle and 15.12 degrees for standing left Q angle and same values 14.80 and 13.86 degrees in the male wrestlers. Q angle values for women footballers were found 17.32 decrees for standing right Q angle and 17.22 degrees for standing left Q angle, and same values 18.90 and 18.58 degrees in the women wrestlers. Standing and supine Q angle values of Wrestlers in both men and women were found to be wider than the Q angle values of soccer athletes (p<0.001). The right Q- angle values of the athletes in the standing and supine position were found higher than the left Q-angle values (p <0.05).Conclusion: The Q angles were within the normal range for footballers and wrestlers. In standing positions Q angle is higher than from supine positions Q angle. Athlete's sex, pelvic width, tibia and femur length and dominant foot may increase the quadriceps Q angle.
Imipramine as an alternative to formamide to detubulate rat ventricular cardiomyocytes
Authors: Bourcier Aurelia , Barthe Marion , Bedioune Ibrahim , Lechêne Patrick , Miled Hela Ben , Vandecasteele Grégoire , Fischmeister Rodolphe , Leroy Jérôme
Published: May 2019

New Findings

What is the central question of this study?

Can imipramine, an antidepressant agent that is a cationic amphiphilic drug that interferes with the phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2) interactions with proteins maintaining the tubular system, be validated as a new detubulating tool?

What is the main finding and its importance?

Imipramine was validated as a more efficient and less toxic detubulating agent of cardiomyocytes than formamide. New insights are provided on how PI(4,5)P2 is crucial to maintaining T‐tubule attachment to the cell surface and on the cardiotoxic effects of imipramine overdoses.

Cardiac T‐tubules are membrane invaginations essential for excitation–contraction coupling (ECC). Imipramine, like other cationic amphiphilic drugs, interferes with phosphatidylinositol 4,5‐bisphosphate (PI(4,5)P2) interactions with proteins maintaining the tubular system connected to the cell surface. Our main purpose was to validate imipramine as a new detubulating agent in cardiomyocytes. Staining adult rat ventricular myocytes (ARVMs) with di‐4‐ANEPPS, we showed that unlike formamide, imipramine induces a complete detubulation with no impact on cell viability. Using the patch‐clamp technique, we observed a ∼40% decrease in cell capacitance after imipramine pretreatment and a reduction of ICa,L amplitude by ∼72%. These parameters were not affected in atrial cells, excluding direct side effects of imipramine. β‐Adrenergic receptor (β‐AR) stimulation of the remaining ICa,L with isoproterenol (Iso) was still effective. ECC was investigated in ARVMs loaded with Fura‐2 and paced at 1 Hz, allowing simultaneous measurement of the Ca2+ transient (CaT) and sarcomere shortening (SS). Amplitude of both CaT and SS was decreased by imipramine and partially restored by Iso. Furthermore, detubulated cells exhibited Ca2+ homeostasis perturbations. Real‐time cAMP variations induced by Iso using a Förster resonance energy transfer biosensor revealed ∼27% decreased cAMP elevation upon β‐AR stimulation. To conclude, we validated a new cardiomyocyte detubulation method using imipramine, which is more efficient and less toxic than formamide. This antidepressant agent induces the hallmark effects of detubulation on ECC and its β‐AR stimulation. Besides, we provide new insights on how an imipramine overdose may affect cardiac function and suggest that PI(4,5)P2 is crucial for maintaining T‐tubule structure.
Dynamic Analysis of Hydro-Turbine Governing System with Multistochastic Factors
Authors: Li Jianling , Chen Diyi , Zhang Hao , Liu Jing
Published: May 2019

This paper explores the stability of a hydro-turbine governing system (HTGS) under simultaneous effects of multistochastic factors. Specifically, three different sets of stochastic factors are introduced into the governing system, and the corresponding mathematical model with multistochastic factors is proposed. Then, seven cases are performed to reveal the dynamic characteristics of the governing system, including the excitations of only single stochastic factor, two stochastic factors, and three stochastic factors with different combinations of stochastic parameters. The results show some interesting phenomena. First, the stability of the system is weakened by introducing stochastic variables ω2 and ω3 into the inlet pressure of hydro-turbine (h2) and the bottom pressure of the surge tank (h3) separately, or both. Second, the negative effects of the stochastic characteristics of h2 and h3 on the governing system are reduced by introducing the stochastic variable (ω1) into the hydro-turbine flow (q1), on the basis of fully considering the influence of the stochastic characteristics of h2 and h3. Third, stochastic factors are generally considered to be unfavorable, but it may help the system to reach a global optimum status under certain conditions, which break through the habit of empirical thinking. Finally, this work not only provides a new insight for stochastic phenomena existing in engineering system, but also lays a theoretical basis for the safe and stable operation of the hydropower stations.
Complete Genome Sequence of Enterococcus faecium QU50, a Thermophilic Lactic Acid Bacterium Capable of Metabolizing Xylose
Authors: Abe Kiyotaka , Kanesaki Yu , Abdel-Rahman Mohamed Ali , Watanabe Satoru , Zendo Takeshi , Chibazakura Taku , Shimizu-Kadota Mariko , Sonomoto Kenji , Yoshikawa Hirofumi
Published: May 2019

Herein, we report the complete genome sequence of
Enterococcus faecium
QU50, isolated from Egyptian soil and exhibiting intermediate susceptibility to vancomycin. The genome contains a 2,535,796-bp circular chromosome and two plasmids of 196,595 bp and 17,267 bp.
Associations between common ECG abnormalities and out-of-hospital cardiac arrest
Authors: Søndergaard Marc Meller , Nielsen Jonas Bille , Mortensen Rikke Nørmark , Gislason Gunnar , Køber Lars , Lippert Freddy , Graff Claus , Haunsø Stig , Svendsen Jesper Hastrup , Kragholm Kristian Hay , Pietersen Adrian Holger , Lind Bent Struer , Hjortshøj Søren Pihlkjær , Holst Anders Gaarsdal , Struijk Johannes Jan , Torp-Pedersen Christian , Hansen Steen Møller
Published: May 2019

Background

Out-of-hospital cardiac arrest (OHCA) is often the first manifestation of unrecognised cardiac disease. ECG abnormalities encountered in primary care settings may be warning signs of OHCA.

Objective

We examined the association between common ECG abnormalities and OHCA in a primary care setting.

Methods

We cross-linked individuals who had an ECG recording between 2001 and 2011 in a primary care setting with the Danish Cardiac Arrest Registry and identified OHCAs of presumed cardiac cause.

Results

A total of 326 227 individuals were included and 2667 (0,8%) suffered an OHCA. In Cox regression analyses, adjusted for age and sex, the following ECG findings were strongly associated with OHCA: ST-depression without concomitant atrial fibrillation (HR 2.79; 95% CI 2.45 to 3.18), left bundle branch block (LBBB; HR 3.44; 95% CI 2.85 to 4.14) and non-specific intraventricular block (NSIB; HR 3.15; 95% CI 2.58 to 3.83). Also associated with OHCA were atrial fibrillation (HR 1.89; 95% CI 1.63 to 2.18), Q-wave (HR 1.75; 95% CI 1.57 to 1.95), Cornell and Sokolow-Lyon criteria for left ventricular hypertrophy (HR 1.56; 95% CI 1.33 to 1.82 and HR 1.27; 95% CI 1.12 to 1.45, respectively), ST-elevation (HR 1.40; 95% CI 1.09 to 1.54) and right bundle branch block (HR 1.29; 95% CI 1.09 to 1.54). The association between ST-depression and OHCA diminished with concomitant atrial fibrillation (HR 1.79; 95% CI 1.42 to 2.24, p < 0.01 for interaction). Among patients suffering from OHCA, without a known cardiac disease at the time of the cardiac arrest, 14.2 % had LBBB, NSIB or ST-depression.

Conclusions

Several common ECG findings obtained from a primary care setting are associated with OHCA.
Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats
Authors: Djuric M. , Nikolic Turnic T. , Kostic S. , Radonjic K. , Jeremic J. , Petkovic A. , Bradic J. , Milosavljevic I. , Srejovic I. , Zivkovic V. , Djuric D. , Jakovljevic V. , Stevanovic P.
Published: May 2019

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 μmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 μmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmaxwere noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.
Effective Factor Analysis for Chromium(VI) Removal from Aqueous Solutions and Its Application to Tunçbilek Lignite Using Design of Experiments
Authors: Orbak Âli Yurdun , Orbak İlkün
Published: May 2019

Poisonous heavy metals in air, water, and soil produce global environmental problems that are considerable threats to humankind. To meet the local and international guidelines for heavy metal release, companies often use different approaches, such as chemical precipitation, chelating agents, or activated carbon produced by adsorption. One of these heavy and toxic metals is chromium(VI). Chromium(VI) is commonly used in many applications, such as dye fixation in the textile industry or as an anticorrosive agent in paints. The aim of this paper is to explore the factors affecting the removal of one of these deadly heavy metals, chromium(VI), from aqueous solutions. For this purpose, activated carbon from Turkish Tunçbilek lignite is prepared with both chemical and physical activation methods to investigate the adsorption behavior of chromium(VI). The effects of initial chromium(VI) concentration, adsorption temperature, and pH on adsorption are studied using a design of experiments method with a full 24 factorial design with center points. The Freundlich and Langmuir adsorption isotherms that are commonly used in chemical engineering are also applied both for predicting the amount of chromium(VI) adsorbed and confirming the validity and advantages of the obtained regression model. The results indicate that the design of experiments and regression can explain and support the design of new materials by using linear and physically meaningful equations instead of local nonlinear and empirical models that are usually insufficient. Additionally, three experiments were carried out in the liquid phase to test the activated carbon samples: chromium, chromium and sucrose, and chromium-sucrose-ion. A change in adsorption capacities of the activated carbon samples was observed. Sucrose was chosen for the experiments because it contains six carbon atoms in a slightly soluble structure. The results indicated that Tunçbilek lignite exhibits good adsorption capability.
Role of TGF-Beta1/SMAD2/3 Pathway in Retinal Outer Deep Vascular Plexus and Photoreceptor Damage in Rat 50/10 Oxygen-Induced Retinopathy
Authors: Li Huijuan , Zhu Ruyuan , Zhao Ruibin , Qian Lijuan , Jiang Li
Published: May 2019

In retinopathy of prematurity (ROP), outer deep vascular plexus (oDVP) was the emerging field, and the mechanisms of photoreceptor dysfunction remained to be explored. ODVP and photoreceptors were related, with oDVP being part of the supplier of oxygen and nutrients to photoreceptors, while their possible relationship in ROP was not clear. TGF-beta1 has been reported indispensable in oDVP development and altered in ROP patients and animal models. We hypothesized that the TGF-beta1 alteration in rat 50/10 oxygen-induced retinopathy (OIR) model contributed to oDVP malformation and exerted consequent effects on photoreceptor development. We first explored the profile of oDVP development in rat after birth and compared the expression of TGF-beta1 and pSMAD2/3 in Normoxia and OIR groups. Afterwards, the inhibitor of the pathway, LY364947, was used to establish the OIR, OIR+LY364947, Normoxia, and Normoxia+LY364947 groups. The oDVP and photoreceptor were examined by Isolectin B4 staining, western-blot of CD31 and Rho, and electron microscopy. ODVP sprouted at postnatal day 10 (D10) and reached the edge of retina at D14. The TGF-beta1/SMAD2/3 pathway was compromised during the critical period of oDVP development. The inhibitor simulated the oDVP retardation, pericyte, and photoreceptor malformation in the Normoxia+LY364947 group and might further compromise the development of oDVP and photoreceptor in the OIR+LY364947 group. The inhibition of the TGF-beta1/SMAD2/3 pathway indicated its critical role in oDVP malformation and photoreceptor damage, suggesting a possible therapeutic target of ROP treatment.
Hibernoma of the Upper Extremity: Complete Case of a Rare but Benign Soft Tissue Tumor
Authors: Reichel Thomas , Rueckl Kilian , Fenwick Annabel , Vogt Niklas , Rudert Maximilian , Plumhoff Piet
Published: May 2019

Hibernoma is a rare benign lipomatous tumor showing differentiation of brown fatty tissue. To the author’s best knowledge, there is no known case of malignant transformation or metastasis. Due to their slow, noninfiltrating growth hibernomas are often an incidental finding in the third or fourth decade of life. The vast majority are located in the thigh, neck, and periscapular region. A diagnostic workup includes ultrasound and contrast-enhanced MRI. Differential diagnosis is benign lipoma, well-differentiated liposarcoma, and rhabdomyoma. An incisional biopsy followed by marginal resection of the tumor is the standard of care, and recurrence after complete resection is not reported. The current paper presents diagnostic and intraoperative findings of a hibernoma of the upper arm and reviews similar reports in the current literature.
The Experimental Study on Geometric Calibration and Material Discrimination for In Vivo Dual-Energy CT Imaging
Authors: Deng Gang , Chen Mianyi , He Peng , Wang Xing , Wu Xiaochuan , Guo Xiaodong , Li Pengcheng , Wei Biao , An Kang , Zheng Xiaolin , Feng Peng
Published: May 2019

Photon-counting detector (PCD) can identify absorption features in the multiple ranges of photon energies, which has a great potential in material discrimination. In this paper, we focused on in vivo dual-energy CT imaging to characterize different biomedical compositions. The precision of material decomposition in post-reconstruction space depends on the quality of reconstructed CT images; we used the locally linear embedding (LLE) based online geometric calibration method and GPU-based reconstruction toolbox to reconstruct high-quality CT images. Then, we performed the real experiment and studied materials decomposition with basis material model to discriminate soft tissue and cortical bone of small animal. Finally, the experimental results demonstrated that the proposed method could reconstruct small animal CT images with more slim structures and details, and improve the precision of materials decomposition in dual-energy CT imaging.
Research Progress on Regulatory B Cells in Systemic Lupus Erythematosus
Authors: Wang Tao , Mei Yongjun , Li Zhijun
Published: May 2019

Systemic lupus erythematosus (SLE) is a chronic, systemic, autoimmune inflammatory disease characterized by the production of numerous autoantibodies and cytokines, as well as multiple organ damage. Specific B cell subsets negatively regulate immune responses and have been termed regulatory B cells (Bregs). Bregs are characterized by the production of the immunoregulatory cytokines interleukin (IL)-10, IL-35, and transforming growth factor (TGF)-β. Bregs suppress other immune cells through the secretion of these immunosuppressive cytokines and have thus been studied extensively for their potential role in the treatment of various autoimmune diseases. The progress of the research on Bregs and SLE in recent years is reviewed in this paper.
Alteration of the Gut Microbiota and Its Effect on AMPK/NADPH Oxidase Signaling Pathway in 2K1C Rats
Authors: Yu Hui , Qin Lei , Hu Hai , Wang Zhanli
Published: May 2019

Background. The purpose of this study was to evaluate the alteration of the gut microbiota and its effect on adenosine monophosphate-activated protein kinase (AMPK)/nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) signaling pathway in two-kidney one-clip (2K1C) rats. Methods. The 2K1C rat models were established. The rats were randomly divided into the following 2 groups: 2K1C group and sham group. Alterations of the gut microbiota were analyzed based on the high throughput sequencing method. Plasma concentrations of short chain fatty acids (SCFAs) were measured by chromatography. The protein expression of phosphorylated AMPK and acetyl-CoA carboxylase (ACC) was determined by western blotting. NADPH oxidase activity was measured by a luminometer. Results. Microbial community analyses revealed that the structure and composition of the gut microbiota were significantly disrupted in 2K1C rats when compared to sham rats. This disruption was associated with the drastic increase in relative abundance of the genera Prevotella and the decrease in SCFA-producing bacterial population. We further confirm that SCFAs produced by the gut microbiota influence NADPH oxidase activity through AMPK. Conclusions. Our data implicated the important role of gut microbiota in the regulation of AMPK/NADPH oxidase signaling pathway.