Convolutional neural network-based automatic liver delineation on contrast-enhanced and non-contrast-enhanced CT images for radiotherapy planning

AimThis study evaluated a convolutional neural network (CNN) for automatically delineating the liver on contrast-enhanced or non-contrast-enhanced CT, making comparisons with a commercial automated technique (MIM Maestro®).BackgroundIntensity-modulated radiation therapy requires careful labor-intensive planning involving delineation of the target and organs on CT or MR images to ensure delivery of the effective dose to the target while avoiding organs at risk.Materials and MethodsContrast-enhanced planning CT images from 101 pancreatic cancer cases and accompanying mask images showing manually-delineated liver contours were used to train the CNN to segment the liver. The trained CNN then performed liver segmentation on a further 20 contrast-enhanced and 15 non-contrastenhanced CT image sets, producing three-dimensional mask images of the liver.ResultsFor both contrast-enhanced and non-contrast-enhanced images, the mean Dice similarity coefficients between CNN segmentations and ground-truth manual segmentations were significantly higher than those between ground-truth and MIM Maestro software (p

Estimation of Completion of Dormancy in Grapevine Bud Based on Cumulative Temperature

　This study was conducted to investigate the relationship between completion of dormancy of grapevine bud and temperature. Canes of ‘Kyoho’ and ‘Pione’ grapevines (Vitis labrusca×V. vinifera) grown in 7 vineyards with different temperature conditions, in Nagano, Northern Okayama, Yamanashi, Okayama, Okayama University, Fukuoka and Miyazaki, were collected at three different chilling exposures, December, January and February. These were then sent to Okayama University all at the same time. Cuttings with one bud were put into growth chambers kept at 25 or 30°C with 14 hours daylength, and budbreak in each cutting was surveyed at two day intervals for 60 days. Cumulative chilling hours (CCH) of exposure to below 7.2°C in each treatment time was largest in Nagano, followed in order by Northern Okayama, Yamanashi, Okayama, Okayama University, Fukuoka and Miyazaki. The CCH in Nagano was 2.5 to 4.8 times larger than in Miyazaki depending on the treatment time. The later the treatment time and the higher the temperature, the fewer were the number of days to first budbreak (NDFB) after treatment, irrespective of cultivar. A similar trend was observed in the number of days to 60% budbreak. In ‘Kyoho’ the NDFB was short in Nagano, Okayama University and Miyazaki, and longer in Okayama, Yamanashi and Fukuoka. In ‘Pione’ the NDFB was short in Fukuoka and Okayama University, and longer in Yamanashi and Okayama. The result was a weak negative correlation observed between CCH and NDFB in 4 of 7 vineyards. However, there was a strong positive correlation between NDFB and cumulative temperature (CT), a summation of temperature and hours of exposure to above 0°C from November 1 to treatment time and hours of exposure to 25 or 30°C from start of treatment to budbreak in each plot, in 6 vineyards excluding Miyazaki. The importance of estimating the completion of dormancy in grapevine bud based on CT is discussed.ブドウの芽の休眠完了と温度との関係を調査するため，温度条件の異なる７園（中信農試，山梨果試，岡山農試，岡山農試北部支場，岡山大学，福岡農試および宮崎）で栽培されている‘巨峰’と‘ピオーネ’から低温遭遇量の異なる３時期（12月，１月，２月）に結果母枝を採取した．直ちに岡山大学に送り，１芽を持つ挿し穂に調整した後，25または30℃のインキュベーター（14時間日長）に入れ，２日間隔で60日間発芽を調査した．処理開始時の7.2℃以下の遭遇量は中信農試で最も多く，次いで岡山農試北部支場，山梨果試，岡山農試，岡山大学，福岡農試，宮崎の順で，中信農試と宮崎では処理時期により2.5～4.8倍の差があった．発芽所要日数は，両品種とも処理時期が遅いほど，また温度が高いほど少なく，60％発芽所要日数もほぼ同様の傾向であった．‘巨峰’の発芽所用日数は中信農試，岡山大学および宮崎で少ない一方，岡山農試，山梨果試および福岡農試で多く，また‘ピオーネ’では福岡農試と岡山大学で少なく，山梨果試と岡山農試で多かった．７園のうち４園で低温遭遇量と発芽所要日数との間に負の相関がみられたが，相関係数は低かった．一方，11月以降処理開始までの０℃以上の温度の積算値と処理開始から発芽までの25または30℃での積算値を合計した積算温度と発芽所要日数との間には１園を除き極めて高い正の相関が認められた．これらの結果を基に，積算温度によるブドウの休眠完了予測の可能性を考察した

Management of Multiple Primary Lung Cancer in Patients with Centrally Located Early Cancer Lesions

BackgroundPatients with centrally located early lung cancer (CLELC) are often heavy smokers with a considerably high risk of multiple primary lung cancer (MPLC) lesions; treatment strategies for such patients must preserve the cardiopulmonary function.MethodsBetween July 2004 and July 2008, patients with CLELC underwent photodynamic therapy (PDT) using NPe6, second-generation photosensitizer at Tokyo Medical University Hospital. Among these patients, we retrospectively analyzed MPLC, which was treated by surgery plus PDT or PDT alone and examined the effectiveness of PDT, and we propose a treatment strategy for patients with MPLC.ResultsA total of 64 patients with CLECL received NPe6-PDT, and MPLCs were found in 22 patients (34.4%) using sputum cytology and a bronchoscopical examination using autofluorescence bronchoscopy. Among these 22 patients, 10 patients underwent surgery for primary lung cancer and underwent NPe6-PDT for the treatment of secondary primary CLELC, one patient underwent PDT for CLELC as a primary lesion followed by an operation for peripheral-type lung cancer as a secondary primary lesion, and 11 patients underwent PDT alone for MPLC lesions (28 lesions) that were roentgenographically occult lung cancers. Among these 22 patients with MPLC including peripheral-type lung cancers, which were resected by surgery, all 39 CLELC lesions exhibited a complete response after PDT, and all patients were alive.ConclusionsFor patients with lung cancer with a long-term history of smoking, careful follow-up examinations after surgical resection are needed considering the incidence of metachronous primary lung cancers. PDT can play an important role for the treatment strategy for MPLC

Nonsense mutation in CFAP43 causes normal-pressure hydrocephalus with ciliary abnormalities

OBJECTIVE: To identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH. METHODS:We performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene.Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus.RESULTS: In WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis.Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia. CONCLUSION: Our results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models

Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia