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BACKGROUND: The use of histogram analysis of computed tomography (CT) values is a potential method for differentiating between benign osteoblastic lesions (BOLs) and malignant osteoblastic lesions (MOLs). PURPOSE: To explore the diagnostic efficacy of histogram analysis in accurately distinguishing between BOLs and MOLs based on CT values. MATERIAL AND METHODS: A total of 25 BOLs and 25 MOLs, which were confirmed through pathology or imaging follow-up, were included in this study. FireVoxel software was used to process the lesions and obtain various histogram parameters, including mean value, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy value, and percentiles ranging from 1st to 99th. Statistical tests, such as two independent-sample t-tests and the Mann-Whitney U test with Bonferroni correction, were employed to compare the differences in histogram parameters between BOLs and MOLs. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of each parameter. RESULTS: Significant differences were observed in several histogram parameters between BOLs and MOLs, including the mean value, coefficient of variation, skewness, and various percentiles. Notably, the 25th percentile demonstrated the highest diagnostic efficacy, as indicated by the largest area under the curve in the ROC curve analysis. CONCLUSION: Histogram analysis of CT values provides valuable diagnostic information for accurately differentiating between BOLs and MOLs. Among the different parameters, the 25th percentile parameter proves to be the most effective in this discrimination process.
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Neoplasias Óseas , Tomografía Computarizada por Rayos X , Humanos , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X/métodos , Femenino , Masculino , Neoplasias Óseas/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Anciano , Adolescente , Adulto Joven , Estudios RetrospectivosRESUMEN
BACKGROUND: Conventional MR pulse sequences result in poor signal from low T2 cortical bone because the minimum achievable echo time is limited. A sequence resulting in improved bone contrast is desirable. PURPOSE: To evaluate the image quality and diagnostic performance of grayscale inversion zero echo time imaging (GI-ZTE) and grayscale inversion T1-weighted imaging (GI-T1WI) compared with computed tomography (CT). STUDY TYPE: Prospective. SUBJECTS: A total of 50 patients with musculoskeletal tumors or tumor-like diseases of the lower extremities having MRI and CT studies. FIELD STRENGTH/SEQUENCE: GI-T1WI and GI-ZTE sequences at 1.5 T. ASSESSMENT: Assessed cortical and medullary bone morphology abnormalities using CT as the reference standard. Three radiologists scored the images quality and recorded nine metrics to assess the diagnostic performance. STATISTICAL TESTS: Differences in image quality were calculated using the Wilcoxon signed-rank test. The intraclass correlation coefficient (ICC) was used to analyze the agreement of quantitative lesion parameters between CT and MR sequences, as well as the interobserver reliability. A P value <0.05 was considered statistically significant. RESULTS: Image quality score was significantly higher for CT images than GI-TIWI images. Except for radiologist 3 [4(0) vs 4 (1)], there was no significant difference in scores between CT and GI-ZTE [radiologist 1: 4 (0) vs 4 (0), P = 0.133; radiologist 2: 4 (0) vs 4 (0), P = 0.085]. There was good-excellent agreement between both MR sequences and CT for size, lesion number, location, sclerotic rim, expanded shell, destruction pattern, and matrix mineralization for all radiologists (ICC: 0.636-1.000). The consistency of periosteal reaction and penetration of the cortex was fair to good (0.481-0.729) between GI-T1WI and CT and good to excellent between GI-ZTE and CT (0.682-0.852). DATA CONCLUSIONS: GI-ZTE images had superior intermodality agreement with CT images and allowed visualization of more cortical bone detail than GI-T1WI images. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.
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Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Humanos , Reproducibilidad de los Resultados , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Imagen por Resonancia Magnética/métodos , Estándares de ReferenciaRESUMEN
In order to investigate the impact of "Blue Sky War" implemented during 2018-2020 on carbonaceous aerosols in Beijing-Tianjin-Hebei (BTH) region, China, fine particulate matter (PM2.5) samples were collected simultaneously in Tianjin and Handan in three consecutive winters from 2018 to 2020. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were measured with the same thermal-optical methods and analysis protocols. Significant reductions in primary organic carbon (POC) and EC concentrations were observed both in Tianjin and Handan, with decreasing rates of 0.65 and 2.95 µg m-3 yr-1 for POC and 0.13 and 0.64 µg m-3 yr-1 for EC, respectively. The measured absorption coefficients of EC (babs, EC) also decreased year by year, with a decreasing rate of 1.82 and 6.16 Mm-1 yr-1 in Tianjin and Handan, respectively. The estimated secondary organic carbon (SOC) concentrations decreased first and then increased in both Tianjin and Handan, accounting for more than half of the total OC in winter of 2020-2021 and with increasing contributions especially in highly polluted days. SOC was recognized as one of key factors influencing EC light absorption. EC in the two cities was relatively more related to coal combustion and industrial sources. The reductions of primary carbonaceous components may be attributed to the air quality regulations targeting coal combustion and industrial sources emissions in BTH area. Potential source contribution function (PSCF) analysis results indicated that the major source areas of OC and EC in Tianjin were the southwest region of the sampling site, while the southeast areas for Handan. These findings demonstrated the effectiveness of air quality regulation in primary emissions in typical polluted cities in BTH region and highlighted the needs for further control and in-depth investigation of SOC formation along with implementation of air pollution control act in the future.
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Contaminantes Atmosféricos , Ciudades , Contaminantes Atmosféricos/análisis , Beijing , Monitoreo del Ambiente , Aerosoles/análisis , Material Particulado/análisis , Carbón Mineral/análisis , Carbono/análisis , Estaciones del Año , ChinaRESUMEN
BACKGROUND: The purpose of this study was to investigate and validate multiparametric magnetic resonance imaging (MRI)-based machine learning classifiers for early identification of poor responders after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: Patients with LARC who underwent nCRT were included in this retrospective study (207 patients). After preprocessing of multiparametric MRI, radiomics features were extracted and four feature selection methods were used to select robust features. The selected features were used to build five machine learning classifiers, and 20 (four feature selection methods × five machine learning classifiers) predictive models for the screening of poor responders were constructed. The predictive models were evaluated according to the area under the curve (AUC), F1 score, accuracy, sensitivity, and specificity. RESULTS: Eighty percent of all predictive models constructed achieved an AUC of more than 0.70. A predictive model using a support vector machine classifier with the minimum redundancy maximum relevance (mRMR) selection method followed by the least absolute shrinkage and selection operator (LASSO) selection method showed superior prediction performance, with an AUC of 0.923, an F1 score of 88.14%, and accuracy of 91.03%. The predictive performance of the constructed models was not improved by ComBat compensation. CONCLUSIONS: In rectal cancer patients who underwent neoadjuvant chemoradiotherapy, machine learning classifiers with radiomics features extracted from multiparametric MRI were able to accurately discriminate poor responders from good responders. The techniques should provide additional information to guide patient-tailored treatment.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias del Recto , Quimioradioterapia , Humanos , Aprendizaje Automático , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Neoadjuvant radiotherapy plays a vital role in the treatment of malignant bone tumors, and non-invasive imaging methods are needed to evaluate the response to treatment. PURPOSE: To assess the value of diffusion kurtosis imaging (DKI) for monitoring early response to radiotherapy in malignant bone tumors. MATERIAL AND METHODS: Treatment response was evaluated in a rabbit VX2 bone tumor model (n = 35) using magnetic resonance imaging (MRI), DKI, and histopathologic examinations. Subjects were divided into three groups: pre-treatment, post-treatment, and control groups. The post-treatment group was subclassified into good response and poor response groups according to the results of histopathologic examination. Apparent diffusion coefficient (ADC) and DKI parameters (mean diffusion coefficient [MD] and mean kurtosis [MK]) were recorded. The relationship between ADC, DKI parameters, and histopathologic changes after radiotherapy was determined using Pearson's correlation coefficient. The diagnostic performance of these parameters was assessed using receiver operating characteristic analysis. RESULTS: MD in the good response group was higher after treatment than before treatment (P < 0.001) and higher than that in the poor response group (P = 0.009). MD was highly correlated with tumor cell density and apoptosis rate (r = -0.771, P < 0.001 and r = 0.625, P < 0.001, respectively). MD was superior to other parameters for determining the curative effect of radiotherapy, with a sensitivity of 75.0%, specificity of 100.0%, and area under the curve of 0.917 (P < 0.001). CONCLUSION: The correlations between MD, tumor cell density, and apoptosis suggest that MD could be useful for assessing the early response to radiotherapy in rabbit VX2 malignant bone tumors.
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Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/radioterapia , Imagen de Difusión por Resonancia Magnética/métodos , Animales , Neoplasias Óseas/patología , Modelos Animales de Enfermedad , Procesamiento de Imagen Asistido por Computador , Masculino , Terapia Neoadyuvante , ConejosRESUMEN
BACKGROUND: The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. METHODS: 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. RESULTS: For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. CONCLUSIONS: For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Tractos Piramidales , Recuperación de la Función/fisiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Estimulación Magnética Transcraneal , Resultado del Tratamiento , Extremidad SuperiorRESUMEN
OBJECTIVES: Preoperative differentiation between benign parotid gland tumors (BPGT) and malignant parotid gland tumors (MPGT) is important for treatment decisions. The purpose of this study was to develop and validate an MRI-based radiomics nomogram for the preoperative differentiation of BPGT from MPGT. METHODS: A total of 115 patients (80 in training set and 35 in external validation set) with BPGT (n = 60) or MPGT (n = 55) were enrolled. Radiomics features were extracted from T1-weighted and fat-saturated T2-weighted images. A radiomics signature model and a radiomics score (Rad-score) were constructed and calculated. A clinical-factors model was built based on demographics and MRI findings. A radiomics nomogram model combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The diagnostic performance of the three models was evaluated and validated using ROC curves on the training and validation datasets. RESULTS: Seventeen features from MR images were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature had an AUC value of 0.952 in the training set and 0.938 in the validation set. Decision curve analysis showed that the nomogram outperformed the clinical-factors model in terms of clinical usefulness. CONCLUSIONS: The above-described radiomics nomogram performed well for differentiating BPGT from MPGT, and may help in the clinical decision-making process. KEY POINTS: ⢠Differential diagnosis between BPGT and MPGT is rather difficult by conventional imaging modalities. ⢠A radiomics nomogram integrated with the radiomics signature, clinical data, and MRI features facilitates differentiation of BPGT from MPGT with improved diagnostic efficacy.
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Nomogramas , Glándula Parótida , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
BACKGROUND: Oxidation-specific epitopes (OSEs) are rich in atherosclerotic plaques. Innate and adaptive immune responses to OSEs play an important role in atherosclerosis. The purpose of this study was to develop novel human single-chain variable fragment (scFv) antibody specific to OSEs to image and inhibit atherosclerosis. RESULTS: Here, we screened a novel scFv antibody, named as ASA6, from phage-displayed human scFv library. ASA6 can bind to oxidized LDL (Ox-LDL) and atherosclerotic plaques. Meanwhile, ASA6 can also inhibit the uptake of Ox-LDL into macrophage to reduce macrophage apoptosis. The atherosclerotic lesion area of ApoE-/- mice administrated with ASA6 antibody was significantly reduced. Transcriptome analysis reveals the anti-atherosclerosis effect of ASA6 is related to the regulation of fatty acid metabolism and inhibition of M1 macrophage polarization. Moreover, we conjugated ASA6 antibody to NaNdF4@NaGdF4 nanoparticles for noninvasive imaging of atherosclerotic plaques by magnetic resonance (MR) and near-infrared window II (NIR-II) imaging. CONCLUSIONS: Together, these data demonstrate the potential of ASA6 antibody in targeted therapy and noninvasive imaging for atherosclerosis.
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Aterosclerosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagen , Animales , Apolipoproteínas E/metabolismo , Aterosclerosis/terapia , Modelos Animales de Enfermedad , Epítopos/metabolismo , Humanos , Lipoproteínas LDL , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados para ApoE , Placa Aterosclerótica/terapia , Anticuerpos de Cadena ÚnicaRESUMEN
BACKGROUND: Assessment of optic nerve sheath diameter (ONSD) is a non-invasive measure of intracranial pressure (ICP). However, it is not clear whether healthy individuals exhibit ONSD variation or whether factors other than ICP affect the ONSD. PURPOSE: To investigate whether ONSD was correlated with age, sex, height, weight, eyeball transverse diameter (ETD), or body mass index (BMI), and to develop a new diagnostic model to increase the diagnostic accuracy of intracranial hypertension (IH). MATERIAL AND METHODS: A total of 145 relatively healthy adults and 40 patients with acute IH who underwent high-resolution magnetic resonance imaging (MRI) were enrolled in this study. Linear regression analyses were used to determine the relationship between ONSD and these variables. If correlations were identified, an index ONSDΔ removing variables effects was calculated. ROC analysis was used to assess the IH predictive value of ONSDΔ in terms of sensitivity and specificity. RESULTS: In relatively healthy adults, there was a correlation between ONSD and BMI (P = 0.002), which can be presented as an index ONSDΔ. The ONSDΔ model better predicted IH than the ONSD model (P = 0.035), with a sensitivity of 70.00%, a specificity of 71.72%, and an AUC of 0.755. CONCLUSION: A correlation between ONSD and body mass index (BMI) was found using high-resolution MRI. This result indicates that the effects of BMI should be considered along with the ONSD during ICP monitoring. Meanwhile, the index ONSDΔ was better than the ONSD in predicting IH and could be used to obtain a more precise estimation of ICP.
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Hipertensión Intracraneal/diagnóstico , Imagen por Resonancia Magnética/métodos , Nervio Óptico/diagnóstico por imagen , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.
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Antineoplásicos/farmacología , Bibliotecas de Moléculas Pequeñas/farmacología , Neoplasias Gástricas/metabolismo , Quinasas p21 Activadas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Invasividad Neoplásica , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
Fine-grained visual categorization in zero-shot setting is a challenging problem in the computer vision community. It requires algorithms to accurately identify fine-grained categories that do not appear during the training phase and have high visual similarity to each other. Existing methods usually address this problem by using attribute information as intermediate knowledge, which provides sufficient fine-grained characteristics of categories and can be transferred from seen categories to unseen categories. However, the learning of attribute visual features is not trivial due to the following two reasons: (i) The visual information about attributes of different types may interfere with the visual feature learning of each other. (ii) The visual characteristics of the same attribute may vary in different categories. To solve these issues, we propose a Multi-Group Multi-Stream attribute Attention network (MGMSA), which not only separates the feature learning of attributes of different types, but also isolates the learning of attribute visual features for categories with big differences in attribute appearance. This avoids the interference between uncorrelated attributes and helps to learn category-specific attribute-related visual features. This is beneficial for distinguishing fine-grained categories with subtle visual differences. Extensive experiments on benchmark datasets show that MGMSA achieves state-of-the-art performance on attribute prediction and fine-grained zero-shot learning.
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[This corrects the article DOI: 10.3389/fpsyt.2023.1197987.].
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BACKGROUND: To explore the potential of different quantitative dynamic contrast-enhanced (qDCE)-MRI tracer kinetic (TK) models and qDCE parameters in discriminating benign from malignant soft tissue tumors (STTs). METHODS: This research included 92 patients (41females, 51 males; age range 16-86 years, mean age 51.24 years) with STTs. The qDCE parameters (Ktrans, Kep, Ve, Vp, F, PS, MTT and E) for regions of interest of STTs were estimated by using the following TK models: Tofts (TOFTS), Extended Tofts (EXTOFTS), adiabatic tissue homogeneity (ATH), conventional compartmental (CC), and distributed parameter (DP). We established a comprehensive model combining the morphologic features, time-signal intensity curve shape, and optimal qDCE parameters. The capacities to identify benign and malignant STTs was evaluated using the area under the curve (AUC), degree of accuracy, and the analysis of the decision curve. RESULTS: TOFTS-Ktrans, EXTOFTS-Ktrans, EXTOFTS-Vp, CC-Vp and DP-Vp demonstrated good diagnostic performance among the qDCE parameters. Compared with the other TK models, the DP model has a higher AUC and a greater level of accuracy. The comprehensive model (AUC, 0.936, 0.884-0.988) demonstrated superiority in discriminating benign and malignant STTs, outperforming the qDCE models (AUC, 0.899-0.915) and the traditional imaging model (AUC, 0.802, 0.712-0.891) alone. CONCLUSIONS: Various TK models successfully distinguish benign from malignant STTs. The comprehensive model is a noninvasive approach incorporating morphological imaging aspects and qDCE parameters, and shows significant potential for further development.
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Medios de Contraste , Imagen por Resonancia Magnética , Neoplasias de los Tejidos Blandos , Humanos , Persona de Mediana Edad , Masculino , Adulto , Anciano , Femenino , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Adolescente , Imagen por Resonancia Magnética/métodos , Anciano de 80 o más Años , Adulto Joven , Diagnóstico Diferencial , CinéticaRESUMEN
Gene drive systems could be a viable strategy to prevent pathogen transmission or suppress vector populations by propagating drive alleles with super-Mendelian inheritance. CRISPR-based homing gene drives convert wild type alleles into drive alleles in heterozygotes with Cas9 and gRNA. It is thus desirable to identify Cas9 promoters that yield high drive conversion rates, minimize the formation rate of resistance alleles in both the germline and the early embryo, and limit somatic Cas9 expression. In Drosophila, the nanos promoter avoids leaky somatic expression, but at the cost of high embryo resistance from maternally deposited Cas9. To improve drive efficiency, we test eleven Drosophila melanogaster germline promoters. Some achieve higher drive conversion efficiency with minimal embryo resistance, but none completely avoid somatic expression. However, such somatic expression often does not carry detectable fitness costs for a rescue homing drive targeting a haplolethal gene, suggesting somatic drive conversion. Supporting a 4-gRNA suppression drive, one promoter leads to a low drive equilibrium frequency due to fitness costs from somatic expression, but the other outperforms nanos, resulting in successful suppression of the cage population. Overall, these Cas9 promoters hold advantages for homing drives in Drosophila species and may possess valuable homologs in other organisms.
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Sistemas CRISPR-Cas , Proteínas de Drosophila , Drosophila melanogaster , Tecnología de Genética Dirigida , Células Germinativas , Regiones Promotoras Genéticas , ARN Guía de Sistemas CRISPR-Cas , Animales , Regiones Promotoras Genéticas/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Tecnología de Genética Dirigida/métodos , Células Germinativas/metabolismo , ARN Guía de Sistemas CRISPR-Cas/genética , Animales Modificados Genéticamente , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/genética , Alelos , Femenino , Masculino , Proteínas de Unión al ARNRESUMEN
Objective: This study aimed to investigate the selected anatomical factors that can potentially influence temporomandibular joint (TMJ) clicking in young adults by assessing TMJ structures and lateral pterygoid muscle (LPM) function using magnetic resonance imaging (MRI). Methods: The patients were divided into four groups: the healthy control group; the clicking on mouth opening group; the clicking on mouth closing group; and the clicking on mouth opening and closing group. Additionally, we used clinical palpation to evaluate the masticatory muscles' functional state and employed MRI using the OCOR-T1WI-FSE-CLOSED, OSAG-PDW-FSE-CLOSED, and OSAG-PDW-FSE-OPEN sequences to analyze the texture of the lateral pterygoid muscle (LPM). Results: The proportion of any articular disc or condylar morphology class did not differ significantly between the TMJ clicking and HC groups. The articular disc position did not differ significantly between the TMJ clicking and HC groups. In the TMJ clicking group, the presence of masticatory muscle dysfunction differed significantly between the clicking and non-clicking sides. Moreover, the LPM accounted for the highest proportion among masticatory muscles with tenderness in all TMJ clicking subgroups (77.78%-100%). Therefore, in the TMJ clicking group, the LPM texture was less defined, more uniform in gray scale, and more similar to local texture (p < 0.0001). Conclusion: The occurrence of TMJ clicking in young adults is unrelated to the TMJ structure but related to the function of masticatory muscles, particularly the LPM.
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Class switch recombination (CSR) diversifies the effector functions of antibodies and involves complex regulation of transcription and DNA damage repair. Here, we show that the deubiquitinase USP7 promotes CSR to immunoglobulin A (IgA) and suppresses unscheduled IgG switching in mature B cells independent of its role in DNA damage repair, but through modulating switch region germline transcription. USP7 depletion impairs Sα transcription, leading to abnormal activation of Sγ germline transcription and increased interaction with the CSR center via loop extrusion for unscheduled IgG switching. Rescue of Sα transcription by transforming growth factor ß (TGF-ß) in USP7-deleted cells suppresses Sγ germline transcription and prevents loop extrusion toward IgG CSR. Mechanistically, USP7 protects transcription factor RUNX3 from ubiquitination-mediated degradation to promote Sα germline transcription. Our study provides evidence for active transcription serving as an anchor to impede loop extrusion and reveals a functional interplay between USP7 and TGF-ß signaling in promoting RUNX3 expression for efficient IgA CSR.
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Subunidad alfa 3 del Factor de Unión al Sitio Principal , Inmunoglobulina A , Cambio de Clase de Inmunoglobulina , Activación Transcripcional , Peptidasa Específica de Ubiquitina 7 , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Animales , Inmunoglobulina A/metabolismo , Peptidasa Específica de Ubiquitina 7/metabolismo , Peptidasa Específica de Ubiquitina 7/genética , Ratones , Factor de Crecimiento Transformador beta/metabolismo , Ratones Endogámicos C57BL , Humanos , Ubiquitinación , Linfocitos B/metabolismo , Linfocitos B/inmunología , Inmunoglobulina G/metabolismo , Inmunoglobulina G/inmunología , Estabilidad ProteicaRESUMEN
Firework (FW) events occur during various festivals worldwide and substantially negatively influence both air quality and human health. However, the effects of FWs on the chemical properties and formation of organic aerosols are far from clear. In this study, fine particulate matter (PM2.5) samples were collected in a suburban area in Qingdao, China during the Chinese Spring Festival. The concentrations of chemical species (especially carbonaceous components) in PM2.5 were measured using a combination of several state-of-the-art techniques. Our results showed that mass concentrations of water-soluble sulfate, potassium and chloride ions, and organic carbon drastically increased and became the predominant components in PM2.5 during FW events. Correspondingly, both the number and fractional contributions of sulfur (S)-containing subgroups (e.g., CHOS and CHONS compounds) and some chlorine (Cl)-containing organic (e.g., CHOSCl and CHONSCl) compounds identified using ultrahigh-resolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) increased. The S- and Cl-containing compounds unique to the FW display period were identified, and their chemical characterization, sources, and formation mechanisms were elucidated by combining FT-ICR MS and quantum chemical calculations. Our results suggest that FW emissions play notable roles in both primary and secondary organic aerosol formation, especially for CHOS- and Cl-containing organic compounds.
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L-asparaginase, which hydrolyzes asparagine into aspartic acid and ammonia, is frequently used to treat acute lymphoblastic leukaemia in children. When combined with other chemotherapy drugs, the event-free survival rate is 90%. Due to immunogenicity and drug resistance, however, not all patients benefit from it, restricting the use of L-asparaginase therapy in other haematological cancers. To solve the problem of immunogenicity, several L-ASNase variants have emerged, such as Erwinia-ASNase and PEG-ASNase. However, even when Erwinia-ASNase is used as a substitute for E. coli-ASNase or PEG-ASNase, allergic reactions occur in 3%-33% of patients. All of these factors contributed to the development of novel L-ASNases. Additionally, L-ASNase resistance mechanisms, such as the methylation status of ASNS promoters and activation of autophagy, have further emphasized the importance of personalized treatment for paediatric haematological neoplasms. In this review, we discussed the metabolic effects of L-ASNase, mechanisms of drug resistance, applications in non-ALL leukaemia, and the development of novel L-ASNase.
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OBJECTIVE: We aimed to evaluate the effectiveness of clinical examination combined with texture analysis of magnetic resonance imaging (MRI) and fasciculation patterns of the lateral pterygoid muscle (LPM) in distinguishing among the different anatomic causes of temporomandibular disorder. METHODS: We divided the patients into four groups: healthy control (HC), disk without displacement (DWoD), disk displacement with reduction (DDWR), and disk displacement without reduction (DDWoR). Demographic information and clinical symptoms of patients in each group were recorded. LPM textures were compared among groups. LPM fasciculation was examined. P<0.05 indicated significant difference. RESULTS: Several clinical symptoms and signs, but not age or sex, differed significantly among groups. Oblique sagittal planar MRI revealed significant differences in the parameters of Angular Second Moment, Contrast, Correlation, Inverse Difference Moment, and Entropy between the healthy controls and the 3 patient groups. MRI of the patients, both without and with disk displacement, demonstrated relative uniformity in gray distribution and correlation of gray values, with greater complexity but an unclear texture and no obvious regularity. The proportion of type B LPM fascicles was significantly higher in the DDWR and DDWoR groups CONCLUSION: Temporomandibular disorder, without and with disk displacement, is associated with clinical symptoms and texture analysis values that differ from healthy muscle. The types of LPM fascicles are related to the position of the articular disk.
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Luxaciones Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Articulación Temporomandibular/patología , Disco de la Articulación Temporomandibular , Músculos Pterigoideos/diagnóstico por imagen , Músculos Pterigoideos/patología , Fasciculación/patología , Luxaciones Articulares/patología , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Postpartum osteoporosis (PO) is a rare condition characterized by low bone mineral density (BMD) and an increased risk of vertebral fragility fracture. We encountered a 34-year-old woman who developed back pain 1 week after delivery. Magnetic resonance imaging of the lumbar spine revealed three vertebral compression fractures. Pretreatment BMD evaluation by dual-energy X-ray absorptiometry revealed a low T-score and Z-score (-2.0 and -2.0, respectively; BMD, 0.876 g/cm2) in the affected region of the spine. The patient was diagnosed with PO and treated with subcutaneous injection of denosumab 60 mg (Prolia; Amgen, Inc., Thousand Oaks, CA, USA) every 6 months. After two treatments, the BMD had significantly increased and the back pain was improved; the patient therefore decided to terminate the treatment. Two months later, her back pain worsened and BMD decreased as measured by dual-energy X-ray absorptiometry examination of the lumbar spine. Therefore, the patient resumed treatment with denosumab, and the BMD of the lumbar spine increased after another two treatments. Therefore, we consider denosumab to be promising in the management of PO with respect to increased BMD and decreased pain.