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STATEMENT OF THE PROBLEM: The concentration of medical students in the classroom is important in promoting their mastery of knowledge. Multiple teaching characteristics, such as speaking speed, voice volume, and question use, are confirmed to be influential factors. PURPOSE: This research aims to analyze how teachers' linguistic characteristics affect medical students' classroom concentration based on a speech recognition toolkit and face recognition technology. MATERIALS AND METHODS: A speech recognition toolkit, WeNet, is used to recognize sentences during lectures in this study. Face recognition technology (FRT) is used to detect students' concentration in class. The study involved 80 undergraduate students majoring in stomatology. The classroom videos of 5 class hours in the dental anatomy course were collected in October 2022. A quantitative research methodology is used in this study. Pearson correlation, Spearman correlation and multiple linear regression analyses were used to analyze the impact of time and teachers' linguistic characteristics on students' concentration. RESULTS: As a result of regression analysis, the explanatory power of the effect of the linguistic characteristics was 7.09% (F = 83.82, P < 0.001), with time, volume and question being significant influencing factors (P < 0.01). The local polynomial smooth of the scatter between the concentration degree and the use of questions with time appears to fluctuate cyclically and suggests a potential inverse relationship between the use of questions and the concentration degree. CONCLUSIONS: The results of this study support the significant positive influence of volume and questioning technique, the negative influence of time, and the insignificant influence of speaking speed and the interval between sentences on students' concentration. This study also suggested that teachers may adjust their questioning frequency based on their observation of students' concentration.
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Software de Reconocimiento del Habla , Estudiantes de Medicina , Humanos , Femenino , Masculino , Educación de Pregrado en Medicina/métodos , Reconocimiento Facial , Evaluación Educacional , Reconocimiento Facial AutomatizadoRESUMEN
Soft tissue seal around the transmucosal region of dental implants is crucial for shielding oral bacterial invasion and guaranteeing the long-term functioning of implants. Compared with the robust periodontal tissue barrier around a natural tooth, the peri-implant mucosa presents a lower bonding efficiency to the transmucosal region of dental implants, due to physiological structural differences. As such, the weaker soft tissue seal around the transmucosal region can be easily broken by oral pathogens, which may stimulate serious inflammatory responses and lead to the development of peri-implant mucositis. Without timely treatment, the curable peri-implant mucositis would evolve into irreversible peri-implantitis, finally causing the failure of implantation. Herein, this review has summarized current surface modification strategies for the transmucosal region of dental implants with improved soft tissue bonding capacities (e.g., improving surface wettability, fabricating micro/nano topographies, altering the surface chemical composition and constructing bioactive coatings). Furthermore, the surfaces with advanced soft tissue bonding abilities can be incorporated with antibacterial properties to prevent infections, and/or with immunomodulatory designs to facilitate the establishment of soft tissue seal. Finally, we proposed future research orientations for developing multifunctional surfaces, thus establishing a firm soft tissue seal at the transmucosal region and achieving the long-term predictability of dental implants.
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In modern magnetic resonance imaging, it is common to use phase constraints to reduce sampling requirements along Fourier-encoded spatial dimensions. In this work, we investigate whether phase constraints might also be beneficial to reduce sampling requirements along spatial dimensions that are measured using non-Fourier encoding techniques, with direct relevance to approaches that use tailored spatially-selective radiofrequency (RF) pulses to perform spatial encoding along the slice dimension in a 3D imaging experiment. In the first part of the paper, we use the Cramér-Rao lower bound to examine the potential estimation theoretic benefits of using phase constraints. The results suggest that phase constraints can be used to improve experimental efficiency and enable acceleration, but only if the RF encoding matrix is complex-valued and appropriately designed. In the second part of the paper, we use simulations of RF-encoded data to test the benefits of phase constraints combined with optimized RF-encodings, and find that the theoretical benefits are indeed borne out empirically. These results provide new insights into the potential benefits of phase constraints for RF-encoded data, and provide a solid theoretical foundation for future practical explorations.
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INTRODUCTION: The estimated dose of radiation to immune cells (EDRIC) has been shown to correlate with the overall survival (OS) of patients who receive definitive thoracic radiotherapy. However, the planning target volume (PTV) may be a confounding factor. We assessed the prognostic value of EDRIC for non-small cell lung cancer (NSCLC) in patients who underwent postoperative radiotherapy (PORT) with homogeneous PTV. METHODS: Patients with NSCLC who underwent PORT between 2004 and 2019 were included. EDRIC was computed as a function of the number of radiation fractions and mean doses to the lungs, heart, and remaining body. The correlations between EDRIC and OS, disease-free survival (DFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using univariate and multivariate Cox models. Kaplan-Meier analysis was performed to assess the survival difference between low- and high-EDRIC groups. RESULTS: In total, 345 patients were analyzed. The mean EDRIC was 6.26 Gy. Multivariate analysis showed that higher EDRIC was associated with worse outcomes in terms of OS (hazard ratio [HR] 1.207, P = .007), DFS (HR 1.129, P = .015), LRFS (HR 1.211, P = .002), and DMFS (HR 1.131, P = .057). In the low- and high-EDRIC groups, the 3-year OS was 81.2% and 74.0%, DFS 39.8% and 35.0%, LRFS 70.4% and 60.5%, and DMFS 73.9% and 63.1%, respectively. CONCLUSIONS: EDRIC is an independent prognostic factor for survival in patients with NSCLC undergoing PORT. Higher doses of radiation to the immune system are associated with tumor progression and poor survival. Organs at risk for the immune system should be considered during radiotherapy planning.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Masculino , Femenino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Dosificación Radioterapéutica , Adulto , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Supervivencia sin Enfermedad , Radioterapia AdyuvanteRESUMEN
Bio-inspired hydrogel robots have become promising due to their advantage of the interaction safety and comfort between robots and humans, while current hydrogel robots mainly focus on underwater movement due to the hydration-dehydration process of thermo-responsive hydrogels, which greatly limits their practical applications. To expand the motion of the thermo-responsive hydrogel robot to the ground, we constructed a hydrogel robot inspired by a caterpillar, which has an anisotropic double-layered structure by the interfacial diffusion polymerization method. Adding PVA and SA to PNIPAm will cause different conformation transitions. Therefore, sticking the two layers of hydrogel together will form a double-layer anisotropic structure. The ultra-high hydrophilicity of PVA and SA significantly reduces the contact angle of the hydrogel from 53.1° to about 10° and reduces its hydration time. The responsive time for bending 30° of the hydrogel robot has been greatly reduced from 1 h to half an hour through the enhancement of photo-thermal conversion and thermal conductivity via the addition of Fe3O4 nanoparticles. As a result, the fabricated hydrogel robot can achieve a high moving speed of 54.5 mm·h-1 on the ground. Additionally, the fabricated hydrogel has excellent mechanical strength and can endure significant flexibility tests. This work may pave the road for the development of soft robots and expand their applications in industry.
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Inositol 1,4,5-Trisphosphate Receptor-Interacting Protein-Like 1 (ITPRIPL1), a single-pass type I membrane protein located in the membrane, functions as an inhibitory ligand of CD3ε. Recent studies have shown that its expression suppresses T cells activation and promote tumor immune evasion. Despite increasing evidence suggesting that ITPRIPL1 plays a significant role in tumor growth, no systematic pan-cancer analysis of ITPRIPL1 has been conducted to date. This study utilized datasets curated from The Cancer Genome Atlas, Genotype Tissue-Expression, and Human Protein Atlas to investigate the relationship between ITPRIPL1 expression and clinical outcomes, immune infiltration, and drug sensitivity across 33 cancer types. We employed multiple methods to assess its prognostic value in pan-cancer, such as univariate Cox regression, survival analysis, and ROC curve analysis and explored the relationship between ITPRIPL1 and tumor mutation burden (TMB), tumor microsatellite instability (MSI), CNV, DNA methylation, immune-related genes, immune cell infiltration, and drug sensitivity to reveal its immunological role. The mRNA expression levels of the ITPRIPL1 gene vary significantly across multiple types of cancer and significantly reduced in breast cancer. Conversely, high ITPRIPL1 expression was associated with a better prognosis in BRCA. Furthermore, the expression of ITPRIPL1 highly correlates with the presence of tumor-infiltrating immune cells and immune checkpoint genes across various types of cancers. Additionally, ITPRIPL1 expression was associated with TMB in 6 cancer types and with MSI in 13 cancer types. High expression of ITPRIPL1 serves as a protective factor in certain cancer types, correlating with longer overall survival in BRCA. Our study further confirms that ITPRIPL1 participates in regulating immune infiltration and affecting the prognosis of patients in pan-cancer. These findings underscore the promising potential of ITPRIPL1 as a therapeutic target for human cancer.
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PURPOSE: To explore the clinical application of one-piece polyetheretherketone (PEEK) removable partial dentures (RPDs) fabricated using a novel digital workflow and to evaluate their weights and fits in vivo and patient satisfaction. MATERIALS AND METHODS: Fifteen cases with posterior partially edentulous situations were selected, and each patient received two types of RPDs, including a novel digital workflow (test group) and a conventional workflow (control group). For the test group, one-piece RPDs were designed through three-dimensional (3D) methods by scanning stone casts and fabricated by milling PEEK discs. Each RPD was weighed. The gaps between the oral tissue and RPDs in each group were duplicated using a polyvinylsiloxane (PVS) replica and measured by 3D analysis. A visual analog scale (VAS) was used to evaluate the patient's satisfaction. Paired t-tests were used to compare the differences in the weight, the gaps of each RPD, and VAS values between the two groups. One-way analysis of variance tests was used to compare the differences in the gap among different components in each group. RESULTS: The RPD in the test group weighed less than that in the control group (p < 0.01). No statistically significant differences in the gaps of denture bases and rests (p > 0.05) were found between the two groups, but the gaps of major connectors in the test group were significantly smaller than in the control group (p < 0.05). The VAS scores for comfortableness and masticatory efficiency were not significantly different between the two groups (p > 0.05) but the scores for the aesthetic appearance of the clasps in the test group were significantly higher than that in the control group (p < 0.05). CONCLUSIONS: One-piece PEEK RPDs manufactured using a novel digital workflow weighed less than conventional RPDs and exhibited a clinically acceptable internal fit. Although the aesthetic appearance of the PEEK clasps was superior to the control, there is still room for improvement.
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Benzofenonas , Diseño de Dentadura , Dentadura Parcial Removible , Cetonas , Satisfacción del Paciente , Polietilenglicoles , Polímeros , Flujo de Trabajo , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Diseño Asistido por Computadora , Arcada Parcialmente Edéntula/rehabilitaciónRESUMEN
Purpose: We aimed to integrate MR radiomics and dynamic hematological factors to build a model to predict pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NCRT) in esophageal squamous cell carcinoma (ESCC). Methods: Patients with ESCC receiving NCRT and esophagectomy between September 2014 and September 2022 were retrospectively included. All patients underwent pre-treatment T2-weighted imaging as well as pre-treatment and post-treatment blood tests. Patients were randomly divided to training set and testing set at a ratio of 7:3. Machine learning models were constructed based on MR radiomics and hematological factors to predict pCR, respectively. A nomogram model was developed to integrate MR radiomics and hematological factors. Model performances were evaluated by areas under curves (AUCs), sensitivity, specificity, positive predictive value and negative. Results: A total of 82 patients were included, of whom 39 (47.6 %) achieved pCR. The hematological model built with four hematological factors had an AUC of 0.628 (95%CI 0.391-0.852) in the testing set. Two out of 1106 extracted features were selected to build the radiomics model with an AUC of 0.821 (95%CI 0.641-0.981). The nomogram model integrating hematological factors and MR radiomics had best predictive performance, with an AUC of 0.904 (95%CI 0.770-1.000) in the testing set. Conclusion: An integrated model using dynamic hematological factors and MR radiomics is constructed to accurately predicted pCR to NCRT in ESCC, which may be potentially useful to assist individualized preservation treatment of the esophagus.
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While previous studies have demonstrated the role of ubiquitin-conjugating enzyme 2C (UBE2C) in promoting ß-cell proliferation and cancer cell lineage expansion, its specific function and mechanism in bone marrow mesenchymal stem/stromal cells (BMSCs) growth and differentiation remain poorly understood. Our findings indicate that mice with conditional Ube2c deletions in BMSCs and osteoblasts exhibit reduced skeletal bone mass and impaired bone repair. A significant reduction in the proliferative capacity of BMSCs was observed in conditional Ube2c knockout mice, with no effect on apoptosis. Additionally, conditional Ube2c knockout mice exhibited enhanced osteoclastic activity and reduced osteogenic differentiation. Furthermore, human BMSCs with stable UBE2C knockdown exhibited diminished capacity for osteogenic differentiation. Mechanistically, we discovered that UBE2C binds to and stabilizes SMAD1/5 protein expression levels. Interestingly, UBE2C's role in regulating osteogenic differentiation and SMAD1/5 expression levels appears to be independent of its enzymatic activity. Notably, UBE2C regulates osteogenic differentiation through SMAD1/5 signaling. In conclusion, our findings underscore the pivotal role of UBE2C in bone formation, emphasizing its contribution to enhanced osteogenic differentiation through the stabilization of SMAD1/5. These results propose UBE2C as a promising target for BMSC-based bone regeneration.
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Diferenciación Celular , Células Madre Mesenquimatosas , Ratones Noqueados , Osteogénesis , Proteína Smad1 , Proteína Smad5 , Enzimas Ubiquitina-Conjugadoras , Animales , Osteogénesis/fisiología , Proteína Smad1/metabolismo , Enzimas Ubiquitina-Conjugadoras/metabolismo , Humanos , Diferenciación Celular/fisiología , Proteína Smad5/metabolismo , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Ratones , Transducción de Señal , Proliferación Celular , Estabilidad Proteica , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoclastos/citologíaRESUMEN
Purpose: Initial studies investigating the combination of local and systemic treatments in advanced esophageal cancer (EC) have conflicting conclusions regarding survival benefits. The objective of this systematic review and meta-analysis is to assess the efficacy of the addition of local therapy to systemic treatments in patients with advanced EC. Methods and Materials: A systematic literature search was conducted in the PubMed, EMBASE, and CENTRAL databases. Key eligibility criteria included studies that enrolled patients with histologically confirmed EC or esophagogastric junction cancer with metastasis or recurrence and compared survival benefits between the combined local and systemic treatment group and the systemic treatment alone group. Survival outcomes, represented by hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), were pooled using a random effects model. The MINORS score was adopted for quality assessment. Risk of bias was statistically examined by Begg's and Egger's tests. Results: A total of 1 randomized controlled trial (RCT) and 10 qualified retrospective studies including 14,489 patients were identified. Addition of local therapy to systemic treatment significantly improved PFS (HR, 0.52; 95% CI, 0.37-0.73; P < .001) and OS (HR, 0.69; 95% CI, 0.58-0.81; P < .0001) compared with systemic treatment alone. The subgroup analysis revealed that combined local and systemic treatment conferred a significant survival advantage in both patients with oligometastasis (PFS: HR, 0.45; 95% CI, 0.31-0.64; P < .0001; OS: HR, 0.62; 95% CI, 0.48-0.79; P < .0001) and recurrence (OS: HR, 0.55; 95% CI, 0.37-0.81; P = .002). Conclusions: In conclusion, addition of local treatment to systemic therapy can improve survival in patients with advanced EC, particularly in those with oligometastasis or recurrent diseases.
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To investigate the application of MRI-based vertebral bone quality (VBQ) score in assessing bone mineral density (BMD) for patients with adolescent idiopathic scoliosis (AIS). We reviewed the data of AIS patients between January 2021 and October 2023 with MRI, whole-spine plain radiographs, quantitative computed tomography (QCT) and general information. VBQ score was calculated using T1-weighted MRI. Univariate analysis was applied to present the differences between variables of patients with normal BMD group (QCT Z-score > - 2.0) and low BMD group (QCT Z-score ≤ - 2.0). The correlation between VBQ score and QCT Z-score was analyzed with Pearson correlation test. A multivariate logistic regression model was used to determine the independent factors related to low BMD. Receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic performance of VBQ score in distinguishing low BMD. A total of 136 AIS patients (mean age was 14.84 ± 2.10 years) were included, of which 41 had low BMD. The low BMD group had a significantly higher VBQ score than that in normal group (3.48 ± 0.85 vs. 2.62 ± 0.62, P < 0.001). The VBQ score was significantly negative correlated with QCT Z score (r = - 0.454, P < 0.001). On multivariate analysis, VBQ score was independently associated with low BMD (OR: 4.134, 95% CI 2.136-8.000, P < 0.001). The area under the ROC curve indicated that the diagnostic accuracy of the VBQ score for predicting low BMD was 81%. A sensitivity of 65.9% with a specificity of 88.4% could be achieved for distinguishing low BMD by setting the VBQ score cutoff as 3.18. The novel VBQ score was a promising tool in distinguishing low BMD in patients with AIS and could be useful as opportunistic assessment for screening and complementary evaluation to QCT before surgery.
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Densidad Ósea , Imagen por Resonancia Magnética , Escoliosis , Humanos , Escoliosis/diagnóstico por imagen , Adolescente , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Curva ROC , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Niño , Tomografía Computarizada por Rayos X/métodos , Estudios RetrospectivosRESUMEN
Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.
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Materiales Biocompatibles , Implantes Dentales , Periimplantitis , Periimplantitis/terapia , Periimplantitis/prevención & control , Periimplantitis/tratamiento farmacológico , Humanos , Implantes Dentales/normas , Materiales Biocompatibles/uso terapéutico , Materiales Biocompatibles/farmacología , Biopelículas/efectos de los fármacos , Propiedades de Superficie , Antibacterianos/uso terapéutico , Antibacterianos/farmacologíaRESUMEN
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into cells of different lineages to form mesenchymal tissues, which are promising in regard to treatment for bone diseases. Their osteogenic differentiation is under the tight regulation of intrinsic and extrinsic factors. Transforming growth factor ß (TGF-ß) is an essential growth factor in bone metabolism, which regulates the differentiation of MSCs. However, published studies differ in their views on whether TGF-ß signaling regulates the osteogenic differentiation of MSCs positively or negatively. The controversial results have not been summarized systematically and the related explanations are required. Therefore, we reviewed the basics of TGF-ß signaling and summarized how each of three isoforms regulates osteogenic differentiation. Three isoforms of TGF-ß (TGF-ß1/ß2/ß3) play distinct roles in regulating osteogenic differentiation of MSCs. Additionally, other possible sources of conflicts are summarized here. Further understanding of TGF-ß signaling regulation in MSCs may lead to new applications to promote bone regeneration and improve therapies for bone diseases.
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Huesos , Diferenciación Celular , Células Madre Mesenquimatosas , Osteogénesis , Transducción de Señal , Factor de Crecimiento Transformador beta , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Factor de Crecimiento Transformador beta/metabolismo , Huesos/metabolismo , Huesos/citología , AnimalesRESUMEN
BACKGROUND: The value of postoperative radiotherapy (PORT) for patients with non-small cell lung cancer (NSCLC) remains controversial. A subset of patients may benefit from PORT. We aimed to identify patients with NSCLC who could benefit from PORT. METHODS: Patients from cohorts 1 and 2 with pathological Tany N2 M0 NSCLC were included, as well as patients with non-metastatic NSCLC from cohorts 3 to 6. The radiomic prognostic index (RPI) was developed using radiomic texture features extracted from the primary lung nodule in preoperative chest CT scans in cohort 1 and validated in other cohorts. We employed a least absolute shrinkage and selection operator-Cox regularisation model for data dimension reduction, feature selection, and the construction of the RPI. We created a lymph-radiomic prognostic index (LRPI) by combining RPI and positive lymph node number (PLN). We compared the outcomes of patients who received PORT against those who did not in the subgroups determined by the LRPI. RESULTS: In total, 228, 1003, 144, 422, 19, and 21 patients were eligible in cohorts 1-6. RPI predicted overall survival (OS) in all six cohorts: cohort 1 (HR = 2.31, 95% CI: 1.18-4.52), cohort 2 (HR = 1.64, 95% CI: 1.26-2.14), cohort 3 (HR = 2.53, 95% CI: 1.45-4.3), cohort 4 (HR = 1.24, 95% CI: 1.01-1.52), cohort 5 (HR = 2.56, 95% CI: 0.73-9.02), cohort 6 (HR = 2.30, 95% CI: 0.53-10.03). LRPI predicted OS (C-index: 0.68, 95% CI: 0.60-0.75) better than the pT stage (C-index: 0.57, 95% CI: 0.50-0.63), pT + PLN (C-index: 0.58, 95% CI: 0.46-0.70), and RPI (C-index: 0.65, 95% CI: 0.54-0.75). The LRPI was used to categorize individuals into three risk groups; patients in the moderate-risk group benefited from PORT (HR = 0.60, 95% CI: 0.40-0.91; p = 0.02), while patients in the low-risk and high-risk groups did not. CONCLUSIONS: We developed preoperative CT-based radiomic and lymph-radiomic prognostic indexes capable of predicting OS and the benefits of PORT for patients with NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Masculino , Femenino , Tomografía Computarizada por Rayos X/métodos , Pronóstico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , RadiómicaRESUMEN
Accumulating evidence has demonstrated that apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs; MSC-apoVs) are vital for bone regeneration, and possess superior capabilities compared to MSCs and other extracellular vesicles derived from MSCs (such as exosomes). The osteoinductive effect of MSC-apoVs is attributed to their diverse contents, especially enriched proteins or microRNAs (miRNAs). To optimize their osteoinduction activity, it is necessary to determine the unique cargo profiles of MSC-apoVs. We previously established the protein landscape and identified proteins specific to MSC-apoVs. However, the features and functions of miRNAs enriched in MSC-apoVs are unclear. In this study, we compared MSCs, MSC-apoVs, and MSC-exosomes from two types of MSC. We generated a map of miRNAs specific to MSC-apoVs and identified seven miRNAs specifically enriched in MSC-apoVs compared to MSCs and MSC-exosomes, which we classified as apoV-specific miRNAs. Among these seven specific miRNAs, hsa-miR-4485-3p was the most abundant and stable. Next, we explored its function in apoV-mediated osteoinduction. Unexpectedly, hsa-miR-4485-3p enriched in MSC-apoVs inhibited osteogenesis and promoted adipogenesis by targeting the AKT pathway. Tailored apoVs with downregulated hsa-miR-4485-3p exhibited a greater effect on bone regeneration than control apoVs. Like releasing the brake, we acquired more powerful osteoinductive apoVs. In summary, we identified the miRNA cargos, including miRNAs specific to MSC-apoVs, and generated tailored apoVs with high osteoinduction activity, which is promising in apoV-based therapies for bone regeneration.
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Exosomas , Vesículas Extracelulares , MicroARNs , MicroARNs/genética , Vesículas Extracelulares/metabolismo , Exosomas/genética , Exosomas/metabolismo , Regeneración Ósea , OsteogénesisRESUMEN
Osteoporosis is a common degenerative bone disease. The treatment of osteoporosis remains a clinical challenge in light of the increasing aging population. Human dental pulp stem cells (DPSCs), a type of mesenchymal stem cells (MSCs), are easy to obtain and have a high proliferation ability, playing an important role in the treatment of osteoporosis. However, MSCs undergo apoptosis within a short time when used in vivo; therefore, apoptotic vesicles (apoVs) have attracted increasing attention. Currently, the osteogenic effect of DPSC-derived apoVs is unknown; therefore, this study aimed to determine the role of DPSC-derived apoVs and their potential mechanisms in bone regeneration. We found that MSCs could take up DPSC-derived apoVs, which then promoted MSC osteogenesis in vitro. Moreover, apoVs could increase the trabecular bone count and bone mineral density in the mouse osteoporosis model and could promote bone formation in rat cranial defects in vivo. Mechanistically, apoVs promoted MSC osteogenesis by activating the extracellular regulated kinase (ERK)1/2 signaling pathway. Consequently, we propose a novel therapy comprising DPSC-derived apoVs, representing a promising approach to treat bone loss and bone defects.
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INTRODUCTION: Clear cell renal cell carcinoma is the most common type of kidney cancer, but the prediction of prognosis remains a challenge. METHODS: We collected whole-slide histopathological images, corresponding clinical and genetic information from the The Cancer Imaging Archive and The Cancer Genome Atlas databases and randomly divided patients into training (nâ¯=â¯197) and validation (nâ¯=â¯84) cohorts. After feature extraction by CellProfiler, we used 2 different machine learning techniques (Least Absolute Shrinkage and Selector Operation-regularized Cox and Support Vector Machine-Recursive Feature Elimination) and weighted gene co-expression network analysis to select prognosis-related image features and genes, respectively. These features and genes were integrated into a joint model using random forest and used to create a nomogram that combines other predictive indicators. RESULTS: A total of 4 overlapped features were identified, represented by the computed histopathological risk score in the random forest model, and showed predictive value for overall survival (test set: 1-year area under the curves (AUC)â¯=â¯0.726, 3-year AUCâ¯=â¯0.727, and 5-year AUCâ¯=â¯0.764). The histopathological-genetic risk score (HGRS) integrating the genetic information computed performed better than the model that used image features only (test set: 1-year AUCâ¯=â¯0.682, 3-year AUCâ¯=â¯0.734, and 5-year AUCâ¯=â¯0.78). The nomogram (gender, stage, and HGRS) achieved the highest net benefit according to decision curve analysis compared to HGRS or clinical model. CONCLUSION: This study developed a histopathological-genetic-related nomogram by combining histopathological features and clinical predictors, providing a more comprehensive prognostic assessment for clear cell renal cell carcinoma patients.
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Carcinoma de Células Renales , Genómica , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Pronóstico , Femenino , Masculino , Genómica/métodos , Persona de Mediana Edad , Nomogramas , AncianoRESUMEN
Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.
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Regeneración Ósea , Proteínas de Unión al Calcio , Colágeno , Durapatita , Proteína Gla de la Matriz , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/inmunología , Regeneración Ósea/genética , Regeneración Ósea/inmunología , Animales , Durapatita/metabolismo , Proteínas de Unión al Calcio/genética , Proteínas de Unión al Calcio/metabolismo , Ratones , Colágeno/metabolismo , Colágeno/genética , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Osteogénesis/inmunología , Diferenciación Celular/genética , Materiales BiocompatiblesRESUMEN
BACKGROUND: In esthetic dentistry, a thorough esthetic analysis holds significant role in both diagnosing diseases and designing treatment plans. This study established a 3D esthetic analysis workflow based on 3D facial and dental models, and aimed to provide an imperative foundation for the artificial intelligent 3D analysis in future esthetic dentistry. METHODS: The established 3D esthetic analysis workflow includes the following steps: 1) key point detection, 2) coordinate system redetermination and 3) esthetic parameter calculation. The accuracy and reproducibility of this established workflow were evaluated by a self-controlled experiment (n = 15) in which 2D esthetic analysis and direct measurement were taken as control. Measurement differences between 3D and 2D analysis were evaluated with paired t-tests. RESULTS: 3D esthetic analysis demonstrated high consistency and reliability (0.973 < ICC < 1.000). Compared with 2D measurements, the results from 3D esthetic measurements were closer to direct measurements regarding tooth-related esthetic parameters (P<0.05). CONCLUSIONS: The 3D esthetic analysis workflow established for 3D virtual patients demonstrated a high level of consistency and reliability, better than 2D measurements in the precision of tooth-related parameter analysis. These findings indicate a highly promising outlook for achieving an objective, precise, and efficient esthetic analysis in the future, which is expected to result in a more streamlined and user-friendly digital design process. This study was registered with the Ethics Committee of Peking University School of Stomatology in September 2021 with the registration number PKUSSIRB-202168136.
Asunto(s)
Estética Dental , Diente , Humanos , Reproducibilidad de los Resultados , Flujo de Trabajo , Cara , Diseño Asistido por ComputadoraRESUMEN
BACKGROUND: In the realm of cancer studies,the differences among the biological behavior of oligometastatic prostate cancer (OPCa), localized prostate cancer (LPCa), and widely prostate cancer (WPCa) are still unclear. OBJECTIVES: The purpose of our study was to assess the clinical and intravoxel incoherent motion (IVIM) parameters of tumor burden in OPCa. In addition, the correlation between clinical and IVIM parameters and the prostate-specific antigen nadir (PSAN) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) in OPCa was explored. It was found that the IVIM parameters could effectively differentiate LPCa and WPCa, as well as LPCa and OPC. Moreover, Gleason score (GS) was positively correlated with PSAN, while prostate volume was positively correlated with TTN. METHODS: About 54 patients were included in this retrospective study (mean age=74±7.4 years). ADC, D, D*, and f were acquired according to the biexponential Diffusion Weighted Imaging (DWI) model. The Kruskal-Wallis test was used to test the differences in clinical and IVIM parameters among the three groups. The Receiver Operating Characteristic (ROC) curve was used to evaluate the discrimination abilities. The Area Under the Curve (AUC) was compared using the DeLong test. Furthermore, Spearman correlation analysis was performed to assess the correlation between clinical and IVIM parameters of PSAN and TTN during initial ADT with OPCa. RESULTS: There were significant differences among the three groups observed for age, PSA, GS, ADC, D and D* values (P<0.05). Multi-parameter pairwise comparison results showed that significant differences between LPCa and WPCa were observed for the age, PSA, GS, ADC, D and D* values (P<0.05). However, D* was different between the LPCa and OPCa groups (P=0.032). GS showed a significant positive correlation with PSAN (Rho=0.594, P=0.042), and prostate volume showed a significant positive correlation with TTN (Rho=0.777, P=0.003). CONCLUSIONS: The IVIM parameters can effectively differentiate LPCa and WPCa, as well as LPCa and OPCa. Moreover, there was a certain trend in their distribution, which could reflect the tumor burden of PCa.