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The challenge of dynamic view synthesis from dynamic monocular videos, i.e., synthesizing novel views for free viewpoints given a monocular video of a dynamic scene captured by a moving camera, mainly lies in accurately modeling the dynamic objects of a scene using limited 2D frames, each with a varying timestamp and viewpoint. Existing methods usually require pre-processed 2D optical flow and depth maps by off-the-shelf methods to supervise the network, making them suffer from the inaccuracy of the pre-processed supervision and the ambiguity when lifting the 2D information to 3D. In this paper, we tackle this challenge in an unsupervised fashion. Specifically, we decouple the motion of the dynamic objects into object motion and camera motion, respectively regularized by proposed unsupervised surface consistency and patch-based multi-view constraints. The former enforces the 3D geometric surfaces of moving objects to be consistent over time, while the latter regularizes their appearances to be consistent across different viewpoints. Such a fine-grained motion formulation can alleviate the learning difficulty for the network, thus enabling it to produce not only novel views with higher quality but also more accurate scene flows and depth than existing methods requiring extra supervision. We will make the code publicly available at https://github.com/mengyou2/DecoulpingNeRF.
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We designed and developed 9MW2821, an anti-Nectin-4 antibody-drug conjugate (ADC) with an enzymatically cleavable valine-citrulline linker and monomethyl auristatin E (MMAE) as the payload. Four bioanalytical assays for total antibodies, conjugated antibodies, conjugated payload, and free payload were then developed and validated for the comprehensive evaluation of the multiple drug forms of 9MW2821. Specific sandwich enzyme-linked immunosorbent assays were used to quantify total antibodies and conjugated antibody, showing good drug-to-antibody ratio (DAR) tolerance. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine free MMAE, and conjugated MMAE was quantified using a combination of ligand-binding assay (LBA) and LC-MS/MS. Based on these four assays, we studied the serum stability and monkey pharmacokinetic profiles of 9MW2821, and the in vivo DAR of 9MW2821 was calculated and dynamically monitored. In conclusion, we developed and validated series of bioanalytical assays to quantify multiple forms of 9MW2821, a new ADC, and used the assays to evaluate the serum stability and monkey pharmacokinetic characteristics. The results indicate good linker stability and suggest that the developed assays can be further used in clinical settings.
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Ensayo de Inmunoadsorción Enzimática , Inmunoconjugados , Oligopéptidos , Espectrometría de Masas en Tándem , Inmunoconjugados/farmacocinética , Inmunoconjugados/química , Inmunoconjugados/sangre , Animales , Espectrometría de Masas en Tándem/métodos , Oligopéptidos/farmacocinética , Oligopéptidos/química , Oligopéptidos/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Cromatografía Liquida/métodos , Humanos , Macaca fascicularis , Masculino , Reproducibilidad de los Resultados , Anticuerpos Monoclonales/sangre , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/farmacocinéticaRESUMEN
Conducting polymers like polypyrrole, polyaniline, and polythiophene with nanostructures offers several advantages, such as high conductivity, a conjugated structure, and a large surface area, making them highly desirable for energy storage applications. However, the direct synthesis of conducting polymers with nanostructures poses a challenge. In this study, we employed a hard template method to fabricate polystyrene@polypyrrole (PS@PPy) core-shell nanoparticles. It is important to note that PS itself is a nonconductive material that hinders electron and ion transport, compromising the desired electrochemical properties. To overcome this limitation, the PS cores were removed using organic solvents to create hollow PPy nanospheres. We investigated six different organic solvents (cyclohexane, toluene, tetrahydrofuran, chloroform, acetone, and N,N-dimethylformamide (DMF)) for etching the PS cores. The resulting hollow PPy nanospheres showed various nanostructures, including intact, hollow, buckling, and collapsed structures, depending on the thickness of the PPy shell and the organic solvent used. PPy nanospheres synthesized with DMF demonstrated superior electrochemical properties compared to those prepared with other solvents, attributed to their highly effective PS removal efficiency, increased specific surface area, and improved charge transport efficiency. The specific capacitances of PPy nanospheres treated with DMF were as high as 350 F/g at 1 A/g. And the corresponding symmetric supercapacitor demonstrated a maximum energy density of 40 Wh/kg at a power density of 490 W/kg. These findings provide new insights into the synthesis method and energy storage mechanisms of PPy nanoparticles.
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OBJECTIVE: To investigate the effects of physiotherapeutic scoliosis-specific exercises (PSSE) on coronal, horizontal, and sagittal deformities of the spine in adolescent idiopathic scoliosis (AIS) as well as how curve severity, intervention duration, and intervention type could modify these effects. DATA SOURCES: Data sources included PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases, which were searched from their inception to September 5, 2023. STUDY SELECTION: Clinical controlled trials reporting the effects of PSSE on the Cobb angle, angle of trunk rotation (ATR), thoracic kyphosis (TK), or lumbar lordosis in patients with AIS aged 10-18 years. The experimental groups received PSSE; the control groups received standard care (observation or bracing) or conventional exercise such as core stabilization exercise, Pilates, proprioceptive neuromuscular facilitation, and other nonspecific exercises. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The quality of the studies was assessed using the Cochrane Handbook version 5.1.0 risk of bias assessment and the JBI Center for Evidence-Based Health Care (2016) of quasi-experimental research authenticity assessment tool. The level and certainty of evidence were rated according to the Grading of Recommendations, Assessment, Development, and Evaluation framework. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The protocol for this study was registered in PROSPERO (CRD42023404996). DATA SYNTHESIS: Twelve randomized controlled trials (RCTs) and 5 non-RCTs were meta-analyzed separately. The results indicated that compared with other nonsurgical management, PSSE significantly improved the Cobb angle, ATR, and TK, whereas the lumbar lordosis improvement was not statistically significant. Additionally, the efficacy of PSSE on Cobb angle was not significant in patients with curve severity ≥30° compared with controls. Nevertheless, the pooled effect of PSSE on Cobb angle was not significantly modified by intervention duration and intervention type and that on ATR was not significantly modified by intervention duration. The overall quality of evidence according to Grading of Recommendations, Assessment, Development, and Evaluation was moderate to low for RCT and very low for non-RCT. CONCLUSIONS: PSSE exhibited positive benefits on the Cobb angle, ATR, and TK in patients with AIS compared with other nonsurgical therapies. In addition, the effectiveness of PSSE may be independent of intervention duration and intervention type but may be influenced by the initial Cobb angle. However, more RCTs are needed in the future to validate the efficacy of PSSE in moderate AIS with a mean Cobb angle ≥30°. Current evidence is limited by inconsistent control group interventions and small sample size of the studies.
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A convenient, efficient, and green dispersive liquid-liquid microextraction based on the in situ formation of solidified supramolecular solvents combined with high performance liquid chromatography was developed for the determination of four phenylurea herbicides in liquid samples, including monuron, monolinuron, isoproturon, and chlortoluron. Herein, a novel supramolecular solvent was prepared by the in situ reaction of [P4448]Br and NH4PF6, which had the advantages of low melting point, high density, and good dispersibility. In addition, the microscopic morphology and physical properties of supramolecular solvent were characterized, and the extraction conditions were optimized. The results showed that the analytes had good linearity (R2 > 0.9998) within the linear range. The limits of detection and quantification for the four phenylurea herbicides were in the range of 0.13-0.19 µg L-1 and 0.45-0.65 µg L-1, respectively. The prepared supramolecular solvent is suitable for the efficient extraction of phenylurea herbicides in water, fruit juice, and milk.
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Jugos de Frutas y Vegetales , Herbicidas , Microextracción en Fase Líquida , Leche , Compuestos de Fenilurea , Solventes , Microextracción en Fase Líquida/métodos , Herbicidas/química , Herbicidas/aislamiento & purificación , Herbicidas/análisis , Leche/química , Compuestos de Fenilurea/aislamiento & purificación , Compuestos de Fenilurea/química , Compuestos de Fenilurea/análisis , Jugos de Frutas y Vegetales/análisis , Solventes/química , Animales , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Contaminación de Alimentos/análisisRESUMEN
OBJECTIVES: This study aimed to use all permanent teeth as the target and establish an automated dental age estimation method across all developmental stages of permanent teeth, accomplishing all the essential steps of tooth determination, tooth development staging, and dental age assessment. METHODS: A three-step framework for automatically estimating dental age was developed for children aged 3 to 15. First, a YOLOv3 network was employed to complete the tasks of tooth localization and numbering on a digital orthopantomogram. Second, a novel network named SOS-Net was established for accurate tooth development staging based on a modified Demirjian method. Finally, the dental age assessment procedure was carried out through a single-group meta-analysis utilizing the statistical data derived from our reference dataset. RESULTS: The performance tests showed that the one-stage YOLOv3 detection network attained an overall mean average precision 50 of 97.50 for tooth determination. The proposed SOS-Net method achieved an average tooth development staging accuracy of 82.97% for a full dentition. The dental age assessment validation test yielded an MAE of 0.72 years with a full dentition (excluding the third molars) as its input. CONCLUSIONS: The proposed automated framework enhances the dental age estimation process in a fast and standard manner, enabling the reference of any accessible population. CLINICAL RELEVANCE: The tooth development staging network can facilitate the precise identification of permanent teeth with abnormal growth, improving the effectiveness and comprehensiveness of dental diagnoses using pediatric orthopantomograms.
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Aprendizaje Profundo , Humanos , Niño , Tercer Molar , Odontogénesis , Radiografía PanorámicaRESUMEN
BACKGROUND: To infer the optimal angulation and height level of mini-implant insertion in the anterior nasal spine (ANS) region from alveolar bone depth (BD) and labial cortical bone thickness (CBT) through cone-beam computed tomography (CBCT), the influences of sex, age, and growth pattern on BD, CBT, and the starting point of the ANS were examined. MATERIAL AND METHODS: BD and CBT were measured on CBCT median sagittal images at specific angles (0, 15, 30, 45, and 60 degrees) to simulate the angulation of insertion. The height level of the first axial image with obvious bone ridge was recorded as the start of ANS. RESULTS: The average height of ANS start was 9.42 mm from the alveolar bone crest between the central incisors. The variations in height level and insertion angle combined, or either of them individually, significantly influenced BD and CBT, demonstrating overall decreasing trends (p < 0.001). BD was not influenced by sex, age, or growth pattern (p > 0.05). However, CBT was found to be correlated with sex and growth pattern, while the height level of ANS start was associated only with growth pattern, particularly in hypodivergent patients (p < 0.05). CONCLUSION: The recommended insertion height level is 14-16 mm from the alveolar bone crest and the recommended angulation is 30-45°. An innovative inequity in the relationship between a certain height level and the insertion angulation is proposed.
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Membrane technology using well-defined pore structure can achieve high ion purity and recovery. However, fine-tuning the inner pore structure of the separation nanofilm to be uniform and enhance the effective pore area is still challenging. Here, we report dendrimers with different peripheral groups that preferentially self-assemble in aqueous-phase amine solution to facilitate the formation of polyamide nanofilms with a well-defined effective pore range and uniform pore structure. The high permeabilities are maintained by forming asymmetric hollow nanostripe nanofilms, and their well-designed ion effective separation pore ranges show an enhancement, rationalized by molecular simulation. The self-assembled dendrimer polyamide membrane provides Cl-/SO42- selectivity more than 17 times that of its pristine polyamide counterparts, increasing from 167.9 to 2883.0. Furthermore, the designed membranes achieve higher Li purity and Li recovery compared to current state-of-the-art membranes. Such an approach provides a scalable strategy to fine-tune subnanometre structures in ion separation nanofilms.
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Artemisia argyi is a traditional Chinese herb with antibacterial, antifungal, and antitumor activities. The essential oil of Artemisia argyi was extracted using the steam distillation method in this study. The chemical composition of the essential oil was analyzed using the gas chromatography-mass spectrometry method. Agar disc diffusion and double-broth dilution assays were used to detect the antimicrobial activity of the essential oil. Subsequently, the antimicrobial mechanisms were explored through cytomembrane permeability assay and electron microscopy. Based on gas chromatography-mass spectrometry analysis, 25 compounds were detected, including 13.76% cineole, 6.77% terpinen-4-ol, 6.68% 3-dione, 1,7,7-trimethyl-, 4.07% 3-cyclohexen-1-ol, 4-methyl-1-(1-methylethyl)-acetate, 3.58% 1-isopropyl-2-methylbenzene, and 1.58% g-terpinene. The essential oil was tested for antimicrobial activity, and the IC50 values for Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Listeria monocytogenes, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Candida albicans were determined to be 25.51 ± 2.29, 49.53 ± 0.86, 52.40 ± 1.49, 52.76 ± 1.60, 73.99 ± 1.38, 65.52 ± 0.95, and 214.98 ± 3.27 µg mL-1, respectively. For essential oil interaction with cytoderm, the microorganisms treated by 1 × IC50 and 2 × IC50 concentration of essential oil both represented positive test results. Additionally, the alkaline phosphatase levels showed a direct correlation with concentration and treatment duration (range from 0 to 8 h). The interaction between essential oils and the cytomembrane was investigated by examining samples containing one of three test strains (Staphylococcus aureus, Escherichia coli, and Candida albicans), essential oil, and voltage-sensitive fluorescent dye disc35. The results demonstrated a significant increase in fluorescence levels within the solution upon introduction of the essential oil-treated strains. The findings of our research suggest that the essential oil disrupts the cytoderm and cytomembrane, thereby exhibiting antimicrobial activity.
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Antiinfecciosos , Artemisia , Aceites Volátiles , Aceites Volátiles/farmacología , Aceites Volátiles/química , Artemisia/química , Pruebas de Sensibilidad Microbiana , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bacterias , Antibacterianos/farmacología , Antibacterianos/química , Hongos , Escherichia coliRESUMEN
To determine how to strengthen the Cd-enriched plant Solanum nigrum L. to remediate cadmium(Cd)-contaminated soil, a pot experiment was conducted with five treatments:control treatment(CK), Glomus mosseae(GM), G. mosseae+citric acid(GM+CA), G. mosseae+Bacillus megaterium(GM+BM), and G. mosseae+B. megaterium+citric acid(GM+BM+CA). We measured soil total Cd, available Cd, plant Cd uptake, and microbial community changes and analyzed the effects of exogenous microbial agents and citric acid addition on the remediation effect of Cd contamination by S. nigrum L. The results showed that relative to that of the CK treatment, the root, stem, and leaf biomass of the GM treatment significantly increased by 35.67%, 41.35%, and 65.38%, and the root and stem biomass of the GM+BM+CA treatment significantly increased by 73.38% and 75.38%. The GM+BM+CA treatment significantly increased Cd accumulation in leaves by 226.84%. The GM+BM+CA treatment significantly increased the Cd transport factor from stem to leaves by 52.47%. The GM+BM+CA treatment significantly increased the leaf bioconcentration factor by 120.53%. In addition, the combined restoration also had an impact on the rhizosphere microbial community structure, especially in inducing the relative abundance of some key microbial groups such as Proteobacteria, Actinobacteria, Glomeromycota, and Olpidiomycota to increase by 2.00%-5.77%, 0.76%-9.96%, 2.11%-3.63%, and 0.54%-2.98%, respectively. According to the RDA analysis, Proteobacteria and Actinobacteria were negatively correlated with soil total Cd, whereas Glomeromycota and Olpidiomycota were negatively correlated with soil total Cd. The changes in key microorganisms enhanced the ability of S. nigrum L. to absorb rhizosphere nutrients and resist Cd stress, increased the Cd accumulation ability of S. nigrum L., and effectively reduced the total Cd content in soil. In conclusion, G. mosseae, citric acid, and B. megaterium activated insoluble Cd in the soil by co-inoculation, which contributed to more Cd accumulation by S. nigrum L. and also produced co-remediation with G. mosseae. The enrichment plant-microorganism combined remediation Cd-contaminated soil has good application potential.
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Glomeromycota , Contaminantes del Suelo , Solanum nigrum , Biodegradación Ambiental , Cadmio/análisis , Suelo/química , Ácido Cítrico/farmacología , Contaminantes del Suelo/análisis , Bacterias , ProteobacteriaRESUMEN
BACKGROUND: Perforation of the lingual cortex while placing dental implants in the interforaminal region of the mandible can cause severe hemorrhage. The purpose of this study was to evaluate the features of mandibular lingual foraminals (MLFs) and locational relationship between them and lingual mucosal vessels (LMVs) by CT/MRI fusion volumetric images. METHODS: 37 images within complete anterior mandibular region using both MSCT and three-dimensional volumetric interpolated breath-hold examination (3D-VIBE) MRI were taken from our imaging archives. After exclusion of 11 for lesions or artifacts, 26 CT/MRI fusion volumetric images were included to evaluate the frequency, diameter, and position of MLFs. The anterior mandibular region was divided into 4 equal segments under each teeth, and 40 regions were got from C5 to D5. Furthermore, the positional relationship between MLFs and LMVs was analyzed in this coordinate system. RESULTS: 62 MLFs (73.81%) were located below the incisors, followed by premolars (21.43%) and canines (4.76%). Female bias, the mean diameter of the female was 0.08 mm while the male was 0.21 mm. The total number of LMVs was most distributed on lingual side of C1 and D1. According to Spearman's correlation coefficient, the location of MLFs was related to LMVs. The MLFs in fourth segment of D1 were positively moderately correlated with LMVs in fourth segment of D4, while the MLFs in third segment of C1 showed a weak positive correlation with LMVs in third segment of D4. CONCLUSIONS: The features and the correlation between MLFs and LMVs in CT/MRI fusion volumetric images may offer reference to dentists when only MLFs can been seen on routine preoperative CT examination of implants. TRIAL REGISTRATION: Retrospectively registered. (D2018-072).
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Implantes Dentales , Humanos , Masculino , Femenino , Tomografía Computarizada por Rayos X , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada de Haz CónicoRESUMEN
Background: Ultrasonography has been applied as an alternative method in the assessment of temporomandibular joint (TMJ) pathology including anterior disc displacement (ADD). However, a concrete screening or diagnostic method which is feasible in clinical practice has not yet been established. The study aimed to establish a quantitative ultrasonographic method and determine its diagnostic efficacy for ADD of the TMJ. Methods: A total of 75 joints were allocated to either the normal disc position (NDP) group or the ADD group using magnetic resonance imaging (MRI) as the reference standard. Longitudinal scans of the lateral articular compartment were obtained by a 14-MHz L-shaped linear array transducer. The width of the lateral joint space (LJS), the upper lateral joint space (ULJS), and the lower lateral joint space (LLJS), as well as the position of the lateral articular disc edge (ADE), were investigated by stepwise logistic regression analysis to identify significant indicators of ADD and to build a diagnostic model. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were computed at the optimal cut-off value. Results: MRI detected 25 joints in the NDP group and 50 joints in the ADD group. Correlation analysis indicated that all 4 variables were associated with ADD. With the best performance of the area under the receiver operating characteristic (ROC) curve (AUC) of 0.939, LJS and ULJS were identified as predictors of ADD and subsequently adopted to build a diagnostic model by stepwise logistic regression. The optimal cut-off value of the 2-variable regression model for diagnosing ADD was 0.800, with a sensitivity of 82%, specificity of 96%, PPV of 97.6%, NPV of 72.7%, and an accuracy of 86.7%. Conclusions: The quantitative ultrasonographic diagnostic method showed promising diagnostic efficacy. It has the potential to be used for ADD screening in future clinical practice.
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In this paper, we explore the problem of 3D point cloud representation-based view synthesis from a set of sparse source views. To tackle this challenging problem, we propose a new deep learning-based view synthesis paradigm that learns a locally unified 3D point cloud from source views. Specifically, we first construct sub-point clouds by projecting source views to 3D space based on their depth maps. Then, we learn the locally unified 3D point cloud by adaptively fusing points at a local neighborhood defined on the union of the sub-point clouds. Besides, we also propose a 3D geometry-guided image restoration module to fill the holes and recover high-frequency details of the rendered novel views. Experimental results on three benchmark datasets demonstrate that our method can improve the average PSNR by more than 4 dB while preserving more accurate visual details, compared with state-of-the-art view synthesis methods. The code will be publicly available at https://github.com/mengyou2/PCVS.
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OBJECTIVES: This study aims to determine the reproducibility and location-stability of cone-beam computed tomography (CBCT) radiomic features. METHODS: Centrifugal tubes with six concentrations of K2HPO4 solutions (50, 100, 200, 400, 600, and 800 mg ml-1) were imaged within a customized phantom. For each concentration, images were captured twice as test and retest sets. Totally, 69 radiomic features were extracted by LIFEx. The reproducibility was assessed between the test and retest sets. We used the concordance correlation coefficient (CCC) to screen qualified features and then compared the differences in the numbers of them under 24 series (four locations groups * six concentrations). The location-stability was assessed using the Kruskal-Wallis test under different concentration sets; likewise, the numbers of qualified features under six test sets were analyzed. RESULTS: There were 20 and 23 qualified features in the reproducibility and location-stability experiments, respectively. In the reproducibility experiment, the performance of the peripheral groups and high-concentration sets was significantly better than the center groups and low-concentration sets. The effect of concentration on the location-stability of features was not monotonic, and the number of qualified features in the low-concentration sets was greater than that in the high-concentration sets. No features were qualified in both experiments. CONCLUSIONS: The density and location of the target object can affect the number of reproducible radiomic features, and its density can also affect the number of location-stable radiomic features. The problem of feature reliability should be treated cautiously in radiomic research on CBCT.
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Tomografía Computarizada de Haz Cónico , Humanos , Reproducibilidad de los Resultados , Tomografía Computarizada de Haz Cónico/métodos , Fantasmas de ImagenRESUMEN
The objective of this study is to provide a comprehensive summary of the clinical and radiological features of zygomatic intraosseous venous malformations (IVM), as well as its treatment strategies. The aim is to establish preoperative diagnostic bases that will aid in the identification of zygomatic IVM and facilitate the implementation of effective treatment. Four cases of pathologically diagnosed zygomatic IVM with typical clinical and radiological features were reported. They exhibited comparable clinical and radiological features, and the En bloc excision and reconstruction yielded satisfactory outcome. Pooled data analysis was performed with additional 74 cases collected from 63 previous studies. The results revealed a higher incidence of zygomatic IVMs in middle-aged females, with swelling, pain and ocular dysfunction being the typical clinical manifestations. The characteristic radiological features of these lesions were well-defined, round bony structures with specific internal trabecular patterns. A diagnostic flow-chart assisting the differential diagnosis of IVM was established. En bloc excision was deemed the most advantageous treatment option, as it presented minimal risk of haemorrhaging and no instances of recurrence. The decision to pursue reconstruction was contingent upon the extent of the defect. Alloplastic material has emerged as the most frequently employed reconstruction material in recent reports. The summarized characteristics of zygomatic IVM and the proposed diagnostic and treatment strategies, derived from the pooled analysis of reported cases, may help to improve diagnosis and management in further clinical practice.
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Malformaciones Vasculares , Cigoma , Persona de Mediana Edad , Femenino , Humanos , Cigoma/diagnóstico por imagen , Cigoma/cirugía , Tomografía Computarizada por Rayos X/métodos , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/cirugía , Resultado del Tratamiento , CaraRESUMEN
The case presented in this study is a rare instance of an ossifying fibroma (OF), a type of benign fibro-osseous lesions, spontaneously regressed without surgical intervention. A 9-year-old boy with an intraosseous lesion in the left maxilla was diagnosed as OF. The surgeon suggested surgical excision, but due to personal reasons, the patient and his parents deferred the surgery and opted for regular follow-up. During a 4-year follow-up, the surgeon found that the lesion had significantly decreased in size and the facial deformity had remitted. At the latest follow-up, the deformity of his left face became almost unnoticeable, and the lesion seemed to be subtle on cone-beam computed tomography images. This case highlights the possibility of spontaneous regression of OF. This phenomenon may occur due to the teeth eruption, which can lead to the formation of periodontal ligaments and engage the regression of OF.
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Fibroma Osificante , Neoplasias Craneales , Masculino , Humanos , Niño , Fibroma Osificante/diagnóstico por imagen , Fibroma Osificante/cirugía , Estudios de Seguimiento , Maxilar/cirugía , Cabeza/patología , Neoplasias Craneales/patologíaRESUMEN
We designed and developed a novel DNA topoisomerase I inhibitor MF-6, which was a more potent cytotoxin and a more potent inducer of immunogenic cell death compared with DXd. To utilize MF-6's ability to induce antitumor immunity, a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) trastuzumab-L6 that included a cleavable linker and MF-6 was developed. Different from traditional cytotoxic ADC, the antitumor activity of trastuzumab-L6 was assessed by inducing tumor cell immunogenic cell death, activating dendritic cells and cytotoxic CD8+ T cells to acquire durable adaptive immune memory. Tumor cells treated with trastuzumab-L6 were committed to immunogenic cell death, with upregulation of damage-associated molecular patterns and antigen presentation molecules. In a syngeneic tumor model with a mouse cell line that expressed human HER2, immunocompetent mice showed greater antitumor efficacy compared with nude mice. The trastuzumab-L6-cured immunocompetent mice acquired adaptive antitumor memory and rejected subsequent tumor cell challenge. The trastuzumab-L6 efficacy was abrogated when cytotoxic CD8+ T cells were depleted and enhanced when regulatory CD4+ T cells were depleted. The combination of trastuzumab-L6 with immune checkpoint inhibitors significantly increased antitumor efficacy. Enhanced T cell infiltration, dendritic cell activation, and decreased type M2 macrophages in tumor post trastuzumab-L6 administration confirmed the immune-activating responses. In conclusion, trastuzumab-L6 was considered to be an immunostimulatory agent, rather than a traditional cytotoxic ADC, and its antitumor efficacy was enhanced when combined with an anti-PD-L1 and anti-CTLA-4 antibody, which suggested a potential therapeutic strategy.
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Inmunoconjugados , Inhibidores de Topoisomerasa I , Humanos , Animales , Ratones , Ratones Desnudos , Anticuerpos , Trastuzumab/farmacología , Células DendríticasRESUMEN
Overexpression of nectin cell adhesion protein 4 correlates with cancer progression and poor prognosis in many human malignancies. Enfortumab vedotin (EV) is the first nectin-4-targeting antibody-drug conjugate (ADC) approved by the FDA for the treatment of urothelial cancer. However, inadequate efficacy has limited progress in the treatment of other solid tumors with EV. Furthermore, ocular, pulmonary, and hematologic toxic side effects are common in nectin-4-targeted therapy, which frequently results in dose reduction and/or treatment termination. Thus, we designed a second generation nectin-4-specific drug, 9MW2821, based on interchain-disulfide drug conjugate technology. This novel drug contained a site specifically conjugated humanized antibody and the cytotoxic moiety monomethyl auristatin E. The homogenous drug-antibody ratio and novel linker chemistry of 9MW2821 increased the stability of conjugate in the systemic circulation, enabling highly efficient drug delivery and avoiding off-target toxicity. In preclinical evaluation, 9MW2821 exhibited nectin-4-specific cell binding, efficient internalization, bystander killing, and equivalent or superior antitumor activity compared with EV in both cell line-derived xenograft and patient-derived xenograft (PDX) models. In addition, 9MW2821 demonstrated a favorable safety profile; the highest nonseverely toxic dose in monkey toxicologic studies was 6 mg/kg, with milder adverse events compared with EV. Overall, 9MW2821 is a nectin-4-directed, investigational ADC based on innovative technology that endowed the drug with compelling preclinical antitumor activity and a favorable therapeutic index. The 9MW2821 ADC is being investigated in a phase I/II clinical trial (NCT05216965 and NCT05773937) in patients with advanced solid tumors.
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Inmunoconjugados , Neoplasias , Humanos , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Nectinas , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias/tratamiento farmacológico , Moléculas de Adhesión Celular , Línea Celular TumoralRESUMEN
We aimed to establish the characteristics and potential etiological risk factors of eruption disturbances in mandibular second molars (MM2). We retrospectively enrolled patients with eruption disturbances in MM2. A total of 143 MM2 with eruption disturbances from 112 patients (mean age 17.45 ± 6.35) were included in this study. Panoramic radiographs were employed to determine the risk factor, angulation type, impaction depth, tooth development stage, and associated pathology. The novel classification method of MM2 was based on impaction depth and angulation. Of 143 MM2, 137 and 6 were diagnosed with impaction and retention, respectively. Insufficient space was the most frequent risk factor for eruption disturbances. There were no significant differences between retention and impaction regarding sex, age, or side. The most frequent impaction type was Type I. The most frequent angulation of impacted MM2 was mesioangular. Impacted MM2 with shallower depth were more frequently associated with the presence of first molar undercut. Impaction types did not differ according to age, side, development stage, or distance from the MM1 distal surface to the anterior border of the ramus. Dentigerous cysts were associated with earlier MM2 development stages and greater MM2 depth. In conclusion, MM2 impaction types differed according to the risk factor, angulation type, MM1 undercut, and presence of cysts. Early MM2 development stage and greater MM2 depth were risk factors for MM2 eruption disturbances with cysts.
RESUMEN
Transition-metal chalcogenides, such as noble metal chalcogenides, hold tremendous potential as efficient agents for photo-induced cancer theranostics due to their unique physicochemical properties. However, a critical bottleneck still lies in exploring simple and controllable methods to synthesize noble metal chalcogenides especially PtS for in vivo photo-induced cancer imaging and simultaneous therapy. Herein, we proposed the albumin-templated synthesis of size-controllable platinum (II) sulfide nanodots (PtS-NDs) for multimodal cancer imaging and potent photothermal therapy. PtS-NDs were precisely synthesized with a tunable size ranging from 2.1 nm to 4.5 nm through a thermodynamically controlled growth inside albumin nanocages. PtS-NDs yielded significant near-infrared (NIR) absorbance and outstanding photothermal conversion under NIR laser irradiation, as well as effective resistance to photobleaching, thereby generating remarkable in vivo photoacoustic signals and distinct hyperthermia at tumor site. Moreover, these nanodots possessed efficient cellular uptake and tumor targeting capabilities in a size-dependent manner, thus leading to controllable diagnostic and thermo-therapeutic efficacy. Specifically, PtS-NDs with core diameter of 4.5 nm displayed preferable in vivo photoacoustic and CT imaging with high sensitivity, spatially and anatomically enhanced imaging contrast, together with hyperthermia mediated tumor ablation. Thus, the albumin-templated biomimetic synthesis provided an insightful strategy on fabricating theranostic PtS-NDs for potential clinical applications. STATEMENT OF SIGNIFICANCE: Noble metal chalcogenides especially PtS are of particular importance in the field of precise nanomedicine to improve both accuracy of cancer diagnosis and efficiency of tumor treatment. However, the intensively preclinical investigation of PtS was limited due to the lack of simple and controllable synthetic methods. Here, we report an albumin-templated biomineralization synthesis of platinum (II) sulfide nanodots (PtS-NDs). Specifically, albumin-templated biomineralization of PtS-NDs was induced by the electrostatic interactions between albumin and Pt2+, followed by the nucleation and growth inside the albumin nanocages. The resulting PtS-NDs showed good dispersibility and biosafety, as well as size-dependent photophysical properties and biological behaviors. Therefore, albumin-based biomineralization is a promising and safe strategy to facilely fabricate Pt-based chalcogenide for tumor theranostics.