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1.
Cell Commun Signal ; 22(1): 3, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38169382

RESUMO

Primary subarachnoid hemorrhage (SAH) is a type of acute stroke, accounting for approximately 10% of cases, with high disability and mortality rate. Early brain injury (EBI) is a critical factor in determining SAH mortality; however, there are no effective treatment interventions for EBI. Based on our results, the transmission of cyclic GMP-AMP (cGAMP) from neurons to microglia is a key molecular event that triggers type I interferon response, amplifies neuroinflammation, and leads to neuronal apoptosis. Abnormal intracytoplasmic mitochondrial DNA (mtDNA) is the initiating factor of the cGAS-cGAMP-STING signaling axis. Overall, the cGAS-cGAMP-STING signaling axis is closely associated with neuroinflammation after subarachnoid hemorrhage. Targeting cGAS triggered by cytoplasmic mtDNA may be useful for comprehensive clinical treatment of patients after SAH. Further studies targeting cGAS-specific antagonists for treating SAH are warranted. Video Abstract.


Assuntos
Interferon Tipo I , Hemorragia Subaracnóidea , Humanos , Microglia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Doenças Neuroinflamatórias , Nucleotidiltransferases/genética , DNA Mitocondrial , Neurônios
2.
Curr Pain Headache Rep ; 28(4): 251-257, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340209

RESUMO

PURPOSE OF REVIEW: Chronic abdominal wall pain is a poorly recognized cause of chronic abdominal pain, and patients frequently go misdiagnosed despite a battery of medical tests. The Carnett's test is a diagnostic tool used to distinguish between abdominal wall pain and visceral pain. This review synthesizes the current literature on the Carnett's test, merges the viewpoints of diverse writers, and evaluates and reports on the Carnett's test's applicability. RECENT FINDINGS: Several clinical investigations have established the usefulness of the Carnett's test in the diagnosis of chronic abdominal wall pain. Furthermore, the Carnett's test is quite useful in determining the depth of the mass and detecting psychogenic abdominal pain. However, its diagnostic use for acute abdominal pain is limited. The Carnett's test is a simple and safe point-of-care diagnostic technique, with several studies supporting its usefulness. Early detection of abdominal wall pain is critical for chronic abdominal wall pain therapy. Carnett's test is very useful in patients with chronic, unexplained local abdominal discomfort who are compliant and do not have a clear rationale for surgery.


Assuntos
Parede Abdominal , Dor Crônica , Dor Visceral , Humanos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/terapia , Músculos Abdominais , Manejo da Dor , Dor Crônica/diagnóstico , Dor Crônica/etiologia
3.
BMC Pulm Med ; 24(1): 323, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965505

RESUMO

BACKGROUND: In the tumor microenvironment (TME), a bidirectional relationship exists between hypoxia and lactate metabolism, with each component exerting a reciprocal influence on the other, forming an inextricable link. The aim of the present investigation was to develop a prognostic model by amalgamating genes associated with hypoxia and lactate metabolism. This model is intended to serve as a tool for predicting patient outcomes, including survival rates, the status of the immune microenvironment, and responsiveness to therapy in patients with lung adenocarcinoma (LUAD). METHODS: Transcriptomic sequencing data and patient clinical information specific to LUAD were obtained from comprehensive repositories of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A compendium of genes implicated in hypoxia and lactate metabolism was assembled from an array of accessible datasets. Univariate and multivariate Cox regression analyses were employed. Additional investigative procedures, including tumor mutational load (TMB), microsatellite instability (MSI), functional enrichment assessments and the ESTIMATE, CIBERSORT, and TIDE algorithms, were used to evaluate drug sensitivity and predict the efficacy of immune-based therapies. RESULTS: A novel prognostic signature comprising five lactate and hypoxia-related genes (LHRGs), PKFP, SLC2A1, BCAN, CDKN3, and ANLN, was established. This model demonstrated that LUAD patients with elevated LHRG-related risk scores exhibited significantly reduced survival rates. Both univariate and multivariate Cox analyses confirmed that the risk score was a robust prognostic indicator of overall survival. Immunophenotyping revealed increased infiltration of memory CD4 + T cells, dendritic cells and NK cells in patients classified within the high-risk category compared to their low-risk counterparts. Higher probability of mutations in lung adenocarcinoma driver genes in high-risk groups, and the MSI was associated with the risk-score. Functional enrichment analyses indicated a predominance of cell cycle-related pathways in the high-risk group, whereas metabolic pathways were more prevalent in the low-risk group. Moreover, drug sensitivity analyses revealed increased sensitivity to a variety of drugs in the high-risk group, especially inhibitors of the PI3K-AKT, EGFR, and ELK pathways. CONCLUSIONS: This prognostic model integrates lactate metabolism and hypoxia parameters, offering predictive insights regarding survival, immune cell infiltration and functionality, as well as therapeutic responsiveness in LUAD patients. This model may facilitate personalized treatment strategies, tailoring interventions to the unique molecular profile of each patient's disease.


Assuntos
Adenocarcinoma de Pulmão , Ácido Láctico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Microambiente Tumoral/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Ácido Láctico/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Idoso , Hipóxia/metabolismo
4.
J Gene Med ; 25(9): e3534, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37259225

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a highly aggressive cancer in advanced stages and has the highest cancer-related death across the world. Anoikis has emerged as a specific form of apoptotic cell death that may play a vital role in the formation and development of tumors. METHODS: Based on The Cancer Genome Atlas dataset, we developed a novel anoikis-related genes (ARGs) signature in LUAD and evaluated the differences between low and high-risk groups in clinical characteristics, expression patterns, immune cell infiltration, and drug sensitivity, etc. According to multivariate Cox regression analysis, the risk score was identified as a significant independent prognostic factor. The possible biological pathways of ARGs' were assessed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The immune infiltration landscape and risk score of ARGs were analyzed by ESTIMATE and CIBERSORT analysis. A nomogram grounded on six key ARGs and clinicopathological features was provided. Moreover, experiment validation of the expression patterns of six hub ARGs in lung cancer cell lines was conducted. RESULTS: We identified 53 survival-related LUAD anoikis-related differentially expressed genes and finally six hub anoikis genes (LDHA, SLC2A1, SERPINB5, ITGB4, BRCA2, and PIK3R1) were selected to construct an ARG model. The risk model could efficiently cluster the patients into low- and high-risk groups which could accurately predict clinical outcomes for LUAD patients. There is evidence that the prognostic risk score is a remarkable prognostic factor in determining overall survival. Different immune statuses and drug sensitivity between low- and high-risk groups were explored according to functional analysis. On the basis of risk scores and LUAD clinicopathological features, a novel nomogram was developed. Ultimately, all six key genes except for PIK3R1 were proved to be upregulated in LUAD tissues and cell lines by bioinformatics analysis and experimental validation. CONCLUSIONS: The result of the present study suggest that ARGs could be carcinogenic to LUAD and could be used as an effective stratification factor to customize therapies and forecast the survival rate in LUAD patients.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , Anoikis/genética , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição
5.
BMC Neurol ; 23(1): 269, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37454067

RESUMO

OBJECTIVE: To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR). METHODS: We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10-8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10-5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls. RESULTS: On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00-6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10-2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01-1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17-0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04-3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13-0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44-124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25-21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32-18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds. CONCLUSION: This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.


Assuntos
Microbioma Gastrointestinal , Aneurisma Intracraniano , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Aneurisma Intracraniano/genética , Análise da Randomização Mendeliana , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética
6.
Digestion ; 104(3): 222-232, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36646064

RESUMO

INTRODUCTION: MIR155HG has been found to play an important role in malignant tumors, but little research has been done on its association with esophageal cancer (ESCC). The aim of this study was to investigate the relationship between MIR155HG polymorphisms and ESCC susceptibility in the Chinese Han population. METHODS: 511 ESCC patients and 487 healthy controls were selected for this study. All subjects were genotyped using the Agena MassARRAY platform. We assessed the association between seven single nucleotide polymorphisms (SNPs) of the MIR155HG and ESCC risk by genetic model analysis. The false discovery rate (FDR) test and Bonferroni correction were usually used to detect false positives for the results. Meanwhile, the interaction between SNPs was analyzed by multifactor dimensionality reduction software to predict the ESCC risk. RESULTS: The C allele of rs4143370 and the A allele of rs34904192 in MIR155HG can increase the risk of ESCC (odds ratio (OR) = 1.33, p = 0.024; OR = 1.30, p = 0.013). Furthermore, rs4143370 and rs34904192 were associated with an increased risk of ESCC. Stratified analysis showed that MIR155HG SNPs (rs4143370 and rs34904192) significantly increased ESCC risk in males. MIR155HG SNPs (rs4143370, rs34904192, and rs928883) were also strongly associated with an increased risk of ESCC in people aged >64 years. In addition, haplotype analysis of the seven SNPs of the MIR155HG showed that the CC haplotype was associated with ESCC risk (OR = 1.34, p = 0.024). CONCLUSION: This study revealed that MIR155HG SNPs were associated with an increased risk of ESCC. The results provided clues for clarifying the role of MIR155HG in ESCC.


Assuntos
Neoplasias Esofágicas , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , População do Leste Asiático , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Genótipo , Fatores de Risco
7.
Sensors (Basel) ; 23(2)2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36679422

RESUMO

k nearest neighbours (kNN) queries are fundamental in many applications, ranging from data mining, recommendation system and Internet of Things, to Industry 4.0 framework applications. In mining, specifically, it can be used for the classification of human activities, iterative closest point registration and pattern recognition and has also been helpful for intrusion detection systems and fault detection. Due to the importance of kNN queries, many algorithms have been proposed in the literature, for both static and dynamic data. In this paper, we focus on exact kNN queries and present a comprehensive survey of exact kNN queries. In particular, we study two fundamental types of exact kNN queries: the kNN Search queries and the kNN Join queries. Our survey focuses on exact approaches over high-dimensional data space, which covers 20 kNN Search methods and 9 kNN Join methods. To the best of our knowledge, this is the first work of a comprehensive survey of exact kNN queries over high-dimensional datasets. We specifically categorise the algorithms based on indexing strategies, data and space partitioning strategies, clustering techniques and the computing paradigm. We provide useful insights for the evolution of approaches based on the various categorisation factors, as well as the possibility of further expansion. Lastly, we discuss some open challenges and future research directions.


Assuntos
Algoritmos , Mineração de Dados , Humanos , Análise por Conglomerados , Resolução de Problemas
8.
Psychooncology ; 31(7): 1186-1195, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35194880

RESUMO

OBJECTIVE: This study examined the relationship between a broad variety of stressors, resources, and outcomes to identify targets of intervention to enhance the quality of life of cancer patients and contribute to a comprehensive model of cancer care. METHODS: Five hundred and sixty persons with a diagnosis of cancer completed measures of stressors (past negative life events, current problems, current symptoms, comorbidities), resources (coping self-efficacy, social support, satisfaction with care) and outcomes (emotional and functional well-being). RESULTS: Multivariate canonical correlations between pairs of canonical variates (stressors-outcomes, Rc  = 0.56; stressors-resources, Rc  = 0.42, resources-outcomes Rc  = 0.66) were significant (all ps < 0.0001), which confirmed the relationship between those components and supported proceeding to more granular levels of analysis. More refined analyses revealed that the most critical variables in relation to outcomes (i.e., emotional and functional well-being), were current problems and symptoms among the stressors and coping self-efficacy, social support and patient satisfaction among the resources. CONCLUSIONS: This study provided an approach to the discernment of the most critical aspects of interventions that may improve supportive care and quality of life outcomes. Thus, efforts to address current problems (e.g., financial, home life, work), as well as effective management of symptoms (e.g., pain, fatigue, sleep), using the coordinated integration of medical care, support services and psycho-social interventions would provide the greatest impact on quality-of-life outcomes. Interventions that focus on problem solving and reinforce patient agency and activation may be most effective in sustaining quality of life outcomes into survivorship.


Assuntos
Neoplasias , Qualidade de Vida , Adaptação Psicológica , Humanos , Análise Multivariada , Neoplasias/psicologia , Neoplasias/terapia , Qualidade de Vida/psicologia , Apoio Social
9.
Multivariate Behav Res ; 57(6): 895-915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33999744

RESUMO

There is an increasing need to analyze multivariate time series data due to the rapid development of data collection tools such as smartphone APPs, wearable sensors, and brain imaging techniques. P-technique factor analysis allows researchers to establish a measurement model for these time series. Analyzing such data is challenging because they are often non-normal (e.g., steps, heart rate, sleep, mood, and brain signals) and correlated at nearby time points. We propose using a bootstrap procedure to accommodate both the non-normality and the dependency of nearby time points. We explore the statistical properties with simulated data and illustrate the test with two empirical data sets. The results of the simulation study include (1) the bootstrap procedure performed better than an existing analytic procedure for time series data with excessive kurtosis (2) an existing analytic procedure performed better than the bootstrap procedure for normal time series and skewed time series.


Assuntos
Projetos de Pesquisa , Fatores de Tempo , Análise Fatorial , Simulação por Computador , Coleta de Dados/métodos
10.
BMC Cancer ; 21(1): 453, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892661

RESUMO

BACKGROUND: Long non-coding RNA (lncRNA) was a vital factor in the progression and initiation of human cancers. This study found a new lncRNA, FGD5-AS1, which can inhibit EMT process, proliferation, and metastasis in vitro and in vivo. METHODS: qRT-PCR was employed to test the expression of lncFGD5-AS1 in 30 gastric cancer patients' cancer tissue and para-cancer tissue. Overexpressed lncFGD5-AS1 cells shown sharply decrease of proliferation, migration, and epithelial-mesenchymal transition (EMT). miR-196a-5p/SMAD6 was confirmed as downstream molecular mechanism of lncFGD5-AS1 by expression correlation analysis and mechanism experiments. In vivo study illustrated overexpression of lncFGD5-AS1 suppression tumor growth. RESULTS: LncFGD5-AS1 served as a ceRNA of miR-196a-5p to release its inhibition on SMAD6, a conventional inhibitor on the BMP pathway. Comparing with normal gastric cancer cells, FGD5-AS1 overexpressed group had fewer migration cells, lower cell viability, and lower EMT transformation rate. Meanwhile, xenografts nude mice injecting with overexpressed-FGD5-AS1 cells also shown smaller tumor weight and volume. CONCLUSION: In conclusion, this research supported the first evidence that FGD5-AS1 suppressed proliferation and metastasis in gastric cancer by regulating miR-196a-5p/SMAD6/BMP axis and suggested a potential therapeutic candidate for gastric cancer.


Assuntos
Transição Epitelial-Mesenquimal , Fatores de Troca do Nucleotídeo Guanina/metabolismo , MicroRNAs/metabolismo , Proteína Smad6/metabolismo , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Animais , Receptores de Proteínas Morfogenéticas Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Feminino , Mucosa Gástrica/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , RNA Longo não Codificante/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Carga Tumoral , Ensaio Tumoral de Célula-Tronco
11.
BMC Gastroenterol ; 21(1): 452, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861854

RESUMO

BACKGROUND: The incidence of congenital bronchoesophageal fistulas in adults is rare. Most fistulas discovered in adulthood are often small and can be repaired with a simple one-step method. CASE PRESENTATION: A 46-year-old female patient complained of a 2-month history of chocking, coughing, and a 12 kg drop in weight. The bronchofiberscopy and gastroscopy showed a large fistula, which extended from the esophagus to the main bronchus on both sides, thus forming a special three-way channel which has never been reported. This case was challenging both to the anesthetists and surgeons. The patient was intubated with a sengstaken-blakemore tube, and then received segmental esophageal resection, anastomotic reconstruction, and double-flap repair with esophagus segment in situ. CONCLUSION: When the fistula in BEF is large or complicated, appropriate surgical methods should be meticulously designed according to the condition of the patient. The problem of anesthesia intubation should be solved first, to allow a smooth operation. Secondly, a double-layer repair of the airway fistula by using esophageal wall tissues as patch materials is proposed.


Assuntos
Fístula Brônquica , Fístula Esofágica , Adulto , Anastomose Cirúrgica , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Tosse , Fístula Esofágica/etiologia , Fístula Esofágica/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade
12.
Genomics ; 112(5): 3465-3472, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32464168

RESUMO

PURPOSE: Lung cancer (LC) is one of the fastest-growing malignant tumors in the world in terms of morbidity and mortality. CYP3A4 plays a crucial role in the occurrence of LC. Little is known about the contribution of CYP3A4 polymorphisms for non-small cell lung cancer (NSCLC) risk. This study aimed to explore the correlation of CYP3A4 genetic variants (rs3735451, rs4646440, rs35564277, and rs4646437) with NSCLC risk. METHODS: Four single nucleotide polymorphisms (SNPs) were genotyped by Agena MassARRAY in this case-control study (507 NSCLC patients and 505 controls) among a Shaanxi Han population. Hardy-Weinberg equilibrium (HWE) of each SNP in controls was evaluated by exact test. The association of CYP3A4 polymorphisms with NSCLC risk was explored by calculating odds ratios (OR) and 95% confidence intervals (CI) using logistic regression analysis with adjustment for age and gender. RESULTS: Our research revealed that rs4646440 was significantly associated with an increased risk of NSCLC (OR 2.64, p = .005), while rs4646437 played a protective role in NSCLC risk (OR 0.48, p = 4.00 × 10-7). Stratified analyses indicated that rs4646440 significantly enhanced the susceptibility of NSCLC in BMI > 24 kg/m2, non-smokers and non-drinkers (OR 14.29, p = .012; OR 1.56, p = .023; OR 1.67, p = .031, respectively). Besides, we observed that rs3735451 exhibited an increased risk of NSCLC in BMI > 24 kg/m2 (OR 2.47, p = .030), whereas rs4646437 had a reduced risk of NSCLC in BMI ≤ 24 kg/m2 (OR 0.47, p = 5.17 × 10-5). We also found that rs35564277 was considered as a protective factor of NSCLC in non-smokers (OR 0.50, p = .032). CONCLUSION: Our study indicated that CYP3A4 genetic variants were associated with NSCLC susceptibility in a Shaanxi Han population.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Citocromo P-450 CYP3A/genética , Neoplasias Pulmonares/genética , Adenocarcinoma/genética , Povo Asiático/genética , Carcinoma Pulmonar de Células não Pequenas/etnologia , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , China/etnologia , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/etnologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
13.
Multivariate Behav Res ; 56(1): 41-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32000534

RESUMO

P-technique factor analysis is an exploratory factor model for multivariate time series data. Assessing model fit of P-technique factor models is non-trivial because time series data are correlated at nearby time points. We present a test statistic that is appropriate for P-technique factor analysis. In addition, the test statistic allows researchers to quantify the amount of model error. We explore the statistical properties of the test statistic with simulated data and we illustrate its use with an empirical study of personality states. Results of the simulation study include (1) the empirical distributions of the test statistic approximately followed their respective theoretical chi-square distributions, (2) the empirical Type I error rates of the test of perfect fit are close to the nominal level and the empirical Type I error rates of the test of close fit are slightly lower than the nominal level, and (3) the empirical power rates of the test of perfect fit are satisfactory but the empirical power rates of the test of close fit are only satisfactory for small models.


Assuntos
Modelos Estatísticos , Distribuição de Qui-Quadrado , Simulação por Computador , Análise Fatorial
14.
Cancer Control ; 27(1): 1073274820978817, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33345608

RESUMO

INTRODUCTION: The mechanistic basis for the development of esophageal squamous cell carcinoma (ESCC) remains poorly understood. The goal of the present study was thus to characterize mRNA and long noncoding RNA (lncRNA) expression profiles associated with ESCC in order to identify key hub genes associated with the pathogenesis of this cancer. MATERIALS AND METHODS: The GSE26866 and GSE45670 datasets from the Gene Expression Omnibus (GEO) database were used to conduct a weighted gene co-expression network analysis (WGCNA), after which Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Cytoscape was additionally used to construct lncRNA-mRNA networks, after which hub genes were identified and validated through the assessment of TCGA datasets and clinical samples. RESULTS: Two gene modules were found to be closely linked to ESCC tumorigenesis. These genes were enriched in cell cycle, MAPK signaling, JAK-STAT signaling, pyrimidine metabolism, arachidonic acid metabolism, and P53 signaling pathway activity, all of which are directly linked with the development of cancer. In total, we identified and validated 9 hub genes associated with ESCC (DDX18, DNMT1, NCAPG, WDHD1, PRR11, VOPP1, ZKSCAN5, LC35C2, and PHACTR2). CONCLUSION: In summary, we identified key gene modules and hub genes associated with ESCC development, and we constructed a lncRNA-mRNA network pertaining to this cancer type. These results provide a foundation for future research regarding the mechanistic basis of ESCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Redes Reguladoras de Genes , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Conjuntos de Dados como Assunto , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Mapas de Interação de Proteínas/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais/genética
15.
Future Oncol ; 15(2): 167-180, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30088776

RESUMO

AIM: We aimed to investigate risk factors and current treatment effects in male breast cancer patients. METHODS: Kaplan-Meier plot, log-rank test, COX model, nomograms and propensity score matching were used. RESULTS: Among stage I-III patients, surgery was associated with better prognosis. In subgroup analysis, performing surgery and no radiation or chemotherapy led to worse prognosis in research group. Among stage IV patients, chemotherapy correlated with better prognosis and radiation led to better breast cancer-specific survival. In addition, brain and liver metastasis correlated with worse prognosis; and lung correlated with worse breast cancer-specific survival. CONCLUSION: For stage I-III patients, surgery and chemotherapy were recommended. And not applying radiation or chemotherapy could be carefully considered for ER(+) HER-2(-) patients. For stage IV patients, chemotherapy and radiation were commended.


Assuntos
Neoplasias da Mama Masculina/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/mortalidade , Nomogramas , Seleção de Pacientes , Mama/patologia , Mama/cirurgia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/terapia , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Quimiorradioterapia/métodos , Seguimentos , Humanos , Masculino , Mastectomia/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Cuidados Paliativos/métodos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Análise de Sobrevida , Resultado do Tratamento
16.
Multivariate Behav Res ; 53(2): 219-230, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29323535

RESUMO

Process factor analysis (PFA) is a latent variable model for intensive longitudinal data. It combines P-technique factor analysis and time series analysis. The goodness-of-fit test in PFA is currently unavailable. In the paper, we propose a parametric bootstrap method for assessing model fit in PFA. We illustrate the test with an empirical data set in which 22 participants rated their effects everyday over a period of 90 days. We also explore Type I error and power of the parametric bootstrap test with simulated data.


Assuntos
Simulação por Computador , Análise Fatorial , Modelos Estatísticos , Humanos , Estudos Longitudinais
17.
Multivariate Behav Res ; 52(6): 720-731, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28952786

RESUMO

In exploratory factor analysis, factor rotation is conducted to improve model interpretability. A promising and increasingly popular factor rotation method is geomin rotation. Geomin rotation, however, frequently encounters multiple local solutions. We report a simulation study that explores the frequency of local solutions in geomin rotation and the implications of such phenomena. The findings include: (1) multiple local solutions exist for geomin rotation in a variety of situations; (2) ϵ = .01 provides satisfactory rotated factor loadings in most situations; (3) 100 random starts appear sufficient to examine the multiple solution phenomenon; and (4) a population global solution may correspond to a sample local solution rather than the sample global solution.


Assuntos
Análise Fatorial , Simulação por Computador
18.
J Urol ; 195(6): 1903-10, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26694905

RESUMO

PURPOSE: Attenuated mycobacterium bacillus Calmette-Guérin is widely used as intravesical immunotherapy of nonmuscle invasive urothelial carcinoma. Currently there are limited data on the relationship between bacillus Calmette-Guérin dose intensity and tumor response. We evaluated the dose-response relationship of bacillus Calmette-Guérin to nonmuscle invasive bladder cancer in vitro using urothelial carcinoma cell lines and in vivo using an orthotopic mouse model. MATERIALS AND METHODS: Two human urothelial carcinoma cell lines were used to study the effect of bacillus Calmette-Guérin dose on the tumor cell response. Internalization, activation of signaling pathways, gene transactivation, cell viability, lactate dehydrogenase and HMGB1 release were study end points. An orthotopic tumor model was used to compare the effect of different doses on the antitumor efficacy of bacillus Calmette-Guérin. RESULTS: Bacillus Calmette-Guérin internalization by urothelial carcinoma cells increased as a function of time and dose with a plateau at higher doses and/or long exposure times. Intracellular signaling demonstrated a similar direct, dose dependent increase. Cytokine expression by urothelial carcinoma cells as a function of dose was variable. Some genes increased progressively but others showed a decrease at the highest dose. While nonviable cell number increased in proportion to dose, the number of cells undergoing necrotic cell death decreased at higher doses. A higher dose of bacillus Calmette-Guérin (1:200) showed a better antitumor effect than a standard dose (1:50) (p <0.01). CONCLUSIONS: Bacillus Calmette-Guérin dose has a direct impact on urothelial carcinoma cell biology. Increased dose intensity, particularly in nonresponders, may represent a strategy to increase bacillus Calmette-Guérin treatment efficacy.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vacina BCG/administração & dosagem , Carcinoma de Células de Transição/terapia , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Animais , Vacina BCG/uso terapêutico , Linhagem Celular Tumoral , Relação Dose-Resposta Imunológica , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Resultado do Tratamento
20.
Tumour Biol ; 36(3): 2163-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25398693

RESUMO

Partner of sld five 1 (PSF1) is a member of the heterotetrameric complex termed GINS. Previous studies have shown that PSF1 is unregulated in several cancer and associated with tumor malignant characters. However, the effects of PSF1 in lung cancer are still unclear. The goal of this study was to investigate the effects of PSF1 on the proliferation capacities of lung cancer. To start with, expression of PSF1 in 22 human lung cancer samples and adjacent non-tumor samples were detected by real-time RT-PCR and Western blotting. Our results showed that PSF1 was overexpressed in lung cancer samples compared to adjacent non-tumor samples. To achieve better insights of PSF1 functions in lung cancer cells, we used PSF1-specific small interfering RNA (siRNA) successfully inhibit the expression of PSF1 in messenger RNA (mRNA) and protein levels. In addition, we used lung cancer cell lines with different p53 gene background (p53 null and p53 wild-type). The results showed that knockdown of PSF1 inhibited cell proliferation and caused cell cycle arrest of lung cancer cells in a p53-independent manner. Our data indicated that PSF1 is functionally involved in lung cancer cell proliferation and is a potential target for lung cancer therapy.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Membro 2 da Subfamília B de Transportadores de Cassetes de Ligação de ATP , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Humanos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Proteína Supressora de Tumor p53/genética
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