bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Gambogic Acid on miR-199a-3p Expression and Cell Biological Behavior in Colorectal Cancer Cells
Authors: Wang Xiaodong , Li Yingchun , Zhou Haihua , Han Ning , Pan Linlin , Yu Chen
Published: August 2021

Colorectal cancer (CC), as a malignancy threatening life and health, has a rising incidence in recent years. It has been reported that gambogic acid (GA) has antitumor activity in various tumors, but its effect on CC remains to be elucidated. In this investigation, the influence of GA nanoparticles on microRNA-199a-3p (miR-199a-3p) in CC was analyzed to provide a reliable reference for future clinical practice. Through PCR detection, we first determined that miR-199a-3p presented low expression in CC and had a significant effect in predicting the onset and prognosis of CC. Through in vitro experiments, the enhanced CC cell viability after inhibition was determined; however, decreased cell viability and increased miR-199a-3p level were also observed after GA nanoparticles addition. Hence, GA nanoparticles may influence CC cell biological behaviors by modulating miR-199a-3p, providing a novel treatment scheme for CC in the future.
A Hypercoagulable Hematological Metastasis Breast Cancer Model
Authors: Yang Wen-Jing , Zhang Gan-Lin , Cao Ke-Xin , Yang Guo-Wang
Published: August 2021

Background. The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. Methods. Based on the tumor‐bearing period (TBP) and postoperative incubation period (PIP), 4T1‐breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression‐based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. Results. The multiple linear regression model was constructed as log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 17) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. Conclusions. In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.
Landscape of Immune Microenvironment in Epithelial Ovarian Cancer and Establishing Risk Model by Machine Learning
Authors: Liu Shi-yi , Zhu Rong-hui , Wang Zi-tao , Tan Wei , Zhang Li , Wang Yan-qing , Dai Fang-fang , Yuan Meng-qin , Zheng Ya-jing , Yang Dong-yong , Wang Fei-yan , Xian Shu , He Juan , Zhang Yu-wei , Wu Ma-li , Deng Zhi-min , Hu Min , Cheng Yan-xiang , Liu Ye-qiang
Published: August 2021

Background. Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME). Method and Result. We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through “xCell” algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes (CXCL9, VSIG4, ALOX5AP, TGFBI, UBD, and CXCL11). And DC-related risk stratify model had been well established and validated. Conclusion. High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC.
Analysis of the Complete Genomes of Enterovirus 71 Subtypes in China
Authors: Wang Lei , Dai Yuzhu , Cheng Jun , Sun Changgui , Chen Yu , Cui Dawei
Published: August 2021

Enterovirus 71 (EV-A71) is one of the most pathogens to hand, foot, and mouth disease (HFMD) as well as neurological complications in young children. Molecular characteristic of EV-A71 is important to prevent the virus outbreak. Here, the complete genomes of EV-A71 from China between 1998 and 2019 were downloaded from GenBank. The phylogenetic trees were developed by MEGA7.0 software, and the complete genetic epidemiological characteristics and amino acid mutations of EV-A71 from China were also analysed. The results showed that major epidemic EV-A71 subtype was C4b before 2004, while it turned to C4a after 2004 in mainland China, and C4 and B5 were major subtypes in Taiwan. VP1, VP4, 2C, 3C, 3D, and complete genome sequence can be used for virus genotyping, and VP1, VP4, and complete genomes have obvious advantages over other segments. There were many significant mutations in the viral complete genome sequence. This study indicated that the major C4 and B5 subtypes will contribute to the development of vaccines and drugs of EV-A71 for prevention and monitoring of EV-A71-associated HFMD in China.
miR‐143‐3p Inhibits the Differentiation of Osteoclast Induced by Synovial Fibroblast and Monocyte Coculture in Adjuvant‐Induced Arthritic Rats
Authors: Jiang Baoping , Yuan Chengchen , Han Jing , Shen Meiyu , Zhou Xueping , Zhou Lingling
Published: August 2021

Osteoclast, which mediates overactive bone resorption, is one of the key factors for bone destruction in rheumatoid arthritis (RA). Existing studies have shown that abnormal miR‐143‐3p expression was observed in both RA patients and arthritis animals, which can participate in osteoclast differentiation, and mitogen‐activated protein kinase (MAPK) signaling pathway was closely related to osteoclast differentiation. The primary objective of the current study was to determine the role of miR‐143‐3p in the progression of osteoclast differentiation and its relationship with MAPK signaling pathways. The results showed that miR‐143‐3p inhibited osteoclast differentiation and decreased the levels of M‐CSF and RANKL during osteoclast differentiation. miR‐143‐3p inhibited the expression of MAPK signaling proteins, which is ERK1/2 in the early stage and JNK in the later stage of osteoclast differentiation. It was also observed that MAPK inhibitors upregulated miR‐143‐3p expression in osteoclast differentiation. Taken together, our results suggested that miR‐143‐3p could inhibit the differentiation of osteoclast, which was related to inhibiting MAPK signaling pathways. This may provide a novel strategy for curing RA.
An Efficient Identification Algorithm to Identify Mobile RFID Tags
Authors: Yao Yonglei , Su Jian
Published: August 2021

Tag identification in a fast‐moving environment is an emerging challenge for future RFID systems. However, existing literatures on the tag reading protocol design primarily apply to stationary scenarios, which fail to cope with mobile environments with unreliable channel condition. In this paper, we first review various types of prior reading protocols and then discuss a new direction of mobile tag reading by proposing a novel partitioning strategy. This analysis and experimental results show its superiority in achieving reading performance for the UHF RFID system under a mobile environment.
Application of Flipped Classroom Model Driven by Big Data and Neural Network in Oral English Teaching
Authors: Zeng Yujun
Published: August 2021

With the advancement of big data and neural network technology, flipped classroom informatization has shifted the traditional order of knowledge transfer and internalization, emphasizing students’ autonomous learning before class, knowledge absorption, and knowledge completion in class with the assistance of teachers. Students’ internalization and consolidation create the conditions for individualized learning. In foreign teaching, the benefits and feasibility of the flipped classroom have been demonstrated, and it is a promising new teaching model. Although recent research on oral English teaching in Chinese universities has yielded promising results, students’ classroom activity and participation remain low, learning initiative is lacking, and opportunities and time for oral training are insufficient. This article uses flipped classroom, big data, and neural network technology to teach college oral English classes, with the goal of determining whether the flipped classroom model can help students improve their oral English proficiency and self‐learning ability, as well as exploring students’ attitudes toward the flipped classroom model. This paper first proposes a big data and deep neural network‐based algorithm for detecting oral English pronunciation errors, which can be used for self‐correction of students in the flipped classroom mode to improve the quality of oral English teaching. Finally, we also conducted simulation experiments, and the experimental results show that our algorithm is 4.12% better than SVM.
COVID‐19 Vaccine, TRIPS, and Global Health Diplomacy: India’s Role at the WTO Platform
Authors: Chattu Vijay Kumar , Singh Bawa , Kaur Jaspal , Jakovljevic Mihajlo
Published: August 2021

In light of the devastation caused by COVID‐19, the Agreement on Trade‐Related Aspects of Intellectual Property Rights (TRIPS) and vaccine research and development (R&D) have been occupying a prominent position in the field of global health diplomacy (GHD). Most countries, international organizations, and charitable organizations have been engaged in the R&D of COVID‐19 vaccines to ensure timely affordability and accessibility to all countries. Concomitantly, the World Trade Organization (WTO) provides some provisions and enforcements regarding copyrights, patents, trademarks, geographical indications, and industrial designs. Given these safeguards, it is considered that intellectual property rights (IPRs) have become major barriers to the affordability and accessibility of vaccines/medicines/technology, particularly to the developing/least developed countries. Realizing the gravity of the pandemic impact, as well as its huge population and size, India has elevated this issue in its global health diplomacy by submitting a joint proposal with South Africa to the World Trade Organization (WTO) for a temporary waiver of IPRs to ensure timely affordability and accessibility of COVID‐19 medical products to all countries. However, the issue of the temporary waive off had become a geopolitical issue. Countries that used to claim per se as strong advocates of human rights, egalitarianism, and healthy democracy have opposed this proposal. In this contrasting milieu, this paper is aimed at examining how the TRIPS has become a barrier for developing countries’ development and distribution of vaccines/technology; secondly, how India strategizes its role in the WTO in pursuant of its global health diplomacy? We conclude that the IPRs regime should not become a barrier to the accessibility/affordability of essential drugs and vaccines. To ensure access, India needs to get more engaged in GHD with all the involved global stakeholders to get strong support for their joint proposal. The developed countries that rejected/resisted the proposal can rethink their full support.
A Context‐Aware Assisted WiFi Positioning Method
Authors: Feng Qi , Jia Bing , Luo Xi , Li Sha
Published: August 2021

With the convenience brought by Location‐based service (LBS), users’ requirements for indoor positioning accuracy are getting higher than ever. However, many traditional indoor WiFi positioning methods may result in limited positioning accuracy because of the limited information of Received Signal Strength (RSS) of WiFi signal. This paper proposed a context‐aware assisted WiFi positioning method (CAA‐PM), which uses context information (i.e., light and sound) to assist WiFi‐RSS for indoor positioning and uses an improved variable weight dynamic KNN fingerprint identification algorithm (VWD‐KNN). Finally, experiments are carried out by using the dataset collected in both a closed laboratory and an open long corridor, and it is shown that the proposed algorithm substantially improves the localization accuracy comparing with other three classical algorithms.
Deep Feature Autoextraction Method for Intrapulse Data of Radar Emitter Signal
Authors: Wang Shiqiang , Gao Caiyun , Luo Chang , Zeng Huiyong , Zheng Guimei , Zhang Qin , Bai Juan , Zong Binfeng
Published: August 2021

Concerned with the problems that the extracted features are the absence of objectivity for radar emitter signal intrapulse data because of relying on priori knowledge, a novel method is proposed. First, this method gets the sparse autoencoder by adding certain restrain to the autoencoder. Second, by optimizing the sparse autoencoder and confirming the training scheme, intrapulse deep features are autoextracted with encoder layer parameters. The method extracts the eigenvectors of six typical radar emitter signals and uses them as inputs to a support vector machine classifier. The experimental results show that the method has higher accuracy in the case of large signal-to-noise ratio. The simulation verifies that the extracted features are feasible.
An Adaptive Nonmonotone Line Search Technique for Solving Systems of Nonlinear Equations
Authors: Hatamian Masoud , Paripour Mahmoud , Mohammadi Yaghoobi Farajollah , Karamikabir Nasrin
Published: August 2021

In this article, a new nonmonotone line search technique is proposed for solving a system of nonlinear equations. We attempt to answer this question how to control the degree of the nonmonotonicity of line search rules in order to reach a more efficient algorithm? Therefore, we present a novel algorithm that can avoid the increase of unsuccessful iterations. For this purpose, we show the robust behavior of the proposed algorithm by solving a few numerical examples. Under some suitable assumptions, the global convergence of our strategy is proved.
Quasi‐Identifier Recognition Algorithm for Privacy Preservation of Cloud Data Based on Risk Reidentification
Authors: Mansour Huda O. , Siraj Maheyzah M. , Ghaleb Fuad A. , Saeed Faisal , Alkhammash Eman H. , Maarof Mohd A.
Published: August 2021

Cloud computing plays an essential role as a source for outsourcing data to perform mining operations or other data processing, especially for data owners who do not have sufficient resources or experience to execute data mining techniques. However, the privacy of outsourced data is a serious concern. Most data owners are using anonymization‐based techniques to prevent identity and attribute disclosures to avoid privacy leakage before outsourced data for mining over the cloud. In addition, data collection and dissemination in a resource‐limited network such as sensor cloud require efficient methods to reduce privacy leakage. The main issue that caused identity disclosure is quasi‐identifier (QID) linking. But most researchers of anonymization methods ignore the identification of proper QIDs. This reduces the validity of the used anonymization methods and may thus lead to a failure of the anonymity process. This paper introduces a new quasi‐identifier recognition algorithm that reduces identity disclosure which resulted from QID linking. The proposed algorithm is comprised of two main stages: (1) attribute classification (or QID recognition) and (2) QID dimension identification. The algorithm works based on the reidentification of risk rate for all attributes and the dimension of QIDs where it determines the proper QIDs and their suitable dimensions. The proposed algorithm was tested on a real dataset. The results demonstrated that the proposed algorithm significantly reduces privacy leakage and maintains the data utility compared to recent related algorithms.
A Mental Health Assessment Model of College Students Using Intelligent Technology
Authors: Li Keke , Yu Weifang
Published: August 2021

College students are under increasing competition pressure, which has a negative impact on their mental health, as the pace of learning and life accelerates, as well as the increasingly difficult employment situation. As a result, emphasizing the importance of college students’ mental health and fully addressing it has become a top priority in the work of colleges and universities. However, some students and even teachers are currently unconcerned about mental illness, making it difficult for students with psychological abnormalities to receive timely detection and effective treatment. As a result, it is the responsibility of student management for colleges and universities to identify and intervene early in the mental health problems of college students. Through the use of multimodal data and neural network models, it is now possible to evaluate and predict the mental state of college students in real time, thanks to the advancement of intelligent technology. Therefore, a novel multimodal neural network model is proposed in this paper. Our model is divided into two branches in particular. The traditional mental health assessment and prediction algorithm, which is based on the improved BP neural network and the International Mental Health Scale SCL‐90, is one of the branches. Given how difficult it is to meet the requirements for the accuracy of college students’ mental health assessments using this method, our other branch is computer vision‐based facial emotion recognition of college students, which is used to aid in the evaluation of mental health assessments. Our model demonstrates competitive performance through simulation and comparative experiments.
An Optimized Collision Avoidance Decision-Making System for Autonomous Ships under Human-Machine Cooperation Situations
Authors: Wu Xiaolie , Liu Kezhong , Zhang Jinfen , Yuan Zhitao , Liu Jiongjiong , Yu Qing
Published: August 2021

Maritime Autonomous Surface Ships (MASSs) are attracting increasing attention in recent years as it brings new opportunities for water transportation. Previous studies aim to propose fully autonomous system on collision avoidance decisions and operations, either focus on supporting conflict detection or providing with collision avoidance decisions. However, the human-machine cooperation is essential in practice at the first stage of automation. An optimized collision avoidance decision-making system is proposed in this paper, which involves risk appetite (RA) as the orientation. The RA oriented collision avoidance decision-making system (RA-CADMS) is developed based on human-machine interaction during ship collision avoidance, while being consistent with the International Regulations for Preventing Collisions at Sea (COLREGS) and Ordinary Practice of Seamen (OPS). It facilitates automatic collision avoidance and safeguards the MASS remote control. Moreover, the proposed RA-CADMS are used in several encounter situations to demonstrate the preference. The results show that the RA-CADMS is capable of providing accurate collision avoidance decisions, while ensuring efficiency of MASS maneuvering under different RA.
Recurrent Bilateral Optic Neuritis Associated with Myelin Oligodendrocyte Glycoprotein Antibody: A Case Report from Nepal
Authors: Shah Sangam , Ojha Rajeev , Sitaula Sanjeeta , Regmi Dosti , Karn Ragesh , Gajurel Bikram Prasad , Rajbhandari Reema , Gautam Niraj , Paudel Sunanda , Shrestha Aashish
Published: August 2021

Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory condition involving spinal cord and optic nerves. Diagnosis of NMOSD is done by aquaporin-4 antibody (AQP4) in patients with optic neuritis. Myelin oligodendrocyte glycoprotein (MOG) expressed on the oligodendrocyte cell surface and on the outermost cell surface of the myelin sheath may also be present in patients with NMOSD bilateral optic neuritis. Here, we describe a case of a thirty-nine-year-old-female with recurrent bilateral optic neuritis with positive anti-MOG antibody, and anti-MOG syndrome has not previously been reported from Nepal.
Decoupling Strategy and Modular Design for Loosely Coupled Organizations
Authors: Zhang Jing , Li Fengyan , Zhang Xiangmin
Published: August 2021

Under the technological innovation network, loosely coupled organizations featured by weak connections and relative independence have formed through the dynamic division of labor and knowledge sharing of enterprises. The loosely coupled organizations greatly enhance cooperation performance, but face problems such as poor flexible matching between partners and low innovation efficiency. Meanwhile, modular organizations can connect with other organizations to realize a specific operational goal via contracts and carry prominent features such as collaborative innovation, adaptive division of labor, and dynamic capabilities, offering an effective network governance model for collaboration between enterprises. Based on the two dimensions (looseness and coupling) between organizations, this paper uses the design dependency matrix (DDM) to map demands for functional/design modules, under the division of labor within products and the decisions on product modules, and preliminarily decouple the functional/design modules. Based on clustering DDM, a decision structure matrix (DSM) was constructed, and the clustering decoupling algorithm was adopted to create clustering design structure modules. Referring to these clustering modules, intraproduct division of labor was performed to realize the modular cooperation between organizations.
Application of Markov Model-Based IoT in Agricultural Insurance and Risk Management
Authors: Chen Wei , Jiang Yuansheng
Published: August 2021

As the foundation of the national economy, agriculture is a high-risk, weak industry. Affected by many factors, agricultural production is subject to catastrophe risks from time to time. Agricultural production is mainly faced with two major threats, natural disaster risk and market risk. As an effective risk management tool, the production and promotion of agricultural insurance have played an essential role in guaranteeing the development of the agricultural industry in some developed countries and major agricultural countries in the world. This article combines the Internet of Things and Markov model for agricultural insurance risk management. First, we combine the structure of the Internet of Things and select relevant statistical data. Then, we build a panel data system, starting from two perspectives in different regions and analyze agricultural insurance’s current development and characteristics at each stage. In addition, we use the Markov model to build a panel data model to explore the specific impact mechanisms deeply. We also study the effects of disaster risk levels in different regions on the development of agricultural insurance. After simulation verification, we believe that this model can effectively promote the balanced regional development of agricultural insurance.
A General Scheme for Solving Systems of Linear First-Order Differential Equations Based on the Differential Transform Method
Authors: Hussein Msmali Ahmed , Alotaibi A. M. , El-Moneam M. A. , Badr Badr S. , Ahmadini Abdullah Ali H.
Published: August 2021

In this study, we develop the differential transform method in a new scheme to solve systems of first-order differential equations. The differential transform method is a procedure to obtain the coefficients of the Taylor series of the solution of differential and integral equations. So, one can obtain the Taylor series of the solution of an arbitrary order, and hence, the solution of the given equation can be obtained with required accuracy. Here, we first give some basic definitions and properties of the differential transform method, and then, we prove some theorems for solving the linear systems of first order. Then, these theorems of our system are converted to a system of linear algebraic equations whose unknowns are the coefficients of the Taylor series of the solution. Finally, we give some examples to show the accuracy and efficiency of the presented method.
A Review on Montmorillonite-Supported Nanoscale Zerovalent Iron for Contaminant Removal from Water and Soil
Authors: Yin Yaru , Zheng Wenjuan , Yan An , Zhang Chenxi , Gou Yuxuan , Shen Chongyang
Published: August 2021

Nanoscale zerovalent iron (nZVI) has shown great promise for water treatment and soil remediation. However, the rapid aggregation of nZVIs significantly affects their mobility and reactivity, which considerably limits the practical applications. Montmorillonite- (Mt-) supported nZVI (Mt-nZVI) has received increasing attention for the past decade because it can prevent the aggregation of nZVI and incorporate the advantages of both nZVI and Mt in soil and water treatment. This work thus had a comprehensive review on the use of Mt-nZVI for soil and water treatment. We first summarized existing methods used to prepare Mt-nZVI, indicating the advantages of using Mt to support nZVI (e.g., increase of the dispersion and mobility of nZVI, reduction of the size and oxidation tendency of nZVI). We then presented the reaction mechanisms of Mt-nZVI for contaminant removal and evaluated the critical factors that influence the removal (e.g., pH, temperature, and dosage of the adsorbent). We further presented examples of applications of Mt-nZVI for the removal of typical contaminants such as heavy metals and organic compounds in soil and water. We finally discussed the limitations of the use of Mt-nZVI for water treatment and soil remediation and presented future directions for the application of nZVI technology for soil and water treatment.
Prostate-Specific Antigen Kinetics Effects on Outcomes of Low-Volume Metastatic Prostate Cancer Patients Receiving Androgen Deprivation Therapy
Authors: Lin Yen-Chi , Lin Po-Hung , Shao I-Hung , Chu Yuan-Cheng , Kan Hung-Cheng , Liu Chung-Yi , Yu Kai-Jie , Chang Ying-Hsu , Pang See-Tong , Huang Jhen-Ling , Chuang Cheng-Keng
Published: August 2021

Background. The present study aimed to analyse factors influencing the effects of androgen deprivation therapy (ADT) in patients with newly diagnosed metastatic castration-naïve prostate cancer (mCNPC), especially in low-volume disease (LVD), according to subclassification of metastatic prostate cancer established by the CHAARTED trial. Materials and Methods. We reviewed 648 patients with newly diagnosed mCNPC receiving ADT at Chang Gung Memorial Hospital from January 2007 to December 2016. Basic characteristics and PSA kinetics profile were subsequently evaluated. Results. 48.3% of LVD patients progressed to castration-resistant prostate cancer (mCRPC). Among them, CRPC group had significantly shorter time to PSA nadir (TTN) and faster time from PSA nadir to CRPC (TFNTC) (

p

 < 0.001) compared to non-CRPC group. PSA doubling time (PSADT) < 4 months tended to be associated with faster disease progression and shorter overall survival (OS). Among all patients with metastatic prostate cancer, those with shorter TTN <9 months, higher nadir PSA level ≥1 ng/mL, and shorter PSADT <3 months had increased tendency for biochemical progression. Conclusions. PSADT is an effective clinical predictor for disease progression and survival in LVD. Other PSA kinetics including TTN and TFNTC, though not the major predictors for disease progression or OS in LVD, might be the predictors for disease control status.
TagNN: A Code Tag Generation Technology for Resource Retrieval from Open‐Source Big Data
Authors: Zeng Lingbin , Guo Xin , Yang Cheng , Lu Yao , Li Xiao
Published: August 2021

With the vigorous development of open‐source software, a huge number of open‐source projects and open‐source codes have been accumulated in open‐source big data, which contains a wealth of code resources. However, effectively and efficiently retrieving the relevant code snippets in such a large amount of open‐source big data is an extremely difficult problem. There are usually large gaps between the user’s natural language description and the open‐source code snippets. In this paper, we propose a novel code tag generation and code retrieval approach named TagNN, which combines software engineering empirical knowledge and a deep learning algorithm. The experimental results show that our method has good effects on code tag generation and code snippet retrieval.
Electroacupuncture Improves Clearance of Amyloid-β through the Glymphatic System in the SAMP8 Mouse Model of Alzheimer’s Disease
Authors: Liang Pei-zhe , Li Li , Zhang Ya-nan , Shen Yan , Zhang Li-li , Zhou Jie , Wang Zhi-jie , Wang Shu , Yang Sha
Published: August 2021

Background. Memory loss and cognitive impairment characterize the neurodegenerative disorder, Alzheimer’s disease (AD). Amyloid-β (Aβ) is the key factor that triggers the course of AD, and reducing the deposition of Aβ in the brain has been considered as a potential target for the treatment of AD. In clinical and animal studies, electroacupuncture (EA) has been shown to be an effective treatment for AD. In recent years, substantial evidence has accumulated suggesting the important role of the glymphatic system in Aβ clearance. Objective. The purpose of this study was to explore whether EA modifies the accumulation of Aβ through the glymphatic system and may thus be applied to alleviate cognitive impairments. Methods. Seven-month-old SAMP8 mice were randomized into a control group (Pc) and an electroacupuncture group (Pe). Age-matched SAMR1 mice were used as normal controls (Rc). Mice in the Pe group were stimulated on Baihui (GV20) and Yintang (GV29) for 10 min and then pricked at Shuigou (GV26) for ten times. EA treatment lasted for 8 weeks. In each week, EA would be applied once a day for the first five consecutive days and ceased at the remaining two days. After EA treatment, Morris water maze (MWM) test was used to evaluate the cognitive function; HE and Nissl staining was performed to observe the brain histomorphology; ELISA, contrast-enhanced MRI, and immunofluorescence were applied to explore the mechanisms underlying EA effects from Aβ accumulation, glymphatic system function, reactivity of astrocytes, and AQP4 polarization, respectively. Results. This EA regime could improve cognition and alleviate neuropathological damage to brain tissue. And EA treatment might reduce Aβ accumulation, enhance paravascular influx in the glymphatic system, inhibit the reactivity of astrocytes, and improve AQP4 polarity. Conclusion. EA treatment might reduce Aβ accumulation from the brain via improving clearance performance of the glymphatic system and thereby alleviating cognitive impairment.
FIG4-Associated Yunis-Varon Syndrome: Identification of a Novel Missense Variant
Authors: Umair Muhammad , Alkharfy Turki M. , Sajjad Sajida , Alfadhel Majid
Published: August 2021

Yunis-Varon syndrome (YVS; OMIM 216340) is a rare heterogeneous autosomal recessive disorder with easy recognition of characteristic severe neurological and skeletal abnormalities involving skeletal muscles and cartilages. This cleidocranial dysplasia is characterized by bone and tooth disorders; it also affects the cardiovascular system and tissues from ectoderm with very poor outcomes. Rarely, mutations of the FIG4 gene, encoding a 50-phosphoinositide phosphatase have been identified as the cause for YVS. We report a neonate born to a consanguineous couple with typical clinical manifestations of YVS. Using whole-exome sequencing, we identified a novel homozygous missense variant (c.968A>G; p.Gln323Arg) in the FIG4 gene. Thus, our study expands the molecular and genetic spectrum of FIG4-associated mutations. To our knowledge, this is the first reported case of YVS from the Saudi population.
Multicentric Carpotarsal Osteolysis Syndrome in a Mother and Daughter with a MAFB Missense Variant and Natural History of the Disease
Authors: Chen Kelin , Zamariolli Malú , Soares Maria de Fátima de Faria , Meloni Vera Ayres , Melaragno Maria Isabel
Published: August 2021

Multicentric carpotarsal osteolysis syndrome (MCTO; MIM #166300) is a rare skeletal disorder characterized by osteolysis affecting particularly the carpal, metacarpal, and tarsal bones, although other bones might be involved. MCTO is an autosomal dominant disease caused by heterozygous variants in the MAFB gene, frequently misdiagnosed as juvenile rheumatoid arthritis due to similar clinical manifestations. This study reports the first Brazilian family diagnosed with MCTO with progressive osteolysis of the carpal and tarsal bones, presenting a c.161C>T (p.Ser54Leu) heterozygous variant in the MAFB gene, describing the clinical, radiological, and molecular findings, compared with literature data, and discussing the different clinical and molecular diagnosis, as well as the natural history of the disease. Since MCTO is a disorder with progressive symptoms, an early diagnosis is important to avoid unnecessary investigations and treatments and to provide the proper follow-up.
Function of Astrocytes in Neuroprotection and Repair after Ischemic Stroke
Authors: Zhang Shufen , Shang Deshu , Shi Han , Teng Weiyu , Tian Li
Published: August 2021

Background: Astrocytes are the most numerous cell types within the central nervous system, and many efforts have been put into determining the exact role of astrocytes in neuroprotection and repair after ischemic stroke. Although numerous studies have been done in recent years, there is still no thorough understanding of the exact function of astrocytes in the whole course of the stroke. Summary: According to the recent literature, there are many structures and factors that play important roles in the process of ischemic stroke, among which blood-brain barrier, various growth factors, gap junctions, AQP4, and glial scars have been studied most comprehensively, and all these factors are closely related to astrocytes. The role of astrocytes in ischemic stroke, therefore, can be analyzed more comprehensively. Key Message: The present review mainly summarized the current knowledge about astrocytes and their potential roles after ischemic stroke.
Seasonal Variation in Incidence of Stroke in a General Population of 1.4 Million Japanese: The Shiga Stroke Registry
Authors: Fujii Takako , Arima Hisatomi , Takashima Naoyuki , Kita Yoshikuni , Miyamatsu Naomi , Tanaka-Mizuno Sachiko , Shitara Satoshi , Urushitani Makoto , Miura Katsuyuki , Nozaki Kazuhiko
Published: August 2021

Introduction: The purpose of this study was to investigate seasonal variation in stroke incidence using data from a large-scale stroke registry of general population in current Japan. Methods: Shiga Stroke Registry (SSR) is an ongoing population-based registry of stroke that occurred in the Shiga Prefecture in central Honshu, Japan. A total 6,688 cases of first-ever stroke, with onset dates ranging from 1 January 2011 to 31 December in 2013 were included in this study. Incidence rates of first-ever stroke in each season were estimated using the person-year approach and adjusted for age and sex using the Poisson regression models. Results: From 2011 to 2013, we identified a total of 6,688 stroke cases (3,570 men, 3,118 women), of which 4,480 cases had ischemic stroke (2,518 men, 1,962 women), 1,588 had intracerebral hemorrhage (857 men, 731 women) and 563 had subarachnoid hemorrhage (166 men, 397 women). Age- and sex-adjusted incidence rates of total stroke were 151 (95% confidence interval [CI] 144–160, p = <0.001 vs. summer) in spring, 130 (95% CI 122–137) in summer, 141 (95% CI 133–149, p = 0.020 vs. summer) in autumn and 170 (95% CI 161–179, p = <0.001 vs. summer) in winter. Seasonal variation was more pronounced in intracerebral hemorrhage than in ischemic stroke. Conclusion: In the present large-scale stroke registry of general population, incidence rates of stroke were highest in winter and lowest in summer in current Japan.
Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Microsimulation Study
Authors: Shangguan Siyi , Mozaffarian Dariush , Sy Stephen , Lee Yujin , Liu Junxiu , Wilde Parke E. , Sharkey Andrea L. , Dowling Erin A. , Marklund Matti , Abrahams-Gessel Shafika , Gaziano Thomas A. , Micha Renata
Published: August 2021

Background:

High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention’s potential effects and cost-effectiveness are unclear.

Methods:

A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person’s transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education.

Results:

Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans.

Conclusions:

Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.
Abstract 01: Thirty-day Readmission Rate For Hypertensive Crisis: A Nationwide Analysis
Authors: Ashraf Muddasir , Zlochiver Viviana , Bolton Alexander , Jan M Fuad
Published: August 2021

Objective:
Hypertensive crisis is a life-threatening condition that leads to poor patient outcomes if not treated urgently. We evaluate the all-cause 30-day readmission rate, resource utilization, predictors of readmission, and the most common causes for readmission in patients admitted with hypertensive crisis.

Methods:
Using the National Readmission Database 2018, patients ≥18 years of age admitted with the principal diagnosis of the hypertensive crisis were included in the study. The primary outcome was the all-cause 30-day readmission rate in these patients.

Results:
We identified 129,239 patients as index admissions. The mean age of index patients was 61±0.14 years, and females were 56.6%. The 30-day readmission rate was 10.6 % (13,768± 355). The in-hospital mortality rate was 0.2 % for index admissions and 1.5 % for readmissions. The cumulative length of stay (LOS) for all readmitted patients was 62,046± 1,802 days. The cumulative total cost of hospital services in readmitted patients was 155 ± 4.6 million USD. Age<65, lower-income, increased LOS, increased comorbidity burden, primary payer, and disposition were important predictors of readmission (Table). The most common causes of readmission were hypertensive crisis (19 %), CHF (12.4%), acute renal failure (4.4%), sepsis (2.6%), ESRD (2%), NSTEMI (2%), and stroke (1.7%)

Conclusion:
In conclusion, the 30-day readmission rate in patients with hypertensive crisis is high (10.6%), with hypertensive crisis and CHF as the most common causes. Resource utilization is also high, with many potential avoidable days and costs. Future strategies should address underlying factors, especially socioeconomic factors.
Abstract 05: Cyclooxygenase-2 Inhibition As A New Tool To Combat Angiogenesis Inhibitor-induced Hypertension And Renal Toxicity
Authors: van Dorst Daan C , Mirabito Colafella Katrina M , van Doorn Leni , van Veghel Richard , Garrelds Ingrid M , Mathijssen Ron H , Danser A. H , Versmissen Jorie
Published: August 2021

Angiogenesis inhibitors are effective anti-cancer agents, but also cause hypertension and renal injury. Earlier, we observed in rats that high-dose aspirin (capable of blocking cyclooxygenase (COX)-1 and -2) prevented these side effects better than low-dose aspirin (blocking COX-1 only). Therefore, we hypothesized that selective COX-2 inhibition would prevent toxicity during angiogenesis inhibition, and that this toxicity involves a reduced ratio of vasodilator/constrictor COX-derived prostanoids, i.e., prostacyclin (PGI
2
) and thromboxane (TXA
2
). Male WKY rats received vehicle, angiogenesis inhibition (sunitinib (SU), 14 mg/kg/day) alone or combined with COX-2 inhibition (celecoxib, 10mg/kg/day), a PGI
2
analogue (iloprost 100 μg/kg/day), or a dual TXA
2
synthase/receptor antagonist (picotamide, 2.5 mg/kg/day) for 8 days (n=7-8/group). Mean arterial pressure (MAP) was measured via radiotelemetry, vascular function was assessed via wire myography, and biochemical measurements were performed by ELISA. SU induced a rapid increase in MAP (16±2 vs. 3±1 mmHg after vehicle on day 6, P<0.001), which was blunted by celecoxib (10±2 mmHg on day 6, P=0.06 versus SU), temporarily attenuated by iloprost (on treatment days 1-2) and unaffected by picotamide. Wire myography demonstrated a trend towards increased vasoconstrictor response to endothelin-1 in iliac arteries after SU, which was prevented by celecoxib (P<0.001). SU increased albuminuria (0.6±0.1 vs. 0.3±0.1 mg/24h after vehicle; P<0.001), and this was prevented by celecoxib only (0.4±0.1 mg/24h, P=0.01 vs. SU). SU increased the PGI
2
/TXA
2
ratio in both plasma (2.7±1.2 vs. 0.6±0.2 after vehicle, P=0.05) and urine (22±2.2 vs. 0.9±0.2 after vehicle, P<0.001). In conclusion, selective COX-2 inhibition combats angiogenesis inhibitor-induced hypertension and renal toxicity. SU paradoxically increases the PGI
2
/TXA
2
ratio, particularly in the kidney. Although this upregulation might initially be protective, it could eventually contribute to renal toxicity, most likely because PGI
2
exerts deleterious effects in excessive concentrations. Targeting excessive renal PGI
2
production might be another promising strategy to prevent renal toxicity during angiogenesis inhibition.
Abstract 14: An Anti-inflammatory Proton Sensing-receptor Contributes To Cardiovascular Protection Of Gut Microbiota-derived Metabolites
Authors: Xie Liang , R Muralitharan Rikeish , Dinakis Evany , Nakai Michael E , Jama Hamdi , Peh Alex Cheng Guan , Ang Caroline , Paterson Madeleine , Salimova Ekaterina , Robert Remy , Mackay Charles , Marques Francine Z
Published: August 2021

High fibre (HF) diet protects against hypertension via the production of acidic metabolites, e.g. short-chain fatty acids, by the gut microbiota. While these metabolites have a direct role in blood pressure (BP) regulation, their acidic nature may activate proton-sensing receptors, which have anti-inflammatory functions. G-protein coupled receptor 65 (GPR65) is a proton-sensing receptor activated around pH 6.5 and is critical for gut homeostasis. We hypothesized that GPR65 is involved in the cardiovascular protection by dietary fibre. We first measured cecal pH of C57BL/6 (WT) mice after a 7-day dietary intervention with either HF or low fibre (LF) diets (n=6/group). HF diet lowered cecal pH to a level where GPR65 is highly activated, compared to the LF diet (6.5±0.1 vs 7.6±0.1, P<0.001). The impact of pH and GPR65 on T cell production of IFNγ, a pro-inflammatory cytokine,
in vitro
was measured by flow cytometry. Acidic pH inhibited the production of IFNγ by CD8+ T cells (pH 6.5 vs pH 7.5, P<0.001). Cells lacking GPR65 had higher IFNγ at both pH (P<0.001). To determine if GPR65 is involved in BP regulation by dietary fibre, WT and GPR65 knockout (

Gpr65
-/-

) mice were implanted with minipumps containing angiotensin II (Ang II, 0.5mg/kg/day, 28 days, n=8-9/group) and fed with HF diet. BP, cardiorenal function and immune cell infiltration were measured.

Gpr65
-/-

mice had higher BP compared to WT mice after 2 weeks (mean arterial pressure ± SEM; WT 79.8±2.4 vs

Gpr65
-/-

95.8±1.6mmHg, P<0.001) and 4 weeks of Ang II infusion (WT 92.3±2.4 vs

Gpr65
-/-

99.5±1.3, P=0.062).

Gpr65
-/-

mice developed cardiac (P=0.035) and renal (P=0.025) hypertrophy, and impaired renal natriuretic (P=0.054) and diuretic (P=0.056) function compared to WT mice. This was accompanied by higher macrophage (P=0.009) and γδ T cell (P=0.014) infiltration in the kidneys. In conclusion, our data suggest that pH-sensing by GPR65 contributes to the protection against hypertension by dietary fibre via inflammatory mechanisms. This is a novel mechanism that contributes to BP regulation via the gut microbiota.