bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategy of BIM Building Operation and Maintenance Management Based on LV-EG Model
Authors: Guo Xiaojian , Hu Huan
Published: October 2020

BIM technology can make building operation and maintenance (O&M) more efficient. This paper analyzes the evolution game (EG) of the three parties related to the O&M of the building. At the same time, it deduces the diffusion (LV) of the O&M management mode of the market in this condition by finding the evolutionary stable points under different conditions. Through the analysis of relevant conditions, the result of BIM-O&M diffusion is obtained as follows: complete market possession, partial market possession, and exit market three kinds of diffusion results, which provides a reference for the future development of BIM-O&M management in China.
Thymoquinone Protects against Hyperlipidemia‐Induced Cardiac Damage in Low‐Density Lipoprotein Receptor‐Deficient (LDL‐R-/-) Mice via Its Anti‐inflammatory and Antipyroptotic Effects
Authors: Pei Zuo-Wei , Guo Ying , Zhu Huo-Lan , Dong Min , Zhang Qian , Wang Fang
Published: October 2020

Hyperlipidemia is a risk factor for cardiac damage and cardiovascular disease. Increasing evidence has shown that dyslipidemia‐related cardiac damage is associated with lipid accumulation, oxidative stress, and inflammation. Thymoquinone (TQ) is the major constituent of Nigella sativa, commonly known as black seed or black cumin, and is globally used in folk (herbal) medicine for treating and preventing a number of diseases and conditions. Several studies have shown that TQ can protect against cardiac damage. This study is aimed at investigating the possible protective effects of TQ on hyperlipidemia‐induced cardiac damage in low‐density lipoprotein receptor‐deficient (LDL‐R-/-) mice. Eight‐week‐old male LDL‐R-/- mice were randomly divided into normal diet (ND), high‐fat diet (HFD), and HFD and TQ (HFD+TQ) groups and were fed the different diets for eight weeks. Blood samples were obtained from the inferior vena cava in serum tubes and stored at ‐80°C until use. Some cardiac tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the cardiac tissues was snap‐frozen in liquid nitrogen for mRNA preparation or immunoblotting. The levels of metabolism‐related factors, such as total cholesterol (TC), low‐density lipoprotein‐cholesterol (LDL‐c), and high‐sensitivity C‐reactive protein (hs‐CRP), were decreased in the HFD+TQ group compared with those in the HFD group. Periodic acid‐Schiff staining demonstrated that lipid deposition was lower in the HFD+TQ group than in the HFD group. The expression of pyroptosis indicators (NOD‐like receptor 3 (NLRP3), interleukin‐ (IL‐) 1β, IL‐18, and caspase‐1), proinflammatory factors (IL‐6 and tumor necrosis factor alpha (TNF‐α)), and macrophage markers (cluster of differentiation (CD) 68) was significantly downregulated in the HFD+TQ group compared with that in the HFD group. Our results indicate that TQ may serve as a potential therapeutic agent for hyperlipidemia‐induced cardiac damage.
Calculation of Free Energy Consumption in Gene Transcription with Complex Promoter Structure
Authors: Huang Lifang , Liu Peijiang , Wen Kunwen , Yu Jianshe
Published: October 2020

From the viewpoint of thermodynamics, gene transcription necessarily consumes free energy due to nonequilibrium processes. On the other hand, regulatory molecules present on the core promoter of a gene interact often in a dynamic, highly combinatorial, and possibly energy-dependent manner, leading to a complex promoter structure. This raises the question of how gene transcription with general promoter topology consumes free energy. We propose a biophysically intuitive approach to calculate energy consumption (quantified by the production rate of entropy) of a gene transcription process. Then, we show that the numbers of the ON and OFF states of a promoter can reduce energy consumption of the gene system and the Fano factor of mRNA, and in contrast to other regulatory ways, the cooperative binding of transcription factors to DNA sites always reduces energy consumption but amplifies the mRNA noise. While our proposed approach is general, our obtained qualitative results can in turn be used to the inference of complex promoter structure.
Research on the Impact of Marine Environment on ICPT Transmission Efficiency
Authors: Li Da , Gao Wei , Wu Xusheng , Gao Jianxin , Yang Shenqin
Published: October 2020

ICPT is one of the most influential solutions in the field of wireless power transmission, but it is also very susceptible to the working environment. The complicated marine environment has a great influence on the performance of ICPT. In the deep-sea high-pressure environment, due to the piezomagnetic effect, the magnetic core in the coupling structure will suddenly change the permeability, and the coupling coefficient, self-inductance, and other parameters will also change accordingly. At the same time, changes in ocean currents in the ocean will cause the ICPT coils to be misaligned, thereby affecting the magnetic field distribution between the coils and the transmission efficiency of the system. In order to provide theoretical support for optimum design of ICPT system in ocean environment, the influence of core performance changes and ICPT coil misalignment on system transmission efficiency is studied.
Choroidal Structural Changes Assessed with Swept-Source Optical Coherence Tomography after Cataract Surgery in Eyes with Diabetic Retinopathy
Authors: Yao Huiping , Gao Sha , Liu Xiaoqing , Zhou Yufeng , Cheng Yu , Shen Xi
Published: October 2020

Objective. To determine the influence of phacoemulsification on choroidal vasculature in patients with diabetic retinopathy (DR) undergoing cataract surgery using swept-source optical coherence tomography (SS-OCT). Methods. The study was conducted in 23 eyes of 23 cataract patients with mild/moderate nonproliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME) and 23 age-matched controls. Choroidal thickness (CT) and choroidal vascularity index (CVI) were measured at baseline and 1 week, 1 month, and 3 months after surgery. Results. The baseline CVI in the DR group was significantly lower than that in the control group (

P
=
0.001

). CVI in DR patients after surgery significantly increased compared with preoperative values (all

P
<
0.001

for 1 week, 1 month, and 3 months after surgery). Postoperative increase of CVI and CT in the DR group was more than in the control group, and the difference was significant 1 month and 3 months after surgery (all

P
<
0.05

). Conclusion. Patients with mild/moderate NPDR have reduced CVI compared with nondiabetic patients at baseline; diabetic cataract surgery tended to induce more increase in CVI and CT as compared with nondiabetic patients. This trial is registered with NCT04499768.
Experimental Study on Bolt‐Spliced Prefabricated Steel Frame Beams
Authors: He Ran , Zhang Zaihua , Li Jingchao
Published: October 2020

The prefabricated steel structural residence is characterized by modularization and standardization, which meets the requirement of industrial development. The steel frame beam needs to be fabricated in segments and assembled in site due to the limitation of transportation. In practical engineering, the steel frame beams need to be spliced along the beam span. A robust connection between the two steel beam segments is necessary as it will influence the load bearing capacity, stiffness, and stability of the steel frame. In total, 12 specimens were tested to investigate the influence of spliced types, loading patterns, and bolt types on the performance of the steel frame. The observed failure modes, load versus displacement curves, and moment versus rotation angle curves are presented. The test results show that the strength and deformability of bolt‐spliced connections are generally good and similar to those of the prototype beam.
Breast Cancer in the United States: A Cross-Sectional Overview
Authors: Bilani Nadeem , Zabor Emily C. , Elson Leah , Elimimian Elizabeth B. , Nahleh Zeina
Published: October 2020

Introduction. Breast cancer remains the most commonly diagnosed malignancy in women. It encompasses considerable heterogeneity in pathology, patient clinical characteristics, and outcome. This study describes factors associated with overall survival (OS) of breast cancer in an updated national database. Methods. We conducted a retrospective analysis of patients with breast cancer diagnosed between 2004 and 2016 based on the National Cancer Database. Categorical variables were summarized using frequencies/percentages, whereas continuous variables were summarized using the median/interquartile range (IQR). OS was explored using the Kaplan-Meier method. Results. Data from

n
=
2,671,549

patients were analyzed. The median age at diagnosis was 61 years (range 18-90). 75% were non-Hispanic (NH) White; 11% were NH-Black; 4.7% were Hispanic-White; 0.1% were Hispanic-Black; and 3.4% were Asian. Most cases (73%) presented with ductal carcinoma histology; while 15% with lobular carcinoma. Rarer subtypes included epithelial-myoepithelial, fibroepithelial, metaplastic, and mesenchymal tumors. OS was associated with molecular subtype, histologic subtype, and AJCC clinical staging. Survival also correlated with race: a cohort including Asians and Pacific Islanders had the best survival, while Black patients had the worst. Finally, facility type also impacted outcome: patients at academic centers had the best survival, while those at community cancer programs had the worst. Conclusion. This large database provides a recent and comprehensive overview of breast cancer over 12 years. Molecular subtype, histologic subtype, stage, race, and facility type were correlated with OS. In addition to the educational perspective of this overview, significant factors impacting the outcome identified here should be considered in future cancer research on disparities.
Development of Learning Media for the Elderly to Promote Child Health in the Community
Authors: Chaimaha Napalai , Putthinoi Supawadee , Lersilp Suchitporn
Published: October 2020

The purpose of this study was to develop learning media for the elderly to promote child health. The participants consisted of 172 elderly people aged 60 years and older in a suburban village of northern Thailand. This study consisted of a survey questionnaire and focus group discussions and was divided in to two phases: (1) exploring the needs of the elderly in the knowledge of child health and (2) developing learning media, so that the elderly can learn how to promote child health and evaluate its efficiency in the trial process. Results showed that the participants mostly preferred the topic of activities of daily living (ADL) in children. The learning media contributes two major contents: (a) knowledge of child development in five types of ADL performance, brushing, eating, dressing, bathing, and toileting, and (b) methods in teaching ADL skills in children. The digital contents in the learning media were proposed to experts for professional approval. Efficiency of the learning media was evaluated after the trial, when the participants expressed their opinion, and the users perceived that the learning media was effective, motivating, easy to use, and simple in the terms used, as well as appropriate in the sequence of contents and pictures and font, size, and color of the text.
Finite-Time Current Tracking in Boost Converters by Using a Saturated Super-Twisting Algorithm
Authors: Velázquez-Velázquez Juan-Eduardo , Galván-Guerra Rosalba , Ortega-Pérez José-Antonio , Lozano-Hernández Yair , Villafuerte-Segura Raúl
Published: October 2020

The power converters are widely used in several industrial applications where it is necessary to obtain from a fixed voltage another one higher or lower than the original. In this paper, we focus on the DC-DC (direct current) boost converters, where to guarantee the desired voltage, an internal current tracking loop is usually used. However, this tracking cannot be assured in the presence of unknown load changes and external perturbations when traditional controller strategies are implemented. In this paper, an advanced control strategy is proposed to ensure the current tracking using a saturated super-twisting controller on the power converter. The finite-time current tracking of a DC-DC boost converter is assured in the presence of bounded Lipschitz perturbations composed by unknown load changes and exogenous signals. The proposed approach generates a continuous bounded control signal applied to the converter by using a sigma-delta modulator

Σ
Δ
M

. The controller gains are tuned to obtain finite-time stabilization of the tracking error, while the control signal remains bounded. To illustrate the effectiveness of the proposed results, the controller is applied to a physical boost converter using the hardware implemented

Σ
Δ
M

and an STM32 Discovery development card. Besides, the controller is compared with a first-order sliding mode controller showing that for small sample times, the energy of the error signal is reduced.
Utility of Circadian Variability Patterns in Differentiating Origins of Premature Ventricular Complexes
Authors: Chen Mu , Wang Qunshan , Sun Jian , Zhang Peng-Pai , Li Wei , Zhang Rui , Mo Bin-Feng , Chen Tai-Zhong , Wan Juyi , Xu Dong-Zhu , Aonuma Kazutaka , Li Yi-Gang
Published: October 2020

Background. Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. Methods. We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. Results. In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. Conclusions. The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.
Wuqinxi Exercise Improves Hand Dexterity in Patients with Parkinson’s Disease
Authors: Wang Tian , Xiao Guiping , Li Zhenlan , Jie Kuncheng , Shen Mengyue , Jiang Yan , Wang Zhen , Shi Xiangrong , Zhuang Jie
Published: October 2020

Objective. This study was designed to evaluate the effect of Wuqinxi after one session and 12‐week intervention on hand dexterity in patients with Parkinson’s disease (PD). Methods. Forty‐six elderly participants with mild‐to‐moderate PD were randomly assigned to the groups trained with Wuqinxi (n = 23) or stretching (n = 23). All participants practiced 60 min session of either of these exercises, 2 sessions a week for 12 weeks in standing position. The score of Purdue Pegboard Test (PPT) and time for Soda Pop Test (SPT) were performed to assess hand dexterity and motor function along assessing the 39 items of Parkinson’s Disease Questionnaire before and after 12‐week interventions. In addition, the PPT scores were compared before vs. after one session of either of these two exercise modes. Results. Single session with either Wuqinxi or stretching exercise tended to improve PPT scores in PD patients. Furthermore, the improved SPT time was significant (P < 0.01) following 12‐week training interventions with Wuqinxi (−1.32 ± 0.38 sec) or stretching (−0.89 ± 0.16 sec), which showed no group difference (P = 0.734). However, only the participants in Wuqinxi group significantly improved the PPT scores of the dominant hand (+0.61 ± 1.34), both hand (+1.83 ± 3.13) and assemble (+2.04 ± 3.44) performance after 12‐week training intervention. In parallel with improved hand dexterity and motor function, 12‐week Wuqinxi training also significantly improved the patient’s emotional wellbeing. Conclusion. The Wuqinxi intervention could be safely and effectively applied to improve hand dexterity following single‐session exercise or 12‐week training, which were accompanied by improved quality of life in patients with mild‐to‐moderate PD.
Approximation of Fixed Points and Best Proximity Points of Relatively Nonexpansive Mappings
Authors: Abdeljawad Thabet , Ullah Kifayat , Ahmad Junaid , De La Sen Manuel , Ulhaq Azhar
Published: October 2020

In this article, we study the Agarwal iterative process for finding fixed points and best proximity points of relatively nonexpansive mappings. Using the Von Neumann sequence, we establish the convergence result in a Hilbert space framework. We present a new example of relatively nonexpansive mapping and prove that its Agarwal iterative process is more efficient than the Mann and Ishikawa iterative processes.
Leveraging Social Relationship-Based Graph Attention Model for Group Event Recommendation
Authors: Liao Guoqiong , Deng Xiaobin
Published: October 2020

Recently, event-based social networks(EBSN) such as Meetup, Plancast, and Douban have become popular. As users in the networks usually take groups as an unit to participate in events, it is necessary and meaningful to study effective strategies for recommending events to groups. Existing research on group event recommendation either has the problems of data sparse and cold start due to without considering of social relationships in the networks or makes the assumption that the influence weights between any pair of nodes in the user social graph are equal. In this paper, inspired by the graph neural network and attention mechanism, we propose a novel recommendation model named leveraging social relationship-based graph attention model (SRGAM) for group event recommendation. Specifically, we not only construct a user-event interaction graph and an event-user interaction graph, but also build a user-user social graph and an event-event social graph, to alleviate the problems of data sparse and cold start. In addition, by using a graph attention neural network to learn graph data, we can calculate the influence weight of each node in the graph, thereby generating more reasonable user latent vectors and event latent vectors. Furthermore, we use an attention mechanism to fuse multiple user vectors in a group, so as to generate a high-level group latent vector for rating prediction. Extensive experiments on real-world Meetup datasets demonstrate the effectiveness of the proposed model.
Liming and Fertilization on the Growth of Eucalyptus benthamii and Eucalyptus dunnii in Brazil
Authors: Pereira da Rosa Diego , Navroski Marcio Carlos , De Oliveira Pereira Mariane , Borsoi Geedre Adriano , Nascimento Bruno , De Andrade Ramon Silveira , Moraes Carolina
Published: October 2020

The use of mineral fertilizers has shown substantial productivity gains for the vast majority of Eucalyptus forests. The objective of the present work is to evaluate the response of Eucalyptus benthamii and Eucalyptus dunnii at 48 months of age, to different doses of limestone, soluble NPK, and natural phosphates. The experiment was conducted in a plantation located in South Brazil. The experimental design was a randomized block with three replications, and the treatments consisted of combinations of doses of natural phosphate (NP) (0, 400, 600, and 800 kg ha−1 of Gafsa reactive NP P2O5), limestone (0, 3, 5, 6, and 10 Mg ha−1 of dolomitic limestone), and mineral fertilizer–NPK (0, 100, 133, and 167 kg ha−1 of mixed mineral fertilizer 6-30-6). Height and diameter measurements were taken after 48 months. There was a positive response with the increase of NPK fertilizer dose, and the dose where the highest averages were obtained was 167 kg ha−1. The doses of NP had significant effects on the increase of the variables up to 600 kg ha−1, also the averages decreased with the increase of the dosage. For liming, positive results were observed from its absence to the maximum dose, justifying its use in minimum dose in order to supply the necessary amounts of Ca and Mg in the soil. The use of NPK, natural phosphate, and limestone is recommended, causing an increase in the growth of both species of Eucalyptus studied.
Quantitative Determination of Marker Compounds and Fingerprint Analysis of the Seeds of Vernonia anthelmintica
Authors: Maimaiti Zulipiya , Turak Ablajan , Ma Qing Ling , Liu Geyu , Aisa Haji Akbar
Published: October 2020

In traditional Chinese medicine, the seeds of Vernonia anthelmintica (L.) Willd. have been widely used for treatment of cough, skin diseases, diarrhea, fever, schistosomiasis, amoebic dysentery, and gastrointestinal problems, especially in the treatment of vitiligo for thousands of years in China. In this study, an effective, reliable, and accurate high-performance liquid chromatography diode array detector (HPLC-DAD) method was developed for quantitative analysis of 3 marker bioactive compounds and chemical fingerprint of the seeds of V. anthelmintica. Data corresponding to common peak areas and HPLC chromatographic fingerprints were analyzed by exploratory hierarchical cluster analysis (HCA) and principal component analysis (PCA) to extract information of the most significant variables contributing to characterization and classification of the analyzed samples. Based on variety and origin, the high-performance thin layer chromatography (HPTLC) method validated the chemical fingerprint results used to screen the in vitro antioxidant activity of V. anthelmintica. The results show that the developed method has potential application values for the quality consistency evaluation and identification of similar instant V. anthelmintica samples. When considered collectively, this research results provide a scientific basis for the improvement of standardization and specification of V. anthelmintica medicinal materials and provide a pathway for the development and utilization of references for the identification of V. anthelmintica herbs.
Numerical Simulation of Fire Resistance Test for Gas Turbine Component Using Coupled CFD/FEM Approach
Authors: Mokhov K. Y. , Kudryavtsev A. Y. , Voronkov O. V. , Voronina E. B. , Sukhov S. V. , Ryabov A. A. , Zhurenkov Y. N. , Soloveva A. V. , Grigoriev A. V.
Published: October 2020

The article presents the implementation of CFD/FEM approach for real oil tank of the gas turbine engine for the purposes of prediction of the component behavior under the local impact of a burner jet. The model takes into account heat and mass transfer problems as well as strength problems that are solved using a one way coupled fluid-structure interaction method. Results of the blind test simulation are compared and show good agreement with available experimental data.
Mimic Encryption Box for Network Multimedia Data Security
Authors: Zhou Xiabing , Li Bin , Qi Yanrong , Dong Wanying
Published: October 2020

With the rapid development of the Internet, the security of network multimedia data has attracted increasingly more attention. The moving target defense (MTD) and cyber mimic defense (CMD) approaches provide a new way to solve this problem. To enhance the security of network multimedia data, this paper proposes a mimic encryption box for network multimedia data security. The mimic encryption box can directly access the network where the multimedia device is located, automatically complete the negotiation, provide safe and convenient encryption services, and effectively prevent network attacks. According to the principles of dynamization, diversification, and randomization, the mimic encryption box uses a reconfigurable encryption algorithm to encrypt network data and uses IP address hopping, port number hopping, protocol camouflage, and network channel change to increase the attack threshold. Second, the mimic encryption box has a built-in pseudorandom number generator and key management system, which can generate an initial random key and update the key with the hash value of the data packet to achieve “one packet, one key.” Finally, through the cooperation of the ARM and the FPGA, an access control list can be used to filter illegal data and monitor the working status of the system in real time. If an abnormality is found, the feedback reconstruction mechanism is used to “clean” the FPGA to make it work normally again. The experimental results and analysis show that the mimic encryption box designed in this paper has high network encryption performance and can effectively prevent data leakage. At the same time, it provides a mimic security defense mechanism at multiple levels, which can effectively resist a variety of network attacks and has high security.
Exophiala Keratitis following Descemet Stripping Automated Endothelial Keratoplasty
Authors: Marta Ana , Costa Paula , Lopes Virgínia , Neves Miguel Mesquita , Gomes Miguel , Oliveira Luís
Published: October 2020

Purpose. To report a case with Exophiala spp. keratitis in a Portuguese patient. Methods. A case report with deep corneal brown-pigmented infiltrates that developed 2 months after a Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) for pseudophakic bullous keratopathy. Results. Diagnosis was established by positive direct examination and cultures from the surgically obtained corneal button. Slit-lamp images and anterior segment optical coherence tomography (AS-OCT) scans were obtained. Conclusion. This is the first described case of fungal keratitis caused by Exophiala spp. in Portugal and, to our knowledge, the first case following DSAEK in the literature.
Assessing the Response of Satellite Solar-Induced Chlorophyll Fluorescence and NDVI to Impacts of Heat Waves on Winter Wheat in the North China Plain
Authors: Xian Chenjie , He Li , He Zhengwei , Xue Dongjian , Li Zhe
Published: October 2020

Global warming has increased the chance of concurrent extreme climate events (weather or climate events that are rare within their statistical reference distributions in a particular place, such as heat waves, floods, and droughts). Crops grow best within specific temperature intervals, and excessive heat is detrimental to the physiological processes of crops and eventually affects yield levels. Analysing historical changes in concurrent extreme high temperatures is critical to preparing for and mitigating the negative effects of climatic change. The North China Plain (NCP) is the most important wheat production area in China. In this study, the spatiotemporal variations in temperature and heat wave trends in the NCP were analysed. Furthermore, we examined the potential of solar-induced chlorophyll fluorescence (SIF) to capture the influence of heat wave impacts on wheat crops in the NCP by comparing satellite remote sensing data of SIF and normalized difference vegetation index (NDVI) and validated ground-based yield data. The results indicate that temperatures and the number of heat wave days in the study region all show increasing trends, especially daily minimum temperature, which has increased by 0.38°C per decade for the past 30 years. Spatially, the southern NCP has suffered greater increasing-temperature trends and more heat wave days than the northern region. Regarding the response of SIF and NDVI to heat waves, SIF can better capture wheat yield decline due to heat waves compared to NDVI; thus, the SIF result indicated more sensitivity to heat waves compared to NDVI.
A Rare CD4−CD8+ Adult T-Cell Leukemia/Lymphoma with Unique Molecular Mutations: A Case Report with Literature Review
Authors: Choudhuri Jui , Geiser Roberts Leah , Zhang Yan , Wang Yanhua , Fang Yanan
Published: October 2020

Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell neoplasm caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1). Most ATLL cases are CD4-positive and CD8-negative. Though rare, there are a few dual negative (CD4−CD8−), dual positive (CD4+CD8+), and CD4−CD8+ cases reported in literature. ATLL is associated with HTLV-1 infection, but HTLV-1 alone cannot cause the malignant transformation of infected T cells. Additional genetic and/or epigenetic events are required for the development of the disease. Here, we report an unusual CD4−CD8+ATLL in a 76-year-old male with a unique molecular genetic profile. Molecular studies revealed alterations in 10 genes. Three of them are predicted to be pathogenic by the computational models, including the frameshift change in ZFHX4 and missense mutations in RHOA and POT1. The specific mutations of POT1 (c.281A > G; p.Q94R), RHOA (c.47G > A; p.C16Y), and ZFHX4 (c.2871delC; p.F958Sfs

∗

31) have never been previously reported in ATLL to the best of our knowledge. The clinical significance of other genetic alterations is unknown. Further research is warranted to correlate this patient’s molecular findings with other ATLL cases. Correlation specifically with other cases of CD8+ ATLL could prove to be useful in understanding the pathogenesis of this rare variant of an already rare form of leukemia/lymphoma.
Study on Key Cost Drivers of Prefabricated Buildings Based on System Dynamics
Authors: Lou Na , Guo Jingjuan
Published: October 2020

The prefabricated building as a major initiative has been put forward by China in recent years to promote the transformation and upgrading of the construction industry, but its rapid development also faces high cost constraints. Therefore, it is necessary and urgent to study the key cost drivers and cost control paths of prefabricated buildings. Most of the current research focuses on the construction cost of prefabricated building as a static object. This article, on the other hand, regards the construction cost of prefabricated building as a dynamic formation process and conducts systematic research from product systems, technical systems, construction processes, and management modes. The influence factors of prefabricated building cost are defined and screened with the help of HSM and previous research results. A cause‐and‐effect model and cost control model of prefabricated building cost driver are established. Based on the model test of the actual project, the cost generation of prefabricated buildings is simulated. Through sensitivity analysis, key cost drivers of prefabricated building are identified and ranked as degree of design standardization, unit price, prefabrication rate, information technology level, transportation mode, labor level, machinery level, transportation distance, etc. Accordingly, corresponding strategies are proposed for the cost control of prefabricated buildings.
Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma
Authors: Apostolidis John , Sayyed Ayman , Darweesh Mohammed , Kaloyannidis Panayotis , Al Hashmi Hani
Published: October 2020

Cancer cells escape immune recognition by exploiting the programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) immune checkpoint axis. Immune checkpoint inhibitors that target PD-1/PD-L1 unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. Following the cancer paradigm, preliminary results of clinical trials in lymphoma have demonstrated that immune checkpoint inhibitors induce remarkable responses in specific subtypes, most notably classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, while in other subtypes, the results vary considerably, from promising to disappointing. Lymphomas that respond to immune checkpoint inhibitors tend to exhibit tumor cells that reside in a T-cell-rich immune microenvironment and display constitutive transcriptional upregulation of genes that facilitate innate immune resistance, such as structural variations of the PD-L1 locus, collectively referred to as T-cell-inflamed lymphomas, while those lacking such characteristics are referred to as noninflamed lymphomas. This distinction is not necessarily a sine qua non of response to immune checkpoint inhibitors, but rather a framework to move the field forward with a more rational approach. In this article, we provide insights on our current understanding of the biological mechanisms of immune checkpoint evasion in specific subtypes of B-cell and T-cell non-Hodgkin lymphomas and summarize the clinical experience of using inhibitors that target immune checkpoints in these subtypes. We also discuss the phenomenon of hyperprogression in T-cell lymphomas, related to the use of such inhibitors when T cells themselves are the target cells, and consider future approaches to refine clinical trials with immune checkpoint inhibitors in non-Hodgkin lymphomas.
Cytotoxic, Antioxidant, and Metabolic Enzyme Inhibitory Activities of Euphorbia cyparissias Extracts
Authors: Alonazi Mona , Horchani Habib , Alwhibi Mona , Ben Bacha Abir
Published: October 2020

Plants of the Euphorbia genus present a wide range of therapeutic applications. This study is aimed at investigating new antidigestive enzyme agents from Euphorbia cyparissias through inhibition of lipid and carbohydrate absorption, to evaluate their potential applications for the treatment of metabolic syndrome. Lipase, phospholipase, protease, α-amylase, β-glucosidase, and xanthine oxidase activities under treatment with aqueous and ethanolic extracts of Euphorbia cyparissias were observed to evaluate the inhibitory effect of these extracts, as well as their antioxidant and cytotoxic effects. Results showed that ethanolic and aqueous extracts exhibited important inhibitory activity in a concentration-related manner on digestive enzymes, which is more effective than the commercial drugs used as controls. Results also showed that, out of the two extracts tested, the ethanolic extract presented the most promising results in inhibiting the activities of all digestive enzymes used. Moreover, the two extracts displayed a higher reducing power than that of the positive control used. The obtained results, together with previous reports in the literature, strongly suggest that Euphorbia cyparissias extracts may be natural inhibitors of the digestive enzymes and thus a potential new drug for metabolic syndrome treatment.
Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity
Authors: Gandhi Shipra , Pandey Manu R. , Attwood Kristopher , Ji Wenyan , Witkiewicz Agnieszka K. , Knudsen Erik S. , Allen Cheryl , Tario Joseph D. , Wallace Paul K. , Cedeno Carlos D. , Levis Maria , Stack Suzanne , Funchain Pauline , Drabick Joseph J. , Bucsek Mark J. , Puzanov Igor , Mohammadpour Hemn , Repasky Elizabeth A. , Ernstoff Marc S.
Published: October 2020

Purpose:

Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti–PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma.

Patients and Methods:

A 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective was to determine the recommended phase II dose (RP2D). Additional objectives included safety, antitumor activity, and biomarker analyses. Responders were defined as patients with complete or partial response per immune-modified RECIST at 6 months.

Results:

Nine patients with metastatic melanoma received increasing doses of propranolol in cohorts of 10, 20, and 30 mg twice a day. No dose-limiting toxicities were observed. Most common treatment-related adverse events (TRAEs) were rash, fatigue, and vitiligo, observed in 44% patients. One patient developed two grade ≥3 TRAEs. Objective response rate was 78%. While no significant changes in treatment-associated biomarkers were observed, an increase in IFNγ and a decrease in IL6 was noted in responders.

Conclusions:

Combination of propranolol with pembrolizumab in treatment-naïve metastatic melanoma is safe and shows very promising activity. Propranolol 30 mg twice a day was selected as RP2D in addition to pembrolizumab based on safety, tolerability, and preliminary antitumor activity.
Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast–Driven Nutritional Support and Immunosuppression
Authors: Francescone Ralph , Barbosa Vendramini-Costa Débora , Franco-Barraza Janusz , Wagner Jessica , Muir Alexander , Lau Allison N. , Gabitova Linara , Pazina Tatiana , Gupta Sapna , Luong Tiffany , Rollins Dustin , Malik Ruchi , Thapa Roshan J. , Restifo Diana , Zhou Yan , Cai Kathy Q. , Hensley Harvey H. , Tan Yinfei , Kruger Warren D. , Devarajan Karthik , Balachandran Siddharth , Klein-Szanto Andres J. , Wang Huamin , El-Deiry Wafik S. , Vander Heiden Matthew G. , Peri Suraj , Campbell Kerry S. , Astsaturov Igor , Cukierman Edna
Published: October 2020

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate and lacks effective therapeutics. Therefore, it is of paramount importance to identify new targets. Using multiplex data from patient tissue, three-dimensional coculturing in vitro assays, and orthotopic murine models, we identified Netrin G1 (NetG1) as a promoter of PDAC tumorigenesis. We found that NetG1+ cancer-associated fibroblasts (CAF) support PDAC survival, through a NetG1-mediated effect on glutamate/glutamine metabolism. Also, NetG1+ CAFs are intrinsically immunosuppressive and inhibit natural killer cell–mediated killing of tumor cells. These protumor functions are controlled by a signaling circuit downstream of NetG1, which is comprised of AKT/4E-BP1, p38/FRA1, vesicular glutamate transporter 1, and glutamine synthetase. Finally, blocking NetG1 with a neutralizing antibody stunts in vivo tumorigenesis, suggesting NetG1 as potential target in PDAC.

Significance:

This study demonstrates the feasibility of targeting a fibroblastic protein, NetG1, which can limit PDAC tumorigenesis in vivo by reverting the protumorigenic properties of CAFs. Moreover, inhibition of metabolic proteins in CAFs altered their immunosuppressive capacity, linking metabolism with immunomodulatory function.

See related commentary by Sherman, p. 230.

This article is highlighted in the In This Issue feature, p. 211
Lenvatinib-Transarterial Chemoembolization Sequential Therapy as an Effective Treatment at Progression during Lenvatinib Therapy for Advanced Hepatocellular Carcinoma
Authors: Kawamura Yusuke , Kobayashi Masahiro , Shindoh Junichi , Kobayashi Yuta , Okubo Satoshi , Tominaga Licht , Kajiwara Akira , Kasuya Kayoko , Iritani Soichi , Fujiyama Shunichiro , Hosaka Tetsuya , Saitoh Satoshi , Sezaki Hitomi , Akuta Norio , Suzuki Fumitaka , Suzuki Yoshiyuki , Ikeda Kenji , Arase Yasuji , Hashimoto Masaji , Kozuka Tokuyo , Kumada Hiromitsu
Published: October 2020

Background: The aims of this study were to evaluate the efficacy of additional treatment, especially lenvatinib-transarterial chemoembolization (TACE) sequential therapy, for unresectable hepatocellular carcinoma (HCC). Methods: Consecutive 56 patients who underwent lenvatinib treatment were reviewed. Oncological aggressiveness of tumor was estimated using a dynamic CT enhancement pattern classification, and clinical impact of subsequent treatment was investigated through analysis of progression-free survival (PFS), post-progression survival (PPS), and multivariate analysis of potential confounders for survival after progression during lenvatinib therapy. Results: Heterogeneous enhancement patterns (Type-3 and -4), which are reportedly associated with higher oncological aggressiveness of HCC, were associated with better objective response to lenvatinib compared to homogeneous enhancement pattern (Type-2) (86 and 85% vs. 53% in modified Response Evaluation Criteria in Solid Tumors), resulting in similar PFS (p = 0.313). Because of significantly worse PPS, overall survival of Type-4 tumor was poor compared to Type-2 or -3 tumors (p = 0.009). However, subgroup of patients who achieved subsequent treatment showed significantly better PPS, regardless of CT enhancement pattern. Multivariate analysis confirmed that use of lenvatinib-TACE sequential treatment after progression during lenvatinib therapy was associated with better PPS (hazard ratio [HR], 0.08; 95% CI, 0.01–0.71; p = 0.023), while Type-4 enhancement pattern was correlated with worse PPS (HR, 2.92; 95% CI, 1.06–8.05; p = 0.039). Conclusion: Oncological aggressiveness of HCC estimated by CT enhancement pattern was predictive of PPS after progression during lenvatinib. Successful subsequent treatment with lenvatinib-TACE sequential therapy may offer survival benefit regardless of CT enhancement pattern of HCC.
Getting the Most Out of Your Zombie: Abdominal Sensors and Neural Manipulations Help Jewel Wasps Find the Roach’s Weak Spot
Authors: Catania Kenneth C.
Published: October 2020

The parasitoid emerald jewel wasp (Ampulex compressa) subdues the American cockroach (Periplaneta americana) with a sting to the 1st thoracic ganglion, followed by a sting to the roach’s brain, causing long-term pacification. The wasp then leads the cockroach to a hole where it lays an egg on the roach middle leg before barricading the entrance and departing. Although many aspects of the wasp’s initial attack have been investigated, few studies have detailed the egg-laying process and the subsequent fate of the larvae. Here I show that larval survival depends on precise egg positioning on the cockroach by the female wasp. Ablation of sensory hairs on the wasp’s abdomen resulted in mislaid eggs, which seldom survived. In addition, the cockroach femur may block the oviposition site. The wasp contended with this challenge with a newly discovered suite of stings, 3 directed into the 2nd thoracic ganglion which resulted in extension of the femur, thus exposing the oviposition site and removing a potential barrier to the wasp’s successful reproduction. When the femur was glued in place, the wasp stung the cockroach over 100 times, in an apparent fixed action pattern triggered by the obscured oviposition target. These findings highlight the importance of proper egg placement by the wasp, and reveal sensors and new neural manipulations that facilitate the process.
Comprehensive Investigation of Circulating Biomarkers and Their Causal Role in Atherosclerosis-Related Risk Factors and Clinical Events
Authors: Zanetti Daniela , Gustafsson Stefan , Assimes Themistocles L. , Ingelsson Erik
Published: October 2020

Background:

Circulating biomarkers have been previously associated with atherosclerosis-related risk factors, but the nature of these associations is incompletely understood.

Methods:

We performed multivariable-adjusted regressions and 2-sample Mendelian randomization analyses to assess observational and causal associations of 27 circulating biomarkers with 7 cardiovascular traits in up to 451 933 participants of the UK Biobank.

Results:

After multiple-testing correction (alpha=1.3×10−4), we found a total of 15, 9, 21, 22, 26, 24, and 26 biomarkers strongly associated with coronary artery disease, ischemic stroke, atrial fibrillation, type 2 diabetes, systolic blood pressure, body mass index, and waist-to-hip ratio; respectively. The Mendelian randomization analyses confirmed strong evidence of previously suggested causal associations for several glucose- and lipid-related biomarkers with type 2 diabetes and coronary artery disease. Particularly interesting findings included a protective role of IGF-1 (insulin-like growth factor 1) in systolic blood pressure, and the strong causal association of lipoprotein(a) in coronary artery disease development (β, −0.13; per SD change in exposure and outcome and odds ratio, 1.28;P=2.6×10−4andP=7.4×10−35, respectively). In addition, our results indicated a causal role of increased ALT (alanine aminotransferase) in the development of type 2 diabetes and hypertension (odds ratio, 1.59 and β, 0.06, per SD change in exposure and outcome;P=4.8×10−11andP=6.0×10−5). Our results suggest that it is unlikely that CRP (C-reactive protein) and vitamin D play causal roles of any meaningful magnitude in development of cardiometabolic disease.

Conclusions:

We confirmed and extended known associations and reported several novel causal associations providing important insights about the cause of these diseases, which can help accelerate new prevention strategies.
Software for Interactive and Collaborative Creation in the Classroom and Beyond: An Overview of the Soundcool Software
Authors: Scarani Stefano , Muñoz Adolfo , Serquera Jaime , Sastre Jorge , Dannenberg Roger B.
Published: October 2020

This article presents a free framework for collaborative creation of interactive and experimental computer music called Soundcool. It is designed to fill a gap between rigid ready-to-use applications and flexible programming languages. The system offers easy-to-use elements for generating and processing sound, much like ready-made applications, but it enables flexible configuration and control, more like programming languages. The system runs on personal computers with an option for control via smartphones, tablets, and other devices using the Open Sound Control (OSC) protocol. Originally developed to support a new music curriculum, Soundcool is being used at different educational institutions in Spain, Portugal, Italy, and Romania through EU-funded Erasmus+ projects. In this article, we present our system and showcase three different scenarios as examples of how our system meets its objectives as an easy-to-use, versatile, and creative tool.
The Role of Nonlinear Dynamics in Musicians' Interactions with Digital and Acoustic Musical Instruments
Authors: Mudd Tom , Holland Simon , Mulholland Paul
Published: October 2020

Nonlinear dynamic processes are fundamental to the behavior of acoustic musical instruments, as is well explored in the case of sound production. Such processes may have profound and under-explored implications for how musicians interact with instruments, however. Although nonlinear dynamic processes are ubiquitous in acoustic instruments, they are present in digital musical tools only if explicitly implemented. Thus, an important resource with potentially major effects on how musicians interact with acoustic instruments is typically absent in the way musicians interact with digital instruments. Twenty-four interviews with free-improvising musicians were conducted to explore the role that nonlinear dynamics play in the participants' musical practices and to understand how such processes can afford distinctive methods of creative exploration. Thematic analysis of the interview data is used to demonstrate the potential for nonlinear dynamic processes to provide repeatable, learnable, controllable, and explorable interactions, and to establish a vocabulary for exploring nonlinear dynamic interactions. Two related approaches to engaging with nonlinear dynamic behaviors are elaborated: edge-like interaction, which involves the creative use of critical thresholds; and deep exploration, which involves exploring the virtually unlimited subtleties of a small control region. The elaboration of these approaches provides an important bridge that connects the concrete descriptions of interaction in musical practices, on the one hand, to the more-abstract mathematical formulation of nonlinear dynamic systems, on the other.