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Harsh synthetic conditions for crystalline covalent triazine frameworks (CTFs) and associated limitations on structural diversities impede not only further development of functional CTFs, but also practical large-scale synthesis. Herein, a mild and universal vapor-solid interface synthesis strategy is developed for highly crystalline CTFs employing trifluoromethanesulfonic acid vapor as catalysts. A series of highly ordered simple and functional CTFs (CTF-TJUs) can be facilely produced. In particular, the porphyrin-involved functional CTF (CTF-TJU-Por1) with high crystallinity is synthesized for the first time via this universal approach. The mechanism of vapor-catalyzed trimerization of nitrile monomers is thoroughly investigated through semi in situ characterizations. As a proof of concept, the photocatalytic performance of synthesized CTFs for water splitting is evaluated. CTF-TJU-133 exhibits significantly greater photocatalytic rates for hydrogen (4.35 µmol h-1) and oxygen (2.18 µmol h-1) evolutions during overall water splitting under visible light irradiations compared to other CTF-TJUs, representing one of the highest values among reported CTF photocatalysts. Further studies reveal that enhanced photocatalytic performance of CTF-TJU-133 results from optimized band structure, extended visible-light absorption, and high carrier separation efficiency. This study provides a promising strategy to synthesize various simple and functional CTFs, which significantly enriched diversities of CTF family for different application purposes.
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BACKGROUND: Primary central nervous system lymphoma (PCNSL) carries a poor prognosis. Radiomics may hold potential value in prognostic assessment. PURPOSE: To develop and validate an MRI-based radiomics model and combine it with clinical factors to assess progression-free survival (PFS) and overall survival (OS) of patients with PCNSL. STUDY TYPE: Retrospective and prospective. POPULATION: Three hundred seventy-nine patients (179 female, 53 ± 7 years) from 2014 to 2022. FIELD STRENGTH/SEQUENCE: T2/fluid-attenuated inversion recovery, contrast-enhanced T1WI and diffusion-weighted echo-planar imaging sequences on 3.0 T. ASSESSMENT: Radiomics features were extracted from enhanced tumor regions on preoperative multi-sequence MRI. Using a least absolute shrinkage and selection operator (LASSO) Cox regression model to select radiomic signatures in training cohort (N = 169). Cox proportional hazards models were constructed for clinical, radiomics, and combined models, with internal (N = 72) and external (N = 32) cohorts validating model performance. STATISTICAL TESTS: Chi-squared, Mann-Whitney, Kaplan-Meier, log-rank, LASSO, Cox, decision curve analysis, time-dependent Receiver Operating Characteristic, area under the curve (AUC), and likelihood ratio test. P-value <0.05 was considered significant. RESULTS: Follow-up duration was 28.79 ± 22.59 months (median: 25). High-risk patients, determined by the median radiomics score, showed significantly lower survival rates than low-risk patients. Compared with NCCN-IPI, conventional imaging and clinical models, the combined model achieved the highest C-index for both PFS (0.660 internal, 0.802 external) and OS (0.733 internal, 0.781 external) in validation. Net benefit was greater with radiomics than with clinical alone. The combined model exhibited performance with AUCs of 0.680, 0.752, and 0.830 for predicting 1-year, 3-year, and 5-year PFS, and 0.770, 0.789, and 0.863 for OS in internal validation, with PFS AUCs of 0.860 and 0.826 and OS AUCs of 0.859 and 0.748 for 1-year and 3-year survival in external validation. DATA CONCLUSION: Incorporating a multi-sequence MR-based radiomics model into clinical models enhances the assess accuracy for the prognosis of PCNSL. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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PURPOSE: Gliomas are the most common primary brain tumor. Currently, topological alterations of whole-brain functional network caused by gliomas are not fully understood. The work here clarified the topological reorganization of the functional network in patients with unilateral frontal low-grade gliomas (LGGs). METHODS: A total of 45 patients with left frontal LGGs, 19 with right frontal LGGs, and 25 healthy controls (HCs) were enrolled. All the resting-state functional MRI (rs-fMRI) images of the subjects were preprocessed to construct the functional network matrix, which was used for graph theoretical analysis. A two-sample t-test was conducted to clarify the differences in global and nodal network metrics between patients and HCs. A network-based statistic approach was used to identify the altered specific pairs of regions in which functional connectivity in patients with LGGs. RESULTS: The local efficiency, clustering coefficient, characteristic path length, and normalized characteristic path length of patients with unilateral frontal LGGs were significantly lower than HCs, while there were no significant differences of global efficiency and small-worldness between patients and HCs. Compared with the HCs, betweenness centrality, degree centrality, and nodal efficiency of several brain nodes were changed significantly in patients. Around the tumor and its adjacent areas, the inter- and intra-hemispheric connections were significantly decreased in patients with left frontal LGGs. CONCLUSION: The patients with unilateral frontal LGGs have altered global and nodal network metrics and decreased inter- and intra-hemispheric connectivity. These topological alterations may be involved in functional impairment and compensation of patients.
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Mapeamento Encefálico , Glioma , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa , Encéfalo/patologia , Glioma/patologiaRESUMO
Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC50 values were 4.7 and 6.4 µM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg-1·d-1, i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers.
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Piridinas , Pironas , Neoplasias Gástricas , Sulfonamidas , Humanos , Animais , Camundongos , Neoplasias Gástricas/patologia , Linhagem Celular Tumoral , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Células-Tronco Neoplásicas , Apoptose , Serina Endopeptidases/metabolismoRESUMO
PURPOSE: Medulloblastoma is the most common childhood malignant brain tumor and is a leading cause of cancer-related death in children. Recent transcriptional studies have shown that medulloblastomas comprise at least four molecular subgroups, each with distinct demographics, genetics, and clinical outcomes. Medulloblastoma subtyping has become critical for subgroup-specific therapies. The use of gene expression assays to determine the molecular subgroup of clinical specimens is a long-awaited application of molecular biology for this pediatric cancer. METHODS: In the current study, we established a medulloblastoma transcriptome database of 460 samples retrieved from three published datasets (GSE21140, GSE37382, and GSE37418). With this database, we identified a 23-gene signature that is significantly associated with the medulloblastoma subgroups and achieved a classification accuracy of 95.2%. RESULTS: The 23-gene signature was further validated in a long-term cohort of 142 Chinese medulloblastoma patients. The 23-gene signature classified 21 patients as WNT (15%), 41 as SHH (29%), 16 as Group 3 (11%), and 64 as Group 4 (45%). For patients of WNT, SHH, Group 3, and Group 4, 5-year overall-survival rate reached 80%, 62%, 27%, and 47%, respectively (p < 0.0001), meanwhile 5-year progression-free survival reached 80%, 52%, 27%, and 45%, respectively (p < 0.0001). Besides, SHH/TP53-mutant tumors were associated with worse prognosis compared with SHH/TP53 wild-type tumors and other subgroups. We demonstrated that subgroup assignments by the 23-gene signature and Northcott's NanoString assay were highly comparable with a concordance rate of 96.4%. CONCLUSIONS: In conclusion, we present a novel gene signature that is capable of accurately and reliably assigning FFPE medulloblastoma samples to their molecular subgroup, which may serve as an auxiliary tool for medulloblastoma subtyping in the clinic. Future incorporation of this gene signature into prospective clinical trials is warranted to further evaluate its clinical.
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Neoplasias Encefálicas , Neoplasias Cerebelares , Meduloblastoma , Humanos , Criança , Meduloblastoma/diagnóstico , Meduloblastoma/genética , Transcriptoma/genética , Estudos Prospectivos , Neoplasias Cerebelares/genética , ChinaRESUMO
Glutamate is excitotoxic to neurons. The entry of glutamine or glutamate from the blood into the brain is limited. To overcome this, branched-chain amino acids (BCAAs) catabolism replenishes the glutamate in brain cells. Branched-chain amino acid transaminase 1 (BCAT1) activity is silenced by epigenetic methylation in IDH mutant gliomas. However, glioblastomas (GBMs) express wild type IDH. Here, we investigated how oxidative stress promotes BCAAs' metabolism to maintain intracellular redox balance and, consequently, the rapid progression of GBMs. We found that reactive oxygen species (ROS) accumulation promoted the nuclear translocation of lactate dehydrogenase A (LDHA), which triggered DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation and enhanced BCAA catabolism in GBM cells. Glutamate derived from BCAAs catabolism participates in antioxidant thioredoxin (TxN) production. The inhibition of BCAT1 decreased the tumorigenicity of GBM cells in orthotopically transplanted nude mice, and prolonged their survival time. In GBM samples, BCAT1 expression was negatively correlated with the overall survival time (OS) of patients. These findings highlight the role of the non-canonical enzyme activity of LDHA on BCAT1 expression, which links the two major metabolic pathways in GBMs. Glutamate produced by the catabolism of BCAAs was involved in complementary antioxidant TxN synthesis to balance the redox state in tumor cells and promote the progression of GBMs.
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Aminoácidos de Cadeia Ramificada , Glioblastoma , Animais , Camundongos , Aminoácidos de Cadeia Ramificada/metabolismo , Antioxidantes , Proliferação de Células , Glioblastoma/genética , Ácido Glutâmico , Lactato Desidrogenase 5 , Camundongos Nus , Tiorredoxinas , HumanosRESUMO
BACKGROUND: It is unclear which core events drive the malignant progression of gliomas. Earlier studies have revealed that the embryonic stem (ES) cell/early PGC state is associated with tumourigenicity. This study was designed to investigate the role of ES/PGC state in poor outcomes of gliomas. METHODS: Crispr-Cas9 technology, RT-PCR and animal experiments were used to investigate whether PGC-like cell formation play crucial roles in the tumorigenicity of human glioma cells. Bioinformatic analysis was used to address the link between ES/PGC developmental axis and glioma overall outcomes. RESULTS: Here, our findings showed that germ cell-like cells were present in human gliomas and cultured glioma cells and that the formation of germ cell-like cells was essential for glioma tumours. Bioinformatic analysis showed that the mRNA levels of genes related to embryonic/germ cell development could be detected in most gliomas. Our findings showed that the activation of genes related to reprogramming or the germ cell-like state alone seemed to be insufficient to lead to a malignant prognosis, whereas increased mRNA levels of genes related to the activation of the embryonic/germ cell-like cycle (somatic PGC-EGC-like cycle and somatic parthenogenetic embryo-like cycle) were positively correlated with malignant prognoses and poor clinical outcomes of gliomas. Genes related to the embryonic/germ cell cycle alone or in combination with the WHO grade or 1p19q codeletion status could be used to subdivide gliomas with distinct clinical behaviours. CONCLUSION: Together, our findings indicated that a crucial role of germ cell-like cell formation in glioma initiation as well as activation of genes related with the parthenogenetic embryo-like cycle and PGC-EGC-like cycle link to the malignant prognosis and poor outcomes of gliomas, which might provide a novel way to better understand the nature of and develop targeted therapies for gliomas as well as important markers for predicting clinical outcomes in gliomas.
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PURPOSE: This study aimed to assess different machine learning models based on radiomic features, Visually Accessible Rembrandt Images features and clinical characteristics in overall survival prediction of glioblastoma and to identify the reproducible features. MATERIALS AND METHODS: Patients with preoperative magnetic resonance scans were allocated into 3 data sets. The Least Absolute Shrinkage and Selection Operator was used for feature selection. The prediction models were built by random survival forest (RSF) and Cox regression. C-index and integrated Brier scores were calculated to compare model performances. RESULTS: Patients with cortical involvement had shorter survival times in the training set (P = 0.006). Random survival forest showed higher C-index than Cox, and the RSF model based on the radiomic features was the best one (testing set: C-index = 0.935 ± 0.023). Ten reproducible radiomic features were summarized. CONCLUSIONS: The RSF model based on radiomic features had promising potential in predicting overall survival of glioblastoma. Ten reproducible features were identified.
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Glioblastoma , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
Paragangliomas are rare neuroendocrine tumors originating from neural crest-derived paraganglion cells. Primary cauda equina paraganglioma (CEP) pose both diagnostic and surgical challenges. We report 12 cases of CEP to characterize the diagnostic and operative approach to these rare tumors. 12 cases with primary CEP were studied; 5 patients were male (41.7%) and 7 were female (56.3%). The median age was 44 years (range: 15-64 years). The most common symptom was lower back pain of variable duration. Radiologically, the lesions were intradural and extramedullary with well-defined margins, and ranged from 1 to 4.5 cm. in diameter (mean: 1.65 cm). 9 tumors were composed of sheets and nests of cells with a neuroendocrine pattern and intense vascularity and displayed a characteristic Zellballen pattern. Interestingly, CAM 5.2 was diffusely or focally positive with a dot-like or membrane pattern in 8/11 cases (72.7%). Similarly, CK was diffusely or focally positive with membrane and cytoplasmic staining or with a dot-like pattern in 7/11 (63.6%) and 2/11 cases (18.2%). None of the cases showed deletion of SDHB nor expression of GATA3. CEP can display aberrant keratin positivity, and this should be considered in the differential diagnosis of these lesions. This finding also raises the possibility that CEP may be an entirely different entity than non-spinal paragangliomas.
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Cauda Equina , Tumores Neuroendócrinos , Paraganglioma , Neoplasias do Sistema Nervoso Periférico , Adulto , Cauda Equina/patologia , Cauda Equina/cirurgia , Feminino , Humanos , Queratinas , Masculino , Tumores Neuroendócrinos/patologia , Paraganglioma/diagnóstico , Paraganglioma/cirurgia , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Neoplasias do Sistema Nervoso Periférico/patologia , Neoplasias do Sistema Nervoso Periférico/cirurgiaRESUMO
In this Letter, high sensitivity and large measurable range distributed acoustic sensing (DAS) based on sub-chirped-pulse extraction algorithm (SPEA) in time domain and dechirp operation is proposed; moreover, Rayleigh-enhanced fiber is used to further improve the quality of Rayleigh scattering (RS) signal. In the proof-of-concept experiment, the RS pattern with 60 µÉ strain range is generated during a single-shot measurement, while $80.7 \; {\rm p}\varepsilon /\sqrt {\rm Hz}$ strain sensitivity and 28.4 cm spatial resolution are achieved on 920 m fiber.
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BACKGROUND: The optimal treatment for recurrent high-grade gliomas (rHGGs) remains uncertain. This study aimed to investigate the efficacy and safety of hypofractionated stereotactic radiosurgery (HSRS) as a first-line salvage treatment for in-field recurrence of high-grade gliomas. METHODS: Between January 2016 and October 2019, 70 patients with rHGG who underwent HSRS were retrospectively analysed. The primary endpoint was overall survival (OS), and secondary endpoints included both progression-free survival (PFS) and adverse events, which were assessed according to Common Toxicity Criteria Adverse Events (CTCAE) version 5. The prognostic value of key clinical features (age, performance status, planning target volume, dose, use of bevacizumab) was evaluated. RESULTS: A total of 70 patients were included in the study. Forty patients were male and 30 were female. Forty-nine had an initial diagnosis of glioblastoma (GBM), and the rest (21) were confirmed to be WHO grade 3 gliomas. The median planning target volume (PTV) was 16.68 cm3 (0.81-121.96 cm3). The median prescribed dose was 24 Gy (12-30 Gy) in 4 fractions (2-6 fractions). The median baseline of Karnofsky Performance Status (KPS) was 70 (40-90). With a median follow-up of 12.1 months, the median overall survival after salvage treatment was 17.6 months (19.5 and 14.6 months for grade 3 and 4 gliomas, respectively; p = .039). No grade 3 or higher toxicities was recorded. Multivariate analysis showed that concurrent bevacizumab with radiosurgery and KPS > 70 were favourable prognostic factors for grade 4 patients with HGG. CONCLUSIONS: Salvage HSRS showed a favourable outcome and acceptable toxicity for rHGG. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of hypofractionated stereotactic radiosurgery (HSRS) in rHGG.
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Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Radiocirurgia/mortalidade , Adulto , Idoso , Neoplasias Encefálicas/patologia , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Adulto JovemRESUMO
Wider bandwidth always means better overall performance for an information system. Naturally, this criterion can also be applied to phase-sensitive optical time domain reflectometry (Φ-OTDR), which is a typical distributed optical fiber sensing (DOFS) system. Thus, an indispensable way to enhance the performance of Φ-OTDR is to increase the available system bandwidth, which is usually limited by the electrical components. As a kind of frequency resources, the negative frequency band (NFB) has been used in communication systems based on coherent receivers and high-order modulation, but is still rarely used in DOFS. In this paper, we make a comprehensive study on how to utilize NFB in Φ-OTDR and thus double the available system bandwidth. Moreover, the related improvement of sensing performance is experimentally demonstrated. The positive and negative frequency multiplexing is utilized together with frequency division multiplexing to break the inherent trade-off between sensing distance and scan-rate. As a result, 21.6 kHz scan-rate is experimentally achieved on a 103 km fiber, with 97 pε/Hz strain resolution and 9.3 m spatial resolution. To the best of our knowledge, this is the best sensing performance in long distance Φ-OTDR > 100 km. The proposed scheme can also be applied to other DOFS systems with heterodyne-detection, opening up new possibilities for performance enhancement in DOFS systems.
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Quasi-distributed acoustic sensing (Q-DAS) based on ultra-weak fiber Bragg grating (UWFBG) is currently attracting great attention, due to its high sensitivity and excellent multiplexing capability. Phase-sensitive optical time-domain reflectometry (Φ-OTDR) based on phase demodulation is one of the most promising interrogation schemes for Q-DAS. In this article, a novel interleaved identical chirped pulse (IICP) approach is proposed on the basis of pulse compression Φ-OTDR with coherent detection. Different from the frequency-division-multiplexing (FDM) method, the identical pulses are used for multiplexing in the IICP scheme, and the mixed reflection signals can be demodulated directly, so the inconsistent phase offsets in FDM can be avoided. As a result, this scheme can enlarge the measurement slew-rate (SR) of Q-DAS by times compared with traditional single pulse scheme. In the proof-of-principle experiment, the SR of 28.9 mÉ/s has been achieved with an 860 m sensing range, which is 5 times as that of the traditional single pulse scheme; meanwhile, the response bandwidth has been enlarged by 5 times. The 277 kHz response bandwidth has been achieved, with 5 m spatial resolution and 2.8 pε/Hz strain sensitivity.
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This paper presents an integrated principal component analysis (IPCA) technique for denoising phase-sensitive optical time domain reflectometry (Φ-OTDR) sensing data for vibration detection. As one of the key distributed optical fiber sensing technologies, it has attracted great attention, mainly due to its high sensitivity, fast response time, dynamic range, and vibration detection abilities. To enhance vibration detection along the sensing fiber, an appropriate denoising method must be carefully selected. Hence, the PCA that can effectively reduce noise on signals while preserving significant details of the denoised signal is identified. It was then applied on the said signal after digital down-conversion where the noise was greatly reduced. Then angle and phase unwrapping was performed and the vibration was clearly detected with a significant enhancement of the signal-to-noise ratio. As proof of concept, the theoretical analysis and an experimental demonstration of a vibration sensing range of 800 m are presented.
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AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. CONCLUSION: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.
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Biomarcadores Tumorais/análise , Glioma/metabolismo , Glioma/patologia , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas de Ligação a RNA/metabolismo , Adolescente , Adulto , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/metabolismo , Epilepsia/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Masculino , Proteínas de Ligação a RNA/genética , Estudos Retrospectivos , Adulto JovemRESUMO
Resistance towards imatinib (IM) remains troublesome in treating many chronic myeloid leukemia (CML) patients. Heme oxygenase-1 (HO-1) is a key enzyme of antioxidative metabolism in association with cell resistance to apoptosis. Our previous studies have shown that overexpression of HO-1 resulted in resistance development to IM in CML cells, while the mechanism remains unclear. In the current study, the IM-resistant CML cells K562R indicated upregulation of some of the histone deacetylases (HDACs) compared with K562 cells. Therefore, we herein postulated HO-1 was associated with HDACs. Silencing HO-1 expression in K562R cells inhibited the expression of some HDACs, and the sensitivity to IM was increased. K562 cells transfected with HO-1 resisted IM and underwent obvious some HDACs. These findings related to the inhibitory effects of high HO-1 expression on the reactive oxygen species (ROS) signaling pathway that negatively regulated HDACs. Increased expression of HO-1 activated HDACs by inhibiting ROS production. In summary, HO-1, which is involved in the development of drug resistance in CML cells by regulating the expression of HDACs, is probably a novel target for improving CML therapy.
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Antineoplásicos/farmacologia , Heme Oxigenase-1/metabolismo , Histona Desacetilases/metabolismo , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Adulto , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/genética , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Adulto JovemRESUMO
OBJECTIVES: The preoperative prediction of the WHO grade of a meningioma is important for further treatment plans. This study aimed to assess whether texture analysis (TA) based on apparent diffusion coefficient (ADC) maps could non-invasively classify meningiomas accurately using tree classifiers. METHODS: A pathology database was reviewed to identify meningioma patients who underwent tumour resection in our hospital with preoperative routine MRI scanning and diffusion-weighted imaging (DWI) between January 2011 and August 2017. A total of 152 meningioma patients with 421 preoperative ADC maps were included. Four categories of features, namely, clinical features, morphological features, average ADC values and texture features, were extracted. Three machine learning classifiers, namely, classic decision tree, conditional inference tree and decision forest, were built on these features from the training dataset. Then the performance of each classifier was evaluated and compared with the diagnosis made by two neuro-radiologists. RESULTS: The ADC value alone was unable to distinguish three WHO grades of meningiomas. The machine learning classifiers based on clinical, morphological features and ADC value could achieve equivalent diagnostic performance (accuracy = 62.96%) compared to two experienced neuro-radiologists (accuracy = 61.11% and 62.04%). Upon analysis, the decision forest that was built with 23 selected texture features and the ADC value from the training dataset achieved the best diagnostic performance in the testing dataset (kappa = 0.64, accuracy = 79.51%). CONCLUSIONS: Decision forest with the ADC value and ADC map-based texture features is a promising multiclass classifier that could potentially provide more precise diagnosis and aid diagnosis in the near future. KEY POINTS: ⢠A precise preoperative prediction of the WHO grade of a meningioma brings benefits to further treatment plans. ⢠Machine learning models based on clinical, morphological features and ADC value could achieve equivalent diagnostic performance compared to experienced neuroradiologists. ⢠The decision forest model built with 23 selected texture features and the ADC value achieved the best diagnostic performance (kappa = 0.64, accuracy = 79.51%).
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Árvores de Decisões , Imagem de Difusão por Ressonância Magnética/métodos , Aprendizado de Máquina , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Estadiamento de Neoplasias/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The purpose of this retrospective review is to determine the MR imaging features of pilocytic astrocytoma (PA) in the spinal cord to help neuroradiologists preoperatively differentiate PA from other intramedullary tumors. METHODS: Neuro-oncology database review revealed 13 consecutive patients with a pathological spinal PA diagnosis and availability of preoperative MR imaging. Three patients had preoperative diffusion-weighted MR imaging. Demographics and conventional and diffusion MR imaging records were retrospectively evaluated. RESULTS: Among 13 cases of spinal PA, six PAs were located in the cervical region, 4 in the cervical-thoracic region, and 3 in the thoracic region. The average length of vertebral segments involved for the tumors were 4.7 ± 4.6 segments. Six tumors had associated syringomyelia. Eight PAs were located eccentrically in the spinal cord, and eleven had well-defined margins. Eight tumors (61.5%) were intermixed cystic and solid. All were contrast-enhanced, and 53.8% of all PAs showed focal nodule enhancement of the solid components. Two PAs showed intratumoral hemorrhages, and only one demonstrated cap sign. The ADC values (n = 3) of the tumors were 1.40 ± 0.28 × 10- 3 mm2/s (min-max: 1.17-1.71 × 10- 3 mm2/s). CONCLUSIONS: PA should be considered in the differential diagnosis of intramedullary tumors that occur in the cervical and thoracic regions. Eccentric growth pattern, well-defined margin, intermixed cystic and solid appearance, focal nodular enhancement of solid components and syringomyelia are relatively frequent features. Relatively high ADC values compared with normal-appearing spinal cord parenchyma are common in spinal PA.
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Astrocitoma/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Medula Espinal/diagnóstico por imagem , Adolescente , Adulto , Medula Cervical/diagnóstico por imagem , Medula Cervical/patologia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: A multi-discipline cardiac and cardiopulmonary bypass (CPB) team simulation scenario was established to compare three different de-airing approaches dealing with massive air embolism in CPB, so as to formulate a standardized procedure to handle this adverse acute event more proficiently and ensure clinical safety. METHOD: A simulation-based clinical CPB massive air embolism scenario was developed by a cardiac and CPB team. Study Objects: Five licensed perfusionists and five CPB trainees were matched randomly into five pairs. Each pair would simulate the three different de-airing approaches separately as followed: (1) Conventional Method: arterial line filter (ALF) de-airing purge line and oxygenator self-recirculation bypass were used to de-air; (2) Arterial-Venous Loop (A-V Loop) Method: surgeons reconnected the arterial and venous lines to de-air by restoring the original priming A-V loop configuration; (3) Isolation of the ALF Method: this ensures de-bubbling of the CPB circuit, but bypasses the ALF function. Assessment Criteria: (1) Times to recovery (duration of the circulation suspension); (2) Subjective evaluation of skill and non-skill performances. RESULTS: As to times to recovery, the Conventional Method group took 290.6 s ± 36.2, the A-V Loop Method group took 196.8 s ± 52.0 and the Isolation of ALF group took 99.4 s ± 15.1. The statistical difference is significant among the three groups (p<0.01). The subjective evaluation of training performance indicates that this simulation-based training is effective in assessing both skill and non-skill abilities. CONCLUSION: CPB simulation-based training was effective in comparing de-airing strategies and can instruct perfusion practices how to optimize techniques. For well-trained, multi-discipline cardiac teams, the A-V Loop Method is highly efficient and reliable in managing CPB massive air embolism. For cardiac teams that do not have this sophisticated training, the Isolation of ALF Method should be their alternative option.
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Ponte Cardiopulmonar/educação , Ponte Cardiopulmonar/métodos , Treinamento por Simulação/métodos , Ponte Cardiopulmonar/instrumentação , China , Humanos , Perfusão/instrumentação , Perfusão/métodosRESUMO
PURPOSE: To assess whether a machine-learning model based on texture analysis (TA) could yield a more accurate diagnosis in differentiating malignant haemangiopericytoma (HPC) from angiomatous meningioma (AM). MATERIALS AND METHODS: Sixty-seven pathologically confirmed cases, including 24 malignant HPCs and 43 AMs between May 2013 and September 2017 were retrospectively reviewed. In each case, 498 radiomic features, including 12 clinical features and 486 texture features from MRI sequences (T2-FLAIR, DWI and enhanced T1WI), were extracted. Three neuroradiologists independently made diagnoses by vision. Four Support Vector Machine (SVM) classifiers were built, one based on clinical features and three based on texture features from three MRI sequences after feature selection. The diagnostic abilities of these classifiers and three neuroradiologists were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: Malignant HPCs were found to have larger sizes, slighter degrees of peritumoural oedema compared with AMs (P<0.05), and more serpentine-like vessels. The AUC of the enhanced T1WI-based classifier was 0.90, significantly higher than that of T2-FLAIR-based or DWI-based classifiers (0.77 and 0.73). The AUC of the SVM classifier based on clinical features was 0.66, slightly but not significantly lower than the performances of 3 neuroradiologists (AUC=0.69, 0.70 and 0.73). CONCLUSION: Machine-learning models based on clinical features alone could not provide a better diagnostic performance than that of radiologists. The SVM classifier built by texture features extracted from enhanced T1WI is a promising tool to differentiate malignant HPC from AM before surgery.