bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissipation of Energy and Generation of Pore Pressure in Load-Controlled and Displacement-Controlled Cyclic Tests
Authors: Polito Carmine P. , Zhang Zhuoyue , Moldenhauer Henry H. M.
Published: October 2024

The amount of energy dissipated in the soil during cyclic loading controls the amount of pore pressure generated under that loading. Because of this, the normalized dissipated energy per unit volume is the basis for both pore pressure generation models and energy-based liquefaction analyses. The pattern of energy dissipation in the soil in load-controlled cyclic triaxial and load-controlled cyclic direct simple shear tests and displacement-controlled cyclic triaxial and displacement-controlled cyclic direct simple shear tests is quite different. As a result, the pattern of pore pressure generation associated with load-controlled tests is markedly different from that in displacement-controlled tests. Pore pressure generation patterns for each of the four test types were proposed based upon the manner in which the load was applied during the test and the soil’s response to that loading. The results of four tests, two load controlled and two displacement controlled, were then used to verify these patterns. Pore pressure generation rates in load-controlled and displacement-controlled tests are different when plotted against their cycle ratios. Conversely, the tests produce nearly identical patterns when plotted against energy dissipation ratio. This occurs because of the relationship between energy dissipation ratio and pore pressure generation is independent of the loading pattern.
Pilot Study on Gaze Characteristics of Older Drivers While Watching Driving Movies
Authors: Kawabata Kaori , Nakajima Yuya , Fujita Kazuki , Sato Mamiko , Hayashi Koji , Kobayashi Yasutaka
Published: October 2024

Objective: This study aims to clarify the gazing characteristics of older drivers while driving cars using a gaze analysis device. Methods: The participants included 16 older and 12 middle-aged drivers who drove cars daily. After conducting cognitive and attentional function tests, eye gaze while watching driving videos was measured using an eye tracker. Ten driving videos were prepared. In addition, a total of 34 hazard areas were analyzed. Results: The results of the gaze measurement parameters were statistically compared between the two groups. In the older group, the gaze analysis results indicated that while viewing driving videos, the search for areas close to the car was expanded. In addition, in several hazard areas, we observed a decrease in the number of drivers gazing at the driver, shortened total gazing time, delay in the timing of gazing, and decrease in the number of visits. Conclusions: Older drivers’ eye movement is increased; however, it is characterized by gazing at unimportant areas, indicating an inefficient scanning pattern. Although these results do not indicate an obvious decline in driving ability among older drivers, the decline in hazard perception may become apparent in some situations. The data contain underpowered results and require revalidation in larger studies.
The Impact of Leadership and Management on the Implementation of Electronic Health Record Systems in the Primary Healthcare Centers
Authors: Alzghaibi Haitham , Hutchings Hayley A.
Published: October 2024

Background: In the last three decades, Electronic Health Records Systems (EHRSs) have become one of the top priorities of policymakers globally. Nowadays, EHRS reform is fast becoming a priority in developed countries. The introduction of EHRSs in Saudi healthcare organizations is considered one of the highest priorities of policymakers. Saudi Arabian e-health strategy pays reasonable attention to the EHRS implementation project. According to Saudi Vision 2030, the e-health transformation will be on top of IT projects in the country. However, an estimated 50% of EHRS implementations have failed. Project leadership and type of project management have been found to be crucial components of effective EHRS implementation. Aim of the study: To evaluate the role of centralized project management (CPM) in the implementation of large-scale EHRSs in Primary Healthcare Centers (PHCs) in Saudi Arabia (SA). Methods: A sequential explanatory mixed-methods approach involving a survey and semi-structured qualitative interview methods were utilized. Results: A total of 39 (75%) out of 53 policymakers at the Saudi Ministry of Health completed the survey, and 14 project team members were interviewed. Findings from both illustrated that adopting centralized project management approaches to implementation was beneficial in facilitating large-scale EHRS implementation and helped to overcome barriers that may have otherwise led to the failure of the project. EHRS interoperability and software selection were the factors that CPM influenced most positively.
Pacemaker Optimization Mechanisms in the Spectrum of Cardiac Disease Rationale to Protocol
Authors: Houck Philip
Published: October 2024

Introduction: The problem can be stated as over three billion choices to improve 14 disease states with nine optimization goals (some of the optimization goals are diametrically opposed) to improve dyspnea, shortness of breath, fatigability, exercise intolerance, edema, swelling, fluid retention, and arrhythmias. The goal is to increase the Left Ventricular Outflow Integral, reduce mitral regurgitation, increase longitudinal conduction velocities, and restore synchrony of the septum to the ventricle that needs it the most. The paper is organized in the following sections: (I) Spectrum of Cardiac Disease and Desired Pacing Outcomes; (II) Echo Evaluation of Disease Processes; (III) Pacing Goals in the Spectrum of Disease; (IV) Remodeling—Mathematical Model; (V) Method of Optimization of the Pacing Devices. Conclusions: Pacing trials provided the basic justification for an additional pacing lead but fell short in optimizing individual patients. The physician needs to recognize the spectrum of disease and use the protocol to improve the quality of life of the individual patient. A method to accomplish this task for the spectrum of cardiac disease is presented.
The Impact of the Sociodemographic Profile on the Tourist Experience of the Fiesta de los Patios of Córdoba: An Analysis of Visitor Satisfaction
Authors: Castaño-Prieto Lucía , García-García Lucía , Aguilar-Rivero Minerva , Ramos-Ruiz José E.
Published: October 2024

The Festival of the Patios of Cordoba, declared an Intangible Cultural Heritage (ICH) by UNESCO in 2012, serves as an emblematic case of how this designation acts as a tourist brand, attracting a greater number of visitors and granting a competitive advantage to the city’s tourist market. This research is focused on analyzing the differences and similarities in the satisfaction, lived experience and behavioral intention of tourists according to their sociodemographic profile during the 2022 edition of the Patios Festival. The study’s main objective is to understand the sociodemographic profile of the tourist who visits this event and if there are features of this profile that influence the satisfaction and lived experience with the event. Using a quantitative methodological approach, field work was carried out during the Fiesta de los Patios of Cordoba (Spain) in its 2022 edition, which took place between 3 and 15 May 2022, obtaining 383 valid surveys. The results reveal differences in the perception and satisfaction of the experience depending on the sociodemographic profile of the visitors. These findings highlight the need to adapt the tourism offerings to improve the visitor experience and also contribute to the scarcity of studies on ICH to help tourism managers formulate strategies that maximize the cultural and economic benefits of these Word Heritage inscriptions.
Intervention Projects in the Rural Alpine Environment: Approaches from the 1990s
Authors: Alonso de los Ríos Silvia
Published: October 2024

The architecture in the rural environment leaves a trail of forgotten pre-existence during depopulation processes. The anonymous practice of continuous updating that these constructions have undergone involves their enlargement and adaptation to new requirements in the sense of primary functionality, but also in the evolving ways of inhabiting. It shows an ability to update the heritage without rhetoric, presenting economic, social, and environmental sustainability. These considerations point towards an investigation of the upgrading of architecture in the rural environment as a source of action strategies in an adaptive reuse context. The methodological approach is based on a case study analysis of two intervention projects from the early 1990s in Grisons, namely the pioneering projects of Peter Märkli in Walenstadtberg in 1992/99 and Peter Zumthor in Versam in 1994. The analysis of both cases demonstrates a tectonic correlation between the spatial form development and the potential of traditional building systems. Furthermore, both cases prove the possibility of typological shifts when it comes to updating the built heritage for preservation. Finally, this study elucidates the exemplary role of both cases with respect to the renewed approaches to old and new in the context of the rural environment.
From CT Scans to Morphable Digital Models: Methodologies for Revealing and Preserving the Internal Structures of Artistic Figurines
Authors: Sakellariou Christina , Makris Dimitrios , Bardis Georgios
Published: October 2024

The revelation of the internal structure of objects through computed tomography (CT scan) contributes to a more comprehensive understanding of their creation, the assessment of their preservation status, and the prediction of their future behavior. Consequently, in the case of Yiannis Pappas’ collection, this knowledge aids in the perpetuation of the models it hosts, which are made from malleable materials, such as wax, plasticine, and mazut, on metallic armature. This publication presents the complete methodology for extracting three-dimensional (3D) models (reconstructions) of the individual construction materials of the figurines, with the aim of subsequently utilizing them in research, as well as in their digital preservation and restoration. The 3D reconstructions were obtained by automatic segmentation algorithms based on the absorption measurements of the materials of the specific figurines, and were furthered edited (post-processing) to obtain the final models.
The Colossus of Mussolini
Authors: Colonnese Fabio , Giunta Marco
Published: October 2024

In 1933, Renato Ricci, President of the Opera Nazionale Balilla, proposed to move the place of Benito Mussolini’s gatherings from Piazza Venezia to the slopes of Monte Mario, into the Foro Mussolini, a complex mainly dedicated to sport activities. Ricci entrusted Luigi Moretti with the design of the vast esplanade of the Arengo delle Nazioni and a huge bronze statue of the Genius of Fascism upon the hill of Monte Mario, which was to incarnate the physiognomy of Mussolini himself. For the first time, the projects produced by a group of engineers, architects—Mansutti and Miozzo, Paniconi and Pediconi, Del Debbio, and Moretti himself—and Aroldo Bellini, the sculptor chosen to create the new Colossus of Rome, are here systematically reordered, analyzed, and discussed in the historical, political, and artistic scenarios of 1930s Italy to reconstruct a forgotten chapter of the megalomaniacal plans promoted by the fascist regime to turn Rome into the capital of a new empire.
Effect of Plant Growth Regulators on Germination and Seedling Growth of Passiflora alata and Passiflora edulis
Authors: Domingues Neto Francisco José , Pimentel Junior Adilson , Putti Fernando Ferrari , Rodrigues João Domingos , Ono Elizabeth Orika , Tecchio Marco Antonio , Leonel Sarita , Silva Marcelo de Souza
Published: October 2024

The yellow (Passiflora edulis) and sweet (Passiflora alata) passion fruit plants hold significant economic importance in tropical fruit cultivation, valued not only for the quality of their fruit but also for their medicinal properties. Conventional propagation through seeds faces challenges due to irregular and slow germination, affecting the time required for seedling formation and the viability and uniformity of plantations. The use of plant growth regulators has been explored as a strategy to overcome these barriers, improving both the rate and uniformity of seed germination. This study aimed to evaluate the influence of seed imbibition with plant growth regulators on the germination and subsequent growth of yellow and sweet passion fruit seedlings. Gibberellic acid (GA3) and GA4+7 combined with 6-benzyladenine (GA4+7+6BA) were applied in five different concentrations (0, 250, 500, 750, and 1000 mg L−1 a.i.). The experiments were conducted in both laboratory and greenhouse conditions, following a completely randomized design with a 2 × 5 factorial scheme. The varieties tested were ‘BRS Mel do Cerrado’ for sweet passion fruit and ‘IAC-275’ for yellow passion fruit. Quantitative parameters, such as germination percentage, germination speed index, fresh and dry biomass of roots and shoots, and enzymatic activity, were assessed. The results indicated that GA3, at higher concentrations, significantly enhanced both germination percentage and speed index in both Passiflora alata and Passiflora edulis when compared to the control. Additionally, seedlings treated with GA3 showed a marked increase in shoot and root biomass, particularly at concentrations of 500 and 750 mg L−1. Enzymatic assays revealed heightened catalase and peroxidase activities in treated seedlings, indicating improved stress tolerance. In contrast, the GA4+7+6BA treatment showed less pronounced effects on seedling growth. Overall, GA3 was more effective in enhancing germination and seedling growth in both species, suggesting its potential application in improving the propagation of passion fruit.
A Long-Term Evaluation of the Ecohydrological Regime in a Semiarid Basin: A Case Study of the Huangshui River in the Yellow River Basin, China
Authors: Fan Lijuan , Liu Lanxin , Hu Jing , Zhao Fen , Li Chunhui , Yi Yujun
Published: October 2024

This study aimed to evaluate the ecohydrological regime and ecological water demand of the Huangshui River Basin under changing environmental conditions, seeking to safeguard its ecosystem. Based on monthly data spanning from 1956 to 2016, the ecohydrological regimes of the Huangshui River and the Datong River were evaluated using methods such as the Pettitt mutation test, the Tennant method, and ecological deficit and surplus analyses. The data were mainly obtained from Xiangtang Station of the Datong River and Minhe Station of the Huangshui River. The results showed the following. (1) The most abrupt increase in measured runoff at Xiangtang Station occurred in 1993, while the point of abrupt change in measured runoff at Minhe Station occurred in 1990. (2) Following an increase in human activities, changes in the ecological surplus at Xiangtang Station were negative in January, April to May, July, and from September to November, while the changes in the ecological deficit were positive from January to April, July to August, and October to December. Changes in the ecological surplus at Minhe Station were negative from March to July and from September to December, while changes in the ecological deficit were positive from January to April and from July to December. (3) The annual average ecological flow of the Datong River, Xiangtang section, was 28.42 m3/s, and the annual average ecological water demand was 896 million m3. The annual average ecological flow of the Minhe section was 19.98 m3/s, and the annual average ecological water demand was 631 million m3. According to a calculation of the degree of ecological water demand and ecological flow satisfaction, prior to the implementation of the Water Diversion Project from the Datong River to Huangshui River, the water volumes in both rivers were generally sufficient to meet the ecological water demand. However, high water consumption during the irrigation period led to an ecological deficit. To address these issues, it is crucial to evaluate the potential impacts of human activities, such as water diversion projects, on river ecological flow. Recommendations include expediting the Water Diversion Project from the Yellow River to Xining to secure sufficient water flow in the Huangshui River and enhancing water conservation efforts in agricultural irrigation.
Impacts of Climate Change on Groundwater in the Al-Badan Sub-Catchment, Palestine: Analyzing Historical Data and Future Scenarios
Authors: Faquseh Hamzah , Shadeed Sameer , Grossi Giovanna
Published: October 2024

Climate change is significantly impacting water resources, especially in arid regions. This study evaluates its effects on groundwater in the Al-Badan sub-catchment, Palestine, by analyzing hydroclimatic data from 1990 to 2020 and the future predicted climate change scenarios. Using the Mann-Kendall test and Sen’s slope estimator, a significant annual decline in annual precipitation of 125 mm and a temperature increase of 1.84 °C were observed, resulting in a spring discharge reduction of 1.2 MCM. Multiple linear regression analysis showed that a 10% increase in precipitation correlates with a 5% discharge increase, while a 1 °C rise in temperature results in a 2.3% discharge decrease. Future scenarios indicate significant changes: for 2040–2060, RCP2.6 forecasts average precipitation of 334.5 mm with temperatures at 18.5 °C, resulting in spring discharge of about 4.6 MCM. In contrast, RCP4.5 and RCP8.5 predict reductions in precipitation to 307.2 mm and 311.2 mm, respectively, with temperatures rising to 18.9 °C and 19.3 °C, leading to discharge declines to 4.2 MCM and 4.0 MCM. For 2080–2100, RCP2.6 anticipates 335.8 mm of precipitation and temperatures rising to 19.5 °C, resulting in average discharge of 4.5 MCM. RCP4.5 and RCP8.5 predict further declines in precipitation and discharge, underscoring the need for effective water management strategies.
QTL Mapping-Based Identification of Visceral White-Nodules Disease Resistance Genes in Larimichthys polyactis
Authors: Li Qian , Zhu Jiajie , Liu Sifang , Liu Haowen , Zhang Tianle , Ye Ting , Lou Bao , Liu Feng
Published: October 2024

Disease outbreaks in aquaculture have recently intensified. In particular, visceral white-nodules disease, caused by Pseudomonas plecoglossicida, has severely hindered the small yellow croaker (Larimichthys polyactis) aquaculture industry. However, research on this disease is limited. To address this gap, the present study employed a 100K SNP chip to genotype individuals from an F1 full-sib family, identify single nucleotide polymorphisms (SNPs), and construct a genetic linkage map for this species. A high-density genetic linkage map spanning a total length of 1395.72 cM with an average interval of 0.08 cM distributed across 24 linkage groups was obtained. Employing post-infection survival time as an indicator of disease resistance, 13 disease resistance-related quantitative trait loci (QTLs) were detected, and these regions included 169 genes. Functional enrichment analyses pinpointed 11 candidate disease resistance-related genes. RT-qPCR analysis revealed that the genes of chmp1a and arg1 are significantly differentially expressed in response to P. plecoglossicida infection in spleen and liver tissues, indicating their pivotal functions in disease resistance. In summary, in addition to successfully constructing a high-density genetic linkage map, this study reports the first QTL mapping for visceral white-nodules disease resistance. These results provide insight into the intricate molecular mechanisms underlying disease resistance in the small yellow croaker.
Prediction of Successful Liberation from Continuous Renal Replacement Therapy Using a Novel Biomarker in Patients with Acute Kidney Injury after Cardiac Surgery—An Observational Trial
Authors: Tichy Johanna , Hausmann Andrea , Lanzerstorfer Johannes , Ryz Sylvia , Wagner Ludwig , Lassnigg Andrea , Bernardi Martin H.
Published: October 2024

An acute kidney injury (AKI) is the most common complication following cardiac surgery, and can lead to the initiation of continuous renal replacement therapy (CRRT). However, there is still insufficient evidence for when patients should be liberated from CRRT. Proenkephalin A 119–159 (PENK) is a novel biomarker that reflects kidney function independently of other factors. This study investigated whether PENK could guide successful liberation from CRRT. Therefore, we performed a prospective, observational, single-center study at the Medical University of Vienna between July 2022 and May 2023, which included adult patients who underwent cardiac surgery for a cardiopulmonary bypass; patients on preoperative RRT were excluded. The PENK levels were measured at the time of AKI diagnosis and at the initiation of and liberation from CRRT, and were subsequently compared to determine whether the patients were successfully liberated from CRRT. We screened 61 patients with postoperative AKI; 20 patients experienced a progression of AKI requiring CRRT. The patients who were successfully liberated from CRRT had mean PENK levels of 113 ± 95.4 pmol/L, while the patients who were unsuccessfully liberated from CRRT had mean PENK levels of 290 ± 175 pmol/L (p = 0.018). For the prediction of the successful liberation from CRRT, we found an area under the curve of 0.798 (95% CI, 0.599–0.997) with an optimal threshold value of 126.7 pmol/L for PENK (Youden Index = 0.53, 95% CI, 0.10–0.76) at the time of CRRT liberation (sensitivity = 0.64, specificity = 0.89). In conclusion, PENK is a novel biomarker that has the potential to predict the successful liberation from CRRT for patients with AKI after cardiac surgery.
Therapeutic and Immunologic Effects of Short-Chain Fatty Acids in Inflammatory Bowel Disease: A Systematic Review
Authors: Ventura Ignacio , Chomon-García Miryam , Tomás-Aguirre Francisco , Palau-Ferré Alma , Legidos-García María Ester , Murillo-Llorente María Teresa , Pérez-Bermejo Marcelino
Published: October 2024

Inflammatory bowel disease is a chronic condition characterized by recurrent intestinal inflammation. Its etiopathogenesis is driven by a series of events that disrupt the mucosal barrier, alter the healthy balance of intestinal microbiota, and abnormally stimulate intestinal immune responses. Therefore, numerous studies suggest the use of short-chain fatty acids and their immunomodulatory effects as a therapeutic approach in this disease. The objective of this systematic review was to synthesize previous evidence on the relevance and therapeutic use of short-chain fatty acids, particularly butyrate, in the immune regulation of inflammatory bowel disease. This systematic review of articles linking inflammatory bowel disease with short-chain fatty acids was conducted according to the PRISMA-2020 guidelines. The Medline and the Web of Science databases were searched in August 2024. The risk of bias was assessed using the Joanna Briggs Institute checklists. A total of 1460 articles were reviewed, of which, 29 met the inclusion criteria. Short-chain fatty acids, particularly butyrate, play a critical role in the regulation of intestinal inflammation and can be used as a strategy to increase the levels of short-chain fatty acid-producing bacteria for use in therapeutic approaches.
Elucidating the Antiglycation Effect of Creatine on Methylglyoxal-Induced Carbonyl Stress In Vitro
Authors: Koike Shin , Mitsuhashi Haruka , Kishida Atsushi , Ogasawara Yuki
Published: October 2024

Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo.
Manganese Oxide-Doped Hierarchical Porous Carbon Derived from Tea Leaf Waste for High-Performance Supercapacitors
Authors: Chung Hsiu-Ying , Chang Hong-Min , Wang Chun-Pang
Published: October 2024

Hierarchical porous carbon derived from discarded biomass for energy storage materials has attracted increasing research attention due to its cost-effectiveness, ease of fabrication, environmental protection, and sustainability. Brewed tea leaves are rich in heteroatoms that are beneficial to capacitive energy storage behavior. Therefore, we synthesized high electrochemical performance carbon-based composites from Tie guan yin tea leaf waste using a facile procedure comprising hydrothermal, chemical activation, and calcination processes. In particular, potassium permanganate (KMnO4) was incorporated into the potassium hydroxide (KOH) activation agent; therefore, during the activation process, KOH continued to erode the biomass precursor, producing abundant pores, and KMnO4 synchronously underwent a redox reaction to form MnO nanoparticles and anchor on the porous carbon through chemical bonding. MnO nanoparticles provided additional pseudocapacitive charge storage capabilities through redox reactions. The results show that the amount of MnO produced is proportional to the amount of KMnO4 incorporated. However, the specific surface area of the composite material decreases with the incorporated amount of KMnO4 due to the accumulation and aggregation of MnO nanoparticles, thereby even blocking some micropores. Optimization of MnO nanocrystal loading can promote the crystallinity and graphitization degree of carbonaceous materials. The specimen prepared with a weight ratio of KMnO4 to hydrochar of 0.02 exhibited a high capacitance of 337 F/g, an increase of 70%, owing to the synergistic effect between the Tie guan yin tea leaf-derived activated carbon and MnO nanoparticles. With this facile preparation method and the resulting high electrochemical performance, the development of manganese oxide/carbon composites derived from tea leaf biomass is expected to become a promising candidate as an energy storage material for supercapacitors.
Regulatory Peptide Pro-Gly-Pro Accelerates Neuroregeneration of Primary Neuroglial Culture after Mechanical Injury in Scratch Test
Authors: Bakaeva Zanda , Goncharov Mikhail , Frolov Fyodor , Krasilnikova Irina , Sorokina Elena , Zgodova Arina , Smolyarchuk Elena , Zavadskiy Sergey , Andreeva Liudmila , Myasoedov Nikolai , Fisenko Andrey , Savostyanov Kirill
Published: October 2024

The scratch test is used as an experimental in vitro model of mechanical damage to primary neuronal cultures to study the mechanisms of cell death in damaged areas. The involvement of NMDA receptors in processes leading to delayed neuronal death, due to calcium dysregulation and synchronous mitochondrial depolarization, has been previously demonstrated. In this study, we explored the neuroregenerative potential of Pro-Gly-Pro (PGP)—an endogenous regulatory peptide with neuroprotective and anti-inflammatory properties and a mild chemoattractant effect. Mechanical injury to the primary neuroglial culture in the form of a scratch caused acute disruption of calcium homeostasis and mitochondrial functions. This was accompanied by neuronal death alongside changes in the profile of neuronal markers (BDNF, NSE and GFAP). In another series of experiments, under subtoxic doses of glutamate (Glu, 33 μM), delayed changes in [Ca2+]i and ΔΨm, i.e., several days after scratch application, were more pronounced in cells in damaged neuroglial cultures. The percentage of cells that restored the initial level of [Ca2+]i (p < 0.05) and the rate of recovery of ΔΨm (p < 0.01) were decreased compared with undamaged cells. Prophylactic application of PGP (100 μM, once) prevented the increase in [Ca2+]i and the sharp drop in mitochondrial potential [ΔΨm] at the time of scratching. Treatment with PGP (30 μM, three or six days) reduced the delayed Glu-induced disturbances in calcium homeostasis and cell death. In the post-glutamate period, the surviving neurons more effectively restored the initial levels of [Ca2+]i (p < 0.001) and Ψm (p < 0.0001). PGP also increased intracellular levels of BDNF and reduced extracellular NSE. In the context of the peptide’s therapeutic effect, the recovery of the damaged neuronal network occurred faster due to reduced astrogliosis and increased migration of neurons to the scratch area. Thus, the peptide PGP has a neuroprotective effect, increasing the survival of neuroglial cells after mechanical trauma in vitro by reducing cellular calcium overload and preventing mitochondrial dysfunction. Additionally, the tripeptide limits the post-traumatic consequences of mechanical damage: it reduces astrogliosis and promotes neuronal regeneration.
The Protective Effect of the Supplementation with an Extract from Aronia melanocarpa L. Berries against Cadmium-Induced Changes of Chosen Biomarkers of Neurotoxicity in the Brain—A Study in a Rat Model of Current Lifetime Human Exposure to This Toxic Heavy Metal
Authors: Ruczaj Agnieszka , Rogalska Joanna , Gałażyn-Sidorczuk Małgorzata , Brzóska Małgorzata M.
Published: October 2024

Since even low-level environmental exposure to cadmium (Cd) can lead to numerous unfavourable health outcomes, including damage to the nervous system, it is important to recognize the risk of health damage by this xenobiotic, the mechanisms of its toxic influence, and to find an effective protective strategy. This study aimed to evaluate, in a female Wistar rat model of current human environmental exposure to Cd (1 and 5 mg/kg of diet for 3–24 months), if the low-to-moderate treatment with this element can harm the brain and whether the supplementation with a 0.1% Aronia melanocarpa L. (Michx.) Elliott berries (chokeberries) extract (AE) can protect against this effect. The exposure to Cd modified the values of various biomarkers of neurotoxicity, including enzymes (acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), phospholipase A2 (PLA2), and nitric oxide synthase 1 (NOS1)) and non-enzymatic proteins (calmodulin (CAM), nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (KEAP1)) crucial for the functioning of the nervous system, as well as the concentrations of calcium (Ca) and magnesium (Mg) and some metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the brain tissue. The co-administration of AE, partially or entirely, protected from most of the Cd-induced changes alleviating its neurotoxic influence. In conclusion, even low-level chronic exposure to Cd may adversely affect the nervous system, whereas the supplementation with A. melanocarpa berries products during the treatment seems a protective strategy.
Antibiofilm and Antimicrobial Potentials of Novel Synthesized Sulfur Camphor Derivatives
Authors: Duda-Madej Anna , Viscardi Szymon , Pacyga Katarzyna , Kupczyński Robert , Mączka Wanda , Grabarczyk Małgorzata , Pacyga Paweł , Topola Ewa , Ostrówka Michał , Bania Jacek , Szumny Antoni , Wińska Katarzyna
Published: October 2024

The question being posed by scientists around the world is how different chemical modifications of naturally occurring compounds will affect their antimicrobial properties. In the current study, sulfur derivatives of camphor containing a sulfur atom were tested to detect their antimicrobial and antibiofilm potentials. The new compounds were tested on eight Gram-positive strains (S. aureus (3 isolates), S. epidermidis (4 isolates), and E. faecalis (1 isolate)) and eight Gram-negative strains (E. coli (6 isolates), A. baumannii (1 isolate), and P. aeruginosa (1 isolate)). The ability of the strains to eradicate a biofilm was evaluated under standard stationary and flow-through conditions using the Bioflux system. Two synthesized compounds, namely rac-thiocamphor (1a) and (S, S)-(+)-thiocamphor (2a), exhibited an effect on the 24 h biofilm formed by the Gram-positive strains. Our results are an important contribution to the science of natural compounds and allow us to classify our sulfur derivatives of camphor as potential prophylactic agents in treating skin infections, antiseptics, and disinfectants. The Gram-negative strains were excluded from further stages of the tests due to their high activity (MIC ≥ 512 µg/mL). On the other hand, the compound with the strongest antimicrobial activity against the Gram-positive strains was 2a, as it led led to a reductions in cell viability of 17–52% (for MIC), 37–66% (for 2MIC), and 40–94% (for 4MIC). In addition, the experimental retention index of thiocamphor was calculated for the first time.
Myeloid GSK3α Deficiency Reduces Lesional Inflammation and Neovascularization during Atherosclerotic Progression
Authors: Patel Sarvatit , Shah Nisarg , D’Mello Brooke , Lee Anson , Werstuck Geoff H.
Published: October 2024

The molecular mechanisms by which cardiovascular risk factors promote the development of atherosclerosis are poorly understood. We have recently shown that genetic ablation of myeloid glycogen synthase kinase (GSK)-3α attenuates atherosclerotic lesion development in low-density lipoprotein receptor-deficient (Ldlr−/−) mice. However, the precise contributions of GSK3α/β in atherogenesis are not known. The aim of this study is to investigate the effect of GSK3α and/or β deficiency on lesional inflammation and plaque vascularization. Five-week-old female Ldlr−/− mice were fed a high-fat diet for 10 weeks to establish atherosclerotic lesions. Mice were harvested at 15 weeks of age and atherosclerotic lesions were characterized. The results indicate that, in addition to significantly reducing plaque volume, GSK3α-deficiency decreases inflammation, reduces vasa vasorum density at the aortic sinus, and reduces plasma c-reactive protein (CRP) levels. GSK3β-deficiency is associated with decreased plasma CRP levels but does not affect lesional inflammation or vascularization. These results suggest GSK3α may be an applicable target for the development of novel anti-atherogenic therapies.
Molecular Characterization of Sterol C4-Methyl Oxidase in Leishmania major
Authors: Ning Yu , Basu Somrita , Hsu Fong-fu , Feng Mei , Wang Michael Zhuo , Zhang Kai
Published: October 2024

Sterol biosynthesis requires the oxidative removal of two methyl groups from the C-4 position by sterol C-4-demethylase and one methyl group from the C-14 position by sterol C-14-demethylase. In Leishmania donovani, a CYP5122A1 (Cytochrome P450 family 5122A1) protein was recently identified as the bona fide sterol C-4 methyl oxidase catalyzing the initial steps of C-4-demethylation. Besides CYP5122A1, Leishmania parasites possess orthologs to ERG25 (ergosterol pathway gene 25), the canonical sterol C-4 methyl oxidase in Saccharomyces cerevisiae. To determine the contribution of CYP5122A1 and ERG25 in sterol biosynthesis, we assessed the essentiality of these genes in Leishmania major, which causes cutaneous leishmaniasis. Like in L. donovani, CYP5122A1 in L. major could only be deleted in the presence of a complementing episome. Even with strong negative selection, L. major chromosomal CYP5122A1-null mutants retained the complementing episome in both promastigote and amastigote stages, demonstrating its essentiality. In contrast, the L. major ERG25-null mutants were fully viable and replicative in culture and virulent in mice. Deletion and overexpression of ERG25 did not affect the sterol composition, indicating that ERG25 is not required for C-4-demethylation. These findings suggest that CYP5122A1 is the dominant and possibly only sterol C-4 methyl oxidase in Leishmania, and inhibitors of CYP5122A1 may have strong therapeutic potential against multiple Leishmania species.
Blood-Based Biomarkers in Alzheimer’s Disease: Advancing Non-Invasive Diagnostics and Prognostics
Authors: Dhauria Mrinmay , Mondal Ritwick , Deb Shramana , Shome Gourav , Chowdhury Dipanjan , Sarkar Shramana , Benito-León Julián
Published: October 2024

Alzheimer’s disease (AD), the most prevalent form of dementia, is expected to rise dramatically in incidence due to the global population aging. Traditional diagnostic approaches, such as cerebrospinal fluid analysis and positron emission tomography, are expensive and invasive, limiting their routine clinical use. Recent advances in blood-based biomarkers, including amyloid-beta, phosphorylated tau, and neurofilament light, offer promising non-invasive alternatives for early AD detection and disease monitoring. This review synthesizes current research on these blood-based biomarkers, highlighting their potential to track AD pathology and enhance diagnostic accuracy. Furthermore, this review uniquely integrates recent findings on protein-protein interaction networks and microRNA pathways, exploring novel combinations of proteomic, genomic, and epigenomic biomarkers that provide new insights into AD’s molecular mechanisms. Additionally, we discuss the integration of these biomarkers with advanced neuroimaging techniques, emphasizing their potential to revolutionize AD diagnostics. Although large-scale validation is still needed, these biomarkers represent a critical advancement toward more accessible, cost-effective, and early diagnostic tools for AD.
Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines
Authors: Domżalski Paweł , Piotrowska Anna , Tuckey Robert C. , Zmijewski Michał A.
Published: October 2024

Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375.
Role of IL3RA in a Family with Lumbar Spinal Stenosis
Authors: Liu Kai-Ming , Yang Chi-Fan , H’ng Weng-Siong , Chuang Hui-Ping , Khor Eunice Han Xian , Tsai Pei-Chun , Khosasih Vivia , Lu Liang-Suei , Yeh Erh-Chan , Lin Wan-Jia , Hsieh Feng-Jen , Chen Chien-Hsiun , Hwang Shiuh-Lin , Wu Jer-Yuarn
Published: October 2024

Lumbar spinal stenosis (LSS) is a degenerative spinal condition characterized by the narrowing of the spinal canal, resulting in low back pain (LBP) and limited leg mobility. Twin and family studies have suggested that genetics contributes to disease progression. However, the genetic causes of familial LSS remain unclear. We performed whole-exome and direct sequencing on seven female patients from a Han Chinese family with LBP, among whom four developed LSS. Based on our genetic findings, we performed gene knockdown studies in human chondrocytes to study possible pathological mechanisms underlying LSS. We found a novel nonsense mutation, c.417C > G (NM_002183, p.Y139X), in IL3RA, shared by all the LBP/LSS cases. Knockdown of IL3RA led to a reduction in the total collagen content of 81.6% in female chondrocytes and 21% in male chondrocytes. The expression of MMP-1, -3, and/or -10 significantly increased, with a more pronounced effect observed in females than in males. Furthermore, EsRb expression significantly decreased following IL3RA knockdown. Moreover, the knockdown of EsRb resulted in increased MMP-1 and -10 expression in chondrocytes from females. We speculate that IL3RA deficiency could lead to a reduction in collagen content and intervertebral disk (IVD) strength, particularly in females, thereby accelerating IVD degeneration and promoting LSS occurrence. Our results illustrate, for the first time, the association between IL3RA and estrogen receptor beta, highlighting their importance and impact on MMPs and collagen in degenerative spines in women.
Isothiocyanate-Rich Moringa Seed Extract Activates SKN-1/Nrf2 Pathway in Caenorhabditis elegans
Authors: Farias-Pereira Renalison , Camayoc Pierre , Raskin Ilya
Published: October 2024

Moringa oleifera is a tropical tree that has its leaves, fruits, and seeds used as medicine and food. A standardized hydroalcoholic moringa seed extract (MSE) contains up to 40% of an isothiocyanate (MIC-1; moringin), a phytochemical known to have antioxidant and anti-inflammatory properties. Animal studies suggest that MSE may help with diseases, such as edema, colitis, obesity, and diabetes. In vitro studies have shown that MIC-1 activates the Nrf2 pathway, involved in detoxification and antioxidant pathways. To broaden the understanding of the molecular pathways regulated by MSE, we hypothesized that MSE improves the health span in Caenorhabditis elegans by activating the Nrf2 homolog (SKN-1). Our whole RNA-seq data showed that MSE at 0.1 mg/mL (100 µM MIC-1) regulated the expression of a total of 1555 genes, including genes related to C. elegans cuticle, molting cycle, and glutathione metabolism. MSE upregulated several glutathione S transferases (GST), involved in the detoxification of xenobiotics, and other SKN-1 downstream targets. MSE and MIC-1 upregulate skn-1 expression and induce SKN-1 nuclear translocation, suggesting that they activate the SKN-1/Nrf2 pathway. Moreover, the regulation of glutathione metabolism is likely dependent on the SKN-1 pathway, as the gst-4 upregulation by MSE was inhibited in skn-1 knockout mutant. However, MSE decreased survivability and delayed growth rate, while purified MIC-1 increased the lifespan of C. elegans. This study shows that MIC-1 is responsible for SKN-1/Nrf2 activation by MSE; however, components other than MIC-1 within MSE likely cause detrimental effects in C. elegans.
Unveiling the Role of Gut Microbiota and Metabolites in Autoimmune Thyroid Diseases: Emerging Perspectives
Authors: Yan Kai , Sun Xin , Fan Chenxi , Wang Xin , Yu Hongsong
Published: October 2024

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system’s structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota–thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.
A Systematic Literature Review on the Global Status of Newborn Screening for Mucopolysaccharidosis II
Authors: Ayodele Olulade , Fertek Daniel , Evuarherhe Obaro , Siffel Csaba , Audi Jennifer , Yee Karen S. , Burton Barbara K.
Published: October 2024

A systematic literature review was conducted to determine the global status of newborn screening (NBS) for mucopolysaccharidosis (MPS) II (Hunter syndrome; OMIM 309900). Electronic databases were searched in July 2023 for articles referencing NBS for lysosomal storage diseases: 53 featured MPS II. Until recently, only Taiwan and two US states (Illinois and Missouri) formally screened newborns for MPS II, although pilot programs have been conducted elsewhere (Japan, New York, and Washington). In 2022, MPS II was added to the US Recommended Uniform Screening Panel, with increased uptake of NBS anticipated across the USA. While the overall MPS II birth prevalence, determined from NBS initiatives, was higher than in previous reports, it was lower in the USA (approximately 1 in 73,000 according to recent studies in Illinois and Missouri) than in Asia (approximately 1 in 15,000 in Japan). NBS programs typically rely on tandem mass spectrometry quantification of iduronate-2-sulfatase activity for first-tier testing. Diagnosis is often confirmed via molecular genetic testing and/or biochemical testing but may be complicated by factors such as pseudodeficiency alleles and variants of unknown significance. Evidence relating to MPS II NBS is lacking outside Taiwan and the USA. Although broad benefits of NBS are recognized, few studies specifically explored the perspectives of families of children with MPS II.