bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerated Fitted Mesh Scheme for Singularly Perturbed Turning Point Boundary Value Problems
Authors: Bullo Tesfaye Aga
Published: March 2022

An accelerated fitted mesh scheme is proposed for the numerical solution of the singularly perturbed boundary value problems whose solution exhibits an interior layer near the turning point. To resolve the interior layer, a mesh of the Shishkin type is used with the help of a transition parameter that separates the layer and regular region. A tridiagonal solver is implemented to solve the system of equation. The stability of the described scheme is analyzed, and the truncation error is obtained. The proposed scheme is of almost second‐order convergent and accelerated to almost sixth‐order convergent by applying the Richardson extrapolation technique. The numerical results obtained by the present scheme have been compared with some existing methods, and it is observed that it gives better accuracy.
Prognostic and Diagnostic Value of Endocan in Kidney Diseases
Authors: Samouilidou Elisabeth , Athanasiadou Virginia , Grapsa Eirini
Published: March 2022

Endocan, previously called endothelial cell-specific molecule-1, is a soluble proteoglycan that is predominantly expressed in vascular endothelial cells of the lungs and kidneys. It is upregulated by proinflammatory cytokines and plays a critical role in inflammatory, proliferative, and neovascularization processes. The utility of endocan as a biomarker in a wide spectrum of diseases is being increasingly acknowledged. In this review, we summarize the current evidence concerning the role of endocan in kidney diseases, with emphasis on its prognostic and diagnostic value. It seems that the determination of plasma endocan levels may provide useful prognostic information in many types of renal failure such as chronic kidney disease, IgA nephropathy, and diabetic nephropathy. Endocan could additionally improve the early diagnostic evaluation of acute kidney disease, chronic renal allograft injury, and acute rejection after kidney transplantation, thus contributing to endothelial cell injury monitoring in a timely manner.
Multimodal Imaging under Artificial Intelligence Algorithm for the Diagnosis of Liver Cancer and Its Relationship with Expressions of EZH2 and p57
Authors: Zhang Yamin , Cui Jie , Wan Wei , Liu Jinpeng
Published: March 2022

Objective. It aimed to explore the diagnostic efficacy of multimodal ultrasound images based on mask region with convolutional neural network (M-RCNN) segmentation algorithm for small liver cancer and analyze the expression of zeste gene enhancer homolog 2 (EZH2) and p57 (P57 Kip2) genes in cancer cells. Methods. A total of 100 patients suspected of small liver cancer were randomly divided into Doppler group (color Doppler ultrasound examination), contrast group (contrast ultrasound examination), elastic group (ultrasound elastography examination), and multimodal group (combined examination of the three methods), with 25 patients in each group. Images were processed by the M-RCNN segmentation algorithm. The results of the pathological biopsy were used to evaluate the diagnostic efficacy of the four methods. The liver tissues were then extracted and divided into observation group 1 (lesion tissue specimen), observation group 2 (liver tissue around cancer lesion), and control group (normal liver tissue), and the expression activities of EZH2 and p57 genes in the three groups were analyzed. Results. The accuracy of M-RCNN (97.23%) and average precision (AP) (71.90%) were higher than other methods (

P
<
0.05

). Sensitivity (88.87%), specific degree of consistency (90.91%), accuracy (89.47%), and consistence (0.68) of the multimodal group were better than the other three groups (

P
<
0.05

). Low and medium differentiated cancer tissues had an irregular shape, unclear boundary, uneven internal echo, unchanged/enhanced posterior echo, blood flow level 1∼2, elastic score 4∼5, and enhancement mode fast in and fast out. The positive expression rate of EZH2 in observation group 1 (75.95%) was higher than that in the other two groups, the positive expression rate of p57 in observation group 1 (80.79%) was lower than that in the other two groups, and the positive expression rate of p57 in the highly differentiated cancer foci (80.79%) was significantly lower than that in the middle and low differentiated cancer foci (

P
<
0.05

). Conclusions. M-RCNN segmentation algorithm had a better segmentation effect. Multimodal ultrasound had a good effect on the benign and malignant diagnosis of small liver cancer and had a high clinical application value. The high expression of EZH2 and the decreased expression of p57 can promote the occurrence of small hepatocellular carcinoma, and the deficiency of the P57 gene was related to the low differentiation of cancer cells.
Bicomplex Landau and Ikehara Theorems for the Dirichlet Series
Authors: Agarwal Ritu , Sharma Urvashi Purohit , Agarwal Ravi P. , Suthar Daya Lal , Purohit Sunil Dutt
Published: March 2022

The aim of this paper is to generalize the Landau‐type Tauberian theorem for the bicomplex variables. Our findings extend and improve on previous versions of the Ikehara theorem. Also boundedness result for the bicomplex version of Ikehara–Korevaar theorem is derived. The purpose of this article is to substantially extend the various complex Tauberian theorems for the Dirichlet series to the bicomplex domain.
Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking
Authors: Ma Chen-Yu , Ma Yu-Qian , Deng Min
Published: March 2022

Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.
Liuwei Dihuang Pill Attenuates Diabetic Nephropathy by Inhibiting Renal Fibrosis via TGF-β/Smad2/3 Pathway
Authors: Shu Shi , Zhang Yue , Wang Qian , Tao Pengyu , Li Zhijie , Xu Zhongju , Lu Haiying , Shi Lin
Published: March 2022

Among all the complications of diabetes, diabetic nephropathy is a significant factor causing the end-stage renal disease associated with high death rates. Current treatment fails to produce an ideal outcome. Thus, searching for a new preventive drug is urgently needed. Liuwei Dihuang pill (LDP), a popular ancient Chinese medicine (TCM) prescription, has been applied to treat DN-like syndromes according to TCM theory. Here, we had established an animal model with DN and LDP therapy was put into use to assess its therapeutic effect in vivo. Our data showed that oxidative stress and TGF-β/Smad2/3 pathway-induced renal fibrosis could be observed in the DN animal model. However, the treatment of LDP impeded the generation of ROS and attenuated renal fibrosis-related proteins in damaged kidneys through interference in the TGF-β/Smad3 pathway. Our results indicated that LDP attenuated oxidative stress, accompanied by preventing the production of renal fibrosis through inhibiting the TGF-β/Smad2/3 pathway.
Coal Mine Safety Evaluation Based on Machine Learning: A BP Neural Network Model
Authors: Bai Guangxing , Xu Tianlong
Published: March 2022

As the core of artificial intelligence, machine learning has strong application advantages in multi-criteria intelligent evaluation and decision-making. The level of sustainable development is of great significance to the safety evaluation of coal mining enterprises. BP neural network is a classical algorithm model in machine learning. In this paper, the BP neural network is applied to the sustainable development level decision-making and safety evaluation of coal mining enterprises. Based on the analysis of the evaluation method for sustainable development of coal enterprises, the evaluation index system of sustainable development of coal enterprises is established, and a multi-layer forward neural network model based on error backpropagation algorithm is constructed. Based on the system theory of man, machine, environment, and management, and taking the four single elements and the whole system in a coal mine as the research object, this paper systematically analyzes and studies the evaluation and continuous improvement of coal mine intrinsic safety. The BP neural network evaluation model is used to analyze and study the intrinsic safety of coal mines, the shortcomings of the intrinsic safety construction of coal mines are found, and then improvement measures are put forward to effectively promote the safe production of coal mines and finally realize the intrinsic safety goal of the coal mine.
Fog Computing Service in the Healthcare Monitoring System for Managing the Real-Time Notification
Authors: Elhadad Ahmed , Alanazi Fulayjan , Taloba Ahmed I. , Abozeid Amr
Published: March 2022

A new computing paradigm that has been growing in computing systems is fog computing. In the healthcare industry, Internet of Things (IoT) driven fog computing is being developed to speed up the services for the general public and save billions of lives. This new computing platform, based on the fog computing paradigm, may reduce latency when transmitting and communicating signals with faraway servers, allowing medical services to be delivered more quickly in both spatial and temporal dimensions. One of the necessary qualities of computing systems that can enable the completion of healthcare operations is latency reduction. Fog computing can provide reduced latency when compared to cloud computing due to the use of only low-end computers, mobile phones, and personal devices in fog computing. In this paper, a new framework for healthcare monitoring for managing real-time notification based on fog computing has been proposed. The proposed system monitors the patient’s body temperature, heart rate, and blood pressure values obtained from the sensors that are embedded into a wearable device and notifies the doctors or caregivers in real time if there occur any contradictions in the normal threshold value using the machine learning algorithms. The notification can also be set for the patients to alert them about the periodical medications or diet to be maintained by the patients. The cloud layer stores the big data into the cloud for future references for the hospitals and the researchers.
Local Privacy Protection for Sensitive Areas in Multiface Images
Authors: Liu Chao , Yang Jing , Zhang Xuan , Zhang Yining , Zhao Weinan , Miao Fengjuan , Shao Yukun
Published: March 2022

The privacy protection for face images aims to prevent attackers from accurately identifying target persons through face recognition. Inspired by goal-driven reasoning (reverse reasoning), this paper designs a goal-driven algorithm of local privacy protection for sensitive areas in multiface images (face areas) under the interactive framework of face recognition algorithm, regional growth, and differential privacy. The designed algorithm, named privacy protection for sensitive areas (PPSA), is realized in the following manner: Firstly, the multitask cascaded convolutional network (MTCNN) was adopted to recognize the region and landmark of each face. If the landmark overlaps a subgraph divided from the original image, the subgraph will be taken as the seed for regional growth in the face area, following the growth criterion of the fusion similarity measurement mechanism (FSMM). Different from single-face privacy protection, multiface privacy protection needs to deal with an unknown number of faces. Thus, the allocation of the privacy budget ε directly affects the operation effect of the PPSA algorithm. In our scheme, the total privacy budget ε is divided into two parts: ε_1 and ε_2. The former is evenly allocated to each seed, according to the estimated number of faces ρ contained in the image, while the latter is allocated to the other areas that may consume the privacy budget through dichotomization. Unlike the Laplacian (LAP) algorithm, the noise error of the PPSA algorithm will not change with the image size, for the privacy protection is limited to the face area. The results show that the PPSA algorithm meets the requirements ε-Differential privacy, and image classification is realized by using different image privacy protection algorithms in different human face databases. The verification results show that the accuracy of the PPSA algorithm is improved by at least 16.1%, the recall rate is improved by at least 2.3%, and F1-score is improved by at least 15.2%.
Biomechanical Analysis and Training Method Research on Head Shot Strength of Football Players
Authors: Yao Yipeng , Xiang Shanshan
Published: March 2022

With the development of intelligent sports in China and the rapid improvement of the strength of colleges and universities, the reform of traditional football players’ header shooting training methods is becoming more and more urgent in order to solve some problems in the development of sports and speed up the intelligent training of Chinese football players. Based on this, this paper studies the biomechanical analysis and training method based on the integration of header strength data of football players. A dynamic header tracking model of football players based on a local search algorithm is designed. The data collection is realized from the aspects of athletes’ header shooting training, skill improvement, physical consumption, and trajectory. The biological data of header shooting power is comprehensively analyzed and evaluated by using a local search algorithm. The results show that the training system based on a local search algorithm has the advantages of high feasibility, high data accuracy, and fast response speed. It can effectively conduct accurate guidance and improve the shooting accuracy according to the biological characteristics of header shooting intensity. This paper studies the biological analysis and training method of header strength of football players based on a local search algorithm. This has certain reference significance for accelerating the construction of intelligent training of Chinese football players.
The Mechanism of Ginseng and Astragalus Decoction in the Treatment of Malignant Pleural Effusion Based on Network Pharmacology and Molecular Docking Technology
Authors: Gong Fengying , Qu Rongmei , Yang Yuchao , Li Yongchun , Cheng Yunshui , Zhang Qiang , Huang Ronglv , Fan Qin , Dai Jingxing , Lv Ying
Published: March 2022

Introduction. The objective of our study is to explore the potential active ingredients and activity of Ginseng and Astragalus decoction (GAD) in the treatment of malignant pleural effusion (MPE) by using network pharmacology and molecular docking technologies. Methods. The active ingredients and corresponding targets of Ginseng and Astragalus were extracted from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The relevant targets of malignant pleural effusion (MPE) were searched in the disease databases. Overlapping targets of Ginseng and Astragalus and the corresponding targets of MPE were obtained to define the effective target of GAD for the treatment of MPE. The STRING database was applied to construct a predicted protein-protein interaction network for intersected targets. The Cytoscape software was used to screen key targets with a therapeutic potential. Using the Metascape database, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis on the targets identified in the study. PyMOL and AutoDock Vina were used to molecularly dock the selected key components to their respective key targets for MPE treatment. Results. The core target network revealed 22 main active ingredients, 26 main targets, and 16 signaling pathways in GAD. Molecular docking revealed 6 targets (AKT serine/threonine kinase 1, intercellular adhesion molecule, Jun proto-oncogene, peroxisome proliferator activated receptor gamma, prostaglandin-endoperoxide synthase 2, and tumor necrosis factor) that could partially dock with kaempferol, frutinone A, ginsenoside RH2, formononetin, and quercetin. Conclusions. Several components, targets, and signaling pathways of GAD contribute to the treatment of MPE, which suggests a rationale for further investigation on GAD’s active molecule and mechanism of action in the clinical application of MPE.
Construction of Mathematical Modeling for Teaching Evaluation Index System Based on the Delphi AHP Method
Authors: Zhang Zhihong
Published: March 2022

China plays an important role in the global basic education of mathematics. Moreover, China has a lot of educational experience and methods and trains many excellent talents in the field of mathematics. However, there are still various disadvantages in the process of mathematics teaching. The traditional exam-oriented education makes the talent thought of mathematics education lack openness. Teachers also focus on difficult problems, partial questions, and exam questions during teaching. When teaching, teachers cannot contact students' daily life, which has low value. Mathematics teaching methods are too rigid and lack attraction. Most teachers focus on contents in textbooks while students cannot understand the value of mathematics in learning. This results in the decline of most students' interest in mathematics courses. To solve this problem, mathematical modeling teaching is put forward. China has a short application time in this field, and mathematical modeling is complex and systematic. When dealing with mathematical modeling problems, we must be able to skillfully use the basic knowledge learned and also involve the knowledge of other disciplines, so we must realize the integration of the knowledge of various disciplines. In addition, mathematical modeling teaching attaches great importance to students' communication ability, mathematical interpretation ability, and teamwork ability. Teachers can improve students' ability; however, our teachers' abilities in mathematical modeling teaching are uneven and there are no relevant standards. Therefore, it is necessary to establish an evaluation index system to accurately judge teachers' abilities. Based on this, this study uses the Delphi AHP method to construct the evaluation index system and selects four criteria level indexes and 12 index level indexes to judge teachers' mathematical modeling teaching ability.
A Research Study to Measure the Efficacy of Terminating Cervical Cancer via Customized Optimum Pathway
Authors: Zhang Xianyu , Ma Huan , Lu Xiurong , Zhang Zhilin
Published: March 2022

Background. To develop a precise prognostic model of overall survival in patients with terminating cervical cancer based on surveillance, epidemiology, and end results (SEER) program. Methods. The patients were retrieved from SEER data who are diagnosed with terminating cervical cancer from 2004 to 2016. The data were performed using univariate and multivariate analyses and constructed nomograms for predicting survival. Use C-index to validate the model accuracy. Results. Totally 15839 patients diagnosed with cervical cancer were independently allocated into the training set (n = 11088) and validation set (n = 4751). The multivariate analysis results indicated that age, race, stage_T, stage_M, and stage_N were confirmed as independent risk predictors, and those factors are applied to construct this clinical model. The C-index of overall survival in the training set was 0.6816 (95% confidence intervene (CI), 0.694–0.763) and that in the validation set was 0.6931(95% CI, 0.613–0.779). All calibration curves of various factors were consistent with predicted and actual survival. Conclusion. The nomogram provides a novel method for predicting the survival of patients with terminating cervical cancer, assisting in accurate therapeutic methods for patients with primary terminating cervical cancer.
Time Period of Thermal-Induced Vibration of Skew Plate with Two-Dimensional Circular Thickness
Authors: Sharma Amit , Bhardwaj Reeta , Lather Neeraj , Ghosh Sudeshna , Mani Naveen , Kumar Kamal
Published: March 2022

In this study, two-dimensional circular thickness effects on time period of skew plate made with nonhomogeneous material properties are computed in variable temperature environment. Clamped

C

, simply supported

S

, and free-edge

F

conditions are the various combinations considered in this work. One-dimensional circular density and two-dimensional parabolic temperature variation on the plate are considered due to the nonhomogeneous nature of the material and variable temperature environment. Rayleigh–Ritz method is used to compute the time period for the first two modes of vibration. A convergence study of frequency modes of skew plate on various edge conditions has also been performed. The present work has been compared with the frequency modes of parallelogram and rectangle plate on various edge conditions. The objective of the study is to present a numerical data of time period as well as to show how one can control the frequencies of plate by taking an appropriate variation in plate parameters.
Using a System Pharmacology Method to Search for the Potential Targets and Pathways of Yinqiaosan against COVID-19
Authors: Cao Li-hua , Jia Xing-yuan , He Hong-juan , Wang Zhen-zhen , Zhao Yi-ying , Yang Xue , Li Xiu-min , Miao Ming-san
Published: March 2022

The first reported case of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei, China. Thereafter, it spread through China and worldwide in only a few months, reaching a pandemic level. It can cause severe respiratory illnesses such as pneumonia and lung failure. Since the onset of the disease, the rapid response and intervention of traditional Chinese medicine (TCM) have played a significant role in the effective control of the epidemic. Yinqiaosan (YQS) was used to treat COVID-19 pneumonia, with good curative effects. However, a systematic overview of its active compounds and the therapeutic mechanisms underlying its action has yet to be performed. The purpose of the current study is to explore the compounds and mechanism of YQS in treating COVID-19 pneumonia using system pharmacology. A system pharmacology method involving drug-likeness assessment, oral bioavailability forecasting, virtual docking, and network analysis was applied to estimate the active compounds, hub targets, and key pathways of YQS in the treatment of COVID-19 pneumonia. With this method, 117 active compounds were successfully identified in YQS, and 77 potential targets were obtained from the targets of 95 compounds and COVID-19 pneumonia. The results show that YQS may act in treating COVID-19 pneumonia and its complications (atherosclerosis and nephropathy) through Kaposi sarcoma-related herpesvirus infection and the AGE-RAGE signaling pathway in diabetic complications and pathways in cancer. We distinguished the hub molecular targets within pathways such as TNF, GAPDH, MAPK3, MAPK1, EGFR, CASP3, MAPK8, mTOR, IL-2, and MAPK14. Five of the more highly active compounds (acacetin, kaempferol, luteolin, naringenin, and quercetin) have anti-inflammatory and antioxidative properties. In summary, by introducing a systematic network pharmacology method, our research perfectly forecasts the active compounds, potential targets, and key pathways of YQS applied to COVID-19 and helps to comprehensively clarify its mechanism of action.
Protecting Check-In Data Privacy in Blockchain Transactions with Preserving High Trajectory Pattern Utility
Authors: Xia Xiufeng , Hou Tingting , Liu Xiangyu , Zong Chuanyu , Mu Shengsheng
Published: March 2022

Because the blockchain is secure and untamperable, it has been widely used in many industries, such as the financial industry, digital tokens, and e-commerce logistics. The remarkable security feature of the blockchain is that the blockchain verifies the transaction initiated on each block through the node, and its process is broadcast throughout the whole network to let everyone know. On the one hand, this ensures the security of every transaction, but on the other hand, it is easy to cause privacy disclosure problems for transaction users. Therefore, under the premise of ensuring the security of the blockchain, it has become a hot issue to protect the sensitive information of transaction users. A check-in privacy protection (CPP) algorithm based on check-in location generalization is proposed in this paper, which can be applied to blockchain transactions to solve the privacy leakage problem of transaction users’ sensitive information. CPP algorithm not only protects the privacy of check-in data but also keeps the high utility of trajectory pattern data. Firstly, location types are recommended in the sensitive check-in location generalization based on the user’s trajectory pattern by using Markov chain technology. Secondly, to make sure that the generalized locations can be scattered as much as possible to prevent the attacker from deducing back, a heuristic rule is designed to select the generalized location based on the recommended location types, and at the same time, the similarity between the anonymous trajectory and the original trajectory is maintained. In addition, a generalized location search strategy is designed to improve the efficiency of the algorithm. Based on the real spatial-temporal check-in data, the results of the experiment indicate that our algorithm can effectively protect the privacy of sensitive check-in while ensuring the high utility of trajectory pattern data.
Study of the Mechanical and Microscopic Properties of Modified Silty Clay under Freeze-Thaw Cycles
Authors: Wenjun Zhou , Qingzhi Wang , Jianhong Fang , Kejin Wang , Xiangqing Zhao
Published: March 2022

Silty clay can be found in the alpine region of the Qinghai province, China, where it is subject to annual freeze-thaw cycles. To investigate the static mechanical properties of silty clay modified by basalt fiber and basalt powder under the action of freeze-thaw cycles, triaxial compression tests and scanning electron microscope tests were conducted on the soil. The test results revealed that varying the number of freeze-thaw cycles resulted to different effects on the soil mechanical strength, which tended to increase after 2 cycles, but then tended to decline when subjected to 5–10 cycles. After 20 freeze-thaw cycles, soil strength reached a dynamic equilibrium state. The shear strength of basalt fiber soil and basalt powder soil increased by 7.55% and 5.12%, respectively, compared with that of normal soil under 30 freeze-thaw cycles. Subsequently increasing of the number of freeze-thaw cycles differentially affected the cohesion and internal friction angle of normal soil and admixture soils, and these soils gradually tended to stabilize at a mechanical strength higher than the initial value. Basalt fibers reinforced the soil to a higher degree than basalt powder at a dosage of 0.4% based on dry soil mass. The stress-strain curves of the three soil types can be simulated using the hyperbolic model. The results of the study can provide some theoretical reference for practical engineering in seasonal frozen soil areas.
On the Twentieth Anniversary of Dendritic Cell Vaccines – Riding the Next Wave
Authors: Linette Gerald P. , Carreno Beatriz M.
Published: March 2022

In the mid 1990's, a convergence of discoveries in dendritic cell (DC) biology and tumor antigen identification led investigators to study DCs as adjuvants for cancer vaccines. On the twentieth anniversary of a seminal clinical study by Jacques Banchereau and colleagues, we revisit the key events that prompted the initial wave of DC vaccine clinical studies and lessons learned that, in our opinion, helped forge the path for the field that we now call immuno-oncology. It is essential to recall that prior to the discovery of immune checkpoint therapy and chimeric antigen receptor (CAR) T-cell therapy, skepticism prevailed regarding the potential therapeutic benefit of immunotherapies. In hindsight, we can now appreciate how the early DC cancer vaccine trials helped investigators sustain their attention on adaptive immunity specific for malignant cells. These vaccines demonstrated clear evidence for induction of antigen-specific T cells and were well tolerated despite low rates of objective clinical response. In the context of the current era some 20 years later, harnessing DC vaccines has been shown to increase the breadth and diversity of tumor-specific T cells, and by trafficking to sites of metastases promote an inflamed tumor microenvironment.

See related article by Banchereau and colleagues, Cancer Res 2001; 61:6451–8
Lung Cancer Cell of Origin: Controversy and Clinical Translational Implications
Authors: Osborne Jihan K. , Minna John D.
Published: March 2022

Identifying the cell(s) of origin for lung cancer including detecting their expansion during “field cancerization” and understanding how to therapeutically target them for beneficial chemoprevention is an urgent need. In this issue of Cancer Research, Yin and colleagues provide new and potentially controversial information to this question using Gprc5a knockout genetically engineered mouse models of lung adenocarcinoma. Prior research identified several different cell types including resident lung stem/progenitor such as alveolar type II cells as well as terminally differentiated cells as candidates for the cancer-initiating cell. Yin and colleagues provide new information that the cancer-initiating cell in this model is the bronchioalveolar stem cell.

See related article by Yin et al., p. 1025
Cervical Edema Extending to the Larynx as Local Cytokine Release Syndrome Following Chimeric Antigen Receptor T-Cell Therapy in a Boy with Refractory Acute Lymphoblastic Leukemia
Authors: Shima Haruko , Kurosawa Takumi , Oikawa Hiroyuki , Kobayashi Hisato , Nishi Emiri , Yamazaki Fumito , Tomita Kentaro , Shimada Hiroyuki
Published: March 2022

Cytokine release syndrome (CRS) is one of the major acute complications caused by massive cytokine release after chimeric antigen receptor (CAR) T-cell therapy. Patients with tumor masses were considered at high risk of local CRS induced by the expansion of CAR T cells in the tumor masses. However, even patients without any tumor burden around the neck are at risk of developing cervical edema as local CRS, which can lead to life-threatening airway obstruction. Here, we present the case of a 15-year-old boy who developed cervical edema as a local CRS after CAR T-cell therapy for refractory acute lymphoblastic leukemia. Despite administration of tocilizumab and methylprednisolone for persistent fever as a symptom of systemic CRS after CAR T-cell therapy, cervical edema occurred and extended to the larynx, resulting in dysphagia and hoarseness. Dexamethasone was remarkably effective, and the laryngeal symptoms resolved within a few hours. Local cytokine syndrome showed exacerbation with tocilizumab but exhibited considerable improvement with dexamethasone administration.
Cardiac Grafting of Engineered Heart Tissue in Syngenic Rats
Authors: Zimmermann Wolfram-Hubertus , Didié Michael , Wasmeier Gerald H. , Nixdorff Uwe , Hess Andreas , Melnychenko Ivan , Boy Oliver , Neuhuber Winfried L. , Weyand Michael , Eschenhagen Thomas
Published: March 2022

Background

Cell grafting has emerged as a novel approach to treat heart diseases refractory to conventional therapy. We hypothesize that survival and functional and electrical integration of grafts may be improved by engineering cardiac tissue constructs
in vitro
before grafting.

Methods and Results

Engineered heart tissue (EHT) was reconstituted by mixing cardiac myocytes from neonatal Fischer 344 rats with liquid collagen type I, matrigel, and serum-containing culture medium. EHTs were designed in circular shape (inner/outer diameter: 8/10 mm; thickness: 1 mm) to fit around the circumference of hearts from syngenic rats. After 12 days in culture and before implantation on uninjured hearts, contractile function of EHT was measured under isometric conditions. Baseline twitch tension amounted to 0.34±0.03 mN (n=33) and was stimulated by Ca
2+
and isoprenaline to 200±12 and 185±10% of baseline values, respectively. Despite utilization of a syngenic model immunosuppression (mg/kg BW: azathioprine 2, cyclosporine A 5, methylprednisolone 2) was necessary for EHT survival in vivo. Echocardiography conducted 7, 14, and 28 days after implantation demonstrated no change in left ventricular function compared with pre-OP values (n=9). Fourteen days after implantation, EHTs were heavily vascularized and retained a well organized heart muscle structure as indicated by immunolabeling of actinin, connexin 43, and cadherins. Ultrastructural analysis demonstrated that implanted EHTs surpassed the degree of differentiation reached before implantation. Contractile function of EHT grafts was preserved in vivo.

Conclusions

EHTs can be employed for tissue grafting approaches and might serve as graft material to repair diseased myocardium.
Brachial Gradient in Cardiac Surgical Patients
Authors: Baribeau Yvon , Westbrook Benjamin M. , Charlesworth David C. , Hearne Michael J. , Bradley William A. , Maloney Christopher T.
Published: March 2022

Background

Review of the clinical and therapeutic implications of difference in arm blood pressure detected preoperatively in patients having heart surgery.

Methods and Results

Prospective study of 53 patients (Group 1) with gradient and comparison with a group of 175 patients without gradient (Group 2). All patients had preoperative carotid duplex interrogation and operative epiaortic scanning. There was no statistical difference regarding age, sex, status, redo, diabetes, ejection fraction, prior myocardial infarct, hyperlipidemia, or creatinine level. Risks factors for Group 1 included peripheral vascular disease (
P
<0.0001) and cerebrovascular symptoms (
P
=0.0196). Severe carotid disease (>80% stenosis) was seen in 41.5% of Group 1 and 13.7% of Group 2 (
P
<0.0001) patients. Severe atherosclerotic proximal aortic disease was found in 39.6% of Group 1 and 10.8% of Group 2 (
P
<0.0001) patients. There were 7 patients with strokes in Group 1 (13.20%) and 9 in Group 2 (5.14%;
P
=0.06). Four patients died in Group 1 (7.54%) and 10 died in Group 2 (5.71%;
P
=0.74).

Conclusion

Brachial gradient is a marker for increased carotid and proximal atherosclerotic aortic disease. Preoperative arch study at the time of catheterization is strongly recommended, as well as preoperative carotid Doppler and operative epiaortic ultrasound.
Expression of Peroxisome Proliferator-Activated Receptor-γ in Vascular Smooth Muscle Cells Is Upregulated in Cystic Medial Degeneration of Annuloaortic Ectasia in Marfan Syndrome
Authors: Sakomura Yasunari , Nagashima Hirotaka , Aoka Yoshikazu , Uto Kenta , Sakuta Akiko , Aomi Shigeyuki , Kurosawa Hiromi , Nishikawa Toshio , Kasanuki Hiroshi
Published: March 2022

Background

Cystic medial degeneration (CMD) is a histological abnormality that is common in annuloaortic ectasia (AAE) and aortic dissection with Marfan syndrome. Apoptosis and loss of vascular smooth muscle cells (VSMCs) is one of the features of CMD, but little is known about its pathogenesis. Peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor of the nuclear receptor superfamily, has been reported to show antiproliferative effects on VSMCs as well as anti-inflammatory effects on macrophages. PPARγ agonist has been recently reported to induce apoptosis of cultured VSMCs.

Methods

We examined the histopathology of ascending aortas in AAE of Marfan patients (n=21) and control patients (n=6) at surgery. RT-PCR was performed to demonstrate expression of PPARγ in CMD. Localization of PPARγ was determined by double immunostaining using antibodies against PPARγ and cell-specific markers (ie, SMCs, macrophages, and T lymphocytes).

Results

PPARγ expression was upregulated in AAE samples but minimal in control samples by RT-PCR (
P
=0.07). Immunoreactivity against PPARγ in numerous nuclei of VSMCs was observed in CMD lesions. Severity of CMD correlated with positive immunoreactivity of PPARγ in medial VSMCs (
P
=0.03). No inflammatory cells (ie, macrophages or T lymphocytes) were detected in CMD lesions.

Conclusion

PPARγ expression is upregulated in SMCs of CMD without any inflammatory response. Activated PPARγ in VSMCs might be involved in the pathogenesis of CMD in Marfan’s aortas. Regulation of PPARγ might lead to clinical implication in protection against progression of AAE.
Left Ventricular Reverse Remodeling After Surgical Therapy for Aortic Stenosis: Correlation to Renin-Angiotensin System Gene Expression
Authors: Walther Thomas , Schubert Andreas , Falk Volkmar , Binner Christian , Walther Claudia , Doll Nico , Fabricius Alex , Dhein Stefan , Gummert Jan , Mohr Friedrich W.
Published: March 2022

Background

Surgical therapy for aortic stenosis leads to reverse remodeling, with normalization of left ventricular hypertrophy (LVH). The aim of this study was to examine Renin-Angiotensin system (RAS) gene expression in this setting.

Methods

Growing sheep (n=44) underwent supracoronary aortic banding for controlled induction of LVH at the age of 6 to 8 months (A=baseline). Surgical revision to completely release the pressure gradient was performed 8.3±1 months later (B). The animals were sacrificed after another 10.1±2 months (C). Along with hemodynamic measurements, subtractive hybridization and competitive polymerase chain reaction were applied to quantify mRNA expression for angiotensin-converting enzyme (ACE) and angiotensin receptors 1 and 2 (AT
1
-R and AT
2
-R).

Results

Left ventricular mass index was 82±21 g (A), 150±33 g (B), and 78±18 g (C),
P
<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter was 11.3±0.8 (A), 15.9±1.2 (B), and 11.4±1 (C) μm,
P
<0.01. Gene expression was as follows: ACE 0.8±0.05 (A), 1.3±0.08 (B), and 0.9±0.06 (C),
P
<0.01; AT
1
-R 0.7±0.06 (A), 0.9±0.07 (B), and 0.3±0.04 (C),
P
<0.01; AT
2
-R 0.5±0.05 (A), 0.2±0.04 (B), and 0.5±0.05 (C),
P
<0.01.

Conclusion

LVH in aortic stenosis coincides with significant alterations of the RAS. Surgical therapy leads to reverse remodeling, which is paralleled by regression of RAS gene expression.
Vitamin C Improves the Outcomes of Cardiopulmonary Resuscitation and Alters Shedding of Syndecan‐1 and p38/MAPK Phosphorylation in a Rat Model
Authors: Xiao Yan , Su Chenglei , Zhang Guozhen , Liang Lian , Jin Tao , Bradley Jennifer , Ornato Joseph P. , Tang Wanchun
Published: March 2022

Background

Post‐resuscitation syndrome, involves a severe inflammatory response following successful cardiopulmonary resuscitation. The potential mechanism of Vitamin C (VitC) after cardiopulmonary resuscitation on myocardial and cerebral function, duration of survival is undefined.

Methods and Results

A first set of experiments were done in 18 male Sprague‐Dawley rats for the investigation of short‐term follow‐up, randomized into 3 groups: (1) sham; (2) controls; (3) VitC. Ventricular fibrillation was electrically induced and untreated for 6 minutes. Cardiopulmonary resuscitation including chest compression and mechanical ventilation were then initiated and continued for 8 minutes followed by defibrillation. At 5 minutes after return of spontaneous circulation, either VitC (200 mg/kg) or placebo was administered by intravenous infusion with a syringe pump for half an hour. There were significant improvements in myocardial function and buccal microcirculation in rats treated with VitC after return of spontaneous circulation 4 hours compared with controls. VitC inhibited proinflammatory cytokines (interleukin‐6 and tumor necrosis factor‐α), SDC‐1 (Syndecan‐1), and hyaluronic acid in plasma compared with controls (
P
<0.01). VitC decreased reactive oxygen species production and inhibited p38/MAPK (mitogen‐activated protein kinase) pathway phosphorylation. A second set with 20 animals was used for assessing the neurological deficit score after return of spontaneous circulation 72 hours, randomized into 2 groups: 1) controls; 2) VitC. The survival rate and neurological deficit score after return of spontaneous circulation 72 hours were improved in VitC‐treated animals compared with those of the control group.

Conclusions

VitC reduces the severity of post‐resuscitation myocardial and cerebral dysfunction and improves the survival. The mechanisms may involve inhibiting transcription of inflammatory cytokines and oxidative stress, thus protecting the integrity of the vascular endothelium. Meanwhile VitC reduces shedding of SDC‐1 and alters p38/MAPK phosphorylation and microcirculation.
Interaction of Ethnicity and Arrival Method on Thrombectomy Delay: The Society of Vascular and Interventional Neurology Collaboration
Authors: Siegler James E. , Ortega‐Gutierrez Santiago , Hester Taryn , Haussen Diogo C. , Nogueira Raul G. , Liebeskind David S. , Zaidat Osama O. , Vora Nirav , Desai Shashvat , Jadhav Ashutosh P. , Roach Eileen , Linfante Italo , Hassan Ameer E. , Farooqui Mudassir , Jillella Dinesh V. , Nahab Fadi , Sharrief Anjail , Czap Alexandra , Bach Ivo , Khandelwal Priyank , Abdalkader Mohamad , Nguyen Thanh N.
Published: March 2022

Background

Compared with non‐Hispanic White patients, non‐Hispanic Black (NHB) and Hispanic populations are less likely to receive acute treatment for ischemic stroke, and when they do, it can be delayed. We evaluated the interaction between arrival method and race or ethnicity on door‐to‐arterial puncture (DTAP) time in thrombectomy.

Methods

We conducted a retrospective observational cohort study of consecutive adults who underwent endovascular thrombectomy from 14 US Comprehensive Stroke Centers (January 1, 2019–July 31, 2020). DTAP was assessed in a linear mixed model including an interaction term for race or ethnicity and arrival method.

Results

Of the 1908 included patients, 356 of whom were Hispanic, Hispanic and NHB patients experienced significant delays in DTAP compared with non‐Hispanic White patients (adjusted β
Hisp
=0.32, 95% CI, 0.08–0.55; β
NHB
=0.23; 95% CI, 0.04–0.41). More severe deficits were associated with shorter DTAP (β
NIHSS
per point −0.03; 95% CI −0.04 to −0.03), and arrival via emergency medical services or private vehicle versus transfer were associated with longer delays (β
EMS
=0.57; 95% CI, 0.41–0.74; β
PV
=1.27; 95% CI, 0.85–1.70). There was a significant interaction between Hispanic ethnicity and emergency medical services (
P
=0.03) or private vehicle arrival (
P
=0.04) in a direction favoring shorter treatment delays. Sites that treated a minority population of Hispanic patients (<50% being Hispanic) experienced a significant delay in DTAP among Hispanic and NHB versus non‐Hispanic White (median 72 minutes [interquartile range (IQR), 49–104] versus 83 minutes [IQR, 50–119] versus 58 minutes [IQR, 27–95],
P
<0.01), whereas sites treating a Hispanic majority showed no difference in DTAP (

P

=0.39).

Conclusions

Endovascular therapy is delayed in Hispanic and NHB patients when compared with non‐Hispanic White patients. Although arrival by emergency medical services or private vehicle also contributed to treatment delays, Hispanic ethnicity modified this effect such that there was less delay in DTAP. This may be related to communication barriers between caregivers and health care providers when a Hispanic patient is suddenly disabled from stroke.
Towards Intelligently Designed Evolvable Processors
Authors: Jones Benedict A. H. , Chouard John L. P. , Branco Bianca C. C. , Vissol-Gaudin Eléonore G. B. , Pearson Christopher , Petty Michael C. , Al Moubayed Noura , Zeze Dagou A. , Groves Chris
Published: March 2022

Evolution-in-Materio is a computational paradigm in which an algorithm reconfigures a material's properties to achieve a specific computational function. This article addresses the question of how successful and well performing Evolution-in-Materio processors can be designed through the selection of nanomaterials and an evolutionary algorithm for a target application. A physical model of a nanomaterial network is developed which allows for both randomness, and the possibility of Ohmic and non-Ohmic conduction, that are characteristic of such materials. These differing networks are then exploited by differential evolution, which optimises several configuration parameters (e.g., configuration voltages, weights, etc.), to solve different classification problems. We show that ideal nanomaterial choice depends upon problem complexity, with more complex problems being favoured by complex voltage dependence of conductivity and vice versa. Furthermore, we highlight how intrinsic nanomaterial electrical properties can be exploited by differing configuration parameters, clarifying the role and limitations of these techniques. These findings provide guidance for the rational design of nanomaterials and algorithms for future Evolution-in-Materio processors.
Assessment of adaptive strategies on life history of the rotifer Euchlanis dilatata (ROTIFERA) at different temperature and food regime
Authors: Santos-Medrano Gustavo Emilio , Rico-Martínez Roberto , Robles-Vargas Daniel
Published: March 2022

The combined effects of two temperatures (20° and 25°C) and food densities (1 × 104 and 1 × 106 cells/mL) of three microalgae, Chlorella vulgaris, Nannochloropsis oculata and Scenedesmus obliquus on the life history of Euchlanis dilatata were evaluated. Our work integrated: effects of temperature on the activation energy (Ea), and evaluation of the rate of decrease or increase through the temperature coefficient (Q10) in the different biological processes of the life table of E. dilatata, including, morphometric values and hatching egg percentages. The best conditions to reach the highest instantaneous growth rate (r) in E. dilatata were 25°C fed with N. oculata (1 × 106 cells/mL) while the lowest r value was registered with C. vulgaris with both temperatures. In the mean generation time and age at first reproduction, the Ea was higher at 20°C, where Q10 values < 1 indicate that these rates decrease with increasing the temperature. We found an exception to the temperature-size rule when rotifer was fed C. vulgaris at 25°C. Moreover, the rotifer fed with S. obliquus reached the maximum size. Our hypothesis is that when temperature increase 5°C, the rotifer may shorten its embryonic development, thereby increasing r and net reproduction rate.