Exploration of the potential association between newer antiseizure medications and arrhythmias: Integrating pharmacovigilance and bioinformatics evidence.

INTRODUCTION: Arrhythmias resulting from newer antiseizure medications (ASMs) may significantly impact the safety and quality of life of patients with epilepsy. This study investigated the potential association between new first-line or second-line ASMs and arrhythmias. METHODS: Pharmacovigilance analysis was conducted using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from 2004 to 2023. A disproportionality analysis was performed to compare newer ASMs with other drugs, using carbamazepine and valproate as positive controls. Newer ASMs were categorized into sodium channel (SCN) main mechanism, SCN possible mechanism, and non-SCN group. The bioinformatics analysis involved retrieving therapeutic gene targets for ASMs from the DrugBank and OMIM databases, as well as identifying arrhythmia disease targets from the GeneCards database. Additionally, enrichment analysis of gene ontology functions and KEGG pathways was conducted. RESULTS: A total of 3,457 cases of arrhythmias associated with newer ASMs were identified in the FAERS database. Disproportionality analysis indicates that brivaracetam (IC025 = 0.08), zonisamide (IC025 = 0.13), eslicarbazepine (IC025 = 0.39), and lacosamide (IC025 = 0.84) exhibited a positive signal for arrhythmias, with signals predominantly observed in the SCN main mechanism group. Furthermore, bioinformatics analysis revealed the involvement of adrenergic signaling in cardiac myocytes, as well as the participation of sodium channel genes in ASM-induced arrhythmias. CONCLUSION: Our findings suggest a potential association between SCN-ASMs and arrhythmias, highlighting the importance of monitoring and evaluating the safety profiles of newer ASMs in clinical practice. Further research is necessary to elucidate the underlying mechanisms and inform patient care strategies.

Study on the Influence of Laser Power on the Heat-Flow Multi-Field Coupling of Laser Cladding Incoloy 926 on Stainless Steel Surface.

In order to explore the influence of laser power on the evolution of molten pool and convective heat transfer of laser cladding Incoloy 926 on stainless steel surface, a three-dimensional thermal fluid multi-field coupled laser cladding numerical model was established in this paper. The variation of latent heat during solid-liquid phase transformation was treated by apparent heat capacity method. The change in the gas-liquid interface was tracked using the mesh growth method in real time. The instantaneous evolution of temperature field and velocity flow field of laser cladding Incoloy 926 on a stainless steel surface under different laser power was discussed. The solidification characteristic parameters of the cladding layer were calculated based on the temperature-time variation curves at different nodes. The mechanism of the impact of laser power on the microstructure of the cladding layer was revealed. The experiment of laser cladding Incoloy 926 on 316L surface was carried out under different laser power. Combined with the numerical simulation results, the effects of laser power on the geometrical morphology, microstructure and element distribution of the cladding layer were compared and analyzed. The results show that with the increase in laser power, the peak temperature and flow velocity of the molten pool surface both increase significantly. The thermal influence of the molten pool center on the edge is enhanced. The temperature gradient, solidification rate, and cooling rate increased gradually. The microstructure parameters (G/R) are relatively small when the laser power is 1000 W. In the experimental range, the dilution rate and wetting angle of the cladding layer both increase with the increase in laser power. When the laser power is 1000 W, the alloying elements of the cladding layer are more evenly distributed and the microstructure is finer. The experimental results are in good agreement with the simulation results.

Optimization of oral isavuconazole dose for population in special physiological or pathological state: a physiologically based pharmacokinetics model-informed precision dosing.

OBJECTIVE: To recommend precision dosing and improve therapeutic efficacy against invasive fungal disease, a physiologically based pharmacokinetic model (PBPK) of oral isavuconazole (ISA) was established and used to explore its disposition across populations in different physiological and pathological states. METHODS: Twenty-five pharmacokinetic (PK) studies of oral ISA were identified through a systematic search of PubMed. Concentration-time data were extracted using WebPlotDigitizer. Physiochemical parameters were obtained from published literature and DrugBank. Model development and simulation used the Simcyp population-based simulator, and visual predictive check and predictive error were used for the model evaluation. Probability of target attainment and the cumulative fraction of response analyses were performed for dose optimization. RESULTS: The developed PBPK model was successfully validated in different populations. Most predicted concentration-time points aligned with the observed data, with acceptable predictive errors for the critical parameters. We predicted the PK profiles and parameters of ISA in a population with severe hepatic impairment (HI), a population with obesity and paediatric patients aged 1 to less than 6 years old. The probability of target attainment and cumulative fraction of response analyses indicated that the population with severe HI should have half the maintenance dose. The population with obesity and population with severe HI should have a loading dose of 300 mg every 8 h for 2 days. For paediatric patients aged 1 to less than 6 years old, a weight-based dosing regimen (5.38 mg/kg) of ISA was suggested. CONCLUSION: The predicted value aligns with observations, suggesting ISA's potential predictability in PK profiles for other populations. The recommended dosing regimens increase our understanding of the use of ISA in special populations.

Multiple Adverse Reactions Associated With the Use of Second-Generation Antipsychotics in People With Alzheimer's Disease: A Pharmacovigilance Analysis Based on the FDA Adverse Event Reporting System.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition leading to memory loss, cognitive impairment, and neuropsychiatric symptoms. Second-generation antipsychotics (SGAs) are commonly used to manage these neuropsychiatric symptoms, but their safety profile in patients with AD requires further investigation. OBJECTIVE: The objective was to evaluate the safety of SGAs in patients with AD by analyzing adverse drug reactions (ADRs) using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: This study conducted a comprehensive analysis of FAERS data from 2014 to 2023, focusing on ADRs in patients with AD treated with SGAs such as risperidone, quetiapine, olanzapine, clozapine, and aripiprazole. Descriptive, disproportionality, time, and dose analysis were performed using the Bayesian confidence propagation neural network, Weibull, and physiologically based pharmacokinetic model. RESULTS: Out of 1289 patients with AD treated with SGAs, the most common ADRs involved the nervous system, gastrointestinal system, and cardiac disorders. Disproportionality analysis identified significant positive signals in cardiac, renal, and vascular systems. Quetiapine, risperidone, and olanzapine showed more positive signals compared with clozapine and aripiprazole. Time analysis indicated that cardiovascular ADRs occurred randomly, whereas renal ADRs increased with prolonged use. Dose analysis suggested that small doses of SGAs did not elevate the risk of multiple cardiac, renal, or vascular ADRs. CONCLUSION AND RELEVANCE: The study underscores the importance of monitoring for ADRs, particularly in the cardiac and renal systems, when using SGAs in patients with AD. Future research incorporating more comprehensive clinical data is warranted to support safe and rational drug utilization.

Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation.

To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.

Exploring the Link Between Exogenous Thyroid Hormones and Dementia Symptoms: A Real-World Disproportionality Analysis of FDA Adverse Event Reporting System.

BACKGROUND: A growing body of evidence indicates a strong association between exogenous thyroid hormone (ETH) and brain health. Establishing the potential relationship between ETH therapy and dementia symptoms is crucial for patients with thyroid disorders. OBJECTIVE: In this study, we investigate the potential association between ETH therapy and dementia symptoms by exploring the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Disproportionality analysis (DPA) was conducted using postmarketing data from the FAERS repository (Q1 2004 to Q4 2023). Cases of dementia symptoms associated with ETH therapy were identified and analyzed through DPA using reporting odds ratios and information component methods. Dose and time-to-onset analyses were performed to assess the association between ETH therapy and dementia symptoms. RESULTS: A total of 9889 cases of ETH-associated symptoms were identified in the FAERS database. Dementia accounted for a consistent proportion of adverse drug reactions each year (3.4%-6.3%). The DPA indicated an association between ETH therapy and dementia symptoms, which remained significant even across sex, age, and indications. The median time-to-onset of dementia symptoms was 7.5 days, and the median treatment time was 40.5 days. No significant dose-response relationship was observed. CONCLUSION AND RELEVANCE: This study provides evidence for a link between ETH therapy and dementia. Clinicians are therefore advised to exercise vigilance, conduct comprehensive monitoring, and consider individualized dosing to mitigate potential reactions to ETH drug administration.

Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database.

BACKGROUND: Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) is crucial for public safety. This study investigated the potential association between GLP-1RAs and SSIBs by exploring the FDA Adverse Event Reporting System (FAERS) database. METHODS: A disproportionality analysis was conducted using post-marketing data from the FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with GLP-1RAs were identified and analyzed through disproportionality analysis using the information component. The parametric distribution with a goodness-of-fit test was employed to analyze the time-to-onset, and the Ω shrinkage was used to evaluate the potential effect of co-medication on the occurrence of SSIBs. RESULTS: In total, 204 cases of SSIBs associated with GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, and albiglutide, were identified in the FAERS database. Time-of-onset analysis revealed no consistent mechanism for the latency of SSIBs in patients receiving GLP-1RAs. The disproportionality analysis did not indicate an association between GLP-1RAs and SSIBs. Co-medication analysis revealed 81 cases with antidepressants, antipsychotics, and benzodiazepines, which may be proxies of mental health comorbidities. CONCLUSIONS: We found no signal of disproportionate reporting of an association between GLP-1RA use and SSIBs. Clinicians need to maintain heightened vigilance on patients premedicated with neuropsychotropic drugs. This contributes to the greater acceptance of GLP-1RAs in patients with type 2 diabetes mellitus or obesity.

Limited Sampling Strategies for Estimating Busulfan Area Under the Concentration-Time Curve: Based on Peak and Trough Concentrations in Saliva.

Therapeutic drug monitoring for busulfan is currently performed by multiple plasma sampling. Saliva is considered a noninvasive therapeutic drug monitoring matrix. This study aimed to investigate intravenous busulfan pharmacokinetics (PK) in plasma and saliva, and establish a limited sampling strategy (LSS) for predicting the area under the concentration-time curve from time zero to infinity in plasma (AUC0-∞,p) by using saliva samples. Therefore, the PK of busulfan was studied in 37 Chinese patients. Pearson correlation analysis was used to evaluate the correlation between the AUC of busulfan in plasma and saliva. LSS models were established by the multiple linear regression analysis. The prediction error, the mean prediction error, and the root mean square error were used to evaluate the predictive accuracy. The agreement between the predicted and observed AUC0-∞ in saliva was investigated by the intraclass correlation coefficient and Bland-Altman analysis. The accuracy and robustness of the models were evaluated by using the bootstrap procedure. The result of PK analysis 62.2% of patients (23/37) was within the target range of AUC0-∞,p . A good correlation between saliva and plasma busulfan AUC0-∞ was observed (r = 0.63, p < .01). The bias and precision of the models 7 and 13 were less than 15%. The intraclass correlation coefficient exceeded 0.9, and the limits of agreement were within ±15%. The 2-point LSS model in saliva is a convenient and desirable approach to predict the AUC0-∞ of 4 times daily intravenous busulfan in plasma, which can be used to design personalized dosing for busulfan.

Highly-Adaptable Optothermal Nanotweezers for Trapping, Sorting, and Assembling across Diverse Nanoparticles.

Optical manipulation of various kinds of nanoparticles is vital in biomedical engineering. However, classical optical approaches demand higher laser power and are constrained by diffraction limits, necessitating tailored trapping schemes for specific nanoparticles. They lack a universal and biocompatible tool to manipulate nanoparticles of diverse sizes, charges, and materials. Through precise modulation of diffusiophoresis and thermo-osmotic flows in the boundary layer of an optothermal-responsive gold film, highly adaptable optothermal nanotweezers (HAONTs) capable of manipulating a single nanoparticle as small as sub-10 nm are designed. Additionally, a novel optothermal doughnut-shaped vortex (DSV) trapping strategy is introduced, enabling a new mode of physical interaction between cells and nanoparticles. Furthermore, this versatile approach allows for the manipulation of nanoparticles in organic, inorganic, and biological forms. It also offers versatile function modes such as trapping, sorting, and assembling of nanoparticles. It is believed that this approach holds the potential to be a valuable tool in fields such as synthetic biology, optofluidics, nanophotonics, and colloidal science.

Untargeted metabolomics analysis reveals the metabolic disturbances and exacerbation of oxidative stress in recurrent spontaneous abortion.

BACKGROUND: Recurrent spontaneous abortion (RSA) is characterized by the occurrence of two or more consecutive spontaneous abortions, with a rising prevalence among pregnant women and significant implications for their physical and mental well-being. The multifaceted etiology of RSA has posed challenges in unraveling the molecular mechanisms underlying that underlie its pathogenesis. Oxidative stress and immune response have been identified as pivotal factors in the development of its condition. METHODS: Eleven serum samples from healthy pregnant women and 17 from RSA were subjected to liquid chromatography/mass spectrometry (LC-MS) analysis. Multivariate statistical analysis was employed to excavate system-level characterization of the serum metabolome. The measurement of seven oxidative stress products, namely superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), glutathione (GPx), glutathione peroxidase (GSH), oxidized glutathione (GSSG), heme oxygenase (HO-1), was carried out using ELISA. RESULTS: Through the monitoring of metabolic and lipid alternations during RSA events, we have identified 816 biomarkers that were implicated in various metabolic pathways, including glutathione metabolism, phosphonate and phosphinate metabolism, nucleotide metabolism, sphingolipid metabolism, lysine degradation and purine metabolism, etc. These pathways have been found to be closely associated with the progression of the disease. Our finding indicated that the levels of MDA and HO-1 were elevated in the RSA group compared to the control group, whereas SOD, CAT and GPx exhibited a contrary pattern. However, no slight difference was observed in GSH and GSSG levels between the RSA group and the control group. CONCLUSION: The manifestation of RSA elicited discernible temporal alternations in the serum metabolome and biochemical markers linked to the metabolic pathways of oxidative stress and immune response. Our investigation furnished a more comprehensive analytical framework encompassing metabolites and enzymes associated with oxidative stress. This inquiry furnished a more nuanced comprehension of the pathogenesis of RSA and established the ground work for prognostication and prophylaxis.

CRISPR-powered optothermal nanotweezers: Diverse bio-nanoparticle manipulation and single nucleotide identification.

Optothermal nanotweezers have emerged as an innovative optical manipulation technique in the past decade, which revolutionized classical optical manipulation by efficiently capturing a broader range of nanoparticles. However, the optothermal temperature field was merely employed for in-situ manipulation of nanoparticles, its potential for identifying bio-nanoparticles remains largely untapped. Hence, based on the synergistic effect of optothermal manipulation and CRIPSR-based bio-detection, we developed CRISPR-powered optothermal nanotweezers (CRONT). Specifically, by harnessing diffusiophoresis and thermo-osmotic flows near the substrate upon optothermal excitation, we successfully trapped and enriched DNA functionalized gold nanoparticles, CRISPR-associated proteins, as well as DNA strands. Remarkably, we built an optothermal scheme for enhancing CRISPR-based single-nucleotide polymorphism (SNP) detection at single molecule level, while also introducing a novel CRISPR methodology for observing nucleotide cleavage. Therefore, this innovative approach has endowed optical tweezers with DNA identification ability in aqueous solution which was unattainable before. With its high specificity and feasibility for in-situ bio-nanoparticle manipulation and identification, CRONT will become a universal tool in point-of-care diagnosis, biophotonics, and bio-nanotechnology.

DNA Assembly of Plasmonic Nanostructures Enables In Vivo SERS-Based MicroRNA Detection and Tumor Photoacoustic Imaging.

Controllable self-assembly of the DNA-linked gold nanoparticle (AuNP) architecture for in vivo biomedical applications remains a key challenge. Here, we describe the use of the programmed DNA tetrahedral structure to control the assembly of three different types of AuNPs (∼20, 10, and 5 nm) by organizing them into defined positioning and arrangement. A DNA-assembled "core-satellite" architecture is built by DNA sequencing where satellite AuNPs (10 and 5 nm) surround a central core AuNP (20 nm). The density and arrangement of the AuNP satellites around the core AuNP were controlled by tuning the size and amount of the DNA tetrahedron functionalized on the core AuNPs, resulting in strong electromagnetic field enhancement derived from hybridized plasmonic coupling effects. By conjugating with the Raman molecule, strong surface-enhanced Raman scattering photoacoustic imaging signals could be generated, which were able to image microRNA-21 and tumor tissues in vivo. These results provided an efficient strategy to build precision plasmonic superstructures in plasmonic-based bioanalysis and imaging.

Experimental Study on Shear Rheological Polishing of Si Surface of 4H-SiC Wafer.

In this study, shear rheological polishing was used to polish the Si surface of six-inch 4H-SiC wafers to improve polishing efficiency. The surface roughness of the Si surface was the main evaluation index, and the material removal rate was the secondary evaluation index. An experiment was designed using the Taguchi method to analyze the effects of four critical parameters (abrasive particle size, abrasive particle concentration, polishing speed, and polishing pressure) on the Si surface polishing of SiC wafers. By evaluating the experimental results for the signal-to-noise ratio, the weight of each factor was calculated using the analysis of variance method. The optimal combination of the process parameters was obtained. Below are the weightings for the influence of each process on the polishing result. A higher value for the percentage means that the process has a greater influence on the polishing result. The wear particle size (85.98%) had the most significant influence on the surface roughness, followed by the polishing pressure (9.45%) and abrasive concentration (3.25%). The polishing speed had the least significant effect on the surface roughness (1.32%). Polishing was conducted under optimized process conditions of a 1.5 µm abrasive particle size, 3% abrasive particle concentration, 80 r/min polishing speed, and 20 kg polishing pressure. After polishing for 60 min, the surface roughness, Ra, decreased from 114.8 to 0.9 nm, with a change rate of 99.2%. After further polishing for 60 min, an ultrasmooth surface with an Ra of 0.5 nm and MRR of 20.83 nm/min was obtained. Machining the Si surface of 4H-SiC wafers under optimal polishing conditions can effectively remove scratches on the Si surface of 4H-SiC wafers and improve the surface quality.

Disproportionality Analysis of Lenvatinib-Caused Gastrointestinal Perforation in Cancer Patients: A Pharmacovigilance Analysis Based on the US Food and Drug Administration Adverse Event Reporting System.

Lenvatinib is a medication that targets multiple tyrosine kinases and is commonly used to treat various types of cancer. With its frequent usage, monitoring and assessing its potential adverse effects has become crucial. This study utilizes the US Food and Drug Administration Adverse Event Reporting System (FAERS) database to analyze the possible link between lenvatinib and gastrointestinal perforation. FAERS was used to analyze adverse drug reactions (ADRs) linked with lenvatinib from the first quarter of 2015 to the last quarter of 2022. The association between lenvatinib and gastrointestinal perforation was evaluated using disproportionality analyses. This study included 464 patients who developed gastrointestinal perforation after using lenvatinib. Perforation involved the entire digestive tract, with the colon among the most commonly affected perforation sites, and previously undetected esophageal perforation was frequently observed. Patients with uterine and liver cancer were at a higher risk of developing gastrointestinal perforation; patients with liver cancer experienced a shorter onset time, whereas patients with endometrial cancer had a slower onset time. Middle-aged and elderly patients exhibited a higher propensity for developing gastrointestinal perforation than younger adults. Patients with gastrointestinal perforation were found to have a significantly higher mortality rate than patients without gastrointestinal perforation. This study has identified several gastrointestinal perforation events not included in the drug instructions. It has also described the perforation site and clinical characteristics based on various types of cancer. These results could provide valuable insights for developing safer and more effective regulatory strategies concerning the use of lenvatinib.

Surface Modification of Silicon Carbide Wafers Using Atmospheric Plasma Etching: Effects of Processing Parameters.

Silicon carbide wafer serves as an ideal substrate material for manufacturing semiconductor devices, holding immense potential for the future. However, its ultra-hardness and remarkable chemical inertness pose significant challenges for the surface processing of wafers, and a highly efficient and damage-free method is required to meet the processing requirements. In this study, atmospheric plasma processing was used to conduct point-residence experiments on silicon carbide wafers by varying process parameters such as Ar, CF4, and O2 flow rate, as well as processing power and the distance between the plasma torch and the workpiece. We investigate the effects of these on the surface processing function of atmospheric plasma etching and technique for surface modification of silicon carbide wafers, evaluating the material removal rates. Then, according to the experimentally derived influence law, suitable parameter ranges were selected, and orthogonal experiments were designed to determine the optimal processing parameters that would enable rapid and uniform removal of the wafer surface. The results indicate that the volume removal rate of the plasma on the silicon carbide wafer achieves its maximum when the input power is 550 W, the processing distance between the plasma torch and workpiece is 3.5 mm, and when the Ar, CF4, and O2 flow rates are 15 SLM, 70 SCCM, and 20 SCCM, respectively.

Saliva as a noninvasive sampling matrix for therapeutic drug monitoring of intravenous busulfan in Chinese patients undergoing hematopoietic stem cell transplantation: A prospective population pharmacokinetic and simulation study.

Therapeutic drug monitoring (TDM) of busulfan (BU) is currently performed by plasma sampling in patients undergoing hematopoietic stem cell transplantation (HSCT). Saliva samples are considered a noninvasive TDM matrix. Currently, no salivary population pharmacokinetics (PopPKs) model for BU available. This study aimed to develop a PopPK model that can describe the relationship between plasma and saliva kinetics in patients receiving intravenous BU. The performance of the model in predicting the area under the concentration-time curve at steady state (AUCss ) based on saliva samples is evaluated. Sixty-six patients with HSCT were recruited and administered 0.8 mg/kg BU intravenously. A PopPK model for saliva and plasma was developed using the nonlinear mixed effects model. Bayesian maximum a posteriori (MAP) optimization was used to estimate the model's predictive performance. Plasma and saliva PKs were adequately described with a one-compartment model and a scaled central compartment. Body surface area correlated positively with both clearance and apparent volume of distribution (Vd), whereas alkaline phosphatase correlated negatively with Vd. Simulations demonstrated that the percentage root mean squared prediction error and lower and upper limits of agreements reduced to 10.02% and -16.96% to 22.86% based on five saliva samples. Saliva can be used as an alternative matrix to plasma in TDM of BU. The AUCss can be predicted from saliva concentration by Bayesian MAP optimization, which can be used to design personalized dosing for BU.

Movement disorders associated with antiseizure medications: A real-world disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System.

AIMS: Patients with epilepsy often require long-term use of antiseizure medications (ASMs) to control their seizures. However, movement disorders (MDs) related to ASMs can significantly impact their quality of life. This study aims to analyse MDs related to ASMs in the Food and Drug Administration Adverse Event Reporting System database to provide recommendations for safe medication. METHODS: All adverse drug reactions associated with 26 marketed ASMs in Food and Drug Administration Adverse Event Reporting System were extracted for analysis. Disproportionality analyses were used to assess the association between ASMs and MDs, and signal colour scale maps were created to identify potential ASM-MD safety signals. RESULTS: A total of 1921 cases experienced MDs while taking ASMs were included. A higher prevalence of MDs was observed in females compared to males. The association between specific MDs with ASMs was revealed, including known and unknown MDs such as tremors, Parkinson and paralysis. Lamotrigine and carbamazepine exhibited multiple significant MDs, while levetiracetam and pregabalin were linked to the earlier onset of MDs. Generally, higher doses were linked to a higher incidence of MDs. CONCLUSION: MDs were the most obvious adverse drug reactions in the nervous system triggered by using ASMs. Fourteen drugs exhibited positive signals for MDs, including some not previously reported. Conversely, 12 ASMs were deemed to have a lower possibility of inducing MDs. The incidence of MDs can be mitigated by selecting appropriate ASMs for epileptic patients. These findings enhance our understanding of the relationship between ASMs and MDs.

Study of Atmospheric Pressure Plasma Temperature Based on Silicon Carbide Etching.

In order to further understand the excitation process of inductively coupled plasma (ICP) and improve the etching efficiency of silicon carbide (SiC), the effect of temperature and atmospheric pressure on plasma etching of silicon carbide was investigated. Based on the infrared temperature measurement method, the temperature of the plasma reaction region was measured. The single factor method was used to study the effect of the working gas flow rate and the RF power on the plasma region temperature. Fixed-point processing of SiC wafers analyzes the effect of plasma region temperature on the etching rate. The experimental results showed that the plasma temperature increased with increasing Ar gas until it reached the maximum value at 15 slm and decreased with increasing flow rate; the plasma temperature increased with a CF4 flow rate from 0 to 45 sccm until the temperature stabilized when the flow rate reached 45 sccm. The higher the RF power, the higher the plasma region's temperature. The higher the plasma region temperature, the faster the etching rate and the more pronounced the effect on the non-linear effect of the removal function. Therefore, it can be determined that for ICP processing-based chemical reactions, the increase in plasma reaction region temperature leads to a faster SiC etching rate. By processing the dwell time in sections, the nonlinear effect caused by the heat accumulation on the component surface is effectively improved.

Rolling Bearing Fault Diagnosis Using Multi-Sensor Data Fusion Based on 1D-CNN Model.

To satisfy the requirements of the end-to-end fault diagnosis of rolling bearings, a hybrid model, based on optimal SWD and 1D-CNN, with the layer of multi-sensor data fusion, is proposed in this paper. Firstly, the BAS optimal algorithm is adopted to obtain the optimal parameters of SWD. After that, the raw signals from different channels of sensors are segmented and preprocessed by the optimal SWD, whose name is BAS-SWD. By which, the sensitive OCs with higher values of spectrum kurtosis are extracted from the raw signals. Subsequently, the improved 1D-CNN model based on VGG-16 is constructed, and the decomposed signals from different channels are fed into the independent convolutional blocks in the model; then, the features extracted from the input signals are fused in the fusion layer. Finally, the fused features are processed by the fully connected layers, and the probability of classification is calculated by the cross-entropy loss function. The result of comparative experiments, based on different datasets, indicates that the proposed model is accurate, effective, and has a good generalization ability.

Pharmacovigilance of triazole antifungal agents: Analysis of the FDA adverse event reporting system (FAERS) database.

Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year. OBJECTIVE: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs. METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals. RESULTS: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile. CONCLUSION: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.