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Background and purpose: The development and approval of inhibitors of cyclin-dependent kinase 4/6 (CDK4/6) is an essential milestone in treating hormone receptor-positive metastatic breast cancer. The efficacy of these drugs is similar, but the adverse events (AE) are different, directly affecting the physician's choice of drug. There is no systematic study on the safety of CDK4/6 inhibitors in the real world. In this study, we compared the differences in AE of CDK4/6 inhibitors through signal mining in the FDA Adverse Event Reporting System (FAERS) and identified unknown AE signals to provide a reference for the clinical choice of treatment and monitoring AE. Methods: All data in the FAERS database were extracted from the first quarter of 2004 to the first quarter of 2023. After removing duplicates, data were analyzed by the disproportionality method for reports ranking palbociclib, abemaciclib, or ribociclib as the primary suspect. Signals were identified using the reporting odds ratio (ROR) and MHRA methods. Positive signals were required to meet the following criteria: the number of reports ≥3, the lower limit of the 95% confidence interval of the ROR >1, proportional reporting ratios (PRR) >2, and the χ2 >4. Results: A total of 85 562 reports of AE associated with CDK4/6 inhibitors were identified. The highest signal intensity of palbociclib was observed in hematologic and lymphatic AE (leukopenia ROR = 20.01). Palbociclib had lower AE signals in the gastrointestinal, hepatic, and renal systems than the other drugs (diarrhea ROR = 1.95, gamma-glutamyltransferase increased ROR = 0.36, blood creatinine increased ROR = 1.01). Abemaciclib had the strongest signal in the gastrointestinal system (diarrhea ROR = 13.54); it also showed a strong AE signal in the hepatic and renal systems (gamma-glutamyltransferase increased ROR = 2.58, blood creatinine increased ROR = 7.74) and a lower AE signal than the other drugs in the blood and lymphatic systems (leukopenia ROR = 5.34). Ribociclib had a lower AE signal intensity in the blood and lymphatic system than palbociclib (leukopenia ROR = 7.55); however, among hepatic AE, ribociclib had the highest signal intensity of increased gamma-glutamyltransferase (ROR = 4.05). In rare severe hepatic systemic AE, abemaciclib had the strongest signal in hepatic failure (ROR = 3.50) and drug-induced liver injury (ROR = 4.68). Erythema multiforme was a newly identified signal in the abemaciclib reports (ROR = 3.06). Conclusion: The safety profile of CDK4/6 inhibitors varies. Analysis of the FAERS database revealed hematologic and lymphatic system toxicities for palbociclib and ribociclib and gastrointestinal and hepatorenal toxicities for abemaciclib. Erythema multiforme was found as a novel severe AE for abemaciclib. Individualized drug selection and monitoring of AE based on the patient’s physiological status and AE are needed during treatment.

Compressed ultrafast photography (CUP) can capture irreversible or difficult‐to‐repeat dynamic scenes at the imaging speed of more than one billion frames per second, which is obtained by compressive sensing‐based image reconstruction from a compressed 2D image through the discretization of detector pixels. However, an excessively high data compression ratio in CUP severely degrades the image reconstruction quality, thereby restricting its ability to observe ultrafast dynamic scenes with complex spatial structures. To address this issue, a discrete illumination‐based CUP (DI‐CUP) with high fidelity is reported. In DI‐CUP, the dynamic scenes are loaded into an ultrashort laser pulse train with controllable sub‐pulse number and time interval, thus the data compression ratio, as well as the overlap between adjacent frames, is greatly decreased and flexibly controlled through the discretization of dynamic scenes based on laser pulse train illumination, and high‐fidelity image reconstruction can be realized within the same observation time window. Furthermore, the superior performance of DI‐CUP is verified by observing femtosecond laser‐induced ablation dynamics and plasma channel evolution, which are hardly resolved in the spatial structures using conventional CUP. It is anticipated that DI‐CUP will be widely and dependably used in the real‐time observations of various ultrafast dynamics. [ABSTRACT FROM AUTHOR]

Vanadium nitride (VN) is an attractive anode material for lithium-ion batteries (LIBs) due to its large theoretical capacity and excellent electrical conductivity; however, its low rate performance and poor cycle life caused by slow reaction kinetics and large volume changes have limited its practical application. Herein, in situ formation of VN quantum nanodots (VNQDs) anchored on a three-dimensional porous N-doped carbon (PNC) skeleton was achieved by a simple and scalable template-assisted and heat treatment strategy to build porous VNQDs@PNC composites as pseudocapacitive anode materials for LIBs. The resulting composites provide abundant active sites (uniform distribution of VNQDs), excellent electrical conductivity (N-doped carbon) and a shortened ion diffusion channel. The pseudo-capacitive controlled behaviour accelerates the fast lithium intercalation and delithiation process. As a result, the VNQDs@PNC-3 anode materials exhibit high lithium-ion storage capacities (687.3 mA h g−1 under 100 mA g−1), excellent rate performance (239 mA h g−1 at 15 A g−1), and long-term stability (372.1 mA h g−1 at 2 A g−1 with a capacity retention of 80.06% over 3000 cycles). When coupled with a LiFePO4 (LFP) cathode, the full battery exhibits a large capacity of 63.4 mA h g−1 over 5000 cycles at 0.5 A g−1. This work further verifies the feasibility of kinetics-compatible electrode material design strategies toward high rate LIBs. [ABSTRACT FROM AUTHOR]

In order to investigate the effects of fly ash and steel fiber on the abrasion resistance of ultra-high performance concrete (UHPC), this paper performed macroscopic mechanical test, underwater abrasion resistance test and microscopic characterization such as SEM and MIP to investigate the effects of fly ash and steel fiber on the workability, mechanical properties, microstructure, and abrasion resistance of UHPC. The results show that the replacement of cement by fly ash delays the emergence of hydration peak by about 3 h, and the cumulative heat flow at 3 d is reduced by 18%, significantly improving the workability of UHPC. The incorporation of fly ash reduces the mechanical properties of UHPC in the early stage and has no effect on the mechanical properties in the later stage. The incorporation of steel fiber improves the flexural strength and compressive strength of UHPC. The flexural strength and compressive strength are increased by 82% and 47% respectively due to the composite mixing of steel fiber and fly ash under steam curing. The addition of fly ash has little effect on the abrasion resistance of UHPC, while the addition of steel fiber improves the abrasion resistance of UHPC, and the composite mixing of steel fiber and fly ash increases the abrasion resistance of UHPC by 58%. The compressive strength and abrasion resistance strength of UHPC show a significant positive correlation. The incorporation of fly ash reduces the most available pore size, porosity and capillary pore content, making the internal structure of matrix more uniform and denser. [ABSTRACT FROM AUTHOR]

With the rapid growth of traffic demand and the development of intelligent technology, autonomous transportation system (ATS) has been considered as future transportation system. The evaluation of a designed physical architecture of ATS is necessary for understanding whether and how ATS operates and evolves automatically without manual works, and architecture simulation is a method for solving such research problem. Therefore, in this study, architecture simulation based on system dynamics modelling has been employed for physical architecture research. Under this methodology, a simulation case for scenario “Autonomous Vehicle on a Crossing in an Autonomous Transportation System” has been studied for understanding the information flow in ATS to evaluate and optimise its physical architecture of ATS. In conclusion, the system dynamic model could help researchers understand and evaluate the physical architecture's operation of ATS by scenario analysis., Author(s): Chen Liang [1]; Zhenwu Chen [1]; Liang Yang [1]; Zihan Guo [1]; Xianglong Feng [1]; Zhijun Huang [1]; Xiang Liu [1]; Yuqing Qian [1]; Yanqing Xu [1]; Xiaochun Zhang [...]

Research on the complicated and indeterminate autonomous transportation system (ATS) has drawn increased interest in order to better address issues associated with contemporary transportation development. Hoping to make transportation more sustainable, economical, safe, convenient, and efficient, researchers try to address the expanding demands with the help of ATS characteristics, i.e., sensing, learning, deciding, and reacting autonomously. The majority of research is focused on the ATS architecture, which is currently in the design phase. To refine the relationship between entities in the architecture, this paper proposes DESIEP, a method based on discrete event simulation (DES) for information exchange pairs (IEPs) in ATS. This method can provide an intelligible description of the information stream while conveniently illustrating the control relationship of sequential logic amongst the entities in the architecture. It helps researchers better understand the running mechanisms driven by internal demands and external technologies of the system so as to diagnose, evaluate, verify, and optimize the designed architecture. Meanwhile, this method also supports further research on the system evolution and architecture analysis, including the functions, logic, and physical architectures of each generation, as well as their mapping relationships and parallel evolution mechanisms., Author(s): Ji Zhang [1]; Zhenwu Chen [1]; Liang Yang [1]; Zihan Guo [1]; Xianglong Feng [1]; Xiang Liu [1]; Zhijun Huang [1]; Puyang Deng [1]; Xiaochun Zhang (corresponding author) [1]; [...]

In this study, we compared the similarities and differences in adverse events (AEs) among CAR T-cell products through signal mining via the FDA Adverse Event Reporting System (FAERS) and identified unknown AEs to provide a reference for safe clinical medication. Data from the FAERS database spanning from the fourth quarter of 2017 to the first quarter of 2024 were extracted. Signals were identified using the reporting odds ratio (ROR) method and the Medicines and Healthcare Products Regulatory Agency (MHRA) method. A total of 11,386 AE reports related to six CAR T-cell products were selected. The top three categories of AEs reported were nervous system disorders, immune system disorders, and general disorders and administration site conditions. However, there were variations in the AE spectra among the different CAR T-cell products. The BCMA-targeting drugs idecabtagene vicleucel (Ide-cel) and ciltacabtagene autoleucel (Cilta-cel) were found to be associated with parkinsonism, which were not observed in CD19-targeting drugs. Tisagenlecleucel (Tisa-cel) and axicabtagene ciloleucel (Axi-cel) exhibited cerebrovascular accident-related AEs, graft versus host disease, and abnormal coagulation indices. Cilta-cel was associated with cerebral hemorrhage, intracranial hemorrhage, cranial nerve disorder, and facial nerve disorder. Cardiopulmonary toxicity, including hypoxia, tachypnoea, cardiorenal syndrome, and hypotension, exhibited strong signal intensities and considerable overlap with CRS. The number of positive signals for cardiopulmonary toxicity associated with drugs targeting CD-19 is greater. Clinicians should assess patients prior to medication and closely monitor their vital signs, mental status, and laboratory parameters during treatment. [ABSTRACT FROM AUTHOR]