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This study was conducted to explore whether polymorphisms of glucose transporter 3 (GLUT3) gene affect the prognosis of patients with non-small cell lung cancer (NSCLC) after surgical resection. Four single nucleotide polymorphisms (SNPs) in GLUT3 were investigated in a total of 782 patients with NSCLC who underwent curative surgery. The association of the SNPs with overall survival (OS) and disease free survival (DFS) was analyzed. Among the four SNPs investigated, GLUT3 rs7309332C>T was significantly associated with OS and DFS in multivariate analyses. The SNP was associated with significantly worse OS (adjusted hazard ratio [aHR] = 1.62, 95% confidence interval [CI] = 1.04–2.53, P = 0.03, under recessive model), and worse DFS (aHR = 1.64, 95% CI = 1.18–2.29, P = 0.003, under recessive model). When stratified by tumor histology, the association between the GLUT3 rs7309332C>T and OS/DFS was not limited to either squamous cell carcinoma (SCC) or adenocarcinoma (AC), although the significant association remained only in AC for OS (P = 0.40 for SCC and P = 0.04 for OS) and only in SCC for DFS (P = 0.03 for SCC and P = 0.08 for OS). When AC patients were stratified according to EGFR mutation status, the SNP was significantly associated with DFS in patients with EGFR mutant tumors (aHR = 2.47, 95% CI = 1.15–5.30, P = 0.02, under recessive model), but not in those with EGFR wild-type tumors. This study suggests that genetic variation in GLUT3 may be useful in predicting survival of patients with early stage NSCLC.

Background: Data regarding community-acquired pneumonia (CAP) identified on chest computed tomography (CT) but not on chest radiography (CR) are limited. Objectives: The present study aimed to investigate the clinical and radiological features of these patients. Methods: We retrospectively compared the clinical characteristics, etiological agents, treatment outcomes, and CT findings between CAP patients with negative CR and positive CT findings (negative CR group) and those with positive CR as well as CT findings (control group). Results: Of 1,925 patients, 94 patients (4.9%) were included in the negative CR group. Negative CR findings could be attributed to the location of the lesions (e.g., those located in the dependent lung) and CT pattern with a low attenuation, such as ground-glass opacity (GGO). The negative CR group was characterized by a higher frequency of aspiration pneumonia, lower incidences of complicated parapneumonic effusion or empyema and pleural drainage, and lower blood levels of inflammatory markers than the control group. On CT, the negative CR group exhibited higher rates of GGO- and bronchiolitis-predominant patterns and a lower rate of consolidation pattern. Despite shorter length of hospital stay in the negative CR group, 30-day and in-hospital mortalities were similar between the two groups. Conclusions: CAP patients with negative CR findings are characterized by lower blood levels of inflammatory markers, a higher incidence of aspiration pneumonia, and a lower incidence of complicated para­pneumonic effusion or empyema than those with positive CR findings. Chest CT scan should be considered in suspected CAP patients with a negative CR, especially in bedridden patients.

International audience; Learning based methods have proved effective at high-quality image synthesis tasks, such as content-preserving image rendering with different style, and the generation of new images depicting learned objects. Some of the properties that make neural networks suitable for such tasks, for example robustness to the input's low-level feature, and the ability to retrieve contextual information, are also desirable in 3D shape domain. During last decades, data-driven methods have shown successful results in 3D shape modeling tasks, such as human face and body shape synthesis. Subtle, abstract properties on the geometry that are instantly detected by our eyes but are nontrivial to synthesize, have successfully been achieved by tuning a shape model built from example shapes. Recent successful learning techniques, e.g. deep neural networks, also exploit this shape model, since the regular grid assumption with 2D images does not have a straightforward equivalent in the common shape representation in 3D, thus do not easily generalize to 3D shapes. Here, we concentrate on the 3D facial expression generation task, an important problem in computer graphics and other application domains, where existing data-driven approaches mostly rely on direct shape capture or shape transfer. At the core of our approach is a recurrent neural network with a landmark-based shape representation. The network is trained to estimate a sequence of pose change, thus generate a specific facial expression, by using a set of motion-captured facial expression sequences. Our technique promises to significantly improve the quality of generated expressions while extending the potential applicability of neural networks to sequence of 3D shapes.

Pleurotus eryngii produces various functional molecules that mediate physiological functions in humans. Recently, we observed that P. eryngii produces molecules that have antidepressant functions. An ethanol extract of the fruiting body of P. eryngii was obtained, and the extract was purified by XAD-16 resin using an open column system. The ethanol eluate was separated by HPLC, and the fraction with an antidepressant function was identified. Using LC-MS, the molecular structure of the HPLC fraction with antidepressant function was identified as that of tryptamine, a functional molecule that is a tryptophan derivative. The antidepressant effect was identified from the ethanol extract, XAD-16 column eluate, and HPLC fraction by a serotonin receptor binding assay and a cell-based binding assay. Furthermore, a forced swimming test (FST) showed that the mice treated with purified fractions of P. eryngii exhibited decreased immobility time compared with nontreated mice. From these results, we suggest that the extract of P. eryngii has an antidepressant function and that it may be employed as an antidepressant health supplement.

Extracellular pH is important in clinical measurements due to its correlation to cell metabolism and disease progression. In MRI, T(1)/T(2) ratiometric analysis and other methods have been previously applied to quantify pH using conventional pulse sequences. However, for nanoparticle-based approaches, heterogeneity in size and surface functionalization tends toward qualitative rather than quantitative results. To address this limitation, we developed a novel DNA-based MRI contrast agent, pH-DMRCA, which utilizes a highly programmable and reproducible nanostructure. The pH-DMRCA is a dendritic DNA scaffold that is functionalized with a pH-responsive MRI-sensitive construct, Gd(NP-DO3A), at the end of each DNA arm. We first evaluated the r(1) and r(2) response of our pH-DMRCA over a range of pH values (pH = 5–9) to establish a relaxometric model of pH. These MRI-based assessments of pH were validated in a separate set of samples using a pH electrode (n = 18) and resulted in a good linear correlation (R(2) = 0.99, slope = 0.98, intercept = 0). A Bland–Altman analysis of the results also showed reasonable agreement between the calculated pH and measured pH. Moreover, these pH comparisons were consistent across three different pH-DMRCA concentrations, demonstrating concentration-independence of the method. This MRI-based pH quantification methodology was further verified in human blood plasma. Given the versatility of the DNA-based nanostructures, the contrast agent has a potential to be applied to a wide variety of imaging applications where extracellular pH is important including cancer, stroke, cardiovascular disease, and other important diseases.

Background To assess pulmonary arteriovenous malformation (PAVM) recanalization after embolization based on PAVM diameter changes on computed tomography (CT), with pulmonary angiography used as a gold standard. Methods A retrospective review was done of patients from 2008 to 2019 with a PAVM treated with endovascular embolization. The treatment outcome was determined by conventional angiography. Follow-up pulmonary angiography was performed when recanalization was suspected on CT, or embolization of all lesions in multiple PAVM patients could not be completed in a single session. Patients who had no preprocedural or follow-up CT were excluded. Draining vein, feeding artery, and venous sac diameter were measured on CT, and diameter reduction rates were compared with the widely-used, binary 70 % criteria. Results Forty-one patients with 114 PAVMs were treated during the study period. Eight patients with 50 PAVMs met the inclusion criteria. Mean vein, artery, and venous sac diameter reduction rates were as follows: 59.2 ± 9.3 %, 47.5 ± 10.6 %, and 62.6 ± 13.2 %, respectively, in the occluded group and 5.4 ± 19.5 %, 11.3 ± 17.7 %, and 26.8 ± 14.2 %, respectively, in the recanalized group. The area under the receiver operating characteristic curves for PAVM recanalization for the draining vein was 1.00, showing a better result than the artery (0.97) and sac (0.99). Patients showed > 42 % draining vein diameter reduction in the occluded group and Conclusions The widely-used 70 % binary criteria showed limited performance in predicting outcomes in this angiographically-confirmed case series. Further investigations are warranted to establish a strategy for detecting recanalization after PAVM embolization.

The cause of epithelioid granulomatous inflammation varies widely depending on the affected organ, geographic region, and whether the granulomas morphologically contain necrosis. Compared with other organs, the etiological distribution and morphological patterns of pleural epithelioid granulomas have rarely been investigated. We evaluated the final etiologies and morphological patterns of pleural epithelioid granulomatous inflammation in a tuberculosis (TB)-prevalent country. Of 83 patients with pleural granulomas, 50 (60.2%) had confirmed TB pleurisy (TB-P) and 29 (34.9%) had probable TB-P. Four patients (4.8%) with non-TB-P were diagnosed. With the exception of microbiological results, there was no significant difference in clinical characteristics and granuloma patterns between the confirmed TB-P and non-TB-P groups, or between patients with confirmed and probable TB-Ps. These findings suggest that most pleural granulomatous inflammation (95.2%) was attributable to TB-P in TB-endemic areas and that the granuloma patterns contributed little to the prediction of final diagnosis compared with other organs., Graphical Abstract

Objectives The Cat Eye Syndrome Critical Region, Candidate 1 (CECR1) gene encoding adenosine deaminase 2 (ADA2) is mainly expressed by macrophages. Given the immunomodulatory functions of butyrate, we examined the effect of butyrate on CECR1 expression of macrophages and the relationship between ADA2 and M1/M2 macrophages-associated chemokines in pleural fluid of patients with tuberculous pleural effusion (TPE). Methods Expression of CECR1 was evaluated in lipopolysaccharide (LPS)-stimulated and/or butyrate treated THP-1 cells. The role of CECR1 on butyrate-induced immune response was evaluated using siRNA transfected THP-1 cells. M1/M2 chemokines and ADA2 were measured in pleural fluid of patients with TPE. Results Butyrate promoted the expression of CECR1 and M2-macrophage markers in THP-1 cells. CECR1 was found to be involved in regulating M2 polarization in THP-1 cells treated with LPS and butyrate. Among chemokines measured in pleural fluid of patients with TPE, there was a significant negative correlation between CCL21 and ADA2 levels and between CCL25 and ADA2 levels, and a significant positive correlation between TGF-β and ADA2 levels and between IL-22 and ADA2 levels. Conclusions CECR1 played an important role in the butyrate-modulated inflammatory responses in LPS-stimulated THP-1 cells. ADA2 may exert anti-inflammatory effects during the process of pleural inflammation in patients with TPE.

Background Data regarding predictors of the outcome for patients with community-acquired complicated parapneumonic effusion (CPPE) or empyema are insufficient. Method Patients with community-acquired pneumonia (CAP) were classified into CPPE or empyema and control groups based on pleural fluid analysis and microbiological data. The patients with CPPE or empyema were further divided into longer and shorter length of stay (LOS) groups, and clinical characteristics, pleural fluid data, and computed tomographic (CT) findings were compared between the two groups. Result Of outcome variables, LOS was significantly longer in CPPE or empyema group than in the control group (13 days [interquartile range, 10-17 days] versus 8 days [6-12 days], p < 0.001), whereas 30-day mortality and in-hospital mortality were not significantly different between the two groups. Patients with CPPE or empyema were divided into the shorter (≤ 13 days) and longer LOS (≥ 14 days) groups. Multivariate analysis demonstrated that pneumonia severity index (PSI) class IV-V (odds ratio [OR] 2.79, 95% CI 1.35-5.76, p=0.006), increased attenuation of extrapleural fat (OR 2.26, 95% CI 1.06-4.80, p=0.034), and air bubbles in pleural space (OR 3.93, 95% CI 1.03-14.98, p=0.045) were independent predictors of prolonged LOS in CAP patients with CPPE or empyema. Conclusion Increased attenuation of extrapleural fat and air bubbles in pleural space assessed with CT and PSI class IV-V independently predicted prolonged LOS in CAP patients with CPPE or empyema. These findings may be helpful to identify patients who need more intensive evaluation and intervention.

BACKGROUND. Ultrasound (US)-guided percutaneous pleural needle biopsy (PCPNB) is widely used to evaluate pleural lesions, although its diagnostic accuracy is variable. OBJECTIVE. The purpose of this study is to assess the diagnostic yield of US-guided PCPNB for small (≤ 2 cm) pleural lesions and the impact of CT and US morphologic and technical factors. METHODS. A total of 103 patients (73 men and 30 women; mean [± SD] age, 68.0 ± 13.3 years) who underwent US-guided PCPNB of a small pleural lesion performed by a single experienced operator from July 2013 to December 2019 were retrospectively analyzed. Final diagnosis was established via histopathologic results, including findings from repeat US-guided and CT-guided biopsies as well as imaging and clinical follow-up. Pleural morphology and thickness were assessed on CT and US, and needle pathway length throughout the pleura was measured on US. Accuracy, sensitivity, specificity, PPV, and NPV were calculated. The association of diagnostic yield with imaging and technical factors was evaluated. ROC curve analysis was used to determine the optimal CT pleural thickness cutoff value. Multivariable logistic regression was performed to identify independent predictors of diagnostic yield. RESULTS. The diagnostic accuracy, sensitivity, specificity, PPV, and NPV of US-guided PCPNB were 85.4%, 84.8%, 100.0%, 100.0%, and 21.1%, respectively. Diagnostic, compared with nondiagnostic, procedures more commonly (p ≤ .002) revealed nodular morphology on CT (96.4% vs 3.6%) and US (97.3% vs 2.7%,), greater pleural thickness on CT (7.5 vs 3.2 mm) and US (7.4 vs 3.0 mm), and a greater needle pathway length (11.0 vs 6.1 mm). The optimal cutoff value for pleural thickness on CT was 4.5 mm. Diagnostic yield was 96.4% for nodular lesions, 95.0% for diffuse lesions that had a thickness of 4.5 mm or greater on CT, 55.6% for diffuse lesions that had a thickness less than 4.5 mm on CT, and 100% for diffuse lesions on CT that had nodular morphology on US. Nodular morphology on US (p = .002) and needle pathway length (p = .04) were independent predictors of diagnostic yield. CONCLUSION. US-guided PCPNB has excellent diagnostic accuracy for small pleural lesions; imaging characteristics influence this accuracy. CLINICAL IMPACT. US-guided PCPNB is highly likely diagnostic for small pleural lesions with nodular morphology on either CT or US or with a pleural thickness of 4.5 mm or greater.

Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the &Delta, afmac1 strain on AMM. In addition, the growth defect of the &Delta, afmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the &Delta, afmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the &Delta, afmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5&prime, CAA(G)GGT-3&prime, was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27–0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12–2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10–3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51–0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33–0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19–1.84, Ptrend = 4 × 10−4, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.

Introduction Few studies have investigated the influence of emphysema on clinical features of patients presenting with community-acquired pneumonia (CAP). Objectives The aim of this study was to examine the clinical and microbiological features of patients with both CAP and emphysema. Methods This retrospective study included patients with CAP who underwent computed tomography (CT) scan at the time of presentation. Patients were allocated into emphysema and control groups, and clinical variables were compared between the 2 groups. The emphysema group was further divided into 3 subgroups (mild, moderate, and severe) according to the extent of emphysema on CT scan. The clinical variables of each subgroup were compared with the control group. Results Of 1676 patients, 431 patients (25.7%) were classified into the emphysema group. CAP patients with emphysema were more likely to have a high CURB-65 score and pneumonia severity index and a lower incidence of complicated parapneumonic effusion or empyema. The emphysema group exhibited longer hospital stay. In addition, 30-day mortality in the severe emphysema group was significantly higher compared with the control group. As etiological agents, Streptococcus pneumoniae, Pseudomonas aeruginosa, Enterobacteriaceae, and multi-drug resistant pathogens were significantly more common in the emphysema group compared with the control group. Conclusions The presence of emphysema in CAP patients was associated with a more severe form of CAP, a longer hospital stay, and a lower incidence of complicated parapneumonic effusion or empyema. Moreover, CAP patients with severe emphysema exhibited higher 30-day mortality than those without emphysema.

The outcome of coronavirus disease 2019 (COVID-19) is associated with organ damage, however, the information about the relationship between acute kidney injury (AKI) and COVID-19 is still rare. We evaluated the clinical features and prognosis of COVID-19 patients with AKI according to the AKI severity. Medical data of hospitalized COVID-19 patients in two university-based hospitals during an outbreak in Daegu, South Korea, were retrospectively analyzed. AKI and its severity were defined according to the Acute Kidney Injury Network. Of the 164 hospitalized patients with COVID-19, 30 patients (18.3%) had AKI, 14, 4, and 12 patients had stage 1, 2, and 3, respectively. The median age was significantly higher in AKI patients than in non-AKI patients (75.5 vs. 67.0 years, p = 0.005). There were 17 deaths (56.7%) among AKI patients, 4 (28.6%), 1 (25.0%), and 12 (100.0%), respectively. In-hospital mortality was higher in AKI patients than in non-AKI patients (56.7% vs. 20.8%, p &lt, 0.001). After adjusting for potential confounding factors, stage 3 AKI was associated with higher mortality than either non-AKI or stage 1 AKI (hazard ratio (HR) = 3.62 (95% confidence interval (CI) = 1.75&ndash, 7.48), p = 0.001, HR = 15.65 (95% CI = 2.43&ndash, 100.64), p = 0.004). Among the AKI patients, acute respiratory distress syndrome and low serum albumin on admission were considered independent risk factors for stage 3 AKI (both p &lt, 0.05). Five patients with stage 3 AKI underwent dialysis and eventually died. In conclusion, COVID-19 patients with severe AKI had fatal outcomes.

Background: This study was conducted to investigate the association between genetic variants in one-carbon metabolism and survival outcomes of surgically resected non-small cell lung cancer (NSCLC). Methods: We genotyped 41 potentially functional variants of 19 key genes in the one-carbon metabolism pathway among 750 NSCLC patients who underwent curative surgery. The association between genetic variants and overall survival (OS)/disease-free survival (DFS) were analyzed. Results: Among the 41 single-nucleotide polymorphisms (SNPs) analyzed, 4 SNPs (MTHFD1L rs6919680T>G and rs3849794T>C, MTR rs2853523C>A, and MTHFR rs4846049G>T) were significantly associated with survival outcomes. MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (adjusted hazard ratio [aHR] = 0.73, 95% confidence interval [CI] = 0.54–0.99, p = 0.04) and worse OS (aHR = 2.14, 95% CI = 1.13–4.07, p = 0.02), respectively. MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.41, 95% CI = 1.08–1.83, p = 0.01; and aHR = 1.97, 95% CI = 1.10–3.53, p = 0.02, respectively). When the patients were divided according to histology, the associations were significant only in squamous cell carcinoma (SCC), but not in adenocarcinoma (AC). In SCC, MTHFD1L rs6919680T>G and MTR rs2853523C>A were significantly associated with better OS (aHR = 0.64, 95% CI = 0.41–1.00, p = 0.05) and worse OS (aHR = 2.77, 95% CI = 1.11–6.91, p = 0.03), respectively, and MTHFD1L rs3849794T>C and MTHFR rs4846049G>T were significantly associated with worse DFS (aHR = 1.73, 95% CI = 1.17–2.56, p = 0.01; and aHR = 2.78, 95% CI = 1.12–6.88, p = 0.03, respectively). Conclusions: Our results suggest that the genetic variants in the one-carbon metabolism pathway could be used as biomarkers for predicting the clinical outcomes of patients with early-stage NSCLC.

Deltex‐1 (DTX1) is a negative regulator of the Notch signaling pathway. Here, we investigated the clinical effect of DTX1 rs1732786A > G, which is associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC), in 261 patients with small cell lung cancer (SCLC). DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in the codominant model (odds ratio = 0.42, 95% confidence interval [CI]: 0.26–0.66, P = 2 × 10−4; hazard ratio = 1.47, 95% CI: 1.17–1.84, P = 0.001, respectively). An in vitro luciferase assay was performed, and the 1732786G allele demonstrated significantly higher promoter activity than the 1732786A allele (P = 2 × 10−7). In summary, DTX1 rs1732786A > G was associated with poor prognosis in patients with SCLC as opposed to patients with NSCLC. Key points Significant findings of the study DTX1 rs1732786A > G was associated with better prognosis in patients with early‐stage non‐small cell lung cancer (NSCLC) in our previous study. What this study adds DTX1 rs1732786A > G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer (SCLC)., DTX1 rs1732786A>G was associated with better prognosis in patients with early‐stage non‐small cell lung cancer, in the previous study. DTX1 rs1732786A>G was associated with a significantly worse chemotherapy response and lower overall survival in small cell lung cancer.

The answer to the letter ‘Absent regulation of iron acquisition by the copper regulator Mac1 in A. fumigatus’ has been prepared. We explained our data and showed supplementary information to answer the questions. And we respect the results of other groups first and explain the differences from our results.

Background We conducted this study to identify regulatory variants in cancer-related pathway genes which can predict clinical outcomes of chemotherapy in advanced NSCLC, using a comprehensive list of regulatory SNPs prioritized by RegulomeDB. Methods A total of 509 potentially functional SNPs in cancer-related pathway genes were evaluated. The SNPs were analyzed in a discovery set (n = 198), and an independent validation set (n = 181). The associations of the SNPs with chemotherapy response and overall survival (OS) were analyzed. Results In the discovery set, 95 SNPs were significantly associated with clinical outcomes. Among the 95 SNPs, only rs10414193A > G in the intronic region of ARID3A, an eQTL for LKB1, was consistently associated with chemotherapy response and OS in the validation set. In combined analysis, the rs10414193A > G was significantly associated with worse response to chemotherapy (adjusted odds ratio = 0.63, 95% CI = 0.47–0.85, P = 0.002), and with worse OS (adjusted hazard ratio = 1.25, 95% CI = 1.08–1.45, P = 0.004). Luciferase assay showed a significantly higher LKB1 promoter activity associated with rs10414193G allele compared with rs10414193A allele (P = 0.0009). Conclusions Our results suggest that rs10414193A > G may be useful for the prediction of clinical outcomes of chemotherapy in advanced NSCLC.

International audience; As the symbol of beauty, floral objects have been one of the most popular subjects of artistic drawing. However, designing 3D floral models is generally time-and resource-consuming, because of their structural and geometrical complexity. In this paper, we address the problem of reconstructing floral objects from sketch input. The user draws a relatively clean sketch of a flower and a few additional guide markings from an arbitrary view to rapidly create quality geometric models of flowers. Our system offers a novel modeling scheme compared to several existing flower modelers accepting sketch as input, where the user is required to work with different views, providing step-by-step sketch input. Given the silhouette and the guide strokes, an assumed, common botanical structure is estimated, i.e. a cone for each ring of petals. The cones and the silhouette sketch that we segment into elementary curves are used to retrieve model elements from the pre-constructed shape database. These elements are then placed together around the cone, where an additional, per-element deformation is performed so as to maximize the silhouette similarity between the user sketch and the 3D flower model from the chosen view. Our system has shown to robustly create a variety of flowers in various configurations, including flower models with several petal layers and various blooming degrees, drawn from different views.

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 5′-TGTGCTCA-3′ found in the promoter region of ctrC, the iron-specific AfMac1-binding motif 5′-AT(C/G)NN(A/T)T(A/C)-3′ was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa. AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.

2-(2,5-Dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine (25N-NBOMe, 2C-N-NBOMe, NBOMe-2C-N) is a novel synthetic psychoactive substance of the phenethylamine chemical class. A few metabolism studies have been conducted for 25I-NBOMe, 25B-NBOMe, and 25C-NBOMe, and others, whereas 25N-NBOMe metabolism has not been researched. In this study, the in vitro metabolism of 25N-NBOMe was investigated with human liver microsomes, and the reaction mixture was analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Formation of 14 metabolites (M1-M14) was yielded with incubation of 25N-NBOMe in human liver microsomes in the presence of NADPH. The metabolites were structurally characterized on the basis of accurate mass analysis and MS/MS fragmentation patterns. The biotransformations included hydroxylation, O-demethylation, N-dealkylation, nitro reduction, dehydrogenation, carbonylation, and combinations thereof. Hydroxyl metabolite was the most abundant compound after the phase I process. These results provide helpful information establishing biomarkers in case of 25N-NBOMe ingestion.

Background Data on the relationship between the clinical and microbiological features of community-acquired pneumonia (CAP) and its computed tomography (CT) findings are limited. The aim of the present study was to investigate the clinic-microbiological features of patients with CAP presenting with ground-glass opacity (GGO) and centrilobular nodules or tree-in-bud pattern on CT images. Methods Patients with CAP who underwent a CT scan at presentation were retrospectively classified using CT findings into consolidation, GGO and bronchiolitis groups. These 3 groups were compared in terms of clinical parameters and microbiological data. Results A total of 40 patients (2.4%) were allocated to the bronchiolitis group and 46 (2.8%) to the GGO group. The most common pathogen in the bronchiolitis group was Mycoplasma pneumoniae, which was significantly more frequently isolated in this group. The bronchiolitis group was characterized by a higher percentage of cough, a lower percentage of chest pain and lower blood levels of inflammatory markers. Common pathogens in the GGO group were not significantly different from those in the other 2 groups. Unlike that observed in the consolidation group, complicated parapneumonic effusion or empyema was not observed in the bronchiolitis or GGO group. Outcome variables were similar in the 3 groups. Conclusions The bronchiolitis group was characterized by a higher frequency of M. pneumoniae and a less severe form of CAP. The GGO and consolidation groups was similar with respect to causative microorganisms and the clinical features of CAP. No patient in the bronchiolitis or GGO group exhibited complicated parapneumonic effusion or empyema.

Predicting drug–drug interactions (DDIs) is an important step during drug development to avoid unexpected side effects. Cytochrome P450 (CYP) 3A4 is the most abundant human hepatic phase I enzyme, which metabolizes >50% of therapeutic drugs. Therefore, it is essential to test the potential of a drug candidate to induce CYP3A4 expression or inhibit its activity. Recently, 3-dimensional (3-D) mammalian cell culture models have been adopted in drug discovery research to assess toxicity, DDIs, and pharmacokinetics. In this study, we applied a human 3-D spheroid culture protocol using HepaRG cells combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess its ability to predict CYP3A4 inhibition. Levels of midazolam, a specific substrate of CYP3A4, were used to determine the long-term metabolic capacity of CYP3A4. Midazolam was decreased in the 3-D HepaRG culture system by ∼80% over 7 days, whereas its primary metabolite, 1-hydroxymidazolam, increased by ∼40%. Next, we assessed hepatotoxicity by determining the cytotoxicity of known hepatotoxicants in HepaRG spheroids, HepG2 cells, and primary human hepatocytes. Significant differences in cytotoxicity were detected in the system using 3-D HepaRG spheroids. These results suggest that 3-D HepaRG spheroids are a good model for prediction of CYP inhibition and hepatotoxicity in screening of early drug candidates.

Ni-rich LiNixCoyMn1-x-yO2 (Ni-rich NCM; x ≥ 0.8, 0 4.3 V). Herein, 2,4-difluorobiphenyl (FBP) is proposed as a fluorine-based cathode electrolyte interphase (CEI)-forming additive for Ni-rich LiNi0.83Co0.11Mn0.06O2 (NCM83). The structural characteristics of FBP originate from the overcharge protection of biphenyl, whereas the fluorine atoms are preferable for high-voltage conditions. The addition of 1 wt% FBP to the electrolyte enhances the cycling stability at the 4.5 V cut-off voltage. Electrochemical impedance spectroscopy and rate capability results indicate a fast kinetics at the NCM83 surface with FBP additive upon the formation of a stable CEI. Images from scanning electron microscopy and transmission electron microscopy after 150 cycles of NCM83 show the thin deposit layer of CEI upon introduction of FBP. The X-ray photoelectron spectroscopy results demonstrate the suppression of electrolyte and salt decomposition. This work suggests an opportunity to develop a completely new functional additive by introducing a fluorine component to existing additives.

Anthrax, a bacteriogenic fatal infectious disease against human beings, demands early and ready detection of its bacterial endospores. We disclose here poly(diacetylene acid) derived liposomes functionalized with Eu(III)-EDTA complexes as a novel ratiometric fluorescence detection system for dipicolinate, an anthrax biomarker and the major component of the endospores. The red fluorescence of the polymerized liposomes offers a biult-in reference signal, allowing us to monitor the relative change of europium luminescence sensitized by the bound dipicolinate with respect to the reference liposome emission. The liposome based integrated sensing system shows reasonable sensitivity as well as remarkable selectivity toward dipicolinate over other structurally related analytes. We also show paper stripe sensors based on the polymerized liposome for the detection of dipicolinate by naked eyes.

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

Zinc performs diverse physiological functions, and virtually all living organisms require zinc as an essential trace element. To identify the detailed function of zinc in fungal pathogenicity, we carried out cDNA microarray analysis using the model system of Aspergillus fumigatus, a fungal pathogen. From microarray analysis, we found that the genes involved in gliotoxin biosynthesis were upregulated when zinc was depleted, and the microarray data were confirmed by northern blot analysis. In particular, zinc deficiency upregulated the expression of GliZ, which encodes a Zn2-Cys6 binuclear transcription factor that regulates the expression of the genes required for gliotoxin biosynthesis. The production of gliotoxin was decreased in a manner inversely proportional to the zinc concentration, and the same result was investigated in the absence of ZafA, which is a zinc-dependent transcription activator. Interestingly, we found two conserved ZafA-binding motifs, 5′-CAAGGT-3′, in the upstream region of GliZ on the genome and discovered that deletion of the ZafA-binding motifs resulted in loss of ZafA-binding activity; gliotoxin production was decreased dramatically, as demonstrated with a GliZ deletion mutant. Furthermore, mutation of the ZafA-binding motifs resulted in an increase in the conidial killing activity of human macrophage and neutrophil cells, and virulence was decreased in a murine model. Finally, transcriptomic analysis revealed that the expression of ZafA and GliZ was upregulated during phagocytosis by macrophages. Taken together, these results suggest that zinc plays an important role in the pathogenicity of A. fumigatus by regulating gliotoxin production during the phagocytosis pathway to overcome the host defense system.

Background Risk stratification is important for the management of community-acquired pneumonia (CAP). The present study aimed to investigate the clinical impact of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on prognosis and to identify clinical characteristics associated with NT-proBNP elevation in CAP patients. Methods This retrospective study included patients hospitalized for CAP at a tertiary referral center and who underwent measurement plasma NT-proBNP levels. Based on 30-day mortality, patients (n = 1,821) were divided into 2 groups, survivors (n = 150) and nonsurvivors (n = 1,671), and clinical and laboratory findings were compared. Results In multivariate analysis, blood levels of NT-proBNP (>942.5 pg/mL), albumin ( 0.018 ng/mL) independently predicted 30-day mortality. Of these blood biomarkers, NT-proBNP exhibited the highest C-statistic, followed by albumin. NT-proBNP level/CURB-65 score and NT-proBNP level/pneumonia severity index (PSI) class exhibited significantly higher C-statistics than CURB-65 score and PSI class alone, respectively. The 3-test combinations of CURB-65 score/NT-proBNP level/albumin level and PSI class/NT-proBNP level/albumin level exhibited significantly higher C-statistics than the 2-test combinations. NT-proBNP elevation was associated with increased age, heart disease and chronic kidney disease and NT-proBNP levels only weakly or moderately correlated with other blood biomarkers. Conclusions NT-proBNP level was a useful marker for the prediction of 30-day mortality in patients hospitalized with CAP, and provided additional prognostic value to PSI or CURB-65 alone.

BACKGROUND: Lymphoma-associated malignant pleural effusions (L-MPE) can mimic tuberculous pleural effusion (TPE) characterized by lymphocytic exudate with high adenosine deaminase (ADA) levels. Furthermore, the low cytological yield of L-MPE makes differentiation between L-MPE and TPE more challenging. However, there are few data regarding differential diagnosis of L-MPE and TPE. METHODS: All consecutive patients diagnosed with L-MPE or TPE between January 2011 and December 2016 were retrospectively recruited using the Electronic Medical Record database. Clinical symptoms and laboratory and pleural fluid data [including serum lactate dehydrogenase (LDH), C-reactive protein, and pleural fluid ADA levels] were compared between L-MPE and TPE. Useful variables in the differential diagnosis of L-MPE and TPE were evaluated by multivariate logistic regression analysis. RESULTS: Seventeen patients with L-MPE and 216 patients with TPE were included in this study. In the multivariate analysis, fever was negatively associated with L-MPE [odds ratio (OR): 0.175, 95% confidence interval (CI): 0.033–0.941, P=0.042], while serum LDH levels were positively associated with L-MPE (OR: 1.005, 95% CI: 1.003–1.007, P460 U/L provided a sensitivity of 76% and a specificity of 81% to distinguish L-MPE and TPE. In contrast, serum C-reactive protein and pleural fluid ADA levels were not significantly different between the groups. CONCLUSIONS: Patients with L-MPE and TPE present very similar clinical, laboratory, and pleural fluid characteristics. Fever and serum LDH levels may be helpful in guiding the differential diagnosis of L-MPE and TPE. Lymphoma should be kept in mind in the differential diagnosis in patients with lymphocytic pleural effusion and high ADA levels.

Objective: This study was conducted to investigate whether polymorphisms in glycolysis-related genes are associated with clinical outcomes of patients with advanced-stage non-small cell lung cancer (NSCLC) undergoing chemotherapy. Methods: A total of 377 patients with NSCLC were enrolled. Sixty-five single-nucleotide polymorphisms in 26 genes involved in the glycolytic pathway were evaluated. The associations of the variants with the chemotherapy response and overall survival (OS) were analyzed. Results: Among the 65 variants investigated, PFKL rs2073436C>G and GPI rs7248411C>G significantly correlated with clinical outcomes after chemotherapy in multivariate analyses. PFKL rs2073436C>G was significantly associated with both a worse response to chemotherapy (adjusted odds ratio [aOR] = 0.64, 95% CI = 0.45–0.90, p = 0.01) and a worse OS (adjusted hazard ratio [aHR] = 1.35, 95% CI = 1.14–1.61, p = 0.001). GPI rs7248411C>G was significantly associated with both a better chemotherapy response (aOR = 1.58, 95% CI = 1.07–2.23, p = 0.02) and a better OS (aHR = 0.80, 95% CI = 0.66–0.98, p = 0.03). When stratified by tumor histology, PFKL rs2073436C>G was significantly associated with OS only in squamous cell carcinoma, whereas GPI rs7248411C>G exhibited a significant association with the chemotherapy response and OS only in adenocarcinoma. Conclusion: This result suggests that the PFKL rs2073436C>G and GPI rs7248411C>G are useful for predicting the clinical outcome of first-line paclitaxel-cisplatin chemotherapy in NSCLC.

INTRODUCTION In comparison with mononuclear leucocyte (MNL)-predominant malignant pleural effusions (MPEs), polymorphonuclear leucocyte (PMNL)-predominant MPEs have rarely been investigated and may be associated with a poorer prognosis. OBJECTIVES To investigate the characteristics and survival impact of PMNL-predominant MPEs secondary to lung cancer. METHODS This retrospective study included patients with MPE secondary to lung cancer, which were classified into the PMNL- and MNL-predominant groups according to cellular predominance in the pleural fluid. Clinical, hematological, radiological, and pleural fluid data were compared between the groups, and the survival impact of PMNL predominance in MPE was evaluated. RESULTS Of the 193 MPEs included, 37 (19%) were characterised by PMNL predominance. Compared to the MNL-predominant group, the PMNL-predominant group showed significantly poorer patient performances (P = .001), higher white blood cell counts (P = .009), higher neutrophil counts, higher blood neutrophil-to-lymphocyte ratio (P = .046), higher serum C-reactive protein (P = .003), lower serum albumin (P

BACKGROUND: Data regarding clinical and radiological features of patients with pulmonary thromboembolism (PTE) and concomitant chronic respiratory disease (CRD) are limited. Accordingly, the aim of the present study was to investigate clinico-radiological features of this patient population. METHODS: Patients with PTE were retrospectively classified into one of two groups: those with and without CRD. Clinical characteristics, blood biomarkers, and computed tomographic (CT) findings were compared between the groups. RESULTS: Of 1,207 PTE patients included, CRD was detected in 128 (11%). The most common CRD was chronic obstructive pulmonary disease [41 (32%)], followed by bronchial anthracofibrosis [32 (25%)]. In multivariate analysis, unprovoked PTE [odds ratio (OR) 1.99, 95% confidence interval (CI): 1.29–3.05, P=0.002], dyspnea (OR 1.54, 95% CI: 1.11–2.34, P=0.041), lower respiratory tract infection (LRTI) (OR 3.90, 95% CI: 2.13–7.14, P

International audience; With the recent advances of data acquisition techniques, the compression of various 3D mesh animation data has become an important topic in computer graphics community. In this paper, we present a new spatio-temporal segmentation-based approach for the compression of 3D mesh animations. Given an input mesh sequence , we first compute an initial temporal cut to obtain a small subsequence by detecting the temporal boundary of dynamic behavior. Then, we apply a two-stage vertex clustering on the resulting subsequence to classify the vertices into groups with optimal intra-affinities. After that, we design a temporal segmentation step based on the variations of the principle components within each vertex group prior to performing a PCA-based compression. Our approach can adaptively determine the temporal and spatial segmentation boundaries in order to exploit both temporal and spatial redundancies. We have conducted many experiments on different types of 3D mesh animations with various segmentation configurations. Our comparative studies show the competitive performance of our approach for the compression of 3D mesh animations.

The NBOMe family is a group of new psychoactive substances (NPSs). In this study, the fragmentation patterns of NBOMe derivatives were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The MS/MS spectral data was used to establish a molecular networking map for NBOMe derivatives. The fragmentation patterns of nine NBOMe derivatives were interpreted on the basis of their product ion spectral data. NBOMe derivatives generally showed similar product ion spectral patterns; among them, the halogen-substituted methoxybenzyl ethanamine type derivatives showed a characteristic product ion of a radical cation. Molecular network analysis of the MS/MS data revealed that all NBOMe derivatives formed one integrated networking cluster that discriminated them from other types of NPSs. NBOMe derivatives were spiked into human urine and identified by connection to the NBOMe database network. Furthermore, the NBOMe compounds that were not registered in the database were also recognized as an NBOMe-related substance by molecular networking. These results demonstrate the potential of using molecular networking-based screening methods for designer drugs, and the proposed method would be useful in forensic or doping analysis.

Background and objective Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community-acquired pneumonia (CAP). Methods This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non-NP groups, and they were compared with respect to various clinical variables. Results Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non-NP. Although the use of mechanical ventilation, vasopressor infusion, 30-day mortality, in-hospital mortality and clinical deterioration did not differ between the NP and non-NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. Conclusion NP affects approximately one-tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients.

With the recent advancement of data acquisition techniques, 3D animation is becoming a new challenging subject for data processing. In this paper, we present a joint entropy-based key-frame extraction method, which further derives a motion segmentation method for 3D animations. We start by applying an existing deformation-based feature descriptor to measure the degree of deformation of each triangle within each frame, from which we compute the statistical joint probability distribution of triangles’ deformation between two consecutive subsequences of frames with a fixed length. Then, we further compute joint entropy between the two subsequences. This allows us to extract key-frames by taking the local maximal from the joint entropy curve (or energy curve) of a given 3D animation. Furthermore, we classify the extracted key-frames by grouping the key-frames with similar motions into the same cluster. Finally, we compute a boundary frame between each of the two neighboring frames with different motions, which is achieved by minimizing the variance of energy between the two motions. The experimental results show that our method successfully extracts representative key-frames of different motions, and the comparisons with existing methods show the effectiveness and the efficiency of our method.

Aim Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota-driven mechanisms involved in the development of nonalcoholic hepatic steatosis. Methods and Results Ob/ob mice and their wild-type lean control mice were fed an AIN-93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine-conjugated BAs compared to their lean controls. The proportions of butyrate-producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol-7α-hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice. Conclusion Microbiota-associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR-SHP pathway, thereby accelerating fat synthesis. Significance and Impact of the Study We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.

The problem of new psychoactive substance (NPS) abuse, which includes synthetic cannabinoids, is emerging globally, and the cardiotoxicity of these synthetic cannabinoids has not yet been evaluated extensively. In the present study, we investigated the effects of synthetic cannabinoids on the cytotoxicity, human Ether-a-go-go-related gene (hERG) channel, action potential duration (APD), and QT interval. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that JWH-030 was more cytotoxic than JWH-210, JWH-250, and RCS4 in H9c2 cells at 0.1 μM. In addition, the cytotoxicity was associated with its pro-apoptotic effects as evidenced by the increase in caspase-3 levels. We demonstrated that a cannabinoid receptor type 2 (CB2) antagonist, AM630, inhibited JWH-030-induced cytotoxicity, whereas a CB1 antagonist, rimonabant, did not. Furthermore, fluorescence polarization assay showed JWH-030 to block the hERG channel (half-maximal inhibitory concentration, IC50 was 88.36 μM). JWH-030 significantly reduced the APD at 90% repolarization (APD90) in rabbit Purkinje fibers and decreased the left ventricular end diastolic pressure (LVEDP) in Langendorff-perfused Sprague-Dawley (SD) rat hearts at 30 μM. In addition, the electrocardiogram (ECG) measurement revealed that the intravenous injection of JWH-030 (0.5 mg kg−1) prolonged the QT interval in SD rats. These results suggest that JWH-030 is cytotoxic and its cytotoxicity is mediated by its action on the CB2 receptor; it prolongs the QT interval by regulating ion current channels and APD.

International audience; In this paper, we present a sketch-based modeler that reconstructs a 3D shape by combining a single descriptive sketch and minimal user intervention. The user provides a single 2D drawing in the form of a descriptive sketch, where solid curves describe the visible silhouette, and dashed curves the hidden outline. The curves are partitioned into a set of closed curves in a semi-automatic manner, each of which is consolidated into a closed surface element by solving a constrained optimization problem. The final 3D shape is generated by assembling these surface elements. The algorithmic reconstruction is complemented by allowing users to optionally guide the shape computation or correct any inaccuracy. This is done by successively specifying different kinds of local constraints on sparsely selected points in rotated views, such as adjustment of volume thickness along the projection line, or curvature discontinuity. Consequently, the range and complexity of shapes that can be created from a singleview sketch are significantly extended. We evaluate our solution by reconstructing a wide range of 3D models from sketches of various sources, and visually comparing the reference models and the shapes reconstructed by users.

Pleural fluid (PF) immune response in anergic tuberculous pleural effusion (TPE) patients is poorly understood. This study aimed to compare PF biochemical parameters and chemokine levels between anergic and non-anergic TPE patients. Chemokine arrays, cytokine measurements, and flow cytometry were performed in 58 patients (TPE [non-anergic (n = 32) and anergic (n = 10)] and malignant pleural effusion (MPE) [n = 16]). PF adenosine deaminase 2 (ADA2) levels were significantly lower in anergic TPE patients than in non-anergic TPE patients (p = 0.048). Among the 40 chemokines tested, PF CCL27 levels were significantly higher in anergic TPE patients than in non-anergic TPE and MPE patients (p 0.001). The percentage of CD4

Background Malignant pleural effusion (MPE) occasionally demonstrates neutrophilic predominance, commonly found in parapneumonic pleural effusion (PPE). In comparison with lymphocytic MPE, neutrophilic MPE may have different characteristics associated with a more intense inflammatory response and poor prognosis. These characteristics of neutrophilic MPE may lead to inappropriate management and delayed diagnosis. Moreover, the limited diagnostic yield of microbiologic and cytologic tests makes early differential diagnosis between neutrophilic MPE and PPE more challenging. This study investigated objective laboratory findings to help distinguish neutrophilic MPE from PPE. Materials and Methods A retrospective study was conducted on patients with neutrophilic MPE and PPE. Routine blood and pleural fluid data of the 2 groups were compared, and the diagnostic performances of predictors for neutrophilic MPE were assessed using receiver-operating characteristic curves. Results Forty-one and 140 patients with neutrophilic MPE and PPE, respectively, were included. In final analysis, serum C-reactive protein, pleural fluid neutrophil-to-lymphocyte ratio, and pleural fluid carcinoembryonic antigen were significantly different between the 2 groups. With cut-off values of C-reactive protein 8.0 ng/mL, the presence of any 2 or more parameters provided an area under the curve of 0.928 (95% CI, 0.851-0.999), yielding a sensitivity of 88%, specificity of 98%, positive predictive value of 92% and negative predictive value of 96% for identifying MPE. Conclusions MPE should be considered even in patients with neutrophilic exudative effusion, especially if at least 1 predictor for neutrophilic MPE is present. Our results may help guide differentiation of neutrophilic MPE from PPE.