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1.
Mol Oncol ; 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356397

RESUMO

Data analysis of clinical samples suggests that higher estrogen receptor α (ERα) expression could be associated with worse overall survival in some patients with non-small cell lung cancer (NSCLC). Immunofluorescence results further showed that higher ERα expression was linked to larger numbers of infiltrated macrophages in NSCLC tissues. However, the detailed mechanisms underlying this phenomenon remain unclear. Results from in vitro studies with multiple cell lines revealed that, in NSCLC cells, ERα can activate the CCL2/CCR2 axis to promote macrophage infiltration, M2 polarization, and MMP9 production, which can then increase NSCLC cell invasion. Mechanistic studies using chromatin immunoprecipitation and promoter luciferase assays demonstrated that ERα could bind to estrogen response elements (EREs) on the CCL2 promoter to increase CCL2 expression. Furthermore, ERα-increased macrophage infiltration can induce a positive feed-back mechanism to increase lung cancer cell ERα expression via the up-regulation of the CXCL12/CXCR4 pathway. Targeting these newly identified pathways, NSCLC ERα-increased macrophage infiltration or the macrophage-to-NSCLC CXCL12/CXCR4/ERα signal, with anti-estrogens or CCR2/CXCR4 antagonists, may help in the development of new alternative therapies to better treat NSCLC.

2.
Cell Death Dis ; 11(4): 230, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286266

RESUMO

Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMP-dependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.

3.
Sci Adv ; 6(13): eaay9789, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32232155

RESUMO

Radiotherapy (RT) is routinely used in cancer treatment, but expansion of its clinical indications remains challenging. The mechanism underlying the radiation-induced bystander effect (RIBE) is not understood and not therapeutically exploited. We suggest that the RIBE is predominantly mediated by irradiated tumor cell-released microparticles (RT-MPs), which induce broad antitumor effects and cause immunogenic death mainly through ferroptosis. Using a mouse model of malignant pleural effusion (MPE), we demonstrated that RT-MPs polarized microenvironmental M2 tumor-associated macrophages (M2-TAMs) to M1-TAMs and modulated antitumor interactions between TAMs and tumor cells. Following internalization of RT-MPs, TAMs displayed increased programmed cell death ligand 1 (PD-L1) expression, enhancing follow-up combined anti-PD-1 therapy that confers an ablative effect against MPE and cisplatin-resistant MPE mouse models. Immunological memory effects were induced.

4.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(4): 463-468, 2020 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-32291982

RESUMO

Objective: To explore the efficacy and safety of intravenous injection of tranexamic acid (TXA) combined with local use of TXA cocktail in intertrochanteric fracture fixation with proximal femoral nail antirotation (PFNA). Methods: Patients with intertrochanteric fractures who underwent close reduction and internal fixation with PFNA between February 2018 and March 2019 were enrolled in the study. Among them, 45 patients who met the selection criteria were included in the study and randomly allocated into 3 groups ( n=15). The patients in group A were not received TXA during perioperative period. The patients were intravenously injected of 1.0 g TXA before operation in group B and combined with local use of TXA cocktail during operation in group C. There was no significant difference in the age, gender, body mass index, fracture classification, disease duration, and complications between groups ( P>0.05). The perioperative blood loss and blood transfusion rate, the visual analogue scale (VAS) score before operation and at 12, 24, and 48 hours after operation, the levels of prostaglandin E2 (PGE2) and bradykinin (BK) before operation and at 1 and 3 days after operation, postoperative complications, and the maximum amplitude (MA) of thromboelastogram were recorded and compared between groups. Results: The total blood loss, hidden blood loss, and visible blood loss were significantly lower in groups B and C than those in group A ( P<0.05), and the total blood loss and hidden blood loss were significantly lower in group C than those in group B ( P<0.05). There was no significant difference in the blood transfusion rate, preoperative VAS scores and the levels of PGE2 and BK between groups ( P>0.05). The postoperative VAS scores and the levels of PGE2 and BK were significantly lower in group C than in groups A and B ( P<0.05). There was no significant difference in pre- and post-operative MA of thromboelastogram between groups ( P>0.05). The incidences of postoperative complications were 33.33% (5/15), 20.00% (3/15), and 13.33% (2/15) in groups A, B, and C, respectively, with no significant difference between groups ( χ 2=1.721, P=0.550). Conclusion: For intertrochanteric fractures, application of intravenous injection of TXA combined with local use of TXA cocktail in PFNA fixation can reduce perioperative blood loss, relieve pain after operation, and do not increase the risk of complications.

5.
ACS Sens ; 5(4): 943-951, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32223138

RESUMO

Monoamine oxidase A (MAO-A) is a promising diagnostic marker for cancer, depression, Parkinson's disease, and liver disease. The fluorescence detection of MAO-A in living animals is of extreme importance for the early diagnosis of related diseases. However, the development of specific and mitochondrial-targeted and near-infrared (NIR) fluorescence MAO-A probes is still inadequate. Here, we designed and synthesized four NIR fluorescence probes containing a dihydroxanthene (DH) skeleton to detect MAO-A in complex biological systems. The specificity of our representative probe DHMP2 displays a 31-fold fluorescence turn-on in vitro, and it can effectively accumulate in the mitochondria and specifically detect the endogenous MAO-A concentrations in PC-3 and SH-SY5Y cell lines. Furthermore, the probe DHMP2 can be used to visualize the endogenous MAO-A activity in zebrafish and tumor-bearing mice. More importantly, it is the first time that the MAO-A activity of hepatic fibrosis tissues is detected through the probe DHMP2. The present study shows that the synthesized DHMP2 might serve as a potential tool for monitoring MAO-A activity in vivo and diagnosing related diseases.

7.
Cell Rep ; 31(3): 107525, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32320661

RESUMO

Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome. Integration of methylome to age-related transcriptome changes, chromatin signatures, and first-order protein-protein interactions uncover an enrichment of DMRs in altered pathways that are associated with rod function, aging, and energy metabolism. In concordance, we detect reduced basal mitochondrial respiration and increased fatty acid dependency with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies a link between DNA methylation and energy metabolism in aging.

8.
Arch Osteoporos ; 15(1): 47, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173776

RESUMO

Association between strength of nonadjacent muscles and bone mineral density is unclear. We used data from the National Health and Nutrition Examination Survey to convince the effect of grip strength on femoral neck and lumbar spine mineral density in the general US population. This research can broaden the area of muscle-bone interaction. INTRODUCTION: Grip test measures the maximum isotonic strength of hand and forearm and is often used as an indicator of general muscle strength. Muscle has been shown to exert positive effects on bone health, and studies are needed to test whether grip strength can be associated with bone mineral density of nonadjacent bones. The aim of this study is to assess whether grip strength is an independent predictor for bone mineral density (BMD) of femoral neck and total lumbar spine in the general US population. METHODS: We used the data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014, and 1850 participants aged from 40 to 80 years old were included in the analysis. Grip strength was recorded as the largest reading of three efforts of one's dominant hand using a handgrip dynamometer. Femoral neck and lumbar spine BMDs were measured through Dual-energy X-ray absorptiometry (DXA) scan. Univariate and multivariate linear regression analyses were done to examine the association between grip strength and BMDs. RESULTS: After adjusting for age, ethnicity, body mass index (BMI), use of female hormones, smoking habit, drinking habit, family history of osteoporosis, use of calcium and vitamin D supplements, physical activity, serum calcium, and phosphorus levels, grip strength is associated with increased femoral neck and total lumbar spine BMDs in men (P < 0.001, P = 0.005), premenopausal women (P = 0.040, P = 0.014), and postmenopausal women (P = 0.016, P = 0.012). CONCLUSIONS: Our results suggest that (1) grip strength can be associated with BMD of nonadjacent bones, and (2) grip strength of dominant hand can be an indicator of BMD in the general US population across genders and menopausal status.

9.
Mol Phylogenet Evol ; 148: 106789, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32173414

RESUMO

The genus Amolops ("torrent frogs") is one of the most species-rich genera in Ranidae, with 59 recognized species. This genus currently includes six species groups diagnosed mainly by morphology. Several recent molecular studies indicated that the classification of species groups within Amolops remains controversial, and key nodes in the phylogeny have been inadequately resolved. In addition, the diversity of Amolops remains poorly understood, especially for those from incompletely sampled regions. Herein, we investigate species-level diversity within the genus Amolops throughout southern China and Southeast Asia, and infer evolutionary relationships among the species using mtDNA data (16S, COI, and ND2). Molecular analyses indicate nine unnamed species, mostly distributed in the Himalayas. We then utilized anchored hybrid enrichment to generate a dataset representing the major mitochondrial lineages to resolve phylogenetic relationships, biogeography, and pattern of species diversification. Our resulting phylogeny strongly supports the monophyly of four previously identified species groups (the A. ricketti, A. daiyunensis, A. hainanensis, and A. monticola groups), but paraphyly for the A. mantzorum and A. marmoratus groups, as previously defined. We erect one new species group, the A. viridimaculatus group, and recognize Dubois' (1992) subgenus Amo as the A. larutensis species group. Biogeographic analysis suggests that Amolops originated on the Indo-Burma/Thai-Malay Peninsula at the Eocene/Oligocene boundary, and dispersed outward, exemplifying a common pattern observed for the origin of Asian biodiversity. The early divergence within Amolops coincides with the Himalayan uplift and the lateral extrusion of Indochina at the Oligocene/Miocene boundary. Our results show that paleoclimatic and geomorphological events have profoundly influenced the patterns of lineage diversification within Amolops.

10.
Mol Biol Evol ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077944

RESUMO

The transition of terrestrial snakes to marine life approximately 10 million years ago (Ma) is ideal for exploring adaptive evolution. Sea snakes possess phenotype specializations including laterally compressed bodies, paddle-shaped tails, valvular nostrils, cutaneous respiration, elongated lungs and salt glands yet knowledge on the genetic underpinnings of the transition remain limited. Herein, we report the first genome of Shaw's sea snake (Hydrophis curtus) and use it to investigate sea snake secondary marine adaptation. A hybrid assembly strategy obtains a high quality genome. Gene family analyses date a pulsed coding-gene expansion to about 20 Ma, and these genes associate strongly with adaptations to marine environments. Analyses of selection pressure and convergent evolution discover the rapid evolution of protein-coding genes, and some convergent features. Additionally, 108 conserved non-coding elements appear to have evolved quickly, and these may underpin the phenotypic changes. Transposon elements may contribute to adaptive specializations by inserting into genomic regions around functionally related coding genes. The integration of genomic and transcriptomic analyses indicates independent origins and different components in sea snake and terrestrial snake venom; the venom gland of the sea snake harbours the highest PLA2 (17.23%) expression in selected elapids and these genes may organize tandemly in the genome. These analyses provide insights into the genetic mechanisms that underlay the secondary adaptation to marine and venom production of this sea snake.

11.
J Cell Mol Med ; 24(7): 4286-4297, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32100392

RESUMO

Oncolytic Newcastle disease virus (NDV) induces immunogenic cell death (ICD), liberating danger-associated molecular patterns (DAMPs) that provokes defiance in neoplastic malignancy. The present study aims to investigate whether and how oncolytic NDV triggers ICD in prostate cancer cells. We show that NDV/FMW, an oncolytic NDV strain FMW, elicited the expression and release of several ICD markers, that is calreticulin (CRT), heat shock proteins (HSP70/90) and high-mobility group box 1 (HMGB1), in prostate cancer cells. Furthermore, pharmacological repression of apoptosis, necroptosis, autophagy or endoplasmic reticulum (ER) stress exerted diverse effects on the HMGB1 and HSP70/90 evacuation in NDV/FMW-infected prostate cancer cells. Moreover, ICD markers induced in prostate cancer cells upon NDV/FMW infection, were enhanced by either treatment with a STAT3 (signal transducer and activator of transcription 3) inhibitor or shRNA-mediated knockdown of STAT3. In nude mice bearing prostate cancer cell-derived tumours, the tumours injected with the supernatants of NDV/FMW-infected cells grew smaller than mock-treated tumours. These results indicate that oncolytic NDV provokes the expression of ICD makers in prostate cancer cells. Our data also suggest that a combination of inhibition of STAT3 with oncolytic NDV could boost NDV-based anti-tumour effects against prostate cancer.

12.
J Anesth ; 34(2): 314, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32002679
13.
Thyroid ; 30(1): 57-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31830859

RESUMO

Background: Based on the new TNM classification, differentiated thyroid carcinomas with extrathyroidal extension (ETE) into the strap muscles are designated as T3b. The current study analyzed the clinical significance of this new stage in patients with papillary thyroid cancer (PTC). Subjects and Methods: This retrospective cohort study included 4045 eligible PTC patients. The patients were divided into four groups according to the extent of ETE: no ETE, ETE into perithyroidal tissue, T3b (ETE into the strap muscles), and ETE beyond the strap muscles. Differences in the clinical characteristics and prognosis of the four groups were assessed. Results: Of these 4045 patients, 2300 (56.9%) had no ETE, 1004 (24.8%) had ETE into perithyroidal tissue, 371 (9.2%) had ETE into the strap muscles, and 370 (9.1%) had ETE beyond the strap muscles. Tumor size, multifocality, lymph node metastasis (LNM), distant metastasis (DM), recurrence, and recurrence-free survival (RFS) between patients with ETE into perithyroidal tissue and patients without ETE did not show differences, but significant differences were observed between patients with T3b and patients without ETE, and only patients with ETE beyond the strap muscles had significantly worse overall survival (OS) than the other three groups. However, T3b did not independently predict worse RFS in univariable and multivariable analyses. Conclusions: T3b, distinguished from minimal ETE, may be related to larger tumor size, higher prevalence of multifocality, LNM, DM, recurrence, and worse RFS than no ETE, but it may not affect OS and may not independently predict recurrence in PTC patients.

15.
Sci Adv ; 5(11): eaaw9120, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31803831

RESUMO

Two-dimensional synthetic polymers (2DSPs) are sheet-like macromolecules consisting of covalently linked repeat units in two directions. Access to 2DSPs with controlled size and shape and diverse functionality has been limited because of the need for monomers to retain their crystallinity throughout polymerization. Here, we describe a synthetic strategy for 2DSPs that obviates the need for crystallinity, via the free radical copolymerization of amphiphilic gemini monomers and their monomeric derivatives arranged in a bilayer at solid-liquid interfaces. The ease of this strategy allowed the preparation of 2DSPs with well-controlled size and shape and diverse functionality on solid templates composed of various materials with wide-ranging surface curvatures and dimensions. The resulting 2DSPs showed remarkable mechanical strength and have multiple applications, such as nanolithographic resist and antibacterial agent. The broad scope of this approach markedly expands the chemistry, morphology, and functionality of 2DSPs accessible for practical applications.

16.
Sci Rep ; 9(1): 18438, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804533

RESUMO

One of the major barriers for a widespread commercial uptake of silicon nitride photonic integrated circuits for cost-sensitive applications is the lack of low-cost monolithically integrated laser light sources directly emitting into single-mode waveguides. In this work, we demonstrate an optically pumped organic solid-state slot-waveguide distributed feedback laser designed for a silicon nitride organic hybrid photonic platform. Pulsed optical excitation of the gain medium is achieved by a 450 nm laser diode. The optical feedback for lasing is based on a second-order laterally coupled Bragg grating with a slot-waveguide core. Optimized material gain properties of the organic dye together with the increased modal gain of the laser mode arising from the improved overlap of the slot-waveguide geometry with the gain material enable single-mode lasing at a wavelength of 600 nm. The straightforward integration and operation with a blue laser diode leads to a cost-effective coherent light source for photonic integrated devices.

17.
World J Clin Cases ; 7(23): 3964-3970, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31832398

RESUMO

BACKGROUND: Stroke is a type of cerebrovascular disease with high prevalence, mortality, and onset of disability. As a neurodevelopmental therapy, neuromuscular joint facilitation (NJF) is widely used in the treatment of orthopedic and neurological disorders in the clinical practice. It is mainly used for central nervous system diseases or orthopedic diseases, movement disorders, and pain rehabilitation. According to related studies, NJF can also be used as a rehabilitation treatment in patients with hemiplegic shoulder pain (HSP). AIM: To investigate the clinical efficacy of acupuncture combined with NJF in patients with HSP. METHODS: Forty patients with HSP were randomly divided into a treatment group and a control group. The treatment group was treated with acupuncture combined with NJF and the control group was treated with acupuncture alone. All patients were assessed by using the visual analogue scale (VAS), Fugl-Meyer assessment (FMA), Barthel index (BI), and passive range of motion (PROM) before and after the training. All the clinical data were analyzed using SPSS 20.0 statistical software. RESULTS: There was no statistical difference in the general characteristics between the two groups. In the terms of duration of treatment, age, and pre-treatment indicators, the two groups were comparable (P > 0.05). After the treatment, VAS, PROM, BI, and FMA scores were significantly improved in the two groups of patients (P < 0.05). The VAS, PROM and FMA scores were significantly higher in the treatment group than in the control group (P < 0.05). However, there was no significant difference in BI scores between the two groups (P > 0.05). CONCLUSION: Both acupuncture alone and acupuncture combined with NJF in the treatment of HSP are effective, and can improve the clinical symptoms of patients. Acupuncture combined with NJF can improve the upper limb motor function, relieve pain, and increase joint mobility in patients with HSP. The combination therapy is better than acupuncture alone. However, there is no significant difference in improving the score of patients' self-care ability.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31773232

RESUMO

PURPOSE: There is a clinical need for agents that target glioma cells for non-invasive and intraoperative imaging to guide therapeutic intervention and improve the prognosis of glioma. Matrix metalloproteinase (MMP)-14 is overexpressed in glioma with negligible expression in normal brain, presenting MMP-14 as an attractive biomarker for imaging glioma. In this study, we designed a peptide probe containing a near-infrared fluorescence (NIRF) dye/quencher pair, a positron emission tomography (PET) radionuclide, and a moiety with high affinity to MMP-14. This novel substrate-binding peptide allows dual modality imaging of glioma only after cleavage by MMP-14 to activate the quenched NIRF signal, enhancing probe specificity and imaging contrast. METHODS: MMP-14 expression and activity in human glioma tissues and cells were measured in vitro by immunofluorescence and gel zymography. Cleavage of the novel substrate and substrate-binding peptides by glioma cells in vitro and glioma xenograft tumors in vivo was determined by NIRF imaging. Biodistribution of the radiolabeled MMP-14-binding peptide or substrate-binding peptide was determined in mice bearing orthotopic patient-derived xenograft (PDX) glioma tumors by PET imaging. RESULTS: Glioma cells with MMP-14 activity showed activation and retention of NIRF signal from the cleaved peptides. Resected mouse brains with PDX glioma tumors showed tumor-to-background NIRF ratios of 7.6-11.1 at 4 h after i.v. injection of the peptides. PET/CT images showed localization of activity in orthotopic PDX tumors after i.v. injection of 68Ga-binding peptide or 64Cu-substrate-binding peptide; uptake of the radiolabeled peptides in tumors was significantly reduced (p < 0.05) by blocking with the non-labeled-binding peptide. PET and NIRF signals correlated linearly in the orthotopic PDX tumors. Immunohistochemistry showed co-localization of MMP-14 expression and NIRF signal in the resected tumors. CONCLUSIONS: The novel MMP-14 substrate-binding peptide enabled PET/NIRF imaging of glioma models in mice, warranting future image-guided resection studies with the probe in preclinical glioma models.

19.
Opt Express ; 27(20): 29350-29356, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31684671

RESUMO

The provision of a coherent light source is a prerequisite for a variety of photonic integrated circuits. The integration of semiconductor laser diodes in disposable photonic devices in fields such as biosensing is, however, impeded by the competitive pricing in this application area. In this work, we demonstrate lasing of an alternative laser light source, namely an integrated hybrid organic solid-state distributed feedback laser for a silicon nitride photonic platform. The laser is optically pumped with a high power 450 nm laser diode and emits in the visible at 630 nm into a waveguide taper to reduce the cross-section to a single mode geometry. Inkjet printing of the organic gain medium enables a local, cost-effective, and flexible processing technology. The fabrication of the presented coherent light source is CMOS compatible and therefore highly interesting for co-integrated sensing platforms.

20.
Sensors (Basel) ; 19(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597308

RESUMO

Moving object segmentation is the most fundamental task for many vision-based applications. In the past decade, it has been performed on the stationary camera, or moving camera, respectively. In this paper, we show that the moving object segmentation can be addressed in a unified framework for both type of cameras. The proposed method consists of two stages: (1) In the first stage, a novel multi-frame homography model is generated to describe the background motion. Then, the inliers and outliers of that model are classified as background trajectories and moving object trajectories by the designed cumulative acknowledgment strategy. (2) In the second stage, a super-pixel-based Markov Random Fields model is used to refine the spatial accuracy of initial segmentation and obtain final pixel level labeling, which has integrated trajectory classification information, a dynamic appearance model, and spatial temporal cues. The proposed method overcomes the limitations of existing object segmentation algorithms and resolves the difference between stationary and moving cameras. The algorithm is tested on several challenging open datasets. Experiments show that the proposed method presents significant performance improvement over state-of-the-art techniques quantitatively and qualitatively.

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