bluuebunny/crossref_metadata_2025 huggingface dataset:
Voltage Distribution on Transformer Windings Subjected to Lightning Strike Using State-Space Method
Authors: Arı İlker , Mamiş Mehmet Salih
Published: February 2025

Transient analysis in power systems is essential for identifying deficiencies in the system, as well as for the protection and design of equipment. Transients can arise from natural events or network operations; in either case, they have the potential to cause significant damage to transmission lines, protection devices, generators, or transformers. This study examines a 20 kA, 1.2/50 µs lightning strike on a distributed-parameter transmission line connected to a power transformer. The voltage distributions across the winding sections on the neutral grounded high-voltage side of a disc-structured power transformer were obtained using the state-space method. An equivalent circuit for the state-space model was also developed in the Alternative Transients Program–Electromagnetic Transients Program (ATP-EMTP), and the results from both methods were compared. Both approaches revealed that the voltage waveforms in the transformer’s winding sections were consistent, with the voltage distribution decreasing linearly. Additionally, the voltage–current waves reached the transformer with a specific delay, depending on the characteristics of the transmission line and the location of the lightning strike. The impact of an increase in the grounding resistance value on the high-voltage side of the transformer on voltage distribution and peak voltage levels was examined. The proposed method effectively captures the voltage–current behavior of the transmission line and transformer windings during transient conditions. It is concluded that the state-space method serves as a viable alternative for transient analysis in power systems and can enhance the design of protection equipment and winding insulation studies.
Innovative EMD-Based Technique for Preventing Coffee Grinder Damage from Stones with FPGA Implementation
Authors: Kok Chiang Liang , Dai Yuwei , Koh Yit Yan , Xiang Maoyang , Teo Tee Hui
Published: February 2025

Coffee is one of the most widely consumed beverages globally, with Americans averaging 3.1 cups per day. However, before coffee beans can be brewed into a drinkable form, they undergo several critical stages, including harvesting, processing, roasting, grinding, and extraction. During the processing and roasting phases, a significant challenge arises: stones that are similar in size and shape to coffee beans can inadvertently mix into the batch. These stones are difficult to detect using conventional methods, and their presence can have severe consequences. When stones are ground alongside coffee beans, they can cause significant damage to the grinder’s burrs. Commercial coffee grinders typically employ conical or flat burrs, which consist of two circular discs or an inner blade and a disc. These burrs undergo specialized heat treatment and surface processing to ensure durability and precision, making them highly expensive components. Replacing damaged burrs is not only costly but also requires meticulous calibration of the parallelism between the inner blade and the disc to maintain grinding quality. The introduction of stones into the grinding process can lead to equipment damage, resulting in operational downtime and financial losses. To address this issue, this paper proposes a novel method based on Empirical Mode Decomposition (EMD) for detecting stones in coffee beans. The approach analyzes the acoustic wave patterns generated when stones impact or rotate within the grinder.
Analysis of Offensive Patterns After Timeouts in Critical Moments in the EuroLeague 2022/23
Authors: Vázquez-Estévez Christopher , Prieto-Lage Iván , Reguera-López-de-la-Osa Xoana , Silva-Pinto Antonio José , Argibay-González Juan Carlos , Gutiérrez-Santiago Alfonso
Published: February 2025

Timeouts are a widely supported strategy in the literature, recognized for directly influencing team performance during basketball games. This study aimed to analyze and define the successful patterns of actions after timeouts (ATOs) during critical moments in the 2022/23 EuroLeague season. The sample was drawn from the last two minutes and overtime of 169 games with a final point difference of 10 points or fewer, totaling 365 ATOs. An observational methodology was used, applying the LINCE PLUS software version 2.1.0 and an ad hoc observational instrument. Descriptive analysis and chi-square tests (χ2) were conducted using SPSS 25.0, and T-pattern analysis was performed with Theme 6 software. Statistical significance was set at p < 0.05. Teams in the lead often concluded successful plays through free throws following opponent fouls, while teams trailing behind attempted to close the gap by committing fouls to force free throws in defense and scoring two-point baskets on offense. The findings offer insights into ATOs strategies that can support coaches and technical staff in training and adapting these actions to meet competition demands during critical game moments. These results may assist in enhancing team performance and decision-making under high-stakes conditions.
LSTM Attention-Driven Similarity Learning for Effective Bug Localization
Authors: Yang Geunseok , Ji Jinfeng , Kim Eontae
Published: February 2025

Objective: The complexity of software systems, with their multifaceted functionalities and intricate source code structures, poses significant challenges for developers in identifying and resolving bugs. This study aims to address these challenges by proposing an efficient bug localization method that improves the accuracy and effectiveness of identifying faulty code based on bug reports. Method: We introduce a novel bug localization approach that integrates a Long Short-Term Memory (LSTM) attention mechanism with top-K code similarity learning. The proposed method preprocesses bug reports and source code files, calculates top-K code similarities using the BM25 algorithm, and trains an LSTM-Attention model to predict the most relevant buggy source code files. Results: The model was evaluated on six open-source projects (Tomcat, AspectJ, Birt, Eclipse, JDT, SWT) and demonstrated significant improvements over the baseline method, DNNLoc. Notably, the proposed approach improved accuracy across all projects, with average gains of 18% in prediction accuracy compared to the baseline. Conclusion: This study highlights the efficacy of combining similarity learning with attention mechanisms for bug localization. By streamlining debugging workflows and enhancing predictive accuracy, the proposed method offers a practical solution for improving software quality and reducing development costs.
Plasticity of Expression of Stem Cell and EMT Markers in Breast Cancer Cells in 2D and 3D Culture Depend on the Spatial Parameters of Cell Growth; Mathematical Modeling of Mechanical Stress in Cell Culture in Relation to ECM Stiffness
Authors: Szostakowska-Rodzoś Małgorzata , Chmielarczyk Mateusz , Zacharska Weronika , Fabisiewicz Anna , Kurzyk Agata , Myśliwy Izabella , Kozaryna Zofia , Postek Eligiusz , Grzybowska Ewa A.
Published: February 2025

The majority of the current cancer research is based on two-dimensional cell cultures and animal models. These methods have limitations, including different expressions of key factors involved in carcinogenesis and metastasis, depending on culture conditions. Addressing these differences is crucial in obtaining physiologically relevant models. In this manuscript we analyzed the plasticity of the expression of stem cell and epithelial/mesenchymal markers in breast cancer cells, depending on culture conditions. Significant differences in marker expression were observed in different growth models not only between 2D and 3D conditions but also between two different 3D models. Differences observed in the levels of adherent junction protein E-cadherin in two different 3D models suggest that spatial parameters of cell growth and physical stress in the culture may affect the expression of junction proteins. To provide an explanation of this phenomenon on the grounds of mechanobiology, these parameters were analyzed using a mathematical model of the 3D bioprinted cell culture. The finite element mechanical model generated in this study includes an extracellular matrix and a group of regularly placed cells. The single-cell model comprises an idealized cytoskeleton, cortex, cytoplasm, and nucleus. The analysis of the model revealed that the stress generated by external pressure is transferred between the cells, generating specific stress fields, depending on growth conditions. We have analyzed and compared stress fields in two different growth conditions, each corresponding to a different elasticity of extracellular matrix. We have demonstrated that soft matrix conditions produce more stress than a stiff matrix in the single cell as well as in cellular spheroids. The observed differences can explain the plasticity of E-cadherin expression in response to mechanical stress. These results should contribute to a better understanding of the differences between various growth models.
Transcriptomics, Proteomics and Bioinformatics in Atrial Fibrillation: A Descriptive Review
Authors: Belfiori Martina , Lazzari Lisa , Hezzell Melanie , Angelini Gianni D. , Dong Tim
Published: February 2025

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia, with an estimated five million cases globally. This condition increases the likelihood of developing cardiovascular complications such as thromboembolic events, with a fivefold increase in risk of both heart failure and stroke. Contemporary challenges include a better understanding AF pathophysiology and optimizing therapeutical options due to the current lack of efficacy and adverse effects of antiarrhythmic drug therapy. Hence, the identification of novel biomarkers in biological samples would greatly impact the diagnostic and therapeutic opportunities offered to AF patients. Long noncoding RNAs, micro RNAs, circular RNAs, and genes involved in heart cell differentiation are particularly relevant to understanding gene regulatory effects on AF pathophysiology. Proteomic remodeling may also play an important role in the structural, electrical, ion channel, and interactome dysfunctions associated with AF pathogenesis. Different devices for processing RNA and proteomic samples vary from RNA sequencing and microarray to a wide range of mass spectrometry techniques such as Orbitrap, Quadrupole, LC-MS, and hybrid systems. Since AF atrial tissue samples require a more invasive approach to be retrieved and analyzed, blood plasma biomarkers were also considered. A range of different sample preprocessing techniques and bioinformatic methods across studies were examined. The objective of this descriptive review is to examine the most recent developments of transcriptomics, proteomics, and bioinformatics in atrial fibrillation.
Biologics in Pediatric Idiopathic Nephrotic Syndrome and Other Kidney Diseases—General Principles and Special Considerations
Authors: Kopač Matjaž
Published: February 2025

Idiopathic nephrotic syndrome (INS) and other pediatric kidney diseases represent significant challenges due to their complex pathogenesis, often involving dysregulated immune responses and renal injury. Biologic therapies, defined as targeted treatments derived from living organisms, have gained traction in managing these conditions, offering a potential shift in therapeutic paradigms. This review examines the current and emerging role of biologics in treating pediatric kidney diseases, focusing on indications, contraindications, adverse effects, therapeutic positioning, and a comparison with alternative immunosuppressive treatments.
The Sex-Dependent Ameliorative Effect of Intermittent Fasting on Urinary System Functions in Genetic Absence Epileptic Rats
Authors: Gökçeoğlu-Kayalı Damla , Berkyürek Mehmet Ali , Özdemir-Kumral Zarife Nigar , Çilingir-Kaya Özlem Tuğçe
Published: February 2025

Epilepsy, a brain condition causing recurrent seizures, can disrupt various body functions, including urination. This study explored how alternate-day fasting (ADF), a type of intermittent fasting, a diet involving one day of eating and fasting, subsequently affects urinary system health in epileptic rats. Using a genetic rat model of epilepsy, we examined bladder and kidney function through tissue analysis, biochemical tests, and physiological assessments, focusing on differences between males and females. The results showed that epilepsy causes significant urinary system damage linked to inflammation and oxidative stress. However, ADF reduces this damage by lowering inflammation and restoring antioxidant balance. Male rats exhibited more oxidative damage, while female rats responded better to ADF, likely due to hormonal differences. These findings suggest ADF as a potential, cost-effective dietary approach to protect against urinary complications in epilepsy and similar conditions. Understanding these effects may lead to improved treatments for both genders and a better quality of life for people with chronic diseases.
Melatonin-Mediated Circadian Rhythm Signaling Exhibits Bidirectional Regulatory Effects on the State of Hair Follicle Stem Cells
Authors: Zhang Yu , Zhao Xuefei , Li Shuqi , Xu Yanchun , Bai Suying , Zhang Wei
Published: February 2025

The development and regulation of hair are widely influenced by biological rhythm signals. Melatonin plays a crucial role as a messenger in transmitting biological rhythm signals, and its impact on hair development has been well documented. During the process of hair follicle reconstruction, hair follicle stem cells (HFSCs) are the most important cell type, but the regulatory effect of melatonin on the state of HFSCs is still not fully understood. Therefore, it is necessary to conduct a more comprehensive characterization of the effects of melatonin on the state of hair follicle stem cells. The research results indicate that HFSCs express retinoic acid receptor-related orphan receptor alpha (Rorα), and melatonin inhibits the expression level of RORA. Experimental results from CUT&Tag, CUT&RUN, and dual luciferase reporter assays demonstrate that Foxc1 is a downstream target gene of RORA, with RORA regulating Foxc1 expression by binding to the promoter region of Foxc1. The CCK-8 assay results show that low doses of melatonin upregulate the survival rate of hair follicle stem cells, while high doses have the opposite effect. The knockdown of Foxc1 reverses the inhibitory effect of high-dose melatonin on the survival rate of hair follicle stem cells. Based on these findings, we believe that melatonin-mediated circadian signals exert a bidirectional regulatory effect on the state of HFSCs.
Biomechanical Evaluation of the Flexor Digitorum Longus and Flexor Hallucis Longus Transfer Used for the Treatment of Adult Acquired Flatfoot Deformity: A Finite Element Study
Authors: Pasapula Chandra , Yanguma Nicolas , Solorzano Brayan David , Kobezda Tamas , Cifuentes-De la Portilla Christian , Aziz Md Abdul
Published: February 2025

Introduction: Management strategies for stage II tibialis posterior tendon dysfunction are centered on tendon transfers and osteotomies. One of the most commonly used tendon transfers is flexor digitorum longus (FDL) tendon to navicular, but its superiority over transfers to other locations or transfers of other tendons, along with the role of spring ligament and tibialis posterior tendons, have not been objectively evaluated. Aims: We aimed to quantify both the location and magnitude of secondary stresses that develop as a consequence of the initial pathology. Methods: In this study, we used a computational model to study flat foot development and evaluate the effects of various tendon transfers and failures of passive structural elements, as well as their effect on the biomechanics of the foot. Results: We found that both FDL and FHL transfers have biomechanical advantages and disadvantages. Neither of these transfers decrease the stress on the tibialis posterior tendon if the underlying pathologies such as spring ligament failure are not addressed. Conclusions: Of the tendon transfers evaluated, FDL transfer to the navicular had the most profound effect on reducing the stresses on the spring ligament.
Early Diagnosis of Pneumonia and Chronic Obstructive Pulmonary Disease with a Smart Stethoscope with Cloud Server-Embedded Machine Learning in the Post-COVID-19 Era
Authors: Sueaseenak Direk , Boonsat Peeravit , Tantisatirapong Suchada , Rujipong Petcharat , Tulatamakit Sirapat , Phokaewvarangkul Onanong
Published: February 2025

Background/Objectives: Respiratory diseases are common and result in high mortality, especially in the elderly, with pneumonia and chronic obstructive pulmonary disease (COPD). Auscultation of lung sounds using a stethoscope is a crucial method for diagnosis, but it may require specialized training and the involvement of pulmonologists. This study aims to assist medical professionals who are non-pulmonologist doctors in early screening for pneumonia and COPD by developing a smart stethoscope with cloud server-embedded machine learning to diagnose lung sounds. Methods: The smart stethoscope was developed using a Micro-Electro-Mechanical system (MEMS) microphone to record lung sounds in the mobile application and then send them wirelessly to a cloud server for real-time machine learning classification. Results: The model of the smart stethoscope classifies lung sounds into four categories: normal, pneumonia, COPD, and other respiratory diseases. It achieved an accuracy of 89%, a sensitivity of 89.75%, and a specificity of 95%. In addition, testing with healthy volunteers yielded an accuracy of 80% in distinguishing normal and diseased lungs. Moreover, the performance comparison between the smart stethoscope and two commercial auscultation stethoscopes showed comparable sound quality and loudness results. Conclusions: The smart stethoscope holds great promise for improving healthcare delivery in the post-COVID-19 era, offering the probability of the most likely respiratory conditions for early diagnosis of pneumonia, COPD, and other respiratory diseases. Its user-friendly design and machine learning capabilities provide a valuable resource for non-pulmonologist doctors by delivering timely, evidence-based diagnoses, aiding treatment decisions, and paving the way for more accessible respiratory care.
Cross-Sectional Study Evaluating the Role of Autonomic Nervous System Functional Diagnostics in Differentiating Post-Infectious Syndromes: Post-COVID Syndrome, Chronic Fatigue Syndrome, and Lyme Disease
Authors: Milovanovic Branislav , Markovic Nikola , Petrovic Masa , Zugic Vasko , Ostojic Milijana , Bojic Milovan
Published: February 2025

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions.
How the Structure and Wettability Properties of Morpho peleides Butterfly Wings Can Be a Source of Inspiration
Authors: Burdin Louise , Brulez Anne-Catherine , Mazurczyk Radoslaw , Leclercq Jean-Louis , Benayoun Stéphane
Published: February 2025

In this study, the wettability of Morpho peleides (M. peleides) wings is studied. Using a goniometer, the contact angles of ~136° were measured. Although few studies have provided a general overview of the static wettability properties of M. peleides and the particularly anisotropic morphology of their wings, a detailed analysis of wettability properties is proposed. The results indicate anisotropic wettability, with a sliding angle of 7° when the wings were tilted away from the insect’s body and 29° when the wings were tilted toward the insect’s body. The Extrand model, coupled with a hierarchical approach, was also employed to describe the wettability behavior of M. peleides wings and its relationship with the dual roughness scale of the wings. Owing to these models, it has been demonstrated that the micrometric scale of the wing structure is primarily responsible for the static wettability properties of the M. peleides, while the nanometric scale influences the dynamic wettability of the wing. Moreover, compared to the topography, the wing’s chemistry has very little effect on the wettability properties of the M. peleides.
Experimental Study on Flexural Performance of Screw Clamping and Welding Joint for Prestressed Concrete Square Piles
Authors: Xu Quanbiao , Zhu Yajun , Chen Gang , Xu Dan
Published: February 2025

To ensure the connection performance of precast concrete square piles, a screw clamping and welding joint connection is applied to the solid square piles. By conducting full-scale bending performance tests on six solid square pile specimens with cross-sectional side lengths of 300, 450, and 600 mm, including pile bodies, screw clamping joints, screw clamping, and welding joints, the bending load-bearing capacity, deformation capacity, and failure characteristics of the screw clamping–welding joint connection are compared and studied. The results show that the bending failure mode of the pile body specimens is shear failure in the flexural shear section and concrete crushing in the compression zone of the pure bending section; the bending failure mode of the screw clamping joint specimens are the pull-out of steel bar heads at the joint end plate; the bending failure mode of the screw clamping and welding joint specimens are concrete crushing in the compression zone of the pure bending section, steel bar breakage in the tension zone of the flexural shear section, and pull-out of steel bar heads at the end plate. It is worth noting that no significant damage occurred at the joints. The cracks in the pure bending section of the bending specimens mainly develop vertically and are evenly distributed, while some cracks in the flexural shear section develop obliquely towards the loading point, with branching. Compared to the pile body specimens, the cracking moment of the joint specimens is up to 16% higher, the ultimate moment is within 15% lower, and the maximum mid-span deflection is within 25% lower, indicating that the provision of anchorage reinforcement can increase the stiffness and cracking moment of the specimens.
Optimizing Urban Ventilation in Heritage Settings: A Computational Fluid Dynamics and Field Study in Zhao’an Old Town, Fujian
Authors: Chen Haoxi , Zhu Shaochuan , Ye Taohua , Miao Yijia
Published: February 2025

This study investigates the optimization of urban ventilation in Zhao’an Old Town, Fujian, through the integration of Computational Fluid Dynamics (CFD) simulations and field measurements. The findings underscore the critical roles of spatial layout indicators, such as the Frontal Area Index (FAI), Opening-to-Facade Ratio (OFR), and Building Volume Density (BVD), in influencing wind flow and thermal performance. The FAI was identified as the most influential factor in shaping airflow, while the OFR and BVD highlighted the importance of open spaces and balanced building density for natural ventilation and thermal comfort. Practical strategies, such as optimizing building orientations, increasing facade permeability, and leveraging natural cooling elements like the Dongxi River, are proposed to address ventilation challenges while preserving the town’s cultural and historical integrity. Unlike previous studies, this research combines CFD simulations with summer field measurements to provide a highly accurate and contextually relevant evaluation of wind flow dynamics in compact urban environments. By systematically analyzing the interplay between urban morphology and ventilation efficiency, this study offers actionable recommendations for improving outdoor comfort in heritage settings. The outcomes serve as a valuable reference for sustainable urban planning, contributing to the development of strategies that balance environmental performance with the preservation of Zhao’an Old Town’s unique cultural heritage.
Enhancing Worker Safety Behaviors Through the Job Demands–Resources Approach: Insights from the Korean Construction Sector
Authors: Seo Hyun Jeong , Rhee Seung-Yoon , Yoon Young-Geun
Published: February 2025

(1) Background: The construction industry faces high occupational accident rates due to complex work environments and physical hazards, significantly impacting worker safety and well-being. Drawing on the Conservation of Resources (COR) theory and the Job Demands–Resources (JD-R) model, this study addresses the challenges posed by the multi-level subcontracting structure in the Korean construction sector. It aims to provide a comprehensive understanding of the job demands and resources factors that shape workers’ safety behaviors. (2) Methods: Hierarchical regression analyses were conducted using data from the 10th Occupational Safety and Health Survey by the Occupational Safety and Health Research Institute, with a sample of 1502 construction firms. (3) Results: Job demands, including hazardous work environments, physically demanding tasks, and mental stress, were found to affect workers’ safety behaviors negatively. Middle managers’ safety competency mitigated the negative effects of these environmental, physical, and mental job demands. Additionally, safety culture and systems moderated the adverse effects of physical job demands, while organizational stress and risk management efforts moderated the impact of environmental job demands. (4) Conclusions: Managerial safety competencies, especially at the middle management level, are vital for improving safety outcomes in the construction industry. This is particularly important in the Korean construction sector, where management responsibilities are often dispersed. Training and development for managers are essential for future safety initiatives.
Advancing Pancreatic Cancer Prediction with a Next Visit Token Prediction Head on Top of Med-BERT
Authors: He Jianping , Rasmy Laila , Zhi Degui , Tao Cui
Published: February 2025

Background: Electronic Health Records (EHRs) encompass valuable data essential for disease prediction. The application of artificial intelligence (AI), particularly deep learning, significantly enhances disease prediction by analyzing extensive EHR datasets to identify hidden patterns, facilitating early detection. Recently, numerous foundation models pretrained on extensive data have demonstrated efficacy in disease prediction using EHRs. However, there remains some unanswered questions on how to best utilize such models, especially with very small fine-tuning cohorts. Methods: We utilized Med-BERT, an EHR-specific foundation model, and reformulated the disease binary prediction task into a token prediction task and a next visit mask token prediction task to align with Med-BERT’s pretraining task format in order to improve the accuracy of pancreatic cancer (PaCa) prediction in both few-shot and fully supervised settings. Results: The reformulation of the task into a token prediction task, referred to as Med-BERT-Sum, demonstrated slightly superior performance in both few-shot scenarios and larger data samples. Furthermore, reformulating the prediction task as a Next Visit Mask Token Prediction task (Med-BERT-Mask) significantly outperformed the conventional Binary Classification (BC) prediction task (Med-BERT-BC) by 3% to 7% in few-shot scenarios with data sizes ranging from 10 to 500 samples. These findings highlight that aligning the downstream task with Med-BERT’s pretraining objectives substantially enhances the model’s predictive capabilities, thereby improving its effectiveness in predicting both rare and common diseases. Conclusions: Reformatting disease prediction tasks to align with the pretraining of foundation models enhances prediction accuracy, leading to earlier detection and timely intervention. This approach improves treatment effectiveness, survival rates, and overall patient outcomes for PaCa and potentially other cancers.
Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
Authors: Muñoz Miguel , Rosso Marisa
Published: February 2025

Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brainstem tumor. The median survival of DIPG is 16–24 months independent of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. Substance P (SP) peptide, through the neurokinin neurokinin-1 receptor (NK-1R), is involved in glioma progression. It induces glioma cell proliferation by activating MAPKs (p38 MAPK, ERK1/2, and JNK), c-Myc, AP-1, and NF-κB and induces antiapoptotic effects via PI3K/Akt/mTOR in glioma cells. SP favors glycogen breakdown that is essential for glycolysis. The SP/NK-1R system also regulates the migration and invasion of glioma cells, stimulates angiogenesis, and triggers inflammation which contributes to glioma progression. Moreover, all glioma cells express NK-1R, and NK-1R is essential for the viability of glioma cells and not of normal cells. In contrast, in glioma, NK-1R antagonists, such as the drug aprepitant, penetrate the brain and reach therapeutic concentrations, thereby inhibiting mitogenesis, inducing apoptosis, and inhibiting the breakdown of glycogen in glioma cells. In addition, they inhibit angiogenesis and exert antimetastatic and anti-inflammatory effects. The combination of radiotherapy with NK-1R antagonists produces radiosensitization and radioneuroprotection, reduces both peritumoral- and radiation-induced inflammation, and also provides antinausea and antivomiting effects. Objective: This review updates the involvement of the SP/NK-1R system in glioma promotion and progression and the potential clinical application of NK-1R antagonist drugs in DIPG therapy. Conclusions: NK-1R plays a crucial role in glioma progression and NK-1R antagonists such as aprepitant could be used in combination with radiotherapy as a potent therapeutic strategy for the treatment of patients with DIPG.
Three-Dimensional Models: Biomimetic Tools That Recapitulate Breast Tissue Architecture and Microenvironment to Study Ductal Carcinoma In Situ Transition to Invasive Ductal Breast Cancer
Authors: Shah Seema , Osuala Kingsley O. , Brock Ethan J. , Ji Kyungmin , Sloane Bonnie F. , Mattingly Raymond R.
Published: February 2025

Diagnosis of ductal carcinoma in situ (DCIS) presents a challenge as we cannot yet distinguish between those lesions that remain dormant from cases that may progress to invasive ductal breast cancer (IDC) and require therapeutic intervention. Our overall interest is to develop biomimetic three-dimensional (3D) models that more accurately recapitulate the structure and characteristics of pre-invasive breast cancer in order to study the underlying mechanisms driving malignant progression. These models allow us to mimic the microenvironment to investigate many aspects of mammary cell biology, including the role of the extracellular matrix (ECM), the interaction between carcinoma-associated fibroblasts (CAFs) and epithelial cells, and the dynamics of cytoskeletal reorganization. In this review article, we outline the significance of 3D culture models as reliable pre-clinical tools that mimic the in vivo tumor microenvironment and facilitate the study of DCIS lesions as they progress to invasive breast cancer. We also discuss the role of CAFs and other stromal cells in DCIS transition as well as the clinical significance of emerging technologies like tumor-on-chip and co-culture models.
Copper-Catalyzed Four-Component A3-Based Cascade Reaction: Facile Synthesis of 3-Oxetanone-Derived Spirocycles
Authors: Zhang Rongkang , Huang Liliang , Gu Aiguo , Feng Huangdi
Published: February 2025

3-Oxetanone-derived spirooxazolidines represent a class of building blocks for accessing diverse saturated heterocycles, but their synthetic methods remain unexplored. Herein, we demonstrate a highly atom-economic approach for the synthesis of diverse 3-oxetanone-derived N-propargyl spirooxazolidines via a CuBr2/TFA co-catalyzed four-component A3-based cascade reaction of a 1,2-amino alcohol, a 3-oxetanone, a formaldehyde, and an alkyne. This strategy is characterized by a wide substrate range and excellent chemoselectivity. In addition, the synthesized spirocycles could also be easily converted into other valuable compounds, facilitating potentially useful synthetic applications.
Portable 3D-Printed Paper Microfluidic System with a Smartphone Reader for Fast and Reliable Copper Ion Monitoring
Authors: Cao Jingzhen , Cheng Nan , Liu Zhengyang , Lu Qian , Li Lei , Lin Yuehe , Zhang Xian , Du Dan
Published: February 2025

Copper ions (Cu2+) are the third most essential transition metal ions critical to human health. Rapid detection of Cu2+ in water and biological fluids is of significant importance. In this study, we develop a sensitive multi-channel paper microfluidic device integrated with a 3D-printed smartphone-based colorimetric reader for the rapid detection of Cu2+. A novel rhodamine derivative, 1-(N,N-dichloromethine) amino-4-rhodamine B hydrazine-benzimide (RBCl), exhibiting high selectivity and sensitivity to Cu2+, was synthesized and applied as the detection reagent. The interaction mechanism between RBCl and Cu2+ was investigated, revealing a structural transition from a colorless spirolactam (closed-ring) to an open-ring amide structure, resulting in a pink color upon Cu2+ binding. A multi-channel paper microfluidic device with eight detection zones was fabricated, enabling the simultaneous analysis of eight samples. To enhance portability and quantification, a 3D-printed smartphone colorimetric reader was integrated, providing a rapid and efficient detection platform. The system achieved highly specific Cu2+ detection within 2 min, with a detection limit as low as 1.51 ng/mL, meeting water monitoring standards in most countries. Excellent recoveries were demonstrated in real samples, including tap water, river water, blood serum, and urine diluent. This integrated paper microfluidic system is highly sensitive and specific, offering a promising solution for water quality monitoring and health assessment through its rapid sample-to-answer capability.
The Growing Behavior of the Ca2Gd8(SiO4)6O2 Dense Reaction Layer in Molten CMAS at High Temperatures
Authors: Mo Zijian , Mo Zupeng , Guo Kaisen , Yu Zhiyun , He Huan , Liang Tianquan
Published: February 2025

Calcium–magnesium–alumina–silicate (CMAS), as an environmental deposit, deposits on engine components and causes serious damage to traditional thermal barrier coatings (TBCs) at high temperatures. The rare-earth silicate apatite dense reaction layer is regarded as a promising strategy to prevent TBCs from molten CMAS penetration and corrosion. The interactions between the Gd2O3 ceramic and CMAS are discussed at various temperatures and times in the study. The main reaction products are gadolinium silicate apatite (Ca2Gd8(SiO4)6O2, Gd-apatite) and melilite phases. Within the first 15 min of interaction, a thin, continuous and dense reaction layer (DRL) consisting of Gd-apatite comes to form, and it thickens with increasing exposure temperature and time. The thickness of the DRL is ~0.8 μm after 15 min of the reaction at 1250 °C and it slowly increases to ~9.1 μm after a duration of 24 h at 1400 °C. This is attributed to CMAS infiltration along the grain boundaries of the Gd-apatite phases in the DRL. The growing rates of the Gd-apatite DRL decrease with reaction time and are significantly influenced by the temperature and the ability of the DRL to inhibit CMAS infiltration.
Investigation of Fatigue Performance for In-Service Asphalt Pavement Mixtures Using Push-Pull Fatigue Test
Authors: Zhang Zhanming , Xu Duo , Fan Yunlong , Ma Hui , Ding Zihao , Jiang Jiwang , Li Jie , Ma Tao
Published: February 2025

With the increasing service life of asphalt pavements, fatigue cracking has become a typical distress that significantly affects the structural lifespan of in-service asphalt pavements. To address the issues of high variability in laboratory fatigue tests and the poor correlation between test results and actual pavement cracking conditions, this study collected field core samples from in-service highways with varying degrees of cracking. The study employed push-pull fatigue tests on asphalt mixtures and linear amplitude sweep tests on extracted and recovered asphalt to evaluate fatigue performance. Quantitative relationships between transverse crack spacing and fatigue indices were established. With the inclusion of laboratory-compacted asphalt mixtures, the relationship between transverse crack spacing and the average pseudo-stiffness degradation rates was well described by a logarithmic function (R2 = 0.928), while the apparent damage capacity achieved a stronger correlation (R2 = 0.945). The findings demonstrate that the push-pull fatigue test, based on a viscoelastic continuum damage model, shows high stability and repeatability, with the coefficients of variation for the indices consistently below 11%. Compared to the average pseudo-stiffness degradation rates, the apparent damage capacity demonstrates better discriminative capability as an evaluation index for the intermediate-temperature fatigue performance of asphalt mixtures. The fatigue life from linear amplitude sweep tests on extracted and recovered asphalt from core samples shows a high degree of consistency with the patterns observed in various parameters of push-pull fatigue tests. The findings confirm the reliability of the push-pull fatigue test for evaluating intermediate-temperature fatigue performance of asphalt mixtures and provide the necessary theoretical support for establishing a fatigue performance evaluation system for in-service asphalt pavements.
Computer Simulation and Speedup of Solving Heat Transfer Problems of Heating and Melting Metal Particles with Laser Radiation
Authors: Gulevskis Arturas , Volkov Konstantin
Published: February 2025

The study of the process of laser action on powder materials requires the construction of mathematical models of the interaction of laser radiation with powder particles that take into account the features of energy supply and are applicable in a wide range of beam parameters and properties of the particle material. A model of the interaction of pulsed or pulse-periodic laser radiation with a spherical metal particle is developed. To find the temperature distribution in the particle volume, the non-stationary three-dimensional heat conductivity equation with a source term that takes into account the action of laser radiation is solved. In the plane normal to the direction of propagation of laser radiation, the change in the radiation intensity obeys the Gaussian law. It is possible to take into account changes in the intensity of laser radiation in space due to its absorption by the environment. To accelerate numerical calculations, a computational algorithm is used based on the use of vectorized data structures and parallel implementation of operations on general-purpose graphics accelerators. The features of the software implementation of the method for solving a system of difference equations that arises as a result of finite-volume discretization of the heat conductivity equation with implicit scheme by the iterative method are presented. The model developed describes the heating and melting of a spherical metal particle exposed by multi-pulsed laser radiation. The implementation of the computational algorithm developed is based on the use of vectorized data structures and GPU resources. The model and calculation results are of interest for constructing a two-phase flow model describing the interaction of test particles with laser radiation on the scale of the entire calculation domain. Such a model is implemented using a discrete-trajectory approach to modeling the motion and heat exchange of a dispersed admixture.
From Data Surveying to the Geometrical Analysis of Historical Constructive Wooden Ceiling Structures: A Renaissance Villa in the North of Italy
Authors: Oreni Daniela
Published: February 2025

Villa Cicogna Mozzoni, located in Bisuschio near Varese and Lake Lugano, on the border between Lombardy and Switzerland, has origins dating back to the 1540s as a hunting lodge owned by the Mozzoni family. In the 16th century, significant renovations transformed it into a “villa di delizia”, adding gardens and elaborate decorative features to the interior and exterior, many of which are still preserved today. This article focuses on a precise geometric analysis of the building’s wooden ceilings, based on laser scanning and photogrammetric data surveying. The ongoing research particularly examines the wooden coffered ceilings on the first floor and the camorcanna wooden fake vault of the Grand Staircase of Honor. By analyzing the geometric data and comparing it with historical, archival, and recent manuals, the study has provided valuable morphological, construction, and conservation insights, forming the basis for the diagnostic and restoration project.
Treatment Patterns of Pancreatic Neuroendocrine Tumor (pNET) Patients at Two Canadian Cancer Centres
Authors: Nair Gautham , Black Morgan , Baer Kathie , Welch Stephen , Laidley David T. , Goodwin Rachel , Leung Macyn , Phillips William J. , Vickers Michael , Asmis Tim , Marginean Horia , Tsvetkova Elena
Published: February 2025

Pancreatic neuroendocrine tumors (pNETs) are rare but increasingly prevalent malignancies with varied prognoses and a diverse range of treatment options, including surgery, somatostatin analogues (SSAs), chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). This retrospective cohort study analyzed treatment patterns among 189 pNET patients treated between January 2010 and June 2021 at two Canadian cancer centres: the Verspeeten Family Cancer Centre (VFCC), which offers PRRT, and the Ottawa Hospital Cancer Centre (TOHCC), which does not at the time of the study. Data on demographics, tumor characteristics, and treatment modalities were collected, and statistical analyses were conducted using chi-square, Fisher’s exact test, and the Kruskal–Wallis test. Among eligible patients, 53% presented with stage IV disease. Surgical resection was the most common treatment, followed by SSAs, chemotherapy, PRRT, and targeted therapy. Stage IV patients at VFCC were significantly more likely to receive PRRT (60%) compared to TOHCC (6%) and underwent more PRRT cycles, with a higher prevalence of well-differentiated tumors observed at VFCC. With these differences it was clear that the non-PRRT centre was unable to provide patients with the same level of PRRT access during the study period compared to patients seen at the PRRT site. The findings underscore the critical role of PRRT availability in influencing treatment patterns and highlight the need for equitable access to specialized therapies across Canada to optimize outcomes for pNET patients.
The Efficacy and Safety of Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Programmed Death (PD)-1 Inhibitors for Unresectable Intrahepatic Cholangiocarcinoma: A Retrospective Study
Authors: Cai Yingxiao , Wen Wu , Xia Yangshuo , Wan Renhua
Published: February 2025

Objectives: Although systemic chemotherapy (SC) is the mainstay for treating unresectable intrahepatic cholangiocarcinoma (ICC), its efficacy is limited and it causes severe systemic side effects. This study focuses on evaluating the effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib plus programmed death-1 (PD-1) inhibitors (HLP), compared to SC in combination with lenvatinib plus PD-1 inhibitors (SCLP) for unresectable ICC. Methods: We analyzed patients initially diagnosed with unresectable ICC at our center between March 2021 and December 2023, classifying them into HLP and SCLP groups according to treatment regimen. This study assessed and compared overall survival (OS), progression-free survival (PFS), tumor response, and safety outcomes across the two treatment groups. Results: This study enrolled 53 subjects in total; 25 were treated with HLP and 28 with SCLP. The two groups showed well-matched baseline characteristics. The HLP group reported an extended median OS (12.8 vs. 11.0 months, p = 0.310) and a prolonged median PFS (8.8 vs. 6.4 months, p = 0.043), compared to the SCLP group. The HLP group had a better objective response rate (ORR) (52% vs. 25%, p = 0.043) and disease control rate (DCR) (96% vs. 78.6%, p = 0.104). Based on OS (p = 0.019) and PFS (p = 0.032) results, those without extrahepatic metastasis seemed to benefit more significantly from the HLP regimen than from the SCLP regimen. The HLP group experienced fewer grade 3–4 adverse events (AEs) than the SCLP group. Conclusions: The HLP regimen for unresectable ICC is an effective and safe strategy and is potentially better suited for patients without extrahepatic metastases.