Severus: accurate detection and characterization of somatic structural variation in tumor genomes using long reads.

Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read sequencing offers the advantage of better mappability and long-range phasing, which results in substantial improvements in germline SV detection. However, current long-read SV detection methods do not generalize well to the analysis of somatic SVs in tumor genomes with complex rearrangements, heterogeneity, and aneuploidy. Here, we present Severus: a method for the accurate detection of different types of somatic SVs using a phased breakpoint graph approach. To benchmark various short- and long-read SV detection methods, we sequenced five tumor/normal cell line pairs with Illumina, Nanopore, and PacBio sequencing platforms; on this benchmark Severus showed the highest F1 scores (harmonic mean of the precision and recall) as compared to long-read and short-read methods. We then applied Severus to three clinical cases of pediatric cancer, demonstrating concordance with known genetic findings as well as revealing clinically relevant cryptic rearrangements missed by standard genomic panels.

Extracellular ATP- and adenosine-mediated purinergic signaling modulates inducible nitric oxide synthase (iNOS) gene expression, enzyme activity and nitric oxide production in common carp (Cyprinus carpio) head kidney macrophages.

Inducible nitric oxide (NO) synthase (iNOS) is a key immune mediator for production of inflammatory mediator NO from l-arginine. Tight regulation of iNOS expression and enzyme activity is critical for proper NO productions under inflammation and infection conditions. However, the regulatory mechanism for iNOS expression and enzyme activity in fish remains largely unknown. Here, we show that extracellular ATP treatment significantly up-regulates iNOS gene expression and enzyme activity, and consequently leads to enhanced NO production in Cyprinus carpio head kidney macrophages (HKMs). We further show that the extracellular ATP-induced iNOS enzyme activity and NO production can be attenuated by pharmacological inhibition of the ATP-gated P2X4 and P2X7 receptors with their respective specific antagonists, but enhanced by overexpression of P2X4 and P2X7 receptors in grass carp ovary cells. In contrast, adenosine administration significantly reduces iNOS gene expression, enzyme activity and NO production in carp HKMs, and these inhibitory effects can be reversed by pharmacological inhibition of adenosine receptors with the antagonist XAC. Furthermore, LPS- and poly(I:C)-induced iNOS gene expression, enzyme activity, and NO production are significantly attenuated by blockade of P2X4 and P2X7 receptors with their respective specific antagonists in carp HKMs, while overexpression of P2X and P2X7 receptors results in enhanced iNOS gene expression, enzyme activity and NO production in LPS- and poly(I:C)-treated grass carp ovary cells. Taken together, we firstly report an opposite role of extracellular ATP/adenosine-mediated purinergic signaling in modulating iNOS-NO system activity in fish.

Heritability of abnormalities in limbic networks of autism spectrum disorder children: Evidence from an autism spectrum disorder twin study.

Although the limbic system is closely related to emotion and social behaviors, little is known about the integrity of limbic pathways and how genetics influence the anatomical abnormalities of limbic networks in children with autism spectrum disorder (ASD). Therefore, we used an ASD twin study design to evaluate the microstructural integrity and autism-related differences in limbic pathways of young children with ASD and to estimate the heritability of limbic tracts microstructure variance. We obtained diffusion tensor imaging scans from 33 pairs of twins with ASD aged 2-9 years and 20 age-matched typically developing children. The ACE model was used to estimate the relative effects of additive genetic factors (A), shared environmental factors (C) and specific environmental factors (E) on the variability of diffusivity measurements. We found a significant decrease in fractional anisotropy (FA) in the bilateral fornix and uncinate fasciculus (UF), as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the bilateral fornix and right UF of ASD children. Correlation analysis showed that FA, MD, and lateralization indices of UF were correlated with autism diagnostic observation schedule scores. The ACE model revealed that genetic effects may drive some of the variability of microstructure in the bilateral fornix, cingulum, and left UF. In conclusion, in children with ASD, there are abnormalities in the white matter microstructure of the limbic system, which is related to the core symptoms; these abnormalities may be related to the relative contribution of genetic and environmental effects on specific tracts. LAY SUMMARY: Autism spectrum disorder (ASD) children have abnormal white matter structure in limbic system related to ASD symptoms, and genetic factors play an important role in the development of limbic tracts.

Automatic detection of pesticide residues on the surface of lettuce leaves using images of feature wavelengths spectrum.

The inappropriate application of pesticides to vegetable crops often results in environmental pollution, which seriously impacts the environment and human health. Given that current methods of pesticide residue detection are associated with issues such as low accuracy, high equipment cost, and complex flow, this study puts forward a new method for detecting pesticide residues on lettuce leaves. To establish this method, spectral analysis was used to determine the characteristic wavelength of pesticide residues (709 nm), machine vision equipment was improved, and a bandpass filter and light source of characteristic wavelength were installed to acquire leaf image information. Next, image preprocessing and feature information extraction were automatically implemented through programming. Several links were established for the training model so that the required feature information could be automatically extracted after the batch input of images. The pesticide residue detected using the chemical method was taken as the output and modeled, together with the input image information, using the convolutional neural network (CNN) algorithm. Furthermore, a prediction program was rewritten to generalize the input images during the prediction process and directly obtain the output pesticide residue. The experimental results revealed that when the detection device and method designed in this study were used to detect pesticide residues on lettuce leaves in a key state laboratory, the coefficient of determination of the equation reached 0.883, and the root mean square error (RMSE) was 0.134 mg/L, indicating high accuracy and that the proposed method integrated the advantages of spectrum detection and deep learning. According to comparison testing, the proposed method can meet Chinese national standards in terms of accuracy. Moreover, the improved machine vision equipment was less expensive, thus providing powerful support for the application and popularization of the proposed method.

The characteristics and factors of the internalizing and externalizing behaviours of children at high risk for autism spectrum disorder.

BACKGROUND: The behavioral characteristics of children with autism spectrum disorder (ASD) are not only affected by their disease, but also by their parenting environment. HR-ASD has the risk of developing internalization and externalization problems. How the early development of these behavioral problems is affected by parent-child interaction is worth exploring. We tested whether parent-child interactions and parenting characteristics were associated with behavioural problems during the infant periods. METHODS: This study collected data from 91 infants at high risk for ASD and 68 matched typically developing (TD) infants, about their internalizing and externalizing behavioural problems and engagement states (i.e. positive, negative, and parent-child interactions), using free play paradigm. Parent measures were assessed using the Broad Autism Phenotypic Questionnaire (BAPQ) and Parenting Stress Index Short Form (PSI-SF) questionnaire. The core symptoms of ASD were assessed using the the Autism Diagnostic Observational Schedule (ADOS). RESULTS: During free play, infants in the HR-ASD group showed more internalizing (P < 0.001) and externalizing (P < 0.05) behaviours and less positive engagement (P < 0.01) than the TD group. In the regression analysis, we found that parenting stress had an impact on the infants' externalizing behaviours (△R2 = 0.215). Parent negative engagement had an impact on the infants' internalizing behaviours (△R2 = 0.451). CONCLUSIONS: The present study revealed that children at high risk for ASD exhibited more severe internalizing and externalizing behavioural problems than TD group. The parent negative engagement is associated with behavioural problems. The findings on the contribution of parents' factors to behavioural problems suggests that the parenting stress and parent-child interactions are important factors for mitigating behavioural problems.

Shared and Distinct Topologically Structural Connectivity Patterns in Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Previous neuroimaging studies have described shared and distinct neurobiological mechanisms between autism spectrum disorders (ASDs) and attention-deficit/hyperactivity disorder (ADHD). However, little is known about the similarities and differences in topologically structural connectivity patterns between the two disorders. METHODS: Diffusion tensor imaging (DTI) and deterministic tractography were used to construct the brain white matter (WM) structural networks of children and adolescents (age range, 6-16 years); 31 had ASD, 34 had ADHD, and 30 were age- and sex-matched typically developing (TD) individuals. Then, graph theoretical analysis was performed to investigate the alterations in the global and node-based properties of the WM structural networks in these groups. Next, measures of ASD traits [Social Responsiveness Scale (SRS)] and ADHD traits (Swanson, Nolan, and Pelham, version IV scale, SNAP-IV) were correlated with the alterations to determine the functional significance of such changes. RESULTS: First, there were no significant differences in the global network properties among the three groups; moreover, compared with that of the TD group, nodal degree (Ki) of the right amygdala (AMYG.R) and right parahippocampal gyrus (PHG.R) were found in both the ASD and ADHD groups. Also, the ASD and ADHD groups shared four additional hubs, including the left middle temporal gyrus (MTG.L), left superior temporal gyrus (STG.L), left postcentral gyrus (PoCG.L), and right middle frontal gyrus (MFG.R) compared with the TD group. Moreover, the ASD and ADHD groups exhibited no significant differences regarding regional connectivity characteristics. Second, the ADHD group showed significantly increased nodal betweenness centrality (Bi) of the left hippocampus (HIP.L) compared with the ASD group; also, compared with the ADHD group, the ASD group lacked the left anterior cingulate gyrus (ACG.L) as a hub. Last, decreased nodal efficiency (Enodal) of the AMYG.R, Ki of the AMYG.R, and Ki of the PHG.R were associated with higher SRS scores in the ASD group. Decreased Ki of the PHG.R was associated with higher SRS scores in the full sample, whereas decreased Bi of the PHG.R was associated with lower oppositional defiance subscale scores of the SNAP-IV in the ADHD group, and decreased Bi of the HIP.L was associated with lower inattention subscale scores of the SNAP-IV in the full sample. CONCLUSION: From the perspective of the topological properties of brain WM structural networks, ADHD and ASD have both shared and distinct features. More interestingly, some shared and distinct topological properties of WM structures are related to the core symptoms of these disorders.

The relationships between the topological properties of the whole-brain white matter network and the severity of autism spectrum disorder: A study from monozygotic twins.

Twins provide a valuable perspective for exploring the pathological mechanism of autism spectrum disorder (ASD). We aim to analyze differences in the topological properties of the white matter (WM) network between monozygotic twins with ASD (MZCo-ASD) and children with typical development (TD). We enrolled 67 subjects aged 2-9 years. Twenty-three pairs of MZCo-ASD and 21 singleton children with TD completed clinical assessments and diffusion tensor imaging (DTI). Graph theory was used to compare the topological properties of the WM network between the two groups, and analyzed their correlations with the severity of clinical symptoms. We found that the global efficiency (Eg) of MZCo-ASD is weaker than that of TD children, while the shortest path length (Lp) of MZCo-ASD is longer than that of TD children, and MZCo-ASD have three unique hubs (the bilateral dorsolateral superior frontal gyrus and right insula). Eg and Lp were both correlated with the repetitive behavior scores of the Autism Diagnostic Interview-Revised (ADI-R) in the MZCo-ASD group, and the nodal efficiency of the dorsal superior frontal gyrus (SFGdor) was correlated with the ADI-R scores of repetitive behaviors. Left SFGdor nodal efficiency was correlated with Repetitive Behavior and Communication, two core symptoms of autism. The results implicated that MZCo-ASD had atypical brain structural network attributes and node distributions. Using MZCo-ASD, we found that the WM topological properties that correlate with the severity of ASD core symptoms were Eg, Lp, and the nodal efficiency of the SFGdor.

Augmented reality navigation for minimally invasive knee surgery using enhanced arthroscopy.

PURPOSE: During the minimally invasive knee surgery, surgeons insert surgical instruments and arthroscopy through small incisions, and implement treatment assisted by 2D arthroscopic images. However, this 2D arthroscopic navigation faces several problems. Firstly, the guidance information is displayed on a screen away from the surgical area, which makes hand/eye coordination difficult. Secondly, the small incision limits the surgeons to view the internal knee structures only from an arthroscopic camera. In addition, arthroscopic images commonly appear obscure visions. METHODS: To solve these problems, we proposed a novel in-situ augmented reality navigation system with the enhanced arthroscopic information. Firstly, intraoperative anatomical locations were obtained by using arthroscopic images and arthroscopy calibration. Secondly, tissue properties-based model deformation method was proposed to update the 3D preoperative knee model with anatomical location information. Then, the updated model was further rendered with glasses-free real 3D display for achieving the global in-situ augmented reality view. In addition, virtual arthroscopic images were generated from the updated preoperative model to provide the anatomical information of the operation area. RESULTS: Experimental results demonstrated that virtual arthroscopic images could reflect the correct structure information with a mean error of 0.32 mm. Compared with 2D arthroscopic navigation, the proposed augmented reality navigation reduced the targeting errors by 2.10 mm and 2.70 mm for the experiments of knee phantom and in-vitro swine knee, respectively. CONCLUSION: Our navigation method is helpful for minimally invasive knee surgery since it can provide the global in-situ information and detail anatomical information.

Description of Salinimonas profundi sp. nov., a deep-sea bacterium harboring a transposon Tn6333.

A Gram-staining-negative bacterium, strain HHU 13199T, was isolated from a marine sediment sample collected from South China Sea (119°19.896'E, 19°41.569'N) at a depth of 2918 m. The 16S rRNA gene sequence analysis indicated that strain HHU 13199T represents a member of the genus Salinimonas with the highest sequence similarity (99.8%) to the type strain S. iocasae KX18D6T. However, the average nucleotide identity values and digital DNA-DNA hybridization between strain HHU 13199T and closely related members of the genus Salinimonas were all below the cut-off level (95-96 % and 70%, respectively) for species delineation. This strain grew with sea salt of 0.5-18% (w/v) (optimum, 2-5%), but no growth observed when using NaCl instead. The major fatty acids are C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The predominant isoprenoid quinone is ubiquinone-8. The polar lipids mainly consist of phosphatidylethanolamine, and phosphatidylglycerol. Genomic characterization revealed that strain HHU 13199T harbors a distinct type I-F CRISPR-Cas system and plenty of genes associated with heavy metal resistance, including a transposon (Tn6333) conferring mercury resistance. In addition, a phylogenetic tree based on the bac120 core genes suggested that the genus Salinimonas should be a subclade within Alteromonas. On the basis of the phenotypic, phylogenetic and chemotaxonomic characterizations, strain HHU 13199T represents a novel species of the genus Salinimonas, for which the name Salinimonas profundi sp. nov. is proposed. The type strain is HHU 13199T (= KCTC 72837T = MCCC 1K04127T).

Atypical Neural Responses of Cognitive Flexibility in Parents of Children With Autism Spectrum Disorder.

Impaired cognitive flexibility has been repeatedly demonstrated in autism spectrum disorder (ASD). There is strong evidence for genetic involvement in ASD. First-degree relatives of individuals with ASD may show mild deficits in cognitive inflexibility. The present study investigated cognitive flexibility and its neuroelectrophysiological mechanisms in first-degree relatives of individuals with ASD to assess its potential familiality. Forty-five biological parents of individuals/children with ASD (pASD) and thirty-one biological parents of typically developing individuals/children (pTD), matched by gender, age, and IQ, were enrolled. The broad autism phenotype questionnaire (BAPQ) and cognitive flexibility inventory (CFI) were used to quantitatively assess autistic traits and cognitive flexibility in daily life, respectively. The task-switching paradigm was used to evaluate the behavioral flexibility in a structured assessment situation. Event-related potentials (ERPs) induced by this paradigm were also collected. Results showed that compared with the pTD group, the pASD group had lower CFI scores (t = -2.756, p < 0.01), while both groups showed an equivalent "switch cost" in the task-switching task (p > 0.05). Compared with the pTD group, the pASD group induced greater N2 amplitude at F3, F4, Fz, and C4 (F = 3.223, p < 0.05), while P3 amplitude and latency did not differ between the two groups. In addition, there was a significant negative correlation between the CFI total scores and BAPQ total scores in the pASD group (r = -0.734, p < 0.01). After controlling for age and IQ, the N2 amplitude in the frontal lobe of pASD was negatively correlated with the CFI total scores under the repetition sequence (r = -0.304, p = 0.053). These results indicated that pASD had deficit in cognitive flexibility at the self-reported and neurological levels. The cognitive flexibility difficulties of parents of children with ASD were related to autistic traits. These findings support that cognitive flexibility is most likely a neurocognitive endophenotype of ASD, which is worthy of further investigation.

Gait acquisition and analysis system for osteoarthritis based on hybrid prediction model.

Osteoarthritis (OA) is the most common type of joint-related diseases, which affects millions of people worldwide. Expensive and time-consuming medical imaging can provide precise structural description of knee joints, but lacks the functional descriptions. Gait analysis can provide functional descriptions of knee joints. However, orthopedic surgeons always observe the patient's gait qualitatively and perform subjective assessments through rating scales at present due to the lack of a quantitative gait analysis system. To solve these problems, a gait acquisition and analysis system is developed to provide a cheap, easy-to-use solution for quantitative recording and functional description of OA patients. Firstly, an automatic gait acquisition platform is designed for the clinical setting based on the RGB-D camera and the developed software of gait data recording. In addition, the effective working space of gait acquisition platform is evaluated for clinical applications by comparing with the ground-truth from infrared optical trackers. Secondly, the acquired gait data is analyzed with a novel hybrid prediction model to assess the gait anomalies quantitatively and objectively. In the hybrid model, the extracted features of gait data contain the manually-extracted features and the automatically-extracted features from Long Short-Term Memory network. Experimental results on real patients demonstrate that the proposed gait analysis system can quantitatively predict gait anomalies with a high accuracy of 98.77 %. Therefore, this gait acquisition and analysis system achieves quantitative recording and objective assessment of gait anomalies for clinical OA treatments.

Sphingomonas hominis sp. nov., isolated from hair of a 21-year-old girl.

A Gram-stain-negative, aerobic, motile strain, HHU CXWT, was isolated from hair of a healthy 21-year-old female student of Hohai University, Nanjing, China. The 16S rRNA gene sequence analysis indicated that HHU CXWT represents a member of the genus Sphingomonas with the highest sequence similarity (97.6%) to the type strain S. aquatilis JSS7T. HHU CXWT grew at 4-35 °C and pH 6-8, with optimum growth at 28 °C and pH 7. Tolerance to NaCl was up to 2% (w/v) with optimum growth in 0.5-1.0% NaCl. The major fatty acids were C16:0, C17:1ω6c, C18:1ω7c11-methyl, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and summed feature 8 (C18:1ω7c and/or C18:1ω6c). The predominant isoprenoid quinone was ubiquinone-10. The polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), sphingoglycolipid (SGL), phosphatidylinositol mannosides (PIM), and an unidentified glycolipid (GL). The DNA G + C content was 67.1%. The average nucleotide identity (ANI) values and digital DNA-DNA hybridization (dDDH) between HHU CXWT and closely related members of the genus Sphingomonas were all below the cut-off level (95-96% and 70%, respectively) for species delineation. On the basis of the phenotypic, phylogenetic and chemotaxonomic characterizations, HHU CXWT represents a novel species of the genus Sphingomonas, for which the name Sphingomonas hominis sp. nov. is proposed. The type strain is HHU CXWT (= KCTC 72946T = CGMCC 1.17504T = MCCC 1K04223T).

Automatic estimation of morphological characteristics of proximal tibia for precise plate treatment using model matching.

Plate treatment is currently the standard treatment of proximal tibia fracture. Morphological characteristics can help orthopedic surgeons understand anatomic information of tibia and choose well-matched plate for reducing difficulties in plate treatment. However, manual measurement of morphological characteristics of patient's tibia is time-consuming and labor-intensive. Therefore, this study proposes an automatic method to accurately estimate the morphological characteristics of patient's tibia for assisting plate treatment. In the off-line stage, an average shape with typical characteristics was computed from 422 tibia models, and the morphological characteristics of the average shape were measured by the orthopedic surgeon. In the on-line stage, the point's correspondence between the average shape and every tibia model was created by the proposed morphable model matching method firstly. Then, the morphological characteristics of tibia for every patient were estimated automatically based on the point's correspondence and characteristics of average shape. The effectiveness of the method was validated by comparing the manual measured and automatic-estimated characteristics. In addition, the basic experiments of virtual and real plate implantation preliminarily confirmed that the automatic-estimated morphological characteristics were helpful for plate treatment. In all, we propose an automatic and accurate estimation method of morphological characteristics for a large-scale library of Chinese tibia models, which provides orthopedic surgeons with scientific and quantitative description of tibia.

Tissue Structure Updating for In Situ Augmented Reality Navigation Using Calibrated Ultrasound and Two-Level Surface Warping.

OBJECTIVE: In minimally invasive surgery (MIS), in situ augmented reality (AR) navigation systems are usually implemented using a glasses-free 3D display to represent the preoperative tissue structure, and can provide intuitive see-through guidance information. However, due to changes in intraoperative tissue, the preoperative tissue structure is not able to exactly correspond to reality, which influences the precision of in situ AR navigation. To solve this problem, we propose a method to update the tissue structure for in situ AR navigation in such way to reflect changes in intraoperative tissue. METHODS: The proposed method to update the tissue structure is based on the calibrated ultrasound and two-level surface warping technologies. Firstly, the particle filter-based calibration is implemented to perform ultrasound calibration and obtain intraoperative position of anatomical points. Secondly, intraoperative positions of anatomical points are inputted in the two-level surface warping method to update the preoperative tissue structure. Finally, the glasses-free real 3-D display of the updated tissue structure is finished, and is superimposed onto a patient by a translucent mirror for in situ AR navigation. RESULTS: we validated the proposed method by simulating liver tissue intervention, and achieved the tissue updating accuracy of 92.86%. Furthermore, the targeting error of AR navigation based on the proposed method was also evaluated through minimally invasive liver surgery, and the acquired mean targeting error was 1.92 mm. CONCLUSION: The results demonstrate that the proposed AR navigation method is effective. SIGNIFICANCE: The proposed method can facilitate MIS, as it provides accurate 3D navigation.

Knee arthroscopic navigation using virtual-vision rendering and self-positioning technology.

PURPOSE: Knee arthroscopy suffers from a lack of depth information and easy occlusion of the visual field. To solve these limitations, we propose an arthroscopic navigation system based on self-positioning technology, with the guidance of virtual-vision views. This system can work without any external tracking devices or added markers, thus increasing the working range and improving the robustness of the rotating operation. METHODS: The fly-through view and global positioning view for surgical guidance are rendered through virtual-vision rendering in real time. The fly-through view provides surgeons with navigating the arthroscope in the internal anatomical structures using a virtual camera perspective. The global positioning view shows the posture of the arthroscope relative to the preoperative model in a transparent manner. The posture of the arthroscope is estimated from the fusion of visual and inertial data based on the visual-inertial stereo slam. A flexible calibration method that transforms the posture of the arthroscope in the physical world into the virtual-vision rendering framework is proposed for the arthroscopic navigation system with self-positioning information. RESULTS: Quantitative experiments for evaluating self-positioning accuracy were performed. For translation, the acquired mean error was 0.41 ± 0.28 mm; for rotation, it was 0.11° ± 0.07°. The tracking range of the proposed system was approximately 1.4 times that of the traditional external optical tracking system for the rotating operation. Simulated surgical operations were performed on the phantom. The fly-through and global positing views were paired with original arthroscopic images for intuitive surgical guidance. CONCLUSION: The proposed system provides surgeons with both fly-through and global positioning views without a dependence on the traditional external tracking systems for surgical guidance. The feasibility and robustness of the system are evaluated, and it shows promise for medical applications.

Real-Time Lens Based Rendering Algorithm for Super-Multiview Integral Photography without Image Resampling.

We propose a computer generated integral photography (CGIP) method that employs a lens based rendering (LBR) algorithm for super-multiview displays to achieve higher frame rates and better image quality without pixel resampling or view interpolation. The algorithm can utilize both fixed and programmable graphics pipelines to accelerate CGIP rendering and inter-perspective antialiasing. Two hardware prototypes were fabricated with two high-resolution liquid crystal displays and micro-lens arrays (MLA). Qualitative and quantitative experiments were performed to evaluate the feasibility of the proposed algorithm. To the best of our knowledge, the proposed LBR method outperforms state-of-the-art CGIP algorithms relative to rendering speed and image quality with our super-multiview hardware configurations. A demonstration experiment was also conducted to reveal the interactivity of a super-multiview display utilizing the proposed algorithm.