Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

INTRODUCTION: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. OBJECTIVES: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). METHODS: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. RESULTS: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

N-Terminal α-Helices in Domain I of Bacillus thuringiensis Vip3Aa Play Crucial Roles in Disruption of Liposomal Membrane.

Bacillus thuringiensis Vip3 toxins form a tetrameric structure crucial for their insecticidal activity. Each Vip3Aa monomer comprises five domains. Interaction of the first four α-helices in domain I with the target cellular membrane was proposed to be a key step before pore formation. In this study, four N-terminal α-helix-deleted truncations of Vip3Aa were produced and, it was found that they lost both liposome permeability and insecticidal activity against Spodoptera litura. To further probe the role of domain I in membrane permeation, the full-length domain I and the fragments of N-terminal α-helix-truncated domain I were fused to green fluorescent protein (GFP), respectively. Only the fusion carrying the full-length domain I exhibited permeability against artificial liposomes. In addition, seven Vip3Aa-Cry1Ac fusions were also constructed by combination of α-helices from Vip3Aa domains I and II with the domains II and III of Cry1Ac. Five of the seven combinations were determined to show membrane permeability in artificial liposomes. However, none of the Vip3Aa-Cry1Ac combinations exhibited insecticidal activity due to the significant reduction in proteolytic stability. These results indicated that the N-terminal helix α1 in the Vip3Aa domain I is essential for both insecticidal activity and liposome permeability and that domain I of Vip3Aa preserved a high liposome permeability independently from domains II-V.

Exploring the relationship between age and prognosis in glioma: rethinking current age stratification.

BACKGROUND: The age of glioma plays a unique role in prognosis. We hypothesized that age is not positively correlated with survival prognosis and explored its exact relationship. METHODS: Glioma was identified from the SEER database (between 2000 and 2018). A multivariate Cox proportional regression model and restricted cubic spline (RCS) plot were used to assess the relationship between age and prognosis. RESULTS: A total of 66465 patients with glioma were included. Hazard ratios (HR) for ten-year by age: 0-9 years, HR 1.06 (0.93-1.20); 10-19 years: reference; 20-29 years, HR 0.90 (0.82-1.00); 30-39 years, HR 1.14 (1.04-1.25); 40-49 years, HR 2.09 (1.91-2.28); 50-59 years, HR 3.48 (3.19-3.79); 60-69 years, HR 4.91 (4.51-5.35);70-79 years, HR 7.95 (7.29-8.66); 80-84 years, HR 12.85 (11.74-14.06). After adjusting for covariates, the prognosis was not positively correlated with age. The smooth curve of RCS revealed this non-linear relationship: HR increased to 10 years first, decreased to 23 years, reached its lowest point, and became J-shaped. CONCLUSION: The relationship between age and glioma prognosis is non-linear. These results challenge the applicability of current age groupings for gliomas and advocate the consideration of individualized treatment guided by precise age.

Efficacy and safety of tumor-treating fields in recurrent glioblastoma: a systematic review and meta-analysis.

BACKGROUND: Tumor-treating fields (TTF) is a novel cancer treatment that uses alternating electric fields to interfere with tumor cell mitosis. It has been approved by the U.S. food and drug administration for the treatment of recurrent glioblastoma (rGBM). We designed this meta-analysis to evaluate the efficacy and safety of TTF in the treatment of rGBM. METHODS: The study was based on the PRISMA guideline. Systematic retrieval was performed in PubMed, Cochrane Library, and Embase databases. The outcomes were overall survival (OS) hazard ratio (HR), 1-year survival rate, and cutaneous toxicity. RESULTS: These studies included a total of 1048 rGBM patients who received TTF treatment. The overall survival time between the TTF group and the control group was HR 0.75 ([95%CI 0.63 to 0.89]; P = 0.001). Pooled 1-year overall survival rate and incidence of cutaneous toxicity were 0.47 and 0.48, respectively. Data were insufficient to evaluate the effect of MGMT methylation status and tumor recurrence times on heterogeneity. CONCLUSIONS: TTF therapy is effective for recurrent glioblastoma. However, most relevant trials should assess rGBM patient baseline characteristics such as age, KPS, MGMT methylation status, and number of tumor recurrence,. In addition, the risk of rashes caused by long-term wearing of devices should also be considered.

Ticagrelor for prevention of stroke and cognitive impairment in patients with vascular high-risk factors: A meta-analysis of randomized controlled trials.

BACKGROUND: In recent randomized controlled studies, the prevention of stroke and cognitive function of ticagrelor has been controversial. We conducted a meta-analysis to compare ticagrelor with other antiplatelet treatment in patients with vascular high-risk factors disease, defined as acute coronary syndrome, stroke or transient ischemic attack, coronary artery disease or peripheral artery disease. METHODS: We searched the PubMed, Embase, and Cochrane libraries for published randomized controlled trials and additional available data from ClinicalTrials.gov. The primary outcome was related adverse stroke events and the secondary outcome was cognitive function related adverse events. The outcomes were statistically analyzed using Peto odds ratio. RESULTS: 12 RCTs with 105,654 patients were included in meta-analysis. PRIMARY OUTCOMES: all stroke (OR 0.84, 95%CI 0.78-0.90, P < 0.001); Secondary outcomes: ischemic stroke (OR 0.83, 95%CI 0.77-0.90, P < 0.001), transient ischemic attack (OR 0.78, 95%CI 0.62-0.97, P = 0.029), intracranial hemorrhage (OR 1.33, 95%CI 1.09-1.61, P = 0.005), Parkinson's disease (OR 0.30, 95%CI 0.12-0.72, P = 0.007), dementia (OR 0.31, 95%CI 0.13-0.77, P = 0.012), dizziness (OR: 1.39, 95%CI 1.03-1.87, P = 0.032), insomnia (OR 1.45, 95%CI 1.05-2.00, P = 0.026). CONCLUSIONS: Ticagrelor may provide more favorable outcomes for all stroke, ischemic stroke, and transient ischemic attack prevention in patients with vascular high-risk factors. However, this benefit may come with the cost of intracranial hemorrhage, dizziness and insomnia. Ticagrelor may reduce the risk of dementia and Parkinson's disease, although available data are limited.

Development and Validation of Prognostic Nomogram in Patients With WHO Grade III Meningioma: A Retrospective Cohort Study Based on SEER Database.

INTRODUCTION: World Health Organization (WHO) Grade III meningioma is a central nervous system tumor with a poor prognosis. In this retrospective cohort study, the authors constructed a nomogram for predicting the prognosis of WHO Grade III meningioma. METHODS: The patients of this nomogram were based on the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018. All patients were randomly divided into a development cohort (964 patients) and a validation cohort (410 patients) in a 7:3 ratio. The least absolute shrinkage and selection operator (LASSO) regression was used to screen the predictors. The Cox hazards regression model was constructed and the prognosis was visualized by nomogram. The performance of the prognostic nomogram was determined by consistency index (C-index), clinical net benefit, and calibration. RESULTS: Eight variables were included in the nomogram: gender, race, age at diagnosis, histology, tumor site, tumor size, laterality, and surgical method. The C-index of the training set and verification set were 0.654 and 0.628. The calibration plots showed that the nomogram was in good agreement with the actual observation. The clinical decision curve indicates that the nomogram has a good clinical net benefit in WHO Grade III meningioma. CONCLUSIONS: A prognostic nomogram of a large cohort of WHO Grade III meningioma was established and verified based on the SEER database. The nomogram we established may help clinicians provide personalized treatment services and clinical decisions for patients.

Development and validation of prognostic nomogram in ependymoma: A retrospective analysis of the SEER database.

BACKGROUND: The prognostic factors for survival in patients with ependymoma (EPN) remain controversial. The aim of this study was to establish a prognostic model for 5- and 10-year survival probability nomograms for patients with EPN. METHODS: Clinical data from the Surveillance, Epidemiology, and End Results (SEER) database were used for patients diagnosed with ependymoma between 2000 and 2018 and were randomized 7:3 into a development set and a validation set. Factors significantly associated with prognosis were screened out using the least absolute shrinkage and selection operator (LASSO) regression. The calibration chart and consistency index (C-index) are used to evaluate the discrimination and consistency of the prediction model. Decision curve analysis (DCA) was used to further evaluate the established model. Finally, prognostic factors selected by LASSO regression were evaluated using Kaplan-Meier (KM) survival curves. RESULTS: A total of 3820 patients were included in the prognostic model. Seven survival predictors were obtained by LASSO regression screening, including age, gender, morphology, location, size, laterality, and resection. The prognostic model of the nomogram showed moderate discriminative ability in the development group and the validation group, with a C-index of 0.642 and 0.615, respectively. In the development set and validation set survival curves, the prognosis index of high risk was less effective than low risk (p < 0.001). CONCLUSIONS: Our nomograms may play an important role in predicting 5 and 10-year outcomes for patients with ependymoma. This will help assist clinicians in personalized medicine.

Oligomer Formation and Insecticidal Activity of Bacillus thuringiensis Vip3Aa Toxin.

Bacillus thuringiensis (Bt) Vip3A proteins are important insecticidal proteins used for control of lepidopteran insects. However, the mode of action of Vip3A toxin is still unclear. In this study, the amino acid residue S164 in Vip3Aa was identified to be critical for the toxicity in Spodoptera litura. Results from substitution mutations of the S164 indicate that the insecticidal activity of Vip3Aa correlated with the formation of a >240 kDa complex of the toxin upon proteolytic activation. The >240 kDa complex was found to be composed of the 19 kDa and the 65 kDa fragments of Vip3Aa. Substitution of the S164 in Vip3Aa protein with Ala or Pro resulted in loss of the >240 kDa complex and loss of toxicity in Spodoptera litura. In contrast, substitution of S164 with Thr did not affect the >240 kDa complex formation, and the toxicity of the mutant was only reduced by 35%. Therefore, the results from this study indicated that formation of the >240 kDa complex correlates with the toxicity of Vip3Aa in insects and the residue S164 is important for the formation of the complex.

Elevated serum uric acid and risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease: A meta-analysis.

BACKGROUND AND AIMS: Serum uric acid (SUA) has been recognized as an independent risk factor for mortality in the general population. We performed this meta-analysis to determine whether elevated SUA levels are associated with greater risk of cardiovascular or all-cause mortality in people with suspected or definite coronary artery disease (CAD). METHODS: The Pubmed and Embase databases were searched up to April 1, 2016 for the longitudinal studies that investigated the association between the elevated SUA and cardiovascular or all-cause mortality risk in people with suspected or definite CAD. Pooled adjusted risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated for the highest vs. the lowest SUA category or each 1 mg/ml SUA rise. RESULTS: Nine studies enrolling 25,229 participants were included in the analyses. The highest vs. lowest SUA category was associated with greater risk of cardiovascular mortality (RR 2.09; 95% CI: 1.45-3.02) and all-cause mortality (RR 1.80; 95% CI: 1.39-2.34) after adjustment for potential confounders in a random effects model. Moreover, each 1 mg/ml SUA rise significantly increased by 12% cardiovascular mortality and by 20% all-cause mortality. CONCLUSIONS: Elevated SUA levels are strongly and independently associated with greater risk of cardiovascular and all-cause mortality in people with suspected or definite CAD.

Contrast response functions with wide-view stimuli in the human visual cortex.

In this manuscript, using a novel wide-view visual presentation system that we developed for vision research and functional magnetic resonance imaging (fMRI), we studied contrast response functions in regions of the brain that are central and peripheral to the entire set of visual areas (V1, V2, V3, V3A, MT+), regions that have not been all investigated in previous vision research. Under the stimulus conditions which were 0-20 deg, 20-40 deg, and 40-60 deg eccentricity black-and-white checkerboard patterns, we measured the blood oxygenation level-dependent fMRI contrast response at five contrast levels (6, 12, 24, 48, and 96%) in the visual areas. On the basis of these data, the central and pericentral visual areas had low-contrast gain, whereas the peripheral visual areas had high-contrast gain. In addition, our results showed that the signals fundamentally shift during visual processing through posterior visual cortical areas (V1, V2, and V3) to superior visual cortical areas (V3A and MT+).

Pump power dependence of femtosecond two-color optical Kerr shutter measurements.

We investigated the pump power dependence of femtosecond two-color optical Kerr shutter (OKS) signals, which showed a damped sinusoidal variation with increasing pump power. The sinusoidal dependence was attributed to the polarization rotation caused by light-induced birefringence effect. The numerical analysis indicated that, the damping of OKS signal intensity could be attributed to the temporal profile change of probe pulse passing through the OKS setup, due to the non-uniform transient refractive index change induced by pump pulse. Because of the large phase shift of probe pulse, the time-resolved OKS signals showed modulated temporal intensity when pump power was increased.