nnDetection for Intracranial Aneurysms Detection and Localization

Intracranial aneurysms are a commonly occurring and life-threatening condition, affecting approximately 3.2% of the general population. Consequently, detecting these aneurysms plays a crucial role in their management. Lesion detection involves the simultaneous localization and categorization of abnormalities within medical images. In this study, we employed the nnDetection framework, a self-configuring framework specifically designed for 3D medical object detection, to detect and localize the 3D coordinates of aneurysms effectively. To capture and extract diverse features associated with aneurysms, we utilized TOF-MRA and structural MRI, both obtained from the ADAM dataset. The performance of our proposed deep learning model was assessed through the utilization of free-response receiver operative characteristics for evaluation purposes. The model's weights and 3D prediction of the bounding box of TOF-MRA are publicly available at https://github.com/orouskhani/AneurysmDetection.Comment: 6 pages, 4 figure

Transplantation of Bone Marrow Mesenchymal Stem Cells Prevents Radiation-Induced Artery Injury by Suppressing Oxidative Stress and Inflammation

The present study aims to explore the protective effect of human bone marrow mesenchymal stem cells (hBMSCs) on radiation-induced aortic injury (RIAI). hBMSCs were isolated and cultured from human bone marrow. Male C57/BL mice were irradiated with a dose of 18-Gy 6MV X-ray and randomly treated with either vehicle or hBMSCs through tail vein injection with a dose of 103 or 104 cells/g of body weight (low or high dose of hBMSCs) within 24 h. Aortic inflammation, oxidative stress, and vascular remodeling were assessed by immunohistochemical staining at 3, 7, 14, 28, and 84 days after irradiation. The results revealed irradiation caused aortic cell apoptosis and fibrotic remodeling indicated by aortic thickening, collagen accumulation, and increased expression of profibrotic cytokines (CTGF and TGF-β). Further investigation showed that irradiation resulted in elevated expression of inflammation-related molecules (TNF-α and ICAM-1) and oxidative stress indicators (4-HNE and 3-NT). Both of the low and high doses of hBMSCs alleviated the above irradiation-induced pathological changes and elevated the antioxidant enzyme expression of HO-1 and catalase in the aorta. The high dose even showed a better protective effect. In conclusion, hBMSCs provide significant protection against RIAI possibly through inhibition of aortic oxidative stress and inflammation. Therefore, hBMSCs can be used as a potential therapy to treat RIAI

The estimation of young water fraction based on isotopic signals: challenges and recommendations

Young water fraction (Fyw) is defined as the fraction of water in a stream with a transit time of less than 2–3 months. Fyw is a metric used to quantify the proportion of precipitation input converted into the runoff in the form of fast flow, which provides new insights for characterizing the mechanisms of water storage and release, understanding the time-scale of ecohydrological processes and indicating water-related risks. However, Fyw has been advanced for a relatively short time, and the research on its applicability conditions and main drivers is still ongoing. Studies estimating Fyw are still very few and this index has not been reported in many landscapes and climate backgrounds, limiting its further application in hydrological studies. On the basis of summarizing the progresses of Fyw in previous studies, this paper provides a preliminary analysis of the potential uncertainties in the Fyw estimation, which can be due to temporal trends in the isotopic composition of precipitation, uneven sampling interval of stream water, and complex hydrological systems. Finally, this paper provides some recommendations for the optimization of the sampling design and the methods used for the Fyw estimation

TRPA1 Activation-Induced Myelin Degradation Plays a Key Role in Motor Dysfunction After Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a devastating disease that is characterized by high morbidity and high mortality. ICH has an annual incidence of 10–30/100,000 people and accounts for approximately 10%–30% of all types of stroke. ICH mostly occurs at the basal ganglia, which is rich in nerve fibers; thus, hemiplegia is quite common in ICH patients with partial sensory disturbance and ectopic blindness. In the clinic, those symptoms are considered to originate from the white matter injury in the area, but the exact mechanisms are unknown, and currently, no effective drug treatments are available to improve the prognosis. Clarifying the mechanisms will contribute to the development of new treatment methods for patients. The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that plays a role in inflammatory pain sensation and nociception and may be a potential regulator in emotion, cognition and social behavior. Here, we report that TRPA1 is involved in myelin damage and oxidative stress injury in a mouse ICH model. Intervention with the TRPA1 channel may be a new method to improve the motor function of patients in the early stage of ICH

Screening and characterization of the scFv for chimeric antigen receptor T cells targeting CEA-positive carcinoma

IntroductionChimeric antigen receptor T (CAR-T) cell therapy presents a promising treatment option for various cancers, including solid tumors. Carcinoembryonic antigen (CEA) is an attractive target due to its high expression in many tumors, particularly gastrointestinal cancers, while limited expression in normal adult tissues. In our previous clinical study, we reported a 70% disease control rate with no severe side effects using a humanized CEA-targeting CAR-T cell. However, the selection of the appropriate single-chain variable fragment (scFv) significantly affects the therapeutic efficacy of CAR-T cells by defining their specific behavior towards the target antigen. Therefore, this study aimed to identify the optimal scFv and investigate its biological functions to further optimize the therapeutic potential of CAR-T cells targeting CEA-positive carcinoma.MethodsWe screened four reported humanized or fully human anti-CEA antibodies (M5A, hMN-14, BW431/26, and C2-45), and inserted them into a 3rd-generation CAR structure. We purified the scFvs and measured the affinity. We monitored CAR-T cell phenotype and scFv binding stability to CEA antigen through flow cytometry. We performed repeated CEA antigen stimulation assays to compare the proliferation potential and response of the four CAR-T cells, then further evaluated the anti-tumor efficacy of CAR-T cells ex vivo and in vivo.ResultsM5A and hMN-14 CARs displayed higher affinity and more stable CEA binding ability than BW431/26 and C2-45 CARs. During CAR-T cell production culture, hMN-14 CAR-T cells exhibit a larger proportion of memory-like T cells, while M5A CAR-T cells showed a more differentiated phenotype, suggesting a greater tonic signal of M5A scFv. M5A, hMN-14, and BW431/26 CAR-T cells exhibited effective tumor cell lysis and IFN-γ release when cocultured with CEA-positive tumor cells in vitro, correlating with the abundance of CEA expression in target cells. While C2-45 resulted in almost no tumor lysis or IFN-γ release. In a repeat CEA antigen stimulation assay, M5A showed the best cell proliferation and cytokine secretion levels. In a mouse xenograft model, M5A CAR-T cells displayed better antitumor efficacy without preconditioning.DiscussionOur findings suggest that scFvs derived from different antibodies have distinctive characteristics, and stable expression and appropriate affinity are critical for robust antitumor efficacy. This study highlights the importance of selecting an optimal scFv in CAR-T cell design for effective CEA-targeted therapy. The identified optimal scFv, M5A, could be potentially applied in future clinical trials of CAR-T cell therapy targeting CEA-positive carcinoma

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

Observer-Based Fault Diagnosis and Fault-Tolerant Tracking Control for T-S Fuzzy Uncertain System Affected by Simultaneous Sensor and Actuator Faults

The work presented in this article seeks to address the fault-tolerant tracking control (FTTC) problem for T-S fuzzy uncertain continuous nonlinear systems affected by sensor and actuator faults (SAFs). The T-S fuzzy model is utilized to deal with nonlinearity and uncertainty of the system. Based on a novel fuzzy observer which is constructed to estimate the values of immeasurable states and SAFs at the same time, a novel PI-type fuzzy fault-tolerant control law is mentioned to deal with the effect of SAFs simultaneously. By using Linear Matrix Inequalities (LMIs), the sufficient design conditions are converted to a convex optimization problem. The gains of reference model, observer and fault tolerant control law are obtained easily by solving the LMI conditions represented in the Theorems. The stability of the target system is ensured by applying the quadratic Lyapunov function. Finally, simulations and comparisons are given to show the validity and effectiveness of the proposed approach by two practical examples: Inverted Pendulum on a Cart and Overhead Crane System. For instance, the results presented that the tracking performance was enhanced by 23% when the faults occurred in Case 3 of Example 1, in which the comparisons are carried out with the method in Bouarar et al., (2013). The estimation error of SAFs in all cases were not exceed 2% at the steady stage of simulation

Robust Control Strategy for Dual-Channel Supply Chain With Free Riding Behavior and Cross-Channel Return

In order to obtain customer satisfaction and promote the overall revenue of the supply chain system, offline purchase and online return strategy, called a new kind of cross channel return strategy (hereinafter referred to as “cross channel return”), has been gradually adopted by more and more enterprises in China. Moreover, free riding behavior is always inevitable in supply chain system. When a supply chain system includes free riding behavior and cross channel return strategy, the system is complex so that its stability can’t be ensured easily. Hence, the management of the complex supply chain system mentioned above is a major challenge. In this article, the inventory and profit control strategy for a dual channel supply chain (DCSC) with cross channel return and free riding behavior is developed. Firstly, the mathematical model of the supply chain is set up based on the discrete state space equation. Secondly, utilizing the Lyapunov stability theory and the linear matrix inequality (LMI) method, a robust $H_{\infty }$ control strategy is designed to suppress the bullwhip effect caused by customer random demand. Thirdly, the impact of consumer channel preference, cross channel return and free riding behavior on inventory, production/ordering and profit in the supply chain system is studied by analyzing four different models, such as N-FC(without free riding behavior or cross channel return), Y-C(with cross channel return only), Y-F(with free riding behavior only), Y-FC(with both free riding behavior and cross channel return). Finally, the simulation tests are carried out to verify the performance of the robust control strategy, and some management insights and conclusions are summarized

Robust Control Strategy for an Uncertain Dual-Channel Closed-Loop Supply Chain With Process Innovation for Remanufacturing

The inventory and total cost control strategy are the core issue in all supply chains. When a supply chain includes parameter uncertainty, dual-channel and process innovation for remanufacturing (PIR), the system is complex so that its stability can’t be guaranteed easily. Therefore, how to manage the complex uncertain dual-channel closed-loop supply chain (CLSC) with PIR is a big challenge. The inventory and total cost control strategy for the CLSC with PIR is studied in this article. First of all, the uncertain mathematical model for the the CLSC with PIR is established based on the current inventory and total operation cost. Secondly, the model is converted to an uncertain multi-model according to different initial operation cases which is then described with a set of switching subsystem based on discrete Takagi-Sugeno(T-S) fuzzy model. Thirdly, a fuzzy robust $H_{\infty }$ control approach is introduced to restrain the bullwhip effect and deal with the impacts caused by parameter uncertainty. Meanwhile, the inventory and total operation cost control strategy of the CLSC system is also obtained by the $H_{\infty }$ control method. At last, three simulation tests are conducted to illustrate the effectiveness of the inventory control strategy