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The A/T/N research framework has been proposed for the diagnosis and prognosis of Alzheimer's disease (AD). However, the spatial distribution of ATN biomarkers and their relationship with cognitive impairment and neuropsychiatric symptoms (NPS) need further clarification in patients with AD. We scanned 83 AD patients and 38 cognitively normal controls who independently completed the mini-mental state examination and Neuropsychiatric Inventory scales. Tau, Aß, and hypometabolism spatial patterns were characterized using Statistical Parametric Mapping together with [18F]flortaucipir, [18F]florbetapir, and [18F]FDG positron emission tomography. Piecewise linear regression, two-sample t-tests, and support vector machine algorithms were used to explore the relationship between tau, Aß, and hypometabolism and cognition, NPS, and AD diagnosis. The results showed that regions with tau deposition are region-specific and mainly occurred in inferior temporal lobes in AD, which extensively overlaps with the hypometabolic regions. While the deposition regions of Aß were unique and the regions affected by hypometabolism were widely distributed. Unlike Aß, tau and hypometabolism build up monotonically with increasing cognitive impairment in the late stages of AD. In addition, NPS in AD were associated with tau deposition closely, followed by hypometabolism, but not with Aß. Finally, hypometabolism and tau had higher accuracy in differentiating the AD patients from controls (accuracy = 0.88, accuracy = 0.85) than Aß (accuracy = 0.81), and the combined three were the highest (accuracy = 0.95). These findings suggest tau pathology is superior over Aß and glucose metabolism to identify cognitive impairment and NPS. Its results support tau accumulation can be used as a biomarker of clinical impairment in AD.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores/metabolismo , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismoRESUMO
PURPOSE: This study aimed to describe 11C-methionine (11C-MET) PET imaging characteristics in patients with paediatric diffuse intrinsic pontine glioma (DIPG) and correlate them with survival and H3 K27M mutation status. METHODS: We retrospectively analysed 98 children newly diagnosed with DIPG who underwent 11C-MET PET. PET imaging characteristics evaluated included uptake intensity, uniformity, metabolic tumour volume (MTV), and total lesion methionine uptake (TLMU). The maximum, mean, and peak of the tumour-to-background ratio (TBR), calculated as the corresponding standardised uptake values (SUV) divided by the mean reference value, were also recorded. The associations between the PET imaging characteristics and clinical outcomes in terms of progression-free survival (PFS) and overall survival (OS) and H3 K27M mutation status were assessed, respectively. RESULTS: In univariate analysis, imaging characteristics significantly associated with shorter PFS and OS included a higher uniformity grade, higher TBRs, larger MTV, and higher TLMU. In multivariate analysis, larger MTV at diagnosis, shorter symptom duration, and no treatment were significantly correlated with shorter PFS and OS. The PET imaging features were not correlated with H3 K27M mutation status. CONCLUSION: Although several imaging features were significantly associated with PFS and OS, only MTV, indicating the size of the active tumour, was identified as a strong independent prognostic factor.
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Neoplasias Encefálicas , Glioma Pontino Intrínseco Difuso , Glioma , Humanos , Criança , Metionina/genética , Neoplasias Encefálicas/genética , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/metabolismo , Estudos Retrospectivos , Glioma Pontino Intrínseco Difuso/diagnóstico por imagem , Glioma Pontino Intrínseco Difuso/genética , Racemetionina , Tomografia por Emissão de Pósitrons , MutaçãoRESUMO
OBJECTIVE: This study aimed to investigate the quantitative relationship between interictal 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and interictal high-frequency oscillations (HFOs) from stereo-electroencephalography (SEEG) recordings in patients with refractory epilepsy. METHODS: We retrospectively included 32 patients. FDG-PET data were quantified through statistical parametric mapping (SPM) t test modeling with normal controls. Interictal SEEG segments with four, 10-min segments were selected randomly. HFO detection and classification procedures were automatically performed. Channel-based HFOs separating ripple (80-250 Hz) and fast ripple (FR; 250-500 Hz) counts were correlated with the surrounding metabolism T score at the individual and group level, respectively. The association was further validated across anatomic seizure origins and sleep vs wake states. We built a joint feature FR × T reflecting the FR and hypometabolism concordance to predict surgical outcomes in 28 patients who underwent surgery. RESULTS: We found a negative correlation between interictal FDG-PET and HFOs through the linear mixed-effects model (R2 = .346 and .457 for ripples and FRs, respectively, p < .001); these correlations were generalizable to different epileptogenic-zone lobar localizations and vigilance states. The FR × T inside the resection volume could be used as a predictor for surgical outcomes with an area under the curve of 0.81. SIGNIFICANCE: The degree of hypometabolism is associated with HFO generation rate, especially for FRs. This relationship would be meaningful for selection of SEEG candidates and for optimizing SEEG scheme planning. The concordance between FRs and hypometabolism inside the resection volume could provide prognostic information regarding surgical outcome.
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Eletroencefalografia , Fluordesoxiglucose F18 , Humanos , Estudos Retrospectivos , Eletroencefalografia/métodos , Tomografia por Emissão de Pósitrons , Resultado do TratamentoRESUMO
PURPOSE: This study aimed to assess the ability of [11C]methionine (MET) PET in distinguishing between tumor progression (TP) and treatment-related changes (TRCs) among different types of adult-type diffuse gliomas according to the 2021 World Health Organization classification and predict overall survival (OS). METHODS: We retrospectively selected 113 patients with adult-type diffuse gliomas with suspected TP who underwent MET PET imaging. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and metabolic tumor volume (MTV) were calculated. Diagnoses were verified by histopathology (n = 50) or by clinical/radiological follow-up (n = 63). The diagnostic performance of MET PET parameters was evaluated through receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculation. Survival analysis employed the Kaplan-Meier method and Cox proportional-hazards regression. RESULTS: TP and TRCs were diagnosed in 76 (67%) and 37 (33%) patients, respectively. ROC analysis revealed TBRmax had the best performance in differentiating TP from TRCs with a cut-off of 1.96 in IDH-mutant astrocytoma (AUC, 0.87; sensitivity, 93%; specificity 69%), 1.80 in IDH-mutant and 1p/19q-codeleted oligodendroglioma (AUC, 0.96; sensitivity, 100%; specificity, 89%), and 2.13 in IDH wild-type glioblastoma (AUC, 0.89; sensitivity, 89%; specificity, 78%), respectively. On multivariate analysis, higher TBRmean and MTV were significantly correlated with shorter OS in all IDH-mutant gliomas, as well as in IDH-mutant astrocytoma subgroup. CONCLUSION: This work confirms that MET PET has varying diagnostic performances in distinguishing TP from TRCs within three types of adult-type diffuse gliomas, and highlights its high diagnostic accuracy in IDH-mutant and 1p/19q-codeleted oligodendroglioma and potential prognostic value for IDH-mutant gliomas, particularly IDH-mutant astrocytoma.
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Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Adulto , Humanos , Metionina , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/terapia , Racemetionina , Tomografia por Emissão de Pósitrons , Isocitrato Desidrogenase/genética , MutaçãoRESUMO
Treatment of schwannomas in patients with neurofibromatosis type 2 (NF2) is extremely unsatisfactory, and innovative therapeutic approaches are urgently needed. However, the lack of clinically relevant NF2-associated schwannoma models has severely hampered drug discovery in this rare disease. Here we report the first establishment and characterization of patient-derived xenograft (PDX) and cell line models of NF2-associated schwannoma, which recapitulates the morphological and histopathological features of patient tumors, retain patient NF2 mutations, and maintain gene expression profiles resembling patient tumor profiles with the preservation of multiple key signaling pathways commonly dysregulated in human schwannomas. Using gene expression profiling, we identified elevated PI3K/AKT/mTOR networks in human NF2-associated vestibular schwannomas. Using high-throughput screening of 157 inhibitors targeting the PI3K/AKT/mTOR pathways in vitro, we identified a dozen inhibitors (such as BEZ235, LY2090314, and AZD8055) with significant growth-suppressive effects. Interestingly, we observed that three cell lines displayed differential therapeutic responses to PI3K/AKT/mTOR inhibitors. Furthermore, we demonstrated that two orally bioavailable inhibitors, AZD8055 and PQR309, suppressed NF2-associated schwannoma growth both in vitro and in vivo. In conclusion, our novel patient-derived models of NF2-associated schwannoma closely mimic the phenotypes and genotypes of patient tumors, making them reliable preclinical tools for testing novel personalized therapies. © 2022 The Pathological Society of Great Britain and Ireland.
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Neurilemoma , Neurofibromatose 2 , Linhagem Celular , Xenoenxertos , Humanos , Neurilemoma/tratamento farmacológico , Neurilemoma/genética , Neurofibromatose 2/tratamento farmacológico , Neurofibromatose 2/genética , Neurofibromatose 2/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genéticaRESUMO
OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.
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Neoplasias do Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Criança , Humanos , Glioma/diagnóstico por imagem , Glioma/terapia , Estudos Retrospectivos , Neoplasias do Tronco Encefálico/diagnóstico por imagem , Neoplasias do Tronco Encefálico/cirurgia , Imagem MultimodalRESUMO
OBJECTIVE: The purpose of this study was to compare the therapeutic effects of Kirschner wire fixation and external fixation in the treatment of proximal humeral fractures in older children and adolescents. METHODS: A retrospective analysis was performed on the clinical data of older children and adolescents who underwent surgery at our institution for proximal humeral fractures between April 2014 and May 2022. One group (n = 28) underwent fracture reduction and Kirschner wire fixation, and the other group (n = 23) underwent external fixation. During the follow-up, the differences in shoulder joint function between the two groups were compared by analysing Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) and Constant-Murley scores. Postoperative complications were also recorded. RESULTS: The operation time of the Kirschner wire group was shorter than that of the external fixation group (69.07 ± 11.34 min vs. 77.39 ± 15.74 min, P = 0.33). The time to remove the fixator in the external fixation group was shorter than that in the Kirschner wire group (6.74 ± 1.57 vs. 7.61 ± 1.22, P = 0.032). The Quick DASH score and Constant-Murley score of the patients in the external fixation group were significantly better than those in the Kirschner wire group at 3 months after surgery (5.63 ± 4.33 vs. 8.93 ± 6.40, P = 0.040; 93.78 ± 2.43 vs. 91.75 ± 2.15, P = 0.003). There was no significant difference in the Quick DASH score or Constant-Murley score between the patients in the external fixator group and those in the Kirschner wire group at 9 months after the operation (2.77 ± 3.14 vs. 3.17 ± 3.68, P = 0.683; 97.39 ± 1.80 vs. 96.57 ± 2.15, P = 0.152). The most common complication of the two groups was pin tract infection. The incidence rate of infection was higher in the external fixation group than that in the Kirschner wire group (9 vs. 4, P = 0.043). CONCLUSION: Both Kirschner wire fixation and external fixation of N-H III and IV proximal humeral fractures in older children and adolescents produce good outcomes. External fixation is a preferred surgical treatment option for paediatric proximal humerus fractures because early mobilization of the affected limb can be realized.
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Fraturas do Úmero , Fraturas do Ombro , Humanos , Criança , Adolescente , Fios Ortopédicos , Fixação de Fratura/efeitos adversos , Fixadores Externos , Fixação Interna de Fraturas/efeitos adversos , Estudos Retrospectivos , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/cirurgia , Resultado do Tratamento , Fraturas do Úmero/cirurgiaRESUMO
KEY MESSAGE: Map-based cloning was used to identify the BrWAX2 gene, which was involved in the cuticular wax biosynthesis. The malfunction of BrWAX2 together with other reduced expression of genes in alkane-forming pathway caused the glossy phenotype. Cuticular wax covering the outer plant surface plays various roles in protecting against biotic and abiotic stresses. Wax-less mutant shows glossy in stem and leaf surface and plays important roles in enriching Chinese cabbage germplasm resources for breeding brilliant green varieties. However, genes responsible for the glossy trait in Chinese cabbage are rarely reported. In this study, we identified a glossy Chinese cabbage line Y1211-1. Genetic analysis indicated that the glossy trait in Y1211-1 was controlled by a single recessive locus, BrWAX2 (Brassica rapa WAX 2). Using bulked segregant sequencing (BSA-Seq) and kompetitive allele-specific PCR (KASP) assays, BrWAX2 was fine-mapped to an interval of 100.78 kb. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra032670, homologous to CER1 in Arabidopsis, was the most likely candidate gene for BrWAX2. The gene Bra032670 was absent in glossy mutant. Cuticular wax composition analysis and RNA-Seq analysis suggested that the absence of BrWAX2 together with the decreased expression of other genes in alkane-forming pathway reduced the wax amount and caused the glossy phenotype. Furthermore, we developed and validated the functional marker BrWAX2-sp for BrWAX2. Overall, these results provide insight into the molecular mechanism underlying cuticular wax biosynthesis and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.
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Brassica rapa , Brassica , Brassica/genética , Brassica rapa/genética , China , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Melhoramento VegetalRESUMO
Algal biomass is a promising feedstock for sustainable production of a range of value-added compounds and products including food, feed, fuel. To further augment the commercial value of algal metabolites, efficient valorization methods and biorefining channels are essential. Algal extracts are ideal sources of biotechnologically viable compounds loaded with anti-microbial, anti-oxidative, anti-inflammatory, anti-cancerous and several therapeutic and restorative properties. Emerging technologies in biomass valorisation tend to reduce the significant cost burden in large scale operations precisely associated with the pre-treatment, downstream processing and waste management processes. In order to enhance the economic feasibility of algal products in the global market, comprehensive extraction of multi-algal product biorefinery is envisaged as an assuring strategy. Algal biorefinery has inspired the technologists with novel prospectives especially in waste recovery, carbon concentration/sequestration and complete utilisation of the value-added products in a sustainable closed-loop methodology. This review critically examines the latest trends in the algal biomass valorisation and the expansive feedstock potentials in a biorefinery perspective. The recent scope dynamics of algal biomass utilisation such as bio-surfactants, oleochemicals, bio-stimulants and carbon mitigation have also been discussed. The existing challenges in algal biomass valorisation, current knowledge gaps and bottlenecks towards commercialisation of algal technologies are discussed. This review is a comprehensive presentation of the road map of algal biomass valorisation techniques towards biorefinery technology. The global market view of the algal products, future research directions and emerging opportunities are reviewed.
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Leaf color is an important characteristic of normal chloroplast development. Variegated plants have green- and white-sectored leaves, which can be used to identify important pathways and molecular mechanisms of chloroplast development. We studied two Brassica napus variegation mutants from same one variegated ancestor, designated ZY-4 and ZY-8, which have different degrees of variegation. When grown in identical conditions, the ratio of white sectors in ZY-4 leaves is higher than in ZY-8. In both mutants, the cells in green sectors contain normal chloroplasts; while, the cells in white sectors contain abnormal plastids. Seedling chloroplasts ultrastructure of both mutants showed that the biogenesis of chloroplasts was blocked in early stages; delayed development and structual damage in ZY-4 were more serious than in ZY-8. Employing bulked segregant analysis(BSA), two bulks (BY142 and BY137) from BC2F1 lines derived from ZY-4 and ZS11, and one bulk (BY56) from BC2F1 lines derived from ZY-8 and ZS11, and screening by Brassica 60K SNP BeadChip Array, showed the candidate regions localized in chromosome A08 (BY142), C04 (BY137), and A08 (BY56), respectively. Transcriptome analysis of five seedling development stages of ZY-4, ZY-8, and ZS11 showed that photosynthesis, energy metabolism-related pathways and translation-related pathways were important for chloroplast biogenesis. The number of down- or up-regulated genes related to immune system process in ZY-4 was more than in ZY-8. The retrograde signaling pathway was mis-regulated in both mutants. DEG analysis indicated that both mutants showed photooxidative damages. By coupling transcriptome and BSA CHIP analyses, some candidate genes were identified. The gene expression pattern of carotene biosynthesis pathway was disrupted in both mutants. However, histochemical analysis of ROS revealed that there was no excessive accumulation of ROS in ZY-4 and ZY-8. Taken together, our data indicate that the disruption of carotene biosynthetic pathways leads to the variegation phenotypes of ZY-4 and ZY-8 and there are some functions that can compensate for the disruption of carotene biosynthesis in ZY-4 and ZY-8 to reduce ROS and prevent seedling mortality.
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Brassica napus/genética , Carotenoides/metabolismo , Plastídeos/genética , Transcriptoma/genética , Arabidopsis/genética , Brassica napus/crescimento & desenvolvimento , Brassica napus/metabolismo , Cloroplastos/genética , Regulação da Expressão Gênica de Plantas/genética , Mutação/genética , Fotossíntese/genética , Desenvolvimento Vegetal/genética , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Plastídeos/metabolismoRESUMO
We address the study of quantum metrology enhanced by indefinite causal order, demonstrating a quadratic advantage in the estimation of the product of two average displacements in a continuous variable system. We prove that no setup where the displacements are used in a fixed order can have root-mean-square error vanishing faster than the Heisenberg limit 1/N, where N is the number of displacements contributing to the average. In stark contrast, we show that a setup that probes the displacements in a superposition of two alternative orders yields a root-mean-square error vanishing with super-Heisenberg scaling 1/N^{2}, which we prove to be optimal among all superpositions of setups with definite causal order. Our result opens up the study of new measurement setups where quantum processes are probed in an indefinite order, and suggests enhanced tests of the canonical commutation relations, with potential applications to quantum gravity.
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PURPOSE: To develop and validate an integrated model for discriminating tumor recurrence from radiation necrosis in glioma patients. METHODS: Data from 160 pathologically confirmed glioma patients were analyzed. The diagnostic model was developed in a primary cohort (n = 112). Textural features were extracted from postoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), 11C-methionine (11C-MET) PET, and magnetic resonance images. The least absolute shrinkage and selection operator regression model was used for feature selection and radiomics signature building. Multivariable logistic regression analysis was used to develop a model for predicting tumor recurrence. The radiomics signature, quantitative PET parameters, and clinical risk factors were incorporated in the model. The clinical value of the model was then assessed in an independent validation cohort using the remaining 48 glioma patients. RESULTS: The integrated model consisting of 15 selected features was significantly associated with postoperative tumor recurrence (p < 0.001 for both primary and validation cohorts). Predictors contained in the individualized diagnosis model included the radiomics signature, the mean of tumor-background ratio (TBR) of 18F-FDG, maximum of TBR of 11C-MET PET, and patient age. The integrated model demonstrated good discrimination, with an area under the curve (AUC) of 0.988, with a 95% confidence interval (CI) of 0.975-1.000. Application in the validation cohort showed good differentiation (AUC of 0.914 and 95% CI of 0.881-0.945). Decision curve analysis showed that the integrated diagnosis model was clinically useful. CONCLUSIONS: Our developed model could be used to assist the postoperative individualized diagnosis of tumor recurrence in patients with gliomas.
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Glioma , Recidiva Local de Neoplasia , Fluordesoxiglucose F18 , Glioma/diagnóstico por imagem , Humanos , Necrose , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: To investigate the effects of 0.05% povidone-iodine (PI) irrigation on the ocular surface structure and bacterial survival rate in patients with cataract. METHODS: Ninety eyes of 90 patients with cataract were included. Before surgery, the operative field was irrigated with 0.05% PI and divided into 30-s, 1-, and 2-min groups. Anterior chamber fluid was cultured bacteriologically. Tear film breakup time (BUT), corneal fluorescein staining (CFS), lacrimal river height (LRH), and Schirmer test I (STI) were conducted to assess ocular surface. RESULTS: In all groups, the patients had significantly shorter postoperative BUT at 1 day, 3 days, and 1 week postoperatively than preoperatively. In addition, there was still lower BUT at 1 month postoperatively in the 1- and 2-min groups. STI and LRH were all decreased postoperatively at different time points (1 day, 3 days, 1 week), while CFS was increased. With the extension of time preoperatively (1 and 3 months), the ocular surface indicators returned to the preoperative level. The bacterial cultures after eye irrigating were negative in all groups. CONCLUSION: 0.05% PI irrigating the conjunctival sac for 30 s can achieve a low bacterial contamination rate. Importantly, it reduced the damage of ocular surface, which is beneficial to the recovery of ocular surface function.
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Anti-Infecciosos Locais/uso terapêutico , Extração de Catarata/métodos , Doenças da Córnea/prevenção & controle , Infecções Oculares Bacterianas/prevenção & controle , Povidona-Iodo/uso terapêutico , Irrigação Terapêutica/métodos , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lágrimas/metabolismoRESUMO
A palladium-catalyzed asymmetric reductive Heck reaction of unactivated aliphatic alkenes, with eliminable ß-hydrogen atoms, has been realized for the first time. A series of optically active bicyclo[3.2.1]octanes bearing chiral quaternary and tertiary carbon stereocenters were obtained in good yields with excellent enantioselectivities, exhibiting good functional-group tolerance and scalability. Moreover, deuterated optically active bicyclo[3.2.1]octanes were also obtained in high efficiency.
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BACKGROUND: This study sought to report the outcomes of a combined cataract extraction, intraocular lens (IOL) insertion and micro-incision vitrectomy (MIVS) procedure for the treatment of Behcet uveitis. METHODS: This investigation involved the retrospective evaluation of a case series of patients with Behcet uveitis who underwent cataract extraction, IOL insertion and MIVS in a single surgical session at the same institution between January 2013 and November 2016. Outcome measures included visual acuity, inflammatory reaction, systemic anti-inflammatory medications, intraocular pressure (IOP) and complications. RESULTS: Seven eyes of seven patients with a mean age of 39.00 ± 5.54 years (range, 32 to 48 years) and a mean follow-up duration of 13.57 ± 5.83 months (range, 6 to 24 months) were studied; five patients with a history of well-controlled uveitis were included. All patients underwent cataract extraction and IOL implantation combined with MIVS. All patients received postoperative steroids, which were slowly tapered during the weeks after surgery. There were no significant complications related to the surgery. Overall, best-corrected visual acuity (BCVA) was improved from log MAR (logarithm of the minimum angle of resolution) 1.67 ± 0.67 preoperatively to log MAR 0.74 ± 0.35 postoperatively; this improvement was statistically significant (p < 0.05). All eyes were deemed quiet at follow-up, and no patients required the escalation of therapy for long-term uveitis control. CONCLUSIONS: This retrospective series indicates that a procedure that combines phacoemulsification, IOL implantation and MIVS is a feasible technique for the removal of cataracts and pathologic vitreous in eyes with Behcet uveitis. This approach can restore vision without obvious complications.
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Síndrome de Behçet/complicações , Extração de Catarata , Implante de Lente Intraocular , Uveíte/cirurgia , Vitrectomia/métodos , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Pressão Intraocular , Implante de Lente Intraocular/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Acuidade VisualRESUMO
Integrin αvß3 is overexpressed in both neovasculature and glioma cells. We aimed to evaluate (68)gallium-BNOTA-PRGD2 ((68)Ga-PRGD2) as a new reagent for noninvasive integrin αvß3 imaging in glioma patients. With informed consent, 12 patients with suspicious brain glioma, as diagnosed by enhanced magnetic resonance imaging (MRI) scanning, were enrolled to undergo (68)Ga-PRGD2 PET/CT and (18)F-FDG PET/CT scans before surgery. The preoperative images were compared and correlated with the pathologically determined WHO grade. Next, the expression of integrin αvß3, CD34, and Ki-67 were determined by immunohistochemical staining of the resected brain tumor tissue. Our findings demonstrated that (68)Ga-PRGD2 specifically accumulated in the brain tumors that were rich of integrin αvß3 and other neovasculature markers, but not in the brain parenchyma other than the choroid plexus. Therefore, (68)Ga-PRGD2 PET/CT was able to evaluate the glioma demarcation more specifically than (18)F-FDG PET/CT. The maximum standardized uptake values (SUVmax) of (68)Ga-PRGD2, rather than those of (18)F-FDG, were significantly correlated with the glioma grading. The maximum tumor-to-brain ratios (TBRmax) of both tracers were significantly correlated with glioma grading, whereas (68)Ga-PRGD2 seemed to be more superior to (18)F-FDG in differentiating high-grade glioma (HGG) from low-grade glioma (LGG). Moreover, (68)Ga-PRGD2 PET/CT showed different accumulation patterns for HGG of WHO grades III and IV. This is the first noninvasive integrin imaging study, to the best of our knowledge, conducted in preoperative patients with different grades of glioma, and it preliminarily indicated the effectiveness of this novel method for evaluating glioma grading and demarcation.
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Neoplasias Encefálicas/diagnóstico por imagem , Complexos de Coordenação , Glioma/diagnóstico por imagem , Glioma/diagnóstico , Peptídeos Cíclicos , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Adulto , Idoso , Antígenos CD34/metabolismo , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico , Plexo Corióideo/metabolismo , Feminino , Fluordesoxiglucose F18/química , Radioisótopos de Gálio , Humanos , Imuno-Histoquímica , Integrina alfaVbeta3/metabolismo , Antígeno Ki-67/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Estudos Prospectivos , Adulto JovemRESUMO
Most of the existing fusion algorithms are not robust to unregistered input images. Even after image registration, nonlinear nonregistration may persist in the local areas of the images, leading to poor quality in the fused image. So, as to tackle these challenges, a progressive remote sensing image registration and fusion network is proposed in this article, and named PRF-Net, which is particularly useful when two images are from different platforms. First, a registration network is designed to register the input image patches, which includes a global spatial transform network (GSTN) and a local spatial warp network (LSWN). The GSTN is primarily used for coarse registration, applying rigid transformation to globally align the input images. After coarse registration, the preliminarily registered moving image is input into the LSWN for local fine-tuning to maximize correlation between the input image patches. Subsequently, the fine registered images are degraded and input into the fusion network to generate the fused image. To maintain sufficient spectral and spatial information of the fused image, a multiscale feature extraction (MSFE) block with a highly interpretable spatial details attention (SDA) block is designed, which can enhance the ability of fusion network to extract and preserve spatial details and spectral information. Three groups of experiments conducted on four types of remote sensing images give evidence of that the proposed PRF-Net exhibits excellent performance in both reduced and full resolutions, showcasing its outstanding registration and fusion quality.
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Despite the development of various novel therapies, glioblastoma (GBM) remains a devastating disease, with a median survival of less than 15 months. Recently, targeted radionuclide therapy has shown significant progress in treating solid tumors, with the approval of Lutathera for neuroendocrine tumors and Pluvicto for prostate cancer by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This achievement has shed light on the potential of targeted radionuclide therapy for other solid tumors, including GBM. This review presents the current status of targeted radionuclide therapy in GBM, highlighting the commonly used therapeutic radionuclides emitting alpha, beta particles, and Auger electrons that could induce potent molecular and cellular damage to treat GBM. We then explore a range of targeting vectors, including small molecules, peptides, and antibodies, which selectively target antigen-expressing tumor cells with minimal or no binding to healthy tissues. Considering that radiopharmaceuticals for GBM are often administered locoregionally to bypass the blood-brain barrier (BBB), we review prominent delivery methods such as convection-enhanced delivery, local implantation, and stereotactic injections. Finally, we address the challenges of this therapeutic approach for GBM and propose potential solutions.
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Glioblastoma , Radioisótopos , Compostos Radiofarmacêuticos , Glioblastoma/radioterapia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Compostos Radiofarmacêuticos/uso terapêutico , Compostos Radiofarmacêuticos/química , Radioisótopos/uso terapêutico , Radioisótopos/química , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos da radiaçãoRESUMO
The aim of this study was to construct a classification model for the automatic diagnosis of pediatric supracondylar humerus fractures using radiomics-based machine learning. We retrospectively collected elbow joint Radiographs of children aged 3 to 14 years and manually delineated regions of interest (ROI) using ITK-SNAP. Radiomics features were extracted using pyradiomics, a python-based feature extraction tool. T-tests and the least absolute shrinkage and selection operator (LASSO) algorithm were used to further select the most valuable radiomics features. A logistic regression (LR) model was trained, with an 8:2 split into training and testing sets, and 5-fold cross-validation was performed on the training set. The diagnostic performance of the model was evaluated using receiver operating characteristic curves (ROC) on the testing set. A total of 411 fracture samples and 190 normal samples were included. 1561 features were extracted from each ROI. After dimensionality reduction screening, 40 and 94 features with the most diagnostic value were selected for further classification modeling in anteroposterior and lateral elbow radiographs. The area under the curve (AUC) of anteroposterior and lateral elbow radiographs is 0.65 and 0.72. Radiomics can extract and select the most valuable features from a large number of image features. Supervised machine-learning models built using these features can be used for the diagnosis of pediatric supracondylar humerus fractures.
Assuntos
Fraturas do Úmero , Aprendizado de Máquina , Humanos , Criança , Fraturas do Úmero/diagnóstico por imagem , Pré-Escolar , Estudos Retrospectivos , Adolescente , Masculino , Feminino , Articulação do Cotovelo/diagnóstico por imagem , Curva ROC , Radiografia/métodos , Algoritmos , RadiômicaRESUMO
BACKGROUND: About 60% of autoimmune encephalitis (AE) patients present psychiatric symptoms, but the underlying mechanism remains unknown. This study examined the role of the cingulate cortex in such patients to identify predictive poor psychiatric factors. METHODS: In this study, 49 AE patients and 39 healthy controls were enrolled. AE patients were further divided into two groups based on the presence/absence of psychiatric symptoms. The ratio of the standardized uptake value (SUVR) and relative cerebral blood flow (rCBF) in different regions of the cingulate cortex were calculated through positron emission tomography-computed tomography (PET/CT) and arterial spin labeling (ASL) MRI, and the results were compared among the three groups. In addition, we followed-up on the psychiatric outcomes and identified the risk factors for poor psychiatric prognosis, focusing on the cingulate cortex. RESULTS: More than half of the AE patients (27/49) exhibited psychiatric symptoms. Agitation and thought blocking were typical psychiatric phenotypes, except for anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, which mainly presented with catatonia and a depressed mood. AE patients with psychiatric symptoms experienced reduced metabolism and perfusion of the anterior cingulate cortex (ACC), midcingulate cortex (MCC), and posterior cingulate cortex (PCC). The SUVR of ACC can be used as an independent risk factor of poor psychiatric outcomes, which had an area under the ROC curve (AUC) of 0.865. CONCLUSION: Impaired cingulate cortex function in AE may be the potential mechanism of psychiatric symptoms. Hypometabolism of ACC is an independent prognostic factor predicting an unfavorable psychiatric prognosis in AE.