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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.

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: 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.

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.

Background Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. Methods Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram. Results Salmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface β2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased β2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation. Conclusions Fibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids.

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.

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

Background Isoniazid (INH) resistance is now the most common type of tuberculosis (TB) infection resistance worldwide. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of patients with low- and high-concentration INH-monoresistant TB. Methods One hundred and thirty-four patients with culture-confirmed INH-monoresistant TB during 2006 January to 2007 December were retrospectively enrolled. INH resistance was classified as either low-concentration or high-concentration resistance according to the critical concentrations of 0.2 µg/mL or 1 µg/mL of INH, respectively. The patients’ clinical outcomes, treatment regimens, and treatment duration were analyzed. Results The treatment success rates between low- and high-concentration INH-resistant TB were similar (81.8% vs. 86.7%). The treatment regimens and treatment duration were similar between both groups. Only a minor percentage of the patients in both groups received 6-month treatment regimens (low vs. high concentration resistance, 9.1% vs. 13.3%; respectively, p = 0.447) The most common reason for treatment duration longer than 6 months was pyrazinamide given for less than 6 months, followed by a delay in clinical response to treatment. Multivariable analysis showed that prior tuberculosis treatment (Odds ratio, 2.82, 95% C.I., 1.02–7.77, p = 0.045) was the only independent risk factor for unsuccessful treatment outcome. Conclusion Different levels of INH resistance did not affect the treatment outcomes of patients with INH-monoresistant tuberculosis. Prolonged Rifampin-containing regimens may achieve those good outcomes in patients with low- and high-concentration INH-monoresistant TB.

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.