Steroid‐refractory (SR) acute graft‐versus‐host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated ...the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR‐aGVHD patients treated with basiliximab in a real‐world setting. Nine hundred and forty SR‐aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second‐line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval CI 76.5%–82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%–29.6%) and 64.3% (95% CI 61.2%–67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III–IV aGVHD, and high‐risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real‐world data suggest that basiliximab is safe and effective for treating SR‐aGVHD.
Induction therapy for acute myeloid leukemia (AML) is an anthracycline-based chemotherapy regimen. However, many patients experience a relapse or exhibit refractory disease (R/R). There is an urgent ...need for more effective regimens to reverse anthracycline resistance in these patients.
In this paper, Twenty-seven R/R AML patients with anthracycline resistance consecutively received chidamide in combination with anthracycline-based regimen as salvage therapy at the Chinese PLA General Hospital.
Of the 27 patients who had received one course of salvage therapy, 13 achieved a complete response and 1 achieved a partial response. We found that the HDAC3-AKT-P21-CDK2 signaling pathway was significantly upregulated in anthracycline-resistant AML cells compared to non-resistant cells. AML patients with higher levels of HDAC3 had lower event-free survival (EFS) and overall survival (OS) rates. Moreover, anthracycline-resistant AML cells are susceptible to chidamide, a histone deacetylase inhibitor which can inhibit cell proliferation, increase cell apoptosis and induce cell-cycle arrest in a time- and dose-dependent manner. Chidamide increases the sensitivity of anthracycline-resistant cells to anthracycline drugs, and these effects are associated with the inhibition of the HDAC3-AKT-P21-CDK2 signaling pathway.
Chidamide can increase anthracycline drug sensitivity by inhibiting HDAC3-AKT-P21-CDK2 signaling pathway, thus demonstrating the potential for application.
The appearance of generative adversarial networks (GAN) provides a new approach and framework for computer vision. Compared with traditional machine learning algorithms, GAN works via adversarial ...training concept and is more powerful in both feature learning and representation. GAN also exhibits some problems, such as non-convergence, model collapse, and uncontrollability due to high degree of freedom. How to improve the theory of GAN and apply it to computer-vision-related tasks have now attracted much research efforts. In this paper, recently proposed GAN models and their applications in computer vision are systematically reviewed. In particular, we firstly survey the history and development of generative algorithms, the mechanism of GAN, its fundamental network structures, and theoretical analysis of the original GAN. Classical GAN algorithms are then compared comprehensively in terms of the mechanism, visual results of generated samples, and Frechet Inception Distance. These networks are further evaluated from network construction, performance, and applicability aspects by extensive experiments conducted over public datasets. After that, several typical applications of GAN in computer vision, including high-quality samples generation, style transfer, and image translation, are examined. Finally, some existing problems of GAN are summarized and discussed and potential future research topics are forecasted.
Assisting traffic control is one of the most important applications on the Internet of Vehicles (IoVs). Traffic information provided by vehicles is desired since drivers or vehicle sensors are ...sensitive in perceiving or detecting nuances on roads. However, the availability and privacy preservation of this information are critical while conflicted with each other in the vehicular communication. In this paper, we propose a semicentralized mode with attribute-based blockchain in IoVs to balance the tradeoff between the availability and the privacy preservation. In this mode, a method of control-by-vehicles is used to control signals of traffic lights to increase traffic efficiency. Users are grouped their attributes such as locations and directions before starting the communication. The users reach an agreement on determining a temporary signal timing by interacting with each other without leaking privacy. Final decisions are verifiable to all users, even if they have no a priori agreement and processes of consensus. The mode not only achieves the aim of privacy preservation but also supports responsibility investigation for historical agreements via ciphertext-policy attribute-based encryption (CP-ABE) and blockchain technology. Extensive experimental results demonstrated that our mode is efficient and practical.
Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, ...we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information.
In this paper, we consider the one-bit precoding problem for the multiuser downlink massive multiple-input multiple-output (MIMO) system with phase shift keying (PSK) modulation. We focus on the ...celebrated constructive interference (CI)-based problem formulation. We first establish the NP-hardness of the problem (even in the single-user case), which reveals the intrinsic difficulty of globally solving the problem. Then, we propose a novel negative <inline-formula> <tex-math notation="LaTeX">\ell _{1} </tex-math></inline-formula> penalty model for the considered problem, which penalizes the one-bit constraint into the objective by a negative <inline-formula> <tex-math notation="LaTeX">\ell _{1} </tex-math></inline-formula>-norm term, and show the equivalence between (global and local) solutions of the original problem and the penalty problem when the penalty parameter is sufficiently large. We further transform the penalty model into an equivalent min-max problem and propose an efficient alternating proximal/projection gradient descent ascent (APGDA) algorithm for solving it, which performs a proximal gradient decent over one block of variables and a projection gradient ascent over the other block of variables alternately. The APGDA algorithm enjoys a low per-iteration complexity and is guaranteed to converge to a stationary point of the min-max problem and a local minimizer of the penalty problem. To further reduce the computational cost, we also propose a low-complexity implementation of the APGDA algorithm, where the values of the variables will be fixed in later iterations once they satisfy the one-bit constraint. Numerical results show that, compared to the state-of-the-art CI-based algorithms, both of the proposed algorithms generally achieve better bit-error-rate (BER) performance with lower computational cost.
Copper complexes are considered as potential candidates for anticancer therapy and medical applications. In this paper, three new Cu(
ii
) complexes, Cu(IPY)
2
(ClO
4
)
2
·H
2
O (
CuI1
), Cu(IPY)(
l
...-Phe)H
2
OClO
4
·0.5H
2
O (
CuI2
) and Cu(IPY)(
l
-Val)H
2
OClO
4
(
CuI3
) (where IPY = 2-(1
H
-imidazol-2-yl)pyridine,
l
-Phe =
l
-phenylalanine, and
l
-Val =
l
-valine), with good amphipathic properties were synthesized and characterized. Their single crystal X-ray diffraction results revealed that
CuI1
was four-coordinated, while
CuI2
and
CuI3
both adopted a five-coordinated tetragonal pyramidal configuration. Multi-spectral methods, viscosity experiment and molecular docking technique showed that the three complexes interacted with DNA through insertion. The results of the gel electrophoresis experiments indicated that DNA was oxidatively cleaved by all the complexes in a concentration-dependent manner. Moreover, singlet oxygen (
1
O
2
), hydrogen peroxide (H
2
O
2
) and superoxide anion radicals (&z.rad;O
2
−
) were associated with the oxidative cleavage of DNA. All the complexes also had good binding affinity with human serum albumin (HSA). The MB degradation assay revealed that all complexes could react with H
2
O
2
to form &z.rad;OH through Fenton-like processes. The complexes displayed good antiproliferative activity against the tested human cancer cells
in vitro
, including cervical carcinoma cells (HeLa), liver cancer cells (HepG2 and BEL-7402) and gastric adenocarcinoma cells (SGC-7901), but showed lower toxicity to normal liver cells (LO2). The anticancer mechanism research revealed that
CuI1
,
CuI2
and
CuI3
arrested the cell cycle at the S phase, elevated intracellular reactive oxygen species (ROS) levels and induced loss of mitochondrial membrane potential (MMP). The results indicated that these Cu(
ii
) complexes could induce DNA damage and ROS-mediated mitochondrial dysfunction, leading to cancer cell apoptosis. Our work provides a theoretical basis for the design of new low-toxicity and highly efficient anticancer Cu(
ii
) complexes by incorporating biological metabolites and aromatic heterocyclic ligands.
New Cu(
ii
) complexes with promising anticancer activity induce apoptosis in HepG2 cells through DNA damage and cytotoxic ROS-mediated mitochondrial dysfunction pathways.
The explosive generation of Internet of Things (IoT) data calls for cloud service providers (CSP) to further provide more secure and reliable transmission, storage, and management services. This ...requirement, however, goes against the honest and curious nature of CSP, to the extent that existing methods introduce the third-party audit (TPA) to check data security in the cloud. TPA solves the problem of unreliable CSP but puts a heavy burden on lightweight users because of the sheer amount of the pre-audit data processing work. In this paper, we establish an audit model based on a designed binary tree assisted by edge computing, which provides computing capability for the resource-constrained terminals. The data pre-processing task is offloaded to the edge, which reduces computing load and improves the efficiency of task processing. We propose an improved correlation mechanism between data blocks and nodes on the binary tree so that all nodes on the binary tree can be fully utilized while existing methods use only leaf nodes and thus are required to establish multiple binary trees. Moreover, to improve audit efficiency, the binary tree in the audit process is designed to be self-balanced. In experiments, we compare our methods with the traditional method and experimental results show that the proposed mechanism is more effective to store and manage big data, which is conducive to providing users with more secure IoT services.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk ...factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.
We propose a family of spectral gradient methods, whose stepsize is determined by a convex combination of the long Barzilai–Borwein (BB) stepsize and the short BB stepsize. Each member of the family ...is shown to share certain quasi-Newton property in the sense of least squares. The family also includes some other gradient methods as its special cases. We prove that the family of methods is
R
-superlinearly convergent for two-dimensional strictly convex quadratics. Moreover, the family is
R
-linearly convergent in the any-dimensional case. Numerical results of the family with different settings are presented, which demonstrate that the proposed family is promising.
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