bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a Cultural Heritage Gesture-Based Puzzle Game and Evaluation of User Experience
Authors: Katsantonis Menelaos N. , Manikas Athanasios , Mavridis Ioannis
Published: April 2023

The Haptic Puzzle was a 3D gesture-based puzzle game developed to be deployed in a museum of ethnology. The Haptic Puzzle was designed according to the conceptual model for puzzle games, which was based on the four-dimensional framework. In this study, we explored the development process of the Haptic Puzzle, providing insight on the manner in which the game was designed and explaining the design choices made. Aiming to measure the experience perceived by the Haptic Puzzle’s users, we evaluated the Haptic Puzzle based on the user experience questionnaire and direct observations, with the involvement of 92 participants who were separated into groups of 9 to 12 or small groups of 2 to 3 according to their ages, which ranged from 10 to 15 years old. We discuss the evaluation results indicating that the Haptic Puzzle accomplished its purpose by engaging users in a creative activity while they experienced pleasant feelings and enjoyment. Moreover, we describe the challenges we faced and the manner in which they were confronted. The presented study provides directions for future work regarding the development and evaluation of cultural heritage gesture-based games for deployment in museums.
Identification of Challenges and Best Practices for Including Users with Disabilities in User-Based Testing
Authors: Šumak Boštjan , Kous Katja , Martínez-Normand Loïc , Pekša Jānis , Pušnik Maja
Published: April 2023

Despite efforts to promote digital inclusion for all, individuals with disabilities continue to experience a significant digital divide. Developing usable and accessible solutions also demands conducting user-based testing with real end users, particularly for users with disabilities, to detect and address real problems and barriers they experience and improve usability and accessibility based on their feedback through a user-centered approach. When including users with disabilities in user testing, additional attention must be paid to ensure that the testing is planned and carried out in such a way as to enable the successful and efficient integration of users with disabilities. In doing so, it is necessary to consider various restrictions related to users’ disabilities. By conducting a systematic literature review, we collected and analyzed the challenges of including users with disabilities in user-based testing and best practices that researchers can apply in future user-based testing with users with disabilities. In the existing literature, a positive trend toward publishing articles describing testing with users with disabilities is noticeable. There is also an apparent need for more reporting on some phases of the testing studies. The main result of this study is a list of challenges and best practices that are important in the different phases of user-based testing with users with disabilities.
Experimental Study on the Rotational Stiffness of Pocket Type Scaffolding Connection According to the Rotation Direction
Authors: Chung Dae-Hyun , Won Jeong-Hun
Published: April 2023

The rotational stiffness of the pocket-type connection used in system scaffolding to join horizontal members and vertical members was evaluated. To investigate the rotational stiffness of connections when subjected to bending moments in the downward, upward, and lateral rotation directions, load tests were performed on 30 specimens with cantilever specimens for each rotational direction. Results showed that failure shapes of pocket-type connections were different depending on the rotation direction. Owing to the differences in the failure phenomena, the maximum moment capacity of the upwardly rotated specimens was the largest, followed by that of the downwardly rotated specimens and the laterally rotated specimens in that order. Compared to the Eurocode 3 connection classification, the pocket-type connections correspond to semi-rigid connections when the rotation direction is downward or upward, and they can be considered nominal pin connections when the rotation direction is lateral. From the moment-rotation curves, it was concluded that the rotational stiffness of the pocket-type connections could be estimated as a bilinear model.
An Optimization-Based Intentional Islanding Scheme for Service Restoration in Distribution Systems Considering Anti-Parallel Operation of Distributed Generations
Authors: Qiu Bangjie , An Jae-Guk , Song Jin-Uk , Oh Yun-Sik
Published: April 2023

An islanding operation of distributed generations (DGs) in emergencies due to a fault in distribution systems can be a means of power supply for important loads in outage areas by facilitating the self-sufficient capability of DGs forming microgrids. This paper presents an optimization-based intentional islanding scheme to derive a near-optimal service restoration (SR) plan. The anti-parallel operation of DGs is considered a new constraint that avoids more than two DGs in an island thereby, enabling simpler control and operation of the distribution system in an emergency. Each island is created by an island partitioning scheme based on the tree representation of the network and fast searching scheme for the tree structure considering load importance, and a genetic algorithm (GA) is utilized to explore possible SR solutions. Case studies on IEEE 69-bus distribution system according to various fault locations are conducted, and the simulation results show that the proposed scheme can restore more loads with higher priority in outage areas by the intentional islanding of DGs. Furthermore, the time for deriving the optimal solution can be reduced since the evaluations for infeasible solutions are not performed.
Thermal Deformation Stability Optimization Design and Experiment of the Satellite Bus to Control the Laser Communication Load’s Acquisition Time
Authors: Shi Yousheng , Chen Shanbo , Yu Meng , Wu You , Yu Jisong , Zhang Lei
Published: April 2023

The optical axis angle fluctuation due to thermal deformation of the satellite bus between the laser communication load and the star sensor must be constrained to within 0.16 mrad to meet the rapid acquisition needs of the laser communication satellite. This paper analyzes the satellite’s in-orbit temperature field distribution, which is then used as the input boundary condition for the thermal deformation analysis. The optical axis angle fluctuation is reduced by the common reference optimization design. Then, adaptable isolation between the satellite bus structure and the reference support structure reduces the thermal deformation coupling. As a result, there will be less optical axis angle fluctuation caused by thermal deformation. The thermal deformation between the optimized laser communication load and the star sensor installation angle is decreased to 14.25″ according to the entire satellite simulation analysis of the modified structure. The maximum angle variation induced by temperature change dropped from 117.74″ to 10.72″ through the ground temperature deviation and prism calibration tests. The on-orbit alignment test confirms that the required capture time of 30 s is met. The aforementioned work minimizes the uncertain region of laser communication load, lessens the in-orbit acquisition time, and satisfies the demand for speedy acquisition.
Deep Convolutional Generative Adversarial Networks-Based Data Augmentation Method for Classifying Class-Imbalanced Defect Patterns in Wafer Bin Map
Authors: Park Sangwoo , You Cheolwoo
Published: April 2023

In the semiconductor industry, achieving a high production yield is a very important issue. Wafer bin maps (WBMs) provide critical information for identifying anomalies in the manufacturing process. A WBM forms a certain defect pattern according to the error occurring during the process, and by accurately classifying the defect pattern existing in the WBM, the root causes of the anomalies that have occurred during the process can be inferred. Therefore, WBM defect pattern recognition and classification tasks are important for improving yield. In this paper, we propose a deep convolutional generative adversarial network (DCGAN)-based data augmentation method to improve the accuracy of a convolutional neural network (CNN)-based defect pattern classifier in the presence of extremely imbalanced data. The proposed method forms various defect patterns compared to the data augmentation method by using a convolutional autoencoder (CAE), and the formed defect patterns are classified into the same pattern as the original pattern through a CNN-based defect pattern classifier. Here, we introduce a new quantitative index called PGI to compare the effectiveness of the augmented models, and propose a masking process to refine the augmented images. The proposed method was tested using the WM-811k dataset. The proposed method helps to improve the classification performance of the pattern classifier by effectively solving the data imbalance issue compared to the CAE-based augmentation method. The experimental results showed that the proposed method improved the accuracy of each defect pattern by about 5.31% on average compared to the CAE-based augmentation method.
Visualization of Emergency Evacuation Physical Behavior under Multi-Agent Decision-Making
Authors: Wang Chen , Zhu Can , Xiao Kun , Tang Yutong , Zhen Haidong
Published: April 2023

Emergency evacuation simulation is significant for architectural design and emergency plan implementation. To explore the influence of evacuees’ physical behavior and evacuees’ decisions on the evacuation process, as well as to address the problems of traditional emergency evacuation models with insufficient detail of the situation (realism), low reusability, poor operability, and lack of subsequent scalability, this paper first analyzed pedestrian characteristics in emergencies. To describe pedestrian decision-making in an emergent evacuation situation, a multi-agent design based on decision theory was proposed, solving the multi-agent decision-making problem in an emergency evacuation environment by the A* algorithm. Then the designed multi-agent was embedded into the social force model by AnyLogic software. Finally, the model reproduces the pedestrian evacuation process in an emergency evacuation situation on the built platform, depicting three kinds of typical behaviors: pedestrian partnering, obstacle avoidance, and exit competition. In addition, this study also analyzed a large student apartment building by example and proposed corresponding optimization solutions to improve its evacuation capacity through simulation results.
Key News Event Detection and Event Context Using Graphic Convolution, Clustering, and Summarizing Methods
Authors: Liu Zheng , Zhang Yu , Li Yimeng , Chaomurilige
Published: April 2023

The detection of key events and identification of the events’ context have been widely studied to detect key events from large volumes of online news and identify trends in such events. In this paper, we propose a Key News Event Detection and Context Method based on graphic convolving, clustering, and summarizing methods. Our method has three main contributions: (1) We propose the use of position vectors as time-embedding feature representations and concatenate semantic and time-embedding features as node features of the graph to distinguish different nodes of the graph. Additionally, a temporal nonlinear function was constructed using time embedding to objectively describe the effect of time on the degree of association between nodes. (2) We update the graph nodes using a graph convolutional neural network to extract deep semantic information about individual nodes of a high-quality phrase graph, thereby improving the clustering capability of graph-based key event detection. (3) We apply a summary generation algorithm to a subset of news data for each key event. Lastly, we validated the effectiveness of our proposed method by applying it to the 2014 Ebola dataset. The experimental results indicate that our proposed method can effectively detect key events from news documents with high precision and completeness while naturally generating the event context of key events, as compared to EvMine and other existing methods.
Large-Scale Road Network Traffic Congestion Prediction Based on Recurrent High-Resolution Network
Authors: Ranjan Sachin , Kim Yeong-Chan , Ranjan Navin , Bhandari Sovit , Kim Hoon
Published: April 2023

Traffic congestion is a significant problem that adversely affects the economy, environment, and public health in urban areas worldwide. One promising solution is to forecast road-level congestion levels in the short-term and long-term, enabling commuters to avoid congested areas and allowing traffic agencies to take appropriate action. In this study, we propose a hybrid deep neural network algorithm based on High-Resolution Network (HRNet) and ConvLSTM decoder for 10, 30, and 60-min traffic congestion prediction. Our model utilizes the HRNet’s multi-scale feature extraction capability to capture rich spatial features from a sequence of past traffic input images. The ConvLSTM module learns temporal information from each HRNet multi-scale output and aggregates all feature maps to generate accurate traffic forecasts. Our experiments demonstrate that the proposed model can efficiently and effectively learn both spatial and temporal relationships for traffic congestion and outperforms four other state-of-the-art architectures (PredNet, UNet, ConvLSTM, and Autoencoder) in terms of accuracy, precision, and recall. A case study was conducted on the dataset from Seoul, South Korea.
Application of Fruit By-Products and Edible Film to Cookies: Antioxidant Activity and Concentration of Oxidized LDL Receptor in Women—A First Approach
Authors: Molnar Dunja , Nikolac Gabaj Nora , Vujić Lovorka , Ščetar Mario , Krisch Judit , Miler Marijana , Štefanović Mario , Novotni Dubravka
Published: April 2023

Cookie consumption can change the serum level of oxidized low-density lipoprotein (oxLDL) and oxLDL receptors, both playing important roles in the pathogenesis of atherosclerosis and cardiovascular diseases. This study investigated the nutritional value and the antioxidant activity of whole grain cookies in which 24% of the cocoa powder was substituted with grape and aronia pomace and were further coated with edible films enriched with grape seed extract (GAP with KGAE) as well as the effects of their consumption on the serum level of oxLDL receptors in women. The proximate composition, mineral content, antioxidant activity, and starch digestibility in vitro of experimental and control cookies were determined. A group of 12–13 healthy women (median age 36) consumed 45 g of GAP with KGAE or commercial cookies for 10 days. The results showed that GAP and KGAE cookies had increased flavonoid content (22%) and antioxidant potential (27–73%) compared to the control. The content of slowly digestible starch prevailed over rapidly digestible starch. The serum concentrations of the oxLDL receptors between the test and control groups were similar. We can conclude that the moderate consumption of whole grain cookies with fruit by-products does not lead to the formation of oxLDL receptors in healthy women.
A Novel Cloud Approach for Connected Vehicles
Authors: Wilhelm Geoffrey , Ayaida Marwane , Fouchal Hacène
Published: April 2023

Cooperative intelligent transport systems (C-ITSs) are being deployed all around the world. Shortly, in addition to vehicles, bicycles, pedestrians, buses, and all moving equipment will be compatible with C-ITS. These systems are connected through wireless local area networks based on WIFI IEEE 802.11p. The large number of C-ITSs and services will lead to a glut in the bandwidth of wireless networks. To overcome this limitation, we propose in this paper a new approach using the information-centric networking (ICN) paradigm which allows vehicles to communicate with the cloud environment. This scheme is denoted by vehicular central data networking (GeoVCDN). Our approach aims to reduce bandwidth consumption and improve data freshness by taking benefit from the existing application beacons and the geographical routing used by C-ITS actors. We have compared the performances (in terms of the network overhead and data freshness) of our solution to two other well-known ICN-based solutions. Each of them represents one of ICN categories, in particular, rendez-vous network (RENE) and named data networking (NDN). To do so, we have proposed a probabilistic model that allows us to evaluate the freshness and the load of the network. Furthermore, we have implemented these methods in a simulator. Our proposal outperforms the other methods in terms of network overhead and data freshness.
Multistage Smoothing Compressor for Multistep Pulse Compressors
Authors: Du Shuman , Shen Xiong , Liang Wenhai , Wang Peng , Liu Jun
Published: April 2023

Ultrahigh peak-power lasers are important scientific tools for frontier laser physics research, in which both the peak power improvement and operating safety are very important. Based on spatial-chirp-induced beam smoothing in both the near field and far field, a multistage-smoothing-based multistep pulse compressor (MS-MPC) is proposed here to further improve safety and operating convenience. In the MS-MPC, beam smoothing is not simply executed in the pre-compressor or main compressor but is separated into multiple stages. As a result, important and expensive optics are directly protected in every stage. The prism-pair-based pre-compressor induces a small spatial chirp, making it both easier to achieve than the previous multistep pulse compressor and sufficient to protect the first grating directly. Furthermore, the asymmetric four-grating compressor, which serves as the main compressor, induces a spatial chirp that further smooths the laser beam, protecting the last grating. In this way, a 10 s to 100 s petawatt laser pulse can be compressed with a single laser beam using the currently available optics. Additionally, an extra beam-smoothing stage can be added before the main amplifier to safeguard the largest amplification crystal from damage. The MS-MPC can be easily integrated into all existing PW laser facilities to improve their potential compressed pulse energy and operational safety.
The Influence of Oscillation Parameters on the Formation of Overhead Welding Seams in the Narrow-Gap GMAW Process
Authors: Bao Yang , Xue Ruilei , Zhou Jianping , Liu Hongsheng , Xu Yan
Published: April 2023

Thick-walled X80 pipelines for oil and gas transportation are difficult to relocate due to their large size. In the process of narrow-gap overhead welding, welding defects, such as bulges and lack of sidewall fusion, can appear easily. To avoid these defects and to improve the welding quality of thick-walled pipelines, the GMAW welding method is adopted in this paper. The formation characteristics of the weld and the influence of arc oscillation parameters, such as the oscillation width and sidewall dwell time, on the formation process of narrow-gap overhead welding seams are studied. In this research, it was found that, in the NG-GMAW overhead welding position, there was a downward trend in the middle of the formed surface of the weld pool. Defects, such as finger-shaped penetrations and lack of sidewall fusion, were prone to occur due to gravity. The increased oscillation width was beneficial for reducing the protrusion in the middle of the weld seam, but an excessive oscillation width can easily cause undercut defects. The sidewall dwell time has little effect on the protrusion in the middle of the weld seam, but it can increase sidewall penetration, thereby avoiding the occurrence of incomplete sidewall penetration.
Ionospheric 14.5 Day Periodic Oscillation during the 2019 Antarctic SSW Event
Authors: Li Jinze , Tang Qiong , Wu Yiyun , Zhou Chen , Liu Yi
Published: April 2023

The International Global Navigation Satellite Systems Service (IGS) ionospheric total electron content (TEC) data are used to study the periodic perturbation in the ionosphere during the 2019 Antarctic sudden stratospheric warming (SSW) event, a rare Southern Hemisphere minor SSW event in the last 40 years. A 14.5 day periodic signal with a zonal wavenumber of 0 is observed in the mesosphere and the lower thermosphere (MLT) region and the ionosphere during this SSW period, which could be related to the lunar tide. The 14.5 day periodic disturbance in the IGS TEC exhibits local time dependence and latitudinal variation, with the maximum amplitude appearing between 1000 and 1600 LT in the equatorial ionization anomaly (EIA) crest regions. Additionally, the 14.5 day periodic oscillation shows an obvious longitudinal variability, with the weakest amplitude appearing in the longitudinal region of 30° W–60° E.
Characteristics and Secondary Organic Aerosol Formation of Volatile Organic Compounds from Vehicle and Cooking Emissions
Authors: Tan Rui , Guo Song , Lu Sihua , Wang Hui , Zhu Wenfei , Yu Ying , Tang Rongzhi , Shen Ruizhe , Song Kai , Lv Daqi , Zhang Wenbin , Zhang Zhou , Shuai Shijin , Li Shuangde , Chen Yunfa , Ding Yan
Published: April 2023

In the present work, volatile organic compounds (VOCs) from vehicle exhaust and cooking fumes were investigated via simulation experiments, which covered engine emissions produced during gasoline direct injection (GDI) using two kinds of fuels and cooking emissions produced by preparing three domestic dishes. The distinct characteristics of VOCs emitted during the two processes were identified. Alkanes (73% mass fraction on average) and aromatics (15% on average) dominated the vehicle VOCs, while oxygenated VOCs (49%) and alkanes (29%) dominated the cooking VOCs. Isopentane (22%) was the most abundant species among the vehicle VOCs. N-hexanal (20%) dominated the cooking VOCs. The n-hexanal-to-n-pentanal ratio (3.68 ± 0.64) was utilized to identify cooking VOCs in ambient air. The ozone formation potential produced by cooking VOCs was from 1.39 to 1.93 times higher than that produced by vehicle VOCs, which indicates the significant potential contribution of cooking VOCs to atmospheric ozone. With the equivalent photochemical age increasing from 0 h to 72 h, the secondary organic aerosol formation by vehicle VOCs was from 3% to 38% higher than that of cooking VOCs. Controlling cooking emissions can reduce SOA pollution in a short time due to its higher SOA formation rate than that of vehicle VOCs within the first 30 h. However, after 30 h of oxidation, the amount of SOAs formed by vehicle exhaust emissions exceeded the amount of SOAs produced by cooking activities, implying that reducing vehicle emissions will benefit particle pollution for a longer time. Our results highlight the importance of VOCs produced by cooking fumes, which has not been given much attention before. Further, our study suggested that more research on semi-volatile organic compounds produced by cooking emissions should be conducted in the future.
A New Approach to Involution in Fuzzy C★-Algebra via Functional Inequality and Python Implementation
Authors: Movahednia Ehsan , De la Sen Manuel
Published: April 2023

This article explores the stability of involution in fuzzy C★-algebras through the use of a functional inequality. We present an approach to obtaining an approximate involution in fuzzy C★-algebras by utilizing a fixed-point method. Moreover, for greater clarity, we implemented Python code for the main theorem.
Effects of Midsole Hardness on the Mechanical Response Characteristics of the Plantar Fascia during Running
Authors: Zhu Xiaolan , Liu Jiaojiao , Liu Hui , Liu Jingxi , Yang Yufeng , Wang Haichun
Published: April 2023

High long-term stress on the plantar fascia (PF) is the main cause of plantar fasciitis. Changes in the midsole hardness (MH) of running shoes are an important factor leading to the alteration of the PF. This study aims to establish a finite-element (FE) model of the foot–shoe, and investigates the effects of midsole hardness on PF stress and strain. The FE foot–shoe model was built in ANSYS using computed-tomography imaging data. Static structural analysis was used to simulate the moment of running push and stretch. Plantar stress and strain under different MH levels were quantitatively analyzed. A complete and valid 3D FE model was established. With an increase in MH from 10 to 50 Shore A, the overall stress and strain of the PF were decreased by approximately 1.62%, and the metatarsophalangeal (MTP) joint flexion angle was decreased by approximately 26.2%. The height of the arch descent decreased by approximately 24.7%, but the peak pressure of the outsole increased by approximately 26.6%. The established model in this study was effective. For running shoes, increasing the MH reduces the stress and strain of PF, but also imposes a higher load on the foot.
Organotypic 3D Co-Culture of Human Pleura as a Novel In Vitro Model of Staphylococcus aureus Infection and Biofilm Development
Authors: Kurow Olga , Nuwayhid Rima , Stock Peggy , Steinert Matthias , Langer Stefan , Krämer Sebastian , Metelmann Isabella B.
Published: April 2023

Bacterial pleural infections are associated with high mortality. Treatment is complicated due to biofilm formation. A common causative pathogen is Staphylococcus aureus (S. aureus). Since it is distinctly human-specific, rodent models do not provide adequate conditions for research. The purpose of this study was to examine the effects of S. aureus infection on human pleural mesothelial cells using a recently established 3D organotypic co-culture model of pleura derived from human specimens. After infection of our model with S. aureus, samples were harvested at defined time points. Histological analysis and immunostaining for tight junction proteins (c-Jun, VE-cadherin, and ZO-1) were performed, demonstrating changes comparable to in vivo empyema. The measurement of secreted cytokine levels (TNF-α, MCP-1, and IL-1β) proved host–pathogen interactions in our model. Similarly, mesothelial cells produced VEGF on in vivo levels. These findings were contrasted by vital, unimpaired cells in a sterile control model. We were able to establish a 3D organotypic in vitro co-culture model of human pleura infected with S. aureus resulting in the formation of biofilm, including host–pathogen interactions. This novel model could be a useful microenvironment tool for in vitro studies on biofilm in pleural empyema.
Effects of a Nanonetwork-Structured Soil Conditioner on Microbial Community Structure
Authors: Cao Jingjing , Zhao Pan , Wang Dongfang , Zhao Yonglong , Wang Zhiqin , Zhong Naiqin
Published: April 2023

Fertilizer application can increase yields, but nutrient runoff may cause environmental pollution and affect soil quality. A network-structured nanocomposite used as a soil conditioner is beneficial to crops and soil. However, the relationship between the soil conditioner and soil microbes is unclear. We evaluated the soil conditioner’s impact on nutrient loss, pepper growth, soil improvement, and, especially, microbial community structure. High-throughput sequencing was applied to study the microbial communities. The microbial community structures of the soil conditioner treatment and the CK were significantly different, including in diversity and richness. The predominant bacterial phyla were Pseudomonadota, Actinomycetota, and Bacteroidota. Acidobacteriota and Chloroflexi were found in significantly higher numbers in the soil conditioner treatment. Ascomycota was the dominant fungal phylum. The Mortierellomycota phylum was found in significantly lower numbers in the CK. The bacteria and fungi at the genus level were positively correlated with the available K, available N, and pH, but were negatively correlated with the available P. Our results showed that the loss of nutrients controlled by the soil conditioner increased available N, which improved soil properties. Therefore, the microorganisms in the improved soil were changed. This study provides a correlation between improvements in microorganisms and the network-structured soil conditioner, which can promote plant growth and soil improvement.
Opposing Spatially Segregated Function of Endogenous GDNF-RET Signaling in Cocaine Addiction
Authors: Garton Daniel R. , Turconi Giorgio , Iivanainen Vilma , Andressoo Jaan-Olle
Published: April 2023

Cocaine addiction is a serious condition with potentially lethal complications and no current pharmacological approaches towards treatment. Perturbations of the mesolimbic dopamine system are crucial to the establishment of cocaine-induced conditioned place preference and reward. As a potent neurotrophic factor modulating the function of dopamine neurons, glial cell line-derived neurotrophic factor (GDNF) acting through its receptor RET on dopamine neurons may provide a novel therapeutic avenue towards psychostimulant addiction. However, current knowledge on endogenous GDNF and RET function after the onset of addiction is scarce. Here, we utilized a conditional knockout approach to reduce the expression of the GDNF receptor tyrosine kinase RET from dopamine neurons in the ventral tegmental area (VTA) after the onset of cocaine-induced conditioned place preference. Similarly, after establishing cocaine-induced conditioned place preference, we studied the effect of conditionally reducing GDNF in the ventral striatum nucleus accumbens (NAc), the target of mesolimbic dopaminergic innervation. We find that the reduction of RET within the VTA hastens cocaine-induced conditioned place preference extinction and reduces reinstatement, while the reduction of GDNF within the NAc does the opposite: prolongs cocaine-induced conditioned place preference and increases preference during reinstatement. In addition, the brain-derived neurotrophic factor (BDNF) was increased and key dopamine-related genes were reduced in the GDNF cKO mutant animals after cocaine administration. Thus, RET antagonism in the VTA coupled with intact or enhanced accumbal GDNF function may provide a new approach towards cocaine addiction treatment.
Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis
Authors: Silva-Reis Rita , Silva Artur M. S. , Oliveira Paula A. , Cardoso Susana M.
Published: April 2023

Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.
β-Glucan and Fatty Acid Based Mucoadhesive Carrier for Gastrointestinal Tract Specific Local and Sustained Drug Delivery
Authors: Esquivel Stephanie Vargas , Bhatt Himanshu N. , Diwan Rimpy , Habib Ahsan , Lee Wen-Yee , Khatun Zehedina , Nurunnabi Md
Published: April 2023

The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β-Glucan And Docosahexaenoic Acid (GADA) to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.
Neopterin, the Cell-Mediated Immune Response Biomarker, in Inflammatory Periodontal Diseases: A Narrative Review of a More than Fifty Years Old Biomarker
Authors: Heneberk Ondrej , Wurfelova Eliska , Radochova Vladimira
Published: April 2023

Neopterin is a biomarker of the activation of cellular immunity. The purpose of this review is to summarise neopterin metabolism, methods of its detection, and its role in inflammation, focusing on periodontal inflammatory diseases. This derivative of guanosine is a non-enzymatic product of 7,8-dihydroneopterin oxidation caused by free radicals which protect activated macrophages from oxidative stress. Various methods, usually based on enzyme-linked immunosorbent essay, high-performance liquid chromatography, or radioimmunoassay were developed for the isolation of neopterin. A wide spectrum of diseases and conditions are known to affect neopterin levels, including cardiovascular, bacterial, viral, and degenerative diseases, as well as malignant tumours. Neopterin levels were found to increase in subjects with periodontitis, especially when the oral fluid and gingival crevicular fluid were evaluated. These findings confirm the role of activated macrophages and cellular immunity in periodontal inflammatory diseases. The gingival crevicular fluid and the oral fluid appear to be the most valuable biologic fluids for the evaluation of neopterin levels in periodontitis. For gingival crevicular fluid, neopterin can be determined as the concentration or the so-called total amount. Nonsurgical periodontal treatment was associated with a decrease in neopterin levels, but an increase was also reported, suggesting the possible role of macrophages in the resolution of the periodontal lesion.
A Combination of an Angiotensin II Receptor and a Neprilysin Inhibitor Attenuates Liver Fibrosis by Preventing Hepatic Stellate Cell Activation
Authors: Suzuki Junya , Kaji Kosuke , Nishimura Norihisa , Kubo Takahiro , Tomooka Fumimasa , Shibamoto Akihiko , Iwai Satoshi , Tsuji Yuki , Fujinaga Yukihisa , Kitagawa Koh , Namisaki Tadashi , Akahane Takemi , Yoshiji Hitoshi
Published: April 2023

The renin–angiotensin–aldosterone system has gained attention due to its role as a mediator of liver fibrosis and hepatic stellate cell (HSC) activation. Meanwhile, the natriuretic peptide (NP) system, including atrial NP (ANP) and C-type NP (CNP), is a counter-regulatory hormone regulated by neprilysin. Although the combination of an angiotensin receptor and a neprilysin inhibitor (sacubitril/valsartan: SAC/VAL) has shown clinical efficacy in patients with heart failure, its potential effects on hepatic fibrosis have not been clarified. This study assessed the effects of SAC/VAL in carbon tetrachloride (CCl4)-induced murine liver fibrosis as well as the in vitro phenotypes of HSCs. Treatment with SAC and VAL markedly attenuated CCl4-induced liver fibrosis while reducing α-SMA+-HSC expansion and decreasing hepatic hydroxyproline and mRNA levels of pro-fibrogenic markers. Treatment with SAC increased plasma ANP and CNP levels in CCl4-treated mice, and ANP effectively suppressed cell proliferation and TGF-β-stimulated MMP2 and TIMP2 expression in LX-2 cells by activating guanylate cyclase-A/cGMP/protein kinase G signaling. Meanwhile, CNP did not affect the pro-fibrogenic activity of LX-2 cells. Moreover, VAL directly inhibited angiotensin II (AT-II)-stimulated cell proliferation and the expression of TIMP1 and CTGF through the blockade of the AT-II type 1 receptor/protein kinase C pathway. Collectively, SAC/VAL may be a novel therapeutic treatment for liver fibrosis.
Effectiveness of Vestibular Rehabilitation in Improving Health Status and Balance in Patients with Fibromyalgia Syndrome: A Single-Blind Randomized Controlled Trial
Authors: Peinado-Rubia Ana Belén , Osuna-Pérez María Catalina , Cortés-Pérez Irene , Rojas-Navarrete Alicia , Ibancos-Losada María del Rocío , Lomas-Vega Rafael
Published: April 2023

Background: Fibromyalgia Syndrome (FMS) is a highly prevalent health problem whose main symptom is widespread pain, although it presents as other manifestations, such as loss of balance, that seem to mainly affect visuo-vestibular information. Objective: to compare the effects of a Vestibular Rehabilitation (VR) program versus those of a Conventional Physical Exercise (CPE) program on the health status of patients with FMS. Methods: A single-blind randomized controlled trial was performed. Patients with FMS were randomly assigned to VR or CPE programs. The protocols were performed in 40 min group sessions, twice weekly, for 16 sessions. Perceived health status, static and dynamic balance, verticality perception, confidence in balance, sensitization and kinesiophobia were measured at baseline, post-treatment and at the three-month follow-up and analyzed using an intention-to-treat approach. Results: Forty-eight subjects were randomly assigned, of whom thirty-five completed the planned VR (n = 19) or CPE (n = 16) program. At the three-month follow-up, there were differences in physical health status measured with the SF-12 (mean = −4.36, SE = 1.88, p = 0.027), balance during walking (mean = 1.90, SE = 0.57, p = 0.002), the perception of verticality in degrees (mean = 3.61, SE = 1.51, p = 0.024) and the anteroposterior position of the center of pressure (mean = −7.88, SE = 2.80, p = 0.009), as well as a decrease in the number of falls (mean = 0.98, SE = 0.44, p = 0.033), favoring the VR group. Conclusions: Vestibular Rehabilitation can be as beneficial as conventional exercise in improving the state of health in patients with Fibromyalgia Syndrome, providing additional improvements in physical health status, body balance, the perception of verticality and the number of falls.
Differential Modulation of Cerebellar Flocculus Unipolar Brush Cells during Vestibular Compensation
Authors: Liu Dan , Wang Jun , Zhou Liuqing , Tian E , Chen Jingyu , Kong Weijia , Lu Yisheng , Zhang Sulin
Published: April 2023

Vestibular compensation is a natural behavioral recovery process following unilateral vestibular injury. Understanding the mechanism can considerably enhance vestibular disorder therapy and advance the adult central nervous system functional plasticity study after injury. The cerebellum, particularly the flocculonodular lobe, tightly modulates the vestibular nucleus, the center for vestibular compensation; however, it is still unclear if the flocculus on both sides is involved in vestibular compensation. Here we report that the unipolar brush cells (UBCs) in the flocculus are modulated by unilateral labyrinthectomy (UL). UBCs are excitatory interneurons targeting granule cells to provide feedforward innervation to the Purkinje cells, the primary output neurons in the cerebellum. According to the upregulated or downregulated response to the mossy fiber glutamatergic input, UBC can be classified into ON and OFF forms of UBCs. Furthermore, we discovered that the expression of marker genes of ON and OFF UBCs, mGluR1α and calretinin, was increased and decreased, respectively, only in ipsilateral flocculus 4–8 h after UL. According to further immunostaining studies, the number of ON and OFF UBCs was not altered during UL, demonstrating that the shift in marker gene expression level in the flocculus was not caused by the transformation of cell types between UBCs and non-UBCs. These findings imply the importance of ipsilateral flocculus UBCs in the acute response of UL, and ON and OFF UBCs may be involved in vestibular compensation in opposite directions.
Polypharmacy, Potentially Inappropriate Medications, and Drug-to-Drug Interactions in Patients with Chronic Myeloproliferative Neoplasms
Authors: Krečak Ivan , Pivac Ljerka , Lucijanić Marko , Skelin Marko
Published: April 2023

Polypharmacy, potentially inappropriate medications (PIMs), and drug-to-drug interactions (DDIs) are highly prevalent in the elderly and may have adverse effects on health-related outcomes. Their occurrence and clinical and prognostic associations in patients with chronic myeloproliferative neoplasms (MPN) are unknown. We retrospectively evaluated polypharmacy, PIMs, and DDIs in a cohort of 124 MPN patients (essential thrombocythemia, ET = 63, polycythemia vera, PV = 44, myelofibrosis = 9, MPN unclassifiable = 8) from a single community hematology practice. There were 761 drug prescriptions with a median of five prescribed medications per patient. Polypharmacy, at least one PIM (calculated for persons >60 years of age, n = 101), and at least one DDI were recorded in 76 (61.3%), 46 (45.5%), and 77 (62.1%) of patients, respectively. Seventy-four (59.6%) and twenty-one (16.9%) patients had at least one C or at least one D interaction, respectively. Among other associations, polypharmacy and DDIs were associated with older age, management of disease-related symptoms, osteoarthritis/osteoporosis, and different CV disorders. In multivariate analyses adjusted for clinically meaningful parameters, both polypharmacy and DDIs were significantly associated with inferior overall survival (OS) and time to thrombosis (TTT), whereas PIMs had no significant associations with neither OS nor TTT. There were no associations with bleeding or transformation risks. Polypharmacy, DDIs, and PIMs are very frequent among MPN patients and may have important clinical associations.
Efficacy of Fractional CO2 Laser Treatment for Genitourinary Syndrome of Menopause in Short-Term Evaluation—Preliminary Study
Authors: Woźniak Andrzej , Woźniak Sławomir , Poleszak Ewa , Kluz Tomasz , Zapała Łukasz , Woźniak Aleksander , Rechberger Tomasz , Wróbel Andrzej
Published: April 2023

The postmenopausal state covers 40% of modern women’s lives and 50–70% of postmenopausal women report GSM symptoms such as vaginal dryness, itching, frequent inflammations, lack of elasticity, or dyspareunia. Consequently, a safe and effective method of treatment is crucial. In a group of 125 patients, a prospective observational study was performed. The aim was to evaluate the clinical effectiveness of fractional CO2 laser in the treatment of GSM symptoms using a protocol of three procedures in 6-week intervals. The vaginal pH, VHIS, VMI, FSFI, and treatment satisfaction questionnaire were used. The fractional CO2 laser treatment was effective in improving all the objective forms of evaluation: vaginal pH (from 5.61 ± 0.50 at the baseline up to 4.69 ± 0.21 in the 6-week follow-up after the third procedure); VHIS (12.02 ± 1.89 at the baseline vs. 21.50 ± 1.76); VMI (21.5 ± 5.66 vs. 48.4 ± 4.46). Similar results were obtained for FSFI: 12.79 ± 5.351 vs. 24.39 ± 2.733, where 79.77% of patients were highly satisfied. Fractional CO2 laser therapy increases the quality of life by having a beneficial effect on the sexual function of women with GSM symptoms. This effect is obtained by restoring the correct structure and proportions of the cellular composition of the vaginal epithelium. This positive effect was confirmed by both objective and subjective forms of evaluating GSM symptom severity.
Biosensors Based on the Binding Events of Nitrilotriacetic Acid–Metal Complexes
Authors: Zhu Lin , Chang Yong , Li Yingying , Qiao Mingyi , Liu Lin
Published: April 2023

Molecular immobilization and recognition are two key events for the development of biosensors. The general ways for the immobilization and recognition of biomolecules include covalent coupling reactions and non-covalent interactions of antigen–antibody, aptamer–target, glycan–lectin, avidin–biotin and boronic acid–diol. Tetradentate nitrilotriacetic acid (NTA) is one of the most common commercial ligands for chelating metal ions. The NTA–metal complexes show high and specific affinity toward hexahistidine tags. Such metal complexes have been widely utilized in protein separation and immobilization for diagnostic applications since most of commercialized proteins have been integrated with hexahistidine tags by synthetic or recombinant techniques. This review focused on the development of biosensors with NTA–metal complexes as the binding units, mainly including surface plasmon resonance, electrochemistry, fluorescence, colorimetry, surface-enhanced Raman scattering spectroscopy, chemiluminescence and so on.
RIPK1-Induced A1 Reactive Astrocytes in Brain in MPTP-Treated Murine Model of Parkinson’s Disease
Authors: Qiao Chenmeng , Niu Guyu , Zhao Weijiang , Quan Wei , Zhou Yu , Zhang Meixuan , Li Ting , Zhou Shengyang , Huang Wenyan , Zhao Liping , Wu Jian , Cui Chun , Shen Yanqin
Published: April 2023

Neuroinflammation is one of the hallmarks of Parkinson’s disease, including the massive activation of microglia and astrocytes and the release of inflammatory factors. Receptor-interacting protein kinase 1 (RIPK1) is reported to mediate cell death and inflammatory signaling, and is markedly elevated in the brain in PD mouse models. Here, we aim to explore the role of RIPK1 in regulating the neuroinflammation of PD. C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20 mg/kg four times/day), followed by necrostatin-1 treatment (Nec-1, RIPK1 inhibitor; 1.65 mg/kg once daily for seven days. Notably, the first Nec-1 was given 12 h before MPTP modeling). Behavioral tests indicated that inhibition of RIPK1 greatly relieved motor dysfunction and anxiety-like behaviors of PD mice. It also increased striatal TH expression, rescue the loss of dopaminergic neurons, and reduce activation of astrocytes in the striatum of PD mice. Furthermore, inhibition of RIPK1 expression reduced A1 astrocytes’ relative gene expression (CFB, H2-T23) and inflammatory cytokine or chemokine production (CCL2, TNF-α, IL-1β) in the striatum of PD mice. Collectively, inhibition of RIPK1 expression can provide neuroprotection to PD mice, probably through inhibition of the astrocyte A1 phenotype, and thus RIPK1 might be an important target in PD treatment.