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BACKGROUND: 5-Hydroxymethylcytosine-enriched gene profiles and regions show tissue-specific and tumor specific. There is a potential value to explore cell-free DNA 5-hydroxymethylcytosine feature biomarkers for early gastric cancer detection. METHODS: A matched caseâcontrol study design with 50 gastric cancer patients and 50 controls was performed to sequence the different 5-hydroxymethylcytosine modification features of cell free DNA. Significantly differential 5-hydroxymethylcytosine modification genes were identified to construct a gastric cancer diagnostic model. Data set from GEO was used as an external testing set to test the robustness of the diagnostic model. RESULTS: Accounting for more than 90% of 5-hydroxymethylcytosine peaks were distributed in the gene body in both the gastric cancer and control groups. The diagnostic model was developed based on five different 5-hydroxymethylcytosine modification genes, FBXL7, PDE3A, TPO, SNTG2 and STXBP5. The model could effectively distinguish gastric cancer patients from controls in the training (AUC = 0.95, sensitivity = 88.6%, specificity = 94.3%), validation (AUC = 0.87, sensitivity = 73.3%, specificity = 93.3%) and testing (AUC = 0.90, sensitivity = 81.9%, specificity = 90.2%) sets. The risk scores of the controls from the model were significantly lower than those of gastric cancer patients in both our own data (P < 0.001) and GEO external testing data (P < 0.001), and no significant difference between different TNM stage patients (P = 0.09 and 0.66). Furthermore, there was no significant difference between the healthy control and benign gastric disease patients in the testing set from GEO (P = 0.10). CONCLUSIONS: The characteristics of 5-hydroxymethylcytosine in cell free DNA are specific to gastric cancer patients, and the diagnostic model constructed by five genes' 5-hydroxymethylcytosine features could effectively identify gastric cancer patients.
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5-Metilcitosina , Biomarcadores Tumorais , Ácidos Nucleicos Livres , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , 5-Metilcitosina/análogos & derivados , Biomarcadores Tumorais/genética , Masculino , Estudos de Casos e Controles , Feminino , Pessoa de Meia-Idade , Ácidos Nucleicos Livres/genética , Idoso , Detecção Precoce de Câncer/métodos , Metilação de DNARESUMO
Multispectral stealth technology including terahertz (THz) band will play an increasingly important role in modern military and civil applications. Here, based on the concept of modularization design, two kinds of flexible and transparent metadevices were fabricated for multispectral stealth, covering the visible, infrared (IR), THz, and microwave bands. First, three basic functional blocks for IR, THz, and microwave stealth are designed and fabricated by using flexible and transparent films. And then, via modular assembling, that is, by adding or removing some stealth functional blocks or constituent layers, two multispectral stealth metadevices are readily achieved. Metadevice 1 exhibits THz-microwave dual-band broadband absorption, with average measured absorptivity of 85% in 0.3-1.2 THz and higher than 90% in 9.1-25.1â GHz, suitable for THz-microwave bi-stealth. Metadevice 2 is for IR and microwave bi-stealth, with measured absorptivity higher than 90% in 9.7-27.3â GHz and low emissivity around 0.31 in 8-14 µm. Both metadevices are optically transparent and able to maintain good stealth ability under curved and conformal conditions. Our work offers an alternative approach for designing and fabricating flexible transparent metadevices for multispectral stealth, especially for applications in nonplanar surfaces.
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BACKGROUND: Previous researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis. METHODS: Histologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith's plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results. RESULTS: A total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74-1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72-0.90) and disease-free survival (HR 0.83, 95%CI: 0.67-0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract. CONCLUSIONS: In conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.
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Infecções por Helicobacter/complicações , Helicobacter pylori , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
In vitro and vivo studies indicate that oxidative stress contributes to bone loss. Fluorescent oxidation products (FlOPs) are novel biomarkers of oxidative stress; they reflect global oxidative damage of lipids, proteins, carbohydrates, and DNA. However, whether FlOPs are associated with bone mineral density (BMD) is still unclear. In the present study, we examined the association between FlOPs and BMD among male veterans. This cross-sectional study was conducted among participants recruited from the Department of Medical Examination, The Second Hospital of Jilin University in Jilin, China. We identified male veterans who were at least 50 y old between June and October of 2019. Plasma FlOPs were measured with a fluorescent microplate reader (excitation/emission wavelength: 320/420 nm). BMD were measured by dual-energy X-ray absorptiometry (DXA). The association between FlOPs and BMD was tested by multivariable linear regression models. A total of 164 male veterans were enrolled in the study, the average age was 56.6 y. After adjusting for covariates, veterans who had FlOP levels in the highest tertile had a statistically significant lower femoral neck (ßâ¯=â¯-0.044; pâ¯=â¯0.007) and total hip BMD (ßâ¯=â¯-0.045; pâ¯=â¯0.020) as compared to those with FlOP levels in the lowest tertile. Similar results were found when FlOPs were treated as a continuous variable (per 1-SD increase, ßâ¯=â¯-0.014 and pâ¯=â¯0.033 for femoral neck BMD; ßâ¯=â¯-0.016 and pâ¯=â¯0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.
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Densidade Óssea , Veteranos , Absorciometria de Fóton , Estudos Transversais , Feminino , Colo do Fêmur , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Rationale: Screening for non-small cell lung cancer is associated with earlier diagnosis and reduced mortality but also increased harm caused by invasive follow-up of benign pulmonary nodules. Lung tumorigenesis activates the immune system, components of which could serve as tumor-specific biomarkers. Objectives: To profile tumor-derived autoantibodies as peripheral biomarkers of malignant pulmonary nodules. Methods: High-density protein arrays were used to define the specificity of autoantibodies isolated from B cells of 10 resected lung tumors. These tumor-derived autoantibodies were also examined as free or complexed to antigen in the plasma of the same 10 patients and matched benign nodule control subjects. Promising autoantibodies were further analyzed in an independent cohort of 250 nodule-positive patients. Measurements and Main Results: Thirteen tumor B-cell-derived autoantibodies isolated ex vivo showed greater than or equal to 50% sensitivity and greater than or equal to 70% specificity for lung cancer. In plasma, 11 of 13 autoantibodies were present both complexed to and free from antigen. In the larger validation cohort, 5 of 13 tumor-derived autoantibodies remained significantly elevated in cancers. A combination of four of these autoantibodies could detect malignant nodules with an area under the curve of 0.74 and had an area under the curve of 0.78 in a subcohort of indeterminate (8-20 mm in the longest diameter) pulmonary nodules. Conclusions: Our novel pipeline identifies tumor-derived autoantibodies that could effectively serve as blood biomarkers for malignant pulmonary nodule diagnosis. This approach has future implications for both a cost-effective and noninvasive approach to determine nodule malignancy for widespread low-dose computed tomography screening.
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Autoanticorpos/imunologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Nódulos Pulmonares Múltiplos/imunologia , Idoso , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To compare the ability of radiological semantic and quantitative texture features in lung cancer diagnosis of pulmonary nodules. MATERIALS AND METHODS: A total of N = 121 subjects with confirmed non-small-cell lung cancer were matched with 117 controls based on age and gender. Radiological semantic and quantitative texture features were extracted from CT images with or without contrast enhancement. Three different models were compared using LASSO logistic regression: "CS" using clinical and semantic variables, "T" using texture features, and "CST" using clinical, semantic, and texture variables. For each model, we performed 100 trials of fivefold cross-validation and the average receiver operating curve was accessed. The AUC of the cross-validation study (AUCCV) was calculated together with its 95% confidence interval. RESULTS: The AUCCV (and 95% confidence interval) for models T, CS, and CST was 0.85 (0.71-0.96), 0.88 (0.77-0.96), and 0.88 (0.77-0.97), respectively. After separating the data into two groups with or without contrast enhancement, the AUC (without cross-validation) of the model T was 0.86 both for images with and without contrast enhancement, suggesting that contrast enhancement did not impact the utility of texture analysis. CONCLUSIONS: The models with semantic and texture features provided cross-validated AUCs of 0.85-0.88 for classification of benign versus cancerous nodules, showing potential in aiding the management of patients. KEY POINTS: ⢠Pretest probability of cancer can aid and direct the physician in the diagnosis and management of pulmonary nodules in a cost-effective way. ⢠Semantic features (qualitative features reported by radiologists to characterize lung lesions) and radiomic (e.g., texture) features can be extracted from CT images. ⢠Input of these variables into a model can generate a pretest likelihood of cancer to aid clinical decision and management of pulmonary nodules.
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Algoritmos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico , Semântica , Tomografia Computadorizada por Raios X/métodos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
OBJECTIVE: The aim of this study was to explore the independent clinical and magnetic resonance imaging (MRI) performance risk factors for predicting placenta accreta. METHODS: From January 2012 to December 2015, we retrospectively reviewed the clinical characteristics and MRI features of 97 patients. Of these, 42 were confirmed to be placenta accreta by pathological results or cesarean delivery findings. We tried to identify the independent risk factors by multivariate logistic regression model for significant differences in variables determined by univariate analysis. RESULTS: The multivariate logistic regression model indicated that 2 or more instances of previous cesarean deliveries and/or abortions, placenta previa, and placenta-myometrial interface interruption were independent risk factors for placenta accreta. The odd ratios were 3.79 for patients who had 2 or more instances of previous cesarean deliveries and/or abortions, 0.04 for marginal/partial placenta previa, 0.024 for complete placenta previa, and 6.56 for placenta-myometrial interface interruption. The values of accuracy and positive prediction by combination of a single clinical risk factor and placenta-myometrial interface interruption and of positive prediction by a combination of all 3 risk factors for predicting placenta accreta were raised to 83.5%, 75%, and 92.9%, respectively. We obtained 3 different risk groups by different combinations of all 3 risk factors. CONCLUSIONS: The study suggested that 2 or more instances of previous cesarean deliveries and/or abortion, placenta previa, and placenta-myometrial interface interruption were independent risk factors for placenta accreta. A combination of a single clinical risk factor and an MRI risk factor can improve the diagnosis of placenta accreta, and a combination of all 3 risk factors could help recognize patients with placenta accreta.
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Imageamento por Ressonância Magnética/métodos , Placenta Acreta/diagnóstico por imagem , Aborto Induzido/efeitos adversos , Adulto , Cesárea/efeitos adversos , Feminino , Humanos , Placenta Acreta/etiologia , Placenta Acreta/patologia , Placenta Prévia , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers. DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3â years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays. RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively. CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.
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Adenoma/sangue , Adenoma/diagnóstico , Biomarcadores Tumorais/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/diagnóstico , Detecção Precoce de Câncer/métodos , Proteínas Adaptadoras de Transdução de Sinal/sangue , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno CA-19-9/metabolismo , Estudos de Casos e Controles , Neoplasias do Colo/metabolismo , Receptor gp130 de Citocina/sangue , Receptor gp130 de Citocina/metabolismo , Receptores ErbB/sangue , Receptores ErbB/metabolismo , Feminino , Humanos , Receptores de Hialuronatos/sangue , Receptores de Hialuronatos/metabolismo , Antígenos CD15/metabolismo , Masculino , Pessoa de Meia-Idade , Oligossacarídeos/metabolismo , Análise Serial de Proteínas , Fator de von Willebrand/metabolismoRESUMO
Micro Fourier transform profilometry (µFTP) is a recently developed computational framework for high-speed dynamic 3D shape measurement of transient scenes based on fringe projection. It has been demonstrated that by using high-frame-rate fringe projection hardware, µFTP can achieve accurate, denser, unambiguous, and motion-artifact-free 3D reconstruction at a speed up to 10,000 Hz. µFTP utilizes a temporal phase unwrapping algorithm, so-called projection distance minimization (PDM), in which multiple wavelengths are used to solve the phase ambiguity optimally in the maximum-likelihood sense. However, it has been found that the choice of the wavelengths is essential to the unambiguous measurement range as well as the unwrapping reliability in the presence of noise. In this work, the relations between the wavelength combination and the noise resistance ability of PDM are analyzed and investigated in detail by analytical, emulational, and experimental means. This leads to a qualitative conclusion that the noise resistance ability of PDM is fundamentally determined by the value of each item in wavelength ratio: a smaller value of each item in wavelength ratio means better noise resistance ability in phase unwrapping. Our result provides a guideline for optimal wavelengths selection in order to improve the noise resistance ability of a practical fringe projection system. Simulations and experiments based on a microscopic fringe projection system are demonstrated to validate the correctness of our conclusion.
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Proteomic studies can offer information on hundreds to thousands of proteins and potentially provide researchers with a comprehensive understanding of signaling response during stress and disease. Large data sets, such as those obtained in high-dimensional proteomic studies, can be leveraged for pathway analysis to discover or describe the biological implications of clinical disease states. Obesity is a worldwide epidemic that is considered a risk factor for numerous other diseases. We performed analysis on plasma proteomic data from 3 separate sample sets of postmenopausal women to identify the pathways that are altered in subjects with a high body mass index (BMI) compared to normal BMI. We found many pathways consistently and significantly associated with inflammation dysregulated in plasma from obese/overweight subjects compared to plasma from normal BMI subjects. These pathways indicate alterations of soluble inflammatory regulators, cellular stress, and metabolic dysregulation. Our results highlight the importance of high-dimensional pathway analysis in complex diseases as well as provide information on the interconnections between pathways that are dysregulated with obesity. Specifically, overlap of obesity related pathways with those activated during cancer and infection could help describe why obesity is a risk factor for disease and help devise treatment options that mitigate its effect.
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Autoimunidade/genética , Citocinas/genética , Obesidade/genética , Pós-Menopausa/genética , Proteoma/genética , Idoso , Autoanticorpos/biossíntese , Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/patologia , Citocinas/imunologia , Feminino , Redes Reguladoras de Genes/imunologia , Humanos , Inflamação , Redes e Vias Metabólicas/genética , Redes e Vias Metabólicas/imunologia , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Obesidade/imunologia , Obesidade/patologia , Pós-Menopausa/imunologia , Estudos Prospectivos , Proteoma/imunologia , ProteômicaRESUMO
BACKGROUND: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited. METHODS: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vß gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients. Differences in liposarcoma subsets also were evaluated. RESULTS: UPS and leiomyosarcoma had high expression levels of genes related to antigen presentation and T-cell infiltration. UPS were found to have higher levels of PD-L1 (P≤.001) and PD-1 (P≤.05) on immunohistochemistry and had the highest T-cell infiltration based on T-cell receptor sequencing, significantly more than SS, which had the lowest (P≤.05). T-cell infiltrates in UPS also were more oligoclonal compared with SS and liposarcoma (P≤.05). A model adjusted for STS histologic subtype found that for all sarcomas, T-cell infiltration and clonality were highly correlated with PD-1 and PD-L1 expression levels (P≤.01). CONCLUSIONS: In the current study, the authors provide the most detailed overview of the immune microenvironment in sarcoma subtypes to date. UPS, which is a more highly mutated STS subtype, provokes a substantial immune response, suggesting that it may be well suited to treatment with immune checkpoint inhibitors. The SS and liposarcoma subsets are less mutated but do express immunogenic self-antigens, and therefore strategies to improve antigen presentation and T-cell infiltration may allow for successful immunotherapy in patients with these diagnoses. Cancer 2017;123:3291-304. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
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Receptor de Morte Celular Programada 1/genética , Sarcoma/genética , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/mortalidade , Linfócitos T/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biópsia por Agulha , Células Clonais , Análise por Conglomerados , Estudos de Coortes , Terapia Combinada , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Análise de Sobrevida , Linfócitos T/imunologia , Adulto JovemRESUMO
Multiple reaction monitoring (MRM) mass spectrometry has been successfully applied to monitor targeted proteins in biological specimens, raising the possibility that assays could be configured to measure all human proteins. We report the results of a pilot study designed to test the feasibility of a large-scale, international effort for MRM assay generation. We have configured, validated across three laboratories and made publicly available as a resource to the community 645 novel MRM assays representing 319 proteins expressed in human breast cancer. Assays were multiplexed in groups of >150 peptides and deployed to quantify endogenous analytes in a panel of breast cancer-related cell lines. The median assay precision was 5.4%, with high interlaboratory correlation (R(2) > 0.96). Peptide measurements in breast cancer cell lines were able to discriminate among molecular subtypes and identify genome-driven changes in the cancer proteome. These results establish the feasibility of a large-scale effort to develop an MRM assay resource.
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Bioensaio/normas , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Proteoma/análise , Proteômica , Espectrometria de Massas em Tandem/métodos , Biomarcadores Tumorais/genética , Neoplasias da Mama/classificação , Neoplasias da Mama/mortalidade , Cromatografia Líquida de Alta Pressão , Eletroforese em Gel Bidimensional , Estudos de Viabilidade , Feminino , Humanos , Projetos Piloto , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of <5%. Detection of resectable disease improves survival rates, but access to tissue and other biospecimens that could be used to develop early detection markers is confounded by the insidious nature of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing â¼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages.
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Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Pancreatite Crônica/genética , Proteínas Serina-Treonina Quinases/genética , Animais , Anticorpos/química , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Ceruletídeo , Diagnóstico Diferencial , Modelos Animais de Doenças , Progressão da Doença , Diagnóstico Precoce , Perfilação da Expressão Gênica , Humanos , Camundongos , Anotação de Sequência Molecular , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/metabolismo , Análise Serial de Proteínas , Proteínas Serina-Treonina Quinases/metabolismo , Proteoma/genética , Proteoma/metabolismo , Transdução de Sinais , Fatores de TempoRESUMO
In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression ≥ 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials.
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Carcinoma de Células Escamosas , Linfonodos , Metástase Linfática , Neoplasias Bucais , Prognóstico , Idoso , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Genômica , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , RNA Interferente Pequeno/genéticaRESUMO
Estrogen receptor (ER)-positive/progesterone receptor (PR)-positive invasive ductal carcinoma accounts for ~45 % of invasive breast cancer (BC) diagnoses in the U.S. Despite reductions in BC mortality attributable to mammography screening and adjuvant hormonal therapy, an important challenge remains the development of clinically useful blood-based biomarkers for risk assessment and early detection. The objective of this study was to identify novel protein markers for ER+/PR+ ductal BC. A nested case-control study was conducted within the Women's Health Initiative observational study. Pre-clinical plasma specimens, collected up to 12.5 months before diagnosis from 121 cases and 121 matched controls, were equally divided into training and testing sets and interrogated using a customized antibody array targeting >2000 proteins. Statistically significant differences (P < 0.05) in matched case versus control signals were observed for 39 candidates in both training and testing sets, and four markers (CSF2, RYBP, TFRC, ITGB4) remained significant after Bonferroni correction (P < 2.03 × 10(-5)). A multivariate modeling procedure based on elastic net regression with Monte Carlo cross-validation achieved an estimated AUC of 0.75 (SD 0.06). Most candidates did not overlap with those described previously for triple-negative BC, suggesting sub-type specificity. Gene set enrichment analyses identified two GO gene sets as upregulated in cases-microtubule cytoskeleton and response to hormone stimulus (P < 0.05, q < 0.25). This study has identified a pool of novel candidate plasma protein biomarkers for ER+/PR+ ductal BC using pre-diagnostic biospecimens. Further validation studies are needed to confirm these candidates and assess their potential clinical utility for BC risk assessment/early detection.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Estudos de Casos e Controles , Biologia Computacional/métodos , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Proteoma , Proteômica/métodos , Curva ROC , Fatores de RiscoRESUMO
Semiconducting SnO2 nanowires have been used to demonstrate high-quality field-effect transistors, optically transparent devices, photodetectors, and gas sensors. However, controllable assembly of rutile SnO2 nanowires is necessary for scalable and practical device applications. Here, we demonstrate aligned, planar SnO2 nanowires grown on A-plane, M-plane, and R-plane sapphire substrates. These parallel nanowires can reach 100 µm in length with sufficient density to be patterned photolithographically for field-effect transistors and sensor devices. As proof-of-concept, we show that transistors made this way can achieve on/off current ratios on the order of 10(6), mobilities around 71.68 cm(2)/V·s, and sufficiently high currents to drive external organic light-emitting diode displays. Furthermore, the aligned SnO2 nanowire devices are shown to be photosensitive to UV light with the capability to distinguish between 254 and 365 nm wavelengths. Their alignment is advantageous for polarized UV light detection; we have measured a polarization ratio of photoconductance (σ) of 0.3. Lastly, we show that the nanowires can detect NO2 at a concentration of 0.2 ppb, making them a scalable, ultrasensitive gas sensing technology. Aligned SnO2 nanowires offer a straightforward method to fabricate scalable SnO2 nanodevices for a variety of future electronic applications.
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Óxido de Alumínio/química , Nanofios/química , Óxido Nítrico/análise , Semicondutores , Compostos de Estanho/química , Nanofios/ultraestruturaRESUMO
Water ice and other volatiles that accumulated in the Moon's polar regions are among the top priority targets for lunar exploration, due to their significances in both lunar geology and extraterrestrial resource utilization. Locating suitable landing sites and determining the provenance of sampled/measured surface materials are critical for future landed missions. Here, we map over 800 sites of plains terrains in the Moon's south polar region, with a total surface area of ~46,000 km2. Orbital measurements and analog studies show that most of these plains have apparently higher albedo and lower iron content than volcanic mare plains, suggesting an origin of ejecta-induced debris flows from distant impact craters, especially from the Schrödinger basin. Our findings suggest that the entire lunar south polar region probably have experienced contributions from distant basin materials. We recommend these plains as priority landing sites for future exploration of lunar polar volatiles and early bombardment history.
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Introduction: Migrant workers in China are migrants from the rural to the urban areas who usually work in the cities and return to the countryside after a certain period. Due to China's strict household registration system, they differ significantly from urban residents' access to public services. However, at the same time, China's workers are facing a severe phenomenon of overwork, and the group of migrant workers is even more hard-hit by overwork, which will cause various adverse effects on workers and society and should attract the attention of all sectors of society. Methods: This paper focuses on the impact of digital financial inclusion on the overwork of migrant workers. This study considered cross-sectional data containing 98,047 samples based on the 2017 China Migrants Dynamic Survey 2017 (CMDS) and China Municipal Statistical Yearbook after robustness tests and heterogeneity analysis using probit models. Results: (1) digital financial inclusion can effectively alleviate overwork among migrant workers; (2) the impact of digital finance on overwork is more significant for the new generation, digitized industries, and self-employed migrant workers; it is also more significant for the South, East, and small and medium-sized cities than for the North, the Midwest, and large cities; (3) job quality and income are crucial factors in how digital financial inclusion affects overwork among migrant workers. Digital financial inclusion can improve the quality of employment for migrant workers and alleviate overwork. However, the income substitution effect partially reduces the inhibitory impact of digital financial inclusion on overwork. Conclusion: Continuously promote the development of digital inclusive finance, improve laws and regulations, and protect the labor rights and interests of migrant workers. At the same time, vocational training and skills upgrading for rural migrant workers should be strengthened to improve the quality of their employment so that they can leave the secondary labor market and enter the primary labor market.
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Migrantes , Humanos , China , Migrantes/estatística & dados numéricos , Estudos Transversais , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Emprego/estatística & dados numéricos , População Rural/estatística & dados numéricosRESUMO
INTRODUCTION: Anemia is a common comorbidity of chronic kidney disease (CKD) that has been associated with increased risk of complications, healthcare expenditure, and reduced quality of life. In China, the treatment of anemia of CKD has been reported to be suboptimal in part because of a lack of awareness of the condition and its management. It is therefore important to raise awareness of the condition by estimating the future health and economic burden of anemia of CKD and also to understand how it may be addressed through proactive policies. This study aims to project the health and economic burden of anemia of CKD, in China, from 2023 to 2027 and to estimate the impact of a hypothetical intervention on related clinical and cost outcomes. METHODS: A virtual Chinese population was simulated using demographic, clinical, and economic statistics within a validated CKD microsimulation model. Each individual was assigned a CKD stage, anemia stage, comorbidity status (type 2 diabetes, hypertension), complication status (stroke, heart failure, and/or myocardial infarction), and a probability of receiving treatments and therapies. Annual direct healthcare costs were assigned and based on these factors. The hypothetical intervention reduced the prevalence of moderate and severe anemia by 5% annually. This hypothetical scenario was chosen to highlight the impact of implementing policies that could reduce anemia of CKD, and is aligned with the Healthy China 2030 policy, which aims to reduce mortality from noncommunicable diseases by 30%. Interventions could consist of early screening and intervention to reduce the escalation of anemia from mild to moderate or severe. Results were compared with a baseline "no change" scenario which reflects current trends. RESULTS: The number of patients with moderate/severe anemia of CKD was projected to increase from 3.0 to 3.2 million patients, with associated costs increasing from ¥22.0 billion (B) to ¥24.4B between 2023 and 2027, respectively. Compared with the no change scenario, the hypothetical intervention reduced the prevalence of moderate and severe anemia of CKD, saving ¥3.9B in healthcare costs in 2027 (¥24.4B vs ¥20.6B, respectively). CONCLUSIONS: Consistent with trends in CKD burden in China, the prevalence of anemia of CKD is projected to increase, leading to greater related healthcare costs. The introduction of healthcare interventions designed to screen for and treat anemia more effectively could therefore reduce its future burden and related costs.
Anemia, a common issue in chronic kidney disease, can lead to complications and increased healthcare costs. In China, anemia treatment for chronic kidney disease is often suboptimal because of a lack of awareness. This study aimed to estimate the future health and economic impact of anemia in chronic kidney disease in China from 2023 to 2027 and assess the effects of a hypothetical intervention. The research used a computer model to simulate a virtual Chinese population based on demographics, clinical data, and economic statistics. In the "no change" scenario, the prevalence of moderate/severe anemia in chronic kidney disease was projected to increase, with associated healthcare costs rising from ¥22.0B to ¥24.4B. A hypothetical intervention, reducing anemia prevalence by 5% annually, resulted in cost savings, lowering healthcare costs to ¥20.58B in 2027. In conclusion, anemia in chronic kidney disease is expected to increase in China, raising healthcare costs. Implementing interventions, such as early screening and treatment, could significantly reduce future burdens and related costs, emphasizing the need for proactive healthcare policies.
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This study was aimed to investigate the accuracy of anteroposterior chest radiography for tip position verification for the umbilical venous catheters in neonates compared to ultrasound. A search in the PubMed, Embase, the Cochrane Library, and EBSCO was conducted to evaluate all the related articles on umbilical venous catheter (UVC), ultrasound AND neonates updated to August, 2020. Study selection, data extraction, and quality assessment were performed independently by two investigators. Random effects model was used to estimate the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). The summary receiver operator characteristic (SROC) curve was constructed, and the area under the SROC curve (AUC) was calculated. Fourteen related studies were finally included for meta-analysis. The overall diagnostic sensitivity and speciï¬city of X-ray on tip verification of UVC were 0.90 (95% CI 0.71-0.97) and 0.82 (95% CI 0.53-0.95), respectively. The pooled DOR was 3.69 (95% CI 1.64-5.71). The AUC was 0.93 (95% CI 0.90-0.95). The meta-regression analysis suggested that study sample size, study design, different US confirming method, and different gold standard in original design might be potential sources of heterogeneity. Our conclusion is that the commonly used anteroposterior X-ray is not reliable in identifying the exact anatomical location of UVC tip in neonates. Studies suggested ultrasound or echocardiography with saline contrast injection could be the gold standard for verification of catheter location and should be considered whenever possible, especially in premature patients. More studies are needed to expand the use of ultrasound or echocardiography in tip position confirming of UVCs.