A generative adversarial neural network with multi-attention feature extraction for fundus lesion segmentation.

PURPOSE: Fundus lesion segmentation determines the location and size of diabetes retinopathy in fundus image, which assists doctors in developing the best eye treatment plan. However, owing to the scattered distribution and the similarity of lesions, it is extremely difficult to extract representative lesions feature and accurately segment lesions area. METHODS: To solve the thorny problem, a generative adversarial network with multi-attention feature extraction is developed to segment diabetic retinopathy region. The main contributions are as follows: (1) An improved residual U-Net network combining with self-attention mechanism is designed as generative network to fully extract local and global feature of lesions while reducing the loss of key feature information. Considering the correlation between the same lesions feature of different samples, external attention mechanism is introduced in the residual U-Net network to focus on the relevant features of the same lesions in different samples throughout the entire dataset. (2) A discriminative network based on the PatchGAN structure is designed to further enhance the segmentation ability of generation network by discriminating between true and false samples. RESULTS: The proposed network is evaluated on the public dataset IDRiD, which achieved the Dice correlation coefficients of 75.7%, 76.53%, 50.06%, and 45.89% for EX, SE, MA, and HE, respectively. CONCLUSION: The experimental results show the generative adversarial neural network qualified for accurate segmentation of diabetic retinopathy from fundus image well.

Effect of pulse duration on the above-threshold ionization of a hydrogen atom irradiated by a 400 nm intense laser.

The photoelectron emission spectra generated by the interaction between ultrashort intense laser pulses and atoms can reveal the ultrafast dynamics of electrons. By using the numerical solution of the time-dependent Schrödinger equation in momentum space, the photoelectron emission spectra of atoms irradiated by 400 nm intense lasers with different durations of the pulse has been investigated. In the photoelectron emission spectrum, in addition to the above-threshold ionization peaks due to ionization interference in multiple cycles and the sideband peaks mainly due to the interference of ionized electrons at different moments along the rising edge of the laser pulse envelope, additional peaks of photoelectron emission whose intensity appears to oscillate with the increasing duration of the laser pulse can also be observed. Based on strong-field approximation and the population's analysis of the bound state, it is found that these photoelectron peaks originate from the ionization of the excited state and the oscillations of these peaks are due to the superposition of their peak energy positions with the sideband energy positions. Furthermore, it is demonstrated that the energy positions of the maximum intensity of the photoelectron emission spectra move towards the higher energy end as the duration of the driving laser pulse extends. This phenomenon can be attributed to the fact that the main moment of ionization of atoms changes with the increasing duration of the driving laser pulse, thus allowing the real-time ionization of atoms to be probed using photoelectron emission spectra.

Multi-Modal Feature Fusion-Based Multi-Branch Classification Network for Pulmonary Nodule Malignancy Suspiciousness Diagnosis.

Detecting and identifying malignant nodules on chest computed tomography (CT) plays an important role in the early diagnosis and timely treatment of lung cancer, which can greatly reduce the number of deaths worldwide. In view of the existing methods in pulmonary nodule diagnosis, the importance of clinical radiological structured data (laboratory examination, radiological data) is ignored for the accuracy judgment of patients' condition. Hence, a multi-modal fusion multi-branch classification network is constructed to detect and classify pulmonary nodules in this work: (1) Radiological data of pulmonary nodules are used to construct structured features of length 9. (2) A multi-branch fusion-based effective attention mechanism network is designed for 3D CT Patch unstructured data, which uses 3D ECA-ResNet to dynamically adjust the extracted features. In addition, feature maps with different receptive fields from multi-layer are fully fused to obtain representative multi-scale unstructured features. (3) Multi-modal feature fusion of structured data and unstructured data is performed to distinguish benign and malignant nodules. Numerous experimental results show that this advanced network can effectively classify the benign and malignant pulmonary nodules for clinical diagnosis, which achieves the highest accuracy (94.89%), sensitivity (94.91%), and F1-score (94.65%) and lowest false positive rate (5.55%).

Influence of multiphoton resonance excitation on the above-threshold ionization of a hydrogen atom.

The photo-electron emission of a hydrogen atom irradiated by an ultraviolet laser pulse is investigated by numerically solving the time-dependent Schrödinger equation in momentum space. A subpeak structure with high intensity is observed in the photo-electron emission spectrum, and the peak of the enhanced structure shifts to a higher energy as the laser intensity increases. Through the strong-field approximation and the analysis of the population of the bound state , it is found that this subpeak structure is generated from the interference between the ionized electrons from the ground state and the ionized electrons from the 2p state after the resonant transition from the ground state to the 2p state. Analyzing the change rule of the photo-electron emission spectrum can further deepen the understanding of the energy change of the dressed bound state for an atom irradiated by an intense laser pulse.

Evaluation of a tablet-based assessment tool for measuring cognition among children 4-6 years of age in Ghana.

OBJECTIVES: To investigate several basic psychometric properties, including construct, convergent and discriminant validity, of the tablet-based Rapid Assessment of Cognitive and Emotional Regulation (RACER) among children aged 4-6 years in Ghana. METHODS: We investigated whether RACER tasks administered to children in Ghana could successfully reproduce expected patterns of performance previously found in high-income countries on similar tasks assessing inhibitory control (e.g., slower responses on inhibition trials), declarative memory (e.g., higher accuracy on previously seen items), and procedural memory (e.g., faster responses on sequence blocks). Next, we assessed the validity of declarative memory and inhibitory control scores by examining associations of these scores with corresponding paper-based test scores and increasing child age. Lastly, we examined whether RACER was more sensitive than paper-based tests to environmental risk factors common in low- and middle-income countries (LMICs). RESULTS: Of the 966 children enrolled, more than 96% completed the declarative memory and inhibitory control tasks; however, around 30% of children were excluded from data analysis on the procedural memory task due to missing more than half of trials. The performance of children in Ghana replicated previously documented patterns of performance. RACER inhibitory control accuracy score was significantly correlated with child age (r (929) = .09, p = .007). However, our findings did not support other hypotheses. CONCLUSIONS: The high task completion rates and replication of expected patterns support that certain RACER sub-tasks are feasible for measuring child cognitive development in LMIC settings. However, this study did not provide evidence to support that RACER is a valid tool to capture meaningful individual differences among children aged 4-6 years in Ghana.

An efficient multi-path 3D convolutional neural network for false-positive reduction of pulmonary nodule detection.

PURPOSE: Considering that false-positive and true pulmonary nodules are highly similar in shapes and sizes between lung computed tomography scans, we develop and evaluate a false-positive nodules reduction method applied to the computer-aided diagnosis system. METHODS: To improve the pulmonary nodule diagnosis quality, a 3D convolutional neural networks (CNN) model is constructed to effectively extract spatial information of candidate nodule features through the hierarchical architecture. Furthermore, three paths corresponding to three receptive field sizes are adopted and concatenated in the network model, so that the feature information is fully extracted and fused to actively adapting to the changes in shapes, sizes, and contextual information between pulmonary nodules. In this way, the false-positive reduction is well implemented in pulmonary nodule detection. RESULTS: Multi-path 3D CNN is performed on LUNA16 dataset, which achieves an average competitive performance metric score of 0.881, and excellent sensitivity of 0.952 and 0.962 occurs to 4, 8 FP/Scans. CONCLUSION: By constructing a multi-path 3D CNN to fully extract candidate target features, it accurately identifies pulmonary nodules with different sizes, shapes, and background information. In addition, the proposed general framework is also suitable for similar 3D medical image classification tasks.

[Correlation Between Microplastics Pollution and Eutrophication in the Near Shore Waters of Dianchi Lake].

Microplastics have been found in many environmental media such as sea water, coastal tidal flats, terrestrial water, sediments, and organisms. Microplastics pollution in inland freshwater lakes have received extensive attention; however, the correlation between eutrophication and microplastics pollution in freshwater lakes remains unclear. In this study, 24 sampling sites were set up in the near shore surface waters of Dianchi Lake, and the pollution characteristics of microplastics such as abundance, composition, particle size, color, and form were evaluated. Water quality parameters related to eutrophication state were analyzed, and the eutrophication indices were further calculated. Specifically, sample pre-treatment was conducted according to the method issued by National Oceanic and Atmospheric Administration (NOAA) of the United States. The color and morphological characteristics of microplastic samples were observed using a stereoscopic microscope, and counts and particle size measurements were performed using Nano Measure 1.2 software. Parts of the samples were selected, and the polymer composition analysis was performed using micro-Fourier Transform infrared (µ-FTIR) spectroscopy. The indices related to eutrophication level evaluation were tested according to the experimental standard methods issued by the Ministry of Ecology and Environment of China. The results showed that the abundance of microplastics in the near shore waters of Dianchi Lake was between 800 and 6000 n·m-3, with an average value of 2867 n·m-3. The types of polymers detected were polyethylene terephthalate (PET), polyetherurethane (PEU), polypropylene (PP), polyethylene (PE), and polyvinyl acetate (PVAc), respectively. The diameter proportion of microplastics in the range of 0.2-0.5 mm was the highest. Fiber microplastics accounted for the most observed type, followed by fragments and films. Among the 24 monitoring sites, it was found that proportions of severe, moderate, and mild eutrophication and mesotrophication sites accounted for 8.33%, 58.33%, 29.17%, and 4.17% of the total sampling sites, respectively, and the main pollutant was total nitrogen (TN). Microplastics abundances in the near shore waters of Dianchi Lake were significantly positively correlated with TN concentrations (P<0.01), whereas they were negatively correlated with chlorophyll a(Chl-a)concentrations, not reaching a significant level (P>0.05). The microplastics abundance and TN concentrations in the north bank water near the main urban area of Kunming were significantly higher than those in the other three banks. Microplastics and TN were considered to potentially have the same origin and be attributed to the tail water discharge from WWTPs.

Applying Item Response Theory Modeling to Identify Social (Pragmatic) Communication Disorder.

Purpose No diagnostic tools exist for identifying social (pragmatic) communication disorder (SPCD), a new Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition category for individuals with social communication deficits but not the repetitive, restricted behaviors and interests (RRBIs) that would qualify them for a diagnosis of autism spectrum disorder (ASD). We explored the value of items from a widely used screening measure of ASD for distinguishing SPCD from typical controls (TC; Aim 1) and from ASD (Aim 2). Method We applied item response theory (IRT) modeling to Social Communication Questionnaire-Lifetime (Rutter, Bailey, & Lord, 2003) records available in the National Database for Autism Research. We defined records from putative SPCD (n = 54), ASD (n = 278), and TC (n = 274) groups retrospectively, based on National Database for Autism Research classifications and Autism Diagnostic Interview-Revised responses. After assessing model assumptions, estimating model parameters, and measuring model fit, we identified items in the social communication and RRBI domains that were maximally informative in differentiating the groups. Results IRT modeling identified a set of seven social communication items that distinguished SPCD from TC with sensitivity and specificity > 80%. A set of five RRBI items was less successful in distinguishing SPCD from ASD (sensitivity and specificity < 70%). Conclusion The IRT modeling approach and the Social Communication Questionnaire-Lifetime item sets it identified may be useful in efforts to construct screening and diagnostic measures for SPCD.

Immunohistochemical quantification of expression of a tight junction protein, claudin-7, in human lung cancer samples using digital image analysis method.

BACKGROUND AND OBJECTIVES: Tight junction proteins are correlated with cancer development. As the pivotal proteins in epithelial cells, altered expression and distribution of different claudins have been reported in a wide variety of human malignancies. We have previously reported that claudin-7 was strongly expressed in benign bronchial epithelial cells at the cell-cell junction while expression of claudin-7 was either altered with discontinued weak expression or completely absent in lung cancers. Based on these results, we continued working on the expression pattern of claudin-7 and its relationship with lung cancer development. We herein proposed a new Digital Image Classification, Fragmentation index, Morphological analysis (DICFM) method for differentiating the normal lung tissues and lung cancer tissues based on the claudin-7 immunohistochemical staining. METHODS: Seventy-seven lung cancer samples were obtained from the Second Affiliated Hospital of Zhejiang University and claudin-7 immunohistochemical staining was performed. Based on C++ and Open Source Computer Vision Library (OpenCV, version 2.4.4), the DICFM processing module was developed. Intensity and fragmentation of claudin-7 expression, as well as the morphological parameters of nuclei were calculated. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis. RESULTS: Agreement between these computational results and the results obtained by two pathologists was demonstrated. The intensity of claudin-7 expression was significantly decreased while the fragmentation was significantly increased in the lung cancer tissues compared to the normal lung tissues and the intensity was strongly positively associated with the differentiation of lung cancer cells. Moreover, the perimeters of the nuclei of lung cancer cells were significantly greater than that of the normal lung cells, while the parameters of area and circularity revealed no statistical significance. CONCLUSIONS: Taken together, our DICFM approach may be applied as an appropriate approach to quantify the immunohistochemical staining of claudin-7 on the cell membrane and claudin-7 may serve as a marker for identification of lung cancer.

Measuring the Diagnostic Features of Social (Pragmatic) Communication Disorder: An Exploratory Study.

Purpose: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition introduced a new neurodevelopmental disorder, social (pragmatic) communication disorder (SPCD), that is characterized by deficits in 4 areas of communication. Although descriptions of these areas are provided, no assessment tools for SPCD are recommended. The purpose of this study was to examine the extent to which items from measurement tools commonly used in assessing pragmatic language impairment and related disorders might be useful in assessing the characteristics of social communication that define SPCD in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Method: Based on a literature search, 594 items from assessment tools commonly used to measure social communication abilities in people with pragmatic language impairment were identified. The first author judged whether each item reflected 1, more than 1, or none of the 4 SPCD diagnostic characteristics. After a brief training process, 5 second raters independently mapped subsets of items to the 6 categories. We calculated the percentage of agreement and Cohen's kappa for each pair of raters in assigning items to categories. Results: Percentages of agreement ranged from 76% to 82%, and Cohen's kappa values ranged from .69 to .76, indicating substantial agreement. Sources and item numbers for the 206 items that both raters assigned to the same SPCD feature are provided. Conclusions: These items may provide guidance in assessing SPCD and in designing standardized screening and diagnostic measures for SPCD.

Osteopontin exacerbates Pseudomonas aeruginosa-induced bacteremia in mice.

Osteopontin (OPN) is a multifunctional protein involved in various pathophysiological processes. However, the role of OPN in Pseudomonas aeruginosa-related sepsis is not yet clear. Here, we found that OPN expression was elevated in plasma and spleen samples from P. aeruginosa-infected mice. To determine the function of OPN in sepsis, we used wild-type (WT) and OPN-knockout (KO) mice with P. aeruginosa-induced bacteremia. We found that OPN-KO mice exhibited reduced mortality compared with WT mice and that OPN exacerbated spleen bleeding and functional impairment. OPN-KO mice exhibited reduced secretion of pro-inflammatory cytokines, such as interferon-γ, interleukin (IL)-1ß, IL-12, and tumor necrosis factor-α, whereas levels of anti-inflammatory cytokine IL-10 and the leukocyte trafficking mediator macrophage inflammatory protein (MIP)-2 were not altered. Additionally, the percentages and absolute numbers of B cells were elevated in the spleens of OPN-KO mice. Thus, OPN promoted sepsis in P. aeruginosa-infected mice and potentially blocked B cell-dependent immunity.

IRF3 Inhibits Neutrophil Recruitment in Mice Infected with Pseudomonas aeruginosa.

Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with ventilator-associated pneumonia. Interferon regulatory factor 3 (IRF3) is a transcription factor that plays an important role in the immune response to viral infection via the IRF3/IFN-ß signaling pathway. Controversial data exist regarding the role of IRF3 in immune cell recruitment during bacterial infections. IRF3 has been shown to promote neutrophil recruitment and bacterial clearance in mice infected with P. aeruginosa by inducing the production of specific chemokines and cytokines. In contrast, our study showed that IRF3 knockout (KO) mice infected with P. aeruginosa exhibited greater survival rates, demonstrated enhanced bacterial clearance, and showed significantly increased neutrophil recruitment to the lungs, when compared with the wild-type (WT) mice. The peritoneal lavage fluid collected from IRF3 KO mice 4 h after intraperitoneal injection with P. aeruginosa or 3% thioglycolate contained a significantly increased number of neutrophils. Furthermore, neutrophils from the bone marrow (BM) of IRF3 KO mice showed greater adhesiveness to the extracellular matrix when compared with those of WT mice, post-P. aeruginosa infection. In addition, IRF3 induced the expression of target genes in WT neutrophils infected with P. aeruginosa. These findings indicate that IRF3 exacerbates P. aeruginosa-induced mortality in mice by inhibiting neutrophil adhesion and recruitment to the lungs. Together, these data indicate that the inhibition of IRF3 might provide a possible mechanism for controlling P. aeruginosa infections.

Reduced neurotrophic factor level is the early event before the functional neuronal deficiency in high-fat diet induced obese mice.

Neurodegeneration is considered one of the possible complications of high fat diet (HFD) induced obesity. Much evidence has shown the close relationship between HFD and dementia at comparatively later stage of neuronal injury. It is so far not clear that the initial events of neuronal injury resulting from HFD and obesity. In the present research, obese mouse model achieved by 3-month HFD was applied for the investigation of the possible neuronal deficiency before the obvious cognitive decline. We found that 3-month HFD has already increased the average level of body weight of mice. But almost no obvious cognitive defect was observed. At such time point, we detected the cleavage of amyloid precursor protein (APP), including the expression and maturation level of α- and ß-secretase and proteolytic fragment soluble APP. Results showed similar readout between HFD and normal diet (ND) mice. Besides, neuronal inflammation and brain-blood barrier permeability were also detected. No obvious changes could be observed between HFD and ND mice. Surprisingly, the first detectable neuronal changes was showed to be the downregulation of some neurotrpic factors, like neuronal growth factor ß and brain derived neurotrophic factor, together with the activity of specific receptors, like Trk receptor phosphorylation. All the data piled up indicated that the early neuronal change in HFD induced obese mice was the downregulation of some neurotrophic factors. The results may provide the potential clue to therapeutic and preventive strategy for HFD induced cognitive decline.

An active part of Artemisia sacrorum Ledeb. attenuates hepatic lipid accumulation through activating AMP-activated protein kinase in human HepG2 cells.

Artemisia sacrorum Ledeb. (Compositae) (ASL) is a traditional Chinese medicine used to treat different hepatic diseases. However, a hypolipidemic effect of ASL on fatty liver disease has not been reported. Therefore, we investigated whether 95% ethanol eluate (EE), an active part of ASL, would attenuate hepatic lipid accumulation in human HepG2 cells by activating AMP-activated protein kinase (AMPK). Significant decreases in triglyceride levels and increases in AMPK and acetyl-CoA carboxylase (ACC) phosphorylation were observed when the cells were treated with 95% EE. EE down-regulated the lipogenesis gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and its target genes, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1), in a time- and dose-dependent manner. In contrast, the lipolytic gene expression of peroxisome proliferator-activated receptor alpha (PPAR-alpha) and CD36 increased in a time- and dose-dependent manner. These effects were abolished by pretreatment with compound C, an AMPK inhibitor. However, there were no differences in the gene expression of SREBP2, low density lipoprotein receptor (LDLR), hydroxymethyl glutaryl CoA reductase (HMG-CoA), or glucose transporter 2 (GLUT2). At the same time, 95% EE significantly increased the gene expression of acyl CoA oxidase (ACOX) in a time- and dose-dependent manner. Thus, AMPK mediated 95% EE induced suppression of SREBP1c and activation of PPAR-alpha respectively. These finding indicate that 95% EE attenuates hepatic lipid accumulation through AMPK activation and may be active in the prevention of serious diseases such as fatty liver, obesity, and type-2 diabetic mellitus.

Characterization of microsomal and mitochondrial phospholipase D activities and cloning of a phospholipase D alpha cDNA from strawberry fruits.

Phospholipase D alpha (PLD, EC 3.1.4.4)) is a key enzyme involved in membrane deterioration that occurs during fruit ripening and senescence. The biochemical and molecular characteristics of PLD was studied in strawberry (Fragaria ananassa Duch) fruits, which are non-climacteric fruits. PLD activity was primarily associated with the mitochondrial and microsomal fractions and showed increased activity during development. Optimal pH levels of activity were observed at 5.5 and 6.5 for mitochondrial PLD and at 5 and 7 for microsomal PLD. Calcium enhanced microsomal PLD activity at 1-40 microM levels. PLD activity followed Michaelis-Menten kinetics. Lineweaver-Burk analysis gave Km values in the range of 114 and 277 microM using dipalmitoylphosphatidylcholine (DPPC) as substrate for mitochondrial and microsomal PLD, respectively. The Vmax value for the microsomal PLD was nearly 12-fold higher than that of mitochondrial PLD. A 2874 bp full-length cDNA for PLD alpha was amplified from strawberry fruit mRNA using RT-PCR and 5'- and 3'-RACE encoding an 810 amino acid-polypeptide. The predicted strawberry PLD sequence showed the characteristic C2 domain and the phospholipase domains conferring calcium sensitivity and the enzyme activity, respectively. The strawberry PLD alpha showed a high degree of similarity to other PLD alphas from plants. The implications of PLD regulation during ripening of fruits are discussed.

[Expressions of LEAFY homologous genes in different organs and stages of Ginkgo biloba].

Expressions of Ginlfy and GinNdly gene were studied by northern blotting in different organs and stages of Ginkgo Biloba. Ginlfy gene was expressed in different organs such as root, stem, leaf of juvenile tree, male tree and female tree, and in different stages of male flower bud and female flower bud. It was inferred that Ginlfy gene could be expressed constitutionally. GinNdly gene was only expressed in leaf of juvenile tree, male tree and female tree and in different stages of male flower bud and female flower bud, while GinNdly gene was not expressed in the other organs. Therefore it was thought that GinNdly gene could be expressed differentially and be a close relation to development of flower.

Molecular variations in Th1-specific cell surface gene Tim-3.

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.