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Since late 2019, coronavirus disease 2019 (COVID-19) has led to a significant increase in the demand for medical resources. To publish data on face mask supplies, the Taiwanese government collaborated with program developers to construct a mask-supply information transitional platform (MITP). To comprehend the adoption of MITP, the study proposes a research model that integrates the health behavior model (HBM) and IS/IT continuance model for examining the factors affecting intention to use an MITP. Survey data collected from 524 respondents indicated that (1) intention to use an MITP is directly influenced by perceived threat of COVID-19 and beliefs toward using the MITP; (2) cues to action directly influence the perceived threat of COVID-19; and (3) perceived ease of use of MITP is a significant determinant of perceived usefulness of MITP. These results provide practical guidelines for health authorities and government to develop health information systems and strategies to control pandemics.

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1.Significance:These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.

Cell tracking in time-lapse microscopy images of primary lung epithelial cells from wild-type (WT), GLK-deficient (KO), and GLK transgenic (Polâ…¡-GLK)) mice. The tracked path of the mGFP-positive cell is shown as the line.

Supplementary Methods, Figures, and Movies - Supplementary File accompanying the manuscript provides additional details regarding the methods of immunoblotting, cell migration and proliferation assays, time-lapse live cell imaging, FRET, and in vitro kinase assays. Additionally, we also provide IHC data of mouse tissues (Fig. S1), cell migration assays using primary lung cells or lung cancer cell lines (Fig. S2-S6), PLA data (Fig. S7), as well as five N-SIM movies (Movies S1-S5).

Video.avi GLK co-localizes with IQGAP1 at filopodia and lamellipodia of a cell (Cell #3).

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Cell tracking in time-lapse microscopy images from of lung epithelial cells from littermate wild-type (WT), GLK transgenic (Polâ…¡-GLK), GLK transgenic/IQGAP1-heterozygous (Polâ…¡-GLK;IQGAP1+/- ), and GLK transgenic/IQGAP1 knockout (Polâ…¡-GLK;IQGAP1-/- ) mice. The tracked path of the migration cell is shown as the line.

Video4.avi GLK co-localizes with IQGAP1 at the leading edge of a migrating cell (Cell #4)

Video 5.avi GLK co-localizes with IQGAP1 at the leading edge of a migrating cell (Cell #5).

Purpose:Fas ligand (FasL) −844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL −844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL −844T/C polymorphism on the clinical outcome of non–small cell lung cancer (NSCLC) remains to be identified.Experimental Design: A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL −844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL −844T/C polymorphism on survival and relapse was determined by Kaplan–Meier analysis and Cox proportional hazards models.Results: The FasL −844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P = 0.008). In addition, patients with the FasL −844CC genotype were more prone to tumor relapse than those with the FasL −844TT+TC genotype (62.1% vs. 37.9%, P = 0.001). Multivariate Cox regression analysis showed that patients with the FasL −844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL −844TT+TC genotype (24.1 vs. 42.8 months for OS, HR = 1.455, P = 0.004; 15.4 vs. 31.4 months for RFS, HR = 1.710, P < 0.001).Conclusions:FasL −844T/C polymorphism may predict survival and relapse in NSCLC. We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group. Clin Cancer Res; 17(18); 5991–9. ©2011 AACR.

Backgrounds: Metabolic syndrome is a subclinical status in promoting atherosclerotic cardiovascular disease and type 2 diabetes mellitus. The significance of metabolic syndrome and pathophysiology in chronic kidney disease is not investigated. Methods: We enrolled adult patients with CKD stages 3 to 5 from December 2006 to December 2007. Metabolic syndrome was defined by the US National Cholesterol Education Programme Adult Treatment Panel III guidelines. Plasma levels of angiogenic growth factors were measured. Univariate and multivariate logistic regression analyses were used. Results: Total 451 patients were analyzed with median estimated glomerular filtration rate of 27.0 ml/min per 1.73m2 (interquartile range 14.3–41.3). Patients with metabolic syndrome were older (P = 0.002), had higher percentage using diuretics (P = 0.002) but lower percentage using pentoxifylline (P = 0.017). Patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein (P < 0.0001), uric acid (P = 0.009) and angiopoietin-2 (P = 0.001). Multivariate logistic regression analyses revealed significant association between plasma levels of angiopoietin-2 and metabolic syndrome (P = 0.042). Conclusion: The prevalence of metabolic syndrome in advanced CKD was higher than general population. CKD patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein, uric acid and angiopoietin-2. Plasma levels of angiopoietin-2 were significantly associated with metabolic syndrome in patients with CKD. Metabolic syndrome in CKD may be not only a prognostic factor but also an interventional target, possibly through ameliorating inflammation. Prospective and interventional studies are necessary to establish the pathophysiology.

It is still a challenging task to make a colorimetric sensor which can respond to multiple responses at the same time. This task is even more difficult in aqueous solutions, as water molecules will significantly interfere the sensing process. Therefore, we have designed the low-cost, simple, efficient and selective dual responsive chemical sensor (DRCS) by capping the aniline trimer with benzoyl isothiocyanate. This sensor combines the advantages of naked eye detection of the CN¯ ion at different pH values. Moreover, DRCS can detect the pH of mixed solvent (DMSO/H2O) by the naked eye. The DRCS has shown high sensitivity to CN¯ ions. Meanwhile, it has no obvious response to other interfering anions, such as F¯, AcO¯, Br¯, HSO4¯, SCN¯, PO43¯, I¯, ClO4¯, Cl¯, NO3¯, PF6¯, and BF4¯. A minimum detection limit of 0.2 μM was achieved by DRCS for CN¯ ions. The feasibility of on-site detection of CN¯ was demonstrated using DRCS coated filter paper stripes. The present study reveals that the DRCS as low-cost material can be used as a potential sensor for the selective sensing of CN¯ ions and pH in the solutions.

This study describes an effective method for the removal of nickel ions (Ni2+) from the water by repetitive absorption and regeneration (desorption) cycles using immobilized adsorbents. Polyethyleneimine (PEI) based epoxy coated gauzes having the high density of active sites were prepared as immobilized adsorbents. The adsorption of Ni2+ by the PEI based epoxy coated gauze was confirmed by the analysis of the immobilized surface using X-ray photoelectron spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The effects of type of the cross-linking agents and PEI/cross-linker molar ratio on the adsorption efficiency were studied. The surface wettability of the immobilized adsorbent was evaluated using dynamic contact angle measurements. The adsorption behaviors can be fitted with the Freundlich isotherm and the pseudo-second-order kinetic model. The adsorption of the Ni2+ was studied at various treatment time and pH. Because of the porous structure and large surface area of the gauze based adsorbent, together with the large amount of oxygen atoms and amine groups on the molecular chain of adsorbent, the optimized adsorption capacity for Ni2+ can reach 650 mg/g. More importantly, the adsorbent has retained its adsorption capability even after repeated adsorption-desorption cycles.

The development of fluorescence molecules for the fast and effective detection of L-tryptophan (L-Trp) has attracted a lot of attention because it is an important amino acid for baby growth, nitrogen equilibrium in adults, improving sleep, and mood regulation. A dimedone-phenylalanine-based chiral sensor (SDPA) was synthesized and exhibited a strong fluorescence quenching by Fe

A new efficient Schiff base sensor SB3 for fluorescent and colorimetric “naked-eye” “turn-on” sensing of cyanide anion (CN–) with excellent sensitivity and selectivity was developed. The 4,4'-(perfluoropropane-2,2-diyl)bisphenol group and two phenyl groups were covalently linked by two C = N bonds to extend the conjugation length. The four hydroxyl groups can improve the water solubility of the SB3 sensor. The SB3 sensor exhibited high specificity towards CN− by interrupting its intramolecular charge transfer, resulting in a color change and remarkable “turn-on” green fluorescence emission. The sensing mechanism is caused by the nucleophilic addition of CN– toward imine groups of the SB3 sensor, leading to breaks of the conjugation, fluorescent spectral changes, and color change. It was confirmed by 1H NMR titration and Mass spectra. The detection limits for CN– and Al3+obtained by fluorescence spectrum are 0.80 µM and 0.25 µM, respectively. The SB3 sensor can act as an efficient chemical sensor for detecting the CN– and Al3+ ions under common environmental and physiological conditions (pH 5–12). Besides, the sensor can also detect CN− in food materials (such as sprouting potatoes and cassava flour) and imaging CN− in living cells with strong “turn-on” fluorescence at 490 nm. SB3 is an excellent CN– sensor that exhibits some advantages, including easy synthesis, distinct fluorescence and color change, high selectivity, low detection limit, and good anti-interference ability to analyze solution and food samples, together with fluorescence cell imaging.

The detection of metal ions and amino acids by the aniline oligomer-based receptor has not been reported yet, to the best of our knowledge. In this study, an efficient multifunctional cation-amino acid sensor (CAS) with aniline moiety and chiral thiourea binding site was synthesized by the reaction of aniline trimer and (S)-(+)-1-phenyl ethyl isothiocyanate. CAS can sense Fe

Chest X-Ray (CXR) images as part of a non-invasive diagnosis method are commonly used in today’s medical workflow. In traditional methods, physicians usually use their experience to interpret CXR images, however, there is a large interobserver variance. Computer vision may be used as a standard for assisted diagnosis. In this study, we applied an encoder-decoder neural network architecture for automatic lung region detection. We compared a three-class approach (left lung, right lung, background) and a two-class approach (lung, background). The differentiation of left and right lungs as direct result of a semantic segmentation on basis of neural nets rather than post-processing a lung-background segmentation is done here for the first time. Our evaluation was done on the NIH Chest X-ray dataset, from which 1736 images were extracted and manually annotated. We achieved 94:9% mIoU and 92% mIoU as segmentation quality measures for the two-class-model and the three-class-model, respectively. This result is very promising for the segmentation of lung regions having the simultaneous classification of left and right lung in mind.

The main objective of the present study is to understand the structure-property relationships of sensor capable of colorimetric response, upon the addition of particular anions, due to hydrogen-bonding association between sensor and anion. Further, hydrogen-bonding association between sensor and anion, and thereby colorimetric response of the receptor in various solvent media was also targeted. For this, we have synthesized chloro-substituted quinone based oligomer sensor (QO-Cl) and cyano-substituted quinone based oligomer sensor (QO-CN), which contain the thiourea as a binding site. These oligomeric sensors were exploited as colorimetric sensors for cyanide anion [CN−]. Further, the sensing abilities of these sensors for CN− recognition in various solvents were monitored to investigate the influence of solvent on the hydrogen bonding association between sensor and anion. Our colorimetric and spectrometric results unveiled that the QO-CN sensor has shown the better binding constant (KQO-CN-CN − = 39,317 M− 1) and detection of limit (DOL = 1.2 μM) for CN− than that of QO-Cl, (KQO-Cl-CN − = 1950 M− 1; DOL = 69 μM). This can be attributed to the higher electron withdrawing nature of C N than the moderately electron-withdrawing substituent Cl.

Single-phase Au nanorods were synthesized using an anodic alumina oxide (AAO) template for methyl mercaptan (CH3SH) gas detection. The Au nanorods were fabricated by pulse electrodeposition on a H2O2 modified template. A Au precursor solution was modified with dimethyl sulfoxide to improve the synthesis of Au nanorods. The deposition parameters of the duty cycle were modulated in multiple groups to produce high-quality Au nanorods. Scanning electron microscopy images illustrated the high regularity of the Au nanorods. X-ray diffraction and transmission electron microscopy images revealed the high composition of the (111) lattice interface. A Au nanorod gas sensor was fabricated after removal of the AAO template. The sensor utilized the self-assembled monolayer property between Au and CH3SH to alter the conductivity of the Au nanorod sensing layer. The sensor exhibited higher sensitivity and selectivity to CH3SH than to N2 and H2S. The sensor had a 0.88% current response under a 0.5 ppm concentration of CH3SH, which increased to 7.82% under 4 ppm CH3SH. The Au nanorods possessed a response 13 times higher than that of a Au thin-film structure.

Indeed, the relative strength of specific ion effect on macromolecule/biomacromolecules increases with increasing concentration. However, the utilization of high ion concentration may lead to aggregation or precipitation of macromolecule/biomacromolecule. Therefore, in the present study, we provided a potential alternative method to tune the strengths of “salting-in” and “salting-out” effects of Hofmeister series anions on the coil-globule transition of poly(N-isopropylacrylamide) (PNIPAM) by using a crown ether, 18-crown-6 (18-C-6) as a crowding agent. The ionic liquids (ILs) having the same cation, 1-butyl-3-methylimidazolium (Bmim+) and commonly used anions such as CH3COO−, Cl− and I− were selected to explore the strengths of “salting-in” and “salting-out” effects of Hofmeister series anions on a coil-globule transition of PNIPAM in the crowded environment of 18-C-6. Our experimental results (differential scanning calorimetry, hydrodynamic radius, fluoresce intensity, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy) demonstrated that the salting-out effect exerted by a kosmotropic anion, CH3COO−, is strengthened, while the salting-in effect exerted by a chaotropic anion, I−, is weakened in the presence of 18-C-6. The results from the present study may certainly provide an alternative method to tune the relative strength of Hofmeister effect without increasing salt concentration.

Due to the increasing awareness of environmental and social issues, sustainable coastal wetland park selection becomes an important problem. The aim of this paper is to develop a new performance evaluation method for multi-attribute decision making (MADM) problems in a group decision environment, based on combining an integrated group Techniques for Order Preferences by Similarity to Ideal Solution (IG-TOPSIS) and interval-valued fuzzy numbers. Coastal wetland park selection often involves uncertain information due to the subjective nature of human judgments. Because human beings are more suitable using linguistic terms rather than crisp values or precise numbers to express what they perceive, the rating values can be expressed in linguistic terms. These linguistic terms, however, are often imprecise or vague. The interval-valued fuzzy sets can provide more flexibility than ordinary fuzzy sets in representing vague or uncertain information. This paper presents an interval-valued fuzzy IG-TOPSIS method, which aims to solve MADM problems in which the preferences of different decision makers are considered and expressed clearly using the concepts of interval-valued fuzzy sets. A case study for evaluating the performances of several sites for coastal wetland park selection is conducted to illustrate the effectiveness of this method.

Objective Thymoma is a rare epithelial tumor arising from the thymus in the anterior mediastinum. Nearly 50% of patients with thymoma develop myasthenia gravis, which is an indication of a poor long-term prognosis. Here, we identified specific and effective molecular markers for predicting in the development of myasthenia gravis patients with thymoma. Material and methods We investigated molecular profiling based on RNA-sequencing (RNA-seq) for myasthenia gravis development in patients with thymoma. RNA was extracted from 34 patients with thymoma, 16 of whom had myasthenic and 18 of whom did not, and transcriptome profiles were analyzed through next-generation sequencing. Results We discovered 140 differential expressed genes associated with myasthenia gravis in thymoma patients. The four genes, hypoxia-inducible factor 3 alpha (HIF3A), insulin-like growth factor-binding protein 1, pyruvate dehydrogenase kinase, and Kruppel-like factor 15 were differentially expressed in patients with thymoma who has myasthenia gravis and were validated by quantitative polymerase chain reaction. HIF3A expression was significantly higher in patients with myasthenia gravis than in those without. Conclusion HIF3A is aberrantly expressed in patient with thymoma who has myasthenia gravis and may be involved in the development of myasthenia gravis in thymoma patient.

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1. Significance: These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.

Quantitative analysis of the L-tryptophan content in commercial products by chemosensor has not been reported yet. In this study, the chiral carbazole based sensor (CCS), bearing a chiral “urea-carboxylic acid” binding site was prepared. CCS was proved to be effective in the consecutive detection of Fe3+, L-tryptophan (Trp), and L-histidine (His) by naked eyes. CCS exhibits different color changes and fluorescent ‘turn-off’ response toward Fe3+ and Fe2+. The discrimination of these two oxidation states of iron by CCS is important to understand the iron-related biological reactions. The limit of detection for Fe3+ by CCS is 84 nM in a high water-content solution (99 % water). CCS sensor can act as a reversible fluorescence quenching sensor for Fe3+. The results of Job’s plot analysis and mass spectra reveal that Fe3+ binds to CCS with a 1:1 stoichiometry. The CCS-Fe3+ complex can sense tryptophan, or histidine by a dose-dependent turn-on fluorescent response in a high water-content solution (99 % water). The mass spectra suggest the sensing of L-histidine or L-tryptophan by CCS-Fe3+ was performed with a CCS-Fe3+: amino acid binding ratio of 1:1. In comparison with other chemosensors reported in the literature, CCS can detect the L-Trp and L-His with a low limit of detection (0.31 μM L-Trp, 7.64 μM L-His) in a high water content environment. Furthermore, the CCS - Fe3+ complex based chemosensor was successfully applied to quantify the L-tryptophan content in commercial sleep-improving capsules containing various ingredients. The measured L-tryptophan contents in two samples are close to the announced values.

The detection of metal ions and amino acids by the aniline oligomer-based receptor has not been reported yet, to the best of our knowledge. In this study, an efficient multifunctional cation-amino acid sensor (CAS) with aniline moiety and chiral thiourea binding site was synthesized by the reaction of aniline trimer and (S)-(+)-1-phenyl ethyl isothiocyanate. CAS can sense Fe3+, Cu2+, Ag+ ions, and L-tryptophan. These results can be recognized by the naked eye. The appropriate pH range for the quantitative analysis of Fe3+, Cu2+, and Ag+ by CAS in DMSO/water (30 vol% water) was evaluated. The interaction between CCS and metal ions was analyzed by 1H NMR titration. The detection limits of CAS for the Cu2+, Ag+, and Fe3+ were 0.214, 0.099, and 0.147 μM, respectively. Moreover, the CAS Cu2+ complex can act as a turn-on fluorescence sensor for L-tryptophan. On the contrary, there is no response upon the addition of other amino acids, such as L-histidine, L-proline, L-phenylalanine, L-threonine, L-methionine, L-tyrosine, and L-cystine to CAS Cu2+ complex.

Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of total lung cancers; 40% to 60% of NSCLC patients die of cancer recurrence after cancer resection. Since GLK (also named MAP4K3) induces activation of NF-κB, which contributes to tumor progression, we investigated the role of GLK in NSCLC. GLK protein levels of 190 samples from pulmonary tissue arrays and 58 pulmonary resection samples from stage I to stage III NSCLC patients were studied using immunohistochemistry or immunoblotting. High levels of GLK proteins were detected in pulmonary tissues from NSCLC patients. Elevated GLK protein levels were correlated with increased recurrence risks and poor recurrence-free survival rates in NSCLC patients after adjusting for pathologic stage, smoking status, alcohol status, and EGFR levels. Thus, GLK is a novel prognostic biomarker for NSCLC recurrence.

The optimal therapeutic intervention of pathologic N2 (pN2) non-small cell lung cancer (NSCLC) is still controversial. The argument and the debate about the selection of patients for multimodality therapy, the role of surgery, the choice of neoadjuvant treatment and sequential therapies have continued for years.

Purpose To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS). Patients and Methods We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated. Results Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS. Conclusion In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma.

Objective CD10 (neutral endopeptidase) is expressed in various normal and tumor cells, and its biological function can be controlled through enzymatic activity and signaling pathways. We investigated whether CD10 expression predicted disease recurrence and whether it correlated with histologic subtypes of stage I lung adenocarcinoma. Materials and methods We reviewed tumor slides of resected pathologic stage I lung adenocarcinomas (1995–2009). Tumors were classified according to the IASLC/ATS/ERS classification. CD10 immunohistochemistry was performed using tissue microarrays ( n =915). We combined the intensity (0–3) and distribution scores (0–2) for CD10 to create a total score (0–5). Risk of recurrence was estimated using competing risks methods. Results In the training cohort ( n =313), risk of recurrence of patients with high tumoral CD10 (score>1, n =57) was significantly higher (5-year cumulative incidence of recurrence [CIR], 37%) than in those with low CD10 (score≤1; n =256; 5-year CIR, 16%; P n =602, P =0.036). High tumoral CD10 was associated with higher risk of recurrence in acinar ( P =0.007) and papillary predominant tumors ( P =0.022). High tumoral CD10 was most frequently identified in micropapillary predominant (41%) and solid predominant tumors (34%). On multivariate analysis of intermediate-grade tumors, high tumoral CD10 remained a significant independent risk factor of recurrence (hazard ratio, 1.88; P =0.025). Conclusion In stage I lung adenocarcinoma, tumoral CD10 correlated with high-grade histology and was an independent predictor of recurrence in intermediate-grade tumors.

The present study explores the effect of the monomer substitution pattern of different copolymers on their volume phase transition temperature (VPTT) and surface wetting properties (SWPs) with the aid of differential scanning calorimetry (DSC), contact angle (CA), scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FT-IR) measurements. The present experimental results unveil that the VPTT and SWPs were greatly governed by the ability of the neighboring side chains to form intramolecular hydrogen bonds and the hydrophobic–hydrophilic balance of the polymer. The substitution of some of the acrylic acid (AA) monomers in the copolymer hydrogel P(NIPAM-co-AA) by the polyethyleneglycolmethacrylate (PEGMA) monomer resulted in the copolymer hydrogel, P(NIPAM-co-PEGMA-co-AA). The PEGMA in P(NIPAM-co-PEGMA-co-AA) can promote the intermolecular hydrogen bonds of the copolymer with the water molecules and thus hinders the formation of the intramolecular hydrogen bonds. Consequently, the VPTT of the P(NIPAM-co-PEGMA-co-AA) occurs at higher temperatures when compared to the P(NIPAM-co-AA) and P(NIPAM-co-PEGMA) systems. Further, in view of the potential applications of ionic liquids (IL) in polymer science, the effect of IL on the VPTT and SWP of the copolymers was investigated. The knowledge from this study can pave the way to engineer stimuli responsive polymers for a wide range of applications in the modern era.

Intrathoracic neoplasms are mainly categorized into three groups: broncho-pulmonary tumor, mediastinal tumor, and pleural tumor. Broncho-pulmonary tumors such as lung cancer are accounted for most cases. Here we present a case of an ectopic thymoma with size over 10 cm which was found in right thoracic cavity. The patient was 40-year-old female who had chronic cough for 3 months. Chest X-ray showed radiopacity in right lower lobe of lung. Chest CT demonstrated a well-defined, solid tumor measuring 11cm in right middle lobe and lower lobe of lung. Thoracotomy and tumor excision were performed. A hard tumor measuring 15 cm × 11 cm × 9 cm was found to adhere to mediastinum with external compression to right middle lobe to lower lobe of lung. The tumor was completely resected and 660 gm in weight. Pathology report diagnosed World Health Organization classification, TypeAB and Masaoka stage IIA. For huge intrathoracic neoplasms, we may consider that the tumor is originated from mediastinum.

Purpose To perform competing risks analysis and determine short- and long-term cancer- and noncancer-specific mortality and morbidity in patients who had undergone resection for stage I non–small-cell lung cancer (NSCLC). Patients and Methods Of 5,371 consecutive patients who had undergone curative-intent resection of primary lung cancer at our institution (2000 to 2011), 2,186 with pathologic stage I NSCLC were included in the analysis. All preoperative clinical variables known to affect outcomes were included in the analysis, specifically, Charlson comorbidity index, predicted postoperative (ppo) diffusing capacity of the lung for carbon monoxide, and ppo forced expiratory volume in 1 second. Cause-specific mortality analysis was performed with competing risks analysis. Results Of 2,186 patients, 1,532 (70.1%) were ≥ 65 years of age, including 638 (29.2%) ≥ 75 years of age. In patients < 65, 65 to 74, and ≥ 75 years of age, 5-year lung cancer–specific cumulative incidence of death (CID) was 7.5%, 10.7%, and 13.2%, respectively (overall, 10.4%); noncancer-specific CID was 1.8%, 4.9%, and 9.0%, respectively (overall, 5.3%). In patients ≥ 65 years of age, for up to 2.5 years after resection, noncancer-specific CID was higher than lung cancer–specific CID; the higher noncancer-specific, early-phase mortality was enhanced in patients ≥ 75 years of age than in those 65 to 74 years of age. Multivariable analysis showed that low ppo diffusing capacity of lung for carbon monoxide was an independent predictor of severe morbidity ( P < .001), 1-year mortality ( P < .001), and noncancer-specific mortality ( P < .001), whereas low ppo forced expiratory volume in 1 second was an independent predictor of lung cancer–specific mortality ( P = .002). Conclusion In patients who undergo curative-intent resection of stage I NSCLC, noncancer-specific mortality is a significant competing event, with an increasing impact as patient age increases.

Fragile histidine triad (FHIT) loss by the two-hit mechanism of loss of heterozygosity and promoter hypermethylation commonly occurrs in non-small cell lung cancer (NSCLC) and may confer cisplatin resistance in NSCLC cells. However, the underlying mechanisms of FHIT loss in cisplatin resistance and the response to cisplatin-based chemotherapy in NSCLC patients have not yet been reported. In the present study, inhibition concentration of 50% cell viability induced by cisplatin (IC50) and soft agar growth and invasion capability were increased and decreased in FHIT-knockdown and -overexpressing cells, respectively. Mechanistically, Slug transcription is upregulated by AKT/NF-κB activation due to FHIT loss and, in turn, Slug suppresses PUMA expression; this decrease of PUMA by FHIT loss is responsible for cisplatin resistance. In addition, cisplatin resistance due to FHIT loss can be conquered by AKT inhibitor-perifosine in xenograft tumors. Among NSCLC patients, low FHIT, high p-AKT, high Slug and low PUMA were correlated with shorter overall survival, relapse-free survival and poorer response to cisplatin-based chemotherapy. Therefore, the AKT inhibitor perifosine might potentially overcome the resistance to cisplatin-based chemotherapy in NSCLC patients with low-FHIT tumors, and consequently improve the outcome.

The dual role of the microRNA-29 (miR-29) family in tumor progression and metastasis in solid tumors has been reported. Evidence for the role of miR-29 in tumor malignancy and its prognostic value in overall survival (OS) and relapse-free survival (RFS) in non-small cell lung cancer (NSCLC) remains conflicting. Mechanistic studies presented herein demonstrated that c-Myc suppressed the expression of miR-29b, promoting soft agar growth and invasion capability in lung cancer cells. Interestingly, the decrease in the expression of miR-29b by c-Myc is responsible for soft agar growth and invasiveness mediated by FHIT loss due to promoter methylation. Among patients, low expression of miR-29b and FHIT was more common in tumors with high c-Myc expression than in tumors with low c-Myc expression. Kaplan-Meier and Cox regression analysis showed that tumors with high c-Myc, low miR-29b and low FHIT expression had shorter OS and RFS periods than their counterparts. In conclusion, the decrease in the expression of miR-29b by c-Myc may be responsible for FHIT loss-mediated tumor aggressiveness and for poor outcome in NSCLC. Therefore, we suggest that restoration of the miR-29b expression using the c-Myc inhibitor might be helpful in suppressing tumor aggressiveness mediated by FHIT loss and consequently improving outcomes in NSCLC patients with tumors with low expression of FHIT.

Subcellular localization of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ape1) has been demonstrated to promote lung tumor malignancy via NF-κB activation. We hypothesized that increased cytoplasmic Ape1 expression might cause NF-κB activation by p53 aberration, and result in poor outcome in non-small cell lung cancer (NSCLC). Herein, knockdown of E6 or p53 and overexpression of E6 were performed in various lung cancer cells to test whether cytoplasmic Ape1 expression could be elevated by p53 aberration. To examine whether cytoplasmic Ape1 could be associated with patients’ outcome, 125 lung tumors from patients with NSCLC were collected to determine Ape1 protein and mRNA expression by immunohistochemistry and real-time RT-PCR. Our data showed that cytoplasmic Ape1 decreased in E6-knockdown TL-1 cells and increased in E6-overexpressed TL-4 and p53-knockdown H520 cells; and cell invasion capability was dependent on the presence of cytoplasmic Ape1. Increases in cytoplasmic Ape1 by p53 aberration may be through activation of Ape1 transcription and S-nitrosation of Ape1 protein. Kaplan–Meier and Cox models showed that patients with high cytoplasmic Ape1 had shorter cancer-specific survival (CSS) and relapse-free survival (RFS) periods than did those with low cytoplasmic Ape1. We suggest that cytoplasmic Ape1 expression elevated by p53 aberration may be used to predict poor survival and relapse in patients with NSCLC.

Purpose: Fas ligand (FasL) −844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL −844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL −844T/C polymorphism on the clinical outcome of non–small cell lung cancer (NSCLC) remains to be identified. Experimental Design: A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL −844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL −844T/C polymorphism on survival and relapse was determined by Kaplan–Meier analysis and Cox proportional hazards models. Results: The FasL −844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P = 0.008). In addition, patients with the FasL −844CC genotype were more prone to tumor relapse than those with the FasL −844TT+TC genotype (62.1% vs. 37.9%, P = 0.001). Multivariate Cox regression analysis showed that patients with the FasL −844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL −844TT+TC genotype (24.1 vs. 42.8 months for OS, HR = 1.455, P = 0.004; 15.4 vs. 31.4 months for RFS, HR = 1.710, P < 0.001). Conclusions: FasL −844T/C polymorphism may predict survival and relapse in NSCLC. We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group. Clin Cancer Res; 17(18); 5991–9. ©2011 AACR.

Disease recurrence and distant metastasis are the major causes of death in resected non-small cell lung cancer (NSCLC). The prognostic marker for never-smokers with this disease remains to be identified. To improve patient outcome, establishing an adjacent molecular marker to predict relapse of NSCLC in never-smokers is needed.Three hundred two lung tumors from NSCLC patients and normal lung tissues from 68 noncancer subjects were enrolled to evaluate XPC (xeroderma pigmentosum group C) mRNA expression by quantitative real-time reverse transcriptase polymerase chain reaction. Receiver operating characteristic curve analysis was used to search for a feasible cutoff point of XPC mRNA levels for predicting recurrence-free survival. Of the 326 patients, 214 were confirmed as only receiving surgical resection. Kaplan-Meier and multivariate Cox regression analysis were used to assess the prognostic value of XPC mRNA level in lung tumors from patients who only received surgical resection.Receiver operating characteristic curve analysis indicated 30.28 as a cutoff point, and thus 150 and 64 tumors with low- and high-XPC mRNA expression were categorized in this study population. Low-XPC mRNA appeared with more frequency in never-smokers and in late-stage (stage II-III) disease than smokers and early-stage disease (stage I). Kaplan-Meier analysis indicated that patients with low-XPC mRNA had shorter recurrence-free survival than that found in never-smokers (P = 0.002), but not in smokers (P = 0.296). Cox regression analysis further revealed that low-XPC mRNA may independently predict relapse in lung cancer of never-smokers (hazard ratio 2.34, 95% confidence interval 1.21-4.51, P = 0.011).Low-XPC mRNA may predict relapse in lung cancer patients who are never-smokers.

Purpose: Inhibitors of antiapoptosis protein (IAP) have been implicated in the resistance to cisplatin. Therefore, verifying which pathway is involved in cIAP2 upregulation may be helpful in finding a feasible pathway inhibitor to increase the chemotherapeutic efficacy in human papillomavirus (HPV)–infected lung cancer. Experimental Design: Specific inhibitors of different pathways were used to verify which pathway is involved in cIAP2 transcription. cIAP2 promoter fragments with various deletions and/or mutations were constructed by site-directed mutagenesis. cIAP2, epidermal growth factor receptor (EGFR), and phospho-AKT (p-AKT) expressions in 136 lung tumors were evaluated by immunohistochemistry. Results: Our data show that two NF-κB (−209 to −200 and −146 to −137) and one CREB (cyclic AMP–responsive element binding protein; −52 to −42) binding sites in cIAP2 promoter region were responsible for cIAP2 upregulated by E6 in TL-1 cells. Moreover, CREB was phosphorylated by EGFR/phosphatidylinositol 3-kinase (PI3K) pathway. To test the involvement of cIAP2 on cisplatin resistance, IC50 was lowered to 8.6 μmol/L in TL-1 cells with cIAP2 short hairpin RNA (shRNA) transfection and compared with 39.7 μmol/L in TL-1 cells with nonspecific shRNA. Pretreatment with EGFR or PI3K inhibitor in TL-1 cells diminished the resistance to cisplatin. Among the tumor groups, cIAP2 expression correlated significantly with HPV16/18 E6, EGFR, and p-AKT. We followed up 46 of 136 patients who had tumor recurrence and/or metastasis and underwent chemotherapy. Tumors with cIAP2-positive immunostaining were associated with a poorer tumor response to chemotherapy compared with those with negative immunostaining. Conclusions: cIAP2 upregulated by E6 via EGFR/PI3K/AKT cascades may contribute to cisplatin resistance, revealing that the EGFR or PI3K inhibitor combined with cisplatin may improve the chemotherapeutic efficacy in HPV-infected lung cancer. Clin Cancer Res; 16(21); 5200–10. ©2010 AACR.

This paper presents measurements of the discharge by image techniques on the surface velocity field and water stage in irrigation canals. The velocity and stage gauge are obtained from a commercial digital video camera. The time series of the surface velocity and stage were collected simultaneously. Particle image velocimetry (PIV) was used to determine the surface velocities in the irrigation canal. PIV proceeds by using bubbles floating on the water surface as tracer particles, and making a cross-correlation analysis between two continuous images. The whole surface velocity distribution in the irrigation canals can be obtained. The water stage of the canal is obtained from the digital video camera images by making use of image segments to separate the stage gauge and the background. The discharge is computed by using the surface velocities and water stage via open channel velocity distribution theory. Comparing the discharge measured using image techniques with Parshall flume data shows that the differences are less then 5%. The results suggest that the image measurement techniques developed can be used in applications to estimate the discharge in irrigation canals effectively.

ObjectivesOur objective was to identify surgical–pathologic factors affecting prognosis in stage IB non–small cell lung cancers.MethodsBetween 1997 and 2006, a cohort of 272 cases of pT2 N0 M0 stage lung cancer were retrospectively analyzed. The patients included 70 women and 202 men with a mean age of 67.0 years. The surgical resections included pneumonectomy in 4, bilobectomy or lobectomy in 217, and limited resections in another 51. The impact of surgical–pathologic characteristics on survival, including cell type, tumor differentiation, tumor size, depth of visceral pleural invasion, type of surgical resection, and extent of lymphadenectomy on patient survival, was compared accordingly.ResultsTumor types included adenocarcinoma/bronchioloalveolar carcinoma in 142, squamous cell carcinoma in 100, and others in 30. Cell differentiations were classified as well, moderately, and poorly differentiated in 23, 151, and 92 cases, respectively. The mean tumor size was 3.9 cm in diameter, and the average resected lymph node number was 14.3. Direct visceral pleural or subpleural invasions (14 nodes). However, the Cox proportional hazard model revealed female gender, well-differentiated tumor, no pleural involvement, no angiolymphatic invasion, and more than 14 nodes retrieved as independent good prognostic factors.ConclusionsStage IB lung cancer can be treated by standard pulmonary resection accompanied by adequate mediastinal lymphadenectomy. Owing to the heterogeneity of stage IB lung cancer and the fact that prognosis can be affected by many surgical–pathologic factors, refinement of the current TNM staging criteria may be needed.

Nrf2 is a key transcription factor for genes coding for antioxidants, detoxification enzymes, and multiple drug resistance and it also confers resistance to anticancer drugs. Here, we hypothesized that mutant p53 could upregulate Nrf2 expression at the transcriptional level, thereby conferring cisplatin resistance in non-small cell lung cancer (NSCLC). Luciferase reporter assays and real-time PCR analysis indicated that the Nrf2 promoter activity and its mRNA levels were markedly suppressed by wild-type p53, but not by mutant p53. Chromatin immunoprecipitation (ChIP) further confirmed that wild-type p53 binds at the p53 putative binding site to block Sp1 binding to the Nrf2 promoter and consequently to suppress the Nrf2 promoter activity. The MTT assay indicated that an increase in Nrf2 expression by mutant p53 is responsible for cisplatin resistance. Among the Nrf2 downstream genes, Bcl-2 and Bcl-xL contribute more strongly to Nrf2-mediated cisplatin resistance when compared with heme oxygenase 1 (HO-1). Cox regression analysis showed that patients with high-Nrf2, high-Bcl-2, high-Bcl-xL mRNA tumors were more commonly occurred unfavorable response to cisplatin-based chemotherapy than their counterparts. The prognostic significance of Nrf2 mRNA levels on OS and RFS was also observed in patients who have received cisplatin-based chemotherapy, particularly in p53-mutant patients. Collectively, mutant p53 may confer cisplatin resistance via upregulation of Nrf2 expression, and Nrf2 mRNA level may predict chemotherapeutic response and outcomes in NSCLC.

This paper presents and applies an improved method of determining cross-sectional depth and discharge of a river. The method used with the universal law and Darcy-Weisbach friction factors to obtain the lateral variation of the roughness height. This method of measurement was successfully used at the Kaoping River during the Xangsane typhoon in Taiwan, and the results show that the surface velocity obtained using an X-band pulse radar system were close to that obtained by the float method. The estimated discharges at four stages were within 3% of the recorded values of the stage-discharge rating curve in the gauging station.

This article describes a non-contact method for measuring surface velocity and discharge in a natural channel. The X-band pulse (9.36 GHz) radar, developed by the Applied Physics Laboratory of the University of Washington, was used to scan instantaneously the lateral distribution of surface velocity across a river section, according to Bragg scattering from short waves produced by turbulent boils on the surface of the river. Based on the assumption that the vertical velocity distribution follows a universal power or logarithmic law, the discharges were estimated.