bluuebunny/crossref_metadata_2025 huggingface dataset:
Pseudo Labels for Unsupervised Domain Adaptation: A Review
Authors: Li Yundong , Guo Longxia , Ge Yizheng
Published: August 2023

Conventional machine learning relies on two presumptions: (1) the training and testing datasets follow the same independent distribution, and (2) an adequate quantity of samples is essential for achieving optimal model performance during training. Nevertheless, meeting these two assumptions can be challenging in real-world scenarios. Domain adaptation (DA) is a subfield of transfer learning that focuses on reducing the distribution difference between the source domain (Ds) and target domain (Dt) and subsequently applying the knowledge gained from the Ds task to the Dt task. The majority of current DA methods aim to achieve domain invariance by aligning the marginal probability distributions of the Ds. and Dt. Recent studies have pointed out that aligning marginal probability distributions alone is not sufficient and that alignment of conditional probability distributions is equally important for knowledge migration. Nonetheless, unsupervised DA presents a more significant difficulty in aligning the conditional probability distributions because of the unavailability of labels for the Dt. In response to this issue, there have been several proposed methods by researchers, including pseudo-labeling, which offer novel solutions to tackle the problem. In this paper, we systematically analyze various pseudo-labeling algorithms and their applications in unsupervised DA. First , we summarize the pseudo-label generation methods based on the single and multiple classifiers and actions taken to deal with the problem of imbalanced samples. Second, we investigate the application of pseudo-labeling in category feature alignment and improving feature discrimination. Finally, we point out the challenges and trends of pseudo-labeling algorithms. As far as we know, this article is the initial review of pseudo-labeling techniques for unsupervised DA.
Bionic Design of a Novel Portable Hand-Elbow Coordinate Exoskeleton for Activities of Daily Living
Authors: Meng Qingyun , Liu Guanxin , Meng Qiaoling , Xu Xin , Qin Liang , Yu Hongliu
Published: August 2023

This paper presents the mechanical design and test of a portable hand-elbow combination linkage upper limb rehabilitation robot, which can realize the joint movement of the hand joint and elbow joint and reproduce the complete grasping action. The joints that need bionic support are determined according to the characteristics of human upper limbs and hands, and the overall bionic mechanism is designed. The Motion module in SolidWorks is used to simulate and analyze the rehabilitation robot. The measurement experiment and grasping experiment of joint mobility are carried out on the experimental prototype. As a result, the angular displacement and linear displacement curves obtained via the simulation results are smooth. The measurement experiment of the joint range of motion confirms that the joint range of motion is also within the range of the normal joint angle of the human body, and the grasping experiment shows that the exoskeleton can grasp and lift a 1.801-kg cylindrical object and other daily necessities of different shapes. This result shows that the design of the portable hand-elbow combination linkage upper limb rehabilitation robot is reasonable, can satisfy the rehabilitation training requirements of the hand and upper limb, and has some ability to assist users in daily life.
Network Resource Allocation Algorithm Using Reinforcement Learning Policy-Based Network in a Smart Grid Scenario
Authors: Zheng Zhe , Han Yu , Chi Yingying , Yuan Fusheng , Cui Wenpeng , Zhu Hailong , Zhang Yi , Zhang Peiying
Published: August 2023

The exponential growth in user numbers has resulted in an overwhelming surge in data that the smart grid must process. To tackle this challenge, edge computing emerges as a vital solution. However, the current heuristic resource scheduling approaches often suffer from resource fragmentation and consequently get stuck in local optimum solutions. This paper introduces a novel network resource allocation method for multi-domain virtual networks with the support of edge computing. The approach entails modeling the edge network as a multi-domain virtual network model and formulating resource constraints specific to the edge computing network. Secondly, a policy network is constructed for reinforcement learning (RL) and an optimal resource allocation strategy is obtained under the premise of ensuring resource requirements. In the experimental section, our algorithm is compared with three other algorithms. The experimental results show that the algorithm has an average increase of 5.30%, 8.85%, 15.47% and 22.67% in long-term average revenue–cost ratio, virtual network request acceptance ratio, long-term average revenue and CPU resource utilization, respectively.
Design and Validation of a V-Gate n-MOSFET-Based RH CMOS Logic Circuit with Tolerance to the TID Effect
Authors: Ki Donghan , Lee Minwoong , Lee Namho , Cho Seongik
Published: August 2023

This study designed a radiation-hardened (RH) complementary metal oxide semiconductor (CMOS) logic circuit based on an RH variable-gate (V-gate) n-MOSFET that was resistant to the total ionizing dose (TID) effect and evaluated its tolerance to radiation. Among the different CMOS logic circuits, NOT, NAND, and NOR gates were designed using V-gate n-MOSFETs by employing layout transformation techniques and standard p-MOSFETs. Before the process design, we predicted the radiation damage using modeling and simulation techniques and validated the tolerance by conducting actual radiation tests after the process design. Furthermore, we implemented the CMOS logic circuit process design in a 0.18 µm CMOS bulk process. The actual radiation test applied a total cumulative radiation dose of 25 kGy at 5 kGy per hour in a high-level gamma-ray irradiation facility. Consequently, the resistance of the RH CMOS logic circuit based on the RH V-gate n-MOSFET to the TID effect was validated through experiments.
IntME: Combined Improving Feature Interactions and Matrix Multiplication for Convolution-Based Knowledge Graph Embedding
Authors: Zhang Haonan , Liu Xuemei , Li Hairui
Published: August 2023

Knowledge graph embedding is a method to predict missing links in knowledge graphs by learning the interactions between embedded entities and relations in a continuous low-dimensional space. Current research on convolution-based models tends to provide sufficient interactions for extracting potential knowledge. However, sufficient interactions do not mean that they are reasonable. Our studies find that reasonable interactions can further stimulate knowledge extraction capability. Reasonable interactions need to ensure that the elements participating in interactions are disordered and in a reasonable number. To model reasonable interactions that cannot be specifically quantified, we propose a concise and effective model IntME to address this challenge. In detail, we utilize checked feature reshaping and disordered matrix multiplication to form two different types of feature maps to ensure the disorder of the interacting elements and control the number of elements before feature fusion by the shapes of the feature maps after channel scaling reshaping. In feature fusion, we employ large convolution filters and pointwise filters for the deep and shallow linear fusion of feature interactions, which can take into account both explicit and implicit knowledge extraction capability. The evaluations of four benchmark datasets show that IntME has a powerful performance in convolution-based models and a lower training cost, and also demonstrate that our proposed approaches based on reasonable interactions can effectively improve knowledge discovery capability.
Design and Performance Analysis of a Grid-Connected Distributed Wind Turbine
Authors: Murshed Mahtab , Chamana Manohar , Schmitt Konrad Erich Kork , Bhatta Rabindra , Adeyanju Olatunji , Bayne Stephen
Published: August 2023

The utilization of wind energy has become increasingly popular in the United States and many European countries due to its abundant nature and optimized design. While existing wind turbines are predominantly large-scale and not suitable for standalone or distributed power production, Lubbock County in West Texas offers a diverse range of renewable energy options to meet its energy needs. The region relies heavily on utility-scale wind energy sources to supply power to the Texas Grid, replacing conventional fossil fuel-based systems. Currently, standalone solar PV systems are the preferred choice for renewable energy generation. However, West Texas possesses an ample supply of wind energy that can be harnessed to establish a microgrid and provide standalone power to rural communities. Distributed wind energy offers localized power generation, reducing transmission losses and grid strain, while conventional wind farms require long-distance transmission, leading to efficiency gains. By employing the latest technology and optimizing efficiency, even in low-scale generation, a 6-kilowatt permanent magnet alternator-based distributed wind turbine has been designed. This paper focuses on analyzing the techno-economic aspects of implementing this wind turbine in a real-world scenario, taking into account wind attributes, such as velocity and available power, at the specific location.
PhloVer: A Modular and Integrated Tracking Photovoltaic Shading Device for Sustainable Large Urban Spaces—Preliminary Study and Prototyping
Authors: Minelli Federico , D’Agostino Diana , Migliozzi Maria , Minichiello Francesco , D’Agostino Pierpaolo
Published: August 2023

In this work, a flower-shaped shading system with integrated tracking photovoltaic, suitable for sustainable extensive urban coverages, is designed. Detailed photovoltaic energy yield simulations with a single-diode model approach are performed to disclose the potential of the proposed tracking photovoltaic shading device (PVSD). Simulations are performed with reference to a case study. A double-layer space truss is used to house the innovative modular photovoltaic tracking system, and the first application is envisaged for the coverage of a public market area of a sunny municipality in Southern Italy. By comparing it with the traditional photovoltaic fixed system, the results of the simulations show a steadier energy generation of the new PVSD, and it also provides better coverage with renewable energy during the hours of the day when the traditional system produces low electric energy. Lastly, an early interactive prototype of the PVSD system is presented. The tracking mechanism is carefully designed, 3D-printed at a small scale and tested with a motorized dynamic system controlled by a microcontroller board. The realization of the physical prototype and the engineering of the movement mechanism confirmed the feasibility and the correct functioning of the conceived system opening to real-scale applications.
Modelling of the Standalone Onshore Charging Station: The Nexus between Offshore Renewables and All-Electric Ships
Authors: Frković Lovro , Ćosić Boris , Pukšec Tomislav , Vladimir Nikola
Published: August 2023

The environmental sustainability of the battery-powered electric ferry (BEF) depends on the share of renewable energy sources (RESs) in the power system. The BEFs impose significant load on the power grid and it is challenging to achieve their sustainability in isolated energy systems (IES), such as islands that have limited land available for integrating RESs. The proposed solution for achieving the sustainability of BEF in such challenging environments is the integration of a standalone onshore charging station (OCS) powered with a hybrid offshore RES. The nexus between the electricity supply of the offshore photovoltaic (PV) and wind power systems and the electricity demand of BEF can reduce the required capacity of the energy storage systems (ESSs) and improve the environmental and economic performance of the standalone OCS. This study considered 45 standalone OCS scenarios to select the share of the offshore RES that matches the BEF electricity demand and improves the economic and environmental indicators of the standalone OCS. The model included characterisation of the offshore RES electricity supply, BEF electricity demand, critical excess of electricity production (CEEP), critical deficit of electricity production (CDEP) and costs. Simulations were conducted in EnergyPLAN, which used a high-resolution spatiotemporal dataset (8784 h) for the Island of Cres for 2030. The results confirmed that standalone OCS with the hybrid offshore RES provides a better match with BEF electricity demand compared to the scenarios based on an individual offshore RES.
Different Response of Plant- and Microbial-Derived Carbon Decomposition Potential between Alpine Steppes and Meadows on the Tibetan Plateau
Authors: Yuan Yanhong , Chen Lan , Wang Jieying , Liu Yanfang , Ren Chengjie , Guo Yaoxin , Wang Jun , Wang Ninglian , Zhao Fazhu , Wang Wenying
Published: August 2023

The alpine grasslands account for approximately 54.5% of the total carbon in China’s grasslands, and carbohydrate-active enzymes (CAZymes) play key roles in the turnover of carbon. However, the variation and factors influencing gene-encoding enzymes for plant- and microbial-derived carbon decomposition in alpine steppes and alpine meadows remain unclear. Here, the trends in microbial carbohydrate-active enzymes (CAZymes) and their responses to the decomposition of biomass of different origins were studied using metagenomics in the alpine steppes and alpine meadows on the Tibetan Plateau. Our results revealed the abundance of GTs and CBMs was higher in the alpine steppes than in the alpine meadows, whereas AAs were higher in the alpine steppes than in the alpine meadows. Soil properties (i.e., soil water content, soil ammonium nitrogen, and nitrate nitrogen) highly related to CAZyme genes (GTs, CBMs, and AAs) showed an abundant pattern between the alpine steppes and alpine meadows. Moreover, our results indicated that the relative abundance of genes encoding CAZymes involved in the decomposition of plant- (indicated by cellulose, hemicellulose, and lignin) and fungal-derived carbon (indicated by chitin and glucans) was higher by 8.7% and 10.1%, respectively, in the alpine steppes than in the alpine meadows, whereas bacterial-derived carbon (indicated by peptidoglycan) was lower by 7.9% in the alpine steppes than in the alpine meadows. Soil water content (SWC), nitrate nitrogen (NO3−), and pH influenced on the abundance of CAZyme genes involved in the decomposition of plant-, fungal-, bacterial-derived carbon. In addition, the dominant microbial phyla (Actinobacteria, Protebacteria, and Acidobacteria) mineralized carbon sources from plant- and microbial-derived carbon through their corresponding CAZyme families. In conclusion, our study compared plant- and microbial-derived carbon decomposition potentials and influencing factors to illustrate the contribution of dead biomass to carbon accumulation in alpine grasslands.
Wavelet Transforms and Machine Learning Methods for the Study of Turbulence
Authors: Alam Jahrul M
Published: August 2023

This article investigates the applications of wavelet transforms and machine learning methods in studying turbulent flows. The wavelet-based hierarchical eddy-capturing framework is built upon first principle physical models. Specifically, the coherent vortex simulation method is based on the Taylor hypothesis, which suggests that the energy cascade occurs through vortex stretching. In contrast, the adaptive wavelet collocation method relies on the Richardson hypothesis, where the self-amplification of the strain field and a hierarchical breakdown of large eddies drive the energy cascade. Wavelet transforms are computational learning architectures that propagate the input data across a sequence of linear operators to learn the underlying nonlinearity and coherent structure. Machine learning offers a wealth of data-driven algorithms that can heavily use statistical concepts to extract valuable insights into turbulent flows. Supervised machine learning needs “perfect” turbulent flow data to train data-driven turbulence models. The current advancement of artificial intelligence in turbulence modeling primarily focuses on accelerating turbulent flow simulations by learning the underlying coherence over a low-dimensional manifold. Physics-informed neural networks offer a fertile ground for augmenting first principle physics to automate specific learning tasks, e.g., via wavelet transforms. Besides machine learning, there is room for developing a common computational framework to provide a rich cross-fertilization between learning the data coherence and the first principles of multiscale physics.
The Manufacturing and Characterisation of Eugenol-Enclosed Liposomes Produced by Microfluidic Method
Authors: Ghodke Jessica , Ekonomou Sotirios I. , Weaver Edward , Lamprou Dimitrios , Doran Olena , Stratakos Alexandros Ch.
Published: August 2023

In this study, liposomes enclosing eugenol were prepared using microfluidics. Two lipids—1,2-dimyristoyl-sn-glycero-3-phosphocholine, 18:0 (DSPC) and 2-dimyristoyl-sn-glycero-3-phosphocholine, 14:0 (DMPC)—and microfluidic chips with serpentine and Y-shaped micromixing designs were used for the liposomal formulation. Minimum bactericidal concentration (MBC) values indicated that eugenol was more effective against Gram-negative than Gram-positive bacteria. Four different flow-rate ratios (FRR 2:1, 3:1, 4:1, 5:1) were explored. All liposomes’ encapsulation efficiency (EE) was determined: 94.34% for DSPC 3:1 and 78.63% for DMPC 5:1. The highest eugenol release of 99.86% was observed at pH 4, DMPC 3:1 (Y-shaped chip). Liposomes were physically stable at 4, 20 and 37 °C for 60 days as determined by their size, polydispersity index (PDI) and zeta potential (ZP). The most stable liposomes were observed at FRR 5:1 for DSPC. EE, stability, and eugenol release studies proved that the liposomal formulations produced can be used as delivery vehicles to increase food safety.
Effects of Multi-Level Eco-Labels on the Product Evaluation of Meat and Meat Alternatives—A Discrete Choice Experiment
Authors: Kolber Anna , Meixner Oliver
Published: August 2023

Eco-labels are an instrument for enabling informed food choices and supporting a demand-sided change towards an urgently needed sustainable food system. Lately, novel eco-labels that depict a product’s environmental life cycle assessment on a multi-level scale are being tested across Europe’s retailers. This study elicits consumers’ preferences and willingness to pay (WTP) for a multi-level eco-label. A Discrete Choice Experiment was conducted; a representative sample (n = 536) for the Austrian population was targeted via an online survey. Individual partworth utilities were estimated by means of the Hierarchical Bayes. The results show higher WTP for a positively evaluated multi-level label, revealing consumers’ perceived benefits of colorful multi-level labels over binary black-and-white designs. Even a negatively evaluated multi-level label was associated with a higher WTP compared to one with no label, pointing towards the limited effectiveness of eco-labels. Respondents’ preferences for eco-labels were independent from their subjective eco-label knowledge, health consciousness, and environmental concern. The attribute “protein source” was most important, and preference for an animal-based protein source (beef) was strongly correlated with consumers’ meat attachment, implying that a shift towards more sustainable protein sources is challenging, and sustainability labels have only a small impact on the meat product choice of average consumers.
Optimization of Ultrasound-Assisted Extraction of Dietary Fiber from Yellow Dragon Fruit Peels and Its Application in Low-Fat Alpaca-Based Sausages
Authors: Vilcapoma Wilber , de Bruijn Johannes , Elías-Peñafiel Carlos , Espinoza Clara , Farfán-Rodríguez Lucero , López Jorge , Encina-Zelada Christian R.
Published: August 2023

The main objective of this study was to optimize the extraction of dietary fiber (insoluble dietary fiber and soluble dietary fiber) and degree of esterification from yellow dragon fruit peels using ultrasound-assisted extraction. Additionally, the study aimed to investigate the potential application of this fiber as a fat replacement in alpaca-based sausages. The optimization process for extracting dietary fiber and degree of esterification involved considering various factors, including the liquid-to-solid ratio, pause time, and total ultrasound application time. A Box–Behnken design consisting of 15 treatments was employed to determine the optimal levels for ultrasound-assisted extraction. The optimized conditions were found to be a liquid-to-solid ratio = 30 mL/g, pause time = 1 s, and total ultrasound application time = 60 min, which resulted in the highest values of insoluble dietary fiber (61.3%), soluble dietary fiber (10.8%), and the lowest value of degree of esterification (39.7%). The predicted values were validated against experimental data and showed no significant differences (p > 0.05). Furthermore, a completely randomized design was utilized to assess the effect of dietary fiber on replacing fat content during the production of alpaca-based sausages. The findings revealed that up to 78% of the fat content could be successfully replaced by soluble dietary fiber obtained from yellow dragon fruit peels when compared to high-fat sausages. Additionally, experimental sausages using soluble dietary fiber showed similar (p > 0.05) quality characteristics, such as hardness (24.2 N), chewiness (11.8 N), springiness (0.900), cohesiveness (0.543), redness (a* = 17.4), and chroma values (20.0), as low-fat commercial sausages.
Impact of Climate Change on the Performance of Permafrost Highway Subgrade Reinforced by Concrete Piles
Authors: Wang Yueyue , Zhao Ying , Mao Xuesong , Yin Shunde
Published: August 2023

Climate change has a detrimental impact on permafrost soil in cold regions, resulting in the thawing of permafrost and causing instability and security issues in infrastructure, as well as settlement problems in pavement engineering. To address these challenges, concrete pipe pile foundations have emerged as a viable solution for reinforcing the subgrade and mitigating settlement in isolated permafrost areas. However, the effectiveness of these foundations depends greatly on the mechanical properties of the interface between the permafrost soil and the pipe, which are strongly influenced by varying thawing conditions. While previous studies have primarily focused on the interface under frozen conditions, this paper specifically investigates the interface under thawing conditions. In this study, direct shear tests were conducted to examine the damage characteristics and shear mechanical properties of the soil-pile interface with a water content of 26% at temperatures of −3 °C, −2 °C, −1 °C, −0.5 °C, and 8 °C. The influence of different degrees of melting on the stress–strain characteristics of the soil-pile interface was also analyzed. The findings reveal that as the temperature increases, the shear strength of the interface decreases. The shear stress-displacement curve of the soil-pile interface in the thawing state exhibits a strain-softening trend and can be divided into three stages: the pre-peak shear stress growth stage, the post-peak shear stress steep drop stage, and the post-peak shear stress reconstruction stage. In contrast, the stress curve in the thawed state demonstrates a strain-hardening trend. The study further highlights that violent phase changes in the ice crystal structure have a significant impact on the peak freezing strength and residual freezing strength at the soil-pile interface, with these strengths decreasing as the temperature rises. Additionally, the cohesion and internal friction angle at the soil-pile interface decrease with increasing temperature. It can be concluded that the mechanical strength of the soil-pile interface, crucial for subgrade reinforcement in permafrost areas within transportation engineering, is greatly influenced by temperature-induced changes in the ice crystal structure.
A Role for Genetic Modifiers in Tubulointerstitial Kidney Diseases
Authors: Leggatt Gary P. , Seaby Eleanor G. , Veighey Kristin , Gast Christine , Gilbert Rodney D. , Ennis Sarah
Published: August 2023

With the increased availability of genomic sequencing technologies, the molecular bases for kidney diseases such as nephronophthisis and mitochondrially inherited and autosomal-dominant tubulointerstitial kidney diseases (ADTKD) has become increasingly apparent. These tubulointerstitial kidney diseases (TKD) are monogenic diseases of the tubulointerstitium and result in interstitial fibrosis and tubular atrophy (IF/TA). However, monogenic inheritance alone does not adequately explain the highly variable onset of kidney failure and extra-renal manifestations. Phenotypes vary considerably between individuals harbouring the same pathogenic variant in the same putative monogenic gene, even within families sharing common environmental factors. While the extreme end of the disease spectrum may have dramatic syndromic manifestations typically diagnosed in childhood, many patients present a more subtle phenotype with little to differentiate them from many other common forms of non-proteinuric chronic kidney disease (CKD). This review summarises the expanding repertoire of genes underpinning TKD and their known phenotypic manifestations. Furthermore, we collate the growing evidence for a role of modifier genes and discuss the extent to which these data bridge the historical gap between apparently rare monogenic TKD and polygenic non-proteinuric CKD (excluding polycystic kidney disease).
The Influence of Social Support on Leisure-Time Physical Activity of the Elderly in the Chinese Village of Fuwen
Authors: Zhou Jiayi , Yang Chen , Yu Jiabin , Zhao Xiaoguang , Wu Jinan , Liu Zhiyong , Li Jianshe , Gu Yaodong
Published: August 2023

The purpose of this study was to examine the associations of social support factors with leisure-time physical activity (LTPA) of older people in Fuwen village. A cross-sectional study included 523 randomly selected elderly people (60+ years) whose LTPA levels were determined using the shortened version of the International Physical Activity Questionnaire (IPAQ-S). A modified version of the Physical Activity Social Support Scale (PASSS) was operated to gather perceived scores of the social support factors. A multivariate linear regression was performed to locate associations of perceived scores of social supports with leisure-time walking (LTW) and moderate and vigorous physical activity (MVPA). The results indicated that social support from family was positively and significantly related to LTW and MVPA in both models. The community factor was positively and significantly correlated with MVPA in both models. The sport club factor was related to LTW and MVPA to some extent. The results suggest that social support from family is the most important motivator for older people’s LTW and MVPA in the village of Fuwen. Social support from the community is the motivator for older people’s MVPA. The sport club factor has some effects on older people’s LTW and MVPA as well. More future studies are needed to extend the database of the relationship between social support and rural older people’s physical activity.
Toxic Epidermal Necrolysis, A Serious Side Effect of Tenoxicam Use: A Case Report
Authors: Neagu Tiberiu Paul , Tiglis Mirela , Peride Ileana , Niculae Andrei
Published: August 2023

Tenoxicam, a selective cyclooxygenase (COX)-2 inhibitor, has potent analgesic and anti-inflammatory effects and is frequently used for out-of-hospital pain control. Even though other non-steroidal anti-inflammatory drugs were incriminated in Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) appearance, the literature is scarce regarding this agent. We report a case of tenoxicam-induced toxic epidermal necrolysis, detailing the multidisciplinary approach in a patient presenting skin detachment of 90% of the total body surface area, with concomitant ocular, oral, nasal, and vaginal mucosae involvement. A skin biopsy confirmed the diagnosis. The immediate cessation of the incriminated drug and rapid initiation of systemic steroids, along with topical therapies, and isolation into a specific environmental condition to limit skin infection were the cornerstones of therapeutic management. The patient was discharged with skin hyperpigmentation area and mild anxiety as long-term sequels. This report emphasized that severe or complicated cases should be transferred to a specialized burn center to reduce mortality risk and long-term morbidity.
Evaluation of a Primary E-Health Intervention for People with Alcohol Use Disorder: Clinical Characteristics of Users and Efficacy
Authors: Stüben Nathalie , Franke Andreas Guenter , Soyka Michael
Published: August 2023

In Germany, only about 10% of patients with alcohol use disorder (AUD) are treated by the professional help system. “The First 30 Days without Alcohol”, an interactive e-health intervention, was developed to support people with “alcohol problems” to abstain from alcohol. The aim of this study was to examine the feasibility of the approach, the program’s target group, if and why it is effective. In March 2022 an email was sent to all users who had completed the program. A link to a web-based survey regarding the target group’s characteristics, its alcohol-use patterns, former attempts to change the problematic drinking behavior and experience with the program was introduced. The Alcohol Use Disorders Identification Test (AUDIT) was used prior and post intervention. A total of 718 participants completed the questionnaire. Of these, 99.2% suffered from AUD; 81.6% of participants were females, and about one third reported some form of psychiatric comorbidity; 46.6% did not use any additional help or assistance apart from the program; 78.3% reported to be abstinent after participation in the 30-day program, and the data show a significant AUDIT score reduction. Primary e-health interventions may contribute to the established addiction-help system. The intervention seems to reach predominantly highly educated and high-functioning females because of their characteristics.
Bioactive Compounds for Customized Brain Health: What Are We and Where Should We Be Heading?
Authors: Begdache Lina , Marhaba Rani
Published: August 2023

Many strides have been made in the field of nutrition that are making it an attractive field not only to nutrition professionals but also to healthcare practitioners. Thanks to the emergence of molecular nutrition, there is a better appreciation of how the diet modulates health at the cellular and molecular levels. More importantly, the advancements in brain imaging have produced a greater appreciation of the impact of diet on brain health. To date, our understanding of the effect of nutrients on brain health goes beyond the action of vitamins and minerals and dives into the intracellular, molecular, and epigenetic effects of nutrients. Bioactive compounds (BCs) in food are gaining a lot of attention due to their ability to modulate gene expression. In addition, bioactive compounds activate some nuclear receptors that are the target of many pharmaceuticals. With the emergence of personalized medicine, gaining an understanding of the biologically active compounds may help with the customization of therapies. This review explores the prominent BCs that can impact cognitive functions and mental health to deliver a potentially prophylactic framework for practitioners. Another purpose is to identify potential gaps in the literature to suggest new research agendas for scientists.
Ivy Leaf Dry Extract EA 575® Has an Inhibitory Effect on the Signalling Cascade of Adenosine Receptor A2B
Authors: Meurer Fabio , Häberlein Hanns , Franken Sebastian
Published: August 2023

Ivy leaf dry extract EA 575® is used to improve complaints of chronic inflammatory bronchial diseases and acute inflammation of the respiratory tract accompanied by coughing. Its mechanism of action has so far been explained by influencing β2-adrenergic signal transduction. In the present study, we investigated a possible influence on adenosine receptor A2B (A2BAR) signalling, as it has been described to play a significant and detrimental role in chronic inflammatory airway diseases. The influence of EA 575® on A2BAR signalling was assessed with measurements of dynamic mass redistribution. Subsequently, the effects on A2BAR-mediated second messenger cAMP levels, β-arrestin 2 recruitment, and cAMP response element (CRE) activation were examined using luciferase-based HEK293 reporter cell lines. Lastly, the impact on A2BAR-mediated IL-6 release in Calu-3 epithelial lung cells was investigated via the Lumit™ Immunoassay. Additionally, the adenosine receptor subtype mediating these effects was specified, and A2BAR was found to be responsible. The present study demonstrates an inhibitory influence of EA 575® on A2BAR-mediated general cellular response, cAMP levels, β-arrestin 2 recruitment, CRE activation, and IL-6 release. Since these EA 575®-mediated effects occur within a time frame of several hours of incubation, its mode of action can be described as indirect. The present data are the first to describe an inhibitory effect of EA 575® on A2BAR signalling. This may offer an explanation for the beneficial clinical effects of the extract in adjuvant asthma therapy.
Insights into the Mechanism of Action of Antipsychotic Drugs Derived from Animal Models: Standard of Care versus Novel Targets
Authors: Grace Anthony A. , Uliana Daniela L.
Published: August 2023

Therapeutic intervention for schizophrenia relies on blockade of dopamine D2 receptors in the associative striatum; however, there is little evidence for baseline overdrive of the dopamine system. Instead, the dopamine system is in a hyper-responsive state due to excessive drive by the hippocampus. This causes more dopamine neurons to be in a spontaneously active, hyper-responsive state. Antipsychotic drugs alleviate this by causing depolarization block, or excessive depolarization-induced dopamine neuron inactivation. Indeed, both first- and second-generation antipsychotic drugs cause depolarization block in the ventral tegmentum to relieve positive symptoms, whereas first-generation drugs also cause depolarization in the nigrostriatal dopamine system to lead to extrapyramidal side effects. However, by blocking dopamine receptors, these drugs are activating multiple synapses downstream from the proposed site of pathology: the loss of inhibitory influence over the hippocampus. An overactive hippocampus not only drives the dopamine-dependent positive symptoms, but via its projections to the amygdala and the neocortex can also drive negative and cognitive symptoms, respectively. On this basis, a novel class of drugs that can reverse schizophrenia at the site of pathology, i.e., the hippocampal overdrive, could be effective in alleviating all three classes of symptoms of schizophrenia while also being better tolerated.
Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer
Authors: Huang Yu , Fan Yali , Zhao Ziyi , Zhang Xin , Tucker Katherine , Staley Allison , Suo Hongyan , Sun Wenchuan , Shen Xiaochang , Deng Boer , Pierce Stuart R. , West Lindsay , Yin Yajie , Emanuele Michael J. , Zhou Chunxiao , Bae-Jump Victoria
Published: August 2023

Ovarian cancer is the deadliest gynecological malignancy of the reproductive organs in the United States. Cyclin-dependent kinase 1 (CDK1) is an important cell cycle regulatory protein that specifically controls the G2/M phase transition of the cell cycle. RO-3306 is a selective, ATP-competitive, and cell-permeable CDK1 inhibitor that shows potent anti-tumor activity in multiple pre-clinical models. In this study, we investigated the effect of CDK1 expression on the prognosis of patients with ovarian cancer and the anti-tumorigenic effect of RO-3306 in both ovarian cancer cell lines and a genetically engineered mouse model of high-grade serous ovarian cancer (KpB model). In 147 patients with epithelial ovarian cancer, the overexpression of CDK1 was significantly associated with poor prognosis compared with a low expression group. RO-3306 significantly inhibited cellular proliferation, induced apoptosis, caused cellular stress, and reduced cell migration. The treatment of KpB mice with RO-3306 for four weeks showed a significant decrease in tumor weight under obese and lean conditions without obvious side effects. Overall, our results demonstrate that the inhibition of CDK1 activity by RO-3306 effectively reduces cell proliferation and tumor growth, providing biological evidence for future clinical trials of CDK1 inhibitors in ovarian cancer.
Plasminogen System in the Pathophysiology of Sepsis: Upcoming Biomarkers
Authors: Napolitano Filomena , Giudice Valentina , Selleri Carmine , Montuori Nunzia
Published: August 2023

Severe hemostatic disturbances and impaired fibrinolysis occur in sepsis. In the most serious cases, the dysregulation of fibrinolysis contributes to septic shock, disseminated intravascular coagulation (DIC), and death. Therefore, an analysis of circulating concentrations of pro- and anti-fibrinolytic mediators could be a winning strategy in both the diagnosis and the treatment of sepsis. However, the optimal cutoff value, the timing of the measurements, and their combination with coagulation indicators should be further investigated. The purpose of this review is to summarize all relevant publications regarding the role of the main components of the plasminogen activation system (PAS) in the pathophysiology of sepsis. In addition, the clinical value of PAS-associated biomarkers in the diagnosis and the outcomes of patients with septic syndrome will be explored. In particular, experimental and clinical trials performed in emergency departments highlight the validity of soluble urokinase plasminogen activator receptor (suPAR) as a predictive and prognostic biomarker in patients with sepsis. The measurements of PAI-I may also be useful, as its increase is an early manifestation of sepsis and may precede the development of thrombocytopenia. The upcoming years will undoubtedly see progress in the use of PAS-associated laboratory parameters.
Dynamic Properties of the DNA Damage Response Mre11/Rad50 Complex
Authors: Vertemara Jacopo , Tisi Renata
Published: August 2023

DNA double-strand breaks (DSBs) are a significant threat to cell viability due to the induction of genome instability and the potential loss of genetic information. One of the key players for early DNA damage response is the conserved Mre11/Rad50 Nbs1/Xrs2 (MRN/X) complex, which is quickly recruited to the DNA’s ruptured ends and is required for their tethering and their subsequent repair via different pathways. The MRN/X complex associates with several other proteins to exert its functions, but it also exploits sophisticated internal dynamic properties to orchestrate the several steps required to address the damage. In this review, we summarize the intrinsic molecular features of the MRN/X complex through biophysical, structural, and computational analyses in order to describe the conformational transitions that allow for this complex to accomplish its multiple functions.
Targeting Epithelium Dysfunction and Impaired Nasal Biofilms to Treat Immunological, Functional, and Structural Abnormalities of Chronic Rhinosinusitis
Authors: Petalas Konstantinos , Goudakos John , Konstantinou George N.
Published: August 2023

Chronic rhinosinusitis (CRS) with (CRSwNP) or without (CRSsNP) nasal polyps is a prevalent and heterogeneous disorder existing as a spectrum of clinical conditions with complex underlying pathomechanisms. CRS comprises a broad syndrome characterized by multiple immunological features involving complex interactions between the genes, the microbiome, host- and microbiota-derived exosomes, the epithelial barrier, and environmental and micromilieu exposures. The main pathophysiological feature is an epithelial barrier disruption, accompanied by microbiome alterations and unpredictable and multifactorial immunologic overreactions. Extrinsic pathogens and irritants interact with multiple epithelial receptors, which show distinct expression patterns, activate numerous signaling pathways, and lead to diverse antipathogen responses. CRSsNP is mainly characterized by fibrosis and mild inflammation and is often associated with Th1 or Th17 immunological profiles. CRSwNP appears to be associated with moderate or severe type 2 (T2) or Th2 eosinophilic inflammation. The diagnosis is based on clinical, endoscopic, and imaging findings. Possible CRS biomarkers from the peripheral blood, nasal secretions, tissue biopsies, and nasally exhaled air are studied to subgroup different CRS endotypes. The primary goal of CRS management is to maintain clinical control by nasal douching with isotonic or hypertonic saline solutions, administration of nasal and systemic steroids, antibiotics, biologic agents, or, in persistent and more severe cases, appropriate surgical procedures.
Regulatory Effects of ABA and GA on the Expression of Conglutin Genes and LAFL Network Genes in Yellow Lupine (Lupinus luteus L.) Seeds
Authors: Klajn Natalia , Kapczyńska Katarzyna , Pasikowski Paweł , Glazińska Paulina , Kugiel Hubert , Kęsy Jacek , Wojciechowski Waldemar
Published: August 2023

The maturation of seeds is a process of particular importance both for the plant itself by assuring the survival of the species and for the human population for nutritional and economic reasons. Controlling this process requires a strict coordination of many factors at different levels of the functioning of genetic and hormonal changes as well as cellular organization. One of the most important examples is the transcriptional activity of the LAFL gene regulatory network, which includes LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) and ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2 (LEAFY COTYLEDON2), as well as hormonal homeostasis–of abscisic acid (ABA) and gibberellins (GA) in particular. From the nutritional point of view, the key to seed development is the ability of seeds to accumulate large amounts of proteins with different structures and properties. The world’s food deficit is mainly related to shortages of protein, and taking into consideration the environmental changes occurring on Earth, it is becoming necessary to search for a way to obtain large amounts of plant-derived protein while maintaining the diversity of its origin. Yellow lupin, whose storage proteins are conglutins, is one of the plant species native to Europe that accumulates large amounts of this nutrient in its seeds. In this article we have shown the key changes occurring in the developing seeds of the yellow-lupin cultivar Taper by means of modern molecular biology techniques, including RNA-seq, chromatographic techniques and quantitative PCR analysis. We identified regulatory genes fundamental to the seed-filling process, as well as genes encoding conglutins. We also investigated how exogenous application of ABA and GA3 affects the expression of LlLEC2, LlABI3, LlFUS3, and genes encoding β- and δ-conglutins and whether it results in the amount of accumulated seed storage proteins. The research shows that for each species, even related plants, very specific changes can be identified. Thus the analysis and possibility of using such an approach to improve and stabilize yields requires even more detailed and extended research.
Resilience and Mitigation Strategies of Cyanobacteria under Ultraviolet Radiation Stress
Authors: Singh Varsha K. , Jha Sapana , Rana Palak , Mishra Sonal , Kumari Neha , Singh Suresh C. , Anand Shekhar , Upadhye Vijay , Sinha Rajeshwar P.
Published: August 2023

Ultraviolet radiation (UVR) tends to damage key cellular machinery. Cells may adapt by developing several defence mechanisms as a response to such damage; otherwise, their destiny is cell death. Since cyanobacteria are primary biotic components and also important biomass producers, any drastic effects caused by UVR may imbalance the entire ecosystem. Cyanobacteria are exposed to UVR in their natural habitats. This exposure can cause oxidative stress which affects cellular morphology and vital processes such as cell growth and differentiation, pigmentation, photosynthesis, nitrogen metabolism, and enzyme activity, as well as alterations in the native structure of biomolecules such as proteins and DNA. The high resilience and several mitigation strategies adopted by a cyanobacterial community in the face of UV stress are attributed to the activation of several photo/dark repair mechanisms, avoidance, scavenging, screening, antioxidant systems, and the biosynthesis of UV photoprotectants, such as mycosporine-like amino acids (MAAs), scytonemin (Scy), carotenoids, and polyamines. This knowledge can be used to develop new strategies for protecting other organisms from the harmful effects of UVR. The review critically reports the latest updates on various resilience and defence mechanisms employed by cyanobacteria to withstand UV-stressed environments. In addition, recent developments in the field of the molecular biology of UV-absorbing compounds such as mycosporine-like amino acids and scytonemin and the possible role of programmed cell death, signal perception, and transduction under UVR stress are discussed.
Label-Free Human Disease Characterization through Circulating Cell-Free DNA Analysis Using Raman Spectroscopy
Authors: Papadakis Vassilis M. , Cheimonidi Christina , Panagopoulou Maria , Karaglani Makrina , Apalaki Paraskevi , Katsara Klytaimnistra , Kenanakis George , Theodosiou Theodosis , Constantinidis Theodoros C. , Stratigi Kalliopi , Chatzaki Ekaterini
Published: August 2023

Circulating cell-free DNA (ccfDNA) is a liquid biopsy biomaterial attracting significant attention for the implementation of precision medicine diagnostics. Deeper knowledge related to its structure and biology would enable the development of such applications. In this study, we employed Raman spectroscopy to unravel the biomolecular profile of human ccfDNA in health and disease. We established reference Raman spectra of ccfDNA samples from healthy males and females with different conditions, including cancer and diabetes, extracting information about their chemical composition. Comparative observations showed a distinct spectral pattern in ccfDNA from breast cancer patients taking neoadjuvant therapy. Raman analysis of ccfDNA from healthy, prediabetic, and diabetic males uncovered some differences in their biomolecular fingerprints. We also studied ccfDNA released from human benign and cancer cell lines and compared it to their respective gDNA, confirming it mirrors its cellular origin. Overall, we explored for the first time Raman spectroscopy in the study of ccfDNA and provided spectra of samples from different sources. Our findings introduce Raman spectroscopy as a new approach to implementing liquid biopsy diagnostics worthy of further elaboration.