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The evolution of fractures in overburden is quantitatively investigated to characterize the effect of mining activity. Scale model testing and numerical modeling were used based on the engineering geological and mining environments of Panel 11050 in the Quandian Coalmine in Henan Province, China. The maximum vertical displacement is 62.76 m, which is 140 m from the initial mining in the scale model test. Based on the fractal geometric theory, the fractal dimensions of the fractures in the overburden are calculated and visualized. The results reveal that if two coal seams are mined at the same time, the fractal dimension of the fracture network in the overburden increase with the progression of mining, but the rate of increase gradually slows. The relationships between the fractal dimension and the maximum height of the overburden failure and maximum overburden subsidence are nonlinear. The structural characteristics of the overburden are represented by the network of fractures. With increasing distance from the coal seam roof, the mining stress is gradually transferred upward to the overlying strata, and the scale of this stress transfer gradually reduces. The variation in the vertical stress gradually weakens and shows a delayed change with the mining process. The maximum principal stress is compressive stress and is distributed in an “arch” shape. The stress on both sides of the “arch” is high, and the intermediate stress is low. The stress within the “arch” shows an opposite trend.

This study aimed to empirically analyze gastrointestinal adverse events associated with Lenvatinib monotherapy and its combination with Pembrolizumab using FDA FAERS data (January 2015-December 2023), focusing on risk profiles, temporal patterns, and influencing factors. Proportional disproportionality analysis (ROR, PRR, BCPNN, EBGM) evaluated drug-AE associations. Kaplan–Meier curves characterized temporal distributions, while Wilcoxon rank-sum test compared median time-to-onset between regimens. Univariate logistic regression identified independent risk factors. A total of 291 severe gastrointestinal AEs reports were included. The gastrointestinal system had the most positive AE signals in both treatment groups. Perforation events showed strong positive signals in both regimens, while haemorrhage and fistula events were unique positive signals in the lenvatinib monotherapy group. In contrast, colitis and pancreatitis positive signals were more common in the combination therapy group. Most gastrointestinal AEs in both groups occurred within the first month of treatment. The monotherapy group had a significantly shorter median onset time than the combination therapy group (27 days vs. 38 days, P = 0.003). Logistic regression indicated that female sex (OR = 0.195, P = 0.022) and low—dose medication (OR = 0.240, P = 0.049) were independent protective factors for gastrointestinal AEs in the monotherapy group. This first comprehensive comparison reveals distinct gastrointestinal toxicity profiles: monotherapy predisposes to acute bleeding/fistulas, while combination therapy increases delayed tumor-related complications. Intensive monitoring during the first treatment month and gender/dosage-adjusted prevention strategies are recommended. These findings provide evidence-based insights for optimizing safety management of targeted-immunotherapy combinations.

Background: Clarithromycin is a widely used antibiotic, but its safety profile, particularly in different age groups, remains inadequately explored. Objectives: This study aims to characterize and illustrate the features of clarithromycin-related adverse events (AEs) across different age groups using the FDA Adverse Event Reporting System (FAERS) database, providing a reference for the clinical detection, prevention, and management of AEs in various age groups. Design: A disproportionality analysis was performed using data from the FAERS database. The study included all AE reports related to clarithromycin, stratified by age groups. Methods: Disproportionality analysis was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multiple gamma Poisson shrinkers. Statistical analyses included descriptive statistics and Chi-square tests. Results: A total of 7319 reports of clarithromycin AEs were retrieved from the FAERS database. Vomiting, diarrhea, drug interactions, and drug interactions were reported most frequently in the age groups 0–17, 18–44, 45–64, and ⩾65 years, respectively. Abnormal product taste, taste disorder, and medication errors related to drug interactions specified in the package insert were the strongest signals in the age groups 0–17, 18–44, 45–64, and ⩾65 years, respectively. A total of 41 Preferred Terms signals were not explicitly included in the clarithromycin package insert and were mainly associated with psychiatric disorders, skin and subcutaneous tissue disorders, and gastrointestinal disorders, among others. Specific signals for age differences were identified, with 18 signals being age-specific, including 3 in children and 15 in elderly individuals. Conclusion: The safety profile of clarithromycin varies across age groups. In children, it is mainly associated with vomiting, hypersensitivity, and dyspnea, while in adults, psychiatric AEs are more common. In the elderly, clarithromycin should be used cautiously, with attention to drug interactions. Plain language summary A study on the adverse effects of clarithromycin Introduction: Clarithromycin is a relatively newer macrolide antibiotic derived from erythromycin, that is included in the WHO Model List of Essential Medicines, and is one of the important drugs needed in basic healthcare systems. Currently, there are no studies mining adverse events and outcomes related to the clinical use of clarithromycin in the FDA Adverse Event Reporting System (FAERS) database. This study investigated the safety signals related to clarithromycin. Methods: Disproportionality analysis, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multiple gamma Poisson shrinker (MGPS) algorithms, were used to quantify signals of clarithromycin-related adverse events (AEs) across different age groups. Results: 7,319 AE reports were identified, 41 PT signals were not explicitly included in the clarithromycin package insert. Specific signals for age differences were identified, with 18 signals being age specific. Conclusion: We discovered important safety concerns related to clarithromycin. The safety of clarithromycin is different in different age groups. Children are more closely associated with adverse events related to vomiting, drug-induced hypersensitivity, and dyspnea. In adults, it is more associated with psychiatric adverse events. In addition, the use of clarithromycin in the elderly should be strictly in accordance with the instructions and be alert to drug interactions.

Background As the application of Chimeric Antigen Receptor T-cell (CAR-T) therapy in cancer treatment becomes increasingly widespread, associated hematologic and lymphatic system adverse events pose significant challenges to its clinical use. Therefore, we aim to comprehensively investigate and summarize the hematologic and lymphatic system AEs associated with CAR-T therapy. Methods We extracted CAR-T-related adverse event reports from the FDA Adverse Event Reporting System (FAERS) database for the period from August 2017 to December 2023. Disproportionality analysis using the Reporting Odds Ratio (ROR) and Information Component (IC) was performed to identify CAR-T-associated hematologic and lymphatic system AEs. We employed LASSO regression analysis to identify hematologic and lymphatic system AEs associated with mortality. Results In the FAERS database, we identified 1,600 individual case safety reports of hematologic and lymphatic system AEs related to CAR-T therapy. The median age of patients was 57 years (interquartile range [IQR] 32–67), with fatal outcomes in 15.3% of cases. We identified 25 significant adverse event signals associated with CAR-T therapy. B-cell aplasia (ROR025 = 1054.56, IC025 = 4.74), cytopenia (ROR025 = 17.27, IC025 = 3.81), hypofibrinogenemia (ROR025 = 100.18, IC025 = 2.46), anemia (ROR025 = 1.87, IC025 = 0.59), febrile bone marrow aplasia (ROR025 = 55.32, IC025 = 2.70), and pancytopenia (ROR025 = 7.18, IC025 = 1.42) were the most significant hematologic and lymphatic system AEs for tisa-cel, axi-cel, brexu-cel, liso-cel, ide-cel, and cilta-cel, respectively. Most hematologic and lymphatic system AEs occurred within 10 days post-CAR-T infusion. Hematologic and lymphatic system AEs were associated with a mortality rate of 15.3%. Our analysis revealed 15 hematologic and lymphatic system AEs closely associated with mortality in CAR-T-treated patients, including splenic hemorrhage, disseminated intravascular coagulation, and pancytopenia. Conclusions Our study found that hematologic and lymphatic system AEs were more closely associated with anti-CD19 CAR-T and CAR-T containing CD28. Splenic hemorrhage, disseminated intravascular coagulation, and pancytopenia were identified as hematologic and lymphatic system AEs that, while less frequently reported clinically, were highly associated with mortality.

Molnupiravir, an urgently approved drug during the Coronavirus Disease 2019 (COVID-19) pandemic, serves as the basis for our study, which relies on the Food and Drug Administration Adverse Event Reporting System (FAERS). The objective is to extract adverse event (AE) signals associated with molnupiravir from the FAERS database, thereby providing a reference for post-marketing monitoring of adverse events. Specifically, we extracted individual case safety reports (ICSRs) from the database, focusing on cases with COVID-19 indications and molnupiravir identified as the primary suspect drug. Descriptive analysis of the extracted data was performed, followed by four disproportionality analyses using the reporting odds ratio (ROR) method. These analyses were conducted across four levels, encompassing overall data, reports by health professionals, as well as age and gender differentiations, ensuring the robustness of the analysis results. In total, 116,576 ICSRs with COVID-19 indications and 2,285 ICSRs with molnupiravir as the primary suspect were extracted. Notably, after excluding cases with unknown age or gender, a higher proportion of molnupiravir-related ICSRs were observed among individuals aged 65 years and older (70.07%) and women (54.06%). The most frequently reported adverse events and AE signals were associated with gastrointestinal disorders, as well as skin and subcutaneous tissue disorders. Moreover, individuals aged 65 years and older exhibited a higher risk of cardiac disorders, hepatobiliary disorders, renal and urinary disorders, and vascular disorders. In conclusion, this study found molnupiravir demonstrated a lower risk of serious adverse events compared to other RNA antiviral drugs like remdesivir in patients under 65 years old. However, close monitoring of its safety is still necessary for elderly patients aged 65 years and above. Further studies are warranted to continuously assess the safety profile of molnupiravir as its usage increases, especially in high risk populations.

In western China coal mines, the mining-induced caving zone is regarded as a main pathway for water and sand inrush mixture hazards. The paper experimentally studied the flow behavior and the mechanism of water and sand mixture through mining-induced caving zones. Transport experiments are performed by using a laboratory-scale model, and the caving zone is modelled by using different sizes of glass beads. Four different sand sizes are used for the sand layer. The test results reveal that the mass flow rate of sand and water mixture increases with the increase of the initial water head. And an equation is proposed for the mass flow rate of sand and water mixtures that correctly reproduces the data for all the conditions. In addition, the sudden decreases in water head loss is monitored at the commencement of the water and sand flow, which would result in a large number of sand particles that rapidly start up and make the kinetic energy transfer from water to sand.

Glacial till deposits in the Greater Toronto Area (GTA) usually comprise fine-grained (clay and silt) and coarse-grained (sand, gravel, cobbles, and boulders) fractions, which are substantially heterogeneous in characteristics. Since coarse-grained fractions are too large to be tested in traditional laboratory equipment, the discrete element method (DEM) is applied in this study to simulate a series of large-scale biaxial tests to study the mechanical characterization of glacial till. This study is based on the results of comprehensive geotechnical investigations for the Eglinton Crosstown Light Rail Transit (LRT) Project in the GTA. The fine-grained till (clayey silt till) examined in this work is collected from the O’Connor Station site. The different proportions, gradations, and sizes of the coarse-grained fractions (gravel) with irregular random shapes and distributions are simulated. The analysis results indicate that the proportion of gravel influences the behavior and mechanical characterization of glacial till. The peak strength and initial modulus of the mixture gradually increase as the volumetric proportion of gravel increases to 30%. Beyond this percentage, the peak strength and initial modulus substantially increase. The failure mode of the sample changes from ductile to brittle with a volumetric proportion of gravel that is greater than 30%. In summary, when the volumetric proportion of gravel is limited to 30%, the gradation and size of the gravel only have a marginal influence on the mechanical characterization of the glacial till. However, a volumetric proportion of the gravel that exceeds 30% has significant impacts on the strength and deformation characteristics of glacial till.

Azithromycin, a widely prescribed macrolide antibiotic, faces emerging safety concerns due to inappropriate use and age-specific adverse drug reactions (ADRs). This study characterises age-stratified safety profiles of azithromycin using pharmacovigilance data. Adverse event (AE) reports for azithromycin prescribed in Mycoplasma pneumoniae pneumonia treatment (2004-2024) were extracted from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses (Reporting Odds Ratio, Proportional Reporting Ratio, Bayesian Confidence Propagation Neural Network, Multi-item Gamma Poisson Shrinker) identified safety signals across four age groups: 0-17, 18-44, 45-64, and ≥65 years. Among 7,496 AE reports, age-specific risks varied significantly. Paediatric populations (0-17 years) exhibited predominant cutaneous/hypersensitivity reactions (rash, pruritus, Stevens-Johnson syndrome) and unlabelled psychiatric signals (hallucinations). Adults (18-44 years) showed pregnancy-related risks (preterm delivery). Geriatric patients (≥65 years) had heightened cardiac risks (QT prolongation, torsades de pointes), often exacerbated by off-label COVID-19 use. The 45-64-year cohort displayed the highest signal frequency, primarily involving drug hypersensitivity. Off-label prescribing accounted for 65% of geriatric AEs. Azithromycin safety profiles differ markedly across age groups. Children face dermatologic and neuropsychiatric risks, while elderly patients are vulnerable to cardiac complications. Strict adherence to labelled indications, age-specific monitoring, and avoidance of off-label use - particularly during public health crises - are critical to mitigating ADRs. These findings underscore the need for stratified clinical decision-making and targeted pharmacovigilance.

In this study, we document several experiments that investigate the speed of the flow of fine sand through a fixed porous bed of packed glass beads under various conditions, including the height of the sand column ( H ) and porous bed ( h ) and the diameter of the glass beads ( D ) and sand grains ( d ). The experiments are conducted with glass beads packed at a constant density and sand at a different dry bulk density. The results show that the height of the sand does not affect the speed of the sand flow. The speed of the sand flow ( v ) decreases with an increase in h until h approaches a certain value. An equation v = a g D l n ( D kd ) is proposed, where a and k are the experimentally determined coefficients. Moreover, the flow of sand through a fixed porous bed could be regarded as parallel flow through multiple pipes, and therefore, the relationship between D and the number and diameter of pipes, N and D p , are discussed. Further investigations are needed for the result that the flow of sand through a porous bed or multiple parallel pipes cannot be simplified to flow through one orifice with a certain diameter.

Background As the application of Chimeric Antigen Receptor T-cell (CAR-T) therapy in cancer treatment becomes increasingly widespread, associated hematologic and lymphatic system adverse events pose significant challenges to its clinical use. Therefore, we aim to comprehensively investigate and summarize the hematologic and lymphatic system AEs associated with CAR-T therapy. Methods We extracted CAR-T-related adverse event reports from the FDA Adverse Event Reporting System (FAERS) database for the period from August 2017 to December 2023. Disproportionality analysis using the Reporting Odds Ratio (ROR) and Information Component (IC) was performed to identify CAR-T-associated hematologic and lymphatic system AEs. We employed LASSO regression analysis to identify hematologic and lymphatic system AEs associated with mortality. Results In the FAERS database, we identified 1,600 individual case safety reports of hematologic and lymphatic system AEs related to CAR-T therapy. The median age of patients was 57 years (interquartile range [IQR] 32-67), with fatal outcomes in 15.3% of cases. We identified 25 significant adverse event signals associated with CAR-T therapy. B-cell aplasia (ROR025 = 1054.56, IC025 = 4.74), cytopenia (ROR025 = 17.27, IC025 = 3.81), hypofibrinogenemia (ROR025 = 100.18, IC025 = 2.46), anemia (ROR025 = 1.87, IC025 = 0.59), febrile bone marrow aplasia (ROR025 = 55.32, IC025 = 2.70), and pancytopenia (ROR025 = 7.18, IC025 = 1.42) were the most significant hematologic and lymphatic system AEs for tisa-cel, axi-cel, brexu-cel, liso-cel, ide-cel, and cilta-cel, respectively. Most hematologic and lymphatic system AEs occurred within 10 days post-CAR-T infusion. Hematologic and lymphatic system AEs were associated with a mortality rate of 15.3%. Our analysis revealed 15 hematologic and lymphatic system AEs closely associated with mortality in CAR-T-treated patients, including splenic hemorrhage, disseminated intravascular coagulation, and pancytopenia. Conclusions Our study found that hematologic and lymphatic system AEs were more closely associated with anti-CD19 CAR-T and CAR-T containing CD28. Splenic hemorrhage, disseminated intravascular coagulation, and pancytopenia were identified as hematologic and lymphatic system AEs that, while less frequently reported clinically, were highly associated with mortality. Keywords: CAR-T therapy, Hematologic and lymphatic system toxicity, Adverse events, FAERS