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To address the shortcomings of traditional reliability theory in characterizing the stability of deep underground structures, the advanced first order second moment of reliability was improved to obtain fuzzy random reliability, which is more consistent with the working conditions. The traditional sensitivity analysis model was optimized using fuzzy random optimization, and an analytical calculation model of the mean and standard deviation of the fuzzy random reliability sensitivity was established. A big data hidden Markov model and expectation-maximization algorithm were used to improve the digital characteristics of fuzzy random variables. The fuzzy random sensitivity optimization model was used to confirm the effect of concrete compressive strength, thick-diameter ratio, reinforcement ratio, uncertainty coefficient of calculation model, and soil depth on the overall structural reliability of a reinforced concrete double-layer wellbore in deep alluvial soil. Through numerical calculations, these characteristics were observed to be the main influencing factors. Furthermore, while the soil depth was negatively correlated, the other influencing factors were all positively correlated with the overall reliability. This study provides an effective reference for the safe construction of deep underground structures in the future.
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BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.
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Aprendizaje Profundo , Órganos en Riesgo , Planificación de la Radioterapia Asistida por Computador , Neoplasias del Recto , Humanos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/patología , Órganos en Riesgo/efectos de la radiación , Estudios Retrospectivos , Planificación de la Radioterapia Asistida por Computador/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Dosificación Radioterapéutica , Tomografía Computarizada por Rayos X , Adulto , Radioterapia de Intensidad Modulada/métodosRESUMEN
Purpose: Repeated cone-beam CT (CBCT) scans for image-guided radiotherapy (IGRT) increase the health risk of radiation-induced malignancies. Patient-enrolled studies to optimize scan protocols are inadequate. We proposed a virtual clinical trial-based approach to evaluate projection-reduced low-dose CBCT for IGRT. Materials and methods: A total of 71 patients were virtually enrolled with 26 head, 23 thorax and 22 pelvis scans. Projection numbers of full-dose CBCT scans were reduced to 1/2, 1/4, and 1/8 of the original to simulate low-dose scans. Contrast-to-noise ratio (CNR) values in fat and muscle were measured in the full-dose and low-dose images. CBCT images were registered to planning CT to derive 6-degree-of-freedom couch shifts. Registration errors were statistically analyzed with the Wilcoxon paired signed-rank test. Results: As projection numbers were reduced, CNR values descended and the magnitude of registration errors increased. The mean CNR values of full-dose and half-dose CBCT were >3.0. For full-dose and low-dose CBCT (i.e. 1/2, 1/4 and 1/8 full-dose), the mean registration errors were< ± 0.4 mm in translational directions (LAT, LNG, VRT) and ±0.2 degree in rotational directions (Pitch, Roll, Yaw); the mean magnitude of registration errors were< 1 mm in translation and< 0.5 degree in rotation. The couch shift differences between full-dose and low-dose CBCT were not statistically significant (p>0.05) in all the directions. Conclusion: The results indicate that while the impact of dose-reduction on CBCT couch shifts is not significant, the impact on CNR values is significant. Further validation on optimizing CBCT imaging dose is required.
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OBJECTIVE: To evaluate the effect of the labiolingual diameter and construction of an endodontically treated (ET) anterior tooth with crown restoration on stress distribution and biomechanical safety under occlusal loading. METHODOLOGY: Three-dimensional finite element models were generated for maxillary central incisors with all-ceramic crown restorations. The labiolingual diameters of the tooth, defined as the horizontal distance between the protrusion of the labial and lingual surfaces, were changed as follows: (D1) 6.85 mm, (D2) 6.35 mm, and (D3) 5.85 mm. The model was constructed as follows: (S0) vital pulp tooth; (S1) ET tooth; (S2) ET tooth with a 2 mm ferrule, restored with a fiber post and composite resin core; (S3) ET tooth without a ferrule, restored with a fiber post and composite resin core. A total of 12 models were developed. In total, two force loads (100 N) were applied to the crown's incisal edge and palatal surface at a 45° oblique angle to the longitudinal axis of the teeth. The Von Mises stress distribution and maximum stress of the models were analyzed. RESULTS: Regardless of the loading location, stress concentration and maximum stress (34.07~66.78MPa) in all models occurred in the labial cervical 1/3 of each root. Both labiolingual diameter and construction influenced the maximum stress of the residual tooth tissue, with the impact of the labiolingual diameter being greater. A reduction in labiolingual diameter led to increased maximum stress throughout the tooth. The ferrule reduced the maximum stress of the core of S2 models (7.15~10.69 MPa), which is lower compared with that of S3 models (19.45~43.67 MPa). CONCLUSION: The labiolingual diameter exerts a greater impact on the biomechanical characteristics of ET anterior teeth with crown restoration, surpassing the influence of the construction. The ferrule can reduce the maximum stress of the core and maintain the uniformity of stress distribution.
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Resinas Compuestas , Coronas , Análisis del Estrés Dental , Análisis de Elementos Finitos , Incisivo , Diente no Vital , Diente no Vital/fisiopatología , Humanos , Fenómenos Biomecánicos , Incisivo/anatomía & histología , Incisivo/fisiología , Resinas Compuestas/química , Análisis del Estrés Dental/métodos , Técnica de Perno Muñón , Reproducibilidad de los Resultados , Estrés Mecánico , Valores de Referencia , Fuerza de la Mordida , Imagenología Tridimensional/métodos , Diseño de Prótesis Dental , Ensayo de Materiales , Corona del Diente/anatomía & histología , Corona del Diente/fisiologíaRESUMEN
PURPOSE: Residual lymph node metastases (RLNM) remained a great concern in the implementation of organ-preserving strategies and led to poor prognosis in locally advanced rectal cancer (LARC). In this study, we aimed to identify the clinicopathological factors correlated with RLNM in LARC patients with ypT0-2 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 417 patients histologically diagnosed middle-low LARC after NCRT and total mesorectal excision (TME), whose pathological staging was ypT0-2. All patients received pelvic magnetic resonance imaging (MRI) before NCRT. The radiation doses were 50-50.6 Gy for the planning gross tumor volume and 41.8-45 Gy for the planning target volume, respectively. A nomogram for predicting RLNM was constructed using a binary logistic regression. Nomogram performance was assessed by receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC). RESULTS: After surgery, 191 patients (45.8%) were ypT0, 43 patients (10.3%) were ypT1 and 183 patients (43.9%) were ypT2, and a total of 49 patients (11.8%) were found the presence of RLNM. Multivariable analyses identified MRI-defined mesorectal fascia (MRF)-positive, high-grade histopathology at biopsy, advanced ypT-category, and the presence of perineural invasion (PNI) as the predictive factors. The nomogram, incorporating all these predictors, showed good discrimination and calibration efficacy, with the areas under the ROC curve of 0.690 (95% CI: 0.610-0.771). Both DCA and CIC demonstrated that this nomogram has good clinical usefulness. CONCLUSION: The nomogram model can predict RLNM in patients with ypT0-2 tumors. It can help select suitable patients for performing organ-preserving strategies after NCRT.
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Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , Metástasis Linfática , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Quimioradioterapia , Quimioradioterapia Adyuvante , Neoplasias Primarias Secundarias/patologíaRESUMEN
The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2 . Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.
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PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Estadificación de Neoplasias , Quimioradioterapia , Pronóstico , Neoplasias del Recto/patologíaRESUMEN
This study evaluated the feasibilities and outcomes following four-dimensional magnetic resonance imaging (4D-MRI) assisted stereotactic body radiation therapy (SBRT) for unresectable colorectal liver metastases (CRLMs). From March 2018 to January 2022, we identified 76 unresectable CRLMs patients with 123 lesions who received 4D-MRI guided SBRT in our institution. 4D-MRI simulation with or without abdominal compression was conducted for all patients. The prescription dose was 50-65 Gy in 5-12 fractions. The image quality of computed tomography (CT) and MRI were compared using the Clarity Score. Clinical outcomes and toxicity profiles were evaluated. 4D-MRI improved the image quality compared with CT images (mean Clarity Score: 1.67 vs 2.88, P < 0.001). The abdominal compression reduced motions in cranial-caudal direction (P = 0.03) with two phase T2 weighted images assessing tumor motion. The median follow-up time was 12.5 months. For 98 lesions assessed for best response, the complete response, partial response and stable disease rate were 57.1 %, 30.6 % and 12.2 %, respectively. The local control (LC) rate at 1 year was 97.3 %. 46.1 % of patients experienced grade 1-2 toxicities and only 2.6 % patients experienced grade 3 hematologic toxicities. The 4D-MRI technique allowed accurate target delineation and motion tracking in unresectable CRLMs patients. Favorable LC rate and mild toxicities were achieved. This study provided evidence for using 4D-MRI assisted SBRT as an alternative treatment in unresectable CRLMs.
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Abstract Objective To evaluate the effect of the labiolingual diameter and construction of an endodontically treated (ET) anterior tooth with crown restoration on stress distribution and biomechanical safety under occlusal loading. Methodology Three-dimensional finite element models were generated for maxillary central incisors with all-ceramic crown restorations. The labiolingual diameters of the tooth, defined as the horizontal distance between the protrusion of the labial and lingual surfaces, were changed as follows: (D1) 6.85 mm, (D2) 6.35 mm, and (D3) 5.85 mm. The model was constructed as follows: (S0) vital pulp tooth; (S1) ET tooth; (S2) ET tooth with a 2 mm ferrule, restored with a fiber post and composite resin core; (S3) ET tooth without a ferrule, restored with a fiber post and composite resin core. A total of 12 models were developed. In total, two force loads (100 N) were applied to the crown's incisal edge and palatal surface at a 45° oblique angle to the longitudinal axis of the teeth. The Von Mises stress distribution and maximum stress of the models were analyzed. Results Regardless of the loading location, stress concentration and maximum stress (34.07~66.78MPa) in all models occurred in the labial cervical 1/3 of each root. Both labiolingual diameter and construction influenced the maximum stress of the residual tooth tissue, with the impact of the labiolingual diameter being greater. A reduction in labiolingual diameter led to increased maximum stress throughout the tooth. The ferrule reduced the maximum stress of the core of S2 models (7.15~10.69 MPa), which is lower compared with that of S3 models (19.45~43.67 MPa). Conclusion The labiolingual diameter exerts a greater impact on the biomechanical characteristics of ET anterior teeth with crown restoration, surpassing the influence of the construction. The ferrule can reduce the maximum stress of the core and maintain the uniformity of stress distribution.
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BACKGROUND: Mutated KRAS may indicate an invasive nature and predict prognosis in locally advanced rectal cancer (LARC). We aimed to establish a radiomic model using pretreatment T2W MRIs to predict KRAS status and explore the association between the KRAS status or model predictions and lung metastasis. METHODS: In this retrospective multicentre study, LARC patients from two institutions between January 2012 and January 2019 were randomly divided into training and testing cohorts. Least absolute shrinkage and selection operator (LASSO) regression and the support vector machine (SVM) classifier were utilized to select significant radiomic features and establish a prediction model, which was validated by radiomic score distribution and decision curve analysis. The association between the model stratification and lung metastasis was investigated by Cox regression and KaplanâMeier survival analysis; the results were compared by the log-rank test. RESULTS: Overall, 103 patients were enrolled (73 and 30 in the training and testing cohorts, respectively). The median follow-up was 38.1 months (interquartile range: 26.9, 49.4). The radiomic model had an area under the curve (AUC) of 0.983 in the training cohort and 0.814 in the testing cohort. Using a cut-off of 0.679 defined by the receiver operating characteristic (ROC) curve, patients with a high radiomic score (RS) had a higher risk for lung metastasis (HR 3.565, 95% CI 1.337, 9.505, p = 0.011), showing similar predictive performances for the mutant and wild-type KRAS groups (HR 3.225, 95% CI 1.249, 8.323, p = 0.016, IDI: 1.08%, p = 0.687; NRI 2.23%, p = 0.766). CONCLUSIONS: We established and validated a radiomic model for predicting KRAS status in LARC. Patients with high RS experienced more lung metastases. The model could noninvasively detect KRAS status and may help individualize clinical decision-making.
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Neoplasias Pulmonares , Neoplasias del Recto , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/genética , Neoplasias del Recto/terapiaRESUMEN
PURPOSE: Manual clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy is pivotal but labor-intensive. This study aims to propose a deep learning (DL)-based workflow towards fully automated clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy. MATERIALS & METHODS: We retrospectively included 141 patients with Stage II-III mid-low rectal cancer and randomly grouped them into training (n = 121) and testing (n = 20) cohorts. We adopted a divide-and-conquer strategy to address CTV and GTV segmentation using two separate DL models with DpuUnet as backend-one model for CTV segmentation in the CT domain, and the other for GTV in the MRI domain. The workflow was validated using a three-level multicenter-involved blind and randomized evaluation scheme. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) metrics were calculated in Level 1, four-grade expert scoring was performed in Level 2, and head-to-head Turing test in Level 3. RESULTS: For the DL-based CTV contours over the testing cohort, the DSC and 95HD (mean ± SD) were 0.85 ± 0.06 and 7.75 ± 6.42 mm respectively, and 96.4% cases achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.3%. For GTV, the DSC and 95HD were 0.87 ± 0.07 and 4.07 ± 1.67 mm respectively, and 100% of the DL-based contours achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.0%. CONCLUSION: The proposed DL-based workflow exhibited promising accuracy and excellent clinical viability towards automated CTV and GTV delineation for rectal cancer neoadjuvant radiotherapy.
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Aprendizaje Profundo , Neoplasias del Recto , Humanos , Terapia Neoadyuvante , Estudios Retrospectivos , Neoplasias del Recto/radioterapia , Neoplasias del Recto/patología , Imagen por Resonancia Magnética , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
OBJECTS: Changes in condylar position and morphology after mandibular reconstruction are important to aesthetic and functional rehabilitation. We evaluated changes in condylar position and morphology at different stages after mandibular reconstruction using vascularized fibular free flap with condyle preservation. MATERIALS AND METHODS: A total of 23 patients who underwent mandibular reconstruction with fibular flap were included in this retrospective study. CT data of all patients were recorded before surgery (T0), 7 to 14 days after surgery (T1), and at least 6 months after surgery (T2). Five parameters describing the condylar position and 4 parameters describing the morphology were measured in sagittal and coronal views of CT images. The association between clinical characteristics and changes in condylar position and morphology was analyzed. A finite element model was established to investigate the stress distribution and to predict the spatial movement tendency of the condyle after reconstruction surgery. RESULTS: The condylar position changed over time after mandibular reconstruction. The ipsilateral condyles moved inferiorly after surgery (T0 to T1) and continually move anteriorly, inferiorly, and laterally during long-term follow-up (T1 to T2). Contrary changes were noted in the contralateral condyles with no statistical significance. No morphological changes were detected. The relationship between clinical characteristics and changes in condylar position and morphology was not statistically significant. A consistent result was observed in the finite element analysis. CONCLUSION: Condylar positions showed obvious changes over time after mandibular reconstruction with condylar preservation. Nevertheless, further studies should be conducted to evaluate the clinical function outcomes and condylar position. CLINICAL RELEVANCE: These findings can form the basis for the evaluation of short-term and long-term changes in condylar position and morphology among patients who have previously undergone mandibular reconstruction by FFF with condyle preservation.
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Objective: The aim of this paper is to analyze the application of machine learning in heart failure-associated diseases using bibliometric methods and to provide a dynamic and longitudinal bibliometric analysis of heart failure-related machine learning publications. Materials and methods: Web of Science was screened to gather the articles for the study. Based on bibliometric indicators, a search strategy was developed to screen the title for eligibility. Intuitive data analysis was employed to analyze the top-100 cited articles and VOSViewer was used to analyze the relevance and impact of all articles. The two analysis methods were then compared to get conclusions. Results: The search identified 3,312 articles. In the end, 2,392 papers were included in the study, which were published between 1985 and 2023. All articles were analyzed using VOSViewer. Key points of the analysis included the co-authorship map of authors, countries and organizations, the citation map of journal and documents and a visualization of keyword co-occurrence analysis. Among these 100 top-cited papers, with a mean of 122.9 citations, the most-cited article had 1,189, and the least cited article had 47. Harvard University and the University of California topped the list among all institutes with 10 papers each. More than one-ninth of the authors of these 100 top-cited papers wrote three or more articles. The 100 articles came from 49 journals. The articles were divided into seven areas according to the type of machine learning approach employed: Support Vector Machines, Convolutional Neural Networks, Logistic Regression, Recurrent Neural Networks, Random Forest, Naive Bayes, and Decision Tree. Support Vector Machines were the most popular method. Conclusions: This analysis provides a comprehensive overview of the artificial intelligence (AI)-related research conducted in the field of heart failure, which helps healthcare institutions and researchers better understand the prospects of AI in heart failure and formulate more scientific and effective research plans. In addition, our bibliometric evaluation can assist healthcare institutions and researchers in determining the advantages, sustainability, risks, and potential impacts of AI technology in heart failure.
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Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.
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Affected by the erosive environment, tunnel lining concrete in the long-term service zprocess often exhibits engineering diseases such as concrete corrosion degradation and loss of strength, decreasing the stability of the tunnel lining structure and the traffic safety. Based on HTG tunnel project, the basic distribution rule of tunnel lining corrosion and macro mechanical properties of corroded concrete were explored in this paper through engineering disease site investigation. Then, on this basis, aiming at large-scale corrosion of tunnel lining structure, two reinforcement and repair schemes are proposed, corrugated steel plate reinforcement method and channel steel reinforcement method. Indoor component tests are carried out on the two reinforcement schemes. The failure characteristics and stress and deformation law of tunnel lining members after reinforcement and repair were verified. The analysis showed that the failure process of the reinforced specimens on the tensile side could be divided into the non-cracking stage and the working stage with cracks, and the cracking load and failure load of the specimens were significantly increased. The bearing capacity of the reinforced specimens was divided into the ultimate bearing capacity against cracking and the ultimate bearing capacity during failure. Finally, the calculation methods of the bearing capacity of the channel steel reinforcement method and the corrugated steel plate reinforcement method were derived. Comparative analysis shows that the results of numerical simulation, experimental testing and theoretical simplification methods are close to each other, and the maximum deviation is less than 8%. The established method for calculating the bearing capacity of corroded components after reinforcement is reliable and can be used for the design calculation of corroded lining reinforcement.
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Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.
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Mitofagia , Neoplasias , Humanos , Biomimética , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/metabolismo , Mitocondrias/metabolismoRESUMEN
Background: Few studies have evaluated the significance of sarcopenia in predicting the outcomes of patients with adenocarcinoma of the esophagogastric junction (AEG), especially those who received neoadjuvant chemoradiotherapy (NCRT). We aimed to identify the sarcopenic status and its impact on the outcomes of patients with locally advanced AEG who received NCRT followed by radical surgery or systemic therapy. Materials and methods: Patients with T3-4N+M0 AEG with accessible abdominal computed tomography (CT) before and after NCRT were retrospectively analyzed. Body composition parameters, particularly the skeletal muscle index (SMI), were assessed using a CT-based method, and sarcopenia was defined using a predetermined SMI cutoff value. Survival analysis was conducted using the Kaplan-Meier method. A Cox proportional hazards regression model was used to identify independent prognostic factors. Receiver operating characteristic curve analysis was carried out, and the area under the curve (AUC) was calculated to test the prognostic accuracy of different factors. Results: A total of 63 patients were enrolled, 65.1 and 79.4% of whom developed pre- and post-NCRT sarcopenia, respectively. Patients with pre-NCRT sarcopenia had lower radical surgery rates (70.7 vs. 95.5%, p = 0.047) than those without sarcopenia; however, sarcopenic status did not affect other short-term outcomes, including treatment-related toxicity and efficacy. Pre-NCRT sarcopenia was identified as an independent predictive factor for poor overall survival (OS) [adjusted hazard ratio (HR), 6.053; p = 0.002] and progression-free survival (PFS) (adjusted HR, 2.873; p = 0.031). Compared with nutritional indices such as the Nutritional Risk Screening 2002, weight loss during NCRT, and post-NCRT sarcopenia, pre-NCRT sarcopenia was regarded as the best predictive index for the 5-year OS (AUC = 0.735) and PFS rates (AUC = 0.770). Conclusion: Pre-NCRT sarcopenia may be an independent predictive factor for OS and PFS rates in patients with locally advanced AEG receiving multimodal treatment.
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BACKGROUND: Hematologic toxicity (HT) is a common adverse tissue reaction during radiotherapy for rectal cancer patients, which may lead to various negative effects such as reduced therapeutic effect, prolonged treatment period and increased treatment cost. Therefore, predicting the occurrence of HT before radiotherapy is necessary but still challenging. PURPOSE: This study proposes a hybrid machine learning model to predict the symptomatic radiation HT in rectal cancer patients using the combined demographic, clinical, dosimetric, and Radiomics features, and ascertains the most effective regions of interest (ROI) in CT images and predictive feature sets. METHODS: A discovery dataset of 240 rectal cancer patients, including 145 patients with HT symptoms and a validation dataset of 96 patients (63 patients with HT) with different dose prescription were retrospectively enrolled. Eight ROIs were contoured on patient CT images to derive Radiomics features, which were then, respectively, combined with the demographic, clinical, and dosimetric features to classify patients with HT symptoms. Moreover, the survival analysis was performed on risky patients with HT in order to understand the HT progression. RESULTS: The classification models in ROIs of bone marrow and femoral head exhibited relatively high accuracies (accuracy = 0.765 and 0.725) in the discovery dataset as well as comparable performances in the validation dataset (accuracy = 0.758 and 0.714). When combining the two ROIs together, the model performance was the best in both discovery and validation datasets (accuracy = 0.843 and 0.802). In the survival analysis test, only the bone marrow ROI achieved statistically significant performance in accessing risky HT (C-index = 0.658, P = 0.03). Most of the discriminative features were Radiomics features, and only gender and the mean dose in Irradvolume was involved in HT. CONCLUSION: The results reflect that the Radiomics features of bone marrow are significantly correlated with HT occurrence and progression in rectal cancer. The proposed Radiomics-based model may help the early detection of radiotherapy induced HT in rectal cancer patients and thus improve the clinical outcome in future.
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Traumatismos por Radiación , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Detección Precoz del Cáncer , Recto , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/radioterapia , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/etiologíaRESUMEN
BACKGROUND: An increasing number of circular RNAs (circRNAs) have been shown to play an important role in the tumorigenesis of breast cancer. The aim of this study was to investigate the expression and function of circ_0001667 and its potential molecular mechanisms in breast cancer. METHODS: The expression levels of circ_0001667, miR-6838-5p and CXC chemokine ligand 10 (CXCL10) in breast cancer tissues and cells were detected by quantitative real-time PCR. Cell counting kit-8 assay, EdU assay, flow cytometry, colony formation and tube formation assays were used to detect cell proliferation and angiogenesis. The binding relationship between miR-6838-5p and circ_0001667 or CXCL10 was predicted using the starBase3.0 database and verified by dual-luciferase reporter gene assay, RIP and RNA pulldown. Animal experiments were performed to assess the function of circ_0001667 knockdown on breast cancer tumor growth. RESULTS: Circ_0001667 was highly expressed in breast cancer tissues and cells, and its knockdown inhibited proliferation and angiogenesis of breast cancer cells. Circ_0001667 sponged miR-6838-5p, and inhibition of miR-6838-5p reversed the inhibitory effect of silencing circ_0001667 on proliferation and angiogenesis of breast cancer cells. MiR-6838-5p targeted CXCL10, and overexpression of CXCL10 reverses the effect of miR-6838-5p overexpression on breast cancer cell proliferation and angiogenesis. In addition, circ_0001667 interference also reduced breast cancer tumor growth in vivo. CONCLUSION: Circ_0001667 is involved in breast cancer cell proliferation and angiogenesis through regulation of the miR-6838-5p/CXCL10 axis.
Asunto(s)
Quimiocinas CXC , MicroARNs , Humanos , Animales , Ligandos , Carcinogénesis , Proliferación Celular , MicroARNs/genética , Quimiocina CXCL10/genéticaRESUMEN
Preoperative neoadjuvant chemoradiotherapy (nCRT) is a standard treatment for locally advanced rectal cancer (LARC) patients, yet little is known about the mediators underlying the heterogeneous patient response. In this longitudinal study, we performed 16S rRNA sequencing on 353 fecal specimens and find reduced microbial diversity after nCRT. Multi-omics data integration reveals that Bacteroides vulgatus-mediated nucleotide biosynthesis associates with nCRT resistance in LARC patients, and nonresponsive tumors are characterized by the upregulation of genes related to DNA repair and nucleoside transport. Nucleosides supplementation or B. vulgatus gavage protects cancer cells from the 5-fluorouracil or irradiation treatment. An analysis of 2,205 serum samples from 735 patients suggests that uric acid is a potential prognosis marker for LARC patients receiving nCRT. Our data unravel the role of intestinal microbiota-mediated nucleotide biosynthesis in the response of rectal tumors to nCRT, and highlight the importance of deciphering the cross-talk between cancer cells and gut microorganisms during cancer therapies.