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Drug–drug interactions between epidermal growth factor receptor tyrosine kinase inhibitors and rivaroxaban in vitro and in vivo
Background Tyrosine kinase inhibitor (TKI) and rivaroxaban co-administration is common for patients with cancer and venous thromboembolism. However, the drug–drug interactions (DDIs) between epidermal growth factor receptor (EGFR) TKIs and rivaroxaban remain uncertain. Methods DDIs were investigated in vitro and in vivo. In vitro experiments were conducted using rat liver microsomes, and rivaroxaban metabolites were tested to identify the two TKIs that exhibit the most significant DDIs. The type of inhibition was investigated using Lineweaver-Burk plots. For in vivo experiments, eighteen rats were randomly divided into three groups and pretreated with CMC-Na together with avitinib or gefitinib, or with CMC-Na alone for 7 days. On day 8, rivaroxaban was orally administered to each group. Blood samples were collected at various time points, and plasma rivaroxaban was quantified. Molecular docking was performed to explore the mechanism of DDIs. Results Avitinib and gefitinib showed the most potent inhibitory effects among multiple EGFR TKIs and inhibited rivaroxaban metabolism in a mixed model of noncompetitive and uncompetitive inhibition. The area under the drug-time curve and maximum plasma concentration of rivaroxaban were significantly higher following avitinib and gefitinib pretreatment, while the apparent volume of distribution and clearance rates were significantly lower. Our molecular docking analysis revealed that these two drugs may inhibit rivaroxaban metabolism by overlapping with its binding site on CYP3A4 and CYP2D6. Conclusion These findings confirm the presence of DDIs between EGFR TKIs and rivaroxaban. Avitinib and gefitinib significantly inhibit rivaroxaban metabolism, and their co-administration may aggravate the risk of bleeding.
Analysis of a nonsteroidal anti inflammatory drug solubility in green solvent via developing robust models based on machine learning technique
Analysis of the inflammatory gene expression characteristics and immune microenvironment regulatory mechanisms in the testicular tissue of patients with non-obstructive azoospermia
Background This study aimed to deepen understanding of the molecular mechanisms and key characteristic genes of non-obstructive azoospermia (NOA). Methods A systematic retrieval method was used to collect the mRNA expression data of NOA and obstructive azoospermia (OA) samples from the GEO database. Data preprocessing, differential gene expression screening, functional annotation, and signal pathway enrichment analysis were conducted using R software. The differences in immune microenvironment between NOA and OA samples were compared through CIBERSORT analysis. LASSO and SVM-RFE, two machine learning algorithms, were applied to select NOA-related characteristic genes. Subsequently, our investigation further identified genes differentially expressed in NOA that are associated with inflammatory responses. NOA samples were clustered based on these inflammation-related genes, while molecular features between different types were explored through pathway enrichment analysis of gene set variation analysis (GSVA). Finally, potential traditional Chinese medicine components targeting these inflammation-related genes were screened from the Chinese medicine database, followed by drug-protein docking simulations. Results The study identified 772 DEGs mainly involved in the generation and maturation of sperm. Immune microenvironment analysis revealed significant differences in the infiltration levels of resting NK cells and activated dendritic cells between NOA and OA samples. Eight NOA-related characteristic genes were identified through LASSO and SVM-RFE algorithms. Further analysis revealed that three inflammation-related genes, namely LAMP3, PROK2, and CD14, exhibited significant differential expression in samples of NOA and OA. After clustering of these NOA samples based on the three inflammation-related DEGs, GSVA pathway enrichment analysis revealed molecular features between different NOA subtypes. Finally, potential traditional Chinese medicine components targeting these inflammation-related genes were selected. Conclusion This study revealed the key molecular mechanisms and characteristic genes of NOA, especially the role of inflammation-related genes, providing new therapeutic targets and directions for the treatment of NOA.
Interpretable machine learning approaches to assess the compressive strength of metakaolin blended sustainable cement mortar
Maternal perception, barriers, and facilitators regarding oral rehydration salt solution in diarrhoeal disease: A qualitative study in Bangladesh
Background Although oral rehydration salt (ORS) solution is a lifesaving management for diarrhoea, its exertion is still surprisingly low among caregivers. As mothers are considered to be the primary caregivers, they bear the responsibility of administering medications to their children. We aimed to evaluate maternal perceptions along with the barriers and facilitators in play that are affecting ORS administration among children in Bangladesh. Methods The study was conducted at Dhaka Hospital of the International Centre for Diarrhoeal Diseases Research, Bangladesh through a qualitative approach. In-depth Interviews (IDIs) were conducted on thirty-one mothers of under-5 children reporting to the hospital from February to April 2024. Qualitative content analysis method was used to describe and analyse the transcribed data. Findings The mothers held several misconceptions regarding the administration of ORS. Majority of the participants thought their child could receive ORS through their breastmilk, which was an interesting finding. Along with this, mothers also lacked proper understanding regarding ORS preparation, storage, and use. Some of the key barriers were the lack of proper knowledge, motivation, and compliance, along with misdirection from the elders and pharmacy drug sellers. Additional key facilitators to ORS use were trust towards doctors, positive attitude towards learning about ORS, community education, instructions written on the packet, and support from the healthcare providers. Conclusion A focused approach should be implemented to educate mothers on the correct preparation and administration of ORS for children, while also addressing and dispelling any misconceptions.
A reliable prognostic model for hepatocellular carcinoma using neutrophil extracellular traps and immune related genes
Comparing the antecedents of green computer behavior at acquisition, use, and disposal consumption stages from the moral norm and consumer attributes perspectives
Computers can have an adverse effect on the environment throughout the consumption stages of their acquisition, use, and disposal. Previous studies have predominantly focused on specific stages of consumption, leading to limited research on the utilization of the values-belief-norm (VBN) model in conjunction with consumer attributes like environmental knowledge, habits, and self-identity to forecast green computer behavior across all three stages of consumption. Consequently, the aim of this research is to identify and compare the VBN factors and consumer attributes that influence green computer behavior during the three consumption stages. An understanding of the differences in the antecedents at each stage can help in the development of a holistic pro-environmental intervention to mitigate the harmful environmental effects of computer consumption. An analysis of the data collected from survey questionnaires administered to Malaysian computer consumers reveals that different factors are prominent at each stage of consumption. Self-identity is only important during computer acquisition, while habits are only important during computer use. Although environmental knowledge and VBN factors are significant at all phases, the effects differ at each stage. Environmental knowledge is the most important factor at the acquisition stage. As for the VBN factors, the ascription of responsibility is the most important factor at the acquisition stage, while the ascription of responsibility and awareness of consequences are the most important factors at the use stage. Personal norms are the most important factor at the computer disposal stage and are the most important predictor of computer disposal behavior. The outcomes of this research can help manufacturers, marketers, government policymakers, and academics engage with consumers to promote green computer behavior. The novelty of this research is in comparison of the antecedents of consumer green computer behavior at each stage of consumption.
Women suffering from overactive bladder syndrome exhibit a higher urethral viral abundance compared to healthy controls: a pilot study
Abstract The interactions between the human bacterial microbiome and essential bodily functions are well established for organ systems such as the oral cavity, gut, and female reproductive tract. However, the urinary microbiome, particularly its viral component, remains largely unexplored. Emerging evidence suggests that the urinary microbiome may play a significant role in the development of overactive bladder syndrome (OAB). This study aims to fill this knowledge gap by investigating the potential link between the urethral virome and female overactive bladder syndrome, and by aligning these findings with the bacterial microbiome. Prospective pilot study including 15 patients with overactive bladder syndrome and five controls. Current urinary tract infection and antibiotic therapy within the last two months were ruled out and controls were matched to cases by age and body mass index. Urethral swabs (Copan eSwab® urethra) were taken from each participant at one single time point. Subsequent viral isolation, purification, and enrichment were conducted using the ViPEP method. Next-generation sequencing was performed on pooled samples, followed by bioinformatic analysis to identify and classify viral contigs. Phylogenetic analysis was conducted to assess genetic relationships among identified viral sequences. The bacterial microbiome was analyzed by sequencing of the variable V3-4 region of the eubacterial 16 S rDNA gene on the Illumina MiSeq platform. We identified twenty-one viruses and bacteriophages only in pooled urethral swab samples of the OAB group, but no valid detections were retained in the control group after analysis. The most abundant human virus in urethral swab samples was human papilloma virus, whereas the most abundant bacteriophages belong to the family of Siphoviridae. In the bacterial microbiome analysis, we identified statistically higher levels of Veillonella and Bacteroides in OAB samples. Results of this pilot study suggest a difference in the urethral virome between women with OAB and healthy controls. When looking deeper into the detected virus families and species, we might postulate a unique microbial pattern of OAB patients. This pattern suggests an interplay of immunosuppression, autoimmune processes and a larger diversity of bacterial and viral microbes. Current evidence strongly suggests a disturbance of the healthy microbiome of the urogenital tract in patients with OAB, leading to subclinical chronic inflammation and thus typical OAB symptoms. Further research should focus on interventions aimed at restoring a healthy microbiome in OAB patients to mitigate inflammation and improve symptom control.
The interaction between cancer and COVID-19: Risk factors and targeted interventions
Background Cancer patients are particularly fragile, and hospitalization represents a significant additional risk for complications and death, especially given the vulnerability of this group during the global pandemic. The study objective entails analyzing the factors associated with severity and death of cancer patients diagnosed with COVID-19 hospitalized between 2020 and 2022, in the city of Rio de Janeiro, Brazil. Materials and Methods This is a cross-sectional study, with hospitalized patients with both diagnoses, cancer and COVID-19, through two national databases. Bivariate and multivariate regression analyses were performed, followed by an interaction analysis between the variables of interest in the multivariate regression. Findings A total of 1,336 cases were analyzed. Have comorbidity and hematological neoplasms were associated with mechanical ventilation (OR = 1.62 and OR = 2.14, respectively) and with ICU admission (OR = 1.44 and OR = 2.25, respectively). The age group of 60 years or older (OR = 1.33), have multimorbidity (OR = 1.38), and use mechanic ventilation (OR = 2.39) were associated with a higher risk of death from COVID-19. The multimorbidity had a synergistic effect with hospitalization before vaccination (AP = 0.29; 95%CI = 0.01 – 0.58) and the use of mechanical ventilation (AP = 0.54; 95%CI = 0.18 – 0.98). Interpretation These findings are crucial to guide clinical decisions, improve the management of care for these patients, and optimize the use of health resources in the epidemiological context imposed by the pandemic.
Predicting mass transfer activation energy and physicochemical properties of dried onion using numerical modeling and artificial intelligence
Abstract The quality of the onion slices was statistically evaluated based on the variables of drying conditions, considering the following characteristics: drying time, color, shrinkage, water activity, and rehydration ratio, critical parameters in evaluating food processing and preservation methods. The onion slices were subjected to drying under the ensuing settings: infrared powers of 1500, 3500, and 5500 W/m2; airflow rates of 0.3, 0.7, and 1.0 m/s; and air temperatures of 40, 50, and 60 °C. The findings indicated that the drying time increased with air velocity to 0.7 and 1.0 m/s at a constant infrared intensity of 5500 W/m2, resulting in a significant increase of 26 and 37%. The water activity values for the sample ranged from 0.40 to 0.49. The maximum vitamin C content was 24 mg/g, followed by an air temperature of 40 °C and 0.3 m/s air velocity under 1500 W/m2. Conditions of 1.5 m/s, 40 °C, and 1500 W/m2 indicate the lowest rehydration ratio. The ANN model proved to be a robust tool for predicting and optimizing drying parameters, including drying duration, energy consumption, and quality. Additionally, it highlights the potential of advanced heating technologies to optimize food drying approaches, providing important insights for the food sector in its quest for increased efficiency.
Asthma status and suicidal behavior risk: A meta-analysis of cohort studies
Objective This meta-analysis investigates the differential risks of suicidal behaviors (ideation, attempts, mortality) associated with current asthma and asthma history. Method Retrieve cohort studies on the association between asthma and suicide from PubMed, Embase, and Cochrane library database. Use the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias. The risk ratio (RR) of 95% confidence interval (CI) was summarized using a random effects model, and publication bias was evaluated using funnel plots and Egger’s trials. Result A total of 12 cohort studies were included and published between 2005 and 2024. The NOS scores for the 12 cohort studies included in this meta-analysis ranged from 7 to 9. Most studies received scores of 7 or 8, indicating a generally high quality. Current asthma conferred a 62% increased risk of suicidal behaviors (RR = 1.62, 95% CI: 1.38–1.88), with suicide attempts showing the strongest association (RR = 2.27, 95% CI: 1.33–3.89). Asthma history was linked only to elevated suicide mortality (RR = 1.87, 95% CI: 1.64–2.14), not non-fatal suicidal behaviors. Conclusion Current asthma status is associated with an increased risk of suicidal behaviors, but a history of asthma correlates only with elevated suicide mortality. This finding highlights the need for proactive mental health screening in asthma management protocols, especially during periods of active disease.
Co-occurrence feature learning for visual recognition of immature leukocytes
The variable selection of two-part regression model for semicontinuous data
In many research fields, measurement data containing too many zeros are often called semicontinuous data. For semicontinuous data, the most common method is the two-part model, which establishes the corresponding regression model for both the zero-valued part and the nonzero-valued part. Considering that each part of the two-part regression model often encounters a large number of candidate variables, the variable selection becomes an important problem in semicontinuous data analysis. However, there is little research literature on this topic. To bridge this gap, we propose a new type of variable selection methods for the two-part regression model. In this paper, the Bernoulli-Normal two-part (BNT) regression model is presented, and a variable selection method based on Lasso penalty function is proposed. To solve the problem that Lasso estimator does not have Oracle attribute, we then propose a variable selection method based on adaptive Lasso penalty function. The simulation results show that both methods can select variables for BNT regression model and are easy to implement, and the performance of adaptive Lasso method is superior to the Lasso method. We demonstrate the effectiveness of the proposed tools using dietary intake data to further analyze the important factors affecting dietary intake of patients.
A randomized controlled trial of teriparatide for accelerating bone union and improving clinical outcomes in patients with pertrochanteric fracture fixation
Abstract This prospective, double-blind, placebo-controlled, randomized trial evaluated the effects of teriparatide following pertrochanteric fracture fixation on bone healing and clinical outcomes. Among 50 participants having fractures and undergoing surgical fixation, 25 were randomly assigned to each group to receive daily teriparatide or placebo for 12 weeks and were followed until 24 weeks postoperatively. The primary outcome was the radiographic bone union. The secondary outcome was clinical results, including Harris hip scores (HHS) and performance-based tests evaluated at the postoperative 2nd, 4th, 6th, 12th, and 24th weeks, and spine and contralateral hip bone mass density (BMD), comparing admission and the 24th week. There were no statistically significant differences in baseline characteristics, including age, sex, fracture classification, affected side, HHS, BMD, and blood test results. The mean and standard deviation of radiographic bone union time of the teriparatide and the placebo groups were 7.44 ± 3.34 weeks and 10.56 ± 4.98 weeks, respectively, with significant differences (p, 0.0083). From the 6th week, both teriparatide and placebo groups had significantly improved HHS (p, 0.008 and 0.0205, respectively) and time up-and-go test (TUGT) (p, 0.0348 and 0.0237, respectively). In the 24th week, the five-time sit-to-stand test (5 × SST) of teriparatide and placebo groups was significantly improved (p, 0.0013 and 0.0412, respectively). However, there were no differences in HHS, TUGT and 5 × SST between groups at all follow-up time points. In the 24th week, the teriparatide group had less decrease in spine, femoral neck, and total hip BMD from baseline to the placebo group; however, these differences were insignificant. In conclusion, a 12-week teriparatide administration following intertrochanteric fracture fixation significantly shortened the fracture healing time. Although there were no differences in improved clinical outcomes, the teriparatide group had less decline in BMD at 24 weeks than the placebo group.
An Enhanced Whale Optimization Algorithm with outpost and multi-population mechanisms for high-dimensional optimization and medical diagnosis
Swarm intelligence optimization algorithms represent a significant branch of nature-inspired computational methods, designed to solve complex optimization problems by simulating the collective behavior of biological systems. Whale optimization algorithm (WOA) is a newly developed meta-heuristic algorithm, which is mainly based on the predation behavior of humpback whales in the ocean. This study proposes an enhanced version of the WOA, named the Outpost-based Multi-population Whale Optimization Algorithm (OMWOA), which integrates two key mechanisms: the outpost mechanism and a multi-population enhanced mechanism. These modifications aim to improve the algorithm’s performance in terms of solution accuracy and convergence rate. The effectiveness of OMWOA is thoroughly evaluated by benchmarking it against state-of-the-art evolutionary algorithms from the IEEE CEC 2017 and IEEE CEC 2022 competitions. Additionally, this study provides a detailed analysis of the influence of the outpost and multi-population mechanisms on OMWOA’s performance, as well as its scalability in problems of varying dimensionalities. To validate its applicability in real-world problems, the proposed algorithm is combined with Kernel Extreme Learning Machine (KELM) for solving medical disease diagnosis tasks. The experimental results demonstrate the superior performance of OMWOA in terms of diagnostic accuracy across five medical datasets, highlighting its potential for real-world applications.
Inkjet printing of amorphous indium aluminum oxide active layers for high-performance thin-film transistors
Health-related quality of life and its predictors among epilepsy patients in Ethiopia: Systematic review and meta-analysis
Introduction Epilepsy is a common non-communicable neurological disorder associated with recurrent seeding of cerebral neurons or brain cells and episodes of unprovoked seizures with or without loss of consciousness. Although there are studies on the health-related quality of life of epilepsy patients in Ethiopia, there are remarkable variations in the estimates of health-related quality of life. Objectives This systematic review and meta-analysis aimed to determine the pooled effect size of the health-related quality of life of adult epilepsy patients in Ethiopia. Methods Original articles about the health-related quality of life among epilepsy patients in Ethiopia were searched through known and international databases (PubMed, Scopus, and Web of Science) and search engines (Google and Google Scholar). Data were extracted using a standard data extraction checklist developed according to Joanna Briggs Institute (JBI). The I2 statistics were used to identify heterogeneity across studies. Funnel plot asymmetry and Egger’s tests were used to check for publication bias. The STATA version 11 software was employed for statistical analysis to pool the mean scores of health-related quality-of-life. Result A total of 16 cross-sectional studies with a sample size of 5294 took part. The pooled overall mean score of health-related quality of life among epilepsy patients in Ethiopia was 52.82 ± 13.24 [95%CI (46.41, 59.21)], I2 = 100%, p-value <0.001. Besides, the overall pooled mean score of health-related quality of life based on the measuring tools WHO-QOL-BREF, QOLIE-31, and QOLIE-10 was 51.50 ± 11.32 (49.11, 53.90), 59.99 ± 12.67 (52.22, 67.77), and 44.33 ± 21.23 (13.09, 75.57) respectively. Conclusion The least overall pooled mean score of HRQOL was the QOLIE-10 measuring tool epileptic patients’ mean score compared to other health-related quality-of-life measuring tools such as WHOQOL-BREF, and QOLIE-31. Moreover, the least overall pooled mean score of HRQOL using the WHOQOL-BREF was the environmental domain followed by the emotional domain, as compared to all other domains in each measuring tool of health-related quality of life.
Mental health outcomes and post-traumatic stress disorder associated with female genital mutilation
Community pharmacists’ perception of knowledge, attitudes, and practices toward oral health promotion: A Cross-sectional study on the influence of training, demographics, and resources in the UAE
Community pharmacists (CPs) are crucial in promoting public health, including oral health, due to their accessibility and frequent patient interaction. This cross-sectional study examined factors influencing oral health promotion among 350 CPs in the UAE, focusing on training, demographic factors, and resource availability. Bivariate analysis showed that gender, years of experience, and the availability of a consultation area significantly influenced CPs’ confidence in providing oral health advice. Male pharmacists exhibited higher confidence in addressing tobacco-related dental issues compared to females. Those with a consultation area were more likely to perceive oral health promotion as part of their role. Multivariate logistic regression revealed that training significantly predicted engagement in oral health promotion. CPs who received formal training were seven times more likely to promote oral health (OR = 7.260, p < 0.001), while self-training had an even more substantial influence (OR = 39.249, p < 0.01). However, pharmacists who lacked sufficient workflow, staffing, and time were 87% less likely to perceive oral health promotion as part of their role (OR = 0.133, p < 0.001). The proximity of a dental clinic did not significantly affect pharmacists’ involvement in oral health promotion. In conclusion, this study emphasizes the importance of targeted training and adequate resources in encouraging CPs’ participation in oral health promotion. Pharmacists with more experience and access to training are more likely to take on proactive roles in promoting oral health.