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CD8+ T cells can recognize peptides presented by class I human leukocyte antigen (HLA-I) of nucleated cells. Exploring this immune mechanism is essential for identifying T-cell vaccine targets in cancer immunotherapy. Over the past decade, the wealth of data generated by experiments has spawned many computational approaches for predicting HLA-I binding, antigen presentation and T-cell immune responses. Nevertheless, existing HLA-I binding and antigen presentation prediction approaches suffer from low precision due to the absence of T-cell receptor (TCR) recognition. Direct modeling of T-cell immune responses is less effective as TCR recognition's mechanism still remains underexplored. Therefore, directly applying these existing methods to screen cancer neoantigens is still challenging. Here, we propose a novel immune epitope prediction method termed IEPAPI by effectively incorporating antigen presentation and immunogenicity. First, IEPAPI employs a transformer-based feature extraction block to acquire representations of peptides and HLA-I proteins. Second, IEPAPI integrates the prediction of antigen presentation prediction into the input of immunogenicity prediction branch to simulate the connection between the biological processes in the T-cell immune response. Quantitative comparison results on an independent antigen presentation test dataset exhibit that IEPAPI outperformed the current state-of-the-art approaches NetMHCpan4.1 and mhcflurry2.0 on 100 (25/25) and 76% (19/25) of the HLA subtypes, respectively. Furthermore, IEPAPI demonstrates the best precision on two independent neoantigen datasets when compared with existing approaches, suggesting that IEPAPI provides a vital tool for T-cell vaccine design.
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Apresentação de Antígeno , Neoplasias , Humanos , Epitopos , Antígenos de Histocompatibilidade Classe I , Receptores de Antígenos de Linfócitos T , PeptídeosRESUMO
Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.
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Circulação Cerebrovascular , Microbioma Gastrointestinal , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Transcriptoma , Humanos , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Microbioma Gastrointestinal/fisiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Circulação Cerebrovascular/fisiologia , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , FenótipoRESUMO
Fusicoccane (FC)-type diterpenoids are a class of diterpenoids characterized by a unique 5-8-5 ring system and exhibit diverse biological activities. Recently, we identified a novel FC-type diterpene synthase MgMS, which produces a myrothec-15(17)-en-7-ol (1) hydrocarbon skeleton, however, its tailoring congeners have not been elucidated. Here, we discovered two additional gene clusters Bn and Np, each encoding a highly homologous terpene synthase to MgMS but distinct tailoring enzymes. Heterologous expression of the terpene synthases BnMS and NpMS yielded the same product as MgMS. Subsequent introduction of three P450 enzymes MgP450, BnP450 and NpP450 from individual gene clusters resulted in four new FC-type diterpenoids 2-5. Notably, MgP450 serves as the first enzyme responsible for hydroxylation of the C19 methyl group, whereas NpP450 functions as a multifunctional P450 enzyme involved in the oxidations at C5, C6, and C19 positions of the 5-8-5 tricyclic skeleton. C5 oxidation of the hydrocarbon skeleton 1 led to broadening of the NMR signals and incomplete spectra, which was resolved by high-temperature NMR spectral analysis.
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BACKGROUND: China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China. METHODS: Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals' services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals. RESULTS: Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services (P = 0.006), numbers of doctors outside of the entity (P = 0.006), numbers of online nurses (P = 0.004), and the ratio of online nurses to offline doctors (P < 0.001). Of the 16 aspects evaluated with regards to the medical staff's self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time. CONCLUSIONS: While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.
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COVID-19 , Telemedicina , Humanos , COVID-19/epidemiologia , Hospitais , Pandemias , China/epidemiologia , InternetRESUMO
OBJECTIVES: To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. METHODS: We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007-2008 and 2017-2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. RESULTS: The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007-2008 to 55.3% in 2017-2018 (P-value for trend = 0.03). The percentage of participants whose glycaemic, lipid or all three risk factor control targets were achieved remained stable temporally (P > 0.05). Some patient characteristics were significantly related to risk factor control, including age 45-64, age ≥65, Asian Americans, non-Hispanic Blacks, higher family income, and being overweight and obese. A trend towards increased use of glucose-lowering medication was found (from 71.0% in 2007-2008 to 94.7% in 2017-2018, P < 0.01), while the prevalence of taking blood pressure-lowering and lipid-lowering medications remained stable (P > 0.05). CONCLUSION: Based on NHANES data, a significant trend towards decreased blood pressure control was observed in patients with gout, while glycaemic and lipid control levelled off. These findings emphasize that more endeavours are needed to improve management of cardiovascular risk factors in patients with gout.
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Gota , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estudos Transversais , Gota/tratamento farmacológico , Gota/epidemiologia , Fatores de Risco , Lipídeos , PrevalênciaRESUMO
Men who have sex with men (MSM) make up the majority of new human immunodeficiency virus (HIV) diagnoses among young people in China. Understanding HIV transmission dynamics among the MSM population is, therefore, crucial for the control and prevention of HIV infections, especially for some newly reported genotypes of HIV. This study presents a metapopulation model considering the impact of pre-exposure prophylaxis (PrEP) to investigate the geographical spread of a hypothetically new genotype of HIV among MSM in Guangdong, China. We use multiple data sources to construct this model to characterize the behavioural dynamics underlying the spread of HIV within and between 21 prefecture-level cities (i.e. Guangzhou, Shenzhen, Foshan, etc.) in Guangdong province: the online social network via a gay social networking app, the offline human mobility network via the Baidu mobility website, and self-reported sexual behaviours among MSM. Results show that PrEP initiation exponentially delays the occurrence of the virus for the rest of the cities transmitted from the initial outbreak city; hubs on the movement network, such as Guangzhou, Shenzhen, and Foshan are at a higher risk of 'earliest' exposure to the new HIV genotype; most cities acquire the virus directly from the initial outbreak city while others acquire the virus from cities that are not initial outbreak locations and have relatively high betweenness centralities, such as Guangzhou, Shenzhen and Shantou. This study provides insights in predicting the geographical spread of a new genotype of HIV among an MSM population from different regions and assessing the importance of prefecture-level cities in the control and prevention of HIV in Guangdong province. This article is part of the theme issue 'Data science approach to infectious disease surveillance'.
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Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Adolescente , China/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , MasculinoRESUMO
BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) rapidly spread across worldwide, posing a significant challenge to public health. Several shortcomings in the existing infectious disease management system were exposed during the pandemic, which hindered the control of the disease globally. To cope with this issue, we propose a window-period framework to reveal the general rule of the progression of management of infectious diseases and to help with decision making at the early stage of epidemics with a focus on healthcare provisions. METHODS: The framework has two significant periods (dark-window period and bright-window period). Outbreak of COVID-19 in China was used as an example for the application of the framework. RESULTS: The framework could reflect the progression of the epidemic objectively. The spread increased slowly in the dark-window period, but rocketed up in the bright-window period. The beginning of the bright-window period was the time when healthcare personnel were exposed to a substantially high risk of nosocomial infection. Additionally, proper and prompt preventive actions during the dark-window and bright-window periods were substantially important to reduce the future spreading of the disease. CONCLUSIONS: It was recommended that when possible healthcare provisions should upgrade to the highest level of alert for the control of an unknown epidemic in the dark-window period, while countermeasures in the bright-window period could be accordingly adjusted with full exploration and considerations. The framework may provide some insights into how to accelerate the control of future epidemics promptly and effectively.
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COVID-19 , Epidemias , China/epidemiologia , Gerenciamento Clínico , Surtos de Doenças , Humanos , SARS-CoV-2RESUMO
We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.
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Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , RNA Viral/genética , Adolescente , Adulto , Idoso , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , China/epidemiologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Fezes/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Faringe/virologia , Pneumonia Viral/diagnóstico , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real , SARS-CoV-2 , Índice de Gravidade de Doença , Escarro/virologia , Fatores de TempoRESUMO
BACKGROUND: Evidence on the relationship between different particle size fractions and emergency ambulance dispatches (EAD) remains limited and sparse. METHODS: We collected daily data of EAD, ambient air pollution and meteorological data from 2014 to 2018 in Guangzhou, China. We used a generalized additive model with covariate adjustments to estimate the associations between different particle size fractions and EAD related to all-cause, cardiovascular diseases, and respiratory diseases. Several subgroup and sensitivity analyses were also performed. RESULTS: Significant associations were observed between PM2.5, PM2.5-10, PM10 and EADs. A 10 µg/m3 increase of PM2.5, PM2.5-10, and PM10 was associated with an increase of 0.98% (95% CI: 0.67, 1.28%), 2.06% (95% CI: 1.44, 2.68%), and 0.75% (95%CI: 0.53, 0.96%) in all-cause EAD, with an increase of 0.69% (95% CI: 0.00, 1.39%), 2.04% (95% CI: 0.64, 3.45%), and 0.60% (95%CI: 0.11,1.10%) in cardiovascular-related EAD, and an increase of 1.14% (95% CI: 0.25, 2.04%), 2.52% (95% CI: 0.72, 4.35%), and 0.89% (95%CI: 0.25,1.52%) in respiratory-related EAD at lag03, respectively. The results were robust in subgroup and sensitivity analyses. CONCLUSIONS: This study revealed that PM2.5, PM2.5-10 and PM10 were significantly related with risks of all-cause and cause-specific EAD. More evidence of high quality may be needed to further support our results in this ecological study.
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Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Ambulâncias/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Tamanho da Partícula , Material Particulado/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Doenças Respiratórias/epidemiologiaRESUMO
PURPOSE: To determine the predictive features of thymic carcinomas and high-risk thymomas using random forest algorithm. METHODS: A total of 137 patients with pathologically confirmed high-risk thymomas and thymic carcinomas were enrolled in this study. Three clinical features and 20 computed tomography features were reviewed. The association between computed tomography features and pathological patterns was analyzed by univariate analysis and random forest. The predictive efficiency of the random forest algorithm was evaluated by receiver operating characteristic curve analysis. RESULTS: There were 92 thymic carcinomas and 45 high-risk thymomas in this study. In univariate analysis, patient age, presence of myasthenia gravis, lesion shape, enhancement pattern, presence of necrosis or cystic change, mediastinal invasion, vessel invasion, lymphadenopathy, pericardial effusion, and distant organ metastasis were found to be statistically different between high-risk thymomas and thymic carcinomas (all P < 0.01). Random forest suggested that tumor shape, lymphadenopathy, and the presence of pericardial effusion were the key features in tumor differentiation. The predictive accuracy for the test data and whole data was 94.73% and 96.35%, respectively. Further receiver operating characteristic curve analysis showed the area under the curve was 0.957 (95% confidence interval, 0.986-0.929). CONCLUSIONS: The random forest model in the present study has high efficiency in predictive diagnosis of thymic carcinomas and high-risk thymomas. Tumor shape, lymphadenopathy, and pericardial effusion are the key features for tumor differentiation. Thymic tumors with irregular shape, the presence of lymphadenopathy, and pericardial effusion are highly indicative of thymic carcinomas.
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Interpretação de Imagem Assistida por Computador/métodos , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Timo/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: The outbreak of COVID-19 has caused a continuing global pandemic. Hospitals are integral to the control and prevention of COVID-19; however, they are facing numerous challenges during the epidemic. OBJECTIVE: Our study aimed to introduce the practical experience of the design and implementation of a web-based COVID-19 service platform at a tertiary hospital in China as well as the preliminary results of the implementation. METHODS: The web-based COVID-19 service platform was deployed within the health care system of the Guangdong Second Provincial General Hospital and Internet Hospital; the function of the platform was to provide web-based medical services for both members of the public and lay health care workers. The focal functions of this system included automated COVID-19 screening, related symptom monitoring, web-based consultation, and psychological support; it also served as a COVID-19 knowledge hub. The design and process of each function are introduced. The usage data for the platform service were collected and are represented by three periods: the pre-epidemic period (December 22, 2019, to January 22, 2020, 32 days), the controlled period (January 23 to March 31, 2020, 69 days), and the postepidemic period (April 1 to June 30, 2020, 91 days). RESULTS: By the end of June 2020, 96,642 people had used the automated COVID-19 screening and symptom monitoring systems 161,884 and 7,795,194 times, respectively. The number of general web-based consultation services per day increased from 30 visits in the pre-epidemic period to 122 visits during the controlled period, then dropped to 73 visits in the postepidemic period. The psychological counseling program served 636 clients during the epidemic period. For people who used the automated COVID-19 screening service, 160,916 (99.40%) of the total users were classified in the no risk category. 464 (0.29%) of the people were categorized as medium to high risk, and 12 people (0.01%) were recommended for further COVID-19 testing and treatment. Among the 96,642 individuals who used the COVID-19 related symptoms monitoring service, 6696 (6.93%) were symptomatic at some point during the monitoring period. Fever was the most frequently reported symptom, with 2684/6696 symptomatic people (40.1%) having had this symptom. Cough and sore throat were also relatively frequently reported by the 6696 symptomatic users (1657 people, 24.7%, and 1622 people, 24.2%, respectively). CONCLUSIONS: The web-based COVID-19 service platform implemented at a tertiary hospital in China is exhibited to be a role model for using digital health technologies to respond to the COVID-19 pandemic. The digital solutions of automated COVID-19 screening, daily symptom monitoring, web-based care, and knowledge propagation have plausible acceptability and feasibility for complementing offline hospital services and facilitating disease control and prevention.
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Teste para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/terapia , Telemedicina/métodos , COVID-19/epidemiologia , China/epidemiologia , Feminino , Humanos , Masculino , SARS-CoV-2/isolamento & purificação , Centros de Atenção TerciáriaRESUMO
OBJECTIVES: The study aimed to explore the effects of codeine-containing cough syrup (CCS) exposure on cortical morphology and the relationship between cortical characteristics and CCS dependence. METHODS: Cortical morphometry based on Computational Anatomy Toolbox (CAT12) was used to compare changes in sulcal depth, gyrification, and cortical thickness of the cerebral cortex from 40 CCS users and 40 healthy controls (HCs) with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between abnormal cortical morphological changes and the duration of CCS use, impulsivity traits, and age of first use were investigated with correlation analysis (p < 0.05, uncorrected). RESULTS: CCS users exhibited significantly increased sulcal depth in the bilateral insula, bilateral lingual, bilateral superior frontal, right precuneus, and right middle frontal regions; increased gyrification in the right precentral cortex; and increased cortical thickness in the bilateral precentral, bilateral precuneus, and right superior temporal cortices compared to HCs. In addition, we found significant correlations between the bilateral insula, right superior frontal cortex, and right precentral gyrus and Barratt Impulsiveness Scale (BIS) total scores. CONCLUSIONS: Chronic CCS abuse may be associated with aberrant sulcal depth, gyrification, and cortical thickness. These morphological changes might serve as an underlying neurobiological mechanism of impulsive behavior in the CCS users. KEY POINTS: ⢠Cortical morphological changes were detected in CCS users. ⢠Increased sulcal depth, gyrification, and cortical thickness of some regions were found in the CCS users. ⢠Positive correlations between cortical morphological changes and BIS total scores were identified.
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Córtex Cerebral/patologia , Codeína/farmacologia , Tosse/diagnóstico , Lobo Frontal/patologia , Imageamento por Ressonância Magnética/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Córtex Cerebral/efeitos dos fármacos , Tosse/tratamento farmacológico , Feminino , Lobo Frontal/efeitos dos fármacos , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: This study investigated alterations of resting-state networks (RSNs) in primary insomnia patients as well as relationships between these changes and clinical features. METHODS: Fifty-nine primary insomnia patients and 53 healthy control subjects underwent a resting-state fMRI scan (rs-fMRI). Ten RSNs were identified using independent component analysis of rs-fMRI data. To assess significant differences between the two groups, voxel-wise analysis of ten RSNs was conducted using dual regression with FSL randomised non-parametric permutation testing and a threshold-free cluster enhanced technique to control for multiple comparisons. Relationships between abnormal functional connectivity and clinical variables were then investigated with Pearson's correlation analysis. RESULTS: Primary insomnia patients showed decreased connectivity in regions of the right frontoparietal network (FPN), including the superior parietal lobule and superior frontal gyrus. Moreover, decreased connectivity in the right middle temporal gyrus and right lateral occipital cortex with the FPN showed significant positive correlations with disease duration and self-rated anxiety, respectively. CONCLUSIONS: Our study suggests that primary insomnia patients are characterised by abnormal organisation of the right FPN, and dysfunction of the FPN is correlated with disease duration and anxiety. The results enhance our understanding of neural substrates underlying symptoms of primary insomnia from the viewpoint of resting-state networks. KEY POINTS: ⢠Primary insomnia patients showed altered functional connectivity in the right FPN. ⢠Middle temporal gyrus FC with FPN was significantly correlated with disease duration. ⢠Lateral occipital cortex FC with FPN was significantly correlated with SAS scores.
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Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Lobo Parietal/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Lobo Temporal/diagnóstico por imagem , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lobo Parietal/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto JovemRESUMO
PURPOSE: To identify codeine-containing cough syrups (CCS)-related modulations of intrinsic connectivity network (ICN) and to investigate whether these changes of ICN can be related to duration of CCS use and to impulsivity behavior in CCS-dependent individuals. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) data in 41 CCS-dependent individuals and 34 healthy controls (HC) were scanned at 1.5T and analyzed using independent component analysis (ICA), in combination with a "dual-regression" technique to identify the group differences of three important resting-state networks, the default mode network (DMN), the executive control network (ECN), and the salience network (SN) between the CCS-dependent individuals and HC. RESULTS: Compared with the HC, CCS-dependent individuals had aberrant intrinsic connectivity within the DMN, ECN, and SN (P < 0.05, AlphaSim corrected). Furthermore, a longer duration of CCS use was associated with greater abnormalities in the intrinsic network functional connectivity (FC, P < 0.05, Bonferroni correction). Intrinsic network FC also correlated with higher impulsivity in CCS-dependent individuals (P < 0.05, AlphaSim corrected). CONCLUSION: Our findings revealed aberrant DMN, ECN, and SN connectivity patterns in CCS-dependent patients, which may provide new insight into how neuronal communication and information integration are disrupted among DMN, ECN, and SN key structures due to long duration of CCS use. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:177-186.
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Antitussígenos/efeitos adversos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Codeína/efeitos adversos , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/fisiopatologia , Humanos , Masculino , Rede Nervosa/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Reprodutibilidade dos Testes , Descanso , Sensibilidade e Especificidade , Adulto JovemRESUMO
OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: ⢠CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum ⢠Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex ⢠Impairment of VMHC correlated with impulsive behaviour in patients ⢠Impairment of VMHC correlated with the CCS duration in patients.
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Codeína , Corpo Caloso/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Adolescente , Adulto , Antitussígenos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Casos e Controles , China , Corpo Caloso/patologia , Corpo Caloso/fisiopatologia , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Tamanho do Órgão , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To explore the abnormal connectivity patterns between the insular and the voxels of the brain in primary insomnia (PI) with insular-based functional connectivity (FC). METHODS: With the resting-state fMRI data acquired from 57 PI patients and 46 healthy controls, a two-sample t test was performed on individual FC correlation maps from two groups. The person correlation analysis was used to evaluate the relationship between the abnormal FC and clinical features. RESULTS: PI patients show enhanced connectivity between the left insula with the right anterior cingulate cortex (p < 0.05 and p < 0.001, AlphaSim-corrected), right frontal sup orb, bilateral thalamus and left precuneus,as well as decreased connectivity with the left middle temporal gyrus and right fusiform (p < 0.05, AlphaSim-corrected). Correlation analysis indicated the enhanced connectivities in the PI patients have significant negative correlations with Self-Rating Depression Scale(SDS)and Self-Rating Anxiety Scale(SAS)scores. In addition, the decreased functional connectivities showed positive correlations with SDS and SAS scores. CONCLUSION: Our study showed the increased connectivity regions with insula were mainly in the emotional circle and decreased connectivity was in cognitive-related regions. These provide additional evidence from functional integration view to understand the possible underlying neural- mechanisms of PI. KEY POINTS: ⢠The aberrant insular-based connectivity pattern of PI patients was detected. ⢠Regions showing increased connectivity with left insular were mainly in emotional circle. ⢠Significant correlations between changed FC and SDS and SAS score were found.
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Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Conectoma , Imageamento por Ressonância Magnética/métodos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Adulto , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologiaRESUMO
Purpose To analyze the integrity of white matter (WM) tracts in primary insomnia patients and provide better characterization of abnormal WM integrity and its relationship with disease duration and clinical features of primary insomnia. Materials and Methods This prospective study was approved by the ethics committee of the Guangdong No. 2 Provincial People's Hospital. Tract-based spatial statistics were used to compare changes in diffusion parameters of WM tracts from 23 primary insomnia patients and 30 healthy control (HC) participants, and the accuracy of these changes in distinguishing insomnia patients from HC participants was evaluated. Voxel-wise statistics across subjects was performed by using a 5000-permutation set with family-wise error correction (family-wise error, P < .05). Multiple regressions were used to analyze the associations between the abnormal fractional anisotropy (FA) in WM with disease duration, Pittsburgh Sleep Quality Index, insomnia severity index, self-rating anxiety scale, and the self-rating depression scale in primary insomnia. Characteristics for abnormal WM were also investigated in tract-level analyses. Results Primary insomnia patients had lower FA values mainly in the right anterior limb of the internal capsule, right posterior limb of the internal capsule, right anterior corona radiata, right superior corona radiata, right superior longitudinal fasciculus, body of the corpus callosum, and right thalamus (P < .05, family-wise error correction). The receiver operating characteristic areas for the seven regions were acceptable (range, 0.60-0.74; 60%-74%). Multiple regression models showed abnormal FA values in the thalamus and body corpus callosum were associated with the disease duration, self-rating depression scale, and Pittsburgh Sleep Quality Index scores. Tract-level analysis suggested that the reduced FA values might be related to greater radial diffusivity. Conclusion This study showed that WM tracts related to regulation of sleep and wakefulness, and limbic cognitive and sensorimotor regions, are disrupted in the right brain in patients with primary insomnia. The reduced integrity of these WM tracts may be because of loss of myelination. (©) RSNA, 2016.
Assuntos
Imageamento por Ressonância Magnética/métodos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To investigate alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after ultra-rapid opioid detoxification under general anaesthesia (UROD) combined with naltrexone treatment (NMT). METHODS: Fourteen CCS-dependent individuals were scanned using resting-state fMRI. After UROD and 2 weeks of NMT, CCS-dependent individuals were rescanned. Fourteen matched controls were studied at baseline and compared. The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function. RESULTS: After UROD and 2 weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral parahippocampal gyrus and right medial orbitofrontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pretreatment. Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals. CONCLUSIONS: We offer the first report describing how regional and integral synchronous neural activity occurs after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity. These findings contribute to the understanding of complex systems involved in UROD-NMT effects. KEY POINTS: ⢠CCS-dependent individuals had reduced ALFF and increased FC at baseline. ⢠UROD treatment can change the regional and integral brain function of CCS-dependent individuals. ⢠Attenuated ALFFs are correlated with the withdrawal syndrome after treatment.
Assuntos
Anestesia Geral , Encéfalo/efeitos dos fármacos , Codeína/intoxicação , Naltrexona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Transtornos Relacionados ao Uso de Opioides/reabilitação , Adulto , Antitussígenos/intoxicação , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Antagonistas de Entorpecentes/uso terapêutico , Estudos Prospectivos , Síndrome de Abstinência a Substâncias/diagnóstico por imagem , Síndrome de Abstinência a Substâncias/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: The study aimed to explore the regional spontaneous activity changes in primary insomnia (PI) patients. MATERIALS AND METHODS: Based on the resting-state fMRI datasets acquired from 59 PI patients and 47 healthy controls, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Relationships between abnormal ReHo values and the Pittsburgh Sleep Quality Index (PSQI), the self-rating anxiety scale (SAS) and the self-rating depression scale (SDS) were investigated with Pearson correlation analysis. RESULTS: In PI patients, we found increased ReHo in the left insula, right anterior cingulate gyrus, bilateral precentral gyrus and left cuneus, as well as decreased ReHo in the right middle cingulate cortex and left fusiform (p < 0.05, AlphaSim-corrected). We also found a significant positive correlation between increased ReHo in the left insula and SAS scores, decreased ReHo in the right middle cingulated cortex and SDS, SAS scores as well as a negative correlation between increased ReHo in the right precentral gyrus and SDS scores (p < 0.05). CONCLUSIONS: Our study found abnormal spontaneous activities in multiple brain regions, especially in emotion-related areas in PI patients. Alterative activities in these regions might contribute to an understanding the intrinsic functional architecture of insomnia and its clinical features. KEY POINTS: ⢠Regional spontaneous activity changes were detected in PI patients. ⢠Decreased or increased ReHo of some regions was identified in PI patients. ⢠Significant correlations between mean ReHo and SDS scores were found.
Assuntos
Córtex Cerebral/patologia , Lobo Frontal/patologia , Imageamento por Ressonância Magnética/métodos , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Adulto , Feminino , Humanos , MasculinoRESUMO
Neuroimaging studies suggested that drug addiction is linked to abnormal brain functional connectivity. However, little is known about the alteration of brain white matter (WM) connectivity in addictive drug users and nearly no study has been performed to examine the alterations of brain WM connectivity in heroin-dependent individuals (HDIs). Diffusion tensor imaging (DTI) offers a comprehensive technique to map the whole brain WM connectivity in vivo. In this study, we acquired DTI datasets from 20 HDIs and 18 healthy controls and constructed their brain WM structural networks using a deterministic fibre tracking approach. Using graph theoretical analysis, we explored the global and nodal topological parameters of brain network for both groups and adopted a network-based statistic (NBS) approach to assess between-group differences in inter-regional WM connections. Statistical analysis indicated the global efficiency and network strength were significantly increased, but the characteristic path length was significantly decreased in the HDIs compared with the controls. We also found that in the HDIs, the nodal efficiency was significantly increased in the left prefrontal cortex, bilateral orbital frontal cortices and left anterior cingulate gyrus. Moreover, the NBS analysis revealed that in the HDIs, the significant increased connections were located in the paralimbic, orbitofrontal, prefrontal and temporal regions. Our results may reflect the disruption of whole brain WM structural networks in the HDIs. Our findings suggest that mapping brain WM structural network may be helpful for better understanding the neuromechanism of heroin addiction.