bluuebunny/crossref_metadata_2025 huggingface dataset:
ALGORITHM FOR ASSESSING THE EFFECTIVENESS OF THE PROCESS OF MAKING CHANGES IN AUTOMATED, INFORMATION AND TELECOMMUNICATION SYSTEMS
Authors: NAUMCHIK N.A. ,   The Main Computing Center is a branch of JSC Russian Railways (MCC), Moscow, Russian Federation
Published: July 2024

The purpose of the research. The article discusses the problem of efficient use of computational resources. Describes the hardware prefetching mechanism. The purpose of the study is to find a solution that provides the ability to evaluate the quantitative use of the memory area in a computer program. This, in turn, is necessary to improve the efficiency of using the hardware capabilities of the computer. Results. As a result of the study, the author comes to the conclusion that the desired solution is an algorithm for determining the intensity of access to data structures in a computer program. The article presents the terminology that explains the name of the indicators used in the algorithm, describes the mathematical model for calculating the indicator and its limitations. A system of equations expressing the range of values of the data access intensity indicator was formulated. A three-dimensional model and two two-plane graphs were constructed to obtain a complete picture of the perception of the range of values. A detailed description of the algorithm and the presented mathematical model of the final and intermediate calculations allow us to develop an automated solution for certain tools (for example, compilers) used in the development of a computer program. The author concludes that the obtained indicator provides a quantitative representation of the use of shares of information (data areas) in a computer program for the subsequent assessment of the effectiveness of the computer program and the data structures used. Based on the results of the assessment, decisions can be made on the conformity / non conformity of the proposed solution and the need to modify the computer program or the data structures used.
DETERMINATION OF PARAMETERS OF HIDDEN THREATS OF EARLY DETECTION IN INFORMATION SYSTEMS FOR MACHINE LEARNING TASKS
Authors: ZOLOTUKHINA M.A. ,   Russian Technological University - MIREA, Moscow, Russian Federation, ZYKOV S.V. ,   Higher School of Economics
Published: July 2024

The purpose of the analysis is to identify new signs in which there is a probability of the presence of components of hidden threats in the system or a forecast of possible states of inactivity of system modules. The diversity of the software used and the problems that arise at the same time are described. The study is carried out under the conditions of creating a simulation model in Anylogic used to determine fault criteria. The detected dependencies are confirmed by output data in the form of graphs. Certain dependencies and features are a contribution for future research and publications, and the data are also applicable to the knowledge base being developed. The created query processing model showed the dependence of the characteristics of the input parameters on the time and noise of the data stream. The analysis also confirms the presence of a malfunction in the data processing flow. The existing solutions for detecting attacks are based on the introduction of software and hardware and on measures of a general nature of protection. In order to establish a hidden threat, such schemes may and will work effectively, but in conditions of long-term hidden threats, an assessment of the situation at different levels is needed, an analysis of signs of all stages of the malfunction state, the use of a predictive model and it is not enough to use disparate means of protection in the form of software, antiviruses, etc. Research in the field of finding dependencies and parameters for predicting cyberattacks on information systems is relevant due to the increasing complexity and frequency of cyberattacks. This allows you to promptly warn about possible threats, take measures to protect information systems, minimize economic losses and develop analytical capabilities in the field of cybersecurity. This direction retains its stability and uniqueness in the field of process research, namely the ability to learn and carry out in-depth analysis of parametric data. implementation of anomaly search within the intrusion detection system.
INTERNATIONAL COMMITTEE OF THE RED CROSS (ICRC) INFORMATION PUBLICATIONS: HISTORY OF CREATION AND DEVELOPMENT
Authors: ZAKHAROV DMITRY N. ,   Ural Federal University named after the First President of Russia B. N. Yeltsin, Yekaterinburg, Russian Federation, ZAPARIY YULIA V.
Published: July 2024

The article traces the history of the emergence and development of official periodicals of the International Committee of the Red Cross (ICRC). During the study, it was possible to establish the reasons for the need for such publications and their connection with other information materials of the ICRC. In addition, the publications allow us to trace changes in the Committee’s communication policy with the outside world: there is a transition from an academically oriented journal to newsletters, the purpose of which is to maintain a positive image of the organization through the publication of personal examples and stories of employees, which, in theory, greatly simplifies the understanding of the essence of the ICRC’s activities among mass readers.
ABOUT THE SYNCHRONIZATION OF RUSSIAN HISTORY AND EUROPE IN THE XX CENTURY: LENIN, TROTSKY, MILYUKOV
Authors: ILIZAROV BORIS S. ,   The Institute of Russian History of the Russian Academy of Sciences, Moscow, Russian Federation
Published: July 2024

The historiosophical concepts of Miliukov, Lenin, and Trotsky are considered. A connection is established between their concepts of history and the transformation of Russia and the pre-revolutionary ideological tradition of Westerners and Slavophiles. The question is raised about further understanding of Stalin’s plan for «building socialism in one country».
NFT FINANCIAL AND LEGAL REGULATION: NECESSITY AND SUFFICIENCY
Authors: SOKOLOVA EKATERINA S. ,   Vladimdir State University named after Alexander and Nikolay Stoletovs, Vladimdir, Russian Federation, FILIMONOVA ANASTASIA I.
Published: July 2024

The article raises the question of the need to create a legal framework capable of regulating new financial elements; examines the diversity of the nature of a non-interchangeable token; analyzes the relationship of NFT with classical structures such as the object of civil relations, copyright and others; concludes the importance of distinguishing the essence of NFT in each case; the result of the study is a proposal to regulate individual manifestations NFT through the adoption of special legislation.
"Whatever Input to Torsion Transfer'': Harvesting energy from a WITT gearbox device
Authors: Kaklamanos Panagiotis , Buttler Emily , Darbar Yatin , Lacey Andrew , Luckins Ellen , Morawiecki Piotr , Nguyen Nam , Peroni Edoardo , Please Colin , Roberts Joe , Spalding Cameron , Whittaker Robert , Xu Henglei , Zyskin Maxim
Published: July 2024

The WITT gearbox is a device that harvests energy from its environment by responding to sufficiently high frequency and amplitude harmonic acceleration in any plane of motion. It is a simple apparatus, consisting of pendula, gears, bearings, clutches, and power conversion electronics, that can be immersed in a sealed way into a harsh, turbulent environment. It then generates uninterrupted power by turning vibration to rotation, always in the same direction, regardless of the direction of the external vibration. In this work, we expand the analysis of the mechanical properties of the WITT device, making more realistic assumptions compared to previous studies. Moreover, we investigate the response of the device to various external configurations and parameter values (e.g. attaching the device to pair of pendula, or to a pole, etc.), exploring how this could enable it to respond to lower-frequency excitation.
ANÁLISE GEOESPACIAL DA PROSTITUIÇÃO MASCULINA NA CIDADE DE ARACAJUSE
Authors: Santos Felipe Alan Souza , Rodrigues Jovenildo Cardoso
Published: July 2024

Nas complexas relações do território, é necessário conhecer a dimensão simbólica, que resulta dos espaços ocupados por determinado grupo social é lhe fornece identidade cultural. O sentindo de valor e função dos objetos sociais existentes nas relações sociais do território integra a esse o sentindo de territorialidade. Após esse entendimento, é fático compreender que novas concepções e ações ocorreram nesses espaços. O objetivo do presente artigo é conhecer simbolicamente os garotos de programa participantes da pesquisa, revelando seu perfil na espacialidade, na cidade de Aracaju/SE. A metodologia aplicada foi a etnografia virtual, campo metodológico que permite conhecer e discutir o fenômeno a partir da interação existente no espaço virtual, seja pela rede social ou por software que introduza uma discussão entre participante e pesquisador. Resultados preliminares expõem uma dinâmica bastante flexível e eclética de garotos de programas da cidade de Aracaju/SE, que revela a disposição da territorialidade para o serviço, ora a fim de contemplar o desejo de consumo do cliente, ora para conseguir realizar suas atividades e serviços.
O BIOGEOGRAFIA: UMA ANÁLISE DA VEGETAÇÃO NAS CIDADES DE BOA ESPERANÇA, FAROL E JANIÓPOLIS
Authors: OLIVEIRA ANDRESSA , M. C. FERREIRA MARIA EUGENIA
Published: July 2024

Esta pesquisa tem por objetivo fazer um estudo biogeográfico da vegetação arbórea viária urbana e da massa vegetal dos quintais nas sedes dos municípios de Boa Esperança, Farol e Janiópolis, com o intuito de compreender o papel da fitogeografia na dinâmica do ecossistema urbano. Nesta pesquisa, serão contemplados os materiais bibliográfico e de campo, além de análises e discussões, envolvendo um inventário universal de indivíduos presentes nas vias públicas dos três municípios e considerando os arruamentos do perímetro urbano. Portanto, esta pesquisa enfatiza os aspectos biogeográficos da vegetação, com enfoque na vegetação das pequenas cidades e na quantificação, na distribuição e na frequência arbórea encontrada nas nelas. Por meio dos trabalhos de campo, foi possível a geração do inventário arbóreo das vias públicas e a geração de dados primários, com os quais foram realizados produtos, análises e discussões, acerca da otimização de recursos, além da utilização do planejamento como ferramenta de gestão urbana. Os principais resultados encontrados foram: visualização da vegetação urbana, a modificação do desenho vegetacional das cidades, composição de espécies presentes na vegetação viária, nas sedes dos municípios; quantitativo de espécies arbóreas presentes nas vias; padrões de vegetação urbana. Os principais resultados, considerando os três municípios, foram os seguintes: em Boa Esperança, foi encontrado o maior quantitativo de indivíduos da pesquisa, com 3.144 espécimes, composto, em sua maioria, pela espécie Alfeneiro, representando 92% da vegetação viária; na sede de Farol, foi georreferenciado o menor quantitativo de espécimes, com apenas 1.240 indivíduos de porte arbóreo, porém com a maior variedade de espécies, representando 79 espécies; já para a cidade de Janiópolis, foram encontrados 1.842 indivíduos e 45 espécies diversas. Como parte dos resultados e análises, foram identificadas lacunas na vegetação viária urbana nas cidades de Farol e Janiópolis, gerando a descontinuidade da vegetação e diminuição na massa urbana privada em virtude do aumento do mobiliário urbano. Conclui-se, portanto, que as áreas de estudo se encontram em déficit vegetacional, o que gera preocupação em virtude da qualidade de vida da sociedade em pleno contato com as áreas, além da diminuição de abrigo à fauna local.
Artificial intelligence assisted preoperative planning and 3D-printing guiding frame for percutaneous screw reconstruction in periacetabular metastatic cancer patients
Authors: Wang Jichuan , Zhao Zhiqing , Liang Haijie , Zhang Ranxin , Liu Xingyu , Zhang Jing , Singh Swapnil , Guo Wei , Yan Taiqiang , Hoang Bang H. , Geller David S. , Tang Xiaodong , Yang Rui
Published: July 2024

Background

The percutaneous screw reconstruction technique, known as the “Tripod Technique,” has demonstrated favorable clinical outcomes in the management of metastatic periacetabular lesions, as evidenced by our prior investigations and corroborated by independent studies. Nevertheless, there is a steep learning curve in handling this technique, with possible complications such as intraarticular screw placement.

Methods

Preoperative pelvic CT scans were acquired before surgery and utilized for the guiding frame design. A convolutional neural network model was trained with annotated data to identify the starting point and trajectory of each potential screw. A model boundary intersection detection technology was used to determine the optimal diameter and length of each screw. A non-rigid registration technology was matched with a prefabricated model of the body surface to design personalized anchoring skin pads. Finally, a polylactic acid-based guiding frame for intraoperative was custom-made with a 3D printer.

Results

12 patients underwent a guiding frame-assisted Tripod procedure for treatment of periacetabular metastatic lesions. An intraoperative CT scan was performed in all cases to confirm screw trajectories. Among 36 screws that were implanted, 26 screws were implanted as designed. The remaining ten screws drifted, but all remained within the intra-osseous conduit without any complications. The mean surgical time was 1.22 h with the guiding frame compared with 2.3 h without the guiding frame. Following the surgical procedure, a noteworthy enhancement in pain management, as evidenced by a reduction in scores on the visual analog scale (p < 0.01), and an improvement in functional status, as assessed through the Eastern Cooperative Oncology Group score (p < 0.01), were observed when compared to the patient’s pre-operative condition.

Conclusion

This proof-of-concept investigation demonstrates that the amalgamation of AI-assisted surgical planning and additive manufacturing can improve surgical accuracy and shorten surgical duration. While access to this technology is currently constrained during its early stages of development, it is anticipated that these limitations will diminish as the potential of AI and additive manufacturing in facilitating complex orthopedic procedures becomes more evident, leading to a surge in interest and adoption of this approach.
The application potential of iMSCs and iMSC-EVs in diseases
Authors: Zhou Xin , Liu Jinyu , Wu Feifeng , Mao Jueyi , Wang Yang , Zhu Junquan , Hong Kimsor , Xie Haotian , Li Binbin , Qiu Xinying , Xiao Xiangbin , Wen Chuan
Published: July 2024

The immune system, functioning as the body’s “defense army”, plays a role in surveillance, defense. Any disruptions in immune system can lead to the development of immune-related diseases. Extensive researches have demonstrated the crucial immunoregulatory role of mesenchymal stem cells (MSCs) in these diseases. Of particular interest is the ability to induce somatic cells under specific conditions, generating a new cell type with stem cell characteristics known as induced pluripotent stem cell (iPSC). The differentiation of iPSCs into MSCs, specifically induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), hold promise as a potential solution to the challenges of MSCs, potentially serving as an alternative to traditional drug therapies. Moreover, the products of iMSCs, termed induced pluripotent stem cell-derived mesenchymal stem cell-derived extracellular vesicles (iMSC-EVs), may exhibit functions similar to iMSCs. With the biological advantages of EVs, they have become the focus of “cell-free therapy”. Here, we provided a comprehensive summary of the biological impact of iMSCs on immune cells, explored the applications of iMSCs and iMSC-EVs in diseases, and briefly discussed the fundamental characteristics of EVs. Finally, we overviewed the current advantages and challenges associated with iMSCs and iMSC-EVs. It is our hope that this review related to iMSCs and iMSC-EVs will contribute to the development of new approaches for the treatment of diseases.
Phase-field modeling of geologic fractures
Authors: Choo Jinhyun
Published: July 2024

Geologic fractures such as joints, faults, and slip surfaces govern the stability and performance of many subsurface systems in the built environment. As such, a variety of approaches have been developed for computational modeling of geologic fractures. Yet none of them lends itself to a straightforward utilization with the classical finite element method widely used in practice. Over the past decade, phase-field modeling has become a popular approach for simulating fracture, because it can be implemented simply with the standard finite element method without any surface-tracking algorithms. However, the standard phase-field formulations do not incorporate several critical features of geologic fractures, including frictional contact, pressure-dependence, quasi-brittleness, mode-mixity, and their combined impacts on cracking. This article provides a brief report of a novel phase-field model that incorporates these features of geologic fractures in a well-verified and validated manner. Remarkably, the phase-field model allows one to simulate the combination of cohesive tensile fracture and frictional shear fracture without any algorithms for surface tracking and contact constraints. It is also demonstrated how phase-field modeling enables us to gain insights into geologic fractures that are challenging to investigate experimentally.
Cultural elements’ influence on visual preferences in urban waterfronts’ walkways in Malaysia
Authors: Liu Tun , Mohd Yunos Mohd Yazid , Muthuveeran Adam Aruldewan S. , Mundher Riyadh , Ismail Nor Atiah
Published: July 2024

With the rapid urbanization in Malaysia, human activities have caused damage to many waterfront areas. Efforts are being made to restore the connection between the community and river waterfronts while creating attractive urban spaces. However, the implementation of modern design development strategies without sufficient consideration of cultural aspects and societal visual preferences has raised a number of questions with regard to the public’s acceptance and appreciation of the newly implemented urban facades. This study aims to comprehensively examine the relationship between cultural elements and visual preferences in the context of urban waterfront walkways in Malaysia. This study implemented a photo survey to assess the visual preferences of the study’s respondents. The results indicated a significant correlation between subjects’ visual preferences and their cultural backgrounds. Additionally, the analysis of the collected data highlights a strong correlation between the presence of green elements and what the respondents perceived as part of the Malaysian culture. Additionally, the historical character of the study area, as represented by historical buildings, significantly influences the preferences of Malaysian respondents. Furthermore, certain elements, such as food carts, high-rise buildings, and water, are among the least preferred compared to other elements. Ultimately, incorporating these elements in the early design stages can contribute to the creation of culturally connected and visually appealing urban waterfront spaces in Malaysia.
Multimodal AI techniques for pain detection: integrating facial gesture and paralanguage analysis
Authors: Gutierrez Rommel , Garcia-Ortiz Joselin , Villegas-Ch William
Published: July 2024

Accurate pain detection is a critical challenge in healthcare, where communication and interpretation of pain often limit traditional subjective assessments. The current situation is characterized by the need for more objective and reliable methods to assess pain, especially in patients who cannot effectively communicate their experiences, such as young children or critically ill individuals. Despite technological advances, the effective integration of artificial intelligence tools for multifaceted and accurate pain detection continues to present significant challenges. Our proposal addresses this problem through an interdisciplinary approach, developing a hybrid model that combines the analysis of facial gestures and paralanguage using artificial intelligence techniques. This model contributes significantly to the field, allowing for more objective, accurate, and sensitive pain detection to individual variations. The results obtained have been notable, with our model achieving a precision of 92%, a recall of 90%, and a specificity of 95%, demonstrating evident efficiency over conventional methodologies. The clinical implications of this model include the possibility of significantly improving pain assessment in various medical settings, allowing for faster and more accurate interventions, thereby improving patients’ quality of life.
Balancing immune responses: regulatory cells in eosinophilic gastrointestinal disorders
Authors: Kheshtchin Nassim , Kanannejad Zahra , Ghahramani Zahra , Esmaeilzadeh Hossein , Sepahi Najmeh
Published: July 2024

Eosinophilic gastrointestinal disorders (EGIDs) are a group of conditions characterized by an abnormal accumulation of eosinophils in the gastrointestinal tract, leading to inflammation and tissue damage. Regulatory cells are a subset of immune cells that are crucial in maintaining the balance of the immune system and preventing the occurrence of autoimmune diseases. In EGIDs, regulatory cells are believed to play a key role in controlling the immune response and overseeing the growth and activation of eosinophils in the gastrointestinal tract. There is evidence indicating that regulatory T cells (Tregs) and regulatory eosinophils may play a role in suppressing the inflammatory response in EGIDs. Regulatory eosinophils are a subgroup of eosinophils that possess an anti-inflammatory role. Recent studies have shown that enhancing the number or effectiveness of regulatory eosinophils can reduce the severity of EGIDs. Regulatory eosinophils dampen inflammation through their regulatory mediators, such as galectin-10 and growth factor beta (TGF-β), which promote Treg expansion and inhibit effector T cell function. Further research on regulatory cells in EGIDs may have significant implications for the advancement of novel therapies for these uncommon and intricate disorders. The aim of this review is to provide complete view of the immune responses connected to EGIDs, examine the regulatory cells that control these responses, and evaluate their potential as therapeutic targets for EGID treatment.
Design of a haptic device for presenting pressure and skin stretching stimuli to the palm
Authors: Kojima Mayuka , Yoshimoto Shunsuke , Yamamoto Akio
Published: July 2024

This paper discusses the design of a two-degree-of-freedom (2-DOF) pseudo-force presentation device for a palm. The device was designed to present pressure stimulation to a palm to invoke a pseudo-force sensation. In addition, the stimulator can rotate to invoke a pseudo-torque sensation through tangential skin stretch in the proximal/distal direction. Whereas the previous devices used for pseudo-force presentation on a palm utilized voice coil motors (VCM) to generate pressure, the developed device uses a DC gear motor, cam, and lever, which comprise a series elastic actuator (SEA). Although the mechanism’s response is slower than the VCM-based device’s, it can realize lower power consumption when generating constant force. The paper discusses the design requirement to provide sufficient pseudo-force sensation. Then, a prototype device was evaluated, which satisfied the requirements regarding size, weight, force, and stroke. The device was utilized in a human-subject experiment to investigate the effect of tangential skin stretch along the proximal/distal direction on a palm. The results showed that the stimulation can invoke the feeling of rotation, or pseudo-torque sensation.
Macrogenomes reveal microbial-mediated microplastic degradation pathways in the porcine gut: a hope for solving the environmental challenges of microplastics
Authors: Wang Tao , Luo Yuheng , Yu Bing , Zheng Ping , Huang Zhiqing , Mao Xiangbing , Yu Jie , Luo Junqiu , Yan Hui , He Jun
Published: July 2024

It is increasingly recognized that microplastics (MPs) are being transmitted through the food chain system, but little is known about the microorganisms involved in MP degradation, functional biodegradation genes, and metabolic pathways of degradation in the intestinal tract of foodborne animals. In this study, we explored the potential flora mainly involved in MP degradation in the intestinal tracts of Taoyuan, Duroc, and Xiangcun pigs by macrogenomics, screened relevant MP degradation genes, and identified key enzymes and their mechanisms. The pig colon was enriched with abundant MP degradation-related genes, and gut microorganisms were their main hosts. The fiber diet did not significantly affect the abundance of MP degradation-related genes but significantly reduced their diversity. We identified a total of 94 functional genes for MP degradation and classified them into 27 categories by substrate type, with polystyrene (PS), polyethylene terephthalate (PET), and di(2-ethylhexyl) phthalate (DEHP) were the most predominant degradation types. The MP degradation functional genes were widely distributed in a variety of bacteria, mainly in the phylum Firmicutes and Bacteroidetes. Based on the identified functional genes for MP degradation, we proposed a hypothetical degradation mechanism for the three major MP pollutants, namely, PS, PET, and DEHP, which mainly consist of oxidoreductase, hydrolase, transferase, ligase, laccase, and isomerase. The degradation process involves the breakdown of long polymer chains, the oxidation of short-chain oligomers, the conversion of catechols, and the achievement of complete mineralization. Our findings provide insights into the function of MP degradation genes and their host microorganisms in the porcine colon.
A novel autism-associated KCNB1 mutation dramatically slows Kv2.1 potassium channel activation, deactivation and inactivation
Authors: Manville Rían W. , Block Samantha D. , Illeck Claire L. , Kottmeier Jessica , Sidlow Richard , Abbott Geoffrey W.
Published: July 2024

KCNB1, on human chromosome 20q13.3, encodes the alpha subunit of the Kv2.1 voltage gated potassium channel. Kv2.1 is ubiquitously expressed throughout the brain and is critical in controlling neuronal excitability, including in the hippocampus and pyramidal neurons. Human KCNB1 mutations are known to cause global development delay or plateauing, epilepsy, and behavioral disorders. Here, we report a sibling pair with developmental delay, absence seizures, autism spectrum disorder, hypotonia, and dysmorphic features. Whole exome sequencing revealed a heterozygous variant of uncertain significance (c. 342 C>A), p. (S114R) in KCNB1, encoding a serine to arginine substitution (S114R) in the N-terminal cytoplasmic region of Kv2.1. The siblings’ father demonstrated autistic features and was determined to be an obligate KCNB1 c. 342 C>A carrier based on familial genetic testing results. Functional investigation of Kv2.1-S114R using cellular electrophysiology revealed slowing of channel activation, deactivation, and inactivation, resulting in increased net current after longer membrane depolarizations. To our knowledge, this is the first study of its kind that compares the presentation of siblings each with a KCNB1 disorder. Our study demonstrates that Kv2.1-S114R has profound cellular and phenotypic consequences. Understanding the mechanisms underlying KCNB1-linked disorders aids clinicians in diagnosis and treatment and provides potential therapeutic avenues to pursue.
M3: using mask-attention and multi-scale for multi-modal brain MRI classification
Authors: Kong Guanqing , Wu Chuanfu , Zhang Zongqiu , Yin Chuansheng , Qin Dawei
Published: July 2024

Introduction

Brain diseases, particularly the classification of gliomas and brain metastases and the prediction of HT in strokes, pose significant challenges in healthcare. Existing methods, relying predominantly on clinical data or imaging-based techniques such as radiomics, often fall short in achieving satisfactory classification accuracy. These methods fail to adequately capture the nuanced features crucial for accurate diagnosis, often hindered by noise and the inability to integrate information across various scales.

Methods

We propose a novel approach that mask attention mechanisms with multi-scale feature fusion for Multimodal brain disease classification tasks, termed M3, which aims to extract features highly relevant to the disease. The extracted features are then dimensionally reduced using Principal Component Analysis (PCA), followed by classification with a Support Vector Machine (SVM) to obtain the predictive results.

Results

Our methodology underwent rigorous testing on multi-parametric MRI datasets for both brain tumors and strokes. The results demonstrate a significant improvement in addressing critical clinical challenges, including the classification of gliomas, brain metastases, and the prediction of hemorrhagic stroke transformations. Ablation studies further validate the effectiveness of our attention mechanism and feature fusion modules.

Discussion

These findings underscore the potential of our approach to meet and exceed current clinical diagnostic demands, offering promising prospects for enhancing healthcare outcomes in the diagnosis and treatment of brain diseases.
LYNSU: automated 3D neuropil segmentation of fluorescent images for Drosophila brains
Authors: Hsu Kai-Yi , Shih Chi-Tin , Chen Nan-Yow , Lo Chung-Chuan
Published: July 2024

The brain atlas, which provides information about the distribution of genes, proteins, neurons, or anatomical regions, plays a crucial role in contemporary neuroscience research. To analyze the spatial distribution of those substances based on images from different brain samples, we often need to warp and register individual brain images to a standard brain template. However, the process of warping and registration may lead to spatial errors, thereby severely reducing the accuracy of the analysis. To address this issue, we develop an automated method for segmenting neuropils in the Drosophila brain for fluorescence images from the FlyCircuit database. This technique allows future brain atlas studies to be conducted accurately at the individual level without warping and aligning to a standard brain template. Our method, LYNSU (Locating by YOLO and Segmenting by U-Net), consists of two stages. In the first stage, we use the YOLOv7 model to quickly locate neuropils and rapidly extract small-scale 3D images as input for the second stage model. This stage achieves a 99.4% accuracy rate in neuropil localization. In the second stage, we employ the 3D U-Net model to segment neuropils. LYNSU can achieve high accuracy in segmentation using a small training set consisting of images from merely 16 brains. We demonstrate LYNSU on six distinct neuropils or structures, achieving a high segmentation accuracy comparable to professional manual annotations with a 3D Intersection-over-Union (IoU) reaching up to 0.869. Our method takes only about 7 s to segment a neuropil while achieving a similar level of performance as the human annotators. To demonstrate a use case of LYNSU, we applied it to all female Drosophila brains from the FlyCircuit database to investigate the asymmetry of the mushroom bodies (MBs), the learning center of fruit flies. We used LYNSU to segment bilateral MBs and compare the volumes between left and right for each individual. Notably, of 8,703 valid brain samples, 10.14% showed bilateral volume differences that exceeded 10%. The study demonstrated the potential of the proposed method in high-throughput anatomical analysis and connectomics construction of the Drosophila brain.
Connectomic insights into the impact of 1p/19q co-deletion in dominant hemisphere insular glioma patients
Authors: Yang Zuo-cheng , Xue Bo-wen , Song Xin-yu , Yin Chuan-dong , Yeh Fang-cheng , Li Gen , Deng Zheng-hai , Sun Sheng-jun , Hou Zong-gang , Xie Jian
Published: July 2024

Objectives

This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas.

Methods

We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion.

Results

The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10–5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion.

Conclusion

The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.
Endoplasmic reticulum associated degradation preserves neurons viability by maintaining endoplasmic reticulum homeostasis
Authors: Wu Shuangchan , Liu Pingting , Cvetanovic Marija , Lin Wensheng
Published: July 2024

Endoplasmic reticulum-associated degradation (ERAD) is a principal quality-control mechanism responsible for targeting misfolded ER proteins for cytosolic degradation. Evidence suggests that impairment of ERAD contributes to neuron dysfunction and death in neurodegenerative diseases, many of which are characterized by accumulation and aggregation of misfolded proteins. However, the physiological role of ERAD in neurons remains unclear. The Sel1L-Hrd1 complex consisting of the E3 ubiquitin ligase Hrd1 and its adaptor protein Sel1L is the best-characterized ERAD machinery. Herein, we showed that Sel1L deficiency specifically in neurons of adult mice impaired the ERAD activity of the Sel1L-Hrd1 complex and led to disruption of ER homeostasis, ER stress and activation of the unfold protein response (UPR). Adult mice with Sel1L deficiency in neurons exhibited weight loss and severe motor dysfunction, and rapidly succumbed to death. Interestingly, Sel1L deficiency in neurons caused global brain atrophy, particularly cerebellar and hippocampal atrophy, in adult mice. Moreover, we found that cerebellar and hippocampal atrophy in these mice resulted from degeneration of Purkinje neurons and hippocampal neurons, respectively. These findings indicate that ERAD is required for maintaining ER homeostasis and the viability and function of neurons in adults under physiological conditions.
Full-fat dairy products and cardiometabolic health outcomes: Does the dairy-fat matrix matter?
Authors: Taormina Victoria M. , Unger Allison L. , Kraft Jana
Published: July 2024

Reducing dairy fat intake is a common dietary guideline to limit energy and saturated fatty acid intake for the promotion of cardiometabolic health. However, research utilizing a holistic, food-based approach to assess the consumption of the fat found in dairy, a broad and diverse food group, may provide new insight into these guidelines. Dairy fat is comprised of a diverse assembly of fatty acids, triacylglycerols, sterols, and phospholipids, all uniquely packaged in a milk fat globule. The physical structure of this milk fat globule and its membrane is modified through different processing methods, resulting in distinctive dairy-fat matrices across each dairy product. The objectives of this narrative review were to first define and compare the dairy-fat matrix in terms of its unique composition, physical structure, and fat content across common dairy products (cow’s milk, yogurt, cheese, and butter). With this information, we examined observational studies and randomized controlled trials published within the last 10 years (2013–2023) to assess the individual effects of the dairy-fat matrix in milk, yogurt, cheese, and butter on cardiometabolic health and evaluate the implications for nutrition guidance. Searches conducted on Ovid MEDLINE and PubMed® utilizing search terms for cardiometabolic health, both broadly and regarding specific disease outcomes and risk factors, yielded 59 studies that were analyzed and included in this review. Importantly, this review stratifies by both dairy product and fat content. Though the results were heterogeneous, most studies reported no association between intake of these individual regular-fat dairy products and cardiometabolic outcome measures, thus, the current body of evidence suggests that regular-fat dairy product consumption may be incorporated within overall healthy eating patterns. Research suggests that there may be a beneficial effect of regular-fat milk and yogurt intake on outcome measures related to body weight and composition, and an effect of regular-fat cheese intake on outcome measures related to blood lipids, but more research is necessary to define the directionality of this relationship. Lastly, we identify methodological research gaps and propose future research directions to bolster the current evidence base available for ascertaining the role of dairy fat in a healthy diet.
Novel insights and therapeutic approaches in secondary AML
Authors: Marconi Giovanni , Rondoni Michela , Zannetti Beatrice Anna , Zacheo Irene , Nappi Davide , Mattei Agnese , Rocchi Serena , Lanza Francesco
Published: July 2024

Secondary acute myeloid leukemia (sAML) presents as a complex and multifaceted ensemble of disorders, positioning itself as both a challenge and an intriguing frontier within hematologic oncology. Its origins are diverse, stemming from antecedent hematologic conditions, germline predisposing mutations, or the sequelae of cytotoxic therapies, and its development is driven by intricate genetic and epigenetic modifications. This complexity necessitates a diverse array of therapeutic strategies, each meticulously tailored to address the distinctive challenges sAML introduces. Such strategies require a personalized approach, considering the variegated clinical backgrounds of patients and the inherent intricacies of the disease. Allogeneic stem cell transplantation stands as a cornerstone, offering the potential for curative outcomes. This is complemented by the emergence of innovative treatments such as CPX-351, venetoclax, and glasdegib, which have demonstrated promising results in enhancing prognosis. The evolving landscape of sAML treatment underscores the importance of continued research and innovation in the field, aiming not only to improve patient outcomes but also to deepen our understanding of the disease’s biological underpinnings, thereby illuminating pathways toward more effective and individualized therapies.
Clinical value of optical coherence tomography in the early diagnosis of cervical cancer and precancerous lesions: a cross-sectional study
Authors: Cui Xiaoli , Yang Di , Zhang Jing , Zhao Yuqian , Cui Zhumei , Wang Chunyan , Qiao Youlin
Published: July 2024

Background

This study aimed to measure the accuracy of optical coherence tomography (OCT) in the early diagnosis of high-grade cervical lesions and assess its diagnostic value in the triage of high-risk HPV infection.

Method

From Jan 2019 to Jan 2021, women who visited the gynecology clinics of 2 hospitals for colposcopy were invited to participate in this study. Women aged 35 to 64 years old who were sexually active and had an intact cervix with a diameter of more than or equal to 2 cm were included in this study. Additionally, individuals with abnormal cytology, positive HPV test results, or other clinically suspicious symptoms or signs were referred. All participants were examined before colposcopy using OCT. Biopsy and/or ECC were conducted under colposcopy. We used the results of histopathology as the gold standard and assessed the accuracy of OCT.

Results

Overall, 883 women were included in the analysis. Approximately 13.25% of women were ASCUS+ in cytological assessments, and 22.31% were positive for high-risk HPV. Nearly 15.18% of women were positive in OCT. Of them, 27 women were diagnosed with CIN2, and 33 were diagnosed with CIN3+ lesions. Among HPV-positive women, the detection rates for CIN2+ and CIN3+ were much lower for those who were negative in OCT, compared with NILM cytology (CIN2+: 20.0% vs. 30.0%, P=0.002, and CIN3+: 18.2% vs. 27.3%, P=0.013). Among women who were positive for HPV16/18, the detection rate for CIN2+ was much lower for negative OCT, compared with NILM cytology (8.3% vs.15.0%, P=0.005). Compared to HPV and cytological tests, HPV combined with OCT had higher specificity for detecting CIN2+ and CIN3+ (96.1% vs. 93.2%, P=0.002; 93.8% vs. 91.3%, P=0.013). OCT triage after HPV genotyping had the highest AUC for detecting CIN2+ and CIN3+ cases among patients with high-risk HPV infection (0.921, 0.920).

Conclusion

OCT is an accurate test for the early diagnosis of high-grade cervical lesions and has great diagnostic value in the triage of patients with high-risk HPV infection.
Therapeutic options for chronic myeloid leukemia following the failure of second-generation tyrosine kinase inhibitor therapy
Authors: George Binsah , Chan Kok Hoe , Rios Adan
Published: July 2024

The management of chronic myeloid leukemia in the chronic phase (CML-CP) has witnessed significant advancements since the identification of a common chromosomal translocation anomaly involving chromosomes 9 and 22, which results in the formation of the Philadelphia chromosome driven by the BCR-ABL1 fusion protein. This discovery paved the way for the development of tyrosine kinase inhibitors (TKIs) that target the adenosine triphosphate (ATP) binding site of ABL1 through the BCR-ABL-1 fusion protein. Following the approval of Imatinib by the Food and Drug Administration (FDA) as the first TKI for CML treatment in 2001, the median overall survival (OS) for chronic phase CML (CML-CP) has significantly improved, approaching that of the general population. However, achieving this milestone crucially depends on reaching certain treatment response milestones. Since the introduction of imatinib, five additional TKIs have been approved for CML-CP treatment. Despite the availability of these treatments, many patients may experience treatment failure and require multiple lines of therapy due to factors such as the emergence of resistance, such as mutations in the ATP binding site of ABL, or intolerance to therapy. This review will primarily focus on exploring treatment options for patients who fail second-generation TKI therapy due to true resistance.
Unearthing phytochemicals as natural inhibitors for pantothenate synthetase in Mycobacterium tuberculosis: A computational approach
Authors: Chouhan Mandeep , Tiwari Prashant Kumar , Mishra Richa , Gupta Saurabh , Kumar Mukesh , Almuqri Eman Abdullah , Ibrahim Nasir A. , Basher Nosiba Suliman , Chaudhary Anis Ahmad , Dwivedi Vivek Dhar , Verma Devvret , Kumar Sanjay
Published: July 2024

Pantothenate synthetase protein plays a pivotal role in the biosynthesis of coenzyme A (CoA), which is a crucial molecule involved in a number of cellular processes including the metabolism of fatty acid, energy production, and the synthesis of various biomolecules, which is necessary for the survival of Mycobacterium tuberculosis (Mtb). Therefore, inhibiting this protein could disrupt CoA synthesis, leading to the impairment of vital metabolic processes within the bacterium, ultimately inhibiting its growth and survival. This study employed molecular docking, structure-based virtual screening, and molecular dynamics (MD) simulation to identify promising phytochemical compounds targeting pantothenate synthetase for tuberculosis (TB) treatment. Among 239 compounds, the top three (rutin, sesamin, and catechin gallate) were selected, with binding energy values ranging from −11 to −10.3 kcal/mol, and the selected complexes showed RMSD (<3 Å) for 100 ns MD simulation time. Furthermore, molecular mechanics generalized Born surface area (MM/GBSA) binding free energy calculations affirmed the stability of these three selected phytochemicals with binding energy ranges from −82.24 ± 9.35 to −66.83 ± 4.5 kcal/mol. Hence, these identified natural plant-derived compounds as potential inhibitors of pantothenate synthetase could be used to inhibit TB infection in humans.
Prognostic impact of metformin in solid cancer patients receiving immune checkpoint inhibitors: novel evidences from a multicenter retrospective study
Authors: Wang Jiaxin , Lin Jie , Guo Huaijuan , Wu Wenjuan , Yang Jingjing , Mao Jingxian , Fan Wenbin , Qiao Hong , Wang Ying , Yan Xuebing , Guo Hong
Published: July 2024

Objective: Metformin as a common antidiabetic drug, has recently found to exert its anti-cancer and immunomodulatory effect in numerous preclinical studies. This study aims to clarify the prognostic impact of metformin use in solid cancer patients receiving immune checkpoint inhibitors (ICIs).

Methods: A retrospective cohort enrolling 516 solid cancer patients who received ICI-based therapy between 2018 and 2023 at three hospitals was analyzed. The primary endpoints included overall survival (OS) and progression-free survival (PFS). In addition, a bioinformatics analysis based on TCGA and GSE cohort was performed to investigate the prognostic significance of metformin target genes (MTGs) and their correlation with immune infiltration in non-small cell lung cancer (NSCLC) patients.

Results: In the entire cohort, a total of 76 patients received metformin before and/or during ICI therapy. The global analysis demonstrated that metformin use was unrelated with the OS (p = 0.064) and PFS (p = 0.059) of ICI-treated cancer patients, which was confirmed in the subgroups of esophagus, hepatobiliary or pancreatic cancer (all p > 0.05). However, metformin use was significantly correlated with better OS (p = 0.012) and PFS (p = 0.005) in ICI-treated lung cancer patients. Metformin use was also identified as an independent favorable prognostic factor for these patients. The bioinformatics analysis identified five favorable prognostic MTGs (RPS6KA5, RORA, SH3BP5, NUPR1, and CD40LG) for NSCLC patients, all of which was downregulated in lung cancer tissues as compared with normal tissues. The expressions of five MTGs not only could effectively stratify the OS of NSCLC patients, but also was correlated with infiltration of immune cells such as CD4+ and CD8+ T cells.

Conclusion: Metformin use was significantly correlated with better OS and PFS in ICI-treated lung cancer patients. MTGs has the potential to serve as novel clinical biomarkers or druggable targets for cancer immunotherapy. Considering study limitations, the actual impact of metformin use on ICI therapy needs to be clarified by more clinical trials.