bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Facial Thermal Nociceptive Response in Female Dogs After Elective Ovariohysterectomy Anesthetized with Isoflurane and Treated with Cannabidiol and Meloxicam Analgesia
Authors: Casas-Alvarado Alejandro , Mora-Medina Patricia , Hernández-Avalos Ismael , Martínez-Burnes Julio , Miranda-Cortes Agatha , Domínguez-Oliva Adriana , Mota-Rojas Daniel
Published: January 2025

Pain management requires the identification of certain indicators to recognize pain. Various tools have been suggested to achieve an objective evaluation, including infrared thermography (IRT). The objective of this study was to assess the facial thermal nociceptive response produced by the use of cannabidiol (CBD) alone and in combination with meloxicam in female dogs undergoing elective ovariohysterectomy anesthetized with isoflurane. Sixty-four female dogs of different breeds were randomly distributed into four study groups according to the treatment received. G1: Placebo group (n = 16); G2: Group receiving intravenous meloxicam as premedication (0.2 mg Kg−1) and every 24 h postoperatively 0.1 mg Kg−1 (n = 16); G3: Group treated with CBD (n = 16) at a dose of 2 mg kg−1 orally every 12 h; and G4: Group medicated with the combination of both treatments (n = 16). All treatments were administered for 48 h postoperatively. After the anesthetic surgical procedure, radiometric images were captured using IRT and physiological parameters during the events EBasal, E30min, E1h, E2h, E3h, E4h, E8h, E12h, E24h and E48h. Overall, it was found that the high, medium and low temperatures of the thermal windows of the eye, upper eyelid and lower eyelid, as well as the average temperature of the lacrimal gland in G1 between events, were significantly lower at E30min, E1h and E2h compared to EBasal (p = 0.01). Among treatments, a significantly higher temperature was observed in groups G2, G3 and G4 compared to G1 (p = 0.001) in the thermal windows of the upper eyelid, lower eyelid, lacrimal gland and ocular areas. Regarding physiological parameters, heart rate (HR) was higher in G1 compared to the animals in G2, G3 and G4 (p = 0.03). The respiratory rate (RR) was significantly lower in all four study groups during the postoperative events compared to their respective EBasal (p < 0.05), while among treatments, G2, G3 and G4 had a lower RR compared to G1 (p = 0.03). Mild hypothermia was observed in all study groups at E30min and E1h compared to EBasal (p = 0.001). No significant correlation was found between the temperatures of the assessed thermal regions and the physiological traits. In conclusion, CBD, whether administered alone or in combination with meloxicam, demonstrated comparable analgesic efficacy, which could control nociceptive cardiorespiratory and hemodynamic autonomic responses, as there were no significant changes in the facial thermal response between treatments G2, G3 and G4.
Analysis of Automotive Suspension System Failures and Reliability Evaluation: A Study Based on V-SIM Simulation
Authors: Kowalski Sławomir
Published: January 2025

This article presents the factors that are conducive to the faster degradation of suspension system components with examples of typical system damage seen at diagnostic stations. Further in the article, the simulation of the deflection of the suspension system was conducted in the V-SIM 5.0 software, and the sample road consequences of damage to the system were presented. The simulation results showed that long-term use of the vehicle on uneven roads often leads to maximum deviations of the suspension system, even 150 mm. The consequence of such a condition may be its damage during driving, resulting in a road accident. The effects of damage to the suspension system were simulated while driving at a speed of 50 and 70 km/h. The article concludes with an estimation of the reliability indicators of the suspension system. Based on the results, it may be concluded that the operation of a fully loaded car in difficult conditions causes a 50% decrease in the system’s reliability as early as at a mileage of approximately 48,000 km.
Utilization of Thermal-Activated Coal Gangue to Enhance the Properties of Sandy Soil Composites
Authors: Fan Wangtao , Liu Ruofan , Zhang Runxia , Chen Xiaoguang , Li Jin , Zhang Aochen , Qian Jing , Gu Zhaolin , Wang Jianyun
Published: January 2025

To effectively solve the problem of land sanding and improve the water- and element-retaining properties of sandy soil, a thermal-activated coal gangue (TACG) was used as an ameliorating material to prepare a composite soil mixed with sandy soil to enhance the water-retaining and fertilizer-fixing properties of the sandy soil and reduce the evaporation of water in the soil. The structure and thermal stability of the gangue were characterized using Fourier transform infrared spectroscopy and thermogravimetric analysis. By applying different dosages and different calcination temperatures of the TACG, the water-holding capacity of the mixed soil was determined, and changes in pore structure were observed. When the dosage was 15% and the calcination temperature was 600 °C, the mixed soil possessed the most excellent distribution of pore structure and could effectively prevent water evaporation. Meanwhile, the application of the TACG in sandy soil improved its adsorption of K+, which showed the potential application of thermally activated gangue materials in the field of soil improvement.
Data Processing and Machine Learning for Assistive and Rehabilitation Technologies
Authors: Tigrini Andrea , Sbrollini Agnese , Mengarelli Alessandro
Published: January 2025

This Special Issue (SI), “Data Processing and Machine Learning for Assistive and Rehabilitation Technologies”, aimed to collect cutting-edge research papers that frame how data-driven approaches and machine learning techniques are advancing the field of assistive and rehabilitation technologies [...]
Alternative Splicing: Emerging Roles in Anti-Aging Strategies
Authors: Gao Lingyue , Jia Rong
Published: January 2025

Alternative splicing plays a fundamental role in gene expression and protein complexity. Aberrant splicing impairs cell homeostasis and is closely associated with aging and cellular senescence. Significant changes to alternative splicing, including dysregulated splicing events and the abnormal expression of splicing factors, have been detected during the aging process or in age-related disorders. Here, we highlight the possibility of suppressing aging and cellular senescence by controlling alternative splicing. In this review, we will summarize the latest research progress on alternative splicing in aging and cellular senescence, discuss the roles and regulatory mechanisms of alternative splicing during aging, and then excavate existing and potential approaches to anti-aging by controlling alternative splicing. Novel therapeutic breakthroughs concerning aging and senescence entail a further understanding of regulating alternative splicing mechanically and accurately.
Development and Evaluation of Polymethacrylate-Based Ophthalmic Nanofiber Inserts Containing Dual Drug-Loaded Dorzolamide and Timolol: In Vivo Study in Rabbit’s Eye
Authors: Karami Ahmad , Mirzaeei Shahla , Rezaei Leila , Nokhodchi Ali
Published: January 2025

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug–polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit’s eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency.
High Frequency of PIK3R1 Alterations in Ovarian Cancers: Clinicopathological and Molecular Associations
Authors: Rzepecka Iwona K. , Tysarowski Andrzej , Konopka Bozena , Dansonka-Mieszkowska Agnieszka , Kupryjanczyk Jolanta
Published: January 2025

Background: The phosphoinositide 3-kinase (PI3K) pathway is activated in multiple cancers. However, the significance of PIK3R1 encoding the PI3K regulatory subunit, an inhibitor of the PI3K catalytic subunit encoded by PIK3CA, in ovarian cancer development is largely unknown. Methods: Here, we investigated PIK3R1 genomic alterations and gene expression by direct sequencing and qPCR methods in 197 ovarian cancers. The results were correlated with clinicopathological and molecular variables and patient outcomes. Results: In addition to mutations (3.5%) and allelic losses (28.4%), we observed a very high frequency of decreased PIK3R1 mRNA levels in ovarian carcinomas (95.8%). Tumors with PIK3R1 mutations mostly represented low-stage cancers of endometrioid and clear-cell type. Tumors with PIK3R1 deletion and underexpression shared similar phenotypes of high-grade carcinomas (p = 0.003 and p = 0.025, respectively). Allelic loss was also associated with advanced stages (p = 0.003) and high-grade serous histotypes (p = 0.004). The PIK3R1 copy number correlated with mRNA levels (p = 0.009). PIK3R1 mutations coexisted with PTEN mutations (p = 0.041), whereas PIK3R1 deletion and underexpression were linked to PIK3CA amplification (p = 0.038 and p = 0.033, respectively). Low PIK3R1 expression diminished the probability of a complete response (OR 0.07, p = 0.03) in patients treated with platinum-based regimens. Conclusions: PIK3R1 alterations may contribute to the development of ovarian cancers with different malignant potential and molecular changes. The high frequency of PIK3R1 aberrations suggests their importance in PI3K pathway deregulation, and they may potentially serve as an alternative to PIK3CA markers for therapy with these pathway inhibitors.
The Immune–Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies
Authors: Cammarota Antonella , Balsano Rita , Pressiani Tiziana , Bozzarelli Silvia , Rimassa Lorenza , Lleo Ana
Published: January 2025

Cholangiocarcinoma (CCA) represents approximately 3% of all gastrointestinal cancers and is a highly heterogeneous and aggressive malignancy originating from the epithelial cells of the biliary tree. CCA is classified by anatomical location into intrahepatic (iCCA), extrahepatic (eCCA), gallbladder cancer (GBC), and ampullary cancers. Although considered a rare tumor, CCA incidence has risen globally, particularly due to the increased diagnosis of iCCA. Genomic and immune profiling studies have revealed significant heterogeneity within CCA, leading to the identification of molecular subtypes and actionable genetic alterations in 40–60% of cases, particularly in iCCA. Among these, FGFR2 rearrangements or fusions (7–15%) and IDH1 mutations (10–20%) are common in iCCA, while HER2 amplifications/overexpression are more frequent in eCCA and GBC. The tumor-immune microenvironment (TIME) of CCAs plays an active role in the pathogenesis and progression of the disease, creating a complex and plastic environment dominated by immune-suppressive populations. Among these, cancer-associated fibroblasts (CAFs) are a key component of the TIME and are associated with worse survival due to their role in maintaining a poorly immunogenic landscape through the deposition of stiff extracellular matrix and release of pro-tumor soluble factors. Improved understanding of CCA tumor biology has driven the development of novel treatments. Combination therapies of cisplatin and gemcitabine with immune checkpoint inhibitors (ICIs) have replaced the decade-long standard doublet chemotherapy, becoming the new standard of care in patients with advanced CCA. However, the survival improvements remain modest prompting research into more effective ways to target the TIME of CCAs. As key mechanisms of immune evasion in CCA are uncovered, novel immune molecules emerge as potential therapeutic targets. Current studies are exploring strategies targeting multiple immune checkpoints, angiogenesis, and tumor-specific antigens that contribute to immune escape. Additionally, the success of ICIs in advanced CCA has led to interest in their application in earlier stages of the disease, such as in adjuvant and neoadjuvant settings. This review offers a comprehensive overview of the immune biology of CCAs and examines how this knowledge has guided clinical drug development, with a focus on both approved and emergent treatment strategies.
Design of Resonant Inverters with Energy Dosing, Based on Optimization with Reference Curve
Authors: Madzharov Nikolay , Gilev Bogdan , Hinov Nikolay
Published: January 2025

This paper presents an optimization-based approach for the design of energy-dosing resonant inverters (RI) using a reference curve. RI are widely used in areas such as wireless charging, induction heating, and high-frequency power supplies due to their high efficiency and soft-switching capability. The proposed methodology uses a reference current curve in the alternating current (AC) circuit that describes the ideal behavior of the inverter during the start-up transient in order to operate in energy metering mode and minimize switching losses. This approach analyzes and optimizes the values of the circuit elements whose initial values are determined by applying a rational design methodology. The results of the study demonstrate increased dynamics of the power circuit and better stability compared to applying traditional design methods. The presented simulation results confirm the effectiveness of the proposed optimization and the improvement of the characteristics of the studied device.
A Reference Architecture for Virtual Human Integration in the Metaverse: Enhancing the Galleries, Libraries, Archives, and Museums (GLAM) Sector with AI-Driven Experiences
Authors: Spyrou Orestis , Hurst William , Krampe Caspar
Published: January 2025

The digital transformation of the GLAM (galleries, libraries, archives, and museums) sector is a multifaceted process that must address a range of requirements and critical challenges, such as traceability, long-term preservation, and sustainability. The potential of disruptive technologies to revolutionize this sector is significant, offering new ways to overcome these challenges and align with the broader objectives of smart cities. While substantial research has been conducted on the digital transformation of the GLAM sector, many opportunities remain unexplored by various stakeholders. This paper contributes to the field by proposing a reference architecture rooted in a design-oriented approach for developing and implementing processes related to the digital transformation within the context of smart cities. To illustrate the practical application of the proposed architecture, a proof of concept was developed in the form of an immersive digital gallery, which features an AI-powered virtual storyteller. The gallery, built using the open, cross-platform, Unreal, incorporates digitized physical art and a virtual metahuman tutor who guides users through the gallery. This interactive 3D environment enables users to explore the space, engage with artworks, and interact with a virtual guide. The environment’s performance was evaluated using a keystroke-level model analysis. Key findings from a pilot study involving 10 users showed that, when directed by the AI storyteller, the average time to locate an artwork was 16.5 s, while the average time to ask a question was 15.8 s. By integrating such technologies, the GLAM sector can contribute to the cultural fabric of smart cities, fostering more sustainable, accessible, and interactive public spaces.
Degradation of Interfacial Bond for FRPs Near-Surface Mounted to Concrete Under Fatigue: An Analytical Approach
Authors: Wang Xun , Cheng Lijuan
Published: January 2025

In this study, an analytical model was developed for the local bond degradation behavior between a near-surface mounted (NSM) fiber-reinforced polymer (FRP) and concrete under fatigue loading. A trilinear local bond stress–slip relationship was adopted to characterize the fundamental bond behavior at the FRP-epoxy-concrete interface at different stages of elastic, softening and debonding. A series of post-fatigue direct pull-out tests (DPTs) of NSM FRP-bonded concrete blocks was conducted to provide the local bond degradation laws for the analytical model. The bond region was discretized into finite elements to include the effect of bond degradation to different extents, and a closed-form solution was derived by virtue of appropriate boundary conditions in each fatigue cycle. The model is capable of predicting the FRP strain distribution, local bond stress distribution and relative slip development at a targeted number of fatigue cycles. The reliability of the analytical model was confirmed by experimental data, and its sensitivity to various parameters such as local bond strength, the residual bond strength ratio and Young’s modulus of FRP reinforcement was also assessed in this study.
Oil Content and Fatty Acid Composition of Safflower (Carthamus tinctorius L.) Germplasm
Authors: Kurt Cemal , Altaf Muhammad Tanveer , Liaqat Waqas , Nadeem Muhammad Azhar , Çil Ayşe Nuran , Baloch Faheem Shehzad
Published: January 2025

Safflower (Carthamus tinctorius L.) is a promising oilseed crop with potential applications in the food, pharmaceutical, and industrial sectors. Understanding the oil content and fatty acid composition of safflower germplasm is crucial for breeding programs aimed at enhancing its agronomic and nutritional traits. This study assessed the oil content and fatty acid composition in 87 safflower accessions. Significant variations were observed, with the oil content ranging from 36.88% to 18.44%. Genotype Egypt 1 exhibited the highest oil content. Among fatty acids, China 1 had the highest myristic acid (0.170%) content, while Remzibey had the lowest (0.100%). Palmitic acid ranged from 6.13% to 8.20%, with Egypt 3 and Bangladesh 3 at the extremes. For palmitoleic acid, Jordan 5 had the highest content (0.53%) and Bangladesh 2/Portugal 2 the lowest (0.03%). Linoleic acid varied from 37.7% (China 7) to 77.73% (Iran 1). A correlation analysis indicated strong positive correlations between protein and oil content, as well as between palmitic and myristic acids, and between palmitic and linoleic acids. Conversely, protein exhibited highly negative correlations with myristic, palmitic, and palmitoleic acids. The protein percentage showed a high heritability but a low genetic advance, while palmitic acid, oil percentage, stearic acid, linoleic acid, palmitoleic acid, and oleic acid showed a high heritability and a moderate genetic advance as a percentage of the mean. These findings can aid in developing cultivars with enhanced fatty acids, oil quality, and nutritional value, facilitating sustainable production for a wide range of industrial applications.
Effect of Indigenous Non-Saccharomyces Yeasts on Lipid Compositions of Maraština Wine
Authors: Boban Ana , Vrhovsek Urska , Masuero Domenico , Milanović Vesna , Budić-Leto Irena
Published: January 2025

This study is the first to investigate the impact of indigenous non-Saccharomyces yeasts, including Hypopichia pseudoburtonii, Metschnikowia sinensis/shanxiensis, Metschnikowia chrysoperlae, Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora uvarum, Hanseniaspora guilliermondii, Hanseniaspora pseudoguilliermondii, Pichia kluyveri, and Starmerella apicola on the lipid composition of sterile Maraština grape juice and wines using the UHPLC-MS/MS method. Yeasts were tested in monoculture and sequential fermentations alongside commercial Saccharomyces cerevisiae. Indigenous non-Saccharomyces yeasts showed the potential to improve fermentation performance and enable the development of new wine styles through the biosynthesis of an unsaturated fatty acid pathway, which was identified as the most significant pathway. In monoculture fermentations, L. thermotolerans, H. uvarum, H. guilliermondii, H. pseudoguilliermondii, and P. kluyveri significantly reduced lignoceric acid, potentially influencing wine aroma through the formation of esters and higher alcohols. Hyp. pseudoburtonii, M. chrysoperlae, M. pulcherrima, P. kluyveri, and S. apicola increased the demand for lipids, such as stearic acid, which may help preserve membrane permeability by integrating into the membrane in response to ethanol shock. The most significant impact on free fatty esters was observed in fermentations with H. pseudoguilliermondii. Furthermore, L. thermotolerans in sequential fermentations significantly reduced arachidic, stearic, and palmitic acid. P. kluyveri reduced the content of erucic and linoleic acid.
Novel Reassortants of Oropouche Virus (OROV) Are Causing Maternal–Fetal Infection During Pregnancy, Stillbirth, Congenital Microcephaly and Malformation Syndromes
Authors: Schwartz David A.
Published: January 2025

Oropouche virus (OROV) is an orthobunyavirus endemic in the Brazilian Amazon that has caused numerous outbreaks of febrile disease since its discovery in 1955. During 2024, Oropouche fever spread from the endemic regions of Brazil into non-endemic areas and other Latin American and Caribbean countries, resulting in 13,014 confirmed infections. Similarly to other orthobunyaviruses, OROV can undergo genetic reassortment events with itself as well as other viruses. This occurred during this current outbreak, resulting in novel strains with increased pathogenicity and levels of transmission. For the first time, pregnant women with Oropouche fever have sustained poor perinatal outcomes, including miscarriage, fetal demise, stillbirths and malformation syndromes including microcephaly. In July 2024, PAHO issued an Epidemiological Alert warning of the association of OROV with vertical transmission. OROV has now been identified in the fetal blood, cerebrospinal fluid, placenta and umbilical cords, and fetal somatic organs including the liver, kidneys, brain, spleen, heart, and lungs using nucleic acid and antigen testing. Perinatal autopsy pathology has confirmed central nervous system infection from OROV in infants with congenital infection including microcephaly, ventriculomegaly, agenesis of corpus callosum, and neuronal necrosis. The latest data from Brazil show 3 confirmed cases of OROV vertical transmission; 2 cases of fetal death; 1 case of congenital malformation; and ongoing investigations into the role of OROV in 15 cases of fetal death, 3 cases of congenital malformations and 5 spontaneous miscarriages. This Commentary discusses the mechanisms and significance of development of novel reassortant strains of OROV during the current outbreak and their recent recognition as causing vertical infection and adverse perinatal outcomes among pregnant women with Oropouche fever.
Portraying the Geography of US Airspace with 3-Dimensional GIS-Based Analysis and Visualization
Authors: Dao Thi Hong Diep , Havlick David G.
Published: January 2025

The United States identifies, monitors, and defends a vast network of controlled airspaces surrounding its own and allied territories. These controlled airspaces include civilian aviation classes (A through G), drone flying regions, and special use (military) air classifications. These controlled spaces are invisible to the naked eye and often go unnoticed. Managing and portraying data that function in two and three dimensions poses significant challenges that have hindered prior analyses or geovisualizations of controlled airspaces, but we demonstrate here how many of these can be surmounted to visually represent the spatial extent and patterns of US-controlled airspace. In this paper, we demonstrate how these complex spaces can be graphically represented and highlight how cartographic and geovisual representations of often-overlooked domains contribute to a richer understanding of the reach and character of US airspace. The methods described for this work can be extended to other types of multidimensional objects and may facilitate more robust considerations of how Geographical Information Science (GIS) can be useful in analyzing and depicting airspace and territorial claims in three dimensions.
Ac/Ds-like Transposon Elements Inserted in ZmABCG2a Cause Male Sterility in Maize
Authors: Wang Le , Arshad Saeed , Li Taotao , Wei Mengli , Ren Hong , Wang Wei , Jia Haiyan , Ma Zhengqiang , Yan Yuanxin
Published: January 2025

Using male sterile (MS) lines instead of normal inbred maternal lines in hybrid seed production can increase the yield and quality with lower production costs. Therefore, developing a new MS germplasm is essential for maize hybrid seed production in the future. Here, we reported a male sterility gene ms*-N125, cloned from a newly found MS mutant ms*-N125. This mutant has an underdeveloped tassel that showed impaired glumes and shriveled anthers without pollen grains. The MS locus of ms*-N125 was mapped precisely to a 112-kb-interval on the chromosome 5. This interval contains only three candidate genes, Zm958, Zm959, and Zm960. Sequencing results showed that only candidate Zm960 harbored a 548-bp transposable element (TE) in its 9th exon, and the two other candidate genes were found to have no genetic variations between the mutant and wild type (WT). Thus, Zm960 is the only candidate gene for male sterility of the mutant ms*-N125. In addition, we screened another recessive MS mutant, ms*-P884, which exhibited similar male sterility phenotypes to ms*-N125. Sequencing Zm960 in ms*-P884 showed a 600-bp TE located in its 2nd exon. Zm960 encodes an ATP-binding cassette in the G subfamily of ABC (ABCG) transporters, ZmABCG2a, with both mutants which harbored an Ac/Ds-like transposon in each. To verify the function of ZmABCG2a for male sterility further, we found an ethyl methanesulfonate (EMS) mutant, zmabcg2a*, which displayed male sterility and tassel phenotypes highly similar to ms*-N125 and ms*-P884, confirming that ZmABCG2a must be the gene for male sterility in maize. In addition, the results of lipid metabolome analysis of ms*-N125 young tassels showed that the total lipid content of the mutant was significantly lower than that of the WT, with 15 subclasses of lipids, including PE (phosphatidylethanolamine), PC (phosphatidylcholine), DG (digalactosyldiacylglycerols), and MGDG (monogalactosyldiacylglycerol) which were significantly down-regulated in the ms*-N125 mutant versus its wild type. In summary, we identified alternate mutations of the ZmABCG2a gene, which may be a potential germplasm for hybrid seed production in maize.
Effect of Monosodium Urate Crystal Deposition on Atherosclerotic Carotid Plaques
Authors: Kashiwazaki Daina , Maruyama Kunitaka , Hamada Saori , Yamamoto Shusuke , Hori Emiko , Akioka Naoki , Noguchi Kyo , Kuroda Satoshi
Published: January 2025

Background/Objectives: The accumulation of uric acid in arteriosclerotic plaques has recently attracted attention. Because the interaction between hyperuricemia and atherosclerosis is complex, the details remain obscure. We aimed to elucidate the clinical effect of monosodium urate monohydrate (MSU) deposition on carotid plaques. Methods: This study enrolled 89 patients with carotid plaques. MSU deposits were confirmed using Gomori’s methenamine silver staining of carotid endarterectomy (CEA) specimens. To evaluate the macrophage and microvessel marker counts, we used CD68 and CD31. Plaque composition was investigated in carotid plaques with MSU deposition and inflammation. We also examined the use of dual-energy computed tomography (DECT) and compensated for pathological findings to detect MSU crystal deposition in carotid plaques. Results: Of the 89 patients who underwent CEA, 31 (34.8%) had hyperuricemia. Overall, 22 (24.7%) participants had MSU deposits and 67 (75.3%) did not. MSU deposits, CD31-positive microvessels, and CD68-positive cells were observed in shoulder lesions. The number of CD31-positive microvessels and CD68-positive cells was higher in patients with MSU deposits than in those without MSU deposits. Most plaques expressing MSU were plaques with intraplaque hemorrhage. The consistency in MSU deposit identification between histopathology and DECT was poor (kappa = 0.34). Conclusions: MSU deposition may be related to the inflammation of carotid plaques.
Clinical Applications of Novel Tools to Personalize Follow-Up and Predict Outcomes in Congenital Heart Disease
Authors: Grutter Giorgia , Leonardi Benedetta
Published: January 2025

Recently, the application of novel tools to predict and personalize outcomes for congenital heart disease (CHD) patients has significantly transformed their treatment [...]
The Impact of Land Development Rights Transfer on Urban–Rural Spatial Justice: A Case Study of Chongqing’s Land Quota Trading
Authors: Wei Siyi , Huang Jing , Zhang Zhanlu
Published: January 2025

Spatial justice, as a fundamental value in social systems, plays a key role in achieving social justice and improving human well-being. Drawing on theories of spatial justice, property rights, and new institutional economics, this study explores the comprehensive impact of land development rights (LDR) transfer on urban–rural spatial economic, resources, social, and ecological equity from the perspective of urban–rural spatial justice. Using the Chongqing land quota trading pilot as the core case, we apply synthetic control methods to analyze the causal effects of this policy. The results show that LDR transfer promotes urban–rural spatial resources equity in the short term, particularly through the marketization of land transactions. Over the long term, it significantly enhances urban–rural spatial economic and social equity, evidenced by the narrowing of the income gap, the growth of the primary industry, and improved connectivity between urban and rural areas. However, the improvement in ecological equity through LDR transfer lacks sustainability, suggesting the need for stronger ecological protection measures in future policies. By establishing a comprehensive framework for urban–rural spatial justice and using comparative spatial indicators to measure equity, this study advances our understanding of how LDR transfer can promote urban–rural spatial justice and provides valuable insights for future policy refinement and institutional reforms.
Two Small Peptides from Buthus martensii Hydrolysates Exhibit Antitumor Activity Through Inhibition of TNF-α-Mediated Signal Transduction Pathways
Authors: Zhu Mengshuang , Zhang Shanshan , Tang Jiyang , Hou Hairong , Wang Lizhen , Lin Houwen , Zhang Xuanming , Jin Meng
Published: January 2025

The scorpion Buthus martensii Karsch is edible and has been an essential resource in traditional Chinese medicine for treating numerous diseases. In this study, two small peptides from B. martensii hydrolysates were examined to elucidate their potential against gastric cancer. The small peptides (AK and GK) were identified using the LC-QTOF-MS-based approach. In silico prediction of therapeutic targets, MGC-803 cells and transgenic zebrafish models, and immunoblotting experiments were used to reveal the molecular mechanism of action of the peptides. The peptides AK and GK competitively bound to the receptor to modulate the TNF/TNFR-signaling cascade and alter the tumor microenvironment. EGFR, TP53, MYC, PTEN, and STAT3 were also identified as major functional targets of the peptides. Mechanistically, AK and GK inactivated the TNF-α/EGFR/STAT3-signaling pathway, decreased c-myc protein expression levels, and upregulated p53 and PTEN expression, thereby preventing TNF-α-induced tumor growth. Our findings indicated that AK and GK played a pivotal role in offsetting the inflammatory stimuli that caused gastric cancer cell invasion and highlighted the use of B. martensii resources as functional products with health benefits.
Assessing the Role of Vaccination in the Control of Hand, Foot, and Mouth Disease Transmission
Authors: Alqahtani Zuhur , DarAssi Mahmoud H. , AbuHour Yousef , Almuneef Areej
Published: January 2025

The impact of vaccination on the dynamics of hand, foot, and mouth disease (HFMD) transmission is explored in this paper, considering a fractional-order derivative system of equations. This model provides vaccination strategies and characterizes local and global stability using Lyapunov functions. This work computes the basic reproduction number (R0) to represent the endemic and epidemic scenarios. Additionally, sensitivity analysis was performed to identify the most critical parameters responsible for the disease dissemination. Our results indicate that vaccination plays a crucial role in controlling HFMD, significantly reducing its prevalence. These findings align with existing research, supporting the importance of effective vaccination strategies and public health interventions against HFMD. The fractional-order model captures the memory effect in infectious disease dynamics, providing further insight into modeling HFMD transmission compared to a traditional integer-order model. The results would contribute to effective vaccination strategies and public health interventions against HFMD.
TIBW: Task-Independent Backdoor Watermarking with Fine-Tuning Resilience for Pre-Trained Language Models
Authors: Mo Weichuan , Chen Kongyang , Xiao Yatie
Published: January 2025

Pre-trained language models such as BERT, GPT-3, and T5 have made significant advancements in natural language processing (NLP). However, their widespread adoption raises concerns about intellectual property (IP) protection, as unauthorized use can undermine innovation. Watermarking has emerged as a promising solution for model ownership verification, but its application to NLP models presents unique challenges, particularly in ensuring robustness against fine-tuning and preventing interference with downstream tasks. This paper presents a novel watermarking scheme, TIBW (Task-Independent Backdoor Watermarking), that embeds robust, task-independent backdoor watermarks into pre-trained language models. By implementing a Trigger–Target Word Pair Search Algorithm that selects trigger–target word pairs with maximal semantic dissimilarity, our approach ensures that the watermark remains effective even after extensive fine-tuning. Additionally, we introduce Parameter Relationship Embedding (PRE) to subtly modify the model’s embedding layer, reinforcing the association between trigger and target words without degrading the model performance. We also design a comprehensive watermark verification process that evaluates task behavior consistency, quantified by the Watermark Embedding Success Rate (WESR). Our experiments across five benchmark NLP tasks demonstrate that the proposed watermarking method maintains a near-baseline performance on clean inputs while achieving a high WESR, outperforming existing baselines in both robustness and stealthiness. Furthermore, the watermark persists reliably even after additional fine-tuning, highlighting its resilience against potential watermark removal attempts. This work provides a secure and reliable IP protection mechanism for NLP models, ensuring watermark integrity across diverse applications.
Sodium Butyrate: A Multifaceted Modulator in Colorectal Cancer Therapy
Authors: Mederle Alexandra Laura , Semenescu Alexandra , Drăghici George Andrei , Dehelean Cristina Adriana , Vlăduț Nicolae-Valentin , Nica Dragoş Vasile
Published: January 2025

Background and Objectives: Sodium butyrate (NaB) is a potent modulator of cancer-related gene networks. However, its precise mechanisms of action and effects at elevated doses remain insufficiently explored. This study investigated the impact of NaB at physiologically relevant doses on key cellular metrics (viability, confluence, cell number, morphology, nuclear integrity) and a comprehensive set of apoptosis and proliferation regulators (including underexplored genes) in colorectal cancer (CRC) cells. Materials and Methods: Human HCT-116 cells were treated with increasing NaB concentrations (0–20 mM). Cell viability, confluence, number, morphology, and nuclear integrity were assessed using MTT and imaging assays. RT-PCR was used to determine changes in the expression of critical pro-apoptotic players (BAX, CASP3, PUMA, TP53), anti-apoptotic facilitators (BCL-2, MCL-1), cell division regulators (PCNA, Ki-67, CDKN1), and inflammation genes (NF-κB). Results: This study provides the first exploration of MCL-1 and PCNA modulation by NaB in the context of CRC and HCT-116 cells, offering significant translational insights. All treatments reduced cell viability, confluence, and number in a dose-dependent manner (p < 0.0001). Gene expression revealed dose-related increases in most pro-apoptotic markers (BAX, CASP3, PUMA; p < 0.001), and decreases for the other genes (p < 0.001). BAX emerged as the most responsive gene to NaB, while TP53 showed minimal sensitivity, supporting NaB’s effectiveness in p53-compromised phenotypes. Nuclear condensation and fragmentation at higher NaB doses confirmed apoptotic induction. Conclusions: NaB can modulate critical apoptotic and cell cycle genes, disrupt tumor cell proliferation, and overcome resistance mechanisms associated with anti-apoptotic regulators such as MCL-1. By targeting both short-term and long-term anti-apoptotic defenses, NaB shows promise as a preventive and therapeutic agent in CRC, particularly in high-risk phenotypes with compromised p53 functionality. These findings support its potential for integration into combination therapies or dietary interventions aimed at enhancing colonic butyrate levels.
Entire Encapsulation of Thymopentin by Extended Biphen[3]arene Carboxylate for Improving Plasma Stability
Authors: Ren Keming , Chen Junyi , Li Chunju
Published: January 2025

Peptide-based therapy is appealing in modern medicine owing to its high activity and excellent biocompatibility. Poor stability, leading to unacceptable bioavailability, severely constrains its clinical application. Here, we proposed a general supramolecular approach for improving the plasma resistance of a commercially available peptide agent, thymopentin. The 1H NMR results indicated that the large-sized extended biphen[3]arene carboxylate (ExBP3C) can entirely encapsulate this peptide at its main chain with a binding stoichiometry of 1:1 and Ka value of (1.87 ± 0.15) × 105 M−1, which varied radically from recognizing specific amino acid residues by carboxylatopillar[5]arene (CP5A). Notably, host–guest complexation by ExBP3C could maintain 24.85% of the original thymopentin amount for 60 min in the presence of rat plasma, whereas free thymopentin, or co-dosed with CP5A and cucurbit[7]uril, underwent rapid degradation and became undetectable within just 30 min. In addition, cytotoxicity and hemolysis assays preliminary demonstrated that the employment of ExBP3C as a supplementary material was relatively nontoxic at a cellular level.
Genetic Variants and Lifestyle Factors in Androgenetic Alopecia Patients: A Case–Control Study of Single Nucleotide Polymorphisms and Their Contribution to Baldness Risk
Authors: Ambra Roberto , Mastroeni Simona , Manca Sonia , Mannooranparampil Thomas J. , Virgili Fabio , Marzani Barbara , Pinto Daniela , Fortes Cristina
Published: January 2025

Single nucleotide polymorphisms (SNPs) found to be associated with Androgenetic Alopecia (AGA) to date, are characterized by an apparent reduced penetrance into the phenotype suggesting a role of other factors in the etiology of AGA. Objective: We conducted a study to investigate the role of specific allelic variants in AGA controlling for nutritional and lifestyle factors. Methods: Individual patterns of SNPs present in the baldness susceptibility locus at 20p11 (rs1160312 and rs6113491) or close to the androgen receptor (AR) gene in chromosome X (rs1041668) were investigated in 212 male subjects. Information on socio-demographic characteristics, medical history, smoking, and diet was also collected. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: After controlling for age, diet, BMI, family history of AGA, and smoking, an increased risk of AGA was found for subjects with [A] alleles for both rs1160312 (OR: 2.97; 95% CI: 1.34–6.62) and rs6113491 (OR: 2.99; 95% CI: 1.37–6.52), and for subjects with the TT genotype for rs1041668 (OR: 4.47; 95% CI: 1.60–12.5). Multivariate logistic regression indicates that diet, familiarity, and BMI, but not smoking, remain statistically significant despite the different SNP genotypes. Conclusions: To our knowledge, this is the first indication that the rs1160312, rs6113491, and rs1041668 polymorphisms are independent risk factors for AGA that can be modulated by diet.
Use of Tick Cell Lines in Co-Infection Studies with a Preliminary Study of Co-Culture of Borrelia burgdorferi and Anaplasma phagocytophilum
Authors: Zając Violetta , Bell-Sakyi Lesley , Wójcik-Fatla Angelina
Published: January 2025

Ixodes ricinus is an important vector of infectious human and livestock diseases in Europe. Co-infections of pathogens in ticks and hosts have been reported. Tick cell lines offer a useful model system for study of co-infections. We present a review of the existing literature on co-infections in tick cell lines. Previous studies have demonstrated the usefulness of tick cell lines in studies on co-infection of different pathogens and their interaction with the tick microbiome. We also carried out a preliminary study to investigate the effects of co-culturing Borrelia burgdorferi and Anaplasma phagocytophilum on their growth and interactions with the Ixodes ricinus cell line IRE/CTVM19 over a 13-day period. Replication of both pathogens was quantified by real-time PCR. The presence of A. phagocytophilum appeared to have a slight inhibitory effect on the multiplication of B. burgdorferi, that were added subsequently. In contrast, the prior presence of B. burgdorferi appeared to have a stimulatory effect on A. phagocytophilum after 6 days in culture. We conclude that the IRE/CTVM19 tick cell line is suitable for simultaneous and continuous cultivation of both bacteria and can be applied in future research.
Nanotechnology-Based Drug Delivery Systems, 2nd Edition
Authors: Kuskov Andrey N. , Kukovyakina Ekaterina V.
Published: January 2025

Nanotechnology is a promising and rapidly developing area in the 21st century, which affects various fields of science: physics, chemistry, biology, engineering, microelectronics, and medicine [...]
A Novel Flip-Filtered Orthagonal Frequency Division Multiplexing-Based Visible Light Communication System: Peak-to-Average-Power Ratio Assessment and System Performance Improvement
Authors: Hujijo Hayder S. R. , Ilyas Muhammad
Published: January 2025

Filtered orthogonal frequency division multiplexing (F-OFDM), employed in visible light communication (VLC) systems, has been considered a promising technique for overcoming OFDM’s large out-of-band emissions and thus reducing bandwidth efficiency. However, due to Hermitian symmetry (HS) imposition, a challenge in VLC involves increasing power consumption and doubling inverse fast Fourier transform IFFT/FFT length. This paper introduces the non-Hermitian symmetry (NHS) Flip-F-OFDM technique to enhance bandwidth efficiency, reduce the peak–average-power ratio (PAPR), and lower system complexity. Compared to the traditional HS-based Flip-F-OFDM method, the proposed method achieves around 50% reduced system complexity and prevents the PAPR from increasing. Therefore, the proposed method offers more resource-saving and power efficiency than traditional Flip-F-OFDM. Then, the proposed scheme is assessed with HS-free Flip-OFDM, asymmetrically clipped optical (ACO)-OFDM, and direct-current bias optical (DCO)-OFDM. Concerning bandwidth efficiency, the proposed method shows better spectral efficiency than HS-free Flip-OFDM, ACO-OFDM, and DCO-OFDM.
Theoretical Study of the Pre-Plasma Density Scale Length’s Influence on the Absorption Efficiency in Laser–Solid Interaction at Relativistic Laser Intensities for PW-Class Lasers
Authors: Vladisavlevici Iuliana-Mariana , Ehret Michael , Filippov Evgeny , García-García Enrique , Mendez Cruz , Ruíz Marta Olivar , Varela Óscar , Volpe Luca , Pérez-Hernández Jose Antonio
Published: January 2025

This work studied the pre-plasma that builds up in interactions of focused high-power PW-class lasers with solid targets at the target surface facing the laser beam, and its impact on the global laser absorption efficiency as well as on the spectral cut-off energy of laser-generated proton beams. Our practical heuristic estimates were derived from the example of the VEGA-3 laser at CLPU. Our modeling results for the pre-plasma expansion due to the laser pedestal of VEGA-3 were benchmarked by hydrodynamic simulations, revealing good agreement for the evolution before the arrival of the main Gaussian laser intensity peak. Our detailed numerical two-dimensional Particle-in-Cell simulations showed the impact of different pre-plasma scale lengths on the absorption efficiency of laser energy into electrons, relevant for the seeding of other types of radiation. It was shown that the absorption can increase manyfold when increasing the pre-plasma scale length. This effect can be beneficial for the spectral cut-off energy of accelerated protons, where a trade-off between absorption and electron dynamics yields an optimum pre-plasma scale length. The findings can be applied to other PW-class laser facilities.