bluuebunny/crossref_metadata_2025 huggingface dataset:
TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells
Authors: Choi Jeong‐Yun , Lee Haeseung , Kwon Eun‐Ji , Kong Hyeon‐Joon , Kwon Ok‐Seon , Cha Hyuk‐Jin
Published: November 2020

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.
miR‐196b‐5p inhibits proliferation of Wharton's jelly umbilical cord stem cells
Authors: Han Xiao , Yang Haoqing , Liu Huina , Zhang Chen , Cao Yangyang , Fan Zhipeng , Shi Ruitang
Published: November 2020

Human umbilical cord mesenchymal stem cells can be obtained from different parts of the umbilical cord, including Wharton's jelly. Transplantation of Wharton's jelly umbilical cord stem cells (WJCMSCs) is a promising strategy for the treatment of various diseases. However, the molecular mechanisms underlying the proliferation of WJCMSCs are incompletely understood. Here, we report that overexpression of miR‐196b‐5p in WJCMSCs suppresses proliferation and arrests the cell cycle in G0/G1 phase, whereas knockdown of miR‐196b‐5p promotes WJCMSC proliferation and cell‐cycle progression. Moreover, miR‐196b‐5p overexpression resulted in decreased levels of Cyclin A, Cyclin D, Cyclin E and cyclin‐dependent kinases 2 and increased levels of p15INK4b, whereas miR‐196b‐5p knockdown had the opposite effects. In conclusion, our data suggests that miR‐196b‐5p inhibits WJCMSC proliferation by enhancing G0/G1‐phase arrest.
p‐Curve analysis of the Taylor Aggression Paradigm: Estimating evidentiary value and statistical power across 50 years of research
Authors: West Samuel J. , Hyatt Courtland S. , Miller Joshua D. , Chester David S.
Published: November 2020

The overall reliability or evidentiary value of any body of literature is established in part by ruling out publication bias for any observed effects. Questionable research practices have potentially undermined the evidentiary value of commonly used research paradigms in psychological science. Subsequently, the evidentiary value of these common methodologies remains uncertain. To quantify the severity of these issues in the literature, we selected the Taylor Aggression Paradigm (TAP) as a case study and submitted 170 hypothesis tests spanning over 50 years of research to a preregistered p‐curve analysis. The TAP literature (N = 24,685) demonstrated significant evidentiary value but yielded a small average effect size (d = 0.29) and inadequate power (38%). The main effects demonstrated greater evidentiary value, power, and effect sizes than interactions. Studies that tested the effects of measured traits did not differ in evidentiary value or power to those that tested the effects of experimentally manipulated states. Exploratory analyses revealed that evidentiary value, statistical power, and effect sizes have improved over time. We provide recommendations for researchers who seek to maximize the evidentiary value of their psychological measures.
A quality assurance tool for daily checks of the gamma knife high definition motion management system
Authors: Corns Robert , Mehta Dhara , Massock Whitney , Roberts Leah
Published: November 2020

Purpose

This note describes the performance of a quality assurance (QA) tool built for daily checks of the Gamma Knife’s high definition motion management (HDMM) system.

Methods

The tool is a three‐dimensional (3D)‐printed platform with a raised corner in the center. A reflector post is placed at the corner and the HDMM tool is zeroed to this position. Gage blocks produce very accurate gaps between the post and corner and the HDMM system’s readout is compared to the gage block thickness. The HDMM system and tool were tested for noise, stability, reproducibility, linearity, accuracy and overall setup times plus ease of use.

Results

The QA tool performed with accuracies better than 0.1 mm. The setup and use of this tool take less than two minutes making it a suitable tool for daily use.

Conclusion

This QA tool is a cost‐effective solution that provides a fast and easy confirmation of the HDMM accuracy, making it suitable for daily QA checks of the HDMM system.
Stereotactic radiotherapy of appropriately selected meningiomas and metastatic brain tumor beds with gamma knife icon versus volumetric modulated arc therapy
Authors: Buatti Jacob S. , Buatti John M. , Yaddanapudi Sridhar , Pennington Edward C. , Wang Dongxu , Gross Brandie , St‐Aubin Joël J. , Hyer Daniel E. , Smith Mark C. , Flynn Ryan T.
Published: November 2020

Purpose

To determine if the gamma knife icon (GKI) can provide superior stereotactic radiotherapy (SRT) dose distributions for appropriately selected meningioma and post‐resection brain tumor bed treatments to volumetric modulated arc therapy (VMAT).

Materials and Methods

Appropriately selected targets were not proximal to great vessels, did not have sensitive soft tissue including organs‐at‐risk (OARs) within the planning target volume (PTV), and did not have concave tumors containing excessive normal brain tissue. Four of fourteen candidate meningioma patients and six of six candidate patients with brain tumor cavities were considered for this treatment planning comparison study. PTVs were generated for GKI and VMAT by adding 1 mm and 3 mm margins, respectively, to the GTVs. Identical PTV V100%‐values were obtained for the GKI and VMAT plans for each patient. Meningioma and tumor bed prescription doses were 52.7–54.0 in 1.7–1.8 Gy fractions and 25 Gy in 5 Gy fractions, respectively. GKI dose rate was 3.735 Gy/min for 16 mm collimators.

Results

PTV radical dose homogeneity index was 3.03 ± 0.35 for GKI and 1.27 ± 0.19 for VMAT. Normal brain D1%, D5%, and D10% were lower for GKI than VMAT by 45.8 ± 10.9%, 38.9 ± 11.5%, and 35.4 ± 16.5% respectively. All OARs considered received lower maximum doses for GKI than VMAT. GKI and VMAT treatment times for meningioma plans were 12.1 ± 4.13 min and 6.2 ± 0.32 min, respectively, and, for tumor cavities, were 18.1 ± 5.1 min and 11.0 ± 0.56 min, respectively.

Conclusions

Appropriately selected meningioma and brain tumor bed patients may benefit from GKI‐based SRT due to the decreased normal brain and OAR doses relative to VMAT enabled by smaller margins. Care must be taken in meningioma patient selection for SRT with the GKI, even if they are clinically appropriate for VMAT.
Long‐Term Association Between Disease Activity and Disability in Early Axial Spondyloarthritis: Results From a Prospective Observational Study of Inflammatory Back Pain
Authors: Carvalho Pedro D. , Ruyssen‐Witrand Adeline , Marreiros Ana , Machado Pedro M.
Published: November 2020

Objective

Our primary objective was to study the long‐term association between disease activity and disability in axial spondyloarthritis (SpA). Our secondary objective was to define patient profiles according to their level of disability.

Methods

We analyzed data collected during the first 5 years of follow‐up of a large early axial SpA cohort, the Devenir des Spondylarthropathies Indifferénciées Récentes (DESIR) cohort. Multivariable models were built to study the association between the Health Assessment Questionnaire for Ankylosing Spondylitis (HAQ‐AS) and the Ankylosing Spondylitis Disease Activity Score with C‐reactive protein (ASDAS‐CRP), adjusting for potential confounders. Hierarchical multivariable analysis was conducted using the chi‐square automatic interaction detector (CHAID) method, to help determine how variables best cluster to explain HAQ‐AS.

Results

Data from 644 patients and 5,152 visits were analyzed. HAQ‐AS was longitudinally, independently, and positively associated with ASDAS‐CRP (adjusted B [adjB] 0.205 [95% confidence interval (95% CI) 0.187, 0.222]), the enthesitis score (adjB 0.011 [95% CI 0.008, 0.015]), the Bath Ankylosing Spondylitis Metrology Index (adjB 0.087 [95% CI 0.069, 0.105]), and female sex (adjB 0.172 [95% CI 0.120, 0.225]). The CHAID decision tree revealed ASDAS‐CRP as the first variable with discriminative power on HAQ‐AS. The cutoffs that separated different patient disability profiles were obtained.

Conclusion

Disease activity contributes longitudinally to disability and is hierarchically superior to any other variable in explaining this health domain. Enthesitis and spinal mobility are also key drivers of disability in early axial SpA. ASDAS‐CRP cutoffs that separated different patient disability profiles largely mimicked the cutoffs previously defined for ASDAS‐CRP disease activity states.
High‐Performance Al2O3/PAALi Composite Separator Prepared by Water‐Based Slurry for High‐Power Density Lithium‐Based Battery
Authors: Xu Rong , Sheng Lei , Gong Hao , Kong Yulong , Yang Yang , Li Menglin , Bai Yaozong , Song Shangjun , Liu Gaojun , Wang Tao , Huang Xianli , He Jianping
Published: November 2020

The ceramic composite separator shows great thermal stability and electrolyte wettability compared with polyolefin separator, which is applied in the supply source of electric vehicles. However, the preparation of ceramic composite separator is involved with large amount of organic solvents, and it is of great harm to health. Herein, lithium polyacrylate (PAALi) is selected as a novel binder to prepare the Al2O3/PAALi ceramic composite separator by water‐based slurry. The production of Al2O3/PAALi composite separator is more environmental‐friendly, and it also exhibits excellent thermal stability. In addition, the Al2O3/PAALi composite separator has obviously improved lithium transference number of 0.41, compared with polyethylene (PE) separator and Al2O3/polyvinylidene fluoride (PVDF) composite separator. It can be attributed to the fact that PAALi with a lot of carboxyl (COO−) functional groups has an interaction with ions and facilitates the desolvation of cation. As a result, the LiCoO2/Li half cell using Al2O3/PAALi composite separator shows higher discharge capacity retention (88%) after 180 cycles and excellent cycling stability. Fortunately, these cells containing Al2O3/PAALi composite separator also have wonderful rate performance; even at 5 C, the discharge capacity retention still keeps 58%, higher than Al2O3/PVDF composite separator. Therefore, this is a promising method to further enhance the battery performance.
All‐Printed Smart Label with Integrated Humidity Sensors and Power Supply
Authors: Pereira Nelson , Correia Vitor , Peřinka Nikola , Costa Carlos M. , Lanceros-Méndez Senentxu
Published: November 2020

Sensing smart labels are an essential component of the Internet of Things (IoT) to provide identification and data. However, the widespread use of these labels into functional devices requires easy integration and power supply. Herein, a smart label is presented with integrated humidity sensor and printed battery. The smart label is composed by detection, communication, control, and energy subsystems. It is based on a screen printed RLC circuit and a printed humidity sensor with electrical linear response. The printed battery based on lithium iron phosphate as an active cathode material is fabricated with six single cells connected in series, leading to ≈100 mAh g−1. The printed humidity sensor has a linear response with a sensitivity of 0.004/% relative humidity (RH). Thus, it demonstrates the development of fully printed smart labels, improving integration into a variety of applications.
Polymer‐Based Solid Electrolytes: Material Selection, Design, and Application
Authors: Xi Guan , Xiao Min , Wang Shuanjin , Han Dongmei , Li Yuning , Meng Yuezhong
Published: November 2020

Polymer‐based solid electrolytes (PSEs) have attracted tremendous interests for the next‐generation lithium batteries in terms of high safety and energy density along with good flexibility. Remarkable performances have been demonstrated in PSEs, which endowed PSEs with the potential to replace liquid electrolytes to meet the market demands. In this review, polymer matrices, different polymer architectures, and functional filler materials used in PSEs are discussed to explore the design concepts, methodologies, working mechanisms, and pros and cons of various PSEs. In addition, their recent notable applications in all‐solid‐state lithium ion batteries, lithium–sulfur batteries, suppression of lithium dendrites, and flexible lithium batteries are also introduced. Finally, the challenges and future prospects are sketched to provide strategies to explore novel PSEs for high‐performance all‐solid‐state lithium batteries.
Palladium Catalyzed Ring Expansion Reaction of Isoxazolones with Isocyanides: Synthesis of 1,3‐Oxazin‐6‐One Derivatives
Authors: Zhu Yi‐Ming , Zhang Wan , Li Hongkun , Xu Xiao‐Ping , Ji Shun‐Jun
Published: November 2020

A palladium catalyzed ring expansion reaction of isoxazolones with isocyanides was disclosed. In the reaction, a cascade process involving ring‐opening/cyclization was suggested. The reaction features high atomic economy due to no elimination of CO2 occurred. Moreover, products obtained demonstrate aggregation‐induced emission properties with relatively high solid‐state emission efficiencies.

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Sustainable Cathodes for Lithium‐Ion Energy Storage Devices Based on Tannic Acid—Toward Ecofriendly Energy Storage
Authors: Ilic Ivan K. , Tsouka Alexandra , Perovic Milena , Hwang Jinyeon , Heil Tobias , Loeffler Felix F. , Oschatz Martin , Antonietti Markus , Liedel Clemens
Published: November 2020

The use of organic materials with reversible redox activity holds enormous potential for next‐generation Li‐ion energy storage devices. Yet, most candidates are not truly sustainable, i.e., not derived from renewable feedstock or made in benign reactions. Here an attempt is reported to resolve this issue by synthesizing an organic cathode material from tannic acid and microporous carbon derived from biomass. All constituents, including the redox‐active material and conductive carbon additive, are made from renewable resources. Using a simple, sustainable fabrication method, a hybrid material is formed. The low cost and ecofriendly material shows outstanding performance with a capacity of 108 mAh g−1 at 0.1 A g−1 and low capacity fading, retaining approximately 80% of the maximum capacity after 90 cycles. With approximately 3.4 V versus Li+/Li, the cells also feature one of the highest reversible redox potentials reported for biomolecular cathodes. Finally, the quinone‐catecholate redox mechanism responsible for the high capacity of tannic acid is confirmed by electrochemical characterization of a model compound similar to tannic acid but without catecholic groups.
Macrocyclic Peptide Inhibitor of PD‐1/PD‐L1 Immune Checkpoint
Authors: Magiera‐Mularz Katarzyna , Kuska Katarzyna , Skalniak Lukasz , Grudnik Przemyslaw , Musielak Bogdan , Plewka Jacek , Kocik Justyna , Stec Malgorzata , Weglarczyk Kazimierz , Sala Dominik , Wladyka Benedykt , Siedlar Maciej , Holak Tad A. , Dubin Grzegorz
Published: November 2020

Immune checkpoint‐targeting antibodies brought a recent breakthrough in cancer immunotherapy, but the development of small molecule checkpoint inhibitors is lagging behind. Here, the characterization of a macrocyclic peptide (p101) capable of blocking the PD‐L1/PD‐1 immune checkpoint is reported at the interface of cancer and immune cells. NMR and other physicochemical data demonstrate that the macrocycle binds to PD‐L1 to sterically hinder its interaction with PD‐1. The crystal structure of the complex highlights the detailed features of the binding site and demonstrates that the interaction is primarily guided by hydrophobic forces. A reporter PD‐L1/PD‐1 blockade bioassay demonstrates that p101 is able to inhibit the interaction in the cellular environment. Finally, it is shown that p101 releases the immune response of primary human T‐cells from PD‐L1 mediated inhibition.
Impact of putting green management on visible wear damage caused by foot traffic
Authors: Nikolai Thomas A. , Karcher Douglas E. , Hathaway Aaron D. , O'Brien Daniel
Published: November 2020

A 2‐yr study was conducted at Michigan State University (MSU) and the University of Arkansas (UARK) to identify creeping bentgrass (Agrostis stolonifera L.) putting green management practices that minimize or exacerbate visible wear damage (VWD) caused by aggressive golf shoes or cleats. Management treatments included different levels of grooming (none vs. three times weekly at a depth of 0.5 mm), lightweight rolling (none vs. three times weekly), sand topdressing (none vs. every 14 d at the rate of 0.6 L m−2), and nitrogen fertility (low N vs. high N every 14 d) applied as urea at the rates of 0.6 or 1.2 g m−2. Rolling significantly increased VWD at UARK in both years and at MSU in 2017. When increases in VWD occurred on rolled plots, there were also significant increases in moisture in the top 3.8 cm of the root zone. Higher fertility consistently increased VWD at UARK throughout the study and after a single traffic event at MSU. Throughout the trial, grooming and sand topdressing occasionally reduced VWD at both locations. These results will help agronomists and golf course superintendents fine‐tune cultural practices to mitigate VWD on intensively managed creeping bentgrass putting greens.
Population structure, diversifying selection, and local adaptation in Pinus patula
Authors: Peláez Pablo , Ortiz‐Martínez Alfredo , Figueroa‐Corona Laura , Montes José Rubén , Gernandt David S.
Published: November 2020

Premise

Climate change is predicted to affect natural and plantation forests. The responses of conifers to overcome changing environments will depend on their adaptation to local conditions; however, intraspecific adaptive genetic variation is unknown for most gymnosperms. Studying genetic diversity associated with phenotypic variability along environmental gradients will enhance our understanding of adaptation and may reveal genetic pools important for conservation and management.

Methods

We used target enrichment and genome skimming to obtain single nucleotide polymorphisms (SNPs) from 61 individuals of Pinus patula, a pine tree native to Mexico widely used in plantation forestry. We investigated the adaptive genetic variation of two varieties with morphological and distributional differences potentially related to genetic and adaptive divergence.

Results

Population structure and haplotype network analyses revealed that genetic diversity between P. patula var. patula and P. patula var. longipedunculata was structured, even within populations of P. patula var. longipedunculata. We observed high genetic diversity, low inbreeding rate, and rapid linkage disequilibrium (LD) decay in the varieties. Based on outlier tests, loci showing signatures of natural selection were detected in geographically distant P. patula var. longipedunculata populations. For both varieties, we found significant correlations between climate‐related environmental variation and SNP diversity at loci involved in abiotic stress, cell transport, defense, and cell wall biogenesis, pointing to local adaptation.

Conclusions

Overall, significant intraspecific adaptive genetic variation in P. patula was detected, highlighting the presence of different genetic pools and signs of local adaptation that should be considered in forestry and conservation.
Association of HECW2 variants with developmental and epileptic encephalopathy and knockdown of zebrafish hecw2a
Authors: Lu Qian , Zhang Meng‐Na , Shi Xiu‐Yu , Zhang Ling‐Qiang , Wang Yang‐Yang , Liu Li‐Ying , He Wen , Chen Hui‐Min , He Bing , Zou Li‐Ping
Published: November 2020

Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.
Direct C(sp3)−H Trifluoromethylation of Unactivated Alkanes Enabled by Multifunctional Trifluoromethyl Copper Complexes
Authors: Choi Geunho , Lee Geun Seok , Park Beomsoon , Kim Dongwook , Hong Soon Hyeok
Published: November 2020

A mild and operationally simple C(sp3)−H trifluoromethylation method was developed for unactivated alkanes by utilizing a bench‐stable CuIII complex, bpyCu(CF3)3, as the initiator of the visible‐light photoinduced reaction, the source of a trifluoromethyl radical as a hydrogen atom transfer reagent, and the source of a trifluoromethyl anion for functionalization. The reaction was initiated by the generation of reactive electrophilic carbon‐centered CF3 radical through photoinduced homolytic cleavage of bpyCu(CF3)3, followed by hydrogen abstraction from an unactivated C(sp3)−H bond. Comprehensive mechanistic investigations based on a combination of experimental and computational methods suggested that C−CF3 bond formation was enabled by radical–polar crossover and ionic coupling between the resulting carbocation intermediate and the anionic CF3 source. The methylene‐selective reaction can be applied to the direct, late‐stage trifluoromethylation of natural products and bioactive molecules.
Cyclic Heterometallic Interactions formed from a Flexible Tripeptide Complex Showing Effective Antiferromagnetic Spin Coupling
Authors: Miyake Ryosuke , Suganuma Eri , Kimura Shun , Mori Hirotoshi , Okabayashi Jun , Kusamoto Tetsuro
Published: November 2020

Developing tunable motifs for heterometallic interactions should be beneficial for fabricating functional materials based on cooperative electronic communications between metal centers. Reported here is the efficient formation of cyclic heterometallic interactions from a complex containing an artificial tripeptide with metal binding sites on its main chain and side chains. X‐ray structural analysis and X‐ray absorption spectroscopy revealed that the cyclic metal–metal arrangements arise from the amide groups connecting four square‐planar CuII centers and four octahedral NiII centers in a cyclic manner. UV/Vis spectral studies suggested that this efficient formation was achieved by the selective formation of the square‐planar CuII centers and a crystallization process. Magnetic measurements using SQUID clarified that the cyclic complex represented the S=2 spin state at low temperatures due to effective antiferromagnetic interactions between the NiII and CuII centers.
C−H Activation by an Iron‐Nitrido Bis‐Pocket Porphyrin Species
Authors: Wang Hai‐Xu , Wu Liangliang , Zheng Bin , Du Lili , To Wai‐Pong , Ko Cheng‐Hoi , Phillips David Lee , Che Chi‐Ming
Published: November 2020

High‐valent iron‐nitrido species are nitrogen analogues of iron‐oxo species which are versatile reagents for C−H oxidation. Nonetheless, C−H activation by iron‐nitrido species has been scarcely explored, as this is often hampered by their instability and short lifetime in solutions. Herein, the hydrogen atom transfer (HAT) reactivity of an Fe porphyrin nitrido species (2 c) toward C−H substrates was studied in solutions at room temperature, which was achieved by nanosecond laser flash photolysis (LFP) of its FeIII‐azido precursor (1 c) supported by a bulky bis‐pocket porphyrin ligand. C−H bonds with bond dissociation enthalpies (BDEs) of up to ≈84 kcal mol−1 could be activated, and the second‐order rate constants (k2) are on the order of 102–104 s−1 m−1. The Fe‐amido product formed after HAT could further release ammonia upon protonation.
Observing Single‐Atom Catalytic Sites During Reactions with Electrospray Ionization Mass Spectrometry
Authors: Hülsey Max J. , Sun Geng , Sautet Philippe , Yan Ning
Published: November 2020

Single‐atom catalysts (SACs) have become a prominent theme in heterogeneous catalysis, not least because of the potential fundamental insight into active sites. The desired level of understanding, however, is prohibited due to the inhomogeneity of most supported SACs and the lack of suitable tools for structure–activity correlation studies with atomic resolution. Herein, we describe the potency of electrospray ionization mass spectrometry (ESI‐MS) to study molecularly defined SACs supported on polyoxometalates in catalytic reactions. We identified the exact composition of active sites and their evolution in the catalytic cycle during CO and alcohol oxidation reactions performed in the liquid phase. Critical information on metal‐dependent reaction mechanisms, the key intermediates, the dynamics of active sites and even the stepwise activation barriers were obtained, which would be challenging to gather via prevailingly adopted techniques in SAC research. DFT calculations revealed intricate details of the reaction mechanisms, and strong synergies between ESI‐MS defined SAC sites and electronic structure theory calculations become apparent.
Activation of Aptamers with Gain of Function by Small‐Molecule‐Clipping of Intramolecular Motifs
Authors: Huang Mengjiao , Li Tingyu , Xu Yuanfeng , Wei Xinyu , Song Jia , Lin Bingqian , Zhu Zhi , Song Yanling , Yang Chaoyong
Published: November 2020

Click reactions have the advantages of high reactivity, excellent orthogonality, and synthetic accessibility. Inspired by click reactions, we propose the concept of “clipped aptamers”, whose binding affinity is regulated by the “clip”‐like specific interaction between a synthetic DNA‐mismatch‐binding small molecule (molecular glue, Z‐NCTS) and the preset CGG/CGG sequences in nucleic acid sequences. In this study, we investigated a Z‐NCTS‐mediated de novo selection of clipped aptamers against epithelial cell adhesion molecule. The generated clipped aptamers can achieve the efficient transition from a binding‐inactive state to an active state by clipping of Z‐NCTS with two CGG sites, which otherwise would not hybridize. The experimental and simulation results showed that the clipped aptamer had ideal binding thermodynamics and the ability to regulate cellular adhesion. Because of this superior activated mechanism and structural diversity, clipped aptamers hold great potential in biosensing, imaging, conditional gene‐ and cellular behavior‐regulation, and drug delivery.
Ir(triscarbene)‐catalyzed sustainable transfer hydrogenation of levulinic acid to γ‐valerolactone
Authors: Sung Kihyuk , Lee Mi‐hyun , Cheong Yeon‐Joo , Jang Hye‐Young
Published: November 2020

Sustainable iridium‐catalyzed transfer hydrogenation using glycerol as the hydride source was employed to convert levulinic acid to γ‐valerolactone (GVL) with exceptionally high turnover numbers (TONs) (500,000) and turnover frequencies (TOFs) (170,000 h−1). The highly efficient triscarbene‐modified iridium catalysts demonstrated good catalytic activities with low catalyst loadings (0.7 ppm) and good recyclability with an accumulated TON of over two million in the fourth reaction. In addition to glycerol, propylene glycol (PG), ethylene glycol (EG), isopropanol (IPA), and ethanol (EtOH) successfully transferred hydrides to levulinic acid, producing GVL with TONs of 339,000 (PG), 242,000 (EG), 334,000 (IPA), and 208,000 (EtOH), respectively. Deuterium‐labeling experiments were conducted to gain insight into the reaction mechanism.
Ethanol‐free extraction of resveratrol and its glycoside from Japanese knotweed rhizome by liquefied dimethyl ether without pretreatments
Authors: Kanda Hideki , Oishi Kazuma , Machmudah Siti , Wahyudiono  , Goto Motonobu
Published: November 2020

Herein, we carried out the extraction of polyphenol resveratrol and its glycoside (piceid) from raw Japanese knotweed via a simple method, employing dimethyl ether (DME) as the solvent. With DME extraction, the conventional drying and cell wall disruption steps can be left out. As a result, more resveratrol and piceid were obtained in DME extraction than in conventional ethanol extraction. Because the Hansen solubility parameters of DME are closer to ethanol than to water, it allowed us to extract resveratrol and piceid from raw Japanese knotweed, unlike water. Simultaneously, 83.5% of the initial water and 213 mg/g dry of organic extracts were extracted from raw Japanese knotweed. As DME extraction does not involve drying and grinding of the decomposed antioxidants, it is highly suitable for extracting antioxidants.
Altered functional connectivity of the amygdala and its subregions in typhoon‐related post‐traumatic stress disorder
Authors: Liu Tao , Ke Jun , Qi Rongfeng , Zhang Li , Zhang Zhiqiang , Xu Qiang , Zhong Yuan , Lu Guangming , Chen Feng
Published: November 2020

Background

New evidence suggests that the centromedial amygdala (CMA) and the basolateral amygdala (BLA) play different roles in threat processing. Our study aimed to investigate the effects of trauma and post‐traumatic stress disorder (PTSD) on the functional connectivity (FC) of the amygdala and its subregions.

Methods

Twenty‐seven patients with typhoon‐related PTSD, 33 trauma‐exposed controls (TEC), and 30 healthy controls (HC) were scanned with a 3‐Tesla magnetic resonance imaging scanner. The FCs of the BLA, the CMA, and the amygdala as a whole were examined using a seed‐based approach, and then, the analysis of variance was used to compare the groups.

Results

We demonstrated that the BLA had a stronger connectivity with the prefrontal cortices (PFCs) and angular gyrus in the PTSD group than in the TEC group. Additionally, compared with the PTSD and the HC groups, the TEC group exhibited decreased and increased BLA FC with the ventromedial PFC and postcentral gyrus (PoCG), respectively. Furthermore, the PTSD group showed abnormal FC between the salience network and default‐mode network, as well as the executive control network. Compared with the HC group, the TEC group and the PTSD group both showed decreased BLA FC with the superior temporal gyrus (STG). Finally, the FCs between the bilateral amygdala (as a whole) and the vmPFC, and between the BLA and the vmPFC have a negative correlation with the severity of PTSD.

Conclusions

Decreased BLA‐vmPFC FC and increased BLA‐PoCG FC may reflect PTSD resilience factors. Trauma leads to decreased connectivity between the BLA and the STG, which could be further aggravated by PTSD.
Perspectives, fears and expectations of patients with gynaecological cancers during the COVID‐19 pandemic: A Pan‐European study of the European Network of Gynaecological Cancer Advocacy Groups (ENGAGe)
Authors: Gultekin Murat , Ak Sertac , Ayhan Ali , Strojna Aleksandra , Pletnev Andrei , Fagotti Anna , Perrone Anna Myriam , Erzeneoglu B. Emre , Temiz B. Esat , Lemley Birthe , Soyak Burcu , Hughes Cathy , Cibula David , Haidopoulos Dimitrios , Brennan Donal , Cola Edoardo , van der Steen‐Banasik Elzbieta , Urkmez Esra , Akilli Huseyin , Zapardiel Ignacio , Tóth Icó , Sehouli Jalid , Zalewski Kamil , Bahremand Kiarash , Chiva Luis , Mirza Mansoor Raza , Papageorgiou Maria , Zoltan Novak , Adámková Petra , Morice Philippe , Garrido‐Mallach Sonia , Akgor Utku , Theodoulidis Vasilis , Arik Zafer , Steffensen Karina D. , Fotopoulou Christina
Published: November 2020

Background

The impact of the COVID‐19 pandemic on European gynaecological cancer patients under active treatment or follow‐up has not been documented. We sought to capture the patient perceptions of the COVID‐19 implications and the worldwide imposed treatment modifications.

Methods

A patient survey was conducted in 16 European countries, using a new COVID‐19‐related questionnaire, developed by ENGAGe and the Hospital Anxiety & Depression Scale questionnaire (HADS). The survey was promoted by national patient advocacy groups and charitable organisations.

Findings

We collected 1388 forms; 592 online and 796 hard‐copy (May, 2020). We excluded 137 due to missing data. Median patients’ age was 55 years (range: 18–89), 54.7% had ovarian cancer and 15.5% were preoperative. Even though 73.2% of patients named cancer as a risk factor for COVID‐19, only 17.5% were more afraid of COVID‐19 than their cancer condition, with advanced age (>70 years) as the only significant risk factor for that. Overall, 71% were concerned about cancer progression if their treatment/follow‐up was cancelled/postponed. Most patients (64%) had their care continued as planned, but 72.3% (n = 892) said that they received no information around overall COVID‐19 infection rates of patients and staff, testing or measures taken in their treating hospital. Mean HADS Anxiety and Depression Scores were 8.8 (range: 5.3–12) and 8.1 (range: 3.8–13.4), respectively. Multivariate analysis identified high HADS‐depression scores, having experienced modifications of care due to the pandemic and concern about not being able to visit their doctor as independent predictors of patients’ anxiety.

Interpretation

Gynaecological cancer patients expressed significant anxiety about progression of their disease due to modifications of care related to the COVID‐19 pandemic and wished to pursue their treatment as planned despite the associated risks. Healthcare professionals should take this into consideration when making decisions that impact patients care in times of crisis and to develop initiatives to improve patients’ communication and education.
Concomitant septal myectomy and mitral valve repair in a child with Noonan syndrome
Authors: Doi Toshio , Toritsuka Daisuke , Higashida Akihiko , Yokoyama Shigeki , Fukahara Kazuaki , Yoshimura Naoki
Published: November 2020

We successfully performed concomitant septal myectomy and mitral valve repair in a child with Noonan syndrome.
Steady‐State Electrocatalytic Activity Evaluation with the Redox Competition Mode of Scanning Electrochemical Microscopy: A Gold Probe and a Boron‐Doped Diamond Substrate
Authors: Henrotte Olivier , Boudet Alice , Limani Ndrina , Bergonzo Philippe , Zribi Bacem , Scorsone Emmanuel , Jousselme Bruno , Cornut Renaud
Published: November 2020

In the current context of energetic transition, investigations of alternative complex systems require tools such as scanning electrochemical microscopy (SECM), offering interesting opportunities as an electroanalytical technique to evaluate innovative catalysts. Herein, we demonstrate how a judicious choice of probe and substrate materials opens up improved performances to achieve steady‐state measurements for oxygen reduction reaction (ORR) catalytic activity detection through redox competition scanning electrochemical microscopy (RC‐SECM). On the probe side, we show that using gold enhances the stability of the local oxygen concentration detection in comparison to the regularly used platinum one. On the substrate side, we evaluate boron‐doped diamond as an appealing alternative to classical support substrate, that shows a low ORR activity, high stability and very good reusability. This work introduces an alternative approach for quantitative measurements with SECM, improving measurement ease, comfort and reproducibility, thus paving the way towards standardized benchmarking and numerical simulation‐based parameter extraction.
In Vitro and In Vivo Sequestration of Phencyclidine by Me4Cucurbit[8]uril**
Authors: Murkli Steven , Klemm Jared , Brockett Adam T. , Shuster Michael , Briken Volker , Roesch Matthew R. , Isaacs Lyle
Published: November 2020

We report investigations of the use of cucurbit[8]uril (CB[8]) macrocycles as an antidote to counteract the in vivo biological effects of phencyclidine. We investigate the binding of CB[8] and its derivative Me4CB[8] toward ten drugs of abuse (3–9, 12–14) by a combination of 1H NMR spectroscopy and isothermal titration calorimetry in phosphate buffered water. We find that the cavity of CB[8] and Me4CB[8] are able to encapsulate the 1‐amino‐1‐aryl‐cyclohexane ring system of phencyclidine (PCP) and ketamine as well as the morphinan skeleton of morphine and hydromorphone with Kd values ≤50 nm. In vitro cytotoxicity (MTS metabolic and adenylate kinase cell death assays in HEK293 and HEPG2 cells) and in vivo maximum tolerated dose studies (Swiss Webster mice) which were performed for Me4CB[8] indicated good tolerability. The tightest host⋅guest pair (Me4CB[8]⋅PCP; Kd=2 nm) was advanced to in vivo efficacy studies. The results of open field tests demonstrate that pretreatment of mice with Me4CB[8] prevents subsequent hyperlocomotion induction by PCP and also that treatment of animals previously dosed with PCP with Me4CB[8] significantly reduces the locomotion levels.
Inversion Symmetry Breaking in Order–Disorder Transitions of Globular Ligands Coordinating to Cobalt(II) and Nickel(II) Bisacetylacetonato Complexes During Heating
Authors: Hoshino Norihisa , Akutagawa Tomoyuki
Published: November 2020

Unexpected inversion‐symmetry breaking was observed in the order–disorder phase transitions of [M(acac)2(abco)2] (1; M=Co2+, 2; Ni2+, acac−=2,4‐pentanedionato, abco=1‐azabicyclo‐[2.2.2]‐octane=quinuclidine) during heating. The isostructural, transition‐free complexes [M(acac)2(cabco)2] (3; M=Co2+, 4; Ni2+, cabco=3‐chloro‐1‐azabicyclo‐[2.2.2]‐octane=3‐chloroquinuclidine) were also studied for comparison. Complexes 1 and 2 crystallized in ordered phases in the centrosymmetric I2/m space group at 100 K, whereas they crystallized in disordered phases in the non‐symmetric I2 space group at 300 K. The 60° step rotation disordering of the abco ligands was observed in the electron density maps of 1 and 2, which was consistent with the transition enthalpies estimated by differential scanning calorimetry (DSC). Gradual phase transitions were observed for 1 and 2 by DSC and powder X‐ray diffraction (PXRD) at approximately 225 K. The inversion‐symmetry disordering was likely induced by the local pseudo‐symmetry of the abco ligands, increasing from trigonal to hexagonal and the increased steric repulsion pathways among them.
A Novel Thermocell System Using Proton Solvation Entropy
Authors: Kobayashi Takashi , Yamada Teppei , Tadokoro Makoto , Kimizuka Nobuo
Published: November 2020

The entropy change associated with proton‐coupled electron transfer (PCET) reactions significantly enhance the Seebeck coefficient (Se) of thermocells. A redox pair of [Ru(Hxim)6]2+/3+ (Him=imidazole, x=0≈1) releases three protons in their one‐electron redox reactions in thermocells, which gave a remarkably high Se of −3.7 mV K−1 as confirmed by temperature‐dependent square wave voltammetry. The value of Se is proportional to the redox reaction entropy (ΔSrc), which increased with the number of dissociating protons. This result demonstrates the utility of PCET reaction toward efficient thermoelectric conversion.
Feng Ligand: Privileged Chiral Ligand in Asymmetric Catalysis
Authors: Wang Ming‐Yang , Li Wei
Published: November 2020

Catalysts and ligands possessing the great ability to tolerate over a wide range of mechanistically unrelated reactions are remarked as "privileged", which are rather scarce but extremely meaningful in asymmetric catalysis. Feng and co‐workers have developed a library of conformationally flexible, C2‐symmetric N,N'‐dioxide amide compounds with original design and featured structure (named as Feng ligand now). They were initially reported as chiral organocatalysts in 2005 and have been further developed as a new class of privileged chiral ligands since 2006. Tremendous success, including versatile coordination chemistry with plenty of metal sources (main‐group metals, transition metals, and rare‐earth metals), a truly broad scope of asymmetric reactions (more than 50 types), diverse areas of catalysis (organocatalysis, Lewis‐acid catalysis, bimetallic relay catalysis, and photocatalysis), numerous synthetic applications of bioactive compounds, has been achieved using Feng N,N'‐dioxide. Besides, they demonstrate that chiral ligands with conformationally flexible property can offer excellent chiral environment as well, which challenges the conventional idea preferring rigid structures in the design of chiral ligands. Herein, we briefly introduced the discovery of Feng ligand and the millstones during the development. We also covered the successful applications of Feng ligand by other scientists as well as novel chiral ligands inspired by them.
Numerical analysis of nanoparticle transport and deposition in a cynomolgus monkey nasal passage
Authors: Dong Jingliang , Ma Jiawei , Tian Lin , Inthavong Kiao , Ito Kazuhide , Tu Jiyuan
Published: November 2020

Environmental exposure to toxic agents is commonly encountered by occupational and residential populations. However, in vivo exposure data in human subjects is limited by measurement and ethical restrictions. Monkey represents a suitable surrogate for human exposure studies, but the particle transport and deposition features in monkey airways are still not well understood. As a response to this research challenge, this paper presents a virtual exposure study that numerically investigated the nanoparticle transport process through a realistic cynomolgus monkey nasal airway. Particles with size of 1 nm to 1 μm were considered and the transport process was modelled by the Lagrangian discrete phase model. Overall and local deposition as well as particle dispersion along the airway were examined by using a variety of non‐dimensional parameters including combined diffusion parameter, deposition enhancement factor and particle flux enhancement factor. Consistent deposition patterns were observed in present and literature nasal models. Most particles tended to pass the nasal airway through certain spatial regions, including the middle section of the nasal valve, the lower half of the middle coronal plane, and the central regions of the choana. While naturally inhaled nanoparticles can hardly be delivered to the olfactory region as it is located apart from the mainstream with high particle flux. Research findings provide insight into nanoparticle inhalation exposure characteristics in the monkey airway and can contribute in formulating data extrapolation schemes between monkey and human airways.
Analysis of hemodynamic changes from aneurysm inception to large sizes
Authors: Salimi Ashkezari Seyedeh Fatemeh , Mut Fernando , Chung Bong Jae , Robertson Anne M. , Frösen Juhana , Cebral Juan R.
Published: November 2020

While previous studies have identified many risk factors for the progression and rupture of cerebral aneurysms, the changes in aneurysm flow characteristics during its evolution are not fully understood. This work analyzes the changes in the aneurysm hemodynamic environment from its initial development to later stages when the aneurysm has substantially enlarged. A total of 88 aneurysms at four locations were studied with image based computational fluid dynamics (CFD). Two synthetic sequences representing the aneurysm geometry at three earlier stages were generated by shrinking the aneurysm sac while keeping the neck fixed or shrinking the neck simultaneously. The flow conditions were then quantitatively compared between these two modes of evolution. As aneurysms enlarged, the inflow rate increased in growing neck sequences, but decreased in fixed neck sequences. The inflow jet became more concentrated in both sequences. The mean aneurysm flow velocity and wall shear stress decreased in both sequences, but they decreased faster in enlarging aneurysms if the neck was fixed. Additionally, the intra‐aneurysmal flows became more complex and more unstable, wall shear stress distribution became more oscillatory, and the area under low wall shear stress increased for both sequences. The evolution of flow characteristics of aneurysms with fixed and growing necks are different. The observed trends suggest that fixed neck aneurysms may evolve towards a flow environment characteristic of stable aneurysms faster than aneurysms with growing necks, which could also evolve towards a more disfavorable environment.
Social rumor detection based on multilayer transformer encoding blocks
Authors: Lin Lijun , Chen Zhiyun
Published: November 2020

The propagation of rumors on social media has been identified as a critical problem in recent years that causes social panic or economic turmoil (to some extent), thereby giving rise to the need for faster identification. With the advancements in deep learning, researches based on neural networks become popular. Most of the existing methods extensively adopt recurrent neural networks (RNNs), such as gated recurrent unit and long short‐term memory. This results in a significant degradation in the concurrency performance of the models, implying an increased consumption of time and resources. This study proposes a model with multilayer transformer encoding blocks for detecting rumors. The self‐attention mechanism in the transformer encoding blocks provides better concurrency to the proposed model and improves its performance. The proposed model performs faster executions using less or no recurrences in comparison to other models based on RNNs. Experiments on two real social datasets verified that our model could achieve significantly better results than baseline methods. The accuracy rate increased by 1.1% and 2.2% on the Weibo and PHEME datasets, respectively. In comparison to the methods that use RNNs as a feature extractor, the training duration in the proposed model was reduced by 16% and 70% in Weibo and PHEME, respectively.
Towards compound identification of synthetic opioids in nontargeted screening using machine learning techniques
Authors: Klingberg Joshua , Cawley Adam , Shimmon Ronald , Fu Shanlin
Published: November 2020

The constant evolution of the illicit drug market makes the identification of unknown compounds problematic. Obtaining certified reference materials for a broad array of new analogues can be difficult and cost prohibitive. Machine learning provides a promising avenue to putatively identify a compound before confirmation against a standard. In this study, machine learning approaches were used to develop class prediction and retention time prediction models. The developed class prediction model used a naïve Bayes architecture to classify opioids as belonging to either the fentanyl analogues, AH series or U series, with an accuracy of 89.5%. The model was most accurate for the fentanyl analogues, most likely due to their greater number in the training data. This classification model can provide guidance to an analyst when determining a suspected structure. A retention time prediction model was also trained for a wide array of synthetic opioids. This model utilised Gaussian process regression to predict the retention time of analytes based on multiple generated molecular features with 79.7% of the samples predicted within ±0.1 min of their experimental retention time. Once the suspected structure of an unknown compound is determined, molecular features can be generated and input for the prediction model to compare with experimental retention time. The incorporation of machine learning prediction models into a compound identification workflow can assist putative identifications with greater confidence and ultimately save time and money in the purchase and/or production of superfluous certified reference materials.