bluuebunny/crossref_metadata_2025 huggingface dataset:
Micro- and Macronutrients in Endometrial Cancer—From Metallomic Analysis to Improvements in Treatment Strategies
Authors: Hunek Gabriela , Zembala Julita , Januszewski Jacek , Bełżek Aleksandra , Syty Kinga , Jabiry-Zieniewicz Zoulikha , Ludwin Artur , Flieger Jolanta , Baj Jacek
Published: September 2024

Endometrial cancer is reported to be one of the most prevalent cancers of the female reproductive organs worldwide, with increasing incidence and mortality rates over the past decade. Early diagnosis is critical for effective treatment. Recently, there has been a growing focus on the role of nutrition and micronutrient and macronutrient status in patients with gynecologic cancers, including endometrial cancer. In the following paper, we have conducted an in-depth narrative literature review with the aim of evaluating the results of metallomic studies specifically concerning the micro- and macronutrient status of patients with endometrial cancer. The main objective of the paper was to analyze the results regarding the nutritional status of endometrial cancer patients and describe the role of chosen elements in the onset and progression of endometrial carcinogenesis. Further, we have focused on the evaluation of the usage of the described elements in the potential treatment of the abovementioned cancer, as well as the possible prevention of cancer considering proper supplementation of chosen elements in healthy individuals. Calcium supplementation has been proposed to reduce the risk of endometrial cancer, although some studies offer conflicting evidence. Deficiencies in phosphorus, selenium, and zinc have been inversely associated with endometrial cancer risk, suggesting they may play a protective role, whereas excessive levels of iron, copper, and cadmium have been positively correlated with increased risk. However, the molecular mechanisms by which these elements affect endometrial carcinogenesis are not fully understood, and current findings are often contradictory. Further research is needed to clarify these relationships and to evaluate the potential of nutritional interventions for the prevention and treatment of endometrial cancer.
The Role of Programmed Types of Cell Death in Pathogenesis of Heart Failure with Preserved Ejection Fraction
Authors: Jankowski Jan , Kozub Kamil Oskar , Kleibert Marcin , Camlet Katarzyna , Kleibert Klaudia , Cudnoch-Jędrzejewska Agnieszka
Published: September 2024

Heart failure with preserved ejection fraction (HFpEF) is a condition that develops in the course of many diseases and conditions, and its pathophysiology is still not well understood, but the involvement of programmed types of cell death in the development of this type of heart failure is becoming increasingly certain. In addition, drugs already widely used in clinical practice, with a good safety profile and efficacy demonstrated in large-group clinical trials, seem to be exerting their beneficial effects on cardiovascular health. Perhaps new drugs that reduce the susceptibility of cells to programmed types of cell death are under investigation and may improve the prognosis of patients with HFpEF. In this article, we summarize the current knowledge about the pathogenesis of HFpEF and the role of programmed types of cell death in its development. Additionally, we have described the future directions of research that may lead to the improvement of a patient’s prognosis and potential treatment.
Chloroplast Genome Variation and Phylogenetic Relationships of Autochthonous Varieties of Vitis vinifera from the Don Valley
Authors: Sharko F. S. , Petrova K. O. , Patrushev M. V. , Fedosov D. Y. , Toshchakov S. V.
Published: September 2024

The autochthonous grape varieties of the Don Valley, situated in southern Russia, constitute a distinctive element of regional cultural heritage. These varieties have been adapted over centuries to the region’s specific local climatic and soil conditions. For the most part, these varieties are not imported from other countries. They are closely related to varieties found in Crimea and the North Caucasus. In this study, we obtained the first complete, unfragmented sequences of the chloroplast genomes of eight autochthonous varieties from the Don Valley and one from Crimea. We also performed a comparative analysis of their genomic features. The size of Vitis vinifera chloroplast genome sequences varied from 160,925 to 160,991 bp, depending on the cultivar, with a uniform GC ratio of 37.38%. Each genome consists of four subregions: a single copy region (LSC) ranging from 89,158 to 89,336 bp, a small single copy region (SSC) ranging from 19,070 to 19,073 bp, and a pair of inverted repeat regions (IRa and IRb) in the range of 26,292 to 26,353 bp. The chloroplast genomes of the studied V. vinifera varieties contained 130 genes, including 85 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. The sequence divergence analysis has enabled the identification of four highly variable regions, which may be utilized as potential markers for phylogenetic analysis. The analysis revealed the presence of 58 to 61 SSRs and multiple long repeated sequences in the chloroplast genomes of these varieties. The phylogenetic analyses of the sequences obtained and complete chloroplast genomes available from public databases indicated that the majority of autochthonous V. vinifera varieties do not have a direct origin from any European variety.
Novel Bioplastic Based on PVA Functionalized with Anthocyanins: Synthesis, Biochemical Properties and Food Applications
Authors: Patanè Giuseppe Tancredi , Calderaro Antonella , Putaggio Stefano , Ginestra Giovanna , Mandalari Giuseppina , Cirmi Santa , Barreca Davide , Russo Annamaria , Gervasi Teresa , Neri Giovanni , Chelly Meryam , Visco Annamaria , Scolaro Cristina , Mancuso Francesca , Ficarra Silvana , Tellone Ester , Laganà Giuseppina
Published: September 2024

Over the last ten years, researchers’ efforts have aimed to replace the classic linear economy model with the circular economy model, favoring green chemical and industrial processes. From this point of view, biologically active molecules, coming from plants, flowers and biomass, are gaining considerable value. In this study, firstly we focus on the development of a green protocol to obtain the purification of anthocyanins from the flower of Callistemon citrinus, based on simulation and on response surface optimization methodology. After that, we utilize them to manufacture and add new properties to bioplastics belonging to class 3, based on modified polyvinyl alcohol (PVA) with increasing amounts from 0.10 to 1.00%. The new polymers are analyzed to monitor morphological changes, optical properties, mechanical properties and antioxidant and antimicrobial activities. Fourier transform infrared spectroscopy (FTIR) spectra of the new materials show the characteristic bands of the PVA alone and a modification of the band at around 1138 cm−1 and 1083 cm−1, showing an influence of the anthocyanins’ addition on the sequence with crystalline and amorphous structures of the starting materials, as also shown by the results of the mechanical tests. These last showed an increase in thickening (from 29.92 μm to approx. 37 μm) and hydrophobicity with the concomitant increase in the added anthocyanins (change in wettability with water from 14° to 31°), decreasing the poor water/moisture resistance of PVA that decreases its strength and limits its application in food packaging, which makes the new materials ideal candidates for biodegradable packaging to extend the shelf-life of food. The functionalization also determines an increase in the opacity, from 2.46 to 3.42 T%/mm, the acquisition of antioxidant activity against 2,2-diphenyl-1-picrylhdrazyl and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, in the ferric reducing power assay, the antimicrobial (bactericidal) activity against different Staphylococcus aureus strains at the maximum tested concentration (1.00% of anthocyanins). On the whole, functionalization with anthocyanins results in the acquisition of new properties, making it suitable for food packaging purposes, as highlighted by a food fresh-keeping test.
Application of Nanostructures in Biology and Medicine
Authors: Lozovoy Kirill
Published: September 2024

At present, nanomaterials are used in a wide range of applications in all spheres of civil needs, including energy, medicine, and industry [...]
R-Methylation in Plants: A Key Regulator of Plant Development and Response to the Environment
Authors: Barré-Villeneuve Clément , Azevedo-Favory Jacinthe
Published: September 2024

Although arginine methylation (R-methylation) is one of the most important post-translational modifications (PTMs) conserved in eukaryotes, it has not been studied to the same extent as phosphorylation and ubiquitylation. Technical constraints, which are in the process of being resolved, may partly explain this lack of success. Our knowledge of R-methylation has recently evolved considerably, particularly in metazoans, where misregulation of the enzymes that deposit this PTM is implicated in several diseases and cancers. Indeed, the roles of R-methylation have been highlighted through the analyses of the main actors of this pathway: the PRMT writer enzymes, the TUDOR reader proteins, and potential “eraser” enzymes. In contrast, R-methylation has been much less studied in plants. Even so, it has been shown that R-methylation in plants, as in animals, regulates housekeeping processes such as transcription, RNA silencing, splicing, ribosome biogenesis, and DNA damage. R-methylation has recently been highlighted in the regulation of membrane-free organelles in animals, but this role has not yet been demonstrated in plants. The identified R-met targets modulate key biological processes such as flowering, shoot and root development, and responses to abiotic and biotic stresses. Finally, arginine demethylases activity has mostly been identified in vitro, so further studies are needed to unravel the mechanism of arginine demethylation.
A Comparison of White and Yellow Seminal Plasma Phosphoproteomes Obtained from Turkey (Meleagris gallopavo) Semen
Authors: Rafalska Katarzyna T. , Orzołek Aleksandra , Ner-Kluza Joanna , Wysocki Paweł
Published: September 2024

Seminal plasma is rich in proteins originating from various male reproductive organs. The phosphorylation of these proteins can significantly impact sperm motility, capacitation, and acrosome reaction. Phosphoproteomics identifies, catalogues, and characterizes phosphorylated proteins. The phosphoproteomic profiling of seminal plasma offers valuable insights into the molecular mechanisms that influence semen quality and male fertility. Thus, the aim of this study was a phosphoproteomic analysis of white and yellow turkey seminal plasma. The experimental material consisted of 100 ejaculates from BIG-6 turkeys between 39 and 42 weeks of age. The collected white and yellow turkey seminal plasmas were analyzed for total protein content; the activity of selected enzymes, i.e., alkaline phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT); and the content of reduced glutathione (GSH) and malondialdehyde (MDA). Phosphoproteins were isolated from white and yellow seminal fluids, and the resulting protein fractions were separated by SDS-PAGE and Western blotting. Phosphorylated residues were immunodetected, and the isolated phosphoproteins were identified (nano LC-MS/MS). Yellow seminal plasmas were characterized by higher levels of total protein, GSH, and MDA, as well as higher levels of ALP, ACP, and GPx activity. There were no significant differences in the activity of SOD and CAT. A total of 113 phosphoproteins were identified in turkey seminal fluids. The functional analysis demonstrated that these phosphoproteins were mainly involved in oocyte fertilization, organization and metabolism of the actin cytoskeleton, amplification of the intracellular signal transduction pathway, general regulation of transport, vesicular transport, proteome composition of individual cellular compartments, and the organization and localization of selected cellular components and macromolecules. Increased phosphorylation of the fractions containing proteins encoded by SPARC, PPIB, TRFE, QSOX1, PRDX1, PRDX6, and FASN genes in white plasmas and the proteins encoded by CKB, ORM2, APOA1, SSC5D, RAP1B, CDC42, FTH, and TTH genes in yellow plasmas was observed based on differences in the optical density of selected bands. The obtained results indicate that the phosphorylation profiles of turkey seminal plasma proteins vary depending on the type of ejaculate.
VEGF, but Not BDNF, Prevents the Downregulation of KCC2 Induced by Axotomy in Extraocular Motoneurons
Authors: Capilla-López Jaime , Hernández Rosendo G. , Carrero-Rojas Génova , Calvo Paula M. , Alvarez Francisco J. , de la Cruz Rosa R. , Pastor Angel M.
Published: September 2024

The potassium–chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation, leading to the depolarizing activity of GABA and glycine. The downregulation of this cotransporter occurs in neurological disorders characterized by hyperexcitability, such as epilepsy, neuropathic pain, and spasticity. KCC2 is also downregulated after axotomy. If muscle reinnervation is allowed, the KCC2 levels recover in motoneurons. Therefore, we argued that target-derived neurotrophic factors might be involved in the regulation of KCC2 expression. For this purpose, we performed the axotomy of extraocular motoneurons via the monocular enucleation of adult rats, and a pellet containing either VEGF or BDNF was chronically implanted in the orbit. Double confocal immunofluorescence of choline acetyl-transferase (ChAT) and KCC2 was carried out in the brainstem sections. Axotomy led to a KCC2 decrease in the neuropil and somata of extraocular motoneurons, peaking at 15 days post-lesion, with the exception of the abducens motoneuron somata. VEGF administration prevented the axotomy-induced KCC2 downregulation. By contrast, BDNF either maintained or reduced the KCC2 levels following axotomy, suggesting that BDNF is involved in the axotomy-induced KCC2 downregulation in extraocular motoneurons. The finding that VEGF prevents KCC2 decrease opens up new possibilities for the treatment of neurological disorders coursing with neuronal hyperactivity due to KCC2 downregulation.
Involvement of Aryl Hydrocarbon Receptor in Longevity and Healthspan: Insights from Humans, Mice, and C. elegans
Authors: Serna Eva , Verdú David , Valls Alicia , Belenguer-Varea Ángel , Tarazona-Santabalbina Francisco José , Borrás Consuelo , Viña José
Published: September 2024

In previous studies, using transcriptomic analysis, we observed higher levels of aryl hydrocarbon receptor (AHR) gene expression in the peripheral blood cells of centenarians compared to octogenarians. This suggests the potential significance of this receptor in maintaining physiological balance and promoting healthy aging, possibly linked to its critical role in detoxifying xenobiotics. In our current study, we confirmed that AHR expression is indeed higher in centenarians. We employed C. elegans as a model known for its suitability in longevity studies to explore whether the AHR pathway has a significant impact on lifespan and healthspan. Our survival assays revealed that two different mutants of AHR-1 exhibited lower longevity. Additionally, we used a mouse model to examine whether supplementation with pomegranate extract modulates the expression of AHR pathway genes in the liver. Furthermore, we studied a nutritional strategy based on pomegranate extract administration to investigate its potential modulation of life- and healthspan in worms.
Whole Mitochondrial Genome Sequencing Analysis of Canine Testicular Tumours
Authors: Tkaczyk-Wlizło Angelika , Kowal Krzysztof , Śmiech Anna , Ślaska Brygida
Published: September 2024

Currently, the molecular background based on mitochondrial DNA (mtDNA) analysis of canine testicular tumours is underestimated. The available data mostly focus on histopathological evaluations, with a few reports of nuclear genome (nDNA) studies. Tumourigenesis represents a highly complex and diverse genetic disorder, which can also encompass defects in mtDNA. The aim of this study was to identify molecular changes in whole mitochondrial genome sequences obtained from dogs affected by testicular tumours. Samples of blood, tumour, and healthy tissue were collected from each animal, and mtDNA (ultimately 45 samples) was subsequently sequenced. Thereafter, protein analyses were performed to assess the impact of the identified molecular alterations on the amino acid level. The total number of observed changes included 722 SNPs, 12 mutations, 62 indels, 5 indel mutations, and 35 heteroplasmic sites. The highest number of mtDNA variants in protein-coding genes COX1, COX3, ATP6, ND1, ND4, and ND5 was observed. Interestingly, SNPs were found in 10 out of 22 tRNA genes. Most of the identified mtDNA defects were synonymous changes at the amino acid level. Also, polymorphisms and heteroplasmy were frequently observed in the variable number of tandem repeat (VNTR) regions, especially in its fragment spanning 16,138–16,358 bp. Based on the obtained results, it was possible to select 11 polymorphisms that occurred in all the tested samples (benign, malignant) and an additional five SNPs identified only in benign neoplasms. The comprehensive analysis of malignant testicular tumours demonstrated a significant diversity in their molecular profiles, with changes ranging from 17 to 101 per sample.
Myxedema in Both Hyperthyroidism and Hypothyroidism: A Hormetic Response?
Authors: Sciacchitano Salvatore , Napoli Angela , Rocco Monica , De Vitis Claudia , Mancini Rita
Published: September 2024

Myxedema is a potentially life-threatening condition typically observed in severe hypothyroidism. However, localized or diffuse myxedema is also observed in hyperthyroidism. The exact cause and mechanism of this paradoxical situation is not clear. We report here the analysis of body fluid distribution by bioelectrical impedance analysis (BIA) in 103 thyroid patients, subdivided according to their functional status. All BIA parameters measured in subclinical thyroid dysfunctions did not significantly differ from those observed in euthyroid controls. On the contrary, they were clearly altered in the two extreme, opposite conditions of thyroid dysfunctions, namely overt hyperthyroidism and severe hypothyroidism, indicating the occurrence of a typical hormetic condition. Surprisingly, differences in BIA parameters related to fluid body composition were even more evident in hyperthyroidism than in hypothyroidism. A hormetic response to thyroid hormone (TH)s was previously reported to explain the paradoxical, biphasic, time- and dose-dependent effects on other conditions. Our results indicate that myxedema, observed in both hypothyroid and hyperthyroid conditions, represents another example of a hormetic-type response to THs. BIA offers no additional valuable information in evaluating fluid body composition in subclinical thyroid dysfunctions, but it represents a valuable method to analyze and monitor body fluid composition and distribution in overt and severe thyroid dysfunctions.
Progress in Research of Nanotherapeutics for Overcoming Multidrug Resistance in Cancer
Authors: Maimaitijiang Ayitila , He Dongze , Li Dingyang , Li Wenfang , Su Zhengding , Fan Zhongxiong , Li Jinyao
Published: September 2024

Chemotherapy has been widely applied in oncotherapy. However, the development of multidrug resistance (MDR) has diminished the effectiveness of anticancer drugs against tumor cells. Such resistance often results in tumor recurrence, metastasis, and patient death. Fortunately, nanoparticle-based drug delivery systems provide a promising strategy by codelivery of multiple drugs and MDR reversal agents and the skillful, flexible, smart modification of drug targets. Such systems have demonstrated the ability to bypass the ABC transporter biological efflux mechanisms due to drug resistance. Hence, how to deliver drugs and exert potential antitumor effects have been successfully explored, applied, and developed. Furthermore, to overcome multidrug resistance, nanoparticle-based systems have been developed due to their good therapeutic effect, low side effects, and high tumor metastasis inhibition. In view of this, we systematically discuss the molecular mechanisms and therapeutic strategies of MDR from nanotherapeutics. Finally, we summarize intriguing ideas and future trends for further research in overcoming MDR.
Evaluating the Role of Vitamin D in Alleviating Chronic Pruritus: A Meta-Analysis
Authors: Li Chen-Pi , Huang Shin-Chuan , Hsiao Yao , Tsai Ru-Yin
Published: September 2024

Chronic pruritus is a distressing condition that significantly impacts patients’ quality of life. Recent research has increasingly focused on the potential role of vitamin D, given its immunomodulatory properties, in managing this condition. This meta-analysis seeks to systematically assess the effectiveness of vitamin D supplementation in alleviating chronic pruritus across diverse clinical contexts. We conducted an extensive search through multiple databases, covering literature up to July 2024, to identify relevant randomized controlled trials (RCTs) that evaluated the effect of vitamin D on chronic pruritus. Eligible studies were those that provided data on changes in pruritus severity, as measured by standardized tools, before and after vitamin D treatment. The data were synthesized using a random-effects model to address variability among the studies. This meta-analysis is registered with PROSPERO (registration number: CRD42024579353). The findings indicate that vitamin D supplementation is associated with a significant reduction in pruritus severity, the skin lesion area, and levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP), compared to controls. These results suggest that vitamin D could be a promising therapeutic option for chronic pruritus, though further rigorous studies are required to validate these findings and to elucidate the mechanisms involved.
Advanced Extraction Techniques Combined with Natural Deep Eutectic Solvents for Extracting Phenolic Compounds from Pomegranate (Punica granatum L.) Peels
Authors: Oliveira Isadora Lopes de , Domínguez-Rodríguez Gloria , Montero Lidia , Viganó Juliane , Cifuentes Alejandro , Rostagno Mauricio Arial , Ibáñez Elena
Published: September 2024

Pomegranate (Punica granatum L.) peel is a potential source of bioactive phenolic compounds such as ellagic acid and α- and β-punicalagin. This work explores the efficiency of natural deep eutectic solvents combined with ultrasound-assisted extraction (UAE) and pressurized liquid extraction (PLE) for their extraction. Five NaDESs were evaluated by employing UAE (25 °C, for 50 min) to determine their total phenolic content (Folin–Ciocalteu assay) and ellagic acid and α- and β-punicalagin contents (high-performance liquid chromatography (HPLC-DAD)). The NaDES composed of choline chloride (ChCl) and glycerol (Gly) (1:2, molar ratio) was the most efficient in the UAE when compared with the rest of the NaDESs and water extracts. Therefore, ChCl:Gly was further evaluated using PLE at different temperatures (40, 80, 120 and 160 °C). The PLE-NaDES extract obtained at 80 °C for 20 min at 1500 psi exhibited the highest contents of ellagic acid and α- and β-punicalagin compared to the rest of the temperatures and PLE-water extracts obtained under the same extraction conditions. Combining UAE or PLE with a NaDES emerges as a sustainable alternative for extracting ellagic acid and α- and β-punicalagin from pomegranate peel.
Sperm Migration and Hyaluronic Acid Binding: Implications for Male Fertility Evaluation
Authors: Marchlewska Katarzyna , Erkiert-Kusiak Marta , Walczak-Jędrzejowska Renata , Słowikowska-Hilczer Jolanta
Published: September 2024

Mature, vital, and motile spermatozoa are essential for reaching the oocyte and binding to hyaluronic acid (HA) in the cumulus oophorus matrix. This study aims to determine the relationship between sperm-migration ability and HA-binding potential, as well as the relationship between sperm concentration and motility. Semen samples were collected from 702 men aged 20–56 years (median 34.8). We evaluated the sperm concentration and motility from basic semen analysis, the swim-up test (expressed as millions per mL and the migration efficiency percentage), and the hyaluronan-binding assay (HBA). A moderate positive correlation was found between the migration test results and HBA (R = 0.48). The highest correlation was observed between the concentration of motile spermatozoa and the migration test results (R = 0.85) and HBA (R = 0.4). The sperm migration efficiency strongly correlated with progressive motility (R = 0.6). Although significantly higher sperm migration was observed in patients with normal HBA results, the results of the functional tests were found to differ in some cases. For infertility treatment, the current diagnostic algorithm should be enhanced with more comprehensive seminological methods that assess the sperm-migration ability and HA-binding potential. We also recommend incorporating the swim-up method into the diagnostic protocol before planning assisted reproductive technology (ART) treatment.
A Modular XR Collaborative Platform for Occupational Safety and Health Training: A Case Study in Circular Logistics Facilities
Authors: Vatankhah Barenji Ali , Garcia Jorge E. , Montreuil Benoit
Published: September 2024

Over the past few years, safety and health have become major concerns in the warehouse and logistics sectors. Each year, warehouse fatalities, injuries, and accidents cause unrecoverable losses and huge financial costs. In spite of all the advancements in methods, tools, equipment, and regulations, the number of accidents, especially fatal ones, has not subsided significantly. As a result, safety professionals and researchers have explored new and innovative ways to combat this problem. In the circular logistics facility (CLF) industry, located inside warehouses and providing human muscle-oriented services to maintain pallets, both short-term safety incidents and long-term health concerns are present. Long-term health training is rarely discussed in the literature compared to short-term safety training. This is because health issues are more complex than safety issues, since biological outcomes may take time to develop, are affected by multiple resources, and cumulative injuries may occur. This paper contributes to warehouse health and safety by designing and developing a modular XR collaborative training and testing platform (MXC-P). The co-design process is applied to design each module in the MXC-P. Three main modules related to health and safety training for CLF were considered, namely personal protection equipment, pallet handling, and pallet repairing. On this platform, a virtual interactive world provides a solid hands-on training environment and generates syntactic data for evaluating long-term health risks. On the other hand, collaborative and modular environments provide a solution to geographically distributed systems, allowing employees to connect and train remotely. The effectiveness of the MXC-P is compared with traditional safety training in a pilot study. Based on the results, we can establish that the MXC-P is effective in teaching and testing hazard identification situations, especially those relating to short-term health. The results also indicate that trainees’ recall of knowledge would improve with the MXC-P. In addition to this, the MXC-P can also be used to test and evaluate a new system and generate syntactic data for evaluating long-term health.
Confrontation of Capitalism and Socialism in Wikipedia Networks
Authors: Ermann Leonardo , Shepelyansky Dima L.
Published: September 2024

We introduce the Ising Network Opinion Formation (INOF) model and apply it to the analysis of networks of six Wikipedia language editions. In the model, Ising spins are placed at network nodes/articles and the steady-state opinion polarization of spins is determined from the Monte Carlo iterations in which a given spin orientation is determined by in-going links from other spins. The main consideration was the opinion confrontation between capitalism, imperialism (blue opinion) and socialism, communism (red opinion). These nodes have fixed spin/opinion orientation while other nodes achieve their steady-state opinions in the process of Monte Carlo iterations. We found that the global network opinion favors socialism, communism for all six editions. The model also determined the opinion preferences for world countries and political leaders, showing good agreement with heuristic expectations. We also present results for opinion competition between Christianity and Islam, and USA Democratic and Republican parties. We argue that the INOF approach can find numerous applications for directed complex networks.
Are Preoperative CT Findings Useful in Predicting the Duration of Laparoscopic Appendectomy in Pediatric Patients? A Single Center Study
Authors: Taskent Ismail , Ece Bunyamin , Narsat Mehmet Ali
Published: September 2024

Background/Objectives: Preoperative computed tomography (CT) imaging plays a vital role in accurately diagnosing acute appendicitis and assessing the severity of the condition, as well as the complexity of the surgical procedure. CT imaging provides detailed information on the anatomical and pathological aspects of appendicitis, allowing surgeons to anticipate technical challenges and select the most appropriate surgical approach. This retrospective study aimed to investigate the correlation between preoperative CT findings and the duration of laparoscopic appendectomy (LA) in pediatric patients. Methods: This retrospective study included 104 pediatric patients diagnosed with acute appendicitis via contrast-enhanced CT who subsequently underwent laparoscopic appendectomy (LA) between November 2021 and February 2024. CT images were meticulously reviewed by two experienced radiologists blinded to the clinical and surgical outcomes. The severity of appendicitis was evaluated using a five-point scale based on the presence of periappendiceal fat, fluid, extraluminal air, and abscesses. Results: The average operation time was 51.1 ± 21.6 min. Correlation analysis revealed significant positive associations between operation time and neutrophil count (p = 0.014), C-reactive protein levels (p = 0.002), symptom-to-operation time (p = 0.004), and appendix diameter (p = 0.017). The total CT score also showed a significant correlation with operation time (p < 0.001). Multiple regression analysis demonstrated that a symptom duration of more than 2 days (p = 0.047), time from CT to surgery (p = 0.039), and the presence of a periappendiceal abscess (p = 0.005) were independent predictors of prolonged operation time. In the perforated appendicitis group, the presence of a periappendiceal abscess on CT was significantly associated with prolonged operation time (p = 0.020). In the non-perforated group, the presence of periappendiceal fluid was significantly related to longer operation times (p = 0.026). Conclusions: In our study, preoperative CT findings, particularly the presence of a periappendiceal abscess, were significantly associated with prolonged operation times in pediatric patients undergoing laparoscopic appendectomy. Elevated CRP levels, the time between CT imaging and surgery, and a symptom duration of more than 2 days were also found to significantly impact the procedure’s duration.
Importance of Coping Strategies on Quality of Life in People with Multiple Sclerosis: A Systematic Review
Authors: Culicetto Laura , Lo Buono Viviana , Donato Sofia , La Tona Antonino , Cusumano Anita Maria Sophia , Corello Graziana Marika , Sessa Edoardo , Rifici Carmela , D’Aleo Giangaetano , Quartarone Angelo , Marino Silvia
Published: September 2024

Multiple sclerosis (MS) is a neurodegenerative disorder of the central nervous system characterized by a variety of symptoms such as fatigue, spasticity, tremors, and cognitive disorders. Individuals with MS may employ different coping strategies to manage these symptoms, which in turn can significantly impact their quality of life (QoL). This review aims to analyze these coping strategies and their impact on QoL. Furthermore, it seeks to identify the key factors that influence the choice and effectiveness of these coping strategies, providing insights into which strategies are most beneficial for enhancing QoL in people with MS. Methods: Systematic searches were performed in Scopus, PubMed, Web of Science, and Scopus databases. This systematic review has been registered in OSF with the number DOI 10.17605/OSF.IO/QY37X. Results: A total of 1192 studies were identified. After reading the full text of the selected studies and applying predefined inclusion criteria, 19 studies were included based on their pertinence and relevance to the topic. The results revealed that emotional variables, demographic factors, personality traits, and family support significantly influence the choice of coping strategies used to manage the symptoms of MS. Problem-solving and task-oriented coping were prevalent among MS patients and associated with better QoL outcomes. Emotional-focused and avoidance strategies were generally linked to poorer QoL, though avoidance provided temporary relief in certain contexts. Social support, emotional health, and cognitive reframing were crucial in enhancing QoL. Conclusions: The findings underscore the importance of tailored psychoeducational and therapeutic interventions focusing on emotional health, social support, and adaptive coping strategies. These interventions can significantly improve the long-term outcomes for individuals with MS. Future research should explore the dynamic interactions between coping strategies and QoL over time, providing a comprehensive understanding of how to best support MS patients in managing their disease.
Long-Term Outcomes after Convergent Procedure for Atrial Fibrillation
Authors: Geršak Borut , Podlogar Veronika , Prolič Kalinšek Tine , Jan Matevž
Published: September 2024

Background: The aim of this single-center retrospective study was to evaluate the long-term outcomes after the convergent procedure (CP) for treatment of AF. Methods: We analyzed the outcomes of patients that underwent CP from January 2009 until July 2020. A total of 119 patients with paroxysmal AF (23.5%), persistent AF (5.9%), or long-standing persistent AF (70.6%) that attended long-term follow-up were included. The outcomes were assessed 1 year after the CP and at long-term follow-up. At the 1-year follow-up, rhythm and AF burden were assessed for patients with an implantable loop recorder (61.2%). For others, rhythm was assessed by clinical presentation and 12-lead ECG. At long-term follow-up, patients with sinus rhythm (SR) or an unclear history were assessed with a 7-day Holter ECG monitor, and AF burden was determined. Long-term success was defined as freedom from AF/atrial flutter (AFL) with SR on a 12-lead ECG and AF/AFL burden < 1% on the 7-day Holter ECG. Results: At 1-year follow-up, 91.4% of patients had SR and 76.1% of patients had AF/AFL burden < 1%. At long-term follow-up (8.3 ± 2.8 years), 65.5% of patients had SR and 53.8% of patients had AF/AFL burden < 1% on the 7-day Holter ECG. Additional RFAs were performed in 32.8% of patients who had AF or AFL burden < 1%. At long-term follow-up, age, body mass index, and left atrial volume index were associated with an increased risk of AF recurrence. Conclusions: CP resulted in high long-term probability of SR maintenance. During long-term follow-up, additional RFAs were required to maintain SR in a substantial number of patients.
Escalating Threat of Drug-Resistant Human Scabies: Current Insights and Future Directions
Authors: Simonart Thierry , Lam Hoai Xuân-Lan
Published: September 2024

Background: Scabies is a prevalent dermatological condition with significant public health implications. The recent rise in drug-resistant scabies presents new challenges for effective disease management and control. Methods: A comprehensive literature review was conducted using PubMed, Cochrane Library, and Web of Science. Studies published from 2000 to August 2024 were considered, focusing on those reporting drug-resistant scabies and advancements in treatment approaches. Results: Clinical studies, in vitro investigations, and case reports show significant resistance of human scabies to permethrin. Main resistance mechanisms involve genetic mutations in the mites’ voltage-gated sodium channels (VGSCs) and enhanced activity or expression of the detoxifying enzyme glutathione S-transferase (GST). Resistance to ivermectin and benzyle benzoate, although suggested by some authors, seems less obvious. The clinical evidence of widespread ivermectin resistance in human scabies infestations is lacking, despite indications of increased tolerance in laboratory settings and anecdotal reports of resistance in patients with crusted scabies. Benzyl benzoate resistance in scabies mites remains unconfirmed. Conclusions: Permethrin-resistant scabies is an escalating threat requiring new management strategies and updated guidelines. Infection control measures, alternative treatments, and ongoing research into new therapeutics are crucial to mitigate the impact of drug-resistant scabies.
Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases
Authors: Igoe Jane M. , Lam Byron L. , Gregori Ninel Z.
Published: September 2024

Inherited retinal diseases (IRDs) encompass a wide spectrum of rare conditions characterized by diverse phenotypes associated with hundreds of genetic variations, often leading to progressive visual impairment and profound vision loss. Multiple natural history studies and clinical trials exploring gene therapy for various IRDs are ongoing. Outcomes for ophthalmic trials measure visual changes in three main categories—structural, functional, and patient-focused outcomes. Since IRDs may range from congenital with poor central vision from birth to affecting the peripheral retina initially and progressing insidiously with visual acuity affected late in the disease course, typical outcome measures such as central visual acuity and ocular coherence tomography (OCT) imaging of the macula may not provide adequate representation of therapeutic outcomes including alterations in disease course. Thus, alternative unique outcome measures are necessary to assess loss of peripheral vision, color vision, night vision, and contrast sensitivity in IRDs. These differences have complicated the assessment of clinical outcomes for IRD therapies, and the clinical trials for IRDs have had to design novel specialized endpoints to demonstrate treatment efficacy. As genetic engineering and gene therapy techniques continue to advance with growing investment from industry and accelerated approval tracks for orphan conditions, the clinical trials must continue to improve their assessments to demonstrate safety and efficacy of new gene therapies that aim to come to market. Here, we will provide an overview of the current gene therapy approaches, review various endpoints for measuring visual function, highlight those that are utilized in recent gene therapy trials, and provide an overview of stage 2 and 3 IRD trials through the second quarter of 2024.
The Role of Topical Tacrolimus in the Management of Inflammatory Bowel Disease: A Comprehensive Review
Authors: Khayatan Danial , Lemberg Daniel A. , Day Andrew S.
Published: September 2024

Management of ulcerative colitis and Crohn’s disease, the main subtypes of inflammatory bowel disease (IBD), focuses on the induction and maintenance of remission. Tacrolimus, a member of a group of drugs termed calcineurin inhibitors, may have a role in the medical management of IBD when given either systemically or topically. This review aimed to evaluate the available data focusing on the use of topical tacrolimus in the management of IBD. Reports of the use of topical tacrolimus in IBD were extracted from databases up to 31 May 2024. Topical tacrolimus therapy appears to have reasonable efficacy in the induction and maintenance of remission in patients with refractory IBD, with an acceptable safety profile. Overall, the available data are supportive of the use of topical tacrolimus in selected patients. Further comparative clinical studies are required to more fully delineate the role of this drug.
Vamifeport: Monography of the First Oral Ferroportin Inhibitor
Authors: Pilo Federica , Angelucci Emanuele
Published: September 2024

Over the last few years, several mechanisms that are involved in congenital diseases characterized by ineffective erythropoiesis have been described. Therefore, multiple new target drugs are being developed in preclinical models against the main regulators of normal erythropoiesis. Above all, the key mechanism that regulates systemic iron homeostasis, represented by the hepcidin–ferroportin axis, is considered to be the target for new therapies. The main hypothesis is that iron restriction, through blocking ferroportin (the unique iron transporter in mammals) in such diseases, ameliorates erythropoiesis. The action of vamifeport is different from the currently approved drugs in this setting since it acts straight on the ferroportin–hepcidin axis. The data presented in the sickle cell disease (SCD) Townes mouse model showed a preclinical proof-of-concept for the efficacy of oral ferroportin inhibitor. Vamifeport reduced hemoglobin concentration in red blood cells (RBCs) and diminished intravascular hemolysis and inflammation, improving hemodynamics and preventing vascular occlusive crises. On this basis, clinical trials were commenced in patients with SCD, non-transfusion-dependent (NTD) thalassemia and transfusion-dependent (TD) thalassemia. Preliminary data in NTD thalassemic patients also confirm the safety and efficacy in decreasing iron level. In conclusion, vamifeport represents a new option in the panorama of drugs targeting the hepcidin–ferroportin axis, but its efficacy is still under investigation as a single agent.
Seasonal Comparison of Pre-Adolescent Soccer Players’ Physical Performance Using an Objective Physical Test Battery
Authors: Villa Giacomo , Papaioannou Foivos , Galli Manuela , Cimolin Veronica
Published: September 2024

Background/Objective: Soccer is a multifactorial sport, requiring physical, psychological, technical, and tactical skills to succeed. Monitoring and comparing physical characteristics over time is essential to assess players’ development, customize training, and prevent injury. The use of wearable sensors is essential to provide accurate and objective physical data. Methods: In this longitudinal study, 128 male adolescent soccer players (from Under 12 to Under 19) were evaluated at two time points (pre- and post-season). Participants completed the Euleria Lab test battery, including stability, countermovement and consecutive jumps, agility, and quick feet tests. A single Inertial Measurement Unit sensor provided quantitative data on fifteen performance metrics. Percentage changes were compared to the Smallest Worthwhile Changes to assess significant changes over time. Results: The results showed significant improvements in most variables, including a 19.7% increase in quick feet, 10.9% in stability, and 9.6% in countermovement jumps. In principal component analysis, we identified four principal components—strength-power, balance, speed-agility, and stiffness—that explained over 80% of the variance. Conclusions: These findings align with previous studies assessing seasonal changes in adolescent soccer players, showing that the proposed test battery seems to be adequate to highlight physical performance changes and provide coaches with meaningful data to customize training and reduce injury rates.
Design, Fabrication, and Commissioning of Transonic Linear Cascade for Micro-Shock Wave Analysis
Authors: Gall Mihnea , Drăgan Valeriu , Dumitrescu Oana , Prisăcariu Emilia Georgiana , Condruz Mihaela Raluca , Paraschiv Alexandru , Petrescu Valentin , Vlăduț Mihai
Published: September 2024

Understanding shock wave behavior in supersonic flow environments is critical for optimizing the aerodynamic performance of turbomachinery components. This study introduces a novel transonic linear cascade design, focusing on advanced blade manufacturing and experimental validation. Blades were 3D-printed using Inconel 625, enabling tight control over the geometry and surface quality, which were verified through extensive dimensional accuracy assessments and surface finish quality checks using coordinate measuring machines (CMMs). Numerical simulations were performed using Ansys CFX with an implicit pressure-based solver and high-order numerical schemes to accurately model the shock wave phenomena. To validate the simulations, experimental tests were conducted using Schlieren visualization, ensuring high fidelity in capturing the shock wave dynamics. A custom-designed test rig was commissioned to replicate the specific requirements of the cascade, enabling stable and repeatable testing conditions. Experiments were conducted at three different inlet pressures (0.7-bar, 0.8-bar, and 0.9-bar gauges) at a constant temperature of 21 °C. Results indicated that the shock wave intensity and position are highly sensitive to the inlet pressure, with higher pressures producing more intense and extensive shock waves. While the numerical simulations aligned broadly with the experimental observations, discrepancies at finer flow scales suggest the need for the further refinement of the computational models to capture detailed flow phenomena accurately.
Optimizing the Die-Sink EDM Machinability of AISI 316L Using Ti-6Al-4V-SiCp Electrodes: A Computational Approach
Authors: Hegde Adithya , Shetty Raviraj , Nayak Rajesh , Shetty Sawan , Shetty SV Uday Kumar
Published: September 2024

Die-sink electric discharge machining (EDM) is essential for shaping complex geometries in hard-to-machine materials. This study aimed to optimize key input parameters, such as the discharge current, gap voltage, pulse-on time, and pulse-off time, to enhance the EDM performance by maximizing the material removal rate while minimizing the surface roughness, residual stress, microhardness, and recast layer thickness. AISI 316L stainless steel was chosen due to its industrial relevance and machining challenges, while a Ti-6Al-4V-SiCp composite electrode was selected for its thermal resistance and low wear. Using Taguchi’s L27 orthogonal array, this study minimized the trial numbers, with analysis of the variance-quantifying parameter contributions. The results showed a maximum material removal rate of 0.405 g/min and minimal values for the surface roughness (1.95 µm), residual stress (1063.74 MPa), microhardness (244.8 Hv), and recast layer thickness (0.47 µm). A second-order model, developed through a response surface methodology, and a feed-forward artificial neural network enhanced the prediction accuracy. Multi-response optimization using desirability function analysis yielded an optimal set of conditions: discharge current of 5.78 amperes, gap voltage of 90 volts, pulse-on time of 100 microseconds, and pulse-off time of 15 microseconds. This setup achieved a material removal rate of 0.13 g/min, with reduced surface roughness (2.46 µm), residual stress (1518.46 MPa), microhardness (259.01 Hv), and recast layer thickness (0.87 µm). Scanning electron microscopy further analyzed the surface morphology and recast layer characteristics, providing insights into the material behavior under EDM. These findings enhance the understanding and optimization of the EDM processes for challenging materials, offering valuable guidance for future research and industrial use.