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To evaluate the effect of deep learning model on cone beam (CB) CT image analysis of patients with acute pulpitis. The improved principle of maximum entropy and minimum energy method (PME-MEM’) was proposed to preprocess CBCT images. The conditional generative adversarial network (cGAN) model of deep learning was adopted to segment images. In this study, 80 cases of acute pulpitis in our hospital were selected as the research objects. CT images of the patients were collected and pretreated with PME-MEM. The denoising effects of different Gaussian noise treatments were compared and analyzed, and cGAN model was used to segment different parts of teeth in the image. The treatment plan was made according to the processed CT images, and patients were rolled into two groups according to the treatment methods, with 40 cases in each group. The modified group received one-off root canal treatment, and the traditional group received multiple root canal treatments. The postoperative treatment effects of the patients were observed. The results showed that the PME-MEM’ had a better denoising effect on CBCT images relative to the original PME-MEM. The deep learning cGAN model can realize the segmentation of caries, enamel, dentin, dental pulp, crown, restoration, and root canal in CBCT images. The clinical treatment results showed that the treatment time and postoperative pain score of the modified group were considerably reduced versus those of the traditional group (P

Background. Overweight/obesity in childhood is suggested to increase the risk of hypertension later in life. We aimed to assess whether and how body mass index (BMI) trajectories during 6–18 years of age are associated with hypertension in young adulthood (18–37 years) in the Chinese population. Methods. Based on the China Health and Nutrition Survey (CHNS), a total of 1,872 participants who received ≥2 measurements of BMI during 6–18 years and had assessment of blood pressure (BP) in young adulthood were included. BMI trajectories were explored using latent class growth mixture models, and associations between identified trajectories with hypertension in young adulthood were examined by logistic regression analyses. Results. Five heterogeneous BMI trajectories were identified: the low slow-increasing (20.03%), low moderate-increasing (56.14%), low rapid-increasing (17.04%), moderate-increasing (3.63%), and elevated-decreasing (3.15%) groups. Compared with the low slow-increasing group, another three increasing groups had gradually elevated risk of hypertension, yielding maximally adjusted odds ratio (95% confidence interval) (OR (95% CI)) of 2.48 (1.39–4.42), 3.24 (1.66–6.31), and 3.28 (1.19–9.08), respectively, whereas the elevated-decreasing group reversed overweight/obesity to normal weight in childhood, rendering its association with hypertension as not statistically significant (OR (95% CI) = 2.74 (0.98–7.65)). Conclusion. Our study indicates that there are varied BMI trajectories from childhood to adulthood and that an elevated BMI trajectory during childhood is related with an increased risk of hypertension in young adulthood. In contrast, weight loss of children with high initial BMI may mitigate or reverse the risk. Our findings emphasize the importance of BMI continuous monitoring during early life.

Radiation therapy (RT) is currently the standard treatment for diffuse intrinsic pontine glioma (DIPG), the most common cause of death in children with brain cancer. A pharmacodynamic model was developed to describe the radiation‐induced tumor shrinkage and overall survival in mice bearing DIPG. CD1‐nude mice were implanted in the brain cortex with luciferase‐labeled patient‐derived orthotopic xenografts of DIPG (SJDIPGx7 H3F3AWT / K27 M and SJDIPGx37 H3F3AK27M / K27M). Mice were treated with image‐guided whole‐brain RT at 1 or 2 Gy/fraction 5‐days‐on 2‐days‐off for a cumulative dose of 20 or 54 Gy. Tumor progression was monitored with bioluminescent imaging (BLI). A mathematical model describing BLI and overall survival was developed with data from mice receiving 2 Gy/fraction and validated using data from mice receiving 1 Gy/fraction. BLI data were adequately fitted with a logistic tumor growth function and a signal distribution model with linear radiation‐induced killing effect. A higher tumor growth rate in SJDIPGx37 versus SJDIPGx7 xenografts and a killing effect decreasing with higher tumor baseline (p

Considering the large-scale networks that can represent construction of components in a unit, a transportation system, a supply chain, a social network system, and so on, some nodes have similar topological structures and thus play similar roles in the network and system analysis, usually complicating the analysis and resulting in considerable duplicated computations. In this paper, we present a graph learning approach to define and identify structural similarity between the nodes in a network or the components in a network system. Based on the structural similarity, we investigate component clustering at various significance levels that represent different extents of similarity. We further specify a spectral-graph-wavelet based graph learning method to measure the structural similarity and present its application in easing computation load of evaluating system survival signature and system reliability. The numerical examples and the application show the insights of structural similarity and effectiveness of the graph learning approach. Finally, we discuss potential applications of the graph-learning based structural similarity and conclude that the proposed structural similarity, component clustering, and graph learning approach are effective in simplifying the complexity of the network systems and reducing the computational cost for complex network analysis.

Background Associations between trajectories of systolic blood pressure (SBP) during pregnancy and pregnant outcomes remain unclear and disparate. Methods Data of 20,353 mothers without chronic hypertension and who delivered live singletons between January, 2014 and November, 2019, was extracted from Taicang register-based cohort. Based on SBP measured during 10 to 40 weeks of gestation, SBP trajectories were explored using latent class growth mixture model, and their associations with maternal and neonatal outcomes were assessed by logistic regression analyses. Results Six heterogeneous SBP trajectories were identified: low delayed-increasing (7.47%), low reverse-increasing (21.88%), low-stable (19.13%), medium-stable (21.64%), medium reverse-increasing (16.47%), and high stable (13.41%) trajectories. The high-stable trajectory had SBP around 125 mmHg in the 10th gestational week, and increased slightly onwards. When compared with the low-stable trajectory, the high-stable trajectory had maximally adjusted odds ratio (95% confidence interval) of 5.28 (2.76–10.10), 1.30 (1.13–1.50), 1.53 (1.12–2.08), 1.32 (1.06–1.65) and 1.64 (1.08–2.48) for gestational hypertension (GH), early-term delivery (ETD), preterm delivery (PTD), small for gestational age and low birth weight (LBW), respectively. Besides, the medium reverse-increasing trajectory showed significantly increased risk of GH and ETD, while the medium-stable trajectory had significantly elevated risk of ETD and PTD. Notably, SBP trajectories slightly but significantly improved risk discrimination of GH, ETD and LBW, over traditional risk factors. Conclusion Women with different SBP trajectories were at varied risk of adverse maternal and fetal outcomes. Meanwhile, our study suggested that BP monitoring during pregnancy is necessary, especially for women with high SBP in early pregnancy or upward trajectory.

Objective: Rhinosinusitis is a global health problem affecting millions of people around the world. Baicalin is a bioactive compound isolated from medicinal plant Scutellaria baicalensis Georgi. The present study aims to investigate potential effects of baicalin on clinicopathological changes in nasal/sinus mucosa in a mouse model. Methods: A mouse model of sinonasal inflammation induced by high dose of ovalbumin was applied to evaluate effects of baicalin. Rhinosinusitis symptoms, histopathological features, levels of histamine, immunoglobulin E (IgE), IL-17A, IL-10, and balance of regulatory T cell (Treg)/T-helper 17 (Th17) responses were examined. Results: Baicalin significantly relieved rhinosinusitis symptoms in mice, reduced histopathological changes, and suppressed serum levels of histamine and IgE in a dose-dependent manner. In lymphocytes of mice, baicalin modulated balance of Treg/Th17 proportions by attenuating Th17 cells and enhancing Treg cells, respectively. The serum IL-17A was decreased and IL-10 was increased in mice treated by baicalin. In addition, baicalin promoted levels of Smad protein 3 (p-Smad3) and forkhead box P3 (FOXP3) to promote Treg cells while suppressed levels of p-Stat3 and retineic-acid-receptor-related orphan nuclear receptor γt ( RORγt) to inhibit Th17 cells. Conclusions: These data demonstrate that baicalin effectively ameliorates sinonasal inflammation in a mouse model by recovering the immunological balance of Treg/Th17 responses. Our finding highlights the potential value of baicalin for the treatment of rhinosinusitis.

Rationale: Among all the diabetic complications, diabetic cardiomyopathy, which is characterized by myocyte loss and myocardial fibrosis, is the leading cause of mortality and morbidity in diabetic patients. Tissue kallikrein-related peptidases (KLKs) are secreted serine proteases, that have distinct and overlapping roles in the pathogenesis of cardiovascular diseases. However, whether KLKs are involved in the development of diabetic cardiomyopathy remains unknown.The present study aimed to determine the role of a specific KLK in the initiation of endothelial-to-mesenchymal transition (EndMT) during the pathogenesis of diabetic cardiomyopathy. Methods and Results-By screening gene expression profiles of KLKs, it was found that KLK8 was highly induced in the myocardium of mice with streptozotocin-induced diabetes. KLK8 deficiency attenuated diabetic cardiac fibrosis, and rescued the impaired cardiac function in diabetic mice. Small interfering RNA (siRNA)-mediated KLK8 knockdown significantly attenuated high glucose-induced endothelial damage and EndMT in human coronary artery endothelial cells (HCAECs). Diabetes-induced endothelial injury and cardiac EndMT were significantly alleviated in KLK8-deficient mice. In addition, transgenic overexpression of KLK8 led to interstitial and perivascular cardiac fibrosis, endothelial injury and EndMT in the heart. Adenovirus-mediated overexpression of KLK8 (Ad-KLK8) resulted in increases in endothelial cell damage, permeability and transforming growth factor (TGF)-β1 release in HCAECs. KLK8 overexpression also induced EndMT in HCAECs, which was alleviated by a TGF-β1-neutralizing antibody. A specificity protein-1 (Sp-1) consensus site was identified in the human KLK8 promoter and was found to mediate the high glucose-induced KLK8 expression. Mechanistically, it was identified that the vascular endothelial (VE)-cadherin/plakoglobin complex may associate with KLK8 in HCAECs. KLK8 cleaved the VE-cadherin extracellular domain, thus promoting plakoglobin nuclear translocation. Plakoglobin was required for KLK8-induced EndMT by cooperating with p53. KLK8 overexpression led to plakoglobin-dependent association of p53 with hypoxia inducible factor (HIF)-1α, which further enhanced the transactivation effect of HIF-1α on the TGF-β1 promoter. KLK8 also induced the binding of p53 with Smad3, subsequently promoting pro-EndMT reprogramming via the TGF-β1/Smad signaling pathway in HCAECs. The in vitro and in vivo findings further demonstrated that high glucose may promote plakoglobin-dependent cooperation of p53 with HIF-1α and Smad3, subsequently increasing the expression of TGF-β1 and the pro-EndMT target genes of the TGF-β1/Smad signaling pathway in a KLK8-dependent manner. Conclusions: The present findings uncovered a novel pro-EndMT mechanism during the pathogenesis of diabetic cardiac fibrosis via the upregulation of KLK8, and may contribute to the development of future KLK8-based therapeutic strategies for diabetic cardiomyopathy.

Background Immunotherapy with chimeric antigen receptor (CAR) T cells is actively being explored for pediatric brain tumors in preclinical models and early phase clinical studies. At present, it is unclear which CAR target antigens are consistently expressed across different pediatric brain tumor types. In addition, the extent of HLA class I expression is unknown, which is critical for tumor recognition by conventional αβTCR T cells. Methods We profiled 49 low- and high-grade pediatric brain tumor patient-derived orthotopic xenografts (PDOX) by flow analysis for the expression of 5 CAR targets (B7-H3, GD2, IL-13Rα2, EphA2, and HER2), and HLA class I. In addition, we generated B7-H3-CAR T cells and evaluated their antitumor activity in vitro and in vivo. Results We established an expression hierarchy for the analyzed antigens (B7-H3 = GD2 >> IL-13Rα2 > HER2 = EphA2) and demonstrated that antigen expression is heterogenous. All high-grade gliomas expressed HLA class I, but only 57.1% of other tumor subtypes had detectable expression. We then selected B7-H3 as a target for CAR T-cell therapy. B7-H3-CAR T cells recognized tumor cells in an antigen-dependent fashion. Local or systemic administration of B7-H3-CAR T cells induced tumor regression in PDOX and immunocompetent murine glioma models resulting in a significant survival advantage. Conclusions Our study highlights the importance of studying target antigen and HLA class I expression in PDOX samples for the future design of immunotherapies. In addition, our results support active preclinical and clinical exploration of B7-H3-targeted CAR T-cell therapies for a broad spectrum of pediatric brain tumors.

Atherosclerosis is a chronic inflammatory disease associated with the development of plaques that can be converted into an acute clinical event by thrombosis or plaque rupture. Mesenchymal stem cells (MSCs) exhibit therapeutic effects for the treatment of various diseases, including atherosclerosis. In this study, we show that microRNA-145 (miR-145) is associated with atherosclerosis by microRNA sequencing and bioinformatics analysis. MSC-derived miR-145-rich exosomes could efficiently deliver miR-145 from MSCs to human umbilical vein endothelial cells (HUVECs). Treatment of miR-145-rich exosomes could downregulate JAM-A, inhibit migration in vitro, and reduce atherosclerotic plaque in vivo. Our study suggests that MSC-derived miR-145-rich exosomes have great potential for atherosclerosis prevention., Graphical Abstract

Highlights • It is the first report about severely abnormal respiratory symptoms in a young patient following ambulatory surgery. • The patients in Ambulatory Surgery Center are in good condition, it’s easy to neglect the importance of preoperative preparation. • More extensive clinical and psychological examinations prior to surgery are necessary in young individuals in the Ambulatory Surgery Center., Introduction Ambulatory surgery has the advantages of shortening the waiting time for hospitalization and reducing medical expenses. It has been more and more widely used in recent years in China. The patients admitted in Ambulatory Surgery Center are generally in good condition (ASA I-II), with clear diagnosis, short operation time, low operation risk and low incidence of postoperative complications. It is easy to paralyze the medical staff, neglecting the importance of preoperative preparation, and then causing physical and psychological damage to the patient. Presentation of case We describe the case of a 21-year-old woman, presented with erratic respiratory rate with a maximum of 40 breaths min−1 and a minimum of 7 breaths min−1 after undergoing arthroscopic meniscectomy. The arterial blood gas analysis revealed a disruption of the acid-base homeostasis with respiratory alkalosis and metabolic acidosis, while all other examinations were normal. Discussion Drug-related adverse reactions, emergence agitation or psychiatric factors may have caused the observed symptoms. Conclusion Our observations demonstrate that more extensive clinical and psychological examinations prior to surgery involving general anesthesia may help in avoiding anesthesia-related complications, even in young individuals from the Ambulatory Surgery Center.

Purpose: To investigate the sterility of autologous serum eye drops used for ocular surface diseases.Methods: A total of 100 patients were enrolled. The serum was prepared as follows: 20% serum (20...

Peripheral nerve regeneration is associated with pain in several preclinical models of neuropathic pain. Some neuropathic pain conditions and preclinical neuropathic pain behaviors are improved by sympathetic blockade. In this study, we examined the effect of a localized "microsympathectomy," ie, cutting the gray rami containing sympathetic postganglionic axons where they enter the L4 and L5 spinal nerves, which is more analogous to clinically used sympathetic blockade compared with chemical or surgical sympathectomy. We also examined manipulations of CCL2 (monocyte chemoattractant protein 1), a key player in both regeneration and pain. We used rat tibial nerve crush as a neuropathic pain model in which peripheral nerve regeneration can occur successfully. CCL2 in the sensory ganglia was increased by tibial nerve crush and reduced by microsympathectomy. Microsympathectomy and localized siRNA-mediated knockdown of CCL2 in the lumbar dorsal root ganglion had very similar effects: partial improvement of mechanical hypersensitivity and guarding behavior, reduction of regeneration markers growth-associated protein 43 and activating transcription factor 3, and reduction of macrophage density in the sensory ganglia and regenerating nerve. Microsympathectomy reduced functional regeneration as measured by myelinated action potential propagation through the injury site and denervation-induced atrophy of the tibial-innervated gastrocnemius muscle at day 10. Microsympathectomy plus CCL2 knockdown had behavioral effects similar to microsympathectomy alone. The results show that local sympathetic effects on neuropathic pain may be mediated in a large part by the effects on expression of CCL2, which in turn regulates the regeneration process.

Background: Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation can induce the secretion of IL-1β and IL-18 and after promoting the development of atherosclerosis. MiR-155 is an important microRNA that modulates inflammation in atherosclerosis, but the role of miR-155 in the regulation of the NLRP3 inflammasome is still unknown. Methods: The atherosclerosis model was set up using ApoE −/− mice, and the lentiviral vector (LV) was used to interfere the expression of miR-155. HE stains was used for plaque morphology, immunohistochemistry (IHC) and western blot were used for protein expression quantification. We used oxidized low-density lipoprotein (ox- LDL) to incubate PMA-preprocessed THP-1 macrophages and detected NLRP3 inflammasome activation and ERK1/2 phosphorylation by western blot and Enzyme-linked immunosorbent assay. Results: HE stains showed that the intravascular plaques in the miR-155-up group were remarkably increased, compared with negative control (NC) group. Results of IHC showed that the expression of caspase-1 and IL-1β in the miR-155-up group was the highest of four groups, consist with the Western blot analysis. The results of in vitro experiment show that ox-LDL promoted NLRP3 inflammasome activation and ERK1/2 phosphorylation. Blocking the ERK1/2 pathway could inhibit ox-LDL-induced NLRP3 inflammasome activation. Moreover, we found that the overexpression of miR-155 promoted the activation of the ox-LDL-induced NLRP3 inflammasome, which could also be blocked by the ERK inhibitor U0126. Conclusions: MiR-155 aggravates the carotid AS lesion in ApoE −/− mice and exerts a regulatory effect on NLRP3 inflammasome activation in ox-LDL-induced macrophages via the ERK1/2 pathway.

Recently, exosomal miRNAs have been reported to be associated with some diseases, and these miRNAs can be used for diagnosis and treatment. However, diagnostic biomarkers of exosomal miRNAs for ischemic stroke have rarely been studied. In the present study, we aimed to identify exosomal miRNAs that are associated with large-artery atherosclerosis (LAA) stroke, the most common subtype of ischemic stroke; to further verify their diagnostic efficiency; and to obtain promising biomarkers. High-throughput sequencing was performed on samples from 10 subjects. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on exosomes and plasma in the discovery phase (66 subjects in total) and the validation phase (520 subjects in total). We identified 5 candidate differentially expressed miRNAs (miR-369-3p, miR-493-3p, miR-379-5p, miR-1296-5p, and miR-1277-5p) in the discovery phase according to their biological functions, 4 of which (miR-369-3p, miR-493-3p, miR-379-5p, and miR-1296-5p) were confirmed in the validation phase. These four exosomal miRNAs could be used to distinguish LAA samples from small artery occlusion (SAO) samples, LAA samples from atherosclerosis (AS) samples, and LAA samples from control samples and were superior to plasma miRNAs. In addition, composite biomarkers achieved higher area under the curve (AUC) values than single biomarkers. According to our analysis, the expression levels of exosomal miR-493-3p and miR-1296-5p were negatively correlated with the National Institutes of Health Stroke Scale (NIHSS) score. The four identified exosomal miRNAs are promising biomarkers for the diagnosis of LAA stroke, and their diagnostic efficiency is superior to that of their counterparts in plasma.

Exercise training exerts protective effects against diabetic nephropathy. This study aimed to investigate whether exercise training could attenuate diabetic renal injury via regulating endogenous hydrogen sulfide (H2 S) production. First, C57BL/6 mice were allocated into the control, diabetes, exercise, and diabetes + exercise groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ). Treadmill exercise continued for four weeks. Second, mice was allocated into the control, diabetes, H2 S and diabetes + H2 S groups. H2 S donor sodium hydrosulfide (NaHS) was intraperitoneally injected once daily for four weeks. STZ-induced diabetic mice exhibited glomerular hypertrophy, tissue fibrosis and increased urine albumin levels, urine protein- and albumin-to-creatinine ratios, which were relieved by exercise training. Diabetic renal injury was associated with apoptotic cell death, as evidenced by the enhanced caspase-3 activity, the increased TdT-mediated dUTP nick-end labeling -positive cells and the reduced expression of anti-apoptotic proteins, all of which were attenuated by exercise training. Exercise training enhanced renal sirtuin 1 (SIRT1) expression in diabetic mice, accompanied by an inhibition of the p53-#ediated pro-apoptotic pathway. Furthermore, exercise training restored the STZ-mediated downregulation of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE) and the reduced renal H2 S production. NaHS treatment restored SIRT1 expression, inhibited the p53-mediated pro-apoptotic pathway and attenuated diabetes-associated apoptosis and renal injury. In high glucose-treated MPC5 podocytes, NaHS treatment inhibited the p53-mediated pro-apoptotic pathway and podocyte apoptosis in a SIRT1-dependent manner. Collectively, exercise training upregulated CBS/CSE expression and enhanced the endogenous H2 S production in renal tissues, thereby contributing to the modulation of the SIRT1/p53 apoptosis pathway and improvement of diabetic nephropathy.

Pancreatic ductal adenocarcinoma (PDAC) is a growing cause of cancer-related mortality worldwide. Kallikrein-related peptidase 8 (KLK8) has potential clinical values in many cancers. However, the clinicopathological significances of KLK8 in PDAC remain unknown. We explored the relationship of KLK8 to clinicopathological features of PDAC based on public databases. KLK8 expression was examined in human PDAC tissues. Cell proliferation and apoptosis were evaluated in KLK8-overexpressed human pancreatic cancer cell lines Mia-paca-2 and Panc-1. The related signaling pathways of KLK8 involved in pancreatic cancer progression were analyzed by gene set enrichment analysis (GSEA) and further verified in in vitro studies. We found that KLK8 was up-regulated in tumor tissues in the TCGA-PAAD cohort, and was an independent prognostic factor for both overall survival and disease-free survival of PDAC. KLK8 mRNA and protein expressions were increased in PDAC tissues compared with para-cancerous pancreas. KLK8 overexpression exerted pro-proliferation and anti-apoptotic functions in Mia-paca-2 and Panc-1 cells. GSEA analysis showed that KLK8 was positively associated with PI3K-Akt-mTOR and Notch pathways. KLK8-induced pro-proliferation and anti-apoptotic effects in Mia-paca-2 and Panc-1 cells were attenuated by inhibitors for PI3K, Akt, and mTOR, but not by inhibitor for Notch. Furthermore, overexpression of KLK8 in Mia-paca-2 and Panc-1 cells significantly increased epidermal growth factor (EGF) levels in the culture media. EGF receptor (EGFR) inhibitor could block KLK8-induced activation of PI3K/Akt/mTOR pathway and attenuate pro-proliferation and anti-apoptotic of KLK8 in Mia-paca-2 and Panc-1 cells. In conclusion, KLK8 overexpression exerts pro-proliferation and anti-apoptotic functions in pancreatic cancer cells via EGF signaling-dependent activation of PI3K/Akt/mTOR pathway. Upregulated KLK8 in PDAC predicts poor prognosis and may be a potential therapeutic target for PDAC.

BACKGROUND: This study aims to understand the job burnout status of female nurses with two children and explore the mediating role of psychological capital between dyadic stress and job burnout. METHODS: We used a random sampling method to select 386 female nurses with two children from four tertiary level hospitals between July and October 2020. A general data questionnaire, dyadic stress scale, psychological capital scale, and job burnout scale were used for the investigation and analysis. RESULTS: The psychological capital score of nurses with two children was 84.87±15.45, the dyadic stress was 34.48±6.18, and the job burnout score was 68.28±14.28. Factors affecting the binary stress score, psychological capital score, and job burnout score of nurses with two children included age, professional title, length of service, monthly income, age of the first child, the type of childcare arrangements, and hospital department. The psychological capital score was negatively correlated with the job burnout score (r=−0.617, P

Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and in vivo disease models reflecting the intimate connection between developmental context and pathogenesis of pHGG are essential to advance understanding and identify therapeutic vulnerabilities. Here we report establishment of 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. These models recapitulate histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and include rare subgroups not well-represented by existing models. We deploy 16 new and existing cell lines for high-throughput screening (HTS). In vitro HTS results predict variable in vivo response to PI3K/mTOR and MEK pathway inhibitors. These unique new models and an online interactive data portal for exploration of associated detailed molecular characterization and HTS chemical sensitivity data provide a rich resource for pediatric brain tumor research., Patient-derived xenografts provide a resource for basic and translational cancer research. Here, the authors generate multiple pediatric high-grade glioma xenografts, use omics technologies to show that they are representative of primary tumours and use them to assess therapeutic response.

Background: Dairy goats are highly susceptible to subclinical hyperketonemia (SCHK) during the transition period. This study aimed to compare the variation in metabolic parameters and surrogate indexes of insulin resistance (sIR) between goats with SCHK and clinically healthy (HEAL) goats during the transition period. Methods: Twenty Guanzhong dairy goats were assorted to HEAL (n = 10) and SCHK (n = 10) groups according to the blood β-hydroxybutyrate (BHBA) concentrations. The blood samples were taken from the jugular vein of each goat at −3, −2, −1, 0 (partum), +1, +2, and +3 weeks relative to kidding to analyses GLU and INS. The sIR was calculated from blood metabolic parameters. Results: Compared with the HEAL goats, the insulin concentrations were significantly higher in SCHK goats during the first three weeks postpartum. The QUICKI, revised QUICKI (RQUICKI), and RQUICKIBHBA were significantly lower in goats with SCHK at 1 week postpartum, while the homeostasis model assessment-IR (HOMA-IR) was significantly higher. Conclusion: Goats with SCHK made more efforts through elevated insulin levels at early lactation than HEAL goats, thereby maintaining the normal glucose concentrations.

We aimed to determine the safety, feasibility and efficacy of interventional radiology method for the management of esophagogastric anastomotic leakage. We retrospectively assessed the medical records of 23 consecutive patients with esophagogastric anastomotic leakage treated using intervention protocol. Patients received three-tube method (abscess drainage tube, gastrointestinal decompression tube and jejunal feeding tube) with or without temporary covered esophageal stent placement. Abscess drainage, anti-inflammatory treatment and nutritional support were performed thereafter. The esophageal stents and three tubes were removed after leakage healing. All patient received three-tube method and eight patients received covered stent placement. All operations were technically successful. After a median of 2.4 months, the stents were successfully removed from five patients. No death, esophageal rupture or massive hemorrhage occurred during procedures. The abscess cavity had markedly decreased in seven patients or disappeared in 16 cases. During follow-up, four patients died of cancer recurrence, one died of heart dysfunction and one died of pulmonary infection. The 1-, 3-, 5-year survival rates were 86.4%, 52.3% and 52.3%, respectively. Interventional radiology protocol is safe, feasible and efficacious for treatment for esophagogastric anastomotic leakage.

According to the tourism-led economic growth (TLEG) hypothesis, the development of tourism encourages economic growth. However, the effects of TLEG are not obvious in the areas of China predominant...

The ability of story comprehension is a strong indicator of natural language understanding. Recently, Story Cloze Test has been introduced as a new task of machine reading comprehension, i.e., selecting a correct ending from two candidate endings given a four-sentence story context. Most existing methods for Story Cloze Test are essentially matching-based that operate by comparing an individual ending with a given context, therefore suffering from the evidence bias issue: both candidate endings can obtain supporting evidence from the story context, which misleads the classifier to choose an incorrect ending. To address this issue, we present a novel idea to improve story comprehension by utilizing the hints that are obtained through comparing two candidate endings. The proposed model firstly anticipates a feature vector for a possible ending solely based on the context, and then refines the feature prediction using the hints which encode the difference between two candidates. The candidate ending whose feature vector is more similar to the predicted ending vector is regarded as correct. Experimental results demonstrate that our approach can alleviate the evidence bias issue and improve story comprehension.

Neonatal inflammation induces long-term effects on brain function. We investigated the effects of systematic neonatal inflammation using lipopolysaccharide (LPS) injection at postnatal day 3 (P3) and P5 in a mouse model of spatial memory capacity measured using a Morris water maze (MWM) task in adulthood. Subsequently, we assessed histone acetylation and immediate-early response gene expression (c-Fos and brain-derived neurotrophic factor) in the hippocampus in response to MWM acquisition training. The LPS-treated mice exhibited a significant spatial cognitive impairment, which was accompanied by insufficient histone acetylation of the H4K12-specific lysine residue and repressed c-Fos gene expression immediately after acquisition training. Moreover, the enrichment of acetyl-H4K12 on the c-Fos promoter following acquisition training was decreased in LPS-treated mice. Administration of trichostatin A (TSA), a histone deacetylase inhibitor, 2 h before each MWM acquisition training session effectively enhanced hippocampal histone acetylation levels and enrichment of acetyl-H4K12 on the c-Fos promoter following acquisition training in LPS-treated mice. TSA also increased c-Fos gene expression underlying synaptic plasticity and memory formation, and consequently rescued impaired spatial cognitive function. These results indicate that the dysregulation of H4K12 acetylation during the ongoing process of memory formation plays a key role in the spatial cognitive impairment associated with a neonatal LPS challenge. The histone deacetylase inhibitor TSA exhibits therapeutic potential for treating cognitive impairment induced by neonatal inflammation, by means of improving hippocampal histone acetylation and downstream c-Fos gene expression in response to a learning task.

Cervical cancer (CC) is highly associated with high-risk human papillomavirus (HPV) infection and genotype distribution of high-risk HPV (HR-HPV) infection varies greatly in different regions. Clinical specimens were collected from 46 365 patients at Beijing Friendship Hospital, Capital Medical University from January 2017 to December 2020. HPV DNA genotype testing was performed using real-time PCR. The infection rates based on disease group were compared using the χ 2 test. The linear-by-linear association test and gamma value were used to assess the changes in HPV prevalence over calendar year and age group. A total of 10 514 women were infected with HR-HPV, with an overall positive rate of 22.7%. The most prevalent HR-HPV types were HPV52, 58, 16, 51, and 66, and HPV59 had a higher prevalence except for HPV16, 58, and 52 in the CC group. Single infection of HR-HPV was dominant among different disease groups. The infection rate of HR-HPV decreased first and then increased from below 20 years old to over 60 years old. There were significant differences in the HR-HPV infection rates among the age and disease groups. Our findings demonstrate that the genotype distribution of HR-HPV varied with age and diseases. The HR-HPV genotypes prevalence was found to be directly useful for local governments to promote HPV targeted vaccination in the study region.

Polycyclic aromatic hydrocarbons (PAHs) exposure is associated with heart rate variability (HRV) reduction, a widely used marker of cardiovascular autonomic dysfunction. The role of DNA methylation in the relationship between PAHs exposure and decreased HRV is largely unknown. This study aims to explore epigenome-wide DNA methylation changes associated with PAHs exposure and further evaluate their associations with HRV alternations among non-current smokers. We measured 10 mono-hydroxylated PAHs (OH-PAHs) in urine and DNA methylation levels in blood leukocytes among participants from three panels of Chinese non-current smokers (152 in WHZH, 99 in SY, and 53 in COW). We conducted linear regression analyses between DNA methylation and OH-PAHs metabolites with adjustment for age, gender, body mass index, drinking, blood cell counts, and surrogate variables in each panel separately, and combined the results by using inverse-variance weighted fixed-effect meta-analysis to obtain estimates of effect size. The median value of total OH-PAHs ranged from 0.92 × 10−2 in SY panel (62.6% men) to 13.82 × 10−2 μmol/mmol creatinine in COW panel (43.4% men). The results showed that methylation levels of cg18223625 (COL20A1) and cg07805771 (SLC16A1) were significantly or marginally significantly associated with urinary 2-hydroxynaphthalene [β(SE) = 0.431(0.074) and 0.354(0.068), FDR = 0.016 and 0.056, respectively], while methylation level of cg09235308 (PLEC1) was positively associated with urinary total OH-PAHs [β(SE) = 0.478(0.079), FDR = 0.004]. Hypermethylations of cg18223625, cg07805771, and cg09235308 were inversely associated with HRV indices among the WHZH and COW non-current smokers. However, we did not observe significant epigenome-wide associations for the other 9 urinary OH-PAHs. These findings provide new evidence that PAHs exposure is linked to differential DNA methylation, which may help better understand the influences of PAHs exposure on HRV alternations.

Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

Background Cumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results. Results We present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA. Conclusions The performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.

BackgroundThe majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.MethodsWe summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.ResultsHigh percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.ConclusionWe demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.

The Maiji District of Tianshui City (Gansu Province, China) is a typical transition region in the ecotone between the Loess Plateau and the Western Qinling Mountains. Exploring the spatiotemporal dynamics of soil erosion in this ecotone is critical for the scientific and impactive mitigation of soil erosion hazards in this ecologically fragile region. With geographic information system (GIS) and remote sensing (RS), we used the revised universal soil loss equation (RUSLE) model to assess soil erosion in the Maiji District and analyzed its dynamic changes between the years 2000, 2005, 2010, and 2015. We also derived a minimum erosion cell for the study region to assess the impacts of different factors upon soil erosion. Our results showed that total soil losses in the study region changed from 2000 to 2015, being steady initially, then increasing, and finally decreasing. Among different erosion classes, slight to light erosion was the most prevalent form, while areas under moderate to higher classes of soil erosion shifted towards a lower class over time. In each year, soil loss consistently increased before it decreased with an increasing class of elevation and slope (respectively, 1500 m a.s.l. and 30° as critical thresholds). However, notable differences were evident between years in soil loss trends with varying classes of vegetation coverage and rainfall erosivity; vegetation coverage could mitigate the adverse impact of rainfall erosivity and thus constrain soil erosion hazards. In conclusion, the situation of soil erosion exhibited an overall trend of improvement in the transition region of the Maiji District. While topography determines the basic pattern of soil erosion occurrence, interactions between vegetation coverage and rainfall erosivity drive the dynamic development of soil erosion in our study region. Since vegetation coverage is a manageable factor, its reasonable and responsible regulation presents an effective way to mitigate soil erosion hazards in this region of China.

The release of metal elements from stainless-steel products in contact with food may endanger human health. To protect human health, different countries or international organisations have formulated corresponding regulations or technical guidelines. Limits for only five metal elements are stipulated in the China National Food Safety Standard (GB 4806.9) and food simulants and test conditions are fixed regardless of the actual use condition. In this study, inductively coupled plasma mass spectroscopy and inductively coupled plasma optical emission spectroscopy were used to measure the concentrations of six metal contaminants and impurities and 11 metals and alloy component released from stainless-steel sheets on Chinese market. The effects were also investigated on metal release of six grades (201, 202, 304, 430, 443, and 30Cr13) and 6 exposure conditions (food simulant 5 g L���1 citric acid or 4 vol% acetic acid, contact temperature 70 ��C or 100 ��C, and contact time 2 h, 0.5 h, or 0.5 h followed by ambient temperature for 24 h). For reusable stainless-steel sheets, especially for grade 30Cr13, it was essential to perform three consecutive release tests to check compliance. However, there was no need to conduct three consecutive release tests for the other five grades if the results of the first test met the regulations. It was recommended that 5 g L���1 citric acid should be used as food simulant and contact temperature and time should be based on the actual using conditions. No relationships were found between metal release amounts and contact test temperature or time. The specific release limits for Pb, Cr, As, Cd, and Ni should be lowered and Al, Mn, and Fe be added in GB 4806.9. The results of this study can be a reference for further analysis of the release behaviour of metal elements in actual stainless-steel products.

Unsupervised commonsense question answering is appealing since it does not rely on any labeled task data. Among existing work, a popular solution is to use pre-trained language models to score candidate choices directly conditioned on the question or context. However, such scores from language models can be easily affected by irrelevant factors, such as word frequencies, sentence structures, etc. These distracting factors may not only mislead the model to choose a wrong answer but also make it oversensitive to lexical perturbations in candidate answers. In this paper, we present a novel SEmantic-based Question Answering method (SEQA) for unsupervised commonsense question answering. Instead of directly scoring each answer choice, our method first generates a set of plausible answers with generative models (e.g., GPT-2), and then uses these plausible answers to select the correct choice by considering the semantic similarity between each plausible answer and each choice. We devise a simple, yet sound formalism for this idea and verify its effectiveness and robustness with extensive experiments. We evaluate the proposed method on four benchmark datasets, and our method achieves the best results in unsupervised settings. Moreover, when attacked by TextFooler with synonym replacement, SEQA demonstrates much less performance drops than baselines, thereby indicating stronger robustness., Comment: Accepted by ACL 2021 (long paper)

Objective The aim of the study was to analyze the clinical outcomes of circular suture at placental attachment site for refractory postpartum hemorrhage (PPH), which could block blood supply of the serosa and myometrium layer. Methods Eighty cases of refractory PPH were enrolled and retrospective analyzed in this study for further analysis from a consecutive single center database between 2010 and 2018. After undergoing circular suture of the uterine serosa and myometrium layer around placental attachment site, surgical and perioperative outcomes were recorded and analyzed. Results Among all the patients enrolled, 28 cases (35.0%) of refractory PPH were mainly caused by uterine inertia, 36 cases (45.0%) caused by ectopic placenta, and 2 cases (2.5%) caused by coagulation disorders. After circular suture of the uterine serosa and myometrium layer at placental attachment site, all the uterine active bleeding was controlled below 40 ml without recurrence. The perioperative results were similar between the vaginal and cesarean sections groups. Conclusions Circular suture of the uterine serosa and myometrium at the placental attachment site could control refractory PPH with few postoperative complications. Circular suture around placenta site could be applied in time to protect the endometrium even in primary hospital.

Pre-trained Language Models (PLMs) have proven to be beneficial for various downstream NLP tasks. Recently, GPT-3, with 175 billion parameters and 570 GB training data, drew a lot of attention due to the capacity of few-shot (even zero-shot) learning. However, applying GPT-3 to address Chinese NLP tasks is still challenging, as the training corpus of GPT-3 is primarily English, and the parameters are not publicly available. In this technical report, we release the Chinese Pre-trained Language Model (CPM) with generative pre-training on large-scale Chinese training data. To the best of our knowledge, CPM, with 2.6 billion parameters and 100 GB Chinese training data, is the largest Chinese pre-trained language model, which could facilitate several downstream Chinese NLP tasks, such as conversation, essay generation, cloze test, and language understanding. Extensive experiments demonstrate that CPM achieves strong performance on many NLP tasks in the settings of few-shot (even zero-shot) learning. The code and parameters are available at https://github.com/TsinghuaAI/CPM .

In CCS 2019, the privacy-preserving deep package inspection (PrivDPI) was proposed to detect anomalies and suspicious activities in encrypted network traffic, which is a provably secure and highly efficient approach for the end-to-end communication model. However, PrivDPI cannot be applied directly on the scenarios of the Internet of Things (IoT) due to its one/many-to-many communication model in which key agreement will bring giant power consumption. In this paper, we propose a group key agreement based encrypted traffic detection scheme for the Internet of Things (GKA_DPI) to solve it. In GKA_DPI, we still use BlindBox for traffic detection, which was used in PrivDPI and Sherry's scheme. The difference is that we use a dynamic group key agreement to replace the original key agreement protocol to reduce power consumption. Then we can perform deep traffic detection over encrypted packages on the widely used protocol Message Queuing Telemetry Transport (MQTT) of IoT. GKA_DPI can detect encrypted traffic without decrypting transmitted messages and find out malicious traffic to ensure the security of sensor network communication. Finally, we prove the forward and backward secrecy of proposed GKA_DPI.

Despite the success of generative pre-trained language models on a series of text generation tasks, they still suffer in cases where reasoning over underlying commonsense knowledge is required during generation. Existing approaches that integrate commonsense knowledge into generative pre-trained language models simply transfer relational knowledge by post-training on individual knowledge triples while ignoring rich connections within the knowledge graph. We argue that exploiting both the structural and semantic information of the knowledge graph facilitates commonsense-aware text generation. In this paper, we propose Generation with Multi-Hop Reasoning Flow (GRF) that enables pre-trained models with dynamic multi-hop reasoning on multi-relational paths extracted from the external commonsense knowledge graph. We empirically show that our model outperforms existing baselines on three text generation tasks that require reasoning over commonsense knowledge. We also demonstrate the effectiveness of the dynamic multi-hop reasoning module with reasoning paths inferred by the model that provide rationale to the generation., accepted by EMNLP 2020

This study examines the economic benefits of food waste treatment projects in China and factors affecting them. National-level pilot projects for food waste treatment located in 29 cities were selected as samples. The economics of food waste recycling from the investors’ perspective, in terms of investment during the construction phase and cost and benefit during the operation phase, was assessed. Results indicate that the average tonnage investment of food waste treatment projects was RMB 700.0±188.9 thousand yuan, with a profit to cost ratio of 0.08±0.37. This ratio increased to 0.95±0.57 following the application of government subsidies. It highlights the limited economic benefits of food waste treatment facilities, which rely on government subsidies to maintain their operations in China. Further analysis using a multi-factor analysis model revealed that regional location, service population size, processing technique, and urban income exerted varying impacts on the economy of food waste treatment. Population size exerted the highest impact (P = 0.016) during the construction stage, and processing techniques notably influenced the project economy during the operation stage. The study highlights the need to prioritize service population size and processing techniques during economic decision-making and management of food waste recycling projects. The results of this study can serve as a valuable practical reference for guiding future policies regarding food waste treatment and related planning.

Ulcerative colitis (UC) is an intractable ailment, in which may chronic inflammations/ulcerations may develop in the mucosal lining of the colon with multiple recurrences. Various drugs such as steroids, immunosuppressants, and antibiotics are extensively used to treat UC. The patients suffer from adverse effects of these advanced drugs. So, they need a harmless therapeutic agent from natural sources. The therapeutic D-carvone has an anti-inflammatory action against the investigational colon cancer models. Therefore, we analyzed the effect of D-carvone on dextran sulfate sodium (DSS) provoked colitis model in mice as follows: Group I: noncolitis healthy control mice; Group II: ulcerative colitis mice models; Group III: D-carvone (40 mg/kg) + ulcerative colitis models; Group IV: sulfasalazine (50 mg/kg) + ulcerative colitis models. On the 8th day, the experimental study was terminated and serum samples and colon tissues were processed for further analysis. The effect of D-carvone at different concentration was studied on the LPS challenged RAW 264.7 cell lines. The D-carvone (40 mg/kg) treatment maintained the colon length and decreased disease activity index (DAI) score in UC animals. The increased antioxidant enzymes status and decreased oxidative stress and pro-inflammatory markers were noted in the D-carvone (40 mg/ kg) + UC mice. Histopathological study of colon tissue of D-carvone (40 mg/kg) treated UC mice displayed less mucosal damage and improved crypt integrity and goblet cells compared with DSS only provoked mice. The im-munohistochemical expression of iNOS and COX-2 was drastically diminished in the D-carvone treated UC mice. D-carvone (40 mg/kg) treatment appreciably diminished the LPS provoked NO production and pro-inflammatory modulators in the RAW 264.7 macrophage cell lines. These findings proved that D-carvone has a potential therapeutic effect to prevent LPS induced inflammation in in vitro cells and chemically induced ulcerative colitis in vivo models.

Background Genotyping of structural variation is an important computational problem in next generation sequence data analysis. However, in cancer genomes, the copy number variant(CNV) often coexists with other types of structural variations which significantly reduces the accuracy of the existing genotype methods. The bias on sequencing coverage and variant allelic frequency can be observed on a CNV region, which leads to the genotyping approaches that misinterpret the heterozygote as a homozygote. Furthermore, other data signals such as split mapped read, abnormal read will also be misjudged because of the CNV. Therefore, genotyping the structural variations with CNV is a complicated computational problem which should consider multiple features and their interactions. Methods Here we proposed a computational method for genotyping indels in the CNV region, which introduced a machine learning framework to comprehensively incorporate a set of data features and their interactions. We extracted fifteen kinds of classification features as input and different from the traditional genotyping problem, here the structure of variant may fall into types of normal homozygote, homozygous variant, heterozygous variant without CNV, heterozygous variant with a CNV on the mutated haplotype, and heterozygous variant with a CNV on the wild haplotype. The Multiclass Relevance Vector Machine (M-RVM) was used as a machine learning framework combined with the distribution characteristics of the features. Results We applied the proposed method to both simulated and real data, and compared it with the existing popular softwares include Gindel, Facets, GATK, and also compared with other machine learning cores: Support Vector Machine, Lanrange-SVM with OVO multiple classification, Naïve Bayes and BP Neural Network. The results demonstrated that the proposed method outperforms others on accuracy, stability and efficiency. Conclusion This work shows that the genotyping of structural variations on the CNV region cannot be solved as a traditional genotyping problem. More features should be used to efficiently complete the five-category task. According to the result, the proposed method can be a practical algorithm to correct genotype structural variations with CNV on the next generation sequence data. The source codes have been uploaded at https://github.com/TrinaZ/Mixgenotypefor academic usage only.

Smart home is an indispensable part of Internet of Things(IoT) owing to the prompt development and application of smart devices. However, the data collected from smart homes usually need to be processed by a cloud server, which means there is a risk of leaking the privacy of users during the transmission. In this situation, edge computing is considered to be an ideal platform for smart home, which enable data to be processed at edge nodes. Unfortunately, because of unsecured Wi-Fi connection and smart devices, edge nodes also have the possibility to encounter malicious attacks. Hence, in this paper, we designed an intrusion detection system (IDS) to be deployed on edge nodes. We convert network traffic to images which are applied to train a convolutional neural network (CNN) to classify the categories of network traffic. Furthermore, Auxiliary Classifier Generative Adversarial Network (AC-GAN) is adopted to generate synthesized samples to expand the intrusion detection dataset. We experiment on the UNSW-NB15 dataset which contains substantial network traffic about the normal and anomalies. The proposed scheme is effective to minor categories of which precision could be improved 12%. Besides, the precision can reach 96% in binary classification about normal and anomaly.

With the rapid development of the mobile Internet and the increasing popularity of smart terminals, various mobile social applications are emerging. Medical data has become a valuable data asset and is being continuously explored and utilized, which has greatly promoted the improvement of the medical service level. However, publishing and using user data makes the user vulnerable to reasoning attacks. Due to the special nature of the medical field, medical data not only carries the health status of patients and medical process information but also involves individual sensitive information of a large number of patients. Allowing users to fully enjoy the advantages brought by social networks while ensuring security is an important issue that needs to be solved urgently in the era of big data. In this paper, we first provide an overview of social network data privacy risks and various types of attacks. Aiming at the privacy leakage of weighted social networks, we propose a privacy protection recommendation algorithm based on differential privacy. The algorithm utilizes the change of edge weight grouping, which greatly reduces the amount of calculation and satisfies the user's rapid response. It minimizes a privacy leak of user private data under data availability while supporting personalized rankings. Compared to the most advanced methods, this method protects users from reasoning attacks and reduces the distortion of ranking results caused by data confusion to ensure the accuracy of recommendations. Experiments on real-world datasets show that our framework can achieve more effective and lasting protection for user-sensitive data.

Rationale: The lung-protective effects of dopamine and its role in the pathology of ventilator-induced lung injury (VILI) are emerging. However, the underlying mechanisms are still largely unknown. Objective: To investigate the contribution of dopamine receptor dysregulation in the pathogenesis of VILI and therapeutic potential of dopamine D1 receptor (DRD1) agonist in VILI. Methods: The role of dopamine receptors in mechanical stretch-induced endothelial barrier dysfunction and lung injury was studied in DRD1 knockout mice, in isolated mouse lung vascular endothelial cells (MLVECs), and in lung samples from patients who underwent pulmonary lobectomy with mechanical ventilation for different time periods. Measurements and Main Results: DRD1 was downregulated in both surgical patients and mice exposed to mechanical ventilation. Prophylactic administration of dopamine or DRD1 agonist attenuated mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. By contrast, pulmonary knockdown or global knockout of DRD1 exacerbated these effects. Prophylactic administration of dopamine attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent endothelial hyperpermeability through DRD1 signaling. We identified that cyclic stretch-induced glycogen-synthase-kinase-3β activation led to phosphorylation and activation of histone deacetylase 6 (HDAC6), which resulted in deacetylation of α-tubulin. Upon activation, DRD1 signaling attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent lung endothelial barrier dysfunction through cAMP/exchange protein activated by cAMP (EPAC)-mediated inactivation of HDAC6. Conclusions: This work identifies a novel protective role for DRD1 against mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. Further study of the mechanisms involving DRD1 in the regulation of microtubule stability and interference with DRD1/cAMP/EPAC/HDAC6 signaling may provide insight into therapeutic approaches for VILI.

To advance multi-domain (cross-domain) dialogue modeling as well as alleviate the shortage of Chinese task-oriented datasets, we propose CrossWOZ, the first large-scale Chinese Cross-Domain Wizard-of-Oz task-oriented dataset. It contains 6K dialogue sessions and 102K utterances for 5 domains, including hotel, restaurant, attraction, metro, and taxi. Moreover, the corpus contains rich annotation of dialogue states and dialogue acts at both user and system sides. About 60% of the dialogues have cross-domain user goals that favor inter-domain dependency and encourage natural transition across domains in conversation. We also provide a user simulator and several benchmark models for pipelined task-oriented dialogue systems, which will facilitate researchers to compare and evaluate their models on this corpus. The large size and rich annotation of CrossWOZ make it suitable to investigate a variety of tasks in cross-domain dialogue modeling, such as dialogue state tracking, policy learning, user simulation, etc., Accepted by TACL

We present ConvLab-2, an open-source toolkit that enables researchers to build task-oriented dialogue systems with state-of-the-art models, perform an end-to-end evaluation, and diagnose the weakness of systems. As the successor of ConvLab (Lee et al., 2019b), ConvLab-2 inherits ConvLab's framework but integrates more powerful dialogue models and supports more datasets. Besides, we have developed an analysis tool and an interactive tool to assist researchers in diagnosing dialogue systems. The analysis tool presents rich statistics and summarizes common mistakes from simulated dialogues, which facilitates error analysis and system improvement. The interactive tool provides a user interface that allows developers to diagnose an assembled dialogue system by interacting with the system and modifying the output of each system component., Accepted by ACL 2020 demo track

While Novelda's XeThru X4 ultra-wideband(UWB) pulse radar, being a monitor device of human signal, has been used in many industries, it is worth to test its safety and influence in human body. Unfortunately, there is not many research report on safety assessment of the device in radiation-sensitive reproductive systems. In this experiment, C57 mice were directly irradiated by XeThru X4, and the control group was placed in a normal environment for continuous observation for 90 days. It was found that the sex hormone levels of C57 mice changed under XeThru X4 radar radiation, especially testosterone (T) and sex hormone binding protein (SHBG), but there was no statistical difference during the 90-day observation period. At the same time, a special phenomenon was observed in the experiment. C57 female mice showed different degrees of hair loss on the back after 60 days, and increased with the XeThru X4 radar irradiation time. However, this phenomenon was not observed in male mice under the same radiation and in normal environments C57 mice, which may be related to sex hormone levels. Other aspects of the damage to mice remain to be investigated.

Story generation, namely generating a reasonable story from a leading context, is an important but challenging task. In spite of the success in modeling fluency and local coherence, existing neural language generation models (e.g., GPT-2) still suffer from repetition, logic conflicts, and lack of long-range coherence in generated stories. We conjecture that this is because of the difficulty of associating relevant commonsense knowledge, understanding the causal relationships, and planning entities and events with proper temporal order. In this paper, we devise a knowledge-enhanced pretraining model for commonsense story generation. We propose to utilize commonsense knowledge from external knowledge bases to generate reasonable stories. To further capture the causal and temporal dependencies between the sentences in a reasonable story, we employ multi-task learning which combines a discriminative objective to distinguish true and fake stories during fine-tuning. Automatic and manual evaluation shows that our model can generate more reasonable stories than state-of-the-art baselines, particularly in terms of logic and global coherence., Accept at Transactions of the Association for Computational Linguistics 2020

In recent years, with the development of mobile terminals, geographic location has attracted the attention of many researchers because of its convenience in collection and its ability to reflect user profile. To protect user privacy, researchers have adopted local differential privacy in data collection process. However, most existing methods assume that location has already been discretized, which we found, if not done carefully, may introduces huge noise, lowering collected result utility. Thus in this paper, we design a differentially private location division module that could automatically discretize locations according to access density of each region. However, as the size of discretized regions may be large, if directly applying existing local differential privacy based attribute method, the overall utility of collected results may be completely destroyed. Thus, we further improve the optimized binary local hash method, based on personalized differential privacy, to collect user visit frequency of each discretized region. This solution improve the accuracy of the collected results while satisfying the privacy of the user’s geographic location. Through experiments on synthetic and real data sets, this paper proves that the proposed method achieves higher accuracy than the best known method under the same privacy budget.

Background The current study aims to detect the serum level of miR-2467 in pregnant women with gestational diabetes mellitus (GDM) and analyze its clinical significance. Methods The study included 67 pregnant women with GDM and 60 pregnant women with normal glucose tolerance as control group. The serum miR-2467 level of pregnant women was detected by RT-PCR. The diagnostic efficiency of serum miR-2467 for GDM was analyzed using Receiver Operating Characteristic (ROC) curve, and the risk factors of GDM were analyzed by logistic regression analysis. Pearson's correlation assay was used to analyze the correlation between serum miR-2467 and clinical indicators. The possible target gene of miR-2467 was predicted using TargetScan and validated using dual luciferase reporter assay. Results The body mass index (BMI), TC, TG, LDL-C, FPG, HbA1c, HOMA-IR, and serum miR-2467 levels in the GDM group were higher than those in the control group. The serum miR-2467 level of GDM pregnant women was positively correlated with the levels of TC, TG, LDL-C, FPG, HbA1c, and HOMA-IR. The AUC of miR-2467 was 0.876 for GDM pregnant women. Logistic analysis showed that serum miR-2467 level was an independent risk factor for GDM. A conserved binding site was identified in the 3'UTR of adiponectin, and dual luciferase reporter assay showed that adiponectin was a target gene of miR-2467. Conclusions Altogether, the high level of serum miR-2467 can be used for the preliminary screening of GDM. Targeting the regulation of miR-2467/adiponectin might be a new strategy for the prevention of GDM.

The advancements of neural dialogue generation models show promising results on modeling short-text conversations. However, training such models usually needs a large-scale high-quality dialogue corpus, which is hard to access. In this paper, we present a large-scale cleaned Chinese conversation dataset LCCC, which contains a base version (6.8 million dialogues) and a large version (12.0 million dialogues). The quality of our dataset is ensured by a rigorous data cleaning pipeline, which is built based on a set of rules and a classifier that is trained on manually annotated 110K dialogue pairs. We also release pre-training dialogue models which are trained on LCCC-base and LCCC-large respectively. The cleaned dataset and the pre-training models will facilitate the research of short-text conversation modeling. All the models and datasets are available at https://github.com/thu-coai/CDial-GPT.