bluuebunny/crossref_metadata_2025 huggingface dataset:
Esports Scholarship Review: Synthesis, Contributions, and Future Research
Authors: Pizzo Anthony D. , Su Yiran , Scholz Tobias , Baker Bradley J. , Hamari Juho , Ndanga Leah
Published: March 2022

Esports, or competitive video gaming competitions, bring together aspects of sports, business, leisure, technology, and digital media, appealing to academics across multiple disciplines. Yet, esports scholarship remains highly fragmented, with scholars operating within traditional academic silos and forgoing opportunities to build on esports’ interdisciplinary nature. The purpose of this integrative review is to synthesize esports scholarship from across disciplines, identify critical scholarly issues, and develop a pragmatic, interdisciplinary research agenda. We find that extant esports scholarship is categorized by literature seeking to conceptualize and legitimize esports via sport parallels, with a focus on the consumers and culture of esports. Scholarly issues include researchers examining esports in their respective academic silos, omitting opportunities to connect conceptually similar streams of literature. Overall, we synthesize esports scholarship, bridge chasms between disjointed streams of literature, and outline a pragmatic research agenda which could benefit from interdisciplinary inquiries based on a shared understanding of esports.
ClpX/P-Dependent Degradation of Novel Substrates in Streptococcus mutans
Authors: Gurung Vivek , Biswas Indranil
Published: March 2022

ClpX/P is a major intracellular proteolytic complex that is responsible for protein quality control in the cell. ClpX, an AAA+ ATPase, distinguishes the potential substrates by recognizing short motifs at the C-terminal end of proteins and delivers the substrates for degradation by ClpP protease.
Special Conditions for the Formation of Large Exogenic Epigenetic Uranium Deposits
Authors: Kochkin B. T.
Published: March 2022

Abstract—For uranium deposits to form from oxidizing waters of surface origin, it is necessary to combine several conditions and processes of different ranks that make up a specific mineral system. Analysis of exogenic deposits of different scales and ore quality from different regions of the world showed that, among all the critical processes necessary for the formation of large deposits and vast provinces, global tectonic movements play a particular role. A geodynamic regime with moderate vertical differentiation of crustal blocks is most favorable for development of a hydrodynamic infiltration ore-forming system under near-surface conditions. An infiltration artesian system is capable of functioning for millions and tens of millions of years, which makes it possible to accumulate large uranium reserves at the geochemical reduction barrier. The required regime is typical of regions with a certain geotectonic position. For example, the peripheral regions of orogenic belts along tectonic plate boundaries, as well as the frames of some long-lived intraplate deep faults. In the same regions, the proximity of infiltration and expulsion hydrodynamic systems is possible. In local areas where groundwater of various origin and composition interact, conditions occur for particularly efficient uranium concentration in ores. Limitations on the productivity of a hydrodynamic infiltration ore-forming system are imposed by historical factors that predetermine the formation of the uranium source and lithological conditions for ore localization, as well as the climatic conditions of the time in which the system functioned and postore conditions determining the preservation of mineralization accumulated in the system. The revealed patterns be used to predict ancient provinces of exogenic uranium deposits.
Combination inhaler is effective in mild asthma
Authors: Saul Helen , Gursul Deniz , Cassidy Samantha , Hinks Timothy
Published: March 2022

The study

Crossingham I, Turner S, Ramakrishnan S, et al. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review.
BMJ Evid Based Med
2021; doi:
10.1136/bmjebm-2021-111764
.

To read the full NIHR Alert, go to:
https://evidence.nihr.ac.uk/alert/combination-inhaler-is-effective-in-mild-asthma/
Practices of public procurement and the risk of corrupt behavior before and after the government transition in México
Authors: Falcón-Cortés Andrea , Aldana Andrés , Larralde Hernán
Published: March 2022

Corruption has a significant impact on economic growth, democracy, and inequality. It has sever consequences at the human level. Public procurement, where public resources are used to purchase goods or services from the private sector, are particularly susceptible to corrupt practices. However, government turnover may bring significant changes in the way public contracting is done, and thus, in the levels and types of corruption involved in public procurement. In this respect, México lived a historical government transition in 2018, with the new government promising a crackdown on corruption. In this work, we analyze data from more than 1.5 million contracts corresponding from 2013 to 2020, to study to what extent this change of government affected the characteristics of public contracting, and we try to determine whether these changes affect how corruption takes place. To do this, we propose a statistical framework to compare the characteristics of the contracting practices within each administration, separating the contracts in different classes depending on whether or not they were made with companies that have now been identified as being involved in corrupt practices. We find that while the amount of resources spent with companies that turned out to be corrupt has decreased substantially, many of the patterns followed to contract these companies were maintained, and some of those in which changes did occur, are suggestive of a larger risk of corruption.
Understanding China’s urban system evolution from web search index data
Authors: Guo Hao , Zhang Weiyu , Du Haode , Kang Chaogui , Liu Yu
Published: March 2022

The spatial inequilibrium phenomenon is apparent during China’s rapid urbanization in the past four decades. As the fertility rate decreases and the population ages, this phenomenon will become more critical. To accurately forecast the future economic development of China, it is necessary to quantify the attractiveness of individual cities. This study introduces web search data to quantify the attractiveness of cities with a fine spatial scale (prefecture-level city) and relatively long-term span (nine years). Results confirm that the estimated city attractiveness can unravel a city’s capability to attract labor force, and suggest that tourism and health care functions of a city have a positive effect to the city’s attractiveness. Additionally, China’s north-south gap in economic development has been widened in the past decade, and 11 cities with nationwide influence have prosperous development potential. This study provides a new lens for predicting China’s economic development, as well as its spatial patterns.
Saving the Colorado River Delta: How Much is It Worth?
Authors: Sarkar Aditi
Published: March 2022

The Colorado River is a river system spanning seven states in the United States (US) and two in Mexico. Water in the river has been over-allocated, which has led the Colorado River Delta in Mexico to dry up, thus endangering the indigenous species. The two nations made several temporary, costly allocation agreements to transfer water to the Delta for ecological restoration. However, there is still no long-term economic solution for the Delta, which is what this study aims to address. In this work, I investigate solutions for rerouting water to the Delta that will minimize costs without causing excessive damage to the agrarian economy in the US. The cost of conserving water for the Delta was analyzed using numerical simulations with crop data from the Imperial Irrigation District in California. The objective is to find a policy that would help allocate 100,000 acre-feet per year to the Colorado River Delta at a minimum lifetime cost. Two scenarios are studied that would yield enough water for a sustainable restoration of the ecosystem: fallowing croplands and changing the irrigation system to be more water-efficient. Results indicate that fallowing 20,000 ac of alfalfa would be the least costly way of accumulating this resource at a cost ranging from $5.5 million to $13 million per year for a 31-year time horizon. This paper provides new insight into ways in which the US and Mexico can secure the future of ecosystems like the Colorado River Delta.
Artificial Intelligence in Underwater Digital Twins Sensor Networks
Authors: Lv Zhihan , Chen Dongliang , Feng Hailin , Wei Wei , Lv Haibin
Published: March 2022

The particularity of the marine underwater environment has brought many challenges to the development of
underwater sensor networks (UWSNs)
. This research realized the effective monitoring of targets by UWSNs and achieved higher quality of service in various applications such as communication, monitoring, and data transmission in the marine environment. After analysis of the architecture, the
marine integrated communication network system (MICN system)
is constructed based on the
maritime wireless Mesh network (MWMN)
by combining with the UWSNs. A distributed hybrid
fish swarm optimization algorithm (FSOA)
based on mobility of underwater environment and
artificial fish swarm (AFS)
theory is proposed in response to the actual needs of UWSNs. The proposed FSOA algorithm makes full use of the perceptual communication of sensor nodes and lets the sensor nodes share the information covered by each other as much as possible, enhancing the global search ability. In addition, a reliable transmission protocol NC-HARQ is put forward based on the combination of
network coding (NC)
and
hybrid automatic repeat request (HARQ)
. In this work, three sets of experiments are performed in an area of 200 × 200 × 200 m. The simulation results show that the FSOA algorithm can fully cover the events, effectively avoid the blind movement of nodes, and ensure consistent distribution density of nodes and events. The NC-HARQ protocol proposed uses relay nodes for retransmission, and the probability of successful retransmission is much higher than that of the source node. At a distance of more than 2,000 m, the successful delivery rate of data packets is as high as 99.6%. Based on the MICN system, the intelligent ship constructed with the digital twins framework can provide effective ship operating state prediction information. In summary, this study is of great value for improving the overall performance of UWSNs and advancing the monitoring of marine data information.
On the Immersive Properties of High Dynamic Range Video
Authors: Hinde Stephen J. , Noland Katy C. , Thomas Graham A. , Bull David R. , Gilchrist Iain D.
Published: March 2022

This paper presents the results from two studies which used a dual-task methodology to measure an audience's experience of immersion while watching video under typical television viewing conditions. Immersion was measured while participants watched either a high dynamic range, wide color gamut video or a standard dynamic range, standard color gamut video, in high definition or ultra-high definition. Other video parameters were carefully measured and controlled.

The study found that high dynamic range, wide color gamut video is significantly more immersive than standard dynamic range, standard color gamut video in the chosen configuration. However, there was no evidence of significant differences in immersion between high-definition and ultra-high-definition resolutions.
Novel Pt-Ni Electrocatalyst for Coal Electrolysis for Hydrogen Production
Authors: Yu Ping , Zheng Ruheng , Ma Hongze , Zhang Jin Z. , Botte Gerardine G.
Published: March 2022

Carbon fiber-supported Pi-Ni binary alloy electrocatalyst (Pi-Ni/CFs) with different nickel contents is synthesized using impregnation-hydrogen reduction method for coal electrolysis to produce hydrogen. The electrode based on the Pt-Ni/CFs is characterized using X-ray diffraction (XRD), scanning electron microscope (SEM) with energy-dispersive X-ray analysis (EDS) and X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The results indicate Pt-Ni alloy formed on the CFs. Electrochemical results show that Pt-Ni/CFs have higher electrocatalytic activity than pure Pt/CFs, with Pt-Ni/CFs (1:1) electrode exhibiting the best performance. Compared with the pure Pt/CFs, the efficiency of coal electrolysis for hydrogen production is increased by 13.8% with Pt-Ni/CFs (1:1). The improved performance of Pt-Ni/CFs is attributed to the modification of surface electronic properties due to metallic alloying.
Kidney stone formation in a novel murine model of polycystic kidney disease
Authors: Riddle Heather A. L. , Zhang Shiqin , Qian Feng , Williams James C. , Stubbs Jason R. , Rowe Peter Stanley N. , Parnell Stephen C.
Published: March 2022

Compound heterozygous Pkd1V/RC mice were found to form calcium phosphate-containing stones within cysts of the renal cortex by 13 wk of age. This is the first polycystic kidney disease animal model exhibiting spontaneous stone formation. A growing body of evidence suggests a link between renal stone formation and cystic kidney disease. This mouse model may be useful for studying the interplay between stone and cyst formation and the functional role of polycystins in mineral homeostasis.
Model‐Based Design, HIL Testing, and Rapid Control Prototyping of a Low‐Cost POC Quadcopter with Stability Analysis and Control
Authors: Irfan Abdullah , Khan Muhammad Gufran , Amin Arslan Ahmed , Mohsin Syed Ali , Adnan Muhammad , Zulfiqar Adil
Published: March 2022

Unmanned aerial vehicles (UAVs), particularly quadcopters, have several medical, agriculture, surveillance, and security applications. However, the use of this innovative technology for civilian applications is still very limited in low‐income countries due to the high cost, whereas low‐cost controllers available in the market are often tuned using the hit and trial approach and are limited for specific applications. This paper addresses this issue and presents a novel proof of concept (POC) low‐cost quadcopter UAV design approach using a systematic Model‐Based Design (MBD) method for mathematical modeling, simulation, real‐time testing, and prototyping. The quadcopter dynamic model is developed, and controllers are designed using Proportional Integral, and Derivative (PID), Pole Placement, and Linear Quadratic Regulator (LQR) control strategies. The stability of the controllers is also checked using Lyapunov stability analysis. For verification and validation (V&V) of the design, Software‐in‐the‐Loop, Processor‐in‐the‐Loop, Hardware‐in‐the‐loop testing, and Rapid Control Prototyping have been performed. The V&V methods of the MBD approach showed practically valid results with a stable flight of the quadcopter prototype. The proposed low‐cost POC quadcopter design approach can be easily modified to have enhanced features, and quadcopters with different design parameters can be assembled using this approach for a diverse range of applications.
The Traditional Chinese Medicine Hua Tuo Zai Zao Wan Alleviates Atherosclerosis by Deactivation of Inflammatory Macrophages
Authors: Yu Zhihua , Zheng Xuanlu , Wang Chenghui , Chen Chuan , Ning Na , Peng Danting , Liu Te , Pan Weidong
Published: March 2022

Introduction. Positive effects have been observed when the traditional Chinese medicine Hua Tuo Zai Zao Wan (HTZZW) has been used for the treatment of atherosclerosis (AS), although with an unclear mechanism. Methods. ApoE-/- C57/BALB mice were used to determine the efficacy of HTZZW by blood lipid biochemical analysis and histopathology H&E staining. qPCR and western blot were used to determine the expression of METTL3/14 and NF-κB. Results. High-fat diet-fed ApoE-/- mice that consumed HTZZW exhibited significantly smaller plaque areas and significantly decreased unstable collagen areas in the aortic arch as well as significantly lower blood levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with the control group. Consumption of HTZZW significantly decreased the proportion of Mφ1 in the peripheral blood. HTZZW not only inhibited the expression of m6A methyltransferases METTL14, METTL3, and overall RNA methylation level, but it also decreased the m6A modification level on specific sites of NF-κB mRNA. Conclusion. HTZZW significantly alleviated the progression of AS by regulating the expression of the m6A methyltransferases METTL14 and METTL3 in macrophages, eliminating m6A modifications of NF-κB mRNA, influencing the stability of NF-κB mRNA, and ultimately resulting in the deactivation of inflammatory macrophages.
Modern Craft Product Design Using Digital Technology Combined with Visual Sensing System in Complex Environment
Authors: Zhao Zhifeng , Chen Du
Published: March 2022

Specified craft production is a major characteristic of all complex civilizations, and archaeologists have frequently utilized craft specialization as a distinguishing element in identifying and researching the evolution of political complexity. This study aims to better realize the design of modern craft products, using a combination of digital image processing technique and visual sensing system. The impact of digital technology combined with a visual sensing system on product design is investigated and an improved oriented fast and rotated brief (ORB) feature matching algorithm is designed for target image feature extraction. To verify the performance of the algorithm, different experiments are designed for the accomplishment of purification effect, scale invariance, rotation invariance, and computation time. Results show that the corresponding performance accuracies after continuous purification using the angle constraint method are 99.6%, 99.3%, and 99.7%, respectively, which are significantly higher than the accuracy of a single action. In addition, the absolute value of the error of the rotation angle measured by the improved ORB feature matching algorithm is 0.14° on average. It shows that the improved ORB feature matching algorithm has high matching accuracy. The proposed algorithm improves the accuracy of target image feature extraction and has important significance in image recognition.
Assessing the Effects of Gamification on Developing EFL Learners’ Idiomatic Knowledge: Do Attitudinal Factors Contribute to the Learning of the Idioms with the Game?
Authors: Ahmed Alim Al Ayub , Widodo Mulyanto , Komariah Aan , Hassan Isyaku , Sukmana Nano , Ali Muneam Hussein , Abbas Ahmed Kamill , Rohi Ali
Published: March 2022

Regarding the attractiveness of educational games for EFL learners, the present research intended to investigate the effects of gamification on improving Iranian EFL learners’ idiomatic knowledge. In addition, the current research examined the attitudes of Iranian EFL learners towards using gamification in English learning in the Iranian EFL context. Firstly, to carry out this research, the researchers administered the Oxford Quick Placement Test (OQPT) to 84 Iranian EFL learners and selected 50 upper-intermediate participants. Secondly, they divided the selected participants into an experimental group (EG) and a control group (CG). Thirdly, the researchers gave an idiom pretest to the participants of both groups to assess their idiomatic knowledge before starting the treatment. Fourthly, the EG was taught the new idioms using game-based instruction, while the CG received traditional idiom instruction. Following the instruction of 70 idioms to both groups, the participants received an idiom posttest to determine the influence of the treatment on their idiomatic knowledge. The EG was then provided an attitude questionnaire, and 15 members of the EG were interviewed as a result of the questionnaire. In the idiom posttest, the data were evaluated using paired samples and independent samples

t

-tests, and the findings revealed that the EG performed significantly better than the CG on the posttest of idioms. In fact, gamification helped EFL learners develop their idiomatic knowledge. The results indicated that Iranian EFL learners presented positive attitudes toward gamification in learning English idioms. In addition, the results revealed that enjoyment, fun, reducing anxiety, involvement, and immediate feedback were the factors that the students mentioned for the instructional games. The implications of this research can encourage English teachers to implement different educational games in their teaching.
ASPM Promotes the Progression of Anaplastic Thyroid Carcinomas by Regulating the Wnt/β-Catenin Signaling Pathway
Authors: Jiang Liang , Zhang Shuai , An Ning , Chai Guoqing , Ye Changhong
Published: March 2022

Background. Abnormal spindle-like microcephaly-associated protein (ASPM) is closely correlated with several malignant tumors, whereas little is known about the role of ASPM in anaplastic thyroid cancer (ATC). Herein, we sought to investigate whether ASPM is involved in the pathogenesis of ATC and the underlying mechanisms. Methods. The data from two data sets (GSE76039 and GSE33630) were extracted and analyzed for the expression of ASPM, followed by a further validation in collected ATC patients using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The effect of ASPM on cell proliferation, migration, invasion, and cell cycle was explored in ATC cell lines by in vitro inhibition of ASPM, while ASPM-mediated tumorigenicity was investigated in a xenograft tumor model. The involvement of Wnt/β-catenin signaling pathway was also investigated. Results. ASPM was overexpressed in ATC patients and cell lines. In vitro knockdown of ASPM inhibited the proliferation, migration, and invasion capabilities of ATC cells and induced cell cycle arrest. Wnt/β-catenin signaling was suppressed in response to ASPM inhibition, while rescue of β-catenin expression restored the impaired biological functions of ATC cells. In vivo transplantation of ASPM-knockdown cells inhibited the growth of tumors. Conclusions. Upregulation of ASPM promotes the malignant properties of ATC cells and contributes to tumorigenesis through the Wnt/β-catenin signaling pathway.
TSN-Based Backbone Network of Train Control Management System
Authors: Bao Feng , Yu Haoyang , Wang Hao
Published: March 2022

Time-sensitive network (TSN), as one of the latest real-time Ethernet techniques, has achieved great success in several scenarios that require strict communication latency and packet loss. This paper reviews the state-of-the-art in time-sensitive networks and investigates the drawbacks of current vehicle networks. By introducing TSN into the TCMS backbone network, next-generation smart vehicles can achieve high-quality data transmissions. This paper also analyzes the priority of the vehicle data and calculates the time-aware shaper slot to ensure that the control data is not affected by the multimedia data. Using the proposed structure, experimental results suggest that the network efficiency can be improved in the rail transit systems.
A Multidisciplinary Team Approach Is Highly Effective in the Management of Nondiagnostic Bone Tumour Biopsies: A 10-Year Retrospective Review at a Specialist Sarcoma Unit
Authors: Osman Khabab , Hussain Shakir , Downes Frederick , Sumathi Vaiyapuri , Botchu Rajesh , Evans Scott
Published: March 2022

Nondiagnostic (ND) biopsies are frequently encountered during the investigation of bone tumours and can lead to treatment delay. We performed a retrospective review of all ND bone tumour biopsies discussed at our regional MDT meeting between 2004 and 2014 with the aim of establishing the incidence of ND biopsies, identifying any factors that could predict the requirement for repeat biopsies, and evaluating the effectiveness of multidisciplinary team (MDT) decisions. We identified 98 ND out of 4949 biopsies. Diagnostic yield (DY) was 98%, 76%, and 40% for the first, second, and third successive biopsy, respectively. With an MDT approach utilising radiological and clinical information, the diagnostic success rate achieved was 99%, 85%, and 80% for the first, second, and third biopsies, respectively. Although a repeat biopsy was only performed in 34% of cases, there were no patients originally diagnosed with a benign lesion that re-presented with the same lesion subsequently being malignant throughout the study period. Malignant primary bone tumours (

p
<
0.01

) and malignant secondary tumours (

p
=
0.02

) were more likely to undergo repeat biopsy compared to benign and infective lesions. Upper limb (

p
=
0.04

) and lower limb (

p
=
0.03

) were more likely than pelvic and spinal tumours to undergo a repeat biopsy. Tumours of haematological origin frequently required multiple biopsies. Our study demonstrated that a specialist MDT approach leads to high diagnostic rates and is a safe and effective method of preventing unnecessary, repeat biopsies where the initial biopsy is ND.
DRD2 Taq1A Polymorphism-Related Brain Volume Changes in Parkinson’s Disease: Voxel-Based Morphometry
Authors: Ohira Kenji , Yokota Hajime , Hirano Shigeki , Nishimura Motoi , Mukai Hiroki , Horikoshi Takuro , Sawai Setsu , Yamanaka Yoshitaka , Yamamoto Tatsuya , Kakeda Shingo , Kuwabara Satoshi , Tanaka Tomoaki , Uno Takashi
Published: March 2022

Taq1A polymorphism is a DRD2 gene variant located in an exon of the ANKK1 gene and has an important role in the brain’s dopaminergic functions. Some studies have indicated that A1 carriers have an increased risk of developing Parkinson’s disease (PD) and show poorer clinical performance than A2 homo carriers. Previous studies have suggested that A1 carriers had fewer dopamine D2 receptors in the caudate and increased cortical activity as a compensatory mechanism. However, there is little information about morphological changes associated with this polymorphism in patients with PD. The study’s aim was to investigate the relationship between brain volume and Taq1A polymorphism in PD using voxel-based morphometry (VBM). Based on Taq1A polymorphism, 103 patients with PD were divided into two groups: A1 carriers (A1/A1 and A1/A2) and A2 homo carriers (A2/A2). The volume of the left prefrontal cortex (PFC) was significantly decreased in A2 homo carriers compared to A1 carriers. This finding supports the association between Taq1A polymorphism and brain volume in PD and may explain the compensation of cortical function in A1 carriers with PD.
Managing the Conflict between Economic and Social Factors in a Lean Context
Authors: Boutayeb A. , Ennadi A. , Chamat A. , Touache A.
Published: March 2022

The Lean approach has been a huge success in various public and private entities throughout the world over the last few decades. However, there are still expected needs regarding the social climate to improve working conditions of the employees. This paper presents the conflict between economic and social factors, which has a huge effect on staff involvement and motivation. This article is based on a descriptive investigation that involved 130 people. According to survey data, more than 60% of individuals believe that Lean degrades social factors, particularly in impoverished nations. A case study was conducted to present a real-life example of Lean’s negative effects on working conditions. This example clearly demonstrates the influence of Lean on ergonomics, safety, and environment (ESE). This paper allows for a better understanding of the negative effects of Lean on social factors and business performance.
Renal Cancer Detection: Fusing Deep and Texture Features from Histopathology Images
Authors: Cai Jianxiu , Liu Manting , Zhang Qi , Shao Ziqi , Zhou Jingwen , Guo Yongjian , Liu Juan , Wang Xiaobin , Zhang Bob , Li Xi
Published: March 2022

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values, with many computer‐aided diagnosis systems using common deep learning methods that have been proposed to save time and labour. Even though deep learning methods are an end‐to‐end method, they perform exceptionally well given a large dataset and often show relatively inferior results for a small dataset. In contrast, traditional feature extraction methods have greater robustness and perform well with a small/medium dataset. Moreover, a texture representation‐based global approach is commonly used to classify histological tissue images expect in explicit segmentation to extract the structure properties. Considering the scarcity of medical datasets and the usefulness of texture representation, we would like to integrate both the advantages of deep learning and traditional machine learning, i.e., texture representation. To accomplish this task, we proposed a classification model to detect renal cancer using a histopathology dataset by fusing the features from a deep learning model with the extracted texture feature descriptors. Here, five texture feature descriptors from three texture feature families were applied to complement Alex‐Net for the extensive validation of the fusion between the deep features and texture features. The texture features are from (1) statistic feature family: histogram of gradient, gray‐level cooccurrence matrix, and local binary pattern; (2) transform‐based texture feature family: Gabor filters; and (3) model‐based texture feature family: Markov random field. The final experimental results for classification outperformed both Alex‐Net and a singular texture descriptor, showing the effectiveness of combining the deep features and texture features in renal cancer detection.
HSP90 Inhibition Overcomes Resistance to Molecular Targeted Therapy in BRAFV600E-mutant High-grade Glioma
Authors: Sasame Jo , Ikegaya Naoki , Kawazu Masahito , Natsumeda Manabu , Hayashi Takahiro , Isoda Masataka , Satomi Kaishi , Tomiyama Arata , Oshima Akito , Honma Hirokuni , Miyake Yohei , Takabayashi Katsuhiro , Nakamura Taishi , Ueno Toshihide , Matsushita Yuko , Iwashita Hiromichi , Kanemaru Yu , Murata Hidetoshi , Ryo Akihide , Terashima Keita , Yamanaka Shoji , Fujii Yukihiko , Mano Hiroyuki , Komori Takashi , Ichimura Koichi , Cahill Daniel P. , Wakimoto Hiroaki , Yamamoto Tetsuya , Tateishi Kensuke
Published: March 2022

Purpose:

Molecular targeted therapy using BRAF and/or MEK inhibitors has been applied to BRAFV600E-mutant high-grade gliomas (HGG); however, the therapeutic effect is limited by the emergence of drug resistance.

Experimental Design:

We established multiple paired BRAFV600E-mutant HGG patient-derived xenograft models based on tissues collected prior to and at relapse after molecular targeted therapy. Using these models, we dissected treatment-resistant mechanisms for molecular targeted therapy and explored therapeutic targets to overcome resistance in BRAFV600E HGG models in vitro and in vivo.

Results:

We found that, despite causing no major genetic and epigenetic changes, BRAF and/or MEK inhibitor treatment deregulated multiple negative feedback mechanisms, which led to the reactivation of the MAPK pathway through c-Raf and AKT signaling. This altered oncogenic signaling primarily mediated resistance to molecular targeted therapy in BRAFV600E-mutant HGG. To overcome this resistance mechanism, we performed a high-throughput drug screening to identify therapeutic agents that potently induce additive cytotoxicity with BRAF and MEK inhibitors. We discovered that HSP90 inhibition combined with BRAF/MEK inhibition coordinately deactivated the MAPK and AKT/mTOR pathways, and subsequently induced apoptosis via dephosphorylation of GSK3β (Ser9) and inhibition of Bcl-2 family proteins. This mediated potent cytotoxicity in vitro and in vivo in refractory models with acquired resistance to molecular targeted therapy.

Conclusions:

The combination of an HSP90 inhibitor with BRAF or MEK inhibitors can overcome the limitations of the current therapeutic strategies for BRAFV600E-mutant HGG.
Venetoclax Cooperates with Ionizing Radiation to Attenuate Diffuse Midline Glioma Tumor Growth
Authors: Madhavan Krishna , Balakrishnan Ilango , Lakshmanachetty Senthilnath , Pierce Angela , Sanford Bridget , Fosmire Susan , Elajaili Hanan B. , Walker Faye , Wang Dong , Nozik Eva S. , Mitra Siddhartha S. , Dahl Nathan A. , Vibhakar Rajeev , Venkataraman Sujatha
Published: March 2022

Purpose:

Tumor relapse after radiotherapy is a major hurdle in treating pediatric H3K27M-mutant diffuse midline gliomas (DMG). Radiotherapy-induced stress increases association of BCL2 family of proteins with BH3 pro-apoptotic activators preventing apoptosis. We hypothesized that inhibition of radiotherapy-induced BCL2 with a clinically relevant inhibitor, venetoclax, will block BCL2 activity leading to increased apoptosis. BCL2 has never been implicated in DMG as a radiotherapy-induced resistant mechanism.

Experimental Design:

We performed an integrated genomic analysis to determine genes responsible for radioresistance and a targeted drug screen to identify drugs that synergize with radiation in DMG. Effect of venetoclax on radiation-naïve and 6 Gy radiation on cells was evaluated by studying cell death, changes in BCL2 phosphorylation, reactive oxygen species (ROS), and apoptosis, as well as BCL2 association with BH3 apoptosis initiators. The efficacy of combining venetoclax with radiation was evaluated in vivo using orthotopic xenograft models.

Results:

BCL2 was identified as a key regulator of tumor growth after radiation in DMGs. Radiation sensitizes DMGs to venetoclax treatment independent of p53 status. Venetoclax as a monotherapy was not cytotoxic to DMG cells. Postradiation venetoclax treatment significantly increased cell death, reduced BCL2–BIM association, and augmented mitochondrial ROS leading to increased apoptosis. Combining venetoclax with radiotherapy significantly enhanced the survival of mice with DMG tumors.

Conclusions:

This study shows that venetoclax impedes the antiapoptotic function of radiation-induced BCL2 in DMG, leading to increased apoptosis. Results from these preclinical studies demonstrate the potential use of the BCL2 inhibitor venetoclax combined with radiotherapy for pediatric DMG.
Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1)
Authors: Neuman Rugina I. , Baars Milan D. , Saleh Langeza , Broekhuizen Michelle , Nieboer Daan , Cornette Jérôme , Schoenmakers Sam , Verhoeven Michel , Koch Birgit C.P. , Russcher Henk , van den Berg Sjoerd A.A. , van den Meiracker Anton H. , Visser Willy , Danser A.H. Jan
Published: March 2022

Background:

Low sFlt-1 (soluble Fms-like tyrosine kinase-1) and ET-1 (endothelin-1) levels have been reported in preeclamptic women using proton pump inhibitors.

Methods:

Here, we examined whether the proton pump inhibitor omeprazole could acutely reduce sFlt-1 and ET-1 (measured as CT-proET-1 [C-terminal pro-endothelin-1]), or increase free PlGF (placental growth factor) in 20 women with confirmed preeclampsia. Primary outcome was specified as the difference in sFlt-1, PlGF, or CT-proET-1 after 4 days of omeprazole versus 20 preeclamptic women not receiving omeprazole.

Results:

Mean maternal age was 30 years, and median gestational age was 30
+3
weeks. Baseline sFlt-1 levels were identical in both groups, and the same was true for PlGF or CT-proET-1. After 4 days, sFlt-1 levels remained similar in women not receiving omeprazole compared with women receiving omeprazole, while the levels of PlGF and CT-proET-1 also did not differ between groups. Women receiving omeprazole had a similar prolongation of pregnancy after inclusion compared with those in the nonomeprazole group (median 15 versus 14 days). Except for a higher neonatal intubation rate in the nonomeprazole group (31% versus 4%,
P
=0.02), there were no differences in maternal/perinatal complications. Finally, making use of the placenta perfusion model, we established that both omeprazole and its S-isomer, esomeprazole, when maternally applied, reached the fetal compartment (fetal-to-maternal ratio’s 0.43–0.59), while only esomeprazole inhibited placental sFlt-1 release.

Conclusions:

Administration of omeprazole to women with confirmed preeclampsia does not alter their circulating levels of sFlt-1, PlGF, or ET-1, arguing against a role of this drug as a treatment for this syndrome.
Constraining Predicate Fronting
Authors: van Urk Coppe
Published: March 2022

A number of languages have been argued to establish basic word order by means of VP-fronting (e.g., Kayne 1994, Massam 2001). However, many such analyses overgenerate: some material thought to be VP-internal never appears fronted and must apparently always be stranded (Chung 2005, Massam 2010). Here, I provide novel evidence for VP-fronting in an SVO language, the understudied Polynesian outlier Imere (Vanuatu), motivated by the placement of adverbial particles. But this analysis too faces the stranding problem: VP-fronting cannot drag along any DPs, PPs, or CPs. To solve this issue, I propose that VP-fronting is accompanied by distributed deletion (Fanselow and Ćavar 2001), driven by a constraint that favors realizing only the verb. I extend this analysis to eight other VP-fronting languages, from five language families. In all these languages, what remains in the fronted VP is a structurally reduced dependent, like an adverbial particle or a determinerless object. Building on Clemens 2014, 2019, I adopt a constraint that requires dependents of a head that spell out in the same phase to remain adjacent, thus surviving distributed deletion.
Deducing the Coordinand Constraint
Authors: Fortuny Jordi
Published: March 2022

Assuming Grosu’s (1973) decomposition of Ross’s (1967) Coordinate Structure Constraint into the Conjunct Constraint and the Element Constraint, this article searches for a principled account for the Conjunct Constraint, rebaptized as the Coordinand Constraint. It defends the proposal that different families of effects of the Coordinand Constraint are related to different factors: (a) the lexical information provided by a coordinator, (b) the economy of syntactic displacement operations, and (c) an interface condition prohibiting self-coordination. These three factors are not primitive, but derive from Chomsky’s (1991) Least Effort Principle. Therefore, the Coordinand Constraint is deduced, ultimately, from the Least Effort Principle.
Nasal Assimilation Counterfeeding and Allomorphy in Haitian: Nothing Is Still Something!
Authors: Lahrouchi Mohamed , Ulfsbjorninn Shanti
Published: March 2022

Haitian has optional regressive nasal assimilation in a vowel-nasal (VN) context: /fami/ [fãmi] ‘family’. It is found also in recent loan-words in contexts where the source lacks phonetic nasalization. This process systematically underapplies in VNs that correspond to vowel- rhotic-nasal (VRN) sequences in French: [ʃãm] chambre ‘room’ vs. [ʃam] charme ‘charm’. We claim that etymological VRN and VR# have a different synchronic description: VRNs have no R, but VR#s do. VRNs crucially contain an empty CV that disrupts the locality between the trigger/target of nasal assimilation, hence the counterfeeding: /ʃam/ = [ʃãm] ‘room’ vs. /ʃaCVm/ = [ʃam] / *[ʃãm] ‘charm’. According to this analysis, only VR#s have synchronic R: [tε] ‘land’ vs. [ã-teʀ-e] ‘to land’. VR# forms interact with the morphology in interesting ways. Haitian has a case of nonoptimizing phonologically conditioned allomorph selection (PCA), /-a/ after V and /-la/ after C: [lapli-a] ‘the rain’ vs. [ʃat-la] ‘the cat’. However, here VR# forms create opaque and nonoptimizing R-less forms: [tε-a] / *[tε-ʀa] ‘the land’ (cf. [ã-teʀ-e] ‘to land’). This is solved with underlying floating consonants and a prevocalic phonological condition on R. PCA selection is eliminated since the surface variants are generated phonologically from unique underlying forms.
Forgotten keyworkers: the experiences of British seafarers during the COVID-19 pandemic
Authors: Devereux Helen , Wadsworth Emma
Published: March 2022

During the COVID-19 pandemic the UK Government designated seafarers as keyworkers. This article explores their experiences in an industry operating under international legislation designed to ensure and maintain their employment and working conditions. Three hundred and fifty-two British seafarers completed an online questionnaire. The findings revealed two key themes: the erosion of the terms and conditions of those who work at sea, and the differing experiences of those who were precariously employed on single voyage contracts in comparison to those in permanent employment. In contrast with precariously employed individuals, more seafarers with permanent contracts were joining the vessel as normal and fewer were not being paid having been unable to join a ship as scheduled. In a similar vein, fewer permanently employed seafarers were adversely financially impacted during the pandemic. The article concludes that those with the weakest employment relationships have experienced the greatest challenges as a result of the COVID-19 pandemic–a scenario which was possible as a result of the limited enforcement of the regulatory framework intended to protect those who work at sea.
Different Exercise Time on 5-HT and Anxiety-like Behavior in the Rat With Vascular Dementia
Authors: Fan Yongzhao , Zhang Linlin , Kong Xiaoyang , Liu Kun , Wu Hao
Published: March 2022

Background

Previous studies have demonstrated that pre-exercise suppresses anxiety-like behavior, but the effects of different exercise times on vascular dementia induced anxiety-like behavior have not been well investigated.

Objective

The present study aims to investigate the underlying neurochemical mechanism of different pre-vascular-dementia exercise times on 5-HT and anxiety-like behavior in rats with vascular dementia.

Methods

32 Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group (S group, n = 8), vascular dementia group (VD group, n = 8), 1-week physical exercise and vascular dementia group (1WVD group, n = 8), and 4 weeks physical exercise and vascular dementia group (4WVD group, n = 8). 1 week and 4 weeks of voluntary wheel running were used as pre-exercise training. The vascular dementia model was established by bilateral common carotid arteries occlusion (BCCAo) for 1 week. But bilateral common carotid arteries were not ligated in the sham group. The level of hippocampal 5-HT was detected with in vivo microdialysis coupled with high-performance liquid chromatography (MD-HPLC). Elevated plus maze (EPM), open field (OF), and light/dark box test were used to test anxiety-like behavior.

Results

Compared with the C group, the hippocampal 5-HT was significantly decreased in the VD group after 1 week of ligated operation. The hippocampal 5-HT levels in 1WVD and 4WVD groups were substantially higher than the level in the VD group. The hippocampal 5-HT level has no significant difference among C, 1WVD, and 4WVD. Behavioral data suggested that the rats in the VD group developed obvious anxiety-like behavior after 1 week of ligation surgery. Still, the rats in 1WVD and 4WVD groups did not show significant anxiety-like behavior.

Conclusion

Both 1 week and 4 weeks of voluntary running wheel exercise can inhibit the anxiety-like behavior in rats with vascular dementia by upregulating 5-HT levels in the hippocampus in the VD model.
Genomic architecture of 5S rDNA cluster and its variations within and between species
Authors: Ding Qiutao , Li Runsheng , Ren Xiaoliang , Chan Lu-yan , Ho Vincy W. S. , Xie Dongying , Ye Pohao , Zhao Zhongying
Published: March 2022

Background

Ribosomal DNAs (rDNAs) are arranged in purely tandem repeats, preventing them from being reliably assembled onto chromosomes during generation of genome assembly. The uncertainty of rDNA genomic structure presents a significant barrier for studying their function and evolution.

Results

Here we generate ultra-long Oxford Nanopore Technologies (ONT) and short NGS reads to delineate the architecture and variation of the 5S rDNA cluster in the different strains of C. elegans and C. briggsae. We classify the individual rDNA’s repeating units into 25 types based on the unique sequence variations in each unit of C. elegans (N2). We next perform assembly of the cluster by taking advantage of the long reads that carry these units, which led to an assembly of 5S rDNA cluster consisting of up to 167 consecutive 5S rDNA units in the N2 strain. The ordering and copy number of various rDNA units are consistent with the separation time between strains. Surprisingly, we observed a drastically reduced level of variation in the unit composition in the 5S rDNA cluster in the C. elegans CB4856 and C. briggsae AF16 strains than in the C. elegans N2 strain, suggesting that N2, a widely used reference strain, is likely to be defective in maintaining the 5S rDNA cluster stability compared with other wild isolates of C. elegans or C. briggsae.

Conclusions

The results demonstrate that Nanopore DNA sequencing reads are capable of generating assembly of highly repetitive sequences, and rDNA units are highly dynamic both within and between population(s) of the same species in terms of sequence and copy number. The detailed structure and variation of the 5S rDNA units within the rDNA cluster pave the way for functional and evolutionary studies.
Effect of age adjustment on two triage methods
Authors: Kemp Kirsi , Alakare Janne , Kätkä Minna , Lääperi Mitja , Lehtonen Lasse , Castrén Maaret
Published: March 2022

Background

Most emergency departments rely on acuity assessment, triage, to recognize critically ill patients that need urgent treatment, and to allocate resources according to need. The accuracy of commonly used triage instruments such as the Emergency Severity Index (ESI) is lower for older adults compared to young patients. We aim to examine, whether adjusting the triage category by age leads to improvement in sensitivity without excessive increase in patient numbers in the higher triage categories. The primary outcome measure was 3-day mortality and secondary outcomes were 30-day mortality, hospital admission, and HDU/ICU admissions.

Methods

We gathered data of all adult patients who had an unscheduled visit to any of our three emergency departments within one month. The data was analysed for 3-day mortality, 30-day mortality, hospital admission, and high dependency unit or intensive care unit (HDU/ICU) admission. The analysis was run for both the standard ESI triage method and a local 3-level Helsinki University Hospital (HUH) method. A further analysis was run for both triage methods with age adjustment. Net reclassification improvement values were calculated to demonstrate the effect of age adjustment.

Results

Thirteen thousand seven hundred fifty-nine patients met the study criteria, median age was 57. 3-day mortality AUCs for unadjusted HUH and ESI triage were 0.77 (0.65–0.88) and 0.72 (0.57–0.87); 30-day mortality AUCs were 0.64 (0.59–0.69) and 0.69 (0.64–0.73); hospital admission AUCs were 0.60 (0.68–0.71) and 0.66 (0.65–0.68) and HDU/ICU admission AUCs were 0.67 (0.64–0.70) and 0.82 (0.79–0.86), respectively. Age adjustment improved accuracy for 30-day mortality and hospital admission. With the threshold age of 80, AUCs for 30-day mortality were 0.73 (0.68–0.77) and 0.77 (0.73–0.81) and for hospital admission, 0.66 (0.65–0.67) and 0.72 (0.71–0.73) for the HUH and ESI triage. The effect was similar with all cut off ages.

Conclusion

Moving older adults into a more urgent triage category based on age, improved the triage instruments’ performance slightly in predicting 30-day mortality and hospital admission without excessive increase in patient numbers in the higher triage categories. Age adjustment did not improve HDU/ICU admission or 3-day mortality prediction.