bluuebunny/crossref_metadata_2025 huggingface dataset:
HCA587 Protein Vaccine Inhibits Tumor Neovascularization by Upregulating Pedf-Activated Apoptosis in Mouse Melanoma Model
Authors: Chen Juanjuan , Tan Yuanfang , Fan Qiuying , Chen Huiyuan , Jiao Wei , Gou Xi , Yang Weiming , Ye Dongxian , Lai Xiaobao
Published: December 2024

Background: HCA587 antigen is called tumor-testicular antigen, which is highly expressed in a large number of malignant tumors and shows superior immunogenicity. Combined with adjuvants is considered to be an effective tumor immunotherapy strategy. Objective: To explore the inhibitory effect and mechanism of HCA587 protein combined with 12 μg self-made ISCOMATRIX and CpG ODN adjuvant (referred to as "HCA587 protein vaccine") on angiogenesis of melanoma in mice. Methods: C57BL/6J mice were subcutaneously inoculated with B16-HCA587 tumor cells on the right side of the abdomen to establish a tumor-bearing mouse model, and HCA587 protein vaccine was used to treat the mice. The effect of HCA587 protein vaccine on tumor neovascularization was analyzed by hematoxylin-eosin (HE) staining, tumor immunohistochemical staining and immunofluorescence staining, and the effect of HCA587 protein vaccine on tumor angiogenesis was detected by alginate encapsulated B16-HCA587 tumor cells in mice immunized with HCA587 protein vaccine. Real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and Western-blot assay were used to detect the expression of angiogenesis-related molecules and apoptosis-related proteins in tumor tissue. TUNEL staining was used to evaluate the apoptosis of mouse melanoma. Results: After treatment with HCA587 protein vaccine, the tumor tissue necrosis and microvessel density decreased significantly. The experiment of alginate encapsulated tumor cells showed that HCA587 protein vaccine inhibited the angiogenesis of mouse melanoma, while HCA587 protein vaccine significantly increased the expression of PEDF in mouse melanoma tissue and promoted cell apoptosis. In addition, the protein vaccine significantly up-regulated the expression of phosphorylated p38 (p-p38), pro-apoptotic proteins Bax, caspase3, caspase8 and caspase9 in tumor tissues. Conclusion: HCA587 protein vaccine significantly inhibits neovascularization of melanoma in mice, which may be mediated by up-regulated PEDF-activated p38/Bax/caspase apoptosis pathway.
Four Polymorphs of Bioactive Diuretic Drug 4-Chloro-5-Chlorosulfonylsalicylic Acid
Authors: Miclaus Maria Olimpia , Borodi Gheorghe , Turza Alexandru
Published: December 2024

4-Chloro-5-chlorosulfonylsalicylic acid [C7H4Cl2O5S] is a derivative of salicylic acid and a diuretic agent. Its ability to form polymorphs through recrystallization from various solvents was demonstrated. As a result, four polymorphs were successfully obtained and analyzed using single-crystal X-ray diffraction and powder X-ray diffraction. The solid-state properties were investigated by evaluating crystal lattice energies and intermolecular interactions.
An Unambiguous Super-Resolution Algorithm for TDM-MIMO-SAR 3D Imaging Applications on Fast-Moving Platforms
Authors: Guan Sheng , Wang Mingming , Liang Xingdong , Liu Yunlong , Li Yanlei
Published: December 2024

Multiple Input Multiple Output (MIMO) radar enjoys the advantages of high degree of freedom and relatively large virtual aperture, so it has various forms of applications in several aspects such as remote sensing, autonomous driving and radar imaging. Among all multiplexing schemes, Time-Division Multiplexing (TDM) MIMO radar gains a wide range of interests, as it has a simple and low-cost hardware system which is easy to implement. However, the time-division nature of TDM-MIMO leads to the dilemma between lower Pulse Repetition Interval (PRI) and more transmitters, as the PRI of a TDM-MIMO system is proportional to the number of transmitters while the number of transmitters significantly affects the resolution of MIMO radar. Moreover, a high PRI is often needed to obtain unambiguous imaging results for MIMO-SAR 3D imaging applications on a fast-moving platform such as a car or an aircraft. Therefore, it is of vital importance to develop an algorithm which can achieve unambiguous TDM-MIMO-SAR 3D imaging even when the PRI is low. Inspired by the motion compensation problem associated with TDM-MIMO radar imaging, this paper proposes a novel imaging algorithm which can utilize the phase shift induced by the time-division nature of TDM-MIMO radar to achieve unambiguous MIMO-SAR 3D imaging. A 2D-Compressed Sensing (CS) based method is employed and the proposed method is verified by simulation data. Finally, a real-world experiment is conducted to show the unambiguous imaging ability of the proposed method compared with the ordinary matched-filter-based method. The effect of velocity error is also analyzed with simulation results.
Monoclonal Protein Evaluation in the Diagnostic Algorithm for Cardiac Amyloidosis
Authors: Bukhari Syed
Published: December 2024

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype.
From Anti-Piracy to Cybersecurity: Leveraging Website Blocking in an Integrated Digital Ecosystem
Authors: Herps Aaron , Watters Paul A. , Simone Daniela , Foster Jeffrey
Published: December 2024

This study evaluates the effectiveness of website blocking as a cybersecurity control to mitigate copyright infringement, focusing on Southeast Asia's diverse legal and technological environments. Using a quasi-experimental design during the COVID-19 pandemic, this research examines the impact of website blocking measures in Indonesia, Vietnam, Malaysia, and Singapore. For the first time, the findings reveal that swift, systematic website blocking—exemplified by Indonesia—serves as an effective cybersecurity control, significantly reducing access to infringing content while redirecting traffic toward legitimate platforms. Jurisdictions with procedural delays and inconsistent enforcement, however, demonstrate limited efficacy, highlighting the need for dynamic responses to evolving threats such as domain hopping and proxy servers. The findings inform broader cybersecurity applications like network segmentation, access control, and threat intelligence. This work links traditional copyright enforcement to proactive incident detection and response strategies, providing insights into broader applications for cybersecurity, such as network segmentation, access control, and threat intelligence.
Exploring Bhutan's Economic Development Trajectory
Authors: Rai Ariti
Published: December 2024

Bhutan's economic development has been shaped by modernization since 1952, marked by land reforms and Five-Year Plans, including the unique Gross National Happiness (GNH) framework. This study evaluates Bhutan's economic trajectory using indicators like GDP, living standards, education, and poverty. While GDP growth is stable, with an average rate of 4.71% (2011–2021), challenges such as rising unemployment and stagnant poverty reduction persist. Bhutan has transitioned from a Least Developed Country to a middle-income economy but remains in the transitional stage of development per Rostow's model. Strengthening secondary and tertiary sectors and equitable resource distribution are vital for sustainable progress.
Integrated Plant Design for Green Hydrogen Production and Power Generation in PV Systems: Balancing Electrolyzer Sizing and Storage
Authors: Franco Alessandro , Carcasci Carlo , Ademollo Andrea , Calabrese Mattia , Giovannini Caterina
Published: December 2024

This study evaluates the performance and feasibility of hybrid photovoltaic-hydrogen systems in-tegrated with 4.2 MW PV installations, focusing on the interplay between electrolyzer capacity, energy storage, and hydrogen production. Key findings reveal that downsizing electrolyzers, such as using a 1 MW unit instead of a 2 MW model, increases operational efficiency by extending nominal power usage, though it reduces total hydrogen output by approximately 50%. Meanwhile, expanding energy storage systems show diminishing returns, with added capacity offering minimal gains in hydrogen production and raising economic concerns. The system's performance is highly weather-dependent, with daily hydrogen production ranging from 26 kg on cloudy winter days to 375 kg during sunny summer conditions. Surplus energy export to the grid peaks at 3300 kWh during periods of high solar generation but is minimal otherwise. For economic and operational viability, the system design must prioritize directing a majority of PV energy to hydrogen production while minimizing grid export, requiring a minimum of 50% PV energy allocation to the hydrogen value chain. Cost analysis estimates a Levelized Cost of Hydrogen (LCOH) as low as €6/kg with an optimized configuration of a 2 MW electrolyzer and 2 MWh battery. Although high production costs challenge economic sustainability, careful component optimization and supportive policies can enable competitive hydrogen pricing and a positive net present value (NPV) over the system's lifetime.
Exploiting GPT-4 for Multimodal Medical Data Processing in Electronic Health Record Systems
Authors: Yuan Jiayu
Published: December 2024

The growing intricacy of medical data presents a significant challenge for electronic health record (EHR) systems, which are required to integrate multimodal data in order to enhance diagnostic precision and treatment efficacy. This paper proposes a novel GPT-4-based approach to enhance medical data processing capabilities in EHR systems. In particular, the GPT-4 was initially employed to encode clinical text data, and a pre-training and fine-tuning strategy was devised based on domain knowledge with the objective of enhancing its comprehension of medical terminology and context in accordance with the specific requirements of the medical field. Secondly, in order to address the issue of incomplete text data in EHRs, we propose a context-based adaptive filling strategy to facilitate the dynamic completion of missing information and enhance the integrity of text data through the analysis of analogous historical records. In order to enhance the model's capacity to comprehend lengthy texts, we have employed a hierarchical attention mechanism to partition lengthy texts into multiple sub-blocks. Through the adjustment of hierarchical attention weights, GPT-4 is capable of effectively capturing cross-paragraph and cross-topic relationships. Furthermore, data augmentation technology has been employed to generate diverse training data through semantic extensions and data augmentation models, thereby enhancing GPT-4's adaptability to diverse inputs. The experimental results demonstrate that the proposed method has led to notable enhancements in prediction accuracy, text generation capability, and data processing efficiency.
The Coincidence of Nitrate Migration and Salinization Processes Led by Soil Moisture Enhancement in the Hula Valley
Authors: Gophen Moshe
Published: December 2024

The drainage of the Hula wetlands and old Lake Hula was completed in 1957. Agricultural development replaced the natural ecosystem land use with agricultural cultivation. The Hula pre-drainage anaerobic conditions were replaced by organic matter oxidation and Sulfur and Nitrate carbonate enrichments. The ecosystem structure of highly diversified fauna and flora was devastated. During the post-drainage period, enhancement of accumulated carbonates and Gypsum (CaSO4) and organic matter oxidation created soil salinization and nitrate accumulation. Ammonia was oxidized to Nitrate and its accumulation concerned Kinneret water quality protection managers. Evaluation of long-term (1994-2024) study through monitoring program of the temporal and seasonal distributional pattern of Nitrate, Sulfate, pH, Alkalinity, and Electrical Conductivity within the Peat soil drained and pore-waters indicates soil moisture as the dominant impact factor which controls two geochemically independent coincide processes, nitrate migration and soil salinization.
Monte-Carlo method and artificial intelligence: application of Monte-Carlo method in reinforcement learning
Authors: Nekrasova Mariia
Published: December 2024

Reinforcement learning is the fastest growing technology used in the creation of artificial intelligent systems. At the moment, this field is quite extensive. Many researchers around the world are actively working with reinforcement learning in various fields: neuroscience, control theory, psychology and many others. The purpose of this paper is to substantiate the possibility of using the Monte Carlo method in reinforcement learning. It is known that the main thing in such learning is to record aspects of a real problem when a learner interacts with the surrounding world to achieve his goal. That is, a learning agent must have a goal associated with the state of the environment. It is also necessary to be able to sense the environment and perform actions that affect it. The formulation of a reinforcement learning problem should take into account all three aspects - sensation, action and goal - in their simplest forms. Monte Carlo methods are able to solve reinforcement learning problems based on averaging sample results. In order to ensure the availability of clearly defined results, this article considers Monte Carlo methods only for episodic problems. Thus, Monte Carlo methods can be incremental at the episode level.
SYSTEM OF THREE COLLINEAR INTERFACE CRACKS IN A FINITE SIZE DOMAIN
Authors: Voiedilo Roman , Loboda Volodymyr
Published: December 2024

A bimaterial region, consisting of two rectangles, connected by their edges is considered. Three cracks of arbitrary length and location have appeared in the interface. It is assumed that the load applied at the outer ends of the rectangles is directed orthogonally to the interface. The Abaqus software package is used to solve the problem. A finite element mesh with thickening near the cracks and especially near their tips is created. Eight-node finite elements of the Lagrangian type are used. A series of calculations are performed on different meshes with different degrees of their thickening, which allows us to assess the dependence of the results on the mesh parameters. To simplify and speed up the modeling process, a program in Python, which is integrated into Abaqus as a script was written. This program allows us to change quickly the parameters of cracks, loads and material properties, as well as automatically create a new mesh for each configuration. The analysis focused on the consideration of the sizes of the crack region and the calculation region dependencies. It was found out that the energy release rate increases with a decrease in the relative size of the calculation region. This is especially evident for the crack tips that are closest to the boundaries of the region. For the case of a region much larger than the crack size, a comparison of numerical results with the corresponding analytical solutions was carried out and their good agreement was shown.
APPLICATION OF MULTI-INDICATOR QUALITY ASSESSMENT OF PARETO APPROXIMATION IN MULTI-CRITERIA DECISION MAKING
Authors: Nekrasova Mariia
Published: December 2024

Supporting multi-criteria decision-making based on multi-indicator quality assessment of Pareto approximation is an important task in the field of multi-criteria optimization. Such assessment allows making more informed and accurate decisions using information about several indicators that determine the quality of solutions. Pareto approximation is an approximate set of solutions that seeks to describe the real Pareto front as accurately as possible. In this case, it is necessary to assess how well the found solutions cover or approximate the real Pareto front. Among the large number of known algorithms for solving this problem, algorithms based on the preliminary construction of an approximation of its Pareto front (set) and called P-algorithms can be named. P-algorithms can be built on the basis of evolutionary and primarily on the basis of genetic algorithms, as well as on the basis of swarm algorithms of global optimization, such as particle swarm algorithms, ant colonies, honey bees, etc. Given the large number of P-algorithms, the problem of choosing the "best" algorithm for a given multi-criteria optimization problem (MCO problem) arises - the problem of meta-optimization. In this regard, a significant number of indicators of the effectiveness of P-algorithms (P-indicators) have been developed, which are based primarily on assessing the quality of the obtained approximation of the Pareto front (set) (P-approximation). Thus, the problem of assessing the quality of the P-algorithm itself becomes multi-criteria, or more precisely, multi-indicator.
MODELLING OF IMPACT FRACTURE PROCESSES OF PLATES USING PERIDIGM SOFTWARE
Authors: Bondar Serhii , Batiuk Oleh , Breslavsky Dmytro
Published: December 2024

The paper considers an approach to numerical modeling of impact inelastic loading of solids. The use of various numerical approaches to describing impact deformation of solid deformed bodies is discussed, the application of the finite element method and methods of peridynamics analysis are compared. The basic theoretical concepts of peridynamics are used for modeling. The Peridigm software is used for computational evaluation of impact interaction and fracture processes. The main relations of the calculation method are considered. A bond-based material model is used in calculations to analyze fracture processes. The implementation of the deployment of computational projects using Docker containers is discussed. The software implementation of the project is analyzed using the modules of the Peridigm software, and class, sequence, component, and activity diagrams intended to describe the properties of projects are considered. The technical possibilities of performing numerical analysis of various mechanical processes using various, including user-defined, software modules for setting constitutive equations, computational procedures, input-output and data management are discussed. The sequence of calculations using the developed computational project is analyzed. Using the example of the problem of impact penetration of a steel plate by a spherical impactor moving at different velocities, the possibilities of numerical analysis of deformation and fracture of structural elements with determination of the shapes of the resulting macroscopic defects are demonstrated. For the given example, various velocity loading modes are analyzed. The velocity ranges at which irreversible plastic deformation occur, fracture begins, and partial or complete plate penetration is realized are established.
Genotyping of Yersinia pseudotuberculosis Strains Isolated in Russia Using MLST
Authors: Meloyan M. G. , Vodop’yanov A. S. , Voskresenskaya E. A. , Pisanov R. V. , Chesnokova M. V. , Klimov V. T. , Kokorina G. I. , Bogumil’chik E. A. , Peretolchina N. P. , Trukhachev A. L.
Published: December 2024

The aim of this study was the genotyping of Yersinia pseudotuberculosis strains isolated in Russia using multilocus sequence typing (MLST), a comparative analysis of MLST results with INDEL typing results. Materials and methods. 348 strains of various serotypes isolated in different regions of the world, including 59 Russian strains, were analyzed. 302 strains from the NCBI database were used. The nucleotide sequences of the strains were determined using the MiSeq technology platform. The author MLSTtyper program was used for MLST analysis. Results and discussion. It has been found out that strains of at least, 2, 9, 19, 26, 32, 42, 43 ST-types circulate in Russia. The majority of the studied Russian strains belong to the ST2 type (58 %). Phylogenetic analysis conducted using MLST data showed that a number of clusters contains strains that have been circulating in Russia for a long time, and strains of these genotypes are not found abroad. Some of the Russian strains are included in clusters containing strains isolated in various regions of the world and can be attributed to strains of either “Asian” or “European” types. The data obtained using the MLSTtyper program coincided with the data of foreign authors when analyzing the same strains using the MLST method. Comparison of the results of genetic differentiation of Y. pseudotuberculosis strains using MLST and INDEL typing indicates that MLST has a greater discriminatory ability; however, in some cases INDEL genotyping allows differentiating those strains that had the same ST genotype.
Biological and Genetic Characteristics of a New Bacteriophage Isolated from Cholera Vibrios from a Patient (Moscow, 2023)
Authors: Sizova Yu. V. , Pogozhova M. P. , Gaevskaya N. E. , Tyurina A. V. , Vodop’yanov A. S.
Published: December 2024

Currently, cholera remains a relevant infectious disease that requires new alternative antimicrobial agents for treatment and prevention, which can be bacteriophages. The aim of the study was to obtain a new bacteriophage from a culture of cholera vibrios isolated from a patient in Moscow in 2023, and characterize its biological and genetic properties. Materials and methods. The toxigenic strain Vibrio cholerae O1 Ogawa 21197 was used in the work. A two-layer agar Grazia method was applied to study biological properties of the bacteriophage (morphology of negative colonies, sensitivity to high and low temperatures and chloroform, lytic activity and specificity). The morphology of phage particles was studied under an electron microscope. The genetic characterization was carried out on the basis of genomewide sequencing using the programs “SeqAnalyzer”, “PhageAnalyzer 2.0”, as well as the algorithms BLASTN 2.2.29 and BLASTX 2.12.0+. Results and discussion. Isolated bacteriophage forms transparent negative colonies with an uneven edge without secondary growth and halo on nutrient media. Electron microscopy revealed that the isolated bacteriophage has a multifaceted head and a short tail. The phage is specific and has high lytic activity against cholera vibrios isolated from humans, is sensitive to heat and resistant to chloroform and freezing. Analysis of the sequencing results has shown that the phage belongs to the Caudoviricetes class of the Zobellviridae family, the genome size is 48,074 bp with a G+C content=42.7 %. The resulting genome was checked for nucleotide sequence homology with DNA sequences of other bacteriophages. 9 Vibrio phage genomes of the Zobellviridae family of the Caudoviricetes class were found, having a high percentage of overlap, isolated out of the water in India.
Spatio-Temporal Analysis of the Tularemia Agent Population in the Rostov Region, DPR, LPR and Ukraine from 1943 to 2023
Authors: Sorokin V. M. , Pavlovich N. V. , Tsimbalistova M. V. , Aronova N. V. , Vodop’yanov A. S. , Pisanov R. V. , Noskov A. K.
Published: December 2024

The aim of the study was to conduct spatio-temporal retrospective and operational genetic analysis of the tularemia agent population in the Rostov Region, Donetsk People’s Republic (DPR), Lugansk PR and Ukraine in the period of 1943–2023. Materials and methods. We used Francisella tularensis strains isolated in the Rostov Region (RR), DPR, LPR and Ukraine between 1943 and 2023. VNTR genotyping was performed by 5 loci. Cluster analysis and construction of a phylogenetic tree were carried out using the GrapeTree software (NJ and MST algorithms). Whole-genome sequencing was performed on the MiSeq Illumina platform. The assembly of genomes in the form of reads was carried out using the Spades program. Results and discussion. A comparative analysis of the VNTR genotypes in 72 F. tularensis strains has been conducted: 35 strains isolated from various natural foci of Russia and the Rostov Region in particular from 1928 to 2023, 11 strains from the DPR and LPR (2022–2023) and 26 strains from the collection of the Rostov-on-Don Anti-Plague Institute, isolated on the territory of Ukraine from 1949 to 1990. In the studied strains, 20 individual genotypes have been identified, distributed among three clonal complexes (CC1 – CC3). Molecular-genetic analysis of F. tularensis strains has made it possible to identify three clonal complexes of tularemia agent (CC1 – CC3), circula ting in the studied areas. All of them are present on the territory of the RR and only complex CC2 shows a geographic confidedness to the southern areas of the RR. Strains isolated in western Ukraine before the 1990s belong exclusively to the CC3 complex. Judging by the range of distribution and diversity of genotypes, the population of strains of the CC3 and CC1 complexes has been existing for a long time in the studied areas. Strains of the same genotype can be found in endemic areas for up to 80 years and at a distance of about 1000 km from each other. On the contrary, the population of the CC2 complex is the most recent in time of origin and is geographically limited to the territory of RR. Geographic data on the origin of the CC1 and CC3 progenitor clones of the tularemia agent clonal complexes suggest an expansion of the genetic diversity of tularemia agent population from east to west.
The Use of the Serologic Monitoring for the Assessment of Possible Contact of the Population with Tularemia Pathogen in the Territories of the Donetsk and Lugansk People’s Republics and Zaporozhe and Kherson Regions
Authors: Tushinsky A. A. , Tsai A. V. , Anisimova A. S. , Aronova N. V. , Pichurina N. L. , Pavlovich N. V. , Noskov A. K.
Published: December 2024

Serological monitoring as a component of the epidemiological surveillance, serves as a method for asses sing the intensity of possible contacts of the population with the natural-focal disease pathogen. The aim of the study was to analyze possible contacts of the population with the causative agent of tularemia, based on the results of serological study of blood sera of the healthy population conducted in 2023 on the territories of Donetsk and Lugansk People’s Republics, Zaporozhe and Kherson Regions. Materials and methods. Applying IHR/IHIR serological methods, we have tested 829 blood sera obtained in 2023, from individuals living in areas at increased risk of aggravation of epidemiological situation on tularemia, who had not previously participated in specific prevention measures against tularemia. Results and discussion. Positive results on the presence of anti-tularemia antibodies in IHR/IHIR in the four studied territories ranged from 18.5 to 40.0 %. The analysis of questionnaires, that were filled out by donors has made it possible to determine the conditions of possible human contact with the pathogen in the foci of infection. According to the results of the study, the contacts of the population with the components of the natural tularemia focus in the surveyed territories can be assessed as intense, since the presence of specific antibodies to the causative agent of tularemia in donors of all the studied regions, on average, amounted to 24.4 %. Analysis of the data from the survey showed that all samples, in which antibodies to tularemia causative agent were detected, were registered from donors who may have had contact with carriers and vectors of the pathogen. According to the results of the study, small mammals contribute the most to the possible contact of the population with the causative agent of tularemia.
Molecular Identification of Yersinia pestis Strains Isolated in the Aksai High-Mountain Focus of the Kyrgyz Republic in 2024
Authors: Eroshenko G. A. , Kubanychbekova G. K. , Kovrizhnikov A. V. , Dzhaparova A. K. , Mukanmetesen uulu Zh. , Abdygazieva A. K. , Sidorin A. S. , Krasnov Ya. M. , Kuznetsov A. A. , Fadeeva A. V. , Nikiforov A. K. , Devdariani Z. L. , Kuklev E. V. , Boiko A. V. , Kutyrev V. V.
Published: December 2024

The Aksai high-mountain focus is part of the Tien Shan focus, which has recently shown constant epizootic activity. In 2024, Yersinia pestis cultures were isolated from the Aksai focus for the first time in the 21st century. The aim of the study was molecular identification of Y. pestis strains collected in the Aksai focus in 2024, their phylogenetic analysis to establish their origin and obtain whole-genome sequences that are reference ones for this focus in the mo dern period. Materials and methods. The genomes of Y. pestis strains were sequenced on a MinIon genetic analyzer (Oxford Nanopore Technologies, UK). Sequencing libraries were prepared using the Native Barcoding Kit 24 v14 (SQKNBD114.24) and sequenced on an R10.4.1 flow cell. Core SNPs were identified applying pair wise alignment of the obtained whole-genome sequences to the genome of Y. pestis CO92 strain using Snippy v4.6.0 software. The Maximum Likelihood dendrogram was constructed using PhyML 3.1. Results and discussion. According to the phylogenetic analysis of whole-genome sequences, it has been established that the Y. pestis strains isolated in the Aksai focus in 2024 belong to the phylogenetic branch 0.ANT3 of antique biovar. The Y. pestis strains of 2024 fall under the 0.ANT3 polytomy, which also includes all 0.ANT3 strains of the 20th century from the Aksai, Upper Naryn and Alai high-mountain foci and strains from the Xinjiang province in China. The genetic differences between the 0.ANT3 strains of the current and last centuries are small, which proves the continuity of the preservation of this population in the 20th–21st centuries and the local origin of the 2024-strains. Strains 0.ANT3 were previously isolated across large areas of the Upper Naryn, Aksai, Alai plague foci and on the adjacent territories of China, which indicates the existence of a mega-focus of 0.ANT3 Y. pestis there. Strains 0.ANT3 are highly virulent and epidemically significant. The activation of the Aksai natural plague focus requires increased epidemiological surveillance of this autonomous plague focus in the Tien Shan.
Retrospective Molecular Investigation of Plague Outbreaks in the Northern Aral Sea Region in the Mid-20th Century
Authors: Karapetyan L. A. , Balykova A. N. , Chervyakova N. S. , Fedorov A. V. , Eroshenko G. A. , Abramova E. G. , Germanchuk V. G. , Kuklev E. V. , Toporkov V. P.
Published: December 2024

The aim of the work is a retrospective molecular examination of plague outbreaks that occurred on the northern coast of the Aral Sea in the middle of the past century, and a phylogenetic analysis of the Yersinia pestis strains that caused them. Materials and methods. Whole-genome sequences of 39 Y. pestis strains from foci of the Northern Aral Sea region, isolated in 1945–1974, were used. Whole-genome sequencing was performed in the Ion S5 XL System (Thermo Fischer Scientific, USA). Data processing and sequence assembly were carried out using the Ion Torrent Suite software package, v5.12, FastQC v0.12.0, unicycler v0.5.0. Phylogenetic reconstruction was carried out using the wholegenome SNP analysis method, the dendrogram was constructed using the Maximum Likelihood algorithm using the PhyML v3.1 program. Molecular typing of strains was performed using the MLVA25 method. Results and discussion. Y. pestis strains isolated in the Northern Aral Sea region between 1945 and 1974 belong to the phylogenetic branch 2.MED1 of the medieval biovar of the main subspecies. Plague outbreaks in the Northern Aral Sea region in 1945, 1955, 1966, and 1969 were caused by strains of the Caspian subbranch 2.MED1, and the outbreak of 1967 – by strains of the Central Asian subbranch, which successively reached this region from the Northern Caspian and Balkhash regions. It is shown that the sources of human infection were epizootics occurring on the northern coast of the Aral Sea. It is established that in the 1960s, Y. pestis strains of the Caspian and Central Asian subbranches 2.MED1 medieval biovar circulated simultaneously in the Northern Aral Sea region. A characteristic feature of the plague outbreak of 1945 was the presence of a large number of SNPs specific to each strain, possibly due to the process of rapid adaptation of the Caspian subbranche 2.MED1 strains to the conditions of the natural biocenosis of the Northern Aral Sea region. Subsequently, the rate of evolution of the emerging Northern Aral population 2.MED1 significantly decreased, which was accompanied by the formation of individual clusters of strains with a small number of individual SNPs.
El gasto público educativo y su efecto en el rendimiento académico: evidencia para Perú durante el periodo 2008 – 2016
Authors:   , Valdez Najarro Zarela Kalu
Published: December 2024

El objetivo de esta investigación es evaluar el efecto del gasto público educativo sobre el rendimiento académico de los alumnos de segundo grado de primaria a nivel nacional en el período del 2008 - 2016. Para ello, se emplean los datos estadísticos de la Evaluación Censal de Estudiantes (ECE), Instituto Nacional de Estadística e Informática (INEI) y del portal de transparencia del Ministerio de Educación (MINEDU). La metodología empírica consiste en estimar un modelo de regresión dinámico para datos de panel a través del estimador Generalizado de Momentos (GMM) propuesto por Blundell y Bond (1998). Los resultados indican que el gasto público educativo por alumno tiene un efecto positivo y estadísticamente significativo sobre el rendimiento académico en matemáticas; sin embargo, el efecto sobre comprensión lectora no es estadísticamente significativo. Además, se encuentra que el rendimiento académico es altamente persistente.
Popping misinformation bubbles: Results from style-based messaging into online misinformation ecosystems
Authors: Lee Jooyoung , Booth Emily , Farid Hany , Rizoiu Marian-Andrei
Published: December 2024

Misinformation is often viewed as an information problem, attributed to people’s poor understanding of consensus-based facts. While this is a contributing factor, we propose that misinformation and conspiracy are simply more engaging explanations for our world. Can we combat misinformation by making facts fun? We present the findings of a controlled experiment testing this hypothesis, in which we tailored messaging about consensus-based information to the communication styles used by three vulnerable cohorts. Our results demonstrate that styled message generated higher engagement from users than the neutral-toned variants. We introduce our theory of the misinformation ecosystem as a way of understanding online communities and their communication styles, and profiles of three personas representative of the cohorts included in our experiment. Our findings suggest that styled messaging for consensus-based information can reach vulnerable fringe communities that are otherwise resistant to external influence, providing considerable implications about possible future interventions to counter misinformation.
Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis
Authors: Wang Nan , Zheng Xingyue , Ma Qianzi , Liu Junjie , Yang Wanchao , Sun Yanan , Che Yanlu , Wang Jingting
Published: December 2024

Background
Hydrogen is known to improve allergic rhinitis. Nasal flora that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the flora can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect flora distribution and diversity. These findings suggest that hydrogen may target the nasal flora and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease.
Methods
The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal flora were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.
Results
There were no adverse reactions during or after hydrogen inhal ation in AR patients, and the safety was good, with significant improvem ents in the VAS, TNSS, EOS, and IgE scores (P<0.05). The results of 16 S rRNA gene sequencing of nasal flora revealed that the distribution and diversity of nasal flora in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(R)-hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abun dant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(R) -Hydroxy-prostaglandin E2 levels were positively correlated with the abund ance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.
Conclusions
H2 may improve symptoms in AR patients by modulating nasalflora distribution and metabolite levels.
Establishing reference curves for vital tissue perfusion using quantitative near-infrared fluorescence imaging with indocyanine green
Authors: Tange Floris P. , Peul Roderick C. , Hoven Pim van den , Koning Stefan , Kruiswijk Mo W. , Faber Robin A. , Verduijn Pieter S. , Rijswijk Carla S.P. van , Galema Hidde A. , Hilling Denise E. , Dijk Sam P.J. van , Ginhoven Tessa M. van , Keereweer Stijn , Mureau Marc A.M. , Feitsma Eline A. , Noltes Milou E. , Kruijff Schelto , Driessen Caroline , Achiam Michael P. , Schepers Abbey , Schaik Jan van , Mieog J. Sven D. , Vahrmeijer Alexander L. , Hamming Jaap F. , Vorst Joost R. van der
Published: December 2024

Purpose
Assessment of tissue perfusion using near-infrared fluorescence (NIR) with indocyanine green (ICG) is gaining popularity, however reliable and objective interpretation remains a challenge. Therefore, this study aimed to establish reference curves for vital tissue perfusion of multiple target tissues using this imaging modality.
Methods
Data from five prospective study cohorts conducted in three Dutch academic medical centres between December 2018 and June 2023 was included. Quantitative analysis of ICG NIR fluorescence video’s using time-intensity curves was performed in ten target tissues, including the colon, ileum, gastric conduit, deep inferior epigastric artery perforator (DIEP) flap, skin of the foot, trachea, sternocleidomastoid muscle (SCM), carotid artery, parathyroid gland, and skin of the neck.
Results
A total of 178 patients were included in this study, representing 303 target tissues. Three different patterns of reference curves were identified. Seven out of ten tissues showed a reference curve with rapid inflow (median time-to-max (tmax): 13.0-17.8 sec, median maximum normalized slope (slope norm): 10.6–12.6%/sec), short outflow (median area-under-the-curve of tmax + 60sec (AUC60): 65.0-85.1%) followed by a gradual/absent outflow. Secondly, the DIEP flap and SCM showed a reference curve with slightly longer inflow (median tmax: 24.0, 22.0 sec, median slope norm: 9.3, 9.7%/sec respectively) and reduced outflow (median AUC60: 89.1, 89.0% respectively). Thirdly, the skin of the foot showed slow inflow (median tmax 141.1sec, median norm slope 2.1%/sec) without outflow.
Conclusion
This study demonstrates reference curves for vital tissue perfusion of multiple target tissues identified with ICG NIR fluorescence imaging, providing a critical step towards the clinical implementation of this technique.
Prediction on the Demand for Preschool Resources in Shaanxi under the Three-Child Policy
Authors: Li Dong , Yu Yanyan , Sui Mengyao
Published: December 2024

The implementation of the three-child policy in China will impact the shifting trends in the newborn population, thereby influencing the size and resource needs of preschool education. In order to accomplish the objective of high-quality and sustainable preschool development, it is crucial to promptly predict the demand for preschool resources based on demographic changes. However, current research on demand forecasting of preschool resources fails to consider the impact of demographic and socioeconomic changes on the preschool system within the context of the three-child policy, potentially resulting in unsatisfactory research outcomes. This paper utilizes the system dynamics method to establish a preschool education resource prediction model based on an analysis of the interplay between population, economy, and various factors within the preschool education system. The model parameters are optimized through the application of the multi-objective lioness optimization algorithm. Subsequently, the study predicts the shifts in demand for preschool education resources (such as preschool education place demand, teacher demand, and capital demand) in Shaanxi from 2022 to 2060. The findings indicate an 'M'-shaped trajectory in both preschool enrollment and teacher demand. Specifically, the number of schools and teachers is projected to increase to 10,491 schools and 188,800 teachers, respectively, in 2022-2023. Subsequently, between 2024 and 2026, there will be a reduction to 8,535 schools and 153,600 teachers. In 2027, a period of rapid growth is anticipated, with an increase to 9,663 schools and 173,900 teachers by 2029. However, between 2030 and 2060, these figures are expected to decline to 6,643 schools and 119,600 teachers. Additionally, the overall trend in the evolving demand for funding in preschool education follows an 'N'-shaped pattern. Specifically, the funding is projected to continue increasing to 23.63 billion Yuan between 2022 and 2024, followed by a reduction to 21.92 billion Yuan from 2025 to 2026. Subsequently, there will be a period of rapid growth from 2027 to 2029, with funding reaching 28.68 billion Yuan. Afterward, the funding will experience a gradual increase, eventually reaching 81.75 billion Yuan from 2030 to 2060. In general, the demand for preschool education resources in Shaanxi will undergo a brief phase of rapid growth in the coming years due to the impact of the three-child policy. However, it will eventually transition into a period of decline. Consequently, the government and relevant education authorities should carefully assess the disparities between short-term and long-term requirements and develop a scientific and prudent plan for preschool resources.
Genome-scale activation screen reveals lncRNA HNF1A-AS1 as a novel therapeutic target for pancreatic cancer metastasis
Authors: Lei Shan , Zhang Zhixue , Zeng Zhirui , Cao Wenpeng , Sun Yating , Li Dahuan , Pan Jigang , Wu Yingmin , Zhang Tuo , Chen Tengxiang
Published: December 2024

Background
Long non-coding RNAs (LncRNAs) have emerged as pivotal biomarkers and regulators across various cancers. In pancreatic cancer (PC), however, the mechanisms underlying the expression and functional roles of lncRNAs remain inadequately elucidated.
Methods
CRISPR/CRISPR-associated protein 9 (Cas9) single-guide RNA (sgRNA)-pooled lncRNA libraries were used to screen for the critical lncRNAs regulating PC metastasis. The expression levels of lncRNA HNF1A-AS1 were quantified in PC cell lines and clinical samples using qRT-PCR. Investigations into HNF1A-AS1's impact on PC cell migration and invasion were conducted through both loss-of-function and gain-of-function approaches. A range of techniques, including fluorescence in situ hybridization (FISH), mRNA sequencing, RNA immunoprecipitation (RIP), bioinformatics analysis, dual-luciferase reporter assays, RNA pull-down assays, ChIP-PCR, and rescue experiments, were employed to unravel the competitive endogenous RNA (ceRNA) network regulated by HNF1A-AS1.
Results
The research identified HNF1A-AS1 as a novel and influential lncRNA that acts as a pro-metastatic factor in PC. Compared to normal controls, HNF1A-AS1 levels were significantly elevated in PC cell lines and tissue samples. Elevated HNF1A-AS1 expression correlated with increased lymph node metastasis and poorer overall survival in patients with PC. Knocking down HNF1A-AS1 substantially reduced metastasis, whereas its overexpression exacerbated it. Mechanistically, HNF1A-AS1 promotes an oncogenic splice switch from the standard isoform CD44s to the variant isoform CD44v (3–10), acting as a scaffold for the binding of CD44 pre-mRNA to U2SURP. The levels of HNF1A-AS1 and CD44v (3–10) serve as indicators of poor prognosis. Furthermore, SNAI2 was shown to specifically bind to the HNF1A-AS1 promoter, thereby activating its transcription. Antisense oligonucleotides (ASOs) targeting HNF1A-AS1 also significantly inhibited cancer metastasis.
Conclusions
SNAI2’s role in enhancing HNF1A-AS1 transcription underscores the critical function of HNF1A-AS1 in promoting PC metastasis through modulation of CD44 alternative splicing via U2SURP. Targeted silencing of HNF1A-AS1 presents a promising therapeutic avenue for patients with PC.