Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell ...therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m
. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 10
cells/kg range, 0.07 to 2.1 × 10
) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval CI, 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM.
ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.
As an emerging material, nanomaterials have attracted extensive attention due to their small size, surface effect and quantum tunneling effect, as well as potential applications in traditional ...materials, medical devices, electronic devices, coatings and other industries. Herein, the influence of nanoparticle selection, production process, grain size, and grain boundary structures on the mechanical properties of nanomaterials is introduced. The current research progress and application range of nano-materials are presented. The unique properties of nano-materials make them superior over traditional materials. Therefore, nanomaterials will have a broader application prospect in the future. Research on nanomaterials is significant for the development and application of materials science.
Inverted generational distance (IGD) has been widely considered as a reliable performance indicator to concurrently quantify the convergence and diversity of multiobjective and many-objective ...evolutionary algorithms. In this paper, an IGD indicator-based evolutionary algorithm for solving many-objective optimization problems (MaOPs) has been proposed. Specifically, the IGD indicator is employed in each generation to select the solutions with favorable convergence and diversity. In addition, a computationally efficient dominance comparison method is designed to assign the rank values of solutions along with three newly proposed proximity distance assignments. Based on these two designs, the solutions are selected from a global view by linear assignment mechanism to concern the convergence and diversity simultaneously. In order to facilitate the accuracy of the sampled reference points for the calculation of IGD indicator, we also propose an efficient decomposition-based nadir point estimation method for constructing the Utopian Pareto front (PF) which is regarded as the best approximate PF for real-world MaOPs at the early stage of the evolution. To evaluate the performance, a series of experiments is performed on the proposed algorithm against a group of selected state-of-the-art many-objective optimization algorithms over optimization problems with 8-, 15-, and 20-objective. Experimental results measured by the chosen performance metrics indicate that the proposed algorithm is very competitive in addressing MaOPs.
Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their ...dynamic changes during the treatment, platelet‐to‐lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single‐center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)‐19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single‐center case series of the 30 hospitalized patients with confirmed COVID‐19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID‐19.
The study’s objective is to examine the impact of teacher ability on student academic performance, identification (self-valued goals; personal importance), and self-regulation skills. Additionally, ...the study examines the mediating effect of identification (self-valued goals; personal importance) and self-regulation skills between teacher ability and student academic performance. The data was collected by the teachers at different colleges and universities in China and 341 samples were used to analyze the data through a convenient sampling technique. Moreover, partial least square structural equation modeling is used in data analysis with Smart PLS software. This research indicates that teacher ability has a positive and significant effect on student academic performance, identification (self-valued goals; personal importance), and self-regulation skills. Further, the study also discovers that identification (self-valued goals; personal importance) and self-regulation skills significantly mediate between teacher ability and student academic performance. The study is helpful for the teachers to adopt the better strategies and abilities in themselves when they are engaged with the student in teaching activities.
A lot of works have shown that frobenius-norm-based representation (FNR) is competitive to sparse representation and nuclear-norm-based representation (NNR) in numerous tasks such as subspace ...clustering. Despite the success of FNR in experimental studies, less theoretical analysis is provided to understand its working mechanism. In this brief, we fill this gap by building the theoretical connections between FNR and NNR. More specially, we prove that: 1) when the dictionary can provide enough representative capacity, FNR is exactly NNR even though the data set contains the Gaussian noise, Laplacian noise, or sample-specified corruption and 2) otherwise, FNR and NNR are two solutions on the column space of the dictionary.
Ten-eleven translocation 1-3 (Tet1-3) proteins have recently been discovered in mammalian cells to be members of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on ...the 5-position of cytosine (5-methylcytosine 5mC), a well-characterized epigenetic modification that has essential roles in regulating gene expression and maintaining cellular identity. Tet proteins can convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) through three consecutive oxidation reactions. These modified bases may represent new epigenetic states in genomic DNA or intermediates in the process of DNA demethylation. Emerging biochemical, genetic, and functional evidence suggests that Tet proteins are crucial for diverse biological processes, including zygotic epigenetic reprogramming, pluripotent stem cell differentiation, hematopoiesis, and development of leukemia. Insights into how Tet proteins contribute to dynamic changes in DNA methylation and gene expression will greatly enhance our understanding of epigenetic regulation of normal development and human diseases.
Hydrogels have recently garnered tremendous interest due to their potential application in soft electronics, human-machine interfaces, sensors, actuators, and flexible energy storage. Benefiting from ...their impressive combination of hydrophilicity, metallic conductivity, high aspect ratio morphology, and widely tuneable properties, when two-dimensional (2D) transition metal carbides/nitrides (MXenes) are incorporated into hydrogel systems, they offer exciting and versatile platforms for the design of MXene-based soft materials with tunable application-specific properties. The intriguing and, in some cases, unique properties of MXene hydrogels are governed by complex gel structures and gelation mechanisms, which require in-depth investigation and engineering at the nanoscale. On the other hand, the formulation of MXenes into hydrogels can significantly increase the stability of MXenes, which is often the limiting factor for many MXene-based applications. Moreover, through simple treatments, derivatives of MXene hydrogels, such as aerogels, can be obtained, further expanding their versatility. This tutorial review intends to show the enormous potential of MXene hydrogels in expanding the application range of both hydrogels and MXenes, as well as increasing the performance of MXene-based devices. We elucidate the existing structures of various MXene-containing hydrogel systems along with their gelation mechanisms and the interconnecting driving forces. We then discuss their distinctive properties stemming from the integration of MXenes into hydrogels, which have revealed an enhanced performance, compared to either MXenes or hydrogels alone, in many applications (energy storage/harvesting, biomedicine, catalysis, electromagnetic interference shielding, and sensing).
When two-dimensional transition metal carbides/nitrides (MXenes) meet hydrogels, they offer versatile platforms for designing novel soft materials with exciting properties.
The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the field of regenerative medicine. However, recent studies on the genetic and epigenetic ...variations in iPSCs have raised concerns that these variations may compromise the utility of iPSCs. In this Perspective, we review the current understanding of genetic and epigenetic variations in iPSCs, trace their causes, discuss the implications of these variations for iPSC applications, and propose approaches to cope with these variations.
This Perspective reviews the current understanding of genetic and epigenetic variations in iPSCs, traces their causes, discusses their implications for iPSC applications, and proposes approaches to cope with these variations.
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