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OBJECTIVES: This study aimed to propose a deep learning (DL)-based framework for identifying the composition of thyroid nodules and assessing their malignancy risk. METHODS: We conducted a retrospective multicenter study using ultrasound images from four hospitals. Convolutional neural network (CNN) models were constructed to classify ultrasound images of thyroid nodules into solid and non-solid, as well as benign and malignant. A total of 11,201 images of 6784 nodules were used for training, validation, and testing. The area under the receiver-operating characteristic curve (AUC) was employed as the primary evaluation index. RESULTS: The models had AUCs higher than 0.91 in the benign and malignant grading of solid thyroid nodules, with the Inception-ResNet AUC being the highest at 0.94. In the test set, the best algorithm for identifying benign and malignant thyroid nodules had a sensitivity of 0.88, and a specificity of 0.86. In the human vs. DL test set, the best algorithm had a sensitivity of 0.93, and a specificity of 0.86. The Inception-ResNet model performed better than the senior physicians (p < 0.001). The sensitivity and specificity of the optimal model based on the external test set were 0.90 and 0.75, respectively. CONCLUSIONS: This research demonstrates that CNNs can assist thyroid nodule diagnosis and reduce the rate of unnecessary fine-needle aspiration (FNA). CLINICAL RELEVANCE STATEMENT: High-resolution ultrasound has led to increased detection of thyroid nodules. This results in unnecessary fine-needle aspiration and anxiety for patients whose nodules are benign. Deep learning can solve these problems to some extent. KEY POINTS: ⢠Thyroid solid nodules have a high probability of malignancy. ⢠Our models can improve the differentiation between benign and malignant solid thyroid nodules. ⢠The differential performance of one model was superior to that of senior radiologists. Applying this could reduce the rate of unnecessary fine-needle aspiration of solid thyroid nodules.
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Aprendizado Profundo , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/patologia , Diagnóstico Diferencial , Sensibilidade e Especificidade , Ultrassonografia/métodos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologiaRESUMO
A 34-year-old male presented with lung shadow and was asymptomatic during medical examination. The patient had a prior history of thyroid tumors. Imaging manifestation showed a nodule in the medial segment of the right middle lobe, with partial obstruction of the distal bronchus within the lesion. Ground-glass and inflammatory nodules were observed in the anterior segment of the right upper lobe, as well as chronic inflammatory changes in the lower lobe of the right lung. Lung histopathological examination suggested invasive adenocarcinoma. A morphological examination of the bronchoalveolar lavage fluid revealed the presence of Tropheryma whipplei (TW) and Nocardia. Although TW infection has been reported in cancer patients, co-infection with Nocardia is a unique occurrence in this case. Opportunistic pathogens are common in immunocompromised patients but in this case, the patient was a young adult with normal immunity and an early-stage tumor with TW and Nocardia co-infection. We demonstrated the presence of rare microorganisms through imaging findings, combined with different staining methods of bronchoalveolar lavage fluid and lung tissue sections and evaluation of morphological characteristics. The aim of the present study was to provide early diagnosis and treatment of patients by improving microbial morphological detection.
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Coinfecção , Neoplasias Pulmonares , Nocardia , Masculino , Adulto Jovem , Humanos , Adulto , Tropheryma , PulmãoRESUMO
Pre-harvest soybean seeds in the field are susceptible to high temperature and humidity (HTH) stress, leading to pre-harvest seed deterioration, which will result in a reduction in grain quality, yield, and seed vigor. To understand the gene expression involved in seed deterioration response under HTH stress, in this study, we conducted an RNA-Seq analysis using two previously screened soybean cultivars with contrasting seed deterioration resistance. HTH stress induced 1081 and 357 differentially expressed genes (DEGs) in the sensitive cultivar Ningzhen No. 1 and resistant cultivar Xiangdou No. 3, respectively. The majority of DEGs in the resistant cultivar were up-regulated, while down-regulated DEGs were predominant in the sensitive cultivar. KEGG pathway analysis revealed that metabolic pathways, biosynthesis of secondary metabolites, and protein processing in endoplasmic reticulum were the predominant pathways in both cultivars during seed deterioration under HTH stress. The genes involved in photosynthesis, carbohydrate metabolism, lipid metabolism, and heat shock proteins pathways might contribute to the different response to seed deterioration under HTH treatment in the two soybean cultivars. Our study extends the knowledge of gene expression in soybean seed under HTH stress and further provides insight into the molecular mechanism of seed deterioration as well as new strategies for breeding soybean with improved seed deterioration resistance.
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Glycine max/genética , Temperatura Alta , Umidade , Sementes/genética , Transcriptoma , Ontologia Genética , RNA-Seq , Glycine max/metabolismoRESUMO
Mitogen-activated protein kinase (MAPK) cascades play critical roles in signal transduction processes in eukaryotes. The MAPK kinases (MAPKKs) that link MAPKK kinases (MAPKKKs) and MAPKs are key components of MAPK cascades. However, the intricate regulatory mechanisms that control MAPKKs under drought stress conditions are not fully understood, especially in cotton (Gossypium hirsutum) Here, we isolated and characterized the cotton group B MAPKK gene GhMKK3 Overexpressing GhMKK3 in Nicotiana benthamiana enhanced tolerance to drought, and the results of RNA sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) assays suggest that GhMKK3 plays an important role in responses to abiotic stresses by regulating stomatal responses and root hair growth. Further evidence demonstrated that overexpressing GhMKK3 promoted root growth and ABA-induced stomatal closure. In contrast, silencing GhMKK3 in cotton using virus-induced gene silencing (VIGS) resulted in the opposite phenotypes. More importantly, we identified an ABA- and drought-induced MAPK cascade that is composed of GhMKK3, GhMPK7 and GhPIP1 that compensates for deficiency in the MAPK cascade pathway in cotton under drought stress conditions. Together, these findings significantly improve our understanding of the mechanism by which GhMKK3 positively regulates drought stress responses.
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Regulação da Expressão Gênica de Plantas , Gossypium/enzimologia , MAP Quinase Quinase 3/metabolismo , Secas , Expressão Gênica , Germinação , Gossypium/efeitos dos fármacos , Gossypium/genética , Gossypium/fisiologia , MAP Quinase Quinase 3/genética , Fenótipo , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/enzimologia , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Estômatos de Plantas/enzimologia , Estômatos de Plantas/genética , Estômatos de Plantas/fisiologia , Plantas Geneticamente Modificadas , Alinhamento de Sequência , Análise de Sequência de RNA , Cloreto de Sódio/farmacologia , Estresse Fisiológico , Nicotiana/enzimologia , Nicotiana/genética , Nicotiana/fisiologia , Técnicas do Sistema de Duplo-HíbridoRESUMO
Ultrasound-targeted microbubble destruction (UTMD) has become a novel gene/drug delivery method in cancer therapeutic application. However, the gene transfection efficiency mediated by UTMD is still unsatisfactory. Here, we introduced iRGD/CCR2 dual-targeted cationic microbubbles (MBiRGD/CCR2) which was modified with PEI-600 and coated with iRGD peptides and anti-CCR-2 antibodies. It showed that MBiRGD/CCR2 had a 25.83 ± 1.57 mV surface zeta potential and good stability. The experiments in vitro showed MBiRGD/CCR2 had higher binding efficiency with both bEnd.3 cells and MCF-7 cells than that of iRGD or CCR2 single-targeted cationic microbubbles (MBiRGD or MBCCR2) (P < 0.05 for both). Agarose gel electrophoresis assay showed that MBiRGD/CCR2 can effectively load pGPU6/GFP/Neo-shAKT2 plasmid DNA. Compared with the plain MBs (MBcontrol) or single-targeted cationic MBs including MBiRGD and MBCCR2 (P < 0.05 for all), the dual-targeted cationic MBiRGD/CCR2 groups had higher gene transfection efficiency under US exposure. It showed that the dual-targeted cationic MBiRGD/CCR2 has a potential value to be used as an ultrasound imaging probe for ultrasound image-guided tumor gene therapy.
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Meios de Contraste , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Terapia Genética/métodos , Proteínas de Fluorescência Verde/genética , Microbolhas , Ultrassom , Feminino , Humanos , Técnicas In Vitro , Células MCF-7 , Plasmídeos/administração & dosagem , TransfecçãoRESUMO
Objective: To establish the chemical mutagenesis in vitro system of Mentha haplocalyx,the effects of different plant hormone combination and Vc on the induction of mint stem adventitious buds and the mutation effects of different concentrations of NaN3 on their calli were studied. Methods: The internodes of mint used as the material,and based on the preliminary experiment, the effects of different concentrations of TDZ,6-BA,NAA and Vc on adventitious buds induction rate were researched. On the basis of screening the best induction formula, the Mentha haplocalyx calli were treated with different concentrations of NaN3ï¼ 0,2,4,6,8,10,12,14,16 mg/Lï¼. Results: The optimum medium for calli induction and adventitious buds formation was MS + 0. 1 mg / L TDZ + 0. 2 mg / L NAA + 1mg / L Vc + 30 g / L sucrose + 5. 5 g / L agar, the treatment concentration of NaN3 for LD50of calli induction was 14 mg / L for 10 d,or 12 mg / L for 20 d,or 10 mg / L for 30 d. Plantlet could differentiate from the calli treated with NaN3. By comparing to the regenerated plants,81 mutants had been selected. Conclusion: A chemical mutagenesis in vitro system for Mentha haplocalyx with NaN3 was preliminarily established.
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Mentha , Reguladores de Crescimento de Plantas , Caules de Planta , Regeneração , Azida Sódica , Técnicas de Cultura de TecidosRESUMO
In the late stages of the COVID-19 pandemic, there's an increasing trend in opportunistic infections, including bacterial and fungal infections. This study discusses the treatment process of two cases of cryptococcal meningitis during the COVID-19 pandemic. It highlights the importance of laboratory testing for these co-infections and stresses the need for vigilance, early diagnosis, and proactive treatment to improve patient outcomes in the post-pandemic era.
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Antifúngicos , COVID-19 , Meningite Criptocócica , SARS-CoV-2 , Humanos , Meningite Criptocócica/tratamento farmacológico , Meningite Criptocócica/diagnóstico , COVID-19/complicações , COVID-19/epidemiologia , Masculino , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Feminino , Coinfecção , Adulto , Cryptococcus neoformans/isolamento & purificação , Resultado do TratamentoRESUMO
In 2020, the world experienced the threat of the COVID-19 epidemic, and seniors and chronic disease patients generally reduced their exercise and social activities to avoid increasing the risk of infection, which could lead to increased loneliness and even many diseases. Combining golf croquet games with a mobile application (App) and AIoT companion robots, this research constructs a home-based intelligent exercise system, uses the technology acceptance model (TAM), deduces users' intention to use this system based on perceived usefulness and perceived ease of use, and adds the needs of love and belonging, esteem, cognitive, aesthetic, and self-actualization in Maslow's hierarchy of needs theory (HNT) to conduct an analysis of system needs. This study collected empirical data, totaling 320 participants including seniors and their caregivers, from elderly care centers in northern Taiwan using a cross-sectional survey and purposive sampling. Based on regression and variance analysis, the results show that participants have a high level of acceptance of this system, believing that it is easy to learn and operate and can increase interaction with others, improve self-confirmation, satisfy the thirst for knowledge, increase the feeling of happiness, and fulfill self-actualization needs. In the future, by collecting and recording the process of seniors using the App, so as to find out their health problems as soon as possible, expand their daily life through this exercise, and achieve the goal of happy living and better healthcare.
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The chest is a common site for traumatic injury; however, rupture of the main airway after chest trauma is a rare and potentially fatal condition. The present study demonstrated that extracorporeal membrane oxygenation (ECMO) may serve a crucial role in the effective conventional treatment of patients with severe chest trauma, ECMO was used before tracheal repair surgery to prevent hypoxia during surgery. When effective ventilation of the patient cannot occur without assistance, ECMO support is considered to be essential in ensuring effective gas exchange. This rescue procedure can provide guidance for the treatment of patients suffering from traumatic tracheal rupture and respiratory failure. To summarize, ECMO may be able to improve the treatment experience of patients with traumatic tracheal rupture and increase the treatment success rate of such patients.
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A 49-year-old male who had been working in welding for more than 30 years was admitted to the hospital for a medical checkup that revealed a lung shadow without specific symptoms such as coughing and sputum. Imaging studies showed diffuse ground-glass changes in both lungs, wall cavities with wall nodules, multiple peripheral nodules, and some nodules with calcification. The patient has been engaged in welding work for more than 30 years and exposed to iron dust. Lung tissue biopsy, routine morphological and pathological fluid basis examination of alveolar lavage fluid, can be considered as pulmonary iron particles, which can be regarded as iron dust lung. Acid-fast bacilli were detected in both fibrobronchoscopic brush extract and alveolar lavage fluid acid-fast staining. As the pathological examination revealed granulomatous inflammation showed caseation necrosis, the patient was judged to have concomitant pulmonary TB. After the diagnosis was made, the patient was no longer exposed to dust and was treated with appropriate anti- tuberculosis (TB) therapy. Lung lesions caused by welding have been reported, but the simultaneous finding of siderosis with pulmonary TB is specific to the case presented here. By describing the imaging features, combining different staining methods of alveolar lavage fluid and pathological examination of lung tissue, we showed various morphological manifestations of this case, aiming at improving the morphological diagnosis level of laboratory physicians and enabling patients to be diagnosed and treated early.
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Background: High-quality medication compliance is critical for the cure of pulmonary tuberculosis (PTB); however, the implementation of directly observed treatment (DOT) under direct interview still faces huge difficulties. Assessment of the effect of digital tool during community management has not been performed in eastern China. Methods: All drug-sensitive PTB cases notified in Yiwu city from June to December 2020 were divided into the routine group and digital tool group based on patients' willingness. The variables influencing the on-time completion level of home visits, medication adherence and treatment outcomes were estimated. Results: A total of 599 eligible patients were enrolled, with 268 participating in the routine group and 331 using a digital tool. Most participants were men (n = 357, 59.6%), and nearly all were new cases (n = 563, 94.0%). Participants' mean age was 44.22 ± 20.32 years. There were significant differences in age, diagnostic type, and source of patients between the two groups. During the study period, the digital tool group had a higher on-time completion rate of home visits (91.5% vs. 82.5%) and medication adherence rate (94.3% vs. 89.6%) than the routine group, whereas there was no significant difference in the treatment success rate between the two groups (91.2% vs. 86.8%). Multivariate logistic regression analysis demonstrated that the digital tool group showed a more positive function in the on-time completion status of home visits, with an adjusted odds ratio of 0.41 (95% confidence interval: 0.25-0.70). Conclusion: Digital tools can be employed to improve the on-time completion rate of home visits in Yiwu city. Further large-scale studies that use digital tools for community management are warranted.
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Adesão à Medicação , Tuberculose Pulmonar , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , China/epidemiologia , Pacientes , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologiaRESUMO
Effects of Si and Sr on solidification microstructure and thermal conductivity of Al-Si binary alloys and Al-9Si-Sr ternary were investigated, respectively, with a special focus on the relationship between solidification microstructure and thermal conductivity. It was found that (i) in Al-Si binary alloys, with increasing Si content, α-Al grain size increases and then decreases when Si content is over 7 wt%, while the percentage of eutectic Si continuously increases, which significantly decreases the thermal conductivity and electrical conductivity, and (ii) in Al-9Si-Sr ternary alloys, the presence of Sr has no significant effect on α-Al grain, but effectively modifies eutectic Si and significantly improves the thermal and electrical conductivity. On this basis, two theoretical calculation models [the Maxwell model and the Hashin-Shtrikman (H-S) model] were used to elucidate the relationship between solidification microstructure and thermal conductivity. Compared with the Maxwell model, the H-S model fits better with the measured values. The obtained results are very helpful to the precise composition control during alloy design and recycling of Al-Si-based alloys with the aim to further improve the thermal conductivity of Al-Si-based alloys. Supplementary Information: The online version contains supplementary material available at 10.1007/s10853-022-07045-7.
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The purpose of this study was to investigate the effects of dietary L-theanine supplementation on apparent nutrient digestibility, milk yield, milk composition, and blood biochemical indices of dairy cows under heat stress. Thirty Chinese Holstein cows (19.84 ± 2.42 kg milk/d, 192.36 ± 40.77 d in milk and 2 ± 0.93 parities) were divided into 3 groups of 10 animals each. The control group was fed a basal total mixed ration (TMR) diet, while treatment 1 (LTA16) and treatment 2 (LTA32) groups were fed a basal TMR diet supplemented with L-theanine at 16 and 32 g/cow per day, respectively. The results showed that feeding the dairy cows with LTA16 treatment decreased (P < 0.05) their rectal temperature, whereas feeding with LTA32 treatment decreased (P < 0.05) their rumen fluid ammonia nitrogen content. In comparison to the control group, the supplementation of L-theanine had no significant effect (P > 0.05) on the dry matter intake, nutrient digestibility, total volatile fatty acid (TVFA) concentration and molar proportion of volatile fatty acid, milk yield, milk composition, feed efficiency and antioxidant capacity of the dairy cows. The triglyceride (TG) content of the LTA32 group was significantly greater (P = 0.014) than that of the control group. With the increase in L-theanine dosage, the serum cholesterol (CHOL) content significantly increased (P = 0.013). The serum albumin (ALB; P = 0.067), low-density lipoprotein cholesterol (LDL-C; P = 0.053), and high-density lipoprotein cholesterol (HDL-C; P = 0.067) contents showed an upward trend as L-theanine dosage increased. Ultimately, the results of this study show that supplementing dairy cow diet with L-theanine could decrease dairy cow rectal temperature, affect lipid metabolism, and potentially relieve the heat stress of dairy cows to some extent.
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PURPOSE: To investigate if artificial intelligence can identify fetus intracranial structures in pregnancy week 11-14; to provide an automated method of standard and non-standard sagittal view classification in obstetric ultrasound examination METHOD AND MATERIALS: We proposed a newly designed scheme based on deep learning (DL) - Fetus Framework to identify nine fetus intracranial structures: thalami, midbrain, palate, 4th ventricle, cisterna magna, nuchal translucency (NT), nasal tip, nasal skin, and nasal bone. Fetus Framework was trained and tested on a dataset of 1528 2D sagittal-view ultrasound images from 1519 females collected from Shenzhen People's Hospital. Results from Fetus Framework were further used for standard/non-standard (S-NS) plane classification, a key step for NT measurement and Down Syndrome assessment. S-NS classification was also tested with 156 images from the Longhua branch of Shenzhen People's Hospital. Sensitivity, specificity, and area under the curve (AUC) were evaluated for comparison among Fetus Framework, three classic DL models, and human experts with 1-, 3- and 5-year ultrasound training. Furthermore, 4 physicians with more than 5 years of experience conducted a reader study of diagnosing fetal malformation on a dataset of 316 standard images confirmed by the Fetus framework and another dataset of 316 standard images selected by physicians. Accuracy, sensitivity, specificity, precision, and F1-Score of physicians' diagnosis on both sets are compared. RESULTS: Nine intracranial structures identified by Fetus Framework in validation are all consistent with that of senior radiologists. For S-NS sagittal view identification, Fetus Framework achieved an AUC of 0.996 (95%CI: 0.987, 1.000) in internal test, at par with classic DL models. In external test, FF reaches an AUC of 0.974 (95%CI: 0.952, 0.995), while ResNet-50 arrives at AUCâ¼0.883, 95% CI 0.828-0.939, Xception AUCâ¼0.890, 95% CI 0.834-0.946, and DenseNet-121 AUCâ¼0.894, 95% CI 0.839-0.949. For the internal test set, the sensitivity and specificity of the proposed framework are (0.905, 1), while the first-, third-, and fifth-year clinicians are (0.619, 0.986), (0.690, 0.958), and (0.798, 0.986), respectively. For the external test set, the sensitivity and specificity of FF is (0.989, 0.797), and first-, third-, and fifth-year clinicians are (0.533, 0.875), (0.609, 0.844), and (0.663, 0.781), respectively.On the fetal malformation classification task, all physicians achieved higher accuracy and F1-Score on Fetus selected standard images with statistical significance (p < 0.01). CONCLUSION: We proposed a new deep learning-based Fetus Framework for identifying key fetus intracranial structures. The framework was tested on data from two different medical centers. The results show consistency and improvement from classic models and human experts in standard and non-standard sagittal view classification during pregnancy week 11-13+6. CLINICAL RELEVANCE/APPLICATION: With further refinement in larger population, the proposed model can improve the efficiency and accuracy of early pregnancy test using ultrasound examination.
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Aprendizado Profundo , Gravidez , Feminino , Humanos , Inteligência Artificial , Sensibilidade e Especificidade , Ultrassonografia , Feto/diagnóstico por imagemRESUMO
Characterization of covalency of intermolecular interactions in the van der Waals distance limit remains challenging because the interactions between molecules are weak, dynamic, and not measurable. Herein, we approach this issue in a series of supramolecular mixed-valence (MV) donor(D)-bridge(B)-acceptor(A) systems consisting of two bridged Mo2 units with a C6H6 molecule encapsulated, as characterized by the X-ray crystal structures. Comparative analysis of the intervalence charge transfer spectra in benzene and dichloromethane substantiates the strong electronic decoupling effect of the solvating C6H6 molecule that breaks down the dielectric solvation theory. Ab initio and DFT calculations unravel that the intermolecular orbital overlaps between the complex bridge and the C6H6 molecule alter the electronic states of the D-B-A molecule through intermolecular nuclear dynamics. This work exemplifies that site-specific intermolecular interaction can be exploited to control the chemical property of supramolecular systems and to elucidate the functionalities of side-chains in biological systems.
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OBJECTIVES: To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of uterosacral ligaments (USL) in patients with clinical suspicion of deep inï¬ltrating endometriosis (DIE). METHODS: Extensive searches were conducted in PubMed, EMBASE and Cochrane libraries to search studies published between January 1989 and September 2, 2019. The inclusion criteria were the preoperative assessment of USL endometriosis by TVS in patients with clinically suspected DIE, using laparoscopy and histological results as the reference standard. The assessment of research quality uses preferred reporting items, including the System Review and Meta Analysis (PRISMA) guidelines, as well as the quality assessment of diagnostic accuracy study 2 (QUADAS-2) tools. RESULTS: During our advanced search, 7562 studies were identified. Finally, 11 of which were recognized as qualified and incorporated into this study. The pooled sensitivity, specificity, positive probability ratio (LR+) and negative probability ratio(LR-) of TVS for detecting DIE in the USL were 65 %(95 %CI:43-83), 92 %(95 %CI:84-96), 7.80 (95 %CI:4.7-13.0) and 0.38(95 %CI:0.22-0.66), respectively. There was significant heterogeneity in sensitivity (I2: 97.40 %; Cochran Q, 385.09; P<0.001) and specificity (I2, 93.89 %; Cochran Q, 163.75; P < 0.001). CONCLUSION: TVS provides an excellent comprehensive diagnostic performance for DIE of the USL. However, further research is required to improve the diagnostic quality.
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Endometriose/diagnóstico por imagem , Endometriose/patologia , Ultrassonografia/métodos , Adolescente , Adulto , Feminino , Humanos , Ligamentos/diagnóstico por imagem , Pessoa de Meia-Idade , Doenças Peritoneais/diagnóstico por imagem , Sacro/diagnóstico por imagem , Sensibilidade e Especificidade , Útero/diagnóstico por imagem , Vagina , Adulto JovemRESUMO
The success of gene therapy depends largely on the development of gene vectors and effective gene delivery systems. It has been demonstrated that cationic microbubbles can be loaded with negatively charged plasmid DNA and thus improve gene transfection efficiency. In this study, we developed dual-targeting cationic microbubbles conjugated with iRGD peptides(Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys)) and CCR2 (chemokine (C-C motif) receptor 2) antibodies (MBiRGD/CCR2) for ultrasound molecular imaging and targeted tumor gene therapy. The ultrasound molecular imaging experiments showed that there were significantly enhanced ultrasound molecular imaging signals in the tumor that received MBiRGD/CCR2, compared with those that received MBiRGD, MBCCR2, or MBcontrol. As a therapy plasmid, pGPU6/GFP/Neo-shAKT2, carrying an expression cassette for the human AKT2 RNA interference sequence, was used. Our results demonstrated that MBiRGD/CCR2 had a significantly higher gene transfection efficiency than MBiRGD, MBCCR2, or MBcontrol under ultrasound irradiation, resulting in much lower AKT2 protein expression and stronger tumor growth inhibition effects in vivo and in vitro. In conclusion, our study demonstrated a novel gene delivery system via MBiRGD/CCR2 for ultrasound molecular-imaging-guided gene therapy of breast cancer.
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Microbolhas , Neoplasias , Terapia Genética , Humanos , Imagem Molecular , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Neoplasias/terapia , Plasmídeos , Transfecção , UltrassonografiaRESUMO
In recent decades, more teachers are using question generators to provide students with online homework. Learning-to-rank (LTR) methods can partially rank questions to address the needs of individual students and reduce their study burden. Unfortunately, ranking questions for students is not trivial because of three main challenges: (1) discovering students' latent knowledge and cognitive level is difficult, (2) the content of quizzes can be totally different but the knowledge points of these quizzes may be inherently related, and (3) ranking models based on supervised, semisupervised, or reinforcement learning focus on the current assignment without considering past performance. In this work, we propose KFRank, a knowledge-fusion ranking model based on reinforcement learning, which considers both a student's assignment history and the relevance of quizzes with their knowledge points. First, we load students' assignment history, reorganize it using knowledge points, and calculate the effective features for ranking in terms of the relation between a student's knowledge cognitive and the question. Then, a similarity estimator is built to choose historical questions, and an attention neural network is used to calculate the attention value and update the current study state with knowledge fusion. Finally, a rank algorithm based on a Markov decision process is used to optimize the parameters. Extensive experiments were conducted on a real-life dataset spanning a year and we compared our model with the state-of-the-art ranking models (e.g., ListNET and LambdaMART) and reinforcement-learning methods (such as MDPRank). Based on top-k nDCG values, our model outperforms other methods for groups of average and weak students, whose study abilities are relatively poor and thus their behaviors are more difficult to predict.
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Aprendizagem , Estudantes , HumanosRESUMO
Phosphate chemical conversion (PCC) ceramic coatings on the surface of 2A12 aluminum alloy substrate have been fabricated by a simple and inexpensive chemical conversion process in CrO3-NaF-H3PO4 solution. Microstructure characterization showed that the average diameter of micro-pores and the thickness of the PCC ceramic coating were about 50 nm and 4 µm, respectively, and the ceramic coating was compact and uniform when the conversion time was 60 min. Meanwhile, we found that the PCC ceramic coating mainly consisted of AlPO4, AlOOH, AlF3, and a few amorphous phases (CrPO4 and CrOOH) via EDS, XRD, XPS analyses. TG-DSC results indicated that the PCC ceramic coatings had excellent thermal stability. Significantly, the adhesion strength (178.55 N) between the PCC ceramic coatings and 2A12 Al substrate was remarkably improved owing to the strong chemical bond between the PCC ceramic coating and 2A12 Al substrate and the increase of surface roughness. Furthermore, a lower corrosion current density (1.382 × 10-7 A cm-2) and a higher corrosion inhibition efficiency (99.91%) confirmed that PCC ceramic coatings had fantastic corrosion resistance because of the presence of crystalline AlPO4/AlF3/AlOOH and amorphous CrPO4/CrOOH as a barrier layer. Additionally, a possible film-forming mechanism of the PCC ceramic coating was proposed during the chemical conversion process, which could be divided into four stages: dissolution of 2A12 aluminum substrate and hydrogen evolution; crystallization of insoluble phosphates and formation of an amorphous phase; growth of insoluble phosphates and dissolution of PCC ceramic coatings; growth and dissolution of PCC coatings to dynamic equilibrium.
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NIR laser-induced photothermal therapy (PTT) through near-infrared agents has demonstrated the great potential in solid tumor ablation. However, the nonuniform heat distribution over tumors from PTT makes it insufficient to kill all tumor cells, resulting in tumor recurrence and inferior outcomes. To improve the tumor treatment efficacy, it is highly desirable to develop the combinational treatment of PTT with other modalities, especially with chemotherapeutic agents. Here we report a smart DOX/IR-780-loaded temperature-sensitive-liposome (DITSL) which can achieve NIR-laser-controlled drug release for chemo-photothermal synergistic tumor therapy. In this system, the liposoluble IR-780 was incorporated into the temperature-sensitive lipid bilayer and the soluble chemotherapeutic doxorubicin (DOX) was encapsulated in the hydrophilic core. The resulting DITSL is proved to be physiologically stable and can provide a fast and laser irradiation-controllable DOX release in the PBS and cellular conditions. We further employed this nanoparticle for tumor treatment, demonstrating significantly higher tumor inhibition efficacy than that of DOX-loaded temperature-sensitive-liposome (DTSL) or IR780-loaded temperature-sensitive-liposome (ITSL) in the in vitro cells and in vivo animals. Histological analysis further revealed much more apoptotic cells, confirming the advantageous anti-tumor effect of DITSL over DTSL or ITSL. Our study provides a promising strategy to realize chemo-photothermal synergistic combination therapy for breast tumors.