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Accurate measurement of the dielectric functions of emerging optical materials is of great importance for advancements in solid-state physics. However, it is rather challenging since most materials are highly active in ambient conditions, which makes in-situ measurements tough. Here, we report an analytical ellipsometry method (AEM) accessible in ambient conditions for measuring the dielectric functions of chemically reactive materials under bulk encapsulation. Taking the highly pursued low-loss plasmonic materials, such as sodium films, as an example, the effectiveness and measuring errors of the proposed AEM have been systematically demonstrated. This verifies AEM's superiority in overcoming the limitations of traditional spectroscopic ellipsometry methodologies, which include complex multi-parameter fitting procedures and the issue of potentially unphysical results, especially in newly developed low-loss materials. Our results will provide a generalized and convenient ellipsometric measurement strategy for sensitive materials under bulk encapsulation.
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BACKGROUND: The prognosis of SCLC is poor and difficult to predict. The aim of this study was to explore whether a model based on radiomics and clinical features could predict the prognosis of patients with limited-stage small cell lung cancer (LS-SCLC). METHODS: Simulated positioning CT images and clinical features were retrospectively collected from 200 patients with histological diagnosis of LS-SCLC admitted between 2013 and 2021, which were randomly divided into the training (n = 140) and testing (n = 60) groups. Radiomics features were extracted from simulated positioning CT images, and the t-test and the least absolute shrinkage and selection operator (LASSO) were used to screen radiomics features. We then constructed radiomic score (RadScore) based on the filtered radiomics features. Clinical factors were analyzed using the Kaplan-Meier method. The Cox proportional hazards model was used for further analyses of possible prognostic features and clinical factors to build three models including a radiomic model, a clinical model, and a combined model including clinical factors and RadScore. When a model has prognostic predictive value (AUC > 0.7) in both train and test groups, a nomogram will be created. The performance of three models was evaluated using area under the receiver operating characteristic curve (AUC) and Kaplan-Meier analysis. RESULTS: A total of 1037 features were extracted from simulated positioning CT images which were contrast enhanced CT of the chest. The combined model showed the best prediction, with very poor AUC for the radiomic model and the clinical model. The combined model of OS included 4 clinical features and RadScore, with AUCs of 0.71 and 0.70 in the training and test groups. The combined model of PFS included 4 clinical features and RadScore, with AUCs of 0.72 and 0.71 in the training and test groups. T stages, ProGRP and smoke status were the independent variables for OS in the combined model, whereas T stages, ProGRP and prophylactic cranial irradiation (PCI) were the independent factors for PFS. There was a statistically significant difference between the low- and high-risk groups in the combined model of OS (training group, p < 0.0001; testing group, p = 0.0269) and PFS (training group, p < 0.0001; testing group, p < 0.0001). CONCLUSION: Combined models involved RadScore and clinical factors can predict prognosis in LS-SCLC and show better performance than individual radiomics and clinical models.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Prognóstico , Radiômica , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/terapia , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To investigate and characterize the performance of a novel orthogonal dual-layer alpha multileaf collimator (αMLC) mounted on the LinaTech VenusX linac. METHODS: We evaluated leaf positioning accuracy and reproducibility using an electronic portal imaging device through the picket fence test. The average, interleaf, intraleaf, and leaf tip transmissions of the single and dual layers were measured using an ionization chamber. Square and rhombus fields were used to evaluate the leaf penumbra of αMLC. To investigate the advantages of the orthogonal dual-layer multileaf collimator (MLC) in field shaping, right triangular and circular pattern fields were formed using both the dual layers and single layers of the αMLC. RESULTS: The average maximum positioning deviations of the upper and lower αMLC over 1 year were 0.76 ± 0.09 mm and 0.62 ± 0.07 mm, respectively. The average transmissions were 1.87%, 1.83%, and 0.03% for the upper-, lower- and dual-layer αMLC, respectively. The maximum interleaf transmissions of the lower- and dual-layer were 2.43% and 0.17%, respectively. The leaf tip transmissions were 9.34% and 0.25%, respectively. The penumbra of the square field was 6.2 mm in the X direction and 8.0 mm in the Y direction. The average penumbras of the rhombus fields with side lengths of 5 and 10 cm were 3.6 and 4.9 mm, respectively. For the right triangular and circular fields, the fields shaped by the dual-layer leaves were much closer to the set field than those shaped by single-layer leaves. The dose undulation amplitude of the 50% isodose lines and leaf stepping angle change of the dual-layer leaves were smaller than those of the single-layer leaves. CONCLUSIONS: The αMLC benefits from its orthogonal dual-layer design. Leaf transmission, dose undulations at the field edge, and MLC field dependence of the leaf stepping angle of the dual-layer αMLC were remarkably reduced.
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Aceleradores de Partículas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Aceleradores de Partículas/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias/radioterapia , Imagens de FantasmasRESUMO
Objectives: To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. Methods: This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. Results: At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Conclusion: Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.
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INTRODUCTION: Although high-dose erythropoiesis-stimulating agent (ESA) has been shown to increase mortality risk and adverse cardiovascular events in hemodialysis patients, the safety of extremely low-dose ESA is unclear. METHODS: We retrospectively analyzed the association between ESA dose and mortality in the monthly dosing range of 0-43,000 U of equivalent epoetin alfa in 304 Taiwan hemodialysis patients by using Cox proportional hazard model and cubic spline model. RESULTS: Compared with mean monthly ESA dose of 15,000-25,000 U (mean ± standard deviation 20,609 ± 2,662 U), monthly ESA dose of less than 15,000 U (mean ± standard deviation 7,413 ± 4,510 U) is associated with increased mortality. Monthly ESA dose of 25,001-43,000 U (mean ± standard deviation 31,160 ± 4,304 U) is not associated with higher mortality risk than monthly ESA dose of 15,000-25,000 U. The results were consistent in Cox proportional hazard models and cubic spline models. Subgroup analyses showed no significant heterogeneities among prespecified subgroups. CONCLUSIONS: Extremely low dose of ESA in hemodialysis patients may be associated with increased mortality risk. Future studies are warranted to prove this association.
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Eritropoetina , Hematínicos , Humanos , Hematínicos/efeitos adversos , Estudos Retrospectivos , Eritropoese , Diálise Renal/métodos , Epoetina alfa , Hemoglobinas , Eritropoetina/efeitos adversosRESUMO
Objective: To observe the therapeutic effect of natamycin combined with voriconazole in the treatment of fungal keratitis (FK). Methods: This is a retrospective study. The subjects of this study were 64 patients with FK who were admitted to Baoding No.1 Central Hospital from February 2019 to July 2022. The enrolled patients were divided into control group (n= 32) and study group (n= 32) by the random number table method. The control group was treated with natamycin alone, and the study group was treated with natamycin combined with voriconazole. The total efficacy, time of disappearance of ocular symptoms, visual acuity level, keratitis severity score, corneal ulcer area, tear fungus index and incidence of adverse reactions were compared between the two groups. Results: The total efficacy,of the study group was significantly higher than that of the control group. The disappearance time of corneal ulcer, photophobia, foreign body sensation and hypopyon in the study group was shorter than those in the control group. Keratitis severity score and (1,3)-ß-D-glucan level in the study group were lower than those in the control group. The corneal ulcer area was narrowed in the study group than that of the control group, and the visual acuity level in the former group was higher than that of the latter group. Besides, there was no significant difference in the frequency of adverse reactions between the two groups. Conclusion: Natamycin combined with voriconazole is safe and effective in the treatment of FK.
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BACKGROUND: Immunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive. METHODS: In this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups. RESULTS: Analysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year, p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116-0.784, p = 0.010). CONCLUSIONS: Our findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.
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Mesângio Glomerular/metabolismo , Imunoglobulina M/metabolismo , Nefrose Lipoide/etiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Accurate segmentation of brain tumors is vital for the gross tumor volume (GTV) definition in radiotherapy. Functional MR images like apparent diffusion constant (ADC) and fractional anisotropy (FA) images can provide more comprehensive information for sensitive detection of the GTV. We synthesize anatomical and functional MRI for accurate and semi-automatic segmentation of GTVs and improvement of clinical efficiency. METHODS: Four MR image sets including T1-weighted contrast-enhanced (T1C), T2-weighted (T2), apparent diffusion constant (ADC) and fractional anisotropy (FA) images of 5 glioma patients were acquired and registered. A new potential field segmentation (PFS) method was proposed based on the concept of potential field in physics. For T1C, T2 and ADC images, global potential field segmentation (global-PFS) was used on user defined region of interest (ROI) for rough segmentation and then morphologically processed for accurate delineation of the GTV. For FA images, white matter (WM) was removed using local potential field segmentation (local-PFS), and then tumor extent was delineated with region growing and morphological methods. The individual segmentations of multi-parametric images were ensembled into a fused segmentation, considered as final GTV. GTVs were compared with manually delineated ground truth and evaluated with segmentation quality measure (Q), Dice's similarity coefficient (DSC) and Sensitivity and Specificity. RESULTS: Experimental study with the five patients' data and new method showed that, the mean values of Q, DSC, Sensitivity and Specificity were 0.80 (±0.07), 0.88 (±0.04), 0.92 (±0.01) and 0.88 (±0.05) respectively. The global-PFS used on ROIs of T1C, T2 and ADC images can avoid interferences from skull and other non-tumor areas. Similarity to local-PFS on FA images, it can also reduce the time complexity as compared with the global-PFS on whole image sets. CONCLUSIONS: Efficient and semi-automatic segmentation of the GTV can be achieved with the new method. Combination of anatomical and functional MR images has the potential to provide new methods and ideas for target definition in radiotherapy.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Anisotropia , Humanos , Imageamento por Ressonância Magnética Multiparamétrica , Sensibilidade e EspecificidadeRESUMO
This study was to explore the feasibility of prediction and classification of cells in different stages of apoptosis with a stain-free method based on diffraction images and supervised machine learning. Apoptosis was induced in human chronic myelogenous leukemia K562 cells by cis-platinum (DDP). A newly developed technique of polarization diffraction imaging flow cytometry (p-DIFC) was performed to acquire diffraction images of the cells in three different statuses (viable, early apoptotic and late apoptotic/necrotic) after cell separation through fluorescence activated cell sorting with Annexin V-PE and SYTOX® Green double staining. The texture features of the diffraction images were extracted with in-house software based on the Gray-level co-occurrence matrix algorithm to generate datasets for cell classification with supervised machine learning method. Therefore, this new method has been verified in hydrogen peroxide induced apoptosis model of HL-60. Results show that accuracy of higher than 90% was achieved respectively in independent test datasets from each cell type based on logistic regression with ridge estimators, which indicated that p-DIFC system has a great potential in predicting and classifying cells in different stages of apoptosis.
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Apoptose , Citometria de Fluxo/métodos , Aprendizado de Máquina Supervisionado , Anexina A5 , Diagnóstico por Imagem/métodos , Estudos de Viabilidade , Humanos , Células K562 , Coloração e RotulagemRESUMO
Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNALys with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site.
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Anticódon/química , Apoproteínas/química , Proteínas de Bactérias/química , Toxinas Bacterianas/química , Endorribonucleases/química , Mycobacterium tuberculosis/química , RNA de Transferência de Lisina/química , Sequência de Aminoácidos , Apoproteínas/genética , Apoproteínas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Toxinas Bacterianas/genética , Toxinas Bacterianas/metabolismo , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Endorribonucleases/genética , Endorribonucleases/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Modelos Moleculares , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/patogenicidade , Conformação de Ácido Nucleico , Ligação Proteica , Domínios Proteicos , Estrutura Secundária de Proteína , RNA de Transferência de Lisina/genética , RNA de Transferência de Lisina/metabolismo , Proteínas Recombinantes , Alinhamento de Sequência , Homologia Estrutural de Proteína , Relação Estrutura-AtividadeRESUMO
Protein-lipid interactions are an essential element of the function of many membrane ion-channel proteins. These potential interactions should be considered alongside the diversity and complexity of membrane lipid composition. Phospholamban (PLN) is an inhibitor of sarcoplasmic reticulum Ca2+ ATPase (SERCA). PLN is a 52-residue transmembrane protein encoded by lncRNA, and PLN monomers form stable pentamers of biological function in a lipid bilayer membrane. Some earlier studies suggest that it can form a cationic selective channel, while others suggest that it can only store ions. Here, we report the distribution of different lipids in the membrane and the structural dynamics and conductance properties of PLN pentamers after coarse-grained (CG) and all-atom (AA) molecular dynamics simulations of different systems. The results show that cholesterol is highly enriched around the protein and stabilizes the structure of the PLN pentamer. The absence of cholesterol increases the flexibility of the protein backbone. The conductance properties of monovalent ions and water suggest that they cannot spontaneously permeate through the PLN pentamer channel pore. However, the energy barrier to overcome is much lower in the absence of cholesterol, underlining the need to fully consider multiple lipid species when investigating small transmembrane protein oligomer ion-channel structure and conductance.
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Bicamadas Lipídicas , Lipídeos de Membrana , Bicamadas Lipídicas/química , Proteínas de Ligação ao Cálcio/química , Cátions/metabolismoRESUMO
Aquaporin 4 (AQP4) facilitates the transport of reactive oxygen species (ROS). Both cancer cells and the ionizing radiation microenvironment can induce posttranslational modifications (PTMs) in AQP4, which may affect its permeability to ROS. Because this ROS diffusion process is rapid, microscopic, and instantaneous within and outside cells, conventional experimental methods are inadequate for elucidating the molecular mechanisms involved. In this study, computational methods were employed to investigate the permeability of exogenous ROS mediated by radiation in AQP4 at a molecular scale. We constructed a simulation system incorporating AQP4 and AQP4-Cysp13 in a complex lipid environment with ROS. Long-timescale molecular dynamics simulations were conducted to assess the structural stability of both AQP4 and AQP4-Cysp13. Free energy calculations were utilized to determine the ROS transport capability of the two AQP4 proteins. Computational electrophysiology and channel structural analysis quantitatively evaluated changes in ROS transport capacity under various radiation-induced transmembrane voltage microenvironments. Our findings demonstrate the distinct transport capabilities of AQP4 channels for water molecules and various types of ROS and reveal a decrease in transport efficiency when AQP4 undergoes palmitoylation modification. In addition, we have simulated the radiation-induced alteration of cell membrane voltage, which significantly affected the ROS transport capacity. We propose that this research will enhance the understanding of the molecular mechanisms governing the transport of exogenous ROS by AQP4 and elucidate the influence of palmitoylation on ROS transport. This study will also help clarify how different structural features of AQP4 affect the transport of exogenous ROS mediated by radiotherapy, thereby providing a theoretical molecular basis for the development of new treatment strategies that combine with radiotherapy.
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Aquaporina 4 , Lipoilação , Aquaporina 4/química , Aquaporina 4/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Membrana Celular/metabolismo , Permeabilidade , Água/metabolismoRESUMO
The M protein of the novel coronavirus 2019 (SARS-CoV-2) is the major structural component of the viral envelope and is also the minimum requirement for virus particle budding. M proteins generally exist as dimers. In virus assembly, they are the main driving force for envelope formation through lateral interactions and interactions with other viral structural proteins that play a central role. We built 100 candidate models and finally analyzed the six most convincing structural features of the SARS-CoV-2 M protein dimer based on long-timescale molecular dynamics (MD) simulations, multiple free energy analyses (potential mean force (PMF) and molecular mechanics Poisson-Boltzmann surface area (MMPBSA)) and principal component analysis (PCA) to obtain the most reasonable structure. The dimer stability was found to depend on the Leu-Ile zipper motif and aromatic amino acids in the transmembrane domain (TMD). Furthermore, the C-terminal domain (CTD) effects were relatively small. These results highlight a model in which there is sufficient binding affinity between the TMDs of M proteins to form dimers through the residues at the interface of the three transmembrane helices (TMHs). This study aims to help find more effective inhibitors of SARS-CoV-2 M dimers and to develop vaccines based on structural information.
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Newly-diagnosed or relapses of immunoglobulin A nephropathy (IgAN) have been associated with COVID-19 vaccination in the literature. Most reported cases were mild clinical diseases characterized by microscopic haematuria and do not require dialysis treatment. This current case report describes a 55-year-old male patient that presented to the emergency department with acute kidney injury after receiving the first dose of the mRNA-1273 COVID-19 vaccine. After admission, his renal function deteriorated rapidly, and then he developed uraemic encephalopathy. He underwent emergency haemodialysis with a rapid improvement in his mental status. Renal biopsy showed newly-diagnosed IgA nephropathy along with markedly elevated plasma level of galactose-deficient-IgA1 (Gd-IgA1) antibody. The patient did not receive immunosuppressive treatment and is now dialysis-free. Immune activation is considered an essential factor in developing or exacerbating IgAN following COVID-19 vaccination. This current case report demonstrates that elevated Gd-IgA1 antibody may be the potential mechanistic link between COVID-19 vaccination and IgAN.
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Vacinas contra COVID-19 , COVID-19 , Glomerulonefrite por IGA , Humanos , Masculino , Pessoa de Meia-Idade , Vacina de mRNA-1273 contra 2019-nCoV , Vacinas contra COVID-19/efeitos adversos , Galactose , Imunoglobulina A , RNA Mensageiro , Vacinação/efeitos adversosRESUMO
Our prior study indicates a close relationship between alternative complement pathway activation, galactose-deficient IgA1 (Gd-IgA1) concentration and clinical severity of IgA nephropathy (IgAN). Nonetheless, the relationship between complement factors and the updated Oxford classification of IgAN remains unclear. This study enrolled eighty-four previously untreated, biopsy-diagnosed IgAN patients. The clinical and laboratory findings were collected at the time of biopsy. Plasma levels of complement factor C5a, factor Ba and Gd-IgA1 were measured and analyzed. It was found that the levels of proteinuria positively correlated with the updated Oxford classification of mesangial hypercellularity (M), endocapillary hypercellularity (E), tubular atrophy/interstitial fibrosis (T) and crescents (C). In addition, plasma Gd-IgA1 titer was significantly elevated in IgAN patients with tubular atrophy/interstitial fibrosis (T). In separate multivariable logistic regression models, both Gd-IgA1 and factor Ba independently predict higher T scores. The results indicate that both the levels of Gd-IgA1 antibody and biomarkers of the alternative complement pathway activation reflect the Oxford classification of IgAN. Whether these biomarkers can be used to guide therapeutic decisions requires further study.
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As a useful tool, artificial intelligence has surpassed human beings in many fields. Artificial intelligence-based automated radiotherapy planning strategies have been proposed in lots of cancer sites and are the future of treatment planning. Postmastectomy radiotherapy (PMRT) decreases local recurrence probability and improves overall survival, and volumetric modulated arc therapy (VMAT) has gradually become the mainstream technique of radiotherapy. However, there are few customized effective automated treatment planning schemes for postmastectomy VMAT so far. This study investigated an artificial intelligence based automated planning using the MD Anderson Cancer Center AutoPlan (MDAP) system and Pinnacle treatment planning system (TPS), to effectively generate high-quality postmastectomy VMAT plans. In this study, 20 patients treated with PMRT were retrospectively investigated, including 10 left- and 10 right-sided postmastectomy patients. Chest wall and the supraclavicular, subclavicular, and internal mammary regions were delineated as target volume by radiation oncologists, and 50 Gy in 25 fractions was prescribed. Organs at risk including heart, spinal cord, left lung, right lung, and lungs were also contoured. All patients were planned with VMAT using 2 arcs. An optimization objective template was summarized based on the dose of clinical plans and requirements from oncologists. Several treatment planning parameters were investigated using an artificial intelligence algorithm, including collimation angle, jaw collimator mode, gantry spacing resolution (GSR), and number of start optimization times. The treatment planning parameters with the best performance or that were most preferred were applied to the automated treatment planning method. Dosimetric indexes of automated treatment plans (autoplans) and manual clinical plans were compared by the paired t-test. The jaw tracking mode, 2-degree GSR, and 3 rounds of optimization were selected in all the PMRT autoplans. Additionally, the 350- and 10-degree collimation angles were selected in the left- and right-sided PMRT autoplans, respectively. The uniformity index and conformity index of the planning target volume, mean heart dose, spinal cord D0.03cc, mean lung dose, and V5Gy and V20Gy of the lung of autoplans were significantly better compared with the manual clinical plans. An artificial intelligence-based automated treatment planning method for postmastectomy VMAT has been developed to ensure plan quality and improve clinical efficiency.
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Toxin-antitoxin (TA) modules widely exist in bacteria, and their activities are associated with the persister phenotype of the pathogen Mycobacterium tuberculosis (M. tb). M. tb causes tuberculosis, a contagious and severe airborne disease. There are 10 MazEF TA systems in M. tb that play important roles in stress adaptation. How the antitoxins antagonize toxins in M. tb or how the 10 TA systems crosstalk to each other are of interest, but the detailed molecular mechanisms are largely unclear. MazEF-mt9 is a unique member among the MazEF family due to its tRNase activity, which is usually carried out by the VapC toxins. Here, we present the cocrystal structure of the MazEF-mt9 complex at 2.7 Å. By characterizing the association mode between the TA pairs through various techniques, we found that MazF-mt9 bound not only its cognate antitoxin but also the noncognate antitoxin MazE-mt1, a phenomenon that could be also observed in vivo. Based on our structural and biochemical work, we propose that the cognate and heterologous interactions among different TA systems work together in vivo to relieve the toxicity of MazF-mt9 toward M. tb cells.
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Proteínas de Bactérias/química , Endorribonucleases/química , Mycobacterium tuberculosis/química , Estresse Fisiológico , Sistemas Toxina-Antitoxina , Adaptação Fisiológica , Proteínas de Bactérias/genética , Cristalização , Endorribonucleases/genética , Mycobacterium tuberculosis/genética , Ligação ProteicaRESUMO
PURPOSE: The study is to explore potential features and develop classification models for distinguishing benign and malignant lung lesions based on CT-radiomics features and PET metabolic parameters extracted from PET/CT images. MATERIALS AND METHODS: A retrospective study was conducted in baseline 18â¯F-flurodeoxyglucose positron emission tomography/ computed tomography (18â¯F-FDG PET/CT) images of 135 patients. The dataset was utilized for feature extraction of CT-radiomics features and PET metabolic parameters based on volume of interest, then went through feature selection and model development with strategy of five-fold cross-validation. Specifically, model development used support vector machine, PET metabolic parameters selection used Akaike's information criterion, and CT-radiomics were reduced by the least absolute shrinkage and selection operator method then forward selection approach. The diagnostic performances of CT-radiomics, PET metabolic parameters and combination of both were illustrated by receiver operating characteristic (ROC) curves, and compared by Delong test. Five groups of selected PET metabolic parameters and CT-radiomics were counted, and potential features were found and analyzed with Mann-Whitney U test. RESULTS: The CT-radiomics, PET metabolic parameters, and combination of both among five subsets showed mean area under the curve (AUC) of 0.820⯱â¯0.053, 0.874⯱â¯0.081, and 0.887⯱â¯0.046, respectively. No significant differences in ROC among models were observed through pairwise comparison in each fold (P-value from 0.09 to 0.81, Delong test). The potential features were found to be SurfaceVolumeRatio and SUVpeak (Pâ¯<â¯0.001 of both, U test). CONCLUSION: The classification models developed by CT-radiomics features and PET metabolic parameters based on PET/CT images have substantial diagnostic capacity on lung lesions.
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Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Área Sob a Curva , Diagnóstico Diferencial , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Máquina de Vetores de SuporteRESUMO
PURPOSE: To investigate the dose depositions to organs at risk (OARs) and associated cancer risk in cancer patients scanned with 4-dimensional computed tomography (4DCT) as compared with conventional 3DCT. METHODS AND MATERIALS: The radiotherapy treatment planning CT image and structure sets of 102 patients were converted to CT phantoms. The effective diameters of those patients were computed. Thoracic scan protocols in 4DCT and 3DCT were simulated and verified with a validated Monte Carlo code. The doses to OARs (heart, lungs, esophagus, trachea, spinal cord, and skin) were calculated and their correlations with patient effective diameter were investigated. The associated cancer risk was calculated using the published models in BEIR VII reports. RESULTS: The average of mean dose to thoracic organs was in the range of 7.82-11.84 cGy per 4DCT scan and 0.64-0.85 cGy per 3DCT scan. The average dose delivered per 4DCT scan was 12.8-fold higher than that of 3DCT scan. The organ dose was linearly decreased as the function of patients' effective diameter. The ranges of intercept and slope of the linear function were 17.17-30.95 and -0.0278--0.0576 among patients' 4DCT scans, and 1.63-2.43 and -0.003--0.0045 among patients' 3DCT scans. Relative risk of cancer increased (with a ratio of 15.68:1) resulting from 4DCT scans as compared to 3DCT scans. CONCLUSIONS: As compared to 3DCT, 4DCT scans deliver more organ doses, especially for pediatric patients. Substantial increase in lung cancer risk is associated with higher radiation dose from 4DCT and smaller patients' size as well as younger age.
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Neoplasias Induzidas por Radiação , Doses de Radiação , Neoplasias Torácicas , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X/métodosRESUMO
The diffusion and perfusion magnetic resonance (MR) images can provide functional information about tumour and enable more sensitive detection of the tumour extent. We aimed to develop a fuzzy feature fusion method for auto-segmentation of gliomas in radiotherapy planning using multi-parametric functional MR images including apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV). For each functional modality, one histogram-based fuzzy model was created to transform image volume into a fuzzy feature space. Based on the fuzzy fusion result of the three fuzzy feature spaces, regions with high possibility belonging to tumour were generated automatically. The auto-segmentations of tumour in structural MR images were added in final auto-segmented gross tumour volume (GTV). For evaluation, one radiation oncologist delineated GTVs for nine patients with all modalities. Comparisons between manually delineated and auto-segmented GTVs showed that, the mean volume difference was 8.69% (±5.62%); the mean Dice's similarity coefficient (DSC) was 0.88 (±0.02); the mean sensitivity and specificity of auto-segmentation was 0.87 (±0.04) and 0.98 (±0.01) respectively. High accuracy and efficiency can be achieved with the new method, which shows potential of utilizing functional multi-parametric MR images for target definition in precision radiation treatment planning for patients with gliomas.