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The mechanism of myopia and the associated retinopathy remains unclear, and dysregulated microRNAs (miRNAs) are implicated in this disease. In this research, we purposed to find out the regulatory function that miRNAs play in myopia and the associated retinopathy. We first performed miRNA microarray analysis in a lens-induced myopia mouse model and found that miR-9-5p, miR-96-5p, miR-182-5p, miR-183-5p, and miR-181a-5p were elevated in the myopic retina. Then, we examined the functions and regulatory mechanisms of miR-181a-5p utilizing the human retinal pigment epithelium (RPE) cell line ARPE-19 by overexpressing miR-181a-5p. RNA sequencing (RNA-Seq) and qRT-PCR analysis were employed to identify differentially expressed genes after transfection. The qRTâPCR outcomes, immunoblotting, and immunofluorescence indicated that the SGSH expression was significantly hindered through miR-181a-5p overexpression. MiR-181a-5p overexpression has the ability to elevate RPE cell proliferation and induce autophagy by targeting SGSH. We validated the negative influence of miR-181a-5p on the SGSH expression through luciferase reporter assays, which demonstrated its ability to target the 3' untranslated region of SGSH. The reversal of implications of miR-181a-5p overexpression was achieved through SGSH upregulation. We provided novel perspectives into the miR-181a-5p function in regulating myopia development and may serve as a target for therapy and molecular biomarker for myopia.
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MicroRNAs , Doenças Retinianas , Animais , Humanos , Camundongos , Autofagia/genética , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para CimaRESUMO
Myopia is a global health and economic issue. Circular RNAs (circRNAs) have been shown to play an important role in the pathogenesis of many ocular diseases. We first evaluated the circRNA profiles and possible roles in vitreous humor samples of individuals with high myopia by a competitive endogenous RNA (ceRNA) array. Vitreous humor samples were collected from 15 high myopic (5 for ceRNA array, and 10 for qPCR) and 15 control eyes (5 for ceRNA array, and 10 for qPCR) with idiopathic epiretinal membrane (ERM) and macular hole (MH). 486 circRNAs (339 upregulated and 147 downregulated) and 264 mRNAs (202 upregulated and 62 downregulated) were differentially expressed between the high myopia and control groups. The expression of hsa_circ_0033079 (hsa-circDicer1), hsa_circ_0029989 (hsa-circNbea), hsa_circ_0019072 (hsa-circPank1) and hsa_circ_0089716 (hsa-circEhmt1) were validated by qPCR. Pearson analysis and multivariate regression analysis showed positive and significant correlations for axial length with hsa-circNbea and hsa-circPank1. KEGG analysis showed that the target genes of circRNAs were enriched in the mTOR, insulin, cAMP, and VEGF signaling pathways. GO analysis indicated that circRNAs mainly targeted transcription, cytoplasm, and protein binding. CircRNA-associated ceRNA network analysis and PPI network analysis identified several critical genes for myopia. The expression of circNbea, circPank1, miR-145-5p, miR-204-5p, Nras, Itpr1 were validated by qPCR in the sclera of form-deprivation myopia (FDM) mice model. CircPank1/miR-145-5p/NRAS and circNbea/miR-204-5p/ITPR1 were identified and may be important in the progression of myopia. Our findings suggest that circRNAs may contribute to the pathogenesis of myopia and may serve as potential biomarkers.
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MicroRNAs , Miopia , Humanos , Animais , Camundongos , RNA Circular/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Corpo Vítreo/metabolismo , RNA Mensageiro/metabolismo , RNA Endógeno Competitivo , Miopia/genéticaRESUMO
A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37â°C, pH 7.0 and with 2.0â% (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6â%), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0â%). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6â% and the percentage of conserved proteins was 48.3â%. The major cellular fatty acid of strain CH-27T (≥10â%) was iso-C15â:â0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7âmol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).
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Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ácidos Graxos/química , Sedimentos Geológicos/microbiologia , China , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Genoma Bacteriano , Fosfolipídeos/químicaRESUMO
OBJECTIVE: To retrospectively evaluate the efficacy and safety of CT-guided microcoil localization of pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: A total of 1059 consecutive patients with 1331 pulmonary nodules treated between July 2018 and April 2021 were included in this study. Of the 1331 nodules, 1318 were localized using the tailed method and 13 were localized using the non-tailed method. The localization technical success rate and complications of the microcoil localization procedure were assessed. Univariate and multivariate logistic regression analyses were used to determine potential risk factors for technical failure, pneumothorax, and pulmonary hemorrhage. RESULTS: The technical success rate of the localization procedure was 98.4% (1310/1331 nodules). Nodule location in the lower lobes (p = 0.015) and need for a longer needle path (p < 0.001) were independent predictors of technical failure. All localization procedure-related complications were minor (grade 1 or 2) adverse events, with the exception of one grade 3 complication. The most common complications were pneumothorax (302/1331 nodules [22.7%]) and pulmonary hemorrhage (328/1331 nodules [24.6%]). Male sex (p = 0.001), nodule location in the middle (p = 0.003) and lower lobes (p = 0.025), need for a longer needle path (p < 0.001), use of transfissural puncture (p = 0.042), and simultaneous multiple localizations (p < 0.001) were independent risk factors for pneumothorax. Female sex (p = 0.015), younger age (p = 0.023), nodules location in the upper lobes (p = 0.011), and longer needle path (p < 0.001) were independent risk factors for pulmonary hemorrhage. CONCLUSIONS: CT-guided microcoil localization of pulmonary nodules before VATS using either the tailed or non-tailed method is effective and safe. CLINICAL RELEVANCE STATEMENT: CT-guided microcoil localization of pulmonary nodules before VATS resection is effective and safe when using either the tailed or non-tailed method. Nodules requiring transfissural puncture and multiple nodules requiring simultaneous localizations can also be successfully localized with this method. KEY POINTS: ⢠Pre-VATS CT-guided microcoil localization of pulmonary nodules by tailed or non-tailed method was effective and safe. ⢠When the feasible puncture path was beyond the scope of wedge resection, localization could be performed using the non-tailed method. ⢠Although transfissural puncture and simultaneous multiple localization were independent risk factors for pneumothorax, they remained clinically feasible.
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Neoplasias Pulmonares , Nódulos Pulmonares Múltiplos , Pneumotórax , Nódulo Pulmonar Solitário , Humanos , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/etiologia , Cirurgia Torácica Vídeoassistida/métodos , Pneumotórax/etiologia , Estudos Retrospectivos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/cirurgia , Tomografia Computadorizada por Raios X/métodos , Hemorragia/etiologia , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgiaRESUMO
PURPOSE: To explore the global research trends, hotspots and frontiers of optic neuritis (ON) over the past decade through qualitative and quantitative analysis of bibliometrics. METHODS: Publications on ON from 2013 to 2022 were retrieved from Web of Science Core Collection (WoSCC). VOSviewer and CiteSpace were mainly used to facilitate bibliometric analysis and visualization. RESULTS: A total of 3027 papers were retrieved from peer-reviewed publications and the annual research output increased over time. Neurosciences neurology was the most published area. The USA was the most productive and influential country, and in the focus of international cooperation. University College London was the most productive organization and Charite Medical University of Berlin had the largest number of cooperating partners. Paul F contributed the largest number of publications and Wingerchuk DM ranked first among the co-cited authors. Multiple Sclerosis and Related Disorders was the most prolific journal publishing ON research. The most co-cited references mainly focused on the diagnostic criteria for neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). The keywords formed the following four clusters: the pathophysiology of MS-ON; the autoantibody markers and diagnostic criteria of NMOSD-ON and myelin oligodendrocyte glycoprotein associated disorder-ON (MOGAD-ON); the epidemiology and clinical characteristics of ON; and the treatment of ON. CONCLUSION: This bibliometrics analysis showed a systematic view of the evolutionary process, research hotspots, and future directions of ON research. It can provide insights for ON research and valuable information for neuro-ophthalmologic specialists to evaluate research policies and promote international cooperation.
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Esclerose Múltipla , Neuromielite Óptica , Neurite Óptica , Humanos , Neurite Óptica/terapia , BibliometriaRESUMO
Candida haemulonii, a relative of C. auris, frequently shows antifungal resistance and is transmissible. However, molecular tools for genotyping and investigating outbreaks are not yet established. We performed genome-based population analysis on 94 C. haemulonii strains, including 58 isolates from China and 36 other published strains. Phylogenetic analysis revealed that C. haemulonii can be divided into 4 clades. Clade 1 comprised strains from China and other global strains; clades 2-4 contained only isolates from China, were more recently evolved, and showed higher antifungal resistance. Four regional epidemic clusters (A, B, C, and D) were identified in China, each comprising ≥5 cases (largest intracluster pairwise single-nucleotide polymorphism differences <50 bp). Cluster A was identified in 2 hospitals located in the same city, suggesting potential intracity transmissions. Cluster D was resistant to 3 classes of antifungals. The emergence of more resistant phylogenetic clades and regional dissemination of antifungal-resistant C. haemulonii warrants further monitoring.
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Antifúngicos , Candida , Candidíase , Farmacorresistência Fúngica , Antifúngicos/uso terapêutico , Candida/efeitos dos fármacos , Candida/genética , Candidíase/tratamento farmacológico , Candidíase/genética , Candidíase/microbiologia , China , Testes de Sensibilidade Microbiana , Filogenia , Células Clonais , Farmacorresistência Fúngica/genéticaRESUMO
BACKGROUND: To investigate the association between computed tomography (CT)-detected extramural venous invasion (EMVI)-related genes and immunotherapy resistance and immune escape in patients with gastric cancer (GC). METHODS: Thirteen patients with pathologically proven locally advanced GC who had undergone preoperative abdominal contrast-enhanced CT and radical resection surgery were included in this study. Transcriptome sequencing was multidetector performed on the cancerous tissue obtained during surgery, and EMVI-related genes (P value for association < 0.001) were selected. A single-sample gene set enrichment analysis algorithm was also used to divide all GC samples (n = 377) in The Cancer Genome Atlas (TCGA) database into high and low EMVI-immune related groups based on immune-related differential genes. Cluster analysis was used to classify EMVI-immune-related genotypes, and survival among patients was validated in TCGA and Gene Expression Omnibus (GEO) cohorts. The EMVI scores were calculated using principal component analysis (PCA), and GC samples were divided into high and low EMVI score groups. Microsatellite instability (MSI) status, tumor mutation burden (TMB), response rate to immune checkpoint inhibitors (ICIs), immune escape were compared between the high and low EMVI score groups. Hub gene of the model in pan-cancer analysis was also performed. RESULTS: There were 17 EMVI-immune-related genes used for cluster analysis. PCA identified 8 genes (PCH17, SEMA6B, GJA4, CD34, ACVRL1, SOX17, CXCL12, DYSF) that were used to calculate EMVI scores. High EMVI score groups had lower MSI, TMB and response rate of ICIs, status but higher immune escape status. Among the 8 genes used for EMVI scores, CXCL12 and SOX17 were at the core of the protein-protein interaction (PPI) network and had a higher priority in pan-cancer analysis. Immunohistochemical analysis showed that the expression of CXCL12 and SOX17 was significantly higher in CT-detected EMVI-positive samples than in EMVI-negative samples (P < 0.0001). CONCLUSION: A CT-detected EMVI gene signature could be a potential negative biomarker for ICIs treatment, as the signature is negatively correlated with TMB, and MSI, resulting in poorer prognosis.
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Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Inibidores de Checkpoint Imunológico/uso terapêutico , Invasividade Neoplásica/patologia , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Tomografia Computadorizada por Raios XRESUMO
The purpose of this study was to investigate whether hydrogen-rich bath has therapeutic effect on psoriasis and its molecular mechanism. Mice with imiquimod-induced psoriasis were established and divided into groups. The mice were respectively treated with hydrogen-rich water bath and distilled water bath. The changes of skin lesions and PSI scores of mice were compared after their treatments. HE staining was used to observe the pathological feature. The changes of inflammatory indexes and immune factors were analysed by ELISA and immunohistochemical staining. Malondialdehyde (MDA) content was measured by the thiobarbituric assay (TBA) method. By naked eye, the severity of skin lesions in hydrogen-rich water bath group was lower than that in distilled water bath group, and the psoriasis severity index (PSI) was lower (p < 0.01). The results of HE staining showed that the mice with distilled water bath had more abnormal keratosis, thickening of the spinous layer and prolongation of the dermal process, and more Munro abscess than the mice with hydrogen-rich water bath. During the course of disease, the overall levels and peaks of IL-17, IL-23, TNF-α, CD3+ and MDA in mice with hydrogen-rich bath were lower than those in mice with distilled water bath (p < 0.05). In the skin, the mice treated with the hydrogen-rich water bath also had lower peak of proliferating cell nuclear antigen (PCNA) levels. It is concluded that hydrogen-rich water bath can inhibit psoriasis inflammation and oxidative stress, relieve psoriasis skin lesions and accelerate the end of abnormal skin proliferation state, which shows a therapeutic and improving effect on psoriasis.
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Psoríase , Animais , Camundongos , Imiquimode/farmacologia , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Pele/patologia , Inflamação/patologia , Água , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
BACKGROUND: Breast MRI has been recommended as supplemental screening tool to mammography and breast ultrasound of breast cancer by international guidelines, but its long examination time and use of contrast material remains concerning. PURPOSE: To develop an unenhanced radiomics model with using non-gadolinium based sequences for detecting breast cancer based on T2-weighted (T2W) and diffusion-weighted (DW) MRI. STUDY TYPE: Retrospective analysis followed by retrospective and prospective cohorts study. POPULATION: 1760 patients: Of these, 1293 for model construction (n = 775 for training and 518 for validation). The remaining patients for model testing in internal retrospective (n = 167), internal prospective (n = 188), and external retrospective (n = 112) cohorts. FIELD STRENGTH/SEQUENCE: 3.0T MR scanners from two institution. T2WI, DWI, and first contrast-enhanced T1-weighted sequence. ASSESSMENT: AUCs in distinguishing breast cancer were compared between combined model with gadolinium agent sequence and unenhanced model. Subsequently, the AUCs in testing cohorts of unenhanced model was compared with two radiologists' diagnosis for this research. Finally, patient subgroup analysis in testing cohorts was performed based on clinical subgroups and different types of malignancies. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis H test, chi-square test, weighted kappa test, and DeLong's test. RESULTS: The unenhanced radiomics model performed best under Gaussian process (GP) classifiers (AUC: training, 0.893; validation, 0.848) compared to support vector machine (SVM) and logistic, showing favorable prediction in testing cohorts (AUCs, 0.818-0.840). The AUCs for the unenhanced radiomics model were not statistically different in five cohorts from those of the combined radiomics model (P, 0.317-0.816), as well as the two radiologists (P, 0.181-0.918). The unenhanced radiomics model was least successful in identifying ductal carcinoma in situ, whereas did not show statistical significance in other subgroups. DATA CONCLUSION: An unenhanced radiomics model based on T2WI and DWI has comparable diagnostic accuracy to the combined model using the gadolinium agent. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.
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OBJECTIVES: To investigate the ability of CT and endoscopic sonography (EUS) in predicting the malignant risk of 1-2-cm gastric gastrointestinal stromal tumors (gGISTs) and to clarify whether radiomics could be applied for risk stratification. METHODS: A total of 151 pathologically confirmed 1-2-cm gGISTs from seven institutions were identified by contrast-enhanced CT scans between January 2010 and March 2021. A detailed description of EUS morphological features was available for 73 gGISTs. The association between EUS or CT high-risk features and pathological malignant potential was evaluated. gGISTs were randomly divided into three groups to build the radiomics model, including 74 in the training cohort, 37 in validation cohort, and 40 in testing cohort. The ROIs covering the whole tumor volume were delineated on the CT images of the portal venous phase. The Pearson test and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature selection, and the ROC curves were used to evaluate the model performance. RESULTS: The presence of EUS- and CT-based morphological high-risk features, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not differ between very-low and intermediate risk 1-2-cm gGISTs (p > 0.05). The radiomics model consisting of five radiomics features showed favorable performance in discrimination of malignant 1-2-cm gGISTs, with the AUC of the training, validation, and testing cohort as 0.866, 0.812, and 0.766, respectively. CONCLUSIONS: Instead of CT- and EUS-based morphological high-risk features, the CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs. KEY POINTS: ⢠The presence of EUS- and CT-based morphological high-risk factors, including calcification, necrosis, intratumoral heterogeneity, irregular border, or surface ulceration, did not correlate with the pathological malignant potential of 1-2-cm gGISTs. ⢠The CT radiomics model could potentially be applied for preoperative risk stratification of 1-2-cm gGISTs.
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Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Tomografia Computadorizada por Raios X/métodosRESUMO
Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information about the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from Mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole.
In this paper, novel ST15 and four diploid VNIII isolates (ST632/ST636) were found in 171 CNSC isolates in Southwest China, including evidence for resistance to fluconazole. Moreover, we clustered the 1019 clinical CNSC isolates reported so far from Mainland China into three major subgroups.
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Criptococose , Cryptococcus neoformans , Infecções por HIV , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Criptococose/microbiologia , Criptococose/veterinária , Diploide , Testes de Sensibilidade Microbiana/veterinária , Genótipo , China/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/veterináriaRESUMO
OBJECTIVE: We aimed to develop and validate a computed tomography (CT)-based radiomics model for early relapse prediction in patients with Ewing sarcoma (ES). METHODS: We recruited 104 patients in this study. Tumor areas and areas with a tumor expansion of 3 mm were used as regions of interest for radiomics analysis. Six different models were constructed: Pre-CT, CT enhancement (CTE), Pre-CT +3 mm , CTE +3 mm , Pre-CT and CTE combined (ComB), and Pre-CT +3 mm and CTE +3 mm combined (ComB +3 mm ). All 3 classifiers used a grid search with 5-fold cross-validation to identify their optimal parameters, followed by repeat 5-fold cross-validation to evaluate the model performance based on these parameters. The average performance of the 5-fold cross-validation and the best one-fold performance of each model were evaluated. The AUC (area under the receiver operating characteristic curve) and accuracy were calculated to evaluate the models. RESULTS: The 6 radiomics models performed well in predicting relapse in patients with ES using the 3 classifiers; the ComB and ComB +3 mm models performed better than the other models (AUC -best : 0.820-0.922/0.823-0.833 and 0.799-0.873/0.759-0.880 in the training and validation cohorts, respectively). Although the Pre-CT +3 mm , CTE +3 mm, and ComB +3 mm models covering tumor per se and peritumoral CT features preoperatively forecasted ES relapse, the model was not significantly improved. CONCLUSIONS: The radiomics model performed well for early recurrence prediction in patients with ES, and the ComB and ComB +3 mm models may be superior to the other models.
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Síndromes de Malabsorção , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/diagnóstico por imagem , Sarcoma de Ewing/cirurgia , Doença Crônica , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
OBJECTIVES: This study aimed to develop and validate radiomics models on the basis of computed tomography (CT) and clinical features for the prediction of pulmonary metastases (MT) in patients with Ewing sarcoma (ES) within 2 years after diagnosis. MATERIALS AND METHODS: A total of 143 patients with a histopathological diagnosis of ES were enrolled in this study (114 in the training cohort and 29 in the validation cohort). The regions of interest (ROIs) were handcrafted along the boundary of each tumor on the CT and CT-enhanced (CTE) images, and radiomic features were extracted. Six different models were built, including three radiomics models (CT, CTE and ComB models) and three clinical-radiomics models (CT_clinical, CTE_clinical and ComB_clinical models). The area under the receiver operating characteristic curve (AUC), and accuracy were calculated to evaluate the different models, and DeLong test was used to compare the AUCs of the models. RESULTS: Among the clinical risk factors, the therapeutic method had significant differences between the MT and non-MT groups (Pï¼0.01). The six models performed well in predicting pulmonary metastases in patients with ES, and the ComB model (AUC: 0.866/0.852 in training/validation cohort) achieved the highest AUC among the six models. However, no statistically significant difference was observed between the AUC of the models. CONCLUSIONS: In patients with ES, clinical-radiomics model created using radiomics signature and clinical features provided favorable ability and accuracy for pulmonary metastases prediction.
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Neoplasias Pulmonares , Sarcoma de Ewing , Humanos , Sarcoma de Ewing/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Área Sob a Curva , Curva ROC , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
OBJECTIVES: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. Lung metastasis (LM) occurs in more than half of patients at different stages of the disease course, which is one of the important factors affecting the long-term survival of OS. To develop and validate machine learning radiomics model based on radiographic and clinical features that could predict LM in OS within 3 years. METHODS: 486 patients (LM = 200, non-LM = 286) with histologically proven OS were retrospectively analyzed and divided into a training set (n = 389) and a validation set (n = 97). Radiographic features and risk factors (sex, age, tumor location, etc.) associated with LM of patients were evaluated. We built eight clinical-radiomics models (k-nearest neighbor [KNN], logistic regression [LR], support vector machine [SVM], random forest [RF], Decision Tree [DT], Gradient Boosting Decision Tree [GBDT], AdaBoost, and extreme gradient boosting [XGBoost]) and compared their performance. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) were used to evaluate different models. RESULTS: The radscore, ALP, and tumor size had significant differences between the LM and non-LM groups (tradscore = -5.829, χ2ALP = 97.137, tsize = -3.437, P < 0.01). Multivariable LR analyses showed that ALP was an important indicator for predicting LM of OS (odds ratio [OR] = 7.272, P < 0.001). Among the eight models, the SVM-based clinical-radiomics model had the best performance in the validation set (AUC = 0.807, ACC = 0.784). CONCLUSION: The clinical-radiomics model had good performance in predicting LM in OS, which would be helpful in clinical decision-making.
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Neoplasias Ósseas , Neoplasias Pulmonares , Osteossarcoma , Adolescente , Humanos , Estudos Retrospectivos , Raios X , Osteossarcoma/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagemRESUMO
Steel rebar corrosion is one of the predominant factors influencing the durability of marine and offshore reinforced concrete structures, resulting in economic loss and the potential threat to human safety. Distributed fiber optic sensors (DFOSs) have gradually become an effective method for structural health monitoring over the past two decades. In this work, a strain transfer model is developed between a steel rebar and a DFOS, considering pitting-corrosion-induced strain variation in the steel rebar. The Gaussian function is first adopted to describe the strain distribution near the corrosion pit of the steel rebar and then is substituted into the governing equation of the strain transfer model, and the strain distribution in the DFOS is analytically obtained. Tensile tests are also conducted on steel rebars with artificially simulated corrosion pits, which are used to validate the developed model. The results show that the Gaussian function can be used to describe the strain variation near a corrosion pit with a depth less than 50% of the steel rebar diameter, and the strain distribution in the DFOS analytically determined based on the developed strain transfer model agrees well with the tensile test results. The corrosion pit depth and loading force in the steel rebars estimated based on the proposed model agree well with the actual values, and therefore, the developed strain transfer model is effective in detecting pitting corrosion and loading force in steel rebars.
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PURPOSE: To evaluate the performance of multisequence magnetic resonance imaging (MRI)-based radiomics models in the assessment of microsatellite instability (MSI) status in endometrial cancer (EC). MATERIALS AND METHODS: This retrospective multicentre study included 338 EC patients with available MSI status and preoperative MRI scans, divided into training (37 MSI, 123 microsatellite stability [MSS]), internal validation (15 MSI, 52 MSS), and external validation cohorts (30 MSI, 81 MSS). Radiomics features were extracted from T2-weighted images, diffusion-weighted images, and contrast-enhanced T1-weighted images. The ComBat harmonisation method was applied to remove intrascanner variability. The Boruta wrapper algorithm was used for key feature selection. Three classification algorithms, logistic regression (LR), random forest (RF), and support vector machine (SVM), were applied to build the radiomics models. The area under the receiver operating characteristic curve (AUC) was calculated to compare the diagnostic performance of the models. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the models. RESULTS: Among the 1980 features, Boruta finally selected nine radiomics features. A higher MSI prediction performance was achieved after running the ComBat harmonisation method. The SVM algorithm had the best performance, with AUCs of 0.921, 0.903, and 0.937 in the training, internal validation, and external validation cohorts, respectively. The DCA results showed that the SVM algorithm achieved higher net benefits than the other classifiers over a threshold range of 0.581-0.783. CONCLUSION: The multisequence MRI-based radiomics models showed promise in preoperatively predicting the MSI status in EC in this multicentre setting.
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Neoplasias do Endométrio , Instabilidade de Microssatélites , Humanos , Feminino , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Curva ROCRESUMO
Trauma, burns, and diabetes result in nonhealing wounds that can cause bone or tendon exposure, a significant health threat. The use of an artificial regeneration template combined with skin grafting as an alternative method to highly invasive flap surgery has been shown to be an effective way to cover full-thickness skin defects with bone or tendon exposure for both functional and aesthetic recovery. However, artificial regeneration templates, such as Pelnac, are overwhelmingly expensive, limiting their clinical use. Here, we demonstrate for the first time that polyurethane film combined with absorbable gelatine sponge, affordable materials widely used for haemostasis, are effective for dermal reconstruction in wounds with bone or tendon exposure. The absorbable gelatine sponge combined with polyurethane film was applied to eight patients, all resulting in adequate granulation that fully covered the exposed bone or tendon. The outcome of absorbable gelatine sponge combined with polyurethane film application indicates that this approach is a potential novel and cost-effective dermal reconstruction strategy for the treatment of severe wounds with bone or tendon exposure.
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Pele Artificial , Cicatrização , Humanos , Poliuretanos/uso terapêutico , Transplante de Pele/métodos , Retalhos Cirúrgicos , TendõesRESUMO
BACKGROUND: EPI-506 is the first of a new class of drugs targeting the N-terminal domain (NTD) of the androgen receptor (AR), potentially overcoming known resistance mechanisms to androgen receptor pathway inhibitors (ARPIs) among men with metastatic castration resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC who had progressed on prior ARPI were enrolled in this phase 1 open-label, adaptive 3 + 3 dose escalation study. The primary outcome was safety and tolerability of oral EPI-506. Secondary objectives included determination of the maximal tolerated dose (MTD), pharmacokinetic profile, and antitumor efficacy. RESULTS: 28 mCRPC patients were enrolled into 7 dose cohorts of EPI-506 ranging from 80-3600 mg given once daily and 1800 mg given twice daily. Six DLTs occurred in 4 patients; Grade 4 elevated amylase; Grade 3 abdominal pain; Grade 3 elevated ALT and Grade 3 elevated AST; Grade 2 nausea and Grade 1 vomiting which resulted in study drug intake of < 75% of the expected dose during the DLT assessment period. The most common drug-related adverse events included diarrhea, nausea and fatigue. Six patients had a PSA decline not meeting PSA response criteria. The study was terminated prior to reaching the MTD due to poor oral bioavailability. CONCLUSIONS: This phase 1 trial established the safety of EPI-506 and provides proof of concept for targeting the AR NTD. Next generation compounds with improved bioavailability and potency are in clinical development.
Assuntos
Antagonistas de Receptores de Andrógenos , Compostos Benzidrílicos , Cloridrinas , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Receptores de Andrógenos/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Cloridrinas/efeitos adversos , Humanos , Masculino , Náusea/induzido quimicamente , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Receptores Androgênicos , Resultado do TratamentoRESUMO
BACKGROUND: Scedosporium species have drawn significant interest as inhabitants of polluted soil and water and as cause of high mortality in near-drowning patients. So far, most cases have been reported from Europe and Australia, while knowledge on their prevalence and genotypic diversity from Asia is scant. OBJECTIVES: To increase the knowledge of the genetic diversity and in vitro antifungal susceptibility of Scedosporium species involved in human infections from China. METHODS: Here, we applied the ISHAM-MLST consensus scheme for molecular typing of Scedosporium species and revealed both high species diversity and high genotypic diversity among 45 Chinese clinical Scedosporium isolates. RESULTS: Among the five species, Scedosporium boydii (n = 22) was the most common, followed by S. apiospermum (n = 18), S. aurantiacum (n = 4) and S. dehoogii (n = 1). S. aurantiacum was reported for the first time from clinical samples in China. The predominant sequence types (STs) were ST17 in S. apiospermum, ST4 in S. boydii and ST92 in S. aurantiacum, including four novel STs (ST40, ST41, ST42 and ST43) in S. apiospermum. Based on the CLSI-M38 A2 criterion, voriconazole was the only antifungal compound with low MIC values (MIC90 ≤ 1 µg/ml) for all Scedosporium isolates in our study. CONCLUSIONS: The genetic diversity of clinical isolates of Scedosporium species from China is extremely high, with S. boydii being predominant and S. aurantiacum being firstly reported here. VOR was the only antifungal compound with low MIC values for all Scedosporium isolates in our study, which should be recommended as the firstline antifungal treatment against scedosporiosis in China.
Assuntos
Scedosporium , Humanos , Scedosporium/genética , Antifúngicos/farmacologia , Tipagem de Sequências Multilocus , Voriconazol/farmacologia , AustráliaRESUMO
BACKGROUND: Myopia (nearsightedness) is currently the most common human eye disorder, worldwide. In the recent years, several studies have addressed the role of microRNAs (miRNAs) in the pathogenesis of myopia. OBJECTIVES: The aim of this study was to perform a meta-analysis on the miRNA-expression profiling studies in myopia to identify commonly dysregulated miRNAs in myopic tissues. METHOD: Seven independent studies were included in the meta-analysis. A vote-counting strategy was employed as the meta-analysis method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) functional enrichment analysis were performed to identify the pathways most strongly affected by the dysregulated mouse miRNAs. RESULTS: According to the vote-counting method, eighteen miRNAs were reported in at least 2 studies with the consistent direction, of which 13 miRNAs were commonly upregulated in myopic samples compared with control samples, and five miRNAs were commonly downregulated. Subgroup analyses divided and compared the differentially expressed miRNAs according to species (human and animal) and ocular tissue types. The KEGG analysis showed that the dysregulated mouse miRNAs were most enriched in extracellular matrix-receptor interaction signal pathway. The most enriched GO process regulated by the dysregulated mouse miRNAs was cellular protein modification process. CONCLUSIONS: Our meta-analysis recommends several miRNAs may provide some clues of the potential biomarkers in myopia. Further mechanistic studies are warranted to elucidate the biological role of the dysregulated miRNAs in the development of myopia.