bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanistic Insights into the Selective Dual BET and PLK1 Inhibitory Activity of a Novel Benzamide Compound in Castration‐Resistant Prostrate Cancer
Authors: Akawa Oluwole B. , Subair Temitayo I. , Omolabi Kehinde F. , Okunlola Felix O. , Soliman Mahmoud E. S.
Published: November 2021

Though multifactorial, BET and PLK1 proteins have been found to be key players in the oncogenic process leading to castration‐resistant prostate cancer through regulation of AR and MYC‐mediated transcription. Hence, dual inhibition of these proteins appears to be an auspicious approach for CRPC therapy. WNY0824 has been reported to exhibit nanomolar range inhibition as well as significant anti‐proliferative activity on AR‐positive CRPC cells in vitro. However, structural, and mechanistic events associated with its dual inhibitory and anti‐proliferative mechanisms remain unclear. Utilizing integrative computer‐assisted atomistic techniques, analyses revealed that the dual‐inhibitory activity of WNY0824 against BRD4 and PLK1 proteins is mediated by conserved residues present in the binding cavities of both proteins which are shown to elicit various strong intermolecular interactions and thus favour binding affinity. Also, binding orientation of the ligand at the protein binding cavities allowed for important hydrophobic interactions which resulted in high binding free energy of −42.50 kcal/mol and −51.64 kcal/mol towards BRD4 and PLK1, respectively. While van der Waals interactions are very important to ligand binding in BRD4‐WNY complex, electrostatic interactions are pertinent to PLK1‐WNY complex. Intriguingly, WNY0824 triggered conformational alterations in both proteins through increased structural instability, decreased structural compactness and mitigation in exposure of residues to solvent surface area. Consequently, critical interactions peculiar to the oncogenic activities of BRD4 and PLK1 were inhibited, a phenomenon that results in an antagonism of CRPC progression. The mechanistic insights presented in this report would further assist in the structure‐based design of improved inhibitors useful in CRPC therapy.
Polyether Cyclization Cascade Alterations in Response to Monensin Polyketide Synthase Mutations
Authors: Heinrich Sascha , Grote Marius , Sievers Sonja , Kushnir Susanna , Schulz Frank
Published: November 2021

The targeted manipulation of polyketide synthases has in recent years led to numerous new‐to‐nature polyketides. For type I polyketide synthases the response of post‐polyketide synthases (PKS) processing enzymes onto the most frequently polyketide backbone manipulations is so far insufficiently studied. In particular, complex processes such as the polyether cyclisation in the biosynthesis of ionophores such as monensin pose interesting objects of research. We present here a study of the substrate promiscuity of the polyether cyclisation cascade enzymes in monensin biosynthesis in the conversion of redox derivatives of the nascent polyketide chain. LC‐HRMS/MS2‐based studies revealed a remarkable flexibility of the post‐PKS enzymes. They acted on derivatized polyketide backbones based on the three possible polyketide redox states within two different modules and gave rise to an altered polyether structure. One of these monensin derivatives was isolated and characterized by 2D‐NMR spectroscopy, crystallography, and bioactivity studies.
Iridium(III) Complexes with [−2, −1, 0] Charged Ligand Realized Deep‐Red/Near‐Infrared Phosphorescent Emission
Authors: Zhang Youming , Kao Hao‐Che , Shi Chao , Wu Chengjun , Zhu Minrong , Li Kai , Wu Chung‐Chih , Yang Chuluo
Published: November 2021

A series of [−2, −1, 0] charged‐ligand based iridium(III) complexes of [Ir(bph)(bpy)(acac)] (1), [Ir(bph)(2MeO‐bpy)(acac)] (2), [Ir(bph)(2CF3‐bpy)(acac)] (3), [Ir(bph)(bpy)(2tBu‐acac)] (4) and [Ir(bph)(bpy)(CF3‐acac)] (5), which using biphenyl as dianionic ligand [−2], acetylacetone (or its derivatives) as monoanionic ligand [−1], and 2,2′‐bipyridine (or its derivatives) as neutral ligand [0] were designed and synthesized. The chemical structures were well characterized. All of the ligands have simple chemical structures, thus further making the complexes have excellent thermal stability and are easy to sublimate and purify. Phosphorescent characteristics with short emission lifetime were demonstrated for these emitters. Notably, all of the complexes exhibit remarkable deep red/near infrared emission, which is quite different from the reported [−1, −1, −1] charged‐ligand based iridium(III) complexes. The photophysical properties of these complexes are regularly improved by introducing electron‐donating or ‐withdrawing groups into [−1] or [0] charged‐ligand. The related organic light‐emitting diodes exhibited deep red/near infrared emission with acceptable external quantum efficiency and low turn‐on voltage (<2.6 V). This work provides a new idea for the construction of new type phosphorescent iridium(III) emitters with different valence states of [−2, −1, 0] charged ligands, thus offering new opportunities and challenges for their optoelectronic applications.
Synthesis Methods of Graphdiyne and Graphdiyne Based Materials
Authors: Sun Quanhu , He Jianjiang , Gao Lei , Lu Tiantian , Ma Xiaodi , Huang Changshui
Published: November 2021

Comprehensive Summary

Graphdiyne (GDY), as a new carbon material with two‐dimensional structure composed by sp2 and sp carbon atoms, has exhibited excellent properties in various fields due to its conjugated pore structure, high specific surface area and stable structure. Various properties can also be tuned through the adjustability of the electronic structure by chemical methods. This article systematically discusses the preparation methods and strategies of GDY and GDY based materials. These preparation methods provide the way for us to obtain various GDY materials targeting specific research and application.
Stimuli‐Responsive DNA Origami Nanodevices and Their Biological Applications
Authors: Pitikultham Piyawat , Wang Zhaoran , Wang Yiming , Shang Yingxu , Jiang Qiao , Ding Baoquan
Published: November 2021

DNA origami nanotechnology has provided predictable static nanoarchitectures and dynamic nanodevices with rationally designed geometries, precise spatial addressability, and marked biocompatibility. Multiple functional elements, such as peptides, aptamers, nanoparticles, fluorescence probes, and proteins, etc. can be easily integrated into DNA origami templates with nanoscale precision, leading to a variety of promising applications. Triggered by chemical/physical stimuli, dynamic DNA origami nanodevices can switch between defined conformations or translocate autonomously, providing powerful tools for intelligent biosensing and drug delivery. In this minireview, we summarize the recent progress of dynamic DNA origami nanodevices with desired reconfigurability and feasibility to perform multiple biological tasks. We introduce varieties of DNA nanodevices that can be controlled by different molecular triggers and external stimuli. Subsequently, we highlight the recent advances in employing DNA nanodevices as biosensors and drug delivery vehicles. At last, future possibilities and perspectives are also discussed.
Fusion of handcrafted and deep convolutional neural network features for effective identification of diabetic foot ulcer
Authors: Das Sujit Kumar , Roy Pinki , Mishra Arnab Kumar
Published: November 2021

Among all diabetic‐related complications, the diabetic foot ulcer (DFU) is severe, demanding serious attention, and timely treatment. The purpose of the present study was to conduct features fusion of machine learning (ML) based handcrafted low‐level and convolutional neural networks (CNNs) based high‐level features for improving automatic diagnosis of DFU. A standard image dataset containing 1038 abnormal (DFU) and 641 normal color skin patches has been used for experimental evaluation. Handcrafted features are extracted to uncover the edge, color, shape, and texture information from the images. Also, a new CNN architecture has been proposed based on deeper residual blocks for extracting high‐level features. Features fusion with several ML classifiers like logistic regression classifier, support vector machine, gradient boosting, and artificial neural network have shown improved DFU identification results compared to the individual feature categories. Thereby, LRC outperformed the state‐of‐the‐art results for all evaluation metrics by achieving 95.23% sensitivity, 95.37% F1‐score, and 96.50% area under the curve (AUC) value. Such impressive experimental observations suggest that the proposed approach is expected to provide efficient decision support to medical practitioners, thereby improving patient care.
The mediating role of personalized psychological flexibility in the association between distress intolerance and psychological distress: A national survey during the fourth waves of COVID‐19 pandemic in Iran
Authors: Akbari Mehdi , Seydavi Mohammad , Zamani Elahe
Published: November 2021

The global COVID‐19 outbreak has put the human race's distress tolerance abilities to the test. And, the distress experienced getting worse with each pandemic wave; however, the more flexible the person, the greater the chance of surviving. Thus, the current study aimed to examine the mediating role of personalized psychological flexibility (PPF) in the link between distress intolerance to psychological distress during the fourth wave of the pandemic in Iran. A total of 576 individuals (Meanage 34.80, ±10.9, females 55.6%) took part in the online survey. In this national sample, PPF partially played a role in mediating the association mentioned above. Interestingly, this mediation was independent of demographic factors (age, gender, marital status, and educational level) and fear of COVID‐19, mindfulness, and satisfaction with life. So, despite the mentioned variables, accepting and using unpleasant emotions as fuel to achieve valued goals rather than avoiding them would mitigate the psychological distress during the pandemic. Consequently, public health services can aim to provide psychological flexibility enhancing interventions to decay COVID‐19‐related mental distress.
Cannabis Growing in Canada: An Expanding Market
Authors: Drohan Joy
Published: November 2021

Many crop advisers in Canada have noticed the recent growth in the cannabis market and are wondering what the future may hold for the crop. What are the challenges to growing this crop efficiently? How is the industry evolving? Earn 1 CEU in Crop Management by reading the article and taking the quiz at https://bit.ly/3iUo5HO. View all CEUs online at https://web.sciencesocieties.org/Learning‐Center/Courses.
LiFePO4 Battery Material for the Production of Lithium from Brines: Effect of Brine Composition and Benefits of Dilution
Authors: Pérez‐Rodríguez Sara , Fitch Samuel D. S. , Bartlett Philip N. , Garcia‐Araez Nuria
Published: November 2021

Lithium battery materials can be advantageously used for the selective sequestration of lithium ions from natural resources, which contain other cations in high excess. However, for practical applications, this new approach for lithium production requires the battery host materials to be stable over many cycles while retaining the high lithium selectivity. Here, a nearly symmetrical cell design was employed to show that LiFePO4 shows good capacity retention with cycling in artificial lithium brines representative of brines from Chile, Bolivia and Argentina. A quantitative correlation was identified between brine viscosity and capacity degradation, and for the first time it was demonstrated that the dilution of viscous brines with water significantly enhanced capacity retention and rate capability. The electrochemical and X‐ray diffraction characterisation of the cycled electrodes also showed that the high lithium selectivity was preserved with cycling. Raman spectra of the cycled electrodes showed no signs of degradation of the carbon coating of LiFePO4, while scanning electron microscopy images showed signs of particle cracking, thus pointing towards interfacial reactions as the cause of capacity degradation.
Zero‐voltage‐switching angle of inductive power transfer system supplied by parallel multi‐inverter
Authors: Bo Qiang , Wang Lifang , Zhang Yuwang
Published: November 2021

To reduce the switching losses in high‐power inductive power transfer (IPT) system, this paper focuses on the zero‐voltage‐switching (ZVS) control strategy for a parallel multi‐inverter IPT system. First, the mathematical models of the parallel multi‐inverter IPT system are studied. Then, the compensation network parameters of the parallel multi‐inverter are designed, and the ZVS angles of #1 and #2 inverters are derived. Finally, a 1.2‐kW IPT system with parallel two‐inverter was built for experimental verification. The experimental results show that the ZVS angles of #1 and #2 inverters are equal whether at different Udc or different Po. This conclusion can provide a reference for the ZVS of the IPT system supplied by parallel multi‐inverter. To reduce the switching losses in high‐power IPT system, this paper focuses on the ZVS control strategy for a parallel multi‐inverter IPT system. A 1.2‐kW IPT system with parallel two‐inverter was built for experimental verification. The experimental results show that the ZVS angles of #1 and #2 inverters are equal whether at different Udc or different Po.
Energy‐efficient routing protocol and optimized passive clustering in WSN for SMART grid applications
Authors: Vinodha Ramalingam , Durairaj Sundarraj , Padmavathi Sakkarai
Published: November 2021

Due to low cost, ease of implementation and flexibility of wireless sensor networks (WSNs), WSNs are considered to be an essential technology to support the smart grid (SG) application. The prime concern is to increase the lifetime in order to find the active sensor node and thereby to find once the sensor node (SN) dies in any region. For this reason, an energy‐efficient Dynamic Source Routing (DSR) protocol needs to provide the right stability region with a prolonged network lifetime. This work is an effort to extend the network's existence by finding and correcting the considerable energy leveraging behaviors of WSN. We build a comprehensive model based on real measures of SG path loss for different conditions by using the characteristics of WSN nodes and channel characteristics. This method also establishes a hierarchical network structure of balanced clusters and an energy‐harvesting SN. The cluster heads (CHs) are chosen by these SN using a low overhead passive clustering strategy. The cluster formation method is focused on the use of passive clustering of the particle swarm optimization (PSO). For the sake of eliminating delayed output in the WSN, energy competent dynamic source routing protocol (EC‐DSR) is used. Chicken swarm optimization (CSO) in which optimum cluster path calculation shall be done where distance and residual energy should be regarded as limitation. Finally, the results are carried out with regard to the packet distribution ratio, throughput, overhead management, and average end‐to‐end delay to demonstrate the efficiency of the proposed system.
Thermally Chargeable Proton Capacitor Based on Redox‐Active Effect for Energy Storage and Low‐Grade Heat Conversion
Authors: An Yufeng , Li Zhiwei , Sun Yao , Chen Zhijie , Jiang Jiangmin , Dou Hui , Zhang Xiaogang
Published: November 2021

Thermal energy is abundantly available in our daily life and industrial production, and especially, low‐grade heat is often regarded as a byproduct. Collecting and utilizing this ignored energy by low‐cost and simple technologies may become a smart countermeasure to relieve the energy crisis. Here, a unique device has been demonstrated to achieve high value‐added conversion of low‐grade heat by introducing redox‐active organic alizarin (AZ) onto N‐doped hollow carbon nanofibers (N–HCNF) surface. As‐prepared N–HCNF/AZ can deliver a high specific capacitance of 514.3 F g−1 (at 1 A g−1) and an outstanding rate capability of 60.3% even at 50 A g−1. Meanwhile, the assembled symmetric proton capacitor can deliver a high energy density of 28.0 Wh kg−1 at 350.0 W kg−1 and a maximum power density of 35.0 kW kg−1 at 17.0 Wh kg−1. Significantly, the thermally chargeable proton capacitors can attain a surprisingly high Seebeck coefficient of 15.3 mV K–1 and a power factor of 6.02 µW g–1. Taking advantage of such high performance, a satisfying open‐circuit voltage of 481.0 mV with a temperature difference of 54 K is achieved. This research provides new insights into construction of high value‐added energy systems requiring high electrochemical performances.
The Thermochemistry of Alkyne Insertion into a Palladacycle Outlines the Solvation Conundrum in DFT
Authors: Milovanović Milan R. , Boucher Mélanie , Cornaton Yann , Zarić Snežana D. , Pfeffer Michel , Djukic Jean‐Pierre
Published: November 2021

In an effort to determine the thermochemistry of established organometallic transformation, the well documented reaction of alkynes with a palladacycle was investigated by isothermal titration calorimetry (ITC). Although the mechanism of the insertion of unsaturated substrates into the Pd−C bond of cyclopalladated compounds is known, no information is available so far about their thermochemistry. The enthalpies of the reactions of Ph−C≡C−Ph and MeOC(O)−C≡C(O)COMe with the bisacetonitrilo salt of the N,N‐benzylamine palladacycle were determined by ITC in chlorobenzene after having optimized the conditions to ensure that only the double and a single insertion of alkynes were occurring respectively. The reaction energy profile established by DFT for the double insertion process involving Ph−C≡C−Ph confirmed earlier conclusions on the rate determining character of the first insertion. Further computations of reaction enthalpies reveal significant discrepancies between ITC and DFT‐D/continuum solvation enthalpies, that are suspected to arise from an unexpected explicit noncovalent interaction of PhCl with the components of the reaction.
Make It Green: Copper‐Catalyzed Olefin Aziridination in Water with an Iminoiodonane
Authors: Borrego Elena , Pérez Pedro J. , Caballero Ana
Published: November 2021

The copper complex Tp(CF3)2,BrCu(NCMe) efficiently catalyses the aziridination of olefins in water using PhI=NTs as the nitrene source, with identical activity than that observed when using dichloromethane as the solvent, under the same experimental conditions. No specific modification of catalyst or substrates are required, nor the presence of additional phase transfer catalyst. Competition experiments and Hammett plots show that the behaviour of the metal centre is the same in both reaction media. This is the first example of a catalytic system employing PhI=NTs for olefin aziridination in water.
An acoustic wave method for evaluating the effectiveness of blast to enhance fragmentation in longwall top coal caving
Authors: Zhao Tielin , Zhou Yuliang , Gao Shengyuan
Published: November 2021

The advanced deep hole blasting (ADHB) is commonly used to improve the fragmentation of thick hard top coal in longwall top coal caving (LTCC) mining. This paper presents an acoustic method to quantitatively evaluate the effectiveness of the ADHB. First, the variations of P‐wave velocity of hard coal samples under uniaxial and triaxial compression are obtained from the laboratory acoustic test. Then, an acoustic wave method based on seismic tomography is proposed to assess the effectiveness of the ADHB by introducing the P‐wave velocity attenuation model into the data processing. Finally, a field seismic tomography test is conducted to obtain the distribution of the P‐wave velocity of top coal before and after the ADHB implementation. And the P‐wave velocity attenuation is calculated to estimate the fragmentation effectiveness of ADHB. The results indicate that the P‐wave velocity attenuation model could well represent the broken degree of hard coal, suggesting that the proposed acoustic wave method could quantitatively evaluate the fragmentation effectiveness by exporting the nephogram of P‐wave velocity attenuation. The present study may provide technical support for improving the recovery ratio of thick hard top coal for LTCC mining.
Enhancement of oil productivity of Mortierella alpine and investigation into the potential of Pickering oil‐in‐water emulsions to improve its oxidative stability
Authors: Esfandiyari Mehni Marjan , Samadlouie Hamid Reza , Rajaei Ahmad
Published: November 2021

Mortierella alpine is an oleaginous fungi known for its tendency to produce oil and polyunsaturated fatty acid. Initial experiment indicated that magnesium oxide nanoparticles (MgONPs) accelerated glucose consumption and, consequently, oil production. After enhancement of Mortierella alpine CBS 754.68' oil production, the oxidative stability of the oil rich in long‐chain polyunsaturated fatty acids (arachidonic acid) encapsulated by modified chitosan (CS) was assayed. To confirm the modification of CS, Fourier transform infrared spectroscopy (FTIR) spectrum indicated that the connection between CS and capric acid (CA) as well as stearic acid (SA) was well formed, leading to a considerable improvement in nanoparticle formation, measured by the SEM photographs, and physical and oxidative stability of emulsions. The oxidative stability of Mortierella alpine' oil emulsion in a period of 20 days at ambient temperature was monitored. Of all treated media, CS‐SA nanoparticles were of the most oxidative stability. The rheological tests showed that viscosity behaviors were dominated by elastic behaviors in the impregnating emulsion with unmodified CS at the applied frequencies, and the elastic behavior of the emulsion sample prepared with CS‐SA was slightly higher than that of the emulsion prepared with CS‐CA. The results of redispersibility indicated that the powdered emulsion stabilized by CS‐SA had the lowest water absorption.
Telephone‐based behavioral activation with mental imagery for depression: A pilot randomized clinical trial in isolated older adults during the Covid‐19 pandemic
Authors: Pellas Johnny , Renner Fritz , Ji Julie L. , Damberg Mattias
Published: November 2021

Objectives

To shield vulnerable persons, particularly the elderly, during the Covid‐19 pandemic governments around the world have advised to use social distancing and self‐isolation. Social isolation might put older adults at an increased risk for mental health problems such as depression. There is a need for brief, easy‐accessible psychological treatments for depressive symptoms that can be delivered remotely. The aim of this study was to investigate the feasibility, acceptability, and preliminary efficacy of telephone‐delivered Behavioral Activation with Mental Imagery (BA‐MI) for the treatment of depressive symptoms in individuals 65 years and older living in isolation during the Covid‐19 pandemic.

Methods

In this open‐label pilot randomized clinical trial, N = 41 individuals aged 65 years or older with clinically significant symptoms of depression were randomly assigned to either a BA‐MI treatment condition, or an Attention‐Assessment control condition delivered over the telephone over a 4‐week period.

Results

Depressive symptoms decreased more in the treatment condition compared to the control condition. At post‐treatment, 2 out of 16 participants in the treatment condition met diagnostic criteria for depression compared to 9 out of 13 in the control condition. Most participants in the treatment condition were satisfied with the treatment and few adverse effects were observed.

Conclusions

This pilot study suggests that behavioral activation with mental imagery delivered over the telephone is feasible, acceptable, and potentially efficacious for the treatment of depressive symptoms in older individuals living in isolation. Replication in larger samples is needed.
Intermittent theta burst stimulation over the parietal cortex has a significant neural effect on working memory
Authors: Deng Xinping , Wang Jue , Zang Yufeng , Li Yang , Fu Wenjin , Su Yanyan , Chen Xiongying , Du Boqi , Dong Qi , Chen Chuansheng , Li Jun
Published: November 2021

The crucial role of the parietal cortex in working memory (WM) storage has been identified by fMRI studies. However, it remains unknown whether repeated parietal intermittent theta‐burst stimulation (iTBS) can improve WM. In this within‐subject randomized controlled study, under the guidance of fMRI‐identified parietal activation in the left hemisphere, 22 healthy adults received real and sham iTBS sessions (five consecutive days, 600 pulses per day for each session) with an interval of 9 months between the two sessions. Electroencephalography signals of each subject before and after both iTBS sessions were collected during a change detection task. Changes in contralateral delay activity (CDA) and K‐score were then calculated to reflect neural and behavioral WM improvement. Repeated‐measures ANOVA suggested that real iTBS increased CDA more than the sham one (p = .011 for iTBS effect). Further analysis showed that this effect was more significant in the left hemisphere than in the right hemisphere (p = .029 for the hemisphere‐by‐iTBS interaction effect). Pearson correlation analyses showed significant correlations for two conditions between CDA changes in the left hemisphere and K score changes (ps <.05). In terms of the behavioral results, significant K score changes after real iTBS were observed for two conditions, but a repeated‐measures ANOVA showed a nonsignificant main effect of iTBS (p = .826). These results indicate that the current iTBS protocol is a promising way to improve WM capability based on the neural indicator (CDA) but further optimization is needed to produce a behavioral effect.
Sugar rush or sugar crash? Experimental evidence on the impact of sugary drinks in the classroom
Authors: Schiltz Fritz , De Witte Kristof
Published: November 2021

Sugary drinks in schools have been demonized for their potential long‐term contribution to rising obesity rates. Surprisingly, there is only little evidence on the immediate effects of sugary drinks in schools. This paper provides experimental evidence on the in‐class effects of sugary drinks on behavior and student achievement. We randomly assigned 462 preschool children to receive sugary drinks or artificially sweetened drinks and collected data before and after consumption. Our findings suggest that the consumption of one sugary drink induces an initial “relaxing” effect for boys, before making them more restless. Girls' behavior is not significantly affected. We find a negative effect on student achievement for boys and a positive effect for girls. We show the robustness of the results across two field experiments.
High Effectiveness of Broad Access Direct‐Acting Antiviral Therapy for Hepatitis C in an Australian Real‐World Cohort: The REACH‐C Study
Authors: Yee Jasmine , Carson Joanne M. , Hajarizadeh Behzad , Hanson Joshua , O’Beirne James , Iser David , Read Phillip , Balcomb Anne , Doyle Joseph S. , Davies Jane , Martinello Marianne , Marks Philiipa , Dore Gregory J. , Matthews Gail V. ,   the REACH‐C Study Group
Published: November 2021

Australia was one of the first countries with unrestricted access to government subsidized direct‐acting antiviral (DAA) therapy for adults with chronic hepatitis C virus. This study assessed real‐world DAA treatment outcomes across a diverse range of Australian clinical services and evaluated factors associated with successful treatment and loss to follow‐up. Real‐world Effectiveness of Antiviral therapy in Chronic Hepatitis C (REACH‐C) consisted a national observational cohort of 96 clinical services including specialist clinics and less traditional settings such as general practice. Data were obtained on consecutive individuals who commenced DAAs from March 2016 to June 2019. Effectiveness was assessed by sustained virological response ≥12 weeks following treatment (SVR) using intention‐to‐treat (ITT) and per‐protocol (PP) analyses. Within REACH‐C, 10,843 individuals initiated DAAs (male 69%; ≥50 years 52%; cirrhosis 22%). SVR data were available in 85% (9,174 of 10,843). SVR was 81% (8,750 of 10,843) by ITT and 95% (8,750 of 9,174) by PP. High SVR (≥92%) was observed across all service types and participant characteristics. Male gender (adjusted odds ratio [aOR] 0.56, 95% confidence interval [CI] 0.43‐0.72), cirrhosis (aOR 0.52, 95% CI 0.41‐0.64), recent injecting drug use (IDU; aOR 0.64, 95% CI 0.46‐0.91) and previous DAA treatment (aOR 0.50, 95% CI 0.28‐0.90) decreased the likelihood of achieving SVR. Multiple factors modified the likelihood of loss to follow‐up including IDU ± opioid agonist therapy (OAT; IDU only: aOR 1.75, 95% CI 1.44‐2.11; IDU + OAT: aOR 1.39, 95% CI 1.11‐1.74; OAT only, aOR 1.36; 95% CI 1.13‐1.68) and age (aOR 0.97, 95% CI 0.97‐0.98). Conclusion: Treatment response was high in a diverse population and through a broad range of services following universal access to DAA therapy. Loss to follow‐up presents a real‐world challenge. Younger people who inject drugs were more likely to disengage from care, requiring innovative strategies to retain them in follow‐up.
The dynamics of diplomatic careers: The shift from traditional to contemporary careers
Authors: Hart Dan , Baruch Yehuda
Published: November 2021

Career research has focused on the changing structures of careers, mainly in the private sector. Recent literature on employment patterns in the public sector suggests that career structures are evolving, gradually moving away from their signature traditional structures to contemporary ones. However, empirical evidence of this change is scarce and inconclusive. This qualitative study examines the changes currently unfolding in the career structure of the civil service by eliciting the experiences and views of senior Foreign Offices (FOs) staff in four countries: 198 state ambassadors from the United States, the United Kingdom, Israel, and Denmark were interviewed about their career trajectories. The data were analyzed using a thematic analysis framework. The findings revealed a gradual breakdown of the structures and policies that support traditional careers, and the emergence of new principles and practices that characterize contemporary careers. However, as they were captured midway through the process of change, all FOs display a combination of traditional and contemporary career structures at this point. The findings offer unique insights into the drivers of this evolution and highlight some of the consequences.
Near‐surface water fluxes and their controls in a sloping heterogeneously layered volcanic soil beneath a supra‐wet tropical montane cloud forest (NW Costa Rica)
Authors: Tobón Conrado , Bruijnzeel L. Adrian
Published: November 2021

Tropical montane cloud forests (TMCF) receive additional (‘occult’) inputs of water from fog and wind‐driven rain. Together with the concomitant reduction in evaporative losses, this typically leads to high soil moisture levels (often approaching saturation) that are likely to promote rapid subsurface flow via macropores. Although TMCF make up an estimated 6.6% of all remaining montane tropical forest and occur mostly in steep headwater areas that are protected in the expectation of reduced downstream flooding, TMCF hillslope hydrological functioning has rarely been studied. To better understand the hydrological response of a supra‐wet TMCF (net precipitation up to 6535 mm y−1) on heterogeneously layered volcanic ash soils (Andosols), we examined temporal and spatial soil moisture dynamics and their contribution to shallow subsurface runoff and stormflow for a year (1 July 2003–30 June 2004) in a small headwater catchment on the Atlantic (windward) slope near Monteverde, NW Costa Rica. Particular attention was paid to the partitioning of water fluxes into lateral subsurface flow and vertical percolation. The presence of a gravelly layer (C‐horizon) at ~25 cm depth of very high hydraulic conductivity (geometric mean: 502 mm h−1) intercalated between two layers of much lower conductivity (7.5 and 15.7 mm h−1 above and below, respectively), controlled both surface infiltration and delayed vertical water movement deeper into the soil profile. Soil water fluxes during rainfall were dominated by rapid lateral flow in the gravelly layer, particularly at high soil moisture levels. In turn, this lateral subsurface flow controlled the magnitude and timing of stormflow from the catchment. Stormflow amount increased rapidly once topsoil moisture content exceeded a threshold value of ~0.58 cm3 cm−3. Responses were not affected appreciably by rainfall intensity because soil hydraulic conductivities across the profile largely exceeded prevailing rainfall intensities.
Social support in bereavement: Developing and validating a new scale
Authors: Li Jie , Li Mei , Reid Jon Kent
Published: November 2021

Although social support has been considered to be beneficial for the bereaved, mixed findings exist in the literature. This may be due to variations in conceptualising and measuring social support. This study aims to offer a new validated scale for research on social support in bereavement. Part 1 describes the generation of the item pool, which was derived from narratives of 28 bereaved Chinese. Part 2 includes the items selected using item analysis and explanatory factor analysis to form the preliminary version of the Scale of Social Support in Bereavement (SSB) based on data collected from 195 bereaved adults. Part 3 examined the psychometric properties of the newly developed SSB with a sample of another 196 bereaved adults. The results of confirmatory factor analysis indicated a useful structure of four factors, including “living support,” “economic support,” “grief processing,” and “emotion restoration.” The convergent validity, internal consistency reliability and test–retest reliability of the measure were shown to be strong. SSB is the first scale which measures comprehensive types of support in bereavement. It can be applied in exploration of the role of social support in bereavement, and validated in different cultural contexts.
Isolated recurrence of prostate cancer to the anterior urethra 5 years after radiation therapy
Authors: Fujiwara Shinnosuke , Ishida Masaru , Arai Eri , Baba Yuto , Anno Tadatsugu , Kobayashi Hiroaki , Miyazaki Yasumasa
Published: November 2021

Introduction

Primary or metastatic urethral tumors are extremely rare. However, treatment strategies differ between primary and metastatic tumors. Therefore, establishing an accurate diagnosis is critically needed for initiating timely and appropriate therapy.

Case presentation

We describe the case of a 79‐year‐old man with prostate cancer treated with radiotherapy and androgen deprivation therapy. He presented with macroscopic hematuria as a symptom of anterior urethral tumor at follow‐up. Endoscopic tumor resection was performed. Hematoxylin and eosin staining showed adenocarcinoma component. Immunohistochemical staining revealed presence of metastatic prostate cancer to the urethra.

Conclusion

Regarding urethral tumors diagnosis, urologists should consider the possibility of metastasis from prostate cancer and perform immunohistochemical examination for establishing accurate diagnosis. Furthermore, if androgen deprivation therapy fails to suppress symptoms, radiotherapy or urethrectomy might be considered.
The role of financial reporting quality in selecting new audit committee member
Authors: Lei Dongliang , Liu Jiaxin
Published: November 2021

In this paper, we examine how the Boards of Directors affect their firm's financial reporting quality (FRQ) through the appointment of new Audit Committee Members (ACM) with a sample of firms from the period 2007 to 2011. Using the appointee firm's financial report quality as a proxy for new ACMs’ financial reporting attributes, we find that appointer firms are more likely to appoint new ACMs with financial reporting attributes similar to firms’ FRQ. We also show that firms appointing ACMs with relatively weak financial reporting attributes are more likely to have decreased subsequent FRQ. Further, we find that firms appointing ACMs with relatively weak financial reporting attributes suffer more deterioration on their subsequent FRQ when their financial reporting qualities are more different from the ACMs’ financial reporting attributes. For the appointment of board members not on the Audit Committee, we find no similarity of financial reporting quality between appointer firms and new directors.
Ameliorating cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90 with omeprazole
Authors: Liu Zhelong , Xiong Jian , Gao Song , Zhu Michael X. , Sun Kai , Li Min , Zhang Guohua , Li Yi‐Ping
Published: November 2021

Background

Cancer cachexia, characterized by muscle and fat tissue wasting, is a major determinant of cancer‐related mortality without established treatment. Recent animal data revealed that cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 as surface proteins on extracellular vesicles (EVs). Here, we test a therapeutic strategy for ameliorating cancer cachexia by inhibiting the release of Hsp70 and Hsp90 using proton pump inhibitor omeprazole.

Methods

Omeprazole effect on Hsp70/90 release through EVs by Lewis lung carcinoma (LLC) cells in vitro, serum levels of Hsp70/90 and Hsp70/90‐carrying EVs in LLC tumour‐bearing mice, and LLC‐induced muscle protein degradation pathways in C2C12 myotubes and mice were determined. Omeprazole effect on endolysosomal pH and Rab27b expression in LLC cells were analysed.

Results

Omeprazole treatment of LLC cells inhibited Hsp70/90 and Hsp70/90‐carrying EV release in a dose‐dependent manner (1 to 10 μM) and attenuated the catabolic activity of LLC cell‐conditioned medium on C2C12 myotubes. Systemic omeprazole administration to LLC tumour‐bearing mice (5 mg/kg/day subcutaneously) for 2 weeks blocked elevation of serum Hsp70, Hsp90, and Hsp70/90‐carrying EVs, abrogated skeletal muscle catabolism, and prevented loss of muscle function as well as muscle and epididymal fat mass without altering tumour growth. Consequently, median survival increased by 23.3%. Mechanistically, omeprazole increased cancer cell endolysosomal pH level dose‐dependently (0.1 to 1 μM) by inhibiting vacuolar H+‐ATPase. Further, omeprazole suppressed the highly elevated expression of Rab27b, a key regulator of EV release, in LLC cells.

Conclusions

Omeprazole ameliorates cancer cachexia by inhibiting cancer cell release of Hsp70 and Hsp90.
Prediction of esophagogastric varices associated with oxaliplatin administration
Authors: Satta Yosuke , Shigefuku Ryuta , Watanabe Tsunamasa , Mizukami Takuro , Tsuda Takashi , Suzuki Tatsuya , Ehira Takuya , Hattori Nobuhiro , Kiyokawa Hirofumi , Nakahara Kazunari , Ikeda Hiroki , Matsunaga Kotaro , Takahashi Hideaki , Matsumoto Nobuyuki , Okuse Chiaki , Suzuki Michihiro , Sunakawa Yu , Yasuda Hiroshi , Itoh Fumio
Published: November 2021

Background

Oxaliplatin is a key drug for the chemotherapy of colorectal cancer; however, it is also known to cause non‐cirrhotic portal hypertension. We aimed to identify the characteristics of patients who developed esophagogastric varices (EGVs) after treatment with oxaliplatin.

Methods

This study retrospectively analyzed patients with colorectal cancer who were treated with chemotherapy including oxaliplatin between 2010 and 2016. All patients were evaluated by contrast‐enhanced computed tomography (CE‐CT) every 3 months both during and after treatment; and endoscopy was performed when appearance of portal hypertension was suspected.

Results

A total of 106 patients were divided into two groups: EGV formation (n = 6) and EGV non‐formation (n = 100). In the EGV group, platelet counts decreased and the size of the spleen calculated by CT (CT spleen index; CT‐SI) increased markedly. The highest area under the receiver operating characteristic curve (AUC) for the change in platelet counts was 0.81 (80% sensitivity and 83% specificity) at 3 months post treatment, and the maximum AUC for CT‐SI was 0.89 (79% sensitivity and 83% specificity) at 6 months post treatment.

Conclusions

EGV formation could be predicted by the assessment of platelet counts and spleen size. If progressive splenomegaly and thrombocytopenia are observed not only during but also after completion of the oxaliplatin‐containing chemotherapy, EGVs should be confirmed by endoscopy for avoiding subsequent rupture.
Planar hypohamiltonian oriented graphs
Authors: Burger Alewyn P. , de Wet Johan P. , Frick Marietjie , Van Cleemput Nico , Zamfirescu Carol T.
Published: November 2021

In 1978 Thomassen asked whether planar hypohamiltonian oriented graphs exist. Infinite families of such graphs have since been described but for infinitely many it remained an open question whether planar hypohamiltonian oriented graphs of order exist. In this paper we develop new methods for constructing hypohamiltonian digraphs, which, combined with efficient graph generation algorithms, enable us to fully characterise the orders for which planar hypohamiltonian oriented graphs exist. Our novel methods also led us to discover the planar hypohamiltonian oriented graph of smallest order and size, as well as infinitely many hypohamiltonian orientations of maximal planar graphs. Furthermore, we answer a question related to a problem of Schiermeyer on vertex degrees in hypohamiltonian oriented graphs, and characterise all the orders for which planar hypotraceable oriented graphs exist.
Identification of liver-specific CD24+ invariant NK T cells with low granzyme B production and high proliferative capacity
Authors: Li Xiang , Jin Chen , Chen Qi , Zheng Xihua , Xie Di , Wu Qielan , Wang Lu , Bai Shiyu , Zhang Huimin , Bai Li
Published: November 2021

Invariant NK T (iNKT) cells are innate-like lymphocytes that can recognize the lipid Ag presented by MHC I like molecule CD1d. Distinct tissue distribution of iNKT cells subsets implies a contribution of these subsets to their related tissue regional immunity. iNKT cells are enriched in liver, an organ with unique immunological properties. Whether liver-specific iNKT cells exist and dedicate to the liver immunity remains elusive. Here, a liver-specific CD24+ iNKT subset is shown. Hepatic CD24+ iNKT cells show higher levels of proliferation, glucose metabolism, and mTOR activity comparing to CD24– iNKT cells. Although CD24+ iNKT cells and CD24– iNKT cells in the liver produce similar amounts of cytokines, the hepatic CD24+ iNKT cells exhibit lower granzyme B production. These liver-specific CD24+ iNKT cells are derived from thymus and differentiate into CD24+ iNKT in the liver microenvironment. Moreover, liver microenvironment induces the formation of CD24+ conventional T cells as well, and these cells exhibit higher proliferation ability but lower granzyme B production in comparison with CD24– T cells. The results propose that liver microenvironment might induce the generation of liver-specific iNKT subset that might play an important role in maintaining liver homeostasis.
Single-cell profiling of T lymphocytes in deficiency of adenosine deaminase 2
Authors: Wu Zhijie , Gao Shouguo , Watanabe Naoki , Batchu Sai , Kajigaya Sachiko , Diamond Carrie , Alemu Lemlem , Raffo Diego Quinones , Feng Xingmin , Hoffmann Patrycja , Stone Deborah , Ombrello Amanda , Young Neal S
Published: November 2021

Deficiency of adenosine deaminase 2 (DADA2) is a monogenic vasculitis syndrome caused by autosomal-recessive loss-of-function mutations in the ADA2 gene (previously known as CECR1). Vasculitis, vasculopathy, and inflammation are dominant clinical features of this disease; the spectrum of manifestations includes immunodeficiency and lymphoproliferation as well as hematologic manifestations. ADA2 is primarily secreted by stimulated monocytes and macrophages. Aberrant monocyte differentiation to macrophages and neutrophils are important in the pathogenesis of DADA2, but little is known about T lymphocytes in this disease. We performed combined single-cell RNA sequencing and single-cell TCR sequencing in order to profile T cell repertoires in 10 patients with DADA2. Although there were no significant alterations of T cell subsets, we observed activation of both CD8+ and CD4+ T cells. There was no clonal expansion of T cells: most TCRs were expressed at basal levels in patients and healthy donors. TCR usage was private to individual patients and not disease specific, indicating as unlikely a common pathogenic background or predisposition to a common pathogen. We recognized activation of IFN pathways as a signature of T cells and STAT1 as a hub gene in the gene network of T cell activation and cytotoxicity. Overall, T cells in DADA2 patients showed distinct cell–cell interactions with monocytes, as compared with healthy donors, and many of these ligand–receptor interactions likely drove up-regulation of STAT1 in both T cells and other immune cells in patients. Our analysis reveals previously undercharacterized cell characteristics in DADA2.
T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination
Authors: Koutsakos Marios , Lee Wen Shi , Wheatley Adam K , Kent Stephen J , Juno Jennifer A
Published: November 2021

Vaccination remains the most effective mechanism to reduce the impact of COVID-19. Induction of neutralizing antibodies is a strong correlate of protection from infection and severe disease. An understanding of the cellular events that underpin the generation of effective neutralizing antibodies is therefore key to the development of efficacious vaccines that target emerging variants of concern. Analysis of the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and vaccination has identified circulating T follicular helper cells (cTFH) as a robust correlate of the neutralizing antibody response. Here, we discuss the analysis of cTFH cells and their lymphoid counterparts in human humoral immune responses during COVID-19, and in response to vaccination with SARS-CoV-2 spike. We discuss the phenotypic heterogeneity of cTFH cells and the utility of cTFH subsets as informative biomarkers for development of humoral immunity. We posit that the analysis of the most effective cTFH will be critical to inducing durable immunity to new variants of SARS-CoV-2.
Cytokine profile in serum and gingival crevicular fluid of children with inflammatory bowel disease: A case‐control study
Authors: Acar Buket , Gümüş Ersin , Özcan‐Bulut Selcen , Özşin‐Özler Cansu , Boyraz Meryem Seda , Tan Çağman , Yaz Ismail , Özbek Begüm , Cagdas Deniz , Saltık‐Temizel İnci Nur , Demir Hülya , Özen Hasan , Karabulut Erdem , Tezcan İlhan , Yüce Aysel , Berker Ezel
Published: November 2021

Background

To evaluate the cytokine profile in gingival crevicular fluid (GCF) and serum of pediatric inflammatory bowel disease (IBD) patients and determine the cluster patterns of cytokines.

Methods

Fifty IBD patients and 21 systemically healthy children were enrolled in the study. The GCF samples were collected from the participants during periodontal examination and periodontal indices were recorded. Based on activity indexes and response to conventional treatment, patients with IBD were further categorized into subgroups as: remission, active disease, and treatment‐resistant. Serum samples were obtained from IBD patients to determine serum levels of cytokines. The levels of pro‐ (interleukin (IL)‐1β, IL‐12, IL‐21, IL‐22, IL‐23, IL‐17A, IL‐17F) and anti‐inflammatory (IL‐4, IL‐10) cytokines in serum and GCF were measured using Enzyme‐linked Immunosorbent Assay (ELISA) kits.

Results

Among 50 IBD patients, 58% were in remission, 20% had active disease, and 22% were defined as treatment‐resistant. The severity of gingival inflammation measured by the criteria of Löe had increasing trends in IBD patients with active disease and treatment resistance. GCF IL‐1β level was lower and GCF IL‐4 and GCF IL‐23 levels were higher in IBD patients compared to healthy controls. In the active disease group, more cytokine clusters occurred compared to the control group and other IBD subgroups, as explained by increased cytokine‐cytokine interactions.

Conclusions

Considering the increased complexity of cytokine interactions and the increased severity of gingival inflammation in patients with active disease, it can be concluded that disease activity might have an impact on gingival inflammation in pediatric patients with IBD.