The hallmark of mechanosensory hair cells is the stereocilia, where mechanical stimuli are converted into electrical signals. These delicate stereocilia are susceptible to acoustic trauma and ...ototoxic drugs. While hair cells in lower vertebrates and the mammalian vestibular system can spontaneously regenerate lost stereocilia, mammalian cochlear hair cells no longer retain this capability. We explored the possibility of regenerating stereocilia in the noise-deafened guinea pig cochlea by cochlear inoculation of a viral vector carrying Atoh1, a gene critical for hair cell differentiation. Exposure to simulated gunfire resulted in a 60-70 dB hearing loss and extensive damage and loss of stereocilia bundles of both inner and outer hair cells along the entire cochlear length. However, most injured hair cells remained in the organ of Corti for up to 10 days after the trauma. A viral vector carrying an EGFP-labeled Atoh1 gene was inoculated into the cochlea through the round window on the seventh day after noise exposure. Auditory brainstem response measured one month after inoculation showed that hearing thresholds were substantially improved. Scanning electron microscopy revealed that the damaged/lost stereocilia bundles were repaired or regenerated after Atoh1 treatment, suggesting that Atoh1 was able to induce repair/regeneration of the damaged or lost stereocilia. Therefore, our studies revealed a new role of Atoh1 as a gene critical for promoting repair/regeneration of stereocilia and maintaining injured hair cells in the adult mammal cochlea. Atoh1-based gene therapy, therefore, has the potential to treat noise-induced hearing loss if the treatment is carried out before hair cells die.
Background
Computed tomography (CT) is essential for pulmonary nodule detection in diagnosing lung cancer. As deep learning algorithms have recently been regarded as a promising technique in medical ...fields, we attempt to integrate a well‐trained deep learning algorithm to detect and classify pulmonary nodules derived from clinical CT images.
Materials and Methods
Open‐source data sets and multicenter data sets have been used in this study. A three‐dimensional convolutional neural network (CNN) was designed to detect pulmonary nodules and classify them into malignant or benign diseases based on pathologically and laboratory proven results.
Results
The sensitivity and specificity of this well‐trained model were found to be 84.4% (95% confidence interval CI, 80.5%–88.3%) and 83.0% (95% CI, 79.5%–86.5%), respectively. Subgroup analysis of smaller nodules (<10 mm) have demonstrated remarkable sensitivity and specificity, similar to that of larger nodules (10–30 mm). Additional model validation was implemented by comparing manual assessments done by different ranks of doctors with those performed by three‐dimensional CNN. The results show that the performance of the CNN model was superior to manual assessment.
Conclusion
Under the companion diagnostics, the three‐dimensional CNN with a deep learning algorithm may assist radiologists in the future by providing accurate and timely information for diagnosing pulmonary nodules in regular clinical practices.
Implications for Practice
The three‐dimensional convolutional neural network described in this article demonstrated both high sensitivity and high specificity in classifying pulmonary nodules regardless of diameters as well as superiority compared with manual assessment. Although it still warrants further improvement and validation in larger screening cohorts, its clinical application could definitely facilitate and assist doctors in clinical practice.
摘要
背景。在肺癌的诊断中，计算机断层扫描 (CT) 对于肺结节的检测必不可少。近几年，随着医学领域逐渐认识到深度学习算法这种技术的价值，本研究试图集成一种训练有素的深度学习算法，对临床 CT 图像中的肺结节进行检测和分类。
材料和方法。本研究使用了开源数据集和多中心数据集。本文设计了一种三维卷积神经网络 (CNN) 来检测肺结节，然后根据病理和实验室证实的结果，判断为恶性或良性结节。
结果。这种训练有素的模型敏感性和特异性分别为 84.4% 95% 可信区间 (CI)， 80.5%‐88.3%和83.0%(95% CI，79.5%‐86.5%)。小结节 (< 10mm) 亚组分析显示的敏感性和特异性显著，与大结节 (10‐30mm) 相似。对比不同级别医生的人工评估结果与三维 CNN 的评估结果，进行了额外的模型验证。结果表明，CNN 模型的表现优于人工评估。
结论。通过伴随诊断可知，加入深度学习算法的三维 CNN 能够提供准确、及时的信息，有助于放射科医生在常规临床实践中的肺结节诊断工作。
实践意义:在对各种直径的肺结节分类中，本文所述的三维卷积神经网络具有较高的敏感性和特异性，与人工评估结果相比具有优越性。虽然仍需在更大的筛选队列中进行进一步改进和验证，但可以肯定的是，临床应用三维卷积神经网络可以促进和协助医生的临床实践工作。
Interest in deep convolutional neural networks (CNN) is growing because of demonstrated accuracy with less manual intervention in computer vision tasks. This article describes efforts to use a pre‐trained CNN model integrating with multi‐centers datasets for detection and classification of pulmonary nodules.
Hong Qu glutinous rice wine (HQGRW), as one of the most typical representatives of Chinese rice wine, is generally brewed from glutinous rice by adding two traditional wine fermentation starters—Hong ...Qu (HQ) and Bai Qu (BQ). The objective of this study was to determine the microbial communities and volatile metabolites of different traditional fermentation starters for HQGRW, and elucidate the potential correlation between microbiota and volatile metabolites. Both heatmap and principal component analysis (PCA) revealed the significant variances in volatile profiles among different wine starters. Microbiological analysis based on high-throughput sequencing (HTS) technology demonstrated that both of bacterial and fungal communities varied significantly in different starters. HQ was dominated mainly by bacteria of Bacillus ginsengihumi (20.17%), Pantoea sp. (10.39%), Elizabethkingia sp. (5.52%), Streptococcus sp. (5.03%) Brevundimonas sp. (3.03%), Rickettsia prowazekii (2.94%), Thermus thermophilus (2.54%), Bacillus amyloliquefaciens (1.48%), Bacillus aryabhattai (1.42%); fungi of Monascus purpureus (39.7%), Aspergillus niger (27.35%), Xeromyces bisporus (8.39%), Aspergillus penicillioides (6.89%), Aspergillus flavus (2.33%) and Pichia farinose (0.79%). By contrast, BQ contained much higher proportions of bacteria of Lactococcus lactis (10.45%), Lactobacillus brevis (9.99%), Pediococcus pentosaceus (8.29%), Weissella paramesenteroides (6.69%), Lactobacillus fermentum (4.83%), Gluconobacter thailandicus (3.93%), Lactobacillus alimentarius (3.59%), fungi of Rhizopus arrhizus (31.47%), Saccharomycopsis fibuligera (27.86%), Aspergillus niger (20.81%), Issatchenkia orientalis (3.79%), Saccharomycopsis malanga (3.15%), Clavispora lusitaniae (2.29%), Candida tropicalis (1.47%), Saccharomyces cerevisiae (1.11%) and Rhizopus microsporus (0.57%). Furthermore, core functional microbiota that might contribute to volatile flavour development was explored through Spearman's correlation-based network analysis. Lactobacillus brevis, Lactobacillus alimentarius, Lactobacillus plantarum and Aspergillus niger were found to be strongly associated with acid compounds (FDR adjusted P < 0.01), while Pichia sp., Candida sp., Monascus purpureus, Lactobacillus brevis and Lactobacillus alimentarius were positively correlated with concentrations of aromatic esters associated with fruity and floral notes (FDR adjusted P < 0.01), implying that these microorganisms might make significant contributions to the flavour of rice wine. These findings demonstrated that the aromatic quality of HQGRW may be critically influenced by the microbiota in traditional fermentation starters. To conclude, this study would contribute to the development of novel defined starter cultures for improving the aromatic quality of HQGRW.
Display omitted
•HQGRW is brewed with two traditional fermentation starters—Hong Qu (HQ) and Bai Qu (BQ).•BQ was mainly dominated by L. lactis, L. brevis, R. arrhizus, and S. fibuligera.•HQ was mainly dominated by B. ginsengihumi, Pantoea sp., M. purpureus, and A. niger.•Microbial communities varied significantly in different traditional fermentation starters.•L. brevis, L. alimentarius, R. microspores, and M. purpureus were related to volatile alcohols and esters.
Despite the great agricultural and ecological importance of efficient use of urea-containing nitrogen fertilizers by crops, molecular and physiological identities of urea transport in higher plants ...have been investigated only in Arabidopsis.
We performed short-time urea-influx assays which have identified a low-affinity and high-affinity (K
m of 7.55 μM) transport system for urea-uptake by rice roots (Oryza sativa).
A high-affinity urea transporter OsDUR3 from rice was functionally characterized here for the first time among crops. OsDUR3 encodes an integral membrane-protein with 721 amino acid residues and 15 predicted transmembrane domains. Heterologous expression demonstrated that OsDUR3 restored yeast dur3-mutant growth on urea and facilitated urea import with a K
m of c. 10 μM in Xenopus oocytes.
Quantitative reverse-transcription polymerase chain reaction (qPCR) analysis revealed upregulation of OsDUR3 in rice roots under nitrogen-deficiency and urea-resupply after nitrogen-starvation. Importantly, overexpression of OsDUR3 complemented the Arabidopsis atdur3-1 mutant, improving growth on low urea and increasing root urea-uptake markedly. Together with its plasma membrane localization detected by green fluorescent protein (GFP)-tagging and with findings that disruption of OsDUR3 by T-DNA reduces rice growth on urea and urea uptake, we suggest that OsDUR3 is an active urea transporter that plays a significant role in effective urea acquisition and utilisation in rice.
Abstract
Context
While fibrosis in endometriosis has recently loomed prominently, the sources of myofibroblasts, the principal effector cell in fibrotic diseases, remain largely obscure. Mesothelial ...cells (MCs) can be converted into myofibroblasts through mesothelial-mesenchymal transition (MMT) in many fibrotic diseases and adhesion.
Objective
To evaluate whether MCs contribute to the progression and fibrogenesis in endometriosis through MMT.
Setting, Design, Patients, Intervention, And Main Outcome Measures
Dual immunofluorescence staining and immunohistochemistry using antibodies against calretinin, Wilms’ tumor-1 (WT-1), and α-smooth muscle actin (α-SMA) were performed on lesion samples from 30 patients each with ovarian endometrioma (OE) and deep endometriosis (DE), and 30 normal endometrial (NE) tissue samples. Human pleural and peritoneal MCs were co-cultured with activated platelets or control medium with and without neutralization of transforming growth factor β1 (TGF-β1) and/or platelet-derived growth factor receptor (PDGFR) and their morphology, proliferation, and expression levels of genes and proteins known to be involved in MMT were evaluated, along with their migratory and invasive propensity, contractility, and collagen production.
Results
The number of calretinin/WT-1 and α-SMA dual-positive fibroblasts in OE/DE lesions was significantly higher than NE samples. The extent of lesional fibrosis correlated positively with the lesional α-SMA staining levels. Human MCs co-cultured with activated platelets acquire a morphology suggestive of MMT, concomitant with increased proliferation, loss of calretinin expression, and marked increase in expression of mesenchymal markers. These changes coincided with functional differentiation as reflected by increased migratory and invasive capacity, contractility, and collagen production. Neutralization of TGF-β1 and PDGFR signaling abolished platelet-induced MMT in MCs.
Conclusions
MCs contribute to lesional progression and fibrosis through platelet-induced MMT.
We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
What's new?
Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
The relative importance of alternatives expressed in terms of interval numbers in the fuzzy analytic hierarchy process aims to capture the uncertainty experienced by decision makers (DMs) when making ...a series of comparisons. Under the assumption of full rationality, the judgements of DMs in the typical analytic hierarchy process could be consistent. However, since the uncertainty in articulating the opinions of DMs is unavoidable, the interval number judgements are associated with the limited rationality. In this paper, we investigate the concept of limited rationality by introducing interval multiplicative reciprocal comparison matrices. By analyzing the consistency of interval multiplicative reciprocal comparison matrices, it is observed that the interval number judgements are inconsistent. By considering the permutations of alternatives, the concepts of approximation-consistency and acceptable approximation-consistency of interval multiplicative reciprocal comparison matrices are proposed. The exchange method is designed to generate all the permutations. A novel method of determining the interval weight vector is proposed under the consideration of randomness in comparing alternatives, and a vector of interval weights is determined. A new algorithm of solving decision making problems with interval multiplicative reciprocal preference relations is provided. Two numerical examples are carried out to illustrate the proposed approach and offer a comparison with the methods available in the literature.
Intercropping is one of the most vital practice to improve land utilization rate in China that has limited arable land resource. However, the traditional intercropping systems have many disadvantages ...including illogical field lay-out of crops, low economic value, and labor deficiency, which cannot balance the crop production and agricultural sustainability. In view of this, we developed a novel soybean strip intercropping model using maize as the partner, the regular maize-soybean strip intercropping mainly popularized in northern China and maize-soybean relay-strip intercropping principally extended in southwestern China. Compared to the traditional maize-soybean intercropping systems, the main innovation of field lay-out style in our present intercropping systems is that the distance of two adjacent maize rows are shrunk as a narrow strip, and a strip called wide strip between two adjacent narrow strips is expanded reserving for the growth of two or three rows of soybean plants. The distance between outer rows of maize and soybean strips are expanded enough for light use efficiency improvement and tractors working in the soybean strips. Importantly, optimal cultivar screening and increase of plant density achieved a high yield of both the two crops in the intercropping systems and increased land equivalent ratio as high as 2.2. Annually alternative rotation of the adjacent maize- and soybean-strips increased the grain yield of next seasonal maize, improved the absorption of nitrogen, phosphorus, and potasium of maize, while prevented the continuous cropping obstacles. Extra soybean production was obtained without affecting maize yield in our strip intercropping systems, which balanced the high crop production and agricultural sustainability.
PDF
