bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Social Media Data to Analyse Issue Engagement During the 2017 German Federal Election
Authors: Meier Florian , Bazo Alexander , Elsweiler David
Published: October 2021

A fundamental tenet of democracy is that political parties present policy alternatives, such that the public can participate in the decision-making process. Parties, however, strategically control public discussion by emphasising topics that they believe will highlight their strengths in voters’ minds. Political strategy has been studied for decades, mostly by manually annotating and analysing party statements, press coverage, or TV ads. Here we build on recent work in the areas of computational social science and eDemocracy, which studied these concepts computationally with social media. We operationalize
issue engagement
and related political science theories to measure and quantify politicians’ communication behavior using more than 366k Tweets posted by over 1,000 prominent German politicians in the 2017 election year. To this end, we first identify issues in posted Tweets by utilising a hashtag-based approach well known in the literature. This method allows several prominent issues featuring in the political debate on Twitter that year to be identified. We show that different political parties engage to a larger or lesser extent with these issues. The findings reveal differing social media strategies by parties located at different sides of the political left-right scale, in terms of which issues they engage with, how confrontational they are and how their strategies evolve in the lead-up to the election. Whereas previous work has analysed the general public’s use of Twitter or politicians’ communication in terms of cross-party polarisation, this is the first study of political science theories, relating to issue engagement, using politicians’ social media data.
Molecular Pathology of Laminopathies
Authors: Shin Ji-Yeon , Worman Howard J.
Published: October 2021

The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding protein components of the lamina and these other nuclear envelope substructures. Mutations in the single gene encoding lamin A and C, which are expressed in most differentiated somatic cells, cause diseases affecting striated muscle, adipose tissue, peripheral nerve, and multiple systems with features of accelerated aging. Mutations in genes encoding other nuclear envelope proteins also cause an array of diseases that selectively affect different tissues or organs. In some instances, the molecular and cellular consequences of laminopathy-causing mutations are known. However, even when these are understood, mechanisms explaining specific tissue or organ pathology remain enigmatic. Current mechanistic hypotheses focus on how alterations in the nuclear envelope may affect gene expression, including via the regulation of signaling pathways, or cellular mechanics, including responses to mechanical stress.
Ideal alveolar gas defined by modal gas exchange in ventilation-perfusion distributions
Authors: Peyton Philip J.
Published: October 2021

The three-compartment model of lung ventilation-perfusion mismatch postulates definitive alveolar deadspace and "ideal gas" lung compartments, but these are in fact widely different for gases of different blood solubility. Physiologically realistic distributions of ventilation, perfusion and gas exchange instead suggest an individual "ideal" ventilation-perfusion ratio for every gas, where its alveolar-capillary uptake or elimination rate is maximal (modal). For carbon dioxide this "ideal" partial pressure is the mean of the arterial and end-tidal partial pressures.
Influencing Factors of Rock Electrical Signal Analysis Based on Artificial Intelligence
Authors: He Fei , Shen Jiabei , Tang Zhi , Qi Xiaomeiao , Li Haoran
Published: October 2021

To get the generation mechanism and influence factors of the coal-rock electrical signal, it provides a reference for coal-rock electric signal prediction and dynamic disaster. Firstly, the law of charge energy relation is deduced by using the universal or functional relation of Newton’s law, and then coal and rock mass with different properties such as coal, granite, and sandstone are selected. Using the established test system, the influence of coal and rock electric signal is analyzed from the coal-rock temperature, coal and rock properties, coal-rock friction, coal-rock loading speed, and coal-rock load size. The chief results can be summarized as follows: in the process of coal-rock rising with temperature, the change rule of electrical signals can be divided into three stages according to the strength of electrical signals generated. The amplitudes of electrical signals generated by uniaxial compression of coal-rock mass with different properties are obviously different. Electrical signals can be generated during the friction of coal and rock. With the augment of loading speed, the electrical semaphore generated when the coal rock is about to fracture tends to be enhanced. The size of the electrical signal is not proportional to the size of the load, but the electrical signal is greatest when the rupture is imminent. The analysis of the influence factors of coal and rock electrical signals can provide a reference for the research on the generation mechanism of coal-rock electrical signals.
Research Progress of PCNA in Reproductive System Diseases
Authors: Pan Jing , Zhang Jianwei
Published: October 2021

Reproductive system diseases have become a public health problem that endangers human physical and mental health. The causes of reproductive diseases are complex and diverse. From a biological point of view, abnormal cell proliferation may affect important physiological functions of reproductive organs and cause various gynecological or andrological diseases. Proliferating cell nuclear antigen (PCNA) is the most commonly used indicator for detecting cell proliferation activity. The up- or downregulation of its expression is of great significance in reproductive system diseases. This review summarizes the significance of the latest research on PCNA expression in reproductive system diseases.
Intelligent Recommendation System of Dance Art Video Resources Based on the Wireless Network
Authors: Chen Jianhua
Published: October 2021

Aiming at the problems of low recommendation accuracy and long recommendation time of the traditional dance art video resource intelligent recommendation system, an intelligent recommendation system of dance art video resource based on the wireless network was designed. In this paper, the hardware part of the smart recommendation system of dance art video resources is designed with the MCU as the system control core, the MAX3232 chip as the hardware transceiver chip, and the RS323 bus circuit. On this basis, according to the user’s existing relationship, a social network is constructed through wireless network technology to obtain user information, Bayesian network is used to predict the user’s preference for dance videos. The probability that users like dance videos is given in the form of data, and related videos of dance art are recommended based on intelligent video resources. The simulation results show that the designed system has higher accuracy and shorter recommendation time for dance art video resources.
An Algorithm for Construction Project Cost Forecast Based on Particle Swarm Optimization-Guided BP Neural Network
Authors: Ye Dan
Published: October 2021

Construction project cost prediction is an important function in construction-related fields; it can provide an important basis for project feasibility study and design scheme comparison and selection, and its accuracy will directly affect the investment decision of the project. The successful realization of construction cost prediction can bring great convenience to the control and management of construction cost. The purpose of this paper is to study a fast, accurate, convenient, deducible, and rational construction project cost prediction method, to provide a basis for the cost management of the whole life cycle of the project. Therefore, this paper uses particle swarm optimization algorithm to improve BP neural network and proposes a novel construction project cost prediction algorithm based on particle swarm optimization-guided BP neural network. Aiming at the defects of BP neural network updating weights and thresholds with the gradient descent method, this paper uses the advantages of particle swarm optimization in the field of parameter optimization to optimize BP neural network with PSO algorithm. The structure of BP neural network weights and the threshold of each neuron in the coding, through intelligent search for each particle, find the most suitable weights and thresholds, so that the BP neural network has faster convergence speed, better generalization ability, and higher prediction precision. Simulation results also show that the proposed algorithm is competitive enough.
Structural Analysis and Improvement Design of Brake Pressure Valve Feedback Stage in Multivalve Parallel Brake System
Authors: Huang Zhi-peng , Yu Bin , Wang Yun-he , Zhang Qi-wei , Xie Yan , Xie Zuo-jian , Kong Xiang-dong
Published: October 2021

The wheel brake device is one of the most widely used landing deceleration devices in modern aircraft. For large aircraft, a multivalve parallel brake system is usually used. When a brake pressure servo valve of a certain type of aircraft is debugged, the output brake pressure of the system shows obvious periodic oscillation with constant amplitude. This paper focuses on the brake pressure servo valve, which is the key component of the system. There are a large number of feedback and adjustment segments in the brake pressure servo valve, which can not only improve the control accuracy but also introduce nonlinear factors to cause system vibration. Therefore, in this paper, the feedback stage structure of the brake pressure servo valve is analyzed and improved, and a new two‐stage pressure servo valve is designed to restrain the output brake pressure vibration of the system. Firstly, the structure principle of the original pressure servo valve is defined, and the function of the feedback stage is analyzed. Secondly, in view of the vibration problem caused by the original brake pressure servo valve, a new two‐stage brake pressure servo valve is designed, which is the main contribution of this paper. Thirdly, the dynamics model of the proposed two‐stage brake pressure servo valve is established, and the simulation model of the brake pressure servo valve‐controlled cylinder system and the multivalve parallel brake servo control system is built. Finally, experiments are carried out on the experimental platform of a multivalve parallel brake system to verify that the proposed two‐stage pressure servo valve can restrain the vibration of the system more effectively than the original brake pressure servo valve. And the two‐stage pressure servo valve prototype is successfully applied to the actual aircraft brake control system; the system can better maintain a stable brake pressure output.
[Retracted] Performance Analysis of Otsu‐Based Thresholding Algorithms: A Comparative Study
Authors: Cao Qinglin , Qingge Letu , Yang Pei
Published: October 2021

Image thresholding is a widely used technology for a lot of computer vision applications, and among various global thresholding algorithms, Otsu‐based approaches are very popular due to their simplicity and effectiveness. While the usage of Otsu‐based thresholding methods is well discussed, the performance analyses of these methods are rather limited. In this paper, we first review nine Otsu‐based approaches and categorize them based on their objective functions, preprocessing, and postprocessing strategies. Second, we conduct several experiments to analyze the model characteristics using different scene parameters both on synthetic images and real‐world cell images. We put more attention to examine the variance of foreground object and the effect of the distance between mean values of foreground and background. Third, we explore the robustness of algorithms by introducing two typical kinds of noises under different intensities and compare the running time of each method. Experimental results show that NVE, WOV, and Xing’s methods are more robust to the distance of mean values of foreground and background. The large foreground variance will cause a larger threshold value. Experiments on cell images show that foreground miss detection becomes serious when the intensities of foreground pixels change drastically. We conclude that almost all algorithms are significantly affected by Salt&Pepper and Gaussian noises. Interestingly, we find that ME increases almost linearly with the intensity of Salt&Pepper noise. In terms of algorithms’ time cost, methods with no preprocessing and postprocessing steps have more advantages. All these findings can serve as a guideline for image thresholding when using Otsu‐based thresholding approaches.
Ultrasonic Pretreatment-Assisted Electrohydrodynamic Drying of Potato Slices
Authors: Cao Zhiyuan , Ding Changjiang , Zhao Rui , Song Zhiqing , Chen Hao
Published: October 2021

To investigate the drying characteristics and mechanism during electrohydrodynamic (EHD) drying with ultrasonic pretreatment, the ultrasonic pretreatment-assisted EHD drying method at different power values was used to carry out the drying experiment of potatoes. To carry out this study, potato slices were pretreated with different ultrasonic power values (150, 180, 210, 240, and 270 W) or without ultrasound for 30 min at 30°C. The corresponding voltage was 18 kV during EHD drying. The moisture ratio, drying rate, color, shrinkage, and rehydration rate of potatoes were determined. The microstructure of potatoes was analyzed using infrared spectroscopy and scanning electron microscopy. Eight mathematical models were used to fit the drying of potatoes. Results showed that, compared with the control group, the ultrasonic pretreatment combined with the EHD drying group had improved the drying rate of potato slices, which was different at varying ultrasonic power values. Ultrasonic pretreatment had a remarkable effect on the color of the potato but had little effect on the shrinkage rate. The maximum rehydration rate is 5.7704 at 180 W. The minimum and maximum values of effective moisture diffusivity (Deff) were 3.4070 × 10−7 m2/s and 4.1160 × 10−7 m2/s, respectively. The effect of ultrasonic power pretreatment on the microstructure of potato in the EHD drying process was significant (

p
>
0.05

). According to the statistical parameter evaluation, eight mathematical models could satisfactorily describe drying curves of potato slices dried under EHD with ultrasonic pretreatment, and the logarithmic model was best suited. This work provides a theoretical basis and practical guidance to further understand the parameter characteristics and mechanism of ultrasonic pretreatment combined with the EHD drying technology.
Influence of Clay Fraction and Mineral Composition on Unsaturated Characteristics of Cohesive Foundation Soil in Airports
Authors: Feng Jun , Zhang Guangze
Published: October 2021

Taking unsaturated clay foundation soil of an airport project in Hefei as the research object, the effects of particle gradation and mineral composition on the unsaturated soil properties were analyzed through two kinds of tests. The results show that there is a good correlation between the residual water content and the clay fraction or silt fraction content in the grading, and the residual water content has a significant positive linear correlation with the clay fraction content, but a negative linear correlation with the silt fraction content. Residual matric suction has a nonlinear correlation with clay fraction or silt fraction content in gradation, which has a significant nonlinear negative correlation with clay fraction content and a positive nonlinear correlation with silt fraction content. The residual water content and the residual matric suction have obvious linear relationship with the content of montmorillonite but have no obvious correlation with the content of illite. The water-storage coefficient of unsaturated airfield foundation soil decreases exponentially with the increase of clay content and montmorillonite content.
Numerical Simulation Analysis of Slope Instability and Failure of Limestone Mine in Weibei
Authors: Liu Kuiming , Li Hui , Pang Shihui , Mi Meng , Chen Jianping , Sun Kui
Published: October 2021

Weibei area is the largest limestone resource area in Shaanxi Province, which is an important boundary to distinguish the climate difference between the south and the north of China, and also a significant ecological safety protection barrier in the northwest of China. The complex geological environment and harsh environment make the mining area have serious geological disaster hidden danger. Based on the site engineering geological data of typical limestone quarry slope in Weibei, this paper constructs a three‐dimensional geological model, uses FLAC3D software to simulate excavation, and analyzes the stress and strain law of the quarry slope. SlopeLE software was used to analyze the safety factor of slope stability and the potential slip surface before and after taking reinforcement measures. The results show the following: (1) Limestone is the main rock component of the mine, followed by mudstone. The joint and fissure are developed, the rock mass is broken, and the hidden danger of engineering geological disaster is high. (2) There is a sliding trend in both sides during excavation, and the maximum vertical displacement is 2.1 cm. (3) If the slope is reinforced according to the design scheme, the slope stability safety factor will be increased from 1.062 to 1.203 in a stable state, which greatly improves the stability of the slope and provides a guarantee for human and financial resources.
Pharmacokinetics and Toxicokinetics of Artemisinin-Hydroxychloroquine Sulfate Tablets in Rats and Dogs
Authors: Li Xiaobo , Hu Jiaoting , Yuan Yueming , Wang Yunhan , Yuan Zheng , Liu Ruidong , Zhang Shouya , Xu Zhiyong , Wang Qi , Xu Qin , Ru Li , Song Jianping
Published: October 2021

Artemisinin-hydroxychloroquine sulfate tablets (AH) are relatively inexpensive and a novel combination therapy for the treatment of all forms of malaria, especially aminoquinine drug-resistant strains of P. falciparum. Our aim was to assess the pharmacokinetics (PK) and toxicokinetics (TK) of AH following oral administration in Sprague Dawley rats and Beagle dogs by using the liquid chromatography tandem mass spectrometry methods (LC-MS/MS). The PK studies were carried out in eighteen rats at three doses and six dogs at three rounds of three doses after a single oral administration of AH. The TK studies in rats and dogs were accompanied by the 14-day repeated dosing studies. The PK results revealed that artemisinin was absorbed and cleared rapidly in rats with obvious gender difference and interindividual variability, and the systemic exposure with regard to AUC was positively correlated with the dosage in female rats. However, the kinetics parameters of artemisinin in dogs were not obtained because the plasma concentration was undetectable. The absorption and elimination of hydroxychloroquine in dogs and rats were relatively slow, and no gender difference was observed. The AUC of hydroxychloroquine showed a linear correlation with the dosage, but Cmax varied significantly among individuals. After 14-day repeated oral administration of AH, hydroxychloroquine shows an increase in systemic exposure and accumulation in rats and dogs, whereas the AUC and Cmax of artemisinin remarkably decreased in female rats due to its autoinduction metabolism. The TK results were basically consistent with the dose- and time-dependent toxic reaction in 14-day repeated dosing studies of AH in rats and dogs. The information from our studies could be helpful for further pharmacological and toxicological research and clinical application of AH.
Expression of Tspan8 in Patients with Intrahepatic Cholangiocarcinoma and Its Relationship with Clinicopathological Features and Prognosis
Authors: Tan Zhenhua , Wan Renrui , Chen Minzhi , Xie Ping , Li Peng , Shen Yan , Pan Zhiping , Qian Hai
Published: October 2021

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan–Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.
Bending of a Viscoelastic Timoshenko Cracked Beam Based on Equivalent Viscoelastic Spring Models
Authors: Fu Chao , Yang Xiao
Published: October 2021

Considering the transverse crack as a massless viscoelastic rotational spring, the equivalent stiffness of the viscoelastic cracked beam is derived by Laplace transform and the generalized Dirac delta function. Using the standard linear solid constitutive equation and the inverse Laplace transform, the analytical expressions of the deflection and rotation angle of the viscoelastic Timoshenko beam with an arbitrary number of open cracks are obtained in the time domain. By numerical examples, the bending results of the analytical expressions are verified with those of the FEM program. Additionally, the effects of the time, slenderness ratio, and crack depth on the bending deformations of the different cracked beam models are revealed.
Mobile Technology and Studies on Transport Behavior: A Literature Analysis, Integrated Research Model, and Future Research Agenda
Authors: Sun Yan , Liu Chengxi , Zhang Chen
Published: October 2021

The prevalence of mobile technology has been significant in transport research. Despite a growing application spectrum of smartphone uses and interests in mobility inference, little effort has been put into discussing theories, models, and research topics based on a systematic study of scholarly sources rooted in the interdisciplinary area of mobile technology and transport. Therefore, a timely and comprehensive synthesis of the current state of research is deemed to be required. A literature analysis, following PRISMA guidelines, aims to identify the successful development and implementation of the mobile technology that can be employed for behavior studies in transport. A review of the Web of Science Core Collections, JSTOR and SAGE databases, is performed. A rigorous screening process is used to collect key articles to construct the general image of existing knowledge. In addition, this study suggests an integrated research model to summarize how previous studies attain behavioral outcomes and a research agenda to identify unresolved research questions that future research can address. Two hundred fourty-eight papers meet the inclusion criteria. This study demonstrates that mobile technology is helpful for a better understanding of the various types of transport behaviors. They can be categorized according to their system designs and research topics: (1) Smartphone apps in sustainable transport and travel planning were studied in a remarkable collection of articles. (2) As individual’s mobility was under question, cellular signaling data were prominent for the formulation of analytical models. (3) CDRs, WiFi, and GPS data have increasingly been used, but the share of the modeling techniques for all mobile information systems has remained low. It shows that system designers could supply more desirable and appealing features in most areas. However, applications for the movement of goods are limited, although freighting has moved toward digitalization.
Construction and Application of Media Corpus Based on Big Data
Authors: Yin Bochun , Fu Lei
Published: October 2021

Aiming at the problems of poor data quality and low application rate in the construction of existing media corpus, this paper proposes the construction and application research of media corpus based on big data. Media corpus data are collected, the data are divided into four categories, the heuristic data item column sorting algorithm is introduced to sort all collection processes, the minimum value of data item collection rate is determined, on this basis, the maximum value of quantity in media corpus is determined, and data collection is realized in media corpus data through sliding window. Then, the state characteristics and probability distribution of feature data are determined by dynamic Bayesian network, the relationship between the state variables and dimensions of media corpus data is determined, and the media corpus data state is processed by component to complete the preprocessing of media corpus data; finally, through the application research of storage and encryption of the designed database through big data technology, the storage structure data and encryption secret key are designed to realize the construction and application of media corpus. The experimental results show that the data quality of the media corpus constructed by the proposed method is high, and its application rate has been improved to a certain extent.
Computation of Edge Resolvability of Benzenoid Tripod Structure
Authors: Ahmad Ali , Husain Sadia , Azeem Muhammad , Elahi Kashif , Siddiqui M. K.
Published: October 2021

In chemistry, graphs are commonly used to show the structure of chemical compounds, with nodes and edges representing the atom and bond types, respectively. Edge resolving set

λ

e

is an ordered subset of nodes of a graph

C

, in which each edge of

C

is distinctively determined by its distance vector to the nodes in

λ

. The cardinality of a minimum edge resolving set is called the edge metric dimension of

C

. An edge resolving set

L

e
,
f

of

C

is fault-tolerant if

λ

e
,
f

∖
b

is also an edge resolving set, for every

b

in

λ

e
,
f

. Resolving set allows obtaining a unique representation for chemical structures. In particular, they were used in pharmaceutical research for discovering patterns common to a variety of drugs. In this paper, we determine the exact edge metric and fault-tolerant edge metric dimension of benzenoid tripod structure and proved that both parameters are constant.
Viral Inactivation with Emphasis on SARS-CoV-2 Using Physical and Chemical Disinfectants
Authors: Fadaei Abdolmajid
Published: October 2021

Background. Recently, an outbreak of a novel human coronavirus SARS-CoV-2 has become a world health concern leading to severe respiratory tract infections in humans. Virus transmission occurs through person-to-person contact, respiratory droplets, and contaminated hands or surfaces. Accordingly, we aim at reviewing the literature on all information available about the persistence of coronaviruses, including human and animal coronaviruses, on inanimate surfaces and inactivation strategies with biocides employed for chemical and physical disinfection. Method. A comprehensive search was systematically conducted in main databases from 1998 to 2020 to identify various viral disinfectants associated with HCoV and methods for control and prevention of this newly emerged virus. Results. The analysis of 62 studies shows that human coronaviruses such as severe acute respiratory syndrome (SARS) coronavirus, Middle East respiratory syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV), canine coronavirus (CCV), transmissible gastroenteritis virus (TGEV), and mouse hepatitis virus (MHV) can be efficiently inactivated by physical and chemical disinfectants at different concentrations (70, 80, 85, and 95%) of 2-propanol (70 and 80%) in less than or equal to 60 s and 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Additionally, glutaraldehyde (0.5–2%), formaldehyde (0.7–1%), and povidone-iodine (0.1–0.75%) could readily inactivate coronaviruses. Moreover, dry heat at 56°C, ultraviolet light dose of 0.2 to 140 J/cm2, and gamma irradiation could effectively inactivate coronavirus. The WHO recommends the use of 0.1% sodium hypochlorite solution or an ethanol-based disinfectant with an ethanol concentration between 62% and 71%. Conclusion. The results of the present study can help researchers, policymakers, health decision makers, and people perceive and take the correct measures to control and prevent further transmission of COVID-19. Prevention and decontamination will be the main ways to stop the ongoing outbreak of COVID-19.
The Embedded IoT Time Series Database for Hybrid Solid-State Storage System
Authors: Cai Tao , Liu Peiyao , Niu Dejiao , Shi Jiancong , Li Lei
Published: October 2021

IoT time series data is an important form of big data. How to improve the efficiency of storage system is crucial for IoT time series database to store and manage massive IoT time series data from various IoT devices. Mixing NVM and SSD is an effective method to improve the I/O performance of storage systems. However, there are great differences between HDD and NVM or SSD. As a result, NVM and SSD cannot be directly used in the current time series database effectively. We design an IoT time series database with an embedded engine in storage device drivers for the hybrid solid-state storage system consisting of NVM and SSD. The I/O software stack of storing and managing IoT time series data can be shortened to improve the efficiency. Based upon the intrinsic characteristics of IoT time series data and different features of NVM and SSD, a redundancy elimination and compression fusion strategy, a hierarchical management strategy, and a heterogeneous time series data index are designed to improve the efficiency. Finally, a prototype of embedded IoT time series database named TS-NSM is implemented, and YCSB-TS is used to measure the IOPS. The results show that TS-NSM can improve the write IOPS up to 243.6 times and 174.3 times, respectively, compared with InfluxDB and OpenTSDB, and improve the read IOPS up to 10.1 times and 14.4 times, respectively.
HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study
Authors: Osada Takuya , Crosby Erika J. , Kaneko Kensuke , Snyder Joshua C. , Ginzel Joshua D. , Acharya Chaitanya R. , Yang Xiao-Yi , Polascik Thomas J. , Spasojevic Ivan , Nelson Rendon C. , Hobeika Amy , Hartman Zachary C. , Neckers Leonard M. , Rogatko Andre , Hughes Philip F. , Huang Jiaoti , Morse Michael A. , Haystead Timothy , Lyerly H. Kim
Published: October 2021

A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of numerous oncogenic drivers, including the androgen receptor and its variants, to detect aggressive prostate cancer. We linked a near-infrared fluorescing molecule to an HSP90 binding drug and demonstrated that this probe (designated HS196) was highly sensitive and specific for detecting implanted prostate cancer cell lines with greater uptake by more aggressive subtypes. In a phase I human study, systemically administered HS196 could be detected in malignant nodules within prostatectomy specimens. Single-cell RNA sequencing identified uptake of HS196 by malignant prostate epithelium from the peripheral zone (AMACR+ERG+EPCAM+ cells), including SYP+ neuroendocrine cells that are associated with therapeutic resistance and metastatic progression. A theranostic version of this molecule is under clinical testing.
Enhanced Antitumor Responses of Tumor Antigen-Specific TCR T Cells Genetically Engineered to Produce IL7 and CCL19
Authors: Tokunaga Yoshihiro , Sasaki Takahiro , Goto Shunsuke , Adachi Keishi , Sakoda Yukimi , Tamada Koji
Published: October 2021

Although adoptive transfer of T cells genetically engineered to express chimeric antigen receptor (CAR) or T-cell receptor (TCR) has been actively developed and applied into clinic recently, further improvement of these modalities is highly demanded, especially in terms of its efficacy. Because we previously revealed the profound enhancement of antitumor effects of CAR T cells by concomitant expression of IL7 and CCL19, this study further explored a potential of IL7/CCL19 production technology to augment antitumor effects of TCR T cells. IL7/CCL19-producing P1A tumor antigen-specific TCR T cells (7 × 19 P1A T cells) demonstrated significantly improved antitumor effects, compared with those without IL7/CCL19 production, and generated long-term memory responses. The antitumor effects of 7×19 P1A T cells were further upregulated by combination with anti–PD-1 antibody, in which blockade of PD-1 signal in both 7×19 P1A T cells and endogenous T cells plays an important role. Taken together, our study demonstrated that concomitant production of IL7 and CCL19 by genetically engineered tumor-reactive T cells could synergize with PD-1 blockade therapy to generate potent and long-lasting antitumor immunity.
Efficacy of Icotinib, an EGFR Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer Patients with Exon 19 Deletion and Exon 21 L858R: A Retrospective Analysis in China
Authors: Wang Yang , Yuan Xiaobin , Yang Min , Shen Zhilin , Chen Hui , He Xiangbo , Ma Yongbin , Ding Lieming
Published: October 2021

Introduction: The effect of icotinib on non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 EGFR mutations. Methods: We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic EGFR mutations. Kinase activity assays were used to reaffirm the preclinical efficacy. Results: Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; p = 0.0039) and disease control rate (98.5 vs. 97.2%; p = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3–23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5–21.7) (p = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC50) of icotinib was lower for EGFR 19-Del than 21-L858R. Conclusion: These results suggest that EGFR 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R.
Socioeconomic and Geographic Characteristics of Hospitals Establishing Transcatheter Aortic Valve Replacement Programs, 2012–2018
Authors: Nathan Ashwin S. , Yang Lin , Yang Nancy , Khatana Sameed Ahmed M. , Dayoub Elias J. , Eberly Lauren A. , Vemulapalli Sreekanth , Baron Suzanne J. , Cohen David J. , Desai Nimesh D. , Bavaria Joseph E. , Herrmann Howard C. , Groeneveld Peter W. , Giri Jay , Fanaroff Alexander C.
Published: October 2021

Background:

Despite the benefits of novel therapeutics, inequitable diffusion of new technologies may generate disparities. We examined the growth of transcatheter aortic valve replacement (TAVR) in the United States to understand the characteristics of hospitals that developed TAVR programs and the socioeconomic status of patients these hospitals served.

Methods:

We identified fee-for-service Medicare beneficiaries aged 66 years or older who underwent TAVR between January 1, 2012, and December 31, 2018, and hospitals that developed TAVR programs (defined as performing ≥10 TAVRs over the study period). We used linear regression models to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs and described the association between core-based statistical area level markers of socioeconomic status and TAVR rates.

Results:

Between 2012 and 2018, 583 hospitals developed new TAVR programs, including 572 (98.1%) in metropolitan areas, and 293 (50.3%) in metropolitan areas with preexisting TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated fewer patients with dual eligibility for Medicaid (difference of −2.83% [95% CI, −3.78% to −1.89%],
P
≤0.01), higher median household incomes (difference $2447 [95% CI, $1348–$3547],
P
=0.03), and from areas with lower distressed communities index scores (difference −4.02 units [95% CI, −5.43 to −2.61],
P
≤0.01). After adjusting for the age, clinical comorbidities, race and ethnicity and socioeconomic status, areas with TAVR programs had higher rates of TAVR and TAVR rates per 100 000 Medicare beneficiaries were higher in core-based statistical areas with fewer dual eligible patients, higher median income, and lower distressed communities index scores.

Conclusions:

During the initial growth phase of TAVR programs in the United States, hospitals serving wealthier patients were more likely to start programs. This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities.
Mitochondrial Telomerase Reverse Transcriptase Protects From Myocardial Ischemia/Reperfusion Injury by Improving Complex I Composition and Function
Authors: Ale-Agha Niloofar , Jakobs Philipp , Goy Christine , Zurek Mark , Rosen Julia , Dyballa-Rukes Nadine , Metzger Sabine , Greulich Jan , von Ameln Florian , Eckermann Olaf , Unfried Klaus , Brack Fedor , Grandoch Maria , Thielmann Matthias , Kamler Markus , Gedik Nilgün , Kleinbongard Petra , Heinen Andre , Heusch Gerd , Gödecke Axel , Altschmied Joachim , Haendeler Judith
Published: October 2021

Background:

The catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), has protective functions in the cardiovascular system. TERT is not only present in the nucleus but also in mitochondria. However, it is unclear whether nuclear or mitochondrial TERT is responsible for the observed protection, and the appropriate tools are missing to dissect this.

Methods:

We generated new mouse models containing TERT exclusively in the mitochondria (mitoTERT mice) or the nucleus (nucTERT mice) to finally distinguish between the functions of nuclear and mitochondrial TERT. Outcome after ischemia/reperfusion, mitochondrial respiration in the heart, and cellular functions of cardiomyocytes, fibroblasts, and endothelial cells, as well, were determined.

Results:

All mice were phenotypically normal. Although respiration was reduced in cardiac mitochondria from TERT-deficient and nucTERT mice, it was increased in mitoTERT animals. The latter also had smaller infarcts than wild-type mice, whereas nucTERT animals had larger infarcts. The decrease in ejection fraction after 1, 2, and 4 weeks of reperfusion was attenuated in mitoTERT mice. Scar size was also reduced and vascularization increased. Mitochondrial TERT protected a cardiomyocyte cell line from apoptosis. Myofibroblast differentiation, which depends on complex I activity, was abrogated in TERT-deficient and nucTERT cardiac fibroblasts and completely restored in mitoTERT cells. In endothelial cells, mitochondrial TERT enhanced migratory capacity and activation of endothelial nitric oxide synthase. Mechanistically, mitochondrial TERT improved the ratio between complex I matrix arm and membrane subunits, explaining the enhanced complex I activity. In human right atrial appendages, TERT was localized in mitochondria and there increased by remote ischemic preconditioning. The telomerase activator TA-65 evoked a similar effect in endothelial cells, thereby increasing their migratory capacity, and enhanced myofibroblast differentiation.

Conclusions:

Mitochondrial, but not nuclear TERT, is critical for mitochondrial respiration and during ischemia/reperfusion injury. Mitochondrial TERT improves complex I subunit composition. TERT is present in human heart mitochondria, and remote ischemic preconditioning increases its level in those organelles. TA-65 has comparable effects ex vivo and improves the migratory capacity of endothelial cells and myofibroblast differentiation. We conclude that mitochondrial TERT is responsible for cardioprotection, and its increase could serve as a therapeutic strategy.
Computed Tomography Perfusion–Based Prediction of Core Infarct and Tissue at Risk: Can Artificial Intelligence Help Reduce Radiation Exposure?
Authors: Bathla Girish , Liu Yanan , Zhang Honghai , Sonka Milan , Derdeyn Colin
Published: October 2021

Background and Purpose:

We explored the feasibility of automated, arterial input function independent, vendor neutral prediction of core infarct, and penumbral tissue using complete and partial computed tomographic perfusion data sets through neural networks.

Methods:

Using retrospective computed tomographic perfusion data from 57 patients, split as training/validation (60%/40%), we developed and validated separate 2-dimensional U-net models for cerebral blood flow (CBF) and time to maximum (Tmax) maps calculation to predict core infarct and tissue at risk, respectively. Once trained, the full sets of 28 input images were sequentially reduced to equitemporal 14, 10, and 7 time points. The averaged structural similarity index measure between the model-derived images and ground truth perfusion maps was compared. Volumes for core infarct and Tmax were compared using the Pearson correlation coefficient.

Results:

Both CBF and Tmax maps derived using 28 and 14 time points had similar structural similarity index measure (0.80–0.81;
P
>0.05) when compared with ground truth images. The Pearson correlation for the CBF and Tmax volumes derived from the model using 28-tp with ground truth volumes derived from the RAPID software was 0.69 for CBF and 0.74 for Tmax. The predicted maps were fully concordant in terms of laterality to the commercial perfusion maps. The mean Dice scores were 0.54 for the core infarct and 0.63 for the hypoperfusion maps.

ConclusionS:

Artificial intelligence model-derived volumes show good correlation with RAPID-derived volumes for CBF and Tmax. Within the constraints of a small sample size, the perfusion map quality is similar when using 14-tp instead of 28-tp. Our findings provide proof of concept that vendor neutral artificial intelligence models for computed tomographic perfusion processing using complete or partial image data sets appear feasible. The model accuracy could be further optimized using larger data sets.
Transcutaneous Auricular Vagus Nerve Stimulation Strengthens Semantic Representations of Foreign Language Tone Words during Initial Stages of Learning
Authors: Phillips Ian , Calloway Regina C. , Karuzis Valerie P. , Pandža Nick B. , O'Rourke Polly , Kuchinsky Stefanie E.
Published: October 2021

Difficulty perceiving phonological contrasts in a second language (L2) can impede initial L2 lexical learning. Such is the case for English speakers learning tonal languages, like Mandarin Chinese. Given the hypothesized role of reduced neuroplasticity in adulthood limiting L2 phonological perception, the current study examined whether transcutaneous auricular vagus nerve stimulation (taVNS), a relatively new neuromodulatory technique, can facilitate L2 lexical learning for English speakers learning Mandarin Chinese over 2 days. Using a double-blind design, one group of participants received 10 min of continuous priming taVNS before lexical training and testing each day, a second group received 500 msec of peristimulus (peristim) taVNS preceding each to-be-learned item in the same tasks, and a third group received passive sham stimulation. Results of the lexical recognition test administered at the end of each day revealed evidence of learning for all groups, but a higher likelihood of accuracy across days for the peristim group and a greater improvement in response time between days for the priming group. Analyses of N400 ERP components elicited during the same tasks indicate behavioral advantages for both taVNS groups coincided with stronger lexico-semantic encoding for target words. Comparison of these findings to pupillometry results for the same study reported in Pandža, N. B., Phillips, I., Karuzis, V. P., O'Rourke, P., and Kuchinsky, S. E. (Neurostimulation and pupillometry: New directions for learning and research in applied linguistics. Annual Review of Applied Linguistics, 40, 56–77, 2020) suggest that positive effects of priming taVNS (but not peristim taVNS) on lexico-semantic encoding are related to sustained attentional effort.
Improving the Performance of Organic Photodetector Using Hf-SnO2 as an Electron Transport Layer
Authors: Lee Seon-Ju , Kim Gyu Min , Oh Se-Young
Published: October 2021

The adequate control of dark current is the key to achieving high detectivity in organic photodetectors (OPDs). In this study, we incorporated hafnium (Hf), a rare earth mineral, into tin oxide (SnO2) to form hafnium doped SnO2 (Hf-SnO2) as an electron
transport layer (ETL) in OPDs. It was observed that the performance of OPDs with a Hf-SnO2 electron transport layer in OPDs is superior to that of conventional SnO2 as it significantly reduces the leakage current recording a high specific detectivity of 8.70 × 1011
Jones and a bandwidth of 229.63 kHz at −1 V and 525 nm. Furthermore, Hf-SnO2 can be processed at a low temperature, thereby broadening the fields of applications such as flexible devices and large area cells.
An Analysis of Virtual Research Experiences for Undergraduates Programs in Light of the COVID-19 Pandemic
Authors: Collins Jennifer , Polen Amy , Jernigan Isabelle , Colón-Burgos Delián , McSweeney Killian , Spandri Melyssa
Published: October 2021

With the continued social distancing requirements of the novel COVID-19 pandemic, many in-person educational programs were halted in 2020, including specialty education and research experiences for undergraduates. However, some Research Experiences for Undergraduates (REUs) progressed in summer 2020 in a fully virtual format. The importance of understanding how these practical STEM skills translated in a virtual REU format, in addition to areas of improvement going forward, are critical to the development of effective online STEM learning through REUs. Two survey instruments were designed to capture data from both the REU mentors (including the PIs) and the students in the programs. Questions included information on the REU they participated in, their perceptions of the best and worst aspects, their overall satisfaction with the experience, and their likelihood to seek out virtual REUs in the future. Overall, both students and faculty involved in virtual REUs were glad to have had the experience and were satisfied with it. The benefits of flexibility, the ease of communication and scheduling, and the increased access to online resources were echoed as the strengths of the virtual format. However, many believe that an in-person REU had benefits that could not be replicated in a virtual environment, including community building and hands-on experiences. Several were bogged down by technical difficulties. With more effort made to include community building to a greater extent, as well as considerations and planning for technical demands, the future of widely accessible online REU experiences is a bright one.