Search Results (64,716)

Background: Kawasaki disease (KD) is a systemic vasculitis of medium arteries, particularly involving coronary arteries. Coronary artery lesions (CALs) is the most serious complication in the acute stage, potentially leading to ischemic cardiomyopathy, myocardial infarction and sudden death. Environmental factors and genetic background contribute to individual susceptibility to develop CALs. The aim of this study was to define the risk factors for CALs in an Italian cohort. Methods: Data of KD patients from 10 Italian sites were registered into a REDCap database where demographic and clinical data, laboratory findings and coronary status were recorded. KD was diagnosed according to AHA definition. We used multiple logistic regression analysis to identify independent risk factors for CALs. Results: A total of 517 patients were enrolled, mainly Caucasians (83.6%). Presentation was complete in 321 patients (62.8%) and IVIG responsiveness in 360 (70%). CALs developed in 136/517 (26.31%). Gender, age, ethnicity, clinical presentation, fever duration, non-coronary cardiac events, Hb, albumin and CRP were significantly different between patients with and without CALs, while seasonality was not. Male gender, age < 18 months, Asian ethnicity, incomplete presentation and fever > 10 days were independent risk factors for CALs. Conclusions: Age younger than 18 months, incomplete KD and longer fever duration are risk factors for CALs. Asian ethnicity also represents a risk factor in our Italian Cohort. Full article

To improve the discharge performance of aluminum–air batteries, CeO₂/Al6061 composites were prepared as an anode using selective laser melting (SLM). Response surface methodology (RSM) was employed, and the test results were linearly fitted. A prediction model for the forming quality of the composite anode was established, and the reliability of the model and the interaction between process parameters were explored based on variance analysis and significance testing. On this basis, with corrosion potential, self-corrosion rate, and discharge voltage as optimization objectives, the optimal solution set of the SLM forming CeO₂/Al6061 anode process parameter was solved through a genetic algorithm, and experimental verification was conducted. The results indicate that the optimal process range for the forming quality and various properties of composite materials is laser power of 265~285 W, scanning speed of 985~1025 mm/s, and scanning spacing of 0.116~0.140 mm. The optimized process parameters were selected for reliability testing, and the errors were all within 3.0%, verifying the accuracy and reliability of the model. Full article

This study aimed to model the pharmacokinetics of lamotrigine (LTG) and efavirenz (EFV) in pregnant women using physiologically based pharmacokinetic (PBPK) and pregnancy-specific PBPK (p-PBPK) models. For lamotrigine, the adult PBPK model demonstrated accurate predictions for pharmacokinetic parameters. Predictions for the area under the curve (AUC) and peak plasma concentration (Cmax) generally agreed well with observed values. During pregnancy, the PBPK model accurately predicted AUC and Cmax with a prediction error (%PE) of less than 25%. The evaluation of the EFV PBPK model revealed mixed results. While the model accurately predicted certain parameters for non-pregnant adults, significant discrepancies were observed in predictions for higher doses (600 vs. 400 mg) and pregnant individuals. The model’s performance during pregnancy was poor, indicating the need for further refinement to account for genetic polymorphism. Gender differences also influenced EFV pharmacokinetics, with lower exposure levels in females compared to males. These findings highlight the complexity of modeling EFV, in general, but specifically in pregnant populations, and the importance of validating such models for accurate clinical application. The study highlights the importance of tailoring dosing regimens for pregnant individuals to ensure both safety and efficacy, particularly when using combination therapies with UGT substrate drugs. Although drug-drug interactions between LTG and EFV appear minimal, further research is needed to improve predictive models and enhance their accuracy. Full article

Transposable elements (TEs) significantly contribute to the evolution and diversity of plant genomes. In this study, we explored the roles of TEs in the genomes of Citrus and Citrus-related genera by constructing a pan-genome TE library from 20 published genomes of Citrus and Citrus-related accessions. Our results revealed an increase in TE content and the number of TE types compared to the original annotations, as well as a decrease in the content of unclassified TEs. The average length of TEs per assembly was approximately 194.23 Mb, representing 41.76% (Murraya paniculata) to 64.76% (Citrus gilletiana) of the genomes, with a mean value of 56.95%. A significant positive correlation was found between genome size and both the number of TE types and TE content. Consistent with the difference in mean whole-genome size (39.83 Mb) between Citrus and Citrus-related genera, Citrus genomes contained an average of 34.36 Mb more TE sequences than Citrus-related genomes. Analysis of the estimated insertion time and half-life of long terminal repeat retrotransposons (LTR-RTs) suggested that TE removal was not the primary factor contributing to the differences among genomes. These findings collectively indicate that TEs are the primary determinants of genome size and play a major role in shaping genome structures. Principal coordinate analysis (PCoA) of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) identifiers revealed that the fragmented TEs were predominantly derived from ancestral genomes, while intact TEs were crucial in the recent evolutionary diversification of Citrus. Moreover, the presence or absence of intact TEs near the AdhE superfamily was closely associated with the bitterness trait in the Citrus species. Overall, this study enhances TE annotation in Citrus and Citrus-related genomes and provides valuable data for future genetic breeding and agronomic trait research in Citrus. Full article

The air suspension system’s superior variable stiffness, low vibration frequency, and resistance to road impacts significantly elevate both the comfort of vehicle occupants and the overall ride quality. By effectively controlling the air suspension system, its superior characteristics can be fully exploited to enhance the overall performance of vehicles. However, the parameter tuning process of the fuzzy PID controller for air suspension involves subjectivity and blindness, which affects the performance of the suspension system. To overcome these shortcomings, a control strategy combining genetic algorithms with fuzzy PID control is proposed. This strategy involves a genetic algorithm-optimized fuzzy PID air suspension control approach specifically targeting the fuzzy PID controller for air suspension. A 1/4 two-degree-of-freedom air suspension fuzzy PID controller is designed in MATLAB 2019a, utilizing genetic algorithms to optimize the PID parameter tuning process. The ride comfort of the fuzzy PID air suspension after tuning is then investigated. In the study of ride comfort on Class B road surfaces, the simulation and experimental results were consistent. Using a genetic algorithm to optimize a fuzzy PID-controlled air suspension resulted in reductions of the root mean square values for vertical body acceleration, suspension deflection, and wheel dynamic load by 30%, 26%, and 9%, respectively, compared to passive suspension. These reductions are further improvements over the corresponding indices controlled by the fuzzy PID alone, which decreased by 23%, 18%, and 6%, respectively. Thus, the control effect of the genetic algorithm-optimized fuzzy PID is superior to that of the fuzzy PID control. This demonstrates that the fuzzy PID control of air suspension optimized by genetic algorithms can further improve the comfort of vehicle occupants and the ride comfort of driving, providing a reference for active control of air suspension systems. Full article

This review presents current knowledge on the surgical treatment of endometrial cancer in young patients. Endometrial cancer is the most common gynecological cancer in Europe. Higher morbidity is correlated with obesity, hypertension and diabetes, which are growing worldwide. However, endometrial cancer at an early age is very rare. The first line of treatment for this cancer is radical hysterectomy, which is controversial in young women. There is an alternative method of fertility-sparing treatment. However, there is a group of young patients for whom surgical treatment is recommended. According to European guidelines, minimally invasive surgery is recommended for endometrial cancer. The aim of the study was to present the advantages of robotic surgery for endometrial cancer detected at a young age. The procedure of radical treatment with robot-assisted laparoscopy is more precise. Better visualization and stabilization of instruments allow a shorter procedure time, a brief hospital stay and fewer complications. Quality of life may be at a similar level. Incisions after trocars are painless and more esthetic than a classical wound. Bilateral adnexectomy in endometrial cancer depends on age, molecular status of the cancer, stage, genetic risk factors and individual decision. Conclusions: Robotic surgery seems to be a better surgical method for endometrial cancer in younger patients. Full article

The efficient operation and intelligent upgrading of public transportation can effectively enhance the attractiveness of conventional public transportation. In order to improve the delicacy management level of bus operations, this study designed a new dynamic optimization model for single-line bus operations with the dual optimization objectives of the lowest passenger travel cost and lowest operation cost, using a combination of the strategy of stop-skipping control and local route optimization. Simulated annealing (SA) was introduced into the genetic algorithm (GA) to design a hybrid heuristic algorithm for model solving. The effectiveness of the optimization model and the hybrid algorithm were verified and evaluated by using the No. 115 bus line in Ganzhou City as an example. The results showed that the proposed optimization model had a good usability, which can effectively improve the average vehicle speed, shorten the overall waiting time of passengers, and enhance the operational efficiency of the line. The hybrid algorithm saw significant improvement in terms of the iteration speed and the quality of the optimal solution compared with the conventional genetic algorithm. Full article

Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n = 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR, n = 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC, n = 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC, n = 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2, CDH1, PALB2, PTEN, and TP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort. ATM, BRIP1, RAD51C, and RAD51D mutations were identified in all cohorts. RAD51C and RAD51D mutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients. Full article

The present research explores the optimization of maintenance strategies for floating offshore wind (FOW) farms using nested genetic algorithms. The primary goal is to provide insights on the decision-making processes required for both immediate and strategic maintenance planning, crucial for the viability and efficiency of FOW operations. A nested genetic algorithm was coupled with discrete-event simulations in order to simulate and optimize maintenance scenarios influenced by various operational and environmental parameters. The study revealed that short-term maintenance timing is significantly influenced by wind conditions, with higher electricity prices justifying on-site spare parts storage to mitigate operational disruptions, suggesting economic incentives for maintaining on-site inventory of spare parts. Long-term strategic findings emphasized the impact of planned intervals between inspections on financial outcomes, identifying optimal strategies that balance operational costs with energy production efficiency. Ultimately, this study highlights the importance of integrating sophisticated predictive models for failure detection with real-time operational data to enhance maintenance decision-making in the evolving landscape of offshore wind energy, where future farms are likely to operate farther from onshore facilities and under potentially highly varying market conditions in terms of electricity prices. Full article

This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age- and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25-hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms rs5488 and rs7041 were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) (p = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous rs7041 (60.7%) and wild-type rs4588 (58.9%) genotypes. The distribution of rs7041 SNP varied significantly among groups (p = 0.0301), while rs4588 SNP distribution did not (p = 0.424). Heterozygous rs4588 patients had significantly lower VDBP levels (p = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type rs4588 (p = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly rs7041 and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies. Full article

Gastric cancer (GC) remains a significant public health concern because of its lethality, underscoring the need for deeper insights into its molecular mechanisms. Recent studies have increasingly highlighted the role of epigenetic modifications as critical players in cancer progression. Despite their importance, research specifically addressing epigenetic factors in GC is relatively scarce. This paper seeks to bridge that gap by examining recent literature that elucidates the epigenetic landscape associated with GC. The investigation of long noncoding RNAs (lncRNAs) has revealed their substantial involvement in gene dysregulation and epigenetic alterations within GC tumors. Notably, lncRNAs such as LINC00853 and LINC01266 have been identified as significant contributors to the epigenetic modulation of gene expression. Furthermore, the overexpression of KAT5 and GPX4 has been shown to mitigate the antiproliferative effects resulting from the depletion of circRHOT1, suggesting a complex interplay between these molecules in GC pathophysiology. Another pivotal aspect of epigenetic regulation in GC involves modifications in N6-methyladenosine (m6A), which play crucial roles in mRNA maturation processes such as splicing, export, degradation, and translation. m6A modifications are known for their influence on various cancer-related pathways, thus presenting a potential avenue for targeted interventions. Our findings indicate that the most pronounced instances of epigenetic dysregulation in GC can be traced back to the effects of long lncRNAs and alterations in m6A modification patterns. This underscores the urgent need for comprehensive investigations into these epigenetic factors, as a deeper understanding could lead to enhanced diagnostic markers and innovative therapeutic strategies. The integration of genetic and epigenetic considerations is essential for advancing the field of GC research. This synthesis of recent findings concerning epigenetic regulation offers valuable insights that could inform future studies and therapeutic developments. There is a critical need for ongoing research to elucidate the complexities of epigenetic modifications in GC, ultimately improving patient outcomes through tailored interventions. Full article

Achieving cyber-security has grown increasingly tricky because of the rising concern for internet connectivity and the significant growth in software-related applications. It also needs a robust defense system to defend itself from multiple cyberattacks. Therefore, there is a need to generate a method for detecting and classifying cyber-attacks. The developed model can be integrated into three phases: pre-processing, feature selection, and classification. Initially, the min-max normalization of original data was performed to eliminate the impact of maximum or minimum values on the overall characteristics. After that, synthetic minority oversampling techniques (SMOTEs) were developed to reduce the number of minority attacks. The significant features were selected using a Hybrid Genetic Fire Hawk Optimizer (HGFHO). An optimized residual dense-assisted multi-attention transformer (Op-ReDMAT) model was introduced to classify selected features accurately. The proposed model’s performance was evaluated using the UNSW-NB15 and CICIDS2017 datasets. A performance analysis was carried out to demonstrate the effectiveness of the proposed model. The experimental results showed that the UNSW-NB15 dataset attained a higher precision, accuracy, F1-score, error rate, and recall of 97.2%, 98.82%, 97.8%, 2.58, and 98.5%, respectively. On the other hand, the CICIDS 2017 achieved a higher precision, accuracy, F1-score, and recall of 98.6%, 99.12%, 98.8%, and 98.2%, respectively. Full article

Biofertilizers are promising technologies for achieving sustainable agriculture. However, high-temperature tolerance is a constraint that limits the function of microbial inoculants. To characterize the genetic changes responsible for the high-temperature tolerance of rhizobia, mutant screening was performed using Bradyrhizobium diazoefficiens USDA110. The wild-type cells were mutagenized with carbon-ion irradiation, and two mutant strains, designated M10 and M14, were obtained after a three-day heat-shock treatment at 43 °C. In particular, M14 showed superior growth at 36 °C, at which temperature growth of the wild type was extremely slow, whereas M14 grew more slowly than the wild type at 32 °C. Whole-genome sequencing revealed that M10 had seven point mutations, whereas M14 had eight point mutations together with a 1.27 Mb inversion. RNA sequencing showed that the number of differentially expressed genes greatly exceeded the actual number of induced mutations. In M14, a gene cluster associated with pyruvate metabolism was markedly downregulated, probably because of disjunction with the promoter region after inversion, and was considered to be the cause of the slow growth rate of M14 at 32 °C. Notably, transmembrane proteins, including porins, were enriched among the genes upregulated in both M10 and M14. M14 was confirmed to retain symbiotic functions with soybeans. These results indicate that high-temperature tolerance was conferred by random mutagenesis while the symbiotic functions of rhizobia was maintained. Full article

A squamous odontogenic tumor (SOT) is an epithelial locally benign neoplasia derived from the periodontium of the jaws. It is considered a lesion of low incidence. Predominantly, it affects the mandible, although both jaw bones may be involved. Here, we discuss the malignant clinical evolution of an SOT lesion in an 80-year-old female patient. The patient exhibited an expansive triangular lesion at the inferior right quadrant. Surgery was performed and an SOT was diagnosed (2019). Two years after, the lesion grew, and the analysis of the biopsy revealed SOT malignization with pleomorphic atypical squamous cells, characteristics of a squamous cell carcinoma (2021). Massive DNA sequencing of formalin-fixed–paraffin-embedded specimens of the initial and relapsed tumors indicated pathogenic mutations in RET and POLE genes in both tumors, loss of ALK, and gain of CDKN1B and MAP2K in the relapse. In addition, the clinical, radiographic, and microscopic features of this neoplasm are discussed and compared with those already published. The case presented contributes to the better understanding of this SOT tumor entity and to indicates its malignant evolution, together with its biological behavior and its histologic, clinical, and radiographic features. Also, it aims to stress the importance of deeper genetic analyses in rare diseases to uncover mutations that help to select a personalized treatment. Full article

Citrus depressa Hayata is a citrus cultivar grown in Japan and Taiwan. To assess the differences in genetic characteristics and volatile organic components (VOCs) in the leaves and edible parts of the fruits of 23 C. depressa accessions from different geographic origins, the tissues were analyzed using cleaved amplified polymorphic sequence markers and gas chromatography-mass spectrometry. A phylogenetic cluster analysis demonstrated that Kagoshima accessions had a close genetic relationship with one another, with Okinawan “Izumi kugani-like” being the most distinct accession. The predominant volatiles in the leaves were γ-terpinene, p-cymene, limonene, and linalool. Multivariate analysis and volcano plots revealed distinct volatiles in the leaves of each cultivation region: piperitone and citronellal (Kagoshima); 5,9,9-trimethyl-spiro[3.5]non-5-en-1-one (Okinawa); and hexanal (Taiwan). Furthermore, the edible parts of Taiwanese fruits contained abundant amounts of monoterpenes, including linalool and 1,8-cineole. In contrast, Kagoshima and Okinawa accessions were rich in aldehydes and esters, respectively. In conclusion, the genetic and volatile profiles of 23 C. depressa accessions of different origins could be distinguished, and multivariate analysis suggested that C. depressa contains diverse VOCs depending on where it is cultivated. These findings demonstrate the exclusivity of C. depressa resources in each region, which could assist farmers and agro-industries in promoting food products derived from C. depressa fruits. Full article