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A total of 69 patients were enrolled in the study, including 23 patients with hypertrophic cardiomyopathy (HCM), 26 patients with Left Ventricle (LV) enlargement comprising 16 dilated cardiomyopathy (DCM) patients and 10 ischemic cardiomyopathy (ICM) patients, and 20 control subjects. All patients underwent 2DE, contrast-enhanced 2DE (Contrast-2DE), 3DE, Contrast-3DE, and single photon emission computed tomography (SPECT) examinations. The 2DE-AL and 3DE methods measured the left ventricular mass (LVM). The results were compared with those measured by SPECT. The measured LVM of the 69 patients was systematically overestimated by 2DE-AL (177.4 ± 56.2 g), Contrast-2DE-AL (174.5 ± 55.5 g), 3DE (167.3 ± 59.2 g), and Contrast-3DE (154.2 ± 46.7 g) when compared with SPECT (148.5 ± 52.4 g) (P < 0.05), while Contrast-3DE provided the best agreement with SPECT in LVM measurement (r = 0.898, P < 0.001) and had the smallest deviation (5.7 ± 23.1 g). 3DE overestimated LVM more compared to Contrast-3DE in LV hypertrophy group (165.5 ± 37.9 g versus 153.5 ± 27.6 g, P = 0.003) and LV enlargement group (204.5 ± 69.3 g versus 183.5 ± 53.5 g, P = 0.006). For 2DE methods, there was no significant difference between the LVM obtained with or without contrast enhancement in control group (132.3 ± 23.6 g versus 128.4 ± 23.3 g), LV hypertrophy group (177.7 ± 38.6 versus 178.3 ± 30.9 g, P = 0.889), and LV enlargement group (211.9 ± 63.2 g versus 206.5 ± 66.0 g, P = 0.386). The difference between LVM measured by 2DE-AL and SPECT was the greatest (27.9 ± 34.0 g), especially in LV hypertrophy group and LV enlargement group (LV hypertrophy group 39.7 ± 26.0 g; LV enlargement group 24.2 ± 42.8 g). To conclude, Contrast-3DE and SPECT show greater consistency in LVM measurement, especially in cardiomyopathy, when compared with 2DE. Administering contrast can effectively reduce the overestimation of LVM by non-contrast DE.
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Ecocardiografia Tridimensional , Disfunção Ventricular Esquerda , Humanos , Ecocardiografia Tridimensional/métodos , Coração , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
Long non-coding RNAs (lncRNAs) are proved to perform critical function in regulating cancer cell behavior. It is reported that LINC00324 promotes lung adenocarcinoma development by regulating miR-615-5p/AKT1 axis. This study aimed to demonstrate whether LINC00324 participates in non-small cell lung cancer (NSCLC) pathogenesis through other molecular mechanism. Relative mRNA, lncRNA, and microRNA levels were analyzed using quantitative real-time-polymerase chain reaction (qRT-PCR). Western blot was used to detect protein level. MTT assay shown proliferation ability and transwell assay shown invasive ability. Luciferase reporter assay illustrated the interaction between RNA molecules. In NSCLC, the high expression of LINC00324 had correlation with the poor prognosis. LINC00324 promoted the proliferation and invasion of NSCLC cells while miR-139-5p inhibited these behaviors. LINC00324 overexpression promoted insulin-like growth factor 1 receptor (IGF1R) expression via absorbing miR-139-5p. The tumor-promoting effects of LINC00324 were attenuated through miR-139-5p overexpression. Highly expressed LINC00324 in NSCLC through sponged miR-139-5p to elevate IGF1R expression and promoted cell proliferation and invasion. This research demonstrated that LINC00324 is a potential NSCLC diagnosis and therapy target.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Receptor IGF Tipo 1/biossíntese , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Receptor IGF Tipo 1/genéticaRESUMO
OBJECTIVES: Lung ultrasound detection of B-lines has become a simple, semiquantitative, noninvasive tool for evaluating pulmonary congestion in heart failure (HF) patients. This study compared the correlation of B-lines with E/e', NT-proBNP, and ejection fraction (EF) in acute decompensated heart failure (ADHF). METHODS: Eighty-two consecutive patients who were diagnosed with acute decompensated HF were divided into two groups: preserved ejection fraction heart failure (HFpEF, EF≥50%, n=32) and reduced ejection fraction heart failure (HFrEF, EF<50%, n=50). Spearman's correlation was used to evaluate associations of B-lines with E/e', NT-proBNP, and EF in the two groups. Receiver operating characteristic (ROC) analysis was performed to compare B-lines with the E/e' ratio. RESULTS: Results revealed no significant differences were observed in the B-lines between the HFpEF and HFrEF groups. However, compared with the control group, B-lines were significantly increased in the HFpEF and HFrEF groups (P<.05). The B-lines were positively correlated with E/e' (r=0.742, r=0.52) and NT-proBNP (r=0.678, r=0.417) but were negatively correlated with EF (r=-0.365, r=-0.337), and the correlation coefficients were higher in the HFpEF group than in the HFrEF group. In ROC analyses, considering E/e' ≥14 as a reference, B-lines yielded a C-statistic value of 0.94 (sensitivity 92%, specificity 83%) in the HFpEF group and 0.84 (sensitivity 86%, specificity 78%) in the HFrEF group. CONCLUSIONS: B-lines were significantly correlated with the more established parameters of ADHF. The correlation between B-lines and E/e' was better, especially in the HFpEF group.
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Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Ultrassonografia/métodos , Doença Aguda , Idoso , Feminino , Humanos , Pulmão , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To compare three-dimensional (3D) and two-dimensional (2D) speckle tracking echocardiography (STE) techniques in the assessment of left ventricular function and myocardial infarct size (MIS). METHODS: Thirty-two patients diagnosed with ST elevation myocardial infarction and 18 healthy control patients underwent 2D echocardiography, 3D echocardiography, and single photon emission computed tomography (SPECT). 3D left ventricular global area strain (GAS), 2D and 3D global longitudinal strain (GLS), global radial strain (GRS) as well as global circumferential strain (GCS) were analyzed to correlate with myocardial infarct size detected by SPECT. 2D and 3D left ventricular ejection fraction (LVEF) as well as 2D and 3D wall motion score index (WMSI) also were measured using conventional echocardiography. RESULTS: The 2D-GLS values were significantly higher than that of 3D-GLS, while 2D-GCS and GRS were significantly lower than 3D-GCS and GRS, respectively. However, no significant differences in LVEF and WMSI could be observed between 2D and 3D echocardiography. Myocardial strain indices, LVEF, and WMSI using 2D and 3D echocardiography also had good correlations with MIS as measured by SPECT. ROC curve analysis showed that the 3D and 2D myocardial indices, LVEF, and WMSI could distinguish between small and large MIS, while 2D-GLS had the highest AUC. CONCLUSION: The 2D and 3D myocardial strain indices correlated well with MIS by SPECT. Among them, the 2D-GLS showed the highest diagnostic value, while 3D-GRS and GCS had better diagnostic value than 2D-GRS and GCS.
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Ecocardiografia/métodos , Infarto do Miocárdio/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ecocardiografia Tridimensional , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Tecnécio Tc 99m Sestamibi , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVE: To analyze the potential association between valvular strands and migraine with aura. METHODS: During a 1-year period,transesophageal echocardiography was performed in 51 consecutive patients with migraine with aura and 75 control subjects who underwent transesophageal echocardiography for other purposes and had no history of migraine. The presence of aortic and mitral valve strands was evaluated. RESULTS: The incidence of valvular strands was 21.5% (11/51) in migraine patients and 28.0% (21/75) in control subjects (Χ²=0.663, P=0.416). The incidence of patent foramen ovale was significantly higher in patients with migraine with aura than in control subjects (50.9% vs.29.3%) (Χ²=6.302, P=0.012). The incidence of aortic valve strands was significantly higher than that of mitral valve strands in migraine patients (Χ²=4.320,P=0.038). CONCLUSION: Valvular strands are not associated with migraine with aura and show little clinical significance.
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Enxaqueca com Aura , Enxaqueca sem Aura , Aorta , Ecocardiografia Transesofagiana , Forame Oval Patente , Humanos , Incidência , Valva MitralRESUMO
Exploring novel diagnostic and therapeutic biomarkers is extremely important for osteosarcoma. YME1 Like 1 ATPase (YME1L), locating in the mitochondrial inner membrane, is key in regulating mitochondrial plasticity and metabolic activity. Its expression and potential functions in osteosarcoma are studied in the present study. We show that YME1L mRNA and protein expression is significantly elevated in osteosarcoma tissues derived from different human patients. Moreover, its expression is upregulated in various primary and immortalized osteosarcoma cells. The Cancer Genome Atlas database results revealed that YME1L overexpression was correlated with poor overall survival and poor disease-specific survival in sarcoma patients. In primary and immortalized osteosarcoma cells, silencing of YME1L through lentiviral shRNA robustly inhibited cell viability, proliferation, and migration. Moreover, cell cycle arrest and apoptosis were detected in YME1L-silenced osteosarcoma cells. YME1L silencing impaired mitochondrial functions in osteosarcoma cells, causing mitochondrial depolarization, oxidative injury, lipid peroxidation and DNA damage as well as mitochondrial respiratory chain complex I activity inhibition and ATP depletion. Contrarily, forced YME1L overexpression exerted pro-cancerous activity and strengthened primary osteosarcoma cell proliferation and migration. YME1L is important for Akt-S6K activation in osteosarcoma cells. Phosphorylation of Akt and S6K was inhibited after YME1L silencing in primary osteosarcoma cells, but was strengthened with YME1L overexpression. Restoring Akt-mTOR activation by S473D constitutively active Akt1 mitigated YME1L shRNA-induced anti-osteosarcoma cell activity. Lastly, intratumoral injection of YME1L shRNA adeno-associated virus inhibited subcutaneous osteosarcoma xenograft growth in nude mice. YME1L depletion, mitochondrial dysfunction, oxidative injury, Akt-S6K inactivation, and apoptosis were detected in YME1L shRNA-treated osteosarcoma xenografts. Together, overexpressed YME1L promotes osteosarcoma cell growth, possibly by maintaining mitochondrial function and Akt-mTOR activation.
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Neoplasias Ósseas , Proliferação de Células , Camundongos Nus , Osteossarcoma , Animais , Feminino , Humanos , Masculino , Camundongos , Apoptose/genética , ATPases Associadas a Diversas Atividades Celulares/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Osteossarcoma/patologia , Osteossarcoma/genética , Osteossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Lung adenocarcinoma (LUAD) is a study that examines the prognostic value of lactate metabolism genes in tumor cells, which are associated with clinical prognosis. We analyzed the expression and clinical data for LUAD from The Cancer Genome Atlas database, using the GSE68465 dataset from the Gene Expression Omnibus and the MSigDB database. LASSO Cox regression and stepwise Cox regression were used to identify the optimal lactate metabolism gene signature. Differences in immune infiltration, tumor mutation burden (TMB), and response to immune checkpoint blockade (ICB) therapy were evaluated between groups. LASSO and Cox regression analyses showed an eight-lactate metabolism gene signature for model construction in both TCGA cohort and GSE68465 data, with higher survival outcomes in high-risk groups. The lactate metabolism risk score had an independent prognostic value (hazard ratio: 2.279 [1.652-3.146], Pâ <â .001). Immune cell infiltration differed between the risk groups, such as CD8+ T cells, macrophages, dendritic cells, mast cells, and neutrophils. The high-risk group had higher tumor purity, lower immune and stromal scores, and higher TMB. High-risk samples had high tumor immune dysfunction and exclusion (TIDE) scores and low cytolytic activity (CYT) scores, indicating a poor response to ICB therapy. Similarly, most immune checkpoint molecules, immune inhibitors/stimulators, and major histocompatibility complex (MHC) molecules were highly expressed in the high-risk group. The 8-lactate metabolism gene-based prognostic model predicts patient survival, immune infiltration, and ICB response in patients with LUAD, driving the development of therapeutic strategies to target lactate metabolism.
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Adenocarcinoma de Pulmão , Inibidores de Checkpoint Imunológico , Ácido Láctico , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/imunologia , Prognóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/metabolismo , Ácido Láctico/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga heracleifolia Kom. (C. heracleifolia) has demonstrated efficacy in treating gastrointestinal disorders, including splenasthenic diarrhea. Ulcerative colitis (UC), a chronic inflammatory bowel disease, shares similarities with splenasthenic diarrhea. However, the pharmacological effects of C. heracleifolia on UC and the underlying mechanisms remain unexplored. AIM OF THE STUDY: The present study investigates the therapeutic potential and mechanisms of C. heracleifolia in UC. METHODS: Initially, network pharmacology analysis, encompassing ingredient screening, target prediction, protein-protein interaction (PPI) network analysis, and enrichment analysis, was employed to predict the mechanisms of C. heracleifolia. The findings were further validated using transcriptomics and functional assays in a dextran sulfate sodium (DSS)-induced UC model. Additionally, bioactive compounds were identified through surface plasmon resonance (SPR) analysis, molecular docking, and cell-based assays. RESULTS: A total of 52 ingredients of C. heracleifolia were screened, and 32 key targets were identified within a PPI network comprising 285 potential therapeutic targets. Enrichment analysis indicated that the anti-UC effects of C. heracleifolia are mediated through immune response modulation and the inhibition of inflammatory signaling pathways. In vivo experiments showed that C. heracleifolia mitigated histological damage in the colon, reduced the expression of phosphorylated Akt1, nuclear factor-kappa B (NF-κB) p65, and inhibitor of Kappa B kinase α/ß (IKKα/ß), suppressed the content of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and enhanced the expression of tight junction proteins. Moreover, cimigenoside, caffeic acid, and methyl caffeate were identified as the bioactive constituents responsible for the UC treatment effects of C. heracleifolia. CONCLUSIONS: In summary, this study is the first to demonstrate that C. heracleifolia exerts therapeutic effects on UC by enhancing the intestinal mucosal barrier and inhibiting the phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signaling pathway. These findings offer valuable insights into the clinical application of C. heracleifolia for UC management.
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Background: Lung adenocarcinoma (LUAD) has a complex tumor heterogeneity. Our research attempts to clearness LUAD subtypes and build a reliable prognostic signature according to the activity changes of the hallmark and immunologic gene sets. Methods: According to The Cancer Genome Atlas (TCGA) - LUAD dataset, changes in marker and immune gene activity were analyzed, followed by identification of prognosis-related differential gene sets (DGSs) and their related LUAD subtypes. Survival analysis, correlation with clinical characteristics, and immune microenvironment assessment for subtypes were performed. Moreover, the differentially expressed genes (DEGs) between different subtypes were identified, followed by the construction of a prognostic risk score (RS) model and nomogram model. The tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) of different risk groups were compared. Results: Two LUAD subtypes were determined according to the activity changes of the hallmark and immunologic gene sets. Cluster 2 had worse prognosis, more advanced tumor and clinical stages than cluster 1. Moreover, a prognostic RS signature was established using two LUAD subtype-related DEGs, which could stratify patients at different risk levels. Nomogram model incorporated RS and clinical stage exerted good prognostic performance in LUAD patients. A shorter survival time and higher TMB were observed in the high-risk patients. Conclusions: Our findings revealed that our constructed prognostic signature could exactly predict the survival status of LUAD cases, which was helpful in predicting the prognosis and guiding personalized therapeutic strategies for LUAD.
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Identification of novel therapeutic oncotargets for human glioma is extremely important. Here we tested expression, potential functions and underlying mechanisms of G protein inhibitory α subunit 2 (Gαi2) in glioma. Bioinformatics analyses revealed that Gαi2 expression is significantly elevated in human glioma, correlating with poor patients' survival, higher tumor grade and wild-type IDH status. Moreover, increased Gαi2 expression was also in local glioma tissues and different glioma cells. In primary and immortalized (A172) glioma cells, Gαi2 shRNA or knockout (KO, by Cas9-sgRNA) potently suppressed viability, proliferation, and mobility, and induced apoptosis. Ectopic Gαi2 overexpression, using a lentiviral construct, further augmented malignant behaviors in glioma cells. p65 phosphorylation, NFκB activity and expression of NFκB pathway genes were decreased in Gαi2-depleted primary glioma cells, but increased following Gαi2 overexpression. There was an increased binding between Gαi2 promoter and Sp1 (specificity protein 1) transcription factor in glioma tissues and different glioma cells. In primary glioma cells Gαi2 expression was significantly reduced following Sp1 silencing, KO or inhibition. In vivo studies revealed that Gαi2 shRNA-expressing AAV intratumoral injection hindered growth of subcutaneous glioma xenografts in nude mice. Moreover, Gαi2 KO inhibited intracranial glioma xenograft in nude mice. Gαi2 depletion, NFκB inhibition and apoptosis induction were observed in subcutaneous and intracranial glioma xenografts with Gαi2 depletion. Together, overexpressed Gαi2 is important for glioma cell growth possibly by promoting NFκB cascade activation.
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Subunidades alfa de Proteínas de Ligação ao GTP , Glioma , Animais , Camundongos , Humanos , Camundongos Nus , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Glioma/genética , Glioma/patologia , Regulação da Expressão Gênica , RNA Interferente Pequeno , Proliferação de Células/genética , NF-kappa B/genética , Linhagem Celular TumoralRESUMO
Mitochondrial DNA is implicated in hypertrophic cardiomyopathy (HCM) development. We aimed to identify valuable mtDNAs that contribute to the development of HCM. Differentially expressed mitochondrial DNAs (DEMGs) between HCM and controls were screened. GO and KEGG functional enrichment analyses were performed, and the optimum genes were explored using the LASSO regression mode and SVM-RFE model. A diagnostic scoring model was constructed and verified using ROC curves. Mitochondria-based subtypes were identified. Immune performance among the subtypes including immune cells, immune checkpoint genes, and HLA family genes was analyzed. Finally, an mRNA-transcription factor (TF)-miRNA network was constructed using Cytoscape software. Twelve DEMGs in HCM were selected. Among them, 6 DEMGs, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B were demonstrated as DEMGs at the point of intersection of Lasso regression and SVM-RFE. The ROC of the model for the training and validation datasets was 0.999 and 0.958, respectively. Two clusters were divided, and 4 immune cell types were significantly different between the 2 clusters, including resting mast cells, macrophages M2, and plasma cells. Nine upregulated KEGG pathways were enriched in cluster 1 vs. cluster 2 including O-glycan biosynthesis, the ErbB signaling pathway, and the GnRH signaling pathway. Meanwhile, 49 down-regulated pathways were enriched such as the toll-like signaling pathway and natural killer cell-mediated cytotoxicity pathway. The 6 gene-based mRNA-TF-miRNA networks included other 133 TFs and 18 miRNAs. Six DEMGs in HCM, including PDK4, MGST1, TOMM40, LYPLAL1, GATM, and CPT1B, can be indicative of HCM prognosis or disease progression.
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Cardiomiopatia Hipertrófica , MicroRNAs , Humanos , DNA Mitocondrial/genética , Mitocôndrias , Prognóstico , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , RNA MensageiroRESUMO
The crystalline morphology of perovskite film plays a key role in determining the stability and performance of perovskite solar cells (PSCs). In addition, the work function and conductivity of hole transport layer (HTL) have a great influence on the effciency of PSCs. Here, we develop a synergistic doping strategy to fabricate high-performance inverted PSCs, doping a functional nanographene (C78-AHM) into the poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine (PTAA) HTL, thus forming an HTL with higher conductivity, lower roughness, and frontier energy levels matching the perovskite absorber work function. On this basis, thiosemicarbazide (TSC) was doped into the precursor solution of perovskite as the grain and interface modifier to further improve the crystalline morphology of perovskite film. Compared with the current single passivation method, this codoping strategy can simultaneously reduce the surface and bulk defects of perovskite film and reduce the interface energy barrier. Eventually, high-quality TSC-doped perovskite films based on C78-AHM-doped PTAA HTL are obtained with over 2 µm sized grains, pinhole-free, and improved crystallinity. As a result, this synergistic doping strategy increases the efficiency of the device from 20.27% to 23.28%. Furthermore, the environmental and thermal stabilities of the devices are significantly improved. Therefore, this work provides a simple way for the preparation of other efficient optoelectronic devices.
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Does Facebook enable ideological segregation in political news consumption? We analyzed exposure to news during the US 2020 election using aggregated data for 208 million US Facebook users. We compared the inventory of all political news that users could have seen in their feeds with the information that they saw (after algorithmic curation) and the information with which they engaged. We show that (i) ideological segregation is high and increases as we shift from potential exposure to actual exposure to engagement; (ii) there is an asymmetry between conservative and liberal audiences, with a substantial corner of the news ecosystem consumed exclusively by conservatives; and (iii) most misinformation, as identified by Meta's Third-Party Fact-Checking Program, exists within this homogeneously conservative corner, which has no equivalent on the liberal side. Sources favored by conservative audiences were more prevalent on Facebook's news ecosystem than those favored by liberals.
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Política , Mídias Sociais , Humanos , Comunicação , EcossistemaRESUMO
OBJECTIVE: Abnormal DNA methylation can regulate carcinogenesis in lung adenocarcinoma (LUAD), while transcription factors (TFs) mediate methylation in a site-specific manner to affect downstream transcriptional regulation and tumor progression. Therefore, this study aimed to explore the TF-methylation-gene regulatory relationships that influence LUAD prognosis. METHODS: Differential analyses of methylation sites and genes were generated by integrating transcriptome and methylome profiles from public databases. Through target gene identification, motif enrichment in the promoter region, and TF prediction, TF-methylation and methylation-gene relation pairs were obtained. Then, the prognostic TF-methylation-gene network was constructed using univariate Cox regression analysis. Prognostic models were constructed based on the key regulatory axes. Finally, Kaplan-Meier curves were created to evaluate the model efficacy and the relationship between candidate genes and prognosis. RESULTS: A total of 1878 differential expressed genes and 1233 differential methylation sites were screened between LUAD and normal samples. Then 10 TFs were predicted to bind 144 enriched motifs. After integrating TF-methylation and methylation-gene relations, a prognostic TF-methylation-gene network containing 4 TFs, 111 methylation sites, and 177 genes was constructed. In this network, ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were selected to construct the prognostic models, which showed robust abilities in predicting 1-, 3-, and 5-year survival probabilities. Finally, ERG and MTURN were downregulated in LUAD samples, whereas FOXM1 and PTPR were upregulated. Their expression levels were related to LUAD prognosis. CONCLUSION: ERG-cg27071152-MTURN and FOXM1-cg19212949-PTPR regulatory axes were proposed as potential biomarkers for predicting the prognosis of LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Prognóstico , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Fatores de Transcrição/genéticaRESUMO
Here, the authors report a highly efficient integrated ideal-bandgap perovskite/bulk-heterojunction solar cell (IPBSC) with an inverted architecture, featuring a near infrared (NIR) polymer DTBTI-based bulk-heterojunction (BHJ) layer atop guanidinium bromide (GABr)-modified FA0.7 MA0.3 Pb0.7 Sn0.3 I3 perovskite film as the photoactive layer. The IPBSC shows cascade-like energy level alignment between the charge-extractionlayer/perovskite/BHJ and efficient passivation effect of BHJ on perovskite. Thanks to the well-matched energy level alignment and high-quality ideal bandgap-based perovskite film, an efficient charge transfer occurs between the charge-extraction-layer/perovskite/BHJ. Moreover, the NIR polymer DTBTI on the perovskite film leads to an improved NIR light response for the IPBSC. In addition, the O, S and N atoms in the DTBTI polymer yield a strong interaction with perovskite, which is conducive to reducing the defects of the perovskite and suppressing charge recombination. As a result, the solar cell achieves a power conversion efficiency (PCE) of 24.27% (certificated value at 23.4% with 0.283-volt voltage loss), currently the recorded efficiency for both IPBSCs and Pb-Sn alloyed PSCs, and which is over the highest efficiency of perovskite-organic tandem solar cell. Moreover, the thermal, humidity and long-term operational stabilities of the IPBSCs are also significantly improved compared with the control PSCs.
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OBJECTIVES: This study sought to develop a deep learning (DL) framework to automatically analyze echocardiographic videos for the presence of valvular heart diseases (VHDs). BACKGROUND: Although advances in DL have been applied to the interpretation of echocardiograms, such techniques have not been reported for interpretation of color Doppler videos for diagnosing VHDs. METHODS: The authors developed a 3-stage DL framework for automatic screening of echocardiographic videos for mitral stenosis (MS), mitral regurgitation (MR), aortic stenosis (AS), and aortic regurgitation (AR) that classifies echocardiographic views, detects the presence of VHDs, and, when present, quantifies key metrics related to VHD severities. The algorithm was trained (n = 1,335), validated (n = 311), and tested (n = 434) using retrospectively selected studies from 5 hospitals. A prospectively collected set of 1,374 consecutive echocardiograms served as a real-world test data set. RESULTS: Disease classification accuracy was high, with areas under the curve of 0.99 (95% CI: 0.97-0.99) for MS; 0.88 (95% CI: 0.86-0.90) for MR; 0.97 (95% CI: 0.95-0.99) for AS; and 0.90 (95% CI: 0.88-0.92) for AR in the prospective test data set. The limits of agreement (LOA) between the DL algorithm and physician estimates of metrics of valve lesion severities compared to the LOAs between 2 experienced physicians spanned from -0.60 to 0.77 cm2 vs -0.48 to 0.44 cm2 for MV area; from -0.27 to 0.25 vs -0.23 to 0.08 for MR jet area/left atrial area; from -0.86 to 0.52 m/s vs -0.48 to 0.54 m/s for peak aortic valve blood flow velocity (Vmax); from -10.6 to 9.5 mm Hg vs -10.2 to 4.9 mm Hg for average peak aortic valve gradient; and from -0.39 to 0.32 vs -0.31 to 0.32 for AR jet width/left ventricular outflow tract diameter. CONCLUSIONS: The proposed deep learning algorithm has the potential to automate and increase efficiency of the clinical workflow for screening echocardiographic images for the presence of VHDs and for quantifying metrics of disease severity.
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Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Doenças das Valvas Cardíacas , Insuficiência da Valva Mitral , Estenose da Valva Mitral , Insuficiência da Valva Aórtica/diagnóstico por imagem , Ecocardiografia , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the human digestive system, which seriously affects people's quality of life. As an effective treatment for GC, traditional Chinese medicine can effectively alleviate patients' clinical symptoms, improve the quality of life, and delay the life cycle. A large number of clinical studies have shown that Banxia Xiexin Decoction has shown a good effect in the treatment of GC. It has achieved good curative effect whether it is used alone or combined with radiotherapy and chemotherapy, which may play a more significant role in the treatment of GC. However, there is still no evidence of evidence-based medicine. Therefore, this study aims to systematically evaluate the efficacy and safety of Banxia Xiexin Decoction as a complementary treatment for GC. METHODS: Two researchers will search the following databases: PubMed, Web of Science, MEDLINE, the Cochrane Library, Embase, China National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, Wanfang Database, and China Biomedical Database. In addition, the Chinese Clinical Trial Register, Chinese Clinical Trial Register, conference papers, and other relevant literature will be searched manually. The retrieval time of these databases is from the establishment of the database to March 2021. The main outcome indicators of this study are the effective rate of treatment and the traditional Chinese medicine syndrome score. According to the inclusion and exclusion criteria of the literature, the data were screened and extracted. The literature quality was evaluated by the bias risk assessment tool of randomized controlled trials recommended by Cochrane Handbook, and meta-analysis was conducted RevMan 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation will be used to evaluate the quality of evidence. RESULTS: This study will comprehensively review the existing evidence of Banxia Xiexin Decoction as a complementary in the treatment of GC. CONCLUSION: The conclusion of this study will provide a basis for judging whether Banxia Xiexin Decoction is an effective and safe intervention for GC patients. UNIQUE INPLASY NUMBER: INPLASY202140060.
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Terapias Complementares/métodos , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Gástricas/terapia , Fármacos Gastrointestinais/farmacologia , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: This study aimed to identify critical genes involved in the tumor biology of lung cancer via datamining of The Cancer Genome Atlas (TCGA) with special focus on gene copy number variation. METHODS: Genomic deletion and amplification were analyzed with cBioportal online tools. Relative expression of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) was analyzed by both real-time polymerase chain reaction (PCR) and Western blot. The abundance of methylthioadenosine phosphorylase (MTAP) and epithelial-mesenchymal transition markers were analyzed by real-time PCR. Cell proliferation was determined by cell counting kit-8 method and cell viability was measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell migration and invasion were measured with transwell chamber assay, and migrative capacity was further evaluated by wound healing assay. RESULTS: We found the frequent loss of CDKN2A was associated with its downregulation in lung cancer, and siRNA-mediated CDNKN2A knockdown significantly stimulated cell proliferation, invasion, and migration. Mechanistically, we unraveled that MTAP, which was positively correlated with CDKN2A, predominantly mediated the antitumoral function of CDKN2A in lung cancer. CONCLUSION: Our study consolidated the involvement of CDKN2A-MTAP signaling in the context of lung cancer.
Assuntos
Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Neoplasias Pulmonares/genética , Células A549 , Biomarcadores Tumorais/deficiência , Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Cromossomos Humanos Par 9/genética , Inibidor p16 de Quinase Dependente de Ciclina/deficiência , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Purina-Núcleosídeo Fosforilase/metabolismoRESUMO
1.5-1.6 eV bandgap Pb-based perovskite solar cells (PSCs) with 30-31% theoretical efficiency limit by the Shockley-Queisser model achieve 21-24% power conversion efficiencies (PCEs). However, the best PCEs of reported ideal-bandgap (1.3-1.4 eV) Sn-Pb PSCs with a higher 33% theoretical efficiency limit are <18%, mainly because of their large open-circuit voltage (Voc ) deficits (>0.4 V). Herein, it is found that the addition of guanidinium bromide (GABr) can significantly improve the structural and photoelectric characteristics of ideal-bandgap (≈1.34 eV) Sn-Pb perovskite films. GABr introduced in the perovskite films can efficiently reduce the high defect density caused by Sn2+ oxidation in the perovskite, which is favorable for facilitating hole transport, decreasing charge-carrier recombination, and reducing the Voc deficit. Therefore, the best PCE of 20.63% with a certificated efficiency of 19.8% is achieved in 1.35 eV PSCs, along with a record small Voc deficit of 0.33 V, which is the highest PCE among all values reported to date for ideal-bandgap Sn-Pb PSCs. Moreover, the GABr-modified PSCs exhibit significantly improved environmental and thermal stability. This work represents a noteworthy step toward the fabrication of efficient and stable ideal-bandgap PSCs.