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Late-onset asthma (LOA) differs from early-onset asthma (EOA) in terms of prognosis and the treatment response because it has a much worse prognosis and a poorer response to standard asthma treatment. This study sought to investigate the characteristics and clinical outcomes of asthma patients with phenotypes distinguished by age at onset and atopy status. We prospectively recruited patients with asthma who were registered in a pay-for-performance program operated by Taiwan’s National Health Insurance Administration (NHIA). These patients received regular outpatient treatment for at least 1 year at every outpatient clinic visit since 2019. Baseline characteristics and clinical outcomes were compared between patients with LOA (≥40 years) and those with EOA (

Background: The immunological features of eosinophils in early-onset asthma (EOA) differs from that in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA. Methods: Eosinophils obtained from well controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes (integrins α4 and β2, CCR3, CCR5, and IL-5Rα, and IL-17RA) and specific markers (IL-4Rα, prostaglandin D2 receptor 2, high-affinity IgE receptor, TGF-β1, aryl hydrocarbon receptor, and endosomal TLR-3, 7, and 9) in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function were further analyzed. Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function. There was no significant correlation between mRNA expression and treatment control levels among LOA or EOA patients Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obese by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.

Background Toll‐like receptor (TLR)‐7‐associated rhinovirus (RV) activation is involved in the pathogenesis of asthma. Plasmacytoid dendritic cells (pDCs) are the main interferon‐α‐producing cells against viruses. Objective To determine whether asthmatic patients and control subjects differ in terms of interferon‐α expression in pDCs under TLR‐7 or RV stimulation. Methods pDCs were identified in BDCA‐2+ and HLA‐DR+ peripheral blood mononuclear cells. Interferon‐α expression of pDCs was analyzed after TLR‐7 stimulation with or without interleukin 4 (IL‐4)/IL‐13 pretreatment. Interferon‐α expression was also analyzed after RV stimulation over periods of 24, 48, or 96 h with or without IL‐4 pretreatment. RV detection and molecular typing were assayed from throat swabs. Results Following TLR‐7 stimulation, the expression of intracellular interferon‐α was higher in the pDCs of normal subjects than those of asthmatic patients; however, pretreatment with IL‐4 was shown to reduce this effect. After 48‐ and 96‐h RV stimulation, we observed a notable increase in the production of interferon‐α of pDCs in normal subjects but not in asthmatic patients. Baseline interferon‐α expression in pDCs and the incidence of asthma exacerbation to emergency was higher among the 13% of patients identified as rhinovirus+ than among their RV counterparts. Conclusion Our study discovered the response to TLR‐7 stimulation in pDCs was compromised and the sustainability of interferon‐α expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings. Further research is required for the modulatory effect of IL‐4 on TLR‐7 stimulated pDCs., Our study discovered the response to TLR‐7 stimulation in pDCs was compromised and the sustainability of interferon‐a expression to RV stimulation was reduced in pDCs of asthmatic patients, which provide further evidence of defective innate response and subspeciality to RV infection in asthma. The high exacerbation history founded in RV+ patients agrees with these findings.

An effective antiseptic agent is an essential component of a central venous catheter (CVC) care bundle, to protect against catheter-related bloodstream infections (CRBSIs). We conducted a trial to compare the incidences of CRBSI and the growth of insertion site flora in patients with CVC using 2% chlorhexidine gluconate–alcohol (CHG) or 10% povidone-iodine–alcohol (PVI) in the CVC care bundle. Patients who were admitted to two medical intensive care units (ICUs) and had CVC placement for >48 h were enrolled. Using a two-way crossover design with two six-month interventions, the ICUs were assigned to use either CHG or PVI in their care bundles. A total of 446 catheters in 390 subjects were enrolled in the study. The detection rate of flora was greater in the PVI group on both day 7 (26.6% versus 6.3%, p < 0.001) and day 14 (43.2% versus 15.8%, p < 0.001). The incidence rate of CRBSI was higher in the PVI group compared to the CHG group (2.15 vs. 0 events per 1000-catheter-days, p = 0.001), although the significance was lost in the multivariate analysis. In conclusion, 2% CHG was superior to 10% PVI in the CVC care bundle in terms of the inhibition of skin flora growth at CVC insertion sites and was potentially associated with lower incidence rates of CRBSI.

When Nd doping in BiNdFeO (BNFO) film exceeds 10%, the two diffraction peaks (104)/(110) merge into one sharp single peak with increasing addition of Nd. It seems that a phase structural distortion can be obtained due to the substitution of Nd3+ ion for Bi3+ ion. For ferroelectric properties, among all Nd-doped (0%–20%) BiFeO3 capacitors, the BNFO capacitor with 10% Nd doping shows a higher Pr value due to a phase structural distortion and a lower leakage current. In a resistive-capacitive circuit diagram, the transient response of the voltage (V FE) across the BNFO capacitor can be measured. We demonstrate that the capacitance value d Q t d V FE t is negative in the spike interval of V FE(t), with the result that the negative capacitance of BNFO with a 10% Nd doping capacitor can obviously improve the I DS–V GS characteristics of a control thin-film transistor.

The circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs.CD34Compared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs.The interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma.

Autonomous vehicle-following systems, including Adaptive Cruise Control (ACC) and Cooperative Adaptive Cruise Control (CACC), improve safety, efficiency, and string stability for a vehicle (the ego vehicle) following its leading vehicle. The ego vehicle senses or receives information, such as the position, velocity, acceleration, or even intention, of the leading vehicle and controls its own behavior. However, it has been shown that sensors and wireless channels are vulnerable to security attacks, and attackers can modify data sensed from sensors or received from other vehicles. To address this problem, in this paper, we design three types of stealthy attacks on ACC or CACC inputs, where the stealthy attacks can deceive a rule-based detection approach and impede system properties (collision-freeness and vehicle-following distance). We then develop two deep-learning models, a predictor-based model and an encoder-decoder- based model to detect the attacks, where the two models do not need attacker models for training. The experimental results demonstrate the respective strengths of different models and lead to a methodology for the design of learning-based intrusion detection approaches.

Background The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. Methods This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). Results The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64–0.97), n = 43) and a desynchronized group (median 0.23 (0.02–0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. Conclusion This is the first result studying the heart–lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Background: Although comorbidites of cardiovascular disease is common in patients with chronic obstructive pulmonary disease (COPD), the interaction between the heart and lungs in COPD patients has yet to be further elucidated. Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Aim: Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. Methods: This is a cross-sectional and a preliminary data from a prospective study, examining 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by six-minute walking test (6MWT).Results: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n=43) and a desynchronized group (median 0.23 (0.02-0.51), n=12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r=0.42, p=0.001) and distance saturation product (r= 0.41, p=0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis.Conclusion: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Background: Cardiovascular disease is a common comorbidity and cause of mortality among patients with chronic obstructive pulmonary disease (COPD). However, the interaction between the heart and lungs in COPD patients has yet to be fully elucidated. Aim: Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiration flow signals. Methods: This prospective study examined 10 normal subjects and 55 COPD patients. Linear regression and forward stepwise regression were used to determine the correlation between the synchrogram index and the six-minute walking test. Results: K-means clustering analysis was used to separate the 55 COPD patients into a synchronized group (median 0.89 (0.64-0.97), n=43) and a desynchronized group (median 0.23 (0.02-0.51), n=12) based on the synchrogram index. In this study, the synchrogram index was significantly correlated with the six-minute walking distance (r2=0.3, sigma T=0.02) and the distance saturation product (r2=0.3, sigma T =0.03). Note that age was a significant confounding factor. Conclusion: The synchrogram index shows clinical potential for the stratification of COPD patients for treatment.

Background : Cardiovascular disease is a common comorbidity and cause of mortality among patients with chronic obstructive pulmonary disease (COPD). However, the interaction between the heart and lungs in COPD patients has yet to be fully elucidated.Aim : Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiration flow signals.Methods : This prospective study examined 10 normal subjects and 55 COPD patients. Linear regression and forward stepwise regression were used to determine the correlation between the synchrogram index and the six-minute walking test.Results : K-means clustering analysis was used to separate the 55 COPD patients into a synchronized group (median 0.89 (0.64-0.97), n=43) and a desynchronized group (median 0.23 (0.02-0.51), n=12) based on the synchrogram index. In this study, the synchrogram index was significantly correlated with the six-minute walking distance (r 2 =0.3, sigma T=0.02) and the distance saturation product (r 2 =0.3, sigma T =0.03). Note that age was a significant confounding factor.Conclusion : The synchrogram index shows clinical potential for the stratification of COPD patients for treatment.

By a sol–gel method, a BiFeO3 (BFO) capacitor is fabricated and connected with the control thin film transistor (TFT). Compared with a control thin-film transistor, the proposed BFO TFT achieves 56% drive current enhancement and 7–28% subthreshold swing (SS) reduction. Moreover, the effect of the proposed BiFeO3 capacitor on IDS-VGS hysteresis in the BFO TFT is 0.1–0.2 V. Because dVint/dVGS > 1 is obtained at a wide range of VGS, it reveals that the incomplete dipole flipping is a major mechanism to obtain improved SS and a small hysteresis effect in the BFO TFT. Experimental results indicate that sol-gel BFO TFT is a potential candidate for digital application.

Effect of ICI-118,551 on salmeterol-mediated reduction in fibrocyte number and differentiation. NANT cells from healthy subjects (n = 6) were treated with salmeterol (10−8 M) in the presence or absence of ICI-118,551 (10−5 M) for 3 days. The number of fibrocytes (Col I+/CD45+ cells; A) and differentiating fibrocytes (α-SMA+ cells; B) was determined. Bars represent mean ± SEM.* p

α–smooth muscle actin-positive cells also express both collagen I and CD45. NANT cells from one healthy subject were harvested after 3 days in culture and stained with antibodies for collagen I (Col I), α- smooth muscle actin (SMA) and CD45 or their respective IgG isotype controls. (A and C). The percentage of Col I+/α-SMA+ (B) and CD45+/ α-SMA+ cells (D) was determined by flow cytometry. (PDF 112 kb)

Number of fibrocytes and differentiating fibrocytes in NANT cells after culture in the absence or presence of salmeterol. The number of fibrocytes (% Col I+/CD45+; A) and differentiating fibrocytes (% α-SMA+; B) within the NANT cell population, were determined in the NANT cells from healthy subjects (n = 8–9) and patients with non-severe (n = 7) or severe asthma (n = 7–9) at day 0 (0 d) or after 3 days (3 d) in the absence or presence of salmeterol (10−9- 10−7 M). Data points represent mean ± SEM. * p

Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare mesenchymal neoplasma. It is a pathological term describing a heterogeneous group of neoplasms of undetermined tumorigenesis and undefined malignancy. Based only on the morphological findings of histopathology, the biological potential of the tumor is indeterminate. Determination of glucose metabolism using FDG-PET revealed mildly increased FDG uptake in the tumor. We propose that FDG accumulation in the ectatic vessel, increased uptake of the pleomorphic cells and/or associated inflammatory cells, and increased permeability of the stroma lead to the imaging feature.

Rationale: Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA. Objectives: We investigated whether there was a defect in the actions of the glucocorticoid receptor (GR) underlying the ability of CS to suppress the inflammatory response in ASMC of patients with SA. ASMC from healthy subjects (n = 10) and subjects with severe (n = 8) and nonsevere asthma (N-SA; n = 8) were cultured from endobronchial biopsies. Measurements and Main Results: GR expression in ASMC from SA and N-SA was reduced compared with that from healthy subjects by 49% (P < 0.01). Although baseline levels of nuclear GR were similar, GR nuclear translocation induced by dexamethasone (10−7 M) in SA was 60% of that measured in either healthy subjects or subjects with N-SA. Tumor necrosis factor (TNF)-α induced greater nuclear factor (NF)-κB (p65) mRNA expression in ASMC from subjects with SA (5.6- vs. 2.0-fold; P < 0.01), whereas baseline and TNF-α–induced nuclear translocation and dexamethasone-mediated suppression of p65 expression were similar between groups. Dexamethasone, although not modulating TNF-α–induced p65 nuclear translocation, attenuated p65 recruitment to the CCL11 promoter in the healthy and N-SA groups, but this suppressive effect was impaired in subjects with SA. Conclusions: Decreased GR expression with impaired nuclear translocation in ASMC, associated with reduced dexamethasone-mediated attenuation of p65 recruitment to NF-κB–dependent gene promoters, may underlie CS insensitivity of severe asthma.

Background Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough. Methods Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed. Results A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010). Conclusion The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.

Background Patients with severe asthma are less responsive to the beneficial effects of corticosteroid therapy. Objective We investigated whether corticosteroid insensitivity was present in airway smooth muscle cells (ASMCs) of patients with severe asthma. Methods ASMCs cultured from bronchial biopsy specimens of nonasthmatic control subjects (n = 12) and patients with nonsevere (n = 10) or severe (n = 10) asthma were compared for the effect of dexamethasone on suppression of TNF-α– and IFN-γ–induced CCL11 (eotaxin), CXCL8 (IL-8), and CX3CL1 (fractalkine) expression. The mechanisms of corticosteroid insensitivity are also determined. Results CCL11 release was higher in ASMCs of patients with nonsevere but not severe asthma and nonasthmatic control subjects; CXCL8 and CX3CL1 release were similar in all groups. In patients with severe asthma, dexamethasone caused less suppression of CCL11 and CXCL8 release induced by TNF-α. Dexamethasone potentiated TNF-α– and IFN-γ–induced CX3CL1 release equally in all 3 groups. TNF-α–induced phosphorylated p38 mitogen-activated protein kinase levels were increased in ASMCs from patients with severe asthma compared with those from patients with nonsevere asthma and nonasthmatic subjects, whereas TNF-α–induced phosphorylated c-Jun N-terminal kinase and phosphorylated extracellular signal-related kinase levels were increased in all asthmatic groups. A p38 inhibitor increased the inhibitory effect of dexamethasone. Conclusions ASMCs of patients with severe asthma are corticosteroid insensitive; this might be secondary to heightened p38 mitogen-activated protein kinase levels.

Rationale: Aberrant airway smooth muscle cell (ASMC) function and overexpression of transforming growth factor (TGF)-β, which modulates ASMC proliferative and inflammatory function and induces oxidant release, are features of asthma. Nuclear factor E2-related factor 2 (Nrf2) activates antioxidant genes conferring protection against oxidative stress. Objectives: To determine the role of Nrf2 in ASMCs and its modulation by TGF-β, and compare Nrf2 activity in ASMCs from subjects with severe and nonsevere asthma and healthy subjects. Methods: ASMCs were cultured from airways of subjects without asthma, and from airway biopsies from patients with severe and nonsevere asthma. We studied Nrf2 activation on antioxidant gene expression and proliferation, the effect of TGF-β on Nrf2 transcriptional activity, and the impact of Nrf2 activation on TGF-β–mediated proliferation and IL-6 release. Nrf2–antioxidant response elements binding and Nrf2-dependent antioxidant gene expression was determined in asthmatic ASMCs. Measurements and Main Results: Activation of Nrf2 led to up-regulation of the antioxidant genes heme oxygenase (HO)-1, NAD(P)H:quinone oxidoreductase, and manganese superoxide dismutase, and a reduction in proliferation. TGF-β reduced Nrf2-mediated antioxidant gene transcription through induction of activating transcription factor-3 expression. Nrf2 activation attenuated TGF-β–mediated reduction in HO-1, ASMC proliferation, and IL-6 release. Nrf2–antioxidant response elements binding was reduced in ASMCs from patients with severe asthma compared with ASMCs from patients with nonsevere asthma and normal subjects. HO-1 expression was reduced in ASMCs from patients with both nonsevere and severe asthma compared with healthy subjects. Conclusions: Nrf2 regulates antioxidant responses and proliferation in ASMCs and is inactivated by TGF-β. Nrf2 reduction may underlie compromised antioxidant protection and aberrant ASM function in asthma.

To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality. The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model. Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 ± 0.5 vs 8.0 ± 0.5 ng/mL, P

Objectives Bronchiectasis is characterized by an irreversible dilatation of bronchi and is associated with lung fibrosis. MMP-1 polymorphism may alter its transcriptional activity, and differentially modulate bronchial destruction and lung fibrosis. Design To investigate the association of MMP-1 polymorphisms with disease severity in non-cystic fibrosis (CF) bronchiectasis patients, 51 normal subjects and 113 patients with bronchiectasis were studied. The associations between MMP-1 polymorphisms, lung function, and disease severity evaluated by high resolution computed tomography (HRCT) were analyzed. Results The frequency of MMP-1(-1607G) allele was significantly higher in patients with bronchiectasis than normal subjects (70.8% vs 45.1%, p

Methods ASMC of the healthy (12), non-severe (NSA; 10) and severe asthma (SA; 10) obtained from endobronchial biopsies were pretreated with dexamethasone (Dex) at 10-10 M followed by stimulation with TNF-a and IFN-g (10 ng/ml each), alone or in combination (T+I). CXCL8 and CCL11 release was determined by ELISA, GR and p65 protein was assessed by Western Blot, mRNA by RT-qPCR and p65 recruitment to the CCL11 promoter by ChIP assay.