bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkable change in the broadband electrical behavior of poly(vinylidene fluoride)–multiwalled carbon nanotube nanocomposites with the use of different processing routes
Authors: Santos João Paulo Ferreira , de Melo Carvalho Benjamim , Suman Bretas Rosario Elida
Published: December 2018

Poly(vinylidene fluoride) (PVDF) nanocomposites have plenty of applications in the electronic realm. In this study, we produced nanocomposites based on PVDF and multiwalled carbon nanotubes (MWCNTs), with various MWCNT loadings, using three different processing routes: solution mixing, melt mixing, and electrospinning. The broadband electrical behavior of these nanocomposites was studied and compared via impedance spectroscopy. The morphologies of the nanocomposites were characterized by transmission electron microscopy and scanning electron microscopy. The results reveal that the electrical behaviors of the samples were completely different according to the processing route used. Solution mixing was the most suitable method for producing nanocomposites with the highest conductivities, at low MWCNT loadings, whereas electrospinning was the most suitable method for producing nanocomposites with the lowest dielectric permittivity. These differences were attributed to the different arrangements of the MWCNTs caused by the different processes. Although the solution‐mixed samples exhibited long and twisted MWCNTs, the melt‐mixed samples had shorter MWCNTs, and the electrospun samples had MWCNTs embedded and aligned inside the insulating polymer nanofibers. Thus, these results project a vast horizon for tailoring the structure and thereby the broadband electrical behavior of PVDF–MWCNT nanocomposites for different types of applications. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47409.
Development of magnetoactive elastomers for sealing eye retina detachments
Authors: Alekhina Yulia A. , Makarova Liudmila A. , Kostrov Sergei A. , Stepanov Gennady V. , Kazimirova Elena G. , Perov Nikolay S. , Kramarenko Elena Yu.
Published: December 2018

Magnetoactive elastomers (MAEs) on the basis of a silicone matrix filled with carbonyl iron microparticles are developed for an envisaged application in eye surgery for treatment of complicated retinal detachments. The proposed magnetic fixator of an eye retina consists of an MAE seal placed inside an eye in the area of a retinal break, and an external silicone sponge with embedded permanent magnets which can be sutured to the sclera to provide magnetic field acting on the internal MAE seal. For MAE seal development, MAEs of various compositions (containing 52–76 mass% of ferromagnetic iron microparticles) are synthesized and their surface, magnetic, mechanical, and rheological properties are investigated in external magnetic fields. To demonstrate MAEs efficacy as an element of the retina magnetic fixator, magnetic forces acting between MAE samples and systems of permanent magnets were measured in the curved configuration corresponding to the human eye geometry. It has been demonstrated that the pressure produced within the fixator can be varied in a wide range by tuning the MAE composition and MAE seal dimensions as well as by optimizing the size and configuration of permanent magnets within the external silicone sponge. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2019,136, 47425.
Nucleation and plasticization with recycled low‐molecular‐weight poly‐3‐hydroxybutyrate toughens virgin poly‐3‐hydroxybutyrate
Authors: Cal Andrew J. , Grubbs Brian , Torres Lennard F. , Riiff Timothy J. , Kibblewhite Rena E. , Orts William J. , Lee Charles C.
Published: December 2018

Poly‐3‐hydroxybutyrate (PHB) is a widely distributed carbon storage molecule in prokaryotes and can serve as a biodegradable plastic replacement. However, the handling and material properties of virgin PHB are not as robust as some traditional petroleum‐based plastics. Additives can be added to PHB to improve its qualities, but these additives are themselves often not biobased. A strategy was developed to utilize lower molecular weight PHB fragments derived from the recycling process as biobased additives. To simulate recycling, PHB was thermolyzed at elevated temperatures, and this degraded PHB (dPHB) was reactively processed with virgin PHB. Incorporation of dPHB nucleated and plasticized the virgin PHB as evidenced by increased crystallization temperature and crystallinity as well as decreased melt viscosity, stiffness, and melting temperature. Additionally, samples containing dPHB had increased toughness. Processing with dPHB decreased Mn, had little effect on Mw, and increased the Z‐average molecular weight, indicating branching. These results demonstrate a route for nucleating, plasticizing, and toughening virgin PHB by using recycled PHB. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47432.
Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti‐IgE Monoclonal Antibody in Systemic Lupus Erythematosus
Authors: Hasni Sarfaraz , Gupta Sarthak , Davis Michael , Poncio Elaine , Temesgen‐Oyelakin Yenealem , Joyal Elizabeth , Fike Alice , Manna Zerai , Auh Sungyoung , Shi Yinghui , Chan Diana , Carlucci Philip , Biehl Ann , Dema Barbara , Charles Nicolas , Balow James E. , Waldman Meryl , Siegel Richard M. , Kaplan Mariana J. , Rivera Juan
Published: December 2018

Objective

Autoreactive IgE antibodies have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We hypothesize that omalizumab, a monoclonal antibody binding IgE, may improve SLE activity by reducing type I interferon (IFN) production by hampering plasmacytoid dendritic cells and basophil activation. This study was undertaken to assess the safety, tolerability, and clinical efficacy of omalizumab in mild to moderate SLE.

Methods

Sixteen subjects with SLE and a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score of ≥4 and elevated autoreactive IgE antibody levels were randomized to receive omalizumab or placebo (2:1) for 16 weeks, followed by 16 weeks of open‐label treatment and a 4‐week washout period. The SLEDAI‐2K score, British Isles Lupus Assessment Group index (BILAG 2004) score, and physician's global assessment of disease activity were recorded at each visit. The type I IFN–induced gene signature was determined using quantitative polymerase chain reaction.

Results

Omalizumab was well tolerated with no allergic reactions, and mostly mild adverse events comparable to those experienced with placebo treatment. SLEDAI‐2K scores improved in the omalizumab group compared to the placebo group at week 16 (P = 0.038), as well as during the open‐label phase in subjects initially receiving placebo (P = 0.02). No worsening in BILAG scores or the physician's global assessment was detected. There was a trend toward a reduction in IFN gene signature in subjects treated with omalizumab (P = 0.11), especially in subjects with a high baseline IFN signature (P = 0.052).

Conclusion

Our findings indicate that omalizumab is well tolerated in SLE and is associated with improvement in disease activity. Larger randomized clinical trials will be needed to assess the efficacy of omalizumab in patients with SLE.
Synthetic biology for bioengineering virus‐like particle vaccines
Authors: Charlton Hume Hayley K. , Vidigal João , Carrondo Manuel J. T. , Middelberg Anton P. J. , Roldão António , Lua Linda H. L.
Published: December 2018

Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus‐like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. Several VLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target‐specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described. When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry.
Development of food‐grade expression system for d‐allulose 3‐epimerase preparation with tandem isoenzyme genes in Corynebacterium glutamicum and its application in conversion of cane molasses to D‐allulose
Authors: Yang Jiangang , Tian Chaoyu , Zhang Tong , Ren Chenxi , Zhu Yueming , Zeng Yan , Men Yan , Sun Yuanxia , Ma Yanhe
Published: December 2018

D‐Allulose 3‐epimerase (DAE) has been applied to produce
D‐allulose, a low‐calorie and functional sweetener. In this study, a new DAE from
Paenibacillus senegalensis was characterized in
Escherichia coli. Furthermore, we presented a tandem isoenzyme gene expression strategy to express multiple DAEs in one cell and construct food‐grade expression systems based on
Corynebacterium glutamicum. Seventeen expression cassettes based on three DAE genes from different organisms were constructed. Among all recombinant strains, DAE16 harboring three DAE genes in an expression vector exhibited the highest enzyme activity with 22.7 U/mg. Whole‐cell transformation of DAE16 produced 225 g/L
D‐allulose with a volumetric productivity of 353 g·g
−1·hr
−1. The catalytic efficiency of strain C‐DAE9 integrating total 11 DAE genes in chromosome was 16.4‐fold higher than strains carrying one DAE. Fed‐batch culture of C‐DAE9 gave enzyme activity of 44,700 U/L. We also expressed a thermostable invertase in
C. glutamicum and obtained enzyme activity of 29 U/mg. Immobilized cells expressing DAE or invertase exhibited 80% of retained activity after 30 cycles of catalytic reactions. Those immobilized cells were coupled to produce 61.2 g/L
D‐allulose from cane molasses in a two‐step reaction process. This study provided an efficient approach for enzyme preparation and allowed access to produce
D‐allulose from other abundant and low‐cost feedstock enriched with sucrose.
Determination of critical shear stress for maturation of human pluripotent stem cell‐derived endothelial cells towards an arterial subtype
Authors: Arora Seep , Lam Adele Jing Ying , Cheung Christine , Yim Evelyn K. F. , Toh Yi‐Chin
Published: December 2018

Human pluripotent stem cell‐derived endothelial cells (hPSC‐ECs) present an attractive alternative to primary EC sources for vascular grafting. However, there is a need to mature them towards either an arterial or venous subtype. A vital environmental factor involved in the arteriovenous specification of ECs during early embryonic development is fluid shear stress; therefore, there have been attempts to employ adult arterial shear stress conditions to mature hPSC‐ECs. However, hPSC‐ECs are naïve to fluid shear stress, and their shear responses are still not well understood. Here, we used a multiplex microfluidic platform to systematically investigate the dose‐time shear responses on hPSC‐EC morphology and arterial‐venous phenotypes over a range of magnitudes coincidental with physiological levels of embryonic and adult vasculatures. The device comprised of six parallel cell culture chambers that were individually linked to flow‐setting resistance channels, allowing us to simultaneously apply shear stress ranging from 0.4 to 15 dyne/cm
2. We found that hPSC‐ECs required up to 40 hr of shear exposure to elicit a stable phenotypic change. Cell alignment was visible at shear stress <1 dyne/cm
2, which was independent of shear stress magnitude and duration of exposure. We discovered that the arterial markers NOTCH1 and EphrinB2 exhibited a dose‐dependent increase in a similar manner beyond a threshold level of 3.8 dyne/cm
2, whereas the venous markers COUP‐TFII and EphB4 expression remained relatively constant across different magnitudes. These findings indicated that hPSC‐ECs were sensitive to relatively low magnitudes of shear stress, and a critical level of ~4 dyne/cm
2 was sufficient to preferentially enhance their maturation into an arterial phenotype for future vascular tissue engineering applications.
Langerhans cell histiocytosis in adults is associated with a high prevalence of hematologic and solid malignancies
Authors: Ma Jennifer , Laird James H. , Chau Karen W. , Chelius Monica R. , Lok Benjamin H. , Yahalom Joachim
Published: December 2018

Background

Langerhans cell histiocytosis (LCH) is a rare disorder of histiocyte proliferation. Previous case studies suggest a higher prevalence of hematologic and solid malignancies among LCH patients, possibly due to treatment with tumorigenic agents such as etoposide. We report the first large, single‐institution experience of adult LCH patients with additional malignancies to study the characteristics of these patients.

Methods

We identified 132 consecutive patients >18 years of age with histologically confirmed LCH at our center between 1990 and 2015. Demographics and detailed oncologic history were recorded to identify patients with additional malignancies.

Results

Of 132 adult LCH patients, 42 (32%) patients had an additional malignancy. There were 53 malignancies among the 42 patients, with 31 (58%) preceding LCH diagnosis, 11 concurrent (≤3 months; 21%) with LCH diagnosis, and 11 (21%) after. Median age was 54 years (range 28‐89) with a median follow‐up of 3.7 years (0.1‐22.2) for this cohort. OS at 3 years was 98% in patients with LCH alone and 82% among patients with additional malignancies, with 30 (71%) alive at last follow‐up. Solid tumors, lymphomas, and other hematologic malignancies were observed as follows: 39 (74%), 9 (17%), and 5 (9%).

Conclusion

Our cohort of adult LCH patients demonstrates an unusually high number of additional malignancies. Our study includes predominantly malignancies diagnosed preceding or concurrent with LCH, suggesting a cause of malignancy independent of LCH treatment. Further exploration of the biology of this rare disease may elucidate the mechanism of frequent additional malignancies.
Synergistic interaction of Deltex and Hrp48 leads to JNK activation
Authors: Dutta Debdeep , Mutsuddi Mousumi , Mukherjee Ashim
Published: December 2018

The communication among the cells plays a seminal role in metazoan development by coordinating multiple cellular processes that, in turn, helps in the maintenance of biological homeostasis. Our previous study demonstrated that Dx and Hrp48 together downregulate Notch signaling and induce cell death in Drosophila. To understand the signaling events behind the Dx and Hrp48‐induced cell death in a greater detail, we performed a set of genetic experiments followed by immunocytochemical analyses. Our data revealed that Dx along with Hrp48 induced JNK activation and consequently cell death in the eye tissue. Additionally, using genetic and molecular approaches, we identified the domain of Dx protein responsible for its synergistic activity with Hrp48. Altogether, our analyses suggest that coexpression of Dx and Hrp48 activates JNK pathway to induce cell death in eye disc of Drosophila melanogaster.
Smart hydrogels with high tunability of stiffness as a biomimetic cell carrier
Authors: Zhao Han , Xu Kang , Zhu Peng , Wang Chunli , Chi Qingjia
Published: December 2018

Human tissues are sophisticated ensembles of various distinct cell types encapsulated in the biomechanical cues of the extracellular matrix. It has been known matrix stiffness plays a pivot role in cellular events and tissue‐scale biological processes. Thus, materials that can mimic mechanical environments of tissues in vitro and possess wide, physiologically relevant elasticity are highly desirable. Hydrogels provide a good cell platform to mimic native cellular environment. However, the limited stiffness tunability, and hinders the efforts to reproduce the biomechanical microenvironment of many in vivo progresses. These problems have been addressed by the recently emerged great quantity of exquisitely designed smart hydrogels. Smart hydrogels that respond sensitively to external stimuli are good choices due to the convenience in regulating their mechanical properties. In this review, we summarize the latest progress in the development of stimuli‐responsive hydrogels as a cell carrier (platform for cell culture) which spans a wide range of stiffness. Different kinds of smart hydrogels corresponding to various stimuli, including pH, temperature, light, metal ions, and forces, are introduced and their stiffness modulation through physicochemical procedures are reported.
Clinical outcomes following implantation of the ION™ paclitaxel‐eluting platinum chromium coronary stent in routine clinical practice: Results of the ION U.S. post‐approval study
Authors: Cannon Louis A. , Kimmelstiel Carey D. , White Anthony , Hill Roger , Grady Timothy P. , Myers Paul R. , Underwood Paul , Dawkins Keith D.
Published: December 2018

Background

The ION Study assessed clinical outcomes for the thin‐strut, ION™ (TAXUS Element) Paclitaxel‐Eluting Platinum Chromium Coronary Stent System (Boston Scientific, Marlborough, MA) in unselected patients.

Methods

This prospective, open‐label registry enrolled the first 1,120 consenting patients treated with the ION stent without clinical or angiographic inclusion criteria at 40 clinical sites. Follow‐up was at discharge, 30 days, 180 days, 1 and 2 years. The primary endpoint, the 1‐year rate of cardiac death or MI (CD/MI) in PERSEUS‐like patients (i.e., patients similar to those enrolled in PERSEUS, the pivotal approval trial), was tested in patients pooled from the ION study (N = 316), the European TAXUS Element post‐approval registry (TE‐PROVE; N = 306 PERSEUS‐like patients), and the PERSEUS WH/SV populations (N = 1,166); and then compared with a prespecified performance goal. Additional outcomes were examined in the overall ION patient population.

Results

A total of 1,111 (out of 1,120) enrolled patients received a study stent. Most patients were male (70%) and mean age was 64 years. At 1 year, the primary endpoint of CD/MI occurred in 2.1% (6/292) of PERSEUS‐like patients in ION, and 2.3% (40/1,729) of patients in the combined analysis. The upper one‐sided 95% confidence interval for the combined analysis was 2.9%, which was significantly less than the performance goal of 7.6% (P < 0.001). Within patients enrolled in the ION study (N = 1,111), the rate of CD/MI was 4.5% at 1 year and 7.5% at 2 years. Definite/probable stent thrombosis occurred in 2.1% of patients at 1 year and 2.5% at 2 years.

Conclusions

The results of the ION Study confirm the mid‐term safety and effectiveness of the ION stent for the treatment of coronary artery disease in everyday clinical practice.
On asymptotic inference in stochastic differential equations with time‐varying covariates
Authors: Maitra Trisha , Bhattacharya Sourabh
Published: December 2018

In this article, we introduce a system of stochastic differential equations (SDEs) consisting of time‐dependent covariates and consider both fixed and random effects. We also allow the functional part associated with the drift function to depend upon unknown parameters. For this general SDE system we establish consistency and asymptotic normality of the maximum likelihood estimator. We consider a Bayesian approach for learning about the population parameters, and prove consistency and asymptotic normality of the corresponding posterior distribution. We supplement our theoretical investigation with simulated and real data analyses, obtaining encouraging results in both cases. The Canadian Journal of Statistics 46: 635–655; 2018 © 2018 Statistical Society of Canada
Estimating prevalence using indirect information and Bayesian evidence synthesis
Authors: Luo Yu , Stephens David A. , Buckeridge David L.
Published: December 2018

We focus on the analysis of health count data, aggregated over disjoint geographical locations, by combining information from data sources in a coherent fashion using a Bayesian hierarchical model. The overall objective is to estimate prevalence of a medical condition in the population given that the sampled counts arise from a subset of all cases, and when there is no additional information available from the data. We develop a hierarchical model to predict the overall prevalence using an external data set for calibration. We demonstrate that the Bayesian methodology can account fully for the uncertainty, variability and spatial dependence for the estimate. We apply our model to dispensing data obtained by the Public Health Agency of Canada for 2014, and assess the prevalence of treated Attention Deficit Hyperactivity Disorder (ADHD) from records of drugs dispensed to treat the condition. We demonstrate that our final model fits the data well in an out‐of‐sample assessment. We estimate the prevalence of treated ADHD in Canada to be 1.14% with 95% credible interval (0.86%, 1.27%), with prevalence noted to be higher in the eastern part of Canada, most notably in Nova Scotia. The Canadian Journal of Statistics 46: 673–689; 2018 © 2018 Société statistique du Canada
A new integrated likelihood for estimating population size in dependent dual‐record system
Authors: Chatterjee Kiranmoy , Mukherjee Diganta
Published: December 2018

Efficient estimation of the population size from dependent dual‐record system (DRS) remains a statistical challenge in the capture‐recapture type experiment. Owing to the non‐identifiability of the suitable time‐behavioural response variation model (denoted as Mtb) under DRS, few methods are developed in the Bayesian paradigm based on informative priors. Our contribution in this article is to develop a new integrated likelihood function from model Mtb motivated by a novel approach developed by Severini (2007). A suitable weight function on the nuisance parameter is derived with the knowledge of the direction of behavioural dependency. A pseudo‐likelihood function is constructed so that the resulting estimator possess some desirable properties including negligible prior (or weight) sensitiveness. Extensive simulations show the superior performance of our proposed method to that of the existing Bayesian methods. Moreover, the proposed estimator is easy to implement from the computational perspective. Applications to two real data sets are presented. The Canadian Journal of Statistics 46: 577–592; 2018 © 2018 Société statistique du Canada
The empirical identity process: Asymptotics and applications
Authors: Bibbona Enrico , Pistone Giovanni , Gasparini Mauro
Published: December 2018

When sampling independent observations drawn from the uniform distribution on the unit interval, as the sample size gets large the asymptotic behaviour of both the empirical distribution function and empirical quantile function is well known. In this article we study analogous asymptotic results for the function that is obtained by composing the empirical quantile function with the empirical distribution function. Since the former is the generalized inverse of the latter, the result will approximate the identity function. We define a scaled and centered version of this function—the empirical identity process—and prove it converges to a highly irregular limit process whose trajectories are not right‐continuous and impossible to study using standard probability in metric spaces. However, when this process is integrated over time, and appropriately rescaled and centered, it becomes possible to define a functional limit theorem for it, which then converges to a randomly pinned Brownian motion. By applying these theoretical results, a new goodness‐of‐fit test is derived. We demonstrate that this test is very efficient when it is applied to data which come from a multimodal or mixture distribution, like the classic Old Faithful dataset. The Canadian Journal of Statistics 46: 656–672; 2018 © 2018 Société statistique du Canada
Rank theory approach to ridge, LASSO, preliminary test and Stein‐type estimators: A comparative study
Authors: Saleh A. K. Md. Ehsanes , Navrátil Radim , Norouzirad Mina
Published: December 2018

In the development of efficient predictive models, the key is to identify suitable predictors to establish a prediction model for a given linear or nonlinear model. This paper provides a comparative study of ridge regression, least absolute shrinkage and selector operator (LASSO), preliminary test (PTE) and Stein‐type estimators based on the theory of rank statistics. Under the orthonormal design matrix of a given linear model, we find that the rank‐based ridge estimator outperforms the usual rank estimator, restricted R‐estimator, rank‐based LASSO, PTE and Stein‐type R‐estimators uniformly. On the other hand, neither LASSO nor the usual R‐estimator, preliminary test and Stein‐type R‐estimators outperform the other. The region of dominance of LASSO over all the R‐estimators (except the ridge R‐estimator) is the sparsity‐dimensional interval around the origin of the parameter space. We observe that the L2‐risk of the restricted R‐estimator equals the lower bound on the L2‐risk of LASSO. Our conclusions are based on L2‐risk analysis and relative L2‐risk efficiencies with related tables and graphs. The Canadian Journal of Statistics 46: 690–704; 2018 © 2018 Société statistique du Canada
Association of acute myocardial infarction cardiac arrest patient volume and in‐hospital mortality in the United States: Insights from the National Cardiovascular Data Registry Acute Coronary Treatment And Intervention Outcomes Network Registry
Authors: Kontos Michael C. , Fordyce Christopher B. , Chen Anita Y. , Chiswell Karen , Enriquez Jonathan R. , de Lemos James , Roe Matthew T.
Published: December 2018

Background

Little is known about how differences in out of hospital cardiac arrest patient volume affect in‐hospital myocardial infarction (MI) mortality.

Hypothesis

Hospitals accepting cardiac arrest transfers will have increased hospital MI mortality.

Methods

MI patients (ST elevation MI [STEMI] and non‐ST elevation MI [NSTEMI]) in the Acute Coronary Treatment Intervention Outcomes Network Registry were included. Hospital variation of cardiac arrest and temporal trend of the proportion of cardiac arrest MI patients were explored. Hospitals were divided into tertiles based on the proportion of cardiac arrest MI patients, and association between in‐hospital mortality and hospital tertiles of cardiac arrest was compared using logistic regression adjusting for case mix.

Results

A total of 252 882 patients from 224 hospitals were included, of whom 9682 (3.8%) had cardiac arrest (1.6% of NSTEMI and 7.5% of STEMI patients). The proportion of MI patients who had cardiac arrest admitted to each hospital was relatively low (median 3.7% [25th, 75th percentiles: 3.0%, 4.5%]).with a range of 4.2% to 12.4% in the high‐volume tertiles. Unadjusted in‐hospital mortality increased with tertile: low 3.8%, intermediate 4.6%, and high 4.7% (P < 0.001); this was no longer significantly different after adjustment (intermediate vs high tertile odds ratio (OR) = 1.02; 95% confidence interval [0.90‐1.16], low vs high tertile OR = 0.93 [0.83, 1.05]).

Conclusions

The proportion of MI patients who have cardiac arrest is low. In‐hospital mortality among all MI patients did not differ significantly between hospitals that had increased proportions of cardiac arrest MI patients. For most hospitals, overall MI mortality is unlikely to be adversely affected by treating cardiac arrest patients with MI.
CHA2DS2‐VASc score predicts atrial fibrillation recurrence after cardioversion: Systematic review and individual patient pooled meta‐analysis
Authors: Vitali Francesco , Serenelli Matteo , Airaksinen Juhani , Pavasini Rita , Tomaszuk‐Kazberuk Anna , Mlodawska Elzbieta , Jaakkola Samuli , Balla Cristina , Falsetti Lorenzo , Tarquinio Nicola , Ferrari Roberto , Squeri Angelo , Campo Gianluca , Bertini Matteo
Published: December 2018

Background

Despite progresses in the treatment of the thromboembolic risk related to atrial fibrillation (AF), the management of recurrences remains a challenge.

Hypothesis

To assess if congestive heart failure or left ventricular systolic dysfunction (CHA2DS2‐VASc) score is predictive of early arrhythmia recurrence after AF cardioversion.

Methods

Systematic review and individual patient pooled meta‐analysis following Preferred Reporting Items for Systematic reviews and Meta‐Analyses guidelines. Inclusion criteria: observational trials in patients with AF undergoing cardioversion, available data on recurrence of AF and available data on CHA2DS2‐VASc score. Clinical studies of interest were retrieved by PubMed, Cochrane Library, and Biomed Central. Seven authors were contacted for joining the patient level meta‐analysis, and three shared data regarding anthropometric measurements, risk factors, major comorbidities, and CHA2DS2‐VASc score. The primary outcome was the recurrence of AF after cardioversion in patients free from antiarrhythmic prophylaxis. Univariate and multivariate logistic regression was performed.

Results

Overall, we collect data of 2889 patients: 61% were male, 50% with hypertension, 12% with diabetes, and 23% with history of ischemic heart disease. The median CHA2DS2‐VASc score was 2.. At the multivariate analysis, chronic kidney disease (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.12‐3.27; P = 0.01), peripheral artery disease (OR 1.65; 95% CI 1.23‐2.19; P < 0,0001), previous use of beta blockers (OR 1.5; 95% CI 1.19‐1.88; P < 0.0001), and CHA2DS2‐VASc score > 2 (OR 1.37; 95% CI 1.1‐1.68; P = 0.002) were independent predictors of early recurrence of AF.

Conclusions

CHA2DS2‐VASc score predicts early recurrence of AF in the first 30 days after electrical or pharmacological cardioversion.

Protocol registration

PROSPERO (CRD42017075107).
Predictive value of a fragmented QRS complex in diagnosing patients with myocardial ischemia
Authors: Cho H. J. , Yoon J. Y. , Kim N. , Jang S. Y. , Bae M. H. , Lee J. H. , Yang D. H. , Park H. S. , Cho Y. , Chae S. C.
Published: December 2018

Background

A fragmented QRS complex (fQRS) is caused by conduction abnormalities of the ventricle secondary to myocardial ischemia and/or scar in patients with myocardial infarction. However, the implications of the fQRS in the development of coronary artery disease with myocardial ischemia in those without a scar remain unknown.

Methods

We studied electrocardiograms (ECGs) obtained from 150 patients (60.5 ± 8.5 years, 102 men) with myocardial ischemia, which was confirmed by performing both, a nuclear exercise stress test and coronary angiography. We also studied ECGs obtained from 601 patients (58.5 ± 10.0 years, 315 men) who showed a negative nuclear exercise stress test (control group). Patients in whom the nuclear exercise stress test showed a myocardial scar were excluded.

Results

An fQRS was more commonly observed in patients with myocardial ischemia (n = 48, 32.0%) than in the control group (n = 133, 22.1%) (P = 0.011). The sensitivity, specificity, positive, and negative predictive values of fQRS in diagnosing myocardial ischemia were 32.0, 77.9, 26.5, and 82.1%, respectively. The fQRS (odds ratio 1.580, 95% confidence interval 1.020‐2.446, P = 0.040) was an independent predictor of myocardial ischemia after adjusting for age, sex, current smoking habits, ST‐T changes on ECG, as well as histories of hypertension, diabetes, and dyslipidemia. Moreover, the fQRS showed an incremental prognostic value over conventional risk factors (χ2 = 5, P = 0.032) and over a combination of conventional factors and ST‐T changes (χ2 = 9, P = 0.014).

Conclusions

The fQRS is a moderately sensitive and independent predictor of myocardial ischemia.
Dynamic organelle localization and cytoskeletal reorganization during preimplantation mouse embryo development revealed by live imaging of genetically encoded fluorescent fusion proteins
Authors: Kiyonari Hiroshi , Kaneko Mari , Abe Takaya , Shioi Go , Aizawa Shinichi , Furuta Yasuhide , Fujimori Toshihiko
Published: December 2018

Live imaging is one of the most powerful technologies for studying the behaviors of cells and molecules in living embryos. Previously, we established a series of reporter mouse lines in which specific organelles are labeled with various fluorescent proteins. In this study, we examined the localizations of fluorescent signals during preimplantation development of these mouse lines, as well as a newly established one, by time‐lapse imaging. Each organelle was specifically marked with fluorescent fusion proteins; fluorescent signals were clearly visible during the whole period of time‐lapse observation, and the expression of the reporters did not affect embryonic development. We found that some organelles dramatically change their sub‐cellular distributions during preimplantation stages. In addition, by crossing mouse lines carrying reporters of two distinct colors, we could simultaneously visualize two types of organelles. These results confirm that our reporter mouse lines can be valuable genetic tools for live imaging of embryonic development.
Estimating uncertainty in the volume and carbon storage of downed coarse woody debris
Authors: Campbell John L. , Green Mark B. , Yanai Ruth D. , Woodall Christopher W. , Fraver Shawn , Harmon Mark E. , Hatfield Mark A. , Barnett Charles J. , See Craig R. , Domke Grant M.
Published: December 2018

Downed coarse woody debris, also known as coarse woody detritus or downed dead wood, is challenging to estimate for many reasons, including irregular shapes, multiple stages of decay, and the difficulty of identifying species. In addition, some properties are commonly not measured, such as wood density and carbon concentration. As a result, there have been few previous evaluations of uncertainty in estimates of downed coarse woody debris, which are necessary for analysis and interpretation of the data. To address this shortcoming, we quantified uncertainties in estimates of downed coarse woody debris volume and carbon storage using data collected from permanent forest inventory plots in the northeastern United States by the Forest Inventory and Analysis program of theUSDAForest Service. Quality assurance data collected from blind remeasurement audits were used to quantify error in diameter measurements, hollowness of logs, species identification, and decay class determination. Uncertainty estimates for density, collapse ratio, and carbon concentration were taken from the literature. Estimates of individual sources of uncertainty were combined using Monte Carlo methods. Volume estimates were more reliable than carbon storage, with an average 95% confidence interval of 15.9 m3/ha across the 79 plots evaluated, which was less than the mean of 31.2 m3/ha. Estimates of carbon storage (and mass) were more uncertain, due to poorly constrained estimates of the density of wood. For carbon storage, the average 95% confidence interval was 11.1 Mg C/ha, which was larger than the mean of 4.6 Mg C/ha. Accounting for the collapse of dead wood as it decomposes would improve estimates of both volume and carbon storage. On the other hand, our analyses suggest that consideration of the hollowness of downed coarse woody debris pieces could be eliminated in this region, with little effect. This study demonstrates how uncertainty analysis can be used to quantify confidence in estimates and to help identify where best to allocate resources to improve monitoring designs.
Implicit attitudes toward dieting and thinness distinguish fat‐phobic and non‐fat‐phobic anorexia nervosa from avoidant/restrictive food intake disorder in adolescents
Authors: Izquierdo Alyssa , Plessow Franziska , Becker Kendra R. , Mancuso Christopher J. , Slattery Meghan , Murray Helen B. , Hartmann Andrea S. , Misra Madhusmita , Lawson Elizabeth A. , Eddy Kamryn T. , Thomas Jennifer J.
Published: December 2018

Objective

The majority of individuals with anorexia nervosa (AN) have a fat‐phobic (FP‐AN) presentation in which they explicitly endorse fear of weight gain, but a minority present as non‐fat‐phobic (NFP‐AN). Diagnostic criteria for avoidant/restrictive food intake disorder (ARFID) specifically exclude fear of weight gain. Differential diagnosis between NFP‐AN and ARFID can be challenging and explicit endorsements do not necessarily match internal beliefs.

Method

Ninety‐four adolescent females (39 FP‐AN, 13 NFP‐AN, 10 low‐weight ARFID, 32 healthy controls [HC]) completed implicit association tests (IATs) categorizing statements as pro‐dieting or non‐dieting and true or false (questionnaire‐based IAT), and images of female models as underweight or normal‐weight and words as positive or negative (picture‐based IAT). We used the Eating Disorder Examination to categorize FP‐ versus NFP‐AN presentations.

Results

Individuals with FP‐AN and NFP‐AN demonstrated a stronger association between pro‐dieting and true statements, whereas those with ARFID and HCs demonstrated a stronger association between pro‐dieting and false statements. Furthermore, while all groups demonstrated a negative implicit association with underweight models, HC participants had a significantly stronger negative association than individuals with FP‐AN and NFP‐AN.

Discussion

Individuals with NFP‐AN exhibited a mixed pattern in which some of their implicit associations were consistent with their explicit endorsements, whereas others were not, possibly reflecting a minimizing response style on explicit measures. In contrast, individuals with ARFID demonstrated implicit associations consistent with explicit endorsements. Replication studies are needed to confirm whether the questionnaire‐based IAT is a promising method of differentiating between restrictive eating disorders that share similar clinical characteristics.
A study on classification algorithm of REM sleep behavior disorder
Authors: Kinoshita Fumiya , Takada Hiroki , Nakayama Meiho
Published: December 2018

Sleep disorders are modern diseases that have recently increased in prevalence. In particular, the rapid eye movement (REM) sleep behavior disorder (RBD) is well known. As a hallmark of the RBD, we can find the loss of skeletal muscle atonia during the REM sleep, which is called the REM sleep without atonia (RWA), in the polysomnography (PSG). Therefore, measurement of muscle activity is required for the diagnosis of RBD. Although close follow‐up of patients’ recovery process is required and several visual inspection methods have been developed for the PSG reading, clear diagnostic criteria for assessing RBD severity have not been established because of the complicated nature of the procedure. In this study, the author constructed automated algorithms based on the American Academy of Sleep Medicine Scoring Manual. The percentage ratio of RWA in the REM sleep period was calculated by the algorithms. The results evaluated by the automated algorithms were compared to the diagnosis by the visual inspection method. In addition, nonlinear discriminant analysis was employed to examine whether the healthy subjects group was significantly different from the group of suspected RBD patients. The author has succeeded in finding an automated algorithm to yield results that are not significantly different from those of visual inspection diagnosis.
Separation of carbohydrates on electrophoresis microchips with controlled electrolysis
Authors: Duarte‐Junior Gerson F. , Lobo‐Júnior Eulício O. , Medeiros Junior Íris , da Silva José A. Fracassi , do Lago Claudimir L. , Coltro Wendell K. T.
Published: December 2018

This study reports the separation of fructose, galactose, glucose, lactose and sucrose on glass microchip electrophoresis (ME) devices using a microfluidic platform adapted with external reservoirs for controlling the electrolysis phenomenon. The connections between external reservoirs and microfluidic platform were performed by saline bridges created using silicone tubing filled with BGE. The separation conditions were optimized and the best results were achieved using a BGE containing 75 mmol/L NaOH and 15 mmol/L trisodium phosphate. Electrophoretic separations were monitored using a capacitively coupled contactless conductivity detection system. The controlled electrolysis has successfully allowed the application of a higher voltage on the separation channel promoting the baseline separation of five carbohydrates within 180 s with great run‐to‐run repeatability (RSD < 1%). The achieved efficiencies ranged from 45 000 ± 6000 to 70 000 ± 3000 plates/m demonstrating a performance better than ME devices without controlled electrolysis. The proposed system offered good linearity from 1 to 10 mmol/L and LODs between 150 and 740 μmol/L. The use of external tubes for controlling the electrolysis phenomenon on ME devices has solved common problems associated to run‐to‐run repeatability and analytical reliability required for routine and quantitative analysis.
Frequent mutations of genes encoding vacuolar H+‐ATPase components in granular cell tumors
Authors: Sekimizu Masaya , Yoshida Akihiko , Mitani Sachiyo , Asano Naofumi , Hirata Makoto , Kubo Takashi , Yamazaki Fumito , Sakamoto Hiromi , Kato Mamoru , Makise Naohiro , Mori Taisuke , Yamazaki Naoya , Sekine Shigeki , Oda Ichiro , Watanabe Shun‐ichi , Hiraga Hiroaki , Yonemoto Tsukasa , Kawamoto Teruya , Naka Norifumi , Funauchi Yuki , Nishida Yoshihiro , Honoki Kanya , Kawano Hirotaka , Tsuchiya Hiroyuki , Kunisada Toshiyuki , Matsuda Koichi , Inagaki Katsunori , Kawai Akira , Ichikawa Hitoshi
Published: December 2018

Granular cell tumors (GCTs) are rare mesenchymal tumors that exhibit a characteristic morphology and a finely granular cytoplasm. The genetic alterations responsible for GCT tumorigenesis had been unknown until recently, when loss‐of‐function mutations of ATP6AP1 and ATP6AP2 were described. Thus, we performed whole‐exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples. From these genomic analyses, we identified mutations in genes encoding vacuolar H+‐ATPase (V‐ATPase) components, including ATP6AP1 and ATP6AP2, in 33 (65%) GCTs. ATP6AP1 and ATP6AP2 mutations were found in 23 (45%) and 2 (4%) samples, respectively, and all were truncating or splice site mutations. In addition, seven other genes encoding V‐ATPase components were also mutated, and three mutations in ATP6V0C occurred on the same amino acid (isoleucine 136). These V‐ATPase component gene mutations were mutually exclusive, with one exception. These results suggest that V‐ATPase function is impaired in GCTs not only by loss‐of‐function mutations of ATP6AP1 and ATP6AP2 but also through mutations of other subunits. Our findings provide additional support for the hypothesis that V‐ATPase dysfunction promotes GCT tumorigenesis.
p75NTR regulates brain mononuclear cell function and neuronal structure in Toxoplasma infection‐induced neuroinflammation
Authors: Düsedau Henning Peter , Kleveman Jan , Figueiredo Caio Andreeta , Biswas Aindrila , Steffen Johannes , Kliche Stefanie , Haak Stefan , Zagrebelsky Marta , Korte Martin , Dunay Ildiko Rita
Published: December 2018

Neurotrophins mediate neuronal growth, differentiation, and survival via tropomyosin receptor kinase (Trk) or p75 neurotrophin receptor (p75NTR) signaling. The p75NTR is not exclusively expressed by neurons but also by certain immune cells, implying a role for neurotrophin signaling in the immune system. In this study, we investigated the effect of p75NTR on innate immune cell behavior and on neuronal morphology upon chronic Toxoplasma gondii (T. gondii) infection‐induced neuroinflammation. Characterization of the immune cells in the periphery and central nervous system (CNS) revealed that innate immune cell subsets in the brain upregulated p75NTR upon infection in wild‐type mice. Although cell recruitment and phagocytic capacity of p75NTRexonIV knockout (p75−/−) mice were not impaired, the activation status of resident microglia and recruited myeloid cell subsets was altered. Importantly, recruited mononuclear cells in brains of infected p75−/− mice upregulated the production of the cytokines interleukin (IL)‐10, IL‐6 as well as IL‐1α. Protein levels of proBDNF, known to negatively influence neuronal morphology by binding p75NTR, were highly increased upon chronic infection in the brain of wild‐type and p75−/− mice. Moreover, upon infection the activated immune cells contributed to the proBDNF release. Notably, the neuroinflammation‐induced changes in spine density were rescued in the p75−/− mice. In conclusion, these findings indicate that neurotrophin signaling via the p75NTR affects innate immune cell behavior, thus, influencing the structural plasticity of neurons under inflammatory conditions.
Treatment outcomes with whole‐field versus split‐field intensity‐modulated radiotherapy for patients with nasopharyngeal carcinoma
Authors: Lin Chun‐Shu , Chen Yuan‐Wu , Liu Shao‐Cheng , Tsao Chih‐Cheng , Lin Kuen‐Tze , Lee Steve P. , Fan Chao‐Yueh , Liu Ming‐Yueh , Shen Po‐Chien , Jen Yee‐Min
Published: December 2018

Background

The purpose of this study was to present our comparison of the clinical outcome of patients with nasopharyngeal carcinoma (NPC) treated with whole‐field intensity‐modulated radiotherapy (whole‐field‐IMRT) or split‐field‐IMRT.

Methods

We retrospectively studied 388 patients with M0 NPC. The median lower neck doses were 50 Gy in 1.35 Gy/fractions for the 240 whole‐field‐IMRT patients, and 50.4 Gy in 1.8 to 2.0 Gy/fractions for the 148 split‐field‐IMRT patients.

Results

The IMRT technique did not affect the overall survival (OS; P = .077) and locoregional control (P = .231) rates. However, the split‐field‐IMRT group had more locoregional recurrences at the whole neck (P = .005) but not at the nasopharynx (P = .968) or the lower neck (P = .485). The patients treated with split‐field‐IMRT (43.2%) had more grade III neck fibrosis than the patients who received whole‐field‐IMRT (18.3%; P < .001). Only 1 patient had temporal lobe necrosis in our study.

Conclusion

Our study shows that whole‐field‐IMRT using a lower dose/fraction for the lower neck results in at least comparable locoregional control and less fibrosis compared to conventional fraction with split‐field‐IMRT.