bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on Surrounding Rock Control Technology of Dongbaowei Deep Mining Roadway
Authors: Wu Chengjia , Qin Tao , Wang Lei , Liu Zhi
Published: January 2021

In order to explore the stability control of surrounding rock in the process of deep mining, comparative analysis of stress, deformation, and fracture characteristics of surrounding rock of deep and shallow mining roadway in dongbaotou coal mine, laboratory experiments, field measurement, numerical simulation, and field industrial experiments were adopted to put forward the control plan of the surrounding rock in deep roadway, which were verified by field industrial experiments. The results of laboratory experiments and field experiments show that the mechanical properties of deep roadway surrounding rock of Dongbaowei Coal Mine are significantly lower than those of the shadow roadway, mainly due to the development of joints and fractures of the overlying strata in the deep stope, serious impact on the disturbance of the roadway which has been made by the strong pressure of the stope, and reduced crushing strength of surrounding rock. Through comparative analysis of deep roadway support plan carried out by numerical simulation, the support scheme suitable for Dongbaowei Coal Mine is put forward, which is applied in the field. Field industrial experiments show that after the optimization of support parameters, the deformation of surrounding rock of roadway is well controlled. The displacement of surrounding rock of roadway is basically stable after 10∼15 days. The support of surrounding rock of roadway has good effect, which achieves the goal of stability control of deep roadway surrounding rock.
Robust Fixed‐Time Inverse Dynamic Control for Uncertain Robot Manipulator System
Authors: Wang Yang , Chen Mingshu , Song Yu
Published: January 2021

This paper proposes a novel robust fixed‐time control for the robot manipulator system with uncertainties. Based on the uniform robust exact differentiator (URED) algorithm, a robust control term is constructed. Then, a robust fixed‐time inverse dynamics control (IDC) is proposed. For the proposed control method, the fixed‐time stability of a closed‐loop system with uncertainties is strictly proved. The newly proposed method exhibits the following two attractive features. First, the proposed control scheme extends the existing fixed‐time IDC for the robot manipulator system to the robust control scheme. Second, the proposed method is strictly nonsingular rather than the commonly used approximate approach. Simulation result demonstrates the effectiveness of the proposed control scheme.
A Matrix Metalloproteinase‐2‐Based Nomogram to Assess the Risk of Encapsulating Peritoneal Sclerosis in Peritoneal Dialysis Patients
Authors: Chou Che-Yi , Tseng Chin-Chung , Chen Jin-Bor , Hung Chin-Chuan , Huang Chiu-Ching
Published: January 2021

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). So far, there is no biomarker‐based prediction tool available for EPS. Matrix metalloproteinase‐2 (MMP‐2) is a protein involved in the breakdown of the extracellular matrix, and the effluent MMP‐2 can be a potential biomarker of EPS. This study is aimed at developing a nomogram for EPS based on effluent MMP‐2 levels. Patients and Methods. We enrolled 18 EPS patients and 90 gender‐matched PD patients without EPS in this cross‐sectional case‐controlled study. The effluent MMP‐2 levels and possible risk factors for EPS were analyzed using multivariable logistic regression, and a nomogram was developed. The nomogram was validated using 200 bootstrap resamples to reduce overfit bias. Results. The effluent MMP‐2 levels in EPS patients were significantly higher than those in normal PD patients (p < 0.001, Manny‐Whitney U test). Effluent MMP‐2 levels and PD duration were independently associated with EPS risks (p < 0.001 and p = 0.001) in multivariate logistic regression. A nomogram based on MMP‐2 levels and PD duration was proposed. The AUC of MMP‐2 was 0.824, and the AUC of the nomogram was 0.907 (p = 0.05). Conclusion. A nomogram based on effluent MMP‐2 levels and PD duration may predict EPS with high accuracy.
Safety Analysis of the Running Train under Earthquake Dynamic Disturbance
Authors: Li Mingfei , Liu Junwei
Published: January 2021

Focusing on the safe operation of rail transit during earthquakes, the finite element method is used to construct a wheel‐track‐subgrade dynamics model in this study. Through spring‐damper units, the relationship between the rail and the track slab and the connection between the track slab and the subgrade are established. A method for establishing a viscoelastic artificial boundary is proposed. Four seismic waves—the Tianjin wave, the El Centro wave, the Taft wave, and the Qian’an wave—are selected as the seismic input waveforms, and only the impact of the lateral ground motion on the wheel‐track‐subgrade system is considered. In this paper, the ground motion problem is transformed into a wave source problem, the seismic input is transformed into an equivalent load acting on the artificial boundary, and the wave input of the viscoelastic artificial boundary is realized. The normalization method is used to process the seismic waves, and a method that converts the input of the seismic waves into equivalent loads is proposed. The changing laws of different dynamic response indexes under the influence of the four waveforms are studied. Under the action of the Tianjin wave, the wheel‐rail dynamic response is very violent near the acceleration peak, whereas, after the peak, all dynamic response indexes are within a safe range. Under the effect of the El Centro wave, the collision between the wheel and the track is relatively violent, and the train is already in a dangerous state. Under the action of the Taft wave, due to the sudden action of the peak ground motion acceleration, the displacement between the wheel and the track increases instantaneously, causing the train to derail. Under the action of the Qian’an wave, the force between the wheel and rail changes approximately linearly with respect to the frequency of the ground motion, and all dynamic response indexes are within a safe range. The vibration intensity of the four seismic waves is amplified by an intensity expansion factor. Except for the Tianjin wave, the amplified seismic wave has a greater impact on safe train operations. This paper can provide a reference for research on the running safety of trains under similar dynamic disturbance conditions.
Removal of Cochannel Interference Using Probabilistic Latent Component Analysis in Passive Bistatic Radar
Authors: Ying Tao , Wang Xuebao , Tian Wei , Zhou Cheng
Published: January 2021

This paper examines the problem of cancellation of cochannel interference (CCI) present in the same frequency channel as the signal of interest, which may bring a reduction in the performance of target detection, in passive bistatic radar. We propose a novel approach based on probabilistic latent component analysis for CCI removal. The highlight is that removing CCI is considered as reconstruction, and extraction of Doppler-shifted and time-delayed replicas of the reference signal exploited fully as training data. The results of the simulation show that the developed method is effective.
On Three Types of Soft Rough Covering-Based Fuzzy Sets
Authors: Atef Mohammed , Nada Shokry , Gumaei Abdu , Nawar Ashraf S.
Published: January 2021

Recently, the concept of a soft rough fuzzy covering (briefly, SRFC) by means of soft neighborhoods was defined and their properties were studied by Zhan’s model. As a generalization of Zhan’s method and in order to increase the lower approximation and decrease the upper approximation, the present work aims to define the complementary soft neighborhood and hence three types of soft rough fuzzy covering models (briefly, 1-SRFC, 2-SRFC, and 3-SRFC) are proposed. We discuss their axiomatic properties. According to these results, we investigate three types of fuzzy soft measure degrees (briefly, 1-SMD, 2-SMD, and 3-SMD). Also, three kinds of

ψ

-soft rough fuzzy coverings (briefly, 1-

ψ

-SRFC, 2-

ψ

-SRFC, and 3-

ψ

-SRFC) and three kinds of

D

-soft rough fuzzy coverings (briefly, 1-

D

-SRFC, 2-

D

-SRFC, and 3-

D

-SRFC) are discussed and some of their properties are studied. Finally, the relationships among these three models and Zhan’s model are presented.
Ascorbic Acid: A New Player of Epigenetic Regulation in LPS‐gingivalis Treated Human Periodontal Ligament Stem Cells
Authors: Marconi Guya D. , Fonticoli Luigia , Guarnieri Simone , Cavalcanti Marcos F. X. B. , Franchi Sara , Gatta Valentina , Trubiani Oriana , Pizzicannella Jacopo , Diomede Francesca
Published: January 2021

Periodontitis is usually sustained from microorganism of oral cavity, like Porphyromonas gingivalis (P. gingivalis). Periodontal disease is an infectious disease that afflicts a large number of people. Researches are investigating on the mesenchymal stem cells (MSCs) response to inflammatory events in combination with antioxidant substances. In particular, ascorbic acid (AA) increased cell proliferation, upregulated the cells pluripotency marker expression, provide a protection from inflammation, and induced the regeneration of periodontal ligament tissue. The purpose of the present research was to investigate the effects of AA in primary culture of human periodontal ligament stem cells (hPDLSCs) exposed to P. gingivalis lipopolysaccharide (LPS‐G). The effect of AA on hPDLSCs exposed to LPS‐G was determined through the cell proliferation assay. The molecules involved in the inflammatory pathway and epigenetic regulation have been identified using immunofluorescence and Western blot analyses. miR‐210 level was quantified by qRT‐PCR, and the ROS generation was finally studied. Cells co‐treated with LPS‐G and AA showed a restoration in terms of cell proliferation. The expression of NFκB, MyD88, and p300 was upregulated in LPS‐G exposed cells, while the expression was attenuated in the co‐treatment with AA. DNMT1 expression is attenuated in the cells exposed to the inflammatory stimulus. The level of miR‐210 was reduced in stimulated cells, while the expression was evident in the hPDLSCs co‐treated with LPS‐G and AA. In conclusion, the AA could enhance a protective effect in in vitro periodontitis model, downregulating the inflammatory pathway and ROS generation and modulating the miR‐210 level.
Prediction of Bending Force in the Hot Strip Rolling Process Using Multilayer Extreme Learning Machine
Authors: Wu Yan , Ni Hongchao , Li Xu , Luan Feng , He Yaodong
Published: January 2021

In the hot strip rolling process, accurate prediction of bending force can improve the control accuracy of the strip flatness and further improve the quality of the strip. In this paper, based on the production data of 1300 pieces of strip collected from a hot rolling factory, a series of bending force prediction models based on an extreme learning machine (ELM) are proposed. To acquire the optimal model, the parameter settings of the models were investigated, including hidden layer nodes, activation function, population size, crossover probability, and hidden layer structure. Four models are established, one hidden layer ELM model, an optimized ELM model (GAELM) by genetic algorithm (GA), an optimized ELM model (SGELM) by hybrid simulated annealing (SA) and GA, and two-hidden layer optimized ELM model (SGITELM) optimized by SA and GA. The prediction performance is evaluated from the mean absolute error (MAE), root-mean-squared error (RMSE), and mean absolute percentage error (MAPE). The results show that the SGITELM has the highest prediction accuracy in the four models. The RMSE of the proposed SGITELM is 11.2678 kN, and 98.72% of the prediction data have an absolute error of less than 25 kN. This indicates that the proposed SGITELM with strong learning ability and generalization performance can be well applied to hot rolling production.
Effects of 830 nm Light-Emitting Diode Therapy on Delayed-Onset Muscle Soreness
Authors: Chang Wen-Dien , Lin Hung-Yu , Chang Nai-Jen , Wu Jih-Huah
Published: January 2021

Objectives. Our study investigated the effects of 830 nm light-emitting diode therapy (LEDT) for postexercise delayed-onset muscle soreness (DOMS). Methods. In this randomized control study, healthy participants were randomized into LEDT and placebo groups. LEDT (output frequency = 10 Hz; wavelength = 830 nm; total output power = 210 mW; and dose = 315 J/cm2) was applied to six sites in the damaged quadriceps for 10 min. The placebo group received sham LEDT with no energy output. The nondominant leg was chosen for DOMS induction, using an eccentric exercise. Visual analog scale (VAS) scores for muscle soreness, pressure pain threshold (PPT), thigh circumference, joint range of motion, and muscle strength were assessed before and immediately after exercise and at 24, 48, 72, and 96 h postexercise. Results. Forty participants were divided into the LEDT group (n = 20) and the placebo group (n = 20). Compared with the placebo group, the LEDT group exhibited significant increases in PPT values at 48, 72, and 96 h postexercise (

p
<
0.05

). The joint range of motion was significantly different between the LEDT and placebo groups at 72 and 96 h postexercise (

p
<
0.05

). No significant intergroup differences were noted in thigh circumference and muscle strength (

p
<
0.05

). Conclusion. The application of 830 nm LEDT on postexercise DOMS pain exerted an analgesic effect but did not affect the muscle repair process. Future studies should elucidate the beneficial effects of 830 nm LEDT on muscle recovery or performance.
A Target-Oriented Multiple-Attribute Decision-Making Approach Based on Probabilistic Linguistic Preference Relations
Authors: Li Chun-Hao , Ma Hui-Xin , Jia Yan-Hui
Published: January 2021

While the approach to multiple-attribute decision-making (MADM) is widely used in a variety of fields, including models with fuzzy sets and corresponding extensions, it cannot solve target-oriented decision problems with both selective and targeted alternatives. Therefore, this study provides the first description of a target-oriented MADM problem and proposes a novel decision framework. An attribute value function for target orientation is defined by integrating range and frequency values derived under cumulative prospect theory and range-frequency theory. A Choquet integral with discrete fuzzy measures is then used to integrate attribute values and determine comprehensive values for selective alternatives. In this determination of comprehensive values, a parameter estimation model is also established, with its input assumed to be the pairwise comparison judgment matrix with probabilistic linguistic preference relation. This model as well as its transformation aims at determining the parameters of both the attribute value function and fuzzy measures. Finally, the process of target-oriented MADM is summarized, and an illustrative example is provided to demonstrate the applicability of the proposed techniques.
Parking Demand vs Supply: An Optimization-Based Approach at a University Campus
Authors: Nadimi Navid , Afsharipoor Sanaz , Mohammadian Amiri Amir
Published: January 2021

Parking management has always been a major concern for universities and other activity centers. Nowadays, many universities are suffering from a lack of campus parking capacity. To tackle this problem, it is necessary to take parking lots assignment into consideration, regarding intercampus users’ needs. These users have different ages, physical characteristics, expectations, and administrative positions that should be considered before any parking assignment. Here, a new method is proposed to optimize parking lots management for those universities where staff (academic and administrative), in contrast to students, are allowed to park inside the campus area. For this purpose, first, the probability of using a specific parking lot by each group is determined. For staff, this is done based on their choices, revealed by the relative frequency of using parking lots. This probability for students can be calculated using a fuzzy inference system model. To develop the model, a survey is conducted to extract students’ preferences, regarding parking spaces assignment inside the campus area. Afterward, an integer linear programming model with the objective function of maximizing parking probability is employed, considering several related constraints. The proposed model is applied to Shahid Bahonar University of Kerman (SBUK), Iran, as the case study. According to the results, it can be concluded that the proposed method can help to reduce wandering time of finding an appropriate parking space for both staff and students. In addition, the proposed application can help increase the satisfaction level of staff and students with regard to parking management.
Syndrome of Inappropriate Antidiuretic Hormone in Esophageal Cancer Patient
Authors: Minhajat Rahmawati , Benyamin Andi Fachruddin , Aman Andi Makbul , Bakri Syakib
Published: January 2021

Syndrome of inappropriate antidiuretic hormone (SIADH) is a disorder of fluid and sodium balance characterized by hypotonic hyponatremia, low plasma osmolality, and increased urine osmolality caused by excessive release of antidiuretic hormone (ADH). Malignancy is one of the most common causes of SIADH, but SIADH in esophageal carcinoma is very rarely reported. In this case report, a 74-year-old male patient of moderate differentiation of squamous cell esophageal carcinoma had a recurrent electrolyte balance disorder despite repeated corrections. The patient experienced improvement after fluid restriction and drug administration.
Vulvar Cancer with Cutaneous and Breast Metastases
Authors: Adhikari Nawaraj , Vennepureddy Adarsh , Parylo Sara , Agarwal Anupma , Dhar Meekoo
Published: January 2021

Vulvar cancer accounts for about 5% of cancer of female genitalia. It may initially present as benign symptoms resulting in potential delay in diagnosis. Few cases of distant metastases to skin or breast have been reported. We present the case of a 76-year-old female with possible delay in diagnosis of her squamous cell carcinoma of vulva. After 4 months of the diagnosis, she presented with concurrent cutaneous and breast metastases.
A Multilevel Monte Carlo Method for the Valuation of Swing Options
Authors: Ghodssi-Ghassemabadi Hakimeh , Yari Gholam Hossein
Published: January 2021

In this study, we propose a novel approach for the valuation of swing options. Swing options are a kind of American options with multiple exercise rights traded in energy markets. Longstaff and Schwartz have suggested a regression-based Monte Carlo method known as the least-squares Monte Carlo (LSMC) method to value American options. In this work, first we introduce the LSMC method for the pricing of swing options. Then, to achieve a desired accuracy for the price estimation, we combine the idea of LSMC with multilevel Monte Carlo (MLMC) method. Finally, to illustrate the proper behavior of this combination, we conduct numerical results based on the Black–Scholes model. Numerical results illustrate the efficiency of the proposed approach.
Digital Twins and Road Construction Using Secondary Raw Materials
Authors: Meža Sebastjan , Mauko Pranjić Alenka , Vezočnik Rok , Osmokrović Igor , Lenart Stanislav
Published: January 2021

Secondary raw materials (SRMs) tend to be a valuable replacement for finite virgin materials especially since construction works (i.e., building and civil engineering work such as road construction) require vast quantities of raw materials. Using SRM originating from recycling a broad range of inorganic waste materials (e.g., mining waste, different industrial wastes, construction, and demolition waste) has been recognized as a promising, generally more cost-efficient, and environmentally friendly alternative to the exploitation of natural resources. Despite the benefits of using SRM, several challenges need to be addressed before using SRM even more. One of them is the long-term durability and little-known response of construction works built using such alternative materials. In this paper, we present the activities to establish a fully functioning digital twin (DT) of a road constructed using SRM. The first part of the paper is devoted to the theoretical justification of efforts and ways of establishing the monitoring systems, followed by a DT case study where an integrated data environment synthesizing a Building Information Model and monitored data is presented. Although the paper builds upon a small scale, the case study is methodologically designed to allow parallels to be drawn with much larger construction projects.
Emodin Induced Necroptosis and Inhibited Glycolysis in the Renal Cancer Cells by Enhancing ROS
Authors: Wang Ke-jie , Meng Xiang-yu , Chen Jun-feng , Wang Kai-yun , Zhou Cheng , Yu Rui , Ma Qi
Published: January 2021

Renal cell carcinoma (RCC) is a tumor with unpredictable presentation and poor clinical outcome. RCC is always resistant to chemotherapy and radiation, and weakly sensitive to immunotherapeutic agents. Therefore, novel agents and approaches are urgently needed for the treatment of RCC. Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese herbs, has been implicated in a wide variety of pharmacological effects, such as anti‐inflammatory, antiviral, and antitumor activities. However, its role in RCC remains unknown. In this study, we found that emodin effectively killed renal cancer cells without significant toxicity to noncancerous cell HK‐2. Flow cytometry assay with Annexin V‐FITC and PI demonstrated that emodin induces necroptosis, but not apoptosis, in renal cancer cells. Meanwhile, the phosphorylation levels of RIP1 and MLKL, the key necroptosis‐related proteins, were significantly increased. To explore how emodin inhibits kidney tumor growth, we tested reactive oxygen species (ROS) levels and found that the levels of ROS increased upon emodin treatment in a dose‐dependent manner. Further studies demonstrated that emodin induces necroptosis through ROS‐mediated activation of JNK signaling pathway and also inhibits glycolysis by downregulation of GLUT1 through ROS‐mediated inactivation of the PI3K/AKT signaling pathway. Our findings revealed the potential mechanisms by which emodin suppresses renal cancer cell growth and will help develop novel therapeutic approaches for patients with JNK‐ or PI3K/AKT‐dysregulated renal cancer.
Danggui Buxue Decoction Ameliorates Inflammatory Bowel Disease by Improving Inflammation and Rebuilding Intestinal Mucosal Barrier
Authors: Li Chengyin , Zhu Fenglin , Wang Shasha , Wang Jing , Wu Bin
Published: January 2021

Objective. This study aimed to determine whether Danggui Buxue decoction (DGBX) can improve inflammatory bowel disease (IBD) by regulating immunity and promoting intestinal mucosal repair. Method. Dextran sulfate sodium (DSS) was used to induce the IBD model. Drugs (DGBX or saline) were administered to mice, which were randomly divided into three groups (control, model, and experimental groups). Hematoxylin and eosin staining of intestinal tissues was conducted to observe for morphological changes. Changes in cytokines and immune cells in the intestinal tissues were detected by enzyme-linked immunosorbent assay and flow cytometry. Immunofluorescence techniques were used to assess the status of the intestinal mucosal repair. Results. This study found that treatment with DGBX can effectively improve the inflammatory state and pathological structure of the IBD model. DGBX not only can significantly change the composition of intestinal mucosal immune cells and promote the regression of inflammation but also significantly increase the proliferation of intestinal epithelial cells and promote the rapid repair of intestinal mucosal barrier injury compared with the model group (

p
<
0.05

). Conclusion. Taking these results, DGBX shows promising protective effects on IBD by regulating immunity and promoting intestinal mucosal repair.
Permeability Evolution of an Intact Marble Core during Shearing under High Fluid Pressure
Authors: Wang Yuan , Jiao Yu , Hu Shaobin
Published: January 2021

The progressive shear failure of a rock mass under hydromechanical coupling is a key aspect of the long-term stability of deeply buried, high fluid pressure diversion tunnels. In this study, we use experimental and numerical analysis to quantify the permeability variations that occur in an intact marble sample as it evolves from shear failure to shear slip under different confining pressures and fluid pressures. The experimental results reveal that at low effective normal stress, the fracture permeability is positively correlated with the shear displacement. The permeability is lower at higher effective normal stress and exhibits an episodic change with increasing shear displacement. After establishing a numerical model based on the point cloud data generated by the three-dimensional (3D) laser scanning of the fracture surfaces, we found that there are some contact areas that block the percolation channels under high effective stress conditions. This type of contact area plays a key role in determining the evolution of the fracture permeability in a given rock sample.
Cardiac Shock Wave Therapy Alleviates Hypoxia/Reoxygenation‐Induced Myocardial Necroptosis by Modulating Autophagy
Authors: Qiu Quan , Shen Tao , Yu Xiaoxue , Jia Na , Zhu Kaiyi , Wang Que , Liu Bing , He Qing
Published: January 2021

Regulated necrosis (necroptosis) is crucially involved in cardiac ischaemia‐reperfusion injury (MIRI). The aim of our study is to investigate whether shock wave therapy (SWT) is capable of exerting protective effects by inhibiting necroptosis during myocardial ischaemia‐reperfusion (I/R) injury and the possible role of autophagy in this process. We established a hypoxia/reoxygenation (H/R) model in vitro using HL‐1 cells to simulate MIRI. MTS assays and LDH cytotoxicity assay were performed to measure cell viability and cell damage. Annexin V/PI staining was used to determine apoptosis and necrosis. Western blotting was performed to assess the changes in cell signaling pathways associated with autophagy, necroptosis, and apoptosis. Reactive oxygen species (ROS) production was detected using DHE staining. Autophagosome generation and degradation (autophagic flux) were analysed using GFP and RFP tandemly tagged LC3 (tfLC3). HL‐1 cells were then transfected with p62/SQSTM1 siRNA in order to analyse its role in cardioprotection. Our results revealed that SWT increased cell viability in the H/R model and decreased receptor‐interacting serine/threonine‐protein kinase 1 (RIPK1) and RIPK3 expression. ROS production was also inhibited by SWT. Moreover, SWT decreased Beclin1 expression and the ratio of LC3‐II/LC3‐I following H/R. Simultaneously, in the tfLC3 assay, the SWT provoked a decrease in the cumulative autophagosome abundance. siRNA‐mediated knockdown of p62 attenuated H/R‐induced necroptosis, and SWT did not exert additive effects. Taken together, SWT ameliorated H/R injury by inhibiting necroptosis. SWT also relieved the blockade of autophagic flux in response to H/R injury. The restoration of autophagic flux by SWT might contribute to its cardioprotective effect on necroptosis following H/R injury.
Experimental Study on Mechanical Behavior of Lean Cemented Sand and Gravel Material in Unloading and Reloading Paths
Authors: Yang Jie , Yang An-yu , Shan Yan-gong , Yang Miao-miao , Zhao Jin-lei , Yu Hang
Published: January 2021

Lean cemented sand and gravel (LCSG) materials are subjected to unloading‐loading when an LCSG dam is opened for water drainage and then refilled or a roadbed base is subjected to repeated wheel loads. To investigate the behavior of the LCSG materials under loading‐unloading, previous studies utilized the complete loading triaxial test. In contrast, in this study, the consolidated drained triaxial tests in the unloading and reloading paths for materials with cementing agent contents of 60 and 100 kg/m3 under different confining pressures, for which each curve generates three loading‐unloading cycles, were applied to investigate the unloading and reloading mechanical behavior. Experimental results indicated that the unloading and reloading behavior of the LCSG materials produced stress‐strain curves exhibiting a crescent‐shaped hysteresis loop, which differs from that exhibited by coarse‐grained soil. Although the shape of the crescent‐like hysteresis loop was preserved as stress levels increasing, it gradually expanded. Compared with that of the typical triaxial test, the cohesive force and the increasing internal friction angle increased. Further, as the confining pressure increased, the crescent‐like hysteresis loops tapered, shear strength increased linearly, and the modulus of resilience increased nonlinearly; the latter’s rate of change, however, decreased. The change in volumetric strain was small during unloading as the stress level changed.
Bladder Tumor Subtype Commitment Occurs in Carcinoma In Situ Driven by Key Signaling Pathways Including ECM Remodeling
Authors: Wullweber Adrian , Strick Reiner , Lange Fabienne , Sikic Danijel , Taubert Helge , Wach Sven , Wullich Bernd , Bertz Simone , Weyerer Veronika , Stoehr Robert , Breyer Johannes , Burger Maximilian , Hartmann Arndt , Strissel Pamela L. , Eckstein Markus
Published: January 2021

Basal and luminal subtypes of invasive bladder tumors have significant prognostic and predictive impacts for patients. However, it remains unclear whether tumor subtype commitment occurs in noninvasive urothelial lesions or in carcinoma in situ (CIS) and which gene pathways are important for bladder tumor progression. To understand the timing of this commitment, we used gene expression and protein analysis to create a global overview of 36 separate tissues excised from a whole bladder encompassing urothelium, noninvasive urothelial lesions, CIS, and invasive carcinomas. Additionally investigated were matched CIS, noninvasive urothelial lesions, and muscle-invasive bladder cancers (MIBC) from 22 patients. The final stage of subtype commitment to either a luminal or basal MIBC occurred at the CIS transition. For all tissues combined, hierarchical clustering of subtype gene expression revealed three subtypes: “luminal,” “basal,” and a “luminal p53-/extracellular matrix (ECM)-like” phenotype of ECM-related genes enriched in tumor-associated urothelium, noninvasive urothelial lesions, and CIS, but rarely invasive, carcinomas. A separate cohort of normal urothelium from noncancer patients showed significantly lower expression of ECM-related genes compared with tumor-associated urothelium, noninvasive urothelial lesions, and CIS. A PanCancer Progression Panel of 681 genes unveiled pathways specific for the luminal p53-/ECM-like cluster, for example, ECM remodeling, angiogenesis, epithelial-to-mesenchymal transition, cellular discohesion, cell motility involved in tumor progression, and cell proliferation and oncogenic ERBB2/ERBB3 signaling for invasive carcinomas. In conclusion, this study provides insights into bladder cancer subtype commitment and associated signaling pathways, which could help predict therapy response and enhance our understanding of therapy resistance.

Significance:

This study demonstrates that CIS is the stage of commitment for determining MIBC tumor subtype, which is relevant for patient prognosis and therapy response.
Insights into the Links between MYC and 3D Chromatin Structure and Epigenetics Regulation: Implications for Cancer Therapy
Authors: Amjadi-Moheb Fatemeh , Paniri Alireza , Akhavan-Niaki Haleh
Published: January 2021

MYC is embedded in the transcriptional oasis of the 8q24 gene desert. A plethora of genomic elements has roles in MYC aberrant expression in cancer development by interacting with transcription factors and epigenetics regulators as well as altering the structure of chromatin at the MYC locus and tissue-specific long-range enhancer–promoter contacts. Furthermore, MYC is a master regulator of several human cancers by modulating the transcription of numerous cancer-related genes through epigenetic mechanisms. This review provides a comprehensive overview of the three-dimensional genomic organization around MYC and the role of epigenetic machinery in transcription and function of MYC as well as discusses various epigenetic-targeted therapeutic strategies in MYC-driven cancers.
Cross-talk between YAP and RAR-RXR Drives Expression of Stemness Genes to Promote 5-FU Resistance and Self-Renewal in Colorectal Cancer Cells
Authors: Bauzone Marjolaine , Souidi Mouloud , Dessein Anne-Frédérique , Wisztorski Maxence , Vincent Audrey , Gimeno Jean-Pascal , Monté Didier , Van Seuningen Isabelle , Gespach Christian , Huet Guillemette
Published: January 2021

The mechanisms whereby the Hippo pathway effector YAP regulates cancer cell stemness, plasticity, and chemoresistance are not fully understood. We previously showed that in 5-fluorouracil (5-FU)–resistant colorectal cancer cells, the transcriptional coactivator YAP is differentially regulated at critical transitions connected with reversible quiescence/dormancy to promote metastasis. Here, we found that experimental YAP activation in 5-FU–sensitive and 5-FU–resistant HT29 colorectal cancer cells enhanced nuclear YAP localization and the transcript levels of the retinoic acid (RA) receptors RARα/γ and RAR target genes CYP26A1, ALDH1A3, and LGR5 through RA Response Elements (RARE). In these two cell models, constitutive YAP activation reinforced the expression of the stemness biomarkers and regulators ALDH1A3, LGR5, and OCT4. Conversely, YAP silencing, RAR/RXR inhibition by the pan-RAR antagonist BMS493, and vitamin A depletion downregulated stemness traits and self-renewal. Regarding the mechanisms engaged, proximity-dependent labeling, nuclear YAP pulldown coupled with mass spectrometry, and chromatin immunoprecipitation (ChIP)/re-ChIP experiments revealed: (i) the nuclear colocalization/interaction of YAP with RARγ and RXRs; and (ii) combined genomic co-occupancy of YAP, RARα/γ, and RXRα interactomes at proximal RAREs of LGR5 and ALDH1A3 promoters. Moreover, activation of the YAP/RAR-RXR cross-talk in colorectal cancer cells promoted RAR self-activation loops via vitamin A metabolism, RA, and active RAR ligands generated by ALDH1A3. Together, our data identify YAP as a bona fide RAR-RXR transcriptional coactivator that acts through RARE-activated stemness genes.

Implications:

Targeting the newly identified YAP/RAR-RXR cross-talk implicated in cancer cell stemness maintenance may lead to multitarget combination therapies for patients with colorectal cancer.
O-GlcNAc Transferase – An Auxiliary Factor or a Full-blown Oncogene?
Authors: Itkonen Harri M. , Loda Massimo , Mills Ian G.
Published: January 2021

The β-linked N-acetyl-d-glucosamine (GlcNAc) is a posttranslational modification of serine and threonine residues catalyzed by the enzyme O-GlcNAc transferase (OGT). Increased OGT expression is a feature of most human cancers and inhibition of OGT decreases cancer cell proliferation. Antiproliferative effects are attributed to posttranslational modifications of known regulators of cancer cell proliferation, such as MYC, FOXM1, and EZH2. In general, OGT amplifies cell-specific phenotype, for example, OGT overexpression enhances reprogramming efficiency of mouse embryonic fibroblasts into stem cells. Genome-wide screens suggest that certain cancers are particularly dependent on OGT, and understanding these addictions is important when considering OGT as a target for cancer therapy. The O-GlcNAc modification is involved in most cellular processes, which raises concerns of on-target undesirable effects of OGT-targeting therapy. Yet, emerging evidence suggest that, much like proteasome inhibitors, specific compounds targeting OGT elicit selective antiproliferative effects in cancer cells, and can prime malignant cells to other treatments. It is, therefore, essential to gain mechanistic insights on substrate specificity for OGT, develop reagents to more specifically enrich for O-GlcNAc–modified proteins, identify O-GlcNAc “readers,” and develop OGT small-molecule inhibitors. Here, we review the relevance of OGT in cancer progression and the potential targeting of this metabolic enzyme as a putative oncogene.
DHEA Moderates the Impact of Childhood Trauma on the HPA Axis in Adolescence
Authors: Taylor-Cavelier Sarah J. , Micol Valerie J. , Roberts Andrea G. , Geiss Elisa G. , Lopez-Duran Nestor
Published: January 2021

Background: Trauma can lead to long-term downregulation of the hypothalamic pituitary adrenal (HPA) axis. However, dehydroepiandrosterone (DHEA) has neuroprotective effects that may reduce the need for downregulation of the axis in response to stress. Furthermore, high DHEA/cortisol ratios are often conceptualized as better markers of DHEA’s availability than DHEA alone, as ratios account for the coupling of DHEA and cortisol in response to stress. Objectives: In this study, we explored if DHEA and DHEA/cortisol ratios moderated the association between childhood maltreatment and the HPA axis stress response. Methods: The sample consisted of 101 adolescents (ages 12–16) who completed the Child Trauma Questionnaire (CTQ) and the Trier Social Stress Test (TSST). Cortisol was modeled using saliva samples at 8 time points throughout the TSST. Cortisol and DHEA ratios were examined at baseline and 35 min after stress initiation. Results: Childhood maltreatment was associated with less steep cortisol activation slope and peak cortisol levels, but DHEA and DHEA/cortisol ratios moderated this effect. At high levels of DHEA, the impact of childhood maltreatment on cortisol peak levels was no longer significant. In contrast, high DHEA/cortisol ratios were associated with an intensification of the impact of childhood maltreatment on peak levels. Conclusions: Results suggest that DHEA can limit the blunting of the HPA axis in response to childhood maltreatment. However, this protective effect was not reflected in high DHEA/cortisol ratios as predicted. Therefore, high DHEA and high DHEA/cortisol ratios may reflect different, and potentially opposite, processes.
Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN
Authors: Thurston Rebecca C. , Aslanidou Vlachos Helen E. , Derby Carol A. , Jackson Elizabeth A. , Brooks Maria Mori , Matthews Karen A. , Harlow Sioban , Joffe Hadine , El Khoudary Samar R.
Published: January 2021

Background

Cardiovascular disease (CVD) in women has unique features, including associations with reproductive factors that are incompletely understood. Vasomotor symptoms (VMS), the classic menopausal symptom, are linked to CVD risk factors and subclinical CVD. Evidence linking VMS to CVD events is limited. We tested whether frequent and/or persistent VMS were associated with increased risk for fatal and nonfatal CVD events in SWAN (Study of Women’s Health Across the Nation).

Methods and Results

A total of 3083 women, aged 42 to 52 years at baseline, underwent up to 16 in‐person visits over 22 years. Assessments included questionnaires on VMS frequency (0, 1–5, or ≥6 days/2 weeks), physical measures, phlebotomy, and reported CVD events (myocardial infarction, stroke, heart failure, and revascularization). A subset of events was adjudicated via medical record. Death certificates were obtained. Relationships between baseline VMS or persistent VMS over the follow‐up (proportion of visits with frequent VMS) with combined incident nonfatal and fatal CVD were tested in Cox proportional hazards models adjusted for demographics, medication use, and CVD risk factors. Participants experienced 231 CVD events over the follow‐up. Women with frequent baseline VMS had an elevated risk of subsequent CVD events (relative to no VMS; ≥6 days: hazard ratio [HR] [95% CI], 1.51 [1.05–2.17],
P
=0.03; 1–5 days: HR [95% CI], 1.02 [0.75–1.39],
P
=0.89, multivariable). Women with frequent VMS that persisted over time also had an increased CVD event risk (>33% versus ≤33% of visits: HR [95% CI], 1.77 [1.33–2.35],
P
<0.0001, multivariable).

Conclusions

Frequent and persistent VMS were associated with increased risk of later CVD events. VMS may represent a novel female‐specific CVD risk factor.
Choline Pathway Nutrients and Metabolites and Cognitive Impairment After Acute Ischemic Stroke
Authors: Zhong Chongke , Lu Zian , Che Bizhong , Qian Sifan , Zheng Xiaowei , Wang Aili , Bu Xiaoqing , Zhang Jintao , Ju Zhong , Xu Tan , Zhang Yonghong
Published: January 2021

Background and Purpose:

Choline metabolism was suggested to play pathophysiological roles in nervous system and atherosclerosis development. However, little is known about the impacts of choline pathway nutrients and metabolites on poststroke cognitive impairment. We aimed to prospectively investigate the relationships between circulating choline, betaine, and trimethylamine N-oxide with cognitive impairment among acute ischemic stroke patients.

Methods:

We derived data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Plasma choline, betaine, and trimethylamine N-oxide concentrations at baseline were measured in 617 participants. Cognitive impairment was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Reclassification and calibration of models with choline-related biomarkers were evaluated.

Results:

Plasma choline and betaine were inversely associated with cognitive impairment. Compared with the lowest tertile, adjusted odds ratios of Mini-Mental State Examination–defined cognitive impairment for participants in the highest tertiles of choline and betaine were 0.59 (95% CI, 0.39–0.90) and 0.60 (95% CI, 0.39–0.92), respectively. In addition, both choline and betaine offered incremental predictive ability over the basic model with established risk factors, shown by increase in net reclassification improvement and integrated discrimination improvement. There were similar significant relationships between choline and betaine with cognitive impairment as defined by the Montreal Cognitive Assessment. However, plasma trimethylamine N-oxide was only associated with cognitive impairment evaluated using the Mini-Mental State Examination; the adjusted odds ratio was 1.33 (95% CI, 1.04–1.72) for each 1-SD increment of trimethylamine N-oxide.

Conclusions:

Patients with higher choline and betaine levels had lower risk of cognitive impairment after ischemic stroke, supporting promising prognostic roles of choline pathway nutrients for poststroke cognitive impairment.
Secondary Medium Vessel Occlusions
Authors: Goyal Mayank , Kappelhof Manon , McDonough Rosalie , Ospel Johanna Maria
Published: January 2021

Medium vessel occlusions (MeVOs, ie, M2, M3, A2, A3, P2, and P3 segment occlusions) are increasingly recognized as a target for endovascular treatment in acute ischemic stroke. It is important to note that not all MeVOs are equal. Primary MeVOs occur de novo with the underlying mechanisms being very similar to large vessel occlusion strokes. Secondary MeVOs arise from large vessel occlusions through clot migration or fragmentation, either spontaneously or following treatment with intravenous thrombolysis or endovascular treatment. Currently, there are little data on the prevalence, management, and prognosis of acute ischemic stroke due to secondary MeVOs. This type of stroke is, however, likely to become more relevant in the future as indications for endovascular treatment continue to broaden. In this article, we describe different types of secondary MeVOs, imaging findings associated with them, challenges related to the diagnosis of secondary MeVOs, and their potential implications for treatment strategies and clinical outcomes.
Tracing the context in disciplinary classifications: A bibliometric
pairwise comparison of five classifications of journals in the social sciences
and humanities
Authors: Sīle Linda , Guns Raf , Vandermoere Frédéric , Sivertsen Gunnar , Engels Tim C. E.
Published: January 2021

Despite the centrality of disciplinary classifications in bibliometric analyses, it is not well known how the choice of disciplinary classification influences bibliometric representations of research in the social sciences and humanities (SSH). This is especially crucial when using data from national databases. Therefore, we examine the differences in the disciplinary profile of an article along with the absolute and relative number of articles across disciplines using five disciplinary classifications for journals. We use data on journal articles (2006–2015) from the national bibliographic databases VABB-SHW in Flanders (Belgium) and Cristin in Norway. Our study is based on pairwise comparisons of the local classifications used in these databases, the Web of Science subject categories, the Science-Metrix, and the ERIH PLUS journal classifications. For comparability, all classifications are mapped to the OECD Fields of Research and Development classification. The findings show that the choice of disciplinary classification can lead to over- or underestimation of the absolute number of publications per discipline. In contrast, if the focus is on the relative numbers, the choice of classification has practically no influence. These findings facilitate an informed choice of a disciplinary classification for journals in SSH when using data from national databases.
Playing the Man in the Book of Ruth: Reshaping the Masculine Ideal
Authors: Purcell Richard Anthony
Published: January 2021

Many scholars have productively analyzed the book of Ruth to explore gender roles and norms. Few studies, though, have brought masculinity theory to bear on the book of Ruth, and those that have primarily focus on the character of Boaz. However, other characters ‘play the man’ in this narrative, notably Ruth herself. Though Boaz is labeled as an אישׁ גבור חיל, Ruth often better performs the masculine ideal represented by this label. She enters dangerous situations to protect and provide for Naomi. Moreover, Ruth initiates and manipulates sexual contact in order to produce progeny. The narrative presents the characters of Ruth, Boaz, and, at times, Yhwh performing masculine roles with varying levels of success. This essay contends that the book takes up previously assumed norms of masculinity and reshapes them in light of a changing socio-political context.
The “Foreigner” and the Eunuch: The Politics of Belonging in Isaiah 56:1–8
Authors: Southwood Katherine E.
Published: January 2021

One important theme that has emerged recently in research concerning exile, migration, and return-migration is the concept of “belonging”, a concept that is quickly destabilising the emphasis on identity. This article will demonstrate the heuristic significance of research concerning belonging for Biblical scholars, focusing on the negative stereotypical identity labels, “the foreigner” and “the eunuch” in Isaiah 56:1–8. It will emphasise the crucial importance of using clear and differentiated analytical language and will illustrate how doing so enables us to perceive new nuances and shades of meaning in the Biblical text. We will emphasise the importance of elective attachment in Isaiah 56:1–8 and will emphasise the significance of recognising that identity labels such as “foreigner” are constructed and unstable. The article surveys material concerning belonging and demonstrates its significance for rethinking and reframing the polemic against ethnic entitlement and exclusionary language.