bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Lab vs. Backcalculated Moduli of Virgin Aggregate and Recycled Aggregate Base Layers
Authors: Zulfiqar Qasim , Haider Syed Waqar , Cetin Bora , Coban Haluk Sinan , Abdollahi Seyed Farhad
Published: October 2024

The resilient modulus (MR) and the backcalculated modulus from the FWD testing (EFWD) of the unbound layers are critical inputs in the analysis/design of pavements. Several studies have tried to develop a conversion factor between these two parameters, while the nonlinear stress dependency of unbound materials and the pavement strain response are mostly missing from the literature. This study aims to compare the laboratory-measured MR of recycled aggregate base (RAB) materials and a virgin aggregate base using field-based EFWD and tries to establish pavement’s responses to loading using vertical strains from both the MR and EFWD values of the respective materials as comparability parameters between the two. For this purpose, a control virgin aggregate (VA, limestone) and three types of RAB materials were selected to construct four test sections. The test sections were modeled in layered elastic- and finite-element-based pavement response models to calculate the vertical strains at the mid-depth of the base and top of the subgrade layers. A comparison of the lab-calculated vertical strains using MR with actual vertical strains in the field from EFWD showed that there was no relationship between the two stiffness parameters in all tested RABs. The vertical strains, based on the lab MR, undermined the stiffness of the recycled aggregates in the field. In contrast, the values of EFWD based on the vertical strains remained close to the MR strains of limestone (VA) throughout the testing period, establishing an EFWD vs. MR relationship (MR = 0.87 EFWD). The results also show that fine RCA was a better-performing material over three years. This research not only explores how the hydration process in RABs limits the development of MR-EFWD correlations but also underscores the need to consider real-world conditions when assessing their performance.
The Application of Computed Tomography to Study the Soil Porosity of Mountain Red Earth
Authors: Ye Hongchen , Xu Zongheng , Zha Linglong , Chen Yunying
Published: October 2024

Mountain red soil, as a special type of soil in the South, has received widespread attention for its soil erosion problems. Its pore structure restricts water infiltration, thereby affecting the occurrence and development of soil erosion. In order to systematically obtain the distribution characteristics of the pore structure within the surface mountain red soil, this paper uses non-destructive CT detection technology to scan the soil column samples taken from the typical mountain red soil distribution area in Chenggong District, Kunming City, Yunnan Province. Image processing technology is applied to CT slices, and ImageJ (1.46r) software is used to obtain the distribution characteristics of pores within the soil column, including pore sizes and the number of pores at each depth, the proportion of pore area, roundness, and box-counting dimension. The results show that with the increase in depth, the proportion of pore area decreases linearly from the maximum value of 52.25% at the top to the minimum value of 2.02% at the bottom; the roundness of pores fluctuates between 0.8 and 0.9, overall increasing; the total number of pores generally first increases then decreases, and small pores are predominant, with the least number of large pores in the topsoil layer; the box-counting dimension shows a gradual linear decrease, with a maximum value of 1.7980 and a minimum value of 0.9878. The number of pores affects both roundness and the box-counting dimension, and the proportion of pore area also affects the box-counting dimension. There is a negative correlation between roundness and the box-counting dimension. The 3D visualization reconstruction of pores shows that most are interconnected, with the pore size significantly reducing with increasing depth. The quantitative analysis of parameters and 3D visualization reveal, to some extent, the impact of pore structure on the occurrence and development of soil erosion in mountain red soil. These research findings form the foundation for studying soil erosion in this region and provide a basis for systematically understanding its processes and mechanisms.
Styrene Migration from Polystyrene for Food Contact: A Case Study on the Processing Chain of Yoghurt Pots
Authors: Guazzotti Valeria , Hendrich Veronika , Gruner Anita , Fiedler Dominik , Störmer Angela , Welle Frank
Published: October 2024

A precautionary specific migration limit of 40 µg/kg for styrene from food contact materials is currently under evaluation in Europe. In the ongoing discussion about applicable methods to demonstrate compliance, testing with food instead of simulants or total transfer calculations has been proposed. In this study, the residual styrene levels in high-impact polystyrene (HIPS) blended with general-purpose polystyrene (GPPS) were determined at several levels of the processing chain of yoghurt pots (from pellets to sheets, then to pots). The styrene migration from extruded sheets and thermoformed pots was analyzed in food simulants at 10 days/20 °C and 40 °C, as well as in yoghurt after storage at 8 °C after 50 days. The obtained results show that the residual styrene content in the PS materials correlates with migration. However, the migration of styrene was far below the total transfer assumption. Styrene migration from the sheets into food simulants and into yoghurt exceeded that migrating from the pots. Styrene migration into food simulants in 20% ethanol at 10 days/20 °C and 40 °C and, more clearly, in 50% ethanol at 10 days/40 °C, was higher than that into yoghurt tested on the best-before date. Styrene migration from PS pots into yoghurt after storage at 8 °C for 50 days reached up to 15 µg/kg (applying the EU cube model), which would be conservatively covered by testing the PS pots with 20% ethanol at 10 days/20 °C.
Close Encounters of the Feathered Kind: Orpheus and the Birds
Authors: Archibald Zofia Halina
Published: October 2024

Birds were observed in divinatory rituals in antiquity. This was the most significant process that regularly involved looking closely at birds. At the same time, birds were intimately connected to human perceptions of the natural world and, through their capacity to ascend skywards, with the supernatural world. By studying two neighbouring areas connected by the myth of Orpheus and divinatory birds, we can begin to appreciate the role of birds (and bird-like beings) in the culture of Macedonia and Thrace. Birds played a central role in prophecy (ornithomancy). Literary, archaeological and zooarchaeological data from the 6th to 4th centuries BCE provide the means of uniting different types of evidence. The literary and archaeological evidence provides a broad perspective for understanding the still-limited zooarchaeological data. Birds of prey were among the key divinatory creatures regularly observed, while cranes and a variety of lacustrine and meadow birds were among those most regularly observed and hunted. Winged creatures (human–animal hybrids) form some of the most important creations of the human imagination in southern Europe, with distinctive local variants in Macedonia and Thrace.
Exhibiting for Purpose: Finnish Art in Moscow in 1934
Authors: Paloposki Hanna-Leena , Lopatkina Katarina
Published: October 2024

This article is a case study that illustrates the complex intersection of art, politics, and diplomacy in the interwar period. Based on Finnish and Soviet archival documents and press publications, it examines the entire process of organising a Finnish art show abroad. The exhibition, held from 28 November to 24 December 1934, in Moscow, was seen as a landmark event, drawing significant attendance and fostering Finnish–Soviet cultural exchange. By analysing various factors contributing to its success, we provide a detailed picture of both artistic and political influences, demonstrating how cultural events can transcend mere aesthetic appreciation to become significant diplomatic tools.
NIR Spectroscopy for the Online Monitoring of Water and Olive Oil Content in Pomace during the Extraction Process
Authors: Leone Alessandro , Berardi Antonio , Antonelli Giovanni , Dellisanti Cosimo Damiano , Tamborrino Antonia
Published: October 2024

The main challenge of this scientific work was the implementation on an industrial olive oil extraction plant of an NIR device for the multispectral analysis of pomace to predict the percentage of humidity and oil contained in it. Subsequent to the implementation of the NIR device on the oil extraction line on the solid’s outlet from the decanter, NIRS interaction measurements in the 761–1081 nm region were used to probe the pomace. NIRS calibration models for the prediction of water and oil content in the pomace were obtained and successfully tested and validated. The correlations of calibration results for oil and water content were 0.700 and 0.829, while the correlations of validation were 0.773 and 0.676, respectively. Low values of root mean square error were found for both the prediction and validation set. The results highlight the good robustness of an NIR approach based on a PLS calibration model to monitor the industrial olive oil process. The results obtained are a first step toward the large-scale implementation of NIR devices for monitoring pomace in oil mills. The possibility of knowing the oil lost in the pomace, moment by moment, would open a new frontier towards system control and the sustainability of the olive oil extraction process.
Impact of City-Wide Diesel Generator Use on Air Quality in Quito, Ecuador, during a Nationwide Electricity Crisis
Authors: Zalakeviciute Rasa , Diaz Valeria , Rybarczyk Yves
Published: October 2024

As climate change intensifies and 2023 sets the record for the hottest year, the Amazonian region faces severe drought, leading to a hydroelectricity crisis. This study examines the effects of using environmentally harmful backup power solutions, which are all too common in developing countries—specifically, diesel-powered generators—on urban air quality in Quito, Ecuador, during the hydroelectric crisis of 2023/2024. The impact of the blackouts on air pollution is assessed by comparing it to a reference period before the crisis and to an earlier year with similar weather conditions. The findings indicate that extended blackouts (up to 8 h per day) considerably increased concentrations of SO2 (180%), CO (43%), NO2 (39%), and PM2.5 (20%) compared to ‘normal’ conditions. Conversely, O3 pollution levels decreased (−6%). Our findings suggest potential respiratory and cardiovascular health risks for the urban population, highlighting the urgent need for improved energy infrastructure and cleaner backup power solutions in the developing world. Addressing these challenges is critical for ensuring a healthier and more sustainable urban future amidst climate change projections.
A Modeling Framework of Atmospheric CO2 in the Mediterranean Marseille Coastal City Area, France
Authors: Nathan Brian , Xueref-Remy Irène , Lauvaux Thomas , Yohia Christophe , Piga Damien , Piazzola Jacques , Oda Tomohiro , Milne Mélissa , Herrmann Maria , Wimart-Rousseau Cathy , Armengaud Alexandre
Published: October 2024

As atmospheric CO2 emissions and the trend of urbanization both increase, the ability to accurately assess the CO2 budget from urban environments becomes more important for effective CO2 mitigation efforts. This task can be difficult for complex areas such as the urban–coastal Mediterranean region near Marseille, France, which contains the second most populous city in France as well as a broad coastline and nearby mountainous terrain. In this study, we establish a CO2 modeling framework for this region for the first time using WRF-Chem and demonstrate its efficacy through comparisons against cavity-ringdown spectrometer measurements recorded at three sites: one 75 km north of the city in a forested area, one in the city center, and one at the urban/coastal border. A seasonal CO2 analysis compares Summertime 2016 and Wintertime 2017, to which Springtime 2017 is also added due to its noticeably larger vegetation uptake values compared to Summertime. We find that there is a large biogenic signal, even in and around Marseille itself, though this may be a consequence of having limited fine-scale information on vegetation parameterization in the region. We further find that simulations without the urban heat island module had total CO2 values 0.46 ppm closer to the measured enhancement value at the coastal Endoume site during the Summertime 2016 period than with the module turned on. This may indicate that the boundary layer on the coast is less sensitive to urban influences than it is to sea-breeze interactions, which is consistent with previous studies of the region. A back-trajectory analysis with the Lagrangian Particle Dispersion Model found 99.83% of emissions above 100 mol km−2 month−1 captured in Summer 2016 by the three measurement towers, providing evidence of the receptors’ ability to constrain the domain. Finally, a case study showcases the model’s ability to capture the rapid change in CO2 when transitioning between land-breeze and sea-breeze conditions as well as the recirculation of air from the industrial Fos region towards the Marseille metroplex. In total, the presented modeling framework should open the door to future CO2 investigations in the region, which can inform policymakers carrying out CO2 mitigation strategies.
Examine the Role of Indo-Pacific Sea Surface Temperatures in Recent Meteorological Drought in Sudan
Authors: Mohammed Awad Hussien Ahmed , Zhang Xiaolin , Alriah Mohamed Abdallah Ahmed
Published: October 2024

Drought poses a serious threat to Sudan, causing water shortages, crop failures, hunger, and conflict. The relationships between Indo-Pacific teleconnections and drought events in Sudan are examined based on the Standardized Precipitation Index (SPI), anomalies, Empirical Orthogonal Function (EOF), correlation, composite analysis, sequential Mann–Kendall test, and MK-trend test during the period of 1993–2022. The results of the SPI-1 values indicate that the extreme drought in Sudan in 2004 was an exceptional case that affected the entire region, with an SPI-1 value of −2 indicating extremely dry conditions. In addition, Sudan experienced moderate to severe drought conditions for several years (1993, 2002, 2008, 2009 and 2015). The Empirical Orthogonal Function showed that the first EOF mode (42.2%) was the dominant variability mode and had positive loading over most of the country, indicating consistent rainfall variation in the central, eastern, and western regions. Correlation analysis showed a strong significant relationship between June–September rainfall and Indian Ocean sea surface temperature (SST) (r ≤ 0.5). Furthermore, a weak positive influence of the Indian Ocean Dipole (IOD) on JJAS precipitation was observed (r ≤ 0.14). Various time lags in the range of ±12 months were examined, with the highest correlation (0.6) found at 9 month among the time lags of ±12 months. This study contributes to a better understanding of drought dynamics and provides essential information for effective drought management in Sudan. Further research is needed to explore the specific mechanisms driving these interactions and to develop tailored strategies to mitigate the impacts of drought events in the future.
Characteristics and Driving Factors of Energy Balance over Different Underlying Surfaces in the Qinghai Plateau
Authors: Liu Xiaoyang , Zhang Lele , Gao Liming , Duan Ziyi
Published: October 2024

The study of the surface energy balance characteristics of different ecosystems in the Qinghai Plateau is of great significance for a deeper understanding of land surface processes, the water cycle, and global climate change. This study aims to compare the seasonal variations in energy balance and partitioning of four typical ecosystems on the Qinghai Plateau—swamp meadows, subalpine mountain meadows, alpine shrublands, and alpine deserts. Mantel analysis and path analysis were used to explore the regulatory mechanisms of meteorological elements on energy fluxes and the Bowen ratio (β). The results showed the following: (1) Net radiation (Rn), sensible heat flux (H), and latent heat flux (LE) all exhibited a single-peak pattern of change, and the energy partitioning was closely related to the hydrothermal conditions. Swamp meadows and subalpine mountain meadows were dominated by LE throughout the year and the growing season, while H dominated in the non-growing season. Meanwhile, alpine shrublands and alpine deserts were dominated by H throughout the year. (2) β reflected the characteristics of turbulent fluxes variations and the moisture level of the underlying surface. Swamp meadows and subalpine mountain meadows were relatively moist, with the value of β all being less than 1. Alpine shrublands and deserts were comparatively arid, with the values of β all exceeding 1. The energy closure rate ranged from 48% to 90%, with better energy closure conditions observed during the growing season compared to the non-growing season. (3) Meteorological factors collectively regulated the variations in energy fluxes and its partitioning, with H and LE being primarily influenced by Rn, relative humidity (RH), and soil moisture (Ms). β was significantly affected by RH, Ms, and the saturated vapor pressure deficit (VPD). The sensitivity of the ecosystems to changes in fluxes increased with decreasing moisture, especially in alpine deserts, with Ms, VPD and RH being the most affected. Swamp meadows were significantly associated with air temperature (Ta), soil temperature (Ts), and wind speed; subalpine mountain meadows with Ta and Ts; and alpine shrublands with Ta. These results provided a basis for further analyses of the energy balance characteristics and partitioning differences of different ecosystems on the Qinghai Plateau.
A Meshless Radial Point Interpolation Method for Solving Fractional Navier–Stokes Equations
Authors: Dabiri Arman , Moghaddam Behrouz Parsa , Taghizadeh Elham , Galhano Alexandra
Published: October 2024

This paper aims to develop a meshless radial point interpolation (RPI) method for obtaining the numerical solution of fractional Navier–Stokes equations. The proposed RPI method discretizes differential equations into highly nonlinear algebraic equations, which are subsequently solved using a fixed-point method. Furthermore, a comprehensive analysis regarding the effects of spatial and temporal discretization, polynomial order, and fractional order is conducted. These factors’ impacts on the accuracy and efficiency of the solutions are discussed in detail. It can be shown that the meshless RPI method works quite well for solving some benchmark problems accurately.
Flash Vacuum Expansion of Maradol Papaya (Carica papaya L.) for Producing an Antioxidant-Potential Dairy Beverage Fermented by Limosilactobacillus fermentum J24
Authors: Ayala Zavala Jesús , Castillo Romero Teresita de Jesús , Méndez Romero José Isidro , Santiago López Lourdes , González Córdova Aarón Fernando , Hernández Mendoza Adrián , Vallejo Cordoba Belinda , Vargas Ortiz Manuel
Published: October 2024

This study aimed to evaluate the fermentative capacity of the strain Limosilactobacillus fermentum J24 in a dairy beverage with papaya puree obtained through the flash vacuum expansion (FVE) process. Changes in phenolic content and antioxidant capacity during fermentation were investigated. Results showed that the dairy beverage with the control puree exhibited higher microbial growth than the FVE puree. Phenolic content increased during fermentation in both formulations. However, the antioxidant capacity was higher in the dairy beverage with control puree. A Pearson correlation analysis revealed a strong positive correlation between microbial load and antioxidant properties in the dairy beverage with control puree. In conclusion, the control puree promoted a higher growth of Limosilactobacillus fermentum J24 and better antioxidant properties in the papaya dairy beverage. These findings lay the groundwork for developing a potential functional dairy beverage based on papaya, effectively utilizing the fruit, reducing pollution, and adding value. This study also opens avenues for further research and development in functional dairy beverages, particularly those incorporating fruit-based ingredients.
Clinical Validation of Deep Learning for Segmentation of Multiple Dental Features in Periapical Radiographs
Authors: Jagtap Rohan , Samata Yalamanchili , Parekh Amisha , Tretto Pedro , Roach Michael D. , Sethumanjusha Saranu , Tejaswi Chennupati , Jaju Prashant , Friedel Alan , Briner Garrido Michelle , Feinberg Maxine , Suri Mini
Published: October 2024

Periapical radiographs are routinely used in dental practice for diagnosis and treatment planning purposes. However, they often suffer from artifacts, distortions, and superimpositions, which can lead to potential misinterpretations. Thus, an automated detection system is required to overcome these challenges. Artificial intelligence (AI) has been revolutionizing various fields, including medicine and dentistry, by facilitating the development of intelligent systems that can aid in performing complex tasks such as diagnosis and treatment planning. The purpose of the present study was to verify the diagnostic performance of an AI system for the automatic detection of teeth, caries, implants, restorations, and fixed prosthesis on periapical radiographs. A dataset comprising 1000 periapical radiographs collected from 500 adult patients was analyzed by an AI system and compared with annotations provided by two oral and maxillofacial radiologists. A strong correlation (R > 0.5) was observed between AI perception and observers 1 and 2 in carious teeth (0.7–0.73), implants (0.97–0.98), restored teeth (0.85–0.89), teeth with fixed prosthesis (0.92–0.94), and missing teeth (0.82–0.85). The automatic detection by the AI system was comparable to the oral radiologists and may be useful for automatic identification in periapical radiographs.
Microbial Community Structure in the Taklimakan Desert: The Importance of Nutrient Levels in Medium and Culture Methods
Authors: Wen Feng , Wu Siyuan , Luo Xiaoxia , Bai Linquan , Xia Zhanfeng
Published: October 2024

Although the Taklimakan Desert lacks the necessary nutrients and conditions to support an extensive ecosystem, it is a treasure trove of extremophile resources with special structures and functions. We analyzed the bacterial communities using oligotrophic medium and velvet cloth replicate combined with an extended culture duration. We isolated numerous uncultured microorganisms and rare microorganisms belonging to genera not often isolated or recently described, such as Aliihoeflea, Halodurantibacterium, and Indioceanicola. A total of 669 strains were isolated from the soil of the Taklimakan Desert, which were classified into 5 phyla, 7 classes, 25 orders, 42 families, 83 genera, and 379 species. Among them, 148 strains were potential new species. Our data show that even when working with samples from extreme environments, simple approaches are still useful for cultivating stubborn microbes. Through comparing the isolation effects of different nutrient levels on microbial diversity and abundance, the results show that reducing the nutrient level of the medium was more conducive to improving the culturability of microorganisms in low-nutrient environments, while the high-nutrient medium was more suitable for the isolation of dominant fast-growing strains. This study helps to better reflect the diversity of microbial resources and lays a foundation for the further research and utilization of soil microbial resources in the Taklimakan Desert.
EMC1 Is Required for the Sarcoplasmic Reticulum and Mitochondrial Functions in the Drosophila Muscle
Authors: Couto-Lima Carlos Antonio , Machado Maiaro Cabral Rosa , Anhezini Lucas , Oliveira Marcos Túlio , Molina Roberto Augusto da Silva , da Silva Rodrigo Ribeiro , Lopes Gabriel Sarti , Trinca Vitor , Colón David Fernando , Peixoto Pablo M. , Monesi Nadia , Alberici Luciane Carla , Ramos Ricardo Guelerman P. , Espreafico Enilza Maria
Published: October 2024

EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER–mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and the protein localizes to the sarcoplasmic reticulum (SR) network. Muscle-specific EMC1 RNAi led to severe motility defects and partial late pupae/early adulthood lethality, phenotypes that are rescued by co-expression with an EMC1 transgene. Motility impairment in EMC1-depleted flies was associated with aberrations in muscle morphology in embryos, larvae, and adults, including tortuous and misaligned fibers with reduced size and weakness. They were also associated with an altered SR network, cytosolic calcium overload, and mitochondrial dysfunction and dysmorphology that impaired membrane potential and oxidative phosphorylation capacity. Genes coding for ER stress sensors, mitochondrial biogenesis/dynamics, and other EMC components showed altered expression and were mostly rescued by the EMC1 transgene expression. In conclusion, EMC1 is required for the SR network’s mitochondrial integrity and influences underlying programs involved in the regulation of muscle mass and shape. We believe our data can contribute to the biology of human diseases caused by EMC1 mutations.
A Structural Investigation of the Interaction between a GC-376-Based Peptidomimetic PROTAC and Its Precursor with the Viral Main Protease of Coxsackievirus B3
Authors: De Santis Alessia , Grifagni Deborah , Orsetti Andrea , Lenci Elena , Rosato Antonio , D’Onofrio Mariapina , Trabocchi Andrea , Ciofi-Baffoni Simone , Cantini Francesca , Calderone Vito
Published: October 2024

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimized host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteasome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR (Nuclear Magnetic Resonance) and biochemical techniques. The crystal structure of CVB3 3CPro bound to the GC-376 PROTAC precursor was obtained at 1.9 Å resolution. The crystallographic data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong (RMSD on C-alpha 0.3 Å). The most notable variation is the orientation of the benzyloxycarbonyl group of GC-376 with the S4 subsite of the proteases. NMR backbone assignment of CVB3 3CPro bound and unbound to the GC-376 PROTAC precursor (80% and 97%, respectively) was obtained. This information complemented the investigation, by NMR, of the interaction of CVB3 3CPro with the GC-376 PROTAC, and its precursor allows us to define that the GC-376 PROTAC binds to CVB3 3CPro in a mode very similar to that of the precursor. The NMR relaxation data indicate that a quench of dynamics of a large part of the protein backbone involving the substrate-binding site and surrounding regions occurs upon GC-376 PROTAC precursor binding. This suggests that the substrate cavity, by sampling different backbone conformations in the absence of the substrate, is able to select the suitable one necessary to covalently bind the substrate, this being the latter reaction, which is the fundamental step required to functionally activate the enzymatic reaction. The inhibition activity assay showed inhibition potency in the micromolar range for GC-376 PROTAC and its precursor. Overall, we can conclude that the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.
Role of Gonadal Steroid Hormones in the Eye: Therapeutic Implications
Authors: Valero-Ochando Javier , Cantó Antolin , López-Pedrajas Rosa , Almansa Inmaculada , Miranda María
Published: October 2024

Gonadal steroid hormones are critical regulatory substances involved in various developmental and physiological processes from fetal development through adulthood. These hormones, derived from cholesterol, are synthesized primarily by the gonads, adrenal cortex, and placenta. The synthesis of these hormones involves a series of enzymatic steps starting in the mitochondria and includes enzymes such as cytochrome P450 and aromatase. Beyond their genomic actions, which involve altering gene transcription over hours, gonadal steroids also exhibit rapid, nongenomic effects through receptors located on the cell membrane. Additionally, recent research has highlighted the role of these hormones in the central nervous system (CNS). However, the interactions between gonadal steroid hormones and the retina have received limited attention, though it has been suggested that they may play a protective role in retinal diseases. This review explores the synthesis of gonadal hormones, their mechanisms of action, and their potential implications in various retinal and optic nerve diseases, such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), or retinitis pigmentosa (RP), discussing both protective and risk factors associated with hormone levels and their therapeutic potential.
Mechanistic Insights into Clinically Relevant Ribosome-Targeting Antibiotics
Authors: Krawczyk Szymon J. , Leśniczak-Staszak Marta , Gowin Ewelina , Szaflarski Witold
Published: October 2024

Antibiotics targeting the bacterial ribosome are essential to combating bacterial infections. These antibiotics bind to various sites on the ribosome, inhibiting different stages of protein synthesis. This review provides a comprehensive overview of the mechanisms of action of clinically relevant antibiotics that target the bacterial ribosome, including macrolides, lincosamides, oxazolidinones, aminoglycosides, tetracyclines, and chloramphenicol. The structural and functional details of antibiotic interactions with ribosomal RNA, including specific binding sites, interactions with rRNA nucleotides, and their effects on translation processes, are discussed. Focus is placed on the diversity of these mechanisms and their clinical implications in treating bacterial infections, particularly in the context of emerging resistance. Understanding these mechanisms is crucial for developing novel therapeutic agents capable of overcoming bacterial resistance.
Cerebrospinal Fluid Total, Phosphorylated and Oligomeric A-Synuclein in Parkinson’s Disease: A Systematic Review, Meta-Analysis and Meta-Regression Study
Authors: Kapsali Ioanna , Brinia Maria-Evgenia , Constantinides Vasilios C.
Published: October 2024

Background: The diagnostic accuracy for Parkinson’s disease (PD), a synucleinopathy, based on diagnostic criteria is suboptimal. A biomarker for synucleinopathies is pivotal both from a clinical and from a research point of view. CSF a-synuclein has been extensively studied over the past two decades as a candidate biomarker of synucleinopathies. Herein, we present data on studies focusing on total, phosphorylated and oligomeric CSF a-synuclein in PD. Methods: Pubmed, Scopus and Web of Science were searched for studies with >10 PD patients and control subjects, with data (mean, SD) on total, phosphorylated or oligomeric a-synuclein. Cohen’s d, as a measure of effect size, was calculated for all a-synuclein forms. Subgroup analysis and meta-regression were performed in an effort to explain between-study heterogeneity. Results: Thirty studies on total, six studies on oligomeric and one study on phosphorylated a-synuclein were included. Total a-synuclein was decreased and oligomeric a-synuclein increased in PD patients vs. controls. The effect size was medium for total and high for oligomeric a-synuclein. A-syn forms provided suboptimal combined sensitivity/specificity for the differentiation of PD from controls. There was significant between-study heterogeneity. The PD cohort characteristics (sex, age, disease duration, UPDRS, H & Y) and study characteristics (study design, healthy vs. neurological controls, control for CSF blood contamination, method of a-syn measurement) could not account for between-study heterogeneity. Publication bias was limited. Conclusions: CSF a-synuclein levels lack sufficient accuracy to be used as biomarkers for PD. The standardization of (pre)analytical variables may improve the discriminatory power of a-synuclein forms in the future.
Exercise-Induced Proteomic Profile Changes in Patients with Advanced Heart Failure
Authors: Drohomirecka Anna , Waś Joanna , Sitkiewicz Ewa , Świderska Bianka , Lutyńska Anna , Rywik Tomasz , Zieliński Tomasz
Published: October 2024

Background/Objectives: The pathophysiological background of the processes activated by physical activity in patients with heart failure (HF) is not fully understood. Proteomic studies can help to preliminarily identify new protein markers for unknown or poorly defined physiological processes. We aimed to analyse the changes in the plasma proteomic profile of HF patients after a cardiopulmonary exercise test (CPET) to define pathways involved in the response to exercise. Methods: The study prospectively enrolled 20 male patients with advanced HF (aged 53.3 ± 8.3 years). Blood samples were taken from the patients before and immediately after the CPET to obtain plasma proteomic profiles. Two-sample t-tests (paired or non-paired) were performed with and without false discovery rate (FDR) correction for multiple testing. Enrichment analysis was performed to associate biological processes and pathways with the study results. Results: A total of 968 plasma proteins were identified, of which 722 underwent further statistical analysis. Of these, 236 proteins showed differential expression when comparing all plasma samples collected before and after CPT (p < 0.05), and for 86 of these the difference remained statistically significant after FDR correction. Proteins whose expression changed after exercise are mostly involved in immune response and inflammatory processes, coagulation, cell adhesion, regulation of cellular response to stimulus and regulation of programmed cell death. There were no differences in resting proteomics according to HF etiology (ischemic vs. non-ischemic). Conclusions: Changes in the proteomic profile revealed a complexity of exercise-induced processes in patients with HF, suggesting that few major physiological pathways are involved. Further studies focusing on specific pathways are needed.
Transitions in Immunoassay Leading to Next-Generation Lateral Flow Assays and Future Prospects
Authors: Fujiuchi Koyu , Aoki Noriko , Ohtake Tetsurou , Iwashita Toshihide , Kawasaki Hideya
Published: October 2024

In the field of clinical testing, the traditional focus has been on the development of large-scale analysis equipment designed to process high volumes of samples with fully automatic and high-sensitivity measurements. However, there has been a growing demand in recent years for the development of analytical reagents tailored to point-of-care testing (POCT), which does not necessitate a specific location or specialized operator. This trend is epitomized using the lateral flow assay (LFA), which became a cornerstone during the 2019 pandemic due to its simplicity, speed of delivering results—within about 10 min from minimal sample concentrations—and user-friendly design. LFAs, with their paper-based construction, combine cost-effectiveness with ease of disposal, addressing both budgetary and environmental concerns comprehensively. Despite their compact size, LFAs encapsulate a wealth of technological ingenuity, embodying years of research and development. Current research is dedicated to further evolving LFA technology, paving the way for the next generation of diagnostic devices. These advancements aim to redefine accessibility, empower individuals, and enhance responsiveness to public health challenges. The future of LFAs, now unfolding, promises even greater integration into routine health management and emergency responses, underscoring their critical role in the evolution of decentralized and patient-centric healthcare solutions. In this review, the historical development of LFA and several of the latest LFA technologies using catalytic amplification, surface-enhanced Raman scattering, heat detection, electron chemical detections, magnetoresistance, and detection of reflected electrons detection are introduced to inspire readers for future research and development.
Extracorporeal Magnetotransduction Therapy as a New Form of Electromagnetic Wave Therapy: From Gene Upregulation to Accelerated Matrix Mineralization in Bone Healing
Authors: Gerdesmeyer Lennart , Tübel Jutta , Obermeier Andreas , Harrasser Norbert , Glowalla Claudio , von Eisenhart-Rothe Rüdiger , Burgkart Rainer
Published: October 2024

Background: Electromagnetic field therapy is gaining attention for its potential in treating bone disorders, with Extracorporeal Magnetotransduction Therapy (EMTT) emerging as an innovative approach. EMTT offers a higher oscillation frequency and magnetic field strength compared to traditional Pulsed Electromagnetic Field (PEMF) therapy, showing promise in enhancing fracture healing and non-union recovery. However, the mechanisms underlying these effects remain unclear. Results: This study demonstrates that EMTT significantly enhances osteoblast bone formation at multiple levels, from gene expression to extracellular matrix mineralization. Key osteoblastogenesis regulators, including SP7 and RUNX2, and bone-related genes such as COL1A1, ALPL, and BGLAP, were upregulated, with expression levels surpassing those of the control group by over sevenfold (p < 0.001). Enhanced collagen synthesis and mineralization were confirmed by von Kossa and Alizarin Red staining, indicating increased calcium and phosphate deposition. Additionally, calcium imaging revealed heightened calcium influx, suggesting a cellular mechanism for EMTT’s osteogenic effects. Importantly, EMTT did not compromise cell viability, as confirmed by live/dead staining and WST-1 assays. Conclusion: This study is the first to show that EMTT can enhance all phases of osteoblastogenesis and improve the production of critical mineralization components, offering potential clinical applications in accelerating fracture healing, treating osteonecrosis, and enhancing implant osseointegration.
Genetic and Neurodevelopmental Markers in Schizophrenia-Spectrum Disorders: Analysis of the Combined Role of the CNR1 Gene and Dermatoglyphics
Authors: Guardiola-Ripoll Maria , Sotero-Moreno Alejandro , Chaumette Boris , Kebir Oussama , Hostalet Noemí , Almodóvar-Payá Carmen , Moreira Mónica , Giralt-López Maria , Krebs Marie-Odile , Fatjó-Vilas Mar
Published: October 2024

Background: Dermatoglyphic pattern deviances have been associated with schizophrenia-spectrum disorders (SSD) and are considered neurodevelopment vulnerability markers based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to prenatal insults and is associated with SSD. Objective: We aimed to investigate whether the Cannabinoid Receptor 1 gene (CNR1) modulates the dermatoglyphics–SSD association. Methods: In a sample of 112 controls and 97 patients with SSD, three dermatoglyphic markers were assessed: the total palmar a-b ridge count (TABRC), the a-b ridge count fluctuating asymmetry (ABRC-FA), and the pattern intensity index (PII). Two CNR1 polymorphisms were genotyped: rs2023239-T/C and rs806379-A/T. We tested: (i) the CNR1 association with SSD and dermatoglyphic variability within groups; and (ii) the CNR1 × dermatoglyphic measures interaction on SSD susceptibility. Results: Both polymorphisms were associated with SSD. The polymorphism rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within C-allele carriers and a higher SSD risk within TT-homozygotes. This result indicates an inverse relationship between the PII and the SSD predicted probability conditional to the rs2023239 genotype. Conclusions: These novel findings suggest the endocannabinoid system’s role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD in future studies.
Deferasirox’s Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma
Authors: Delgado Yamixa , Torres-Sanchez Anamaris , Perez Daraishka , Torres Grace , Estrada Sthephanie , Ortiz Alvelo Natalia , Vega Jaisy , Santos Laurie , Torres Aracelis , Madera Bismark A. , Ferrer-Acosta Yancy
Published: October 2024

Clinically approved iron chelators, originally designed to address iron overload disorders, have emerged as potential anticancer agents. Deferasirox (Def), a tridentate iron chelator, has demonstrated antiproliferative effects in cancer. Background/Objectives: This study aims to elucidate the mechanism of action of Def and its impact on non-small cell lung carcinoma (NSCLC). Methods: NSCLC A549 cells were treated with Def to assess cytotoxicity, the effect on nuclear and mitochondrial pathways, and iron-containing proteins and genes to evaluate anti-metastasis and chemoresistance. A lung carcinoma mouse model was used for in vivo studies. Results: Our findings revealed that Def induced cytotoxicity, effectively chelated intracellular iron, and triggered apoptosis through the increase in phosphatidylserine externalization and caspase 3 activity. Additionally, Def caused G0/G1 cell cycle arrest by downregulating the ribonucleotide reductase catalytic subunit. Furthermore, Def perturbed mitochondrial function by promoting the production of reactive oxygen species and the inhibition of glutathione as a measurement of ferroptosis activation. Def demonstrated inhibitory effects on cell migration in scratch assays, which was supported by the upregulation of n-myc downstream-regulated gene 1 and downregulation of the epidermal growth factor receptor protein. Also, Def downregulated one of the main markers of chemoresistance, the ABCB1 gene. In vivo experiments using a lung carcinoma mouse model showed that Def treatment did not affect the animal’s body weight and showed a significant decrease in tumor growth. Conclusions: This investigation lays the groundwork for unraveling Def action’s molecular targets and mechanisms in lung carcinoma, particularly within iron-related pathways, pointing out its anti-metastasis and anti-chemoresistance effect.
Modelling a Western Lifestyle in Mice: A Novel Approach to Eradicating Aerobic Spore-Forming Bacteria from the Colonic Microbiome and Assessing Long-Term Clinical Outcomes
Authors: Horwell Edward , Ferreira William , Hong Huynh , Bearn Philip , Cutting Simon
Published: October 2024

Introduction: The environmentally acquired aerobic spore-forming (EAS-Fs) bacteria that are ubiquitous in nature (e.g., soil) are transient colonisers of the mammalian gastro-intestinal tract. Without regular exposure, their numbers quickly diminish. These species of bacteria have been suggested to be essential to the normal functioning of metabolic and immunogenic health. The modern Western lifestyle restricts exposure to these EAS-Fs, possibly explaining part of the pathogenesis of many Western diseases. To date, the only animal studies that address specific microbiome modelling are based around germ-free animals. We have designed a new animal model that specifically restricts exposure to environmental sources of bacteria. Methodology: A new protocol, termed Super Clean, which involves housing mice in autoclaved individually ventilated cages (IVCs), with autoclaved food/water and strict ascetic handling practice was first experimentally validated. The quantification of EAS-Fs was assessed by heat-treating faecal samples and measuring colony-forming units (CFUs). This was then compared to mice in standard conditions. Mice were housed in their respective groups from birth until 18 months. Stool samples were taken throughout the experiment to assess for abundance in transiently acquired environmental bacteria. Clinical, biochemical, histological, and gene expression markers were analysed for diabetes, hypercholesterolaemia, obesity, inflammatory bowel disease, and non-alcoholic fatty liver disease (the “diseases of the West”). Results: Our results show that stringent adherence to the Super Clean protocol produces a significantly decreased abundance of aerobic spore-forming Bacillota after 21 days. This microbiomic shift was correlated with significantly increased levels of obesity and impaired glucose metabolism. There was no evidence of colitis, liver disease or hypercholesterolaemia. Conclusions: This new murine model successfully isolates EAS-Fs and has potential utility for future research, allowing for an investigation into the clinical impact of living in relative hygienic conditions.
Infrared Thermography Sensor in the Analysis of Acute Metabolic Stress Response during Race Walking Competition
Authors: Cabizosu Alessio , Marín-Pagan Cristian , Alcaraz Pedro E. , Martínez-Noguera Francisco Javier
Published: October 2024

Introduction: Due to the possible impact of the thermoregulatory process on sports performance, it is necessary to explore the existing relationships between kinetic, mechanical, and physiological variables. The objective of this study was to evaluate metabolic stress using thermography in the lower limb after the Spanish Championship 2023 walk. Method: A descriptive study was carried out on national and international race walkers before and after the 2023 Spanish Championships. The participants performed different tests within the same circuit. Five walkers completed the long-distance race of 35 km, four walkers completed the middle-distance race of 20 km and finally, two walkers completed the short-distance race of 10 km. Result: Statistically significant changes were observed in the lower limbs of the walkers after completing the test. We observed a decrease in skin temperature in all the anatomical regions analyzed, except for the back of the leg. More specifically, the decrease was in the hip (−1.92 °C: p = 0.004), quadriceps, hamstrings (−1.23 °C: p = 0.002), and tibia (−1.23 °C: p = 0.030). However, in the posterior region of the leg, a significant increase in temperature was observed (+0.50 °C: p = 0.011) following the competition. Discussion and Conclusions: The findings in this descriptive investigation support the notion that thermography may serve as a useful tool in the acute analysis of muscle functional activation and metabolic response in professional marching athletes. Moreover, the results confirmed that the change in skin temperature is the result of a variation in acute metabolic and functional activation in the lower extremities of race walkers during competition, with infrared thermography representing an instrument capable of detecting such a change in a rapid and non-invasive manner.