bluuebunny/crossref_metadata_2025 huggingface dataset:
CPE Regulates Proliferation and Apoptosis of Primary Myocardial Cells Mediated by Ischemia and Hypoxia Injury
Authors: Li Jin , Dong Zishuang , Pan Yuxiong , Wang Luchen , Zhao Wei , Jian Zhang
Published: March 2022

Objective. To observe the effect of carboxypeptidase E (CPE) on the ischemia and hypoxia (I/H) injury of primary cardiomyocytes. Methods. Quantitative real-time polymerase chain reaction (qRT-PCR) technology was used to detect the expression of CPE in sham and myocardial infarction (MI) rat heart tissue, and the plasmid was transferred into primary cardiomyocytes by transfection technology. The apoptosis rate of cardiomyocytes was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, Annexin V-PI staining, and Cell Counting Kit-8 (CCK-8) assay. In addition, Caspase kit and qRT-PCR technology were used to detect the expression of apoptosis-related factors. The cell proliferation was detected by 5-ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, and qRT-PCR technology. In addition, Western blotting (WB) and qRT-PCR techniques were used to detect the Wnt/β-catenin pathway. Results. First, we found that the expression of CPE in the marginal zone of MI was obviously reduced. Overexpression of CPE in primary cardiomyocytes can effectively inhibit ischemia/hypoxia (I/H)-induced apoptosis and decreased cell activity. In addition, CPE can promote cell proliferation and relieve the inhibitory effect of I/H on cardiomyocytes. At the same time, CPE can promote the expression of β-catenin and c-myc. Conclusion. Overexpression of CPE in primary cardiomyocytes can effectively alleviate the decreased cell activity, increased apoptosis, and decreased proliferation caused by I/H and regulated by Wnt/β-catenin pathway.
Comparative Analysis of the Antioxidant and Antidiabetic Potential of Nelumbo nucifera Gaertn. and Nymphaea lotus L. var. pubescens (Willd.)
Authors: Pokhrel Tamlal , Shrestha Dipesh , Dhakal Kamal , Yadav Paras Mani , Adhikari Achyut
Published: March 2022

Background. Nelumbo nucifera Gaertn. and Nymphaea lotus L. var. pubescens (Willd.) are both aquatic rhizomatous perennial plants mostly found in the tropical region of Nepal, India, Bangladesh, China, and Eastern Asia. Nymphaea pubescens and Nelumbo nucifera plants are famous for their different biological activities such as antidiabetic, antioxidant, hepatoprotective, antidiarrheal, and anti-inflammatory properties. Objective. The present study majorly focused on the determination of in vitro antioxidant and antidiabetic properties of Nelumbo nucifera and Nymphaea pubescens. Methods. In vitro α-glucosidase inhibition was performed using PNPG as a substrate. Antioxidant property of the plant extract was determined by DPPH free radical scavenging assay. The aluminium trichloride method was done for the estimation of total flavonoid content. Likewise, Folin–Ciocalteu reagent was used for determining total phenolic content. Results. The total phenolic content of N. nucifera and N. pubescens was found to be 172.827 ± 0.41 and 194.87 ± 0.93 mg GAE/g, respectively, while the total flavonoid content was reported 17.12 ± 1.04 and 34.59 ± 1.73 mg QE/g, respectively. The IC50 values of the crude extract and its fractions of N. nucifera against the DPPH free radical ranged from 33.46 ± 0.6 to 3.52 ± 0.09 μg/mL, while that of the N. pubescens ranged from 14.30 ± 0.43 to 1.43 ± 0.08 μg/mL. Similarly, for the in vitro α-glucosidase inhibition activity, the IC50 of the crude extract and its fractions of N. nucifera varied from 349.86 ± 2.91 to 29.06 ± 0.24 μg/mL and that of N. pubescens ranged from 224.4 ± 6.85 to 5.29 ± 0.39 μg/mL. Conclusion. Both aquatic plants N. nucifera and N. pubescens show antioxidant properties and can inhibit α-glucosidase in in vitro. Further research is required to identify the inhibiting compounds.
Left Nonrecurrent Laryngeal Nerve: A Very Unusual Finding during Thyroid Surgery
Authors: Ahumada Nicolas Galat , Hojaij Flavio Carneiro , Cunico Caroline , Akahane Hugo Genki Kagawa , Leitão Cleverson Alex , Matias Jorge Eduardo Fouto
Published: March 2022

Background. Identifying the inferior laryngeal nerve is one of the main concerns in thyroid surgery. The typical recurrent position occurs due the relative position between the vagus nerve and the larynx during the last 3 branchial arches development. In rare cases, this nerve does not loop under the right subclavian artery or the aortic arch. This abnormality is present in 0.7% of patients and is associated with the presence of anatomical vascular anomalies. The left non-recurrent inferior laryngeal nerve is an even rarer abnormality, with only six cases described in the literature to date. Method. A 46- years old female patient referred to total thyroidectomy for symptomatic multinodular benign goiter. Results. A left non-recurrent inferior laryngeal nerve was found with difficulty and then a partial thyroidectomy was performed. CT scan showed dextroposition of the vessels of the base of the heart and an aberrant left subclavian artery. Conclusion. An association of a right-sided aortic arch and aberrant left subclavian artery, or the presence of situs inversus, although rare anatomical variations, are associated to a non-recurrent inferior left laryngeal nerve. Proper identifying these abnormalities may help to properly identify and salvage this structure.
Evaluation of Antioxidant Activities and Tyrosinase Inhibitory Effects of Ginkgo biloba Tea Extract
Authors: Klomsakul Pongsathorn , Aiumsubtub Arisara , Chalopagorn Pornchanok
Published: March 2022

Ginkgo biloba L. (Ginkgoaceae) is one of the best-selling products, popular in nutritional properties and health benefits. In the present study, the total phenolic compounds and flavonoid content of the ethanolic extract from G. biloba tea were also evaluated. Furthermore, the antioxidant activity was determined using DPPH assay and tyrosinase inhibitory activity was also determined with L-DOPA as a substrate. The extract showed the total phenolic compound and flavonoid content were 14.13 mg GE g−1 extract and 71.33 mg rutin equivalence g−1 DW, respectively. Taking into account the results of the DPPH, the antioxidant property at the concentration of 500 µg ml−1 was 95.29% that is similar to that of the BHT, ascorbic acid, and gallic acid used as positive controls. The inhibitory capacity of the sample against tyrosinase is lower than that of positive controls at all concentrations. The results of inhibition in terms of IC50 confirm the inhibition patterns. On the other hand, the statistical similarity of the anti-DOPA auto-oxidation (IC50) of G. biloba leaf extract and kojic acid was found (456.27 and 418.5 µg ml−1) but was lower than that of ascorbic acid (IC50 989.61 µg ml−1). A relationship was observed between the potential of antioxidant activity, tyrosinase inhibition, and anti-DOPA auto-oxidation with concentration levels of the extracts. The results of phytochemical analysis revealed the presence of tannins, flavonoids, terpenoids, and reducing sugars.
Preserved Left Ventricular Function despite Myocardial Fibrosis and Myopathy in the Dystrophin-Deficient D2.B10-Dmdmdx/J Mouse
Authors: Hayes Holly M. , Angerosa Julie , Piers Adam T. , White Jason D. , Koleff Jane , Thurgood Madeline , Moody Jessica , Cheung Michael M. , Pepe Salvatore
Published: March 2022

Duchenne muscular dystrophy involves an absence of dystrophin, a cytoskeletal protein which supports cell structural integrity and scaffolding for signalling molecules in myocytes. Affected individuals experience progressive muscle degeneration that leads to irreversible loss of ambulation and respiratory diaphragm function. Although clinical management has greatly advanced, heart failure due to myocardial cell loss and fibrosis remains the major cause of death. We examined cardiac morphology and function in D2.B10-Dmdmdx/J (D2-mdx) mice, a relatively new mouse model of muscular dystrophy, which we compared to their wild-type background DBA/2J mice (DBA/2). We also tested whether drug treatment with a specific blocker of mitochondrial permeability transition pore opening (Debio-025), or ACE inhibition (Perindopril), had any effect on dystrophy-related cardiomyopathy. D2-mdx mice were treated for six weeks with Vehicle control, Debio-025 (20 mg/kg/day), Perindopril (2 mg/kg/day), or a combination (

n
=
8

/group). At 18 weeks, compared to DBA/2, D2-mdx hearts displayed greater ventricular collagen, lower cell density, greater cell diameter, and greater protein expression levels of IL-6, TLR4, BAX/Bcl2, caspase-3, PGC-1α, and notably monoamine oxidases A and B. Remarkably, these adaptations in D2-mdx mice were associated with preserved resting left ventricular function similar to DBA/2 mice. Compared to vehicle, although Perindopril partly attenuated the increase in heart weight and collagen at 18 weeks, the drug treatments had no marked impact on dystrophic cardiomyopathy.
A Robust Adaptive Control Algorithm for Multimissile Cooperative Formation
Authors: Gong Zheng , Wang Mingang , He Jingang , Zhang Jin
Published: March 2022

To improve the probability of missile coordinated detection, this paper investigates the control method of multimissile cooperative formation. Based on the missile’s nonlinear dynamics modeling, the formation control algorithm based on the position of the leader missile (or virtual leader missile) is studied. Meanwhile, considering the influence of the communication time delay, a robust adaptive cooperative controller satisfying the time delay network is designed. The simulation verification result indicates that cooperative formation can be achieved quickly with small velocity and position tracking errors when the missiles are fully connected. Therefore, the multimissile cooperative formation control algorithm designed in this paper can meet the requirements of multimissile coordinated detection, thus improving the missile’s cooperative attack capability.
Economic Viability and Use Dynamics of the Enset Food System in Ethiopia: Its Implications for Food Security
Authors: Sirany Teshome , Tadele Esubalew , Hibistu Tewabe , Kefalew Alemayehu , Reta Haimanot
Published: March 2022

Food security is a key issue worldwide and must be considered in both spatial and temporal contexts. Securing the availability of food somewhere in a country does not ensure food security in other areas. Similarly, securing food available today does not guarantee its availability tomorrow. Therefore, parameters such as rapid population growth, urbanization, changing consumption patterns, and globalization, as well as climate change and depletion of natural resources, must be kept in mind while planning the issue of food security. In this regard, Enset, which is a large perennial herbaceous crop native to Ethiopia, is highly stapled to approximately 20 million people in the southern, eastern, and central parts of Ethiopia. It is a common practice in the agricultural system of these areas, making these areas Enset belt regions of the country. On the other hand, the remaining parts of the country often do not practice such farming systems despite the fact that there are good opportunities to do so. One way of expanding the experience of Enset culture is through promoting its food system and multiple-use dynamics. Hence, decision-makers and policy designers in the area of agriculture would consider intensifying Enset to its nonbelt areas, to transform agricultural and food systems to end hunger, achieve food security, and improve nutrition.
Rotating Machinery Fault Diagnosis Using HHO-RSSD and RCGmvMAAPE
Authors: Zhang Ning
Published: March 2022

Rotating machinery has played an enormous role in industrial production, and its stable operation is related to whether production can proceed smoothly. At present, multichannel entropy-based methods are usually be adopted to analyze multichannel vibration signals. However, the collected signal may only have one channel in the actual situation. At this time, analyzing only a single channel signal cannot effectively utilize the advantages of multivariate analysis. For this reason, this paper presents a novel multivariate analysis approach and applies it to the fault diagnosis of machinery. Firstly, the parameter-optimized resonance sparse decomposition (RSSD) algorithm is adopted to decompose the single-channel vibration signal into high and low resonance components. Then, the two components are regarded as dual-channel vibration signals and input into the refined composite generalized multivariate multiscale amplitude aware permutation entropy (RCGmvMAAPE) method to gain fault features. Eventually, the features are input to the deep belief network (DBN) classifier to perform fault judgment. The experiments of rotating machinery are carried to verify the effectiveness of the developed approach. The results display that the proposed fault diagnosis method can achieve the classification accuracy of 100% and 98% when only a single-channel vibration signal is used, which is better than the fault diagnosis method based on a multichannel vibration signal and enjoys strong stability.
The Role of Knowledge Creation-Oriented Convolutional Neural Network in Learning Interaction
Authors: Zhang Hongyan , Luo Xiaoguang
Published: March 2022

When convolutional neural network (CNN) applications have different tasks in the source domain and target domain, but both have labels, it is easy to ignore the difference between the source domain and target domain by using the current traditional method, and the recognition effect of image features is not ideal. This paper proposes a deep migration learning method based on improved ResNet based on existing research to avoid this problem. This method extracts high-order statistical features of images by increasing the number of network layers for classification when performing model transfer learning. The ImageNet dataset is used as the source domain, and a Deep Residual Network (DRN) is used for model transfer based on homogeneous data. Firstly, the ResNet model is pretrained. Then, the last fully connected layer of the source model is modified, and the final deep model is constructed by fine-tuning the network by adding an adjustment module. The impact of content differences between datasets on recognizing transfer learning features is reduced through model transfer and deep feature extraction. The deep transfer learning methods after improving ResNet are compared through experiments. The identification algorithm is based on Support Vector Machine (SVM), the deep transfer learning method on Visual Geometry Group (VGG)-19, and the deep transfer learning method based on Inception-V3. Four experiments are performed on MNIST and CIFAR-10 datasets. By analyzing the experimental data, ResNet’s improved deep transfer learning method achieves 97.98% and 90.45% accuracy on the MNIST and CIFAR-10 datasets, and 95.33% and 85.07% on the test set. The accuracy and recognition accuracy on the training and test sets have been improved to a certain extent. The combination of CNN and transfer learning can effectively alleviate the difficulty of obtaining labeled data. Therefore, the application of a CNN in transfer learning is significant.
The Inflammasome NLRC4 Protects against Cryptococcus gattii by Inducing the Classic Caspase-1 to Activate the Pyroptosis Signal
Authors: Wang Yongbin , Feng Feifei , Wang Hui , Zhang Ying , Chen Yuqing
Published: March 2022

Cryptococcus is one of the most pathogenic invasive fungi, and its interaction with the host’s natural immunity, especially the role of the inflammasome family, has not been fully elucidated. As an important member of the inflammasome family, NOD-like receptor (NLR) family caspase recruitment domain (CARD) containing 4 (NLRC4) has been proven to protect lungs from damage from a variety of pathogens. In this study, we investigated the protective effect and mechanism of NLRC4 on cryptococcal pulmonary infection using NLRC4-/-mice in vivo and NLRC4-/-macrophages in vitro models stimulated by cryptococcal cells. We apply small animal fluorescence imaging to detect the fungal burden in the lungs and living body micro-CT scans of mice and in vitro tissue micro-CT scans to compare differences in infection foci nodules and histopathological lesions, and the activation of caspase-1 and downstream cytokines were detected by Western bolt and ELISA, etc. The results demonstrated that cryptococcal infection can activate the Nod-like receptors of caspase-1 activation and NLRC4 inflammasomes in macrophages and dendritic cells and affect downstream IL-1β and IL-18 release. After cryptococcal infection, the survival rate, lung fungal burden, and histopathological damage of NLRC4-/- mice were significantly impaired. NLRC4-/- macrophages showed a lower release of inflammatory factors, reactive oxygen species (ROS), and lactate dehydrogenase (LDH). Collectively, our results demonstrated that the activation of caspase-1 and downstream cytokines mediated by NLRC4 inflammasome in immune cells during Cryptococcus infection can enhance pyroptosis of macrophages, affect the phagocytic ability of macrophages, and inhibit the intracellular parasitism of cryptococcus, eventually reducing the burden of fungi.
Performance Analysis of TDOA and FDOA Estimation for Pulse Signals
Authors: Liu Yan , Guo Fucheng
Published: March 2022

Time difference of arrival (TDOA) and frequency difference of arrival (FDOA) are effective measurements for localizing emitters’ radiating pulse signals, such as radar. Temporal sparsity of pulse signals makes their TDOA and FDOA estimation precisions much different from that of continuous communication and acoustic signals. The way how the precisions are affected by various parameters, e.g., temporal duration of signals, may also deviate significantly in scenarios of pulse signals from that of continuous ones. In this paper, theoretical analyses are carried out to reveal the Cramer–Rao lower bounds (CRLBs) of TDOA and FDOA estimation precisions of pulse signals and also to obtain insights on how the CRLBs are affected by various parameters, including pulse number, signal-to-noise ratio (SNR), pulse width, and pulse repetition interval (PRI). Simulation results verify the correctness of the derived CRLBs and their variations with different parameters.
Liquiritin Attenuates Angiotensin II-Induced Cardiomyocyte Hypertrophy via ATE1/TAK1-JNK1/2 Pathway
Authors: Mo Jiajia , Zhou Peng , Chu Zhaoxing , Zhao Yan , Wang Xiang
Published: March 2022

Objective. To investigate the protective effect and mechanism of liquiritin (LIQ) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II). Methods. H9c2 cells were pretreated with LIQ before and after Ang II treatment. CCK8 assay was performed to evaluate cell viability. The cell surface area was measured by phalloidin staining. The mRNA expression of atrial and B-type natriuretic peptides (ANP and BNP, respectively) and β-myosin heavy chain (β-MHC) was determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR); the protein levels of arginyltransferase 1 (ATE1), transforming growth factor beta-activated kinase 1 (TAK1), phos-TAK1, c-Jun N-terminal kinases1/2 (JNK1/2), and phos-JNK1/2 were determined by Western blotting. After constructing the ATE1 overexpression cell models with the pcDNA3.1/ATE1, the abovementioned indicators were tested using the introduced methods. Results. LIQ at a concentration of ≤30 μM was not cytotoxic to H9c2 cells before exposure to Ang II. The protective effect of LIQ was best observed at 30 μM after Ang II treatment. Phalloidin staining and RT-qPCR results indicated that the deposition of Ang II increased the cell surface area and levels of ANP, BNP, and β-MHC. On the other hand, Western blotting results showed that Ang II increased the ATE1 protein levels and TAK1 and JNK1/2 phosphorylation, which were significantly alleviated after LIQ treatment. LIQ also directly inhibited the ATE1 overexpression in H9c2 cells transfected with pcDNA3.1/ATE1 and further inhibited TAK1 and JNK1/2 phosphorylation. Conclusion. LIQ can attenuate Ang II-induced cardiomyocyte hypertrophy by regulating the ATE1/TAK1-JNK1/2 pathway.
Assured Deletion: A Scheme Based on Strong Nonseparability
Authors: Xie Zhenjie , Fu Wei , Xu Jianqiao , Zhu Tingting
Published: March 2022

Cloud storage services bring great convenience to users, but also make data owners lose direct control of their data. How to ensure that deleted cloud data can never be recovered by cloud servers or attackers is a key issue in the field of cloud storage security, which is important to protect user privacy and data confidentiality in the cloud environment. Most existing schemes have the drawbacks of overreliance on key destruction and having the ability to decrypt part of the ciphertext after cracking the key. To solve these problems, a novel cloud data assured deletion scheme based on strong nonseparability is presented. By combining XOR operation with the block cipher, the cipher data become strongly nonseparable; thus, destroying any piece of cipher data will result in unrecoverable original data. Theoretical analysis and experimental results both show that the scheme achieves the expected goals of assured deletion, which has obvious performance advantages and stronger security compared with similar schemes.
The Relationships among Plasma Fetuin-B, Thyroid Autoimmunity, and Fertilization Rate In Vitro Fertilization and Embryo Transfer
Authors: Zhang Rui , Cheng Feifei , Cheng Wei , Wang Xin , Zhang Binghan , Tian Mingyuan , Li Ke , Liu Dongfang
Published: March 2022

Objective. The objective of the study is to investigate the relationships between fetuin-B, thyroid autoimmunity (TAI), and pregnancy outcomes in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Design, Patients, and Measurements. In this prospective study, 180 women who were preparing for pregnancy with IVF-ET were included. There were 120 women with TAI positive and 60 negative controls matched with age and BMI. Results. The 180 women had mean ± SD age of 31.4 ± 4.0 years, with a mean ± SD BMI of 21.0 ± 1.6 kg/m2. There was a significant difference in the level of fetuin-B in women with TAI positive compared with TAI negative group (65.2 ± 18.5 vs. 76.4 ± 25.1,

P
=
0.001

). Fetuin-B had a negative relationship with thyroid antibodies even after adjusting for other variables (OR (95%CI) = 0.98 (0.96–0.99),

P
=
0.002

). Compared with women with TAI negative, those with TAI positive had a significantly higher risk of low fertilization (20.0% vs. 6.7%;

P
=
0.035

). And we found no difference in terms of pregnancy, abortion, implantation, and live birth rate between the two groups. Logistic regression analysis showed that both fetuin-B and TAI were the independent factors to lead the low fertilization of IVF-ET (OR (95%CI) = 0.96 (0.94–0.99) and 4.084 (1.39–15.30),

P
=
0.004

and 0.019, respectively). Conclusion. Fetuin-B was significantly associated with TAI and low fertilization rate in women undergoing IVF-ET. Decreased fetuin-B in women with TAI may be the underlying reason for the lower IVF-ET success rate.
Bioinformatics Methods Reveal the Biomarkers and the miRNA-mRNA Network in Hepatocellular Carcinoma
Authors: Liu Yang , Zhang Haoliang , Han Xue , Xing Xiaowei
Published: March 2022

Hepatocellular carcinoma (HCC) has threatened the health of humans, and few therapeutic strategies can completely uproot this illness. Bioinformatics methods have been widely used for investigating the pathological mechanisms of disease. In this study, datasets including GSE20077 and GSE108724, obtained from the Gene Expression Omnibus (GEO) database, were used for investigating the biomarker and molecular mechanism of HCC. The differentially expressed genes (DEGs) in the datasets were identified, and the targets of the miRNAs were searched in the miRDIP and miRNET databases. Enrichment analysis was performed for delving the molecular mechanism of DEGs, and protein-protein interaction (PPI) networks and miRNA-mRNA networks were used to reveal the hub nodes and the related interaction relationships. Moreover, the expression and diagnostic values of hub nodes were analyzed with the GEPIA2 database. The results showed that 53 upregulated miRNAs and 48 downregulated miRNAs were found in GSE20077, and 55 upregulated miRNAs and 69 downregulated miRNAs were found in GSE108724. Moreover, seven common miRNAs including miR-146b-5p, miR-338-3p, miR-375, miR-502-3p, miR-532-3p, miR-532-5p, and miR-557 were found in the datasets. The targets of the common miRNAs were related with the P53, HIF1, Wnt, and NF-κB pathways. Besides, YWHAZ and CDC42 were identified as the hub nodes and served as the downstream targets of miR-375-3p. The GEPIA2 database showed that YWHAZ and CDC42 were related with the survival rate of the patients. In conclusion, this study suggests that miR-375-3p functions as a tumor suppressor which could inhibit the progression of HCC via targeting YWHAZ and CDC42.
3D TDOA/AOA Localization in MIMO Passive Radar with Transmitter and Receiver Position Errors
Authors: Huang Donghua , Zhao Yongsheng , Hu Dexiu , Zhao Yongjun
Published: March 2022

This paper deals with the problem of determining the position of a single target from time difference of arrival (TDOA) and angle of arrival (AOA) measurements using multitransmitter multireceiver passive radar system with widely separated antennas. A practically motivating scenario where the transmitter and receiver positions are contaminated by errors is addressed. First, the reduction in localization accuracy due to the presence of transmitter and receiver position errors is derived through the Cramér-Rao lower bound (CRLB) analysis. Then, a novel algebraic localization algorithm based on weighted least squares minimization is proposed that takes the transmitter and receiver position errors into consideration to reduce the estimation error. The proposed solution is shown theoretically to reach the CRLB even when the transmitter and receiver positions have errors. Simulation results also verify the theoretical developments and the performance improvement of the proposed solution over existing algorithms.
Preclinical Development and Evaluation of Allogeneic CAR T Cells Targeting CD70 for the Treatment of Renal Cell Carcinoma
Authors: Panowski Siler H. , Srinivasan Surabhi , Tan Nguyen , Tacheva-Grigorova Silvia K. , Smith Bryan , Mak Yvonne S.L. , Ning Hongxiu , Villanueva Jonathan , Wijewarnasuriya Dinali , Lang Shanshan , Melton Zea , Ghosh Adit , Dusseaux Mathilde , Galetto Roman , Heyen Jonathan R. , Sai Tao , Van Blarcom Thomas , Chaparro-Riggers Javier , Sasu Barbra J.
Published: March 2022

CD70 is highly expressed in renal cell carcinoma (RCC), with limited expression in normal tissue, making it an attractive CAR T target for an immunogenic solid tumor indication. Here we generated and characterized a panel of anti-CD70 single-chain fragment variable (scFv)–based CAR T cells. Despite the expression of CD70 on T cells, production of CAR T cells from a subset of scFvs with potent in vitro activity was achieved. Expression of CD70 CARs masked CD70 detection in cis and provided protection from CD70 CAR T cell–mediated fratricide. Two distinct classes of CAR T cells were identified with differing memory phenotype, activation status, and cytotoxic activity. Epitope mapping revealed that the two classes of CARs bind unique regions of CD70. CD70 CAR T cells displayed robust antitumor activity against RCC cell lines and patient-derived xenograft mouse models. Tissue cross-reactivity studies identified membrane staining in lymphocytes, thus matching the known expression pattern of CD70. In a cynomolgus monkey CD3-CD70 bispecific toxicity study, expected findings related to T-cell activation and elimination of CD70-expressing cells were observed, including cytokine release and loss of cellularity in lymphoid tissues. Finally, highly functional CD70 allogeneic CAR T cells were produced at large scale through elimination of the T-cell receptor by TALEN-based gene editing. Taken together, these efficacy and safety data support the evaluation of CD70 CAR T cells for the treatment of RCC and has led to the advancement of an allogeneic CD70 CAR T-cell candidate into phase I clinical trials.

Significance:

These findings demonstrate the efficacy and safety of fratricide-resistant, allogeneic anti-CD70 CAR T cells targeting renal cell carcinoma and the impact of CAR epitope on functional activity.

See related commentary by Adotévi and Galaine, p. 2517
Targeting Stearoyl-CoA Desaturase in Solid Tumors
Authors: Kubota Casie S. , Espenshade Peter J.
Published: March 2022

Cancer cells are demarcated from normal cells by distinct biological hallmarks, including the reprogramming of metabolic processes. One of the key players involved in metabolic reprogramming is stearoyl-CoA desaturase (SCD), which converts saturated fatty acids to monounsaturated fatty acids in an oxygen-dependent reaction that is crucial for maintaining fatty acid homeostasis. As such, SCD has been identified as a potential therapeutic target in numerous types of cancers, and its inhibition suppresses cancer cell growth in vitro and in vivo. This review summarizes the evidence implicating SCD in cancer progression and proposes novel therapeutic strategies for targeting SCD in solid tumors.
Three-Year Follow-Up and Response–Survival Relationship of Nivolumab in Previously Treated Patients with Advanced Esophageal Squamous Cell Carcinoma (ATTRACTION-3)
Authors: Okada Morihito , Kato Ken , Cho Byoung Chul , Takahashi Masanobu , Lin Chen-Yuan , Chin Keisho , Kadowaki Shigenori , Ahn Myung-Ju , Hamamoto Yasuo , Doki Yuichiro , Yen Chueh-Chuan , Kubota Yutaro , Kim Sung-Bae , Hsu Chih-Hung , Holtved Eva , Xynos Ioannis , Matsumura Yasuhiro , Takazawa Akira , Kitagawa Yuko
Published: March 2022

Purpose:

Limited long-term data are available on immune checkpoint inhibitor use in patients with advanced esophageal squamous cell carcinoma (ESCC). We report 3-year follow-up data from our study of nivolumab versus chemotherapy (paclitaxel or docetaxel) in patients with previously treated ESCC.

Patients and Methods:

ATTRACTION-3 was a randomized, multicenter, open-label, phase III trial. Overall survival (OS), time from randomization to death from any cause, was the primary endpoint. An exploratory subanalysis assessed OS according to the best overall response (BOR) with and without landmark at 4 months.

Results:

Of the enrolled patients, 210 received nivolumab and 209 received chemotherapy. With a minimum follow-up of 36.0 months, OS was longer in the nivolumab versus the chemotherapy group (median, 10.9 vs. 8.5 months; HR, 0.79; P = 0.0264), with 3-year OS rates of 15.3% and 8.7%, respectively. The median OS was longer with nivolumab versus chemotherapy irrespective of the BOR (complete response/partial response: 19.9 vs. 15.4 months; stable disease: 17.4 vs. 8.8 months; and progressive disease: 7.6 vs. 4.2 months). Grade 3 or higher treatment-related adverse events were reported in 40 patients (19.1%) in the nivolumab group and 133 patients (63.9%) in the chemotherapy group.

Conclusions:

Nivolumab as second-line therapy demonstrated clinically meaningful long-term improvement in OS compared with chemotherapy in previously treated patients with advanced ESCC. The OS was consistently improved in the nivolumab group compared with the chemotherapy group regardless of BOR. Nivolumab was well tolerated over the 3-year follow-up.

See related commentary by Yoon et al., p. 3173
Ghrelin Relieves Obesity-Induced Myocardial Injury by Regulating the Epigenetic Suppression of miR-196b Mediated by lncRNA HOTAIR
Authors: Lang Yuan-Yuan , Xu Xin-Yue , Liu Yan-Ling , Ye Chun-Feng , Hu Na , Yao Qing , Cheng Wen-Shu , Cheng Zu-Gen , Liu Yang
Published: March 2022

Introduction: Obesity has been believed to be closely linked with many kinds of diseases including atherosclerosis, hypertension, cerebrovascular thrombosis, and diabetes. Ghrelin and Homeobox transcript antisense RNA (HOTAIR) were believed to be involved in the regulation of myocardial injury. Methods: The obesity mice model was established through feeding mice (C57BL/6J, male, eight-week-old) with high-fat diet and palmitate (PA)-induced cardiomyocyte injury. RNA and protein levels were detected with Quantitative real-time PCR and Western blotting. The levels of TG, TCH, LDL, CK-MB, cTnl, and BNP in the serum or cell medium supernatant were measured using ELISA kits. The ROS level was detected with the DCFH-DA method. Binding sites between different targets were identified using detection of dual luciferase reporter assay. Cell apoptosis was analyzed by flow cytometry. RNA-binding protein immunoprecipitation and chromatin immunoprecipitation were used to detect the binding of DNMT3B with HOTAIR or miR-196b promoter. Results: The expression of HOTAIR was downregulated, and miR-196b was upregulated in the obese myocardial injury. Ghrelin attenuated PA-induced cardiomyocyte injury by increasing HOTAIR. HOTAIR regulated the expression of miR-196b by recruiting DNMT3B to induce methylation of the miR-196b gene promoter. The binding site between miR-196b and IGF-1 was identified. Discussion/Conclusion: We demonstrated that ghrelin attenuated PA-induced cardiomyocyte injury by regulating the HOTAIR/miR-196b/IGF-1 signaling pathway. Our findings might provide novel thought for the prevention and treatment of obesity-induced myocardial injury by targeting HOTAIR/miR-196b.
The Deep Vascular Plexus Density Is Closely Related to Myopic Severity
Authors: Yao Hongyan , Xin Danli , Li Zijing
Published: March 2022

Objectives: The aim of the study was to investigate the relationship between myopic severity and the retinal microvasculature based on quantitative variables using optical coherence tomography angiography (OCTA) and to identify OCTA indicators of microvascular network loss in myopia. Methods: This cross-sectional study included 123 eyes of 123 myopic subjects. The included eyes were divided into three groups according to the spherical equivalent (SE) and axial length (AL): low myopia (LM) (−3.00 D ≤ SE ≤ −0.50 D), moderate myopia (MM) (−6.00 D ≤ SE < −3.00 D), and high myopia (HM) (−9.00 D ≤ SE < −6.00 D or AL >26 mm). All the eyes underwent OCTA scans. The densities and thicknesses of the macular and peripapillary zones, including the foveal avascular zone (FAZ) area, superficial vascular plexus (SVP) density, deep vascular plexus (DVP) density, ganglion cell complex (GCC) thickness, full retinal thickness, radial peripapillary capillary plexus (RPCP) density, and retinal nerve fiber layer (RNFL) thickness, were automatically exported. Results: Compared to the LM or MM group, the HM group had a significantly reduced FAZ area (p < 0.05). In most sectors of the parafoveal and perifoveal areas, the HM group had significantly lower DVP density and higher retinal thickness than the LM and MM groups (all p < 0.05). However, significant differences among the three groups in only one or several sectors were observed with regard to SVP density, GCC thickness, and RNFL thickness, and no significant differences among the three groups in any sector were noticed in RPCP density. Perifoveal DVP density and perifoveal full retinal thickness were positively associated with SE and negatively associated with AL in stepwise multiple linear regression analyses adjusted for sex and age. Conclusion: DVP density was closely related to myopic severity. Reduced perifoveal DVP density may serve as an indicator of microvascular network loss in myopia. OCTA may provide useful and crucial information for monitoring the progression of myopia.
Crohn’s Disease-Related Stoma Complications and Their Impact on Postsurgical Course
Authors: Angriman Imerio , Buzzi Gianluca , Giorato Edoardo , Barbierato Maria , Cavallin Francesco , Ruffolo Cesare , Degasperi Silvia , Mari Valentina , De Simoni Ottavia , Campi Michela , Zingales Francesca , Roveron Gabriele , Iafrate Massimo , Pucciarelli Salvatore , Bardini Romeo , Scarpa Marco
Published: March 2022

Introduction: Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. The diversion through a colostomy or an ileostomy is sometimes required for disease control. In these patients, common stoma-related complications sum up with CD-related complications and often require revisional surgery. Methods: The aim of the study was to assess stoma morbidity after surgery for CD and to identify the burden of CD-related or CD-associated complications. Thus, details of past medical history, surgery, and follow-up of 54 consecutive patients operated on for CD with any sort of stoma were retrieved from the stoma therapist prospectively maintained database. Results: In our series, 23 patients had a colostomy, and 31 patients had an ileostomy. Complications occurred after stoma creation in 38 patients (70%) at a median of 1.3 months (interquartile range 0.6–7.2). CD-related complications arose in 8 patients (including pyoderma gangrenosum in 3 patients, peristomal fistulae in 2, granulomas in 2, and peristomal abscess in 1). Patients with CD-related complications tended to have a shorter disease duration (p = 0.07) and higher occurrence of CD-related complications was associated with end-stoma (p = 0.006). In this cohort, 11 cases had to be surgically treated for peristomal fistulae or abscess, parastomal hernia, prolapse, pyoderma gangrenosum, and recurrent CD. Discussion/Conclusions: In patients with CD, stoma creation is burdened by a high rate of postoperative complication and a relevant rate is specifically related to CD. Often these patients are required to be reoperated on to redo the stoma. Moreover, end-stoma configuration and aggressive CD phenotype are associated to a higher rate of complications.
Effect of the bus voltage level on the power system design for microsatellites
Authors: Bekhti Mohammed , Beldjehem Mohammed , Faiza Arezki
Published: March 2022

Each time there is a need for a satellite mission analysis, engineers need to coordinate together the choice of one technology with regard to the other (i.e. solar cells technology, transistors, microcontrollers, and batteries). The process of selecting one technology to another or a component to another is called ‘trade off’. This concept is a hard and situational decision that involves diminishing one quality, of a system or a design in return for gains in other aspects such as weight, performance, speed and so on. The present paper will focus essentially on the use of the 28 V unregulated bus voltage because early satellites, all used, a 14 V unregulated bus voltage. The paper will also show trade-offs made when using the 28 V unregulated bus voltage with different topologies.
A Grande Estiagem por João das Neves
Authors: Carbone Roberta
Published: March 2022

Pretende-se a análise de certos expedientes épico-dialéticos utilizados por João das Neves na encenação de A grande estiagem, de Isaac Gondim Filho, por meio do exame de depoimentos do encenador e de uma crítica de Barbara Heliodora ao espetáculo, a fim de verificar a constituição do teatro político brasileiro no pré-64 e as forças historicamente a ele contrárias.
Cerebrovascular Variants and the Role of the Selfish Brain in Young-Onset Hypertension
Authors: Manghat Nathan E. , Robinson Elizabeth , Mitrousi Konstantina , Rodrigues Jonathan C.L. , Hinton Thomas , Paton Julian F.R. , Wise Richard G. , Nightingale Angus K. , Hart Emma C.
Published: March 2022

Background:

Variants in the posterior anatomy of the cerebral circulation are associated with hypertension and lower cerebral blood flow in midlife (age ≈55 years); however, whether these variants are a result of aging or long-term exposure to high blood pressure is unclear. Additionally, the role these variants play in early onset of hypertension (<40 years) and poor cerebral perfusion in this population is unknown.

Methods:

We retrospectively examined whether specific cerebrovascular variants (vertebral artery hypoplasia and absent/hypoplastic posterior communicating arteries (an incomplete posterior circle of Willis) measured via magnetic resonance angiography) were associated with a diagnosis of hypertension in 220 young adults (<40 years; n=164 primary hypertensive [mean age±SD, 32±6 years] and n=56 [30±6 years] normotensive adults). Whether cerebrovascular variants were associated with lower cerebral blood flow (phase-contrast angiography) was measured in the hypertensive group only (n=146).

Results:

Binary logistic regression (adjusted for age, sex, and body mass index) showed that vertebral artery hypoplasia with an incomplete posterior circle of Willis was associated with hypertension diagnosis (
P
<0.001, odds ratio; 11.79 [95% CI, 3.34–41.58]). Vertebral artery hypoplasia plus an incomplete circle of Willis was associated with lower cerebral blood flow in young adults with hypertension (
P
=0.0172).

Conclusions:

Vertebral artery hypoplasia plus an incomplete posterior circle of Willis independently predicts hypertension in young adults suggesting that this variant is not acquired with aging into midlife. Importantly this variant combination was associated with lower cerebral perfusion, which may have long-term consequences on cerebrovascular health in young adults with hypertension.
Streamlining Acute Stroke Care by Introducing National Institutes of Health Stroke Scale in the Emergency Medical Services: A Prospective Cohort Study
Authors: Larsen Karianne , Jæger Henriette S. , Hov Maren R. , Thorsen Kjetil , Solyga Volker , Lund Christian G. , Bache Kristi G.
Published: March 2022

Background:

National Institutes of Health Stroke Scale (NIHSS) is the most validated clinical scale for stroke recognition, severity grading, and symptom monitoring in acute care and hospital settings. Numerous modified prehospital stroke scales exist, but these scales contain less clinical information and lack compatibility with in-hospital stroke scales. In this real-life study, we aimed to investigate if NIHSS conducted by paramedics in the field is a feasible and accurate prehospital diagnostic tool.

Methods:

This prospective cohort study is part of Treat-NASPP (Treat-Norwegian Acute Stroke Prehospital Project) conducted at a single medical center in Østfold, Norway. Sixty-three paramedics were trained and certified in NIHSS, and the prehospital NIHSS scores were compared with the scores obtained by in-hospital stroke physicians. Interrater agreement was assessed using a Bland-Altman plot with 95% limits of agreement. In secondary analysis, Cohen κ was used for the clinical categories NIHSS score of 0 to 5 and ≥6. As a safety measure, prehospital time was compared between paramedics conducting NIHSS and conventional paramedics.

Results:

We included 274 patients. The mean difference in NIHSS scores between the paramedics and the stroke physicians was 0.92 with limits of agreement from −5.74 to 7.59. Interrater agreement for the 2 clinical categories was moderate with a κ of 0.58. The prehospital NIHSS scoring was performed mean (SD) 42 (14) minutes earlier than the in-hospital scoring. Prehospital time was not significantly increased in the NIHSS-trained paramedic group compared with conventional paramedics (median [interquartile range] on-scene-time 18 [13–25] minutes versus 16 [11–23] minutes,
P
=0.064 and onset-to-hospital time 86 [65–128] minutes versus 84 [56–140] minutes,
P
=0.535).

Conclusions:

Paramedics can use NIHSS as an accurate and time efficient prehospital stroke severity quantification tool. Introducing NIHSS in the emergency medical services will enable prehospital evaluation of stroke progression and provide a common language for stroke assessment between paramedics and stroke physicians.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03158259.
ÖRGÜTSEL İNSANDIŞILAŞTIRMA VE İŞTEN AYRILMA NİYETİ ARASINDAKİ İLİŞKİDE, İŞE ANGAJE OLMA VE İŞ TATMİNİNİN ARACI ROLÜ
Authors: BİLGİNOĞLU Elif , YOZGAT Ugur
Published: March 2022

Örgütsel insandışılaştırma; bir çalışanın örgütü tarafından nesneleştirildiğini, kişisel öznelliğinin reddedildiğini ve sanki örgütün amaçlarına yönelik bir araç ya da aletmiş gibi hissettirildiğine dair hissi deneyimidir. İnsandışılaştırma tutum ve davranışlarına örgütsel ortamlarda sıklıkla rastlanmaktadır ve bu konunun detaylı bir şekilde araştırılması önem taşımaktadır. Sosyal psikoloji alanında mevcut olan çok sayıda insandışılaştırma araştırmasının aksine, örgütsel ortamlardaki insandışılaştırmaya yönelik ilgi oldukça yenidir. Bu alanda, görgül araştırmalar halen yetersizdir ve bu olgunun öncülleri ve sonuçlarının araştırılması için daha fazla çaba harcanmalıdır. Bu araştırma örgütsel insandışılaştırma üzerine teorik bir çerçeve sunuyor olması yanı sıra, örgütsel insandışılaştırmanın işe angaje olma, iş tatmini ve işten ayrılma niyeti üzerindeki etkisini inceleyen bir çalışmayı da içermektedir. Bu amaçla İstanbul’da çalışan 520 kişi üzerinde anket uygulanmıştır. Bu araştırmanın sonuçları örgütsel insandışılaştırmanın çalışanların işe angaje olmaları ve iş tatminleri üzerinde olumsuz, işten ayrılma niyetleri üzerinde ise olumlu etkisi olduğunu, bununla birlikte örgütsel insandışılaştırma ve çalışanların işten ayrılma niyetleri üzerindeki ilişkide çalışanların işe angaje olmaları ve iş tatminlerinin aracı role sahip olduğunu ortaya koymaktadır.
KALKINMA AJANSLARININ PERSONEL YÖNETİMİNDE KISITLAYICI KURALLAR
Authors: DURU Ahmet Alptekin
Published: March 2022

Bu çalışmanın amacı, kalkınma ajansları personel yönetimindeki kısıtlayıcı kurallara riayet düzeyini ölçmek ve bu konudaki sorunları tespit etmektir. Çalışmada doküman analizi araştırma yöntemi kullanılarak ilgili literatür ve mevzuat taranmış, resmi raporlar kullanılarak elde edilen veriler analiz edilmiştir. Türkiye’de 2006 yılından itibaren kurulmaya başlanan kalkınma ajanslarının personel yönetimi düzenlenirken başlıca iki kısıtlayıcı kural koyulmuştur. İlk kurala göre bir ajansın destek personeli sayısı ajans toplam personel sayısının %20’sini geçemez. İkinci kurala göre de bir ajansın yıllık personel giderleri toplamı bir önceki yıl bütçe gelirlerinin %15’ini aşamaz. Taşeron işçiler hariç tutulduğunda 2018 yılına kadar ilk kurala riayet edilmiştir fakat bazı ajanslar ikinci kısıtlayıcı kurala uymakta zorlanmıştır. 2018 yılında taşeron işçilerin ajansların kadrolarına geçirilmesinin ardından kısıtlayıcı kuralların uygulama kabiliyeti kalmamıştır. Bu sebeple ajansların personel yönetimindeki kısıtlayıcı kuralların değiştirilmesi ihtiyacı doğmuştur.