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OBJECTIVE: To analyze the diagnostic value of HR-VWI in intracranial arterial stenosis and occlusion and compare it with DSA. METHODS: A retrospective analysis of clinical data of 59 patients with intracranial arterial stenosis in our hospital was conducted to compare the diagnostic results of the two methods for different degrees of intracranial stenosis and various morphological plaques. RESULTS: The diagnosis of stenosis and occlusion by both methods showed no significant difference (p > 0.05). Comparison of plaque morphology detected by HR-VWI with pathological examination results showed no significant difference (p > 0.05); however, there was a significant difference between plaque morphology detected by DSA and pathological examination results (p < 0.05). Additionally, there was a significant difference between plaque morphology detected by HR-VWI and DSA (p < 0.05). CONCLUSION: HR-VWI technique is comparable to DSA technique in diagnosing intracranial arterial stenosis and occlusion, but it is superior to DSA in plaque morphology diagnosis.
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BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Anciano , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Espirometría , Prueba de Esfuerzo , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Tolerancia al Ejercicio , Factores de Riesgo , Ventilación PulmonarRESUMEN
PURPOSE: The present study aimed to investigate the clinical characteristics and lung function impairment in young people diagnosed with chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: We retrospectively enrolled patients with COPD who underwent symptom assessment and comprehensive pulmonary function tests at the First Affiliated Hospital of Guangzhou Medical University between August 2017 and March 2022. The patients were categorized into two groups based on age: a young COPD group (aged 20-50 years) and an old COPD group (aged > 50 years). RESULTS: A total of 1282 patients with COPD were included in the study, with 76 young COPD patients and 1206 old COPD patients. Young COPD patients exhibited a higher likelihood of being asymptomatic, lower rates of smoking, and a lower smoking index compared to old COPD patients. Although young COPD patients had higher median post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) (1.4 vs.1.2 L, P = 0.019), diffusing capacity of the lung for carbon monoxide (DLCO) (7.2 vs. 4.6, P<0.001), and a lower median residual volume to total lung capacity ratio (RV/TLC) compared to their older counterparts, there were no differences observed in severity distribution by GOLD categories or the proportion of lung hyperinflation (RV/TLC%pred > 120%) between two groups. Surprisingly, the prevalence of reduced DLCO was found to be 71.1% in young COPD, although lower than in old COPD (85.2%). CONCLUSION: Young COPD showed fewer respiratory symptoms, yet displayed a similar severity distribution by GOLD categories. Furthermore, a majority of them demonstrated lung hyperinflation and reduced DLCO. These results underscore the importance of a comprehensive assessment of lung function in young COPD patients.
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Enfermedad Pulmonar Obstructiva Crónica , Pruebas de Función Respiratoria , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Pulmón/fisiopatología , Volumen Espiratorio Forzado , Factores de Edad , China/epidemiología , Índice de Severidad de la Enfermedad , Capacidad Pulmonar Total , Fumar/epidemiología , Capacidad de Difusión PulmonarRESUMEN
To investigate the stability of a super-large section chamber group, an analysis was conducted based on the in-situ geological conditions of a super-large section chamber group utilized as a coal gangue separation system at the Longgu Coal Mine. Field measurement and numerical simulation were employed to analyze the failure area and stress state of the surrounding rock under varying chamber spacings. The results indicate that the extent of the plastic zone significantly expands when the spacing between chambers is less than 2.0 times the chamber width. When the distance between chambers is 1.5 times the chamber width, it results in the rock pillars being entirely within the plastic zone. As the chamber spacing decreases, the tangential stress within the rock pillar range increases. When the chamber spacing is 2.5, 2.0, and 1.5 times the chamber width, the maximum tangential stress is 1.19, 1.46, and 1.18 times that in the case of a single chamber, respectively. Based on the displacement analysis, it was observed that as the distance between the chambers decreases, there is a notable increase in the displacement of the pillar sides and chamber top, indicating a higher risk of collapse. Integrating the plastic area and stress analysis allows for the categorization of the rock pillar area into four sections: the broken area, loose area, stable area, and firm area. Drawing upon the theoretical solution of the plastic zone of a circular chamber and the equivalent radius method, an approximate solution for the plastic zone of a non-circular chamber has been provided. Furthermore, the minimum reasonable spacing between chambers in a super-large section chamber group is provided as a distance criterion for the failure of a double chamber.
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Objective: Triple-negative breast cancer (TNBC) poses significant diagnostic challenges due to its aggressive nature. This research develops an innovative deep learning (DL) model based on the latest multi-omics data to enhance the accuracy of TNBC subtype and prognosis prediction. The study focuses on addressing the constraints of prior studies by showcasing a model with substantial advancements in data integration, statistical performance, and algorithmic optimization. Methods: Breast cancer-related molecular characteristic data, including mRNA, miRNA, gene mutations, DNA methylation, and magnetic resonance imaging (MRI) images, were retrieved from the TCGA and TCIA databases. This study not only compared single-omics with multi-omics machine learning models but also applied Bayesian optimization to innovatively optimize the neural network structure of a DL model for multi-omics data. Results: The DL model for multi-omics data significantly outperformed single-omics models in subtype prediction, achieving a 98.0% accuracy in cross-validation, 97.0% in the validation set, and 91.0% in an external test set. Additionally, the MRI radiomics model showed promising performance, especially with the training set; however, a decrease in performance during transfer testing underscored the advantages of the DL model for multi-omics data in data consistency and digital processing. Conclusion: Our multi-omics DL model presents notable innovations in statistical performance and transfer learning capability, bearing significant clinical relevance for TNBC classification and prognosis prediction. While the MRI radiomics model proved effective, it requires further optimization for cross-dataset application to enhance accuracy and consistency. Our findings offer new insights into improving TNBC classification and prognosis through multi-omics data and DL algorithms.
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Optical detection is an indispensable part of microfluidic systems for nutrient determination in seawater. Coupling total internal reflection capillaries with microfluidic chips is a practical alternative to increase the optical path length for high-sensitivity and a low detection limit in colorimetric assays, which has not been applied in microfluidic devices for seawater nutrients. Here, we present an online microfluidic system which integrated a total internal reflection capillary made of Teflon AF 2400 for the high-sensitivity detection of nitrite and nitrate in seawater. The off-chip capillary lengthens the optical path without changing the internal flow path of the microfluidic chip, enhancing the sensitivity, reducing the detection limit and widening the dynamic range of the system, which significantly improves the performance of the microfluidic system based on wet-chemistry. The detection limit for nitrite is 0.0150 µM using an external 20 cm capillary and 0.0936 µM using an internal 5 cm absorption cell, providing an over 6-fold improvement. Laboratory analysis of surface seawater samples collected from the South China Sea with this system and a one-month online deployment of an autonomous analyzer developed based on this system at a station revealed correlations between the nitrite and nitrate with tide, salinity and chlorophyll over slight variations and narrow ranges, demonstrating the high-sensitivity of this method.
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Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.
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Tamaño del Genoma , Especificidad del Huésped , Hojas de la Planta , Simbiosis , Hojas de la Planta/microbiología , Bacterias/genética , Bacterias/clasificación , Genoma Bacteriano , Árboles/microbiologíaRESUMEN
Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.
Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called 'cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age essentially, how old their body seems based on various health factors, which can differ from their actual age.We also found that these DNA changes could indicate how aging might make the body's defense system which fights off diseases react more intensely. Understanding this could be crucial for managing health as we get older.Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.
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Envejecimiento , Ácidos Nucleicos Libres de Células , Islas de CpG , Metilación de ADN , Epigénesis Genética , Inflamación , Humanos , Envejecimiento/genética , Ácidos Nucleicos Libres de Células/sangre , Ácidos Nucleicos Libres de Células/genética , Femenino , Inflamación/genética , Masculino , Anciano , Persona de Mediana Edad , Adulto , Biomarcadores/sangre , Anciano de 80 o más AñosRESUMEN
BACKGROUND: The prevalence, Medicaid use and mortality risk associated with low forced expiratory volume in 1 s (FEV1) among young adults aged 20-35 years are not well understood, despite its potential implications for the development of chronic pulmonary disease and overall prognosis. METHODS: A retrospective cohort study was conducted among young adults aged 20-35 years old, using data from the National Health and Nutrition Examination Survey, National Death Index and Centers for Medicare & Medicaid Services. Participants were categorised into a low FEV1 group (pre-bronchodilator FEV1%pred <80%) and a normal FEV1 group (FEV1%pred ≥80%). Weighted logistic regression analysis was employed to identify the risk factors associated with low FEV1, while Cox proportional hazard models were used to calculate the hazard ratio (HR) for Medicaid use and the all-cause mortality between the two groups. RESULTS: A total of 5346 participants aged 20-35 were included in the study, with 329 in the low FEV1 group and 5017 in the normal group. The weighted prevalence of low FEV1 among young adults was 7.1% (95% CI 6.0 to 8.2). Low body mass index (OR=3.06, 95% CI 1.79 to 5.24), doctor-diagnosed asthma (OR=2.25, 1.28 to 3.93), and wheezing or whistling (OR=1.57, 1.06 to 2.33) were identified as independent risk factors for low FEV1. Over a 15-year follow-up, individuals in the low FEV1 group exhibited a higher likelihood of Medicaid use compared with those in the normal group (HR=1.73, 1.07 to 2.79). However, there was no statistically significant increase in the risk of all-cause mortality over a 30-year follow-up period (HR=1.48, 1.00 to 2.19). CONCLUSIONS: A considerable portion of young adults demonstrated low FEV1 levels, a characteristic that was associated with a higher risk of Medicaid use over a long-term follow-up, yet not linked to an augmented risk of all-cause mortality.
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Medicaid , Humanos , Adulto , Estados Unidos/epidemiología , Estudios Retrospectivos , Masculino , Adulto Joven , Femenino , Medicaid/estadística & datos numéricos , Prevalencia , Volumen Espiratorio Forzado , Factores de Riesgo , Encuestas Nutricionales , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/epidemiologíaRESUMEN
Excessive bone marrow adipocytes (BMAds) accumulation often occurs under diverse pathophysiological conditions associated with bone deterioration. Estrogen-related receptor α (ESRRA) is a key regulator responding to metabolic stress. Here, we show that adipocyte-specific ESRRA deficiency preserves osteogenesis and vascular formation in adipocyte-rich bone marrow upon estrogen deficiency or obesity. Mechanistically, adipocyte ESRRA interferes with E2/ESR1 signaling resulting in transcriptional repression of secreted phosphoprotein 1 (Spp1); yet positively modulates leptin expression by binding to its promoter. ESRRA abrogation results in enhanced SPP1 and decreased leptin secretion from both visceral adipocytes and BMAds, concertedly dictating bone marrow stromal stem cell fate commitment and restoring type H vessel formation, constituting a feed-forward loop for bone formation. Pharmacological inhibition of ESRRA protects obese mice against bone loss and high marrow adiposity. Thus, our findings highlight a therapeutic approach via targeting adipocyte ESRRA to preserve bone formation especially in detrimental adipocyte-rich bone milieu.
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Adipocitos , Médula Ósea , Leptina , Osteogénesis , Receptores de Estrógenos , Animales , Osteogénesis/genética , Adipocitos/metabolismo , Adipocitos/citología , Ratones , Leptina/metabolismo , Leptina/genética , Médula Ósea/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Células Madre Mesenquimatosas/metabolismo , Obesidad/metabolismo , Obesidad/patología , Obesidad/genética , Receptor Relacionado con Estrógeno ERRalfa , Receptor alfa de Estrógeno/metabolismo , Receptor alfa de Estrógeno/genética , Femenino , Masculino , Ratones Endogámicos C57BL , Transducción de Señal , Células de la Médula Ósea/metabolismo , Ratones NoqueadosRESUMEN
BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica
, Espirometría
, Humanos
, Masculino
, Femenino
, Enfermedad Pulmonar Obstructiva Crónica/fisiopatología
, Enfermedad Pulmonar Obstructiva Crónica/epidemiología
, Enfermedad Pulmonar Obstructiva Crónica/diagnóstico
, Persona de Mediana Edad
, China/epidemiología
, Anciano
, Volumen Espiratorio Forzado
, Capacidad Vital
, Fumar/epidemiología
, Fumar/efectos adversos
, Pulmón/fisiopatología
, Pronóstico
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OBJECTIVES: To explore the changes in gut microbiota and levels of short-chain fatty acids (SCFA) in infants with cow's milk protein allergy (CMPA), and to clarify their role in CMPA. METHODS: A total of 25 infants diagnosed with CMPA at Children's Hospital Affiliated to Zhengzhou University from August 2019 to August 2020 were enrolled as the CMPA group, and 25 healthy infants were selected as the control group. Fecal samples (200 mg) were collected from both groups and subjected to 16S rDNA high-throughput sequencing technology and liquid chromatography-mass spectrometry to analyze the changes in gut microbial composition and metabolites. Microbial diversity was analyzed in conjunction with metabolites. RESULTS: Compared to the control group, the CMPA group showed altered gut microbial structure and significantly increased α-diversity (P<0.001). The abundance of Firmicutes, Clostridiales and Bacteroidetes was significantly decreased, while the abundance of Sphingomonadaceae, Clostridiaceae_1 and Mycoplasmataceae was significantly increased in the CMPA group compared to the control group (P<0.001). Metabolomic analysis revealed reduced levels of acetic acid, butyric acid, and isovaleric acid in the CMPA group compared to the control group, and the levels of the metabolites were positively correlated with the abundance of SCFA-producing bacteria such as Faecalibacterium and Roseburia (P<0.05). CONCLUSIONS: CMPA infants have alterations in gut microbial structure, increased microbial diversity, and decreased levels of SCFA, which may contribute to increased intestinal inflammation.
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Microbioma Gastrointestinal , Hipersensibilidad a la Leche , Lactante , Niño , Femenino , Animales , Bovinos , Humanos , Hipersensibilidad a la Leche/diagnóstico , Ácidos Grasos Volátiles , Bacterias/genética , Ácido Butírico , Proteínas de la LecheRESUMEN
Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD. Methods: Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases. Results: A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1. Conclusions: Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.
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Reposicionamiento de Medicamentos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad Pulmonar Obstructiva Crónica , Sitios de Carácter Cuantitativo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humanos , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
The relationship between long-term ozone (O3) exposure and readmission for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains elusive. In this study, we collected individual-level information on AECOPD hospitalizations from a standardized electronic database in Guangzhou from January 1, 2014, to December 31, 2015. We calculated the annual mean O3 concentration prior to the dates of the index hospitalization for AECOPD using patients' residential addresses. Employing Cox proportional hazards models, we assessed the association between long-term O3 concentration and the risk of AECOPD readmission across several time frames (30 days, 90 days, 180 days, and 365 days). We estimated the disease and economic burden of AECOPD readmissions attributable to O3 using a counterfactual approach. Of the 4574 patients included in the study, 1398 (30.6%) were readmitted during the study period, with 262 (5.7%) readmitted within 30 days. The annual mean O3 concentration was 90.3 µg/m3 (standard deviation [SD] = 8.2 µg/m3). A 10-µg/m3 increase in long-term O3 concentration resulted in a hazard ratio (HR) for AECOPD readmission within 30 days of 1.28 (95% confidence interval [CI], 1.09 to 1.49), with similar results for readmission within 90, 180, and 365 days. Older patients (aged 75 years or above) and males were more susceptible (HR, 1.33; 95% CI, 1.10-1.61 and HR, 1.29; 95% CI, 1.09-1.53, respectively). The population attributable fraction for 30-day readmission due to O3 exposure was 29.0% (95% CI, 28.4%-30.0%), and the attributable mean cost per participant was 362.3 USD (354.5-370.2). Long-term exposure to elevated O3 concentrations is associated with an increased risk of AECOPD readmission, contributing to a significant disease and economic burden.
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Ozono , Enfermedad Pulmonar Obstructiva Crónica , Masculino , Humanos , Readmisión del Paciente , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Hospitalización , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Representation learning on temporal interaction graphs (TIG) aims to model complex networks with the dynamic evolution of interactions on a wide range of web and social graph applications. However, most existing works on TIG either (a) rely on discretely updated node embeddings merely when an interaction occurs that fail to capture the continuous evolution of embedding trajectories of nodes, or (b) overlook the rich temporal patterns hidden in the ever-changing graph data that presumably lead to sub-optimal models. In this paper, we propose a two-module framework named ConTIG, a novel representation learning method on TIG that captures the continuous dynamic evolution of node embedding trajectories. With two essential modules, our model exploits three-fold factors in dynamic networks including latest interaction, neighbor features, and inherent characteristics. In the first update module, we employ a continuous inference block to learn the nodes' state trajectories from time-adjacent interaction patterns using ordinary differential equations. In the second transform module, we introduce a self-attention mechanism to predict future node embeddings by aggregating historical temporal interaction information. Experiment results demonstrate the superiority of ConTIG on temporal link prediction, temporal node recommendation, and dynamic node classification tasks of four datasets compared with a range of state-of-the-art baselines, especially for long-interval interaction prediction.
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Aprendizaje AutomáticoRESUMEN
Staphylococcus aureus can form biofilms on biotic surfaces or implanted materials, leading to biofilm-associated diseases in humans and animals that are refractory to conventional antibiotic treatment. Recent studies indicate that the unique ArlRS regulatory system in S. aureus is a promising target for screening inhibitors that may eradicate formed biofilms, retard virulence and break antimicrobial resistance. In this study, by screening in the library of FDA-approved drugs, tilmicosin was found to inhibit ArlS histidine kinase activity (IC50 = 1.09 µM). By constructing a promoter-fluorescence reporter system, we found that tilmicosin at a concentration of 0.75 µM or 1.5 µM displayed strong inhibition on the expression of the ArlRS regulon genes spx and mgrA in the S. aureus USA300 strain. Microplate assay and confocal laser scanning microscopy showed that tilmicosin at a sub-minimal inhibitory concentration (MIC) had a potent inhibitory effect on biofilms formed by multiple S. aureus strains and a strong biofilm-forming strain of S. epidermidis. In addition, tilmicosin at three-fold of MIC disrupted USA300 mature biofilms and had a strong bactericidal effect on embedded bacteria. Furthermore, in a BioFlux flow biofilm assay, tilmicosin showed potent anti-biofilm activity and synergized with oxacillin against USA300.
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Background: Reference equations for forced expiratory flow at 50% and 75% of forced vital capacity (FVC) (FEF50 and FEF75) in the Chinese population are lacking. It is of great importance to establish equations covering most age groups and to study their applicability in clinical practice. Methods: Using the lambda-mu-sigma (LMS) method, reference equations for FEF50 and FEF75 were constructed based on pulmonary function data from healthy subjects collected from January 2007 to June 2010 at 24 centers throughout China. Differences between the established equations and extraneous equations were compared using standardized means (Z values) and percentage errors (PE). The proportion of small airway dysfunction (SAD) defined by the present equations was calculated. The Fisher precision probability test and the Mann-Whitney test were used to analyze the magnitude of changes in small and large airway indices after bronchodilator inhalation in patients with suspected asthma and chronic obstructive pulmonary disease (COPD). Results: Reference equations for FEF50 and FEF75 were established based on data from 7,115 healthy individuals (aged 4 to 80 years, 50.9% female, height between 95 and 190 cm). The present equations (all Z values were -0.0 and PE ranged from 2.0% to 4.2%) showed advantages over the European Community for Steel and Coal (ECSC) equations in 1993 (with Z values ranging from -0.7 to -0.2 and PE ranged from -23.4% to -4.5%). A total of 4,356 patients with suspected asthma (51.1% female; a mean age of 45.4 years) and 6,558 patients with suspected COPD (10.1% female; a mean age of 65.0 years) were included. The present equations defined 95.7% and 99.9% of SAD in these patients. After bronchodilator inhalation, greater mean improvement rates in small airway indices were observed both in patients with suspected asthma [mean ± standard deviation (SD) =48%±47%] and in patients with suspected COPD (mean ± SD =20%±30%) (P<0.05). Conclusions: The reference equations for FEF50 and FEF75 established in this study should be considered for use in China. Further studies are needed to validate their value in the diagnosis of some chronic respiratory diseases.
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BACKGROUND: Clinically important deterioration (CID) is a composite endpoint used to holistically assess the complex progression of chronic obstructive pulmonary disease (COPD). Tiotropium improves lung function and reduces the rate of COPD exacerbations in patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate). However, whether tiotropium reduces CID risk in patients with mild-to-moderate COPD remains unclear. METHODS: This was a post hoc analysis of the 24-month Tie-COPD study comparing 18 µg tiotropium with placebo in patients with mild-to-moderate COPD. CID was defined as a decrease of ≥100 mL in trough forced expiratory volume in 1 s, an increase of ≥2 unit in COPD Assessment Test (CAT) score, or moderate-to-severe exacerbation. The time to the first occurrence of one of these events was recorded as the time to the first CID. Subgroup analyses were conducted among patients stratified by CAT score, modified Medical Research Council (mMRC) dyspnea score, and GOLD stage at baseline. RESULTS: Of the 841 randomized patients, 771 were included in the full analysis set. Overall, 643 patients (83.4 %) experienced at least one CID event. Tiotropium significantly reduced the CID risk and delayed the time to first CID compared with placebo (adjusted hazard ratio = 0.58, 95 % confidence interval = 0.49-0.68, P < 0.001). Significant reductions in CID risk were also observed in various subgroups, including patients with a CAT score <10, mMRC score <2, and mild COPD. CONCLUSIONS: Tiotropium reduced CID risk in patients with mild-to-moderate COPD, even in patients with fewer respiratory symptoms or mild disease, which highlights tiotropium's effectiveness in treating COPD patients with mild disease. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (Tie-COPD, NCT01455129).