Background: Mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) ...treatment. A recent study has suggested that 33% of NSCLC showed primary tumor/metastasis discordance of EGFR expression by immunohistochemistry analysis. We intended to find out whether the EGFR mutations of primary lung cancers are concordant to that of corresponding metastatic tumors. Materials and methods: We analyzed EGFR exons 18–21 from paired primary and metastatic tumors in 67 lung cancer patients who had not received TKI before tissues were sampled. Results: Using the direct sequencing method, 9 of 18 (50%) patients with EGFR mutation-positive primary lung tumors had lost the mutations in metastases. For 26 patients who were EGFR mutation positive in the metastatic tumors, 17 (65%) were negative in the primary tumors. We analyzed these paired tissues with discrepant EGFR mutations by the Scorpion Amplified Refractory Mutation System assay. Finally, the discordant rate reached 27% (18 of 67 cases). Conclusion: EGFR mutations in primary lung tumors do not always reflect the same situation in metastases. Analysis of EGFR mutations in the primary lung tumor would be inadequate for planning the use of TKI for advanced NSCLC.
Background and aims
Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative ...reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells.
Methods
The stability of mast cell lines, HMC1 cells, RBL‐2H3 cells, p815 cells, and mouse bone marrow‐derived mast cells (BMMC) was tested in the presence or absence of VitD3.
Results
Mast cells activated automatically in a VitD‐deficient environment. Exposure to calcitriol in the culture increased the expression of VitD receptor (VDR) in mast cells. VDR formed complexes with Lyn in mast cells to inhibit the binding of Lyn to the β chain of FcεRI and MyD88, which decreased the phosphorylation of Syk, decreased the levels of MAPK and NF‐κB. VDR bound to the promoter of TNF‐α to decrease the acetylation of histone H3/H4, RNA polymerase II and OCT1 (a transcription factor of TNF‐α) at the promoter locus and repressed the expression of TNF‐α in mast cells.
Conclusions
The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.
Summary
Background
Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified ...Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease.
Aim
To externally validate the efficacy of the CLIF‐SOFA score and evaluate other scoring systems for 6‐month mortality in critically ill cirrhotic patients.
Methods
This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10‐bed specialised hepatogastroenterology ICU in a 2000‐bed tertiary care referral hospital during the period from September 2010 to August 2013.
Results
The overall in‐hospital and 6‐month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF‐SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6‐month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF‐SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6‐month survival rates differed significantly for patients with a CLIF‐SOFA score ≤11 and those with a CLIF‐SOFA score >11 on the ICU admission day.
Conclusion
Both CLIF‐SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.
Broadband strong light absorption of unpolarized light over a wide range of angles in a large-area ultrathin film is critical for applications such as photovoltaics, photodetectors, thermal emitters ...and optical modulators. Despite long-standing efforts in design and fabrication, it has been challenging to achieve all these desired properties simultaneously. We experimentally demonstrate a 12.5 cm2, 90-nm-thick graphene metamaterial with approximately 85% absorptivity of unpolarized, visible and near-infrared light covering almost the entire solar spectrum (300–2,500 nm). The metamaterial consists of alternating graphene and dielectric layers; a grating couples the light into waveguide modes to achieve broadband absorption over incident angles up to 60°. The very broad spectral and angular responses of the absorber are ideal for solar thermal applications, as we illustrate by showing heating to 160 °C in natural sunlight. These devices open a novel approach to applications of strongly absorbing large-area photonic devices based on two-dimensional materials.Eighty-five per cent absorptivity of unpolarized light over the wavelength range 300–2,500 nm is realized in a 90-nm-thick, 12.5 cm2 metamaterial.
Repeated isolation of multidrug-resistant Acinetobacter baumannii (MDRAB) from respiratory secretions poses a great challenge for infection control. We conducted a retrospective case-control study to ...evaluate the efficacy and adverse effect of inhaled colistin methanesulfonate (CMS) in the eradication of MDRAB from the respiratory tract. Patients who were admitted to Taipei Veterans General Hospital between February 2009 and June 2010, had at least two sets of monomicrobial culture of MDRAB from respiratory secretions, and remained in hospital for at least 14 days after the first isolation of MDRAB (index day) were included. Patients who received intravenous CMS were excluded. Patients who received CMS inhalation for ≥3 days were selected as cases whereas the controls were matched for age and Acute Physiology and Chronic Health Evaluation II score. Thirty-nine cases and controls were identified. The duration of CMS inhalation was 10.9 ± 3.6 days. The use of inhaled CMS was the only independent factor associated with the eradication of MDRAB within 14 days after the index day (OR 266.33; 95% CI 11.26–6302.18, p <0.001), and shortened the duration of MDRAB recovery from the respiratory tract by 13.3 ± 1.45 days. The adverse effects were similar for both groups. The increase of colistin minimal inhibitory concentrations in the last isolate compared with the index isolate from the same patient did not differ between the two groups. In conclusion, our study demonstrated that inhaled CMS enhanced the eradication of MDRAB from the respiratory tract without significant clinical adverse effect or impact on colistin resistance.
Transition-metal dichalcogenides (TMDs) are renowned for their rich and varied bulk properties, while their single-layer variants have become one of the most prominent examples of two-dimensional ...materials beyond graphene. Their disparate ground states largely depend on transition metal d-electron-derived electronic states, on which the vast majority of attention has been concentrated to date. Here, we focus on the chalcogen-derived states. From density-functional theory calculations together with spin- and angle-resolved photoemission, we find that these generically host a co-existence of type-I and type-II three-dimensional bulk Dirac fermions as well as ladders of topological surface states and surface resonances. We demonstrate how these naturally arise within a single p-orbital manifold as a general consequence of a trigonal crystal field, and as such can be expected across a large number of compounds. Already, we demonstrate their existence in six separate TMDs, opening routes to tune, and ultimately exploit, their topological physics.
Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of ...an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.
The CrackNet, an efficient architecture based on the Convolutional Neural Network (CNN), is proposed in this article for automated pavement crack detection on 3D asphalt surfaces with explicit ...objective of pixel‐perfect accuracy. Unlike the commonly used CNN, CrackNet does not have any pooling layers which downsize the outputs of previous layers. CrackNet fundamentally ensures pixel‐perfect accuracy using the newly developed technique of invariant image width and height through all layers. CrackNet consists of five layers and includes more than one million parameters that are trained in the learning process. The input data of the CrackNet are feature maps generated by the feature extractor using the proposed line filters with various orientations, widths, and lengths. The output of CrackNet is the set of predicted class scores for all pixels. The hidden layers of CrackNet are convolutional layers and fully connected layers. CrackNet is trained with 1,800 3D pavement images and is then demonstrated to be successful in detecting cracks under various conditions using another set of 200 3D pavement images. The experiment using the 200 testing 3D images showed that CrackNet can achieve high Precision (90.13%), Recall (87.63%) and F‐measure (88.86%) simultaneously. Compared with recently developed crack detection methods based on traditional machine learning and imaging algorithms, the CrackNet significantly outperforms the traditional approaches in terms of F‐measure. Using parallel computing techniques, CrackNet is programmed to be efficiently used in conjunction with the data collection software.
Background and aims
The function of interleukin (IL)‐10‐producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease‐activated receptor (PAR)‐2 has immunoregulatory ...functions. This study aimed to elucidate the role of PAR2 in the suppression of IL‐10 expression in peripheral B cells.
Methods
Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2‐like protein 12 (Bcl2L12) and IL‐10 in the B cells was analyzed. An AR mouse model was developed.
Results
We observed that the expression of IL‐10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL‐10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS‐induced IL‐10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12‐shRNA‐carrying liposomes reversed the capability of IL‐10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA‐carrying liposomes attenuated experimental AR in mice.
Conclusions
Activation of PAR2 inhibits the expression of IL‐10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA‐carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.
MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from ...the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
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