bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeleton‐Based Action Recognition Based on Distance Vector and Multihigh View Adaptive Networks
Authors: Zhang Min , Yang Haijie , Li Pengfei , Jiang Ming
Published: August 2021

Skeleton‐based human action recognition has attracted much attention in the field of computer vision. Most of the previous studies are based on fixed skeleton graphs so that only the local physical dependencies among joints can be captured, resulting in the omission of implicit joint correlations. In addition, under different views, the content of the same action is very different. In some views, keypoints will be blocked, which will cause recognition errors. In this paper, an action recognition method based on distance vector and multihigh view adaptive network (DV‐MHNet) is proposed to address this challenging task. Among the mentioned techniques, the multihigh (MH) view adaptive networks are constructed to automatically determine the best observation view at different heights, obtain complete keypoints information of the current frame image, and enhance the robustness and generalization of the model to recognize actions at different heights. Then, the distance vector (DV) mechanism is introduced on this basis to establish the relative distance and relative orientation between different keypoints in the same frame and the same keypoints in different frame to obtain the global potential relationship of each keypoint, and finally by constructing the spatial temporal graph convolutional network to take into account the information in space and time, the characteristics of the action are learned. This paper has done the ablation study with traditional spatial temporal graph convolutional networks and with or without multihigh view adaptive networks, which reasonably proves the effectiveness of the model. The model is evaluated on two widely used action recognition benchmarks (NTU‐RGB + D and PKU‐MMD). Our method achieves better performance on both datasets.
Mechanical Damage and Chemical Dissolution Kinetic Features of Limestone under Coupled Mechanical-Hydrological-Chemical Effects
Authors: Ding Wuxiu , Wang Hongyi , Chen Huajun , Ma Tao
Published: August 2021

To address the mechanical damages of limestone under the coupled mechanical(M)-hydrological(H)-chemical(C) effects, we performed uniaxial compression experiments and dissolution kinetics experiments on limestone in flowing and static solutions for different lengths of time. Through experiments, the peak strengths of the limestone under coupled MHC effects for different time lengths and the major ion concentrations in solutions were obtained. By analyzing the strength damage and chemical dissolution kinetic characteristics, we achieved the strength damage equations and chemical dissolution kinetic equations. Results show that when the solution shifted from the static state to the flowing state, and as its acidity increased, the peak strength loss of the limestone rose as well. The solution mobility had a more significant impact on the peak strength loss than the solution pH value. The limestone dissolution in flowing water was higher than in static water, indicating that solution mobility would promote the limestone dissolution. Among the contributing factors to limestone dissolution, the solution pH value showed the strongest impact, followed by the common-ion effect and then the salt effect. The research result is expected to provide a theoretical basis for maintaining the stability of rocks in geotechnical engineering practice and protection of stone cultural relics.
Baicalein Mediates Mitochondrial Autophagy via miR-30b and the NIX/BNIP3 Signaling Pathway in Parkinson’s Disease
Authors: Chen Min , Peng Li , Gong Ping , Zheng Xiaoli , Sun Tao , Zhang Xiaoqiao , Huo Jiangtao
Published: August 2021

Parkinson’s disease (PD) is regarded as a severe neurodegenerative disorder. Baicalein is involved in the treatment of PD. This study explored the mechanism of baicalein in PD. The PD rat model was established using 6-hydroxydopamine. The neurologic score, dopamine (DA) content, apoptotic cells, and neuronal damage were evaluated after rats were treated with baicalein. Autophagy in PD rats was inhibited using 3-methyladenine (3-MA). The mitochondrial membrane potential (MMP) and autophagy-related proteins (LC3, P62) were detected. Next, agomiR-30b was transfected into PD rats. The targeting relation between miR-30b and NIX was predicted and verified. Then, sh-NIX was transfected into PD rats, and the effects of miR-30b and NIX on MMP, LC3, and P62 were assessed. When miR-30b was overexpressed using agomiR-30b, the NIX and BNIP3 levels were detected. Baicalein increased the neurological score and restored DA content, neurons, MMP, and mitochondrial autophagy protein levels. Baicalein inhibited miR-30b expression and miR-30b targeted NIX. miR-30b upregulation or NIX silencing reversed the effect of baicalein on MMP and mitochondrial autophagy. Baicalein upregulated NIX and BNIP3 expressions, while miR-30b overexpression inhibited NIX and BNIP3 expressions. In summary, baicalein mediated mitochondrial autophagy and restored neuronal activity by downregulating miR-30b and activating the NIX/BNIP3 pathway, thus protecting against PD.
Analysis of Shear Characteristics of Deep, Anchored Rock Mass under Creep Fatigue Loading
Authors: Li Xiaofeng , Yin Zhixiang
Published: August 2021

To study the influence of earthquakes and engineering disturbances on the deformation of deeply buried rock masses, shear tests were carried out on anchored sandstone rock masses, anchored marble rock masses, and anchored granite rock masses under creep fatigue loading, and a new creep fatigue model was established to characterize the deformation characteristics of anchored rock masses under creep fatigue loading. The creep fatigue curves of different lithologies clearly show three stages: creep attenuation, steady‐state creep, and accelerated creep. Fatigue loading can increase the creep of anchored specimens, and the lower the rock strength is, the higher the creep variable under fatigue loading is. However, for the same rock strength, with the increase in load level, the creep variable produced by creep fatigue load presents a linear downward trend. Considering the changes in the mechanical properties of the anchored rock mass under creep fatigue loading, the creep fatigue model of anchored rock masses is established by introducing a function of the fatigue shear modulus, and the accuracy and applicability of the model are verified by laboratory creep fatigue test data. The model provides a theoretical basis for the study of anchored rock mass support under low‐frequency earthquakes or blasting loads.
An Improved Genetic Algorithm and Neural Network‐Based Evaluation Model of Classroom Teaching Quality in Colleges and Universities
Authors: Zhang Huaying , Xiao Bin , Li Jinqiong , Hou Min
Published: August 2021

Research on educational quality has gotten a lot of attention as the current higher education teaching reform continues to deepen and grow. The key to improving education quality is to improve teaching quality, and teacher evaluation is an important tool for doing so. As a result, educational management requires the development and refinement of a system for evaluating teaching quality. Traditional approaches to assessing teaching quality, on the other hand, are problematic due to their limitations. As a result, a scientific and reasonable model for evaluating the teaching quality of college undergraduate teachers must be developed. We present a unique model for evaluating the quality of classroom teaching in colleges and universities, which is based on improved genetic algorithms and neural networks. The basic idea is to use adaptive mutation genetic algorithms to refine the initial weights and thresholds of the BP neural network. The teaching quality evaluation findings were improved by improving the neural network’s prediction accuracy and convergence speed, resulting in a more practical scheme for evaluating college and university teaching quality. We have conducted simulation experiments and comparative analysis, and the mean square error of the results of the proposed model is very low, which proves the effectiveness and superiority of the algorithm.
FLS-Based Nonuniform Trajectory Tracking AILC for Uncertain Nonlinear Systems with Nonsymmetric Dead-Zone Input and Initial State Error
Authors: Zhang Chunli , Tian Xu , Yan Lei
Published: August 2021

This paper proposes an AILC method for uncertain nonlinear system to solve different target tracking problems. The method uses fuzzy logic systems (FLS) to approximate every uncertain term in systems. All closed-loop signals are bounded on

0
,
T

according to the Lyapunov theory. A time-varying boundary layer and a typical convergent series are introduced to handle initial state error, unknown bounds of errors, and nonuniform target tracking, respectively. The result is that the tracking error’s norm can converge to a small neighborhood along iteration increasing asymptotically. Finally, the simulation results of mass-spring mechanical system show the correctness of the theory and validity of the method.
RBFNN‐Based Singularity‐Free Terminal Sliding Mode Control for Uncertain Quadrotor UAVs
Authors: Tao Meiling , He Xiongxiong , Xie Shuzong , Chen Qiang
Published: August 2021

In this article, a singularity‐free terminal sliding mode (SFTSM) control scheme based on the radial basis function neural network (RBFNN) is proposed for the quadrotor unmanned aerial vehicles (QUAVs) under the presence of inertia uncertainties and external disturbances. Firstly, a singularity‐free terminal sliding mode surface (SFTSMS) is constructed to achieve the finite‐time convergence without any piecewise continuous function. Then, the adaptive finite‐time control is designed with an auxiliary function to avoid the singularity in the error‐related inverse matrix. Moreover, the RBFNN and extended state observer (ESO) are introduced to estimate the unknown disturbances, respectively, such that prior knowledge on system model uncertainties is not required for designing attitude controllers. Finally, the attitude and angular velocity errors are finite‐time uniformly ultimately bounded (FTUUB), and numerical simulations illustrated the satisfactory performance of the designed control scheme.
Functional Coupled Systems with Generalized Impulsive Conditions and Application to a SIRS-Type Model
Authors: Minhós Feliz , Carapinha Rui
Published: August 2021

In this paper, we consider a first-order coupled impulsive system of equations with functional boundary conditions, subject to the generalized impulsive effects. It is pointed out that this problem generalizes the classical boundary assumptions, allowing two-point or multipoint conditions, nonlocal and integrodifferential ones, or global arguments, as maxima or minima, among others. Our method is based on lower and upper solution technique together with the fixed point theory. The main theorem is applied to a SIRS model where to the best of our knowledge, for the first time, it includes impulsive effects combined with global, local, and the asymptotic behavior of the unknown functions.
Biomarkers of Inflammation and Inflammation-Related Indexes upon Emergency Department Admission Are Predictive for the Risk of Intensive Care Unit Hospitalization and Mortality in Acute Poisoning: A 6-Year Prospective Observational Study
Authors: Lionte Catalina , Bologa Cristina , Sorodoc Victorita , Petris Ovidiu Rusalim , Puha Gabriela , Stoica Alexandra , Ceasovschih Alexandr , Jaba Elisabeta , Sorodoc Laurentiu
Published: August 2021

Patients poisoned with drugs and nonpharmaceutical substances are frequently admitted from the emergency department (ED) to a medical or ICU department. We hypothesized that biomarkers of inflammation and inflammation-related indexes based on the complete blood cell (CBC) count can identify acutely poisoned patients at increased risk for ICU hospitalization and death. We performed a 6-year prospective cohort study on 1548 adult patients. The demographic data, the levels of hs-CRP (high-sensitivity C-reactive protein), CBC, and inflammation-related indexes based on CBC counts were collected upon admission and compared between survivors and nonsurvivors, based on the poison involved. Both a multivariate logistic regression model with only significant univariate predictors and a model including univariate predictors plus each log-transformed inflammation-related indexes for mortality were constructed. The importance of the variables for mortality was graphically represented using the nomogram. hs-CRP (odds ratio (OR), 1.38; 95% CI, 1.16–1.65,

p
<
0.001

for log-transformed hs-CRP), red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were significantly associated with the risk of ICU hospitalization, after multivariable adjustment. Only RDW, NLR, and monocyte-lymphocyte ratio (MLR) were significantly associated with mortality. The predictive accuracy for mortality of the models which included either NLR (AUC 0.917, 95% CI 0.886-0.948) or MLR (AUC 0.916, 95% CI 0.884-0.948) showed a high ability for prognostic detection. The use of hs-CRP, RDW, NLR, and MLR upon ED admission are promising screening tools for predicting the outcomes of patients acutely intoxicated with undifferentiated poisons.
Immune Characters and Plasticity of the Sentinel Lymph Node in Colorectal Cancer Patients
Authors: Li Xiaoyun , Tang Jingling , Du Hang , Wang Xinjun , Wu Liyun , Hu Pingsheng , Zhang Hua , Zhang Ruyi , Yang Yuan
Published: August 2021

Purpose. This study is aimed at immunologically characterizing sentinel lymph nodes (SNs) in colorectal cancer (CRC) patients and identifying changes in immunological phenotype and function of SNs isolated from the tumor immunosuppressive microenvironment. Methods. A total of 53 pairs of matched SNs and non-SNs (NSNs) were collected by using a lymph node tracer dye. Flow cytometry was performed to detect the immunophenotype of T cells as well as the expression of activation and inhibitory markers. Differential expression and distribution of characteristic immune cell markers were analyzed by multiplex immunohistochemistry (mIHC). Transcriptomics analysis was conducted to compare the differences in the expression of immune-related genes among lymph nodes. The ex vivo culture of lymph nodes was carried out to examine changes in immunological phenotypes and functions. Results. Compared with NSNs, SNs harbored a significantly higher percentage of regulatory T cells (Tregs) but a lower proportion of MoMDSCs. As indicated in the mIHC assays, Tregs, T follicular helper (Tfh) cells, and M2 macrophages were mainly distributed in cortical areas, germinal centers, and subcapsular sinus areas, respectively, while significantly higher numbers of Tregs and Tfh cells were detected in SNs as compared to NSNs. Moreover, GSEA revealed that T cell activation genes and CD8+ T cell exhaustion-related genes are enriched in SNs and NSNs, respectively. The ex vivo culture led to an increase in the proportion of CD4+ cells, while activating T cells in SNs. In addition, SNs displayed a higher increase in the expression of cytokines IFN-γ, TNF-α, and sFas than NSNs. Conclusion. SNs are shown to be in an immune active state in vivo, while highly expressing inhibitory cytokines and suppressive markers. The ex vivo culture enhanced antitumor immunological function of SN-T cells, providing a starting material for adoptive cell therapy for CRC.
Research on Business English Translation Architecture Based on Artificial Intelligence Speech Recognition and Edge Computing
Authors: Xu Yunwei
Published: August 2021

In today’s society, the continuous deepening of international cultural integration has become the background of the times. China has become more and more closely connected with the world, and many physical or online news media have become a platform for China to receive world information and spread Chinese culture. Business English translation is therefore valued by translation researchers and translators. Aiming at the shortcomings of current business English translation research, this paper designs and develops a business English translation architecture based on artificial intelligence speech recognition and edge computing. First of all, considering the relevance and complementarity between speech and text modalities, this paper uses the deep neural network feature fusion method to effectively fuse the extracted monomodal features and perform speech recognition. Secondly, adopt the edge computing method to establish the business English translation system architecture. Finally, the simulation test analysis verifies the efficiency of the business English translation framework established in this paper. Compared with the existing methods, our proposal improved the accuracy than others at least 10% and the time of model building also decreased obviously. The purpose of this research is to discuss how to deal with the many differences between the source language and the target language, and how to enhance the readability of the translation and meet the reader’s cultural cognition and needs.
Method to Correct the Velocity Variation Information of an Automatic Crash Notification System in Vehicle‐to‐Rigid Barrier Frontal Collisions
Authors: Lu Ying , Ji Xiaojie , Shu Yu
Published: August 2021

Automatic crash notification systems (ACNSs) play a key role in post‐accident safety. To improve the accuracy and efficiency of ACNSs, a method to correct the velocity variation information of ACNSs was established. First, after the acceleration data of sled crash tests were analysed, the factors affecting the accuracy of the velocity variation information were determined, and the influence of the discrimination threshold and acceleration curve shape on the velocity variation information was examined. Second, according to the acceleration data generated by the simulation model of a sled crash, the correlation between the accuracy of the velocity variation information and influencing factors was modelled. Third, an automatic crash notification algorithm involving a velocity variation correction function (VVCF) was proposed based on the correlation model. Finally, to verify its reliability, the improved algorithm was applied to an automatic crash notification system (ACNS) terminal. The validation results show that the ACNS terminal can accurately identify collisions and transmit accident information. Moreover, more accurate velocity variation information can be retrieved.
Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Coptis chinensis Franchin Polycystic Ovary Syndrome
Authors: Ma Jian Xiong , Ye Miaoyong , Ma Ke , Zhou Kang , Zhang Yingying , Wang Xiting , Tong Hongxuan
Published: August 2021

Background. Polycystic ovary syndrome (PCOS) causes low fertility in females. Coptis chinensis (C. chinensis) is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although C. chinensis has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of C. chinensis, their targets, and molecular mechanisms underlying their effects. Methods and Results. Network pharmacology was used to analyze the bioactive components of C. chinensis, their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of C. chinensis. The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of C. chinensis for the treatment of PCOS included JUN, MAPK, IL6, CXCL8, FOS, and IL1B. A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of C. chinensis. The results showed that C. chinensis treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1β). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy. Conclusions. This preliminary study verified the basic pharmacological effects and mechanisms of C. chinensis, a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of C. chinensis on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine.
Circuit Implementation Synchronization between Two Modified Fractional-Order Lorenz Chaotic Systems via a Linear Resistor and Fractional-Order Capacitor in Parallel Coupling
Authors: Liu Juan , Cheng Xuefeng , Zhou Ping
Published: August 2021

In this study, a modified fractional-order Lorenz chaotic system is proposed, and the chaotic attractors are obtained. Meanwhile, we construct one electronic circuit to realize the modified fractional-order Lorenz chaotic system. Most importantly, using a linear resistor and a fractional-order capacitor in parallel coupling, we suggested one chaos synchronization scheme for this modified fractional-order Lorenz chaotic system. The electronic circuit of chaos synchronization for modified fractional-order Lorenz chaotic has been given. The simulation results verify that synchronization scheme is viable.
Fragility Comprehensive Assessment of Low‐Rise Cold‐Formed Steel Framed Wall Structure Subjected to Wind Load
Authors: Zhang Hao , Hou Shiwei , Ding Yiming , Li Chao , Liu Pengfei
Published: August 2021

This paper presents a comprehensive assessment method of the fragility of low‐rise cold‐formed steel (CFS) framed wall structures subjected to wind hazards considering the fragility of both the main structure and the cladding system. The effects of wind directions on the fragility of CFS framed wall structures were also studied. For the main structure, the fragility curve is established using the maximum interstory drift ratio (ISDRmax) as the performance index for assessing the wind fragility of the structure. For the cladding system, the probabilistic models of the wind load and the cladding component resistance are established based on Monte Carlo simulation, and then methods for the fragility assessment of single cladding components and the cladding system under wind hazards considering the influence of the number and arrangement of the cladding components are proposed. The results indicated that, under strong wind, the cladding system may be damaged before the required wind resistance capacity of the main structure is exhausted. In particular, the roof sheathing is the most prone to damage, followed by the stud wall. That is, before the main structure is severely damaged or collapses, the cladding systems may be severely damaged, rendering the structure unusable. Therefore, the comprehensive assessment of the fragility of this type of structure subjected to wind hazard considering the fragility of both the main structure and the cladding system is more accurate. This study is of great significance for the improvement of the wind resistance performance of CFS structures and the popularization of this type of structure.
Innovative Control Technique for the Floor Heave in Goaf-Side Entry Retaining Based on Pressure Relief by Roof Cutting
Authors: Yu Guangyuan , Wang Jiong , Hu Jinzhu , Zhu Daoyong , Sun Han , Ma Xingen , Ming Wei , Li Wenfei
Published: August 2021

To solve the difficulty in controlling floor heave of a retained goaf-side roadway, a new control technique was investigated from the perspective of the pressure relief by roof cutting by combining mechanical analysis, numerical simulation, and engineering tests. The mechanical principle of controlling the floor heave based on pressure relief by roof cutting was attained by analyzing the movement of overlying strata and mechanical characteristics of key blocks before and after the roof cutting. A new technique for controlling the floor heave based on pressure relief by roof cutting was proposed. Research results have shown that after performing pressure relief by roof cutting, the caved gangues in the goaf can support the overlying strata and, thereby, change the movement law thereof and weaken the abutment pressure on the coal wall. Furthermore, the pressure exerted on the roadway floor by the coal wall is lowered to prevent plastic deformation of the floor, thus controlling floor heave in the roadway; a new integrated technique for controlling the floor heave based on pressure relief by roof cutting, flexible yielding, controlling with double-direction-control anchor bolts, and controlling with reinforcing anchor cables is developed, and the technological processes of support, cutting, and protection are summarised. The results of field testing showed that, after applying the new technique, the average floor heave amount of the roadway declines by 64% and the average speed of the floor heave up to 231 m behind the working face decreases by 61%.
Quercetin Protects H9c2 Cardiomyocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Oxidative Stress and Mitochondrial Apoptosis by Regulating the ERK1/2/DRP1 Signaling Pathway
Authors: Li Fen , Li Dongsheng , Tang Shifan , Liu Jianguang , Yan Jie , Chen Haifeng , Yan Xisheng
Published: August 2021

Reperfusion of blood flow during ischemic myocardium resuscitation induces ischemia/reperfusion (I/R) injury. Oxidative stress has been identified as a major cause in this process. Quercetin (QCT) is a member of the flavonoid family that exerts antioxidant effects. The aim of this study was to investigate the preventive effects of QCT on I/R injury and its underlying mechanism. To this end, H9c2 cardiomyocytes were treated with different concentrations of QCT (10, 20, and 40 μM) and subsequently subjected to oxygen-glucose deprivation/reperfusion (OGD/R) administration. The results indicated that OGD/R-induced oxidative stress, apoptosis, and mitochondrial dysfunction in H9c2 cardiomyocytes were aggravated following 40 μM QCT treatment and alleviated following the administration of 10 and 20 μM QCT prior to OGD/R treatment. In addition, OGD/R treatment inactivated ERK1/2 signaling activation. The effect was mitigated using 10 and 20 μM QCT prior to OGD/R treatment. In conclusion, these results suggested that low concentrations of QCT might alleviate I/R injury by suppressing oxidative stress and improving mitochondrial function through the regulation of ERK1/2-DRP1 signaling, providing a potential candidate for I/R injury prevention.
Congestion‐Aware Routing Algorithm for NoC Using Data Packets
Authors: Ahmad Khurshid , Sethi Muhammad Athar Javed , Ullah Rehmat , Ahmed Imran , Ullah Amjad , Jan Naveed , Karami Ghulam Mohammad
Published: August 2021

Network on Chip (NoC) is a communication framework for the Multiprocessor System on Chip (MPSoC). It is a router‐based communication system. In NoC architecture, nodes of MPSoC are communicating through the network. Different routing algorithms have been developed by researchers, e.g., XY, intermittent XY, DyAD, and DyXY. The main problems in these algorithms are congestion and faults. Congestion and faults cause delay, which degrades the performance of NoC. A congestion‐aware algorithm is used for the distribution of traffic over NoC and for the avoidance of congestion. In this paper, a congestion‐aware routing algorithm is proposed. The algorithm works by sending congestion information in the data packet. The algorithm is implemented on a 4 × 4 mesh NoC using FPGA. The proposed algorithm decreases latency, increases throughput, and uses less bandwidth in sharing congestion information between routers in comparison to the existing congestion‐aware routing algorithms.
Synergistic Regulation of Microglia Gene Expression by Natural Molecules in Herbal Medicine
Authors: Qiburi Qiburi , Temuqile Temuqile , Baigude Huricha
Published: August 2021

The activated microglia contribute to stroke-induced neuroinflammation by upregulating the expression of a pleura of genes that are characterized as either proinflammatory or anti-inflammatory. The natural products alantolactone (Ala) and dehydrodiisoeugenol (Deh) found in Inula helenium L. and Myristica fragrans Houtt., respectively, are regularly used in traditional herb medicine, which play anti-inflammatory and antioxidant roles via regulation of canonical pathways such as nuclear factor kappa B (NF-κB) in microglia and microphages. To illustrate the full spectra of gene expression alteration in microglia treated with Ala, Deh, and the mixture of Ala and Deh (denoted as Mix), we performed RNA-seq analysis of total RNA extracted from lipopolysaccharide- (LPS-) treated microglia subsequently exposed to Ala, Deh, and Mix. While both chemicals regulated the gene expression that facilitates an anti-inflammatory polarization, the mixture exerted some distinctive synergic regulatory effect, which differed from either of the chemicals alone. Our data provide important evidence for further research on the therapeutic mechanism of traditional medicine including Eerdun Wurile (EW).
Seepage Flow Properties of a Columnar Jointed Rock Mass in a True Triaxial Experiment
Authors: He Yanxin , Zhu Zhende , Lu Wenbin , Hu Yunjin , Xie Xinghua , Wang Sijing
Published: August 2021

A columnar jointed rock mass is a type of rock mass with strong geometric anisotropy and high interface permeability. Its seepage characteristics pose new challenges to the construction and maintenance of the Baihetan Hydropower Station on the Jinsha River. The research object in this study is the columnar jointed rock mass (basalt) in the dam area of Baihetan Hydropower Station. Similar-material model samples of the columnar jointed rock mass with different column dip angles (

α
=

0

°

~90°) were prepared following a similar principle. A true triaxial seepage–stress coupling test was conducted to evaluate the seepage characteristics of similar-material samples with different dip angles under intermediate principal stress and minimum principal stress. The experimental results showed that the columnar jointed rock mass exhibited apparent seepage anisotropy. The relationship curve between the volume flow rate

Q

and the pressure gradient

−
d
P
/
d
L

of the samples with different dip angles showed evident nonlinear seepage under intermediate principal stress, which could be well expressed using the Forchheimer equation. It shows the characteristics of a typical linear Darcy flow under minimum principal stress. The law of variations in the permeability of the samples with different dip angles under intermediate principal stress can be well expressed using the one-dimensional quadratic function equation

k
=
a
+
b

σ

2

+
c

σ

2

2

, and the law of variations in the permeability of the samples with different dip angles under minimum principal stress can be well expressed using the logarithmic function

k
=
a
+
b
ln

σ

3

. The permeabilities of the columnar jointed rock mass with dip angles of 0°, 15°, 30°, and 60° were most sensitive to changes in stress, and the seepage characteristics increased in complexity after changes in stress.
Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma
Authors: Seitter Samantha J. , Sherry Richard M. , Yang James C. , Robbins Paul F. , Shindorf Mackenzie L. , Copeland Amy R. , McGowan Christine T. , Epstein Monica , Shelton Thomas E. , Langhan Michelle M. , Franco Zulmarie , Danforth David N. , White Donald E. , Rosenberg Steven A. , Goff Stephanie L.
Published: August 2021

Purpose:

Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL.

Patients and Methods:

Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2. Clinical characteristics of enrolled patients and treatment characteristics of TIL infusion products over two decades of ACT were analyzed to identify predictors of objective response.

Results:

Adoptive transfer of TILs mediated an objective response rate of 56% (108/192) and median melanoma-specific survival of 28.5 months in patients naïve to anti–programmed cell death-1 (PD-1) therapy compared with 24% (8/34) and 11.6 months in patients refractory to anti–PD-1 (aPD-1). Among patients with BRAF V600E/K–mutated disease, prior treatment with targeted molecular therapy was also associated with a decreased response rate (21% vs. 60%) and decreased survival (9.3 vs. 50.7 months) when compared with those patients naïve to targeted therapy. With a median potential follow-up of 89 months, 46 of 48 complete responders in the aPD-1–naïve cohort have ongoing responses after a single treatment and 10-year melanoma-specific survival of 96%.

Conclusions:

Patients previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to ACT-TIL. While ACT-TIL is currently being investigated for treatment-refractory patients, it should also be considered as an initial treatment option for eligible patients with metastatic melanoma.

See related commentary by Sznol, p. 5156
TIL in Melanoma—Similar Approaches, Different Results, Unanswered Questions
Authors: Sznol Mario
Published: August 2021

Prior treatment with anti-PD-1 and/or BRAF-targeted therapies was associated with limited activity of tumor infiltrating lymphocytes (TIL) in metastatic melanoma. Recent insights into mechanisms of action for TIL and anti-PD-1 provide the foundation for understanding differences in outcomes in different trials or populations, and a roadmap for developing improved products.

See related article by Seitter et al., p. 5289
The FDA-Approved Anthelmintic Pyrvinium Pamoate Inhibits Pancreatic Cancer Cells in Nutrient-Depleted Conditions by Targeting the Mitochondria
Authors: Schultz Christopher W. , McCarthy Grace A. , Nerwal Teena , Nevler Avinoam , DuHadaway James B. , McCoy Matthew D. , Jiang Wei , Brown Samantha Z. , Goetz Austin , Jain Aditi , Calvert Valerie S. , Vishwakarma Vikalp , Wang Dezhen , Preet Ranjan , Cassel Joel , Summer Ross , Shaghaghi Hoora , Pommier Yves , Baechler Simone A. , Pishvaian Michael J. , Golan Talia , Yeo Charles J. , Petricoin Emanuel F. , Prendergast George C. , Salvino Joseph , Singh Pankaj K. , Dixon Dan A. , Brody Jonathan R.
Published: August 2021

Pancreatic ductal adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA-approved antihelminthic pyrvinium pamoate (PP) has previously been shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50 values (9–93 nmol/L) against a panel of PDAC, patient-derived, and murine organoid cell lines. In vivo, we demonstrated that PP inhibited PDAC xenograft tumor growth with both intraperitoneal (IP; P < 0.0001) and oral administration (PO; P = 0.0023) of human-grade drug. Metabolomic and phosphoproteomic data identified that PP potently inhibited PDAC mitochondrial pathways including oxidative phosphorylation and fatty acid metabolism. As PP treatment reduced oxidative phosphorylation (P < 0.001), leading to an increase in glycolysis (P < 0.001), PP was 16.2-fold more effective in hypoglycemic conditions similar to those seen in PDAC tumors. RNA sequencing demonstrated that PP caused a decrease in mitochondrial RNA expression, an effect that was not observed with established mitochondrial inhibitors rotenone and oligomycin. Mechanistically, we determined that PP selectively bound mitochondrial G-quadruplexes and inhibited mitochondrial RNA transcription in a G-quadruplex–dependent manner. This subsequently led to a 90% reduction in mitochondrial encoded gene expression. We are preparing to evaluate the efficacy of PP in PDAC in an IRB-approved window-of-opportunity trial (IND:144822).
Uptake and Predictors of Opportunistic Salpingectomy for Ovarian Cancer Risk Reduction in the United States
Authors: Karia Pritesh S. , Joshu Corinne E. , Visvanathan Kala
Published: August 2021

Evidence suggesting that high-grade serous ovarian cancers originate in the fallopian tubes has led to the emergence of opportunistic salpingectomy (OS) as an approach to reduce ovarian-cancer risk. In the U.S., some national societies now recommend OS in place of tubal ligation for sterilization or during a benign hysterectomy in average-risk women. However, limited data exist on the dissemination of OS in clinical practice. We examined the uptake and predictors of OS in a nationwide sample of inpatient and outpatient claims (N = 48,231,235) from 2010 to 2017. Incidence rates of OS were calculated, and an interrupted time-series analysis was used to quantify changes in rates before (2010–2013) and after (2015–2017) national guideline release. Predictors of OS use were examined using Poisson regression. From 2010 to 2017, the age-adjusted incidence rate of OS for sterilization and OS during hysterectomy increased 17.8-fold [95% confidence interval (CI), 16.2–19.5] and 7.6-fold (95% CI, 5.5–10.4), respectively. The rapid increase (age-adjusted increase in quarterly rates of between 109% and 250%) coincided with the time of national guideline release. In multivariable-adjusted analyses, OS use was more common in young women and varied significantly by geographic region, rurality, family history/genetic susceptibility, surgical indication, inpatient/outpatient setting, and underlying comorbidities. Similar differences in OS uptake were noted in analyses limited to women with a family history/genetic susceptibility to breast/ovarian cancer. Our results highlight significant differences in OS uptake in both high- and average-risk women. Defining subsets of women who would benefit most from OS and identifying barriers to equitable OS uptake is needed.

Prevention Relevance:

Opportunistic salpingectomy for ovarian-cancer risk reduction has been rapidly adopted in the U.S., with significant variation in uptake by demographic and clinical factors. Studies examining barriers to opportunistic salpingectomy access and the long-term effectiveness and potential adverse effects of opportunistic salpingectomy are needed.
Successful Treatment of Placental Chorangiomas by Ultrasound-Guided Percutaneous in utero Microcoil Embolization
Authors: Fisher James , Howley Lisa , Lillegard Joseph , Amin Vinit , Engstrom Bjorn , Snowise Saul
Published: August 2021

Placental chorangiomas can cause a high-output fetal state and increase neonatal morbidity and mortality. There is a paucity of data published describing the optimal treatment of these cases, and methods for occlusion to date include placement of vascular clips, bipolar cautery, injection of alcohol or surgical glue, interstitial laser, and microcoil embolization. We report 2 cases of prenatally diagnosed chorangiomas that caused a high-output fetal state and were successfully treated with microcoil embolization. This case series describes our technique and supports microcoil embolization as a potentially safe and effective antenatal treatment option in symptomatic chorangiomas.
Atypical Association of Autoimmune Limbic Encephalitis with Anti-NMDA Receptor Antibodies in a Young Male Patient: Clinical, Imaging, and Neuropsychological Characteristics
Authors: Choreño-Parra José Alberto , de la Rosa-Arredondo Tania , Garibay-Gracián André , Montes de Oca-Vargas Ingrid , Capi-Casillas Deyanira , González-Pérez Karla Valeria , Guadarrama-Ortiz Parménides
Published: August 2021

The spectrum of autoimmune encephalitis (AE) encompasses several entities characterized by a variable frequency of psychiatric symptoms, cognitive dysfunction, focal deficits, and seizures. Although patients with AE can be categorized in specific syndromes, overlapping manifestations are also common. Furthermore, atypical correlations between clinical phenotypes and autoantibody profiles could occur in rare cases. Here, we report the rare case of a young adult man attending due to new-onset seizures and a history of memory loss, autonomic disturbances, headache, behavioral changes, and visual and olfactory hallucinations. The patient was subjected to a complete diagnostic approach that included a comprehensive laboratory workup, neuropsychological testing, electroencephalogram, cerebrospinal fluid (CSF) analysis, brain MRI, and positron emission tomography/computed tomography scan that revealed a functional and structural compromise of the bilateral medial temporal lobes. Together with the clinical manifestations of the patient, these findings were compatible with the diagnosis of autoimmune limbic encephalitis (ALE). Strikingly, further analysis of the CSF showed autoantibodies against the N-methyl-D-aspartate (NMDA) receptor. We found very few cases of the co-occurrence of anti-NMDA receptor antibodies and nonparaneoplastic ALE in the literature, especially in male patients. Our report exemplifies the complicated differential diagnosis of ALE and adds clinical information of the association with anti-NMDA receptor antibodies.
Autophagy Prevents Osteocyte Cell Death under Hypoxic Conditions
Authors: Kurihara Mai , Mukudai Yoshiki , Watanabe Hitoshi , Asakura Mariko , Abe Yuzo , Houri Asami , Chikuda Junichiro , Shimane Toshikazu , Shirota Tatsuo
Published: August 2021

Hypoxia occurs under important clinical conditions such as cancers, heart disease, and ischemia. However, the relationship between hypoxia and autophagy in osteocytes is still unclear. The objective of the present study was to uncover the regulatory mechanisms that prevent regulated cell death, such as apoptosis, necrosis, and autophagy, under hypoxia. MLO-Y4 cells, a mouse osteocyte cell line, were exposed to various O2 partial pressures (PO2). Subsequently, the cells underwent apoptosis, autophagy, autophagic cell death, and/or necrosis, and thereby we designated PO2 = 2% as a representative hypoxic condition. Immunofluorescence staining showed an increase of LC3 and a decrease of p62 in MLO-Y4 cells exposed to hypoxia, indicating the induction of autophagy. We then hypothesized that β-estradiol (E2) and vitamin D play an important role in apoptosis and autophagy of osteocytes under hypoxia. 1,25α-dihydroxyvitamin D3 (VitD) protected MLO-Y4 cells from cell death and induced autophagy. However, E2 showed little effect. Finally, Western blotting for phosphorylated mTOR and Akt was carried out in order to investigate the altered autophagy signaling pathways affected by the addition of VitD and E2. However, neither E2 nor VitD were capable of recovering the decreased phosphorylation of those factors. Our results indicated that the effects of VitD on autophagy under hypoxia were dependent on the Akt and mTOR pathways. Thus, the results of the present study showed that VitD suppresses osteocyte cell death in an mTOR pathway-dependent manner in hypoxic conditions. This suggests the potential of VitD as a therapeutic intervention for diseases in which the cell death of osteocytes mainly occurs via hypoxia.
Memória e transcendência na poesia de Dora Ferreira da Silva
Authors: Bonafim Alexandre
Published: August 2021

Na poesia de Dora Ferreira, a comunhão com o cosmos representa uma fecunda ligação com o sagrado e a memória. Lembrar, mais do que reconstruir o que se perdeu, representa, antes de tudo, um encontro com um tempo singular, o tempo da duração proustiana, instante epifânico capaz de libertar-nos do tempo e do espaço técnicos delineados pela tirania da racionalidade científica. Seguindo a premissa de Bachelard para quem sonhar será sempre mais que viver, a poeta mergulha nessa força motriz da memória poética, atingindo assim aquele tempo mítico tão bem delineado por Mircea Eliade em seu livro O sagrado e o profano.
Olga Savary (1933-2020) & Maria Lúcia Alvim (1932-2021): homenagem a duas grandes poetas levadas pela Covid 19
Authors: Dias Ayana Moreira , Marinho Cecilia Silva Furquim , Morais Maira Luana , Mendes Mariana Diniz
Published: August 2021

Uma  homenagem feita por poetas e (ou) tradutores, que possuíam forte vínculo com as escritoras Olga e Maria Lúcia. Prisca Agustoni e Laisa Kaos falam de Olga Savary, enquanto Álvaro Antunes e Guilherme Gontijo Flores rendem seus tributos a Maria Lúcia Alvim. Além de contar com ilustrações de cada uma das escritoras, exclusivamente elaboradas, por Isabela Sancho (em técnica de lápis e grafite).
Suplementi u prehrani zdravstvenih djelatnika tijekom pandemije COVID-19
Authors: Rugole Vedrana , Pucarin-Cvetković Jasna , Milošević Milan
Published: August 2021

Cilj: Cilj provedenog istraživanja bio je ispitati utjecaj pandemije COVID-19 na učestalost potrošnje suplemenata u prehrani zdravstvenih radnika. Ispitanici i metode: Ispitivanje je provedeno tijekom prosinca 2020. i siječnja 2021. godine na području grada Zagreba, a obuhvatilo je 279 zdravstvenih djelatnika DZ Centar (liječnici, medicinske sestre / medicinski tehničari, farmaceuti). Podaci su prikupljani putem upitnika prilagođenog potrebama ovog istraživanja. Razlike između skupine koja je imala promjenu u uzimanju suplementacije u odnosu na skupinu koja nije imala promjenu u uzimanju suplementacije tijekom pandemije COVID-19 analizirane su χ2 testom. Sve P vrijednosti manje od 0,05 smatrane su značajnima. Rezultati: Dobiveni rezultati ukazuju na značajnu naviku konzumiranja nekih dodataka prehrani među zdravstvenim djelatnicima, a pojava pandemije COVID-19 utjecala je na trećinu ispitanika da započnu s uzimanjem suplementa (11,5 %) ili da ih uzimaju više i češće nego prije pandemije (21,9 %). Od vitamina, tijekom pandemije COVID-19 među zdravstvenim djelatnicima, povećala se upotreba vitamina C (P = 0,001), vitamina D (P = 0,001) te kompleksa B vitamina (P = 0,048). Najveće povećanje odnosilo se na učestalost uzimanja vitamina D gdje se svakodnevno uzimanje povećalo 3,63 puta. Značajne razlike u uzimanju minerala, proteina i aminokiselina između skupine koja je imala promjenu u uzimanju suplementacije u odnosu na skupinu koja nije imala promjenu odnosile su se na uzimanje magnezija i cinka (P < 0,001). Od ostalih dodataka prehrani značajno se povećao unos beta-glukana (P < 0,001), ginko bilobe (P = 0,012), kolagena (P = 0,038) te homeopatskih pripravaka (P = 0,006). Zaključak: Pandemija COVID-19 značajno je utjecala na povećani unos dodataka prehrani kod zdravstvenih djelatnika. Na temelju najnovijih znanstvenih spoznaja i preporuka o prehrani za vrijeme COVID-19 trebalo bi više pažnje usmjeriti na principe pravilne prehrane te dnevne potrebe za vitaminima, mineralima, proteinima i antioksidansima zadovoljiti konzumacijom namirnica iz različitih kategorija hrane, a u slučajevima povećanog rizika od bolesti COVID-19 ili deficita pojedinih nutrijenata upotrebljavati i suplemente.