bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Frequent or Chronic Primary Headaches in Children and Adolescents: Focus on Acupuncture
Authors: Bonemazzi Ilaria , Nosadini Magherita , Pelizza Maria Federica , Paolin Chiara , Cavaliere Elena , Sartori Stefano , Toldo Irene
Published: September 2023

Background: Acupuncture is a spreading and promising intervention, which has proven to be very useful in the treatment and prevention of chronic pain, in particular chronic headaches, in adults; the literature about the treatment of pediatric chronic headaches is scarce. In addition, few guidelines advise its use in children. The aim of this review is to collect all relevant studies with available data about the use, effect, and tolerability of acupuncture as a treatment for pediatric primary headaches. Methods: This is a narrative review based on eight studies selected from 135 papers including pediatric cases treated with acupuncture for headache. Results: Despite the differences in tools, procedures, and application sites, acupuncture demonstrated a positive effect on both the frequency and intensity of headaches and was well tolerated. There are no studies considering the long-term efficacy of acupuncture. Conclusion: Further additional studies are needed on acupuncture in children and adolescents, with larger series and standardized procedures, in order to better assess efficacy, tolerability, and long-term prognosis and to define guidelines for the use of this promising and safe treatment. It is particularly relevant to identify safe and well-tolerated treatment options in pediatric patients affected by recurrent and debilitating headaches.
Effects of Stress State, Crack—γ/γ′ Phase Interface Relative Locations and Orientations on the Deformation and Crack Propagation Behaviors of the Ni-Based Superalloy—A Molecular Dynamics Study
Authors: Qin Xinmao , Liang Yilong , Gu Jiabao
Published: September 2023

In this study, we systematically investigate the influence of stress states, relative locations, and orientations of crack—γ/γ′ phase interfaces on the deformation and crack propagation behaviors of the Ni-based superalloy through molecular dynamics simulations. The stress state with high stress triaxiality will impede the plastic deformation process of the system, thereby promoting brittle crack propagation within the system. But the stress state of low stress triaxiality results in obvious plastic deformation and plastic crack propagation behaviors of the system. The deformation system with cracks located in both the γ and γ′ phase exhibits the slowest growth rate, regardless of applied stress states. Additionally, the deformation process demonstrates prominent plastic behavior. For the deformation system with cracks perpendicular to the γ/γ′ phase interface, the γ/γ′ phase interface will hinder the crack propagation. Our research provides interesting observations on deformation and crack propagation behaviors at an atomic level and at a nano-scale which are important for understanding deformation and fracture behaviors at a macroscopic scale for the Ni-based superalloy.
Evaluation of Laser Lap Weldability between the Titanium Alloy Ti-6Al-4V and Aluminum Alloy 6060-T6
Authors: Fernandes Fábio A. O. , Gonçalves José J. M. , Pereira António B.
Published: September 2023

This work investigates laser weldability between non-ferrous dissimilar metallic materials, specifically the aluminum 6060-T6 alloy and titanium Ti-6Al-4V. These materials are used in several engineering applications, including aerospace. In a simple lap joint configuration, these were welded with a pulsed Nd:YAG laser, with direct incidence on the titanium piece. Preheating and post-weld heating were introduced to mitigate cracking issues. Based on the primary experiments, the main variables were the peak laser power, which varied between 60 and 70%, and the number of beads (a single bead and double beads). The quality of the welds was assessed via uniaxial tensile tests, subjecting the joint to shear loading. Additionally, SEM micrographs were obtained to analyze the quality of the fusion between the dissimilar alloys. The higher strength of the welded samples achieved was 90 MPa, which is close to the reported value for the aluminum base material. A fracture occurred near the weld bead in the heat-affected zone (HAZ). The observed microporosities and cracks explain the lower value as compared to the base material. Although these were mitigated through the thermal cycle strategy employed and the shielding gas, they were not entirely avoided.
Schiff Base Derivatives in Zinc(II) and Cadmium(II) Complexation with the closo-Dodecaborate Anion
Authors: Nikiforova Svetlana E. , Khan Nadezhda A. , Kubasov Alexey S. , Koshchienko Yurii V. , Burlov Anatolii S. , Divaeva Lyudmila N. , Goeva Lyudmila V. , Avdeeva Varvara V. , Malinina Elena A. , Kuznetsov Nikolay T.
Published: September 2023

A series of Schiff base derivatives, namely N-(4-methoxyphenyl)-1-(1-methylbenzimidazol-2-yl)methanimine (L1), 4-methoxy-N-[(1-methylbenzimidazol-2-yl)methyl]aniline (L2), and 2-[(E)-(1-propylbenzimidazol-2-yl)iminomethyl]phenol (L3), were synthesized. These compounds feature different linker groups, including –CH=N–, –CH2–NH–, and –N=CH–, respectively. During the process of zinc(II) and cadmium(II) complexation in the presence of the closo-dodecaborate [B12H12]2– anion, it was observed that ligand L3 underwent degradation. Consequently, two compounds were isolated, [Zn(Bz-NH2)2(CH3COO)2] and (HBz-NH2)2[B12H12]∙2CH3CN, both containing 1-propyl-2-aminobenzimidazole (Bz-NH2), which is a degraded fragment of the ligand. Several new zinc(II) and cadmium(II) coordination compounds were synthesized and characterized using various physicochemical analysis methods, including elemental analysis, IR, and UV spectroscopy. Additionally, X-ray diffraction and Hirshfeld surface analysis were performed for compounds [Cd(L2)2(CH3CN)(H2O)][B12H12], [Zn(Bz-NH2)2(CH3COO)2], and (HBz-NH2)2[B12H12]∙2CH3CN, as well as for ligand L2.
Monitoring of Joint Gap Formation in Laser Beam Butt Welding using Neural Network-Based Acoustic Emission Analysis
Authors: Gourishetti Saichand , Schmidt Leander , Römer Florian , Schricker Klaus , Kodera Sayako , Böttger David , Krüger Tanja , Kátai András , Bös Joachim , Straß Benjamin , Wolter Bernd , Bergmann Jean Pierre
Published: September 2023

This study aimed to explore the feasibility of using airborne acoustic emission in laser beam butt welding for the development of an automated classification system based on neural networks. The focus was on monitoring the formation of joint gaps during the welding process. To simulate various sizes of butt joint gaps, controlled welding experiments were conducted, and the emitted acoustic signals were captured using audible-to-ultrasonic microphones. To implement an automated monitoring system, a method based on short-time Fourier transformation was developed to extract audio features, and a convolutional neural network architecture with data augmentation was utilized. The results demonstrated that this non-destructive and non-invasive approach was highly effective in detecting joint gap formations, achieving an accuracy of 98%. Furthermore, the system exhibited promising potential for the low-latency monitoring of the welding process. The classification accuracy for various gap sizes reached up to 90%, providing valuable insights for characterizing and categorizing joint gaps accurately. Additionally, increasing the quantity of training data with quality annotations could potentially improve the classifier model’s performance further. This suggests that there is room for future enhancements in the study.
Nivolumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Retrospective Tertiary Centre’s Real-World Experience
Authors: Du Yue (Jennifer) , Fu Rui , Levinsky Justin T. , Kamalraj Pabiththa , Chan Kelvin K. W. , Parmar Ambica , Eskander Antoine , Smoragiewicz Martin
Published: September 2023

Nivolumab, a PD-1 checkpoint inhibitor, was approved in Canada in 2017 for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on the phase 3 trial CHECKMATE-141. We aimed to examine the demographics and efficacy of nivolumab in a Canadian, real-world setting. A retrospective chart review was performed on patients who received nivolumab for R/M HNSCC from 2017 to 2020 at a high-volume cancer centre. Data were abstracted from 34 patients, based on physician notes and imaging reports. The median patient age at nivolumab initiation was 61, 24% were female, and 62% were current or former smokers. Prior to nivolumab, 44% of patients underwent surgery, 97% radiation, and 100% chemotherapy. Most (97%) therapies were for primary disease. Overall survival at 6 and 12 months following drug initiation was 38% and 23%, respectively. Progression-free survival at 6 and 12 months was 33% and 22%, respectively. Eighteen percent of patients experienced an immune-related adverse event, the most common of which was pneumonitis (3/8) and endocrine events (3/8). Seven out of eight of the immune adverse events were grade 1–2; 1/8 was grade 3. Nivolumab appears to have decreased survival rates in our single-centre Canadian population compared to CHECKMATE-141 and presented a manageable adverse event profile for R/M HNSCC.
Environmental Correlates to Genetic Diversity and Structure in Invasive Apple Snail (Pomacea canaliculata) Populations in China
Authors: Liu Xiongjun , Zhou Yu , Ouyang Shan , Wu Xiaoping
Published: September 2023

Invasive species are one of the most serious threats to biodiversity. Pomacea canaliculata is considered one of the world’s 100 worst invasive species. Major determinants of invasive species distribution are their environmental tolerances, and an understanding of correlations between local environmental variables (e.g., pH, concentration of dissolved oxygen) and genetic diversity is necessary to better prevent and manage the spread of invasive species. However, while such studies have demonstrated associations between the distribution and density of P. canaliculata and water quality correlates, the principal mechanisms relating genetic and these environmental correlates have not been fully articulated. Here, the correlation between physicochemical parameters and genetics of P. canaliculata were analyzed. The results showed that P. canaliculata among the six collection locations had robust genetic diversity, significant genetic differentiation, limited gene flow, and stable population dynamics. RDA analysis showed that genetic variation in P. canaliculata was significantly correlated with concentration of dissolved oxygen and pH. These results will provide a basis for effectively preventing and managing the spread of invasive species and identifying which habitats may be more at risk of invasion.
Diversity of Inland Wetlands: Important Roles in Mitigation of Human Impacts
Authors: Zelnik Igor , Germ Mateja
Published: September 2023

Inland wetlands are one of the most vulnerable ecosystems on Earth and have one of the highest rates of decline in surface and biodiversity [...]
A Unmanned Aerial Vehicle (UAV)/Unmanned Ground Vehicle (UGV) Dynamic Autonomous Docking Scheme in GPS-Denied Environments
Authors: Cheng Cheng , Li Xiuxian , Xie Lihua , Li Li
Published: September 2023

This study designs a navigation and landing scheme for an unmanned aerial vehicle (UAV) to autonomously land on an arbitrarily moving unmanned ground vehicle (UGV) in GPS-denied environments based on vision, ultra-wideband (UWB) and system information. In the approaching phase, an effective multi-innovation forgetting gradient (MIFG) algorithm is proposed to estimate the position of the UAV relative to the target using historical data (estimated distance and relative displacement measurements). Using these estimates, a saturated proportional navigation controller is developed, by which the UAV can approach the target, making the UGV enter the field of view (FOV) of the camera deployed in the UAV. Then, a sensor fusion estimation algorithm based on an extended Kalman filter (EKF) is proposed to achieve accurate landing. Finally, a numerical example and a real experiment are used to support the theoretical results.
Complexity Synchronization of Organ Networks
Authors: West Bruce J. , Grigolini Paolo , Kerick Scott E. , Franaszczuk Piotr J. , Mahmoodi Korosh
Published: September 2023

The transdisciplinary nature of science as a whole became evident as the necessity for the complex nature of phenomena to explain social and life science, along with the physical sciences, blossomed into complexity theory and most recently into complexitysynchronization. This science motif is based on the scaling arising from the 1/f-variability in complex dynamic networks and the need for a network of networks to exchange information internally during intra-network dynamics and externally during inter-network dynamics. The measure of complexity adopted herein is the multifractal dimension of the crucial event time series generated by an organ network, and the difference in the multifractal dimensions of two organ networks quantifies the relative complexity between interacting complex networks. Information flows from dynamic networks at a higher level of complexity to those at lower levels of complexity, as summarized in the ‘complexity matching effect’, and the flow is maximally efficient when the complexities are equal. Herein, we use the scaling of empirical datasets from the brain, cardiovascular and respiratory networks to support the hypothesis that complexity synchronization occurs between scaling indices or equivalently with the matching of the time dependencies of the networks’ multifractal dimensions.
Deep-Learning-Based Classification of Cyclic-Alternating-Pattern Sleep Phases
Authors: Kahana Yoav , Aberdam Aviad , Amar Alon , Cohen Israel
Published: September 2023

Determining the cyclic-alternating-pattern (CAP) phases in sleep using electroencephalography (EEG) signals is crucial for assessing sleep quality. However, most current methods for CAP classification primarily rely on classical machine learning techniques, with limited implementation of deep-learning-based tools. Furthermore, these methods often require manual feature extraction. Herein, we propose a fully automatic deep-learning-based algorithm that leverages convolutional neural network architectures to classify the EEG signals via their time-frequency representations. Through our investigation, we explored using time-frequency analysis techniques and found that Wigner-based representations outperform the commonly used short-time Fourier transform for CAP classification. Additionally, our algorithm incorporates contextual information of the EEG signals and employs data augmentation techniques specifically designed to preserve the time-frequency structure. The model is developed using EEG signals of healthy subjects from the publicly available CAP sleep database (CAPSLPDB) on Physionet. An experimental study demonstrates that our algorithm surpasses existing machine-learning-based methods, achieving an accuracy of 77.5% on a balanced test set and 81.8% when evaluated on an unbalanced test set. Notably, the proposed algorithm exhibits efficiency and scalability, making it suitable for on-device implementation to enhance CAP identification procedures.
Compliance Prediction for Structural Topology Optimization on the Basis of Moment Invariants and a Generalized Regression Neural Network
Authors: Zhao Yunmei , Chen Zhenyue , Dong Yiqun
Published: September 2023

Topology optimization techniques are essential for manufacturing industries, such as designing fiber-reinforced polymer composites (FRPCs) and structures with outstanding strength-to-weight ratios and light weights. In the SIMP approach, artificial intelligence algorithms are commonly utilized to enhance traditional FEM-based compliance minimization procedures. Based on an effective generalized regression neural network (GRNN), a new deep learning algorithm of compliance prediction for structural topology optimization is proposed. The algorithm learns the structural information using a fourth-order moment invariant analysis of the structural topology obtained from FEA at different iterations of classical topology optimization. A cantilever and a simply supported beam problem are used as ground-truth datasets, and the moment invariants are used as independent variables for input features. By comparing it with the well-known convolutional neural network (CNN) and deep neural network (DNN) models, the proposed GRNN model achieves a high prediction accuracy (R2 > 0.97) and drastically shortens the training and prediction cost. Furthermore, the GRNN algorithm exhibits excellent generalization ability on the prediction performance of the optimized topology with rotations and varied material volume fractions. This algorithm is promising for the replacement of the FEA calculation in the SIMP method, and can be applied to real-time optimization for advanced FRPC structure design.
Prediction of Battery Return Volumes for 3R: Remanufacturing, Reuse, and Recycling
Authors: Kampker Achim , Heimes Heiner Hans , Offermanns Christian , Frank Merlin , Klohs Domenic , Nguyen Khanh
Published: September 2023

Life cycle strategies for traction batteries, such as remanufacturing, reuse, and recycling of retired automotive lithium-ion batteries (LIBs), have received growing attention, as large volumes of LIBs will retire in the near future and the demand for LIBs continues to grow. At the same time, the relevance of the sustainability of a battery system over its entire life cycle is increasing as factors such as the EU Battery Regulation provide greater market and product transparency. As a result, research and industry require forecasts in order to assess the future market situation and to make well-founded decisions. Therefore, this paper provides forecasts of the return volumes of battery systems from BEVs and PHEVs up to 2035. Additionally, a representative European battery pack for PHEVs and BEVs was evaluated for each year since 2013, based on the ten vehicles with the largest market share in each year until 2021. In addition, the battery return streams are divided into three different 3R strategies based on expert interviews in order to evaluate the upcoming workload in these areas. The term “3R” refers to the sum of the currently existing pathways around reuse, remanufacturing, and recycling. In 2030, about 38.8 GWh will return and enter the recycling process annually. For battery reuse, about 13 GWh will return every year from 2030 onwards, ready to be used in stationary storage for energy transition. Compared to this, battery remanufacturing is expected to be supplied with a slightly lower volume of approximately 11 GWh per year.
Design of Zonal E/E Architectures in Vehicles Using a Coupled Approach of k-Means Clustering and Dijkstra’s Algorithm
Authors: Maier Jonas , Reuss Hans-Christian
Published: September 2023

Electromobility and autonomous driving has started a transformation in the automotive industry, resulting in new requirements for vehicle systems. Due to its functions, the electrical/electronic (E/E) architecture is one of the essential systems. Zonal E/E architecture is a promising approach to tackle this issue. The research presented in this paper describes a methodology for determining the optimal number of zones, the position of the zone control units (ZCU), and the assignment of electric components to these zones and ZCUs. Therefore, the design of the power supply and the wiring harness is essential. This approach aims to identify the most suitable system architecture for a given vehicle geometry and a set of electric components. For this purpose, the assignment of electric components is accomplished by k-means clustering, and Dijkstra’s algorithm is used to optimize the cable routing. As ZCUs will be the hubs for the in-vehicle data and information transport in zonal architectures, their position and their number are crucial for the architecture and wiring harness development. Simulations show a suitable zonal architecture reduces wiring harness length as well as weight and brings functional benefits. However, the number of zones must be chosen with care, as there may also be functional limitations.
Simple Strategy for Torque Ripple Minimization in Switched Reluctance Motor Drives
Authors: Almirante Italo , Lorenzani Emilio
Published: September 2023

This article proposes a new simulation strategy to support the calculation of the angular interval of the current supply to minimize the torque ripple in switched reluctance machines, focusing on the motor working condition. Supposing the best angular interval is strongly linked to the working condition of the machine, a formula is needed to calculate the boundary angles of the intervals of the current supply for each phase, starting from real-time speed and electromagnetic torque. Starting from the dataset of simulations made with this new strategy, linear regression was used to train a model that computes useful formulas. The aim of this research is to show how the application of simple calculations allows torque ripple and power losses to be reduced, i.e., RMS phase currents, without altering the geometry of the machine. Simulations on a virtual four-phase 8/6 SRM are carried out to verify the model’s feasibility and effectiveness, even though this strategy can be easily applied to all other configurations of SRMs.
Creep Performance and Life Prediction of Bamboo Scrimber under Long-Term Tension in Parallel-to-Grain
Authors: Liu Caimei , Wu Xizhi , Liu Xiubo , Li Xianjun
Published: September 2023

Creep performance is a crucial factor that must be considered in structural design. This paper aims to investigate the creep failure mode, creep strain, creep compliance, and other creep properties of bamboo scrimber under long-term tension in parallel-to-grain. To establish a general creep life prediction method for the full stress level of the bamboo scrimber, a multi-branch Kelvin–Voigt model, a generalized Maxwell model, and a creep finite element simulation were employed. The results showed that the creep strain curve of bamboo scrimber included the unsteady creep stage and the stable creep stage, but not the accelerated creep stage. When the stress ratio was less than 0.3, the residual strength decreased gradually. Below 70% of the ultimate load capacity, the creep characteristics of the bamboo scrimber were linear viscoelastic, and the creep compliance was generally independent of the load level. The creep finite element model of bamboo scrimber could accurately calculate the creep deformation of specimens. Based on this creep finite element model and creep failure rules, a life prediction model for the full stress level of bamboo scrimber was established, which could accurately predict the creep life. This paper provides theoretical guidance for the creep design of bamboo scrimber in engineering structures.
Enhancing Breeding Potential and Genetic Conservation: A Comprehensive Approach to Plus-Tree Selection for Tilia amurensis Improvement
Authors: Lee Kyungmi , Kim In-Sik , Choi Wan-Yong
Published: September 2023

The timber degradation and overexploitation of Tilia amurensis necessitate strategic genetic resource management. This study presents a comprehensive approach to plus-tree selection, focusing on growth evaluation. Drawing from the procedures developed for evergreen oak, it encompasses base population selection, criteria establishment, forest stand investigation, standardized measurements, and tree selection. This study advances the baseline selection methods by emphasizing growth differentiation through age and environmental adjustments. A total of 62 superior individuals were selected from 176 candidates across 20 populations, effectively expanding the geographical boundaries. This growth-centric improved approach offers practical insights for selective breeding and genetic conservation, and addresses the ecological characteristics of the species. This study underscores the need for further exploration of genetic differentiation and biological traits to provide a foundation for refining T. amurensis tree improvement programs. In a broader context, these findings contribute to the understanding and sustainable management of diverse broadleaf forests.
Deeper Insights into the Effect of Humic Acid on Kitchen Waste Anaerobic Digestion: Enzyme Activities, Microbial Community Dynamics, and Key Metabolic Pathways
Authors: Lyu Lin , Li Yanzeng , Zhang Shenghua , Chen Zhou
Published: September 2023

Anaerobic digestion (AD) represents one of the most eco-friendly approaches for recovering the energy from kitchen waste (KW). This study investigated the impact of humic acid (HA) on AD of KW. Batch experiments were conducted using KW as the substrate, with varying HA dosages. The results revealed that an increase in HA dosage led to an inhibition of methanogenic efficiency by 29.51% and a delayed start-up of AD. The HA exhibited dual effects on enzyme activities during AD, inhibiting hydrolytic enzymes while stimulating acidogenic enzymes. This unique interaction ultimately resulted in a significant 12.32% increase in volatile fatty acid production. Furthermore, HA induced the generation of reactive oxygen species and had a discernible impact on the activity of the electron transfer system. A bioinformatics analysis highlighted that HA promoted the abundance of microorganisms with mediated interspecies electron transfer ability, including DMER64 and Methanosaeta, as well as the Firmicutes phylum, while significantly reducing the abundance of Methanobacterium. Moreover, the KEGG pathway analysis revealed a decrease in hydrolysis and methanogenesis-related genes and an increase in acidogenesis-related genes.
Temporal-Guided Knowledge Graph-Enhanced Graph Convolutional Network for Personalized Movie Recommendation Systems
Authors: Chen Chin-Yi , Huang Jih-Jeng
Published: September 2023

Traditional movie recommendation systems are increasingly falling short in the contemporary landscape of abundant information and evolving user behaviors. This study introduced the temporal knowledge graph recommender system (TKGRS), a ground-breaking algorithm that addresses the limitations of existing models. TKGRS uniquely integrates graph convolutional networks (GCNs), matrix factorization, and temporal decay factors to offer a robust and dynamic recommendation mechanism. The algorithm’s architecture comprises an initial embedding layer for identifying the user and item, followed by a GCN layer for a nuanced understanding of the relationships and fully connected layers for prediction. A temporal decay factor is also used to give weightage to recent user–item interactions. Empirical validation using the MovieLens 100K, 1M, and Douban datasets showed that TKGRS outperformed the state-of-the-art models according to the evaluation metrics, i.e., RMSE and MAE. This innovative approach sets a new standard in movie recommendation systems and opens avenues for future research in advanced graph algorithms and machine learning techniques.
Assessing the Expression of Long INterspersed Elements (LINEs) via Long-Read Sequencing in Diverse Human Tissues and Cell Lines
Authors: Rybacki Karleena , Xia Mingyi , Ahsan Mian Umair , Xing Jinchuan , Wang Kai
Published: September 2023

Transposable elements, such as Long INterspersed Elements (LINEs), are DNA sequences that can replicate within genomes. LINEs replicate using an RNA intermediate followed by reverse transcription and are typically a few kilobases in length. LINE activity creates genomic structural variants in human populations and leads to somatic alterations in cancer genomes. Long-read RNA sequencing technologies, including Oxford Nanopore and PacBio, can directly sequence relatively long transcripts, thus providing the opportunity to examine full-length LINE transcripts. This study focuses on the development of a new bioinformatics pipeline for the identification and quantification of active, full-length LINE transcripts in diverse human tissues and cell lines. In our pipeline, we utilized RepeatMasker to identify LINE-1 (L1) transcripts from long-read transcriptome data and incorporated several criteria, such as transcript start position, divergence, and length, to remove likely false positives. Comparisons between cancerous and normal cell lines, as well as human tissue samples, revealed elevated expression levels of young LINEs in cancer, particularly at intact L1 loci. By employing bioinformatics methodologies on long-read transcriptome data, this study demonstrates the landscape of L1 expression in tissues and cell lines.
Influence of Genotype and Environment on Fruit Phenolic Composition of Olive
Authors: Yılmaz-Düzyaman Hande , Medina-Alonso María G. , Sanz Carlos , Pérez Ana G. , de la Rosa Raúl , León Lorenzo
Published: September 2023

Extra virgin olive oil (EVOO) is renowned for its numerous minor compounds, particularly phenols, which contribute to its health-promoting properties and commercial quality. The phenolic composition of EVOO largely relies on the initial phenolic content of the olive fruits, which represents, therefore, an important trait to be considered in olive breeding programs. However, only limited studies have been conducted so far to compare the relative influence of genotype and environment in the variability of this trait. For that reason, this study aims to assess the influence of genotype (cultivars ‘Arbequina’, ‘Coratina’, ‘Hojiblanca’, ‘Koroneiki’, ‘Martina’, and ‘Picual’) and environment (harvest date, season, and location) on the fruit phenolic content and composition. A wide general variability was obtained in the whole dataset, with total phenols ranging from 6019 to 38,380 μg/g. A stronger effect of the genotype than the environment was observed for total phenolic content (representing 76–90% of total sums of squares) and the different groups of compounds. Notably, significant variations were found among cultivars not only in the total phenol content but also in the percentage of individual compounds within each main phenolic group. Overall, taking into account the entire dataset available, a clear grouping of samples according to genotypes was observed. The results obtained highlight the prominent influence of the genotype (cultivar) over the environment and genotype–environment interactions on the phenolic content and composition in olive fruits; even when considering very contrasting environments as the Mediterranean and subtropical in the present work. These findings suggest the feasibility of breeding selection of new cultivars with distinctive phenolic content and composition.
Contraceptive Behavior in Appalachia: Exploring Use, Nonuse, and Contraceptive Attitudes
Authors: Auerbach Samantha , Agbemenu Kafuli , Lorenz Rebecca , Hequembourg Amy , Ely Gretchen E.
Published: September 2023

Very little is known about contraceptive behavior in Appalachia, a large geographic region in the eastern United States where even basic prevalence estimates of contraceptive use/nonuse are lacking. This study characterizes contraceptive behavior among Appalachians, including contraceptive use, reasons for use, and methods used; contraceptive nonuse and reasons for nonuse; and attitudes about contraception, including acceptability. This is a secondary analysis of a subsample of survey data collected on sexual and reproductive health attitudes, behaviors, and needs among reproductive-age women (18–49 years) living in the Appalachian region (n = 332). Results identify rates of contraceptive use (66.6%) and nonuse (33.1%) among Appalachian residents. Methods used most frequently included those that did not require prescription (i.e., external condoms and natural family planning methods) though many reported the use of intrauterine devices (IUDs). Among nonusers, fear of side effects from contraception and ambivalence towards pregnancy were most commonly selected as the most important reason for not using contraception. Contraception was considered acceptable by this sample overall, and these acceptability attitudes were significantly associated with contraceptive behavior.
Stem Cell Therapy in Children with Traumatic Brain Injury
Authors: Lin Wen-Ya , Wu Kang-Hsi , Chen Chun-Yu , Guo Bei-Cyuan , Chang Yu-Jun , Lee Tai-An , Lin Mao-Jen , Wu Han-Ping
Published: September 2023

Pediatric traumatic brain injury is a cause of major mortality, and resultant neurological sequelae areassociated with long-term morbidity. Increasing studies have revealed stem cell therapy to be a potential new treatment. However, much work is still required to clarify the mechanism of action of effective stem cell therapy, type of stem cell therapy, optimal timing of therapy initiation, combination of cocurrent medical treatment and patient selection criteria. This paper will focus on stem cell therapy in children with traumatic brain injury.
Silencing GMPPB Inhibits the Proliferation and Invasion of GBM via Hippo/MMP3 Pathways
Authors: Huang Zi-Lu , Abdallah Aalaa Sanad , Shen Guang-Xin , Suarez Milagros , Feng Ping , Yu Yan-Jiao , Wang Ying , Zheng Shuo-Han , Hu Yu-Jun , Xiao Xiang , Liu Ya , Liu Song-Ran , Chen Zhong-Ping , Li Xiao-Nan , Xia Yun-Fei
Published: September 2023

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.
Novel Approaches to the Establishment of Local Microenvironment from Resorbable Biomaterials in the Brain In Vitro Models
Authors: Kolotyeva Nataliya A. , Gilmiyarova Frida N. , Averchuk Anton S. , Baranich Tatiana I. , Rozanova Nataliya A. , Kukla Maria V. , Tregub Pavel P. , Salmina Alla B.
Published: September 2023

The development of brain in vitro models requires the application of novel biocompatible materials and biopolymers as scaffolds for controllable and effective cell growth and functioning. The “ideal” brain in vitro model should demonstrate the principal features of brain plasticity like synaptic transmission and remodeling, neurogenesis and angiogenesis, and changes in the metabolism associated with the establishment of new intercellular connections. Therefore, the extracellular scaffolds that are helpful in the establishment and maintenance of local microenvironments supporting brain plasticity mechanisms are of critical importance. In this review, we will focus on some carbohydrate metabolites—lactate, pyruvate, oxaloacetate, malate—that greatly contribute to the regulation of cell-to-cell communications and metabolic plasticity of brain cells and on some resorbable biopolymers that may reproduce the local microenvironment enriched in particular cell metabolites.
Clinical Significance of Extracellular Vesicles in Prostate and Renal Cancer
Authors: Chen Tzu-Yi , Mihalopoulos Meredith , Zuluaga Laura , Rich Jordan , Ganta Teja , Mehrazin Reza , Tsao Che-Kai , Tewari Ash , Gonzalez-Kozlova Edgar , Badani Ketan , Dogra Navneet , Kyprianou Natasha
Published: September 2023

Extracellular vesicles (EVs)—including apoptotic bodies, microvesicles, and exosomes—are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC.
Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss
Authors: Gu Dong Ryun , Yang Hyun , Kim Seong Cheol , Hwang Youn-Hwan , Ha Hyunil
Published: September 2023

Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica’s radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption.
Cyclodextrin-Mediated Cholesterol Depletion Induces Adiponectin Secretion in 3T3-L1 Adipocytes
Authors: Chiang Yu-Ting , Wu Ying-Yu , Lin Yu-Chun , Huang Yu-Yao , Lu Juu-Chin
Published: September 2023

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-β-cyclodextrin (MβCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MβCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MβCD-induced adiponectin secretion. MβCD-induced adiponectin secretion was reduced after 10 μg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann–Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MβCD-induced adiponectin secretion. Furthermore, treatment with 1 μM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MβCD-induced adiponectin secretion. Finally, MβCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MβCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.
Circulating Levels of IL-8 and MCP-1 in Healthy Adults: Changes after an Acute Aerobic Exercise and Association with Body Composition and Energy Metabolism
Authors: Lagzdina Rudite , Rumaka Maija , Gersone Gita , Tretjakovs Peteris
Published: September 2023

The most recent WHO recommendations about physical activity emphasise the importance of total exercise volume above the significance of the duration of each bout. This study examined whether acute aerobic exercise changes circulating levels of IL-8 and MCP-1 and if these changes are associated with body composition and energy metabolism. Healthy adult volunteers completed a 10 min walking–running exercise on a treadmill. Indirect calorimetry was used to determine their resting metabolic rate (RMR) and energy expenditure (EE) during the exercise. Pre-exercise levels of IL-8 and MCP-1 were similar in both sexes. There were positive correlations of pre-exercise IL-8 with body mass, waist circumference, and lean body mass in men and pre-exercise MCP-1 with RMR in women. The exercise led to an increase in IL-8 of 68% and a decrease in MCP-1 of 74% of participants. An increase in post-exercise IL-8 in men was associated with greater walking EE and a greater increase in walking EE. The increase in post-exercise MCP-1 was associated with a lower RMR and running EE in women. There are both sex and individual variations in changes in chemokine secretion in response to the same exercise situation and their associations with values of metabolic parameters.
Effects of an Adipose Mesenchymal Stem Cell-Derived Conditioned medium and TGF-β1 on Human Keratinocytes In Vitro
Authors: Ademi Hyrije , Michalak-Micka Katarzyna , Moehrlen Ueli , Biedermann Thomas , Klar Agnes S.
Published: September 2023

Human keratinocytes play a crucial role during skin wound healing and in skin replacement therapies. The secretome of adipose-derived stem cells (ASCs) has been shown to secrete pro-healing factors, among which include TGF-β1, which is essential for keratinocyte migration and the re-epithelialization of cutaneous wounds during skin wound healing. The benefits of an ASC conditioned medium (ASC-CM) are primarily orchestrated by trophic factors that mediate autocrine and paracrine effects in keratinocytes. Here, we evaluated the composition and the innate characteristics of the ASC secretome and its biological effects on keratinocyte maturation and wound healing in vitro. In particular, we detected high levels of different growth factors, such as HGF, FGFb, and VEGF, and other factors, such as TIMP1 and 4, IL8, PAI-1, uPA, and IGFBP-3, in the ASC-CM. Further, we investigated, using immunofluorescence and flow cytometry, the distinct effects of a human ASC-CM and/or synthetic TGF-β1 on human keratinocyte proliferation, migration, and cell apoptosis suppression. We demonstrated that the ASC-CM increased keratinocyte proliferation as compared to TGF-β1 treatment. Further, we found that the ASC-CM exerted cell cycle progression in keratinocytes via regulating the phases G1, S, and G2/M. In particular, cells subjected to the ASC-CM demonstrated increased DNA synthesis (S phase) compared to the TGF-β1-treated KCs, which showed a pronounced G0/G1 phase. Furthermore, both the ASC-CM and TGF-β1 conditions resulted in a decreased expression of the late differentiation marker CK10 in human keratinocytes in vitro, whereas both treatments enhanced transglutaminase 3 and loricrin expression. Interestingly, the ASC-CM promoted significantly increased numbers of keratinocytes expressing epidermal basal keratinocyte markers, such DLL1 and Jagged2 Notch ligands, whereas those ligands were significantly decreased in TGF-β1-treated keratinocytes. In conclusion, our findings suggest that the ASC-CM is a potent stimulator of human keratinocyte proliferation in vitro, particularly supporting basal keratinocytes, which are crucial for a successful skin coverage after transplantation. In contrast, TGF-β1 treatment decreased keratinocyte proliferation and specifically increased the expression of differentiation markers in vitro.
Pathomechanism of Pruritus in Psoriasis and Atopic Dermatitis: Novel Approaches, Similarities and Differences
Authors: Kaczmarska Agnieszka , Kwiatkowska Dominika , Skrzypek Katarzyna Konstancja , Kowalewski Zbigniew Tadeusz , Jaworecka Kamila , Reich Adam
Published: September 2023

Pruritus is defined as an unpleasant sensation that elicits a desire to scratch. Nearly a third of the world’s population may suffer from pruritus during their lifetime. This symptom is widely observed in numerous inflammatory skin diseases—e.g., approximately 70–90% of patients with psoriasis and almost every patient with atopic dermatitis suffer from pruritus. Although the pathogenesis of atopic dermatitis and psoriasis is different, the complex intricacies between several biochemical mediators, enzymes, and pathways seem to play a crucial role in both conditions. Despite the high prevalence of pruritus in the general population, the pathogenesis of this symptom in various conditions remains elusive. This review aims to summarize current knowledge about the pathogenesis of pruritus in psoriasis and atopic dermatitis. Each molecule involved in the pruritic pathway would merit a separate chapter or even an entire book, however, in the current review we have concentrated on some reports which we found crucial in the understanding of pruritus. However, the pathomechanism of pruritus is an extremely complex and intricate process. Moreover, many of these signaling pathways are currently undergoing detailed analysis or are still unexplained. As a result, it is currently difficult to take an objective view of how far we have come in elucidating the pathogenesis of pruritus in the described diseases. Nevertheless, considerable progress has been made in recent years.
Transcriptome Analysis of Cisplatin, Cannabidiol, and Intermittent Serum Starvation Alone and in Various Combinations on Colorectal Cancer Cells
Authors: Cherkasova Viktoriia , Ilnytskyy Yaroslav , Kovalchuk Olga , Kovalchuk Igor
Published: September 2023

Platinum-derived chemotherapy medications are often combined with other conventional therapies for treating different tumors, including colorectal cancer. However, the development of drug resistance and multiple adverse effects remain common in clinical settings. Thus, there is a necessity to find novel treatments and drug combinations that could effectively target colorectal cancer cells and lower the probability of disease relapse. To find potential synergistic interaction, we designed multiple different combinations between cisplatin, cannabidiol, and intermittent serum starvation on colorectal cancer cell lines. Based on the cell viability assay, we found that combinations between cannabidiol and intermittent serum starvation, cisplatin and intermittent serum starvation, as well as cisplatin, cannabidiol, and intermittent serum starvation can work in a synergistic fashion on different colorectal cancer cell lines. Furthermore, we analyzed differentially expressed genes and affected pathways in colorectal cancer cell lines to understand further the potential molecular mechanisms behind the treatments and their interactions. We found that synergistic interaction between cannabidiol and intermittent serum starvation can be related to changes in the transcription of genes responsible for cell metabolism and cancer’s stress pathways. Moreover, when we added cisplatin to the treatments, there was a strong enrichment of genes taking part in G2/M cell cycle arrest and apoptosis.