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1.
Gastric Cancer ; 27(4): 735-746, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38584223

RESUMEN

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 case‒control 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.


Asunto(s)
5-Metilcitosina , Biomarcadores de Tumor , Ácidos Nucleicos Libres de Células , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , 5-Metilcitosina/análogos & derivados , Biomarcadores de Tumor/genética , Masculino , Estudios de Casos y Controles , Femenino , Persona de Mediana Edad , Ácidos Nucleicos Libres de Células/genética , Anciano , Detección Precoz del Cáncer/métodos , Metilación de ADN
2.
Opt Express ; 31(5): 8650-8667, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36859976

RESUMEN

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 9.1-25.1 GHz, suitable for THz-microwave bi-stealth. Metadevice 2 is for IR and microwave bi-stealth, with measured absorptivity higher than 90% in 9.7-27.3 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.

3.
BMC Cancer ; 22(1): 155, 2022 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-35135494

RESUMEN

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.


Asunto(s)
Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Adulto Joven
4.
J Clin Densitom ; 25(2): 141-149, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34716086

RESUMEN

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 (ß = -0.044; p = 0.007) and total hip BMD (ß = -0.045; p = 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, ß = -0.014 and p = 0.033 for femoral neck BMD; ß = -0.016 and p = 0.047 for total hip BMD). Higher FlOP levels were associated with lower BMD among male veterans.


Asunto(s)
Densidad Ósea , Veteranos , Absorciometría de Fotón , Estudios Transversales , Femenino , Cuello Femoral , Humanos , Masculino , Persona de Mediana Edad
5.
Am J Respir Crit Care Med ; 199(10): 1257-1266, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-30422669

RESUMEN

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.


Asunto(s)
Autoanticuerpos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Detección Precoz del Cáncer/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/inmunología , Nódulos Pulmonares Múltiples/inmunología , Anciano , Biomarcadores de Tumor/inmunología , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Neoplasias Pulmonares/fisiopatología , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X
6.
Eur Radiol ; 29(11): 6100-6108, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31115618

RESUMEN

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.


Asunto(s)
Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmón/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico , Semántica , Tomografía Computarizada por Rayos X/métodos , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas
7.
J Comput Assist Tomogr ; 43(5): 775-779, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31356517

RESUMEN

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.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Placenta Accreta/diagnóstico por imagen , Aborto Inducido/efectos adversos , Adulto , Cesárea/efectos adversos , Femenino , Humanos , Placenta Accreta/etiología , Placenta Accreta/patología , Placenta Previa , Valor Predictivo de las Pruebas , Embarazo , Estudios Retrospectivos , Factores de Riesgo
8.
Gut ; 67(3): 473-484, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-27821646

RESUMEN

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 <3 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.


Asunto(s)
Adenoma/sangre , Adenoma/diagnóstico , Biomarcadores de Tumor/sangre , Neoplasias del Colon/sangre , Neoplasias del Colon/diagnóstico , Detección Precoz del Cáncer/métodos , Proteínas Adaptadoras Transductoras de Señales/sangre , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenoma/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Antígeno CA-19-9/metabolismo , Estudios de Casos y Controles , Neoplasias del Colon/metabolismo , Receptor gp130 de Citocinas/sangre , Receptor gp130 de Citocinas/metabolismo , Receptores ErbB/sangre , Receptores ErbB/metabolismo , Femenino , Humanos , Receptores de Hialuranos/sangre , Receptores de Hialuranos/metabolismo , Antígeno Lewis X/metabolismo , Masculino , Persona de Mediana Edad , Oligosacáridos/metabolismo , Análisis por Matrices de Proteínas , Factor de von Willebrand/metabolismo
9.
Appl Opt ; 57(10): 2352-2360, 2018 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-29714215

RESUMEN

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.

10.
J Proteome Res ; 16(1): 274-287, 2017 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-27769113

RESUMEN

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.


Asunto(s)
Autoinmunidad/genética , Citocinas/genética , Obesidad/genética , Posmenopausia/genética , Proteoma/genética , Anciano , Autoanticuerpos/biosíntesis , Enfermedades Transmisibles/genética , Enfermedades Transmisibles/inmunología , Enfermedades Transmisibles/patología , Citocinas/inmunología , Femenino , Redes Reguladoras de Genes/inmunología , Humanos , Inflamación , Redes y Vías Metabólicas/genética , Redes y Vías Metabólicas/inmunología , Persona de Mediana Edad , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Obesidad/inmunología , Obesidad/patología , Posmenopausia/inmunología , Estudios Prospectivos , Proteoma/inmunología , Proteómica
11.
Cancer ; 123(17): 3291-3304, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28463396

RESUMEN

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.


Asunto(s)
Receptor de Muerte Celular Programada 1/genética , Sarcoma/genética , Sarcoma/mortalidad , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/mortalidad , Linfocitos T/citología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biopsia con Aguja , Células Clonales , Análisis por Conglomerados , Estudios de Cohortes , Terapia Combinada , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Sarcoma/patología , Sarcoma/terapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/terapia , Análisis de Supervivencia , Linfocitos T/inmunología , Adulto Joven
12.
Nat Methods ; 11(2): 149-55, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24317253

RESUMEN

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.


Asunto(s)
Bioensayo/normas , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Proteoma/análisis , Proteómica , Espectrometría de Masas en Tándem/métodos , Biomarcadores de Tumor/genética , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/mortalidad , Cromatografía Líquida de Alta Presión , Electroforesis en Gel Bidimensional , Estudios de Factibilidad , Femenino , Humanos , Proyectos Piloto , Tasa de Supervivencia , Células Tumorales Cultivadas
13.
Mol Cell Proteomics ; 13(12): 3484-96, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25225358

RESUMEN

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 ∼2500 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.


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Pancreatitis Crónica/genética , Proteínas Serina-Treonina Quinasas/genética , Animales , Anticuerpos/química , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Ceruletida , Diagnóstico Diferencial , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Diagnóstico Precoz , Perfilación de la Expresión Génica , Humanos , Ratones , Anotación de Secuencia Molecular , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Pancreatitis Crónica/inducido químicamente , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/metabolismo , Análisis por Matrices de Proteínas , Proteínas Serina-Treonina Quinasas/metabolismo , Proteoma/genética , Proteoma/metabolismo , Transducción de Señal , Factores de Tiempo
14.
PLoS Genet ; 9(1): e1003169, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23341773

RESUMEN

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.


Asunto(s)
Carcinoma de Células Escamosas , Ganglios Linfáticos , Metástasis Linfática , Neoplasias de la Boca , Pronóstico , Anciano , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Genómica , Humanos , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Estadificación de Neoplasias , Polimorfismo de Nucleótido Simple , ARN Interferente Pequeño/genética
15.
Breast Cancer Res Treat ; 153(2): 445-54, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26319120

RESUMEN

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.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Carcinoma Ductal de Mama/sangre , Estudios de Casos y Controles , Biología Computacional/métodos , Detección Precoz del Cáncer , Femenino , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Proteoma , Proteómica/métodos , Curva ROC , Factores de Riesgo
16.
Nano Lett ; 14(6): 3014-22, 2014 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-24837617

RESUMEN

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.


Asunto(s)
Óxido de Aluminio/química , Nanocables/química , Óxido Nítrico/análisis , Semiconductores , Compuestos de Estaño/química , Nanocables/ultraestructura
17.
Nat Commun ; 15(1): 5783, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38987267

RESUMEN

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.

18.
Front Public Health ; 12: 1357481, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903568

RESUMEN

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.


Asunto(s)
Migrantes , Humanos , China , Migrantes/estadística & datos numéricos , Estudios Transversales , Adulto , Masculino , Femenino , Persona de Mediana Edad , Encuestas y Cuestionarios , Empleo/estadística & datos numéricos , Población Rural/estadística & datos numéricos
19.
Adv Ther ; 41(10): 3905-3921, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39162981

RESUMEN

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.


Asunto(s)
Anemia , Insuficiencia Renal Crónica , Humanos , Anemia/epidemiología , China/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Costos de la Atención en Salud/estadística & datos numéricos , Costo de Enfermedad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Prevalencia , Comorbilidad , Simulación por Computador , Calidad de Vida , Adulto , Pueblos del Este de Asia
20.
J Vasc Access ; 24(5): 1051-1060, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34784827

RESUMEN

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 specificity 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.


Asunto(s)
Ecocardiografía , Dispositivos de Acceso Vascular , Recién Nacido , Humanos , Ultrasonografía , Radiografía , Catéteres
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