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BACKGROUND: The identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI. METHODS: In this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated. DISCUSSION: The tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT05868928).
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Neoplasias Encefálicas , Recidiva Local de Neoplasia , Radiocirurgia , Humanos , Radiocirurgia/métodos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/radioterapia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Adulto , Idoso , Medição de Risco/métodosRESUMO
There is a growing interest in perfusion or continuous processes to achieve higher productivity of biopharmaceuticals in mammalian cell culture, specifically Chinese hamster ovary (CHO) cells, towards advanced biomanufacturing. These intensified bioprocesses highly require concentrated feed media in order to counteract their dilution effects. However, designing such condensed media formulation poses several challenges, particularly regarding the stability and solubility of specific amino acids. To address the difficulty and complexity in relevant media development, the biopharmaceutical industry has recently suggested forming dipeptides by combining one from problematic amino acids with selected pairs to compensate for limitations. In this study, we combined one of the lead amino acids, L-tyrosine, which is known for its poor solubility in water due to its aromatic ring and hydroxyl group, with glycine as the partner, thus forming glycyl-L-tyrosine (GY) dipeptide. Subsequently, we investigated the utilization of GY dipeptide during fed-batch cultures of IgG-producing CHO cells, by changing its concentrations (0.125 × , 0.25 × , 0.5 × , 1.0 × , and 2.0 ×). Multivariate statistical analysis of culture profiles was then conducted to identify and correlate the most significant nutrients with the production, followed by in silico model-guided analysis to systematically evaluate their effects on the culture performance, and elucidate metabolic states and cellular behaviors. As such, it allowed us to explain how the cells can more efficiently utilize GY dipeptide with respect to the balance of cofactor regeneration and energy distribution for the required biomass and protein synthesis. For example, our analysis results uncovered specific amino acids (Asn and Gln) and the 0.5 × GY dipeptide in the feed medium synergistically alleviated the metabolic bottleneck, resulting in enhanced IgG titer and productivity. In the validation experiments, we tested and observed that lower levels of Asn and Gln led to decreased secretion of toxic metabolites, enhanced longevity, and elevated specific cell growth and titer. KEY POINTS: ⢠Explored the optimal Tyr dipeptide for the enhanced CHO cell culture performance ⢠Systematically analyzed effects of dipeptide media by model-guided approach ⢠Uncovered synergistic metabolic utilization of amino acids with dipeptide.
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Aminoácidos , Técnicas de Cultura Celular por Lotes , Cricetinae , Animais , Cricetulus , Células CHO , Meios de Cultura/química , Técnicas de Cultura Celular por Lotes/métodos , Aminoácidos/metabolismo , Tirosina , Dipeptídeos , Imunoglobulina G , Simulação por ComputadorRESUMO
Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.
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Doenças do Cão , Neoplasias Mamárias Animais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Cães , Feminino , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Doenças do Cão/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proliferação de Células/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transdução de Sinais , Inibidores de Fosfoinositídeo-3 Quinase/farmacologiaRESUMO
The human palate can discern multiple tastes; however, it predominantly perceives five fundamental flavors: sweetness, saltiness, sourness, bitterness, and umami. Sweetness is primarily mediated through the sweet taste receptor, a membrane-bound heterodimeric structure comprising T1R2-T1R3. However, unraveling the structural and mechanistic intricacies of the sweet taste receptor has proven challenging. This study aimed to address this knowledge gap by expressing an extracellular N-terminal domain encompassing the cysteine-rich domain of human hT1R3 (hT1R3-TMD) in Escherichia coli. The expressed protein was obtained as inclusion bodies, purified by metal affinity chromatography, and refolded using the dilution-refolding method. Through rigorous analysis, we confirmed the successful refolding of hT1R3-TMD and elucidated its structural characteristics using circular dichroism spectroscopy. Notably, the refolded protein was found to exist as either a monomer or a dimer, depending on its concentration. A tryptophan fluorescence quenching assay revealed that the dissociation constants for sucrose, sucralose, and brazzein were >9500 µM, 2380 µM and 14.3 µM, respectively. Our findings highlight the utility of this E. coli expression system for producing functional hT1R3-TMD for investigations and demonstrate the efficacy of the tryptophan fluorescence quenching assay in revealing complex interactions between sweet taste receptors and various sweeteners.
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Objective: The current study aimed to identify distinctive functional brain connectivity characteristics that differentiate patients with restless legs syndrome (RLS) from those with primary insomnia. Methods: Quantitative electroencephalography (QEEG) was employed to analyze connectivity matrices using the phaselocking value technique. A total of 107 patients with RLS (RLS group) and 17 patients with insomnia without RLS (primary insomnia group) were included in the study. Demographic variables were compared using t tests and chi-square tests, while differences in connectivity were examined through multiple analyses of covariance. Correlation analysis was conducted to explore the relationship between connectivity and the severity of RLS. Results: The results indicated significant differences in the primary somatosensory cortex (F = 4.377, r = 0.039), primary visual cortex (F = 4.215, r = 0.042), and anterior prefrontal cortex (F = 5.439, r = 0.021) between the RLS and primary insomnia groups. Furthermore, the connectivity of the sensory cortex, including the primary somatosensory cortex (r = -0.247, p = 0.014), sensory association cortex (r = -0.238, p = 0.028), retrosplenial region (r = -0.302, p = 0.002), angular gyrus (r = -0.258, p = 0.008), supramarginal gyrus (r = -0.230, p = 0.020), primary visual cortex (r = -0.275, p = 0.005) and secondary visual cortex (r = -0.226, p = 0.025) exhibited an inverse association with RLS symptom severity. Conclusion: The prefrontal cortex, primary somatosensory cortex, and visual cortex showed potential as diagnostic biomarkers for distinguishing RLS from primary insomnia. These findings indicate that QEEG-based functional connectivity analysis shows promise as a valuable diagnostic tool for RLS and provides insights into its underlying mechanisms. Further research is needed to explore this aspect further.
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Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth.
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Recém-Nascido de muito Baixo Peso , Aprendizado de Máquina , Humanos , Recém-Nascido , República da Coreia/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Bases de Dados Factuais , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/diagnóstico , Algoritmos , Hemorragia Cerebral Intraventricular/epidemiologia , Hemorragia Cerebral Intraventricular/mortalidade , Recém-Nascido PrematuroRESUMO
Evaluating the performance of a binary diagnostic test, including artificial intelligence classification algorithms, involves measuring sensitivity, specificity, positive predictive value, and negative predictive value. Particularly when comparing the performance of two diagnostic tests applied on the same set of patients, these metrics are crucial for identifying the more accurate test. However, comparing predictive values presents statistical challenges because their denominators depend on the test outcomes, unlike the comparison of sensitivities and specificities. This paper reviews existing methods for comparing predictive values and proposes using the permutation test. The permutation test is an intuitive, non-parametric method suitable for datasets with small sample sizes. We demonstrate each method using a dataset from MRI and combined modality of mammography and ultrasound in diagnosing breast cancer.
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Neoplasias da Mama , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Humanos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Sensibilidade e Especificidade , Algoritmos , Ultrassonografia Mamária/métodosRESUMO
PURPOSE: To evaluate the efficacy and safety of Amplatzer Vascular Plug 4 (AVP4) embolization in pulmonary arteriovenous malformations (PAVMs) with small- to medium-sized feeding arteries (<6 mm) and to identify factors affecting persistence and the main persistence patterns after embolization. METHODS: Between June 2013 and February 2023, we retrospectively reviewed 100 patients with 217 treated PAVMs. We included PAVMs with feeding arteries <6 mm, treated with AVP4 embolization, and followed adequately with computed tomography (CT). Technical success was defined as flow cessation observed on angiography. Persistence was defined as less than a 70% reduction of the venous sac on CT. We evaluated adverse events for each embolization session. Patterns of persistence were assessed using follow-up angiography. Univariate and multivariate analyses were performed to evaluate factors affecting persistence based on the 70% CT criteria. RESULTS: Fifty-one patients (48 women, 3 men; mean age: 50.8 years; age range: 16-71 years) with 103 PAVMs met the inclusion criteria. The technical success rate was 100%. The persistence rate was 9.7% (10/103), and the overall adverse event rate was 2.9% (3/103) during a mean follow-up of 556 days (range: 181-3,542 days). In two cases, the persistence pattern confirmed by follow-up angiography involved reperfusion via adjacent pulmonary artery collaterals. The location of embolization relative to the last normal branch of the pulmonary artery was the only factor substantially affecting persistence. CONCLUSION: Embolization with AVP4 appears to be safe and effective for small- to medium-sized PAVMs. The location of the embolization relative to the last normal branch of the pulmonary artery was found to be the main determinant of persistence. CLINICAL SIGNIFICANCE: Given the increasing demand for the treatment of small PAVMs, AVP4 embolization could be considered a viable and effective option for managing PAVMs with feeding arteries <6 mm.
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INTRODUCTION: Although extracorporeal membrane oxygenation (ECMO) is a well-established treatment for supporting severe cardiopulmonary failure, the morbidity and mortality of patients requiring ECMO support remain high. Evaluating and correcting potential risk factors associated with any ECMO-related complications may improve care and decrease mortality. This study aimed to assess the predictors of ECMO-related vascular and cerebrovascular complications among adult patients and to test the hypothesis that ECMO-related complications are associated with higher in-hospital mortality rates. METHODS: This single-center, retrospective study included 856 ECMO runs administered via cannulation of the femoral vessels of 769 patients: venoarterial (VA) ECMO (n = 709, 82.8%) and venovenous (VV) ECMO (n = 147, 17.2%). The study outcomes included the occurrence of ECMO-related vascular and cerebrovascular complications and in-hospital death. The association of ECMO-related complications with the risk of in-hospital death was analyzed. RESULTS: The incidences of ECMO-related vascular and cerebrovascular complications were 20.2% and 13.6%, respectively. The overall in-hospital mortality rate was 48.7%: 52.8% among VA ECMO runs and 29.3% among VV ECMO runs. Multivariable analysis indicated that age (P < 0.01), cardiopulmonary cerebral resuscitation (P < 0.01), continuous renal replacement therapy (P < 0.01), and initial platelet count [<50×103/µL (P = 0.02) and 50-100(×103)/µL (P < 0.01)] were associated with an increased risk of in-hospital death. ECMO-related vascular and cerebrovascular complications were not independently associated with higher in-hospital mortality rates for VA or VV ECMO runs. CONCLUSION: ECMO-related vascular and cerebrovascular complications were not associated with an increased risk of in-hospital death among adult patients.
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Oxigenação por Membrana Extracorpórea , Adulto , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Estudos Retrospectivos , Mortalidade Hospitalar , Cateterismo , Fatores de RiscoRESUMO
Recombinant adeno-associated virus (rAAV) is one of the prominent gene delivery vehicles that has opened promising opportunities for novel gene therapeutic approaches. However, the current major viral vector production platform, triple transfection in mammalian cells, may not meet the increasing demand. Thus, it is highly required to understand production bottlenecks from the host cell perspective and engineer the cells to be more favorable and tolerant to viral vector production, thereby effectively enhancing rAAV manufacturing. In this review, we provided a comprehensive exploration of the intricate cellular process involved in rAAV production, encompassing various stages such as plasmid entry to the cytoplasm, plasmid trafficking and nuclear delivery, rAAV structural/non-structural protein expression, viral capsid assembly, genome replication, genome packaging, and rAAV release/secretion. The knowledge in the fundamental biology of host cells supporting viral replication as manufacturing factories or exhibiting defending behaviors against viral production is summarized for each stage. The control strategies from the perspectives of host cell and materials (e.g., AAV plasmids) are proposed as our insights based on the characterization of molecular features and our existing knowledge of the AAV viral life cycle, rAAV and other viral vector production in the Human embryonic kidney (HEK) cells.
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Dependovirus , Mamíferos , Humanos , Animais , Dependovirus/genética , Citoplasma , TransfecçãoRESUMO
Microbial communities in nature are dynamically evolving as member species change their interactions subject to environmental variations. Accounting for such context-dependent dynamic variations in interspecies interactions is critical for predictive ecological modeling. In the absence of generalizable theoretical foundations, we lack a fundamental understanding of how microbial interactions are driven by environmental factors, significantly limiting our capability to predict and engineer community dynamics and function. To address this issue, we propose a novel theoretical framework that allows us to represent interspecies interactions as an explicit function of environmental variables (such as substrate concentrations) by combining growth kinetics and a generalized Lotka-Volterra model. A synergistic integration of these two complementary models leads to the prediction of alterations in interspecies interactions as the outcome of dynamic balances between positive and negative influences of microbial species in mixed relationships. The effectiveness of our method was experimentally demonstrated using a synthetic consortium of two Escherichia coli mutants that are metabolically dependent (due to an inability to synthesize essential amino acids) but competitively grow on a shared substrate. The analysis of the E. coli binary consortium using our model not only showed how interactions between the two amino acid auxotrophic mutants are controlled by the dynamic shifts in limiting substrates but also enabled quantifying previously uncharacterizable complex aspects of microbial interactions, such as asymmetry in interactions. Our approach can be extended to other ecological systems to model their environment-dependent interspecies interactions from growth kinetics.IMPORTANCEModeling environment-controlled interspecies interactions through separate identification of positive and negative influences of microbes in mixed relationships is a new capability that can significantly improve our ability to understand, predict, and engineer the complex dynamics of microbial communities. Moreover, the prediction of microbial interactions as a function of environmental variables can serve as valuable benchmark data to validate modeling and network inference tools in microbial ecology, the development of which has often been impeded due to the lack of ground truth information on interactions. While demonstrated against microbial data, the theory developed in this work is readily applicable to general community ecology to predict interactions among macroorganisms, such as plants and animals, as well as microorganisms.
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Escherichia coli , Interações Microbianas , Interações Microbianas/fisiologia , Cinética , Escherichia coli/metabolismo , Modelos Biológicos , Meio AmbienteRESUMO
Genome-scale metabolic models (GEMs) of Chinese hamster ovary (CHO) cells are valuable for gaining mechanistic understanding of mammalian cell metabolism and cultures. We provide a comprehensive overview of past and present developments of CHO-GEMs and in silico methods within the flux balance analysis (FBA) framework, focusing on their practical utility in rational cell line development and bioprocess improvements. There are many opportunities for further augmenting the model coverage and establishing integrative models that account for different cellular processes and data for future applications. With supportive collaborative efforts by the research community, we envisage that CHO-GEMs will be crucial for the increasingly digitized and dynamically controlled bioprocessing pipelines, especially because they can be successfully deployed in conjunction with artificial intelligence (AI) and systems engineering algorithms.
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Afferent loop syndrome (ALS) is a rare complication of gastrectomies and gastrointestinal reconstruction. This can predispose patients to fatal conditions, such as cholangitis, pancreatitis, and duodenal perforation with peritonitis. Therefore, emergency decompression is necessary to prevent these complications. Herein, we report two cases in which transcholecystic duodenal drainage, an alternative decompression treatment, was performed in ALS patients without bile duct dilatation. Two patients who underwent distal gastrectomy with Billroth II anastomosis sought consultation in an emergency department for epigastric pain and vomiting. On CT, ALS with acute pancreatitis was diagnosed. However, biliary access could not be achieved because of the absence of bile duct dilatation. To overcome this problem, a duodenal drainage catheter was placed to decompress the afferent loop after traversing the cystic duct via a transcholecystic approach. The patients were discharged without additional surgical treatment 2 weeks and 1 month after drainage.
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Ectopic breast tissue can develop along the mammary ridge from the axilla to the groin, and the most common site is the axillae. Primary carcinoma of ectopic breast tissue is extremely rare. We report a rare case of a 61-year-old woman with a palpable mass in her left axilla who had a history of surgical excision of accessory breast tissue in the same area. Mammography (MMG), including axillary tail view, ultrasound (US), and breast MRI were performed. We evaluated the extent and characteristics of the microcalcifications in the axillary tail view. A US-guided biopsy was done, and histopathology revealed an invasive ductal carcinoma. Enhanced abdominal CT revealed multiple hepatic masses consistent with metastases, and the patient received palliative chemotherapy. Herein, we present a rare case of breast cancer arising from accessory breast tissue in the axilla, best appreciated on the axillary tail view of the patient's MMG.
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BACKGROUND: Primary thymic mucinous adenocarcinoma is an extremely rare and aggressive tumor with poor prognosis. The tumor may present as a heterogeneous solid or cystic mass accompanied by calcifications. However, clinical and radiologic features of the tumor are not well known due to the rarity of the disease, which makes accurate diagnosis difficult. CASE PRESENTATION: Here we present a rare case of primary thymic mucinous adenocarcinoma in the anterior mediastinum, including computed tomography (CT) and magnetic resonance imaging (MRI) findings. Chest computed tomography revealed a large anterior mediastinal mass with extensive calcifications with poor enhancement. MRI showed that anterior mediastinal mass showed intermediate signal intensity on T1-weighted images (T1WI), high SI on T2-weighted images (T2WI), and heterogeneous enhancement. Biopsy was performed and the anterior mediastinal tumor was diagnosed as thymic mucinous adenocarcinoma by histopathologic examination and immunohistochemical staining. CONCLUSION: Thymic mucinous adenocarcinomas could be included in differential diagnoses of anterior mediastinal tumors showing extensive calcification, and common imaging findings of mucinous adenocarcinoma such as T2 high signal intensity and heterogeneous enhancement on MRI may be helpful to diagnose thymic mucinous adenocarcinoma.
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Adenocarcinoma Mucinoso , Humanos , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/patologia , Diagnóstico Diferencial , Tomografia Computadorizada por Raios X , Imageamento por Ressonância MagnéticaRESUMO
Objective: : Numerous studies have identified hemodynamic changes in adults with major depressive disorder (MDD) by using functional near-infrared spectroscopy (fNIRS). However, studies on adolescents with MDD are limited. As adolescence is a stage of rapid brain development, differences may occur depending on age. This study used fNIRS as an objective tool to investigate hemodynamic changes in the frontal lobe according to depression severity and age in adolescents with MDD. Methods: : Thirty adolescents (12 aged 12-15 years and 18 aged 16-18 years) were retrospectively investigated. The Children's Depression Inventory was used as a psychiatric evaluation scale, fNIRS was used as an objective brain function evaluation tool, and the Verbal Fluency Test was performed. Results: : During the Verbal Fluency Test, in the younger MDD group, oxygenated-hemoglobin concentration increased in the right dorsolateral prefrontal cortex region as the severity of depression increased. In the older MDD group, the oxygenated-hemoglobin concentration decreased in the right dorsolateral prefrontal cortex region as the severity of depression increased. Conclusion: : These results suggest that fNIRS may be an objective tool for identifying age differences among adolescents with MDD. To generalize the results and verify fNIRS as a potential biomarker tool, follow-up studies with a larger sample group should be conducted.
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Cytochrome P450s (CYPs) regulate plant growth and stress responses by producing diverse primary and secondary metabolites. However, the function of many plant CYPs remains unknown because, despite their structural similarity, predicting the enzymatic activity of CYPs is difficult. In this study, one member of the CYP736A subfamily (CYP736A61) from tomatoes was isolated and characterized its enzymatic functions. CYP736A61 was successfully expressed in Escherichia coli through co-expression with molecular chaperones. The purified CYP736A61 showed hydroxylation activity toward 7-ethoxycoumarin, producing 7-hydroxycoumarin or 3-hydroxy 7-ethoxycoumarin. Further substrate screening revealed that dihydrochalcone and stilbene derivates (resveratrol and polydatin) are the substrates of CYP736A61. CYP736A61 also mediated the hydroxylation of resveratrol and polydatin, albeit with low activity. Importantly, CYP736A61 mediated the cleavage of resveratrol and polydatin as well as pinostilbene and pterostilbene. Interestingly, CY736A61 also converted phloretin to naringenin chalcone. These results suggest that CYP736A61 is a novel CYP enzyme with stilbene cleavage activity.
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Glucosídeos , Solanum lycopersicum , Estilbenos , Resveratrol , Estilbenos/química , Estilbenos/metabolismo , CatáliseRESUMO
BACKGROUND: Surgically resected grade 1-2 (G1-2) pancreatic neuroendocrine tumors (PanNETs) exhibit diverse clinical outcomes, highlighting the need for reliable prognostic biomarkers. Our study aimed to develop and validate CT-based radiomics model for predicting postsurgical outcome in patients with G1-2 PanNETs, and to compare its performance with the current clinical staging system. METHODS: This multicenter retrospective study included patients who underwent dynamic CT and subsequent curative resection for G1-2 PanNETs. A radiomics-based model (R-score) for predicting recurrence-free survival (RFS) was developed from a development set (441 patients from one institution) using least absolute shrinkage and selection operator-Cox regression analysis. A clinical model (C-model) consisting of age and tumor stage according to the 8th American Joint Committee on Cancer staging system was built, and an integrative model combining the C-model and the R-score (CR-model) was developed using multivariable Cox regression analysis. Using an external test set (159 patients from another institution), the models' performance for predicting RFS and overall survival (OS) was evaluated using Harrell's C-index. The incremental value of adding the R-score to the C-model was evaluated using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The median follow-up periods were 68.3 and 59.7 months in the development and test sets, respectively. In the development set, 58 patients (13.2%) experienced recurrence and 35 (7.9%) died. In the test set, tumors recurred in 14 patients (8.8%) and 12 (7.5%) died. In the test set, the R-score had a C-index of 0.716 for RFS and 0.674 for OS. Compared with the C-model, the CR-model showed higher C-index (RFS, 0.734 vs. 0.662, p = 0.012; OS, 0.781 vs. 0.675, p = 0.043). CR-model also showed improved classification (NRI, 0.330, p < 0.001) and discrimination (IDI, 0.071, p < 0.001) for prediction of 3-year RFS. CONCLUSIONS: Our CR-model outperformed the current clinical staging system in prediction of the prognosis for G1-2 PanNETs and added incremental value for predicting postoperative recurrence. The CR-model enables precise identification of high-risk patients, guiding personalized treatment planning to improve outcomes in surgically resected grade 1-2 PanNETs.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Prognóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Radiômica , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: To spatially validate intratumoral subregions (tumor habitat) using physiologic MRI on pathology of the isocitrate dehydrogenase (IDH)-wildtype whole-glioblastoma sample. METHODS: Data of 20 patients (168 slides) were obtained from the Ivy Glioblastoma Atlas Project. On MRI, tumor habitats were defined using voxel-wise clustering of apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps for contrast-enhancing lesion (CEL) and non-enhancing lesion (NEL). On pathology slides, normalized areas of leading edge (LE), infiltrating tumor (IT), cellular tumor (CT), hypervascular lesion (CThypervascular), and perinecrotic lesion (CTperinecrotic) were obtained. Gross specimen was co-registered on MRI and correlation between pathology-MRI habitats was calculated. RNA sequencing of 67 samples was assessed using 4 Neftel subtypes and further correlated with pathology. RESULTS: Six tumor habitats were identified: hypervascular, hypovascular cellular, and hypovascular hypocellular habitats for CEL and NEL. CT was correlated with hypovascular cellular habitat in CEL (r= 0.238, p =.005). IT was correlated with hypovascular cellular habitat in NEL (r= 0.294, p =.017). CThypervascular was correlated with hypervascular habitat in NEL (r= 0.195, p = .023). CTperinecrotic was correlated with imaging necrosis (r= 0.199, p =.005). Astrocyte-like subtypes were correlated with IT (r= 0.256, p <.001), while mesenchymal-like subtypes were correlated with CTperinecrotic area (r= 0.246, p <.001). CONCLUSION: Pathologically matched tumor subregions were cellular tumor with hypovascular cellular habitat in CEL and infiltrative tumor with hypovascular cellular habitat in NEL. Identification of the most aggressive as well as infiltrative tumor portion can be achieved using non-invasive MRI tumor habitats.
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PURPOSE: This study aimed to investigate the impact of FDG PET/CT timing for biopsy site selection in patients with stage IV lung cancer regarding complications and diagnostic yield. METHODS: This retrospective analysis was performed on 1297 patients (924 men and 373 women with a mean age of 71.4 ± 10.2 years) who underwent percutaneous needle biopsy (PNB) for stage IV lung cancer diagnosis in two hospitals. Data collected included the patient's characteristics, order date of the biopsy and PET/CT exams, biopsy target site (lung or non-lung), guidance modality, complications, sample adequacy, and diagnostic success. Based on the order date of the PNB and PET/CT exams, patients were categorized into upfront and delayed PET/CT groups. RESULTS: PNB for non-lung targets resulted in significantly lower rates of minor (8.1% vs. 16.2%), major (0.2% vs. 3.4%), and overall complications (8.3% vs. 19.6%) compared to PNB for lung targets (p < 0.001 for all types of complications). Compared to the delayed PET/CT group, the upfront PET/CT group exhibited a lower probability of lung target selection of PNB (53.9% vs. 67.1%, p < 0.001), including a reduced incidence of major complications (1.0% vs. 2.9%, p = 0.031). Moreover, there was no significant difference in the occurrence of minor and total complications between the two groups. Upfront PET/CT and delayed PET/CT groups showed no significant difference regarding sample adequacy and diagnostic success. CONCLUSIONS: Upfront PET/CT may have an impact on the selection of the biopsy site for patients with advanced lung cancer, which could result in a lower rate of major complications with no change in the diagnostic yield. Upfront PET/CT demonstrates potential clinical implications for enhancing the safety of lung cancer diagnosis in clinical practice.