bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of N52R Mutation at the SPN-ARR Interface on the Conformational Dynamics of SHANK3
Authors: Almaadani Hiba K. , Mattaparthi Venkata Satish Kumar 
Published: August 2024

Background:
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition.
The genetic basis of ASD involves numerous loci converging on neural pathways, particularly
affecting excitatory synapses. SHANK3, an essential protein in the post-synaptic neurons,
has been implicated in ASD, with mutations affecting its N-terminal, including the SPN domain.

Objective:
This study aims to investigate the impact of the N52R mutation on SHANK3 and assess
the dynamics, stability, flexibility, and compactness of the N52R mutant compared to
SHANK3 WT.

Methods:
Molecular dynamics simulations were conducted to investigate the structural dynamics
of SHANK3 WT and the N52R mutant. The simulations involved heating dynamics, density
equilibrium, and production dynamics. The trajectories were analyzed for RMSD, RMSF, Rg, hydrogen
bond analysis, and secondary structure.

Results:
The simulations revealed that the N52R mutant disrupts the stability and folding of
SHANK3, affecting intramolecular contacts between SPN and ARR. This disruption opens up the
distance between SPN and ARR domains, potentially influencing the protein's interactions with
partners, including αCaMKII and α-Fodrin. The altered conformation of the SPN-ARR tandem in
the N52R mutant suggests a potential impact on dendritic spine shape and synaptic plasticity.

Conclusion:
The findings shed light on the structural consequences of the N52R mutation in
SHANK3, emphasizing its role in influencing intramolecular interactions and potential effects on
synaptic function. Understanding these molecular dynamics contributes to unraveling the intricate
relationship between genetic variations in SHANK3 and clinical traits associated with ASD. Further
investigations are warranted to explore the physiological implications of these structural alterations
in vivo.
Design, Synthesis, Biological and in silico Evaluation of Novel Indazole-pyridine Hybrids for the Treatment of Breast Cancer
Authors: Panchal Ishan , Tripathi Rati Kailash Prasad , Yadav Mange Ram , Valera Meet , Parmar Kinjal 
Published: August 2024

Introduction:
The prevalence of breast cancer presents a substantial global health
concern, underscoring the ongoing need for the development of inventive therapeutic remedies

Methods:
In this investigation, an array of novel indazole-pyridine hybrids (5a-h) have been
designed and synthesized to assess their potential as candidates for treating breast cancer. Subsequently,
we have conducted biological evaluations to determine their cytotoxic effects on the
human MCF-7 breast cancer cell line. Furthermore, in silico analysis was conducted to estimate
the inhibition potential of the compounds against TrkA (Tropomyosin receptor kinase A), a specific
molecular target associated with breast cancer, through molecular docking. In silico physicochemical
and pharmacokinetic predictions were made to assess the compounds’ drug-like
properties.

Results:
Compound 5a emerged as the most active compound among the others with GI50 < 10
μg/ml. Besides, compound 5a showed high binding energy (BE -10.7 kcal/mol) against TrkA
and was stabilized within the TrkA binding pocket through hydrophobic, H-bonding, and van
der Waals interactions. In silico physicochemical and pharmacokinetic prediction studies indicated
that compound 5a obeyed both Lipinski’s and Veber’s rule and displayed a versatile
pharmacokinetic profile, implying compound 5a to appear as a viable candidate and that it could
be further refined to develop therapeutic agents for potentially treating breast cancer.

Conclusion:
This study offers a promising direction for the advancement of innovative breast
cancer treatments, highlighting the effectiveness of indazole-pyridine hybrids as potential anticancer
agents. Further optimization and preclinical development are necessary to advance these
compounds to clinical trials.
Methimazole-Induced Pancytopenia in a Patient with Graves' Disease:
A Case Report and Literature Review
Authors: Concepción-Zavaleta Marcio José , Quiroz-Aldave Juan Eduardo , Rivera Fabián Katia Eugenia , Ildefonso-Najarro Sofía Pilar , Moscol Chavez Karol Magdalena , Concepción-Urteaga Luis Alberto , Paz-Ibarra José 
Published: August 2024

Introduction:
Methimazole is an antithyroid drug known to cause hematological toxicity,
including agranulocytosis and, very rarely, pancytopenia. We herein present a case of a patient
with Graves' Disease (GD) who developed methimazole-induced pancytopenia.

Case Report:
A 53-year-old Peruvian woman with GD, initially treated with methimazole 20 mg
BID, experienced odynophagia, fever, and malaise after 37 days of treatment. The initial diagnosis
was agranulocytosis, leading to the discontinuation of methimazole and initiation of antibiotics.
Due to persistent neutropenia, a Granulocyte Colony-stimulating Factor (G-CSF) was administered.
Eight days later, she developed pancytopenia and was managed with hematopoietic
agents and platelet transfusions. The patient recovered with normalization of the blood count,
eliminating the need for Bone Marrow (BM) examination. Radioiodine therapy was chosen as
the definitive treatment, resulting in hypothyroidism. Currently, the patient is thyroidal and hematologically
stable.

Conclusion:
Methimazole-induced pancytopenia is a rare and serious complication; however,
with appropriate treatment, complete recovery can be achieved.
Vanek's Tumour as a Rare Cause of Dyspeptic Syndrome in a Patient with Primary Biliary Cholangitis: A Case Report
Authors: Gravina Antonietta Gerarda , Pellegrino Raffaele , Romeo Mario , Cipullo Marina , Lucà Stefano , Panarese Iacopo , Federico Alessandro 
Published: August 2024

Background:
Inflammatory Fibroid Polyp (IFP), also known as Vanek’s tumour, is a
rare mesenchymal gastrointestinal tumour, potentially causing a wide range of clinical manifestations
(even though it can be completely asymptomatic) primarily related to the location of the formation.
The available evidence suggests a fundamentally non-neoplastic behaviour of IFP.

Case Presentation:
A 67-year-old female was presented with persistent dyspepsia despite symptomatic
therapy. The patient's medical history included primary biliary cholangitis, managed with ursodeoxycholic
acid, non-haemorrhagic uterine fibroids, and right knee arthrosis. Clinical examination
revealed mild epigastric tenderness, and esophagogastroduodenoscopy identified a sessile mucosal
formation. Histological analysis of biopsy samples revealed a gastric hyperplastic polyp,
leading to a subsequent esophagogastroduodenoscopy for polypectomy. The excised specimen
confirmed the diagnosis of gastric IFP. Post-polypectomy, the patient experienced progressive
symptom amelioration, leading to complete resolution within three weeks.

Discussion:
This case thus describes a rare cause of dyspeptic syndrome associated with the presence
of a gastric IFP, promptly managed and resolved after endoscopic removal of the polyp, with
no histological signs of neoplasia within the en bloc resected sample.

Conclusion:
IFP is a possible and rare cause of dyspeptic syndrome. There remain significant challenges
in diagnosing this rare condition, which lacks pathognomonic or specific signs and symptoms
of its presence (especially when it causes symptoms). Endoscopy, when feasible, remains a
cornerstone in the resective management of such lesions.
Recent Updates on Novel Carrier Systems for the Delivery of Herbal Bioactives with Poor Bioavailability and their Clinical Trial Status
Authors: Yadav Swati , Harwansh Ranjit K. , Mazumder Rupa 
Published: August 2024

Abstract:
Herbal medicine and its active phytochemicals have been used since ancient times to
cure, mitigate, and treat various health issues, such as inflammation, wounds, fever, cough, cold,
diabetes, viral diseases, cancers, etc. Different databases, such as Scopus, Google Scholar,
Pubmed, Pubchem, and ScienceDirect, were searched exhaustively to find potent herbal leads and
their novel carrier systems. Literature was collected from these databases for the last twenty years.
Various research articles, review articles, books, and patents were referred for screening of the herbal
bioactives. In the recent past, herbal medicine-derived bioactives like curcumin, paclitaxel, catechin,
betulinic acid, ferulic acid, gallic acid, rutin, quercetin, resveratrol, glycyrrhizin, silybin,
berberine and many more have been reported for several pharmacological activities, including anticancer,
antidiabetic, hepatoprotective, antioxidant, antiinflammatory, antipyretic, antimicrobial,
etc. However, they have limitations like low aqueous solubility and poor bioavailability, which restrict
their therapeutic efficacy and clinical use. In this context, Novel Carrier Systems (NCSs) are
promising to overcome the problems of herbal bioactives. NCSs, such as liposomes, nanoparticles,
nanocapsules, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, nanoemulsions,
phytosomes, transfersomes, ethosomes, etc., have been utilized to encapsulate the bioactives
and drugs to enhance their solubility, permeability, elimination half-life, bioavailability, pharmacokinetics,
and therapeutic efficacy. Moreover, they protect the drugs/herbal bioactive from the
gastric environment and minimize the dose-associated toxicity. Recent advances in the various approaches,
including new methodology, analytical techniques, delivery mechanism, materials, loading
capacity, encapsulation efficiency, and in vitro and in vivo models, were considered in the
compilation of this review article. It was found that NCSs are pioneering in drug delivery and targeting.
The present study highlights the importance of herbal bioactives, advanced NCSs, patents,
and their clinical trial status.
Development of national economic systems in the context of transformation of globalization and regionalization processes
Authors: Plotnikov V. A. , Pshenichnikova S. N. , Fedotov V. A. 
Published: August 2024

Relevance. In the context of the formation of a multipolar world and the increasing sanctions pressure from unfriendly countries, Russia needs to adjust the models of integration into the system of world economic relations. In this context, an in-depth analysis of the mechanisms of internationalization, globalization and regionalization is required.The purpose is to consider the peculiarities of the impact of globalization and regionalization processes on national economies, taking into account the transformation of their internationalization models.Objectives: to consider the concepts of internationalization, regionalization and globalization, to identify their relationship; to identify the advantages and disadvantages of globalization, on the basis of which to describe the directions of transformation of forms of internationalization of economies; based on the analysis of available statistical data, to identify promising areas of integration of the national economy into the system of world economic relations.Methodology. The methods of quantitative and qualitative analysis, monographic and retrospective analysis, methods of comparing economic phenomena and processes, methods of abstraction, generalization of analyzed economic information are used.Results. The internationalization of national economies is a long-term sustainable trend. Their development is confirmed by sufficiently convincing quantitative data. Recently, the dynamics of the corresponding time series has become unstable, volatile and turbulent, with a tendency to decrease the level of indicators. There are transformations of the processes of globalization and regionalization, they acquire not only a new quality, but also institutional consolidation.Conclusions. The traditional model of globalization has exhausted itself. Due to the formation of a multipolar political and economic global space, in addition to the "center" and "periphery", countries of the "semi-periphery" stand out in it. They have sufficient economic sovereignty to refuse to participate in globalization projects, the balance of effects of which for these countries becomes negative. Russia is one of these countries. An additional incentive for reconfiguring the Russian model of internationalization of the economy is the anti-Russian sanctions imposed by the countries of the "center". In this regard, it is necessary to open up new opportunities for the national economy to integrate into the global economic space based on models of regionalization and glocalization.
Factor analysis of innovative activity of the regional economic system
Authors: Kudryakov R. I. 
Published: August 2024

Relevance. Innovation activity is one of the fundamental indicators of the effectiveness of innovation activity in the region. In the context of external challenges and economic instability, innovation is a fundamental vector of development of the domestic economy. However, the effectiveness of innovation activity is currently reduced due to the influence of risk factors of various etiologies. Therefore, the assessment of the factors influencing the innovative activity of the region determines the relevance and significance of the study.The purpose is to determine the influence of factors on the innovative activity of the region and its subjects, taking into account the ranking according to the degree of impact and the possibility of a restraining influence on the innovative potential of the region.Objectives. The following tasks were set and consistently solved in the study: to conduct a theoretical review of the concept of "innovative activity"; to identify factors; to classify and identify the degree of influence on the innovative activity of the region.Methodology. The paper uses a theoretical review of domestic and foreign authors dealing with the issues of factorial influence on the innovative activity of the region and its subjects. During the research, special methods were used: regression analysis, statistical analysis, expert approach, etc.Results. Based on the factor analysis, factors were identified, grouped, classified, and the degree of influence on the innovative activity of the region was determined, which helped to identify the cause of problems in the region (using the example of the Vladimir region).Conclusions. During the study, it was concluded that factor analysis allows us to examine the current state of innovation activity in the region and find the causes that have the greatest destructive effect on the indicator of innovation activity.
Organizational and economic transformations in the agro-industrial complex of the region as part of the implementation of the federal project
Authors: Tkacheva T. Yu. , Belousova S. N. , Erpuleva D. A. 
Published: August 2024

Relevance. The agro-industrial complex is one of the key sectors of the country's economy and includes such areas as: agriculture (livestock and crop production), processing of agricultural raw materials, production of fertilizers, chemicals, and feed. The agro-industrial complex works closely with enterprises involved in the transportation, storage, and processing of agricultural products, as a result, any changes in the agro-industrial complex affect the country's economy.The purpose of the study is to assess the impact of the implementation of the federal project of the Russian Federation “Development of industries and technical modernization of the agro-industrial complex” (hereinafter referred to as the Federal Project) on structural changes in the agro-industrial complex.Objectives: consideration of the objectives of the Federal project, its financial support for 2022-2024, analysis and assessment of economic and statistical indicators, identification and consideration of current problems within the framework of the project.Methodology. The information base of the study consisted of official regulations, works of domestic researchers in the field of agriculture, collections of articles with collective authors, articles from magazines, statistical data, official websites of relevant departments and ministries.Results. There are many problems in the development of the Russian agro-industrial complex, but there are also many promising areas for its development. These prospects are determined primarily by state policy in the field of supporting agriculture, the goal of which is the development of Russian farmers and increasing their role in the domestic and foreign markets.Conclusions. A promising direction for the development of the agro-industrial complex is the revision of the entire financing system in order to provide business executives with funds for the purchase of mineral fertilizers, fuels and lubricants, materials, and high-quality feed in the volumes necessary for efficient production. Also requiring attention are such pressing issues as increasing wages for agricultural workers, which will attract young specialists to the village and, thereby, resolve the issue of shortage of qualified personnel.
Optimization of the process of communication with customers when organizing sales on Internet platforms
Authors: Shamina O. V. , Paderina K. S. 
Published: August 2024

Relevance. Currently, the field of online trading on Internet platforms is actively developing. Online resources allow customers to familiarize themselves with the assortment, read reviews based on them and personal preferences, make a choice and, in general, make purchases without leaving home. Marketplaces are becoming the main platform for online sales.The purpose of the research is to develop a model for optimizing the process of communication with customers when organizing sales on Internet platforms.Objectives: to study the theoretical aspects of the concept of "communication process in the marketplace"; to identify the key problems of the communication process between customers and the seller on the marketplace, to develop a project to optimize the business process of "Communication between customer and seller" in RTK; to form recommendations for optimizing the process of processing information from customers.Methodology. The research is aimed at implementing the tasks set and is based on a review of scientific research by national and international market participants and a statistical analysis of the functioning of online trading platforms.Results. During the analysis of the work of the communications department of RTK LLC, a method for automating the communication process between customers and the seller was proposed, namely, optimizing the process of processing customer feedback, while implementing an automated software product.Conclusions. There are a huge number of technologies that can be implemented into the work of brands engaged in sales on the marketplace, and now this is becoming the most relevant, as the number of sellers in the market increases and competition between them becomes stronger. Mastering new digital technologies will allow trading companies to radically change the business ecosystem, make it faster and more efficient in order to meet the changing needs of customers.Optimizing the process of communication with customers when organizing sales on Internet platforms will help reduce time costs and increase the efficiency of sales organizations.
Migration agenda of the Kaliningrad region in the context of socio-economic development of Russia
Authors: Abramov A. P. , Gavrikov F. A. 
Published: August 2024

Relevance. The socio-economic context of the importance of migration policy is represented by a wide range of areas. First of all, the intensity of migration processes significantly correlates with the state of the labor market, influencing the balance of supply and demand. The relevance of the research topic is due to the importance of migration policy, both for the socio-economic development of the state and for ensuring national security in the strategic management horizon. The importance of building an effective migration policy has a significant level of importance for modern Russia. Taking into account the author’s position, the geopolitical situation and the retrospective history of international communications make Russia the center of gravity of migration flows, which requires the establishment of high-quality control not only over their intensity, but also over their structural content.The purpose is to determine the most effective tools for improving migration policy, taking into account territorial specifics.Objectives: to clarify the theoretical and methodological aspects of the implementation of state migration policy in Russia; reveal the features, analytical indicators and organizational mechanisms for implementing migration policy in Russia, taking into account the territorial specifics of the Kaliningrad region.Methodology. The methodological “portfolio” of the study is built on the basis of the provisions of socioeconomic theories of migration process management using quantitative methods of data collection and analysis.Results. A targeted analysis was carried out, as a result of which effective tools were identified for improving migration policy in the Kaliningrad region based on the adaptation of the universal migration project in the Kaliningrad city management system, creating the prerequisites for increasing its effectiveness and achieving target indicators.Conclusion. Improving migration policy is an objective necessity in order to solve a number of socio-economic problems and minimize risks to national security.
Substantiation of theoretical and methodological approaches to the determination of economic efficiency
Authors: Krakhina V. A. 
Published: August 2024

Relevance. An analysis of the problems of modern science and practice shows that the process of transition from one model of economic development to another, better one, implies the emergence of a number of phenomena characteristic of a market economy. For example, such a concept as “economic efficiency”. This concept is used by almost all business entities at different levels, since it allows quantitative and qualitative assessment of the condition of the object. Scientists from different times have studied this concept; accordingly, there are different interpretations and methods for determining economic efficiency. The works contain completely different interpretations of the concept under consideration, implying its different properties and elements. The situation is caused by the versatility and multidimensionality of this concept. Therefore, the formation of modern approaches to determining economic efficiency, which will sufficiently correspond to the general theory of performance management and modern requirements of the economy and society, is extremely necessary.The purpose is to substantiate theoretical and methodological approaches to determining economic efficiency.Objectives: consider the concept of “efficiency”; establish the relationship between “efficiency” and the concepts of “effect” and “effectiveness”; identify common and distinctive features of these concepts; determine the essence of economic efficiency; consider the main approaches to evaluating effectiveness.Methodology: comparative analysis, methods of induction and deduction, analysis and synthesis, logical analysis.Results. The article discusses the concept of “efficiency”, their relationship with the concepts of “effect” and “effectiveness”. The general and distinctive features of these concepts are established, the essence of economic efficiency is determined, and the main approaches to their assessment are considered.Conclusions. As a result of the work carried out, it was substantiated that economic efficiency consists of such elements as: the ability to assess the degree of achievement of the set goal, both from a quantitative and qualitative point of view; the need to use a systematic approach to calculate economic efficiency; taking into account the time factor and the limitation of all resources necessary to calculate economic efficiency.