bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of Intelligent Autonomous Agents Inspired by Biological Theory in Cognitive Environment
Authors: Refonaa J. , Porselvi A. , Shabu S. L. Jany , Santhosh Krishna B. V. , Siddiquee Kazy Noor-E-Alam
Published: April 2022

The paper investigates a naturally motivated meaning of wise shrewd self-ruling specialists of humans. Knowledge is identified with whether the conduct of a framework adds to its self-upkeep. Conduct turns out to be clearer (or adapts to more biological issue factors) when it is able to make and utilize portrayals. The thought of portrayal ought not to be confined to formal articulations with neuro hypothetical semantics. The element at different degrees of canny frameworks assumes a fundamental part in shaping portrayals. The paper investigates an organically roused meaning of shrewd self-ruling specialists of humans. Insight is identified with whether the conduct of a framework adds to its self-upkeep. Conduct turns out to be keener when it is proficient to make and utilize portrayals. The idea of portrayal also focused on formal articulations with sentimental hypothetical semantics.
The Relationship between Digital Marketing, Customer Engagement, and Purchase Intention via OTT Platforms
Authors: Habib Sufyan , Hamadneh Nawaf N. , Hassan Asif
Published: April 2022

The Internet and digital technologies have grown exponentially and have become a part of billions of people’s daily lives around the world. Over‐the‐top (OTT) services are delivered directly over the Internet, providing customers access to films and TV series. In India, there has been a tremendous surge in the consumption of video material on OTT platforms. The significant growth in the digital marketing application in online businesses and its ability to engage customers has enhanced its importance. The emergence of the Internet and digital technologies has provided a modernized setting and a fertile ground for business organizations to reach millions of customers at affordable prices with effective and customized promotion content. The present study aims to investigate the relationship between digital media marketing (DMM), consumer engagement, brand image, and OTT platform purchase intention in the Indian context. The researchers will also investigate the mediating role of consumer engagement and brand image in mediating the relationship between digital marketing practices and OTT platform purchase intention. In a survey of 417 Indian consumers, it was found that there was no direct effect of DMM on the purchase intention of OTT platforms. In addition, there is a strong indirect effect through brand image and consumer engagement, supporting the hypothesis that brand image and consumer engagement mediate the relationship between DMM practices and the purchase intention of OTT platforms. Some of the managerial implications, limitations, and scope of future research are also presented in the study.
The Deep Participation of Zhejiang Private Science and Technology Enterprises in the Integrated Development of the Yangtze River Delta
Authors: Yin Xiaomin , Yu Siqi
Published: April 2022

Private science and technology enterprises are the main force in building a high-level innovative province in Zhejiang, and are also the driving force for the province’s high-quality integration into the Yangtze River Delta. At present, the integration of private science and technology enterprises in Zhejiang into the Yangtze River Delta has problems such as low integration ratio, high integration difficulty, low integration level, and insufficient integration confidence. The causes of the problem mainly include the concept bottlenecks and capacity limitations of private technology companies, the institutional dilemma of cooperation between regional governments and regional business environment synergy is not high, the role of non-governmental organizations is not fully developed. To create a powerful engine that drives private technology enterprises to deeply participate in the development of the Yangtze River Delta, it should be built and strengthened from the perspective of the main role of enterprises themselves, the role of government guidance, industry associations, and other non-governmental organizations to play the role of service coordination and supervision.
TiO2-DNA Nanosensor In Situ for Quick Detection of Nasal Flora in Allergic Rhinitis Patients
Authors: Chen Weihua , Zhang Kaiyang , Zhong Zewei
Published: April 2022

Background. A relevant study found that allergic rhinitis (AR) may be related to the imbalance of nasal flora. Therefore, if the nasal flora of AR patients can be detected quickly, it is of great significance to study the distribution law of nasal flora in AR patients and explore its correlation with AR. Objective. To design a new and convenient nano-DNA sensor for quick screening of nasal flora in allergic rhinitis (AR) patients, so as to provide experimental basis for the prevention and treatment of AR. Methods. We create a synthesized nanostructured DNA biosensor called Nano-TiO2-DNA sensor which can be combined with samples from nasal mucosa or secretion with high efficiency and detect certain flora in situ without DNA extraction or RNA sequencing. In a physical property test, firstly, we tested the permeability, solubility, and storage temperature of nano-TiO2, so as to provide experimental basis for the synthesis of Nano-TiO2-DNA sensor. Subsequently, the permeability of Nano-TiO2-DNA sensor in Staphylococcus aureus was further tested. In a clinical experiment, we selected 60 AR patients treated in our hospital from September 2020 to September 2021 as the AR group and 60 healthy people who underwent physical examination at the same time as the control group. The Nano-TiO2-DNA sensor was used to detect typical nasal flora in AR patients, and Pearson’s correlation analysis was used to explore the correlation between nasal flora with serum IgE and eosinophils. Results. As for physicochemical characteristics, this sensor can permeate into certain bacteria directly and specifically. It has high affinity ability with a target, and the combination can be detected by evaluating the released fluorescence qualitatively and quantitatively. It can be stored at −20°C in ethyl alcohol stably. By this sensor, we have successfully detected Staphylococcus aureus, Klebsiella pneumoniae, and viridans streptococci in AR patients compared with healthy people, which will help these patients in the prevention of acute sinusitis and acute or subacute pneumonia. Furthermore, we found Proteus had the strongest positive correlation with AR while Actinomyces had the biggest negative correlation. Conclusion. The Nano-TiO2-DNA sensor will help an outpatient doctor more for quick screening certain nasal flora in AR patients and improve the prevention of AR-related complications.
Phytochemical Analysis and Antifungal Potentiating Activity of Extracts from Loquat (Eriobotrya japonica) against Cryptococcus neoformans Clinical Isolates
Authors: Bisso Borel Ndezo , Kayoka-Kabongo Prudence Ngalula , Tchuenguem Roland Tchuenteu , Dzoyem Jean Paul
Published: April 2022

Eriobotrya japonica (loquat) has been used in African traditional medicine with numerous beneficial health effects. The extracts from loquat contain several bioactive compounds with a plethora of pharmacological properties. However, a scientific study on the activity against the aetiological agent of cryptococcosis has not yet been reported. Therefore, this study aimed to investigate the antifungal potential of various extracts from Eriobotrya japonica against clinical isolates of Cryptococcus neoformans. Quantitative and qualitative phytochemical analyses of extracts were made by following standard procedures. The broth microdilution method and the checkerboard methods were used to determine the antifungal activity and the combination of extracts with antifungals drugs. The methanol extract of seeds and the hexane extract of leaves exhibited the best significant antifungal activity with MIC values of 32 µg/mL. Furthermore, the combination of both extracts with nystatin and clotrimazole showed synergistic interactions with a 32-fold reduction in the MIC values of nystatin. Our findings indicate that Eriobotrya japonica extracts are a potential source of new antifungals that could be developed for use in the treatment of cryptococcosis. The anticryptococcal and antifungal activities potentiating activity of the studied extracts indicate their potential in the management of cryptococcosis. Further study should be considered to identify the bioactive principles against Cryptococcus neoformans.
A Choice Behavior Model of Bike-Sharing Based on User Perception, Psychological Expectations, and Loyalty
Authors: Xue Xingjian , Wang Zixu , Liu Xuejiao , Zhou Zhou , Song Rui
Published: April 2022

In the midst of sharing concepts, bike sharing has made innovative changes to people’s travel modes. Providing high-quality services is essential to promoting the usage of bike sharing and to reducing traffic congestion by shifting people away from private car use. This research explores the factors that influence users’ selection of bike sharing as a transportation mode by identifying and describing relationships to user perception, psychological expectations, and loyalty. The effects of value identity, convenience, economy, comfort, perceived safety, travel characteristics (TC), and sociodemographic factors (SD) on the selection and usage of bike-sharing systems in Changsha, China, were analyzed. The mediating effect of user satisfaction (US) on the relationship between perceived quality (PQ) and use loyalty was examined. A total of 700 questionnaires were distributed at 20 bike-sharing locations, to which 569 users effectively responded. The results of the analysis indicate that loyalty to bike sharing was predicted by all of the studied constructs except for gender. The results of this study help us better understand the influencing factors of bike-sharing usage and can aid policymakers in formulating effective guidance strategies for bike-sharing travel demand based on a model structure.
Pramipexole Inhibits Neuronal Apoptosis in Rats with Parkinson’s Disease
Authors: Sun Yongqi , Cui Baohong , Ye Lin , Hu Yunxin , Pan Yujun
Published: April 2022

To explore the inhibition of pramipexole on the neuronal apoptosis and its influences on the expressions of brain tissue brain-derived neurotrophic factor (BDNF), and serum miR-103a and miR-30b and inflammatory factors in rats with Parkinson’s disease. A total of 36 Sprague-Dawley rats were randomly divided into normal group (n = 12), model group (n = 12) and pramipexole group (n = 12). Compared with that in normal group, the positive expression of BDNF was substantially increased in model group and pramipexole group, and its positive expression in pramipexole group was notably higher than that in model group. The WB results revealed that compared with those in normal group, the relative protein expression levels of Bax and Bcl-2 were markedly increased and decreased, respectively, in the other two groups, and that pramipexole group exhibited a remarkable decline in the relative protein expression level of Bax and a considerable increase in that of Bcl-2, compared with model group. The relative expression levels of miR-103a and miR-30b in model and pramipexole groups were markedly higher than those in normal group, and pramipexole group had remarkably higher relative expression levels of miR-103a and miR-30b than model group. It was found through ELISA that model and pramipexole groups had markedly raised IL-1β and IL-18 content compared with normal group, and their content in pramipexole group was remarkably lower than that in model group. Based on the TUNEL results, compared with that in normal group, the apoptosis rate of cells rose substantially in the other two groups, and the apoptosis rate in pramipexole group was notably lower than that in model group. Pramipexole may up-regulate the expressions of BDNF, miR-103a and miR-30b to inhibit the apoptosis and inflammation in Parkinson’s disease model rats.
Machining Performance of AA2024/5Al2O3/5Gr Hybrid Composites under Al2O3 Mixed Dielectric Medium
Authors: Kaliappan Nandagopal , Balaji M. , CH Anil Kumar T. , Arshad Haqqani , Prakash Tiruveedula N. B. , Hemavathi S. , Sahile Kibebe
Published: April 2022

In this research work, AA2024/5Al2O3/5Gr hybrid composites fabricated through stir casting were machined utilising an electric discharge machine (EDM). Experiments were performed by varying current, pulse on time (POT), gap voltage (GV), and Al2O3 powder concentration (PC). The experiments were designed using response surface methodology in which material removal rate (MRR), tool wear rate (TWR), and surface roughness (Ra) were recorded as responses. The addition of Al2O3 particles has a positive impact on MRR and Ra, whereas it has a negative impact on TWR. The interaction impact of process parameters (p-p) on responses was thoroughly analyzed using contour plots. A mathematical model was developed and validated for all the responses. The experimental results were compared with the predicted values. It was found that all the values have a maximum deviation of 3.5%. The ANOVA table reveals that the PC was the most influential factor followed by the current.
A Simplified Finite Element Model for Modular Steel Structure Building Wallboard through Experimental Research and Finite Element Analysis
Authors: Cong Jun , Zheng Shanzuo , Lin Bing , Zhang Lei , Peng Lin
Published: April 2022

The traditional research on steel plate shear wall structure mainly focuses on the overall performance of the wall, and the mechanical properties of the connection between plates and plates and between plates and frames are not clear. In this paper, the experimental research on the wallboard structure of bending plate was carried out and the mechanical properties and failure modes of five walls were analyzed. In addition, the connection properties between plates and frames were studied by finite element analysis. A simplified finite element model is presented by experimental study and finite element analysis. The results show that the finite element analysis results are in good agreement with the experimental results. The finite element model with the two-point binding constraint between the end of the bending plate and the angle steel can well simulate the mechanical properties of the steel plate shear wall structure.
A Grey BP Neural Network-Based Model for Prediction of Court Decision Service Rate
Authors: Zhao Gang , Shi Huibin , Wang Jifa
Published: April 2022

The judgment service rate is an important index to reflect the fairness of the judgment of legal cases in a certain area, which is of great significance to verify the accuracy of a court judgment. In this paper, a grey neural network model combining grey system theory and BP neural network algorithm is proposed to predict the index. Analyze the judgment service rate of the court judgment system, and build a prediction system based on the completion rate, completion rate, plaintiff satisfaction, defendant satisfaction, litigation time, property preservation cycle, document delivery time, implementation information disclosure rate, and other key indicators. Through example analysis, it is proved that the combined model of the grey prediction model and BP neural network has a small error and good simulation effect on the prediction of court decision-making service rate, which can better promote the development of court and society.
Enhanced Map-Aided GPS/3D RISS Combined Positioning Strategy in Urban Canyons
Authors: Song Xiang , Ren Chunxiao , Jiang Huilin , Li Liping , Wu Wei , Li Ling , Yan Shun , Zhang Bingyu , Wu Jiaen
Published: April 2022

To realize the effective positioning in urban canyons, an enhanced map-aided Global Positioning System (GPS)/three-dimensional (3D) reduced inertial sensor system (RISS) tightly combined positioning strategy is proposed. First, the 3D RISS is only based on the built-in controller area network (CAN). CAN bus sensor without additional sensors is first constructed to lower the cost. Then, a simple but effective enhanced map is created to assist positioning. Based on the map, a Kalman filtering (KF) tightly coupled method is proposed to fuse the 3D RISS with GPS information and to achieve the preliminary positioning. In KF-based preliminary positioning method, a simply observation noise variance optimization algorithm based on 2D enhanced map is proposed to improve KF method. In this algorithm, the value of the observation noise variance matrix is determined only according to the building plane information which is contained in the enhanced map. Further, a multiweight map matching algorithm is proposed for optimizing the initial positioning results. In this algorithm, factors such as distance, direction, road network topology, and lane change are considered and applied to map matching to further increase the positioning performance and form the final positioning results. Finally, the effectiveness of the strategy is proved by field test. The results show that this method has better accuracy and reliability than the conventional method.
Higher Mean Arterial Pressure during Cardiopulmonary Bypass May Not Prevent Acute Kidney Injury in Elderly Patients Undergoing Cardiac Surgery
Authors: Ge Yunfen , Behera Tapas Ranjan , Yu Ming , Xie Shuyang , Chen Yue , Mao Hui , Xu Qiong , Zhao Yu , Zhang Shuijun , Shen Quanquan
Published: April 2022

We aimed to evaluate the role of higher mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) in preventing development of acute kidney injury (AKI). Methods. We evaluated a population of elderly individuals >60 years of age undergoing CPB to find correlation of MAP during CPB with development of AKI after the surgery. Patients who experienced sustained low MAP during the CPB defined as that of <65 mmHg were compared with those that had sustained high MAP of >65 mmHg for their outcome with regard to AKI. The KDIGO criteria were used to define presence of acute kidney injury. Results. Of the total 92 patients, 50 were in the low-pressure group and 42 were in the high-pressure group. The MAP was 61.14 ± 5.54 mmHg in the low-pressure group and 68.97 ± 3.65 mmHg in the high-pressure group (

p

 < 0.001). 13 (26%) in the low-pressure group and 17 (40.48%) in the high-pressure group developed AKI (

p

 = 0.140). Male sex was associated with an increased incidence of cardiac surgery-associated AKI (

p

 = 0.034). Conclusions. A higher MAP in the range of 65–75 mmHg during the cardiopulmonary bypass does not significantly prevent acute kidney injury in elderly patients undergoing cardiac valve surgery.
Building Image Feature Extraction Using Data Mining Technology
Authors: Deng Yi , Xing Chengyue , Cai Ling
Published: April 2022

At present, data mining technology is continuously researched in science and application. With the rapid development of remote sensing satellite industry, especially the launch of remote sensing satellites with high-resolution sensors, the amount of information obtained from remote sensing images has increased dramatically, which has largely promoted the application of remote sensing data in various industries. This technique mines useable information from less complete and accurate data while ensuring low program complexity. In order to determine the impact of data mining techniques on feature extraction of graphic images, this paper explores the relevant steps in the image recognition process, especially the image preenhancement and image extraction processes. This paper develops a preliminary set of relevant data and investigates two different extraction methods based on the availability or absence of nursing information. Aiming at the advantages and disadvantages of the two house extraction methods, this work discusses how to effectively integrate remote sensing data. It uses different data sources to describe different characteristics of buildings, analyzes and extracts effective information, and finally derives building information. The research results show that, using the SVM algorithm in data mining for image feature extraction, in the verified filtering window, the accuracy can be effectively improved by about 20%. Buildings are important objects in high-resolution remote sensing images, and their feature extraction and recognition technology is of great significance in many fields such as digital city construction, urban planning, and military reconnaissance.
Treatment of Modified Dahuang Fuzi Decoction on Cognitive Impairment Induced by Chronic Kidney Disease through Regulating AhR/NF-κB/JNK Signal Pathway
Authors: Gu Mingjia , Ying Pu , Miao Zhiwei , Yu Xiang , Bao Rui , Xiao Jian , Gao Leiping , Chen Juping
Published: April 2022

Aim. An increasing widespread of chronic kidney disease (CKD) has been established lately around the globe. In addition to renal function loss, CKD can also cause cognitive impairment (CI). Modified Dahuang Fuzi Decoction (MDFD) is used as a traditional Chinese therapy for CKD. The effect of MDFD on cognitive impairment induced by chronic kidney disease (CKD-CI), and therapeutic mechanisms were investigated. Methods. The CKD animals’ model was developed in the 5/6 nephrectomized mice. Sham operation and model groups received normal saline, while positive control and MDFD high/medium/low dose received Aricept (10 mg/kg/day) and different doses of MDFD (24, 16, and 8 g/kg/day), respectively. Cognitive function was detected with the Morris water maze test, while related factors were determined by ELISA. Histopathology and mechanism were studied using HE, western blot, and qRT-PCR. Results. In the CKD-CI mice model, escape latency decreased significantly, whereas time of crossing platform and time spent within the platform quadrant increased substantially

P
<
0.05

after MDFD treatment. Moreover, renal function and brain injury in CKD-CI improved dose-dependently, while the effect of MDFD-L was worse. Proteins such as aryl hydrocarbon receptor, nuclear factor-kappa B and c-Jun-N-terminal kinase, and mRNA in the kidney and brain of all the treatment groups decreased substantially

P
<
0.05

. Expression of tropomyosin receptor kinase B and brain-derived neurotrophic factor at protein and mRNA levels in the brain were significantly enhanced

P
<
0.05

. Conclusion. MDFD presumably activated the BDNF/TrkB pathway by inhibiting the AhR/NF-κB/JNK signaling pathway to treat CKD-CI.
Bushen Jianpi Quyu Formula Alleviates Myelosuppression of an Immune-Mediated Aplastic Anemia Mouse Model via Inhibiting Expression of the PI3K/AKT/NF-κB Signaling Pathway
Authors: Li Hangchao , Ji Lina , Shen Yingying , Fu Danqing , Wu Dijiong , Ye Baodong
Published: April 2022

Bushen Jianpi Quyu Formula (BSJPQYF), an experienced formula, has been used to treat aplastic anemia (AA) more than three decades. To determinate the effect of BSJPQYF on AA, we constructed an immune-mediated AA mouse model. All mice were divided into four groups: control, model, low dose (0.85 g/mL), and high dose (1.7 g/mL BSJPQYF) group. They were administered with different concentrations of BSJPQYF or normal saline for 14 days. Besides, components of BSJPQYF were analyzed by electrospray ionization and mass spectrometry (ESI-MS). Subsequently, mouse peripheral blood and femurs were collected, and bone marrow mesenchymal stem cells (BMSCs) were isolated by fluorescence-activated cell sorting (FACS). Among them, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ) were measured by ELISA assay, PI3K, AKT, p-AKT, NF-κB, p-NF-κB, TNF-α, and cleaved caspase-3 proteins were detected by western blot. Compared with standard compounds, we identified three compounds of BSJPQYF, namely, icariin, kaempferol and tanshinone iia, as potentially effective compounds for the treatment of AA. Through an in vivo study, we found the administration of BSJPQYF in high dose for 14 days could significantly increase peripheral blood count and bone marrow (BM) cells, meanwhile decrease TNF-α, TGF-β, and IFN-γ levels. Besides, it could suppress the protein expression of PI3K and the phosphorylation of AKT and NF-κB to restrict the protein expression of TNF-α, eventually reduce the protein expression of cleaved caspase-3. This study demonstrated the therapeutic effects of BSJPQYF in AA, which could alleviate myelosuppression through inhibiting the expression of the PI3K/AKT/NF-κB signaling pathway.
Screening of Medications for Idiopathic Membranous Nephropathy Using Glomerular Whole-Genome Sequencing
Authors: Hou Yawei , Li Yameng , Li Wenpu , Xiao Zhenwei
Published: April 2022

Objective. To explore medications that have a therapeutic effect on idiopathic membranous nephropathy (IMN) using the Gene Expression Omnibus (GEO), the Connectivity Map (CMap) database, and bioinformatics approaches. Methods. IMN patients’ glomerular whole-genome sequencing data were retrieved and screened in the GEO database, differentially expressed genes were identified using GEO2R analysis, a PPI network was built in the STRING database, node degree values were calculated, and topological analysis was performed using the degree value to identify core genes. The WebGestalt database was used to perform GO enrichment and KEGG pathway analyses on the core genes. Candidate medications for the therapy of IMN were collected from the CMap database, and the candidate medications were then searched and analyzed. Results. 113 core genes were identified by topological analysis from the 1157 genes that were shown to be differentially expressed. The enrichment analysis identified several important gene functions and signaling pathways related to IMN. Some possible medications for the treatment of IMN have been found using the CMap database. Naringin, with the lowest CMap score, meaningful

P

value, and specificity score, was predicted as the most likely medication. Conclusion. The GEO and CMap databases can be used to understand the molecular changes of IMN and to provide new ideas for medication research. However, medication candidates must undergo clinical and experimental testing.
Three-Dimensional Conformal Radiotherapy Combined with Gemcitabine and Docetaxel in the Treatment of Advanced Bladder Cancer and Its Effects on Inflammatory Factors and Immune Function
Authors: Li Jianwei , Liu Min , Sun Pengyu , Zhao Wanli , Song Miaomiao , Liu Yang
Published: April 2022

Objective. To assess the efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with GT chemotherapy (gemcitabine+docetaxel) in the treatment of advanced bladder cancer and its influence on inflammatory factors and immune function. Methods. A total of 42 elderly patients with advanced bladder cancer who were admitted to our hospital from January 2019 to January 2020 were included and assigned to the GT group (21 cases) receiving GT chemotherapy and combination group (21 cases) given 3D-CRT combined with GT chemotherapy. The clinical efficacy, immune function, inflammatory factors, tumor markers, urinary angiogenesis molecules before and after treatment, 1-year survival rate, 2-year survival rate, and incidence of adverse reactions of the two groups were compared. SPSS 22.0 statistical software was used for data processing and analysis. Results. The combination group had 5 cases of CR, 12 cases of PR, 3 cases of SD, and 1 case of PD, with an ORR of 80.95% (17/21), which was remarkably higher than the ORR of 57.14% (12/21) in the GT group which had 3 cases of CR, 9 cases of PR, 5 cases of SD, and 4 cases of PD (

P
<
0.05

). The 1-year survival rate of the combination group was 76.19% (16/21), and the 2-year survival rate was 47.62% (10/21), which were higher than the 1-year survival rate of 47.62% (10/21) and 2-year survival rate of 19.05% (4/21) in the GT group (

P
<
0.05

). The two groups presented similar results in terms of adverse reactions rate (

P
>
0.05

). After treatment, the combination group obtained significantly lower levels of urinary bladder cancer antigen (UBC), nuclear matrix protein-22 (NMP-22), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) than the GT group (

P
<
0.05

). The CD3+, CD4+, and CD4+/CD8+ levels of the two groups of patients were lower than those before treatment (

P
<
0.05

), but no statistical difference was observed between the two groups after treatment (

P
>
0.05

). The levels of interleukin-6 (IL-6) and interferon-γ (IFN-γ) of the two groups witnessed a decline after treatment, with lower results in the combination group as compared to the control group (

P
<
0.05

). Before treatment, no significant difference in the Generic Quality of Life Inventory-74 (GQOLI-74) score between the two groups was found (

P
>
0.05

). After treatment, the combination group had higher GQOLI-74 scores than the GT group (

P
<
0.05

). Conclusion. 3D-CRT combined with GT chemotherapy yields a significant effect on the treatment of elderly advanced bladder cancer by effectively protecting immune function, mitigating inflammation, inhibiting tumor marker levels and the expression of angiogenic molecules, and improving patients’ survival.
Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies
Authors: van Putten Erik H.P. , Kleijn Anne , van Beusechem Victor W. , Noske David , Lamers Cor H.J. , de Goede Anna L. , Idema Sander , Hoefnagel Daphna , Kloezeman Jenneke J. , Fueyo Juan , Lang Frederick F. , Teunissen Charlotte E. , Vernhout René M. , Bakker Cathy , Gerritsen Winald , Curiel David T. , Vulto Arnold , Lamfers Martine L.M. , Dirven Clemens M.F.
Published: April 2022

Purpose:

Testing safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of patients with recurrent glioblastoma.

Patients and Methods:

Dose-escalation phase I study with 3+3 cohorts, dosing 107 to 1 × 1011 viral particles (vp) in 20 patients. Besides clinical parameters, adverse events, and radiologic findings, blood, cerebrospinal fluid (CSF), brain interstitial fluid, and excreta were sampled over time and analyzed for presence of immune response, viral replication, distribution, and shedding.

Results:

Of 20 enrolled patients, 19 received the oncolytic adenovirus Delta24-RGD, which was found to be safe and feasible. Four patients demonstrated tumor response on MRI, one with complete regression and still alive after 8 years. Most serious adverse events were attributed to increased intracranial pressure caused by either an inflammatory reaction responding to steroid treatment or viral meningitis being transient and self-limiting. Often viral DNA concentrations in CSF increased over time, peaking after 2 to 4 weeks and remaining up to 3 months. Concomitantly Th1- and Th2-associated cytokine levels and numbers of CD3+ T and natural killer cells increased. Posttreatment tumor specimens revealed increased numbers of macrophages and CD4+ and CD8+ T cells. No evidence of viral shedding in excreta was observed.

Conclusions:

CED of Delta24-RGD not only in the tumor but also in surrounding brain is safe, induces a local inflammatory reaction, and shows promising clinical responses.
Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression
Authors: Hemming Matthew L. , Bhola Patrick , Loycano Michael A. , Anderson Justin A. , Taddei Madeleine L. , Doyle Leona A. , Lavrova Elizaveta , Andersen Jessica L. , Klega Kelly S. , Benson Morgan R. , Crompton Brian D. , Raut Chandrajit P. , George Suzanne , Letai Anthony , Demetri George D. , Sicinska Ewa
Published: April 2022

Purpose:

Leiomyosarcoma (LMS) is a neoplasm characterized by smooth muscle differentiation, complex copy-number alterations, tumor suppressor loss, and the absence of recurrent driver mutations. Clinical management for advanced disease relies on the use of empiric cytotoxic chemotherapy with limited activity, and novel targeted therapies supported by preclinical research on LMS biology are urgently needed. A lack of fidelity of established LMS cell lines to their mesenchymal neoplasm of origin has limited translational understanding of this disease, and few other preclinical models have been established. Here, we characterize patient-derived xenograft (PDX) models of LMS, assessing fidelity to their tumors of origin and performing preclinical evaluation of candidate therapies.

Experimental Design:

We implanted 49 LMS surgical samples into immunocompromised mice. Engrafting tumors were characterized by histology, targeted next-generation sequencing, RNA sequencing, and ultra-low passage whole-genome sequencing. Candidate therapies were selected based on prior evidence of pathway activation or high-throughput dynamic BH3 profiling.

Results:

We show that LMS PDX maintain the histologic appearance, copy-number alterations, and transcriptional program of their parental tumors across multiple xenograft passages. Transcriptionally, LMS PDX cocluster with paired LMS patient-derived samples and differ primarily in host-related immunologic and microenvironment signatures. We identify susceptibility of LMS PDX to transcriptional cyclin-dependent kinase (CDK) inhibition, which disrupts an E2F-driven oncogenic transcriptional program and inhibits tumor growth.

Conclusions:

Our results establish LMS PDX as valuable preclinical models and identify strategies to discover novel vulnerabilities in this disease. These data support the clinical assessment of transcriptional CDK inhibitors as a therapeutic strategy for patients with LMS.
Serodominance Profile in a Dust Mite Complex Region
Authors: López-Rodríguez Raquel , Rial Manuel Jorge , Esteban-Gorgojo Ignacio , Veleiro Pérez Beatriz , López-Araújo Gustavo Adolfo , Pérez-Quintero Olinda , Carballas Clara , Parra Antonio , Pineda Fernando
Published: April 2022

Background/Objective: The objective of this study was to describe the molecular sensitization profile of mite allergy in an area with a high environmental exposure of house dust mites (HDM) and storage mites. Methods: Skin prick tests were performed with standardized extracts (DIATER, Madrid, Spain). A specific commercial molecular panel (MADx) for Dermatophagoides pteronyssinus (Dpt), Dermatophagoides farinae (Dfar), Lepidoglyphus destructor (Ldt), Tyrophagus putrescentiae (Tput), and Blomia tropicalis (Blot) was correlated with clinical parameters in Galician (northwestern of Spain) HDM allergic patients. Results: Fifty patients (60% female) met the inclusion and exclusion criteria. All of the patient’s present rhinitis (50), 28% (14) rhinitis and asthma, and 18% (9) atopic dermatitis (AD). Hundred patients had a positive prick test for Dpt, followed by Dfar (92%), Ldt and Tput (74%), and Blot (68%). More than 50% recognized specific IgE for Der p 1, Der p 2, reaching 86% in the case of Der p 23. No statistically significant differences in IgE levels were found between patients with/without asthma and those with mild or moderate-severe rhinitis. Der p 7 was higher among rhinitis patients (p value 0.05). AD relative risk (RR) was increased in patients sensitized to Der f 2, Der p 2, and Der p 23. Der p 10 decreases the risk to have AD (RR 0.80). Conclusion: The evaluation of IgE results in a comprehensive panel of allergens allows differentiation of serological reactivity profiles with their clinical expression, to perform an optimal management. Improvements in component resolved diagnosis and more research on the clinical relevance of mite allergens are needed to achieve a genuine diagnosis leading to specific immunotherapy.
Association between Depression and Clinical Outcomes following Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Zhang Yifan , Zhai You , Niu Bohan , Liu Xiaolu , Zhang Xiaoxiao , Wu Shangwen , Zhu Cuiling
Published: April 2022

Background: Several studies suggested that depression was associated with poor prognosis following percutaneous coronary intervention (PCI) in coronary heart disease (CHD), whereas other studies showed that there were no associations between depression and poor outcomes. Objectives: Considering these problems, this meta-analysis was conducted to evaluate the relationship between depression and clinical outcomes after PCI. Methods: Articles published before July 2021 were analyzed from the databases: PubMed, Web of Science, EMBASE, Medline, and Google Scholar. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed to generate a pooled effect size and 95% CI with a random or fixed effects model. Q test and I2 were used to assess heterogeneities between studies. Results: The meta-analysis indicated that depression was associated with a higher risk of major adverse cardiac events (MACE) after PCI with a random effects model (HR = 1.89, 95% CI: 1.33–2.68, I2 = 57.0%, p = 0.023). The study indicated that depression was associated with a higher risk of all-cause mortality after PCI with a fixed effects model (HR = 1.71, 95% CI: 1.43–2.05, I2 = 0.0%, p = 0.756). The study indicated no significant association between depression and risk of repeat revascularization after PCI with a random effects model (HR = 2.10, 95% CI: 0.96–4.58, I2 = 68.9%, p = 0.022). Conclusion: Results indicated that depression is associated with adverse clinical outcomes in CHD patients’ post-PCI. Appropriate mental health check and psychological treatment may be necessary for the prognosis of CHD patients who receive PCI.
Cerebral Hemorrhage: Pathophysiology, Treatment, and Future Directions
Authors: Magid-Bernstein Jessica , Girard Romuald , Polster Sean , Srinath Abhinav , Romanos Sharbel , Awad Issam A. , Sansing Lauren H.
Published: April 2022

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. This review article focuses on the epidemiology, cause, mechanisms of injury, current treatment strategies, and future research directions of ICH. Incidence of hemorrhagic stroke has increased worldwide over the past 40 years, with shifts in the cause over time as hypertension management has improved and anticoagulant use has increased. Preclinical and clinical trials have elucidated the underlying ICH cause and mechanisms of injury from ICH including the complex interaction between edema, inflammation, iron-induced injury, and oxidative stress. Several trials have investigated optimal medical and surgical management of ICH without clear improvement in survival and functional outcomes. Ongoing research into novel approaches for ICH management provide hope for reducing the devastating effect of this disease in the future. Areas of promise in ICH therapy include prognostic biomarkers and primary prevention based on disease pathobiology, ultra-early hemostatic therapy, minimally invasive surgery, and perihematomal protection against inflammatory brain injury.
Post-Stroke Cognitive Impairment and Dementia
Authors: Rost Natalia S. , Brodtmann Amy , Pase Matthew P. , van Veluw Susanne J. , Biffi Alessandro , Duering Marco , Hinman Jason D. , Dichgans Martin
Published: April 2022

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbid neurodegenerative pathology, which is common in elderly individuals and can contribute to the clinical expression of PSCID. Manifestations of cerebral small vessel disease, such as covert brain infarcts, white matter lesions, microbleeds, and cortical microinfarcts, are also common in patients with stroke and likewise contribute to cognitive outcomes. Although studies of PSCID historically varied in the approach to timing and methods of diagnosis, most of them demonstrate that older age, lower educational status, socioeconomic disparities, premorbid cognitive or functional decline, life-course exposure to vascular risk factors, and a history of prior stroke increase risk of PSCID. Stroke characteristics, in particular stroke severity, lesion volume, lesion location, multiplicity and recurrence, also influence PSCID risk. Understanding the complex interaction between an acute stroke event and preexisting brain pathology remains a priority and will be critical for developing strategies for personalized prediction, prevention, targeted interventions, and rehabilitation. Current challenges in the field relate to a lack of harmonization of definition and classification of PSCID, timing of diagnosis, approaches to neurocognitive assessment, and duration of follow-up after stroke. However, evolving knowledge on pathophysiology, neuroimaging, and biomarkers offers potential for clinical applications and may inform clinical trials. Preventing stroke and PSCID remains a cornerstone of any strategy to achieve optimal brain health. We summarize recent developments in the field and discuss future directions closing with a call for action to systematically include cognitive outcome assessment into any clinical studies of poststroke outcome.
Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination
Authors: De Michele Manuela , Kahan Joshua , Berto Irene , Schiavo Oscar G. , Iacobucci Marta , Toni Danilo , Merkler Alexander E.
Published: April 2022

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.
Long-Term Survival, Stroke Recurrence, and Life Expectancy After an Acute Stroke in Australia and New Zealand From 2008–2017: A Population-Wide Cohort Study
Authors: Peng Yang , Ngo Linh , Hay Karen , Alghamry Alaa , Colebourne Kathryn , Ranasinghe Isuru
Published: April 2022

Background:

Data on long-term outcomes following an acute stroke are sparse. We assessed survival, risk of recurrent stroke and loss in life expectancy following an acute stroke using population-wide data from Australia and New Zealand.

Methods:

We included all adults with the first stroke hospitalization during 2008 and 2017 at all public and most private hospitals. Patients were followed up to 10 years after the stroke by linkage to each region’s Registry of Deaths and subsequent hospitalizations. Flexible parametric survival modeling was used to estimate all-cause mortality, stroke recurrence, and loss in life expectancy. Competing risk model was used when estimating the risk of stroke recurrence.

Results:

Three hundred thirteen thousand one hundred sixty-two patients were included (mean age 73.0±14.6 y, 52.0% males) with ischemic stroke (175 547, 56.1%) being the most common, followed by hemorrhagic stroke (77 940, 24.9%) and unspecified stroke (59 675, 19.1%). The overall survival probability was 79.4% at 3 months, 73.0% at 1 year, 52.8% at 5 years, and 36.4% at 10 years. Cumulative incidence of stroke recurrence was 7.8% at 3 months, 11.0% at 1 year, 19.8% at 5 years, and 26.8% at 10 years. Hemorrhagic stroke was associated with greater mortality (hazard ratio, 2.02 [95% CI, 1.99–2.04]) and recurrent stroke (hazard ratio, 1.63 [95% CI, 1.59–1.67]) compared with ischemic stroke. Female sex (hazard ratio, 1.10 [95% CI, 1.09–1.11]) and increasing age (≥85 years versus 18–54 years: hazard ratio, 7.36 [95% CI, 7.15–7.57]) were also associated with increased mortality. Several risk factors including atherosclerotic coronary and noncoronary vascular disease, cardiac arrhythmia, and diabetes were associated with increased risk of mortality and recurrent stroke. Compared with the general population, an acute stroke was associated with a loss of 5.5 years of life expectancy, or 32.7% of the predicted life expectancy, and was pronounced in patients with a hemorrhagic stroke (7.4 years and 38.5% of predicted life expectancy lost).

Conclusions:

In this population-wide study, death and recurrence of stroke were common after an acute stroke and an acute stroke was associated with considerable loss in life expectancy. Further improvements in treatment and secondary prevention of stroke are needed to reduce these risks.
How Do Right-Wing Populist Parties Influence Climate and Renewable Energy Policies? Evidence from OECD Countries
Authors: Lockwood Ben , Lockwood Matthew
Published: April 2022

There is increasing evidence that right-wing populist parties (RWPPs) and their supporters are hostile to climate and low-carbon energy policies. In this article, we provide a quantitative analysis of the effects of RWPP representation in the legislature and executive on climate and renewable energy policy for a number of countries in the Organisation for Economic Co-operation and Development over the period 2007–2018. After controlling for other political, economic, and environmental factors, we find evidence for a significant and large negative effect of RWPPs in power on climate policy. Importantly, we also show that these negative effects vary with the proportionality of the electoral system and European Union membership. Both of these factors significantly moderate the negative influence of RWPPs. In countries with majoritarian electoral systems, the effects of RWPPs on climate policy work through both indirect legislative and direct executive routes. In contrast to climate policy, there is no overall significant relationship with renewable policy.
Impacts of Serving a Mission for the Church of Jesus Christ of Latter-Day Saints on Individuals’ Attitudes toward Immigrants
Authors: Chou Hui-Tzu Grace , Shiles Alisse
Published: April 2022

This study examines how serving a mission for the Church of Jesus Christ of Latter-day Saints (LDS) affects individuals’ attitudes toward immigrants. Several hypotheses were developed based on intergroup contact theory. An online survey was filled out by 1,290 undergraduate students taking classes at a state university in Utah. Multivariate analyses yielded several findings. First, those who have served an LDS mission hold a more positive attitude toward immigrants than other individuals. Second, missionaries serving in some mission fields hold a more positive attitude toward immigrants than their counterparts, including those who needed to learn and speak a new language during their mission, those who served the mission in Latin America, those who received help from people of other countries during their mission, and those serving in places with either a lower or similar living standard. Surprisingly, being a victim of violence from people of other countries during the mission did not exert a significant impact on respondents’ attitudes toward immigrants.