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1.
Artigo em Inglês | MEDLINE | ID: mdl-34678791

RESUMO

Electrochemical N2 reduction reaction (NRR) for NH3 synthesis, which usually needs highly-efficient electrocatalysts for N2 activation, is a carbon-neutral alternation compared to the traditional Haber-Bosch process. Although Ti-based compounds is widely used as electrocatalysts, what Ti defect affects NRR activity is still illusive. In this work, our systematic density functional calculations on Ti defect-decorated titanium oxide disclose that the unsaturated-Ti with the orbital splitting of defect electron states is the necessary feature for N2 binding and activation, which can be further enhanced by increasing the splitting degree. The bonding/antibonding orbital population and projected density of states indicate that the nature of N2 binding and activation on Ti-defect site is attributed to the elimination of the bonding orbital population in the conduction bands and the formation of *π back-bonding in the valence bands. For the whole NRR process, the synergy role of Ti-defect and oxygen vacancy(VO) promotes N2 reduction, and the required maximum energy input scales quite well with the adsorption strength of *NNH. Finally, the formed volcano shape successfully predicts new candidate catalysts for ammonia synthesis, such as TiO2 combined VO with Ti interstitial or H atom. This work provides disclosure of the key elements on the rational design of Ti-based nanomaterial electrocatalysts for artificial N2 fixation.

2.
Entropy (Basel) ; 23(10)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34681992

RESUMO

In this paper, variational sparse Bayesian learning is utilized to estimate the multipath parameters for wireless channels. Due to its flexibility to fit any probability density function (PDF), the Gaussian mixture model (GMM) is introduced to represent the complicated fading phenomena in various communication scenarios. First, the expectation-maximization (EM) algorithm is applied to the parameter initialization. Then, the variational update scheme is proposed and implemented for the channel parameters' posterior PDF approximation. Finally, in order to prevent the derived channel model from overfitting, an effective pruning criterion is designed to eliminate the virtual multipath components. The numerical results show that the proposed method outperforms the variational Bayesian scheme with Gaussian prior in terms of root mean squared error (RMSE) and selection accuracy of model order.

3.
BMC Med Imaging ; 21(1): 150, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34656085

RESUMO

OBJECTIVE: This study investigated the feasibility of predicting the expression levels of Ki-67 in breast cancer using ultrasonographic findings and clinical features. METHODS: Fifty-eight breast cancer patients, with 82 lesions confirmed by surgical pathology, were selected retrospectively for this study. Conventional ultrasound examination and elastography examination were performed before surgery. Clinical features (age, estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor-2 expression levels), ultrasonographic findings, and elastography scores, including the maximum size, location, number, margin, borderline, blood flow, and elastography score of the mass, were collected. The expression of Ki-67 was recorded using immunohistochemical staining, and the patients were divided into a high (≥ 20%) expression group and a low (< 20%) expression group. SPSS 23.0 software was used for statistical analysis. An independent sample t-test was used for measurement data, and a χ2 test was used for enumeration data. Logistic regression analysis was performed for meaningful indicators, and the receiver operating characteristic curve was used to calculate the best diagnostic cut-off point. RESULTS: Monofactorial analysis showed that there was a statistically significant difference (p < 0.05) between the high expression of Ki-67 and the maximum diameter of the mass, the margin of the mass, the color Doppler flow imaging of the blood flow, and the resistance index of the blood flow. There were no significant differences in age, mass location, number, morphology, borderline, microcalcification, and elastography score (p > 0.05). Multiple factor regression analysis showed that a large mass and a mass with a rich blood flow had an independent predictive value for Ki-67. When the diameter was > 21.5 mm, the diagnostic sensitivity and specificity were 91.9% and 71.3%, respectively. The expression level of Ki-67 was negatively correlated with that of ER. CONCLUSION: The tumor size and blood flow of breast cancer is correlated with the expression level of Ki-67 and, thus, it could be used to predict the expression level of Ki-67 in ultrasound diagnosis. The margin condition and the expression level of ER of an ultrasonic mass could also indirectly reflect the Ki-67 expression level of the mass.

4.
J Med Primatol ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664268

RESUMO

BACKGROUND: Golden snub-nosed monkey (Rhinopithecus roxellana) is an endangered primate species, whose molecular material for conservation purposes has not yet been maintained. Although small-molecule compounds (SMCs) have been reported to improve induced pluripotent stem cells (iPSCs), their efficiency in the interspecies-transferred nucleus is still unknown. METHODS: We thus used the fibroblasts from the golden snub-nosed monkey treated with SMC as donor cells, injected into the enucleated oocytes of goats, to test such efficiency. Gene expression profiles in the cell-constructed embryos with and without SMCs were compared by qPCR. RESULTS: The results show that cell morphology undergoes remarkable changes (volume is smaller than normal cells, and many black spots in the cytoplasm were found); pluripotent genes (Oct4, Sox2, and Nanog) significantly increased with SMC treatment. CONCLUSIONS: This study demonstrates that SMCs alter the properties of donor cells and promote the expression of pluripotent genes in hybrid embryos.

6.
Biomed Mater ; 16(6)2021 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-34507313

RESUMO

Cartilage damage is one of the main causes of disability, and 3D bioprinting technology can produce complex structures that are particularly suitable for constructing a customized and irregular tissue engineering scaffold for cartilage repair. Alginate is an attractive biomaterial for bioinks because of its good biological safety profile and fast ionic gelation. However, ionically crosslinked alginate hydrogels are recognized as lacking enough mechanical property and long-term stability due to ion exchange. Here, we developed a double crosslinked alginate (DC-Alg) hydrogel for 3D bioprinting, and human umbilical cord mesenchymal stem cells (huMSCs) could differentiate into chondrocytes on its printed 3D scaffold after 4 weeks' culture. We performed sequential modification of alginate with L-cysteine and 5-norbornene-2-methylamine, and the DC-Alg hydrogels were obtained in the presence of CaCl2and ultraviolet light with stronger mechanical properties than those of the single ionic crosslinked alginate hydrogels, which was similar to natural cartilage. They also had better stability and could be maintained in DMEM medium for over 1 month, as well good viability for huMSCs. Moreover, the DC-Alg as 3D printing inks demonstrated a better printing accuracy (∼200 µm). After 4 weeks culture of huMSCs in the 3D printed DC-Alg scaffolds, the expressions of chondrogenic genes such asaggrecan (agg), collagen II (col II), and SRY-box transcription factor9(sox-9) were obviously observed, indicating the differentiation of huMSCs into cartilage. Immumohistochemical staining analysis further exhibited cartilage tissue developed well in the 3D printed scaffolds. Our study is the first demonstration of DC-Alg in 3D printing for MSC differentiation into cartilage, which shows a potential application in cartilage defect repair.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34487499

RESUMO

Unsupervised dimension reduction and clustering are frequently used as two separate steps to conduct clustering tasks in subspace. However, the two-step clustering methods may not necessarily reflect the cluster structure in the subspace. In addition, the existing subspace clustering methods do not consider the relationship between the low-dimensional representation and local structure in the input space. To address the above issues, we propose a robust discriminant subspace (RDS) clustering model with adaptive local structure embedding. Specifically, unlike the existing methods which incorporate dimension reduction and clustering via regularizer, thereby introducing extra parameters, RDS first integrates them into a unified matrix factorization (MF) model through theoretical proof. Furthermore, a similarity graph is constructed to learn the local structure. A constraint is imposed on the graph to guarantee that it has the same connected components with low-dimensional representation. In this spirit, the similarity graph serves as a tradeoff that adaptively balances the learning process between the low-dimensional space and the original space. Finally, RDS adopts the ℓ 2,1 -norm to measure the residual error, which enhances the robustness to noise. Using the property of the ℓ 2,1 -norm, RDS can be optimized efficiently without introducing more penalty terms. Experimental results on real-world benchmark datasets show that RDS can provide more interpretable clustering results and also outperform other state-of-the-art alternatives.

8.
Biosens Bioelectron ; 194: 113629, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534949

RESUMO

Accurate and accessible nucleic acid diagnostics is critical to reducing the spread of COVID-19 and resuming socioeconomic activities. Here, we present an integrated platform for the direct detection of SARS-CoV-2 RNA targets near patients. Termed electrochemical system integrating reconfigurable enzyme-DNA nanostructures (eSIREN), the technology leverages responsive molecular nanostructures and automated microfluidics to seamlessly transduce target-induced molecular activation into an enhanced electrochemical signal. Through responsive enzyme-DNA nanostructures, the technology establishes a molecular circuitry that directly recognizes specific RNA targets and catalytically enhances signaling; only upon target hybridization, the molecular nanostructures activate to liberate strong enzymatic activity and initiate cascading reactions. Through automated microfluidics, the system coordinates and interfaces the molecular circuitry with embedded electronics; its pressure actuation and liquid-guiding structures improve not only analytical performance but also automated implementation. The developed platform establishes a detection limit of 7 copies of RNA target per µl, operates against the complex biological background of native patient samples, and is completed in <20 min at room temperature. When clinically evaluated, the technology demonstrates accurate detection in extracted RNA samples and direct swab lysates to diagnose COVID-19 patients.


Assuntos
Técnicas Biossensoriais , COVID-19 , Nanoestruturas , Humanos , Microfluídica , RNA Viral/genética , SARS-CoV-2
9.
BMC Cancer ; 21(1): 953, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433454

RESUMO

BACKGROUND: Abnormal activation of the coagulation system has been reported in patients with malignancies, but its prognostic significance in biliary tract cancer (BTC) remains unclear. This study aims to analyze and compare the prognostic value of coagulation indices in patients with BTC. METHODS: The medical records of 450 patients with BTC who underwent surgical resection at our hospital between 2003 and 2017 were retrospectively analyzed. Time-dependent receiver operating characteristic curves were plotted to compare the predictive accuracy of coagulation indices. A predictive nomogram for overall survival (OS) was established based on the Cox regression analysis and validated in both the training and validation cohorts. A novel stratification model was created according to the total points of the nomogram. RESULTS: Fibrinogen and international normalized ratio (INR) had the best predictive accuracy among the coagulation indices considered and were also the independent prognostic factors for OS. The nomogram and the novel stratification model had satisfactory performance and outperformed TNM staging. CONCLUSIONS: The study demonstrated that coagulation indices are valuable in predicting OS in BTC, with fibrinogen and INR having the best predictive ability. The nomogram and the novel stratification model could be applied to predict survival for patients with BTC.


Assuntos
Neoplasias do Sistema Biliar/mortalidade , Biomarcadores Tumorais/análise , Fibrinogênio/análise , Nomogramas , Avaliação de Resultados em Cuidados de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/sangue , Neoplasias do Sistema Biliar/patologia , Neoplasias do Sistema Biliar/cirurgia , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida , Adulto Jovem
11.
Liver Cancer ; 10(4): 296-308, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34414118

RESUMO

Introduction: Atezolizumab plus bevacizumab significantly improved overall survival (OS) and progression-free survival (PFS) versus sorafenib in patients with unresectable hepatocellular carcinoma (HCC) in IMbrave150. Efficacy and safety data from the Chinese subpopulation are reported. Methods: IMbrave150, a global, randomized, open-label, phase 3 study in patients with systemic treatment-naive unresectable HCC, included an extension phase that enrolled additional patients from mainland China. Patients were randomized (2:1) to receive intravenous atezolizumab 1,200 mg plus bevacizumab 15 mg/kg once every 3 weeks or sorafenib 400 mg twice a day until unacceptable toxicity or loss of clinical benefit. Co-primary endpoints were OS and independent review facility-assessed PFS per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population. Results: Of 194 Chinese patients enrolled from April 16, 2018, to April 8, 2019 (137 in the global study and 57 in the China extension phase), 133 received atezolizumab plus bevacizumab and 61 received sorafenib. At the data cutoff (August 29, 2019), the stratified hazard ratio for OS was 0.44 (95% CI, 0.25-0.76) and for PFS was 0.60 (95% CI, 0.40-0.90). The respective median OS and PFS with atezolizumab plus bevacizumab were not reached (NR; 95% CI, 13.5 months to NR) and 5.7 months (95% CI, 4.2-8.3) versus 11.4 months (95% CI, 6.7 to NR) and 3.2 months (95% CI, 2.6-4.8) with sorafenib. Grade 3-4 adverse events (AEs) occurred in 78 of 132 (59.1%) atezolizumab plus bevacizumab-treated and 27 of 58 (46.6%) sorafenib-treated patients. The most common grade 3-4 AE with atezolizumab plus bevacizumab was hypertension, occurring in 15.2% of patients; however, other high-grade AEs were infrequent. Conclusion: Clinically meaningful improvements in OS and PFS observed with atezolizumab plus bevacizumab versus sorafenib suggest that atezolizumab plus bevacizumab may become a practice-changing treatment for Chinese patients with unresectable HCC.

12.
Hepatobiliary Surg Nutr ; 10(4): 434-442, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34430522

RESUMO

Background: A combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported. Methods: Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed. Results: Nine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension. Conclusions: Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.

13.
Nat Commun ; 12(1): 4753, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362903

RESUMO

Gallbladder carcinoma is the most common cancer of the biliary tract with dismal survival largely due to delayed diagnosis. Biliary tract intraepithelial neoplasia (BilIN) is the common benign tumor that is suspected to be precancerous lesions. However, the genetic and evolutionary relationships between BilIN and carcinoma remain unclear. Here we perform whole-exome sequencing of coexisting low-grade BilIN (adenoma), high-grade BilIN, and carcinoma lesions, and normal tissues from the same patients. We identify aging as a major factor contributing to accumulated mutations and a critical role of CTNNB1 mutations in these tumors. We reveal two distinct carcinoma evolutionary paths: carcinoma can either diverge earlier and evolve more independently or form through the classic adenoma/dysplasia-carcinoma sequence model. Our analysis suggests that extensive loss-of-heterozygosity and mutation events in the initial stage tend to result in a cancerous niche, leading to the subsequent BilIN-independent path. These results reframes our understanding of tumor transformation and the evolutionary trajectory of carcinogenesis in the gallbladder, laying a foundation for the early diagnosis and effective treatment of gallbladder cancer.


Assuntos
Evolução Biológica , Carcinoma/genética , Neoplasias da Vesícula Biliar/genética , Genômica , Neoplasias/genética , Carcinogênese/genética , Carcinoma in Situ/patologia , Feminino , Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Lesões Pré-Cancerosas/genética
14.
Front Psychiatry ; 12: 676914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393844

RESUMO

Background: The COVID-19 has grown into a global pandemic. This study investigated the public psychosocial and behavioral responses through different time periods of the pandemic, and assessed whether these changes are different in age, gender, and region. Methods: A three-phase survey was conducted through the DaDui Social Q&A Software for COVID-19. A total of 13,214 effective responses of COVID-19 were collected. Statistical analysis was performed based on their basic information and psychosocial responses. Results: The degree of attention, understanding, and cooperation with preventive and control measures of the disease increased and then decreased. The panic level gradually increased with the epidemic process. The degree of satisfaction with management measures and of confidence in defeating COVID-19 increased throughout the survey. Compared with residents in other areas, respondents from the COVID-19 epicenter (Wuhan) reported a higher degree of self-protection during the outbreak and a significantly lower degree of satisfaction with respect to government prevention and control measures during all phases. Shortages of medical supplies and low testing capacity were reported as the biggest shortcoming in the prevention and control strategies during COVID-19, and an abundance of disorderly and inaccurate information from different sources was the primary cause of panic. Conclusions and Relevance: Major public health events elicit psychosocial and behavioral changes that reflect the different phases of the biologic curve. Sufficient medical supplies and improved organization and accurate information during epidemics may reduce panic and improve compliance with requested changes in behavior. We need to recognize this natural phenomenon and our public policy preparedness should attempt to move the social/psychological curve to the left in order to minimize and flatten the biologic curve.

17.
BMC Med ; 19(1): 154, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34284787

RESUMO

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy elicits durable antitumor responses in patients with many types of cancer. Genomic mutations may be used to predict the clinical benefits of ICI therapy. NOTCH homolog-4 (NOTCH4) is frequently mutated in several cancer types, but its role in immunotherapy is still unclear. Our study is the first to study the association between NOTCH4 mutation and the response to ICI therapy. METHODS: We tested the predictive value of NOTCH4 mutation in the discovery cohort, which included non-small cell lung cancer, melanoma, head and neck squamous cell carcinoma, esophagogastric cancer, and bladder cancer patients, and validated it in the validation cohort, which included non-small cell lung cancer, melanoma, renal cell carcinoma, colorectal cancer, esophagogastric cancer, glioma, bladder cancer, head and neck cancer, cancer of unknown primary, and breast cancer patients. Then, the relationships between NOTCH4 mutation and intrinsic and extrinsic immune response mechanisms were studied with multiomics data. RESULTS: We collected an ICI-treated cohort (n = 662) and found that patients with NOTCH4 mutation had better clinical benefits in terms of objective response rate (ORR: 42.9% vs 25.9%, P = 0.007), durable clinical benefit (DCB: 54.0% vs 38.1%, P = 0.021), progression-free survival (PFS, hazard ratio [HR] = 0.558, P < 0.001), and overall survival (OS, HR = 0.568, P = 0.006). In addition, we validated the prognostic value of NOTCH4 mutation in an independent ICI-treated cohort (n = 1423). Based on multiomics data, we found that NOTCH4 mutation is significantly associated with enhanced immunogenicity, including a high tumor mutational burden, the expression of costimulatory molecules, and activation of the antigen-processing machinery, and NOTCH4 mutation positively correlates activated antitumor immunity, including infiltration of diverse immune cells and various immune marker sets. CONCLUSIONS: Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Neoplasias Pulmonares , Neoplasias Gástricas , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Receptor Notch4
18.
Front Immunol ; 12: 673248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211467

RESUMO

Background: Hepatocellular carcinoma (HCC) has a high risk of recurrence after surgical resection, particularly among patients with multifocal HCC. Genomic heterogeneity contributes to the early recurrence. Few studies focus on targeted next-generation sequencing (tNGS) to depict mutational footprints of heterogeneous multifocal HCC. Methods: We conducted tNGS with an ultra-deep depth on 31 spatially distinct regions from 11 resected multifocal HCC samples. Matched preoperative peripheral circulating-free DNA (cfDNA) were simultaneously collected. Genomic alterations were identified and compared to depict the heterogeneity of multifocal HCC. Results: Widespread intertumoral heterogeneity of driver mutations was observed in different subfoci of multifocal HCC. The identified somatic mutations were defined as truncal drivers or branchy drivers according to the phylogenetic reconstruction. TP53 and TERT were the most commonly altered truncal drivers in multifocal HCC, while the most frequently mutated branchy driver was TSC2. HCC patients with a higher level of intertumoral heterogeneity, defined by the ratio of truncal drivers less than 50%, had a shorter RFS after surgical resection (HR=0.17, p=0.028). Genome profiling of cfDNA could effectively capture tumor-derived driver mutations, suggesting cfDNA was a non-invasive strategy to gain insights of genomic alterations in patients with resected multifocal HCC. Conclusions: Truncal mutations and the level of genomic heterogeneity could be identified by tNGS panel in patients with resected multifocal HCC. cfDNA could serve as a non-invasive and real-time auxiliary method to decipher the intertumoral heterogeneity and identify oncodrivers of multifocal HCC.


Assuntos
Carcinoma Hepatocelular/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Hepáticas/genética , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/sangue , DNA Tumoral Circulante/sangue , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Análise de Sequência de DNA/métodos
19.
Nat Commun ; 12(1): 4039, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193867

RESUMO

The controlled assembly of nanomaterials into desired architectures presents many opportunities; however, current preparations lack spatial precision and versatility in developing complex nano-architectures. Inspired by the amphiphilic nature of surfactants, we develop a facile approach to guide nanomaterial integration - spatial organization and distribution - in metal-organic frameworks (MOFs). Named surfactant tunable spatial architecture (STAR), the technology leverages the varied interactions of surfactants with nanoparticles and MOF constituents, respectively, to direct nanoparticle arrangement while molding the growing framework. By surfactant matching, the approach achieves not only tunable and precise integration of diverse nanomaterials in different MOF structures, but also fast and aqueous synthesis, in solution and on solid substrates. Employing the approach, we develop a dual-probe STAR that comprises peripheral working probes and central reference probes to achieve differential responsiveness to biomarkers. When applied for the direct profiling of clinical ascites, STAR reveals glycosylation signatures of extracellular vesicles and differentiates cancer patient prognosis.


Assuntos
Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/métodos , Neoplasias Colorretais/diagnóstico , Vesículas Extracelulares/metabolismo , Estruturas Metalorgânicas/química , Nanoestruturas/química , Tensoativos/química , Ascite/metabolismo , Neoplasias Colorretais/metabolismo , Glicosilação , Humanos , Prognóstico
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