bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantic‐Based Sports Music Information Fusion and Retrieval in Wireless Sensor Networks
Authors: Yu Qiaolin , Liu Xiaofei , Li Sihui , Hou Lei , Zhu Chengdong , Lin Ying
Published: September 2021

The wireless sensor network has developed rapidly in recent years. It is formed by the intersection of multiple disciplines. It integrates embedded technology, sensor technology, distributed technology, wireless communication technology, and modern networks. It is a brand new information acquisition platform. The characteristics of sensor networks determine that information fusion technology is a hot spot in the research of wireless sensor networks. Information fusion can achieve high performance and low cost in terms of energy and communication, which is of great significance to the research of sensor networks. This paper is aimed at studying the semantic‐based sports music information fusion and retrieval research in wireless sensor networks. WSNs may face various attacks including eavesdropping attacks, replay attacks, Sybil attacks, and DOS attacks. Therefore, they are designing sensor network solutions. It is necessary to consider the network security issues. This article summarizes and analyzes the existing WSN security data fusion solutions for this issue and compares them by classification. This paper proposes methods and theories such as the spatial correlation detection algorithm, CBA algorithm, FTD algorithm, and DFWD algorithm, which enriches the research of information fusion and retrieval in wireless sensor networks, which is of exploratory significance, and it also establishes this problem. The model was studied, and reliable data was obtained. The experimental results of this paper show that when using these methods to diagnose faults in WSN, the correct rate of model diagnosis is higher than 77%.
Automatic Quantification of Atherosclerosis in Contrast-Enhanced MicroCT Scans of Mouse Aortas Ex Vivo
Authors: Stadelmann Vincent A. , Boyd Gabrielle , Guillot Martin , Bienvenu Jean-Guy , Glaus Charles , Varela Aurore
Published: September 2021

Objective. While microCT evaluation of atherosclerotic lesions in mice has been formally validated, existing image processing methods remain undisclosed. We aimed to develop and validate a reproducible image processing workflow based on phosphotungstic acid-enhanced microCT scans for the volumetric quantification of atherosclerotic lesions in entire mouse aortas. Approach and Results. 42 WT and 42 apolipoprotein E knockout mouse aortas were scanned. The walls, lumen, and plaque objects were segmented using dual-threshold algorithms. Aortic and plaque volumes were computed by voxel counting and lesion surface by triangulation. The results were validated against manual and histological evaluations. Knockout mice had a significant increase in plaque volume compared to wild types with a plaque to aorta volume ratio of 0.3%, 2.8%, and 9.8% at weeks 13, 18, and 26, respectively. Automatic segmentation correlated with manual (

r

2

≥
0.89

;

p
<
.001

) and histological evaluations (

r

2

>
0.96

;

p
<
.001

). Conclusions. The semiautomatic workflow enabled rapid quantification of atherosclerotic plaques in mice with minimal manual work.
The Role of Staking and Pruning Methods on Yield and Profitability of Tomato (Solanum lycopersicum L.) Production in the Guinea Savanna Zone of Ghana
Authors: Lamptey S. , Koomson E.
Published: September 2021

Tomato is one of the most widely consumed and produced vegetables in Ghana. The low yield of tomatoes in Ghana has resulted in huge importation of the produce from neighboring countries. Good agronomic practices are among the key strategies involved in increasing the yield of horticultural produce. This study seeks to evaluate the response of staking and pruning on tomato fruit yield, quality, and cost of production. To achieve this, a field experiment was conducted to investigate the effect of staking and pruning methods on fruit yield and profitability of tomato (Solanum lycopersicum L.) produced in the northern region of Ghana. Treatments were applied in a randomized complete block design with three replications. Treatments were no pruning + no staking (control), single pole staking (SPS), wire trellis (WT), one-stem pruning (1SP), one-stem pruning + single pole staking (1SP + SPS), one-stem pruning + wire trellis (1SP + WT), two-stem pruning (2SP), two-stem pruning + single pole staking (2SP + SPS), and two-stem pruning + wire trellis (2SP + WT). Results showed that 2SP + WT increased fruit diameter, fruit length, and marketable fruit weight by 52%, 32%, and 69%, respectively, compared to the control. The maximum number and weight of marketable fruits obtained from 2SP + WT increased total fruit yield by 76% compared to the control. In all, the performance of the treatments in terms of yield was in the following order: 2SP + WT > 1SP + WT > SPS > WT > 2SP + SPS > 1SP > 2SP > control. Though 2SP + WT increased production cost by 42%, it greatly increased yield by 69% which resulted in 83% net profit compared to the control. Thus, 2SP + WT could be tested on-farm for possible adoption to increase tomato yield, quality, and profit.
Artemisinin Reverses Glucocorticoid‐Induced Injury in Bone Marrow‐Derived Mesenchymal Stem Cells through Regulation of ERK1/2‐CREB Signaling Pathway
Authors: Fang Jiankang , Silva Marta , Lin Ruohong , Zhou Wenshu , Chen Yitan , Zheng Wenhua
Published: September 2021

Glucocorticoids are the most common cause of secondary osteoporosis, which affects both women (pre‐ and postmenopausal) and men. In cases of prolonged treatment, glucocorticoids promote the loss and inactivation of the differentiational function of bone marrow mesenchymal stromal cells (BMSCs), risking the development of skeletal system diseases such as osteoporosis. This study reports for the first time the protective effect of the antimalarial artemisinin against glucocorticoid‐induced insults on primary cultured rat BMSCs. At relatively low concentrations, artemisinin treatment improved BMSC survival by promoting a decline of reactive oxygen species (ROS) production that correlated with the decrease of caspase‐3 activation, LDH release, mitochondrial membrane potential (Δψm) loss, and apoptosis induced by dexamethasone (DEXA). In addition, artemisinin improved the osteogenic differentiation of DEXA‐damaged cells. DEXA inhibited extracellular‐signal‐regulated kinase 1/2 (ERK1/2) and cAMP response element binding protein (CREB) phosphorylation, and artemisinin treatment promoted their activation in a concentration‐dependent manner. PD98059, the specific inhibitor of the ERK1/2 pathway, blocked ERK1/2 phosphorylation and artemisinin protection. Similarly, siCREB attenuated the protective effect of artemisinin, strongly suggesting the involvement of the ERK1/2‐CREB pathway in the protective action of artemisinin against DEXA‐induced damage in BMSCs. In addition, we found that the expression of antiapoptotic protein B‐cell lymphoma 2 protein (BCL‐2) was also upregulated by artemisinin. These studies demonstrate the therapeutic potential of artemisinin in the survival improvement of BMSCs exposed to glucocorticoid‐induced apoptosis and suggest that artemisinin‐mediated protection may occur via the activation of ERK1/2‐CREB signaling pathway.
[Retracted] Epi‐Gene: An R‐Package for Easy Pan‐Genome Analysis
Authors: Awan Furqan , Ali Muhammad Muddassir , Hamid Muhammad , Awan Muhammad Huzair , Mushtaq Muhammad Hassan , Kalsoom Saeeda , Ijaz Muhammad , Mehmood Khalid , Liu Yongjie
Published: September 2021

The main aim of this study was to develop a set of functions that can analyze the genomic data with less time consumption and memory. Epi‐gene is presented as a solution to large sequence file handling and computational time problems. It uses less time and less programming skills in order to work with a large number of genomes. In the current study, some features of the Epi‐gene R‐package were described and illustrated by using a dataset of the 14 Aeromonas hydrophila genomes. The joining, relabeling, and conversion functions were also included in this package to handle the FASTA formatted sequences. To calculate the subsets of core genes, accessory genes, and unique genes, various Epi‐gene functions have been used. Heat maps and phylogenetic genome trees were also constructed. This whole procedure was completed in less than 30 minutes. This package can only work on Windows operating systems. Different functions from other packages such as dplyr and ggtree were also used that were available in R computing environment.
Research on Damping Engagement Methodology in Dynamic Analysis of Isolated Structure
Authors: Han Miao , Jiang Jinwei , Du Hongkai , Feng Sijia
Published: September 2021

Damping has a significant influence on the calculation of structural seismic response. In this paper, we compare the commonly used viscous damping (Rayleigh damping (RD) and Caughey damping (CD)) in combination with the isolated structure test. To avoid the arbitrariness of choosing two reference vibration frequencies in constructing RD, all the combinations of the first several vibration frequencies were calculated. Because the material characteristics of the isolation layer and the superstructure are significantly different and the deformation of the isolation layer is large, we construct nonproportional damping according to these two kinds of damping and make a comparative analysis. Analyzing experimental data, we can obtain the optimal frequency combination of RD and nonproportional damping during dynamic analysis of the isolated structure, the priority order of choosing damping models. For the calculation of RD, the 1st modal frequency of the structure should be included, and the 2nd and 3rd modal frequencies of the nonisolated structure are proposed to calculate the nonproportional damping based on Rayleigh damping (NP‐RD) for the three‐story frame structure in this paper. RD and nonproportional damping based on Caughey damping (NP‐CD) are firstly recommended to be used in the calculation of the isolated structure, followed by NP‐RD and then CD.
Study on Road-Crossing Violations among Young Pedestrians Based on the Theory of Planned Behavior
Authors: Xiao Yun , Liu Yang , Liang Zijun
Published: September 2021

Young pedestrians have a high rate of traffic violations and are vulnerable. In this study, theory of planned behavior (TPB) questionnaires were collected from a sample of 395 young pedestrians. Reliability analysis demonstrated that the TPB questionnaire was effective and credible. An analysis model was established based on the TPB. The motivations for traffic violation behaviors among young pedestrians on intersections were studied from the perspective of social psychology. The results revealed that the most common violation behavior of young pedestrians was crossing on yellow light (29.7%). Male young pedestrians reported the higher intention of violating regulations. Behavioral attitude (0.14), subjective norm (0.17), and perceived behavioral control (0.12) all affected young pedestrians’ behavioral intentions. Relatives and friends played a positive role in mitigating young pedestrians’ intentions to commit violations at intersections. Perceived behavior control had the weakest influence on young pedestrians’ intentions to violate regulations. Behavioral intention (0.31) was the most direct and significant predictor of behavior. The results of the study are valuable for the identification of the causes of traffic violations among young pedestrians, and they can serve as a reference for the implementation of effective interventions.
Three Mediating Pathways of Anxiety and Security in the Relationship between Coping Style and Disordered Eating Behaviors among Chinese Female College Students
Authors: Han Wenyue , Zheng Zheng , Zhang Ning
Published: September 2021

Background. According to previous studies, eating disorders and disordered eating behaviors are associated with coping style, anxiety, and sense of security. However, the specific mechanism between them has not been elucidated. The purpose of this study was to explore whether anxiety and sense of security play mediating roles in coping style and disordered eating behaviors among Chinese female college students. Method. Six hundred and ninety-one female college students (

mean
 
age
=
19.36

;

SD
=
1.06

) completed the Simple Coping Style Questionnaire, the Eating Disorder Inventory, the Security Questionnaire, the Hospital Anxiety and Depression Scale, and a brief demographic survey. The percentage bootstrap method of deviation correction was conducted to determine the mediating effect of anxiety and sense of security on coping style and disordered eating behaviors. Results. Coping style had direct and indirect effects on disordered eating behaviors. Anxiety and sense of security were not only independent mediators in the relationship between coping style and disordered eating behaviors but also chain mediators. Conclusions. The results of the current study provide preliminary evidence that preventive interventions targeting anxiety and sense of security may be feasible for young women who develop disordered eating behaviors due to stress in their lives.
A Node Location Algorithm Based on Improved Whale Optimization in Wireless Sensor Networks
Authors: Gou Pingzhang , He Bo , Yu Zhaoyang
Published: September 2021

With the popularity of swarm intelligence algorithms, the positioning of nodes to be located in wireless sensor networks (WSNs) has received more and more attention. To overcome the disadvantage of large ranging error and low positioning accuracy caused by the positioning algorithm of the received signal strength indication (RSSI) ranging model, we use the RSSI modified by Gaussian to reduce the distance measurement error and introduce an improved whale optimization algorithm to optimize the location of the nodes to be positioned to improve the positioning accuracy. The experimental results show that the improved whale algorithm performs better than the whale optimization algorithm and other swarm intelligence algorithms under 20 different types of benchmark function tests. The positioning accuracy of the proposed location algorithm is better than that of the original RSSI algorithm, the hybrid exponential and polynomial particle swarm optimization (HPSO) positioning algorithms, the whale optimization, and the quasiaffine transformation evolutionary (WOA‐QT) positioning algorithm. It can be concluded that the cluster intelligence algorithm has better advantages than the original RSSI in WSN node positioning, and the improved algorithm in this paper has more advantages than several other cluster intelligence algorithms, which can effectively solve the positioning requirements in practical applications.
Using Distribution Alliance to Signal the Seller’s Service Quality in Online Retailing Platforms
Authors: Yan Yufei , Ye Zuoliang , Gong Xiaoxiao
Published: September 2021

Signal plays a significant role in the online retailing market, especially where the service quality of sellers is unobservable. In the current study, a game‐theoretical model was formulated to help examine whether the new delivery service called distribution alliance in the electronic market can serve as a superior signal in revealing online seller’s service quality. Our results showed that the certification accuracy and the application fee are closely related to the signaling effect of the distribution alliance. Specifically, we found a concrete analytical boundary where a certain high level of certification accuracy is required to guarantee the existence of market equilibrium, and a corresponding application fee can convoy the signal’s effectiveness. In addition, the potential extensions and limitations of this research were also discussed.
Adaptive Fractional‐Order Nonsingular Fast Terminal Sliding Mode Control for Manipulators
Authors: Zhang Xin , Shi Ran
Published: September 2021

When the manipulator system is subject to unknown disturbance, in order to improve the tracking accuracy of the manipulator, this paper designs a fractional‐order nonsingular fast terminal sliding mode (FONFTSM) controller. The controller is divided into three parts. First of all, in order to improve the performance of the sliding stage, this paper designs a FONFTSM surface. By introducing a fractional‐order operator, the convergence speed and accuracy of the system state are effectively improved. Secondly, in view of the problems of large chattering and slow convergence speed in the reaching stage, this paper designs a variable exponential power‐reaching law (VEPRL), which has the ability to change the exponential coefficients according to the system state adaptively. At the same time, an adaptive law is designed to adjust the coefficients of the reaching law adaptively, which enhances the robustness of the control system. Finally, a disturbance observer is used to estimate the unknown external disturbance in real time so as to perform feedforward compensation for the control system, which effectively improves the accuracy of the manipulator control system. The stability of the manipulator control system is proved by the Lyapunov function. Simultaneously, the controller designed in this paper is compared with different controllers, which proves that the controller designed in this paper has strong robustness, high control accuracy, and fast convergence speed.
Dynamic Radiation Effects Induced by Short‐Pulsed GeV U‐Ion Beams in Graphite and h‐BN Targets
Authors: Bolz Philipp , Drechsel Philipp , Prosvetov Alexey , Simon Pascal , Trautmann Christina , Tomut Marilena
Published: September 2021

Targets of isotropic graphite and hexagonal boron nitride were exposed to short pulses of uranium ions with ∼1 GeV kinetic energy. The deposited power density of ∼3 MW/cm³ generates thermal stress in the samples leading to pressure waves. The velocity of the respective motion of the target surface was measured by laser Doppler vibrometry. The bending modes are identified as the dominant components in the velocity signal recorded as a function of time. With accumulated radiation damage, the bending mode frequency shifts towards higher values. Based on this shift, Young’s modulus of irradiated isotropic graphite is determined by comparison with ANSYS simulations. The increase of Young’s modulus up to 3 times the pristine value for the highest accumulated fluence of 3 × 1013 ions/cm2 is attributed to the beam‐induced microstructural evolution into a disordered structure similar to glassy carbon. Young’s modulus values deduced from microindentation measurements are similar, confirming the validity of the method. Beam‐induced stress waves remain in the elastic regime, and no large‐scale damage can be observed in graphite. Hexagonal boron nitride shows lower radiation resistance. Circular cracks are generated already at low fluences, risking material failure when applied in high‐dose environment.
The Effects of Tormentic Acid and Extracts from Callistemon citrinus on Candida albicans and Candida tropicalis Growth and Inhibition of Ergosterol Biosynthesis in Candida albicans
Authors: Bvumbi Chido , Chi Godloves Fru , Stevens Marc Y. , Mombeshora Molly , Mukanganyama Stanley
Published: September 2021

Candida albicans and Candida tropicalis are the leading causes of human fungal infections worldwide. There is an increase in resistance of Candida pathogens to existing antifungal drugs leading to a need to find new sources of antifungal agents. Tormentic acid has been isolated from different plants including Callistemon citrinus and has been found to possess antimicrobial properties, including antifungal activity. The study aimed to determine the effects of tormentic and extracts from C. citrinus on C. albicans and C. tropicalis and a possible mode of action. The extracts and tormentic acid were screened for antifungal activity using the broth microdilution method. The growth of both species was inhibited by the extracts, and C. albicans was more susceptible to the extract compared to C. tropicalis. The growth of C. albicans was inhibited by 80% at 100 μg/ml of both the DCM: methanol extract and the ethanol: water extract. Tormentic acid reduced the growth of C. albicans by 72% at 100 μg/ml. The effects of the extracts and tormentic acid on ergosterol content in C. albicans were determined using a UV/Vis scanning spectrophotometer. At concentrations of tormentic acid of 25 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml, the content of ergosterol was decreased by 22%, 36%, 48%, and 78%, respectively. Similarly, the DCM: methanol extract at 100 μg/ml and 200 μg/ml decreased the content by 78% and 88%, respectively. A dose-dependent decrease in ergosterol content was observed in cells exposed to miconazole with a 25 μg/ml concentration causing a 100% decrease in ergosterol content. Therefore, tormentic acid inhibits the synthesis of ergosterol in C. albicans. Modifications of the structure of tormentic acid to increase its antifungal potency may be explored in further studies.
Intestinal Organoids in Colitis Research: Focusing on Variability and Cryopreservation
Authors: zur Bruegge Talke F. , Liese Andrea , Donath Sören , Kalies Stefan , Kosanke Maike , Dittrich-Breiholz Oliver , Czech Sandra , Bauer Verena N. , Bleich André , Buettner Manuela
Published: September 2021

In recent years, stem cell-derived organoids have become a cell culture standard that is widely used for studying various scientific issues that were previously investigated through animal experiments and using common tumor cell lines. After their initial hype, concerns regarding their standardization have been raised. Here, we aim to provide some insights into our experience in standardizing murine colonic epithelial organoids, which we use as a replacement method for research on inflammatory bowel disease. Considering good scientific practice, we examined various factors that might challenge the design and outcome of experiments using these organoids. First, to analyze the impact of antibiotics/antimycotics, we performed kinetic experiments using ZellShield® and measured the gene expression levels of the tight junction markers Ocln, Zo-1, and Cldn4, the proliferation marker Ki67, and the proinflammatory cytokine Tnfα. Because we found no differences between cultivations with and without ZellShield®, we then performed infection experiments using the probiotic Escherichia coli Nissle 1917 as an already established model setup to analyze the impact of technical, interexperimental, and biologic replicates. We demonstrate that interexperimental differences pose the greatest challenge for reproducibility and explain our strategies for addressing these differences. Additionally, we conducted infection experiments using freshly isolated and cryopreserved/thawed organoids and found that cryopreservation influenced the experimental outcome during early passages. Formerly cryopreserved colonoids exhibited a premature appearance and a higher proinflammatory response to bacterial stimulation. Therefore, we recommend analyzing the growth characteristics and reliability of cryopreserved organoids before to their use in experiments together with conducting several independent experiments under standardized conditions. Taken together, our findings demonstrate that organoid culture, if standardized, constitutes a good tool for reducing the need for animal experiments and might further improve our understanding of, for example, the role of epithelial cells in inflammatory bowel disease development.
Modeling the Spatial Correlations among Energy Consumption, Economic Growth, and the Ecological Environment
Authors: Zhao Feng , Sun Yi , Zhang Jie , Sun Pingping
Published: September 2021

To clarify whether there is a spatial correlation problem among China’s provincial energy consumption, economic growth, and ecological environment, this paper adopts the panel data of 31 provinces in China from 2008 to 2019 and uses a spatial data analysis method. This work studies economic growth and the spatial distribution pattern of the ecological environment, as well as the spatial effects of its energy consumption and economic growth on the ecological environment. Moreover, the spatial autocorrelation model, spatial-temporal transition method, and generalized moment estimation method are adopted to conduct empirical analysis on the research object. The results show that (1) there are spatial correlations among energy consumption, economic growth, and the ecological environment in China’s provinces, and there are obviously different agglomeration areas in spatial distribution; (2) energy consumption, economic growth, and the ecological environment level show different growth trends, and the differences between different provinces in provincial units are shrinking; and (3) regarding energy consumption, the spatial impact of economic growth on the ecological environment is obvious, and there are obvious “path dependence” characteristics in the spatial distribution and positive correlations. Finally, this paper puts forward research conclusions and relevant suggestions on the basis of empirical analysis.
Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation
Authors: Wang Canhong , Peng Deqian , Liu Yangyang , Wu Yulan , Guo Peng , Wei Jianhe
Published: September 2021

Background. Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. Methods. Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days’ pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. Results. Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. Conclusions. These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.
Occupational Difference in Association of Poor Sleep Quality and Metabolic Syndrome: Differences between Workers and Employees
Authors: Hashemipour Sima , Yazdi Zohreh , Ghorbani Azam
Published: September 2021

Background. Regarding insufficient data about interaction of job in association of sleep quality with metabolic syndrome (MS), this study has been designed to evaluate this association in workers and employees. Methods. This cross-sectional study was conducted on 448 municipal staff (employee group:

N
=
295

; worker group:

N
=
153

) referring for periodic examinations. The relationship between sleep quality and MS and their relevant components was investigated in both groups. Results. In the worker group, poor sleep quality was independently associated with the risk of MS by 3.04 times (

P
<
0.01

). Among the components of metabolic syndrome, hypertriglyceridemia was associated with a greater number of sleep disorder components. There was no association between metabolic syndrome and sleep quality in the employee group. Conclusion. Poor sleep quality exerts different effects on metabolic complications in employees and workers.
Traditional Chinese Medicine for Postoperative Care following Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis
Authors: Chang Hokyung , Kim Hyungsuk , Kim Koh-Woon , Cho Jae-Heung , Song Mi-Yeon , Chung Won-Seok
Published: September 2021

Objectives. This review verifies the clinical effects of traditional Chinese medicine (TCM) combined with conventional rehabilitation after anterior cruciate ligament reconstruction (ACLR). Methods. MEDLINE/PubMed, EMBASE, CENTRAL, JMAS, CNKI, and seven Korean databases were searched using predetermined strategies. The risk of bias was assessed using Cochrane Collaboration’s tool and a meta-analysis was conducted accordingly. Results. Nineteen randomized controlled trials involving 1283 participants were included in this systematic review and meta-analysis. The TCM treatment group showed more significant improvements in pain (MD −0.74, 95% CI [−0.93, −0.54]; I2 = 89%), range of motion (ROM) (SMD 1.19, 95% CI [0.78, 1.59]; I2 = 78%), and knee swelling (SMD −1.72, 95% CI [−2.38, −1.07]; I2 = 76%). The Lysholm score of the TCM treatment group significantly improved (MD 5.62, 95% CI [3.93, 7.32]; I2 = 84%) relative to the control group. The IKDC subjective score (MD 3.40, 95% CI [−0.61, 7.41]; I2 = 97%) and the hospital for special surgery (HSS) score did not improve initially (MD 6.79, 95% CI [−1.27, 14.86]; I2 = 97%) but did so during the subgroup analysis. TCM showed a long-term effect on the IKDC subjective score (MD −0.51, 95% CI [−1.69, 0.67]; I2 = 30%). A longer treatment period of 12 weeks showed more improvement (MD 5.96, 95% CI [0.69, 11.22]; I2 95%). Conclusion. TCM can be used as an adjuvant therapy to conventional rehabilitation for relieving pain, improving ROM and oedema, and facilitating better function of the knee joint after ACLR. However, this recommendation should be cautiously applied in clinical practice owing to the low quality of the included studies.
An Analytical Solution for the Vibration and Far‐Field Sound Radiation Analysis of Finite, Semisubmerged Cylindrical Shells
Authors: Guo Wenjie , Yang Zhou , Han Yueyang
Published: September 2021

The vibration response and far‐field sound radiation of a semisubmerged, finite cylindrical shell with low‐frequency excitation are studied. The solution to this problem can be divided into two steps. The first step is to apply the wave propagation approach to determine the vibration response of the cylindrical shell. In the cylindrical coordinate system, the Flügge shell equations and Laplace equation are used to describe the cylindrical shell and surrounding fluid so that the vibration responses of the shell can be addressed analytically. The fluid free surface effect is taken into account by applying the sine series to force the velocity potential on the free surface to be zero. Furthermore, compared with the FEM (the finite element method), the present method is not only reliable but also effective. In the second step, the far‐field sound radiation is solved by the Fourier transform technique and the stationary phase method in accordance with the vibration responses of the shell from the previous step. The boundary element method is applied to validate the reliability of the acoustical radiation calculation. The circumferential directivity of far‐field sound pressure is discussed, and it is found that the maximum value of the sound pressure always appears directly under the structure when the driving frequencies are relatively low. Besides, in consideration of simplicity and less computation effort, the present method can be used for the rapid prediction of the vibration and far‐field sound pressure of a semisubmerged cylindrical shell with low‐frequency excitation.
Therapeutic Potential of Chemically Modified, Synthetic, Triplex Peptide Nucleic Acid–Based Oncomir Inhibitors for Cancer Therapy
Authors: Dhuri Karishma , Gaddam Ravinder Reddy , Vikram Ajit , Slack Frank J. , Bahal Raman
Published: September 2021

miRNA-155 (miR-155) is overexpressed in various types of lymphomas and leukemias, suggesting that targeting miR-155 could be a potential platform for the development of precision medicine. Here, we tested the anticancer activity of novel, chemically modified, triplex peptide nucleic acid (PNA)–based antimiRs compared with the current state-of-the-art conventional full-length antimiRs. Next-generation modified PNAs that bound miR-155 by Watson–Crick and Hoogsteen domains possessed superior therapeutic efficacy in vivo and ex vivo compared with conventional full-length anti–miR-155. The efficacy of anti–miR-155 targeting in multiple lymphoma cell lines was comprehensively corroborated by gene expression, Western blot analysis, and cell viability–based functional studies. Finally, preclinical testing in vivo in xenograft mouse models containing lymphoma cell lines demonstrated that treatment with the miR-155-targeting next-generation antimiR resulted in a significant decrease in miR-155 expression, followed by reduced tumor growth. These findings support the effective therapeutic application of chemically modified triplex PNAs to target miR-155 to treat lymphoma. Overall, the present proof-of-concept study further implicates the potential for next-generation triplex gamma PNAs to target other miRNAs for treating cancer.

Significance:

This study demonstrates the utility of novel oncomiR inhibitors as cancer therapeutics, providing a new approach for targeting miRNAs and other noncoding RNAs.
Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures
Authors: Katzke Verena A. , Le Cornet Charlotte , Mahfouz Rayaan , Brauer Bianca , Johnson Theron , Canzian Federico , Rebours Vinciane , Boutron-Ruault Marie-Christine , Severi Gianluca , Schulze Matthias B. , Olsen Anja , Tjønneland Anne , Overvad Kim , Crous-Bou Marta , Molina-Montes Esther , Amiano Pilar , Huerta José María , Ardanaz Eva , Perez-Cornago Aurora , Masala Giovanna , Pala Valeria , Tumino Rosario , Sacerdote Carlotta , Panico Salvatore , Bueno-de-Mesquita Bas , Vermeulen Roel , Sund Malin , Franklin Oskar , Christakoudi Sofia , Dossus Laure , Weiderpass Elisabete , Olek Sven , Kaaks Rudolf
Published: September 2021

Background:

Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing.

Methods:

We conducted a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale.

Results:

Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up.

Conclusions:

These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease.

Impact:

We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development.

See related commentary by Michaud and Kelsey, p. 2176
Is Hodgkin Lymphoma Associated with Hepatitis B and C Viruses? A Systematic Review and Meta-analysis
Authors: Mullen Callum J.R. , Volesky Karena D. , Greenwald Zoë R. , El-Zein Mariam , Franco Eduardo L.
Published: September 2021

Background:

Apart from the Epstein–Barr virus (EBV), the etiology of the hematologic malignancy Hodgkin lymphoma (HL) is not well defined. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with some lymphoproliferative diseases with similarities to HL.

Methods:

We performed a systematic review and meta-analysis, by searching Embase, MEDLINE, and Web of Science databases on March 9, 2021, for studies reporting a measure of association for HBV and HL or HCV and HL. We calculated pooled relative risks (RR) and their 95% confidence intervals (CI).

Results:

Pooling nine HBV studies with 1,762 HL cases yielded an RR of 1.39 (95% CI, 1.00–1.94) and pooling 15 HCV studies with 4,837 HL cases resulted in an RR of 1.09 (95% CI, 0.88–1.35). Meta-analyzing by study design, hepatitis detection method, and region revealed two subgroups with statistically significant associations—HCV studies that used hospital-based controls and/or were conducted in the West Pacific. No included study assessed age or EBV tumor status in relation to HL.

Conclusions:

Although we did not find an association between HBV or HCV and HL, research assessing the impact of age and EBV tumor status was lacking.

Impact:

The effect of HBV or HCV infection in the development of HL remains unclear.
Precision Dosing of Targeted Therapies Is Ready for Prime Time
Authors: Groenland Stefanie L. , Verheijen Remy B. , Joerger Markus , Mathijssen Ron H.J. , Sparreboom Alex , Beijnen Jos H. , Beumer Jan H. , Steeghs Neeltje , Huitema Alwin D.R.
Published: September 2021

Fixed dosing of oral targeted therapies is inadequate in the era of precision medicine. Personalized dosing, based on pharmacokinetic (PK) exposure, known as therapeutic drug monitoring (TDM), is rational and supported by increasing evidence. The purpose of this perspective is to discuss whether randomized studies are needed to confirm the clinical value of precision dosing in oncology. PK-based dose adjustments are routinely made for many drugs and are recommended by health authorities, for example, for patients with renal impairment or for drug–drug interaction management strategies. Personalized dosing simply extrapolates this paradigm from selected patient populations to each individual patient with suboptimal exposure, irrespective of the underlying cause. If it has been demonstrated that exposure is related to a relevant clinical outcome, such as efficacy or toxicity, and that exposure can be optimized by PK-guided dosing, it could be logically assumed that PK-guided dosing would result in better treatment outcomes without the need for randomized confirmatory trials. We propose a path forward to demonstrate the clinical relevance of individualized dosing of molecularly-targeted anticancer drugs.
Whole-body PET Imaging of T-cell Response to Glioblastoma
Authors: Nobashi Tomomi W. , Mayer Aaron T. , Xiao Zunyu , Chan Carmel T. , Chaney Aisling M. , James Michelle L. , Gambhir Sanjiv S.
Published: September 2021

Purpose:

Immunotherapy is a promising approach for many oncological malignancies, including glioblastoma, however, there are currently no available tools or biomarkers to accurately assess whole-body immune responses in patients with glioblastoma treated with immunotherapy. Here, the utility of OX40, a costimulatory molecule mainly expressed on activated effector T cells known to play an important role in eliminating cancer cells, was evaluated as a PET imaging biomarker to quantify and track response to immunotherapy.

Experimental Design:

A subcutaneous vaccination approach of CpG oligodeoxynucleotide, OX40 mAb, and tumor lysate at a remote site in a murine orthotopic glioma model was developed to induce activation of T cells distantly while monitoring their distribution in stimulated lymphoid organs with respect to observed therapeutic effects. To detect OX40-positive T cells, we utilized our in-house–developed 89Zr-DFO-OX40 mAb and in vivo PET/CT imaging.

Results:

ImmunoPET with 89Zr-DFO-OX40 mAb revealed strong OX40-positive responses with high specificity, not only in the nearest lymph node from vaccinated area (mean, 20.8%ID/cc) but also in the spleen (16.7%ID/cc) and the tumor draining lymph node (11.4%ID/cc). When the tumor was small (<106 p/sec/cm2/sr in bioluminescence imaging), a high number of responders and percentage shrinkage in tumor signal was indicated after only a single cycle of vaccination.

Conclusions:

The results highlight the promise of clinically translating cancer vaccination as a potential glioma therapy, as well as the benefits of monitoring efficacy of these treatments using immunoPET imaging of T-cell activation.
First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: September 2021

Purpose:

A novel, selective, next-generation transforming growth factor beta (TGFβ) receptor type-1 small molecule inhibitor, LY3200882, demonstrated promising preclinical data. This first-in-human trial evaluated safety, tolerability, recommended phase II dose (RP2D), pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of LY3200882 as monotherapy or with other anticancer agents in patients with advanced cancer.

Patients and Methods:

This phase I multicenter study of oral LY3200882 (NCT02937272) comprised dose escalation, monotherapy expansion in grade 4 glioma, and combination therapy in solid tumors (LY3200882 and PD-L1 inhibitor LY3300054), pancreatic cancer (LY3200882, gemcitabine, and nab-paclitaxel), and head and neck squamous cell cancer (LY3200882, cisplatin, and radiation).

Results:

Overall, 139 patients with advanced cancer were treated. The majority (93.5%) of patients experienced ≥1 treatment-emergent adverse events (TEAE), with 39.6% LY3200882-related. Grade 3 LY3200882-related toxicities were only observed in combination therapy arms. One patient in the pancreatic cancer arm experienced cardiovascular toxicity. The LY3200882 monotherapy RP2Ds were established in two schedules: 50 mg twice a day 2-weeks-on/2-weeks-off and 35 mg twice a day 3-weeks-on/1-week-off. Four patients with grade 4 glioma had durable Revised Assessment in Neuro Oncology (RANO) partial responses (PR) with LY3200882 monotherapy (n = 3) or LY3200882-LY3300054 combination therapy (n = 1). In treatment-naïve patients with advanced pancreatic cancer, 6 of 12 patients achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 PR and 3 of 12 patients demonstrated stable disease, for an overall 75% disease-control rate with the combination of LY3200882, gemcitabine, and nab-paclitaxel.

Conclusions:

LY3200882 as monotherapy and combination therapy was safe and well tolerated with preliminary antitumor activity observed in pancreatic cancer. Further studies to evaluate the efficacy of LY3200882 with gemcitabine and nab-paclitaxel in advanced pancreatic cancer are warranted.
Mesenchymal Lineage Heterogeneity Underlies Nonredundant Functions of Pancreatic Cancer–Associated Fibroblasts
Authors: Helms Erin J. , Berry Mark W. , Chaw R. Crystal , DuFort Christopher C. , Sun Duanchen , Onate M. Kathrina , Oon Chet , Bhattacharyya Sohinee , Sanford-Crane Hannah , Horton Wesley , Finan Jennifer M. , Sattler Ariana , Makar Rosemary , Dawson David W. , Xia Zheng , Hingorani Sunil R. , Sherman Mara H.
Published: September 2021

Cancer-associated fibroblast (CAF) heterogeneity is increasingly appreciated, but the origins and functions of distinct CAF subtypes remain poorly understood. The abundant and transcriptionally diverse CAF population in pancreatic ductal adenocarcinoma (PDAC) is thought to arise from a common cell of origin, pancreatic stellate cells (PSC), with diversification resulting from cytokine and growth factor gradients within the tumor microenvironment. Here we analyzed the differentiation and function of PSCs during tumor progression in vivo. Contrary to expectations, we found that PSCs give rise to a numerically minor subset of PDAC CAFs. Targeted ablation of PSC-derived CAFs within their host tissue revealed nonredundant functions for this defined CAF population in shaping the PDAC microenvironment, including production of specific extracellular matrix components and tissue stiffness regulation. Together, these findings link stromal evolution from distinct cells of origin to transcriptional heterogeneity among PDAC CAFs and demonstrate unique functions for CAFs of a defined cellular origin.

Significance:

By tracking and ablating a specific CAF population, we find that a numerically minor CAF subtype from a defined cell of origin plays unique roles in establishing the pancreatic tumor microenvironment. Together with prior studies, this work suggests that mesenchymal lineage heterogeneity and signaling gradients diversify PDAC CAFs.

See related commentary by Cukierman, p. 296.

This article is highlighted in the In This Issue feature, p. 275
Choroidal Effusion Mimicking Uveal Melanoma: A Novel Presentation of Idiopathic Systemic Capillary Leak Syndrome
Authors: Brewington Beatrice Y. , Kondapalli Srinivas , Kothari Shaili S. , Parikh Samir V. , Cebulla Colleen M.
Published: September 2021

Background: Idiopathic systemic capillary leak syndrome (ISCLS, also known as Clarkson’s disease) is a rare medical condition characterized by episodes of capillary endothelial cell dysfunction with leakage of fluid into the interstitial space resulting in severe hypotension, hemoconcentration, hypoalbuminemia, and generalized edema. Each episode can result in multiorgan failure due to systemic hypoperfusion. Case Presentation: We report a case of uveal effusion, mimicking uveal melanoma, associated with ISCLS following viral infection. A 74-year-old white male was evaluated in our ocular tumor clinic for a large intraocular mass in the right eye concerning for choroidal melanoma. We completed a review of the literature and list clinical recommendations for these cases. ISCLS, although rare, was a significant diagnostic consideration in this patient. Due to the high mortality rate of this condition, accurate diagnosis and prompt treatment was critical. We hypothesize that the mechanism of choroidal effusion development was due to reduced oncotic pressure from rapid decrease in serum albumin. Increased permeability of choroidal capillaries may be an additional mechanism leading to uveal effusion. Conclusion: With treatment, the patient had complete resolution of his choroidal effusion with no recurrence of his ISCLS. Further research should be considered on the role of viral infections in the pathogenesis of ISCLS.
Chloroma of the Bladder: A Case Report of Leukemia Progression Presenting as Hematuria
Authors: Pearson Laurie K. , Hamal Ruchi , Yu Sanhong , Miller Kenneth B. , Mensah Felix
Published: September 2021

Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myelogenous leukemia (AML). The mass is composed of primitive myeloid cells that can occur in a variety of organs, most commonly the skin, lymph nodes, GI tract, bone, breast, and CNS. Involvement of the genitourinary tract is rare. Consensus on treatment of MS has not been established, but management typically involves systemic therapy, such as chemotherapy or allogeneic hematopoietic stem cell transplant as well as palliative local therapies such as radiation or surgery. Outcomes of MS using novel AML therapies, such as BCL-2 inhibitors or IDH inhibitors, remain undescribed. We describe a rare case of a 70-year-old man presenting with MS of the urinary bladder complicating known secondary AML (RUNX1 and IDH2 mutated). Prior to development of bladder MS, the patient had received decitabine, enasidenib, and venetoclax. Following diagnosis, he was treated with cytarabine and venetoclax. To our knowledge, this is the first case of bladder MS treated with a BCL-2 inhibitor.