Glioblastoma is the most common primary brain malignancy with limited treatment options. EphA2 is a tumor-associated-antigen overexpressed in glioblastoma. Pre-clinical studies have demonstrated the promise of EphA2-redirected CAR T-cells against glioblastoma. We conduct the first-in-human trial of EphA2-redirected CAR T-cells in patients with EphA2-positive recurrent glioblastoma and report the results of three patients enrolled as the first cohort receiving the starting dosage (1×106 cells/kg). A single infusion of EphA2-redirected CAR T-cells was administrated intravenously, with the lymphodepletion regimen consisting of fludarabine and Cyclophosphamide. In two patients, there was grade 2 cytokine release syndrome accompanied by pulmonary edema, which resolved completely with dexamethasone medication. Except that, there was no other organ toxicity including neurotoxicity. In both the peripheral blood and cerebral-spinal-fluid, we observed the expansion of CAR T-cells which persisted for more than four weeks. In one patient, there was a transit diminishment of the tumor. Among these three patients, one patient reported SD and two patients reported PD, with overall survival ranging from 86 to 181 days. At the tested dose level (1×106 cells/kg), intravenously infusion of EphA2-rediretected CAR T-cells were preliminary tolerable with transient clinical efficacy. Future study with adjusted dose and infusion frequency of CAR T-cells is warranted.Trial Registration NumbersNCT 03423992
The occurrence and development of gastric adenocarcinoma (gADC) is closely related to the interaction between tumor cells and immune cells in the tumor microenvironment (TME). Our objective was to characterize the repertoire of immune cells in the TME of gADC. To analyze the transcriptomic, immune, and spatial information of TME in gADC, we constructed single-cell RNA sequencing, 10 × Genomics V(D)J analysis, multiple immunofluorescence techniques, and OSCmap analysis of 49,765 single cells in seven samples from four gADC patients. Our integrative analysis of B cells demonstrated that a large number of mucosal associated lymphoid tissue (MALT)-B cells were detected in the gADC tissues, which have mature tertiary lymphatic structures (mTLSs), and almost no MALT-B cells in peripheral blood sample. Moreover, MALT-B cells are a class of IgA + plasma cells, which are characterized with high expression of complement pathway activation-related genes. Next, natural killer T (NKT) cells mainly exist in gADC tissues accompanied by mTLSs. This study also classified monocytes/macrophages and epithelial cells into benign and malignant types. Interestingly, CSOmap ( q < .05) and multiple immunofluorescence ( p < .05) results indicated more types of immune cells can be enriched in tissues with mTLSs than normal TLSs, and the density of mTLSs were higher than normal TLSs. Our findings provide novel insights for the signature of immune cells and tumor cells in the TME of gADC with TLSs and highlight the potential importance of IgA-mediated humoral immunity in gADC patients with TLSs.
This paper studies resource scheduling for delay minimization in multi-server cellular edge computing systems. The traditional method defines queue length-based Lyapunov functions and designs scheduling algorithms which solve the corresponding queue length control problem. Different from the traditional method, this paper defines the delay-based Lyapunov function. Specifically, the formulas of the communication delay and computing delay in cellular edge computing systems are derived without needing the assumptions about traffic's statistics. Then, a resource scheduling algorithm which directly minimizes the weighted sum of the communication delay and computing delay is proposed. The simulation results show that the total delay of the proposed scheduling algorithm is decreased as compared to that of the traditional method. The impact of parameters on the delay performance is also evaluated.INDEX TERMS Cellular edge computing, delay, Lyapunov, scheduling. I. INTRODUCTIONIn cellular edge computing systems, users' computing tasks are offloaded to the computing servers located in the base stations (BSs) [1]-[8]. Hence, there are two types of resources to be scheduled: the first is the communication resource which is used to transmit the requests of tasks, the second is the computing resource which is used to execute the tasks. This paper studies the joint communication and computing resource scheduling in cellular edge computing systems. Further, since low delay has been considered one of the most important performance targets [9]-[12], this paper focuses on the delay aspect of the resource scheduling in cellular edge computing systems.This work mainly considers the following two types of delay in cellular edge computing systems [2].• Communication Delay: The sum of the transmission delay (i.e., the time of physical layer procession) and communication queueing delay (i.e., the time spent in the queue in the user buffer waiting to transmit).The associate editor coordinating the review of this manuscript and approving it for publication was Jose Saldana.
The Alataw Pass, near the Ebinur Lake Wetland (northwest of China) and Taldykorgan (east of Kazakhstan), is a natural habitat for wild rodents. To date, little has been done on the surveillance of Bartonella spp. and Wolbachia spp. from fleas in the region. Here we molecularly detected Bartonella spp. and Wolbachia spp. in wild rodent fleas during January and October of 2016 along the Alataw Pass-Kazakhstan border. A total of 1,706 fleas belonging to 10 species were collected from 6 rodent species. Among the 10 flea species, 4 were found to be positive for Wolbachia, and 5 flea species were positive for Bartonella. Molecular analysis indicated that i) B. rochalimae was firstly identified in Xenopsylla gerbilli minax and X. conforms conforms, ii) B. grahamii was firstly identified in X. gerbilli minax, and iii) B. elizabethae was firstly detected in Coptopsylla lamellifer ardua, Paradoxopsyllus repandus, and Nosopsyllus laeviceps laeviceps. Additionally, 3 Wolbachia endosymbionts were firstly found in X. gerbilli minax, X. conforms conforms, P. repandus, and N. laeviceps laeviceps. BLASTn analysis indicated 3 Bartonella species showed genotypic variation. Phylogenetic analysis revealed 3 Wolbachia endosymbionts were clustered into the non-Siphonaptera Wolbachia group. These findings extend our knowledge of the geographical distribution and carriers of B. rochalimae, B. grahamii, B. elizabethae, and Wolbachia spp. In the future, there is a need for China-Kazakhstan cooperation to strengthen the surveillance of flea-borne pathogens in wildlife.
SummaryWe investigate the terminal location method in 5G‐Low Earth Orbit (5G‐LEO) satellite communication systems. To overcome the dependence on the external Global Navigation Satellite System (GNSS), we propose to use a single LEO satellite in 5G‐LEO satellite communication systems for terminal location and utilize the downlink synchronization detection for pseudorange differential measurement. Then, a data clustering method of unsupervised machine learning is proposed to classify the measured data into line‐of‐sight (LOS) and non‐line‐of‐sight (NLOS) signals. Furthermore, the NLOS data are excluded, and the Taylor series expansion iteration method is used to calculate the terminal coordinates. Simulation results show that the proposed method can effectively reduce the influence of NLOS error on measurement results and improve the accuracy of terminal location. In simulated urban scenario, the average location accuracy is improved from 10 km by traditional methods to 0.7 km and the convergence time is reduced from 400 to 250s.
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