127 research outputs found

    Computer-aided diagnosis of lung nodule using gradient tree boosting and Bayesian optimization

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    We aimed to evaluate computer-aided diagnosis (CADx) system for lung nodule classification focusing on (i) usefulness of gradient tree boosting (XGBoost) and (ii) effectiveness of parameter optimization using Bayesian optimization (Tree Parzen Estimator, TPE) and random search. 99 lung nodules (62 lung cancers and 37 benign lung nodules) were included from public databases of CT images. A variant of local binary pattern was used for calculating feature vectors. Support vector machine (SVM) or XGBoost was trained using the feature vectors and their labels. TPE or random search was used for parameter optimization of SVM and XGBoost. Leave-one-out cross-validation was used for optimizing and evaluating the performance of our CADx system. Performance was evaluated using area under the curve (AUC) of receiver operating characteristic analysis. AUC was calculated 10 times, and its average was obtained. The best averaged AUC of SVM and XGBoost were 0.850 and 0.896, respectively; both were obtained using TPE. XGBoost was generally superior to SVM. Optimal parameters for achieving high AUC were obtained with fewer numbers of trials when using TPE, compared with random search. In conclusion, XGBoost was better than SVM for classifying lung nodules. TPE was more efficient than random search for parameter optimization.Comment: 29 pages, 4 figure

    Differences in clinicopathologic features and subtype distribution of invasive breast cancer between women older and younger than 40 years

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    OBJECTIVES: We investigated and compared clinicopathologic features and subtype distribution of invasive breast cancer among women <40 and ≥40 years of age. METHODS: We retrospectively compared clinicopathologic characteristics and subtype distribution of invasive breast cancer in women <40 and ≥40 years of age, in a cohort of 1,130 patients. Subtypes included luminal A (positive for hormone receptors [HR]—estrogen receptor [ER] and/or progesterone receptor [PR]—and negative for human epidermal growth factor receptor 2 [HER2] with low Ki67), luminal B (HER2(–)) (HR(+)/HER2(–)/Ki67(High)), luminal B (HER2(+)) (HR(+)/HER2(+)), HER2-overexpressing (HR(–)/HER2(+)), and triple negative (ER(–)/PR(–)/HER2(–)). RESULTS: Breast cancers in younger women had unfavorable clinicopathologic characteristics, including larger tumors and more frequent node involvement. Subtypes among the 1,130 tumors were luminal A: 36.4%, luminal B (HER2(–)): 35.0%, luminal B (HER2(+)): 7.5%, HER2-overexpressing: 7.1%, and triple negative: 14.0%. The age groups significantly differed in subtype distribution (P<0.001). Luminal A subtype was more common in the older group (38.5%) than the younger group (16.2%), and luminal B (HER2(–)) was more common in the younger group (52.2%) than in the older group (33.2%; P<0.001). CONCLUSIONS: Breast cancers in women younger than 40 years have unfavorable clinicopathologic characteristics and are more likely to be luminal B (HER2(–)) and less likely to be luminal A than breast cancers in older women

    Repression of interleukin-4 in T helper type 1 cells by Runx/Cbfβ binding to the Il4 silencer

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    Interferon γ (IFNγ) is the hallmark cytokine produced by T helper type 1 (Th1) cells, whereas interleukin (IL)-4 is the hallmark cytokine produced by Th2 cells. Although previous studies have revealed the roles of cytokine signaling and of transcription factors during differentiation of Th1 or Th2 cells, it is unclear how the exclusive expression pattern of each hallmark cytokine is established. The DNaseI hypersensitivity site IV within the mouse Il4 locus plays an important role in the repression of Il4 expression in Th1 cells, and it has been named the Il4 silencer. Using Cbfβ- or Runx3-deficient T cells, we show that loss of Runx complex function results in derepression of IL-4 in Th1 cells. Binding of Runx complexes to the Il4 silencer was detected in naive CD4+ T cells and Th1 cells, but not in Th2 cells. Furthermore, enforced expression of GATA-3 in Th1 cells inhibited binding of Runx complexes to the Il4 silencer. Interestingly, T cell–specific inactivation of the Cbfβ gene in mice led to elevated serum immunoglobulin E and airway infiltration. These results demonstrate critical roles of Runx complexes in regulating immune responses, at least in part, through the repression of the Il4 gene

    Chemotherapy with low-dose capecitabine as palliative treatment in a patient with metastatic breast cancer: a case report

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    Chemotherapeutic agents are rarely used for symptom management in patients under palliative care setting. This is because chemotherapeutic agents not only have limited efficacy in palliative treatment but are also known to exert severe adverse effects. We describe our experience with a patient with metastatic breast cancer who was successfully treated with low-dose capecitabine, without the development of any severe toxicities and with significant improvement in activities of daily living (ADL) and quality of life (QOL)

    S-Nitrosated alpha-1-acid glycoprotein exhibits antibacterial activity against multidrug-resistant bacteria strains and synergistically enhances the effect of antibiotics

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    Alpha-1-acid glycoprotein (AGP) is a major acute-phase protein. Biosynthesis of AGP increases markedly during inflammation and infection, similar to nitric oxide (NO) biosynthesis. AGP variant A (AGP) contains a reduced cysteine (Cys149). Previously, we reported that S-nitrosated AGP (SNO-AGP) synthesized by reaction with a NO donor, possessed very strong broad-spectrum antimicrobial activity (IC50 = 10−9-10−6 M). In this study, using a cecal ligation and puncture animal model, we confirmed that AGP can be endogenously S-nitrosated during infection. Furthermore, we examined the antibacterial property of SNO-AGP against multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa to investigate the involvement of SNO-AGP in the host defense system. Our results showed that SNO-AGP could inhibit multidrug efflux pump, AcrAB-TolC, a major contributor to bacterial multidrug resistance. In addition, SNO-AGP decreased biofilm formation and ATP level in bacteria, indicating that SNO-AGP can revert drug resistance. It was also noteworthy that SNO-AGP showed synergistic effects with the existing antibiotics (oxacillin, imipenem, norfloxacin, erythromycin, and tetracycline). In conclusion, SNO-AGP participated in the host defense system and has potential as a novel agent for single or combination antimicrobial therapy
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