bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity‐Oriented Synthesis of Spirocyclohexene Indane‐1,3‐diones and Coumarin‐Fused Cyclopentanes via an Organobase‐Controlled Cascade Reaction
Authors: Wang Min , Tseng Ping‐Yao , Chi Woei‐Jye , Suresh Sundaram , Edukondalu Athukuri , Chen Yi‐Ru , Lin Wenwei
Published: June 2020

An organobase‐controlled, divergent cascade reaction to construct spirocyclohexene indane‐1,3‐diones and coumarin‐fused cyclopentanes is reported. The cascade reaction is triggered by the 1,6‐addition of 3‐homoacylcoumarins to the indanedione‐derived acceptors and further regio/chemoselective reaction that preferentially resulted in spiro systems and fused cyclopentanes in a diversity‐oriented manner. The 1,6‐addition/aldol and 1,6‐addition/vinylogous Michael addition cascade processes were controlled by different base/solvent systems to the predominant formation of one of the two carbocyclic compounds.

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Dynamic Assembly of Active Colloids: Theory and Simulation
Authors: Ma Zhan , Yang Mingcheng , Ni Ran
Published: June 2020

Because they consume energy to drive their motion, systems of active colloids are intrinsically out of equilibrium. In past decades, a variety of intriguing dynamic patterns have been observed in systems of active colloids, which offer a new platform for studying non‐equilibrium physics, in which computer simulation and analytical theory have played an important role. Recent progress in understanding the dynamic assembly of active colloids by using numerical and analytical tools is reviewed, including progress in understanding the motility induced phase separation in the past decade, followed by discussion on the effect of shape anisotropy and hydrodynamics on the dynamic assembly of active colloids.
Fatigue‐Free Aurivillius Phase Ferroelectric Thin Films with Ultrahigh Energy Storage Performance
Authors: Pan Zhongbin , Wang Peng , Hou Xu , Yao Lingmin , Zhang Guangzu , Wang Jie , Liu Jinjun , Shen Meng , Zhang Yujing , Jiang Shenglin , Zhai Jiwei , Wang Qing
Published: June 2020

Dielectric capacitors have become a key enabling technology for electronics and electrical systems. Although great strides have been made in the development of ferroelectric ceramic and thin films for capacitors, much less attention has been given to preventing polarization fatigue, while improving the energy density, of ferroelectrics. Here superior capacitive properties and outstanding stability are reported over 107 charge/discharge cycles and a wide temperature range of −60 to 200 °C of ferroelectric Aurivillius phase Bi3.25La0.75Ti3O12‐BiFeO3 (BLT‐BFO), which represents one of the best capacitive performances recorded for the ferroelectric materials. The modification of BLT thin films with BFO overcomes the constraints of ferroelectric Aurivillius compounds and presents an unprecedented combination of the ideal features including improved polarization, reduced ferroelectric hysteresis, and lowered leakage current for high‐energy‐density capacitors. Given the lead‐free and fatigue‐free nature of this Aurivillius phase ferroelectric, this work unveils a new approach towards high‐performance eco‐friendly ferroelectric materials for electrical energy storage applications.
Do diverse cover crop mixtures perform better than monocultures? A systematic review
Authors: Florence A. M. , McGuire A. M.
Published: June 2020

Multi‐species cover crop mixtures have been increasing in popularity. It has been hypothesized these mixtures produce more biomass, suppress more weeds, scavenge more N, conserve more soil water, stimulate more soil biology, promote higher yields of subsequent crops, and have higher production stability than the best of their monoculture counterparts. This systematic review synthesizes a growing body of cover crop mixture research to assess, for these metrics, whether cover crop mixtures can perform better than their constituent species when planted alone. Searching three databases, we identified 27 studies which compared cover crop mixtures (containing at least three species) to all their constituent species. The studies contained 119 sampled cover crop plantings that met our eligibility criteria. From these, we extracted 243 full comparisons of the best‐performing mixture and best‐performing monoculture for the selected metrics. In 88% of these comparisons, the monoculture and mixture performed comparably. In 10% of the comparisons, the monoculture did better, and in 2% of comparisons the mixture performed better. Overall, there are few published studies documenting the superiority of cover crop mixtures over monocultures for our selected metrics.
Automating Analogue AI Chip Design with Genetic Search
Authors: Krestinskaya Olga , Salama Khaled N. , James Alex P.
Published: June 2020

Optimization of analogue neural circuit designs is one of the most challenging, complicated, time‐consuming, and expensive tasks. Design automation of analogue neuromemristive chips is made difficult by the need to design chips at low cost, ease of scaling, high‐energy efficiency, and small on‐chip area. The rapid progress in edge AI computing applications generates high demand for developing smart sensors. The integration of high‐density analogue computing AI chips as coprocessing units to sensors is gaining popularity. This article proposes a hardware–software codesign framework to speed up and automate the design of analogue neuromemristive chips. This work uses genetic algorithms with objective functions that take into account hardware nonidealities such as limited precision of devices, the device‐to‐device variability, and device failures. The optimized neural architectures and hyperparameters successfully map with the library of relevant neuromemristive analogue hardware blocks. The results demonstrate the advantage of proposed automation to speed up the analogue circuit design of large‐scale neuromemristive networks and reduce overall design costs for AI chips.
N,N′‐bridged binuclear NHC palladium complexes: A combined experimental catalytic and computational study for the Suzuki reaction
Authors: Chen Ming‐Tsz , Hsieh Bing‐Yan , Liu Yi‐Hung , Wu Kuo‐Hui , Lussari Natália , Braga Ataualpa A.C.
Published: June 2020

This work examines how N‐donor bridged spacer ligands affect N‐heterocyclic carbene (NHC) palladium complexes catalytic activities for Suzuki coupling reaction. Different degrees of structural flexibility binuclear NHC palladium complexes were synthesized. The more flexible nitrogen‐based alkyl chain ligand shows similar performance with cycloamine counterparts in the Suzuki coupling reaction. Suzuki coupling examples were used in air and ambient temperature to reach moderate to completion yields in short time. Density functional theory calculations showed that the chelate effect, associated with a single Pd complex mechanism, plays a fundamental role in the pre‐catalysis stage, supporting a reasonable of the kinetic activity observed experimentally.
Choline chloride‐urea deep eutectic solvent as an efficient media for the synthesis of propargylamines via organocuprate intermediate
Authors: Abtahi Bahareh , Tavakol Hossein
Published: June 2020

A facile method for the synthesis of various propargylamines derivatives with different structural parts has been reported. The reaction has consisted of one‐pot coupling between aldehydes, secondary amines and terminal alkynes using CuCl as a catalyst and choline chloride/urea DES as a cheap and biocompatible reaction media. The procedure is free of using toxic solvents and used CuCl as an available, inexpensive and non‐toxic catalyst. Using this methodology, 15 different propargylamine derivatives were successfully synthesized at 60 °C in 15 hr, mostly in good yields.
The β2‐Glycoprotein I/HLA–DR Complex As a Major Autoantibody Target in Obstetric Antiphospholipid Syndrome
Authors: Tanimura Kenji , Saito Shigeru , Nakatsuka Mikiya , Nagamatsu Takeshi , Fujii Tomoyuki , Fukui Atsushi , Deguchi Masashi , Sasagawa Yuki , Arase Noriko , Arase Hisashi , Yamada Hideto
Published: June 2020

Objective

The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, β2‐glycoprotein I (β2GPI) complexed with HLA class II molecules (β2GPI/HLA‐DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the β2GPI/HLA II complex as a potential risk factor for RPL in women.

Methods

Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti–β2GPI antibodies, and lupus anticoagulant as well as anti‐β2GPI/HLA–DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross‐sectional study, women with RPL and their partners underwent HLA–DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti‐β2GPI/HLA–DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential).

Results

Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti‐β2GPI/HLA–DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti‐β2GPI/HLA–DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti‐β2GPI/HLA–DR antibodies.

Conclusion

The anti‐β2GPI/HLA–DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.
Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis
Authors: Bernstein Elana J. , Jaafar Sara , Assassi Shervin , Domsic Robyn T. , Frech Tracy M. , Gordon Jessica K. , Broderick Rachel J. , Hant Faye N. , Hinchcliff Monique E. , Shah Ami A. , Shanmugam Victoria K. , Steen Virginia D. , Khanna Dinesh
Published: June 2020

Objective

Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc). Although pulmonary function tests (PFTs) are commonly used to screen for ILD in patients with SSc, studies have shown that they lack sensitivity for the detection of ILD in general SSc cohorts. This study was undertaken to assess the performance characteristics of PFTs for the detection of ILD in patients with early diffuse cutaneous SSc (dcSSc), a population at high risk for the development of ILD.

Methods

We performed a retrospective cohort study of patients enrolled in the Prospective Registry of Early Systemic Sclerosis at 11 sites in the US between April 2012 and January 2019. Patients were included if they underwent spirometry and high‐resolution computed tomography (HRCT) of the chest. We calculated the performance characteristics of PFTs for the detection of ILD on HRCT.

Results

The study included 212 patients, 54% of whom had radiographic ILD. For the detection of ILD on HRCT imaging, a forced vital capacity (FVC) <80% predicted had a sensitivity of 63%. The combination of FVC <80% predicted or diffusing capacity for carbon monoxide (DLco) <80% predicted improved the sensitivity to 85%. An FVC <80% predicted had a negative predictive value (NPV) of 61%, while the combination of FVC <80% predicted or DLco <80% predicted had an NPV of 70%.

Conclusion

PFTs alone are an inadequate screening tool for the diagnosis of ILD in patients with early dcSSc. HRCT should be part of the ILD screening algorithm in patients with dcSSc.
The Effectiveness of an Augmented Reality Head‐Mounted Display in Learning Skull Anatomy at a Community College
Authors: Duncan‐Vaidya Elizabeth A. , Stevenson Erica L.
Published: June 2020

Despite an increase in the use of technology in undergraduate anatomy education, and the rising popularity of online anatomy courses at community colleges in the United States, there have been no reports on the efficacy of augmented reality on anatomy education in this population. The purpose of this study was to test the hypothesis that augmented reality is an effective and engaging tool for learning anatomy in community college students. Participants recruited from Cuyahoga Community College (Cleveland, OH) studied skull anatomy using either traditional tools (i.e., textbook and plastic skull model) or an augmented reality head‐mounted display with an interactive virtual skull application. Comparison of knowledge before and following the study period revealed that augmented reality was an effective tool for learning skull anatomy: pre‐quiz = 32.7% (± 25.2); mean (± SD), post‐quiz = 61.8% (± 19.5); n = 15; t(28) = 3.53; P = 0.001. The traditional tools were equally effective: pre‐quiz = 44.9 % (± 18.6), post‐quiz = 67.9 % (± 17.3); n = 17; t(32) = 3.73; P = 0.0007. Students rated the augmented reality device as 9.6 (± 1.0); mean (± SD) when asked if it fit the statement “fun to use” on a semantic differential scale from 1 (poor) to 10 (excellent). In conclusion, this study found that augmented reality is an effective and engaging tool for the instruction of skull anatomy at a community college.
Review of life‐cycle greenhouse‐gas emissions assessments of hydroprocessed renewable fuel (HEFA) from oilseeds
Authors: Zemanek Debrah , Champagne Pascale , Mabee Warren
Published: June 2020

Renewable fuel from the hydroprocessed esters and fatty acids (HEFA) pathway represents a promising short‐term option for reducing fossil fuel use in transportation. However, some life‐cycle assessments (LCAs) have shown that HEFA diesel and jet fuel may have higher life‐cycle greenhouse gas (GHG) emissions than the fossil fuels they replace. Many of these studies examined HEFA fuel derived from oilseed feedstocks. Here, results and methodology from 20 LCAs of HEFA fuel from oilseeds are reviewed in an effort to determine the sources of variability in the reported life‐cycle GHG emissions of HEFA fuels. Although there was a 61–63% reduction in median life cycle GHG emissions of HEFA biojet and renewable diesel compared to conventional petroleum fuels, this review highlights the importance of standardized methodologies for life‐cycle assessment (e.g., CORSIA, RSB) and indicates the need to prevent the conversion of forest land for biofuel production, as well as the potential opportunity for alternative oilseeds such as camelina and carinata as feedstocks to produce HEFA fuels with lower life‐cycle GHG emissions. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd
The effect of perceived financial vulnerability on prosocial activity
Authors: Motsenok Marina , Ritov Ilana
Published: June 2020

Our research examines the effect of subjective financial vulnerability on prosocial activity. First, data from the European Survey of Health, Aging and Retirement (SHARE) revealed that higher assessment of one's financial vulnerability might be associated with prosocial motivation for social activities. Next, we manipulated participants' perception of their relative financial position compared to their peers and found that participants randomly assigned to the low financial position condition were more willing to volunteer than participants assigned to the high financial position condition. In Study 3, we manipulated participants' financial advantage. Participants who were disadvantaged in the experimental settings were more willing to volunteer and donate to charity compared to participants with financial advantage. In our final study, we examined willingness to donate to in‐group and out‐group help organizations and found that individuals of lower perceived financial standing may be motivated by the goal of increasing the strength of the social group, rather than by expectations of direct reciprocity. We also found that emotional distress mediates the relationship between perceived financial vulnerability and prosocial behavior. In line with earlier research illustrating that lower financial status promotes prosociality on an interpersonal level, we demonstrate that even momentary perception of relative financial disadvantage and vulnerability promotes prosociality in the broader social context.
Teaching now, facing the future
Authors: Lu Xiaoyun , Ding Yan
Published: June 2020

To obtain knowledge is not the purpose of education, but to develop one's potential ability and to obtain wisdom is. We are living in a fast changing world and knowledge is growing explosively. Therefore, what facts or information students have known in your class is not the most important thing. What really matters is how efficiently students could learn and how those knowledge they have learned can help them to deal with their own tasks in the future. This article introduces our four‐dimensional comprehensive course design and the teaching activities we used to optimize and improve students' learning and developing process.
Investigating the relationship between interleukin‐6 serum levels and outcome in acute ischemic CVA
Authors: Mosarrezaii Arash , Amiri‐Nikpour Mohammad Reza , Mehryar Hamid Reza , Choobi Anzali Babak , Nourooz‐Zadeh Sarmad , Babaei Shadi , Farrokhi Hedieh
Published: June 2020

Introduction

Interleukin‐6 (IL‐6) is among the inflammatory mediators exhibiting elevated levels in ischemic stroke (IS) patients. The present study set out to evaluate the relationship between serum levels of interleukin‐6 with long‐term and at‐hospital outcomes of acute ischemic stroke in patients hospitalized at Imam Khomeini Hospital, Urmia, Iran, from 2017 to 2018.

Method and materials

This cross‐sectional descriptive study enrolled 29 and 31 acute stroke patients for long‐term and at‐hospital observation, respectively. Evaluation of stroke severity was performed using the National Institute of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) on days 1, 5, and 90. Serum IL‐6 level was measured via enzyme‐linked immunosorbent assay (ELISA) on days one and five.

Results

In the present cohort study, the following population were enrolled: for long‐term evaluation, 11 (38%) men and 18 (63%) women with a mean age of 64.5 ± 14.9 years, and for at‐hospital evaluation: 11 (37.5%) men and 20 (64.5%) with a mean age of 65.25 ± 14.37 years. A significant positive correlation was observed between IL‐6 levels with NIHSS and mRS scores of the patients from time of admission until the end of the follow‐up period (long‐term: p < .001; at‐hospital: 0.022).

Conclusion

The evidence from the present study suggests that IL‐6 contributes to the determination of the severity of ischemic strokes and may be useful in predicting prognosis. However, larger scale studies are required to further establish these finds.
Implementing the circular economy in the Amsterdam Metropolitan Area: The interplay between market actors mediated by transition brokers
Authors: Cramer Jacqueline M.
Published: June 2020

This paper analyses the interplay between regime and niche actors in implementing the circular economy through mediation by transition brokers. The study is based on ‘action research’ carried out in the Amsterdam Metropolitan Area. Innovation science is adopted as theoretical approach. First, the analysis shows that more ambitious initiatives could be taken than by individual market actors. Whether these circular initiatives represent just incremental change—as other studies suggest—cannot be concluded. Rather, it is plausible to conceptualise the transition process as a continuous transformational change. Second, in creating circular initiatives, the interplay between regime and niche actors was evident but varied. Actors could team up more easily where their interests aligned. This conclusion corresponds with recent innovation literature, which emphasises the importance of linkages between processes at niche, regime and landscape levels. Before generalising the results, similar studies in other regional contexts would be valuable.

Short informative

In moving to a circular economy, the willingness of market actors to innovate is crucial.

Real‐life experiments on the implementation of circular initiatives built by market actors at local level through the mediation of independent intermediaries (here called ‘transition brokers’) are scarce. This study aims to bridge this knowledge gap by focussing on the interplay between niche and regime actors.

Action research on implementing the circular economy programme in the Amsterdam Metropolitan Area (2015–2020) represents an example.

Innovation science is adopted as leading theoretical approach.

The case shows that more advanced ambitions could be achieved than through individual market actors by themselves. Whether the circular initiatives built represent just incremental change—as suggested in the few other studies—is considered too simplistic. It is concluded to conceptualise the CE transition rather as a continuous, transformational change which takes time.

The interplay between niche and regime actors was evident in the case but varied. Niche actors could team up more easily with regime actors where their interests coincided. Niche CE innovations did not necessarily develop in protected environments, as suggested by early MLP studies. They could diffuse more widely if they link up with ongoing processes at regime and landscape level. This conclusion corresponds with the more recent innovation literature.
Longitudinal analysis of pediatric distal radius alignment parameters in a cohort of serial radiographs
Authors: Knapik Derrick M. , Kolaczko Jensen G. , Drummond Ian , Liu Raymond W.
Published: June 2020

Background

Growth in pediatric patients necessitates changes to bony structures throughout the entire body to suit development. Changes in the distal radius during growth are of interest in the pediatric population due to the high incidence of fractures. The purpose of this study was to assess for trends in three radiographic measurements (height of the radial styloid process, radial inclination, ulnar variance) of the distal radius using serial radiographs in subjects aged between 6 and 14 years of age.

Materials and Methods

Longitudinal radiographs from 68 healthy children (n = 34 males, 34 females) with a minimal of three annual radiographs between 6 and 14 years of age were analyzed. Measurements of height of the radial styloid process, radial inclination, and ulnar variance were performed in each available radiograph. Repeated measures analysis of variance (ANOVA) was performed to measure the association between alignment values and subject age.

Results

A total of 436 images in 68 subjects were analyzed, comprising a mean of 6.5 ± 2.0 radiographs per subject. Repeated measures ANOVA demonstrated that all measurement variables changed significantly with age (p < .001). Ulnar variance demonstrated the most variability with negative ulnar variance in younger children, and trends towards a more neutral ulnar variance by approximately 7 years in females and 11 years in males, while height of the radial styloid process and radial inclination changed relatively minimally with development.

Conclusions

In the adolescent age range, ulnar variance, height of the radial styloid process and inclination are all relatively stable and adult parameter values can be used to judge restoration of distal radius alignment.
Trabecular bone deterioration in differentiated thyroid cancer: Impact of long‐term TSH suppressive therapy
Authors: Hawkins Carranza Federico , Guadalix Iglesias Sonsoles , Luisa De Mingo Domínguez María , Martín‐Arriscado Arroba Cristina , López Álvarez Begoña , Allo Miguel Gonzalo , Martínez Díaz‐Guerra Guillermo
Published: June 2020

Background

Conflicting results has been reported regard osteoporosis and fractures in patients with Differentiated Thyroid Cancer (DTC). Our objective was to evaluate the long‐term effects of TSH suppression therapy with Levothyroxine (LT4) on trabecular bone score (TBS) and bone mineral density (BMD) in females with DTC after thyroidectomy.

Methods

About 145 women with resected DTC and receiving long‐term TSH therapy, were stratified according to the degree of TSH suppression. Mean duration of follow‐up was 12.3 ± 6.1 years. BMD and TBS, were assessed using dual‐energy X‐ray absorptiometry (DXA) and TBS iNsight (Med‐Imaps), at baseline (1‐3 months after surgery) and at the final study visit.

Results

In patients stratified by duration of TSH suppression therapy (Group I, 5‐10 years; Group II, >10 years), slight increases from baseline TSH levels were observed. Significant decreases in LS‐BMD and FN‐BMD were seen in patients after >10 years. TBS values were lower in Groups I (1.289 ± 0.122) and II (1.259 ± 0.129) compared with baseline values (P = .0001, both groups). Regarding the degree of TSH suppression, TBS was significantly reduced in those with TSH < 0.1 µU/mL (P = .0086), and not in patients with TSH suppression of 0.1.‐0.5 or >0.5 µU/mL.

Conclusions

We found deterioration of trabecular structure in patients with DTC and TSH suppression therapy below 0.1 µU/mL and after 5‐10 years of follow‐up. Significant changes in BMD according to TSH levels were not observed. Trabecular Bone Score is a useful technique for identifying thyroid cancer patients with risk of bone deterioration.
Synthesis of Novel Aryloxyethylamine Derivatives and Evaluation of Their in Vitro and in Vivo Neuroprotective Activities
Authors: Zhong Yan , Gao Yarong , Xu Yi , Qi Changyong , Wu Bin
Published: June 2020

A series of aryloxyethylamine derivatives were designed, synthesized and evaluated for their biological activity. Their structures were confirmed by 1H‐NMR, 13C‐NMR, FT‐IR and HR‐ESI‐MS. The preliminary screening of neuroprotection of compounds in vitro was detected by MTT, and the anti‐ischemic activity in vivo was tested using bilateral common carotid artery occlusion in mice. Most of these compounds showed potential neuroprotective effects against the glutamate‐induced cell death in differentiated rat pheochromocytoma cells (PC12 cells), especially for (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone, (4‐bromophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, (4‐chlorophenyl)(1‐{2‐[(naphthalen‐2‐yl)oxy]ethyl}piperidin‐4‐yl)methanone, (4‐chlorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone and {1‐[2‐(4‐bromophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone, which exhibited potent protection of PC12 cells at three doses (0.1, 1.0, 10 μM). Compounds (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, (4‐fluorophenyl){1‐[2‐(naphthalen‐2‐yloxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed the significant prolongation of the survival time of mice subjected to acute cerebral ischemia and decreased the mortality rate at all five doses tested (200, 100, 50, 25, 12.5 mg/kg) and had significant neuroprotective activity. In addition, (4‐fluorophenyl){1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}methanone, {1‐[2‐(4‐methoxyphenoxy)ethyl]piperidin‐4‐yl}(4‐methoxyphenyl)methanone and {1‐[2‐(4‐chlorophenoxy)ethyl]piperidin‐4‐yl}(4‐chlorophenyl)methanone possessed outstanding neuroprotection in vitro and in vivo. These compounds can be used as a promising neuroprotective agents for future development of new anti‐ischemic stroke agents. Basic structure–activity relationships are also presented.
NLRC3 silencing accelerates the invasion of hepatocellular carcinoma cell via IL‐6/JAK2/STAT3 pathway activation
Authors: Kang Jian‐Hua , Li Ming‐Jie , Luan Pei‐Pei , Jiang De‐Ke , Chen Yuan‐Wen , Xu Xu , Yu Qing , Xu Ya‐Wei , Su Qing , Peng Wen‐Hui , Jian Wei‐Xia
Published: June 2020

Nucleotide‐binding domain, leucine‐rich repeat family with a caspase activation and recruitment domain 3 (NLRC3) participates in both immunity and cancer. The aim of this study was to determine the role of NLRC3 in human hepatocellular carcinoma (HCC) and the underlying mechanisms. We collected human liver tissues from nonalcoholic steatohepatitis (NASH), HCC, and adjacent normal tissues to characterize the pattern of NLRC3 expression by real‐time quantitative polymerase chain reaction and immunohistochemistry. Then, we used the HCC cell line, HuH‐7, transfected with small interfering RNA to silence the NLRC3 expression. 5‐Ethynyl‐2'‐deoxyuridine assay, scratch assay, and transwell invasion assay were used for assessing proliferation, migration, and invasion, respectively. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay were conducted to assess cell apoptosis. The expression of NLRC3 was reduced in human HCC tissues, compared with normal liver and nonalcoholic steatohepatitis tissues. After knocking down of NLRC3, the proliferation, migration, and invasion were increased in HuH‐7 cells. And flow cytometry and TUNEL assay showed that HuH‐7 cell apoptosis was suppressed after NLRC3 knockdown. As for the underlying mechanisms, knockdown of NLRC3 in HuH‐7 cells was associated with the activation of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) pathway under interleukin‐6 (IL‐6) stimulation. NLRC3 expression was downregulated in human HCC tissues. NLRC3 silencing in HuH‐7 cells can promote the proliferation, migration, and invasion of hepatocellular carcinoma cells. JAK2/STAT3 pathway activation induced by IL‐6 may be the underlying mechanism for HCC when NLRC3 expression is silenced. And the invasion of HuH‐7 cells was partially suppressed by the STAT3 specific inhibitor (cryptotanshinone). Therefore, NLRC3 may play a significant role in HCC and might be a therapeutic target for the treatment of HCC.
Single stick access using a VA‐ECMO arterial return cannula for coronary intervention in cardiogenic shock
Authors: Kapur Navin K. , Hirst Colin S. , Davila Carlos D. , Garcia Ron
Published: June 2020

Use of veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) is growing exponentially for cardiogenic shock and cardiac arrest, and many of these patients require percutaneous coronary intervention (PCI). In some cases, radial arterial access may not feasible among patients with peripheral vascular disease or if larger diameter guide catheters are required. Further, VA‐ECMO is commonly used in combination with an intra‐aortic balloon pump or Impella, thereby limiting vascular access options and increasing the risk of vascular complications including bleeding and limb ischemia. For these reasons, new approaches to perform PCI without the need for an additional arterial puncture are required. We describe a case of a 70‐year‐old man with cardiogenic shock referred for high‐risk PCI while supported with VA‐ECMO and an Impella CP and illustrate a novel method for single‐stick access for PCI through the return cannula of the VA‐ECMO circuit.
Towards More Photostable, Brighter, and Less Phototoxic Chromophores: Synthesis and Properties of Porphyrins Functionalized with Cyclooctatetraene
Authors: Ostapko Jakub , Gorski Aleksander , Buczyńska Joanna , Golec Barbara , Nawara Krzysztof , Kharchenko Anastasiia , Listkowski Arkadiusz , Ceborska Magdalena , Pietrzak Mariusz , Waluk Jacek
Published: June 2020

Free base and zinc porphyrins functionalized with cyclooctatetraene (COT), a molecule known as a good triplet‐state quencher, have been obtained and characterized in detail by structural, spectral, and photophysical techniques. Substitution with COT leads to a dramatic decrease of the intrinsic lifetime of the porphyrin triplet. As a result, photostability in oxygen‐free solution increases by two to three orders of magnitude. In non‐degassed solutions, improvement of photostability is about tenfold for zinc porphyrins, but the free bases become less photostable. Similar quantum yields of photodegradation in free base and zinc porphyrins containing the COT moiety indicate a common mechanism of photochemical decomposition. The new porphyrins are expected to be much less phototoxic, since the quantum yield of singlet oxygen formation strongly decreases because of the shorter triplet lifetime. The reduction of triplet lifetime should also enhance the brightness and reduce blinking in porphyrin chromophores emitting in single‐molecule regime, since the duration of dark OFF states will be shorter.
Near‐Infrared BODIPY‐Acridine Dyads Acting as Heavy‐Atom‐Free Dual‐Functioning Photosensitizers
Authors: Deckers Jasper , Cardeynaels Tom , Penxten Huguette , Ethirajan Anitha , Ameloot Marcel , Kruk Mikalai , Champagne Benoît , Maes Wouter
Published: June 2020

Boron dipyrromethene (BODIPY) dyes represent a particular class within the broad array of potential photosensitizers. Their highly fluorescent nature opens the door for theragnostic applications, combining imaging and therapy using a single, easily synthesized chromophore. However, near‐infrared absorption is strongly desired for photodynamic therapy to enhance tissue penetration. Furthermore, singlet oxygen should preferentially be generated without the incorporation of heavy atoms, as these often require additional synthetic efforts and/or afford dark cytotoxicity. Solutions for both problems are known, but have never been successfully combined in one simple BODIPY material. Here, we present a series of compact BODIPY‐acridine dyads, active in the phototherapeutic window and showing balanced brightness and phototoxic power. Although the donor–acceptor design was envisioned to introduce a charge transfer state to assist in intersystem crossing, quantum‐chemical calculations refute this. Further photophysical investigations suggest the presence of exciplex states and their involvement in singlet oxygen formation.
Chronic Imaging of Mouse Brain: From Optical Systems to Functional Ultrasound
Authors: Kılıç Kıvılcım , Tang Jianbo , Erdener Ş. Evren , Sunil Smrithi , Giblin John T. , Lee Blaire S. , Postnov Dmitry D. , Chen Anderson , Boas David A.
Published: June 2020

Utilization of functional ultrasound (fUS) in cerebral vascular imaging is gaining popularity among neuroscientists. In this article, we describe a chronic surgical preparation method that allows longitudinal studies and therefore is applicable to a wide range of studies, especially on aging, stroke, and neurodegenerative diseases. This method can also be used with awake mice; hence, the deleterious effects of anesthesia on neurovascular responses can be avoided. In addition to fUS imaging, this surgical preparation allows researchers to take advantage of common optical imaging methods to acquire complementary datasets to help increase the technical rigor of studies. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Surgical preparation of mouse chronic cranial windows using polymethylpentene

Basic Protocol 2: Imaging of mice with chronic cranial windows
Salt tolerance in Argentine wheatgrass is related to shoot sodium exclusion
Authors: Zabala Juan M. , Marinoni Lorena del R. , Taleisnik Edith L. , Ribero Gustavo , Schrauf Gustavo E.
Published: June 2020

This is the first report about Na and K fluxes and heritability of Na exclusion in the Elymus genus. Argentine wheatgrass [Elymus scabrifolius (Döll) J.H. Hunz.] is an important forage genetic resource for saline environments. A previous study showed that salt‐sensitive lines accumulated toxic levels of Na in shoots. The aim of this study was to increase the understanding of Na exclusion in Argentine wheatgrass. Growth and Na and K accumulation rates were analyzed in two homozygous salt‐tolerant genotypes (T1 and T2) and a salt‐sensitive genotype (S1), under different salt stress levels. The Na accumulation rate in shoots was 1.5 times higher in the sensitive line than in the tolerant ones at 100 mM NaCl, and five times higher at 200 mM NaCl. A negative association was found between Na concentration and leaf weight in parent genotypes, F1, and segregating F2 populations generated by crossing homozygous S1 and T2, suggesting that growth in the third leaf was more affected in Na‐including genotypes. The inheritance of Na exclusion was estimated under salt stress conditions in a segregating F2 population and in F2:3 families obtained by crossing two homozygous genotypes with contrasting values of shoot Na exclusion. In the F2 population and F2:3 families, Na concentration segregation was compatible with intermediate inheritance (with very low partial dominance). High heritability values estimated for Na exclusion suggest that this trait might be used as a priority selection criterion for salt tolerance. Results will be useful to design breeding strategies for salt tolerance in this and related species of the Elymus genus.
Risk assessment of pollen‐mediated gene flow from Ga1‐m field corn to dent‐sterile Ga1‐s popcorn
Authors: Barnes Ethann R. , Barnes Allison C. , Knezevic Stevan Z. , Lawrence Nevin C. , Jhala Amit J.
Published: June 2020

The popcorn industry in the United States is at risk of genetic contamination because it utilizes the gametophyte factor 1 gene (Ga1) as a barrier against pollen‐mediated gene flow (PMGF) from field corn (Zea mays L.). Popcorn with the Ga1‐s allele accepts pollen only from Ga1‐s corn, allowing for field corn and popcorn to be nearby without isolation. Germplasm is being introduced to the United States to increase field corn diversity that unknowingly contains the Ga1‐m allele, which can overcome Ga1‐s selectivity and pollinate popcorn. The risk to the popcorn industry has been underassessed. Experiments were conducted to model the frequency of PMGF from Ga1‐m field corn to Ga1‐s popcorn under field conditions and to evaluate the role of wind speed and direction using a concentric donor–receptor design in 2017 and 2018 in Nebraska, USA. The PMGF to white popcorn was detected using a field corn pollen donor with yellow kernel color (dominate) and further confirmed with a molecular test. Popcorn kernels were harvested from cardinal and ordinal directions from 1 to 70 m. More than 7 million kernels were screened to detect the PMGF. Information‐theoretic criteria were used to select the best‐fit model. The greatest PMGF (1.6– 4.1%) was detected at 1 m and declined with distance. The PMGF was detected at 70 m, the maximum distance tested. Amplification of Ga1 followed by restriction enzyme digest confirmed that yellow kernelled progeny were hybrids from the result of PMGF. This is the first assessment of PMGF from field corn to popcorn, and the results are alarming for the popcorn industry and export market.
OMIP‐065: Dog Immunophenotyping and T‐Cell Activity Evaluation with a 14‐Color Panel
Authors: Pantelyushin Stanislav , Ranninger Elisabeth , Bettschart‐Wolfensberger Regula , vom Berg Johannes
Published: June 2020

Purpose and Appropriate Sample Types

Companion dogs are increasingly recognized as large‐animal models of diseases such as cancer, infectious‐, inflammatory‐, or autoimmune diseases. At the same time, compared to human clinics, veterinarians have only a fraction of the treatment options available. To study the immunological aspects of canine diseases and ultimately develop or adapt human treatments for the dog, the methodology also needs to be in place. Such tools include robust and reliable flow cytometric panels.

The purpose of the panel described here is to assess the immune cell composition and their functionality in the peripheral blood mononuclear cells (PBMCs) of dogs. Moreover, its “plug and play” composition allows for an in‐depth analysis of T‐cell responses in ex vivo assays (Table 1).

Initially, this panel has been designed for the analysis of cryopreserved PBMCs to allow batched analysis and to reduce interexperimental variation. Withers and colleagues published a comparable and—to our knowledge—currently the most extensive canine panel to date (1). While their study focused on the aging and activation status of T cells in dogs, our panel is designed to look at a broader range of cells with a higher number of markers. This allows a more in‐depth analysis of functional extracellular and intracellular markers. In addition, all antibodies in our proposed panel are directly labeled. In combination with suitable lymphocyte isolation protocols, this panel could potentially also be adapted to analyze tissue biopsies from various different organs. © 2020 International Society for Advancement of Cytometry
A cell type annotation Jamboree—Revival of а communal science forum
Authors: Peshkin Leonid , Kirschner Marc W.
Published: June 2020

Cell Atlases are currently being constructed for human tissues as well as several model organisms. New technologies make creation of vast datasets in many species possible, but the value of such data crucially depends on the quality of annotation. The tools of annotating single cell data and creating knowledge representations comparable across organisms have been lagging. We argue that successfully creating Cell Atlases will require a revival of a boot‐camp style forum for communal annotation combined with an intensive learning workshop, dubbed a “Jamboree”. We report on our experience of successfully developing a structure and curriculum and running such a Jamboree for Xenopus Embryonic Cell Types at the Janelia Farms campus of the Howard Hughes Medical Institute.
Census data aggregation decisions can affect population‐level inference in heterogeneous populations
Authors: Engbo Søs , Bull James C. , Börger Luca , Stringell Thomas B. , Lock Kate , Morgan Lisa , Jones Owen R.
Published: June 2020

Conservation and population management decisions often rely on population models parameterized using census data. However, the sampling regime, precision, sample size, and methods used to collect census data are usually heterogeneous in time and space. Decisions about how to derive population‐wide estimates from this patchwork of data are complicated and may bias estimated population dynamics, with important implications for subsequent management decisions.

Here, we explore the impact of site selection and data aggregation decisions on pup survival estimates, and downstream estimates derived from parameterized matrix population models (MPMs), using a long‐term dataset on grey seal (Halichoerus grypus) pup survival from southwestern Wales. The spatiotemporal and methodological heterogeneity of the data are fairly typical for ecological census data and it is, therefore, a good model to address this topic.

Data were collected from 46 sampling locations (sites) over 25 years, and we explore the impact of data handling decisions by varying how years and sampling locations are combined to parameterize pup survival in population‐level MPMs. We focus on pup survival because abundant high‐quality data are available on this developmental stage.

We found that survival probability was highly variable with most variation being at the site level, and poorly correlated among sampling sites. This variation could generate marked differences in predicted population dynamics depending on sampling strategy. The sample size required for a confident survival estimate also varied markedly geographically.

We conclude that for populations with highly variable vital rates among sub‐populations, site selection and data aggregation methods are important. In particular, including peripheral or less frequently used areas can introduce substantial variation into population estimates. This is likely to be context‐dependent, but these choices, including the use of appropriate weights when summarizing across sampling areas, should be explored to ensure that management actions are successful.
Direct oral anticoagulants compared to vitamin K antagonist for the management of left ventricular thrombus
Authors: Iqbal Hansa , Straw Sam , Craven Thomas P. , Stirling Katherine , Wheatcroft Stephen B. , Witte Klaus K.
Published: June 2020

Aims

Left ventricular (LV) thrombus is increasingly detected in patients with and without ischaemic heart disease due to the increased availability of cardiac magnetic resonance imaging. Risk factors include anterior ST elevation myocardial infarction, delayed reperfusion therapy, and non‐ischaemic cardiomyopathy with severe LV systolic dysfunction. We aimed to report the characteristics and outcomes of patients with LV thrombus treated with either vitamin K antagonist (VKA) or direct oral anticoagulants (DOAC) with a view to describing differences in efficacy, specifically, subsequent thromboembolic events, thrombus resolution, and also side effects of therapy including clinically significant bleeding.

Methods and results

We conducted a retrospective, observational cohort study of patients diagnosed with LV thrombus between 1 December 2012 and 30 June 2018 and treated with either DOAC or VKA. We recorded patient demographics, past medical history, prescribed medications, and baseline investigations. The primary outcomes were rates of thromboembolism and clinically significant bleeding, with secondary outcomes of thrombus resolution on repeat cardiac imaging, repeat hospitalization, and all‐cause mortality. During the study period, 84 patients were diagnosed with and managed for LV thrombus. Of these, 62 received VKA and 22 DOAC including 13 prescribed rivaroxaban, eight apixaban, and one dabigatran. Most patients 75 (89%) were male with an average age of 62 ± 14 years. Ischaemic heart disease was the cause of LV impairment in 73 (87%) patients. Baseline characteristics were similar between groups at baseline. Most n = 55 (65%) were co‐prescribed a single antiplatelet agent and 32 (38%) received dual‐antiplatelet therapy. During an average follow‐up of 3.0 ± 1.4 years, there were no statistically significant differences between VKA and DOAC in rates of stroke (2% vs. 0%, P = 0.55), other thromboemboli (2% vs. 0%, P = 0.55), or clinically significant bleeding (10% vs. 0%, P = 0.13). The average interval to cardiac imaging follow‐up was 233 ± 251 days and was not different between groups (P = 0.83), and there was no difference in the rate of resolution of thrombus (76% vs. 65% P = 0.33). Rehospitalization (50% vs. 45%: P = 0.53) and all‐cause mortality (10% vs. 14%; P = 0.61) were also similar.

Conclusions

Our data suggest that DOACs are likely to be at least as effective and safe as VKA for stroke prevention in patients with LV thrombus and, despite their lack of a licence for this indication, are therefore likely to represent a reasonable and more convenient option for this setting. The optimal timing and type of anticoagulation for LV thrombus, as well as the role of screening for high‐risk patients, should be tested in prospective, randomized trials.
MnO2 Nanoclusters Decorated on GrapheneModified Pencil Graphite Electrode for Non‐Enzymatic Determination of Cholesterol
Authors: Rison Sherin , Akshaya K. B. , Bhat Vinay S , Shanker G. , Maiyalagan T. , Joice E. K. , Hegde Gurumurthy , Varghese Anitha
Published: June 2020

Electrochemically deposited MnO2 on graphene coated Pencil Graphite Electrode (PGE) has been used to develop a facile electrochemical sensor for the determination of Cholesterol. Cyclic voltammetric (CV) studies and electrochemical impedance spectroscopic (EIS) technique were used to investigate the electrochemical properties of the modified sensing platform. The physicochemical properties of the modified electrodes were characterized by X‐ray photoelectron spectroscopy (XPS), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), X‐ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The experimental conditions such as effect of scan rate, concentration and pH were optimized. The linear dynamic range for the determination of Cholesterol was found to be 12×10−10 M–240×10−10 M under optimum conditions. The ultralow level of detection limit (0.42 nM) demonstrates the high sensitivity of the proposed method. The developed method was successfully applied for the non‐enzymatic determination of Cholesterol in human blood samples at ultralow levels.