bluuebunny/crossref_metadata_2025 huggingface dataset:
Kompetencje Prezydenta Republiki Macedonii w sferze spraw zagranicznych i ich realizacja
Authors: Woźnica Rafał
Published: October 2024

The research objective is to analyse the competences of the President of the Republic of Macedonia in the sphere of external relations of the state. The determination of the formal prerequisites shaping the role of the Head of State in the sphere of Macedonia’s relations with other states and international organisations requires an analysis of the constitutional matter and other normative acts, with regard to the constitutional position of the President, as well as the competency reality. For this purpose, the provisions of the 1991 Constitution of the Republic of Macedonia and the Law on Foreign Affairs will be analysed, as well as the analysis of the practice of this function by successive officeholders.
Przemiany migracyjne i demograficzne w Albanii oraz w Bośni i Hercegowinie – wprowadzenie do dalszych analiz
Authors: Ickiewicz-Sawicka Magdalena
Published: October 2024

The Balkan region, and especially the Western Balkans region, has been an area of constant migration movements and regularly changing national and ethnic groups inhabiting this space since ancient times. It has always been the result of numerous wars, forced resettlements, ethnic cleansing, etc., both in the past and now, and the consequence of which is the current bad economic situation, in this case in Albania and Bosnia and Herzegovina. This trend is inversely proportional to global trends, mainly in the countries of the global south, where we are observing a demographic explosion. However, in European countries there is an increasing decline in birth rates and the phenomenon of mass emigration, mainly economic, in search of better living conditions than in their home countries. The text contains statistical data with appropriate analysis and commentary, and the conclusion contains conclusions based on the considerations contained in the text.
Effect of P Reduction on phoD-Harboring Bacteria Community in Solar Greenhouse Soil
Authors: Bian Ting , Wang Zhen , Wang Shuang , Shan Xuan , Wang Tianqi , Fu Hongdan , Sun Zhouping
Published: October 2024

Phosphorus (P) enrichment frequently occurs in the soil used in greenhouse vegetable production (GVP). Minimizing the application of P fertilizer represents a crucial approach to mitigating the accumulation of P in the soil and enhancing its utilization efficiency. However, the changes in bacterial communities and the turnover mechanism of soil P fractions related to soil P cycling after P fertilizer reduction are still unclear. To unravel these complexities, we devised three experimental treatments: conventional nitrogen (N), P, and potassium (K) fertilizer (N1P1K1); conventional N and K fertilizer without P (N1P0K1); and no fertilizer (N0P0K0). These experiments were conducted to elucidate the effects of P reduction on cucumber plant growth, soil P fractions, and the phoD-harboring bacterial community in the P-rich greenhouse soil. The results showed that there were no significant differences between the N1P1K1 and N1P0K1 treatments in terms of plant growth, yield, and P uptake, and the values for the N0P0K0 treatment were significantly lower than those for the N1P1K1 treatment. In a state of P depletion (N0P0K0, N1P0K1), the main P sources were Resin-Pi, NaHCO3-Pi, NaHCO3-Po, and NaOH-Pi. The contents of NaOH-Po and CHCl-Po in the N1P0K1 treatment increased significantly. Without P fertilizer, alkaline phosphatase (ALP) activity, phoD gene abundance, and bacterial community diversity were significantly increased. The abundance of Ensifer in the N0P0K0 and N1P0K1 treatments was 8 and 10.58 times that in the N1P1K1 treatment, respectively. Additionally, total phosphorus (TP) and available nitrogen (AN) were key factors affecting changes in the phoD bacterial community, while Shinella, Ensifer and Bradyrhizobium were the main factors driving the change in soil P fractions, and NaHCO3-Pi and NaOH-Pi were key factors affecting crop yield. Therefore, reducing the application of P fertilizer will increases the diversity of phoD-gene-harboring bacterial communities and promote organic P mineralization, thus maintaining the optimal crop yield.
Role of Chitosan in the Coloring of Berries and Phytochemical Changes in Physalis angulata L. During Harvest Maturity
Authors: Heydarnajad Giglou Rasoul , Ghahremani Zahra , Barzegar Taher , Rabiei Vali , Torabi Giglou Mousa , Sobhanizadeh Ali , Nicola Silvana , Adamski Maciej , Wińska Katarzyna
Published: October 2024

Physalis angulata L. berries are green in the initial stage of maturity and turn yellow when fully mature due to an increase in carotenoids. However, the coloration of the epidermis of the berry should not be the reference for harvesting maturity, since the calyx is fully closed. The use of an edible chitosan coating delays the color changes in the berry by reducing the respiration rate. This work studies the effect of harvest maturity and chitosan on the shelf life and berry coloring in Physalis angulata L. Three factors were considered, being harvest maturity stage (green mature (GM), yellowish-green (YG) and yellow (Y)), chitosan coating (0, 0.5, and 1%), and storage time (10, 20, 30 days). The fruits were stored at 20 °C and 85% Rh. The results showed that on the harvesting stage, chitosan coating had a significant effect on the quality and shelf life of berries during storage time. The value of carotenoid and phenol contents, flavor index, chroma, and hue significantly increased with berry maturity. Chitosan delayed the decrease in chlorophyll, phenol contents, antioxidant capacity, berry maturity, and color change. The results show that in the berries coated with 1% chitosan during storage, changes in color were less in comparison with the control condition (no chitosan). The highest decrease of hue angle and color index (17.92°) was observed in the control. The highest total antioxidant (78.42%) was observed after 30 days of storage in MG berries treated with a 0.5% chitosan coating.
Research on the Tensile and Impact Mechanical Properties of Millet Ear Petals
Authors: Qiu Shujin , Pan Ben , Wang Zeze , Fang Shige , Hu Jiangfan , Yang Shubo , Wang Wei , Cui Qingliang , Yuan Xiangyang
Published: October 2024

In response to the low threshing efficiency of millet ear petals, this study investigated the tensile and impact mechanical properties of millet petals during the millet threshing process. Jingu 21, Zhangza 16, and Changza 466 were used as experimental subjects to study the effects of tensile angle and growth part on fracture strength, and to determine the influence of impulse and growth part on drop and breakage rates. The results indicated that both growth part and tensile angle have a highly significant impact on the tensile fracture strength of the millet petals. The tensile fracture strength decreases with the increase in the tensile angle, and increases with the growth part from top to bottom. The variety, growth part, and impulse significantly affect the impact drop and breakage rates of the millet petals, with the main factors affecting the drop rate being impulse, variety, and growth part, in that order. When the impulse is 2.296 N·s, the threshing effect for Jingu 21 is optimal, with a drop rate of 65.091% and a breakage rate of 13.487%. This research provides theoretical insights into the simulation of the millet ear threshing process and the optimization of the performance of millet threshing equipment.
The Effects of Omega-3 Supplementation on the Omega-3 Index and Quality of Life and Pain Scores in Dogs
Authors: Carlisle Carolina , Metzger Brandon T. , Tintle Nathan L. , Polley Kristine , Jackson Kristina H. , Le Brun-Blashka Sara , Griffiths Jody , Harris William S.
Published: October 2024

This study in dogs had two objectives: first, to determine whether a daily supplement of marine omega-3 (EPA and DHA) would (1) increase red blood cell EPA + DHA levels (i.e., the Omega-3 Index derived from dried blood spot analysis) and (2) impact health-related measures. Dogs were recruited from five private veterinary clinics in the United States and supplemented with about 70 mg of EPA + DHA per kg body weight (BW) for 16 weeks. Health-related outcomes included quality of life (QOL) and pain scores using validated questionnaires. Twenty-nine dogs (8.4 ± 3.6 years old) finished this study. After 16 weeks of supplementation with 68 ± 19 mg EPA + DHA/kg/day, the O3I increased from 1.4% ± 1.0% at baseline to 3.3% ± 1.1% (p = <0.0001). Concomitantly, overall pain scores declined from 7.4 ± 5.8 to 6.2 ± 5.4 (p = 0.012), primarily in small and medium-sized dogs. QOL scores improved slightly but only in small dogs (p = 0.03). Thus, supplementation with about 70 mg of EPA + DHA/kg/day improved the O3I and, in smaller dogs, pain and QOL scores. Future studies are needed to more clearly define doses of EPA + DHA that would improve the health of dogs.
Elevated RBP4 in Subclinical Ketosis Cows Inhibits Follicular Granulosa Cell Proliferation and Steroid Hormone Synthesis
Authors: Zhao Chang , Xu Ruru , Yan Weizhe , Jiang Benzheng , Feng Shibin , Wang Xichun , Ding Hongyan
Published: October 2024

The mechanism by which subclinical ketosis (SCK) causes postpartum reproductive disorders in dairy cows remains unclear. In this study, cows within the day 14 to 21 postpartum period were categorized into the SCK group or the control group. Subsequently, they were monitored until 45 d to 60 d postpartum and divided into the SCK anestrus group (SCK-AE, n = 12) and the control estrus group (C-E, n = 12). In comparison to the C-E group, the RBP4 and p-AKT of the SCK-AE group exhibited increased levels in serum, liver, and ovaries. In the in vitro experimental cultivation of granulosa cells (GCs), after adding RBP4, cell proliferation, steroid hormone secretion and synthesis, and GLUT4 secretion were inhibited, and cell apoptosis was exacerbated. After silencing STRA6 (RBP4 receptor), cell proliferation and steroid hormone secretion and synthesis, as well as the inhibition of GLUT4, were alleviated, and the situation of cell apoptosis also improved. The SC79 activator could promote the phosphorylation of AKT, thus alleviating the increased cell proliferation, steroid hormone secretion and synthesis, GLUT4 inhibition, and apoptosis rate in cow GCs induced by RBP4 stimulation. Our research indicates that elevated RBP4 levels in SCK cows inhibit the proliferation, apoptosis, and steroid hormone synthesis of GCs through the STRA6 receptor and the PI3K/AKT pathway.
Beneficial Effects on Oxidative Stress and Human Health by Dietary Polyphenols
Authors: Alia Sonila , Di Paolo Alice , Membrino Valentina , Di Crescenzo Tiziana , Vignini Arianna
Published: October 2024

During the past few years, researchers have dedicated themselves to studying phytochemicals which make up the nutritional and non-nutritional bioactive compounds found in fruits, vegetables, cereals, and other plant foods [...]
Research on Complete Coverage Path Planning of Agricultural Robots Based on Markov Chain Improved Genetic Algorithm
Authors: Han Jiangyi , Li Weihao , Xia Weimin , Wang Fan
Published: October 2024

Due to the limitations of low coverage, high repetition rate, and slow convergence speed of the basic genetic algorithm (GA) in robot complete coverage path planning, the state transition matrix of the Markov chain is introduced to guide individual mutation based on the genetic mutation path planning algorithm, which can improve the quality of population individuals, enhancing the search ability and convergence speed of the genetic algorithm. The proposed improved genetic algorithm is used for complete coverage path planning simulation analysis in different work areas. The analysis results show that compared to traditional genetic algorithms, the improved genetic algorithm proposed in this paper reduces the average path length by 21.8%, the average number of turns by 6 times, the repetition rate by 83.8%, and the coverage rate by 7.76% in 6 different work areas. The results prove that the proposed improved genetic algorithm is applicable in complete coverage path planning. To verify whether the Markov chain genetic algorithm (MCGA) proposed is suitable for agricultural robot path tracking and operation, it was used to plan the path of an actual land parcel. An automatic navigation robot can track the planned path, which can verify the feasibility of the MCGA proposed.
Numerical Investigation of the Slope Stability in the Waste Dumps of Romanian Lignite Open-Pit Mines Using the Shear Strength Reduction Method
Authors: Popescu Florin Dumitru , Andras Andrei , Radu Sorin Mihai , Brinas Ildiko , Iladie Corina-Maria
Published: October 2024

Open-pit mining generates significant amounts of waste material, leading to the formation of large waste dumps that pose environmental risks such as land degradation and potential slope failures. The paper presents a stability analysis of waste dump slopes in open-pit mining, focusing on the Motru coalfield in Romania. To assess the stability of these dumps, the study employs the Shear Strength Reduction Method (SSRM) implemented in the COMSOL Multiphysics version 6 software, considering both associative and non-associative plasticity models. (1) Various slope angles were analyzed, and the Factor of Safety (FoS) was calculated, showing that the FoS decreases as the slope angle increases. (2) The study also demonstrates that the use of non-associative plasticity leads to lower FoS values compared to associative plasticity. (3) The results are visualized through 2D and 3D models, highlighting failure surfaces and displacement patterns, which offer insight into the rock mass behavior prior to failure. (4) The research also emphasizes the effectiveness of numerical modeling in geotechnical assessments of stability. (5) The results suggest that a non-associative flow rule should be adopted for slope stability analysis. (7) Quantitative results are obtained, with small variations compared to those obtained by LEM. (6) Dilatation angle, soil moduli, or domain changes cause differences of just a few percent and are not critical for the use of the SSRM in engineering.
Pharmacoinformatics, Molecular Dynamics Simulation, and Quantum Mechanics Calculation Based Phytochemical Screening of Croton bonplandianum Against Breast Cancer by Targeting Estrogen Receptor-α (ERα)
Authors: Saha Shuvo , Biswas Partha , Tareq Mohaimenul Islam , Rahman Sakib Musfiqur , Akter Rakhi Suraia , Zilani Md. Nazmul Hasan , Harrath Abdel Halim , Rahman Md. Ataur , Hasan Md. Nazmul
Published: October 2024

Breast cancer progression is strongly influenced by estrogen receptor-α (ERα), a ligand-activated transcription factor that regulates hormone binding, DNA interaction, and transcriptional activation. ERα plays a key role in promoting cell proliferation in breast tissue, and its overexpression is associated with the advancement of breast cancer through estrogen-mediated signaling pathways. Targeting ERα is, therefore, a promising therapeutic strategy for breast cancer. However, there are currently no phytochemical-based drug candidates approved for effectively inhibiting breast cancer progression driven by elevated ERα expression. This study aims to identify phytochemical inhibitors from Croton bonplandianum against ERα using pharmacoinformatics approaches. Eighty-three bioactive compounds from C. bonplandianum were retrieved from the IMPPAT (Indian Medicinal Plants, Phytochemistry, and Therapeutics) database and screened through molecular docking for their binding affinity to ERα. The top candidates were further evaluated through molecular dynamics simulations, ADME analysis, toxicity assessment, and quantum mechanics-based DFT calculations. The thermodynamic properties and HOMO-LUMO energy gap values indicated that the selected compounds were both stable and active. Among them, 2,3-oxidosqualene (CID-5366020) and 5,8,11-eicosatriynoic acid, trimethylsilyl ester (CID-91696396) demonstrated the most potent inhibitory activity against ERα. These findings suggest that these compounds have significant potential as therapeutic agents for breast cancer treatment by targeting ERα.
Experimental Investigation on Rock Failure Characteristics of Large-Span Goafs Using Digital Image Correlation Analysis and Acoustic Emission Monitoring
Authors: Hou Chenglu , Li Xibing , Yin Tubing , Dong Longjun , Sun Daoyuan
Published: October 2024

Rockmass in deep mining is highly susceptible to large-scale collapses under high stress and blast-induced disturbances, leading to casualties and economic losses. To investigate the evolution characteristics of goaf instability and the types of seismic sources that induce instability, an experiment on goaf instability was designed under uniaxial compression conditions based on actual mining operations. The entire experimental process was monitored using digital image correlation analysis and acoustic emission monitoring. By calculating the digital speckle field on the surface of the rock specimen during the experiment, the evolution characteristics of the deformation and strain fields from the beginning of loading to complete failure were analyzed. The study explored the dynamic behavior of cracks from initiation to propagation and eventually inducing large-scale collapse. The results show that the instability process of the goaf begins with the formation of tensile cracks. As stress increases, shear cracks occur in the specimen, leading to macroscopic failure. Furthermore, based on the differences in overall microfracture types measured by RA-AF characteristic parameters during specimen failure, large amplitude acoustic emission events corresponding to the formation of dominant macroscopic cracks were selected, and the focal mechanisms of these events were inverted. The results indicate that shear failure sources are significantly more prevalent than tensile failure sources in acoustic emission events leading to goaf instability. These findings can provide useful guidance for the support design and the prevention and control of rockmass instability disasters.
Adaptive Control for Hydronic Radiant Heating System Using Occupant Behaviors in Residential Building
Authors: Wee Junghoon , Hong Yeonghun , Chae Young Tae
Published: October 2024

This study proposes an occupant-centric control strategy for residential heating systems, aiming to enhance thermal comfort and reduce energy consumption. A sensor station utilizing a frequency-modulated continuous wave radar sensor was developed to detect occupancy and infer activities within residential spaces. By analyzing field measurement data, schedules for occupancy and activities were established. These schedules were then used to implement a variable control strategy for the hydronic radiant heating system, adjusting its operating characteristics based on the identified activities. The proposed control strategy, which includes resetting the indoor set temperature during unoccupied periods and adjusting it during sleep to account for changes in metabolic rate and clothing insulation, resulted in significant energy savings. Compared to continuous operation, the hydronic radiant heating system’s energy consumption was reduced by approximately 21% on peak load days and up to 34% over three winter months. This study demonstrates the potential of occupant-centric control for achieving substantial energy savings in residential buildings while maintaining occupant thermal comfort.
Deep Learning-Based Low-Frequency Passive Acoustic Source Localization
Authors: Joshi Arnav , Hickey Jean-Pierre
Published: October 2024

This paper develops benchmark cases for low- and very-low-frequency passive acoustic source localization (ASL) using synthetic data. These cases can be potentially applied to the detection of turbulence-generated low-frequency acoustic emissions in the atmosphere. A deep learning approach is used as an alternative to conventional beamforming, which performs poorly under these conditions. The cases, which include two- and three-dimensional ASL, use a shallow and inexpensive convolutional neural network (CNN) with an appropriate input feature to optimize the source localization. CNNs are trained on a limited dataset to highlight the computational tractability and viability of the low-frequency ASL approach. Despite the modest training sets and computational expense, detection accuracies of at least 80% and far superior performance compared with beamforming are achieved—a result that can be improved with more data, training, and deeper networks. These benchmark cases offer well-defined and repeatable representative problems for comparison and further development of deep learning-based low-frequency ASL.
Nanostructured Magnetite Coated with BiOI Semiconductor: Readiness Level in Advanced Solar Photocatalytic Applications for the Remediation of Phenolic Compounds in Wastewater from the Wine and Pisco Industry
Authors: Gallegos-Alcaíno Alejandra , Barría Gabriela Paz , Moreno Yanko , Fernández Iván , Poblete Rodrigo , Maureira-Cortés Héctor , Figueroa Alvarado Antonia Cristal , Hernández Constanza Belén , Flores José
Published: October 2024

Heterogeneous photocatalysis is an advanced, efficient oxidation process that uses solar energy to be sustainable and low-cost compared to conventional wastewater treatments. This study synthesized BiOI/Fe3O4 using the solvothermal technique, evaluating stoichiometric ratios of Bi/Fe (2:1, 3:1, 5:1, and 7:1) under simulated solar irradiation to optimize the degradation of caffeic acid, a pollutant found in wastewater from the wine and pisco industry. The nanomaterial with a 5:1 ratio (BF-5) was the most effective, achieving a degradation of 77.2% in 180 min. Characterization by X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Brunauer–Emmett–Teller (BET), Barrett–Joyner–Halenda (BJH), Fourier Transform Infrared Spectroscopy (FTIR), Diffuse Reflectance Spectroscopy (DRS), and Vibrating Sample Magnetometry (VSM) showed that BF-5 has a porous three-dimensional structure with BiOI nanosheets coating the Fe3O4 surface, while retaining the pristine BiOI properties. The magnetite provided magnetic properties that facilitated the recovery of the photocatalyst, reaching 89.4% recovery. These findings highlight the potential of BF-5 as an efficient and recoverable photocatalyst for industrial applications. The technical, economic, and environmental feasibility were also evaluated at the technological readiness level (TRL) to project solar photocatalysis in real applications.
Predicting Shot Accuracy in Badminton Using Quiet Eye Metrics and Neural Networks
Authors: Tan Samson , Teoh Teik Toe
Published: October 2024

This paper presents a novel approach to predicting shot accuracy in badminton by analyzing Quiet Eye (QE) metrics such as QE duration, fixation points, and gaze dynamics. We develop a neural network model that combines visual data from eye-tracking devices with biomechanical data such as body posture and shuttlecock trajectory. Our model is designed to predict shot accuracy, providing insights into the role of QE in performance. The study involved 30 badminton players of varying skill levels from the Chinese Swimming Club in Singapore. Using a combination of eye-tracking technology and motion capture systems, we collected data on QE metrics and biomechanical factors during a series of badminton shots for a total of 750. Key results include: (1) The neural network model achieved 85% accuracy in predicting shot outcomes, demonstrating the potential of integrating QE metrics with biomechanical data. (2) QE duration and onset were identified as the most significant predictors of shot accuracy, followed by racket speed and wrist angle at impact. (3) Elite players exhibited significantly longer QE durations (M = 289.5 ms) compared to intermediate (M = 213.7 ms) and novice players (M = 168.3 ms). (4) A strong positive correlation (r = 0.72) was found between QE duration and shot accuracy across all skill levels. These findings have important implications for badminton training and performance evaluation. The study suggests that QE-based training programs could significantly enhance players’ shot accuracy. Furthermore, the predictive model developed in this study offers a framework for real-time performance analysis and personalized training regimens in badminton. By bridging cognitive neuroscience and sports performance through advanced data analytics, this research paves the way for more sophisticated, individualized training approaches in badminton and potentially other fast-paced sports. Future research directions include exploring the temporal dynamics of QE during matches and developing real-time feedback systems based on QE metrics.
Detecting Suicidal Ideations in Online Forums with Textual and Psycholinguistic Features
Authors: Yeskuatov Eldar , Chua Sook-Ling , Foo Lee Kien
Published: October 2024

Suicide is a global public health problem that takes hundreds of thousands of lives each year. The key to effective suicide prevention is early detection of suicidal ideations and timely intervention. However, several factors hinder traditional suicide risk screening methods. Primarily, the social stigma associated with suicide presents a challenge to suicidal ideation detection, as existing methods require patients to explicitly communicate their suicidal propensities. In contrast, progressively more at-risk people choose online platforms—such as Reddit—as their preferred avenues for sharing their suicidal experiences and seeking emotional support. As a result, these online platforms have become an unobtrusive source of user-generated textual data that can be used to detect suicidality with supervised machine learning and natural language processing techniques. In this paper, we proposed a suicidal ideation detection approach that combines textual and psycholinguistic features extracted from the Reddit forum. Subsequently, we selected the most informative features using the Boruta algorithm and employed four classifiers: logistic regression, naïve Bayes, support vector machines, and random forest. The naïve Bayes models trained with the combination of term frequency-inverse document frequency (TF-IDF) and National Research Council (NRC) features demonstrated the highest performance, obtaining a F1 score of 70.99%. Our experimental results illustrate that a combination of textual and psycholinguistic features yields better classification performance compared to using those features separately.
Behavioural Monitoring Underlines Habituation to Repeated Stressor Stimuli in Farmed Gilthead Sea Bream (Sparus aurata) Reared at a High Stocking Density
Authors: Holhorea Paul G. , Naya-Català Fernando , Domingo-Bretón Ricardo , Moroni Federico , Belenguer Álvaro , Calduch-Giner Josep À. , Pérez-Sánchez Jaume
Published: October 2024

A confinement stress test with 75% tank space reduction and behavioural monitoring through tri-axial accelerometers externally attached to the operculum was designed. This procedure was validated by demonstrating the less pronounced stress response in gilthead sea bream than in European sea bass (950–1200 g). Our study aimed to assess habituation to high stocking densities with such procedure in gilthead sea bream. Animals (420–450 g) were reared (June–August) in a flow-through system at two stocking densities (CTRL: 10–15 kg/m3; HD: 18–24 kg/m3), with natural photoperiod and temperature (21–29 °C), and oxygen levels at 5.2–4.2 (CTRL) and 4.2–3.2 ppm (HD). At the end, blood and muscle were sampled for haematology and transcriptomic analyses, and external tissue damage was assessed by image-based scoring. Four days later, fish underwent a 45 min confinement stress test over two consecutive days. HD fish showed reduced feed intake, growth rates and haematopoietic activity. Muscle transcriptome changes indicated a shift from systemic to local growth regulation and a primed muscle regeneration over protein accretion in HD animals with slight external injuries. After stress testing, HD fish exhibited a decreased recovery time in activity and respiration rates, which was shorter after a second stressor exposure, confirming habituation to high densities.
Identifying Hub Genes and Metabolic Pathways in Collagen VI-Related Dystrophies: A Roadmap to Therapeutic Intervention
Authors: Ceyhan Atakan Burak , Kaynar Ali , Altay Ozlem , Zhang Cheng , Temel Sehime Gulsun , Turkez Hasan , Mardinoglu Adil
Published: October 2024

Collagen VI-related dystrophies (COL6RD) are a group of rare muscle disorders caused by mutations in specific genes responsible for type VI collagen production. It affects muscles, joints, and connective tissues, leading to weakness, joint problems, and structural issues. Currently, there is no effective treatment for COL6RD; its management typically addresses symptoms and complications. Therefore, it is essential to decipher the disease’s molecular mechanisms, identify drug targets, and develop effective treatment strategies to treat COL6RD. In this study, we employed differential gene expression analysis, weighted gene co-expression network analysis, and genome-scale metabolic modeling to investigate gene expression patterns in COL6RD patients, uncovering key genes, significant metabolites, and disease-related pathophysiological pathways. First, we performed differential gene expression and weighted gene co-expression network analyses, which led to the identification of 12 genes (CHCHD10, MRPS24, TRIP10, RNF123, MRPS15, NDUFB4, COX10, FUNDC2, MDH2, RPL3L, NDUFB11, PARVB) as potential hub genes involved in the disease. Second, we utilized a drug repurposing strategy to identify pharmaceutical candidates that could potentially modulate these genes and be effective in the treatment. Next, we utilized context-specific genome-scale metabolic models to compare metabolic variations between healthy individuals and COL6RD patients. Finally, we conducted reporter metabolite analysis to identify reporter metabolites (e.g., phosphatidates, nicotinate ribonucleotide, ubiquinol, ferricytochrome C). In summary, our analysis revealed critical genes and pathways associated with COL6RD and identified potential targets, reporter metabolites, and candidate drugs for therapeutic interventions.
Chronic Hyperhomocysteinemia Impairs CSD Propagation and Induces Cortical Damage in a Rat Model of Migraine with Aura
Authors: Gerasimova Elena , Enikeev Daniel , Yakovlev Aleksey , Zakharov Andrey , Sitdikova Guzel
Published: October 2024

Hyperhomocysteinemia (hHCY) is a metabolic disorder characterized by elevated levels of homocysteine in plasma. hHCY correlates with a high risk of migraine headaches, especially migraine with aura. Cortical spreading depression (CSD) is a wave of depolarization passing through neurons and glial cells of the cortex and is considered an electrophysiological correlate of migraine aura. The aim of the present study was to analyze neuronal activity and CSD in the somatosensory cortex of rats in vivo with prenatal hHCY and to assess cortex viability after 2 h of CSD generation. Female rats were fed a diet high in methionine, and their offspring with high homocysteine levels in plasma were further used in experiments. Recurrent CSD was evoked by local KCl application on the dura surface. Neuronal viability was assessed by measuring the activity of lactate dehydrogenase (LDH) in the brain and 2,3,5-triphenyltetrazolium chloride staining of the somatosensory cortex after two hours of CSD generation. Animals with hHCY exhibited higher neuronal activity, and more CSDs were generated in response to KCl, indicating higher cortical excitability. Propagation of recurrent CSD was impaired in supragranular cortical layers, and the recovery of multiple unit activity and evoked sensory potentials after CSD was delayed in the hHCY group. Finally, in animals with prenatal hHCY, an ischemic focus was identified as a consequence of multiple CSDs, along with elevated levels of LDH activity in brain tissues, suggestive of diminished neuronal viability. These findings imply that prolonged elevated levels of homocysteine may not only predispose to migraine with aura but also potentially elevate the risk of migrainous infarction.
Otorhinolaryngological Problems in Mucopolysaccharidoses: A Review of Common Symptoms in a Rare Disease
Authors: Waśniewska-Włodarczyk Anna , Pepaś Renata , Rosiak Oskar , Konopka Wiesław
Published: October 2024

Background: The mucopolysaccharidoses (MPSs) are very rare lysosomal diseases. MPSs belong to inherited diseases; however, newborns are usually asymptomatic. A deficiency of one of the enzymes, which is responsible for glycosaminoglycan (GAG) catabolism, results in the accumulation of this material. GAGs lead to progressive damage to tissues. More than 90% of patients with MPS suffer from otitis media with effusion or recurrent otitis media, craniofacial dysmorphia, obstructive sleep apnea, different types of hearing loss, and progressive upper and lower airway dysfunction. Patients visit otolaryngologists often before the diagnosis of MPS. Thus, the awareness of symptoms of MPS is crucial for otolaryngologists and pediatricians. The earlier the diagnosis is made, the more effective treatment is. Ineffective or delayed treatment leads to premature death. Two principal treatments for MPS are currently available: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). In recent years, there has been a growing interest in gene therapy as a potential treatment for patients with MPS. Mortality in patients with MPS typically occurs during childhood and early adolescence as a consequence of upper and lower respiratory diseases. Methods: This systematic review is based on papers available in the following scientific databases: MEDLINE (via PubMed), Web of Science, Scopus, and the Cochrane Library. Results: After screening, 72 articles met our inclusion criteria. Conclusions: It is of paramount importance that otolaryngologists are involved in this field. This narrative review examines and synthesizes the otolaryngologic issues encountered in patients with MPS.
Research on Coordinated Relationship Between Deformation and Force in Shaft Foundation Pit Support Structures
Authors: Xu Chuanzhao , Hou Jian , Liu Bingfeng , Lei Fangchao , Song Li
Published: October 2024

In order to investigate the coordinated relationship between lateral deformation of the diaphragm wall and axial force of the internal strut, this paper first carried out a scaled model test on the mechanical features of a foundation pit support system based on a novel axial force servo device. Then, a finite element model was established to simulate the scaled model test, and the correctness of the finite element modeling approach was validated by comparing test results. After that, the same finite element modeling method was used to analyze the coordinated relationship between axial force and lateral deformation in the prototype foundation pit support structure. The results show that the axial force of the inner strut is negatively correlated with the lateral deformation in the diaphragm wall. The initial maximum lateral deformation in the diaphragm wall of the shaft foundation pit occurs at the bottom of the foundation pit, so changing the length of bottom strut simultaneously is the most effective way to adjust the mechanical behavior of the support structure. Under various support conditions, the maximum lateral deformation of the diaphragm wall in the prototype project is 0.59~0.66‰ of the total excavation depth of the foundation pit, and the maximum axial force of internal support is 11~30% of the yield load of a single steel strut.
Study on Impact Resistance of Alkali-Activated Slag Cementitious Material with Steel Fiber
Authors: Liu Pan , Chen Guangjing , Liu Gang , Liu Hao , Zhang Jia , Chen Pang , Su Yumeng
Published: October 2024

Alkali-activated slag cementitious materials (AASCMs) use alkaline activators to activate blast furnace slag and waste slag to replace traditional Portland cement, which can reduce CO2 emissions. An impact resistance test and scanning electron microscopy (SEM) microscopic performance analysis of alkali-activated slag cementitious material specimens with four different steel-fiber contents are performed. The effects of steel-fiber volume content and strain rate on the dynamic elastic modulus Ed, dynamic compressive strength σd, dynamic peak compressive strain εc, and energy absorption of the AASCM-SS are studied. The results indicate that the dynamic elastic modulus Ed, dynamic compressive strength σd, and energy absorption of the AASCM-SS increase with the increase of strain rate, and the dynamic peak compressive strain εc decreases with the increase of strain rate. The dynamic elastic modulus Ed, dynamic compressive strength σd, and dynamic peak compressive strain εc of the SS-AASCM increase first and then decrease with the increase of steel-fiber content. When the steel-fiber content is 0.5%, the σd and εc of the AASCM-SS are the highest, increased by 9.9% and 19.3%. The energy absorption of AASCM-SS increases with the increase of steel-fiber content. A dynamic constitutive model of the FR-AASCM considering the influence of damage, strain rate, and steel-fiber volume fraction is established. The proposed constitutive model is in acceptable agreement with the experimental AASCM-SS dynamic stress–strain curve, and the correlation coefficient is 0.91.
Experimental Investigations on the On-Site Crack Control of Pier Concrete in High-Altitude Environments
Authors: Hu Xiaochuan , Liu Lei , Liao Manping , Li Ming , Lu Cun , Yao Zaifeng , Huang Qiuming , Zhuang Mei-Ling
Published: October 2024

Concrete structures in high-altitude environments face many challenges. Establishing concrete crack control methods in high-altitude environments is crucial for enhancing the service capacity of concrete structures. In this study, a multi-field (hydration-temperature–humidity-constraint) coupling model was used to quantitatively assess the cracking risk of pier bodies at high altitude. On-site crack control tests were conducted on pier bodies using a micro-expansion anti-cracking agent to demonstrate the effectiveness of deformation shrinkage compensation in crack control at high altitudes. The results indicated that there was a risk of cracking in the pier body at high-altitude conditions, especially within 0.3 m from the pile cap and ±2.5 m from the center of the pier side surface. Compared with conventional piers, the micro-expansion anti-cracking agent approximately doubled the unit expansion deflection of piers at high temperatures while reducing the unit shrinkage deflection of piers by 11% to 12% at low temperatures. The concrete in conventional pier bodies was in a tension state after long-term hardening, while the concrete treated with the micro-expansive anti-cracking agent was in compression. Therefore, the deformation compensation effect of the micro-expansive anti-cracking agent was significant and reduced the risk of concrete cracking. In addition, early freezing had a significant impact on concrete strength, underscoring the importance of effective temperature control during the early stages of concrete placement in high-altitude environments.
Nutritional Supplement with Fermented Soy in Patients Under Active Surveillance for Low-Risk or Intermediate-Risk Prostate Cancer: Results from the PRAEMUNE Trial
Authors: Van der Eecken Hans , De Cock Diederik , Roussel Eduard , Giesen Alexander , Vansevenant Bram , Goeman Lieven , Quackels Thierry , Joniau Steven
Published: October 2024

Background/Objectives: To investigate the effect of a fermented soy supplement during 18 months in patients under active surveillance (AS) for low-risk and selected favorable intermediate-risk prostate cancer (PCa), with an emphasis on PSA modulation. Methods: Low-risk patients with ISUP grade 1, clinical stage cT1 or cT2a, PSA < 10 ng/mL and favorable intermediate-risk patients with ISUP grade 2 (<10% pattern 4), clinical stage T2b-c, PSA 10–20 ng/mL. The primary outcome was PSA response defined as maximum PSA rise less than or equal to 0.87 ng/mL after 1 year, based on the weighted average of PSA velocity (PSAV) in previous studies in similar populations. Secondary outcomes were disease progression, adverse histology on repeat biopsy or switch to active therapy. In addition, primary and secondary outcomes with imputed data were also determined as sensitivity analyses, using Mann–Whitney U or Chi-squared tests. Results: Overall, 92 (61.3%) of 150 patients showed a PSA level response. This was more evident in ISUP 1 patients and resulted in fewer follow-up MRIs and fewer control biopsies, as well as a fewer number of positive control biopsies with statistical significance in the imputed dataset. Obtaining a PSA response was numerically associated with less initiated therapy. Conclusions: a fermented soy supplement in patients under AS for low-risk and selected favorable intermediate-risk PCa could be useful in selecting patients who may remain under AS or who may need to switch to active therapy.
Evolving Artificial Intelligence (AI) at the Crossroads: Potentiating Productive vs. Declining Disruptive Cancer Research
Authors: Sharma Nilesh Kumar , Sarode Sachin C.
Published: October 2024

Artificial intelligence (AI), encompassing several tools and platforms such as artificial “general” intelligence (AGI) and generative artificial intelligence (GenAI), has facilitated cancer research, enhancing productivity in terms of research publications and translational value for cancer patients. AGI tools, such as ChatGPT, assist preclinical and clinical scientists in identifying tumor heterogeneity, predicting therapy outcomes, and streamlining research publications. However, this perspective review also explores the potential of AI’s influence on cancer research with regard to its impact on disruptive sciences and discoveries by preclinical and clinical scientists. The increasing reliance on AI tools may compromise biological intelligence, disrupting abstraction, creativity, and critical thinking. This could contribute to the declining trend of disruptive sciences, hindering landmark discoveries and innovations. This perspective review narrates the role of different forms of AI in the potentiation of productive cancer research and the potential disruption of disruptive sciences due to AI’s influence.
High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis
Authors: Dreyer Verena J. , Shi Jia-Xin , Rose Michael , Onyuro Maureen T. , Steib Florian , Hilgers Lars , Seillier Lancelot , Dietrich Jana , Riese Janik , Meurer Steffen K. , Weiskirchen Ralf , Neumann Ulf , Heij Lara , Luedde Tom , Loosen Sven H. , Lurje Isabella , Lurje Georg , Gaisa Nadine T. , Jonigk Danny , Bednarsch Jan , Dahl Edgar , Brüchle Nadina Ortiz
Published: October 2024

Background: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene ITIH5, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis. Methods: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA). Results: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI). Conclusions: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.
The Association Between Lymphovascular or Perineural Invasion in Radical Prostatectomy Specimen and Biochemical Recurrence
Authors: Siech Carolin , Wenzel Mike , Grosshans Nico , Cano Garcia Cristina , Humke Clara , Koll Florestan Johannes , Tian Zhe , Karakiewicz Pierre I. , Kluth Luis A. , Chun Felix K. H. , Hoeh Benedikt , Mandel Philipp
Published: October 2024

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.