bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut Microbiome Modulation in Hepatocellular Carcinoma: Preventive Role in NAFLD/NASH Progression and Potential Applications in Immunotherapy-Based Strategies
Authors: Monti Elisa , Vianello Clara , Leoni Ilaria , Galvani Giuseppe , Lippolis Annalisa , D’Amico Federica , Roggiani Sara , Stefanelli Claudio , Turroni Silvia , Fornari Francesca
Published: January 2025

Hepatocellular carcinoma (HCC) is a heterogeneous tumor associated with several risk factors, with non-alcoholic fatty liver disease (NAFLD) emerging as an important cause of liver tumorigenesis. Due to the obesity epidemics, the occurrence of NAFLD has significantly increased with nearly 30% prevalence worldwide. HCC often arises in the background of chronic liver disease (CLD), such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Gut microbiome (GM) alterations have been linked to NAFLD progression and HCC development, with several investigations reporting a crucial role for the gut–liver axis and microbial metabolites in promoting CLD. Moreover, the GM affects liver homeostasis, energy status, and the immune microenvironment, influencing the response to immunotherapy with interesting therapeutic implications. In this review, we summarize the main changes in the GM and derived metabolites (e.g., short-chain fatty acids and bile acids) occurring in HCC patients and influencing NAFLD progression, emphasizing their potential as early diagnostic biomarkers and prognostic tools. We discuss the weight loss effects of diet-based interventions and healthy lifestyles for the treatment of NAFLD patients, highlighting their impact on the restoration of the intestinal barrier and GM structure. We also describe encouraging preclinical findings on the modulation of GM to improve liver functions in CLD, boost the antitumor immune response (e.g., probiotic supplementations or anti-hypercholesterolemic drug treatment), and ultimately delay NAFLD progression to HCC. The development of safe and effective strategies that target the gut–liver axis holds promise for liver cancer prevention and treatment, especially if personalized options will be considered.
Methyl Canthin-6-one-2-carboxylate Inhibits the Activation of the NLRP3 Inflammasome in Synovial Macrophages by Upregulating Nrf2 Expression
Authors: Chen Yuanyuan , Zhang Zongying , Yao Yuan , Zhou Xiaorong , Ling Yong , Mao Liming , Gu Zhifeng
Published: January 2025

Rheumatoid arthritis (RA) is an autoimmune disorder that leads to severe cartilage deterioration and synovial impairment in the joints. Previous studies have indicated that the aberrant activation of the NLRP3 inflammasome in synovial macrophages plays a significant role in the pathogenesis of RA and has been regarded as a therapeutic target for the disease. In this study, we synthesized a novel canthin-6-one alkaloid, namely methyl canthin-6-one-2-carboxylate (Cant), and assessed its effects on NLRP3 inflammasome activation in macrophages. Our data reveal that exposure to Cant significantly suppressed the transcription and secretion of multiple pro-inflammatory mediators, including IL-1β, IL-6, IL-18, TNF-α, NO, and COX2, in a dose-dependent manner. These alterations were associated with changes in the activation of various signaling pathways, including NF-kB, MAPK, and PI3K-AKT pathways. Notably, pretreatment with Cant significantly reduced LPS/ATP-induced activation of the NLRP3 inflammasome, as evidenced by the decline in the cleaved forms of IL-1β and caspase-1 in cell culture supernatants of BMDMs. Regarding the mechanisms, our data show that Cant could enhance the expression of Nrf2 in macrophages, which play an inhibitory role in ROS production. Collectively, our data demonstrate that Cant might suppress the activation of the NLRP3 inflammasome by upregulating the production of Nrf2, suggesting that Cant could serve as a candidate for the further development of anti-RA drugs.
The Strong Inhibition of Pancreatic Lipase by Selected Indonesian Medicinal Plants as Anti-Obesity Agents
Authors: Rahminiwati Min , Iswantini Dyah , Trivadila  , Sianipar Rut Novalia Rahmawati , Sukma Rani Melati , Indariani Susi , Murni Anggia
Published: January 2025

Obesity is characterized by the accumulation of excessive fat, potentially leading to degenerative diseases. Pancreatic lipase, an enzyme responsible for converting 50–70% of dietary fat into monoglycerides, free fatty acids, and various other smaller molecules, plays a crucial role in fat metabolism. Therefore, this study aimed to review selected Indonesian medicinal plants with the potential to inhibit the activity of the pancreatic lipase enzyme. The results showed that kunci pepet (Kaempferiae angustifolia Rosc.), asam gelugur (Garcinia atroviridis), temulawak (Curcuma xanthorrhiza), jombang (Taraxacum officinale F. H. Wigg), pegagan (Centella asiatica), and pala (Myristica fragrans) had strong inhibitory effects, exceeding 50% for both in vitro and in vivo studies. Therefore, further studies are needed to explore the potential of these medicinal plants as anti-obesity treatments.
A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca Lepidium meyenii
Authors: Turpo-Peqqueña Albert Gabriel , Luna-Prado Sebastian , Valencia-Arce Renato Javier , Del-Carpio-Carrazco Fabio Leonardo , Gómez Badhin
Published: January 2025

Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor’s ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)–polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively. This study explored the inhibitory potential of natural compounds from Lepidium meyenii (Peruvian Maca) on the YAP-1 and PARP-1 protein systems to develop novel therapeutic strategies for GBM. By molecular dynamics simulations, we identified N-(3-Methoxybenzyl)-(9Z,12Z,15Z)- octadecatrienamide (DK5) as the most promising natural inhibitor for PARP-1 and stearic acid (GK4) for YAP-1. Although synthetic inhibitors, such as Olaparib (ODK) for PARP-1 and Verteporfin (VER) for YAP-1, only VER was superior to the naturally occurring molecule and proved a promising alternative. In conclusion, natural compounds from Lepidium meyenii (Peruvian Maca) offer a potentially innovative approach to improve GBM treatment, complementing existing therapies with their inhibitory action on PARP-1 and YAP-1.
Plant miRNAs for Improved Gene Regulation in a Wide Range of Human Cancers
Authors: Zoziuk Maksym , Colizzi Vittorio , Krysenko Pavlo , Mattei Maurizio , Bernardini Roberta , Zanzotto Fabio Massimo , Marini Stefano , Koroliouk Dmitri
Published: January 2025

Determining the relationships between miRNA expression, target genes, and cancer development is critical to cancer research. The possibility of correlating miRNA expression with plant or artificial ones provides prerequisites for cancer treatment. Based on the broad database of human miRNA expression for all cancer types, we grade human miRNAs by their expression level. The identified deficient miRNAs are compared with their target genes for coincidences in their expression directions. The replacement of human miRNAs is proposed to be implemented, using plant miRNAs closest to the human-deficient ones. Such plant substitutes are identified by analyzing the average complementarity of all human under-expressed miRNAs. It was established that the number of downregulated miRNAs is almost 2.5 times greater than that of upregulated miRNAs. There is no significant correlation between the expression of miRNA and genes, implying many other expression regulation mechanisms exist. Working on the organization of experimental verification of the obtained statistical studies, we present significant regularities that provide grounds for considering some plant microRNAs as possible means of compensating for insufficient expression of regulatory microRNAs in humans and animals in a wide range of oncological diseases.
Measuring Complexity in Manufacturing: Integrating Entropic Methods, Programming and Simulation
Authors: Herrera-Vidal Germán , Coronado-Hernández Jairo R. , Derpich-Contreras Ivan , Paredes Breezy P. Martínez , Gatica Gustavo
Published: January 2025

This research addresses complexity in manufacturing systems from an entropic perspective for production improvement. The main objective is to develop and validate a methodology that develops an entropic metric of complexity in an integral way in production environments, through simulation and programming techniques. The methodological proposal is composed of six stages: (i) Case study, (ii) Hypothesis formulation, (iii) Discrete event simulation, (iv) Measurement of entropic complexity by applying Shannon’s information theory, (v) Entropy analysis, and (vi) Statistical analysis by ANOVA. The results confirm that factors such as production sequence and product volume significantly influence the structural complexity of the workstations, with station A being less complex (0.4154 to 0.9913 bits) compared to stations B and C, which reached up to 2.2084 bits. This analysis has shown that optimizing production scheduling can reduce bottlenecks and improve system efficiency. Furthermore, the developed methodology, validated in a case study of the metalworking sector, provides a quantitative framework that combines discrete event simulation and robust statistical analysis, offering an effective tool to anticipate and manage complexity in production. In synthesis, this research presents an innovative methodology to measure static and dynamic complexity in manufacturing systems, with practical application to improve efficiency and competitiveness in the industrial sector.
Quantum Contextual Hypergraphs, Operators, Inequalities, and Applications in Higher Dimensions
Authors: Pavičić Mladen
Published: January 2025

Quantum contextuality plays a significant role in supporting quantum computation and quantum information theory. The key tools for this are the Kochen–Specker and non-Kochen–Specker contextual sets. Traditionally, their representation has been predominantly operator-based, mainly focusing on specific constructs in dimensions ranging from three to eight. However, nearly all of these constructs can be represented as low-dimensional hypergraphs. This study demonstrates how to generate contextual hypergraphs in any dimension using various methods, particularly those that do not scale in complexity with increasing dimensions. Furthermore, we introduce innovative examples of hypergraphs extending to dimension 32. Our methodology reveals the intricate structural properties of hypergraphs, enabling precise quantifications of contextuality. Additionally, we investigate several promising applications of hypergraphs in quantum communication and quantum computation, paving the way for future breakthroughs in the field.
“We Should Not Be Like a Dinosaur”—Using AI Technologies to Provide Formative Feedback to Students
Authors: Burner Tony , Lindvig Yngve , Wærness Jarl Inge
Published: January 2025

Artificial intelligence (AI) technologies have the potential to enhance learning, teaching, and assessment by providing AI-generated feedback to students. This study used five different AI plug-ins and four different knowledge bases for the optimization of feedback in classroom formative assessments. The sample consisted of 26 students and 13 teachers at five secondary schools in Norway. Interviews and unstructured observations were used to collect data. The findings indicate that AI-generated feedback is appreciated by both students and teachers. It provides immediate subject-specific, concrete, and relevant feedback. High-performing students were motivated to further improve their writing. However, some students found the feedback to be too general or complicated, and the teachers who had not conducted whole-term periodic planning struggled with using AI for formative assessment purposes. Finally, both students and teachers contend that the teacher needs to have the last word when AI takes over formative feedback procedures.
Detection of Sealing Surface of Electric Vehicle Electronic Water Pump Housings Based on Lightweight YOLOv8n
Authors: Sun Li , Shen Yi , Li Jie , Jiang Weiyu , Bian Xiang , Yuan Mingxin
Published: January 2025

Due to the characteristics of large size differences and shape variations in the sealing surface of electric vehicle electronic water pump housings, and the shortcomings of traditional YOLO defect detection models such as large volume and low accuracy, a lightweight defect detection algorithm based on YOLOv8n (You Only Look Once version 8n) is proposed for the sealing surface of electric vehicle electronic water pump housings. First, on the basis of introducing the MoblieNetv3 module, the YOLOv8n network structure is redesigned, which not only achieves network lightweighting but also improves the detection accuracy of the model. Then, DualConv (Dual Convolutional) convolution is introduced and the CMPDual (Cross Max Pooling Dual) module is designed to further optimize the detection model, which reduces redundant parameters and computational complexity of the model. Finally, in response to the characteristics of large size differences and shape variations in sealing surface defects, the Inner-WIoU (Inner-Wise-IoU) loss function is used instead of the CIoU (Complete-IoU) loss function in YOLOv8n, which improves the positioning accuracy of the defect area bounding box and further enhances the detection accuracy of the model. The ablation experiment based on the dataset constructed in this paper shows that compared with the YOLOv8n model, the weight of the proposed model is reduced by 61.9%, the computational complexity is reduced by 58.0%, the detection accuracy is improved by 9.4%, and the mAP@0.5 is improved by 6.9%. The comparison of detection results from different models shows that the proposed model has an average improvement of 6.9% in detection accuracy and an average improvement of 8.6% on mAP@0.5, which indicates that the proposed detection model effectively improves defect detection accuracy while ensuring model lightweighting.
Enhancing Thermal Comfort in Historic Buildings by Wind-Driven Ventilation Systems—A Case Study of the Praterateliers in Vienna
Authors: Shayegani Aida , Joklova Viera , Kristianova Katarina , Illes Juraj
Published: January 2025

This study investigates the effectiveness of natural wind-driven ventilation systems in enhancing thermal comfort and energy efficiency within the context of Central European climates, specifically Vienna. By addressing the unique challenges posed by cultural heritage buildings, such as the Praterateliers’ Pavilions, this research highlights the role of sustainable ventilation strategies in mitigating urban overheating, which is exacerbated by climate change. A novel focus is placed on integrating windcatchers with passive systems like earth tubes and solar ventilation to reduce reliance on mechanical cooling and achieve lower carbon emissions while adhering to heritage preservation regulations. Using DesignBuilder simulations and future climate data (2020–2030), this research evaluates the thermal performance of key zones within the Praterateliers under different operational scenarios. The selected analysis period (May to September) captures the peak thermal stress conditions in Vienna, with wind rose diagrams and temperature characteristics providing insights into the ventilation potential during these months. The quantitative results demonstrate that cross-ventilation, combined with windcatchers and subterranean air exchange systems, improved thermal comfort metrics—such as predicted mean vote indices—by up to 30%, particularly in windward and leeward zones. These findings underscore the viability of non-invasive natural ventilation systems in achieving optimal thermal conditions, demonstrating an innovative yet preservation-friendly approach to sustainable architecture. This research not only advances the application of passive cooling strategies in heritage buildings but also provides scalable solutions for addressing urban overheating in modern constructions.
Co-Pyrolysis of Plastic Waste and Lignin: A Pathway for Enhanced Hydrocarbon Recovery
Authors: Kudelytė Vilmantė , Eimontas Justas , Paulauskas Rolandas , Striūgas Nerijus
Published: January 2025

Various plastics and biomass wastes, such as polypropylene (PP), low- or high-density polyethylene (LDPE/HDPE), and lignin, have become some of the most concerning wastes nowadays. In this context, this study aimed to investigate the possibility of applying thermochemical processes for the valorization of these materials. The experiments were carried out using a thermogravimetric analyzer on individual plastic and lignin samples and their mixtures at different mass ratios of 1:1, 1:2, 1:3, and 1:4. The gaseous products evolved during the pyrolysis process were analyzed by combined thermogravimetric and Fourier-transform infrared spectroscopy (TG-FTIR) and chromatography-mass spectrometry (Py-GC/MS) to analyze the functional groups and chemical composition of the obtained pyrolysis products. The results showed that the main functional groups of lignin monitored by TG-FTIR were aromatic and aliphatic hydrocarbons, while all plastics showed the same results for hydrocarbons. The investigation confirmed that mixing these types of plastics with lignin at different mass ratios led to increased recovery of higher-value-added products. Py-GC/MS analysis showed that the greatest results of compound recovery were achieved with lignin and LDPE/HDPE mixtures at 600 °C. At this temperature and with a mass ratio of 1:3, the plastic’s radicals enhanced the depolymerization of lignin, encouraging its wider decomposition to hydrocarbons that can be applied for the production of value-added chemicals and bio-based energy.
Understanding the Role of Irisin in Longevity and Aging: A Narrative Review
Authors: Plácido Ana I. , Azevedo Daniela , Herdeiro Maria Teresa , Morgado Manuel , Roque Fátima
Published: January 2025

Irisin is a protein resulting from a proteolytic cleavage of fibronectin type III domain-containing protein 5 (FND5). The ability of irisin to modulate adipocyte and control glucose metabolism in human metabolic diseases gave rise to the hypothesis that irisin could have a pivotal role in aging-related diseases. Although in animal models, increased levels of irisin have been positively associated with better health outcomes, in humans, its role remains controversial. To provide an overview of the main finding on irisin in older adults, a comprehensive search was performed through the MEDLINE-PubMed, Web of Science, Scopus, and Cochrane databases for studies conducted in older adults (≥60 years) published since 2012. After grouping and analyzing the articles based on diseases associated with older adults, the main conclusion of this narrative review is that the included studies did not yield consistent evidence regarding the association between irisin and health or disease in older adults. Further studies are necessary to clarify the effective role of this protein in promoting health and longevity.
Comparison and Evaluation the Forest Spatial Data in the Context of Modeling Terrain Passability for Operational Purposes
Authors: Pokonieczny Krzysztof , Dawid Wojciech
Published: January 2025

This article addresses a significant aspect of evaluating and comparing spatial forest data from various databases developed and maintained in Poland and globally. The study focused on the application of these data to create terrain passability maps, which are useful in planning military and crisis operations. The research was conducted in a test area near Warsaw, encompassing the Kampinos Forest. In the study, the “forest” layers from the tested databases were compared. Their spatial extents were analyzed, and terrain passability maps were generated in different configurations, which were comprehensively compared with one another. The results indicated that the quality and detail of forest data are not critical for generating passability maps. Only in the case of creating highly detailed maps does the use of precise data prove justified. As the level of detail in the maps decreases, they become increasingly similar, reducing the influence of the forest data on their accuracy and operational applicability. The study enabled the selection of the most accurate data sources on forested areas—those that most faithfully represent the structure of forested regions in Poland.
Methodology for Analyzing Powder-Based Fire Extinguishing and Its Optimization
Authors: Shalel Amir , Katoshevski David , Bar-Kohany Tali
Published: January 2025

Powder-based fire extinguishing methods are widely used to suppress fires of all kinds efficiently. However, these methods have several drawbacks, the most significant being the large powder residue left behind, which can complicate cleanup and damage sensitive equipment. The present paper investigates reacting flows and develops a methodology for analyzing the interaction of powder particles with fire, addressing both homogeneous and heterogeneous fire inhibition mechanisms. To achieve this, a simplified model was developed using the common principles of the general dynamic equation (GDE) and the population balance equation (PBE) coupled with the reacting flow equations. The model examines the interplay between the initial particles’ diameter and their extinguishing flow rate (concentration), also known as minimal extinguishing concentration (MEC), establishing the relation between the two. Notably, the relation exhibits three different zones, each influenced by different governing mechanisms of combustion inhibition, providing critical insights into optimizing powder-based extinguishing systems. A minimal value of the MEC is found where there is no significant change with the MEC in terms of particle diameter, and the chemical homogeneous mechanism is dominating. The methodology also offers a pathway for finding the maximal extinguishing particle diameter (MED) when the heterogeneous extinguishing mechanism acquires its maximal impact.There is no benefit with a larger particle diameter as it would not practically achieve better extinguishment, but would lead to a potential waste of powder and hence damage equipment. A significant advantage of using extinguishing powders with micro-sized/ultrafine particles is demonstrated where the homogeneous inhibition mechanism becomes predominant. The developed methodology and finding suggest that micro-sized powders are more effective in extinguishing fires, as they offer improved dispersion and reactivity, enhancing the overall efficiency of the fire suppression process. However, considering economic factors such as micron-sized-powder production cost and maintenance may require considering a shift of this set point.
Mechanical and Thermal Properties and Moisture Sorption of Puffed Cereals Made from Brown Rice, Barley, Adlay, and Amaranth
Authors: Takahashi Atsuko , Fujii Keiko
Published: January 2025

The moisture sorption, rheological, and glass transition properties of puffed cereals, such as brown rice, barley, adlay, and amaranth, were assessed. The puffed cereals were stored in desiccators until their moisture content reached equilibrium. Moisture sorption isotherms were measured, and monomolecular adsorption moisture content was calculated through Brunauer−Emmett−Teller (BET) analysis. The glass transition temperature (Tg) was determined, and the internal structure was observed using a scanning electron microscope. The rupture force and apparent elastic modulus of puffed cereals decreased with increasing relative humidity (RH). The puffed cereals exhibited ductile fracture ,when the moisture content was >8%. The Tg of puffed cereals with 8% moisture content was approximately 40 °C. It was inferred that puffed cereals demonstrated a crispy texture in the glassy state when stored at <40 °C, but transitioned to a rubbery state at >40 °C, resulting in the loss of crispy texture.
Implications of the Intriguing Constant Inner Mass Surface Density Observed in Dark Matter Halos
Authors: Sánchez Almeida Jorge
Published: January 2025

It has long been known that the observed mass surface density of cored dark matter (DM) halos is approximately constant, independently of the galaxy mass (i.e., ρcrc≃constant, with ρc and rc being the central volume density and the radius of the core, respectively). Here, we review the evidence supporting this empirical fact as well as its theoretical interpretation. It seems to be an emergent law resulting from the concentration–halo mass relation predicted by the current cosmological model, where the DM is made of collisionless cold DM particles (CDM). We argue that the prediction ρcrc≃constant is not specific to this particular model of DM but holds for any other DM model (e.g., self-interacting) or process (e.g., stellar or AGN feedback) that redistributes the DM within halos conserving its CDM mass. In addition, the fact that ρcrc≃constant is shown to allow the estimate of the core DM mass and baryon fraction from stellar photometry alone is particularly useful when the observationally expensive conventional spectroscopic techniques are unfeasible.
Thermosensitive Porcine Myocardial Extracellular Matrix Hydrogel Coupled with Proanthocyanidins for Cardiac Tissue Engineering
Authors: Hidalgo-Vicelis José Luis , Rivera-Contreras Angélica Raquel , Hernández-Téllez Beatriz , Piñón-Zárate Gabriela , Jarquín-Yáñez Katia , Fiordelisio-Coll Tatiana , Saniger-Blesa José Manuel , González-Gómez Gertrudis Hortensia , Falcón-Neri María Alicia , Canales-Martínez María Margarita , Castell-Rodríguez Andrés Eliú
Published: January 2025

Currently, there are no therapies that prevent the negative myocardial remodeling process that occurs after a heart attack. Injectable hydrogels are a treatment option because they may replace the damaged extracellular matrix and, in addition, can be administered minimally invasively. Reactive oxygen species generated by ischemia-reperfusion damage can limit the therapeutic efficacy of injectable hydrogels. In order to overcome this limitation, grape seed proanthocyanidins were incorporated as antioxidant compounds into a thermosensitive myocardial extracellular matrix hydrogel in this study. For the fabrication of the hydrogel, the extracellular matrix obtained by decellularization of porcine myocardium was solubilized through enzymatic digestion, and the proanthocyanidins were incorporated. After exposing this extracellular matrix solution to 37 °C, it self-assembled into a hydrogel with a porous structure. According to the physicochemical and biological evaluation, the coupling of proanthocyanidins in the hydrogel has a positive effect on the antioxidant capacity, gelation kinetics, in vitro degradation, and cardiomyocyte viability, indicating that the hydrogel coupled with this type of antioxidants represents a promising alternative for potential application in post-infarction myocardial regeneration. Furthermore, this study proposes the best concentrations of proanthocyanidins that resulted in the hydrogels for future studies in cardiac tissue engineering.
Liquid Biopsy and Challenge of Assay Heterogeneity for Minimal Residual Disease Assessment in Colon Cancer Treatment
Authors: Crisafulli Giovanni
Published: January 2025

This review provides a comprehensive overview of the evolving role of minimal residual disease (MRD) for patients with Colon Cancer (CC). Currently, the standard of care for patients with non-metastatic CC is adjuvant chemotherapy (ACT) for all patients with stage III and high-risk stage II CC following surgical intervention. Despite a 5–20% improvement in long-term survival outcomes, this approach also results in a significant proportion of patients receiving ACT without any therapeutic benefit and being unnecessarily exposed to the risks of secondary side effects. This underscores an unmet clinical need for more precise stratification to distinguish patients who necessitate ACT from those who can be treated with surgery alone. By employing liquid biopsy, it is possible to discern MRD enabling the categorization of patients as MRD-positive or MRD-negative, potentially revolutionizing the management of ACT. This review aimed to examine the heterogeneity of methodologies currently available for MRD detection, encompassing the state-of-the-art technologies, their respective advantages, limitations, and the technological challenges and multi-omic approaches that can be utilized to enhance assay performance. Furthermore, a discussion was held regarding the clinical trials that employ an MRD assay focusing on the heterogeneity of the assays used. These differences in methodology, target selection, and performance risk producing inconsistent results that may not solely reflect biological/clinical differences but may be the consequence of the preferential use of particular products in studies conducted in different countries. Standardization and harmonization of MRD assays will be crucial to ensure the liquid revolution delivers reliable and clinically actionable outcomes for patients.
Exploring Literacy and Knowledge Gaps and Disparities in Genetics and Oncogenomics Among Cancer Patients and the General Population: A Scoping Review
Authors: Nikitara Katerina , Cardoso Maria Luis , Vicente Astrid Moura , Batalha Silva Rasga Célia Maria , De Angelis Roberta , Chamoun Morel Zeina , De Nicolo Arcangela , Nomikou Maria , Karamanidou Christina , Kakalou Christine
Published: January 2025

Background: Genetic and genomic literacy is pivotal in empowering cancer patients and citizens to navigate the complexities of omics sciences, resolve misconceptions surrounding clinical research and genetic/genomic testing, and make informed decisions about their health. In a fast-evolving scenario where routine testing has become widespread in healthcare, this scoping review sought to pinpoint existing gaps in literacy and understanding among cancer patients and the general public regarding genetics and genomics. Methods: Adhering to the PRISMA framework, the review included 43 studies published between January 2018 and June 2024, which evaluated the understanding of genetics and genomics among cancer patients, caregivers, and citizens. Results: Although the selected studies had significant heterogeneity in populations and evaluation tools, our findings indicate inadequate literacy levels, with citizens displaying lower proficiency than cancer patients and caregivers. This review highlighted consistent knowledge gaps in understanding the genetic and genomic underpinnings of diseases, encompassing misconceptions about mutation types and inheritance patterns, limited awareness of available genetic testing options, and difficulties in interpreting test results. Ethical and privacy concerns and the psychological impact of genetic testing were also common, highlighting the imperative need for effective communication between healthcare providers and patients. Conclusions: Given the dynamic nature of genomic science, the review underscores the need for continuously evolving educational programs tailored to diverse populations. Our findings could guide the development of educational resources addressed explicitly to cancer patients, caregivers, and the lay public.
A Systems Thinking Approach to the Development of HBIM: Part 1—The Problematic Situation
Authors: Lovell Lucy J. , Davies Richard J. , Hunt Dexter V. L.
Published: January 2025

Building Information Modelling (BIM) is an information management and modelling technique frequently employed by the Architecture, Engineering, and Construction (AEC) sector. The application of BIM to Cultural Heritage (CH), otherwise known as Historic BIM (HBIM), will assist with the ongoing sustainable management of CH. However, the application of HBIM is currently limited by a lack of defined end-user requirements and standard methodology in its application. To address this, the authors propose a systems thinking approach, utilising both the Soft Systems Methodology (SSM) and hard Systems Engineering (SE), for the development of HBIM. Subsequently, this paper presents the results of an extensive survey undertaken with the United Kingdom (UK) Heritage Community to identify challenges faced by the CH sector and utilises the SSM to propose the core purpose of HBIM within the CH sector. The responses to the survey suggest that the development of HBIM should prioritise the promotion of structured information management instead of the generation of detailed geometric models, a key theme of much existing research. Future work by the authors (Part 2 of this work) will continue the analysis of the survey results and utilise SE processes to define end-user requirements for HBIM.
Analysis of Genetic Diversity and Relationships of Local Walnut Populations in the Western Caspian Region of the North Caucasus
Authors: Suprun Ivan , Stepanov Ilya , Anatov Dzhalaludin
Published: January 2025

Common walnut (Juglans regia L.) is a valuable nut crop widely distributed within the temperate climate zone. It has several secondary centers of origin associated with refugia formed during the LGM (Last Glacial Maximum) period, one of which was presumably located in the Caucasus region. Currently, walnut populations of the Caucasus are studied fragmentarily, especially in the northeast. Our study is aimed at investigating the genetic diversity, population structure, and possible walnut introduction processes in the Caspian region of the Northeast Caucasus (Dagestan). Genotyping using 11 SSR markers was performed for 158 samples from local walnut populations. Also, to identify the introduction facts, 42 varieties of different geographical origin were added to research. The SSR markers genetic diversity in the analysis of population varied from four to 20 alleles per locus, with an average value of 9.82. Analysis of the genetic structure revealed significant genetic differences between the subpopulations of the Mountain and Flatland Dagestan. Presumably, the structure of the gene pool could have been influenced by terrain factors and ethnocultural characteristics. Subpopulations of Flatland Dagestan have an intermediate position between the western cultivars and the gene pool of Mountain Dagestan, which subpopulations showed significant genetic isolation. In the studied samples set of population selections, the established introduction facts were rare. We have suggested that a significant part of the walnut gene pool from Mountain Dagestan has an autochthonous origin from plants that survived the LGM in the Caucasian refugia. Our results are the basis for further studies of the local gene pool and verification of hypothesis about the presence of an indigenous germplasm preserved in this region from the LGM period.
Exploring the Perspectives of Canadian Clinicians Regarding Digitally Delivered Psychotherapies Utilized for Trauma-Affected Populations
Authors: Yap Sidney , Allen Rashell R. , Bright Katherine S. , Brown Matthew R. G. , Burback Lisa , Hayward Jake , Winkler Olga , Wells Kristopher , Jones Chelsea , Sevigny Phillip R. , McElheran Megan , Zukiwski Keith , Greenshaw Andrew J. , Brémault-Phillips Suzette
Published: January 2025

Many clinical sites shifted towards digital delivery of mental health services during the COVID-19 pandemic. There is still much to learn regarding tailoring digitally delivered interventions for trauma-affected populations. The current study examined the perceptions of Canadian mental health clinicians who provided digitally delivered psychotherapies utilized for trauma-affected populations. Specifically, we explored the shift to digital health use, what changed with this rapid shift, what needs, problems, and solutions arose, and important future considerations associated with delivering trauma-focused and adjunct treatments digitally. Survey data were collected from 12 Canadian mental health clinician participants. Surveys were adapted from the Alberta Quality Matrix of Health and Unified Theory of Acceptance and Use of Technology model. As a follow-up, the participants were invited to participate in either a semi-structured qualitative interview or focus group to further explore their perspectives on digitally delivered trauma-focused and adjunct therapies. Twenty-four clinician participants partook in an interview or focus group. The participants in this study supported the use of digitally delivered psychotherapies utilized for trauma-affected populations, sharing that these interventions appeared to offer similar quality of care to in-person delivery. Further research is required to address clinicians’ concerns with digital delivery (e.g., patient safety) and identify other avenues in which digitally delivered psychotherapies utilized for trauma-affected populations can be engaged with and improved upon.
Molecular Characterization of Cancer Preventive and Therapeutic Potential of Three Antistress Compounds, Triethylene Glycol, Withanone, and Withaferin A
Authors: Zhang Huayue , Kim Hyonchol , Yuan Tian , Zhang Zhenya , Kaul Sunil C. , Wadhwa Renu
Published: January 2025

The molecular link between stress and carcinogenesis and the positive outcomes of stress intervention in cancer therapy have recently been well documented. Cancer stem cells (CSCs) facilitate cancer malignancy, drug resistance, and relapse and, hence, have emerged as a new therapeutic target. Here, we aimed to investigate the effect of three previously described antistress compounds (triethylene glycol, TEG; Withanone, Wi-N, and Withaferin A, Wi-A) on the stemness and differentiation characteristics of cancer cells. Breast carcinoma, glioblastoma, and neuroblastoma cells were treated with a non-toxic concentration of TEG (0.1%), Wi-N (5 µM), and Wi-A (0.1 µM) in 2D and 3D cultures. The results demonstrated that TEG, Wi-N, and Wi-A suppressed the stemness properties, which was linked with their inhibition of epithelial–mesenchymal transition (EMT) signaling. In particular, Wi-N and TEG caused a stronger reduction in the self-renewal capability of CSCs than Wi-A, as evidenced by a tumor spheroid formation assay and analyses of stemness-related genes (ALDH1, CD44, NANOG, CD133, SOX2). Furthermore, TEG and Wi-N caused the differentiation of cancer cells. Each of these was supported by (i) the upregulation of KRT18, KRT19, E-cadherin, and downregulation of vimentin in breast carcinoma; (ii) increased levels of GFAP, MAP2, and PSD-95 in astrocytoma; and (iii) increased NeuN, GAP-43, and NF200 levels in neuroblastoma. Furthermore, a reduction in cancer progression-related proteins (PI3K, N-myc) was recorded in treated cells. Our results suggest that TEG and Wi-N may be recruited to target cancer cell stemness and differentiation therapy.
Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1
Authors: Wang Tingting , Becker Daniel , Twizerimana Augustin Penda , Luedde Tom , Gohlke Holger , Münk Carsten
Published: January 2025

The peptidyl-prolyl isomerase A (PPIA), also known as cyclophilin A (CYPA), is involved in multiple steps of the HIV-1 replication cycle. CYPA regulates the restriction of many host factors by interacting with the CYPA-binding loop on the HIV-1 capsid (CA) surface. TRIM5 (tripartite motif protein 5) in primates is a key species-specific restriction factor defining the HIV-1 pandemic. The incomplete adaptation of HIV-1 to humans is due to the different utilization of CYPA by pandemic and non-pandemic HIV-1. The enzymatic activity of CYPA on the viral core is likely an important reason for regulating the TRIM5 restriction activity. Thus, the HIV-1 capsid and its CYPA interaction may serve as new targets for future anti-AIDS therapeutic agents. This article will describe the species-specificity of the restriction factor TRIM5, understand the role of CYPA in regulating restriction factors in retroviral infection, and discuss important future research issues.
Astragalus mongholicus and Scutellaria baicalensis Extracts Mixture Target Pyroptosis in Ischemic Stroke via the NLRP3 Pathway
Authors: Ko Geon , Kim Jinho , Hong Yongjae , Jeon Yeong-Jae , Baek Hyun-Man , Lee Donghun , Chang Keun-A
Published: January 2025

Ischemic stroke, caused by blocked cerebral blood flow, requires prompt intervention to prevent severe motor and cognitive impairments. Despite extensive drug development efforts, the failure rate of clinical trials remains high, highlighting the need for novel therapeutic approaches. This study investigated the therapeutic potential of a natural herbal extract mixture of Astragalus mongholicus Bunge (AM) and Scutellaria baicalensis Georgi (SB), traditionally used in Eastern Asian herbal medicine (EAHM) for ischemic stroke treatment. Using transient middle cerebral artery occlusion (tMCAO) and photothrombotic (PTB) mouse models, oral administration of the AM-SB mixture was evaluated during both acute and chronic phases. Results showed that AM-SB significantly reduced infarction volume, inflammation (IL-1β, TNF-α), and pyroptosis-related markers (NLRP3, GSDMD, ASC, Caspase-1), while decreasing gliosis and improving cerebral metabolites. Behavioral assessments revealed that early and sustained AM-SB intervention enhanced motor and cognitive functions, as measured by mNSS, Rotarod, Novel Object Recognition, and Passive Avoidance tests. These findings suggest that AM-SB extract is a promising alternative therapy for ischemic stroke management.
Hybridization Design and High-Throughput Screening of Peptides with Immunomodulatory and Antioxidant Activities
Authors: Wang Junyong , Zhang Rijun , Zhao Xuelian , Zhang Jing , Tong Yucui , Abbas Zaheer , Li Zhenzhen , Zhang Haosen , Si Dayong , Wei Xubiao
Published: January 2025

With the increasing recognition of the role of immunomodulation and oxidative stress in various diseases, designing peptides with both immunomodulatory and antioxidant activities has emerged as a promising therapeutic strategy. In this study, a hybridization design was applied as a powerful method to obtain multifunctional peptides. A total of 40 peptides with potential immunomodulatory and antioxidant activities were designed and screened. First, molecular docking was employed to screen peptides with a high binding affinity to MD2, a key receptor protein in the NFκB immune pathway. For the in vitro high-throughput screening, we constructed a reporter gene-based stable cell line, IPEC-J2-Lucia ARE cells, which was subsequently used to screen peptides with antioxidant activity. Furthermore, the biocompatibility, immunomodulatory, and antioxidant activities of these peptides were assessed. Among the candidates, the hybrid peptide VA exhibited the strongest immune-enhancing activity through the activation of the NF-κB pathway and significant antioxidant activity via the Nrf2-ARE pathway. Additionally, VA demonstrated protective effects against H2O2-induced oxidative damage in HepG2 cells. This study not only demonstrates the potential of peptide hybridization, but also develops a screening platform for multifunctional peptides. It provides a new tool for the treatment of autoimmune diseases and oxidative stress-related diseases.
Anti-Inflammatory and Anti-Fibrotic Effects of a Mixture of Polyphenols Extracted from “Navelina” Orange in Human Hepa-RG and LX-2 Cells Mediated by Cannabinoid Receptor 2
Authors: Saponara Ilenia , Aloisio Caruso Emanuela , Cofano Miriam , De Nunzio Valentina , Pinto Giuliano , Centonze Matteo , Notarnicola Maria
Published: January 2025

Navelina oranges (Citrus sinensis) are rich in phytonutrients and bioactive compounds, especially flavonoids like hesperidin. This study investigates the anti-inflammatory and anti-fibrotic properties of hesperidin (HE) and a polyphenol mixture from Navelina oranges (OE) in human hepatocytes (Hepa-RG) and hepatic stellate cells (LX-2), in order to elucidate the underlying molecular mechanisms. In Hepa-RG cells, HE treatment increased expression of cannabinoid receptor 2 (CB2R), which was associated with down-regulation of p38 mitogen-activated protein kinases (p38 MAPK) but had minimal impact on cyclooxygenase-2 (COX-2) and transforming growth factor-β (TGF-β) levels. Conversely, OE treatment not only enhanced CB2R levels and reduced p38 MAPK, but also promoted a significant reduction in both COX-2 and TGF-β levels, suggesting that OE might be more effective in mitigating inflammatory and fibrotic processes than HE. In LX-2 cells, HE treatment caused a notable decrease in both COX-2 and TGF-β levels, reflecting its efficacy in targeting fibrosis-associated inflammation. OE treatment, on the other hand, reduced Nuclear Factor-Kappa B p65 (NF-κB) expression, a critical transcription factor involved in inflammatory responses, though it did not significantly affect COX-2. LX-2 cells induced to fibrosis with TGF-β and treated with HE and OE showed a reduction in the expression levels of several fibrosis markers. In addition, HE and OE showed antioxidant effects by increasing protein levels of Cu, Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and catalase (CAT) and influencing the state of lipid peroxidation. Further research is needed to explore the effects of the treatments in activated hepatic stellate cells and in vivo liver disease models.
Porcine-Derived Chondroitin Sulfate Sodium Alleviates Osteoarthritis in HTB-94 Cells and MIA-Induced SD Rat Models
Authors: Kim Hyelim , Kim Jinhee , Park Seong-Hoo , Kim Jinhak , Gwon Yuri , Lee Minhee , Park Soo-Jeung
Published: January 2025

Osteoarthritis (OA) is a chronic disease characterized by cartilage degradation, leading to bone friction, inflammation, stiffness, pain, and reduced mobility. This study investigates the therapeutic effects of porcine-derived chondroitin sulfate sodium (CS) on OA symptoms at both cellular and animal levels. In vitro study, HTB-94 chondrocytes were treated with inflammatory stimuli and CS (10, 50, 100, and 200 μg/mL) to assess the release of inflammatory mediators and the expression of genes and proteins related to cartilage synthesis and degradation. In vivo study, an MIA-induced OA rat model was used, and CS (62, 124, and 248 mg/kg b.w.) was orally administered for 4 weeks. Key parameters, such as exercise capacity, micro-CT, histological evaluation of joint tissues, serum inflammatory markers, and the expression of mRNA and proteins (inflammatory, cartilage synthesis and degradation, and apoptosis markers), were analyzed. Porcine-derived CS significantly reduced PGE2, NO, and extracellular matrix degradation marker (COMP and CTX-II) levels and increased the expression of cartilage synthesis-related genes and proteins in both HTB-94 cells and the MIA-induced rats. Additionally, CS modulated cartilage degradation pathways and notably inhibited apoptosis in vivo. The effects of porcine CS were comparable to the NSAID ibuprofen, demonstrating its potential as an anti-inflammatory and chondroprotective agent for OA management and dietary supplementation.