bluuebunny/crossref_metadata_2025 huggingface dataset:
New Approach for Risk Estimation Algorithms of BRCA1/2 Negativeness Detection with Modelling Supervised Machine Learning Techniques
Authors: Yazici Hulya , Odemis Demet Akdeniz , Aksu Dogukan , Erdogan Ozge Sukruoglu , Tuncer Seref Bugra , Avsar Mukaddes , Kilic Seda , Turkcan Gozde Kuru , Celik Betul , Aydin Muhammed Ali
Published: December 2020

BRCA1/2 gene testing is a difficult, expensive, and time-consuming test which requires excessive work load. The identification of the BRCA1/2 gene mutations is significantly important in the selection of treatment and the risk of secondary cancer. We aimed to develop an algorithm considering all the clinical, demographic, and genetic features of patients for identifying the BRCA1/2 negativity in the present study. An experimental dataset was created with the collection of the all clinical, demographic, and genetic features of breast cancer patients for 20 years. This dataset consisted of 125 features of 2070 high-risk breast cancer patients. All data were numeralized and normalized for detection of the BRCA1/2 negativity in the machine learning algorithm. The performance of the algorithm was identified by studying the machine learning model with the test data.

k

nearest neighbours (KNN) and decision tree (DT) accuracy rates of 9 features involving Dataset 2 were found to be the most effective. The removal of the unnecessary data in the dataset by reducing the number of features was shown to increase the accuracy rate of algorithm compared with the DT. BRCA1/2 negativity was identified without performing the BRCA1/2 gene test with 92.88% accuracy within minutes in high-risk breast cancer patients with this algorithm, and the test associated result waiting stress, time, and money loss were prevented. That algorithm is suggested be useful in fast performing of the treatment plans of patients and accurately in addition to speeding up the clinical practice.
Effect of Gap and Shims on the Strain and Stress State of the Composite-Aluminum Hybrid Bolted Structure
Authors: Yue Xuande , An Luling , Ye Xin , Wang Chufan , Cai Yuebo , Xiao Ruiheng
Published: December 2020

The composite-aluminum hybrid bolted structures are widely used in aircraft. Due to low molding accuracy of composite components, gaps always occur between components during assembly. In this case, the bolt connection can cause a complex strain and stress state of component. It may adversely affect the mechanical properties or cause local damage of the structure. A simplified model of the composite-aluminum assembly structure was established in this paper. Then, the influence of forced assembly, liquid shim, and peelable fiberglass shim on the strain and stress state of the composite-aluminum hybrid bolted structure was studied. A bolt connection experimental device was designed to apply a preload to the specimen. The strain field on the specimen surface was measured using the 3D-DIC strain measurement system. The finite element model was established to study the interlaminar stress and damage state of composite laminates. It is found that the strain of specimen in the

X

-direction is mainly affected by the bending deformation, while the strain in the

Y

-direction is mainly affected by the compression of bolt head. For composite laminates, the strain value in the

X

-direction can be reduced by 8.31%-70.97% with shims. As for the strain value in the

Y

-direction, the liquid shim can only reduce it up to 23.93%when the gap is large. In addition, the liquid shim and peelable fiberglass shim cannot reduce the stress value of all interlaminar elements, but it can make the stress distribution more uniform and improve the stress state of the interlaminar element when the shim was more than 0.8 mm.
Significance of the Nested Structure in Multiplex World Trade Networks
Authors: Ren Zhuo-Ming , Pan Xiao , Zhang Yi-Cheng
Published: December 2020

The hierarchically nested structure is widely observed in a broad range of real systems, encompassing ecological networks, economic and trade networks, communication networks, among many others. However, there remain statistical challenges of the prevalence of nestedness. In response to this problem, we focus on the effect of incomplete information and the inputted matrix size, the role of network density and degree sequences, and the relevance of degree-degree correlation to conduct systematic research on the significance of the nested structure according to multiplex world trade networks. Firstly, the nested structure can observe significantly when suffering incomplete information and varying inputted matrix size. Secondly, to analyze the role of network density and degree sequences in nested structure, we use “swappable rows, swappable columns” null model which conserves the network size and density, and “fixed in-degree, fixed out-degree” null model which not only preserves the network size and density but also keeps node degree to do randomization tests of nestedness. The randomizations of two null models remark that most nested structures are not determined by network density and degree sequences but closely related to them. Finally, we investigate degree-degree correlation in nested networks, and the results show that the nested structure is negatively related with degree-degree correlation of the network. Following the empirical analysis train of thought, we argue that nestedness is still a unique feature of the network.
A Comparative Analysis of Different Outlier Detection Techniques in Cognitive Radio Networks with Malicious Users
Authors: Ahmed Arshed , Khan Muhammad Sajjad , Gul Noor , Uddin Irfan , Kim Su Min , Kim Junsu
Published: December 2020

In a cognitive radio (CR), opportunistic secondary users (SUs) periodically sense the primary user’s (PU’s) existence in the network. Spectrum sensing of a single SU is not precise due to wireless channels and hidden terminal issues. One promising solution is cooperative spectrum sensing (CSS) that allows multiple SUs’ cooperation to sense the PU’s activity. In CSS, the misdetection of the PU signal by the SU causes system inefficiency that increases the interference to the system. This paper introduces a new category of a malicious user (MU), i.e., a lazy malicious user (LMU) with two operating modes such as an awakened mode and sleeping mode. In the awakened mode, the LMU reports accurately the PU activity like other normal cooperative users, while in the sleeping mode, it randomly reports abnormal sensing data similar to an always yes malicious user (AYMU) or always no malicious user (ANMU). In this paper, statistical analysis is carried out to detect the behavior of different abnormal users and mitigate their harmful effects. Results are collected for the different hard combination schemes in the presence of the LMU and opposite categories of malicious users (OMUs). Simulation results collected for the error probability, detection probability, and false alarm at different levels of the signal-to-noise ratios (SNRs) and various contributions of the LMUs and OMUs confirmed that out of the many outlier detection tests, the median test performs better in MU detection by producing minimum error probability results in the CSS. The results are further compared by keeping minimum SNR values with the mean test, quartile test, Grubbs test, and generalized extreme studentized deviate (GESD) test. Similarly, performance gain of the median test is examined further separately in the AND, OR, and voting schemes that show minimum error probability results of the proposed test as compared with all other outlier detection tests in discarding abnormal sensing reports.
Application of Improved Single‐Hole Superposition Theory in Nonequal Cross‐Section Tunnel Intersection
Authors: Liu Ning , Huang Yi-Xiong , Cai Wei , Chen Kun
Published: December 2020

With the excavation towards the intersecting tunnels’ direction, the impact on the surrounding rock stress between the two tunnels will gradually decrease, but how it decreased is not clear. At present, engineers often directly superimpose the stress in the triangular area of the crossing tunnel when calculating the stress in this area (single‐hole superposition theory). The theory is also used as the main theory to consider the surrounding rock stress for support which is difficult to explain the situation of nonuniform cross‐section centers not in the same plane. The safety level of support is mainly determined by construction experience which is unable to determine how to adjust the support level with the increase in the horizontal distance of intersecting tunnel, causing the insufficient utilization of materials. This paper derives theoretically the stress calculation of the triangular area of circular cross tunnels with different cross sections and analyzes the surrounding rock stress law of the intersecting tunnels triangular area from different cross‐section dimensions (the difference in diameter between the two tunnels is twice, 3 times, and 4 times) and different intersection angles. And the results show that, compared with the case of equal tunnel diameters, the stress influence area of the surrounding rock in the triangle area mainly expands to the side of the small section with the increase of the cross‐section difference of the intersecting tunnels; the dangerous area of the surrounding rock in the triangle area moves vertically to the small section; the safest condition is the two tunnels with 90° intersecting angle. The theoretical calculation model of this paper is verified by the previous research results.
Influence of Oxidation Damages on Mechanical Properties of SiC/SiC Composite Using Domestic Hi-Nicalon Type SiC Fibers
Authors: Jin Enze , Ma Denghao , Yuan Zeshuai , Sun Wenting , Wang Hao , Zhang Jiajia , Gong Xiaodong , Huang Lina , Han Botao , Sun Xin , Feng Zhihai , Li Junping
Published: December 2020

Here, we show that when the oxidation treatment temperature exceeded 600°C, the tensile strength of SiC/SiC begins to decrease. Oxidation leads to the damages on the PyC fiber/matrix interface, which is replaced by SiO2 at higher temperature. The fracture mode converts from fiber pull-out to fiber-break as the fiber/matrix interface is filled with SiO2. Oxidation time also plays an important role in affecting the tensile strength of SiC/SiC. The tensile modulus decreases with temperature from RT to 800°C, then increases above 800°C due to the decomposition of remaining CSi

x

O

y

and crystallization of the SiC matrix. A special surface densification treatment performed in this study is confirmed to be an effective approach to reduce the oxidation damages and improve the tensile strength of SiC/SiC after oxidation.
Effective Estimation of Hourly Global Solar Radiation Using Machine Learning Algorithms
Authors: Guher Abdurrahman Burak , Tasdemir Sakir , Yaniktepe Bulent
Published: December 2020

The precise estimation of solar radiation is of great importance in solar energy applications with respect to installation and capacity. In estimate modelling on selected target locations, various computer-based and experimental methods and techniques are employed. In the present study, the Multilayer Feed-Forward Neural Network (MFFNN),

K

-Nearest Neighbors (

K

-NN), a Library for Support Vector Machines (LibSVM), and M5 rules algorithms, which are among the Machine Learning (ML) algorithms, were used to estimate the hourly average solar radiation of two geographic locations on the same latitude. The input variables that had the most impact on solar radiation were identified and grouped as a result of 29 different applications that were developed by using 6 different feature selection methods with Waikato Environment for Knowledge Analysis (WEKA) software. Estimation models were developed by using the selected data groups and all input variables for each target location. The results show that the estimations developed with the feature selection method were more successful for target locations, and the radiation potentials were similar. The performance of the estimation models was evaluated by comparing each model with different statistical indicators and with previous studies. According to the RMSE, MAE,

R

2

, and SMAPE statistical scales, the results of the most successful estimation models that were developed with MFFNN were 0.0508-0.0536, 0.0341-0.0352, 0.9488-0.9656, and 7.77%-7.79%, respectively.
Dynamics of a Diffusive Multigroup SVIR Model with Nonlinear Incidence
Authors: Xu Jinhu , Geng Yan
Published: December 2020

In this paper, a multigroup SVIR epidemic model with reaction-diffusion and nonlinear incidence is investigated. We first establish the well-posedness of the model. Then, the basic reproduction number

ℜ

0

is established and shown as a threshold: the disease-free steady state is globally asymptotically stable if

ℜ

0

<
1

, while the disease will be persistent when

ℜ

0

>
1

. Moreover, applying the classical method of Lyapunov and a recently developed graph-theoretic approach, we established the global stability of the endemic equilibria for a special case.
Probabilistic Seismic Analysis of the Deep Sliding Stability of a Concrete Gravity Dam‐Foundation System
Authors: Liang Hui , Guo Shengshan , Tian Yifu , Tu Jin , Li Deyu , Yan Chunli
Published: December 2020

There are various uncertainties in the design, construction, and operation of dams. These uncertainties have an important impact on the seismic response and seismic safety evaluation of concrete dams. In this research, a typical nonoverflow monolith of a concrete gravity dam is selected as a case study for the sliding stability analysis. Based on the analysis and demonstration of parameter sensitivity of friction coefficients and cohesion and their influence on the deep antisliding stability of the dam‐foundation system, the probabilistic seismic analysis of a gravity dam‐foundation system is carried out through Monte Carlo analysis with a large sample number. Damage levels are defined based on the sliding instability failure mode along with the corresponding threshold values of the damage index. Thus, seismic fragility analysis is investigated, and seismic fragility curves are obtained for the vulnerability assessment under earthquake hazards. The overall seismic stability of the gravity dam is evaluated, which provides the basis for the seismic safety evaluation in the probabilistic framework.
Estimation Method of Carbon Emissions in the Embodied Phase of Low Carbon Building
Authors: Liu Hongwei , Li Jun , Sun Yafei , Wang Yanshu , Zhao Haichun
Published: December 2020

The carbon emission at the embodied phase is a complex combination, extending the life cycle of the building, defining the process of the embodied phase scientifically and finding out the direct and indirect carbon emission sources in the embodied phase. Building materials have the characteristics of “low carbon surface, hidden high carbon.” Emission factor calculation method is used to establish carbon emission model for building materials. Considering the effect of design optimization on the carbon emissions of the whole life cycle of the building, a low carbon level system is set up to optimize the target of low carbon design. In the construction phase, the carbon emission sources, emission boundary, and calculation model are determined according to the subdivisional engineering division method. Through a series of process decomposition, the total amount of carbon emissions at the embodied phase can be obtained, and the carbon emission quota list at the embodied phase can be compiled to provide technical support for the carbon trading mechanism of the building.
Analyzing the Characteristics and Causes of Location Spatial Agglomeration of Listed Companies: An Empirical Study of China’s Yangtze River Economic Belt
Authors: Meng Deyu , Wei Guoen , Sun Pingjun
Published: December 2020

Enhancing urban development vitality and optimizing the allocation of regional industrial factors require a comprehensive analysis of listed companies, such as the overall distribution network, agglomeration evolution trend, industrialization layout, and driving mechanism. Using 1,624 A-share listed companies in China's Yangtze River Economic Belt as research area, this study integrated trend surface analysis (TSA), exploratory spatial data analysis (ESDA), standard deviation ellipse (SDE), and spatial regression model methods. The main results are as follows: (1) The overall quantity scale of the listed companies in the Yangtze River Economic Belt has achieved significant growth, but the spatial difference of location selection persists. The spatial configuration formed a hierarchical urban distribution pattern with the Yangtze River Delta region as the agglomeration core and the provincial capitals as the fulcrum. (2) Listed companies accelerate the expansion of the Yangtze River Delta region. Chengdu, Wuhan, Changsha, and other central-western provincial capitals gradually increased the region’s attractiveness. High-high and low-low agglomerations remain the main forms of agglomeration. (3) There are significant differences in the location selection of listed companies with varying specialization levels, forming a relatively different alienated high-value distribution structure among various industry types. (4) The levels of knowledge spillover, city scale, and policy support level are major factors affecting the location selection process of listed companies in the Yangtze River Economic Belt. For low-level city network with few listed companies, city scale and knowledge spillover levels are significant determinants for the development of headquarters’ economy. For high-level city network, along with the level of knowledge spillovers and policy support, globalization level has an important contribution to the shaping of the location advantages of attracting the layout of listed companies.
BIM Adoption for Facility Management in Urban Rail Transit: An Innovation Diffusion Theory Perspective
Authors: Xu Xiaodong , Wang Guangbin , Cao Dongping , Zhang Zhujing
Published: December 2020

Although building information modeling (BIM) has demonstrated to be an effective tool for the construction of urban rail transit worldwide, it has not gained the same popularity in the facility management (FM) of urban rail transit. The objective of this study is to investigate the BIM application areas for FM in urban rail transit from an innovation diffusion theory perspective, in order to gain efficient operation and maintenance (O&M) in urban rail transit. A total of 18 BIM application areas were first identified through semistructured interviews. A questionnaire survey was then conducted to further quantitatively characterize the relative advantage, ease of use, trialability, observability, and compatibility of these areas. Statistical analysis of the survey results provided evidence that, currently, BIM application areas directly related with facilities and equipment are most likely to be adopted. Correlation analysis further indicates that the perceived innovation diffusion characteristics of these BIM application areas significantly correlate with the development level of urban rail transit in different regions. The findings contribute to a broadened understanding of the complex innovation diffusion process of BIM for FM in urban rail transit and provide insights into how BIM can be more effectively adopted in the domain.
A Streamlined Approach to Rapidly Detect SARS-CoV-2 Infection Avoiding RNA Extraction: Workflow Validation
Authors: Mio Catia , Cifù Adriana , Marzinotto Stefania , Bergamin Natascha , Caldana Chiara , Cattarossi Silvia , Cmet Sara , Cussigh Annarosa , Martinella Romina , Zucco Jessica , Verardo Roberto , Schneider Claudio , Marcon Barbara , Zampieri Stefania , Pipan Corrado , Curcio Francesco
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide from the beginning of 2020. The presence of viral RNA in samples by nucleic acid (NA) molecular analysis is the only method available to diagnose COVID-19 disease and to assess patients’ viral load. Since the demand for laboratory reagents has increased, there has been a worldwide shortage of RNA extraction kits. We, therefore, developed a fast and cost-effective viral genome isolation method that, combined with quantitative RT-PCR assay, detects SARS-CoV-2 RNA in patient samples. The method relies on the addition of Proteinase K followed by a controlled heat-shock incubation and, then, E gene evaluation by RT-qPCR. It was validated for sensitivity, specificity, linearity, reproducibility, and precision. It detects as low as 10 viral copies/sample, is rapid, and has been characterized in 60 COVID-19-infected patients. Compared to automated extraction methods, our pretreatment guarantees the same positivity rate with the advantage of shortening the time of the analysis and reducing its cost. This is a rapid workflow meant to aid the healthcare system in the rapid identification of infected patients, such as during a pathogen-related outbreak. For its intrinsic characteristics, this workflow is suitable for large-scale screenings.
A New Generative Neural Network for Bearing Fault Diagnosis with Imbalanced Data
Authors: You Wei , Shen Changqing , Chen Liang , Que Hongbo , Huang Weiguo , Zhu Zhongkui
Published: December 2020

Intelligent bearing fault diagnosis has received much research attention in the field of rotary machinery systems where miscellaneous deep learning methods are generally applied. Among these methods, convolution neural network is particularly powerful because of its ability to learn fruitful features from the original data. However, normal convolutions cannot fully utilize the information along the data flow while the features are being abstracted in deeper layers. To address this problem, a new supervised learning model is proposed for small sample size bearing fault diagnosis with consideration of imbalanced data. This model, which is developed based on a convolution neural network, has a high generalization ability, and its performance is verified by conducting two experiments that use data collected from a self-made bearing test rig. The proposed model demonstrates a favorable performance and is more effective and robust than other deep learning methods.
Fault Diagnosis of Rotating Machinery Based on One-Dimensional Deep Residual Shrinkage Network with a Wide Convolution Layer
Authors: Yang Jingli , Gao Tianyu , Jiang Shouda , Li Shijie , Tang Qing
Published: December 2020

In actual engineering applications, inevitable noise seriously affects the accuracy of fault diagnosis for rotating machinery. To effectively identify the fault classes of rotating machinery under noise interference, an efficient fault diagnosis method without additional denoising procedures is proposed. First, a one-dimensional deep residual shrinkage network, which directly takes the raw vibration signals contaminated by noise as input, is developed to realize end-to-end fault diagnosis. Then, to further enhance the noise immunity of the diagnosis model, the first layer of the model is set to a wide convolution layer to extract short time features. Moreover, an adaptive batch normalization algorithm (AdaBN) is introduced into the diagnosis model to enhance the adaptability to noise. Experimental results illustrate that the fault diagnosis model for rotating machinery based on one-dimensional deep residual shrinkage network with a wide convolution layer (1D-WDRSN) can accurately identify the fault classes even under noise interference.
Exposing Spoofing Attack on Flocking-Based Unmanned Aerial Vehicle Cluster: A Threat to Swarm Intelligence
Authors: Huang Xinyu , Tian Yunzhe , He Yifei , Tong Endong , Niu Wenjia , Li Chenyang , Liu Jiqiang , Chang Liang
Published: December 2020

With the rapid development of wireless communication technology and intelligent mobile devices, unmanned aerial vehicle (UAV) cluster is becoming increasingly popular in both civilian and military applications. Recently, a swarm intelligence-based UAV cluster study, aiming to enable efficient and autonomous collaboration, has drawn lots of interest. However, new security problems may be introduced with such swarm intelligence. In this work, we perform the first detailed security analysis to a kind of flocking-based UAV cluster with 5 policies, an upgrade version of the well-known Boids model. Targeting a realistic threat in a source-to-destination flying task, we design a data spoofing strategy and further perform complete vulnerability analysis. We reveal that such design and implementation are highly vulnerable. After breaking through the authentication of ad hoc on-demand distance vector (AODV) routing protocol by rushing attack, an attacker can masquerade as the first-arrival UAV within a specific scope of destination and generate data spoofing of arrival status to the following UAVs, so as to interfere with their normal flying paths of destination arrival and cause unexpected arrival delays amid urgent tasks. Experiments with detailed analysis from the 5-UAV cluster to the 10-UAV cluster are conducted to show specific feature composition-based attack effect and corresponding average delay. We also discuss promising defense suggestions leveraging the insights from our analysis.
GC‐MS Evaluation, Antioxidant Content, and Cytotoxic Activity of Propolis Extract from Peninsular Malaysian Stingless Bees, Tetrigona Apicalis
Authors: Mohamed Wan Ahmad Syazani , Ismail Noor Zafirah , Omar Eshaifol Azam , Abdul Samad Nozlena , Adam Siti Khadijah , Mohamad Sharlina
Published: December 2020

Introduction. Propolis has been used traditionally in several countries for treating various diseases as it possessed healing properties including antioxidant and anticancer qualities. In Peninsular Malaysia, Tetrigona apicalis is one of the species of stingless bees mainly found in virgin jungle reserves which largely contribute to propolis production. Therefore, this study is designed to evaluate the phytochemical contents, antioxidant properties, and the cytotoxic effect of ethanolic crude of propolis extract against MCF7 and MCF 10A cell lines. Method. The ethanolic extract of propolis (EEP) was extracted using 80% ethanol. Identification of phytochemical contents and antioxidant properties of EEP was analysed by gas chromatography‐mass spectrometry (GC‐MS) and using 2, 2′‐azinobis (3‐ethylbenzothiazoline‐6‐sulphonic acid) (ABTS) method, respectively. The EEP cytotoxic activity was evaluated on MCF7 and MCF 10A using 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide (MTT) assay. Results. Phytochemical contents of EEP demonstrated 28 compounds in which caryophyllene (99%), β‐amyrin (96%), α‐amyrin (93%), and caryophyllene oxide (93%) were the main compounds. The percentage of ABTS+ scavenging activity of EEP showed an inhibition of 9.5% with half‐inhibitory concentration (IC50) value of 1.68 mg/mL. The EEP reduced MCF7 cells viability at IC50 value of 62.24 μg/mL, 44.15 μg/mL, and 32.70 μg/mL at 24, 48, and 72 hours, respectively. The IC50 value of MCF 10A was 49.55 μg/mL, 56.05 μg/mL, and 72.10 μg/mL at 24, 48, and 72 hours, respectively. The EEP cytotoxic effect of T. apicalis was more selective towards MCF7 at 72‐hour incubation with a selectivity index (SI) of 2.20. Conclusion. The EEP has been shown to have antioxidants and potential bioactive compounds and inhibited proliferation of the MCF7 cells. Further studies on the EEP role in the apoptosis pathway and its screening towards other cell lines will be evaluated.
4D Trajectory Planning of Aircraft Taxiing considering Time and Fuel
Authors: Zhao Ningning , Li Nan , Sun Yu , Gao Zheng
Published: December 2020

Most of the traditional taxi path planning studies assume that the aircraft is in uniform speed, and the model is optimized based on the shortest taxi time. Although it is easy to solve, it does not consider the change of the speed profile when the aircraft turns, and the optimal taxiing time of the aircraft does not necessarily bring the optimal taxiing fuel consumption. In this paper, the aircraft’s taxi distance and the number of turns in the taxi are considered. The aircraft path planning model with the shortest total distance of the airport surface is established. The improved A

∗

algorithm is used to obtain the shortest path P. Based on this, the shortest path P is established. Considering the multitarget velocity profile model of time and fuel consumption, a heuristic search is used to generate an accurate velocity profile for each path to obtain a 4D trajectory of the aircraft and then quantitative analysis of the impact of aircraft pollutant emissions on the airport environment based on 4D trajectory taxi time. The experimental results show that, compared with the traditional optimization method without considering the turning times, the total taxiing distance and turning times of the aircraft are greatly reduced. By balancing the taxiing time and fuel consumption, a set of Pareto-optimal velocity profiles is generated for the aircraft taxiing path; at the same time, it will help the airport save energy and reduce emissions and improve the quality of the airport environment. It has a high practical application value and is expected to be applied in the real-time air traffic control decision of aircraft surface in the future.
Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case–Control Study in Southern China
Authors: Feng Ruimei , Chang Ellen T. , Liu Qing , Cai Yonglin , Zhang Zhe , Chen Guomin , Huang Qi-Hong , Xie Shang-Hang , Cao Su-Mei , Zhang Yu , Yun Jing-Ping , Jia Wei-Hua , Zheng Yuming , Liao Jian , Chen Yufeng , Huang Tingting , Lin Longde , Ernberg Ingemar , Huang Guangwu , Zeng Yi-Xin , Adami Hans-Olov , Ye Weimin
Published: December 2020

Background:

The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial.

Methods:

In a population-based case–control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose–response trends were evaluated using restricted cubic spline analysis.

Results:

Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93–1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95–1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64–0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose–response relation with NPC risk.

Conclusions:

Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose–response association complicates causal inference.

Impact:

Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
N-Acetyl-L-cysteine Promotes Ex Vivo Growth and Expansion of Single Circulating Tumor Cells by Mitigating Cellular Stress Responses
Authors: Teng Teng , Kamal Mohamed , Iriondo Oihana , Amzaleg Yonatan , Luo Chunqiao , Thomas Amal , Lee Grace , Hsu Ching-Ju , Nguyen John D. , Kang Irene , Hicks James , Smith Andrew , Sposto Richard , Yu Min
Published: December 2020

Circulating tumor cells (CTC) can be isolated via a minimally invasive blood draw and are considered a “liquid biopsy” of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for ex vivo expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small-molecule drug screen to identify compounds that can improve ex vivo culture efficiency for single CTCs. We found that N-acetyl-L-cysteine (NAC) and other antioxidants can promote ex vivo expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single-cell expansion. RNA-seq analysis of growing clones and nongrowing clones confirmed the effect by NAC, but also indicates that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with predominant senescent features. Despite the challenge in expanding all CTCs, NAC treatment led to establishment of single CTC clones that have similar tumorigenic features.

Implications:

Through a small molecule screen and validation study, we found that NAC could improve the success of ex vivo expansion of single CTCs by mitigating the initial stress, with the potential to facilitate the investigation of functional heterogeneity in CTCs.
AKT1 E17K Inhibits Cancer Cell Migration by Abrogating β-Catenin Signaling
Authors: Gao Sizhi Paul , Kiliti Amber J. , Zhang Kai , Vasani Naresh , Mao Ninghui , Jordan Emmet , Wise Hannah C. , Shrestha Bhattarai Tripti , Hu Wenhuo , Dorso Madeline , Rodrigues James A. , Kim Kwanghee , Hanrahan Aphrothiti J. , Razavi Pedram , Carver Brett , Chandarlapaty Sarat , Reis-Filho Jorge S. , Taylor Barry S. , Solit David B.
Published: December 2020

Mutational activation of the PI3K/AKT pathway is among the most common pro-oncogenic events in human cancers. The clinical utility of PI3K and AKT inhibitors has, however, been modest to date. Here, we used CRISPR-mediated gene editing to study the biological consequences of AKT1 E17K mutation by developing an AKT1 E17K–mutant isogenic system in a TP53-null background. AKT1 E17K expression under the control of its endogenous promoter enhanced cell growth and colony formation, but had a paradoxical inhibitory effect on cell migration and invasion. The mechanistic basis by which activated AKT1 inhibited cell migration and invasion was increased E-cadherin expression mediated by suppression of ZEB1 transcription via altered β-catenin subcellular localization. This phenotypic effect was AKT1-specific, as AKT2 activation had the opposite effect, a reduction in E-cadherin expression. Consistent with the opposing effects of AKT1 and AKT2 activation on E-cadherin expression, a pro-migratory effect of AKT1 activation was not observed in breast cancer cells with PTEN loss or expression of an activating PIK3CA mutation, alterations which induce the activation of both AKT isoforms. The results suggest that the use of AKT inhibitors in patients with breast cancer could paradoxically accelerate metastatic progression in some genetic contexts and may explain the frequent coselection for CDH1 mutations in AKT1-mutated breast tumors.

Implications:

AKT1 E17K mutation in breast cancer impairs migration/invasiveness via sequestration of β-catenin to the cell membrane leading to decreased ZEB1 transcription, resulting in increased E-cadherin expression and a reversal of epithelial–mesenchymal transition.
Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China
Authors: Xu Xiao-Qian , Rezhake Remila , Hu Shang-Ying , Chen Feng , Zhang Xun , Pan Qin-Jing , Zhang Wen-Hua , Ma Jun-Fei , Qiao You-Lin , Zhao Fang-Hui , Cruickshank Margaret
Published: December 2020

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35–45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%–74.4%) following 15 years HPV persistence to 3.5% (1.2%–9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%–29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%–100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%–39.1%) and lowest colposcopy referral of 33.2% (27.4%–39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round.

Prevention Relevance:

The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.
Association of IgG Glycosylation and Esophageal Precancerosis Beyond Inflammation
Authors: Wu Zhiyuan , Pan Huiying , Liu Di , Zhou Di , Tao Lixin , Zhang Jie , Wang Xiaonan , Wang Youxin , Wang Wei , Guo Xiuhua
Published: December 2020

This study aimed to investigate the association of IgG glycosylation and esophageal precancerosis for squamous cell carcinoma and determine its role in inflammation. Primary glycans selected by the least absolute shrinkage and selection operator (LASSO) algorithm were validated using univariate and multivariate logistics models plus restricted cubic spline functions. In total, 24 direct glycans and 27 derived traits were detected, among which four glycans and three derived traits were primarily selected. Then, GP5 (adjusted OR: 0.805), GP17 (adjusted OR: 1.305), G12n (adjusted OR: 1.271), Gal_1 (adjusted OR: 0.776) and Fuc (adjusted OR: 0.737) were validated and significantly associated with esophageal precancerosis. In addition, there was a consistent positive association in GP17 and G12n and a negative association in GP5, Gal_1, and Fuc by restricted cubic spline function. Compared with esophageal inflammation, GP17, G12n, and Fuc were still independently associated with precancerosis. In brief, the IgG glycosylation profile was independently associated with esophageal precancerosis beyond inflammation, which could be an early biomarker for esophageal cancer.

Prevention Relevance: IgG glycosylation profile is associated with esophageal precancerosis and specific IgG glycans involves in the early stage of esophageal cancer, which is independent of inflammation.
Toll-Like Receptors Regulate the Development and Progression of Renal Diseases
Authors: Liu Minghui , Zen Ke
Published: December 2020

Background: Stimulated by both microbial and endogenous ligands, toll-like receptors (TLRs) play an important role in the development and progression of renal diseases. Summary: As a highly conserved large family, TLRs have 11 members in humans (TLR1∼TLR11) and 13 members in mouse (TLR1∼TLR13). It has been widely reported that TLR2 and TLR4 signaling, activated by both exogenous and endogenous ligands, promote disease progression in both renal ischemia-reperfusion injury and diabetic nephropathy. TLR4 also vitally functions in CKD and infection-associated renal diseases such as pyelonephritis induced by urinary tract infection. Stimulation of intracellular TLR7/8 and TLR9 by host-derived nucleic acids also plays a key role in systemic lupus erythematosus. Given that certain microRNAs with GU-rich sequence have recently been found to be able to serve as TLR7/8 ligands, these microRNAs may initiate pro-inflammatory signal via activating TLR signal. Moreover, as microRNAs can be transferred across different organs via cell-secreted exosomes or protein-RNA complex, the TLR signaling activated by the miRNAs released by other injured organs may also result in renal dysfunction. Key Messages: In this review, we sum up the recent progress in the role of TLRs in various forms of glomerulonephritis and discuss the possible prevention or therapeutic strategies for clinic treatment to renal diseases.
Screening for GJB2-R143W-Associated Hearing Impairment: Implications for Health Policy and Practice in Ghana
Authors: Adadey Samuel M. , Quaye Osbourne , Amedofu Geoffrey K. , Awandare Gordon A. , Wonkam Ambroise
Published: December 2020

Genetic factors significantly contribute to the burden of hearing impairment (HI) in Ghana as there is a high carrier frequency (1.5%) of the connexin 26 gene founder variant GJB2-R143W in the healthy Ghanaian population. GJB2-R143W mutation accounts for nearly 26% of causes in families segregating congenital non-syndromic HI. With HI associated with high genetic fitness, this indicates that Ghana will likely sustain an increase in the number of individuals living with inheritable HI. There is a universal newborn hearing screening (UNHS) program in Ghana. However, this program does not include genetic testing. Adding genetic testing of GJB2-R143W mutation for the population, prenatal and neonatal stages may lead to guiding genetic counseling for individual and couples, early detection of HI for at-risk infants, and improvement of medical management, including speech therapy and audiologic intervention, as well as provision of the needed social service to enhance parenting and education for children with HI. Based on published research on the genetics of HI in Ghana, we recommend that the UNHS program should include genetic screening for the GJB2-R143W gene variant for newborns who did not pass the initial UNHS tests. This will require an upgrade and resourcing of public health infrastructures to implement the rapid and cost-effective GJB2-R143W testing, followed by appropriate genetic and anticipatory guidance for medical care.
The Dynamic Platelet Transcriptome in Obesity and Weight Loss
Authors: Ezzaty Mirhashemi Marzieh , Shah Ravi V. , Kitchen Robert R. , Rong Jian , Spahillari Aferdita , Pico Alexander R. , Vitseva Olga , Levy Daniel , Demarco Danielle , Shah Sajani , Iafrati Mark D. , Larson Martin G. , Tanriverdi Kahraman , Freedman Jane E.
Published: December 2020

Objective:

Adiposity is associated with oxidative stress, inflammation, and glucose intolerance. Previous data suggest that platelet gene expression is associated with key cardiometabolic phenotypes, including body mass index but stable in healthy individuals over time. However, modulation of gene expression in platelets in response to metabolic shifts (eg, weight reduction) is unknown and may be important to defining mechanism.

Approach and Results:

Platelet RNA sequencing and aggregation were performed from 21 individuals with massive weight loss (>45 kg) following bariatric surgery. Based on RNA sequencing data, we measured the expression of 67 genes from isolated platelet RNA using high-throughput quantitative reverse transcription quantitative PCR in 1864 FHS (Framingham Heart Study) participants. Many transcripts not previously studied in platelets were differentially expressed with bariatric surgical weight loss, appeared specific to platelets (eg, not differentially expressed in leukocytes), and were enriched for a nonalcoholic fatty liver disease pathway. Platelet aggregation studies did not detect alteration in platelet function after significant weight loss. Linear regression models demonstrated several platelet genes modestly associated with cross-sectional cardiometabolic phenotypes, including body mass index. There were no associations between studied transcripts and incident diabetes or cardiovascular end points.

Conclusions:

In summary, while there is no change in platelet aggregation function after significant weight loss, the human platelet experiences a dramatic transcriptional shift that implicates pathways potentially relevant to improved cardiometabolic risk postweight loss (eg, nonalcoholic fatty liver disease). Further studies are needed to determine the mechanistic importance of these observations.
Coronary
18
F-Fluoride Uptake and Progression of Coronary Artery Calcification
Authors: Doris Mhairi K. , Meah Mohammed N. , Moss Alastair J. , Andrews Jack P.M. , Bing Rong , Gillen Rebecca , Weir Nick , Syed Maaz , Daghem Marwa , Shah Anoop , Williams Michelle C. , van Beek Edwin J.R. , Forsyth Laura , Dey Damini , Slomka Piotr J. , Dweck Marc R. , Newby David E. , Adamson Philip D.
Published: December 2020

Background

Positron emission tomography (PET) using
18
F-sodium fluoride (
18
F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between
18
F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease.

Methods

Patients with established multivessel coronary atherosclerosis underwent
18
F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume.

Results

In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased
18
F-fluoride uptake in at least one vessel. Individuals with increased
18
F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39–166] versus 35 [7–93] AU;
P
<0.0001). Indeed, the calcium score only increased in coronary segments with
18
F-fluoride uptake (from 95 [30–209] to 148 [61–289] AU;
P
<0.001) and remained unchanged in segments without
18
F-fluoride uptake (from 46 [16–113] to 49 [20–115] AU;
P
=0.329). Baseline coronary
18
F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively;
P
<0.0001 for all). At the segmental level, baseline
18
F-fluoride activity was an independent predictor of calcium score at 12 months (
P
<0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score (
P
=0.50).

Conclusions

Coronary
18
F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02110303.