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

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

Lexical analysis on learners’ oral production of French

PDF/A形式により利用可能アクセス:WWWによる東京外国語大学大学院総合国際学研究科博士 (学術) 論文 (2013年11月)博甲第175号参考文献: p356-369その他のタイトルは英文要旨による東京外国語大学 (Tokyo University of Foreign Studies)博士 (学術

Evaluation of alkylating pyrrole-imidazole polyamide conjugates by a novel method for high-throughput sequencer

N-Methylpyrrole-N-methylimidazole (PI) polyamides are a class of DNA minor groove binders with DNA sequence-specificity. DNA-alkylating PI polyamide conjugates are attractive candidates as anticancer drugs acting through DNA damage and its subsequent inhibition of cell proliferation. One example is a chlorambucil-PI polyamide conjugate targeting the runt-related transcription factor (RUNX) family. RUNX1 has pro-oncogenic properties in acute myeloid leukemia, and recently the chlorambucil-PI polyamide conjugate was demonstrated to have anticancer effects. Herein, we apply another DNA-alkylating agent, seco-CBI, to target the consensus sequence of the RUNX family. Two types of CBI conjugates were prepared and their binding properties were characterized by Bind-n-Seq analysis using a high-throughput sequencer. The sequencing data were analyzed by two methods, MERMADE and our new MR (motif identification with a reference sequence), and the resultant binding motif logos were as predicted from the pairing rules proposed by Dervan et al. This is the first report to employ the MR method on alkylating PI polyamide conjugates. Moreover, cytotoxicity of conjugates 3 and 4 against a human non-small cell lung cancer, A549, were examined to show promising IC[50]s of 120 nm and 63 nm, respectively. These findings suggest seco-CBI-PI polyamide conjugates are candidates for oncological therapy

Strong and Specific Recognition of CAG/CTG Repeat DNA (5'-dWGCWGCW-3') by a Cyclic Pyrrole-Imidazole Polyamide

Abnormally expanded CAG/CTG repeat DNA sequences lead to a variety of neurological diseases, such as Huntington's disease. Here, we synthesized a cyclic pyrrole-imidazole polyamide (cPIP), which can bind to the minor groove of the CAG/CTG DNA sequence. The double-stranded DNA melting temperature (Tm ) and surface plasmon resonance assays revealed the high binding affinity of the cPIP. In addition, next-generation sequencing showed that the cPIP had high specificity for its target DNA sequence

Linear and non-linear associations of device-measured sedentary time with older adults' skeletal muscle mass

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole-body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on the metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2−/− mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 mediates prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cance

A Synthetic Transcriptional Activator of Genes Associated with the Retina in Human Dermal Fibroblasts.

Small molecules capable of modulating epigenetic signatures can activate the transcription of tissue-restricted genes in a totally unrelated cell type and have potential use in epigenetic therapy. To provide an example for an initial approach, we report here on one synthetic small-molecule compound-termed "SAHA-PIP X"-from our library of conjugates. This compound triggered histone acetylation accompanied by the transcription of retinal-tissue-related genes in human dermal fibroblasts (HDFs)

Joint associations of physical activity and screen time with overweight among japanese adults

Background: although both insufficient physical activity (PA) and high screen time (ST) are independent risk factors for obesity, how the combination of sufficient/insufficient PA and high/low ST could increase obesity risk among the adult population of Japan is not known. This study examined joint associations of PA and ST with overweight among Japanese adults. Methods: an Internet-based survey collected data on height, weight, self-reported time spent in PA and ST, and sociodemographic variables from 2832 adults. Respondents were categorized into sufficient PA/low ST, sufficient PA/high ST, insufficient PA/low ST, or insufficient PA/high ST categories as per public PA guidelines and the median of ST. Logistic regression analysis examined the odds ratios (OR) of being overweight (body mass index, ≥ 25 kg/m2) according to the categories of PA and ST. Results: in comparison with the sufficient PA/low ST category, participants in the insufficient PA/high ST category were significantly more likely overweight (OR, 1.48; 95% confidence interval [95%CI), 1.14, 1.93) after adjusting for sociodemographic variables. A significantly higher OR for overweight (including obesity) among insufficient PA/high ST category was also observed in men, but no significant association was found in women. Conclusions: both insufficient PA and prolonged ST contribute to overweight and obesity among Japanese adults. Public health initiatives addressing obesity in Japan need to consider both promoting PA and reducing ST, especially in me

Associations of sedentary behavior and physical activity with older adults’ physical function: an isotemporal substitution approach

BackgroundsThe purpose of this study was to examine, in a sample of Japanese older adults, the associations of objectively-assessed sedentary behavior (SB) and physical activity (PA) with performance-based physical function. The isotemporal substitution (IS) approach was used to model simultaneously the effects of the specific activity being performed and the activity being displaced, in an equal time-exchange manner.MethodsAmong 287 older adults (65–84 years), we used accelerometers to identify the daily average time spent on SB (≤1.5 METs); light-intensity PA (LIPA) (>1.5 to <3.0 METs); and moderate- to vigorous-intensity PA (MVPA) (≥3.0 METs). Physical function was assessed using five performance-based measures: hand grip strength, usual and maximum gait speeds, timed up and go, and one-legged stance with eyes open. We employed three linear regression models – a single-activity model, a partition model, and an IS model – to assess the associations of SB, LIPA, and MVPA with each of the five measures of physical function.ResultsThere were significant positive associations in the single-activity and partition models between MVPA and the measures of physical function (with the exception of hand grip strength). The IS models found that replacing SB or LIPA with MVPA was significantly and favorably associated with physical function measures.ConclusionsThese findings indicate that replacing small amounts of SB and LIPA with MVPA (such as 10 min) may contribute to improvements in older adults’ physical function

A questionnaire-based comparative study of postoperative quality of life between laryngotracheal separation and tracheoesophageal diversion

Purpose: Whether tracheoesophageal diversion (TED) is preferable to laryngotracheal separation (LTS) is unclear. This study examined the need for tracheoesophageal anastomosis by reviewing complications after TED and LTS and administering a questionnaire on postoperative quality of life.Patients and methods: Medical records of TED/LTS cases performed at a single institution from 2003 to 2015 were retrospectively reviewed and a questionnaire was administered to parents of patients at an outpatient visit.Results: A total of 40 TED and 18 LTS cases were included. Complications occurred in six TED cases and one LTS case, with no significant differences between groups (P=0.42). A total of 22 parents of patients (TED 16 cases; LTS six cases) completed the questionnaire. Voice production was reported in three TED cases and two LTS cases. Patients indicated that suctions were ‘decreased’ in 13 and ‘unchanged’ in two TED cases, but ‘decreased’ in one and ‘unchanged’ in five LTS cases (P=0.0055). Readmissions were ‘increased’ in one and ‘decreased’ in 14 TED cases, but ‘decreased’ in three and ‘unchanged’ in three LTS cases (P=0.015).Conclusion: Postoperative complication rate was equivalent between groups, and the numbers of suctions and readmissions were decreased in the TED group. Therefore, tracheoesophageal anastomosis should be performed more commonly.Keywords: complication, laryngotracheal separation, quality of life questionnaire, tracheoesophageal diversio

Targeting 24 bp within Telomere Repeat Sequences with Tandem Tetramer Pyrrole-Imidazole Polyamide Probes

Synthetic molecules that bind sequence-specifically to DNA have been developed for varied biological applications, including anticancer activity, regulation of gene expression, and visualization of specific genomic regions. Increasing the number of base pairs targeted by synthetic molecules strengthens their sequence specificity. Our group has been working on the development of pyrrole-imidazole polyamides that bind to the minor groove of DNA in a sequence-specific manner without causing denaturation. Recently, we reported a simple synthetic method of fluorescent tandem dimer polyamide probes composed of two hairpin moieties with a linking hinge, which bound to 12 bp in human telomeric repeats (5′-(TTAGGG)n-3′) and could be used to specifically visualize telomeres in chemically fixed cells under mild conditions. We also performed structural optimization and extension of the target base pairs to allow more specific staining of telomeres. In the present study, we synthesized tandem tetramer polyamides composed of four hairpin moieties, targeting 24 bp in telomeric repeats, the longest reported binding site for synthetic, non-nucleic-acid-based, sequence-specific DNA-binding molecules. The novel tandem tetramers bound with a nanomolar dissociation constant to 24 bp sequences made up of four telomeric repeats. Fluorescently labeled tandem tetramer polyamide probes could visualize human telomeres in chemically fixed cells with lower background signals than polyamide probes reported previously, suggesting that they had higher specificity for telomeres. Furthermore, high-throughput sequencing of human genomic DNA pulled down by the biotin-labeled tandem tetramer polyamide probe confirmed its effective binding to telomeric repeats in the complex chromatinized genome