The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation ...(allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.
The recent advances in information and communication technology (ICT) have further extended Internet of Things (IoT) from the sole “things” aspect to the omnipotent role of “intelligent connection of ...things”. Meanwhile, the concept of internet of everything (IoE) is presented as such an omnipotent extension of IoT. However, the IoE realization meets critical challenges including the restricted network coverage and the limited resource of existing network technologies. Recently, Unmanned Aerial Vehicles (UAVs) have attracted significant attentions attributed to their high mobility, low cost, and flexible deployment. Thus, UAVs may potentially overcome the challenges of IoE. This article presents a comprehensive survey on opportunities and challenges of UAV-enabled IoE. We first present three critical expectations of IoE: (1) scalability requiring a scalable network architecture with ubiquitous coverage, (2) intelligence requiring a global computing plane enabling intelligent things, (3) diversity requiring provisions of diverse applications. Thereafter, we review the enabling technologies to achieve these expectations and discuss four intrinsic constraints of IoE (i.e., coverage constraint, battery constraint, computing constraint, and security issues). We then present an overview of UAVs. We next discuss the opportunities brought by UAV to IoE. Additionally, we introduce a UAV-enabled IoE (Ue-IoE) solution by exploiting UAVs’s mobility, in which we show that Ue-IoE can greatly enhance the scalability, intelligence and diversity of IoE. Finally, we outline the future directions in Ue-IoE.
Traffic flow prediction has received extensive attention recently, since it is a key step to prevent and mitigate traffic congestion in urban areas. However, most previous studies on traffic flow ...prediction fail to capture fine-grained traffic information (like link-level traffic) and ignore the impacts from other factors, such as route structure and weather conditions. In this paper, we propose a deep and embedding learning approach (DELA) that can help to explicitly learn from fine-grained traffic information, route structure, and weather conditions. In particular, our DELA consists of an embedding component, a convolutional neural network (CNN) component and a long short-term memory (LSTM) component. The embedding component can capture the categorical feature information and identify correlated features. Meanwhile, the CNN component can learn the 2-D traffic flow data while the LSTM component has the benefits of maintaining a long-term memory of historical data. The integration of the three models together can improve the prediction accuracy of traffic flow. We conduct extensive experiments on realistic traffic flow dataset to evaluate the performance of our DELA and make comparison with other existing models. The experimental results show that the proposed DELA outperforms the existing methods in terms of prediction accuracy.
The best donor for a related donor for a human leukocyte antigen (HLA) haplotype-mismatched transplant for hematological neoplasms is controversial. We studied outcomes in 1210 consecutive transplant ...recipients treated on a uniform protocol. Younger donors and male donors were associated with less nonrelapse mortality (NRM; hazard ratio HR = 0.30; 95% confidence interval CI = 0.01-0.39; P = .008 and HR = 0.65; 95% CI = 0.49-0.85; P = .002) and better survival (HR = 0.73; 95% CI = 0.54-0.97; P = .033 and HR = 0.73; 95% CI = 0.59-0.91; P = .005). Father donors were associated with less NRM (HR = 0.65; 95% CI = 0.45-0.95; P = .02), acute graft-versus-host disease (GVHD) (HR = 0.69; 95% CI = 0.55-0.86; P = .001), and better survival (HR = 0.66; 95% CI = 0.50-0.87; P = .003) compared with mother donors. Children donors were associated with less acute GVHD than sibling donors (HR = 0.57; 95% CI = 0.31-0.91; P = .01). Older sister donors were inferior to father donors with regard to NRM (HR = 1.87; 95% CI = 1.10-3.20; P = .02) and survival (HR = 1.59; 95% CI = 1.05-2.40; P = .03). Noninherited maternal antigen-mismatched sibling donors were associated with the lowest incidence of acute GVHD compared with parental donors and noninherited paternal antigen-mismatched sibling donors. Specific HLA disparities were not significantly correlated with transplant outcomes. Our data indicate which HLA haplotype-mismatched related donors are associated with the best transplant outcomes in persons with hematological neoplasms.
•There is a need to identify the best HLA haplotype-mismatched related donor.•Use of young, male, NIMA-mismatched donors results in the best survival after HLA haplotype-mismatched related donor transplants.
Atherosclerosis (AS) is characterized as progressive arterial plaque, which is easy to rupture under low stability. Macrophage polarization and inflammation response plays an important role in ...regulating plaque stability. Ginsenoside Rb1 (Rb1), one of the main active principles of Panax Ginseng, has been found powerful potential in alleviating inflammatory response. However, whether Rb1 could exert protective effects on AS plaque stability remains unclear. This study investigated the role of Rb1 on macrophage polarization and atherosclerotic plaque stability using primary peritoneal macrophages isolated from C57BL/6 mice and AS model in ApoE−/− mice. In vitro, Rb1 treatment promoted the expression of arginase‐I (Arg‐I) and macrophage mannose receptor (CD206), two classic M2 macrophages markers, while the expression of iNOS (M1 macrophages) was decreased. Rb1 increased interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13) secretion in supernatant and promoted STAT6 phosphorylation. IL‐4 and/or IL‐13 neutralizing antibodies and leflunomide, a STAT6 inhibitor attenuated the up‐regulation of M2 markers induced by Rb1. In vivo, the administration of Rb1 promoted atherosclerotic lesion stability, accompanied by increased M2 macrophage phenotype and reduced MMP‐9 staining. These data suggested that Rb1 enhanced atherosclerotic plaque stability through promoting anti‐inflammatory M2 macrophage polarization, which is achieved partly by increasing the production of IL‐4 and/or IL‐13 and STAT6 phosphorylation. Our study provides new evidence for possibility of Rb1 in prevention and treatment of atherosclerosis.
We studied the impact of risk stratification–directed interventions for minimal residual disease (MRD) on relapse and disease-free survival (DFS) prospectively in 814 subjects with standard-risk ...acute leukemia receiving allotransplantation in first or second complete remission. A total of 709 subjects were MRD− after transplantation (Group A); 105 subjects were MRD+, 49 received low-dose IL-2 (Group B), and 56 received modified donor lymphocyte infusion (DLI) with or without low-dose IL-2 (Group C). Posttransplantation immune suppression for GVHD was also modified based on MRD state. The cumulative risk of relapse was significantly less and DFS was significantly better in subjects in Group C than in subjects in Group B (P = .001 and P = .002, respectively), but was not different from subjects in Group A (P = .269 and P = .688, respectively). Multivariate analyses confirmed that MRD state and modified DLI were significantly correlated with relapse (P = .000, odds ratio OR = 0.255 and P = .000, OR = 0.269) and DFS (P = .001, OR = 0.511 and P = .006, OR = 0.436, respectively). These data suggest that risk stratification–directed interventions with modified DLI in patients with standard-risk acute leukemia who are MRD+ after transplantation may improve transplantation outcomes.
Consider a multi-user orthogonal frequency division multiple access (OFDMA) system where multiple users share multiple discrete subcarriers, but at most one user is allowed to transmit power on each ...subcarrier. To adapt fast traffic and channel fluctuations and improve the spectrum efficiency, the system should have the ability to dynamically allocate subcarriers and power resources to users. Assuming perfect channel knowledge, two formulations for the joint subcarrier and power allocation problem are considered in this paper: the first is to minimize the total transmission power subject to the quality of service constraints and the OFDMA constraint, and the second is to maximize some system utility function subject to the total transmission power constraint per user and the OFDMA constraint. In spite of the existence of various heuristics approaches, little is known about the computational complexity status of the above problem. This paper aims at filling this theoretical gap, i.e., characterizing the complexity of the joint subcarrier and power allocation problem for the multi-user OFDMA system. It is shown in this paper that both formulations of the joint subcarrier and power allocation problem are strongly NP-hard. Several subclasses of the problem which can be solved efficiently in polynomial time are also identified. These complexity results suggest that there are not polynomial time algorithms that are able to solve the general joint subcarrier and power allocation problem to global optimality (unless P=NP), and determining an approximately optimal subcarrier and power allocation strategy is more realistic in practice.
The t(8;21) fusion product, AML1/ETO, and hypoxia-inducible factor 1α (HIF1α) form a feed-forward transcription loop that cooperatively transactivates the DNA methyltransferase 3a gene promoter that ...leads to DNA hypermethylation and drives leukemia cell growth. Suppression of the RNA N
-methyladenosine (m
A)-reader enzyme YTH N
-methyladenosine RNA binding protein 2 (YTHDF2) specifically compromises cancer stem cells in acute myeloid leukemia (AML) but promotes hematopoietic stem cell expansion without derailing normal hematopoiesis. However, the relevance of expression between AML1/ETO-HIF1α loop and YTHDF2, and its functional relationship with t(8;21) AML have not been documented. Here, we show that YTHDF2 is highly expressed in t(8;21) AML patients and associated with a higher risk of relapse and inferior relapse-free survival. Knockdown of YTHDF2 in leukemia cells causes an impaired cell proliferation rate in vitro and in mice. Mechanistically, HIF1α is able to bind to the hypoxia-response elements of the 5'-untranslated region of the YTHDF2 gene and promotes the transactivity of the YTHDF2 promoter. Knockdown and overexpression of either AML1/ETO or HIF1α resulted in decreased and increased YTHDF2 protein and mRNA expression in t(8;21) AML cells. In particular, knockdown of YTHDF2 resulted in increased global mRNA m
A levels in t(8;21) AML cells, accompanied by increased TNF receptor superfamily member 1b (TNFRSF1b) mRNA and protein expression levels. Last, we demonstrated that the m
A methylation and expression levels of the TNFRSF1b gene were both negatively correlated with HIF1α expression levels. In conclusion, YTHDF2 is a downstream target of the AML1/ETO-HIF1α loop and promotes cell proliferation probably by modulating the global m
A methylation in t(8;21) AML.
Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Recently, a new strategy was developed for ...HLA-mismatched/haploidentical transplantation from family donors without in vitro T cell depletion (TCD).
Over the past 9 years, 756 patients underwent haploidentical transplantation using a protocol developed by the authors, which combines granulocyte-colony stimulating factor-primed bone marrow (G-BM) and peripheral blood stem cells without in vitro TCD. The long-term outcome with this treatment modality was reported, and a risk-factor analysis was provided.
Of these patients, 752 (99%) achieved sustained, full donor chimerism. The incidence of grades 2 through 4 acute graft-versus-host disease (GVHD) was 43%, and the 2-year cumulative incidence of total chronic GVHD was 53%. The 3-year cumulative incidence of nonrelapse mortality was 18%. The 2-year cumulative incidences of relapse were 15% and 26% in the standard-risk and high-risk groups, respectively. Of the 756 patients, 480 survived throughout the follow-up period of 1154 days (range: 335-3511 days) with the 3-year leukemia-free survival rates of 68% and 49% in the standard-risk and high-risk groups, respectively. Lower leukemia-free survival was associated with high-risk disease status (P = .001), chronic myelogenous leukemia disease type (P = .004), neutrophil engraftment beyond 13 days after transplant (P = .012), and the occurrence of grades 2 through 4 acute GVHD (P = .019).
The results from the authors' 9-year experience showed that G-BM combined with peripheral blood stem cells from haploidentical donors, without in vitro TCD, is a reliable source of stem cells for transplantation by using the protocol developed by the authors.
In a cellular wireless system, users located at cell edges often suffer significant out-of-cell interference. Assuming each base station is equipped with multiple antennas, we can model this scenario ...as a multiple-input single-output (MISO) interference channel. In this paper we consider a coordinated beamforming approach whereby multiple base stations jointly optimize their downlink beamforming vectors in order to simultaneously improve the data rates of a given group of cell edge users. Assuming perfect channel knowledge, we formulate this problem as the maximization of a system utility (which balances user fairness and average user rates), subject to individual power constraints at each base station. We show that, for the single-carrier case and when the number of antennas at each base station is at least two, the optimal coordinated beamforming problem is NP-hard for both the harmonic mean utility and the proportional fairness utility. For general utilities, we propose a cyclic coordinate descent algorithm, which enables each transmitter to update its beamformer locally with limited information exchange and establish its global convergence to a stationary point. We illustrate its effectiveness in computer simulations by using the space matched beamformer as the benchmark.
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