bluuebunny/crossref_metadata_2025_split huggingface dataset:
The novel late Na+ current inhibitor, GS‐6615 (eleclazine) and its anti‐arrhythmic effects in rabbit isolated heart preparations
Authors: Rajamani Sridharan , Liu Gongxin , El‐Bizri Nesrine , Guo Donglin , Li Cindy , Chen Xiao‐Liang , Kahlig Kristopher M , Mollova Nevena , Elzein Elfatih , Zablocki Jeff , Belardinelli Luiz 
Published: July 2016

Background and PurposeEnhanced late Na+ current (late INa) in the myocardium is pro‐arrhythmic. Inhibition of this current is a promising strategy to stabilize ventricular repolarization and suppress arrhythmias. Here, we describe GS‐6615, a selective inhibitor of late INa, already in clinical development for the treatment of long QT syndrome 3 (LQT3).Experimental ApproachThe effects of GS‐6615 to inhibit late INa, versus other ion currents to shorten the ventricular action potential duration (APD), monophasic APD (MAPD) and QT interval, and decrease to the incidence of ventricular arrhythmias was determined in rabbit cardiac preparations. To mimic the electrical phenotype of LQT3, late INa was increased using the sea anemone toxin (ATX‐II).Key ResultsGS‐6615 inhibited ATX‐II enhanced late INa in ventricular myocytes (IC50 = 0.7 μM), shortened the ATX‐II induced prolongation of APD, MAPD, QT interval, and decreased spatiotemporal dispersion of repolarization and ventricular arrhythmias. Inhibition by GS‐6615 of ATX‐II enhanced late INa was strongly correlated with shortening of myocyte APD and isolated heart MAPD (R2 = 0.94 and 0.98 respectively). In contrast to flecainide, GS‐6615 had the minimal effects on peak INa. GS‐6615 did not decrease the maximal upstroke velocity of the action potential (Vmax) nor widen QRS intervals.Conclusions and ImplicationsGS‐6615 was a selective inhibitor of late INa, stabilizes the ventricular repolarization and suppresses arrhythmias in a model of LQT3. The concentrations at which the electrophysiological effects of GS‐6615 were observed are comparable to plasma levels associated with QTc shortening in patients with LQT3, indicating that these effects are clinically relevant.
Hydrus microstent compared to selective laser trabeculoplasty in primary open angle glaucoma: one year results
Authors: Fea Antonio M , Ahmed Iqbal Ike K , Lavia Carlo , Mittica Pietro , Consolandi Giulia , Motolese Ilaria , Pignata Giulia , Motolese Eduardo , Rolle Teresa , Frezzotti Paolo 
Published: July 2016

AbstractBackgroundTo compare the reduction of intraocular pressure (IOP) and glaucoma medications following selective laser trabeculoplasty (SLT) versus stand‐alone placement of the Hydrus microstent, a microinvasive glaucoma surgery device.DesignProspective interventional case‐series. University practice.ParticipantsFifty six eyes (56 patients) with uncontrolled primary open‐angle glaucoma.MethodsPatients received either SLT (n = 25) or Hydrus implantation (n = 31) in two centres. Patients were evaluated at baseline and 1, 7 days, 1, 3, 6 and 12 months after surgery.Main Outcome MeasuresIntraocular pressure and number of glaucoma medications variations inter‐groups and intra‐groups.ResultsThere were no significant differences at baseline between groups, but the mean deviation was worse in the Hydrus group (−8.43 ± 6.84 dB, confidence limits (CL)−2.8/−3.3 vs.−3.04 ± 0.65 dB, CL−6/−10.8; P < 0.001). After 12 months, there was a significant decrease in IOP and medications in the Hydrus group compared with baseline values. In the SLT group, only the decrease in IOP was significant. There was 3‐fold greater reduction in medication use in the Hydrus group compared with SLT (−1.4 ± 0.97 vs.−0.5 ± 1.05, P = 0.001). 47% of patients were medication free at 12 months in the Hydrus group (4% in the SLT group). No complications were recorded in the SLT group. In the Hydrus group, three patients experienced a temporary reduction of visual acuity post‐operatively, and two patients had post‐operative IOP spikes that resolved within one week.ConclusionsBoth SLT and Hydrus implantation reduced IOP without serious adverse events. Hydrus implantation led to a significant and further reduction in medication dependence at 12 months.
A mathematical model provides new insights into solid organ transplant‐associated acute graft‐versus‐host disease
Authors: Rashidi Armin 
Published: July 2016

AbstractSolid organ transplantation‐associated acute graft‐versus‐host disease (SOT‐aGvHD) is a rare but highly fatal condition. Our poor understanding of this entity in addition to its rarity has hampered treatment progress and most patients succumb to the disease. A mechanistic mathematical model is developed to replicate and explain the complex pathogenesis of SOT‐aGvHD. The model captures a number of important features of SOT‐aGvHD including (i) the occurrence of stable and persistent mixed chimerism in some, but not all, cases, (ii) fluctuation in chimerism in some persistently mixed chimeric cases, (iii) rare occurrence of full donor chimerism, and (iv) beneficial effect of escalating immunosuppression in some cases of SOT‐aGvHD and detrimental effect in others. In addition, the model predicts the conditions under which escalation or de‐escalation of immunosuppression would be the preferred treatment strategy. In an exceedingly rare condition such as SOT‐aGvHD, where prospective trials are not feasible, mathematical modeling can provide useful insights into pathogenesis and treatment.
The Use of Fictional Stories in Science Exhibits: The Emperor Who Only Believed His Own Eyes
Authors: Murmann Mai , Avraamidou Lucy 
Published: July 2016

AbstractThe authors explore how fictional narratives (stories) can be used as a learning tool in the context of informal science environments and specifically science centers. They base their argument on an analysis of the theoretical, structural and epistemological properties of stories and how those can serve to establish a story as a cognitive tool. They offer an example of an application of these properties to a story‐based learning design called “The Emperor who only Believed his own Eyes” in the context of a large, public science center, and specifically an exhibition about “senses”. This paper focuses on the idea of a “hack,” a museum sanctioned strategy for exploring the potential and implications of narrative‐based design as a way to reinterpret science exhibits in a way that can engage young users in content exploration and offer recommendations for future research.
Parameterisation and validation of a resource budget model for masting using spatiotemporal flowering data of individual trees
Authors: Abe Tomoyuki , Tachiki Yuuya , Kon Hirokazu , Nagasaka Akiko , Onodera Kensuke , Minamino Kazuhiro , Han Qingmin , Satake Akiko 
Published: July 2016

AbstractSynchronised and fluctuating reproduction by plant populations, called masting, is widespread in diverse taxonomic groups. Here, we propose a new method to explore the proximate mechanism of masting by combining spatiotemporal flowering data, biochemical analysis of resource allocation and mathematical modelling. Flowering data of 170 trees over 13 years showed the emergence of clustering with trees in a given cluster mutually synchronised in reproduction, which was successfully explained by resource budget models. Analysis of resources invested in the development of reproductive organs showed that parametric values used in the model are significantly different between nitrogen and carbon. Using a fully parameterised model, we showed that the observed flowering pattern is explained only when the interplay between nitrogen dynamics and climatic cues was considered. This result indicates that our approach successfully identified resource type‐specific roles on masting and that the method is suitable for a wide range of plant species.
Efficacy of vasopressin V2 receptor antagonist tolvaptan in treatment of hepatic edema
Authors: Hiramine Yasunari , Uto Hirofumi , Imamura Yasushi , Hiwaki Takuya , Kure Takeshi , Ijuin Sho , Oda Kohei , Mawatari Seiichi , Kumagai Kotaro , Tokunaga Koki , Higashi Hirofumi , Kanetsuki Ichiro , Kubozono Osamu , Maenohara Shigeho , Ido Akio 
Published: July 2016

AimTolvaptan, an oral active vasopressin V2 receptor antagonist, is widely used for hepatic edema in Japan, but its clinical benefits have yet to be fully clarified. The present study evaluated the efficacy of tolvaptan in hepatic edema.MethodsThe efficacy and treatment regimen of tolvaptan were evaluated in 150 patients with hepatic edema by analyzing the initial (day 14) and long‐term (day 90) responses to the drug and their predictive factors. All patients were divided into good (Child–Pugh classification B, and absent of advanced hepatocellular carcinoma) and poor hepatic condition groups, and the response rates were compared between the two groups.ResultsThe initial response rate was 62%, and the long‐term response rate was 47%. The assessment of predictive factors for response to tolvaptan showed that serum creatinine and C‐reactive protein levels were important predictors of initial response, and that hepatic conditions, such as the Child–Pugh score or presence of hepatocellular carcinoma, as well as initial response, were significant predictors of long‐term response. In addition, both the initial and long‐term response rates and the cumulative survival rate were found to be higher in the good hepatic condition group than in the poor hepatic condition group, respectively (71% vs. 57%, P = 0.113; 62% vs. 39%, P = 0.009; log–rank test, P < 0.001).ConclusionThese results suggest that tolvaptan may provide high response rates when used early in the course of hepatic edema, or when both hepatic and renal functions are still retained, leading to an improved disease prognosis.
Effect of dextran glycation on nanofibril assembly of soya β‐conglycinin at pH 2.0 and the pH stability of nanofibrils
Authors: Zou Yuan , Chen Yanqiong , Wang Mengping , Wang Jinmei , Yang Xiaoquan 
Published: July 2016

SummaryIn this study, we investigated the effects of dextran glycation on soya β‐conglycinin self‐assembly into nanofibrils at 85 °C and pH 2.0, as well as their stability at pH 2.0–10.0. Although the hydrolysis rate of β‐conglycinin decreased, glycation significantly increased the structural change rate in the initial stage of nanofibril formation and the growth of nanofibril. It is suggested that the glycation of three subunits (α′, α, β) in β‐conglycinin may promote fibril assembly because the extension regions of α′ and α subunits play an important role in affecting the rate of structural changes in fibril formation. At neutral pH, conjugate nanofibrils are highly dispersible and transparent and remained greater structural stability compared with mixture. The improvement stability of conjugate nanofibrils may be contributed to dextran which provides some steric hindrance to prevent the aggregation of nanofibrils; this would also facilitate the application of soya β‐conglycinin nanofibrils in food industry.
Effect of clove extract pretreatment and drying conditions on lipid oxidation and sensory discrimination of dried omena (Rastrineobola argentea) fish
Authors: Slavin Margaret , Dong Mengyi , Gewa Constance 
Published: July 2016

SummarySun‐drying is a low‐cost, low‐technology fish preservation method frequently employed in developing areas. However, the process promotes lipid oxidation and its associated undesired flavours and odours. This study investigated low‐technology solutions for impact on lipid oxidation and sensory attributes of oven‐dried omena fish (Rastrineobola argentea). Two oven‐drying conditions and four doses of clove water extract ‘dip’ pretreatments were studied in a complete factorial design. Lipid oxidation in dried fish was assessed by TBARS, peroxide value and fatty acid analysis by GC‐FID. Results showed that soaking in 10 g L−1 clove water extract for 1 h and oven‐drying at 150 °C × 30 min significantly reduced TBARS and peroxide values in omena fish by 77% and 79%, respectively, and polyene index showed improved retention of long‐chain polyunsaturated fats, compared to original drying condition. Lastly, panellists of a triangle test were able to discriminate between biscuits made with the modified and original dried fish.
Too Good to be True? An Analysis of the Options Market's Reactions to Earnings Releases
Authors: Lu Yan , Ray Sugata 
Published: July 2016

AbstractUsing option implied risk neutral return distributions before and after earnings announcements, we study the option market's reaction to extreme events over earnings announcements. While earnings announcements generally reduce short‐term uncertainty about the stock price, very good news does not reduce uncertainty and slightly bad news actually increases uncertainty. We also find that left tail probabilities decrease over earnings releases while right tail probabilities increase. We interpret these findings as evidence of maintained investor expectations that very good news is generally not released during earnings announcements, combined with skepticism in the form of lingering uncertainty at the release of such very good news.
Response time variability under slow and fast‐incentive conditions in children with ASD, ADHD and ASD+ADHD
Authors: Tye Charlotte , Johnson Katherine A. , Kelly Simon P. , Asherson Philip , Kuntsi Jonna , Ashwood Karen L. , Azadi Bahare , Bolton Patrick , McLoughlin Gráinne 
Published: July 2016

BackgroundAttention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) show significant behavioural and genetic overlap. Both ADHD and ASD are characterised by poor performance on a range of cognitive tasks. In particular, increased response time variability (RTV) is a promising indicator of risk for both ADHD and ASD. However, it is not clear whether different indices of RTV and changes to RTV according to task conditions are able to discriminate between the two disorders.MethodsChildren with ASD (n = 19), ADHD (n = 18), ASD + ADHD (n = 29) and typically developing controls (TDC; n = 26) performed a four‐choice RT task with slow‐baseline and fast‐incentive conditions. Performance was characterised by mean RT (MRT), standard deviation of RT (SD‐RT), coefficient of variation (CV) and ex‐Gaussian distribution measures of Mu, Sigma and Tau.ResultsIn the slow‐baseline condition, categorical diagnoses and trait measures converged to indicate that children with ADHD‐only and ASD + ADHD demonstrated increased MRT, SD‐RT, CV and Tau compared to TDC and ASD‐only. Importantly, greater improvement in MRT, SD‐RT and Tau was demonstrated in ADHD and ASD + ADHD from slow‐baseline to fast‐incentive conditions compared to TDC and ASD‐only.ConclusionsSlower and more variable RTs are markers of ADHD compared to ASD and typically developing controls during slow and less rewarding conditions. Energetic factors and rewards improve task performance to a greater extent in children with ADHD compared to children with ASD. These findings suggest that RTV can be distinguished in ASD, ADHD and ASD + ADHD based on the indices of variability used and the conditions in which they are elicited. Further work identifying neural processes underlying increased RTV is warranted, in order to elucidate disorder‐specific and disorder‐convergent aetiological pathways.
Authentic leadership and followers' in‐role and extra‐role performance: The mediating role of followers' learning goal orientation
Authors: Mehmood Qaiser , Hamstra Melvyn R. W. , Nawab Samina , Vriend Tim 
Published: July 2016

This study examined whether and why authentic leadership predicts followers' performance. We hypothesized that authentic leadership predicts followers' learning goal orientation (goal to develop and improve), which, in turn, predicts followers' in‐role and (civic virtue) extra‐role performance. A multilevel, multisource, time‐lagged study, conducted in telecommunications companies in Pakistan, among 115 supervisors and 345 reports supported indirect relations between authentic leadership and (1) follower in‐role and (2) extra‐role performance (civic virtue) mediated by followers' learning goal orientation.Practitioner points

Authentic leadership is considered to promote employees' developmental focus through authenticity on the part of the leader (e.g., being aware of one's strengths and weaknesses).

We discuss and analyse authentic leadership as an approach that involves managers' modelling of a learning goal orientation to followers.

Direct supervisors' authentic leadership was found to predict employees' in‐role and extra‐role (civic virtue) performance because it may model a focus on learning goals in followers.

Hence, important organizational outcomes can be improved through authentic leadership.
Fibroblast growth factor 23 and soluble Klotho in patients with autosomal dominant polycystic kidney disease
Authors: Akiyama Kenichi , Mochizuki Toshio , Kataoka Hiroshi , Tsuchiya Ken , Nitta Kosaku 
Published: July 2016

AbstractAimThis study aimed to examine the roles of fibroblast growth factor 23 (FGF23) and soluble Klotho in phosphate metabolism in autosomal‐dominant polycystic kidney disease (ADPKD) patients.MethodsWe measured these two factors and phosphate metabolism parameters in 80 patients with ADPKD and 53 patients with non‐diabetic chronic kidney disease (CKD).ResultsThe mean serum FGF23 level in the ADPKD group was significantly (twofold) higher than in the non‐diabetic CKD patients, but the mean soluble Klotho level in the ADPKD group was significantly lower in the non‐diabetic CKD group. The mean serum phosphate levels of the two groups were similar. The estimated glomerular filtration rate (eGFR) was approximately 45 mL/min per 1.73 m2 in both groups, and their serum vitamin D metabolite levels were in the normal range.ConclusionThe serum FGF23 levels were significantly higher and soluble Klotho levels significantly lower in the ADPKD group than in the non‐diabetic CKD group matched for eGFR, and these findings may be associated with resistance of renal phosphate excretion.
Improving biofeedback for the treatment of fecal incontinence in women: implementation of a standardized multi‐site manometric biofeedback protocol
Authors: Markland A. D. , Jelovsek J. E. , Whitehead W. E. , Newman D. K. , Andy U. U. , Dyer K. , Harm‐Ernandes I. , Cichowski S. , McCormick J. , Rardin C. , Sutkin G. , Shaffer A. , Meikle S. ,   the Pelvic Floor Disorders Network
Published: July 2016

AbstractBackgroundStandardized training and clinical protocols using biofeedback for the treatment of fecal incontinence (FI) are important for clinical care. Our primary aims were to develop, implement, and evaluate adherence to a standardized protocol for manometric biofeedback to treat FI.MethodsIn a Pelvic Floor Disorders Network (PFDN) trial, participants were enrolled from eight PFDN clinical centers across the United States. A team of clinical and equipment experts developed biofeedback software on a novel tablet computer platform for conducting standardized anorectal manometry with separate manometric biofeedback protocols for improving anorectal muscle strength, sensation, and urge resistance. The training protocol also included education on bowel function, anal sphincter exercises, and bowel diary monitoring. Study interventionists completed online training prior to attending a centralized, standardized certification course. For the certification, expert trainers assessed the ability of the interventionists to perform the protocol components for a paid volunteer who acted as a standardized patient. Postcertification, the trainers audited interventionists during trial implementation to improve protocol adherence.Key ResultsTwenty‐four interventionists attended the in‐person training and certification, including 46% advanced practice registered nurses (11/24), 50% (12/24) physical therapists, and 4% physician assistants (1/24). Trainers performed audio audits for 88% (21/24), representing 84 audited visits. All certified interventionists met or exceeded the prespecified 80% pass rate for the audit process, with an average passing rate of 93%.Conclusions & InferencesA biofeedback protocol can be successfully imparted to experienced pelvic floor health care providers from various disciplines. Our process promoted high adherence to a standard protocol and is applicable to many clinical settings.
Activation of the TREM‐1 pathway in human monocytes by periodontal pathogens and oral commensal bacteria
Authors: Varanat M. , Haase E.M. , Kay J.G. , Scannapieco F.A. 
Published: July 2016

SummaryPeriodontitis is a highly prevalent disease caused in part by an aberrant host response to the oral multi‐species biofilm. A balance between the oral bacteria and host immunity is essential for oral health. Imbalances in the oral microbiome lead to an uncontrolled host inflammatory response and subsequent periodontal disease (i.e. gingivitis and periodontitis). TREM‐1 is a signaling receptor present on myeloid cells capable of acting synergistically with other pattern recognition receptors leading to amplification of inflammatory responses. The aim of this study was to investigate the activation of the TREM‐1 pathway in the human monocyte‐like cell line THP‐1 exposed to both oral pathogens and commensals. The relative expression of the genes encoding TREM‐1 and its adapter protein DAP12 were determined by quantitative real‐time polymerase chain reaction. The surface expression of TREM‐1 was determined by flow cytometry. Soluble TREM‐1 and cytokines were measured by enzyme‐linked immunosorbent assay. The results demonstrate that both commensal and pathogenic oral bacteria activate the TREM‐1 pathway, resulting in a proinflammatory TREM‐1 activity‐dependent increase in proinflammatory cytokine production.
Memory responses of jasmonic acid‐associated Arabidopsis genes to a repeated dehydration stress
Authors: Liu Ning , Staswick Paul E. , Avramova Zoya 
Published: July 2016

AbstractDehydration stress activates numerous genes co‐regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre‐stressed levels (‘revised‐response’ genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA‐signaling and JA‐mediated stress responses. How these JA‐associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory‐mechanism is stress‐specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA‐mediated and JA‐mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory‐type genes suggests biological relevance for transcriptional memory as a gene‐regulating mechanism during recurring bouts of drought.