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[This corrects the article DOI: 10.1007/s42994-022-00082-5.].
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BACKGROUND: Raiomics is an emerging auxiliary diagnostic tool, but there are still differences in whether it can be applied to predict early recurrence of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to systematically evaluate the predictive power of radiomics in the early recurrence (ER) of HCC. METHODS: Comprehensive studies on the application of radiomics to predict ER in HCC patients after hepatectomy or curative ablation were systematically screened in Embase, PubMed, and Web of Science. RESULTS: Ten studies which is involving a total of 1929 patients were reviewed. The overall estimates of radiomic models for sensitivity and specificity in predicting the ER of HCC were 0.79 (95% confidence interval [CI]: 0.68-0.87) and 0.83 (95% CI: 0.73-0.90), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.88 (95% CI: 0.85-0.91). CONCLUSIONS: The imaging method is a reliable method for diagnosing HCC. Radiomics, which is based on medical imaging, has excellent power in predicting the ER of HCC. With the help of radiomics, we can predict the recurrence of HCC after surgery more effectively and provide a useful reference for clinical practice.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Recidiva Local de Neoplasia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Humanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Hepatectomia/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , RadiômicaRESUMO
We report the discovery that the molecule 1-(pyridin-2-ylmethylamino)propan-2-ol (HL) can reduce oxidative stress in neuronal C6 glioma cells exposed to reactive oxygen species (O2-â¢, H2O2, and â¢OH) and metal (Cu+) stress conditions. Furthermore, its association with Cu2+ generates [Cu(HL)Cl2] (1) and [Cu(HL)2](ClO4)2 (2) complexes that also exhibit antioxidant properties. Potentiometric titration data show that HL can coordinate to Cu2+ in 1:1 and 1:2 Cu2+:ligand ratios, which was confirmed by monocrystal X-ray studies. The subsequent ultraviolet-visible, electrospray ionization mass spectrometry, and electron paramagnetic resonance experiments show that they can decompose a variety of reactive oxygen species (ROS). Kinetic studies revealed that 1 and 2 mimic the superoxide dismutase and catalase activities. Complex 1 promotes the fastest decomposition of H2O2 (kobs = 2.32 × 107 M-1 s-1), efficiently dismutases the superoxide anion (kcat = 3.08 × 107 M-1 s-1), and scavenges the hydroxyl radical (RSA50 = 25.7 × 10-6 M). Density functional theory calculations support the formation of dinuclear Cu-peroxide and mononuclear Cu-superoxide species in the reactions of [Cu(HL)Cl2] with H2O2 and O2â¢-, respectively. Furthermore, both 1 and 2 also reduce the oxidative stress of neuronal glioma C6 cells exposed to different ROS, including O2â¢- and â¢OH.
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Antioxidantes , Complexos de Coordenação , Cobre , Estresse Oxidativo , Cobre/química , Cobre/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Teoria da Densidade Funcional , Espécies Reativas de Oxigênio/metabolismo , Catálise , Animais , Estrutura Molecular , Linhagem Celular Tumoral , Ratos , HumanosRESUMO
RATIONALE AND OBJECTIVES: To develop and validate a clinical-radiomics model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of Vessels encapsulating tumor clusters (VETC)- microvascular invasion (MVI) and prognosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 219 HCC patients from Institution 1 were split into internal training and validation groups, with 101 patients from Institution 2 assigned to external validation. Histologically confirmed VETC-MVI pattern categorizing HCC into VM-HCC+ (VETC+/MVI+, VETC-/MVI+, VETC+/MVI-) and VM-HCC- (VETC-/MVI-). The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI. Six radiomics models (intratumor and peritumor in AP, PP, and DP of DCE-MRI) and one clinical model were developed for assessing VM-HCC. Establishing intra-tumoral and peri-tumoral models through combining intratumor and peritumor features. The best-performing radiomics model and the clinical model were then integrated to create a Combined model. RESULTS: In institution 1, pathological VM-HCC+ were confirmed in 88 patients (training set: 61, validation set: 27). In internal testing, the Combined model had an AUC of 0.85 (95% CI: 0.76-0.93), which reached an AUC of 0.75 (95% CI: 0.66-0.85) in external validation. The model's predictions were associated with early recurrence and progression-free survival in HCC patients. CONCLUSIONS: The clinical-radiomics model offers a non-invasive approach to discern VM-HCC and predict HCC patients' prognosis preoperatively, which could offer clinicians valuable insights during the decision-making phase.
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The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.
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Antineoplásicos , Proliferação de Células , Descoberta de Drogas , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Humanos , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Animais , Estrutura Molecular , Camundongos , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Proteólise/efeitos dos fármacos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Camundongos NusRESUMO
Cetuximab in combination with FOLFIRI/FOLFOX is the standard first-line treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, some patients experience rapid tumor progression after treatment with cetuximab (primary resistance). Our previous research identified a gene mutation, REV1 p.R704Q, which may be a key biomarker for primary cetuximab resistance. This study aimed to study the mechanism of cetuximab resistance caused by REV1 p.R704Q mutation and reveal a novel mechanism to induce cetuximab resistance. Sanger sequencing and multivariate clinical prognostic analysis of 208 patients with mCRC showed that REV1 p.R704Q mutation is an independent risk factor for tumor progression after treatment with cetuximab in patients with RAS wild-type mCRC (Hazard ratio = 2.481, 95 % Confidence interval: 1.389-4.431, P = 0.002). The sensitivity of REV1 p.R704Q mutant cell lines to cetuximab decreased in vitro Cell Counting Kit-8 assay and in vivo subcutaneous tumor model. In vitro, we observed that decreased stability and accelerated degradation of REV1 mutant protein results in REV1 dysfunction, which activated autophagy and mediated cetuximab resistance. These findings suggested that REV1 p.R704Q mutation could predict cetuximab primary resistance in mCRC. REV1 p.R704Q mutation caused decreased stability and degradation of REV1 protein, as well as dysfunction of p.R704Q protein. REV1 p.R704Q mutation activates autophagy and mediates cetuximab resistance; further, inhibition of autophagy could reverse cetuximab resistance.
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Autofagia , Cetuximab , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Mutação , Humanos , Cetuximab/farmacologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Autofagia/efeitos dos fármacos , Autofagia/genética , Masculino , Feminino , Animais , Camundongos , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Camundongos Nus , PrognósticoRESUMO
The translocase of the outer membrane (TOM) complex serves as the main gate for preproteins entering mitochondria and thus plays a pivotal role in sustaining mitochondrial stability. Precursor proteins, featuring amino-terminal targeting signals (presequences) or internal targeting signals, are recognized by the TOM complex receptors Tom20, Tom22, and Tom70, and then translocated into mitochondria through Tom40. By using chemical cross-linking to stabilize Tom20 in the TOM complex, this study unveils the structure of the human TOM holo complex, encompassing the intact Tom20 component, at a resolution of approximately 6 Å by cryo-electron microscopy. Our structure shows the TOM holo complex containing only one Tom20 subunit, which is located right at the center of the complex and stabilized by extensive interactions with Tom22, Tom40, and Tom6. Based on the structure, we proposed a possible translocation mode of TOM complex, by which different receptors could work simultaneously to ensure that the preproteins recognized by them are all efficiently translocated into the mitochondria.
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How alien pests invade new areas has always been a hot topic in invasion biology. The spread of the Bactrocera dorsalis from southern to northern China involved changes in food sources. In this paper, in controlled conditions, we take Bactrocera dorsalis as an example to study how plant host transformation affects gut bacteria by feeding it its favorite host oranges in the south, its favorite host peaches and apples in the north, and feeding it cucumbers as a non-favorite host plant, thereby further affecting their fitness during invasion. The result showed that, after three generations of feeding on cucumbers, Bactrocera dorsalis took longer to develop as a larva while its longevity and fecundity decreased and pre-adult mortality increased. Feeding it cucumbers significantly reduced the overall diversity of gut microbiota of Bactrocera dorsalis. The relative abundance of Enterobacter necessary for survival decreased, while the Empedobacter and Enterococcus increased, resulting in decreased carbohydrate transport and metabolism and increased lipid transport and metabolism. Feeding Bactrocera dorsalis Empedobacter brevis and Enterococcus faecalis resulted in a 26% increase in pre-adult mortality and a 2-3 d increase in adult preoviposition period (APOP). Additionally, Enterococcus faecalis decreased the longevity of female and male adults by 17 and 12 d, respectively, and decreased fecundity by 11%. We inferred that the shifted plant hosts played an important role in posing serious harm to Bactrocera dorsalis invading from the south to the north. Therefore, after an invasion of Bactrocera dorsalis into northern China, it is difficult to colonize cucumbers for a long time, but there is still a risk of short-term harm. The findings of this study have established that the interactions between an insect's food source and gut bacteria may have an important effect on insect invasions.
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Petrocodonliboensis Sheng H.Tang & Jia W.Yang is a new species of Gesneriaceae from Guizhou, southwestern China. The new taxon has a pale-yellow corolla and is most similar to P.luteoflorus. However, it differs from the latter by having a urceolate (vs. cannulate) corolla tube, an abaxial corolla lip 0.8-1.1 mm (vs. 2-2.2 mm) long, and filaments 1.5-1.7 mm (vs. ca. 7 mm) long that are straight (vs. S-shaped or geniculate near the middle). The new taxon is assessed as "Data Deficient" (DD) according to the IUCN standards.
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Introduction: Nitrososphaeria, formerly known as Thaumarchaeota, constitute a diverse and widespread group of ammonia-oxidizing archaea (AOA) inhabiting ubiquitously in marine and terrestrial environments, playing a pivotal role in global nitrogen cycling. Despite their importance in Earth's ecosystems, the cellular organization of AOA remains largely unexplored, leading to a significant unanswered question of how the machinery of these organisms underpins metabolic functions. Methods: In this study, we combined spherical-chromatic-aberration-corrected cryo-electron tomography (cryo-ET), scanning transmission electron microscopy (STEM), and energy dispersive X-ray spectroscopy (EDS) to unveil the cellular organization and elemental composition of Nitrosopumilus maritimus SCM1, a representative member of marine Nitrososphaeria. Results and Discussion: Our tomograms show the native ultrastructural morphology of SCM1 and one to several dense storage granules in the cytoplasm. STEM-EDS analysis identifies two types of storage granules: one type is possibly composed of polyphosphate and the other polyhydroxyalkanoate. With precise measurements using cryo-ET, we observed low quantity and density of ribosomes in SCM1 cells, which are in alignment with the documented slow growth of AOA in laboratory cultures. Collectively, these findings provide visual evidence supporting the resilience of AOA in the vast oligotrophic marine environment.
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Impatiensbeipanjiangensis Jian Xu & H. F. Hu (Balsaminaceae), a new species of Impatienssubg.Clavicarpa discovered in Guizhou, China, is described and illustrated in this study along with its molecular phylogenetic analysis. I.beipanjiangensis is similar to I.liboensis, I.chishuiensis and I.clavigera in morphology, but I.tubulosa has the closest relationship to it. However, there are various ways in which the new species can be easily distinguished from these four species: Inferior nodes swollen rhizoid, pale green and with hooked outer sepals, longer lateral united petals, subovate auricle, deeper lower sepal and shorter spur that is reflexed towards the lower sepal. Furthermore, I.beipanjiangensis is distinguished from other Impatiens species, based on morphological, micromorphological and palynological evidence and molecular data (PP 0.967).
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Cnaphalocrocis medinalis granulovirus (CnmeGV), belonging to Betabaculovirus cnamedinalis, can infect the rice pest, the rice leaf roller. In 1979, a CnmeGV isolate, CnmeGV-EP, was collected from Enping County, China. In 2014, we collected another CnmeGV isolate, CnmeGV-EPDH3, at the same location and obtained the complete virus genome sequence using Illumina and ONT sequencing technologies. By combining these two virus isolates, we updated the genome annotation of CnmeGV and conducted an in-depth analysis of its genome features. CnmeGV genome contains abundant tandem repeat sequences, and the repeating units in the homologous regions (hrs) exhibit overlapping and nested patterns. The genetic variations within EPDH3 population show the high stability of CnmeGV genome, and tandem repeats are the only region of high genetic variation in CnmeGV genome replication. Some defective viral genomes formed by recombination were found within the population. Comparison analysis of the two virus isolates collected from Enping showed that the proteins encoded by the CnmeGV-specific genes were less conserved relative to the baculovirus core genes. At the genomic level, there are a large number of SNPs and InDels between the two virus isolates, especially in and around the bro genes and hrs. Additionally, we discovered that CnmeGV acquired a segment of non-ORF sequence from its host, which does not provide any new proteins but rather serves as redundant genetic material integrated into the viral genome. Furthermore, we observed that the host's transposon piggyBac has inserted into some virus genes. Together, dsDNA viruses could acquire non-coding genetic material from their hosts to expand the size of their genomes. These findings provide new insights into the evolution of dsDNA viruses.
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Variação Genética , Genoma Viral , Animais , Filogenia , China , Granulovirus/genética , Granulovirus/classificação , Granulovirus/isolamento & purificação , Sequenciamento Completo do Genoma , Oryza/virologia , Sequências de Repetição em Tandem/genética , Doenças das Plantas/virologia , Recombinação GenéticaRESUMO
Groundwater depletion in intensively exploited aquifers of China has been widely recognized, whereas an overall examination of groundwater storage (GWS) changes over major aquifers remains challenging due to limited data and notable uncertainties. Here, we present a study to explore GWS changes over eighteen major aquifers covering an area of 1,680,000 km2 in China using data obtained from the Gravity Recovery and Climate Experiments (GRACE), global models, and in-situ groundwater level observations. The analysis aims to reveal the discrepancy in annual trends, amplitudes, and phases associated with GWS changes among different aquifers. It is found that GWS changes in the studied aquifers represent a spatial pattern of 'Wet-gets-more, Dry-gets-less'. An overall decreasing trend of -4.65 ± 0.34 km3/yr is observed by GRACE from 2005 to 2016, consisting of a significant (p < 0.05) increase of 47.28 ± 3.48 km3 in 7 aquifers and decrease of 103.56 ± 2.4 km3 (â¼2.6 times the full storage capacity of the Three Gorges Reservoir) in 10 aquifers summed over the 12 years. The annual GWS normally reaches a peak in late July with an area-weighted average annual amplitude of 19 mm, showing notable discrepancy in phases and amplitudes between the losing aquifers (12 mm in middle August) in northern China and gaining aquifers (28 mm in early July) mostly in southern China. GRACE estimates are generally comparable, but can be notably different, with the results obtained from model simulations and in-situ observations at aquifer scale, with the area-weighted average correlation coefficients of 0.6 and 0.5, respectively. This study highlights different GWS changes of losing and gaining aquifers in response to coupled impacts of hydrogeology, climate and human interventions, and calls for divergent adaptions in regional groundwater management.
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Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 Mâ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.
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Due to low immobilized ligand density, limited binding capacity, and severe interference from serum proteins, developing ideal peptide-based biomaterials for precise recognition and in vivo analysis of biopharmaceuticals remains a huge challenge. In this study, mimotope peptide modified pompon mum-like biomimetic magnetic microparticles (MMPs, 3.8 µm) that mimic the specific functionalities of CD20 on malignant B cells were developed for the first time. Benefit from the numerous ligand binding sites (Ni2+) on the pompon mum-like MMPs, these novel materials achieved ≥10 times higher peptide ligand densities (>2300 mg/g) and antibody binding capacities (1380 mg/g) compared to previous reported biomaterials. Leveraging the high specificity of the mimotope peptide, rituximab can be precisely recognized and enriched from cell culture media or serum samples. We also established an LCâMS/MS method using the MMPs for tracking rituximab biotransformation in patient serum. Intriguingly, deamidation of Asn55 and Asn33, as well as oxidation of Met81 and Met34 were observed at the key complementarity determining regions of rituximab, which could potentially influence antibody function and require careful monitoring. Overall, these versatile biomimetic MMPs demonstrate superior recognition and enrichment capabilities for target antibodies, offering interesting possibilities for biotransformation analysis of biopharmaceuticals in patient serum.
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The effectiveness of the SAR object detection technique based on Convolutional Neural Networks (CNNs) has been widely proven, and it is increasingly used in the recognition of ship targets. Recently, efforts have been made to integrate transformer structures into SAR detectors to achieve improved target localization. However, existing methods rarely design the transformer itself as a detector, failing to fully leverage the long-range modeling advantages of self-attention. Furthermore, there has been limited research into multi-class SAR target detection. To address these limitations, this study proposes a SAR detector named CCDN-DETR, which builds upon the framework of the detection transformer (DETR). To adapt to the multiscale characteristics of SAR data, cross-scale encoders were introduced to facilitate comprehensive information modeling and fusion across different scales. Simultaneously, we optimized the query selection scheme for the input decoder layers, employing IOU loss to assist in initializing object queries more effectively. Additionally, we introduced constrained contrastive denoising training at the decoder layers to enhance the model's convergence speed and improve the detection of different categories of SAR targets. In the benchmark evaluation on a joint dataset composed of SSDD, HRSID, and SAR-AIRcraft datasets, CCDN-DETR achieves a mean Average Precision (mAP) of 91.9%. Furthermore, it demonstrates significant competitiveness with 83.7% mAP on the multi-class MSAR dataset compared to CNN-based models.
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Genetic variants can influence complex traits by altering gene expression through changes to regulatory elements. However, the genetic variants that affect the activity of regulatory elements in pigs are largely unknown, and the extent to which these variants influence gene expression and contribute to the understanding of complex phenotypes remains unclear. Here, we annotate 90,991 high-quality regulatory elements using acetylation of histone H3 on lysine 27 (H3K27ac) ChIP-seq of 292 pig livers. Combined with genome resequencing and RNA-seq data, we identify 28,425 H3K27ac quantitative trait loci (acQTLs) and 12,250 expression quantitative trait loci (eQTLs). Through the allelic imbalance analysis, we validate two causative acQTL variants in independent datasets. We observe substantial sharing of genetic controls between gene expression and H3K27ac, particularly within promoters. We infer that 46% of H3K27ac exhibit a concomitant rather than causative relationship with gene expression. By integrating GWAS, eQTLs, acQTLs, and transcription factor binding prediction, we further demonstrate their application, through metabolites dulcitol, phosphatidylcholine (PC) (16:0/16:0) and published phenotypes, in identifying likely causal variants and genes, and discovering sub-threshold GWAS loci. We provide insight into the relationship between regulatory elements and gene expression, and the genetic foundation for dissecting the molecular mechanism of phenotypes.
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Histonas , Sequências Reguladoras de Ácido Nucleico , Animais , Suínos/genética , Histonas/genética , Histonas/metabolismo , Fenótipo , Locos de Características Quantitativas , Fígado/metabolismoRESUMO
PURPOSE: This study aimed to build and evaluate a deep learning (DL) model to predict vessels encapsulating tumor clusters (VETC) and prognosis preoperatively in patients with hepatocellular carcinoma (HCC). METHODS: 320 pathologically confirmed HCC patients (58 women and 262 men) from two hospitals were included in this retrospective study. Institution 1 (n = 219) and Institution 2 (n = 101) served as the training and external test cohorts, respectively. Tumors were evaluated three-dimensionally and regions of interest were segmented manually in the arterial, portal venous, and delayed phases (AP, PP, and DP). Three ResNet-34 DL models were developed, consisting of three models based on a single sequence. The fusion model was developed by inputting the prediction probability of the output from the three single-sequence models into logistic regression. The area under the receiver operating characteristic curve (AUC) was used to compare performance, and the Delong test was used to compare AUCs. Early recurrence (ER) was defined as recurrence within two years of surgery and early recurrence-free survival (ERFS) rate was evaluated by Kaplan-Meier survival analysis. RESULTS: Among the 320 HCC patients, 227 were VETC- and 93 were VETC+ . In the external test cohort, the fusion model showed an AUC of 0.772, a sensitivity of 0.80, and a specificity of 0.61. The fusion model-based prediction of VETC high-risk and low-risk categories exhibits a significant difference in ERFS rates, akin to the outcomes observed in VETC + and VETC- confirmed through pathological analyses (p < 0.05). CONCLUSIONS: A DL framework based on ResNet-34 has demonstrated potential in facilitating non-invasive prediction of VETC as well as patient prognosis.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Neoplasias Vasculares , Masculino , Humanos , Feminino , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética , PrognósticoRESUMO
BACKGROUND: Vessels encapsulating tumor cluster (VETC) is a critical prognostic factor and therapeutic predictor of hepatocellular carcinoma (HCC). However, noninvasive evaluation of VETC remains challenging. PURPOSE: To develop and validate a deep learning radiomic (DLR) model of dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative discrimination of VETC and prognosis of HCC. STUDY TYPE: Retrospective. POPULATION: A total of 221 patients with histologically confirmed HCC and stratified this cohort into training set (n = 154) and time-independent validation set (n = 67). FIELD STRENGTH/SEQUENCE: A 1.5 T and 3.0 T; DCE imaging with T1-weighted three-dimensional fast spoiled gradient echo. ASSESSMENT: Histological specimens were used to evaluate VETC status. VETC+ cases had a visible pattern (≥5% tumor area), while cases without any pattern were VETC-. The regions of intratumor and peritumor were segmented manually in the arterial, portal-venous and delayed phase (AP, PP, and DP, respectively) of DCE-MRI and reproducibility of segmentation was evaluated. Deep neural network and machine learning (ML) classifiers (logistic regression, decision tree, random forest, SVM, KNN, and Bayes) were used to develop nine DLR, 54 ML and clinical-radiological (CR) models based on AP, PP, and DP of DCE-MRI for evaluating VETC status and association with recurrence. STATISTICAL TESTS: The Fleiss kappa, intraclass correlation coefficient, receiver operating characteristic curve, area under the curve (AUC), Delong test and Kaplan-Meier survival analysis. P value <0.05 was considered as statistical significance. RESULTS: Pathological VETC+ were confirmed in 68 patients (training set: 46, validation set: 22). In the validation set, DLR model based on peritumor PP (peri-PP) phase had the best performance (AUC: 0.844) in comparison to CR (AUC: 0.591) and ML (AUC: 0.672) models. Significant differences in recurrence rates between peri-PP DLR model-predicted VETC+ and VETC- status were found. DATA CONCLUSIONS: The DLR model provides a noninvasive method to discriminate VETC status and prognosis of HCC patients preoperatively. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.
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Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Teorema de Bayes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagem , Prognóstico , Imageamento por Ressonância MagnéticaRESUMO
The safety of drinking water has always been a concern for people all over the world. N-nitrosamines (NAs), a kind of nitrogenous disinfection by-products (N-DBPs), are generally detected as a mixture in drinking water at home and abroad. Studies have shown that individual NAs posed strong carcinogenicity at high concentrations. However, health risks of NAs at environmental levels (concentrations in drinking water) are still unclear. Therefore, the potential health risks of environmentally relevant NAs exposure in drinking water needs to be conducted. In this study, blood biochemical analysis and metabolomics based on nuclear magnetic resonance (NMR) were performed to comprehensively investigate NAs induced metabolic disturbance in infant rats at environmental levels. Results of blood biochemical indices analysis indicated that AST in the serum of male rats in NAs-treated group exhibited a significant gender-specific difference. Multivariate statistics showed that two and eight significantly disturbed metabolic pathways were identified in the serum samples of NAs-treated male and female rats, respectively. In the urine samples of NAs-treated female rats, glycine, serine, and threonine metabolism pathway was significantly disturbed; while three significantly disturbed metabolic pathways were found in the urine of NAs-treated male rats. Finally, results of spearman correlation coefficients suggested that the disturbances of metabolism profile in serum and urine were correlated with changes in the gut microbiota (data derived from our published paper). Data presented here aimed to generate new health risk data of NAs mixture exposure at environmental levels and provide theoretical support for drinking water safety management. ENVIRONMENTAL IMPLICATION: N-nitrosamines (NAs) are a kind of nitrogenous disinfection by-products (N-DBPs) generated during drinking water disinfection processes. Herein, health risks of NAs at environmental levels (concentrations in drinking water) are investigated using blood biochemical analysis and nuclear magnetic resonance (NMR)-based metabolomics. Results confirmed NAs induced gender-specific on the metabolism in rat and the disturbances of metabolism profile in serum and urine were correlated with changes in the gut microbiota. Data presented here aimed to generate new health risk data of NAs mixture exposure at environmental levels and provide theoretical support for drinking water safety management.