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The utilization of avidity to drive and tune functional responses is fundamental to antibody biology and often underlies the mechanisms of action of monoclonal antibody drugs. There is increasing evidence that antibodies leverage homotypic interactions to enhance avidity, often through weak transient interfaces whereby self-association is coupled with target binding. Here, we comprehensively map the FabFab interfaces of antibodies targeting DR5 and 4-1BB that utilize homotypic interaction to promote receptor activation and demonstrate that both antibodies have similar self-association determinants primarily encoded within a germline light chain complementarity determining region 2 (CDRL2). We further show that these determinants can be grafted onto antibodies of distinct target specificity to substantially enhance their activity. An expanded characterization of all unique germline CDRL2 sequences reveals additional self-association sequence determinants encoded in the human germline repertoire. Our results suggest that this phenomenon is unique to CDRL2, and is correlated with the less frequent antigen interaction and lower somatic hypermutation associated with this loop. This work reveals a previously unknown avidity mechanism in antibody native biology that can be exploited for the engineering of biotherapeutics.
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Afinidade de Anticorpos , Regiões Determinantes de Complementaridade , Células Germinativas , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/genética , Tratamento Farmacológico , Fragmentos Fab das ImunoglobulinasRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called leading eigenvector dynamics analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, intergroup differences in brain dynamic activity indicators are examined, and the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual region activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state and more active in limbic region activity state and visual region activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.NEW & NOTEWORTHY Alzheimer's disease (AD) is a neurodegenerative disease, but few studies have explored the characteristics of abnormal dynamic brain activity in AD patients. Here, our report reveals the abnormal dynamic activity of the patients' resting-state network, providing new insights into the dynamic analysis of brain networks and helping to gain a deeper understanding of the abnormal spatial dynamic patterns in AD patients.
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Doença de Alzheimer , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Rede Nervosa , Humanos , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/diagnóstico por imagem , Feminino , Idoso , Masculino , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Pessoa de Meia-Idade , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Descanso , Idoso de 80 Anos ou maisRESUMO
During leaf senescence, the final stage of leaf development, nutrients are recycled from leaves to other organs, and therefore proper control of senescence is thus critical for plant fitness. Although substantial progress has been achieved in understanding leaf senescence in annual plants, the molecular factors that control leaf senescence in perennial woody plants are largely unknown. Using RNA sequencing, we obtained a high-resolution temporal profile of gene expression during autumn leaf senescence in poplar (Populus tomentosa). Identification of hub transcription factors (TFs) by co-expression network analysis of genes revealed that senescence-associated NAC family TFs (Sen-NAC TFs) regulate autumn leaf senescence. Age-dependent alternative splicing (AS) caused an intron retention (IR) event in the pre-mRNA encoding PtRD26, a NAC-TF. This produced a truncated protein PtRD26IR, which functions as a dominant-negative regulator of senescence by interacting with multiple hub Sen-NAC TFs, thereby repressing their DNA-binding activities. Functional analysis of senescence-associated splicing factors identified two U2 auxiliary factors that are involved in AS of PtRD26IR. Correspondingly, silencing of these factors decreased PtRD26IR transcript abundance and induced early senescence. We propose that an age-dependent increase of IR splice variants derived from Sen-NAC TFs is a regulatory program to fine tune the molecular mechanisms that regulate leaf senescence in trees.
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Processamento Alternativo/genética , Folhas de Planta/genética , Proteínas de Plantas/genética , Populus/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Modelos Biológicos , Proteínas de Plantas/metabolismo , Populus/crescimento & desenvolvimento , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estações do Ano , Fatores de Tempo , Fatores de Transcrição/metabolismoRESUMO
Innovating food additives stands as a cornerstone for the sustainable evolution of future food systems. Peptides derived from food proteins exhibit a rich array of physicochemical and biological attributes crucial for preserving the appearance, flavor, texture, and nutritional integrity of foods. Leveraging these peptides as raw materials holds great promise for the development of novel food additives. While numerous studies underscore the potential of peptides as food additives, existing reviews predominantly focus on their biotic applications, leaving a notable gap in the discourse around their abiotic functionalities, such as their physicochemical properties. Addressing this gap, this review offers a comprehensive survey of peptide-derived food additives in food systems, accentuating the application of peptides' abiotic properties. It furnishes a thorough exploration of the underlying mechanisms and diverse applications of peptide-derived food additives, while also delineating the challenges encountered and prospects for future applications. This well-time review will set the stage for a deeper understanding of peptide-derived food additives.
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OBJECTIVES: This study aimed to establish a hematoma expansion (HE) prediction model for hypertensive intracerebral hemorrhage (HICH) patients by combining CT radiomics, clinical information, and conventional imaging signs. METHODS: A retrospective continuous collection of HICH patients from three medical centers was divided into a training set (n = 555), a validation set (n = 239), and a test set (n = 77). Extract radiomics features from baseline CT plain scan images and combine them with clinical information and conventional imaging signs to construct radiomics models, clinical imaging sign models, and hybrid models, respectively. The models will be evaluated using the area under the curve (AUC), clinical decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: In the training, validation, and testing sets, the radiomics model predicts an AUC of HE of 0.885, 0.827, and 0.894, respectively, while the clinical imaging sign model predicts an AUC of HE of 0.759, 0.725, and 0.765, respectively. Glasgow coma scale score at admission, first CT hematoma volume, irregular hematoma shape, and radiomics score were used to construct a hybrid model, with AUCs of 0.901, 0.838, and 0.917, respectively. The DCA shows that the hybrid model had the highest net profit rate. Compared with the radiomics model and the clinical imaging sign model, the hybrid model showed an increase in NRI and IDI. CONCLUSION: The hybrid model based on CT radiomics combined with clinical and radiological factors can effectively individualize the evaluation of the risk of HE in patients with HICH. CLINICAL RELEVANCE STATEMENT: CT radiomics combined with clinical information and conventional imaging signs can identify HICH patients with a high risk of HE and provide a basis for clinical-targeted treatment. KEY POINTS: HE is an important prognostic factor in patients with HICH. The hybrid model predicted HE with training, validation, and test AUCs of 0.901, 0.838, and 0.917, respectively. This model provides a tool for a personalized clinical assessment of early HE risk.
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Under hydrothermal and solvent-thermal conditions, we synthesized two novel polyoxometalate (POM)-based hybrids: [CuI4(Pz)2(H2O)8(PMoVI11MoVO40)]·3.5H2O (1, Pz = pyrazine) and [(C2H8N)5(HPMoVI9MoV3O40)]·DMF·4H2O (2). Single-crystal X-ray diffraction indicates that compound 1 is a three-dimensional structure consisting of Cu (I), {PMo12} anions, Pz, and water, where Cu (I) can be considered as Lewis acid sites. Furthermore, both compounds 1 and 2 possess favorable catalysis activity in catalyzing the conversion of chemical warfare agent simulant 2-chloroethylethyl sulfide (CEES) to nontoxic production of 2-chloroethylethyl sulfoxide (CEESO) under ambient temperature. Significantly, 1 could realize 98% conversion and 100% selectivity of CEES owing to the multisite synergy in the {PMoVI11MoVO40CuI8} units in which the tricoordinated Cu (I) could interact with S and O atoms from CEES and H2O2, respectively. This interaction not only decreases the distance of CEES from peroxomolybdenum species formed by H2O2 but also activates CEES.
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Photocatalytic reduction of U(VI) is a promising method for removing uranium containing pollutants. However, using polyoxometalate-based metal-organic frameworks (POMOFs) for photoreduction of U(VI) is rare, and the relevant charge transfer pathway is also not yet clear. In this article, we demonstrate a highly efficient strategy and revealed a clearly electron transfer pathway for the photoreduction of U(VI) with 99% removal efficiency by using a novel POMOF, [Cu(4,4'-bipy)]5·{AsMo4VMo6VIV2VO40(VIVO)[VIVO(H2O)]}·2H2O (1), as catalyst. The POMOF catalyst was constructed by the connection of reduced {AsMo10V4} clusters and Cu(I)-MOF chains through Cu-O coordination bonds, which exhibits a broader and stronger light absorption capacity due to the presence of reduced {AsMo10V4} clusters. Significantly, the transition of electrons from Cu(I)-MOF to {AsMo10V4} clusters (Cu â Mo/V) greatly inhibits the recombination of photogenerated carriers, thereby advancing electron transfer. More importantly, the {AsMo10V4} clusters are not only adsorption sites but also catalytically active sites. This causes the fast transfer of photogenerated electrons from Mo/V to UO22+(Mo/V â O â U) via the surface oxygen atoms. The shorter electron transmission distance between catalytic active sites and UO22+ achieves faster and more effective electron transport. All in all, the highly effective photocatalytic removal of U(VI) using the POMOF as a catalyst is predominantly due to the synergistic interaction between Cu(I)-MOFs and reduced {AsMo10V4} clusters.
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OBJECTIVE: This study used random forest model to explore the feasibility of radial artery calcification in prediction of coronary artery calcification in hemodialysis patients. MATERIAL AND METHODS: We enrolled hemodialysis patients and performed ultrasound examinations on their radial arteries to evaluate the calcification status using a calcification index. All involved patients received coronary artery computed tomography scans to generate coronary artery calcification scores (CACS). Clinical variables were collected from all patients. We constructed both a random forest model and a logistic regression model to predict CACS. Logistic regression model was used to identify the risk factors of radial artery calcification. RESULTS: One hundred eighteen patients were included in our analysis. In random forest model, the radial artery calcification index, age, serum C-reactive protein, body mass index (BMI), diabetes, and hypertension history were related to CACS based on the average decrease of the Gini coefficient. The random forest model achieved a sensitivity of 76.9%, specificity of 75.0%, and area under receiver operating characteristic of 0.869, while the logistic regression model achieved a sensitivity of 75.2%, specificity of 68.7%, and area under receiver operating characteristic of 0.742 in prediction of CACS. Sex, BMI index, smoking history, hypertension history, diabetes history, and serum total calcium were all the risk factors related to radial artery calcification. CONCLUSIONS: A random forest model based on radial artery calcification could be used to predict CACS in hemodialysis patients, providing a potential method for rapid screening and prediction of coronary artery calcification.
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Doença da Artéria Coronariana , Aprendizado Profundo , Artéria Radial , Diálise Renal , Calcificação Vascular , Humanos , Masculino , Feminino , Diálise Renal/efeitos adversos , Artéria Radial/diagnóstico por imagem , Pessoa de Meia-Idade , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia , Calcificação Vascular/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Idoso , Fatores de Risco , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Valor Preditivo dos TestesRESUMO
AIM: To investigate the possible covariation of grey matter volume (GMV) and white matter fractional anisotropy in infants with spastic cerebral palsy (CP) and periventricular white matter injury. METHOD: Thirty-nine infants with spastic CP and 25 typically developing controls underwent structural magnetic resonance imaging and diffusion tensor imaging. Multimodal canonical correlation analysis with joint independent component analysis were used to capture differences in GMV and fractional anisotropy between groups. Correlation analysis was performed between imaging findings and clinical features. RESULTS: Infants with spastic CP showed one joint group-discriminating component (i.e. GMV-fractional anisotropy) associated with regions in the cortico-basal ganglia-thalamo-cortical loop and in the corpus callosum compared to typically developing controls and one modality-specific group-discriminating component (i.e. GMV). Significant negative correlations were found between loadings in certain regions and the motor function score in spastic CP. INTERPRETATION: In infants with spastic CP, covarying GMV-fractional anisotropy and altered GMV in specific regions were implicated in motor dysfunction, which confirmed that simultaneous GMV and fractional anisotropy changes underly motor deficits, but might also extend to sensory, cognitive, or visual dysfunction. These findings also suggest that multimodal fusion analysis allows for a more comprehensive understanding of the relevance between grey and white matter structures and its crucial role in the neuropathological mechanisms of spastic CP.
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Paralisia Cerebral , Substância Branca , Lactente , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Espasticidade Muscular , EncéfaloRESUMO
Mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been reported to result in abnormal cross-frequency integration. However, previous studies have failed to consider specific abnormalities in receiving and outputting information among frequency bands during integration. Here, we investigated heterogeneity in receiving and outputting information during cross-frequency integration in patients. The results showed that during cross-frequency integration, information interaction first increased and then decreased, manifesting in the heterogeneous distribution of inter-frequency nodes for receiving information. A possible explanation was that due to damage to some inter-frequency hub nodes, intra-frequency nodes gradually became new inter-frequency nodes, whereas original inter-frequency nodes gradually became new inter-frequency hub nodes. Notably, damage to the brain regions that receive information between layers was often accompanied by a strengthened ability to output information and the emergence of hub nodes for outputting information. Moreover, an important compensatory mechanism assisted in the reception of information in the cingulo-opercular and auditory networks and in the outputting of information in the visual network. This study revealed specific abnormalities in information interaction and compensatory mechanism during cross-frequency integration, providing important evidence for understanding cross-frequency integration in patients with MCI and AD.
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Doença de Alzheimer , Disfunção Cognitiva , Humanos , Encéfalo , Córtex InsularRESUMO
BACKGROUND: Risk assessment of vascular thrombosis in SLE patients with the presence of antiphospholipid antibodies (aPL) remains a challenge. The adjusted global antiphospholipid syndrome score (aGAPSS) has been validated and used to predict aPL-related thrombosis in SLE patients in some countries. Relevant data of aGAPSS in thrombotic evaluation in SLE population from China has not been reported. We aim to validate aGAPSS in thrombosis assessment in Chinese patients with SLE and to explore the correlations of aGAPSS with routine laboratory parameters and their clinical significance as well. METHODS: A total of 166 consecutive SLE patients were retrospectively analyzed. Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters in recurrent thrombosis risk in SLE. ROC was conducted to explore the discriminative ability of aGAPSS and platelet (PLT), activated partial thromboplastin time (APTT), alone or in combination. RESULTS: Significantly higher value of aGAPSS was seen in SLE patients with vascular thrombosis. ROC curve indicated that aGAPSS of 3.5 or more had the best diagnostic accuracy for the prediction of aPL-related thrombosis in SLE patients. PLT with cutoff of 187.5 x 109/L and APTT with 37.5 seconds were predictors of aPL-related thrombosis as well. The combination of aGAPSS with PLT and APTT improved AUC compared to aGAPSS alone. CONCLUSIONS: The aGAPSS could predict the risk of aPL-related vascular thrombosis in SLE patients from China. The combination of aGAPSS with PLT and APTT was first time proved to have better predictive performance in thrombosis risk assessment in SLE.
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Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombose , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Estudos Retrospectivos , Tempo de Tromboplastina Parcial , Fatores de Risco , Trombose/diagnóstico , Trombose/etiologia , Medição de Risco , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
Background: Pediatric cardiac surgery is associated with a high risk of mortality and morbidity. The aim of this study was to determine if intraoperative dexmedetomidine therapy could improve survival after pediatric cardiac surgery. Methods: We conducted a retrospective review of 1384 consecutive children who underwent pediatric cardiac surgery. Amongst these, 889 received dexmedetomidine therapy and 495 did not. All children were followed for 1 year. Their in-hospital and long-term outcomes were compared by multivariate logistic regression to minimize bias, and propensity-score matched adjustment was used. Results: Children who received dexmedetomidine had lower mortality during the 30-day postoperative period compared to children who did not (1.57% vs. 4.24%; adjusted hazard ratio [HR]: 0.448; 95% confidence interval [CI]: 0.219-0.916, p = 0.028), as well as after 1 year (2.36% vs. 6.67%; adjusted [HR]: 0.487; 95% [CI]: 0.274-0.867, p = 0.014). The two groups showed no significant differences in cardiovascular complications. Conclusions: Dexmedetomidine administered intraoperatively reduced 30-day and 1-year mortality in children undergoing pediatric cardiac surgery.
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Two new three-dimensional (3D) polyoxometalate-based metal-organic frameworks (POMOFs), [M2(btap)4(H2O)4(HPMo10VI Mo2VO40)] (M = Co (1) and Cd (2); btap = 3, 5-bis(1', 2', 4'-triazol-1'-yl)pyridine), have been synthesized under mild hydrothermal conditions and characterized in detail. Single-crystal X-ray diffraction (SXRD) analysis indicates that 1 and 2 are isostructural. In complexes 1 and 2, the metal ion is coordinated with the ligand to form two different left and right helical one-dimensional chains, which are alternately connected in a twisted form to build a two-fold interpenetrated three-dimensional structure, and the polyoxometalate is encapsulated into in the pores generated by the interpenetrating structure. It is noteworthy that 1 and 2, as recyclable catalysts, possess favorable heterogeneous catalytic activity and excellent sulfoxide selectivity in sulfide oxidation reactions, with H2O2 as an oxidant. By reason of the high dispersion of polyoxometalate with good intrinsic activity in the skeleton structure, the title complex has high activity. In addition, no obvious decrease of sulfoxide yield is observed after at least five cycles. These results indicate the excellent catalytic activity and sustainability of 1 and 2.
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AIM: To investigate the effectiveness of de-escalation of ticagrelor (from ticagrelor 90 mg to clopidogrel 75 mg or ticagrelor 60 mg) on the prognosis of patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after 3 months of oral dual antiplatelet therapy (DAPT). METHODS: From March 2017 to August 2021, 1056 patients with STEMI in a single centre, through retrospective investigation and analysis, were divided into intensive (ticagrelor 90 mg), standard (clopidogrel 75 mg after PCI) and de-escalation groups (clopidogrel 75 mg or ticagrelor 60 mg after 3 months of treatment with 90 mg ticagrelor) based on the type and dose of P2Y12 inhibitor 3 months after PCI, and the patients had a ≥ 12-month history of oral DAPT. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during the 12-month follow-up period, including composite end points of cardiac death, myocardial infarction, ischaemia-driven revascularization and stroke. The major safety endpoint was bleeding events. RESULTS: The results showed that during the follow-up period, there was no statistically significant difference in the incidence of MACCEs between the intensive and de-escalation groups (P > 0.05). The incidence of MACCEs in the standard treatment group was higher than that in the intensive treatment group (P = 0.014), but the incidence of bleeding events in the de-escalation group was significantly lower than that in the standard group (9.3% vs. 18.4%, χ²=7.191, P = 0.027). The Cox regression analysis showed that increases in haemoglobin (HGB) (HR = 0.986) and estimated glomerular filtration rate (eGFR) (HR = 0.983) could reduce the incidence of MACCEs, while old myocardial infarction (OMI) (P = 0.023) and hypertension (P = 0.013) were independent predictors of MACCEs. CONCLUSION: For STEMI patients undergoing PCI, the de-escalation scheme of ticagrelor to clopidogrel 75 mg or ticagrelor 60 mg at 3 months after PCI was related to the reduction of bleeding events, especially minor bleeding events, without an increase in ischaemic events.
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Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Clopidogrel/efeitos adversos , Ticagrelor/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/efeitos adversos , Estudos Retrospectivos , Infarto do Miocárdio/terapia , Infarto do Miocárdio/tratamento farmacológico , Hemorragia/epidemiologia , Prognóstico , Resultado do TratamentoRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
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Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêuticoRESUMO
The aim of the study was to test whether the cytokine profile could be used as a marker to differentiate between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and Kawasaki disease (KD). A total of 70 hospitalized children with HLH and KD admitted to hospital for the first time from March 2017 to December 2021 were enrolled in this study. Fifty-five healthy children were enrolled as normal controls. All patients and normal controls were tested for the six cytokines including interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) by flow cytometry. IL-10 and IFN-γ levels were significantly higher in children with EBV-HLH than in the KD, IL-6 was lower in EBV-HLH patients than in the KD. IL-10/IL-6 ratio, IFN-γ/IL-6 ratio and IL10/IFN-γ ratio in children with EBV-HLH were significantly much higher than children in the KD group. When the diagnostic cutoff values of IL-10, IFN-γ, IL-10/IL-6 ratio and IFN-γ/IL-6 ratio were >13.2 pg/ml, >71.0 pg/ml, >0.37 and >1.34, respectively, the sensitivity and specificity of the diagnosis of EBV-HLH disease were 91.7% and 97.1%, 72.2% and 97.1%, 86.1% and 100.0%, and 75.0% and 97.1%, respectively. Notably high IL-10 and IFN-γ and moderately elevated IL-6 suggest the diagnosis of EBV-HLH, while high IL-6 levels with low IL-10 or IFN-γ concentration would suggest KD. Additionally, IL-10/IL-6 ratio or IFN-γ/IL-6 ratio could be used as an index to differentiate between EBV-HLH and KD.
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Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Citocinas , Interleucina-10 , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/etiologia , Infecções por Vírus Epstein-Barr/complicações , Interleucina-6 , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Herpesvirus Humano 4 , Interferon gamaRESUMO
OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23+5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION: The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.
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Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Feminino , Humanos , Gravidez , Linhagem , Cerebelo/diagnóstico por imagem , Cerebelo/anormalidades , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Anormalidades do Olho/genética , Anormalidades do Olho/diagnóstico , Doenças Renais Císticas/genética , Doenças Renais Císticas/diagnóstico , Monoéster Fosfórico Hidrolases/genética , Retina/diagnóstico por imagem , Retina/anormalidades , População do Leste Asiático , MutaçãoRESUMO
Background: Yolk sac tumor is a germ cell tumor (GCT) that occurs in infants and adolescents and affects various sites. There is a trend to treat pediatric renal tumors before a tissue diagnosis. We report a renal yolk sac tumor clinically misdiagnosed as Wilms tumor, based on ultrasound (US) and MRI.Case Report: This 21-month-old male infant was discovered to have a space occupying lesion in the right kidney. Because the tumor was large, initial radiotherapy preceded surgical resection. Histologically, the tumor was a yolk sac tumor.Conclusion: Imaging examination of renal yolk sac tumor can easily be misdiagnosed as Wilms tumor. SIOP treatment plan for Wilms tumor requires preoperative chemotherapy, which is different from the treatment regimen for yolk sac tumor. Preoperative alpha-fetoprotein could have been helpful in avoiding this clinical misdiagnosis.
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Tumor do Seio Endodérmico , Neoplasias Renais , Tumor de Wilms , Lactente , Criança , Adolescente , Humanos , Masculino , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/terapia , Tumor do Seio Endodérmico/patologia , Tumor de Wilms/diagnóstico , Tumor de Wilms/terapia , Neoplasias Renais/diagnóstico , Ultrassonografia , Rim/patologiaRESUMO
Adsorption reactions of amino acids (AAs) on TiO2 nanoparticles (NPs) play an important role in the available nutrients in soils and sediments. The pH effects on glycine adsorption have been studied, but little is known about its coadsorption with Ca2+ at the molecular level. Combined attenuated total reflectance Fourier transform infrared (ATR-FTIR) flow-cell measurements and density functional theory (DFT) calculations were used to determine the surface complex and corresponding dynamic adsorption/desorption processes. The structures of glycine adsorbed onto TiO2 were closely associated with its dissolved species in the solution phase. The presence of Ca2+ exerted different influences on glycine adsorption within pH 4-11, thus affecting its migration rate in soils and sediments. The mononuclear bidentate complex at pH 4-7, involving the COO- moiety of zwitterionic glycine, remained unchanged in the absence and presence of Ca2+. At pH 11, the mononuclear bidentate complex with deprotonated NH2 can be removed from the TiO2 surface upon coadsorption with Ca2+. The bonding strength of glycine on TiO2 was much weaker than that of the Ca-bridged ternary surface complexation. Glycine adsorption was inhibited at pH 4 but was enhanced at pH 7 and 11.
Assuntos
Glicina , Água , Espectroscopia de Infravermelho com Transformada de Fourier , Adsorção , Água/químicaRESUMO
The human brain dynamically shifts between a predominantly integrated state and a predominantly segregated state, each with different roles in supporting cognition and behavior. However, no studies to date have investigated lesions placed in different regions of the cerebral cortex to determine the effects on the temporal balance of integration and segregation. Here, we used the integrated state occurrence rate to measure the temporal balance of integration and segregation in the resting brain. Based on dynamic mean-field models coupled through the individual's structural white matter connections, neural activity was modeled. By lesioning different individual nodes from the model, our results implied that the impact of lesions reaches far beyond focal damage and could impair cognition by affecting system-level dynamics. Lesions in a portion of the nodes in the visual, somatomotor, limbic, and default networks significantly compromised the temporal balance of integration and segregation. Crucially, the effects of lesions in different regions could be predicted based on the hierarchical axis inferred from the T1w/T2w map and specific graph measures of structural brain networks. Taken together, our findings indicate the possibility of significant contributions of anatomical heterogeneity to the dynamics of functional network topology. Although still in its infancy, computational modeling may provide an entry point for understanding brain disorders at a causal mechanistic level, possibly leading to novel, more effective therapeutic interventions.