bluuebunny/crossref_metadata_2025 huggingface dataset:
Leg Locomotion Adaption for Quadruped Robots with Ground Compliance Estimation
Authors: Zhang Songyuan , Zhang Hongji , Fu Yili
Published: September 2020

Locomotion control for quadruped robots is commonly applied on rigid terrains with modelled contact dynamics. However, the robot traversing different terrains is more important for real application. In this paper, a single-leg prototype and a test platform are built. The Cartesian coordinates of the foot-end are obtained through trajectory planning, and then, the virtual polar coordinates in the impedance control are obtained through geometric transformation. The deviation from the planned and actual virtual polar coordinates and the expected force recognized by the ground compliance identification system are sent to the impedance controller for different compliances. At last, several experiments are carried out for evaluating the performance including the ground compliance identification, the foot-end trajectory control, and the comparison between pure position control and impedance control.
A Vehicular Service-Oriented Dynamical Routing Searching Algorithm in Software-Defined BusNet
Authors: Zeng Lingqiu , Cheng Sheng , Han Qingwen , Ye Lei
Published: September 2020

With the development of the vehicular network, BusNet-based service is of great interest to both bus companies and public users. How to provide service and ensure service quality is considered as key points for the promotion of such kinds of applications. In this paper, a system architecture, which is designed based on multiaccess edge computing (MEC) architecture and software-defined network (SDN), is proposed. Moreover, considering the problem of the dynamicity of the network, a new routing path optimization algorithm, SPSO (serial particle swarm optimization), is proposed, while a dynamic weight matrix is used to improve routing performance. The comprehensive simulation results demonstrate that the proposed method can well adapt to the dynamic change of network topology and improve communication performance significantly.
Stability Analysis of a Dynamical Model for Malware Propagation with Generic Nonlinear Countermeasure and Infection Probabilities
Authors: Zhang Xulong , Song Xiaoxia
Published: September 2020

The dissemination of countermeasures is widely recognized as one of the most effective strategies of inhibiting malware propagation, and the study of general countermeasure and infection has an important and practical significance. On this point, a dynamical model incorporating generic nonlinear countermeasure and infection probabilities is proposed. Theoretical analysis shows that the model has a unique equilibrium which is globally asymptotically stable. Accordingly, a real network based on the model assumptions is constructed, and some numerical simulations are conducted on it. Simulations not only illustrate theoretical results but also demonstrate the reasonability of general countermeasure and infection.
EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus
Authors: Zhang Zhinan , Cai Xiaowen , Yao Zengyu , Wen Feng , Fu Zhiyi , Zhang Jiping , Zhong Zheng , Huang Yong , Qu Shanshan
Published: September 2020

Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both p<0.05), but these two therapies had nonsignificant difference between each other (p>0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p<0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.
Determination of Vitamins D2 and D3 in Edible Fungus by Reversed-Phase Two-Dimensional Liquid Chromatography
Authors: Huang Bai-Fen , Pan Xiao-Dong , Zhang Jing-Shun , Xu Jiao-Jiao , Cai Zeng-Xuan
Published: September 2020

Vitamin D is the name given to a series of compounds with antirachitic activity. In this study, we developed a method for quantification of the common Vitamin D, ergocalciferol (vitamin D2), and cholecalciferol (vitamin D3), in edible fungus by reversed-phase two-dimensional liquid chromatography. The sample was saponified by KOH ethanol solution and extracted with ethyl acetate and n-hexane. After reconcentration, the sample was directly injected for instrumental analysis. The results showed that the spiking recoveries of vitamin D2 and vitamin D3 were 80.4–93.8% and 82.3–92.0%, respectively. The relative standard deviations (RSDs) were all less than 5%. Comparing to the results of isotope dilution liquid chromatography tandem mass spectrometry, there were no significant differences (P>0.05). The method was applied for testing vitamin D2 and D3 in 9 kinds of edible mushrooms. It showed that vitamin D3 was not detected. The content of vitamin D2 ranged from 0.11 μg/100 g to 123 μg/100 g. The content of vitamin D2 in dried mushroom was the highest, while that in fresh mushroom was the lowest. The limit of quantification was 0.025 μg/100 g.
Cytotoxicity Potential of Endophytic Fungi Extracts from Terminalia catappa against Human Cervical Cancer Cells
Authors: Majoumouo Michèle Stella , Tincho Marius Belmondo , Kouipou Toghueo Rufin Marie , Morris Thureyah , Hiss Donavon Charles , Boyom Fabrice Fekam , Mandal Chitra
Published: September 2020

Endophytic fungi are potential sources of novel bioactive metabolites from a natural product drug discovery perspective. This study reports the bioactivity-directed fractionation of the secondary metabolites of the ethyl acetate extract of a fermentation culture of endophytic fungi from Terminalia catappa which were then evaluated for their cytotoxicity against human cervical cancer (HeLa) cells and human foreskin fibroblast (HFF) cells. Furthermore, apoptosis was determined using the Annexin V/propidium iodide (PI) flow cytometry assay. Endophyte extracts N2, N7, N8, N97, N169, and N233 were obtained from Trichoderma sp, Phoma sp, Phomopsis phyllanticola, Fusarium oxyporum, Collectotrichum sp, and Cryptococcus flavescens, respectively. The N97 extract was most active with a 50% inhibitory concentration (IC50) of 33.35 µg/ml. A 50% cytotoxic concentration (CC50) of 268.4 µg/ml was obtained with HFF cells and the selectivity index (SI) was 8.01. The percentages of cell populations were increased at late apoptosis (Annexin+/PI+), with the percentages of 27.4 ± 0.3 and 19.2 ± 0.01 obtained, respectively, for 50 µg/ml and 80 µg/ml of the N97 extract and 2.1 ± 0.1 obtained for the control in late apoptosis (Annexin V+/PI+) . Moreover, a higher reduction in the percentage of viable cells was observed in the HeLa control cells (93.6 ± 0.3), but the percentages of viable HeLa cells were 37 ± 0.05 and 45 ± 0.1, respectively, for the 50 µg/ml and 80 µg/ml treatments with the N97 extract. Also, the percentages of 34.7 ± 0.1 and 33.9 ± 0.4 were, respectively, obtained for 50 µg/ml and 80 µg/ml compared to the control with 4.6 ± 0.2, in early apoptosis (Annexin V+/PI-). These findings highlight the anticancer potential of the N97 extract of endophytic fungi from Terminalia catappa, which is mediated through apoptosis and presumably also attenuation of chemoresistance.
Feature Selection Based on Cross-Correlation for the Intrusion Detection System
Authors: Farahani Gholamreza
Published: September 2020

One of the important issues in the computer networks is security. Therefore, trusted communication of information in computer networks is a critical point. To have a safe communication, it is necessary that, in addition to the prevention mechanisms, intrusion detection systems (IDSs) are used. There are various approaches to utilize intrusion detection, but any of these systems is not complete. In this paper, a new cross-correlation-based feature selection (CCFS) method is proposed and compared with the cuttlefish algorithm (CFA) and mutual information-based feature selection (MIFS) features with use of four different classifiers: support vector machine (SVM), naive Bayes (NB), decision tree (DT), and K-nearest neighbor (KNN). The experimental results on the KDD Cup 99, NSL-KDD, AWID, and CIC-IDS2017 datasets show that the proposed method has a better performance in accuracy, precision, recall, and F1-score criteria in comparison with the other two methods in different classifiers. Also, the results on different classifiers show that the usage of the DT classifier for the proposed method is the best.
Mucocutaneous Leishmaniasis with Rare Manifestation in the Nasal Mucosa and Cartilage Bone Septal
Authors: Casalle Nicole , de Barros Pinto Grifoni Laís , Bosco Mendes Ana Carolina , Delort Sérgio , Massucato Elaine Maria Sgavioli
Published: September 2020

Backgroud. Leishmaniasis is an infectious disease caused by protozoan of the genusLeishmaniathat can affect mucosal or cutaneous surfaces. It can manifest via buccal mucosa, associated with a skin lesion or as a secondary effect. Over the last 20 years, the number of cases of this disease is progressively increasing in Brazil. Therefore, the knowledge of this disease by health professionals is important in order to achieve a correct and early diagnosis, manly to prevent the deformities it may cause to the face.Case presentation. The aim of the present study was to report a case of mucocutaneous leishmaniasis with lesions on the palatine and pharyngeal mucosa in a patient with a previous report of rare lesions in the nasal mucosa and cartilage bone septal.Conclusions. We believe that the disclosure of such cases may be important for the correct and early diagnosis of these secondary injuries that may affect the oral mucosa.
Predisposition of Neonatal Maternal Separation to Visceral Hypersensitivity via Downregulation of Small-Conductance Calcium-Activated Potassium Channel Subtype 2 (SK2) in Mice
Authors: Wu Ke , Gao Jing-hua , Hua Rong , Peng Xiao-han , Wang Hui , Zhang Yong-mei
Published: September 2020

Background. Visceral hypersensitivity is a common occurrence of gastrointestinal diseases such as irritable bowel syndrome (IBS), wherein early-life stress (ELS) may have a high predisposition to the development of visceral hypersensitivity in adulthood, with the specific underlying mechanism still elusive. Herein, we assessed the potential effect of small-conductance calcium-activated potassium channel subtype 2 (SK2) in the spinal dorsal horn (DH) on the pathogenesis of visceral hypersensitivity induced by maternal separation (MS) in mice. Methods. Neonatal mice were subjected to the MS paradigm, an established ELS model. In adulthood, the visceral pain threshold and the abdominal withdrawal reflex (AWR) were measured with an inflatable balloon. The elevated plus maze, open field test, sucrose preference test, and forced swim test were employed to evaluate the anxiety- and depression-like behaviors. The expression levels of SK2 in the spinal DH were determined by immunofluorescence and western blotting. The mRNA of SK2 and membrane palmitoylated protein 2 (MPP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Electrophysiology was applied to evaluate the neuronal firing rates and SK2 channel-mediated afterhyperpolarization current (IAHP). The interaction between MPP2 and SK2 was validated by coimmunoprecipitation. Results. In contrast to the naïve mice, ethological findings in MS mice revealed lowered visceral pain threshold, more evident anxiety- and depression-like behaviors, and downregulated expression of membrane SK2 protein and MPP2 protein. Moreover, electrophysiological results indicated increased neuronal firing rates and decreased IAHP in the spinal DH neurons. Nonetheless, intrathecal injection of the SK2 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) in MS mice could reverse the electrophysiological alterations and elevate the visceral pain threshold. In the naïve mice, administration of the SK2 channel blocker apamin abated IAHP and elevated spontaneous neuronal firing rates in the spinal DH neurons, reducing the visceral pain threshold. Finally, disruption of the MPP2 expression by small interfering RNA (siRNA) could amplify visceral hypersensitivity in naïve mice. Conclusions. ELS-induced visceral pain and visceral hypersensitivity are associated with the underfunction of SK2 channels in the spinal DH.
Fracture Behavior of Rock with Initial Damage: Theoretical, Experimental, and Numerical Investigations
Authors: Zhang Hui , Guo Panpan , Wang Yixian , Zhao Yanlin , Lin Hang , Liu Yan , Shao Yahui
Published: September 2020

Geomaterials such as rock mass often have initial damage under the influence of long-term geological action and hydration corrosion environment. The initial damage affects the integrity and stability of the rock mass, resulting in a difference in the mechanical properties of jointed rock mass and intact one. Therefore, the study of the fracture and failure characteristics of the jointed rock mass is of great significance. Most of the previous researches into the fracture behavior of rock with initial damage are based on model testing, theoretical analysis, and numerical simulation of rock mass with preexisting flaws. This review concentrates on the theoretical, experimental, and numerical efforts that have been devoted to the fracture characteristics of rock or rock-like specimens with preexisting flaws under compression. Some suggestions on the future research work in this field are also given.
EH-UWSN: Improved Cooperative Routing Scheme for UWSNs Using Energy Harvesting
Authors: Ahmed Sheeraz , Ali Malik Taimur , Alothman Asma A. , Nawaz Asif , Shahzad M. , Shah Ahmed Ali , Ahmad Awais , Khan M. Yousaf Ali , Najam Zeeshan , Shaheen Asma
Published: September 2020

The harsh testing environments of underwater scenarios make it extremely hard to plan a reasonable routing protocol for Underwater Sensor Networks (UWSNs). The main challenge in UWSNs is energy confinement. It is needed to plan an energy effective scheme which increases the life span of the network and also reduces the energy usage in data transfer from supplier to sink. In this research, we present the design of a routing protocol known as Energy Harvesting in UWSN (EH-UWSN). EH-UWSN is a compact, energy efficient, and high throughput routing protocol, in which we present utilization of energy gaining with coordinating transfer of data packets through relay nodes. Through Energy Harvesting, the nodes are capable to recharge their batteries from the outside surrounding with the ultimate objective to improve the time span of network and proceed data through cooperation, along with restricting energy usage. At the sink node, the mixing plan applied is centered on Signal-to-Noise Ratio Combination (SNRC). Outcomes of EH-UWSN procedure reveal good results in terms of usage of energy, throughput, and network life span in comparing with our previous Cooperative Routing Scheme for UWSNs (Co-UWSN). Simulation results show that EH-UWSN has consumed considerably lesser energy when compared with Co-UWSN along with extending network lifetime and higher throughput at the destination.
Direct Evidence of Plasticity within Human Primary Motor and Somatosensory Cortices of Patients with Glioblastoma
Authors: Gibb William R. , Kong Nathan W. , Tate Matthew C.
Published: September 2020

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders.
Land Cover and Forest Type Classification by Values of Vegetation Indices and Forest Structure of Tropical Lowland Forests in Central Vietnam
Authors: Nguyen Trong Hung , Nguyen The Dung , Kappas Martin
Published: September 2020

This paper aims to (i) optimize the application of multiple bands of satellite images for land cover classification by using random forest algorithms and (ii) assess correlations and regression of vegetation indices of a better-performed land cover classification image with vertical and horizontal structures of tropical lowland forests in Central Vietnam. In this study, we used Sentinel-2 and Landsat-8 to classify seven land cover classes of which three forest types were substratified as undisturbed, low disturbed, and disturbed forests where forest inventory of 90 plots, as ground-truth, was randomly sampled to measure forest tree parameters. A total of 3226 training points were sampled on seven land cover types. The performance of Landsat-8 showed out-of-bag error of 31.6%, overall accuracy of 68%, kappa of 67.5%, while Sentinel-2 showed out-of-bag error of 14.3% and overall accuracy of 85.7% and kappa of 83%. Ten vegetation indices of the better-performed image were extracted to find out (i) the correlation and regression of horizontal and vertical structures of trees and (ii) assess the variation values between ground-truthing plots and training sample plots in three forest types. The result of thettest on vegetation indices showed that six out of ten vegetation indices were significant atp<0.05. Seven vegetation indices had a correlation with the horizontal structure, but four vegetation indices, namely, Enhanced Vegetation Index, Perpendicular Vegetation Index, Difference Vegetation Index, and Transformed Normalized Difference Vegetation Index, had better correlationsr = 0.66, 0.65, 0.65, 0.63 and regression results were ofR2 = 0.44, 0.43, 0.43, and 0.40, respectively. The correlations of tree height werer = 0.46, 0.43, 0.43, and 0.49 and its regressions were ofR2 = 0.21, 0.19, 0.18, and 0.24, respectively. The results show the possibility of using random forest algorithm with Sentinel-2 in forest type classification in line with vegetation indices application.
Boswellia dalzielii-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest
Authors: Adebayo Ismail Abiola , Usman Adamu Ibrahim , Shittu Fatimah Bukola , Ismail Noor Zafirah , Arsad Hasni , Muftaudeen Taoheed Kolawole , Samian Mohammed Razip
Published: September 2020

Background. Acute myeloid leukemia (AML) persists to be a major health problem especially among children as effective chemotherapy to combat the disease is yet to be available.Boswellia dalzieliiis a well-known herb that is traditionally used for treatment and management of many diseases including degenerative diseases. In this study, silver nanoparticles were synthesized from the phytochemicals ofB. dalzieliistem bark aqueous extract. The silver nanoparticles were characterized by carrying out Fourier Transform Infrared (FTIR) spectroscopy, Energy Filtered Scanning Electron Microscopy (FESEM), X-ray diffraction, and Dynamic Light Scattering (DLS) analyses. Antioxidant capacity of the nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the antiproliferative effect of the nanoparticles on Kasumi-1 leukemia cells was investigated using PrestoBlue assay. Flow cytometry analysis was performed to observe the effect of the nanoparticles on the leukemia cell cycle progression.Results. Our findings revealed that the synthesized silver nanoparticles were formed from electrons of the plant phytochemicals which include aromatic compounds, ethers, and alkynes. FESEM analysis revealed that the sizes of the nanoparticles range from 12 nm to 101 nm; however, DLS analysis estimated a larger average size of the nanoparticles (108.3 nm) because it measured the hydrodynamic radii of the nanoparticles. The zeta potential of the nanoparticles was −16 nm, and the XRD pattern of the nanoparticles has distinct peaks at 38.02°, 42.94°, 64.45°, 77.20°, and 81.47°, which is typical of face-centered cubic (fcc) structure of silver. The Trolox Equivalence Antioxidant Capacity (TEAC) of the nanoparticles was estimated to be 300.91 μM Trolox/mg silver nanoparticles. The nanoparticles inhibited Kasumi-1 cell proliferation. The half minimal inhibitory concentrations (IC50s) that inhibited Kasumi-1 cell proliferation are 49.5 μg/ml and 13.25 μg/ml at 48 and 72 hours, respectively. The nanoparticles induced cell cycle arrest in the Kasumi-1 cells at S (5% increase) and G2/M (3% increase) phases.Conclusion. The nanoparticles synthesized from the stem bark extract ofB. dalzieliiinhibit the growth of Kasumi-1 leukemia cells by activating cell cycle arrest; thus, they are potential antileukemic agents.
Effects of Preexisting Psychotropic Medication Use on a Cohort of Patients with Ischemic Stroke Outcome
Authors: Jun-O’Connell Adalia H. , Jayaraman Dilip K. , Henninger Nils , Silver Brian , Moonis Majaz , Rothschild Anthony J.
Published: September 2020

Background. Several studies investigated the use of selective serotonin reuptake inhibitors (SSRI) after ischemic stroke to improve motor recovery. However, little is known about the effects of preexisting psychotropic medication use (PPMU), such as antidepressants, on a long-term ischemic stroke functional disability. Objective. We sought to determine the prevalence of PPMU and whether PPMU relates to the long-term clinical outcome in a cohort of patients presenting with acute ischemic strokes. Methods. We retrospectively analyzed 323 consecutive patients who presented with an acute ischemic stroke in a single institution between January 2015 and December 2017. Baseline characteristics, functional disability as measured by the modified Rankin Scale (mRS), and major adverse cardiovascular complications (MACE) within 365 days were recorded. The comparison groups included a control group of ischemic stroke patients who were not on psychotropic medications before and after the index ischemic stroke and a second group of poststroke psychotropic medication use (PoMU), which consisted of patients started on psychotropic medication during the index admission. Results. The prevalence of PPMU in the studied cohort was 21.4% (69/323). There was a greater proportion of females in the PPMU than in the comparison groups (P<0.001), while vascular risk factors were similar in all groups, except for an increased presence of posterior circulation infarcts in the PPMU (37.4% vs. 18.8%, P<0.001). Among the patients with available 1-year follow-up data (n=246), we noted significantly greater improvement in stroke deficits, measured by National Institute of Health Stroke Scale (NIHSS) between PPMU and PoMU vs. control (3 (0-7) versus 1 (0-4), P=0.041). The 1-year mRS was worse in PPMU and PoMU compared to the control group (2 (IQ 1-3) vs. 2 (IQ 0-3) vs. 1 (IQ 0-2), respectively, P=0.013), but delta mRS reflecting the degree of mRS improvement showed no significant difference between any PMU and control patients (P=0.76). There was no statistically significant difference in MACE. Conclusion. PPMU in ischemic stroke is common; it can be beneficial in ischemic stroke in the long-term clinical outcome and is not associated with increased risks of MACE.
On Characterizations of ∗-Hyperconnected Ideal Topological Spaces
Authors: Boonpok Chawalit
Published: September 2020

In the present paper, some characterizations of ∗-hyperconnected ideal topological spaces are investigated. Moreover, we introduce the notion of S∗-ℐ-hyperconnected ideal topological spaces. Several characterizations of S∗-ℐ-hyperconnected ideal topological spaces are discussed. Furthermore, we introduce and study θ-ℐ-irreducible ideal topological spaces.
Comparatively Evaluating the Role of Herb Pairs Containing Angelicae Sinensis Radix in Xin‐Sheng‐Hua Granule by Withdrawal Analysis
Authors: Pang Han-Qing , Xu Ding-Qiao , Tang Yu-Ping , Zhou Gui-Sheng , Xu Hui-Qin , Jin Yi , Zhu Zhen-Hua , Shi Xu-Qin , Yue Shi-Jun , Chen Yan-Yan , Huang Sheng-Liang , Duan Jin-Ao
Published: September 2020

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin‐Sheng‐Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC‐TQ‐MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC‐TQ‐MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui‐Yimucao) decreased significantly, which could partly explain why herb pair Danggui‐Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula.
Approximating Fixed Points of Operators Satisfying (RCSC) Condition in Banach Spaces
Authors: Abdeljawad Thabet , Ullah Kifayat , Ahmad Junaid , de la Sen Manuel , Khan Junaid
Published: September 2020

Let K be a nonempty subset of a Banach space E. A mapping T:K→K is said to satisfy (RCSC) condition if each a,b∈K, 1/2a−Fa≤a−b⇒Fa−Fb≤1/3a−b+a−Fb+b−Fa. In this paper, we study, under some appropriate conditions, weak and strong convergence for this class of maps through M iterates in uniformly convex Banach space. We also present a new example of mappings with condition (RCSC). We connect M iteration and other well-known processes with this example to show the numerical efficiency of our results. The presented results improve and extend the corresponding results of the literature.
Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk
Authors: Ghoneim Dalia H. , Zhu Jingjing , Zheng Wei , Long Jirong , Murff Harvey J. , Ye Fei , Setiawan Veronica Wendy , Wilkens Lynne R. , Khankari Nikhil K. , Haycock Philip , Antwi Samuel O. , Yang Yaohua , Arslan Alan A. , Beane Freeman Laura E. , Bracci Paige M. , Canzian Federico , Du Mengmeng , Gallinger Steven , Giles Graham G. , Goodman Phyllis J. , Kooperberg Charles , Le Marchand Loïc , Neale Rachel E. , Scelo Ghislaine , Visvanathan Kala , White Emily , Albanes Demetrius , Amiano Pilar , Andreotti Gabriella , Babic Ana , Bamlet William R. , Berndt Sonja I. , Brais Lauren K. , Brennan Paul , Bueno-de-Mesquita Bas , Buring Julie E. , Campbell Peter T. , Rabe Kari G. , Chanock Stephen J. , Duggal Priya , Fuchs Charles S. , Gaziano J. Michael , Goggins Michael G. , Hackert Thilo , Hassan Manal M. , Helzlsouer Kathy J. , Holly Elizabeth A. , Hoover Robert N. , Katske Verena , Kurtz Robert C. , Lee I-Min , Malats Núria , Milne Roger L. , Murphy Neil , Oberg Ann L. , Porta Miquel , Rothman Nathaniel , Sesso Howard D. , Silverman Debra T. , Thompson Ian M. , Wactawski-Wende Jean , Wang Xiaoliang , Wentzensen Nicolas , Yu Herbert , Zeleniuch-Jacquotte Anne , Yu Kai , Wolpin Brian M. , Jacobs Eric J. , Duell Eric J. , Risch Harvey A. , Petersen Gloria M. , Amundadottir Laufey T. , Kraft Peter , Klein Alison P. , Stolzenberg-Solomon Rachel Z. , Shu Xiao-Ou , Wu Lang
Published: September 2020

Background:

Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome.

Methods:

We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data.

Results:

Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex.

Conclusions:

Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk.

Impact:

These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
Short-term CDK4/6 Inhibition Radiosensitizes Estrogen Receptor–Positive Breast Cancers
Authors: Pesch Andrea M. , Hirsh Nicole H. , Chandler Benjamin C. , Michmerhuizen Anna R. , Ritter Cassandra L. , Androsiglio Marlie P. , Wilder-Romans Kari , Liu Meilan , Gersch Christina L. , Larios José M. , Pierce Lori J. , Rae James M. , Speers Corey W.
Published: September 2020

Purpose:

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor–positive (ER+) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand the effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy in multiple preclinical breast cancer models.

Experimental Design:

Transcriptomic and proteomic analyses were used to identify significantly altered pathways after CDK4/6i. Clonogenic assays were used to quantify the radiotherapy enhancement ratio (rER). DNA damage was quantified using γH2AX staining and the neutral comet assay. DNA repair was assessed using RAD51 foci formation and nonhomologous end joining (NHEJ) reporter assays. Orthotopic xenografts were used to assess the efficacy of combination therapy.

Results:

Palbociclib significantly radiosensitized multiple ER+ cell lines at low nanomolar, sub IC50 concentrations (rER: 1.21–1.52) and led to a decrease in the surviving fraction of cells at 2 Gy (P < 0.001). Similar results were observed in ribociclib-treated (rER: 1.08–1.68) and abemaciclib-treated (rER: 1.19–2.05) cells. Combination treatment decreased RAD51 foci formation (P < 0.001), leading to a suppression of homologous recombination activity, but did not affect NHEJ efficiency (P > 0.05). Immortalized breast epithelial cells and cells with acquired resistance to CDK4/6i did not demonstrate radiosensitization (rER: 0.94–1.11) or changes in RAD51 foci. In xenograft models, concurrent palbociclib and radiotherapy led to a significant decrease in tumor growth.

Conclusions:

These studies provide preclinical rationale to test CDK4/6i and radiotherapy in women with locally advanced ER+ breast cancer at high risk for locoregional recurrence.
Long-term Sculpting of the B-cell Repertoire following Cancer Immunotherapy in Patients Treated with Sipuleucel-T
Authors: Zhang Li , Kandadi Harini , Yang Hai , Cham Jason , He Tao , Oh David Y. , Sheikh Nadeem A. , Fong Lawrence
Published: September 2020

Sipuleucel-T is an autologous cellular immunotherapy, administered as three infusions, for metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T induces T- and B-cell responses to prostatic acid phosphatase (PAP), correlating to improved survival. The long-term impact of sipuleucel-T on tumor antigen–specific immunologic memory remains unknown, in particular, B-cell responses, as measured by antigen-specific antibody responses and B-cell receptor (BCR) sequences. To evaluate whether sipuleucel-T could induce long-term immunologic memory, we examined circulating B-cell responses before and after sipuleucel-T treatment in two groups of patients with mCRPC: those who had previously received sipuleucel-T (treated; median, 8.9 years since the previous treatment) versus those who had not (naïve). Before re-treatment, previously treated patients exhibited persistent antibody responses as well as more focused and convergent BCR repertoires with distinct V(D)J gene usage compared with naïve patients. After re-treatment, previously treated patients maintained high-frequency clones and developed more convergent BCRs at earlier time points unlike naïve patients. With the first sipuleucel-T infusion specifically, previously treated patients had less shuffling within the 100 most abundant baseline clones. In contrast, naïve patients exhibited great BCR turnover with a continued influx of new B-cell clones. Social network analysis showed that previously treated patients had more highly organized B-cell repertoires, consistent with greater clonal maturation. Higher treatment-induced BCR clonality correlated with longer survival for naïve patients. These results demonstrated the capacity of sipuleucel-T to induce long-term immune memory and lasting changes to the B-cell repertoire.
Aging of Preleukemic Thymocytes Drives CpG Island Hypermethylation in T-cell Acute Lymphoblastic Leukemia
Authors: Roels Juliette , Thénoz Morgan , Szarzyńska Bronisława , Landfors Mattias , De Coninck Stien , Demoen Lisa , Provez Lien , Kuchmiy Anna , Strubbe Steven , Reunes Lindy , Pieters Tim , Matthijssens Filip , Van Loocke Wouter , Erarslan-Uysal Büşra , Richter-Pechańska Paulina , Declerck Ken , Lammens Tim , De Moerloose Barbara , Deforce Dieter , Van Nieuwerburgh Filip , Cheung Laurence C. , Kotecha Rishi S. , Mansour Marc R. , Ghesquière Bart , Van Camp Guy , Berghe Wim Vanden , Kowalczyk Jerzy R. , Szczepański Tomasz , Davé Utpal P. , Kulozik Andreas E. , Goossens Steven , Curtis David J. , Taghon Tom , Dawidowska Małgorzata , Degerman Sofie , Van Vlierberghe Pieter
Published: September 2020

Cancer cells display DNA hypermethylation at specific CpG islands in comparison with their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T cells and that display a reciprocal association with H3K27me3 binding. In addition, we reveal that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in preleukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent decitabine. Altogether, we provide conceptual evidence for the involvement of a preleukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.

Significance:

We developed a DNA methylation signature that reveals the epigenetic history of thymocytes during T-cell transformation. This human signature was recapitulated by murine self-renewing preleukemic thymocytes that build an age-related CpG island hypermethylation phenotype, providing conceptual evidence for the involvement of a preleukemic thymic phase in human T-cell leukemia.

This article is highlighted in the In This Issue feature, p. 215
Clinical Characteristics of Testicular Torsion and Identification of Predictors of Testicular Salvage in Children: A Retrospective Study in a Single Institution
Authors: Feng Shaoguang , Yang Huajun , Lou Yi , Ru Wei , Wang Aihe , Liu Weiguang
Published: September 2020

Purpose: Testicular torsion (TT) is a serious surgical emergency. Prompt diagnosis and treatment of TT are essential to improve the incidence of salvaged testes. The aim of this study was to evaluate the historical features, physical examination findings, laboratory tests, and ultrasound examinations in children with TT, as well as to identify the predictors of testicular salvage in children. Materials and Methods: We retrospectively reviewed the records of 136 males who presented with TT to our institution. Clinical findings, physical examinations, laboratory data, color Doppler ultrasound findings, operating results, and the results of follow-up were collected and analyzed. Patients with neonatal torsion, negative scrotal exploration, or testicular appendix torsion were excluded. A multivariable logistic regression model was used to identify predictors of testicular salvage. Receiver operator characteristics analyses were performed to determine the probability of a non-salvageable torsed testis based on time and degree of twisting. Results: A total of 136 children with TT were identified. Patients were aged from 1 to 16 years, with a mean age of 9.7 years (median, 12; range, 1–16 years). The peak incidences of TT were found between ages of 12 and 14 years. Acute TT is significantly more common in the winter. Testicular salvage occurred in 49 (36%) cases. Of the 49 cases of testicular salvage, 5 patients developed subsequent testicular atrophy. Cutoff values of 13.5 h and 530 degrees of torsion would provide sensitivities of 96 and 61%, with specificity of 80 and 70%, respectively. Multivariate analysis showed that time to surgery and degree of testicular twist were correlated with the risk of a non-salvageable testis. Conclusions: Testicular salvage can be predicted by the duration of symptoms along with degree of twisting. Early scrotal exploration based on careful physical examination decreases the risk of misdiagnosis of spermatic cord torsion. A certain percentage of children with TT presenting with lower abdominal pain should have their testicles checked to make sure that they do not have torsion, especially those visitors in cold season.
Thyroid Disease and Active Smoking May Be Associated with More Severe Hidradenitis Suppurativa: Data from a Prospective Cross Sectional Single-Center Study
Authors: Liakou Aikaterini I. , Kontochristopoulos Georgios , Marnelakis Ioannis , Tsantes Andreas G. , Papadakis Marios , Alevizou Antigoni , Rotsiamis Nikolaos , Rigopoulos Dimitris
Published: September 2020

Introduction: Hidradenitis suppurativa (HS) is an obscure disease presenting with painful, deep-seated nodules and abscess formation in body areas rich in apocrine glands. Several factors, including thyroid disease and active smoking, have been reported to be associated with HS, but it remains unclear if such associations are related to clinical HS severity. The aim of this prospective cross-sectional study is to investigate the association between active smoking and thyroid disease and HS, as well as to determine if these associations are related to HS severity. Methods: Eligible were all patients seen in our HS outpatient clinic between September 2018 and February 2020. Data regarding demographic characteristics, clinical disease severity, comorbidities, and treatment modalities were registered. Descriptive statistics of demographic and disease characteristics was conducted. In order to evaluate the association between the disease stage and certain variables of interest, ordered logistic regression was performed. Results: A total of 290 patients were included in the study. Of these, 48.9% were males, and 51.1% females. The patients had a mean age of 37.3 years. A total of 42.4% of the patients were at Hurley stage I, 43.1% at stage II, and 14.5% at stage III. According to the IHS4 score system, 30.7% of the patients had mild, 50.3% moderate, and 19.0% severe disease. The median duration of disease was 10 years. Among the patients, 56.5% were active smokers, and 55.5% patients reported that stress triggers the disease’s flares. Univariable analyses demonstrated that among the various covariates, active smoking and thyroid disease were associated with a higher stage of disease. Conclusion: We conclude that thyroid disease and active smoking may be associated with more severe HS.
Impact of Preprocedural Aortic Valve Calcification on Conduction Disturbances after Transfemoral Aortic Valve Replacement
Authors: Stachon Peter , Steinfurt Johannes , van de Loo Tim , Trolese Luca , Faber Thomas , Kaier Klaus , Heidt Timo , Bothe Wolfgang , Krauss Tobias , Wolf Dennis , Duerschmied Daniel , Zehender Manfred , Bamberg Fabian , Bode Christoph , von zur Mühlen Constantin
Published: September 2020

Aim: The present study analyzes in depth the impact of different calcification patterns on disturbances of the conduction system in transcatheter aortic valve replacement (TAVR) patients. Methods and Results: A total of 169 preprocedural TAVR multislice computed tomography scans from consecutive transfemoral (TF) TAVRs performed between 2014 and 2017 using either Edwards SAPIEN or Medtronic Evolut R valves were retrospectively evaluated. The volume, distribution, and orientation of annular and valvular aortic valve calcification were measured and their impact on postoperative conduction disturbances was determined using linear and logistic regression analyses. The total volume of calcification and distribution at the aortic annulus or valve did not influence the conduction system. Oval calcification of the left aortic cusp was independently associated with an elevated risk for an increase in atrioventricular block degree (+0.6, p = 0.03). Moreover, orthogonal calcifications at the level of the aortic annulus were associated with an increased risk for QRS prolongation (+26 ms, p = 0.004) and an increased risk for permanent pacemaker implantation (OR 4.3, p = 0.03) after TF TAVR. This was more pronounced in patients undergoing TF TAVR using a balloon-expandable Edwards SAPIEN 3 valve (QRS +38.195 ms, p < 0.001; OR permanent pacemaker 15.48, p = 0.013). Conclusion: Orthogonal annular calcification confers an increased risk for conduction disturbances after TAVR. This is even more pronounced after implantation of balloon-expandable valves.
Parcellation of the Subthalamic Nucleus in Parkinson’s Disease: A Retrospective Analysis of Atlas- and Diffusion-Based Methods
Authors: Zolal Amir , Polanski Witold H. , Klingelhoefer Lisa , Kitzler Hagen H. , Linn Jennifer , Podlesek Dino , Sitoci-Ficici Kerim Hakan , Reichmann Heinz , Leonhardt Georg Karl , Schackert Gabriele , Sobottka Stephan B.
Published: September 2020

Background: Deep brain stimulation (DBS) is an established method of treatment for Parkinson’s disease (PD). A stimulation sweet spot at the interface between the motor and associative clusters of the subthalamic nucleus (STN) has recently been postulated. The aim of this study was to analyze the available clustering methods for the STN and their correlation to outcome. Methods: This is a retrospective analysis of a group of 20 patients implanted with a DBS device for PD. Atlas-based and diffusion tractography-based parcellation of the STN was performed. The distances of the electrode to the obtained clusters were compared to each other and to outcome parameters, which included levodopa equivalent dose (LED) reduction, Unified Parkinson’s Disease Rating Scale (UPDRS)-III scores, and reduction in scores for items 32 and 36 of the UPDRS-IV. Results: The implanted electrodes were located nearest to the motor clusters of the STN. The following significant associations with postoperative LED reduction were found: (1) distance of the electrode to the motor cluster in the Accolla and DISTAL atlases (p < 0.01) and (2) distance of the electrode to the supplementary motor area cluster (p = 0.02). There was no association with either the UPDRS-III or the UPDRS-IV score. Conclusions: The results of this study suggest the possibility that atlas-based clustering, as well as diffusion tractography-based parcellation, can be useful in estimating the stimulation target (“sweet spot”) for STN-DBS in PD patients. Atlas-based as well as diffusion-based clustering might become a useful tool in DBS trajectory planning.