bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Stimulus Polarity on the Auditory Brainstem Response From Level-Specific Chirp
Authors: Dzulkarnain Ahmad Aidil Arafat , Salamat Sabrina , Shahrudin Fatin Amira , Jamal Fatin Nabilah , Zakaria Mohd Normani
Published: August 2021

Background and Objectives: No known studies have investigated the influence of stimulus polarity on the Auditory Brainstem Response (ABR) elicited from level-specific (LS) chirp. This study is important as it provides a better understanding of the stimulus polarity selection for ABR elicited from LS chirp stimulus. We explored the influence of stimulus polarity on the ABR from LS chirp compared to the ABR from click at 80 dBnHL in normal-hearing adults.Subjects and Methods: Nineteen adults with normal hearing participated. The ABRs were acquired using click and LS chirp stimuli using three stimulus polarities (rarefaction, condensation, and alternating) at 80 dBnHL. The ABRs were tested only on the right ear at a stimulus rate of 33.33 Hz. The ABR test was stopped when the recording reached the residual noise level of 0.04 µV. The ABRs amplitudes, absolute latencies, inter-peak latencies (IPLs), and the recorded number of averages were statistically compared among ABRs at different stimulus polarities and stimuli combinations.Results: Rarefaction polarity had the largest ABR amplitudes and SNRs compared with other stimulus polarities in both stimuli. There were marginal differences in the absolute latencies and IPLs among stimulus polarities. No significant difference in the number of averages required to reach the stopping criteria was found.Conclusions: Stimulus polarities have a significant influence on the ABR to LS chirp. Rarefaction polarity is recommended for clinical use because of its larger ABR peak I, III, and V amplitudes than those of the other stimulus polarities.
Identification and Typing of Canine Parvovirus Using Molecular Techniques
Authors: Vasavi Koppu , Kaur Gurpreet , Chandra Mudit , Dwivedi P. N. , Kaur Navjot
Published: August 2021

Aim: Canine parvovirus 2, the causative agent of acute hemorrhagic enteritis in dogs, is one of the most important pathogenic viruses. It causes a highly contagious and often fatal disease. The disease condition is complicated further due to emergence of a number of variants namely CPV-2a, CPV-2b, CPV-2c, new CPV 2a, new CPV 2b over the years and involvement of domestic and wild canines. The virus is shed in large numbers in the feces of infected dog and upto 7 to 10 days post-infection, therefore, the present study was designed to detect CPV and to identify the prevailing antigenic types of CPV using molecular techniques from rectal swabs of affected dogs.

Methods: The rectal swabs were collected from dogs suspected of Canine Parvovirus and subjected to PCR, Nested PCR and Realtime PCR for identification and typing of CPV in infected dogs.

Results: From the study it was found that the per cent positivity was high in dogs and was found to be 50% and 89% by PCR and nested polymerase reaction respectively when considered in suspected dogs. The most prevailing antigenic type as detected by Real time PCR was found to be CPV 2a.

Conclusions: The study indicated the animals vaccinated for CPV were also found positive for the disease. This study helps to detect percent positivity of CPV in dogs and also is important to identify the prevailing antigenic types of CPV in the region.
ASPM promotes hepatocellular carcinoma progression by activating Wnt/β‐catenin signaling through antagonizing autophagy‐mediated Dvl2 degradation
Authors: Zhang Haifeng , Yang Xiaobei , Zhu Lili , Li Zhihui , Zuo Peipei , Wang Peng , Feng Jingyu , Mi Yang , Zhang Chengjuan , Xu Yan , Jin Ge , Zhang Jianying , Ye Hua
Published: August 2021

Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. In this article, we show that expression of abnormal spindle‐like microcephaly‐associated protein (ASPM) is up‐regulated in liver cancer samples, and this up‐regulation is significantly associated with tumor aggressiveness and reduced survival times of patients. Down‐regulation of ASPM expression inhibits the proliferation, invasion, migration and epithelial‐to‐mesenchymal transition of HCC cells in vitro and inhibits tumor formation in nude mice. ASPM interacts with disheveled‐2 (Dvl2) and antagonizes autophagy‐mediated Dvl2 degradation by weakening the functional interaction between Dvl2 and the lipidated form of microtubule‐associated proteins 1A/1B light chain 3A (LC3II), thereby increasing Dvl2 protein abundance and leading to Wnt/β‐catenin signaling activation in HCC cells. Thus, our results define ASPM as a novel oncoprotein in HCC and indicate that disruption of the Wnt–ASPM–Dvl2–β‐catenin signaling axis might have potential clinical value.
A Property‐Driven Stepwise Design Strategy for Multiple Low‐Melting Alloys via Machine Learning
Authors: Chen Huimin , Shang Zhongwen , Lu Wencong , Li Minjie , Tan Fuping
Published: August 2021

Low‐melting alloys (LMAs) have an extensive application prospect due to their extremely low melting points for further research of other properties. However, it is difficult to design new multiple alloys with required melting point based on experiments in vast chemical space. Herein, a property‐driven stepwise design strategy for multiple alloys design based on complete machine learning process is developed. The R‐X‐S integrated model based on Ridge Regression (RR), eXtreme Gradient Boosting (XGBoost), and Support Vector Regression (SVR) performs well in melting point prediction with the root mean squared error (RMSE) and correlation coefficient (R) on the validation set of 4.578 and 0.988, respectively. After model construction, the stepwise strategy is used to design potential LMAs with smaller estimation error according to the prediction error function combining variance and bias. The candidates with melting point of 90 °C provide the possibility for solder applications with melting points below 100 °C, and the low‐cost candidates with melting point of 16 °C may be used to replace the expensive 75Ga–25In alloy. The stepwise strategy with different step length can improve the search efficiency and map the relationship between LMAs compositions and melting points, which may also be applied to explore other functional materials with high performance.
Ultrareproducible Capacitive Soft Pressure Sensor Using a Self‐Integrated Fibrous Network of Urethane Equipped with Diels–Alder Adducts
Authors: Bin Shin Yoo , Jong Han Chul , Kim Youngmin , Kim Jong-Woong
Published: August 2021

A pressure sensor based on a composite structure comprising air and polymer fibers is suggested to develop a capacitive pressure sensor that is virtually unaffected by repeated pressurization. Reversibly cross‐linkable urethane (RCU) derived from polybutadiene is newly synthesized for electrospinning, which exhibits the Diels–Alder (DA) reaction under mild conditions. RCU‐based microfibril film is fabricated and it succeeds in welding the intersections of the fibers without a collapse of their shape at mild temperature. This is accomplished via the DA reaction to prevent shearing between microfibrils when physical stress is applied to the film. The porous film is mechanically robust and reacts stably when the film is deformed or pressed. Electrodes are formed on both surfaces of the film using Ag nanowires (AgNWs). Vapor‐assisted partial melting of retro‐DA adducts is used to promote fusion of the polymer through the surface of the AgNWs and implement a robust stretchable electrode. The capacitance changes exceptionally uniformly with the magnitude of the applied pressure and deformation. Using this sensor, its functionality is successfully demonstrated by implementing a pressure sensor array composed of 9 px and measuring the external force applied to the balloon injected with air.
Development of Ti3C2Tx/NiSe2 Nanohybrid‐Based Large‐Area Pressure Sensors as a Smart Bed for Unobtrusive Sleep Monitoring
Authors: Adepu Vivek , Kamath Krutarth , Mattela Venkat , Sahatiya Parikshit
Published: August 2021

Sleep is a very important biological activity for humans as insufficient sleep can cause various issues such as depression, memory and attention problems, etc. Even though there are sleep tracking systems, the assessment methods are tiresome, expensive, and time‐consuming. In this context, smart textiles are provoking a growing interest owing to their capability to use them in sleep monitoring and various other applications. Further, in search of materials for E‐textiles, MXene‐based hybrids have emerged as an excellent choice for physical sensors. Herein, Ti3C2Tx/NiSe2 hybrid‐based pressure sensor on the cotton cloth is fabricated to be used as a smart bed for sleep monitoring. The fabricated Ti3C2Tx/NiSe2 hybrid‐based pressure sensor exhibits an enhanced value of sensitivity, i.e., ≈2.41 kPa−1 in comparison to the pristine Ti3C2Tx‐based sensor (≈1.58 kPa−1). The physical pressure sensing mechanism is explained using the concept of Schottky barrier height reduction and decrease in contact resistance between the as‐formed metal–semiconductor junction along with the shrinking of interlayer spacing of the layered NiSe2 and Ti3C2Tx. Finally, the fabricated sensor is used for real‐time sleep monitoring, which monitors the movement of an individual and also the breath rate, which possesses potential application in personal health‐care diagnosis.
Multicomponent Synthesis of Benzothiophen‐2‐acetic Esters by a Palladium Iodide Catalyzed S‐cyclization – Alkoxycarbonylation Sequence
Authors: Mancuso Raffaella , Lettieri Melania , Ziccarelli Ida , Russo Patrizio , Piccionello Antonio Palumbo , Gabriele Bartolo
Published: August 2021

A catalytic carbonylative approach to the multicomponent synthesis of benzothiophene derivatives from simple building blocks [1‐(2‐(methylthio)phenyl)prop‐2‐yn‐1‐ols, carbon monoxide, and an alcohol)] is presented. It is based on an S‐cyclization‐demethylation‐alkoxycarbonylation‐reduction sequence promoted by the PdI2/KI catalytic system, occurring under relatively mild conditions (40 atm, 80 °C, 15 h). Benzothiophene‐2‐acetic esters are obtained in moderate to good yields (35–70%) starting from variously substituted substrates in combination with different alcohols as external nucleophiles (17 examples).

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Iodine‐Promoted Synthesis of Dipyrazolo/Diuracil‐Fused Pyridines and o‐Amino Diheteroaryl ketones via Oxidative Domino Annulation of 2/4‐Methylazaarenes
Authors: Zhang Xin‐Ke , Miao Xiao‐Yu , Jiang Hui‐Ru , Ge Fei , Sun Jia‐Chen , Zhang Rui‐Ying , Ouyang Qin , Fan Wei‐Yu , Zhu Yan‐Ping , Sun Yuan‐Yuan
Published: August 2021

The iodine‐promoted oxidative domino annulation and carbonylation process has been developed for the synthesis of biologically important azaarene‐substituted bis‐pyrazolo[3,4‐b:4′,3′‐e]pyridines (BPPs), diuracilpyridines and o‐amino diheteroaryl ketones. The domino procedure proceeded with easily available methyl azaarenes, 5‐aminouracils and substituted 5‐aminopyrazoles. This protocol is a simple and metal‐free approach which exhibits high functional group compatibility and broad substrates scope. Moreover, this transformation can be applied for the preparation of dipyrazolo/diuracil‐fused pyridines on a gram scale.

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General model for artificial photosynthesis with capsule‐immobilized enzyme
Authors: Sun Guoming , Shi Jiafu , Jia Shengkun , Luo Yiqing , Jiang Zhongyi , Yuan Xigang
Published: August 2021

In this work, a general model for artificial photosynthesis with capsule‐immobilized enzyme was established based on ordinary differential equations, and a solution sequence was developed to get the analytical solution of the model equations. A coenzymes decomposition mechanism was incorporated into the model to improve the prediction ability for dynamic behavior of the reaction process. Then we showed that, based on the proposed model and the solution method, the rate constants for the kinetics of both the photocatalytic reaction and the enzyme reaction and the mass transfer coefficient across the capsule wall can be obtained effectively by using process experimental data. Finally, based on the analysis using the proposed method, we found that the across‐wall mass transfer coefficient of the capsule may determine the transitional time needed for the process to get into steady state, and the enzyme reaction may limit the enzyme‐photocatalytic reaction processes.
Versatile 3D‐Printed Micro‐Reference Electrodes for Aqueous and Non‐Aqueous Solutions
Authors: Schuett Fabian M. , Zeller Sven J. , Eckl Maximilian J. , Matzik Felix M. , Heubach Maren‐Kathrin , Geng Tanja , Hermann Johannes M. , Uhl Matthias , Kibler Ludwig A. , Engstfeld Albert K. , Jacob Timo
Published: August 2021

While numerous reference electrodes suitable for aqueous electrolytes exist, there is no well‐defined standard for non‐aqueous electrolytes. Furthermore, reference electrodes are often large and do not meet the size requirements for small cells. In this work, we present a simple method for fabricating stable 3D‐printed micro‐reference electrodes. The prints are made from polyvinylidene fluoride, which is chemically inert in strong acids, bases, and commonly used non‐aqueous solvents. We chose six different reference systems based on Ag, Cu, Zn, and Na, including three aqueous and three non‐aqueous systems to demonstrate the versatility of the approach. Subsequently, we conducted cyclic voltammetry experiments and measured the potential difference between the aqueous homemade reference electrodes and a commercial Ag/AgCl‐electrode. For the non‐aqueous reference electrodes, we chose the ferrocene redox couple as an internal standard. From these measurements, we deduced that this new class of micro‐reference electrodes is leak‐tight and shows a stable electrode potential.
Radical‐Bridged Ln4 Metallocene Complexes with Strong Magnetic Coupling and a Large Coercive Field
Authors: Mavragani Niki , Errulat Dylan , Gálico Diogo A. , Kitos Alexandros A. , Mansikkamäki Akseli , Murugesu Muralee
Published: August 2021

Inducing magnetic coupling between 4f elements is an ongoing challenge. To overcome this formidable difficulty, we incorporate highly delocalized tetrazinyl radicals, which strongly couple with f‐block metallocenes to form discrete tetranuclear complexes. Synthesis, structure, and magnetic properties of two tetranuclear [(Cp*2Ln)4(tz.)4]⋅3(C6H6) (Cp*=pentamethylcyclopentadienyl; tz=1,2,4,5‐tetrazine; Ln=Dy, Gd) complexes are reported. An in‐depth examination of their magnetic properties through magnetic susceptibility measurements as well as computational studies support a highly sought‐after radical‐induced “giant‐spin” model. Strong exchange interactions between the LnIII ions and tz. radicals lead to a strong magnet‐like behaviour in this molecular magnet with a large coercive field of 30 kOe.
Luminescent Behavior Elucidation of a Disilane‐Bridged D–A–D Triad Composed of Phenothiazine and Thienopyrazine
Authors: Nakae Toyotaka , Nishio Masaki , Usuki Tsukasa , Ikeya Minako , Nishimoto Chika , Ito Suguru , Nishihara Hiroshi , Hattori Mineyuki , Hayashi Shigenobu , Yamada Teppei , Yamanoi Yoshinori
Published: August 2021

A σ–π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si−Si bridges (compound 1). X‐ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand‐held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol−1. The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO–LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO−1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi‐axial conformers allows intramolecular charge‐transfer type emission via energy transfer from dominant quasi‐equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli‐responsive materials with controlled excited states.
Capillary‐Bound Dense Micelle Brush Supports for Continuous Flow Catalysis
Authors: Lin Geyu , Cai Jiandong , Sun Yan , Cui Yan , Liu Qiuwen , Manners Ian , Qiu Huibin
Published: August 2021

Flow reactors are appealing alternatives to conventional batch reactors for heterogeneous catalysis. However, it remains a key challenge to firmly immobilize the catalysts in a facile and flexible manner and to simultaneously maintain a high catalytic efficiency and throughput. Herein, we introduce a dense cylindrical micelle brush support in glass capillary flow reactors through a living crystallization‐driven self‐assembly process initiated by pre‐immobilized short micelle seeds. The active hairy corona of these micellar brushes allows the flexible decoration of a diverse array of nanocatalysts, either through a direct capture process or an in situ growth method. The resulting flow reactors reveal excellent catalytic efficiency for a broad range of frequently utilized transformations, including organic reductions, Suzuki couplings, photolytic degradations, and multistep cascade reactions, and the system was both recyclable and durable. Significantly, this approach is readily applicable to long capillaries, which enables the construction of flow reactors with remarkably higher throughput.
Assessment of blue crab Shell (Callinectes sapidus) particles as bio‐based filler to EPDM rubber
Authors: Akbay İsmail Kutlugün , Güngör Ahmet , Özdemir Tonguç
Published: August 2021

The use of waste and biodegradable materials as alternative substitutes in different areas is supporting green production in recent years. The utilization of such materials is supporting an economical way, while an environmentally and friendly approach is increased sustainability. In this context, the replacement of carbon black, which is frequently used in the rubber industry but has many drawbacks, with waste and a biodegradable filling material has attracted the attention of researchers over the past decades. In this study, ethylene propylene diene termonomer (EPDM) and EPDM with different blue crab shell (BCS) incorporated into rubber matrix were produced. The effect of carbon black and BCS content within the EPDM matrix on the rheological, mechanical, morphological, and thermal properties were investigated. The rheological analysis revealed that BCS added to the EPDM matrix enhanced the vulcanization parameters. Moreover, the addition of BCS into the EPDM matrix up to 12 phr increased the value of T50 temperature, tensile strength, and crosslinking density of composite material. In conclusion, it was revealed that BCS could be used as an alternative filling material in rubber industry, such biodegradable and bio‐based materials could become an important substitute with the economic and environmental benefits.
Taxonomic and functional macroinvertebrate diversity of high‐altitude ponds in the Macun Cirque, Switzerland
Authors: Hill Matthew J. , Wood Paul J. , Mathers Kate L.
Published: August 2021

Global environmental change is threatening freshwater biodiversity with ecological impacts predicted to be particularly severe in high‐altitude regions. Despite this, an ecological understanding of high‐altitude pond networks remains patchy, with only limited knowledge of the environmental and spatial predictors of taxonomic and functional diversity. Moreover, previous studies of pond ecosystems have focused primarily on taxonomic richness and largely overlooked functional diversity.

This study examined the influence of local environmental and spatial factors on taxonomic and functional α and β diversity (including the turnover and nestedness‐resultant components) of 17 high‐altitude (~2,500 m above sea level) pond macroinvertebrate communities, in the Macun Cirque, Switzerland.

Spatial processes (pond connectivity) were important drivers for taxonomic α diversity, while local environmental variables (pond permanence and surface area) were important determinants of functional α diversity. Species turnover was the most important component of β diversity for taxonomic composition, and functional composition demonstrated a nested spatial pattern.

Variation in taxonomic and functional composition (and the turnover and nestedness components of β diversity) were determined by local environmental variables despite the limited environmental gradients within the pond network. No significant effects of spatial variables on community composition were recorded for either facet of diversity, indicating that compositional variation was determined at a local scale. Water temperature, depth and pond permanence were consistently the most important measured drivers of diversity.

Given the importance of both spatial and environmental variables in structuring taxonomic and functional diversity, landscape‐scale conservation and management activities that aim to improve or protect high‐altitude freshwater biodiversity should focus on maintaining connectivity among ponds and environmental heterogeneity, particularly pond surface area, water depth, and hydroperiod. Understanding the mechanisms driving taxonomic and functional diversity will be critically important for the management and conservation of macroinvertebrate communities in high‐altitude pond networks in the face of climatic warming.
The effects of quercetin combined with nucleopolyhedrovirus on the growth and immune response in the silkworm (Bombyx mori)
Authors: Shi Guiqin , Kang Zhaoyang , Liu Huijuan , Ren Fei , Zhou Yuan
Published: August 2021

Flavonoids are secondary metabolites that help plants resist insect attack. It can resist insect attack by inhibiting insect immune defense, and pathogens can also inhibit insect immune defense. It is speculated that the combination of flavonoids and pathogens may inhibit the immune defense and have stronger toxicity to silkworm. In this study, the combined treatment of quercetin with Bombyx mori nuclear polyhedrosis virus (BmNPV) had significant negative effects on the growth and survival of silkworm compared with BmNPV group. The detoxifying enzyme activity of BmNPV group was significantly increased at 96 h, while the activity of the combined treatment group was significantly decreased with the increase of quercetin exposure time (72 or 96 h). The activity of antioxidant enzymes also showed a similar trend, that was, the activity of antioxidant enzymes in the combined treatment group also decreased significantly with the increase of quercetin exposure time, which led to the increase of reactive oxygen species content. The silkworm cells would produce lipid peroxidation, malondialdehyde content was significantly increased, so that the expression of immune‐related genes (the antimicrobial peptide, Toll pathway, IMD pathway, JAK‐STAT pathway, and melanin genes) were decreased, leading to the damage of the immune system of silkworm. These results indicated that quercetin combined with BmNPV could inhibit the activities of protective enzymes and lead to oxidative damage to silkworm. It can also affect the immune response of the silkworm, and thus resulting in abnormal growth. This study provides the novel conclusion that quercetin accumulation will increase the susceptibility of silkworm to pathogens.
Binding of boswellic acids to functional proteins of the SARS‐CoV‐2 virus: Bioinformatic studies
Authors: Caliebe Reinhard H. , Scior Thomas , Ammon Hermann P. T.
Published: August 2021

Boswellic acids (BAs) have been shown to possess antiviral activity. Using bioinformatic methods, it was tested whether or not acetyl‐11‐keto‐β‐boswellic acid (AKBA), 11‐keto‐β‐boswellic acid (KBA), β‐boswellic acid (BBA), and the phosphorylated active metabolite of Remdesivir® (RGS‐P3) bind to functional proteins of SARS‐CoV‐2, that is, the replicase polyprotein P0DTD1, the spike glycoprotein P0DTC2, and the nucleoprotein P0DTC9. Using P0DTD1, AKBA and KBA showed micromolar binding affinity to the RNA‐dependent RNA polymerase (RdRp) and to the main proteinase complex Mpro. Phosphorylated BAs even bond in the nanomolar range. Due to their positive and negative charges, BAs and RGS‐P3 bond to corresponding negative and positive areas of the protein. BAs and RGS‐P3 docked in the tunnel‐like cavity of RdRp. BAs also docked into the elongated surface rim of viral Mpro. In both cases, binding occurred with active site amino acids in the lower micromolecular to upper nanomolar range. KBA, BBA, and RGS‐P3 also bond to P0DTC2 and P0DTC9. The binding energies for BAs were in the range of −5.8 to −6.3 kcal/mol. RGS‐P3 and BAs occluded the centrally located pore of the donut‐like protein structure of P0DTC9 and, in the case of P0DTC2, RGS‐P3 and BAs impacted the double‐wing‐like protein structure. The data of this bioinformatics study clearly show that BAs bind to three functional proteins of the SARS‐CoV‐2 virus responsible for adhesion and replication, as does RGS‐P3, a drug on the market to treat this disease. The binding effectiveness of BAs can be increased through phosphate esterification. Whether or not BAs are druggable against the SARS‐CoV‐2 disease remains to be established.
Recent Progress and Perspectives on Cell Surface Modification
Authors: Zhang Shi‐Yi , Zhou Ze‐Rui , Qian Ruo‐Can
Published: August 2021

The cell membrane is a biological interface consisting of phospholipid bilayer, saccharides and proteins that maintains a stable metabolic intracellular environment as well as regulating and controlling the exchange of substances inside and outside the cell. Cell membranes provide a highly complex biological surface carrying a variety of essential surfaces ligands and receptors for cells to receive various stimuli of external signals, thereby inducing corresponding cell responses regulating the life activities of the cell. These surface receptors can be manipulated via cell surface modification to regulate cellular functions and behaviors Thus, cell surface modification has attracted considerable attention due to its significance in cell fate control, cell engineering and cell therapy. In this minireview, we describe the recent developments and advances of cell surface modification, and summarize the main modification methods with corresponding functions and applications. Finally, the prospect for the future development of the modification of the living cell membrane is discussed.
Joint attention and intelligence in children with autism spectrum disorder without severe intellectual disability
Authors: Sano Masuhiko , Yoshimura Yuko , Hirosawa Tetsu , Hasegawa Chiaki , An Kyung‐min , Tanaka Sanae , Naitou Nobushige , Kikuchi Mitsuru
Published: August 2021

In children with autism spectrum disorder (ASD), joint attention is regarded as a predictor of language function, social skills, communication, adaptive function, and intelligence. However, existing information about the association between joint attention and intelligence is limited. Most such studies have examined children with low intelligence. For this study, we investigated whether joint attention is related to intelligence in young children with autism spectrum disorder (ASD) without severe intellectual disability. We analyzed 113 children with ASD aged 40–98 months. Their Kaufman Assessment Battery (K‐ABC) Mental Processing Index (MPI) scores are 60 and more (mean 93.4). We evaluated their intelligence using K‐ABC and evaluated their joint attention using ADOS‐2. After we performed simple regression analyses using K‐ABC MPI and its nine subscales as dependent variables, using joint attention as the independent variable, we identified joint attention as a positive predictor of the MPI and its two subscales. From this result, we conclude that joint attention is related to intelligence in young children with ASD without severe intellectual disability. This result suggests a beneficial effect of early intervention targeting joint attention for children with ASD.

Lay Summary

Joint attention is the ability to coordinate visual attention with another person and then shift one's gaze toward an object or event. Impairment of joint attention is regarded as an early marker of autism spectrum disorder (ASD). This study revealed impairment of joint attention as associated with lower intelligence in ASD children. These results are expected to constitute a rationale for future studies, particularly addressing beneficial effects of early intervention targeting joint attention for children with ASD.
Biophysical targeting of high‐risk cerebral aneurysms
Authors: Epshtein Mark , Levi Moran , Kraitem Afif M. , Zidan Hikaia , King Robert M. , Gawaz Meinrad , Gounis Matthew J. , Korin Netanel
Published: August 2021

Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high‐risk aneurysms is of paramount importance. Moreover, treatment of unruptured aneurysms with invasive surgery or minimally invasive neurointerventional surgery poses relatively high risk and there is presently no medical treatment of aneurysms. Here, leveraging the endogenous biophysical properties of brain aneurysms, we develop particulate carriers designed to localize in aneurysm low‐shear flows as well as to adhere to a diseased vessel wall, a known characteristic of high‐risk aneurysms. We first show, in an in vitro model, flow guided targeting to aneurysms using micron‐sized (2 μm) particles, that exhibited enhanced targeting (>7 folds) to the aneurysm cavity while smaller nanoparticles (200 nm) showed no preferable accumulation. We then functionalize the microparticles with glycoprotein VI (GPVI), the main platelet receptor for collagen under low‐medium shear, and study their targeting in an in vitro reconstructed patient‐specific aneurysm that contained a disrupted endothelium at the cavity. Results in this model showed that GPVI microparticles localize at the injured aneurysm an order of magnitude (>9 folds) more than control particles. Finally, effective targeting to aneurysm sites was also demonstrated in an in vivo rabbit aneurysm model with a disrupted endothelium. Altogether, the presented biophysical strategy for targeted delivery may offer new treatment opportunities for cerebral aneurysms.
Improved survival with enasidenib versus standard of care in relapsed/refractory acute myeloid leukemia associated with IDH2 mutations using historical data and propensity score matching analysis
Authors: de Botton Stéphane , Brandwein Joseph M. , Wei Andrew H. , Pigneux Arnaud , Quesnel Bruno , Thomas Xavier , Legrand Ollivier , Recher Christian , Chantepie Sylvain , Hunault‐Berger Mathilde , Boissel Nicolas , Nehme Salem A. , Frattini Mark G. , Tosolini Alessandra , Marion‐Gallois Roland , Wang Jixian J. , Cameron Chris , Siddiqui Muhaimen , Hutton Brian , Milkovich Gary , Stein Eytan M.
Published: August 2021

Background

The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT).

Methods

Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221‐C‐001 trial and SoC outcomes obtained from a real‐world chart review of patients in France.

Results

Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61–1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47–0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72–13.24) and 4.76 months for SoC (95% CI, 3.81–8.21). Results remained robust across all sensitivity analyses conducted.

Conclusions

PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.
Intra‐cardiac thrombosis in the setting of heparin‐induced thrombocytopenia
Authors: Mohamed Amr
Published: August 2021

Key clinical message is to know that HIT is a massive thrombotic storm. Atrial fibrillation cardioversion might not be safe in HIT using the standard 48‐hour cutoff from arrhythmia onset. Also, the case serves as a reminder of how to suspect, diagnose, and treat HIT.
Intermetallic Compounds: Liquid‐Phase Synthesis and Electrocatalytic Applications
Authors: Yuan Yuliang , Yang Zhilong , Lai Wenchuan , Gao Lei , Li Mengfan , Zhang Jiawei , Huang Hongwen
Published: August 2021

Characterized by long‐range atomic ordering, well‐defined stoichiometry, and controlled crystal structure, intermetallics have attracted increasing attention in the area of chemical synthesis and catalytic applications. Liquid‐phase synthesis of intermetallics has arisen as the promising methodology due to its precise control over size, shape, and resistance toward sintering compared with the traditional metallurgy. This short review tends to provide perspectives on the liquid‐phase synthesis of intermetallics in terms of both thermodynamics and methodology, as well as its applications in various catalytic reactions. Specifically, basic thermodynamics and kinetics in the synthesis of intermetallics will be first discussed, followed by discussing the main factors that will affect the formation of intermetallics during synthesis. The application of intermetallics in electrocatalysis will be demonstrated case by case at last. We conclude the review with perspectives on the future developments with respect to both synthesis and catalytic applications.
Breathing‐Assisted Selective Adsorption of C8 Alkyl Aromatics in Zn‐Based Metal‐Organic Frameworks
Authors: Lee Jihyun , Kim Younghoon , Son Younghu , Kim Hyehyun , Nam Choi Yong , D'Alessandro Deanna , Chandra Rao Purna , Yoon Minyoung
Published: August 2021

The breathing phenomenon in metal‐organic frameworks (MOFs) has revealed supramolecular host‐guest interactions that could be beneficial for chemical separation in numerous industrial applications. The cost‐effective purification of C8 alkyl aromatics such as o‐xylene, m‐xylene, p‐xylene, and ethylbenzene remains challenging owing to their similar molecular structures, boiling points, kinetic diameters, polarities, etc. Herein, we report two Zn‐based pillar‐bilayered MOFs, denoted [Zn2(aip)2(pillar)] (aip=5‐aminoisophthalic acid; pillar: bpy=4,4’‐bipyridine or bpe=1,2‐bis(4‐pyridyl)ethane) that exhibit a breathing effect depending on the adsorbed guest molecules. Guest‐dependent sorption studies in organic solvents such as N,N‐dimethylformamide, methanol, benzene, and water vapor display reversible structural flexibility through the breathing effect in both framework compounds. The experiments conducted on C8‐alkyl aromatics resulting in both MOF compounds can access these isomers in the shrunken pores, and thereby expand the pore size by framework breathing. In C8 binary mixtures, these Zn‐MOFs exhibit selective sorption properties based on the different interactions between guest C8 aromatics and the framework structure.
Revised Structures of Dehydrostenines A and B: Total Syntheses of (±)‐Dehydrostenine A and Structure Assigned to Dehydrostenine B
Authors: Olivier Wesley J. , Lucas Nigel T. , Bissember Alex C. , Smith Jason A.
Published: August 2021

The first total syntheses of the Stemona alkaloid dehydrostenine A and the structure assigned to dehydrostenine B have been completed from a simple pyrrole substrate in 10 and 11 steps, respectively. Two independent Brønsted‐acid‐mediated intramolecular Michael additions were exploited to construct the tetracyclic dehydrostenine core. As a result of synthetic studies and associated analysis of the relevant literature, revisions of the structures originally assigned to dehydrostenines A and B are proposed.
Recovery of Al, Co, Cu, Fe, Mn, and Ni from Spent LIBs after Li Selective Separation by the COOL‐Process. Part 1: Leaching of Solid Residue from COOL‐Process
Authors: Kaiser Doreen , Pavón Sandra , Bertau Martin
Published: August 2021

Lithium recycling from spent LIBs along the COOL‐process produces a Li‐free metal rich black mass, which still contains the entire fraction of valuable metal such as Co, Ni, and Mn. A recycling process was developed, which allows for mobilizing these metals. The first process stage is the selective leaching of Li via COOL‐process. Subsequently, two inorganic (H2SO4 and HCl) and two organics acids (citric and gluconic acid) were tested for mobilizing the metals from the solid residue. To optimize this process stage, acid concentration as well as addition of H2O2 as a reduction reagent were investigated. The optimal conditions to dissolve valuable metals such as Co, Cu, Fe, Mn, and Ni was identified as 2 N H2SO4 and 2 vol % H2O2.
“Who’s that girl?” The entrepreneur as a super(wo)man
Authors: De Simone Silvia , Priola Vincenza
Published: August 2021

Gender and entrepreneurship research emphasize the masculine symbolic domain of entrepreneurial practices, but mostly neglects to analyze the gender complexity of doing entrepreneurship. This article examines entrepreneurial femininities as constructed and performed by Italian women. Theoretically, it employs postfeminism as a globalized discourse to offer a nuanced reading of the relationship between gender inequalities, entrepreneurship, and postfeminism. Through the analysis of 51 interviews with entrepreneurs, the paper explores how postfeminist ideals and discourses (the “super(wo)man” who is “free” to choose) are adapted to reflect the Italian cultural context. In doing so, it discusses how these women manage the coexistence of feminist (i.e., autonomy, empowerment) and anti‐feminist (i.e., traditional division of household labour) expectations concerning women’s place in work and society.
Age distributions of breast cancer diagnosis and mortality by race and ethnicity in US women
Authors: Hendrick R. Edward , Monticciolo Debra L. , Biggs Kelly W. , Malak Sharp F.
Published: August 2021

Background

Surveillance, Epidemiology, and End Results (SEER) data from 1973‐2010 have been used to show that minority women have disproportionately higher percentages of breast cancers diagnosed at younger ages in comparison with White women.

Methods

The authors analyzed SEER 21 invasive breast cancer incidence data for 2014‐2017 and National Center for Health Statistics mortality data for 2014‐2018 and compared invasive incidence and mortality by age in non‐Hispanic Black (NH‐Black), Asian American/Pacific Islander (AAPI), Native American, and Hispanic women with those in non‐Hispanic White (NH‐White) women. They evaluated incidence rates and percentages of invasive breast cancer cases and breast cancer deaths occurring before the age of 50 years along with advanced‐stage incidence rates and percentages in minority women versus NH‐White women.

Results

Recent SEER data showed that invasive breast cancers were diagnosed at significantly younger ages in minority women versus NH‐White women. Among women diagnosed with invasive breast cancer, compared with NH‐White women, minority women were 72% more likely to be diagnosed under the age of 50 years (relative risk [RR], 1.72; 95% confidence interval [CI], 1.70‐1.75), 58% more likely to be diagnosed with advanced‐stage breast cancer under the age of 50 years (RR, 1.58; 95% CI, 1.55‐1.61), and 24% more likely to be diagnosed with advanced‐stage (regional or distant) breast cancer at all ages (RR, 1.24; 95% CI, 1.23‐1.25). Among women dying of breast cancer, minority women were 127% more likely to die under the age of 50 years than NH‐White women.

Conclusions

NH‐Black, AAPI, Native American, and Hispanic women have higher proportions of invasive breast cancers at younger ages and at advanced stages and breast cancer deaths at younger ages than NH‐White women.

Lay Summary

This study analyzes the most recently available data on invasive breast cancers and breast cancer deaths in US women by age and race/ethnicity.

Its findings show that non‐Hispanic Black, Asian American/Pacific Islander, Native American, and Hispanic women have a higher percentage of invasive breast cancers at younger ages and at more advanced stages and a higher percentage of breast cancer deaths at younger ages than non‐Hispanic White women.
Intensity of end‐of‐life care for dual‐eligible beneficiaries with cancer and the impact of delivery system affiliation
Authors: Herrel Lindsey A. , Zhu Ziwei , Ryan Andrew M. , Hollenbeck Brent K. , Miller David C.
Published: August 2021

Background

Dual‐eligible beneficiaries, who qualify for Medicare and Medicaid, are a vulnerable population with much to gain from efforts to improve quality. Integrated delivery networks and cancer centers, with their emphasis on care coordination and communication, may improve quality of care for dual‐eligible patients with cancer at the end of life.

Methods

This study used Surveillance, Epidemiology, and End Results registry data linked with Medicare claims to evaluate quality for beneficiaries who died of cancer and were diagnosed from 2009 to 2014. High‐intensity care was evaluated with 7 end‐of‐life quality measures according to dual‐eligible status with multivariable logistic regression models. Regression‐based techniques were used to assess the effect of delivery system affiliation (ie, cancer center or integrated delivery network vs no affiliation).

Results

Among 100,549 beneficiaries who died during the study interval, 22% were dually eligible. Inferior outcomes were identified for dual‐eligible beneficiaries in comparison with nondual beneficiaries across nearly every quality measure assessed, including >1 hospitalization in the last 30 days (12.6% vs 11.3%; P < .001) and a greater proportion of deaths occurring in a hospital setting (30.2% vs 26.2%; P < .001). Receipt of care in an affiliated delivery system was associated with reduced deaths in a hospital setting and increased hospice utilization for dual‐eligible beneficiaries.

Conclusions

Dual‐eligible status is associated with higher intensity care at the end of life. Delivery system affiliation has a modest impact on quality at the end of life, and this suggests that targeted efforts may be needed to optimize quality for this group of vulnerable patients.
EGFR‐plasma mutations in prognosis for non‐small cell lung cancer treated with EGFR TKIs: A meta‐analysis
Authors: Phan Thang Thanh , Tran Vinh Thanh , Tran Bich‐Thu , Ho Toan Trong , Pho Suong Phuoc , Le Anh Tuan , Le Vu Thuong , Nguyen Hang Thuy , Nguyen Son Truong
Published: August 2021

Background

The plasma‐based epidermal growth factor receptor (EGFR) mutation testing is approved recently to use in clinical practice. However, it has not been used as a prognostic marker yet because of contradictory results.

Aim

This meta‐analysis aims to clarify the role of the EGFR‐plasma test in prognosis for non‐small cell lung cancer (NSCLC) who have mutant tumors and receive EGFR tyrosine kinase inhibitors (TKIs).

Methods and Results

The PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases were searched for relevant studies by April 10, 2021. The hazard ratio (HR) from reports was extracted and used to assess the correlation of EGFR‐plasma status with progression‐free survival (PFS) and overall survival (OS). A total of 35 eligible studies with 4106 patients were enrolled in the final analysis. Patients with concurrent EGFR mutations in pretreatment plasma have shorter PFS (HR = 2.00, 95% confidence interval [CI]: 1.73–2.31, p < .001) and OS time (HR = 2.31, 95% CI: 1.89–2.83, p < .001) compared to the tumor‐only mutation cases. Besides, the persistence of EGFR‐activating mutations in post‐treatment plasma is associated with worse PFS (HR = 3.84, 95% CI: 2.96–4.99, p < .001) and OS outcome (HR = 3.22, 95% CI: 2.35–4.42, p < .001) compared to others. Notably, the prognostic value of the EGFR‐plasma test is also validated in treatment with third‐generation EGFR TKI and significance regardless of different detection methods.

Conclusion

The presence of EGFR‐plasma mutations at pretreatment and after EGFR TKI initiation is the worse prognostic factor for PFS and OS in NSCLC.
Randomized, Double‐Blind, Controlled Study to Evaluate Safety and Pharmacokinetics of Single Ascending Doses of ASP5354, an Investigational Imaging Product, in Healthy Adult Volunteers
Authors: Murase Tosei , Takizawa Masaomi , Galitz Lawrence , Flach Stephen , Murray Valene , Gufford Brandon , Suwa Akira
Published: August 2021

Intraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real‐time ureter visualization are approved. ASP5354 (TK‐1) is a novel indocyanine green derivative. In this first‐in‐human phase 1, double‐blind, sequential ascending‐dose study, urethral catheters were placed in 6 healthy volunteers who were randomized to single‐dose, intravenous ASP5354 0.1 mg (n = 4) or placebo (n = 2). Sequential dose escalations to 0.5‐, 2‐, 8‐, and 24‐mg ASP5354 in new cohorts were contingent upon Dose‐Escalation Committee approval after review of pharmacokinetic (PK) and safety data. Blood and urine samples were collected over 24 hours following dose administration. Objectives were to assess the safety/tolerability and PK of ASP5354. Treatment‐emergent adverse events (TEAEs) were reported in 3 (15%) and 2 (20%) participants in the ASP5354 and placebo groups, respectively. In the former, there were 6 TEAEs (5/6 grade 1‐2). One ASP5354 participant experienced grade 3 pyelonephritis, attributed to the catheter. No TEAEs were related to ASP5354. Mean plasma terminal elimination half‐life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administration. Linear and dose‐proportional PK were observed. These results support further evaluation of ASP5354 at doses up to 24 mg for intraoperative near‐infrared fluorescence ureter visualization.