bluuebunny/crossref_metadata_2025 huggingface dataset:
The Little-Known Ribbon-Shaped Piriform Cortex: A Key Node in Temporal Lobe Epilepsy—Anatomical Insights and Its Potential for Surgical Treatment
Authors: Ochoa-Lantigua Pamela , Moreira-Mendoza Jhinson , García Ríos Cecilia Alejandra , Rodas Jose A. , Leon-Rojas Jose E.
Published: December 2024

The piriform cortex (PC) plays a pivotal role in the onset and propagation of temporal lobe epilepsy (TLE), making it a potential target for therapeutic interventions. This review delves into the anatomy and epileptogenic connections of the PC, highlighting its significance in seizure initiation and resistance to pharmacological treatments. Despite its importance, the PC remains underexplored in surgical approaches for TLE. We examine the specific neuroanatomy of the PC as well as the limitations of current imaging techniques and surgical interventions, emphasizing the need for improved imaging protocols to safely target the PC, especially in minimally invasive procedures. Furthermore, the PC’s proximity to vital structures, such as the lenticulostriate arteries, presents challenges that must be addressed in future research. By developing multimodal imaging techniques and refining surgical strategies, the PC could emerge as a crucial node in improving seizure freedom outcomes for TLE patients.
Equipping Teachers for Success in Rural Communities: Unveiling the Key Characteristics and Attributes of Thriving Rural Teachers
Authors: Leach Tania , Bradbury Ondine
Published: December 2024

Australian education faces persistent challenges in preparing and retaining teachers within rural contexts. This qualitative study examines the attributes of thriving rural teachers through focus group discussions with 103 rural educational leaders. Utilising a theoretical framework combining attribution theory and ecological systems perspectives, the study synthesised leaders’ perceptions of key dispositions and behaviours contributing to rural teachers’ success. Four interconnected dimensions emerged: being community, classroom, professionally and personally equipped. This study revealed that while individual teacher attributes are crucial, school support and community context significantly influence teacher success. The application of attribute theory further revealed that findings attributed teacher’s success to internal, stable, and controllable factors, suggesting that key traits could be developed through targeted professional development and experience. This study provides nuanced insights into ’rural readiness’, informing education policy decisions and practices, initial teacher education institutions, schools, and communities. The study emphasises the need for a holistic approach to teacher preparation and support that considers both individual and systemic factors.
Integrating Digital Twins and Cyber-Physical Systems for Flexible Energy Management in Manufacturing Facilities: A Conceptual Framework
Authors: Rolofs Gerrit , Wilking Fabian , Goetz Stefan , Wartzack Sandro
Published: December 2024

This paper presents a conceptual framework aimed at integrating Digital Twins and cyber-physical production systems into the energy management of manufacturing facilities. To address the challenges of rising energy costs and environmental impacts, this framework combines digital modeling and customized energy management for direct manufacturing operations. Through a review of the existing literature, essential components such as physical models, a data platform, an energy optimization platform, and various interfaces are identified. Key requirements are defined in terms of functionality, performance, reliability, safety, and additional factors. The proposed framework includes the physical system, data platform, energy management system, and interfaces for both operators and external parties. The goal of this framework is to set the basis for allowing manufacturers to reduce energy consumption and costs during the lifecycle of assets more effectively, thereby improving energy efficiency in smart manufacturing. The study highlights opportunities for further research, such as real-world applications and sophisticated optimization methods. The advancement of Digital Twin technologies holds significant potential for creating more sustainable factories.
Modeling Energy–Environment–Economy Interrelations
Authors: Halkos George E.
Published: December 2024

Energy has become a significant research issue across many disciplines under different methodological approaches, indicating the importance of theoretical and practical implications to structure and implement robust decision-making processes at a global level [...]
Towards Efficient Memory Architectures: Low-Power Noise-Immune RRAM
Authors: Edward Nermine M. , Hamed Sahar M. , Anis Wagdy R. , Elaraby Nahla
Published: December 2024

The performance of Static Nanomaterials Random-Access Memories (SRAMs) is often degraded in the sub-threshold region as it is susceptible to increased access energy and leakage power. However, the low-power operation of SRAM is very much essential for efficient device functioning. Accordingly, designing robust SRAM cells that maintain stability and minimize power consumption is a key challenge. In this regard, with this ongoing work, the authors present novel designs of SRAMs using memristor technology by mitigating the shortcomings discussed above. This paper proposes a novel SRAM architecture of four transistors and five memristors, by integrating memristor technology to achieve drastic improvement in performance at subthreshold regions. Further, it performs an analysis of the metrics of static noise margin and power consumption to comprehensively evaluate the proposed SRAM designs. Simulation using Cadence Virtuoso for 65 nm technology demonstrates that power consumption for a 4T5M cell is about two and a half times lower than for 4T4M and 1.2 times lower than for 4T3M, hence proving that it will be promising for extremely low-power applications.
Investigating the Full Process of Flexibility Provision from Decentralised Energy Systems: From Quantification of Flexibility Potential to the Evaluation of Flexibility Provision Impacts
Authors: Maitanova Nailya , Schlüters Sunke , Hanke Benedikt , von Maydell Karsten
Published: December 2024

Although they are primarily installed for specific applications, decentralised energy systems, storage systems, and controllable loads can provide flexibility. However, this varies over time. This study investigates the fundamentals of flexibility provision, including quantification, aggregation, simulation, and impact on energy systems and the power grid. We extended our methods by integrating adjustments to calculate the flexibility potential of heat pumps (HPs) and heat storage (HS) systems, as well as by incorporating variability and uncertainty. The simulations revealed the relevance of energy systems operation to flexibility, e.g., 2 K deviation in HS temperature increased theoretical coverage by 16 percentage points. The results also proved that aggregating multiple systems could obviously enhance their flexibility potential, e.g., six investigated battery storage (BS) systems could have covered up to 20 percentage points more external flexibility requests than any individual unit. The provision of flexibility by decentralised energy systems can lead to energy surpluses or deficits. Such imbalances could have been fully balanced in a system- and grid-oriented manner in 44% of BS simulations and in 32% of HP-HS ones. Overall, the findings highlight the importance of the system- and grid-oriented operation of decentralised energy systems, alongside local optimisation, for a future energy infrastructure.
Conservation Implications of Population Structure and Dynamics in Medicinal Arbor Albizia odoratissima on Hainan Island, China
Authors: Yang Yong , Ke Xinran , Ji Qiaomiao , Lang Tao , Lai Zongrui , Guan Yali
Published: December 2024

Albizia odoratissima Benth is a perennial evergreen tree valued for its medicinal properties and is indigenous to the mountainous regions of southwestern China. The population status of A. odoratissima has been sparsely studied. This study systematically evaluated the population structure and dynamics of A. odoratissima in the central mountainous region of Hainan Island, China, with the objective of informing the development of sustainable conservation strategies for the ecological restoration of its natural populations. Using the methodologies of population ecology, including the development of static life tables, population survival curves, population dynamics analysis, and time-series predictions, the results indicated that the populations of A. odoratissima on Hainan Island were geographically isolated into three groups. The age class distribution revealed that young, middle-aged, and mature individuals accounted for 5.73%, 74.94%, and 19.33%, respectively, suggesting a declining trend in the population. Moreover, the A. odoratissima population on Hainan Island was highly sensitive to anthropogenic disturbances, with significant increases in mortality rates observed at both the juvenile and mature stages. These results were likely due to the intraspecific and interspecific competitions, as well as external factors including human-induced disturbances, climate variability, and extreme weather events, which might potentially lead to the species’ future endangerment. Based on the current status of the A. odoratissima population, we develop adaptive management and forbid anthropogenic deforestation, conserving in situ and expanding populations, protecting ex situ germplasm resources, and replanting artificially, in order to manage the long-term conservation and management of A. odoratissima.
Microbial and Sensory Quality Changes in Broiler Chicken Breast Meat During Refrigerated Storage
Authors: Augustyńska-Prejsnar Anna , Kačániová Miroslava , Hanus Paweł , Sokołowicz Zofia , Słowiński Mirosław
Published: December 2024

The aim of the study was to assess the bacterial flora of broiler chicken breast meat using the MALDI method, as well as its sensory evaluation while stored refrigerated at a stable temperature (0.5 °C+/−0.5 °C). Bacterial identification based on peptidic spectra obtained by matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF MS) mass spectrometry is a rapid, inexpensive, and accurate method for identifying isolates that belong to certain bacterial phyla. The microbiological and sensory quality was assessed on the 1st and 3rd, 5th, 7th, 8th, 9th, 10th, 11th, and 12th day of refrigerated storage. The study identified psychrophilic bacteria to be the dominant microflora during the entire period of refrigerated storage. The species profile of the bacteria, however, varied in the subsequent days of storage. From the 8th day of storage, the profile was dominated by bacteria of the genus Pseudomonas. The proportionate content of Pseudomonas bacteria ranged from 89% on day 8 to 95% on day 11th of storage. The majority of the unfavourable microflora (Aeromonas species, Alcaligenes spp., Klebsiella spp., and Yersinia spp.) were observed on the 11th day of storage, which indicates that meat spoilage processes had commenced. The quality of breast meat from broiler chickens stored at 0.5 °C+/−0.5 °C was sensorially acceptable up to the 8th day of storage.
Novel Ultrasonic Pretreatment for Improving Drying Performance and Physicochemical Properties of Licorice Slices During Radio Frequency Vacuum Drying
Authors: Li Jun , Wan Fangxin , Huang Xiaopeng , Yang Xiaoping , Zang Zepeng , Xu Yanrui , Wu Bowen , Zhang Kaikai , Ma Guojun
Published: December 2024

To enhance the physicochemical quality, drying efficiency, and nutrient retention of dried Licorice products, this study investigated the effects of ultrasonic pretreatment on the radio frequency vacuum (RFV) drying characteristics, microstructure, and retention of natural active substances in Licorice slices. The ultrasonic time, power, and frequency were considered as experimental factors. The results showed that, compared with conventional RFV drying, ultrasonic pretreatment reduced the drying time of Licorice slices by 20–60 min. The Weibull model accurately described the moisture ratio changes under different pretreatment conditions (R2 > 0.9984, χ2 < 2.381 × 10−5). The optimal retention of polysaccharides, total phenols, total flavonoids, and antioxidants was achieved under pretreatment conditions of 30 min of ultrasonic time, 180 W of ultrasonic power, and 40 kHz of ultrasonic frequency. Furthermore, ultrasonic pretreatment preserved the internal cellular structure of Licorice slices, maintaining intact tissue cells and well-defined microchannels. However, a slight reduction in sample color was observed following ultrasound application. In conclusion, ultrasonic pretreatment significantly improved the RFV drying process for Licorice slices by enhancing drying efficiency, preserving active ingredients, and optimizing the physicochemical quality of the dried product. This study provides novel insights and methods for optimizing the drying process of Licorice, offering a foundation for further research and industrial applications.
Immunoregulatory Effects of Codonopsis pilosula Polysaccharide Modified Selenium Nanoparticles on H22 Tumor-Bearing Mice
Authors: Long Yan , Ji Hongfei , Yang Jiajing , Ji Haiyu , Dai Keyao , Ding Wenjie , Zheng Guoqiang , Yu Juan
Published: December 2024

Codonopsis pilosula polysaccharide (CPP) and rare element selenium (Se) have been proved to exert various biological activities, and our previous study demonstrated that selenium nanoparticles modified with CPP (CPP-SeNPs) possessed significantly enhanced tumor cytotoxicity in vitro. This study aimed to investigated the inhibitory effects of CPP-SeNPs complex on H22 solid tumors via immune enhancement. In this study, the H22 tumor-bearing mice model was constructed, and the potential mechanisms of CPP-SeNPs antitumor effects were further explored by evaluating cytokines expression levels, immune cells activities and tumor cells apoptotic indicators in each group. The results demonstrated that CPP-SeNPs effectively exerted dose-dependent protective effects on the immune organs of tumor-bearing mice in vivo, leading to increase in peripheral white blood cell counts and inhibition of solid tumor growth with inhibitory rate of 47.18% in high-dose group (1.5 mg/kg). Furthermore, CPP-SeNPs treatment significantly elevated the levels of TNF-α, IFN-γ, and IL-2 in mice sera, enhanced NK cell cytotoxicity, augmented macrophage phagocytosis capacity, as well as increased both the amounts and proliferation activity of lymphocyte subsets. CPP-SeNPs improved the immune system’s ability to clear tumor cells by up-regulating Bax expression while down-regulating Bcl-2 expression within solid tumors, indicating the potential activation of mitochondrial apoptosis pathway. Therefore, CPP-SeNPs administration can effectively inhibit tumor growth by enhancing immune response in tumor-bearing mice, which might be relevant to the regulation of gut microbiota short-chain fatty acids metabolisms. These findings could provide theoretical support and data foundation for further development of CPP-SeNPs as functional food and drug adjuvants.
Triboelectric Separation for Protein Enrichment of Wheat Flour Compared with Gluten–Starch Mixtures as a Benchmark
Authors: Ozcelik Mine , Foerst Petra
Published: December 2024

Triboelectric separation, a solvent-free method, was investigated as a tool for protein enrichment in wheat flour. Gluten–starch model mixtures, flour, and reground flour fractions were evaluated for their separation characteristics (selectivity and efficiency). Mass yield, protein content, particle size distribution, and SEM analysis were used to assess performance. Selectivity and efficiency increased with gluten concentration, peaking at 63% for the 50% gluten mixture, but declined at higher concentrations. The 15% gluten benchmark demonstrated effective protein separation, with protein enrichment occurring in the ground electrode fraction and a corresponding depletion in the positive electrode fraction. In contrast, flour and reground flour fractions exhibited reduced separation efficiency, showing protein depletion in both electrode fractions due to agglomeration. The benchmark achieved the highest separation efficiency (47%), followed by reground flour (41%) and flour (7%). Finer particles in reground flour enhanced chargeability and GE deposition, while larger agglomerates in flour reduced efficiency, leading to material accumulation in the cups. Pre-milling helped detach protein and starch to some extent but also triggered re-agglomeration. Larger particles were influenced more by gravitational forces. These findings highlight the complexity of wheat flour fractionation and the need to optimize particle size and charge distribution to improve protein enrichment through triboelectric separation.
Preparation of Chitosan Oleogel from Capillary Suspension and Its Application in Pork Meatballs
Authors: Wang Shishuai , Fan Zhongqin , Huang Xinya , Gao Yue , Sui Hongwei , Yang Jun , Li Bin
Published: December 2024

In the oil dispersion of chitosan, the formation of a capillary bridge was triggered by adding a small amount of water to obtain an oleogel. With this method, the types of liquid oil and the ratio of oil/chitosan/water were explored to achieve an optimal oleogel. MCT performed best, followed by soybean oil, which was chosen for its edibility and cost. Increasing chitosan from 15% to 45% reduced oil loss from 46% to 13%, and raising the water/chitosan ratio from 0 to 0.8 lowered oil loss from 37% to 13%. After normalization, the optimal soybean oil, chitosan, and water ratio was 1:0.45:0.36, yielding a solid-like appearance, minimal oil loss of 13%, and maximum gel strength and viscosity. To assess the potential application of the optimized oleogel, it was incorporated into pork meatballs as a replacement for pork fat. Textural and cooking experiments revealed that as the oleogel content increased, the hardness of the pork meatballs increased, while the cooking loss decreased. It suggested that the chitosan oleogel could enhance the quality of pork meatballs while also contributing to a healthier product by reducing saturated fat content.
Gukurahundi as a Cultural Event: Cultural Politics and the Culture of Violence in Matabeleland
Authors: Sibanda Nkululeko
Published: December 2024

The desire of Gukurahundi survivors for cultural platforms that enable them to discuss, mourn, and commemorate their loved ones is now very loud in Zimbabwe’s Matabeleland and Midlands provinces. While community-based organisations have provided platforms for Gukurahundi survivors, the children of survivors, and academics to interface and interact, the government’s gatekeeping processes remain a challenge for the community-wide memorialisation and documentation of the genocide. In this conceptual paper, I frame Gukurahundi as a meteorological event within a general Zimbabwean cultural context, foregrounding the desecration of the Ndebele people’s cultural practices, rituals, and ceremonies. Drawing from the documented legacies of this cultural violence within Matabeleland and south-western parts of the Midlands, through videos and the literature, I argue that this cultural violence resulted in the silencing of the remembrance of Gukurahundi, which remains critical to the resolution of the stand-off between the ZANU-PF government and the communities. In this paper, I further argue that this ecological symbolism provided a justification and legitimated direct brutal violence on presumed ZAPU and ex-ZPRA veterans who were largely Ndebele-speaking or of ethnic descent. Finally, I argue that it is not that the absence of alternative narratives but the sociopolitical and cultural environment that constrains these from being available and implemented.
Genetic Composition of Polish Hucul Mare Families: mtDNA Diversity
Authors: Błaszczak Aleksandra , Stefaniuk-Szmukier Monika , Długosz Bogusława , Musiał Adrianna Dominika , Olczak Katarzyna , Ropka-Molik Katarzyna
Published: December 2024

Backround: The Hucul horse breed formed in the region of the Eastern Carpathians, likely through the natural crossbreeding of oriental horses. After World War II, their population significantly decreased, leading to the breeding being based on only 14 female lines, whose founders often had unknown origins. To preserve the breed’s unique characteristics, it is now part of a Genetic Resources Conservation Program, which prioritizes the maintenance of genetic diversity. This study aims to clarify the maternal relatedness of founder mares and assess genetic diversity using mitochondrial DNA (mtDNA). Methods: The hyper-variable region of the mitochondrial genome was analyzed in 57 horses. Pedigree records were used to trace genealogical lines, and molecular analysis focused on identifying maternal relationships between founder mares. Results: The analysis revealed close maternal kinships between the lines of Jagoda and Bajkałka, as well as Sekunda and Sroczka. In the Hucul population, seventeen mitochondrial haplotypes were identified, with three that did not match any established lines. The findings reveal discrepancies between pedigree records and mitochondrial DNA data, suggesting potential inaccuracies in the Hucul horse studbook. Conclusions: The findings highlight the importance of combining pedigree and molecular data to refine strategies to preserving genetic diversity, minimizing inbreeding, and improving the management the Genetic Resources Conservation Program.
Optimizing Nurse Rostering: A Case Study Using Integer Programming to Enhance Operational Efficiency and Care Quality
Authors: Mystakidis Aristeidis , Koukaras Christos , Koukaras Paraskevas , Kaparis Konstantinos , Stavrinides Stavros G. , Tjortjis Christos
Published: December 2024

Background/Objectives: This study addresses the complex challenge of Nurse Rostering (NR) in oncology departments, a critical component of healthcare management affecting operational efficiency and patient care quality. Given the intricate dynamics of healthcare settings, particularly in oncology clinics, where patient needs are acute and unpredictable, optimizing nurse schedules is paramount for enhancing care delivery and staff satisfaction. Methods: Employing advanced Integer Programming (IP) techniques, this research develops a comprehensive model to optimise NR. The methodology integrates a variety of constraints, including legal work hours, staff qualifications, and personal preferences, to generate equitable and efficient schedules. Through a case study approach, the model’s implementation is explored within a clinical setting, demonstrating its practical application and adaptability to real-world challenges. Results: The implementation of the IP model in a clinical setting revealed significant improvements in scheduling efficiency and staff satisfaction. The model successfully balanced workload distribution among nurses, accommodated individual preferences to a high degree, and ensured compliance with work-hour regulations, leading to optimised shift schedules that support both staff well-being and patient care standards. Conclusions: The findings underscore the effectiveness of IP in addressing the complexities of NR in oncology clinics. By facilitating a strategic allocation of nursing resources, the proposed model contributes to operational excellence in healthcare settings, underscoring the potential of Operations Research in enhancing healthcare delivery and management practices.
Role of Multimodal Imaging in Clinical Practice for the Diagnosis of Infective Endocarditis: A Case Series
Authors: Tordi Sara , Gonnelli Giacomo , Benvenuto Maria Carolina , Rosignoli Daniele , Malincarne Lisa , Francisci Daniela
Published: December 2024

Background: The 2023 European Society of Cardiology (ESC) guidelines for the management of infective endocarditis (IE) highlighted the essential role of multimodal imaging in the diagnostic algorithm of IE and its complications. Methods: We hereby report a case series of IE in which the diagnosis was confirmed or excluded by the use of multimodal imaging during the period between January 2024 and July 2024 at the Infectious Diseases Clinic, Perugia Hospital, Italy. Results: Six patients were retrospectively included. Prosthetic valve endocarditis (PVE) was suspected in four patients and native valve endocarditis (NVE) in two cases. In patients with prosthetic valves, 18F FDG-PET/CT was performed, except in one case (P1) where cardiac CTA was performed for suspicion of perigraft aneurysm. Patients underwent transesophageal echocardiography (TOE), which was diagnostic in two cases and inconclusive in the remaining cases. In case of inconclusive TOE, the use of multimodal imaging added a major criterion and allowed us to consider (from ‘rejected’ to ‘possible’) or confirm (from ‘possible’ to ‘definite’) the diagnosis of EI based on the 2023 Duke–ESC Criteria. In one case (P6), it was possible to exclude the diagnosis. For patients with diagnostic TOE, 18F FDG-PET/CT allowed for the enhancement of diagnostic accuracy, identifying the site of valve involvement and the extension of the infection to the device (cases P3 and P5, respectively). Conclusions: In clinical practice, the use of cardiac CTA and/or 18F FDG-PET/CT based on the latest ESC guidelines demonstrated a significant impact on the diagnosis and therapeutic management of IE.
Being Cynical Is Bad for Your Wellbeing: A Structural Equation Model of the Relationship Between Cynicism and Mental Health in First Responders in South Africa
Authors: Padmanabhanunni Anita , Pretorius Tyrone B.
Published: December 2024

Cynicism has been associated with adverse mental and physical health outcomes. This study investigated the role of cynicism in relation to indices of mental health among South African first responders. Research has highlighted that first responders are at increased risk of adverse mental health outcomes owing to the nature of their work. The sample consisted of 429 participants who completed a brief demographic questionnaire and several research instruments: Turner Cynicism Scale, Chalder Fatigue Scale, Patient Health Questionnaire-9, and Generalized Anxiety Disorder Scale-7. Structural equation modeling was used to explore the relationship between cynicism and mental health indicators. It included a measurement model, which identified four latent variables—cynicism, fatigue, depression, and anxiety—and their respective indicators, and a structural model, which defined the relationships among these latent variables. Path analysis was used to explore the potential mediating role of fatigue in the relationship between cynicism and indices of mental health. The results demonstrated significant associations between cynicism and anxiety, depression, and fatigue. Fatigue also mediated the relationship between cynicism and indices of mental health. The results underscore the importance of recognizing and addressing cynicism as a critical factor in the mental health of individuals working in high-stress occupations.
Natural Cubic Spline Approximation of Risk-Neutral Density
Authors: Zhou Shuang , Jiang Liyuan , Li Keren , Wang Fangfang , Yang Jie
Published: December 2024

The risk-neutral density is a fundamental concept in pricing financial derivatives, risk management, and assessing financial markets’ perceptions over significant political or economic events. In this paper, we propose a new nonparametric method for estimating the risk-neutral density using natural cubic splines (NCS). The estimated density is twice continuously differentiable with linear tails at both ends. Our method targets the logarithm of the underlying asset price, releasing the restriction to the positive domain. We theoretically prove the consistency of our NCS method. We conduct a comprehensive empirical study comparing the proposed NCS method with a piecewise constant method, a uniform quartic B-spline method, and a cubic spline method from the literature using 20 years of S&P 500 index option data. The empirical results show that our NCS method is more robust than the piecewise constant method, which can only produce a discontinuous density, especially for options with maturities longer than six months. Moreover, our NCS method outperforms other historical continuous methods in terms of optimization feasibility and option price estimation.
Comprehensive Evaluation of Advanced Imputation Methods for Proteomic Data Acquired via the Label-Free Approach
Authors: Wryk Grzegorz , Gawor Andrzej , Bulska Ewa
Published: December 2024

Mass-spectrometry-based proteomics frequently utilizes label-free quantification strategies due to their cost-effectiveness, methodological simplicity, and capability to identify large numbers of proteins within a single analytical run. Despite these advantages, the prevalence of missing values (MV), which can impact up to 50% of the data matrix, poses a significant challenge by reducing the accuracy, reproducibility, and interpretability of the results. Consequently, effective handling of missing values is crucial for reliable quantitative analysis in proteomic studies. This study systematically evaluated the performance of selected imputation methods for addressing missing values in proteomic dataset. Two protein identification algorithms, FragPipe and MaxQuant, were employed to generate datasets, enabling an assessment of their influence on im-putation efficacy. Ten imputation methods, representing three methodological categories—single-value (LOD, ND, SampMin), local-similarity (kNN, LLS, RF), and global-similarity approaches (LSA, BPCA, PPCA, SVD)—were analyzed. The study also investigated the impact of data logarithmization on imputation performance. The evaluation process was conducted in two stages. First, performance metrics including normalized root mean square error (NRMSE) and the area under the receiver operating characteristic (ROC) curve (AUC) were applied to datasets with artificially introduced missing values. The datasets were designed to mimic varying MV rates (10%, 25%, 50%) and proportions of values missing not at random (MNAR) (0%, 20%, 40%, 80%, 100%). This step enabled the assessment of data characteristics on the relative effectiveness of the imputation methods. Second, the imputation strategies were applied to real proteomic datasets containing natural missing values, focusing on the true-positive (TP) classification of proteins to evaluate their practical utility. The findings highlight that local-similarity-based methods, particularly random forest (RF) and local least-squares (LLS), consistently exhibit robust performance across varying MV scenarios. Furthermore, data logarithmization significantly enhances the effectiveness of global-similarity methods, suggesting it as a beneficial preprocessing step prior to imputation. The study underscores the importance of tailoring imputation strategies to the specific characteristics of the data to maximize the reliability of label-free quantitative proteomics. Interestingly, while the choice of protein identification algorithm (FragPipe vs. MaxQuant) had minimal influence on the overall imputation error, differences in the number of proteins classified as true positives revealed more nuanced effects, emphasizing the interplay between imputation strategies and downstream analysis outcomes. These findings provide a comprehensive framework for improving the accuracy and reproducibility of proteomic analyses through an informed selection of imputation approaches.
Mechanisms and Therapeutic Potential of Multiple Forms of Cell Death in Myocardial Ischemia–Reperfusion Injury
Authors: Tsurusaki Shinya , Kizana Eddy
Published: December 2024

Programmed cell death, especially programmed necrosis such as necroptosis, ferroptosis, and pyroptosis, has attracted significant attention recently. Traditionally, necrosis was thought to occur accidentally without signaling pathways, but recent discoveries have revealed that molecular pathways regulate certain forms of necrosis, similar to apoptosis. Accumulating evidence indicates that programmed necrosis is involved in the development of various diseases, including myocardial ischemia–reperfusion injury (MIRI). MIRI occurs when blood flow and oxygen return to an ischemic area, causing excessive production of reactive oxygen species. While this reperfusion is critical for treating myocardial infarction, it inevitably causes cellular damage via oxidative stress. Furthermore, this cellular damage triggers multiple forms of cardiomyocyte death, which is the primary cause of inflammation, cardiac tissue remodeling, and ensuing heart failure. Therefore, understanding the molecular mechanisms of various forms of cell death in MIRI is crucial for therapeutic target discovery. Developing therapeutic strategies to inhibit multiple cell death pathways simultaneously could provide effective protection against MIRI. In this paper, we review the fundamental molecular pathways and MIRI-specific mechanisms of apoptosis, necroptosis, ferroptosis, and pyroptosis. Additionally, we suggest that the simultaneous suppression of multiple cell death pathways could be an effective therapy and identify potential therapeutic targets for implementing this strategy.
The Influence of Genetic Polymorphisms in Cytochrome P450 (CYP1A1 and 2D6) Gene on the Susceptibility to Philadelphia Negative Chronic Myeloid Leukemia in Sudanese Patients
Authors: Elderdery Abozer Y. , Idris Hadeil M. E. , Alruwaili Saud Nahar L. , Tebien Entesar M. , Alsrhani Abdullah , Alenazy Fawaz O. , Alzahrani Badr , Manni Emad , Elkhalifa Ahmed M. E. , Mills Jeremy
Published: December 2024

The most frequent type of leukemia in Africa is chronic myeloid leukemia (CML). The genetic background of the rarer Philadelphia chromosome (Ph) Ph-ve (BCR-ABL-ve) subform of CML is largely unknown in African patients. Therefore, in this study, we aimed to investigate the role of CYP1A1 and 2D6 SNPs in the pathogenesis of Ph-ve CML in the Sudanese population. A total of 126 patients were selected for analysis. DNA was isolated from Ph-ve CML patients and a control group for PCR-RFLP analysis of SNPs CYP1A1*2C and CYP2D6*4. The CYP1A1 gene significantly expressed the GG variant genotype (p < 0.05) in 23.1% of the Ph-ve CML patients and 8% of the control group. In contrast, the CYP2D6 GA genotype was strongly associated with a reduced risk of developing Ph-ve CML (p < 0.005) with a frequency of 50% in Ph-ve patients and 93% in the control group. CYP1A1 GG polymorphism was prevalent among patients with Ph-ve CML, suggesting its role in disease development. CYP2D6 GA (IM) polymorphism was uncommon among patients, compared with the control group, possibly indicating a protective role of the polymorphisms from Ph-ve CML. This study demonstrates an association between key metabolic SNPs and Ph-ve CML and highlights the role that altered xenobiotic metabolism may play in the development of several human leukemias.
Intradomain Allosteric Regulation of Soluble Epoxide Hydrolase by Its Substrates
Authors: Matsumura Shin , Shida Ayano , Tsuchii Moeno , Wada Mika , Charneau Jimmy , Tsuji Motonori , Hasumi Keiji , Suzuki Eriko
Published: December 2024

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid phosphomonesters, including the signaling molecules of lysophosphatidic acid (LPA). Here, we report that the C-EH and N-phos are reciprocally regulated by their respective substrates. Full-length sEH (sEH-FL) showed positive cooperativity toward the substrate for each domain. Similar cooperativity was found when truncated enzymes having only C- and N-terminal domains, sEH-C and sEH-N, respectively, were used, suggesting an intra-domain nature of the cooperativity. In addition, the N-phos substrate LPA inhibited C-EH activity in sEH-FL and sEH-C equally. Similarly, the C-EH substrate EET inhibited N-phos activity. Structural and kinetic data suggest the presence of allosteric sites in each domain of the sEH enzyme, which share the binding of LPA and EET. Thus, each of the two sEH activities is regulated by a substrate of its own and by that of the other domain. This mechanism may explain why sEH has evolved to have two different enzyme activities, which possibly allows sEH to balance the metabolism of bioactive lipids.
Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab–Paclitaxel Therapy Outcomes in Advanced Gastric Cancer
Authors: Piccinno Emanuele , Schirizzi Annalisa , Scalavino Viviana , De Leonardis Giampiero , Donghia Rossella , Fantasia Alessia , Ricci Angela Dalia , Lotesoriere Claudio , Giannelli Gianluigi , Serino Grazia , D’Alessandro Rosalba
Published: December 2024

Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37, p = 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.
Systematic Review of IL-1, IL-4, IL-6, IL-10, IL-15, and IL-18 Gene Polymorphisms and Meta-Analysis of IL-6 Variant and Its Association with Overweight and Obesity Risk in Men
Authors: Bojarczuk Aleksandra , Garbacz Aleksandra , Żekanowski Cezary , Borzemska Beata , Cięszczyk Paweł , Maculewicz Ewelina
Published: December 2024

Obesity is a complex health risk influenced by genetic, environmental, and lifestyle factors. This review systematically assessed the association between interleukin gene polymorphisms (rs16944, rs17561, rs1143623, rs1143633, rs1143634, rs1800587, rs2234677, and rs4848306), IL-4 (rs180275, rs1805010, IL-6 rs13306435, rs1800795, rs1800796, rs1800797, rs2228145, rs2228145, rs2229238, and rs4845623), IL-10 (rs1518110, rs1518111, rs1800871, rs1800872, rs1800896, rs1878672, rs2834167, rs3024491, rs3024496, rs3024498, and rs3024505), IL-15 (rs3136617, rs3136618, and rs2296135), and IL-18 (rs187238, rs1946518, rs2272127, rs2293225, and rs7559479) and the risk of overweight and obesity in adults, focusing on IL-6 rs1800795 through a meta-analysis. The focus on IL-6 in this review arises from its pleiotropic nature and unclear effect on obesity risk. The review included studies published from 1998 to 2023, sourced from Science Direct, EBSCOhost, Web of Science, and Google Scholar. Bias was assessed with the Cochrane Collaboration tool, and funnel plots were used for publication bias. Results were synthesized into pooled odds ratios (ORs) and confidence intervals (CIs). Thirty studies comprising approximately 29,998 participants were included. The selection criteria required that the articles include participants who were overweight or obese, and this condition needed to be linked to IL polymorphisms. In a meta-analysis, in the dominant model, the pooled OR was 1.26 (95% CI 1.08 to 1.47), indicating those with the GC/CC genotype for IL-6 rs1800795 are 1.26 times more likely to be overweight/obese than GG genotype carriers. For the recessive model, the OR was 1.25 (95% CI 1.04 to 1.51). The overdominant model showed no significant association (OR 1.08, 95% CI 0.94 to 1.25). Interleukin gene variation, particularly the IL-6 rs1800795 variant, is modestly associated with obesity risk. This suggests that other factors, such as the environment, also play a role in obesity. Thus, individuals with this particular IL-6 variant may have a slightly higher likelihood of being overweight or obese compared to those without it, but this is just one of many factors influencing obesity risk.
Sulforaphane and Benzyl Isothiocyanate Suppress Cell Proliferation and Trigger Cell Cycle Arrest, Autophagy, and Apoptosis in Human AML Cell Line
Authors: Bertova Anna , Kontar Szilvia , Ksinanova Martina , Vergara Alberto Yoldi , Sulova Zdena , Breier Albert , Imrichova Denisa
Published: December 2024

Isothiocyanates (ITCs) are naturally occurring sulfur-containing compounds with diverse biological effects. This study investigated the effects of sulforaphane (SFN, an aliphatic ITC) and benzyl isothiocyanate (BITC, an aromatic ITC) on human acute myeloid leukemia SKM-1 cells, focusing on cell proliferation, cell death, and drug resistance. Both drug-sensitive SKM-1 cells and their drug-resistant SKM/VCR variant, which overexpresses the drug transporter P-glycoprotein, were used. SFN and BITC reduced cell viability in a dose-dependent manner, with BITC showing greater potency. IC50 values ranged from 7.0–8.0 µM for SFN and 4.0–5.0 µM for BITC in both cell types, with only slight differences between the variants. Both ITCs induced autophagy as evidenced by increased LC3-II production and caused a significant increase in the sub-G0/G1 cell population, especially with BITC. Apoptosis was more pronounced after BITC treatment, whereas SFN had a weaker effect. These results suggest that autophagy may act as a defense mechanism in response to ITC-induced apoptosis in human AML cells.
Preliminary Study to Investigate Possible Cyto-Genotoxic and Oxidative Effects of Few-Layer Graphene in Human Bronchial Cells
Authors: Fresegna Anna Maria , Ciervo Aureliano , Ursini Cinzia Lucia , Maiello Raffaele , Tombolini Francesca , Del Frate Valentina , Gentile Marco , Cavallo Delia
Published: December 2024

Graphene and its various derivatives, known as graphene-based nanomaterials (GBNs), hold tremendous potential across many fields due to their exceptional properties. As with any novel material, concerns about their safety have emerged alongside their widespread production and use. Several studies have shown that GBNs can have diverse effects on various cell lines and organisms under different exposure conditions. This study intends to evaluate the potential toxicity of few-layer graphene (FLG) in human bronchial BEAS-2B. Cells were exposed to different concentrations of FLG for 24 h, and the cyto-genotoxic, oxidative, and inflammatory effects were evaluated. We found an increase in cytotoxicity in terms of cell death, cell apoptosis, and membrane damage at the highest concentration. We also detected a slight increase in direct DNA damage and the percentage of comets. Oxidative DNA damage was observed at the highest concentration. FLG exposure did not induce notable cytokine release. Overall, this study suggests that exposure to FLG can induce cytotoxicity, apoptosis, and DNA damage in BEAS-2B, particularly at high concentrations. These findings contribute to a better understanding of the potential health effects of FLG and highlight the importance of considering dose-dependent effects when assessing the safety of GBNs.
Organic vs. Conventional Milk: Uncovering the Link to Antibiotic Resistance in Bacillus cereus sensu lato
Authors: Bartoszewicz Marek , Czyżewska Urszula , Zambrzycka Monika , Święcicka Izabela
Published: December 2024

Bacillus cereus sensu lato (B. cereus s.l.) comprises mesophilic and psychrotolerant bacteria commonly found in natural environments as well as in organic and conventional milk. Due to their potential toxigenicity and antibiotic resistance, these bacteria pose a significant threat to consumer health. Organic milk production, which prohibits the use of antibiotics and artificial additives, may influence the composition of microbiota between milk types. This study aimed to compare the antibiotic resistance profiles and enterotoxic potential of B. cereus s.l. isolates from organic and conventional milk. The results indicate that, although conventional milk contains on average 3 times fewer B. cereus s.l. isolates, it has 10–15% more resistant isolates to selected beta-lactams, macrolides, and aminoglycosides. Regarding drug resistance, 21% of B. cereus s.l. isolates were multidrug-resistant, and as many as 42% were non-susceptible to two classes of antibiotics. Even among the sensitive isolates, bacteria from conventional milk exhibited on average 2.05 times higher MICs (minimal inhibitory concentrations) for beta-lactams, 1.49 times higher for erythromycin, 1.38 times higher for vancomycin, and 1.38 times higher for azithromycin. Antibiotic resistance was mostly associated with the origin of the isolates. These findings underscore the need for ongoing monitoring of antibiotic resistance and enterotoxicity among opportunistic B. cereus s.l. strains, which may pose challenges for public health and veterinary medicine. The results highlight that selective pressure associated with antibiotic use can drive resistance development in bacteria that are not the primary targets of antimicrobial therapy.
Neural Network-Based Parameter Estimation in Dynamical Systems
Authors: Kastoris Dimitris , Giotopoulos Kostas , Papadopoulos Dimitris
Published: December 2024

Mathematical models are designed to assist decision-making processes across various scientific fields. These models typically contain numerous parameters, the values’ estimation of which often comes under analysis when evaluating the strength of these models as management tools. Advanced artificial intelligence software has proven to be highly effective in estimating these parameters. In this research work, we use the Lotka–Volterra model to describe the dynamics of a telecommunication sector in Greece, and then we propose a methodology that employs a feed-forward neural network (NN). The NN is used to estimate the parameter’s values of the Lotka–Volterra system, which are later applied to solve the system using a fourth-algebraic-order Runge–Kutta method. The application of the proposed architecture to the specific case study reveals that the model fits well to the experiential data. Furthermore, the results of our method surpassed the other three methods used for comparison, demonstrating its higher accuracy and effectiveness. The implementation of the proposed feed-forward neural network and the fourth-algebraic-order Runge–Kutta method was accomplished using MATLAB.
Impact of Environmental Factors and Management Practices on Bee Health
Authors: Tlak Gajger Ivana , Mutinelli Franco
Published: December 2024

The honey bee is a symbol of One Health, a holistic approach to animal, human and environment health, and beekeeping is an economic branch of exceptional importance for public health [...]