bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical assessment of geometric distortion for a 0.35T MR‐guided radiotherapy system
Authors: Neylon John , Cook Kiri A. , Yang Yingli , Du Dongsu , Sheng Ke , Chin Robert K. , Kishan Amar U. , Lamb James M. , Low Daniel A. , Cao Minsong
Published: July 2021

Purpose

To estimate the overall spatial distortion on clinical patient images for a 0.35 T MR‐guided radiotherapy system.

Methods

Ten patients with head‐and‐neck cancer underwent CT and MR simulations with identical immobilization. The MR images underwent the standard systematic distortion correction post‐processing. The images were rigidly registered and landmark‐based analysis was performed by an anatomical expert. Distortion was quantified using Euclidean distance between each landmark pair and tagged by tissue interface: bone‐tissue, soft tissue, or air‐tissue. For baseline comparisons, an anthropomorphic phantom was imaged and analyzed.

Results

The average spatial discrepancy between CT and MR landmarks was 1.15 ± 1.14 mm for the phantom and 1.46 ± 1.78 mm for patients. The error histogram peaked at 0–1 mm. 66% of the discrepancies were <2 mm and 51% <1 mm. In the patient data, statistically significant differences (p‐values < 0.0001) were found between the different tissue interfaces with averages of 0.88 ± 1.24 mm, 2.01 ± 2.20 mm, and 1.41 ± 1.56 mm for the air/tissue, bone/tissue, and soft tissue, respectively. The distortion generally correlated with the in‐plane radial distance from the image center along the longitudinal axis of the MR.

Conclusion

Spatial distortion remains in the MR images after systematic distortion corrections. Although the average errors were relatively small, large distortions observed at bone/tissue interfaces emphasize the need for quantitative methods for assessing and correcting patient‐specific spatial distortions.
Adaptive neural network asymptotic tracking control for a class of stochastic nonlinear systems with unknown control gains and full state constraints
Authors: Su Wei , Niu Ben , Wang Huanqing , Qi Wenhai
Published: July 2021

This article addresses the issue of adaptive intelligent asymptotic tracking control for a class of stochastic nonlinear systems with unknown control gains and full state constraints. Unlike the existing systems in the literature in which the prior knowledge of the control gains is available for the controller design, the salient feature of our considered system is that the control gains are allowed to be unknown but have a positive sign. By introducing an auxiliary virtual controller and employing the new properties of Numbness functions, the major technique difficulty arising from the unknown control gains is overcome. At the same time, the‐type barrier Lyapunov functions are introduced to prevent the violation of the state constraints. What's more, neural networks' universal online approximation ability and gain suppression inequality technology are combined in the frame of adaptive backstepping design, so that a new control method is proposed, which cannot only realize the asymptotic tracking control in probability, but also meet the requirement of the full state constraints imposed on the system. In the end, the simulation results for a practical example demonstrate the effectiveness of the proposed control method.
Alternating Current Electrolysis as Efficient Tool for the Direct Electrochemical Oxidation of Hydroxamic Acids for Acyl Nitroso Diels–Alder Reactions
Authors: Fährmann Jan , Hilt Gerhard
Published: July 2021

The acyl nitroso Diels–Alder reaction of 1,3‐dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro‐induced decomposition could be suppressed in favour of the 1,2‐oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3‐dienes and hydroxamic acids, giving up to 96 % isolated yield.
Simultaneous Chiral Resolution of Two Racemic Compounds by Preferential Cocrystallization**
Authors: Zhou Fuli , Shemchuk Oleksii , Charpentier Maxime D. , Matheys Chloé , Collard Laurent , ter Horst Joop H. , Leyssens Tom
Published: July 2021

We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS‐mandelic acid (MAN) and RS‐etiracetam (ETI) can be combined together as enantiospecific R‐MAN⋅R‐ETI and S‐MAN⋅S‐ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee>98 %) and mandelic acid (ee≈95 %) enantiomers.
Highly efficient dye‐sensitized solar cells: A comparative study with two different system of solvent‐free binary room‐temperature ionic liquid‐based electrolytes
Authors: Syawal Hilmi , Farhana Nur Khuzaimah , Goh Zhi Ling , Bashir Shahid , Saidi Norshahirah Mohamad , Rachagan Elizer , Ramesh Subramaniam , Kasi Ramesh
Published: July 2021

In this work, novel redox electrolytes based on poly (ethylene oxide) (PEO) were prepared using binary ionic liquid 1‐methyl‐3‐propylimidazolium iodide (MPII) with 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide (EMIMTFSI) or 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIMBF4) to reduce the high viscosity of MPII. The addition of low viscosity ionic liquids is to overcome the low mass transportation of redox mediator faced by the single ionic liquid. Therefore, different ratios of ionic liquids were added, and their effect on the electrical properties of the ionic liquid‐based gel polymer electrolytes (GPE) was observed. It was confirmed that all the system dominant by ions rather than electron. The binary ionic liquid system containing 37.5 wt.% of BMIMBF4 showed the highest ionic conductivity of 24.2 mS cm−1. Fourier‐transform infrared and X‐ray diffraction studies confirmed that complexation occurred between all materials. The combination of two alkyl side chain length has enhanced the efficiency of the DSSC with short‐circuit current density (JSC) of 26.81 mA cm−1, open‐circuit voltage (VOC) of 0.67 V, fill factor of 44.5% and photovoltaic conversion efficiency (η) of 7.8%. This work has provided valuable insight for further stability of binary ionic liquid‐based GPE compared to single ionic liquid electrolytes.
Selective experimental parameters for preparative TREF of propylene‐ethylene random copolymers: Limiting undercooling of PP
Authors: Chitta Rajesh , Steenbakkers Rieky , Tacx Jacques , Meppelder Anika
Published: July 2021

Temperature rising elution fractionation (TREF) is a highly valuable and widely used tool for chemical composition separation of semicrystalline polyolefins. However, TREF operational conditions should be carefully selected due to their high impact on separation quality. This is especially true for polypropylene (PP)‐based polymers due to their slow crystallizing nature and defect distribution, which can further complicate the fractionation. In order to more fully understand this behavior, a systematic investigation was designed to determine the influence of support and cooling rate on preparative TREF of PP random copolymers. Possible measures to limit undercooling of PP and thus preventing so called co‐elution of different microstructures in TREF were demonstrated using glass beads as support during fractionation and cooling rate of 0.02°C/min. Support presence during fractionation acted as a nucleating agent to limit the elution of long isotactic chains in the low temperature fractions. Slow cooling rate along with support presence further improved the separation quality by giving the polymer chains enough time to overcome the undercooling.
The best of both worlds: Combining lineage‐specific and universal bait sets in target‐enrichment hybridization reactions
Authors: Hendriks Kasper P. , Mandáková Terezie , Hay Nikolai M. , Ly Elfy , Hooft van Huysduynen Alex , Tamrakar Rubin , Thomas Shawn K. , Toro‐Núñez Oscar , Pires J. Chris , Nikolov Lachezar A. , Koch Marcus A. , Windham Michael D. , Lysak Martin A. , Forest Félix , Mummenhoff Klaus , Baker William J. , Lens Frederic , Bailey C. Donovan
Published: July 2021

Premise

Researchers adopting target‐enrichment approaches often struggle with the decision of whether to use universal or lineage‐specific probe sets. To circumvent this quandary, we investigate the efficacy of a simultaneous enrichment by combining universal probes and lineage‐specific probes in a single hybridization reaction, to benefit from the qualities of both probe sets with little added cost or effort.

Methods and Results

Using 26 Brassicaceae libraries and standard enrichment protocols, we compare results from three independent data sets. A large average fraction of reads mapping to the Angiosperms353 (24–31%) and Brassicaceae (35–59%) targets resulted in a sizable reconstruction of loci for each target set (x̄ ≥ 70%).

Conclusions

High levels of enrichment and locus reconstruction for the two target sets demonstrate that the sampling of genomic regions can be easily extended through the combination of probe sets in single enrichment reactions. We hope that these findings will facilitate the production of expanded data sets that answer individual research questions and simultaneously allow wider applications by the research community as a whole.
Historical abundance and distributions of Salpa thompsoni hot spots in the Southern Ocean and projections for further ocean warming
Authors: Słomska Angelika Wanda , Panasiuk Anna , Weydmann‐Zwolicka Agata , Wawrzynek‐Borejko Justyna , Konik Marta , Siegel Volker
Published: July 2021

In contrast to Antarctic krill Euphausia superba, Antarctic salps (Salpa thompsoni) respond positively to warmer water temperatures and have the ability to create massive blooms under favourable conditions. Therefore, they can compete with krill for primary production. Over the last three decades, significant variability in S. thompsoni occurrence has been observed as a response to the environmental fluctuations of the Southern Ocean ecosystem (e.g. changes in sea surface temperature and ice‐cover shrinkage around the cold Antarctic waters).

This study presents historical abundance data of salps from the south‐west Atlantic Sector of the Southern Ocean, covering a time span of 26 years. These data allow tracking of fluctuations in Antarctic salp abundance and their distribution with bottom depth, temperature, and ice conditions, aiming to reveal salp hot spots and to predict the future range of S. thompsoni distribution with upcoming climate warming in the next 50 years.

Results showed the highest salp density in shallow shelf waters with ice cover and low temperatures between 1 and −1°C. In the studied area, S. thompsoni hot spots were located mostly around Elephant Island, but also the islands around Brensfield and Gerlache Straits, as well as to the south near the Bellingshausen Sea. Inferences made of future salp distribution suggest that the range of S. thompsoni will move southwards, enlarging their habitat area by nearly 500,000 km2, which may have significant implications on the whole Antarctic food web. The information presented herein may be used for Antarctic ecosystem management, protection, and conservation.
1H 0707‐495: An AGN is dimming its X‐ray light
Authors: Boller Thomas
Published: July 2021

We report on one of the first science observations obtained during the Calibration and Verification phase of extended ROentgen Survey with an Imaging Telescope Array (eROSITA) aboard the Spectrum‐Roentgen‐Gamma (SRG) mission on the famous Narrow‐Line Seyfert 1 Galaxy 1H 0707‐495. 1H 0707‐495 is a highly variable AGN, with a complex, steep X‐ray spectrum, which has been the subject of intense studies with XMM‐Newton in the past. During the eROSITA observations, 1H 0707‐495 showed a dramatic flux drop in about 1 day. The source is brightest at the beginning of the observations, with rapid fluctuations in count rate, followed by a subsequent decline in count rate going down close to the background level. The mean amplitude variability is a factor of 58, with a 1 error confidence interval with factors between 31 and 235. Similar, large‐amplitude count‐rate changes are deduced from the XMM‐Newton EPIC‐pn and MOS2 light curves. The energy band up to only 0.8 keV is dominating the amplitude variability, followed by a sudden drop in variability above 0.8 keV. Such extreme ultrasoft and large‐amplitude flux variability in active galactic nuclei has not been detected with other X‐ray observations so far. A physical explanation for the timing and spectral properties is a combination of strong relativistic effects close to the black hole and absorption by an ionized partial coverer. From the high‐ to the low‐flux state, the partial coverer is obscuring an increasing part of the emitted X‐ray radiation. Ionized outflowing absorbers are more transparent in the soft X‐rays than neutral absorbers and thus show leakage effects in the soft X‐rays, explaining the ultrasoft light curve.
Melatonin inhibits embryonic rat H9c2 cells growth through induction of apoptosis and cell cycle arrest via PI3K‐AKT signaling pathway
Authors: Zhao Anda , Zhao Kena , Xia Yuanqing , Lyu Jiajun , Chen Yiting , Li Shenghui
Published: July 2021

Background

Our recent epidemiological study revealed that maternal sleep during the periconceptional period should be involved in the risk of congenital heart disease (CHD) in offspring. Melatonin, a sleep related hormone, has been suggested to play a crucial role in embryonic development based on the emerging evidence. In this study, we set out to assess the effect of melatonin on the embryonic cardiac cell growth and to explore the underlying mechanisms.

Methods

We observed the effect of different gradient doses of melatonin as 10, 100, or 1,000 μM on cell proliferation in H9c2 embryonic rat cardiac cells. Furthermore, flow cytometry was applied to evaluate the impact on apoptosis and cell cycle. RNA‐seq was conducted to screen the changes in expression of mRNA and signaling pathways. Quantitative Real‐Time‐PCR (qRT‐PCR) was then conducted to validate the results.

Results

It was observed that melatonin could inhibit H9c2 cell growth, at the doses of 100 and 1,000 μM, but not at 10 μM. Moreover, melatonin ranged from 100 to 1,000 μM could instigate cell cycle arrest at G1 phase and simulate apoptosis, in a dose‐dependent manner. In addition, melatonin was found to down‐regulate the expression of a number of genes, which are related to heart development (SPARC, IFITM3, TNNT2, LOX), and PI3K‐Akt signaling pathway activation (FN1, HSP90B1, THBS1, MFGE8, and CLU).

Conclusions

Our findings suggested that high level of melatonin could be capable of inhibiting growth through the induction of apoptosis and cell cycle arrest via PI3K‐AKT signaling pathway, thereby interfering with embryonic heart development. Considering this study is based on H9c2 embryonic rat cardiac cells, future additional studies using human embryonic cardiac cell are warranted.
Temporal rank of clinical characteristics and prognosis of anti‐N‐methyl‐d‐aspartate receptor encephalitis
Authors: Yang Runnan , Ge Fenfen , Jiang Jingwen , Wang Yue , Wan Mengtong , Zhang Wei
Published: July 2021

Objectives

Early recognition and intervention of patients with the anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis are important to achieve a better prognosis. The study aims to summarize the real‐world perspectives of anti‐NMDAR encephalitis patients in China via electronic medical records (EMRs).

Methods

Using EMRs of patients from 2013 to 2019 from West China Hospital in China, a retrospective research was conducted to demonstrate the temporary rank of clinical characteristics and disease prognosis of anti‐NMDAR encephalitis. The modified Rankin Scale (mRS) scores were used to divide the anti‐NMDAR‐encephalitis into two groups (poor prognosis vs. good prognosis). Chi‐square test and logistic regression were used to analyze factors associated with prognosis.

Results

Here, 78 patients were included. The most common clinical characteristics are cognitive dysfunction (86.0%) and thought disorder (86.0%). Cognitive dysfunction, thought disorder, and seizures tended to appear soon after prodrome symptoms. Logistics analysis results showed that cognitive dysfunction (OR = 4.48, 95% CI = 1.09–18.47), the score of (GCS ≤ 8) (OR = 4.52, 95% CI = 1.18–17.32), positive antibodies in serum (OR = 4.89, 95% CI = 1.19–20.13) and delay immunotherapy (OR = 4.76, 95% CI = 1.79–12.60) were risk factors of poor clinical outcomes.

Conclusions

There are two peaks in the development of autoimmune encephalitis (AE). The first peak is cognitive dysfunction, and the second peak is autonomic dysfunction. Cognitive dysfunction and GCS score ≤8 at admission, antibodies positive in serum, and delay immunotherapy were risk factors for a poor prognosis at discharge.
Constructing a Compelling Case: Nurses' Experiences of Communicating Abuse and Neglect
Authors: Lines Lauren Elizabeth , Hutton Alison , Grant Julian Maree
Published: July 2021

Child abuse and neglect is a complex problem that needs to be addressed through a multidisciplinary approach. Nurses internationally have frequent contact with children and are ideally placed to respond to children experiencing abuse and neglect. Nurses' roles can include reporting abuse to child protection services (CPS). This paper reports on one aspect of the findings of a qualitative study exploring Australian nurses' perceptions and experiences of keeping children safe from abuse. Specifically, this paper reports on the theme relating to nurses' experiences of communicating their concerns to CPS and the family when reporting abuse and neglect. This qualitative study was underpinned by social constructionism, with data collected through semi‐structured interviews with 21 nurses working with children in Australia. Key findings reported are: (1) being heard; (2) [feeling] disappointed, discouraged and disenfranchised; and (3) managing tensions between engagement and reporting. Nurses at times perceived that they were not taken seriously by CPS and felt powerless to enact change for children. Nurses subsequently had to decide how, and if, to discuss their report with families to mitigate negative reactions and maintain engagement. This study highlights the need for more effective multidisciplinary collaboration between nurses and CPS to promote change for children affected by abuse in Australia.

‘This paper reports on… nurses' experiences of communicating their concerns to CPS and the family’

Key Practitioner Messages

Nurses often perceived that they were not taken seriously by CPS and felt powerless to make a difference for children.

Nurses experienced a tension between openly discussing their intention to report with families and minimising negative reactions such as disengagement and mistrust.

This study highlights the need for greater collaboration between CPS and nurses to promote shared understanding and effective action to promote the wellbeing of children experiencing abuse and neglect.
Antiparasitic Properties of Propolis Extracts and Their Compounds
Authors: de L. Paula Lucas A. , Cândido Ana C. B. B. , Santos Mario F. C. , Caffrey Conor R. , Bastos Jairo K. , Ambrósio Sérgio R. , Magalhães Lizandra G.
Published: July 2021

Propolis is a bee product that has been used in medicine since ancient times. Although its anti‐inflammatory, antioxidant, antimicrobial, antitumor, and immunomodulatory activities have been investigated, its anti‐parasitic properties remain poorly explored, especially regarding helminths. This review surveys the results obtained with propolis around the world against human parasites. Regarding protozoa, studies carried out with the protozoaTrypanosomaspp. andLeishmaniaspp. have demonstrated promising results in vitro and in vivo. However, there are fewer studies forPlasmodiumspp., the etiological agent of malaria and less so for helminths, particularly forFasciolaspp. andSchistosomaspp. Despite the favorable in vitro results with propolis, helminth assays need to be further investigated. However, propolis has shown itself to be an excellent natural product for parasitology, thus opening new paths and approaches in its activity against protozoa and helminths.
A Theoretical Framework for the Electrochemical Characterization of Anisotropic Micro‐Emulsions**
Authors: Tichter Tim , Borah Rohan , Nann Thomas
Published: July 2021

Micro emulsions (MEs) offer an exceptionally broad spectrum of applications covering sensing, electrosynthesis, supercapacitors and redox‐flow batteries. Herein, we develop the theory for a sophisticated electrochemical characterizion of MEs with a spatially and time‐invariant anisotropy in the diffusion domain by means of cyclic voltammerty (CV). By introducing spatially dependent diffusion coefficients into Ficks' first law, we derive a modified diffusion equation to simulate any inherent anisotropy of the ME under investigation. Moreover, by formulating an extended second‐order homogeneous six‐member square scheme for a kinetically controlled two‐step two‐electron reaction we capture the intricate entanglement of chemical and electrochemical equilibria. Our theoretical concept is finally validated by experimental CV data for the ME based two‐step redox reaction of methyl‐viologen which paves the way for a quantitative electrochemical characterization MEs.
A modified acid system to enhance carbonate matrix acid stimulation: An experimental study
Authors: Zhu Ding , Hill Dan , Ugursal Assiya , Shuchart Chris , Purdy Clay , Weissenberger Markus , Uribe Julian
Published: July 2021

In carbonate matrix acidizing, the critical design parameters are interstitial velocity and pore volume to breakthrough for wormhole propagation (vi, opt and PVBT,opt). Hydrochloric acid (HCl), the most commonly used acid in carbonate acidizing, sometimes shows low efficiency because the injection rate needed for optimal wormhole propagation is not attainable, especially for when long completion intervals, low permeability carbonates, or coiled tubing operations are involved. It also raises safety, corrosion, and environmental concerns. When conventional retarded acid systems are used to overcome these challenges, the efficiency of acid stimulation often suffers from low reaction rate. This study presents testing results of a modified acid system that has controlled reaction rate with favourable wormhole propagation characteristics, especially at low interstitial velocities. Due to the increased activation energy barriers utilized in these modified‐acid systems, it is possible to control the reaction rate of the hydrogen proton and optimize the wormholing effect based on the completion method and formation specifications. Laboratory linear core flooding experiments and acid jetting experiments were conducted to study the wormhole efficiency with the new acid systems. The experimental results showed clear advantages of the modified acid systems. The modified acids have similar or better wormhole efficiency parameters compared with HCl having comparable dissolving power. When combined with acid jetting, further improvement in wormhole growth in low permeability limestone is achieved. In addition to minimizing the hazardous exposure levels and corrosion rates compared with HCl, the new acid system provides the positive aspects of solubilizing ability, thus improving optimal wormhole conditions.
Approach to Malignant Effusions in Metastatic Sarcoma
Authors: Chebib Ivan
Published: July 2021

For practicing pathologists, Sharma et al have provided an excellent overview and algorithm for approaching sarcoma in effusion specimens. It is recommended that a copy of this algorithm be kept as a reference for the rare situations in which one is confronted with a possible metastatic sarcoma in a fluid specimen.
Diagnostic challenges and successful organ‐preserving therapy in a case of secretory carcinoma of minor salivary glands
Authors: Bill Ruben , Deschler Daniel G. , Pittet Mikael J. , Pai Sara I. , Sadow Peter M. , Park Jong Chul
Published: July 2021

Background

Secretory carcinoma is a more recently described subtype of salivary gland carcinoma that may pose diagnostic challenges and frequently harbors NTRK fusions that may successfully be targeted by TRK inhibitors in advanced disease.

Case

We present the case of a female patient with secretory carcinoma arising in the base of tongue with persistent disease after debulking surgery and definitive chemoradiation. As an alternative to salvage surgery, which would have resulted in significant impairment of swallowing and speech function, a targeted therapy with the TRK‐inhibitor larotrectinib against an identified ETV6‐NTRK3 fusion product was initiated. Larotrectinib treatment has been well tolerated, resulted in durable complete response and the patient maintains good swallowing and speech function.

Conclusion

The presented case underscores the importance of the accurate diagnosis of secretory carcinoma. It further highlights the impact of molecular testing as targeted therapies may play an important role in the management of advanced salivary gland cancers.
Novel activation function with pixelwise modeling capacity for lightweight neural network design
Authors: Liu Yi , Guo Xiaozhou , Tan Kaijun , Gong Guoliang , Lu Huaxiang
Published: July 2021

The development of lightweight networks makes neural networks more efficient to be widely applied to various tasks. Considering the deployment of hardware like edge devices and mobile phones, we prioritize lightweight networks. However, their accuracy has always lagged far behind SOTA networks. In this article, we present a simple yet effective activation function, called WReLU, to improve the performance of lightweight networks significantly by adding a residual spatial condition. Moreover, we use a strategy to switch activation functions after determining which convolutional layer to use. We perform experiments on ImageNet 2012 classification dataset in CPU, GPU, and edge devices. Experiments demonstrate that WReLU improves the accuracy of classification significantly. Meanwhile, our strategy balances the effect of additional parameters and multiply accumulate. Our method improves the accuracy of SqueezeNet and SqueezeNext by more than 5% without increasing extensive parameters and computation. For the lightweight network with a large number of parameters, such as MobileNet and ShuffleNet, there is also a significant improvement. Additionally, the inference speed of most lightweight networks using our WReLU strategy is almost the same as the baseline model on different platforms. Our approach not only ensures the practicability of the lightweight network but also improves its performance.
Cricket: A virtualization layer for distributed execution of CUDA applications with checkpoint/restart support
Authors: Eiling Niklas , Baude Jonas , Lankes Stefan , Monti Antonello
Published: July 2021

In high‐performance computing and cloud computing the introduction of heterogeneous computing resources, such as GPU accelerator have led to a dramatic increase in performance and efficiency. While the benefits of virtualization features in these environments are well researched, GPUs do not offer virtualization support that enables fine‐grained control, increased flexibility, and fault tolerance. In this article, we present Cricket: A transparent and low‐overhead solution to GPU virtualization that enables future research into other virtualization techniques, due to its open‐source nature. Cricket supports remote execution and checkpoint/restart of CUDA applications. Both features enable the distribution of GPU tasks dynamically and flexibly across computing nodes and the multitenant usage of GPU resources, thereby improving flexibility and utilization for high‐performance and cloud computing.
Adverse Cardiovascular Outcomes and Antihypertensive Treatment: A Genome‐Wide Interaction Meta‐Analysis in the International Consortium for Antihypertensive Pharmacogenomics Studies
Authors: McDonough Caitrin W. , Warren Helen R. , Jack John R. , Motsinger‐Reif Alison A. , Armstrong Nicole D. , Bis Joshua C. , House John S. , Singh Sonal , El Rouby Nihal M. , Gong Yan , Mychaleckyj Joesyf C. , Rotroff Daniel M. , Benavente Oscar R. , Caulfield Mark J. , Doria Alessandrio , Pepine Carl J. , Psaty Bruce M. , Glorioso Valeria , Glorioso Nicola , Hiltunen Timo P. , Kontula Kimmo K. , Arnett Donna K. , Buse John B. , Irvin Marguerite R. , Johnson Julie A. , Munroe Patricia B. , Wagner Michael J. , Cooper‐DeHoff Rhonda M.
Published: July 2021

We sought to identify genome‐wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome‐wide antihypertensive drug‐single nucleotide polymorphism (SNP) interaction tests for four drug classes (β‐blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide‐like diuretics, n = 3,516; ACE‐inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta‐analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome‐wide significance in the β‐blocker‐SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10−8). rs139945292 was validated through BP response to β‐blockers, with the T‐allele associated with less BP reduction (systolic BP response P = 6 × 10−4, Beta = 3.09, diastolic BP response P = 5 × 10−3, Beta = 1.53). The T‐allele was also associated with increased adverse cardiovascular risk within the β‐blocker treated patients’ subgroup (P = 2.35 × 10−4, odds ratio = 1.57, 95% confidence interval = 1.23–1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in β‐blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome‐wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE‐inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in β‐blocker treated patients. Further investigation into this region is warranted.
Validation of Circular RNAs Using RT‐qPCR After Effective Removal of Linear RNAs by Ribonuclease R
Authors: Vromman Marieke , Yigit Nurten , Verniers Kimberly , Lefever Steve , Vandesompele Jo , Volders Pieter‐Jan
Published: July 2021

Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that have been shown to play a role in normal development, homeostasis, and disease, including cancer. CircRNAs are formed through a process called back‐splicing, which results in a covalently closed loop with a nonlinear back‐spliced junction (BSJ). In general, circRNA BSJs are predicted in RNA sequencing data using one of numerous circRNA detection algorithms. Selected circRNAs are then typically validated using an orthogonal method such as reverse transcription quantitative PCR (RT‐qPCR) with circRNA‐specific primers. However, linear transcripts originating from endogenous trans‐splicing can lead to false‐positive signals both in RNA sequencing and in RT‐qPCR experiments. Therefore, it is essential to perform the RT‐qPCR validation step only after linear RNAs have been degraded using an exonuclease such as ribonuclease R (RNase R). Several RNase R protocols are available for circRNA detection using RNA sequencing or RT‐qPCR. These protocols—which vary in enzyme concentration, RNA input amount, incubation times, and cleanup steps—typically lack a detailed validated standard protocol and fail to provide a range of conditions that deliver accurate results. As such, some protocols use RNase R concentrations that are too high, resulting in partial degradation of the target circRNAs. Here, we describe an optimized workflow for circRNA validation, combining RNase R treatment and RT‐qPCR. First, we outline the steps for circRNA primer design and qPCR assay validation. Then, we describe RNase R treatment of total RNA and, importantly, a subsequent essential buffer cleanup step. Lastly, we outline the steps to perform the RT‐qPCR and discuss the downstream data analyses. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: CircRNA primer design and qPCR assay validation

Basic Protocol 2: RNase R treatment, cleanup, and RT‐qPCR
Pharmacogenomics in Cardiovascular Diseases
Authors: McDonough Caitrin W.
Published: July 2021

Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug−related outcomes, or cardiovascular drug−related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC.

Basic Protocol: Designing a cardiovascular pharmacogenomics study
Dual‐band modified rectangular shaped dielectric resonator antenna with diversified polarization feature
Authors: Dwivedi Ajay Kumar , Sharma Anand , Ranjan Pinku
Published: July 2021

In this communication, the aperture coupled modified rectangular dielectric resonator antenna (rDRA) is designed and studied. The modified rectangular DRA is the same as Swastik shape. An asymmetrical microstrip line‐fed aperture stimulated a triple radiating mode pattern inside the ceramic material, that is,
, respectively. Swastik‐shaped ceramic radiator provides two important advantages: (a) lower Q‐factor, which in turn improves the impedance bandwidth, and (b) the creation of degenerated orthogonal mode with 90° phase shifts, which provides CP waves in one of the operating bands. Experimental outcomes confirm that the proposed antenna is working in dual‐frequency bands, that is, 6.41–7.38 GHz and 10.2–12.8 GHz, respectively. It supports left‐handed CP waves from 11.51 to 11.89 GHz. The proposed antenna is widely employable for fixed service satellite (FSS) for defense applications.
SixMeVproton acceleration from plasma generated by high‐intensity laser using advanced thin polyethylene targets
Authors: Torrisi L. , Cutroneo M. , Torrisi A.
Published: July 2021

Proton acceleration can be induced by non‐equilibrium plasma developed by high‐intensity laser pulses, at 1016 W/cm2, irradiating different types of thin polyethylene targets. The process of proton acceleration and directive yield emission was investigated, optimizing the laser parameters, the irradiation conditions, and the target properties. The use of 600 J pulse energy, a laser focalization inducing self‐focusing effects and advanced targets with embedded nanoparticles and optimal thicknesses, has permitted to accelerate forward protons up to the energies of about 6 MeV and amount of the order of 1015H+/pulse. High proton energy is obtained using thin foils enriched with gold nanoparticles, whereas high proton yield is obtained using targets with a thickness of about 10 μm. The plasma diagnostics using SiC semiconductor detectors in time‐of‐flight configuration was fundamental to monitor the optimal conditions to improve the plasma processes concerning the ion acceleration and the X‐ray and relativistic electron emission.
A multi‐level routing method in vehicular ad hoc networks using unnamed aerial vehicle nodes
Authors: Palizian Raziyeh , Barati Hamid , AnsariAsl Abdolnabi
Published: July 2021

Vehicular ad hoc networks (VANETs) are a subset of mobile ad hoc networks (MANETs) that can be used to communicate in intelligent transportation systems. In VANETs, each node in the network is a vehicle that exchanges data wirelessly with other vehicles. Many authors have considered using unnamed aerial vehicle (UAV) nodes to improve connectivity in VANETs. In recent years, UAVs have been used to enhance communications in VANETs. In this paper, a routing method for VANETs using UAV nodes is presented. The proposed method has three phases. The first phase deals with routing operations between vehicles. In this phase, whenever a vehicle has a packet to send, it selects the next hop to send the packet from the neighbor vehicles based on the parameters of distance, speed difference, and direction difference. The second phase is dedicated to routing operations between the vehicle and the UAV. In this phase, the roadside unit selects the best UAV based on distance and remaining energy, and the vehicle sends data to the UAV. The third phase is dedicated to UAV routing operations, and a greedy routing method between the UAVs based on distance and energy is presented. The proposed method is compared with U2RV and UVAR methods in terms of packet delivery rate, end‐to‐end delay, number of hops, and control overhead. The simulation results showed that the proposed method has improved in terms of packet delivery rate, the number of hops, and end‐to‐end delay.
Machine learning based study of longitudinal HbA1c trends and their association with all‐cause mortality: Analyses from a National Diabetes Registry
Authors: Cahn Avivit , Zuker Inbar , Eilenberg Roni , Uziel Moshe , Tsadok Meytal Avgil , Raz Itamar , Lutski Miri
Published: July 2021

Objective

The association of long‐term HbA1c variability with mortality has been previously suggested. However, the significance of HbA1c variability and trends in different age and HbA1c categories is unclear.

Research Design and Methods

Data on patients with diabetes listed in the Israeli National Diabetes Registry during years 2012–2016 (observation period) were collected. Patients with >4 HbA1c measurements, type 1 diabetes, eGFR < 30mg/ml/min, persistent HbA1c < 6% or malignancy were excluded. Utilizing machine learning methods, patients were classified into clusters according to their HbA1c trend (increasing, stable, decreasing). Mortality risk during 2017–2019 was calculated in subgroups defined by age (35–54, 55–69, 70–89 years) and last HbA1c (≤7% and >7%) at end of observation period. Models were adjusted for demographic, clinical and laboratory measurements including HbA1c, standard deviation (SD) of HbA1c and HbA1c trend.

Results

This historical cohort study included 293,314 patients. Increased HbA1c variability (high SD) during the observation period was an independent predictor of mortality in patients aged more than 55 years (p < 0.01). The HbA1c trend was another independent predictor of mortality. Patients with a decreasing versus stable HbA1c trend had a greater mortality risk; this association persisted in all age groups in patients with HbA1c > 7% at the end of the observation period (p = 0.02 in age 35–54; p < 0.01 in aged >55). Patients with an increasing versus stable HbA1c trend had a greater mortality risk only in the elderly group (>70), yet in both HbA1c categories (p < 0.01).

Conclusions

HbA1c variability and trend are important determinants of mortality risk and should be considered when adjusting glycaemic targets.
Polymer‐/Ceramic‐based Dielectric Composites for Energy Storage and Conversion
Authors: Wu Honghui , Zhuo Fangping , Qiao Huimin , Kodumudi Venkataraman Lalitha , Zheng Mupeng , Wang Shuize , Huang He , Li Bo , Mao Xinping , Zhang Qiaobao
Published: July 2021

Dielectric composites boost the family of energy storage and conversion materials as they can take full advantage of both the matrix and filler. This review aims at summarizing the recent progress in developing high‐performance polymer‐ and ceramic‐based dielectric composites, and emphases are placed on capacitive energy storage and harvesting, solid‐state cooling, temperature stability, electromechanical energy interconversion, and high‐power applications. Emerging fabrication techniques of dielectric composites such as 3D printing, electrospinning, and cold sintering are addressed, following by highlighted challenges and future research opportunities. The advantages and limitations of the typical theoretical calculation methods, such as finite‐element, phase‐field model, and machine learning methods, for designing high‐performance dielectric composites are discussed. This review is concluded by providing a brief perspective on the future development of composite dielectrics toward energy and electronic devices.
Boosted Storage Kinetics in Thick Hierarchical Micro–Nano Carbon Architectures for High Areal Capacity Li‐Ion Batteries
Authors: Wu Yang , Ouyang Ting , Xiong Tuzhi , Jiang Zhao , Hu Yuwen , Deng Jianqiu , Wang Zhongmin , Huang Yongchao , Balogun M.‐Sadeeq (Jie Tang)
Published: July 2021

A practical and effective approach to increase the energy storage capacity of lithium ion batteries (LIBs) is to boost their areal capacity. Developing thick electrodes is one of the most crucial ways to achieve high areal capacity but limited by sluggish ion/electron transport, poor mechanical stability, and high‐cost manufacturing strategies. Here we address these constraints by engineering a unique hierarchical‐networked 10 mm thick all‐carbon electrode, providing a scalable strategy to produce high areal capacity LIB electrodes. The hierarchical‐networked structure utilizes micrometer‐sized carbon fibers (MCFs) as building blocks, nano‐sized carbon nanotubes (CNTs) as good continuous network with excellent electrical conductivity, and pyrolytic carbon as the binder and active material with excellent storage capacity. The combination of the above features endows our HNT‐MCF/CNT/PC electrode with excellent performance including high reversible capacity of 15.44 mAh cm−2 at 2.0 mA cm−2 and exhibits excellent rate capability of 2.50 mAh cm−2 under 10.0 mA cm−2 current density. The Li‐ion storage mechanism in HNT‐MCF/CNT/PC involves dual‐storage mechanism including intercalation and surface adsorption (pseudocapacitance) confirmed by the cyclic voltammetry and symmetric cell analysis. This work provides insights into the construction of high mechanical stability thick electrode for the next generation high areal capacity LIBs and beyond.
Factors that contribute to the elongation of drumlins beneath the Green Bay Lobe, Laurentide Ice Sheet
Authors: Zoet Lucas K. , Rawling J. Elmo , Woodard Jacob B. , Barrette Nolan , Mickelson David M.
Published: July 2021

Drumlin shape has been hypothesized to correlate with ice‐flow duration and slip speed, but modern‐day analogues and the Coulomb nature of till render the basis of these correlations in question. The evolution of flow‐parallel subglacial landforms is of importance for ice flow because the form drag they provide may be a dominant factor in regulating glacier slip speeds. Here we examine the relationship between drumlin shape and cumulative slip displacement (i.e. time‐integrated slip speed) as a dominant glaciological control on drumlin shape. First, a new method is developed that allows slip speed to be estimated for deformable bedded glaciers along a flow line from an ice surface profile. Then, reconstructed surface profiles for ice margin chronologies of the Green Bay Lobe (GBL) are used to construct and estimate the spatially varying cumulative slip displacement for use in comparison with drumlin elongation ratios. We focus on a sector of the GBL near the central flow line where the geology is simple and glaciological controls are likely to dominate bedform development. Using Bayesian statistical analysis, a positive and statistically robust relationship between cumulative slip displacement and drumlin elongation ratio is found. Our analysis indicates that drumlin shape could be used to infer palaeo glacier slip speeds if time under the ice can be well constrained and geologic influences are minimal. These findings also suggest that drumlin‐supplied drag could decrease with increased cumulative slip displacement in the absence of rigid geologic features that fix drumlin positions.
Inventory and evolution of glacial lakes since the Little Ice Age: Lessons from the case of Switzerland
Authors: Mölg Nico , Huggel Christian , Herold Thilo , Storck Florian , Allen Simon , Haeberli Wilfried , Schaub Yvonne , Odermatt Daniel
Published: July 2021

Retreating glaciers give way to new landscapes with lakes as an important element. In this study, we combined available data on lake outlines with historical orthoimagery and glacier outlines for six time periods since the end of the Little Ice Age (LIA; ~1850). We generated a glacial lake inventory for modern times (2016) and traced the evolution of glacial lakes that formed in the deglaciated area since the LIA. In this deglaciated area, a total of 1192 lakes formed over the period of almost 170 years, 987 of them still in existence in 2016. Their total water surface in 2016 was 6.22 ± 0.25 km2. The largest lakes are > 0.4 km2 (40 ha) in size, while the majority (> 90%) are smaller than 0.01 km2. Annual increase rates in area and number peaked in 1946–1973, decreased towards the end of the 20th century, and reached a new high in the latest period 2006–2016. For a period of 43 years (1973–2016), we compared modelled overdeepenings from previous studies to actual lake genesis. For a better prioritization of formation probability, we included glacier‐morphological criteria such as glacier width and visible crevassing. About 40% of the modelled overdeepened area actually got covered by lakes. The inclusion of morphological aspects clearly aided in defining a lake formation probability to be linked to each modelled overdeepening. Additional morphological variables, namely dam material and type, surface runoff, and freeboard, were compiled for a subset of larger and ice‐contact lakes in 2016, constituting a basis for future hazard assessment.
Economically high‐order unstructured‐grid methods: Clarification and efficient FSR schemes
Authors: Nishikawa Hiroaki
Published: July 2021

In this article, we clarify reconstruction‐based discretization schemes for unstructured grids and discuss their economically high‐order versions, which can achieve high‐order accuracy under certain conditions at little extra cost. The clarification leads to one of the most economical approaches: the flux‐and‐solution‐reconstruction (FSR) approach, where highly economical schemes can be constructed based on an extended ‐scheme combined with economical flux reconstruction formulas, achieving up to fifth‐order accuracy (sixth‐order with zero dissipation) when a grid is regular. Various economical FSR schemes are presented and their formal orders of accuracy are verified by numerical experiments.