RESUMO
Electroencephalography (EEG)-based applications in brain-computer interfaces (BCIs), neurological disease diagnosis, rehabilitation, etc., rely on supervised approaches such as classification that requires given labels. However, with the ever-increasing amount of EEG data, incomplete or incorrectly labeled or unlabeled EEG data are increasing. It likely degrades the performance of supervised approaches. In this work, we put forward a novel unsupervised exploratory EEG analysis solution by clustering based on low-dimensional prototypes in latent space that are associated with the respective clusters. Having the prototype as a baseline of each cluster, a compositive similarity is defined to act as the critic function in clustering, which incorporates similarities on three levels. The approach is implemented with a Generative Adversarial Network (GAN), termed W-SLOGAN, by extending the Stein Latent Optimization for GANs (SLOGAN). The Gaussian Mixture Model (GMM) is utilized as the latent distribution to adapt to the diversity of EEG signal patterns. The W-SLOGAN ensures that images generated from each Gaussian component belong to the associated cluster. The adaptively learned Gaussian mixing coefficients make the model remain effective in dealing with an imbalanced dataset. By applying the proposed approach to two public EEG or intracranial EEG (iEEG) epilepsy datasets, our experiments demonstrate that the clustering results are close to the classification of the data. Moreover, we present several findings that were discovered by intra-class clustering and cross-analysis of clustering and classification. They show that the approach is attractive in practice in the diagnosis of the epileptic subtype, multiple labelling of EEG data, etc.
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Interfaces Cérebro-Computador , Eletroencefalografia , Eletroencefalografia/métodos , Humanos , Análise por Conglomerados , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Algoritmos , Processamento de Sinais Assistido por Computador , Redes Neurais de ComputaçãoRESUMO
Abstracting causal knowledge from process measurements has become an appealing topic for decades, especially for fault root cause analysis (RCA) based on signals recorded by multiple sensors in a complex system. Although many causality detection methods have been developed and applied in different fields, some research communities may have an idiosyncratic implementation of their preferred methods, with limited accessibility to the wider community. Targeting interested experimental researchers and engineers, this paper provides a comprehensive comparison of data-based causality detection methods in root cause diagnosis across two distinct domains. We provide a possible taxonomy of those methods followed by descriptions of the main motivations of those concepts. Of the two cases we investigated, one is a root cause diagnosis of plant-wide oscillations in an industrial process, while the other is the localization of the epileptogenic focus in a human brain network where the connectivity pattern is transient and even more complex. Considering the differences in various causality detection methods, we designed several sets of experiments so that for each case, a total of 11 methods could be appropriately compared under a unified and reasonable evaluation framework. In each case, these methods were implemented separately and in a standard way to infer causal interactions among multiple variables to thus establish the causal network for RCA. From the cross-domain investigation, several findings are presented along with insights into them, including an interpretative pitfall that warrants caution.
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Encéfalo , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Análise de Causa Fundamental/métodos , Algoritmos , Rede Nervosa/fisiopatologia , Eletroencefalografia/métodosRESUMO
BACKGROUND: Patients with chronic kidney disease (CKD) are at higher risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). Complex PCI (CPCI) is associated with higher rates of ischemic complications. Whether CPCI confers an additive risk of adverse events in CKD patients is unclear. METHODS: Patients who underwent PCI at a single tertiary-care-center between 2012 and 2019 were stratified by CKD status and CPCI. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1-year follow-up. Secondary outcomes included the individual components of the primary outcome and major bleeding. RESULTS: Out of 15,071 patients, 4537 (30.1%) had CKD and 10,534 (69.9%) had no CKD. Patients undergoing CPCI were 1151 (25.4%) and 2983 (28.3%) in the two cohorts, respectively. At one year, CPCI compared with no CPCI was associated with higher risk of MACE in both CKD (Adj. HR 1.72, 95% confidence interval [CI] 1.45-2.06, p < 0.001) and no-CKD patients (Adj. hazard ratios [HR] 2.19, 95% CI 1.91-2.51, p < 0.001; p of interaction 0.057), determined by an excess of death, MI and TVR in CKD patients and of TVR and MI only in no-CKD. CPCI was related with a consistent increase of major bleeding in the CKD (Adj. HR 1.49, 95% CI 1.18-1.87, p < 0.001) and no-CKD group (Adj. HR 1.23, 95% CI 0.98-1.54, p = 0.071, p of interaction 0.206). CONCLUSION: At 1-year follow-up, CPCI was associated with higher risk of MACE and major bleeding irrespective of concomitant CKD. CPCI predicted mortality in CKD patients only.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Intervenção Coronária Percutânea , Insuficiência Renal Crônica , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Infarto do Miocárdio/etiologia , Hemorragia/etiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapiaRESUMO
BACKGROUND: Repetitive mild traumatic brain injury (mTBI) can result in chronic visual dysfunction. G-protein receptor 110 (GPR110, ADGRF1) is the target receptor of N-docosahexaenoylethanolamine (synaptamide) mediating the anti-neuroinflammatory function of synaptamide. In this study, we evaluated the effect of an endogenous and a synthetic ligand of GPR110, synaptamide and (4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-hydroxy-2-methylpropyl) docosa-4,7,10,13,16,19-hexaenamide (dimethylsynaptamide, A8), on the mTBI-induced long-term optic tract histopathology and visual dysfunction using Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), a clinically relevant model of mTBI. METHODS: The brain injury in wild-type (WT) and GPR110 knockout (KO) mice was induced by CHIMERA applied daily for 3 days, and GPR110 ligands were intraperitoneally injected immediately following each impact. The expression of GPR110 and proinflammatory mediator tumor necrosis factor (TNF) in the brain was measured by using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in an acute phase. Chronic inflammatory responses in the optic tract and visual dysfunction were assessed by immunostaining for Iba-1 and GFAP and visual evoked potential (VEP), respectively. The effect of GPR110 ligands in vitro was evaluated by the cyclic adenosine monophosphate (cAMP) production in primary microglia isolated from adult WT or KO mouse brains. RESULTS: CHIMERA injury acutely upregulated the GPR110 and TNF gene level in mouse brain. Repetitive CHIMERA (rCHIMERA) increased the GFAP and Iba-1 immunostaining of glia cells and silver staining of degenerating axons in the optic tract with significant reduction of N1 amplitude of visual evoked potential at up to 3.5 months after injury. Both GPR110 ligands dose- and GPR110-dependently increased cAMP in cultured primary microglia with A8, a ligand with improved stability, being more effective than synaptamide. Intraperitoneal injection of A8 at 1 mg/kg or synaptamide at 5 mg/kg significantly reduced the acute expression of TNF mRNA in the brain and ameliorated chronic optic tract microgliosis, astrogliosis, and axonal degeneration as well as visual deficit caused by injury in WT but not in GPR110 KO mice. CONCLUSION: Our data demonstrate that ligand-induced activation of the GPR110/cAMP system upregulated after injury ameliorates the long-term optic tract histopathology and visual impairment caused by rCHIMERA. Based on the anti-inflammatory nature of GPR110 activation, we suggest that GPR110 ligands may have therapeutic potential for chronic visual dysfunction associated with mTBI.
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Concussão Encefálica/complicações , Etanolaminas/metabolismo , Etanolaminas/farmacologia , Gliose/tratamento farmacológico , Gliose/metabolismo , Trato Óptico/efeitos dos fármacos , Trato Óptico/patologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Concussão Encefálica/patologia , Técnicas de Cultura de Células , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Eletrorretinografia , Potenciais Evocados Visuais , Gliose/complicações , Inflamação , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Trato Óptico/lesões , Fator de Necrose Tumoral alfa/metabolismo , Visão OcularRESUMO
Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing on solubility and chemical stability. A lead solution formulation was advanced to a scaleup campaign. An unexpected stability issue was encountered, and the root cause was attributed to the heterogeneous liquid freezing process of the formulated solution at -20°C, which had not been captured in the lab setting. A lyophilized product was then designed to overcome the issue and supplied to the phase I clinical trial.
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Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Desenvolvimento de Medicamentos/métodos , Inibidores Enzimáticos/síntese química , Estabilidade de Medicamentos , Inibidores Enzimáticos/administração & dosagem , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Liofilização , Congelamento , Injeções , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/síntese química , SolubilidadeRESUMO
Previous studies suggest that long-term supplementation and dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) may have neuroprotective effects following brain injury. The objective of this study was to investigate potential neuroprotective effects of omega-3 PUFAs on white matter following closed-head trauma. The closed-head injury model of engineered rotational acceleration (CHIMERA) produces a reproducible injury in the optic tract and brachium of the superior colliculus in mice. Damage is detectable using diffusion tensor imaging (DTI) metrics, particularly fractional anisotropy (FA), with sensitivity comparable to histology. We acquired in vivo (n = 38) and ex vivo (n = 41) DTI data in mice divided into sham and CHIMERA groups with two dietary groups: one deficient in omega-3 PUFAs and one adequate in omega-3 PUFAs. We examined injury effects (reduction in FA) and neuroprotection (FA reduction modulated by diet) in the optic tract and brachium. We verified that diet did not affect FA in sham animals. In injured animals, we found significantly reduced FA in the optic tract and brachium (~10% reduction, p < 0.001), and Bayes factor analysis showed strong evidence to reject the null hypothesis. However, Bayes factor analysis showed substantial evidence to accept the null hypothesis of no diet-related FA differences in injured animals in the in vivo and ex vivo samples. Our results indicate no neuroprotective effect from adequate dietary omega-3 PUFA intake on white matter damage following traumatic brain injury. Since damage from CHIMERA mainly affects white matter, our results do not necessarily contradict previous findings showing omega-3 PUFA-mediated neuroprotection in gray matter.
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Lesões Encefálicas Traumáticas/diagnóstico por imagem , Dieta , Ácidos Graxos Ômega-3/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Substância Branca/diagnóstico por imagem , Substância Branca/lesões , Animais , Teorema de Bayes , Imagem de Tensor de Difusão , Substância Cinzenta/patologia , Traumatismos Cranianos Fechados/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Trato Óptico/diagnóstico por imagem , Trato Óptico/lesões , Colículos Superiores/diagnóstico por imagem , Colículos Superiores/lesõesRESUMO
BACKGROUND: Stroke represents a potentially calamitous complication among patients with acute coronary syndrome (ACS) undergoing percutaneous intervention (PCI). Data on the distribution of stroke occurrence post-PCI and its impact on mortality are scarce. OBJECTIVES: We sought to determine the incidence, predictors and impact of stroke on mortality in ACS patients undergoing PCI. METHODS: A total of 19,914 ACS patients underwent PCI in the PROMETHEUS multicenter observational study. We calculated the cumulative stroke incidence at 30 days and 1 year using the Kaplan Meier method. We also compared the distribution of stroke, myocardial infarction (MI), and bleeding across time and evaluated their overlap. Predictors of stroke were identified through multivariable Cox-regression. Stroke, MI, and bleeding were assessed as time-updated covariates to estimate how each impacts subsequent mortality. RESULTS: We found that 244 patients had a stroke within 1 year, a cumulative incidence of 1.5%. Previous cerebrovascular disease was the strongest predictor for post-PCI stroke, followed by ST-elevation MI presentation, hypertension, non-ST-elevation MI presentation, smoking, female sex, and age. Mortality risk was significantly higher among those who had a stroke versus those who did not (adjusted HR 4.84, p < .0001). However, the association attenuated over time with a much larger effect in the first 30 days of its occurrence (adjusted HR 17.7; 95% CI: 12.3-25.4, p < .0001) versus beyond 30 days (adjusted HR 1.22; 95% CI: 0.6-2.46, p = .58). CONCLUSIONS: Stroke occurrence within 1 year was not uncommon for ACS patients undergoing PCI. When compared with MI and bleeding, stroke had a substantial impact on mortality that attenuated rapidly over time.
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Síndrome Coronariana Aguda/terapia , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/mortalidade , Acidente Vascular Cerebral/mortalidade , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Hemorragia/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Recidiva , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Neuroinflammation is a widely accepted underlying condition for various pathological processes in the brain. In a recent study, synaptamide, an endogenous metabolite derived from docosahexaenoic acid (DHA, 22:6n-3), was identified as a specific ligand to orphan adhesion G-protein-coupled receptor 110 (GPR110, ADGRF1). Synaptamide has been shown to suppress lipopolysaccharide (LPS)-induced neuroinflammation in mice, but involvement of GPR110 in this process has not been established. In this study, we investigated the possible immune regulatory role of GPR110 in mediating the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. METHODS: For in vitro studies, we assessed the role of GPR110 in synaptamide effects on LPS-induced inflammatory responses in adult primary mouse microglia, immortalized murine microglial cells (BV2), primary neutrophil, and peritoneal macrophage by using quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) as well as neutrophil migration and ROS production assays. To evaluate in vivo effects, wild-type (WT) and GPR110 knock-out (KO) mice were injected with LPS intraperitoneally (i.p.) or TNF intravenously (i.v.) followed by synaptamide (i.p.), and expression of proinflammatory mediators was measured by qPCR, ELISA, and western blot analysis. Activated microglia in the brain and NF-kB activation in cells were examined microscopically after immunostaining for Iba-1 and RelA, respectively. RESULTS: Intraperitoneal (i.p.) administration of LPS increased TNF and IL-1ß in the blood and induced pro-inflammatory cytokine expression in the brain. Subsequent i.p. injection of the GPR110 ligand synaptamide significantly reduced LPS-induced inflammatory responses in wild-type (WT) but not in GPR110 knock-out (KO) mice. In cultured microglia, synaptamide increased cAMP and inhibited LPS-induced proinflammatory cytokine expression by inhibiting the translocation of NF-κB subunit RelA into the nucleus. These effects were abolished by blocking synaptamide binding to GPR110 using an N-terminal targeting antibody. GPR110 expression was found to be high in neutrophils and macrophages where synaptamide also caused a GPR110-dependent increase in cAMP and inhibition of LPS-induced pro-inflammatory mediator expression. Intravenous injection of TNF, a pro-inflammatory cytokine that increases in the circulation after LPS treatment, elicited inflammatory responses in the brain which were dampened by the subsequent injection (i.p.) of synaptamide in a GPR110-dependent manner. CONCLUSION: Our study demonstrates the immune-regulatory function of GPR110 in both brain and periphery, collectively contributing to the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. We suggest GPR110 activation as a novel therapeutic strategy to ameliorate inflammation in the brain as well as periphery.
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Anti-Inflamatórios/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Etanolaminas/farmacologia , Inflamação/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos KnockoutRESUMO
Thermal diffusivity is one of the main parameters to characterize the thermo-physical properties of materials, and advances in its measurement technique will have significant impact on materials science and related applications. Here a photoacoustic (PA) thermorelaxation microscopy is proposed as a new noncontact method to measure the thermal diffusivity. By delivering co-focused heating/probing laser pulse pairs with tunable time delays, the sample's in situ thermal relaxation behavior after the heating pulse excitation can be photoacoustically monitored based on the temperature-dependent property of the Grueneisen parameter. We theoretically deduced the dependence of the obtained PA thermorelaxation time on the thermal diffusivity, and the results coincided well with simulations. The feasibility of this method was validated by various industrial and biological samples. This method provides a new strategy for high-resolution thermal diffusivity measurement with flexible measurement conditions, prefiguring great potential for material and biological applications.
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Microscopia/métodos , Técnicas Fotoacústicas/métodos , Temperatura , Difusão Térmica , Dimetilpolisiloxanos/química , Nylons/químicaRESUMO
BACKGROUND: Adequate consumption of polyunsaturated fatty acids (PUFA) is vital for normal development and functioning of the central nervous system. The long-chain n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid are anti-inflammatory and neuroprotective in the models of central nervous system injury including traumatic brain injury (TBI). In the present study, we tested whether a higher brain DHA status in a mouse model on an adequate dietary α-linolenic acid (ALA) leads to reduced neuroinflammation and improved spontaneous recovery after TBI in comparison to a moderately lowered brain DHA status that can occur in humans. METHODS: Mice reared on diets with differing ALA content were injured by a single cortical contusion impact. Change in the expression of inflammatory cytokines was measured, and cellular changes occurring after injury were analyzed by immunostaining for macrophage/microglia and astrocytes. Behavioral studies included rotarod and beam walk tests and contextual fear conditioning. RESULTS: Marginal supply (0.04 %) of ALA as the sole dietary source of n-3 PUFA from early gestation produced reduction of brain DHA by 35 % in adult offspring mice in comparison to the mice on adequate ALA diet (3.1 %). The DHA-depleted group showed significantly increased TBI-induced expression of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in the brain as well as slower functional recovery from motor deficits compared to the adequate ALA group. Despite the reduction of pro-inflammatory cytokine expression, adequate ALA diet did not significantly alter either microglia/macrophage density around the contusion site or the relative M1/M2 phenotype. However, the glial fibrillary acidic protein immunoreactivity was reduced in the injured cerebral cortex of the mice on adequate ALA diet, indicating that astrocyte activation may have contributed to the observed differences in cellular and behavioral responses to TBI. CONCLUSIONS: Increasing the brain DHA level even from a moderately DHA-depleted state can reduce neuroinflammation and improve functional recovery after TBI, suggesting possible improvement of functional outcome by increasing dietary n-3 PUFA in human TBI.
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BACKGROUND: Brain inflammation has been implicated as a critical mechanism responsible for the progression of neurodegeneration and characterized by glial cell activation accompanied by production of inflammation-related cytokines and chemokines. Growing evidence also suggests that metabolites derived from docosahexaenoic acid (DHA) have anti-inflammatory and pro-resolving effects; however, the possible role of N-docosahexaenoylethanolamine (synaptamide), an endogenous neurogenic and synaptogenic metabolite of DHA, in inflammation, is largely unknown. (The term "synaptamide" instead of "DHEA" was used for N-docosahexaenoylethanolamine since DHEA is a widely used and accepted term for the steroid, dehydroepiandrosterone.) In the present study, we tested this possibility using a lipopolysaccharide (LPS)-induced neuroinflammation model both in vitro and in vivo. METHODS: For in vitro studies, we used P3 primary rat microglia and immortalized murine microglia cells (BV2) to assess synaptamide effects on LPS-induced cytokine/chemokine/iNOS (inducible nitric oxide synthase) expression by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). To evaluate in vivo effects, mice were intraperitoneally (i.p.) injected with LPS followed by synaptamide, and expression of proinflammatory mediators was measured by qPCR and western blot analysis. Activation of microglia and astrocyte in the brain was examined by Iba-1 and GFAP immunostaining. RESULTS: Synaptamide significantly reduced LPS-induced production of TNF-α and NO in cultured microglia cells. Synaptamide increased intracellular cAMP levels, phosphorylation of PKA, and phosphorylation of CREB but suppressed LPS-induced nuclear translocation of NF-κB p65. Conversely, adenylyl cyclase or PKA inhibitors abolished the synaptamide effect on p65 translocation as well as TNF-α and iNOS expression. Administration of synaptamide following LPS injection (i.p.) significantly reduced neuroinflammatory responses, such as microglia activation and mRNA expression of inflammatory cytokines, chemokine, and iNOS in the brain. CONCLUSIONS: DHA-derived synaptamide is a potent suppressor of neuroinflammation in an LPS-induced model, by enhancing cAMP/PKA signaling and inhibiting NF-κB activation. The anti-inflammatory capability of synaptamide may provide a new therapeutic avenue to ameliorate the inflammation-associated neurodegenerative conditions.
Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Endocanabinoides/farmacologia , Microglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Amidoidrolases/deficiência , Amidoidrolases/genética , Animais , Animais Recém-Nascidos , Encéfalo/citologia , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Inibidores Enzimáticos/farmacologia , Ácidos Graxos/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND AND OBJECTIVE: Esophageal cancer is a serious disease with a high prevalence in Eastern Asia. Histopathology tissue analysis stands as the gold standard in diagnosing esophageal cancer. In recent years, there has been a shift towards digitizing histopathological images into whole slide images (WSIs), progressively integrating them into cancer diagnostics. However, the gigapixel sizes of WSIs present significant storage and processing challenges, and they often lack localized annotations. To address this issue, multi-instance learning (MIL) has been introduced for WSI classification, utilizing weakly supervised learning for diagnosis analysis. By applying the principles of MIL to WSI analysis, it is possible to reduce the workload of pathologists by facilitating the generation of localized annotations. Nevertheless, the approach's effectiveness is hindered by the traditional simple aggregation operation and the domain shift resulting from the prevalent use of convolutional feature extractors pretrained on ImageNet. METHODS: We propose a MIL-based framework for WSI analysis and cancer classification. Concurrently, we introduce employing self-supervised learning, which obviates the need for manual annotation and demonstrates versatility in various tasks, to pretrain feature extractors. This method enhances the extraction of representative features from esophageal WSI for MIL, ensuring more robust and accurate performance. RESULTS: We build a comprehensive dataset of whole esophageal slide images and conduct extensive experiments utilizing this dataset. The performance on our dataset demonstrates the efficiency of our proposed MIL framework and the pretraining process, with our framework outperforming existing methods, achieving an accuracy of 93.07% and AUC (area under the curve) of 95.31%. CONCLUSION: This work proposes an effective MIL method to classify WSI of esophageal cancer. The promising results indicate that our cancer classification framework holds great potential in promoting the automatic whole esophageal slide image analysis.
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Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/diagnóstico por imagem , Fontes de Energia Elétrica , Processamento de Imagem Assistida por Computador , Carga de TrabalhoRESUMO
The role of muscular left ventricular (LV) false tendons (FTs) is poorly understood. To gain insight into their pathophysiologic significance, we adapted echocardiographic LV strain imaging software to measure LVFT longitudinal strain in subjects with normal left ventricles and in patients who sustained previous anterior wall myocardial infarction (AWMI). GE EchoPAC software was used to measure longitudinal strain in LVFTs ≥0.3 cm in diameter. Tendinous strain was measured in 11 patients with LVFTs confined to the left anterior descending artery territory (connecting the anteroseptum or anterior wall to the apex) ≥6 months after AWMI (myocardial infarction [MI]+FT+ group) and in 25 patients with normal hearts containing LVFTs (MI-FT+ group). We also compared the indexed LV end-diastolic volumes in the MI+FT+ group to that of 25 patients with previous AWMI without LVFTs (MI+FT- group). The mean LVFT strain in MI+FT+ group was 5.5 ± 6.2% and -28.9 ± 4.7% in the MI-FT+ group (p <0.0001). The indexed LV end-diastolic volume in the MI+FT+ group did not differ from the MI+FT- group (88.4 ± 17.8 vs 87.9 ± 17 ml/m2, p = 0.90). In conclusion, the negative strain (contraction) developed by LVFTs in the MI-FT+ group may help maintain normal LV size and shape by generating inward restraining forces. The development of positive strain (stretch) in LVFTs in patients in the MI+FT+ group suggests they become infarcted after AWMI. This implies that they are incapable of generating inward restraining forces that might otherwise mitigate adverse remodeling. Of note, LV volumes after AWMI do not differ whether or not LVFTs are present.
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Infarto Miocárdico de Parede Anterior , Cardiopatias Congênitas , Infarto do Miocárdio , Humanos , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Remodelação Ventricular , Infarto do Miocárdio/diagnóstico por imagem , Ecocardiografia , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular EsquerdaRESUMO
Supraventricular tachycardia with aberrancy and ventricular tachycardia can often be differentiated on the basis of subtle findings. We present an electrocardiogram with findings of Coumel's sign, which is diagnostic of atrioventricular re-entrant tachycardia using an accessory pathway. (Level of Difficulty: Advanced.).
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Brain tumor segmentation is a key step in brain cancer diagnosis. Segmentation of brain tumor sub-regions, including necrotic, enhancing, and edematous regions, can provide more detailed guidance for clinical diagnosis. Weakly supervised brain tumor segmentation methods have received much attention because they do not require time-consuming pixel-level annotations. However, existing weakly supervised methods focus on the segmentation of the entire tumor region while ignoring the challenging task of multi-label segmentation for the tumor sub-regions. In this article, we propose a weakly supervised approach to solve the multi-label brain tumor segmentation problem. To the best of our knowledge, it's the first end-to-end multi-label weakly supervised segmentation model applied to brain tumor segmentation. With well-designed loss functions and a contrastive learning pre-training process, our proposed Transformer-based segmentation method (WS-MTST) has the ability to perform segmentation of brain tumor sub-regions. We conduct comprehensive experiments and demonstrate that our method reaches the state-of-the-art on the popular brain tumor dataset BraTS (from 2018 to 2020).
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Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Encéfalo , Fontes de Energia Elétrica , Conhecimento , Processamento de Imagem Assistida por ComputadorRESUMO
Activation of adhesion receptor GPR110 by the endogenous ligand synaptamide promotes neurogenesis, neurite growth, and synaptogenesis in developing brains through cAMP signal transduction. However, interacting partners of GPR110 and their involvement in cellular function remain unclear. Here, we demonstrate using chemical crosslinking, affinity purification, and quantitative mass spectrometry that GPR110 interacts with the tight junction adhesion protein occludin. By removing non-specific partners by comparing the binding proteins of GPR110 WT and an inactive mutant exhibiting impaired surface expression, occludin was distinguished as a true binding partner which was further confirmed by reciprocal co-immunoprecipitation assay. Deletion of GPR110 in mice led to the disruption of blood-brain barrier (BBB) and reduced occludin phosphorylation at Y285 in the brain. The Y285 phosphorylation increased upon the ligand-induced activation of GPR110. These data suggest an important role of GPR110-occludin interaction in BBB function and association of previously unknown GPR110-dependent occludin phosphorylation at Y285 with BBB integrity.
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Traumatic brain injury (TBI) is a worldwide endemic that results in unacceptably high morbidity and mortality. Secondary injury processes following primary injury are composed of intricate interactions between assorted molecules that ultimately dictate the degree of longer-term neurological deficits. One comparatively unexplored molecule that may contribute to exacerbation of injury or enhancement of recovery is the posttranslationally modified polysialic acid form of neural cell adhesion molecule, PSA-NCAM. This molecule is a critical modulator of central nervous system plasticity and reorganization after injury. In this study, we used controlled cortical impact (CCI) to produce moderate or severe TBI in the mouse. Immunoblotting and immunohistochemical analysis were used to track the early (2, 24, and 48 hour) and late (1 and 3 week) time course and location of changes in the levels of PSA-NCAM after TBI. Variable and heterogeneous short- and long-term increases or decreases in expression were found. In general, alterations in PSA-NCAM levels were seen in the cerebral cortex immediately after injury, and these reductions persisted in brain regions distal to the primary injury site, especially after severe injury. This information provides a starting point to dissect the role of PSA-NCAM in TBI-related pathology and recovery.
Assuntos
Química Encefálica/fisiologia , Lesões Encefálicas/metabolismo , Córtex Cerebral/lesões , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Ácidos Siálicos/metabolismo , Actinas/metabolismo , Animais , Western Blotting , Hemorragia Encefálica Traumática/metabolismo , Hemorragia Encefálica Traumática/patologia , Lesões Encefálicas/patologia , Córtex Cerebral/patologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função FisiológicaRESUMO
The immense potential of temperature-responsive nanomaterials for use as contrast agents has propelled much recent research and development in the field of photoacoustic (PA) imaging, while the exorbitant transition temperature exceeding the human-tolerable range and the low reversibility of the reported temperature-sensitive nanosystems are still two severe issues that hinder effective imaging and long-term monitoring in practical applications. Herein, we propose a high-performing thermoresponsive polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO2@PEG) nanoprobe (NP) with strong and switchable optical absorption in the near-infrared-II (NIR-II) biowindow (1000-1700 nm) near human-body temperature, to achieve deep and contrast-enhanced PA imaging. Our study shows that the PA signal amplitude of W-VO2@PEG NPs at 1064 nm increases up to 260% when the temperature increases from 35 °C to 45 °C, with a signal fluctuation of less than 10% after 10 temperature cycles, therefore enabling great potential of "off-to-on" dynamic contrast-enhanced imaging capability in deep-seated tissues. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that, by levering the prepared W-VO2@PEG NPs and dynamically modulating the temperature field with an external NIR optical stimulus, contrast-enhanced PA images of the target can be obtained with an imaging depth up to 1.5 cm. Furthermore, in vivo potential of the prepared thermoresponsive NPs for the detection and identification of deep-seated tumors by directly comparing to conventional "always on" NPs has been demonstrated. Our work will offer feasible guidance for the development of smart temperature-activatable PA NPs with improved imaging depth and imaging contrast.
Assuntos
Nanopartículas , Técnicas Fotoacústicas , Diagnóstico por Imagem , Humanos , Transição de Fase , Técnicas Fotoacústicas/métodos , Temperatura , TungstênioRESUMO
Imaging is central to the care of patients with infective endocarditis. Although transthoracic and transesophageal echocardiography are the principal imaging techniques, additional modalities including positron emission tomography and cardiac computed tomography, and to a lesser extent intracardiac echocardiography, play an increasing role. This review discusses the role of cardiac imaging in establishing the diagnosis of endocarditis, in predicting its embolic risk, and in making decisions regarding the need for and timing of surgery.
Assuntos
Endocardite Bacteriana , Endocardite , Próteses Valvulares Cardíacas , Ecocardiografia/métodos , Ecocardiografia Transesofagiana , Endocardite/diagnóstico por imagem , Endocardite Bacteriana/diagnóstico por imagem , HumanosRESUMO
Repeated mild traumatic brain injury (TBI) can cause persistent neuropathological effects and is a major risk factor for chronic traumatic encephalopathy. PUFAs (n-3 polyunsaturated fatty acids) were shown to improve acute TBI outcomes in single-injury models in most cases. In this study, we demonstrate positive effects of dietary n-3 PUFA on long-term neuropathological and functional outcome in a clinically relevant model of repeated mild TBI using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Adult mice, reared on n-3 PUFA adequate (higher n-3 PUFA) or deficient (lower n-3 PUFA) diets, were given a mild CHIMERA daily for 3 consecutive days. At 2 months after injury, visual function and spatial memory were evaluated. Glia cell activation was assessed by immunostaining using antibodies of ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein, and axonal damage was examined using silver staining. Repeated CHIMERA (rCHIMERA)-induced gliosis was significantly suppressed in the optic tract, corpus callosum, and hippocampus of mice fed the n-3 PUFA adequate diet compared to the deficient diet group. Considerable axonal damage was detected in the optic tract after rCHIMERA, but the adequate diet group displayed less axonal damage compared to the deficient diet group. rCHIMERA induced a drastic reduction in N1 amplitude of the visual evoked potential in both diet groups and the a-wave amplitude of the electroretinogram in the deficient diet group. However, reduction of N1 and a-wave amplitude were less severe in the adequate diet group. The Morris water maze probe test indicated a significant decrease in the number of platform crossings in the deficient diet group compared to the adequate group. In summary, dietary n-3 PUFA can attenuate persistent glial cell activation and axonal damage and improve deficits in visual function and spatial memory after repeated mild TBI. These data support the neuroprotective potential of a higher n-3 PUFA diet in ameliorating the adverse outcome of repeated mild TBI.