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1.
BMC Cancer ; 22(1): 11, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979982

RESUMO

BACKGROUND: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. METHODS: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. RESULTS: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. CONCLUSIONS: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.

2.
Neural Netw ; 145: 300-307, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34785445

RESUMO

Clipping on learning rates in Adam leads to an effective stochastic algorithm-AdaBound. In spite of its effectiveness in practice, convergence analysis of AdaBound has not been fully explored, especially for non-convex optimization. To this end, we address the convergence of the last individual output of AdaBound for non-convex stochastic optimization problems, which is called individual convergence. We prove that, with the iteration of the AdaBound, the cost function converges to a finite value and the corresponding gradient converges to zero. The novelty of this proof is that the convergence conditions on the bound functions and momentum factors are much more relaxed than the existing results, especially when we remove the monotonicity and convergence of the bound functions, and only keep their boundedness. The momentum factors can be fixed to be constant, without the restriction of monotonically decreasing. This provides a new perspective on understanding the bound functions and momentum factors of AdaBound. At last, numerical experiments are provided to corroborate our theory and show that the convergence of AdaBound extends to more general bound functions.


Assuntos
Algoritmos , Aprendizagem
3.
Am J Cancer Res ; 11(11): 5485-5495, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34873474

RESUMO

Although thyroid cancer is the most prevalent endocrine malignancy, overall patients with thyroid cancer have a good long-term survival. However, a small percentage of patients with progressive thyroid cancer have poor outcomes, and the genetic drivers playing a key role thyroid cancer progression are mostly unknown. Here, we investigated the role of the PINX1 in thyroid cancer progression. Interestingly, PINX1 expression was significantly higher in ATC than in PTC in both patients and cell lines. When PINX1 was knockdown in ATC cells, cell proliferation rates, colony formation capacity, and cell cycle progression were significantly reduced. Furthermore, cell motility and the expression of EMT drivers were reduced by PINX1 downregulation. In contrast, the overexpression of PINX1 in PTC cells significantly increased those phenotypes of tumor progression, which demonstrates that PINX1 could promote tumor proliferation and malignant transformation in both PTC and ATC cells. To further understand whether PINX1 is also involved in the progression of PTC to ATC, we examined PI3K/AKT, MAPK, and ß-catenin signaling activation after PINX1 modulation. Decreased PINX1 expression reduced the levels of p-AKT, p-ERK, p-p38, and ß-catenin in ATC cells, but the increase of PINX1 expression upregulated the phosphorylation of AKT, ERK, and p38 and the levels of ß-catenin in PTC cells. These results were all confirmed in xenograft mouse tumors. Our findings suggest that PINX1 regulates thyroid cancer progression by promoting cell proliferation, EMT, and signaling activation, and support the hypothesis that PINX1 could be a prognostic marker and a therapeutic target of thyroid cancer.

5.
Artif Intell Med ; 121: 102180, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763802

RESUMO

Glioma is a relatively common brain tumor disease with high mortality rate. Humans have been seeking a more effective therapy. In the course of treatment, the specific location of the tumor needs to be determined first in any case. Therefore, how to segment tumors from brain tissue accurately and quickly is a persistent problem. In this paper, a new dual-stream decoding CNN architecture combined with U-net for automatic segmentation of brain tumor on MR images namely DDU-net is proposed. Two edge-based optimization strategies are used to enhance the performance of brain tumor segmentation. First, we design a separate branch to process edge stream information. Here, high level edge features are reduced in dimension of channel and integrated into the conventional semantic stream in the way of residual. Second, a regularization loss function is used to encourage the predicted segmentation mask to align with ground truth around the edge mainly by penalizing pixels where the predicted segmentation masks and labels do not match around the edge. In training, we employ a novel edge extraction algorithm for providing edge labels with higher quality. Moreover, we add a self-adaptive balancing class weight coefficient into the cross entropy loss function for solving the serious class imbalance problem in the backpropagation of edge extraction. Our experiments show that this leads to a very efficient architecture which can produce clearer prediction at the edge of the tumor. Our method achieves ideal performance on BraTS2017 and BraTS2018 in terms of Dice coefficient.


Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Algoritmos , Neoplasias Encefálicas/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Compostos Organofosforados , Triazóis
6.
Pharm Res ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773183

RESUMO

PURPOSE: The objective of the present study was to prepare stable and high bioavailability ocular atropine loaded films (ATR-films) as potential ocular drug delivery systems for the treatment of myopia. METHODS: ATR-films were prepared by the solvent casting method and the physical properties of films were evaluated including thickness, water content, light transparency, disintegration time, and mechanical properties. FT-IR, DSC, XRD, TGA, AFM, and Raman spectroscopy were performed to characterize the film. The stability test was conducted under different conditions, such as high humidity, high temperature, and strong light. The pharmacokinetic study and irritation assessment were conducted in rabbits. The efficacy of ATR-films was evaluated by refraction and ocular biometry in myopia guinea pigs. RESULT: After optimizing the formulation, the resulting ATR-film was flexible and transparent with lower water content (8.43% ± 1.25). As expected, the ATR-film was stable and hydrolysate was not detected, while the content of hydrolysate in ATR eye drops can reach up to 8.1867% (limit: < 0.2%) in the stability study. The safety assessment both in vitro and in vivo confirmed that the ATR-film was biocompatible. Moreover, the bioavailability (conjunctiva 3.21-fold, cornea 2.87-fold, retina 1.35-fold, sclera 2.05-fold) was greatly improved compared with the ATR eye drops in vivo pharmacokinetic study. The pharmacodynamic study results showed that the ATR-film can slow the progress of form-deprivation myopia (~ 100 ± 0.81D), indicating that it has a certain therapeutic effect on form-deprivation myopia. CONCLUSION: The ATR-film with good stability and high bioavailability will have great potential for the treatment of myopia.

7.
RSC Med Chem ; 12(10): 1771-1779, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34778778

RESUMO

In anti-tumour therapy, the toll-like receptor 2/4 (TLR2/4) signalling pathway has been a double-edged sword. TLR2/4 agonists are commonly considered adjuvants for immune stimulation, whereas TLR2/4 antagonists demonstrate more feasibility for anti-tumour therapy under specific chronic inflammatory situations. In individuals with cancer retaliatory proliferation and metastasis after surgery, blocking the TLR2/4 signalling pathway may produce favourable prognosis for patients. Therefore, here, we developed a small-molecule co-inhibitor that targets the TLR2/4 signalling pathway. After high-throughput screening of a compound library containing 14 400 small molecules, followed by hit-to-lead structural optimisation, we finally obtained the compound TX-33, which has effective inhibitory properties against the TLR2/4 signalling pathways. This compound was found to significantly inhibit multiple pro-inflammatory cytokines released by RAW264.7 cells. This was followed by TX-33 demonstrating promising efficacy in subsequent anti-tumour experiments. The current results provide a novel understanding of the role of TLR2/4 in cancer and a novel strategy for anti-tumour therapy.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34650348

RESUMO

Geometric computation can be heavy duty for spatial queries, in particular for complex geometries such as polygons with many edges based on a vector-based representation. While many techniques have been provided for spatial partitioning and indexing, they are mainly built on minimal bounding boxes or other approximation methods, which will not mitigate the high cost of geometric computation. In this paper, we propose a novel vector-raster hybrid approach through rasterization, where pixel-centric rich information is preserved to help not only filtering out more candidates but also reducing geometry computation load. Based on the hybrid model, we develop an efficient rasterization based ray casting method for point-in-polygon queries and a circle buffering method for point-to-polygon distance calculation, which is a common operation for distance based queries. Our experiments demonstrate that the hybrid model can boost the performance of spatial queries on complex polygons by up to one order of magnitude.

9.
Sensors (Basel) ; 21(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34695972

RESUMO

Graph Convolutional Networks (GCNs) have attracted a lot of attention and shown remarkable performance for action recognition in recent years. For improving the recognition accuracy, how to build graph structure adaptively, select key frames and extract discriminative features are the key problems of this kind of method. In this work, we propose a novel Adaptive Attention Memory Graph Convolutional Networks (AAM-GCN) for human action recognition using skeleton data. We adopt GCN to adaptively model the spatial configuration of skeletons and employ Gated Recurrent Unit (GRU) to construct an attention-enhanced memory for capturing the temporal feature. With the memory module, our model can not only remember what happened in the past but also employ the information in the future using multi-bidirectional GRU layers. Furthermore, in order to extract discriminative temporal features, the attention mechanism is also employed to select key frames from the skeleton sequence. Extensive experiments on Kinetics, NTU RGB+D and HDM05 datasets show that the proposed network achieves better performance than some state-of-the-art methods.


Assuntos
Redes Neurais de Computação , Esqueleto , Atividades Humanas , Humanos , Reconhecimento Psicológico
10.
Healthcare (Basel) ; 9(9)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34574907

RESUMO

An online community is one of the important ways for people with mental disorders to receive assistance and obtain support. This study aims to help users with mental disorders to obtain more support and communication through online communities, and to provide community managers with the possible influence mechanisms based on the information adoption model. We obtained a total of 49,047 posts of an online mental health communities in China, over a 40-day period. Then we used a combination of text mining and empirical analysis. Topic and sentiment analysis were used to derive the key variables-the topic of posts that the users care about most, and the emotion scores contained in posts. We then constructed a theoretical model based on the information adoption model. As core independent variables of information quality, on online mental health communities, the topic of social experience in posts (0.368 ***), the topic of emotional expression (0.353 ***), and the sentiment contained in the text (0.002 *) all had significant positive relationships with the number of likes and reposts. This study found that the users of online mental health communities are more attentive to the topics of social experience and emotional expressions, while they also care about the non-linguistic information. This study highlights the importance of helping community users to post on community-related topics, and gives administrators possible ways to help users gain the communication and support they need.

11.
Front Immunol ; 12: 720354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539656

RESUMO

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.

12.
Proc IEEE Int Symp Biomed Imaging ; 2021: 1827-1830, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34548902

RESUMO

Three-dimensional (3D) digital pathology has been emerging for next-generation tissue based cancer research. To enable such histopathology image volume analysis, serial histopathology slides need to be well aligned. In this paper, we propose a histopathology image registration fine tuning method with integrated landmark evaluations by texture and spatial proximity measures. Representative anatomical structures and image corner features are first detected as landmark candidates. Next, we identify strong and modify weak matched landmarks by leveraging image texture features and landmark spatial proximity measures. Both qualitative and quantitative results of extensive experiments demonstrate that our proposed method is robust and can further enhance registration accuracy of our previously registered image set by 31.15% (correlation), 4.88% (mutual information), and 41.02% (mean squared error), respectively. The promising experimental results suggest that our method can be used as a fine tuning module to further boost registration accuracy, a premise of histology spatial and morphology analysis in an information-lossless 3D tissue space for cancer research.

13.
Sensors (Basel) ; 21(16)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34450762

RESUMO

Recently, deep learning-based image deblurring and deraining have been well developed. However, most of these methods fail to distill the useful features. What is more, exploiting the detailed image features in a deep learning framework always requires a mass of parameters, which inevitably makes the network suffer from a high computational burden. We propose a lightweight fusion distillation network (LFDN) for image deblurring and deraining to solve the above problems. The proposed LFDN is designed as an encoder-decoder architecture. In the encoding stage, the image feature is reduced to various small-scale spaces for multi-scale information extraction and fusion without much information loss. Then, a feature distillation normalization block is designed at the beginning of the decoding stage, which enables the network to distill and screen valuable channel information of feature maps continuously. Besides, an information fusion strategy between distillation modules and feature channels is also carried out by the attention mechanism. By fusing different information in the proposed approach, our network can achieve state-of-the-art image deblurring and deraining results with a smaller number of parameters and outperform the existing methods in model complexity.


Assuntos
Processamento de Imagem Assistida por Computador , Armazenamento e Recuperação da Informação
14.
Comput Methods Programs Biomed ; 208: 106291, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333205

RESUMO

BACKGROUND AND OBJECTIVE: Computerized pathology image analysis is an important tool in research and clinical settings, which enables quantitative tissue characterization and can assist a pathologist's evaluation. The aim of our study is to systematically quantify and minimize uncertainty in output of computer based pathology image analysis. METHODS: Uncertainty quantification (UQ) and sensitivity analysis (SA) methods, such as Variance-Based Decomposition (VBD) and Morris One-At-a-Time (MOAT), are employed to track and quantify uncertainty in a real-world application with large Whole Slide Imaging datasets - 943 Breast Invasive Carcinoma (BRCA) and 381 Lung Squamous Cell Carcinoma (LUSC) patients. Because these studies are compute intensive, high-performance computing systems and efficient UQ/SA methods were combined to provide efficient execution. UQ/SA has been able to highlight parameters of the application that impact the results, as well as nuclear features that carry most of the uncertainty. Using this information, we built a method for selecting stable features that minimize application output uncertainty. RESULTS: The results show that input parameter variations significantly impact all stages (segmentation, feature computation, and survival analysis) of the use case application. We then identified and classified features according to their robustness to parameter variation, and using the proposed features selection strategy, for instance, patient grouping stability in survival analysis has been improved from in 17% and 34% for BRCA and LUSC, respectively. CONCLUSIONS: This strategy created more robust analyses, demonstrating that SA and UQ are important methods that may increase confidence digital pathology.


Assuntos
Processamento de Imagem Assistida por Computador , Humanos , Incerteza
15.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229053

RESUMO

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumonia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
16.
Huan Jing Ke Xue ; 42(8): 3585-3594, 2021 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-34309245

RESUMO

To further study the effect of volatile organic compounds (VOCs) on ozone pollution, the characteristics and sources of VOCs at different ozone (O3) concentration levels were analyzed, using high-resolution online monitoring data obtained from Tianjin in the summer of 2019. Results showed that VOCs concentrations were 32.94, 38.10, 42.41, and 47.12 µg ·m-3, when the O3 concentration levels were categorized as excellent, good, light pollution, and moderate pollution, respectively. VOCs were composed of alkanes, alkenes, alkynes and aromatics, which accounted for 61.72%-63.36%, 14.96%-15.51%, 2.73%-4.13%, and 18.53%-19.10%, respectively, of VOCs concentrations at different O3 concentration levels. Among them, the proportion of alkanes was slightly higher when O3 concentration was categorized as good or light pollution, alkenes and alkynes accounted for the highest proportion when O3 concentration was excellent, and the proportion of aromatics was highest during periods of moderate pollution. The main VOCs species were propane, ethane, ethylene, toluent, n-butane, isopentane, m/p-xylene, propylene, acetylene, n-hexane, isobutene, benzene, n-pentane, isoprene, and 1,2,3-trimethylbenzene. The concentration percentage of isopentane, n-pentane, benzene, ethylene, propylene, n-butane, and isobutane increased gradually as O3 concentration increased. Significant increases in isoprene and 1,2,3-trimethylbenzene were observed during periods of light and moderate pollution. Alkenes and aromatics had higher ozone formation potential (OFP), and the contribution of alkenes to OFP declined as the O3 level rose, whereas that of aromatics increased. Ethylene, propylene, m/p-xylene, 1,2,3-trimethylbenzene, toluene, isoprene, trans-2-butene, and cis-2-pentene were the key species for O3 generation, and the contribution ratio of 1,2,3-trimethylbenzene, isoprene, propylene, and ethylene to OFP increased significantly during light or moderate O3 pollution. Positive matrix factorization was applied to estimate the source contributions of VOCs. Automobile exhaust, solvent usage, liquefied petroleum gas (LPG)/gasoline evaporation, combustion, petrochemical industrial emissions, natural sources, and other industrial emissions were identified as major sources of VOCs in summer. As O3 concentration level rose, the contribution percentage of automobile exhaust, LPG/gasoline evaporation, petrochemical industrial emissions, and natural sources increased gradually, whereas the contribution of combustion and other industrial emissions decreased overall. The contribution of solvent usage was lower when O3 levels indicated light or moderate pollution than when it was good.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Emissões de Veículos/análise , Compostos Orgânicos Voláteis/análise
17.
Dev Comp Immunol ; 125: 104212, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34310970

RESUMO

Previous studies have shown that ribosomal proteins play important roles in ribosome assembly and protein translation, but other biological functions remain ill-defined. Here it is clearly demonstrated that RPS18 is a newly identified PGN-binding protein which is present abundantly in the eggs/embryos of zebrafish. Recombinant RPS18 not only identifies the bacterial signature molecule PGN, LPS, and LTA, and binds the bacteria as a pattern recognition receptor, but also kills the Gram-positive and Gram-negative bacteria as an antibacterial effector molecule. What is important is that, we reveal that microinjection of rRPS18 into early embryos significantly improved the resistance of the embryos against pathogenic Aeromonas hydrophila challenge, and co-injection of anti-RPS18 antibody could markedly reduced this improved bacterial resistance. In summary, these results indicate that RPS18 is a maternal immune factor that can protect the early embryos of zebrafish against pathogenic attacks. This work also provides another angle for understanding the biological functions of ribosomal proteins.

18.
Leuk Lymphoma ; 62(12): 2949-2956, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34196252

RESUMO

To evaluate the efficacy of interferon-α (IFN-α) as maintenance therapy in patients with favorable-risk acute myeloid leukemia (AML), this retrospective study enrolled 84 patients with favorable-risk AML: 42 patients who received IFN-α maintenance therapy and 42 patients who did not (control). The median follow-up time and duration of IFN-α treatment was 26 (6-54) months and 18 (2-24) months, respectively. The 4-year estimated relapse-free survival (RFS) after the last consolidation chemotherapy was 86.8% (95% confidence interval (CI), 75.8-97.8%) in the IFN-α group and 55.7% (95% CI, 37.2-74.3%) in the control group (p=.007). The 4-year estimated overall survival was 94.4% (95% CI, 86.8-102%) and 76.4% (95% CI, 61.9-90.9%) in IFN-α and control groups, respectively (p=.040). The Cox regression analysis showed that IFN-α treatment was the only independent factor affecting RFS (p=.004). Maintenance therapy with IFN-α may prevent relapse in favorable-risk AML after consolidation chemotherapy.

19.
Ann Hematol ; 100(10): 2557-2566, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34278524

RESUMO

Recent studies have shown that approximately 50% of patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy with a sustained deep molecular response (DMR) (BCR-ABL1IS ≤ 0.01%) can achieve treatment-free remission (TFR, stopping TKI without relapse) and that prior interferon (IFN)-α therapy and higher NK cell counts at and after TKI discontinuation are associated with TFR. We recently reported that post-TKI discontinuation of IFN-α therapy could prevent molecular relapse (MR, BCR-ABL1IS > 0.1%). Here, we evaluated whether NK cells are associated with MR and investigated the effects of post-TKI discontinuation IFN-α therapy on lymphocyte subsets. A total of 34 patients measuring blood lymphocyte subclasses were included. In the 22 patients who did not receive IFN-α therapy, at 1 month after TKI discontinuation, the nonrelapsed patients showed a significantly higher proportion and count of NK cells than the relapsed patients. In particular, the proportion and count of CD56dim NK cells were significantly higher in the nonrelapsed patients than in the relapsed patients. In the 12 patients who received IFN-α therapy, the level of CD56bright NK cells increased significantly after 3 and 6 months of IFN-α therapy. In summary, NK cells, in particular CD56dim NK cells, were associated with MR after TKI discontinuation in patients with CML. Additionally, IFN-α therapy gradually increased the level of CD56bright NK cells in patients with CML.


Assuntos
Fatores Imunológicos/uso terapêutico , Interferon-alfa/uso terapêutico , Células Matadoras Naturais/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Adulto Jovem
20.
Bioinformatics ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081103

RESUMO

MOTIVATION: In most tissue-based biomedical research, the lack of sufficient pathology training images with well-annotated ground truth inevitably limits the performance of deep learning systems. In this study, we propose a convolutional neural network with foveal blur enriching datasets with multiple local nuclei regions of interest derived from original pathology images. We further propose a human-knowledge boosted deep learning system by inclusion to the convolutional neural network new loss function terms capturing shape prior knowledge and imposing smoothness constraints on the predicted probability maps. RESULTS: Our proposed system outperforms all state-of-the-art deep learning and non-deep learning methods by Jaccard coefficient, Dice coefficient, Accuracy, and Panoptic Quality in three independent datasets. The high segmentation accuracy and execution speed suggest its promising potential for automating histopathology nuclei segmentation in biomedical research and clinical settings. AVAILABILITY: The codes, the documentation, and example data are available on an open source at: https://github.com/HongyiDuanmu26/FovealBoosted. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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