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The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities., Graphical abstract Hedgehog pathway (HH) is one of the most important modulators of gastrointestinal cancer. This review concludes the role of HH pathway in gastrointestinal carcinogenesis as well as the development of tumor microenvironment, which indicates the mechanisms of immune tolerance and drug resistance in gastrointestinal cancers and highlights the potential therapeutics.Image 1

Successful deep learning critically depends on the representation of the learned objects. Recent state-of-the-art pharmaceutical deep learning models successfully exploit graph-based de novo learning of molecular representations. Nonetheless, the combined potential of human expert knowledge of molecular representations and convolution neural networks has not been adequately explored for enhanced learning of pharmaceutical properties. Here we show that broader exploration of human-knowledge-based molecular representations enables more enhanced deep learning of pharmaceutical properties. By broad learning of 1,456 molecular descriptors and 16,204 fingerprint features of 8,506,205 molecules, a new feature-generation method MolMap was developed for mapping these molecular descriptors and fingerprint features into robust two-dimensional feature maps. Convolution-neural-network-based MolMapNet models were constructed for out-of-the-box deep learning of pharmaceutical properties, which outperformed the graph-based and other established models on most of the 26 pharmaceutically relevant benchmark datasets and a novel dataset. The MolMapNet learned important features that are consistent with the literature-reported molecular features. While deep learning models have allowed the extraction of fingerprints from the structural description of molecules, they can miss information that is present in the molecular descriptors that chemists use. Shen and colleagues present a method to combine both sources of information into two-dimensional fingerprint maps, which can be used in a wide variety of pharmaceutical tasks to predict the properties of drugs.

Cancers resist targeted therapeutics by drug-escape signaling. Multitarget drugs co-targeting cancer and drug-escape mediators (DEMs) are clinically advantageous. DEM coverage may be expanded by drug combinations. This work evaluated to what extent the kinase DEMs (KDEMs) can be optimally co-targeted by drug combinations based on target promiscuities of individual drugs. We focused on 41 approved and 28 clinical trial small molecule kinase inhibitor drugs with available experimental kinome and clinical pharmacokinetic data. From the kinome inhibitory profiles of these drugs, drug combinations were assembled for optimally co-targeting an established cancer target (EGFR, HER2, ABL1, or MEK1) and 9-16 target-associated KDEMs at comparable potency levels as that against the cancer target. Each set of two-, three-, and four-drug combinations co-target 36-71%, 44-89%, 50-88%, and 27-55% KDEMs of EGFR, HER2, ABL1, and MEK1, respectively, compared with the 36, 33, 38, and 18% KDEMs maximally co-targeted by an existing drug or drug combination approved or clinically tested for the respective cancer. Some co-targeted KDEMs are not covered by any existing drug or drug combination. Our work suggested that novel drug combinations may be constructed for optimally co-targeting cancer and drug escape by the exploitation of drug target promiscuities.

Background An increase in the incidence of central venous catheter (CVC)-associated deep venous thrombosis (CADVT) has been reported in pediatric patients over the past decade. At the same time, current screening guidelines for venous thromboembolism risk have low sensitivity for CADVT in hospitalized children. This study utilized a multimodal deep learning model to predict CADVT before it occurs. Methods Children who were admitted to intensive care units (ICUs) between December 2015 and December 2018 and with CVC placement at least 3 days were included. The variables analyzed included demographic characteristics, clinical conditions, laboratory test results, vital signs and medications. A multimodal deep learning (MMDL) model that can handle temporal data using long short-term memory (LSTM) and gated recurrent units (GRUs) was proposed for this prediction task. Four benchmark machine learning models, logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT) and a published cutting edge MMDL, were used to compare and evaluate the models with a fivefold cross-validation approach. Accuracy, recall, area under the ROC curve (AUC), and average precision (AP) were used to evaluate the discrimination of each model at three time points (24 h, 48 h and 72 h) before CADVT occurred. Brier score and Spiegelhalter’s z test were used measure the calibration of these prediction models. Results A total of 1830 patients were included in this study, and approximately 15% developed CADVT. In the CADVT prediction task, the model proposed in this paper significantly outperforms both traditional machine learning models and existing multimodal deep learning models at all 3 time points. It achieved 77% accuracy and 90% recall at 24 h before CADVT was discovered. It can be used to accurately predict the occurrence of CADVT 72 h in advance with an accuracy of greater than 75%, a recall of more than 87%, and an AUC value of 0.82. Conclusion In this study, a machine learning method was successfully established to predict CADVT in advance. These findings demonstrate that artificial intelligence (AI) could provide measures for thromboprophylaxis in a pediatric intensive care setting.

Influenza A virus infection is usually associated with acute lung injury, which is typically characterized by tracheal mucosal barrier damage and an interleukin 17A (IL-17A)-mediated inflammatory response in lung tissues. Although targeting IL-17A has been proven to be beneficial for attenuating inflammation around lung cells, it still has a limited effect on pulmonary tissue recovery after influenza A virus infection. In this research, interleukin 22 (IL-22), a cytokine involved in the repair of the pulmonary mucosal barrier, was fused to the C-terminus of the anti-IL-17A antibody vunakizumab to endow the antibody with a tissue recovery function. The vunakizumab-IL22 (vmab-IL-22) fusion protein exhibits favorable stability and retains the biological activities of both the anti-IL-17A antibody and IL-22 in vitro. Mice infected with lethal H1N1 influenza A virus and treated with vmab-mIL22 showed attenuation of lung index scores and edema when compared to those of mice treated with saline or vmab or mIL22 alone. Our results also illustrate that vmab-mIL22 triggers the upregulation of MUC2 and ZO1, as well as the modulation of cytokines such as IL-1β, HMGB1 and IL-10, indicating the recovery of pulmonary goblet cells and the suppression of excessive inflammation in mice after influenza A virus infection. Moreover, transcriptome profiling analysis suggest the downregulation of fibrosis-related genes and signaling pathways, including genes related to focal adhesion, the inflammatory response pathway, the TGF-β signaling pathway and lung fibrosis upon vmab-mIL22 treatment, which indicates that the probable mechanism of vmab-mIL22 in ameliorating H1N1 influenza A-induced lung injury. Our results reveal that the bifunctional fusion protein vmab-mIL22 can trigger potent therapeutic effects in H1N1-infected mice by enhancing lung tissue recovery and inhibiting pulmonary inflammation, which highlights a potential approach for treating influenza A virus infection by targeting IL-17A and IL-22 simultaneously.

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off—PVO2 − 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2

Background Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mm Hg measured by right heart catheterization. However, the upper limit of a normal mean PAP is 20 mm Hg. There is a gap between the upper limit of normal and the threshold for diagnosing PH. Therefore, we aimed to investigate whether individuals with a mildly elevated PAP, defined as 20 mm Hg < mean PAP Methods and Results We reviewed studies evaluating the risk of progression to PH and/or mortality in individuals with a mildly elevated PAP versus those with a normal PAP. The mean PAP value of each participant was confirmed by right heart catheterization. We reviewed 1213 studies and 8 fulfilled our inclusion criteria. Our results indicated that individuals with a mildly elevated PAP were 1.81 to 2.45 times more likely to progress to PH than individuals with a normal PAP. There was a statistically significant difference in mortality between the mildly elevated PAP and normal PAP groups (hazard ratio, 2.48; 95% CI, 1.69–3.64). We also pooled survival probabilities in each arm to obtain a summary survival curve for each group, and the pooled survival rates in the mildly elevated PAP group were numerically lower than those in the normal PAP group. Conclusions Our study revealed that individuals with a mildly elevated PAP were at an increased risk of progression to PH and mortality than those with a normal PAP.

Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end‐stage renal disease (ESTD). Interleukin‐22 (IL‐22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL‐22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL‐22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL‐22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL‐22 are certificated in cisplatin‐induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL‐22 on kidneys and highlight the therapeutic opportunities of IL‐22 and the involved metabolic regulators in various kidney diseases., IL‐22 attenuates kidney injury via metabolic reprogramming of renal TECs, regulates mitochondrial function and glycolysis in damaged TECs, and alleviates the accumulation of mitochondrial ROS and dysfunctional mitochondria via the induction of AMPK/AKT and PFBFK3 activities. Ameliorating kidney injury of IL‐22 via regulation of metabolism relevant signaling is certificated in cisplatin‐induced kidney damage and diabetic nephropathy animal models.

Background. West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. Methods. Using the keywords “Xpert” and “Ebola virus”, relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. Results. Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. Conclusions. Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.

Purpose : We aimed to introduce an explainable machine learning technology to help clinicians understand the risk factors for neonatal postoperative mortality at different levels. Methods : A total of 1481 neonatal surgeries performed between May 2016 and December 2019 at a children's hospital were included in this study. Perioperative variables, including vital signs during surgery, were collected and used to predict postoperative mortality. Several widely used machine learning methods were trained and evaluated on split datasets. The model with the best performance was explained by SHAP (SHapley Additive exPlanations) at different levels. Results : The random forest model achieved the best performance with an area under the receiver operating characteristic curve of 0.72 in the validation set. TreeExplainer of SHAP was used to identify the risk factors for neonatal postoperative mortality. The explainable machine learning model not only explains the risk factors identified by traditional statistical analysis but also identifies additional risk factors. The visualization of feature contributions at different levels by SHAP makes the “black-box” machine learning model easily understood by clinicians and families. Based on this explanation, vital signs during surgery play an important role in eventual survival. Conclusions : The explainable machine learning model not only exhibited good performance in predicting neonatal surgical mortality but also helped clinicians understand each risk factor and each individual case.

Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end-stage renal disease (ESTD). Interleukin 22 (IL-22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here we first provide evidence that IL-22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL-22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL-22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL-22 are certificated in cisplatin induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL-22 on kidney and highlight the therapeutic opportunities of IL-22 and the involved metabolic regulators in various kidney diseases.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complex chronic disease in which pulmonary artery stenosis or obstruction caused by organized thrombus can lead to increased pulmonary artery pressure and pulmonary vascular resistance, ultimately triggering progressive right heart failure and death. Currently, its exact mechanism is not fully understood. Pulmonary endarterectomy (PEA) has immediate effects with low perioperative mortality and satisfactory prognosis in experienced expert centers for CTEPH patients with proximal lesions. Nevertheless, 37% of patients are deemed unsuitable for PEA surgery due to comorbidities and other factors, and nearly half of the operated patients have residual or recurrent pulmonary hypertension. Riociguat is the only approved drug for CTEPH, although its effect is limited. Balloon pulmonary angioplasty (BPA) is a promising alternative treatment for patients with CTEPH. After more than 30 years of development and refinements, emerging evidence has confirmed its role in patients with inoperable CTEPH or residual/recurrent pulmonary hypertension, with acceptable complications and comparable long-term prognosis to PEA. This review summarizes the pathophysiology of CTEPH, BPA history and development, therapeutic principles, indications and contraindications, interventional procedures, imaging modalities, efficacy and prognosis, complications and management, bridging and hybrid therapies, ongoing clinical trials and future prospects.

Background Variants in the gene encoding bone morphogenetic protein receptor type II (BMPR2) are the most common genetic cause of pulmonary arterial hypertension (PAH), whereas biallelic variants in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH). Racial background may influence the clinical characteristics of patients diagnosed with PAH or PVOD/PCH. Here, we compared the clinical characteristics and survival between patients with BMPR2 variants or EIF2AK4 variants in a Chinese population. Methods Heterozygous variants in BMPR2 and homozygous or compound heterozygous biallelic EIF2AK4 variants predicted to be deleterious were identified as potentially causal. Clinical and radiological data were collected and analysed. The primary outcomes were death or lung transplantation. Hazard ratios (HRs) for death or transplantation associated with the presence of BMPR2 or biallelic EIF2AK4 variants were calculated using Cox proportional hazards models to analyse patient survival. Results Two hundred thirty-two patients with PAH were enrolled for genetic testing, and PAH patients with associated conditions were excluded from the study. Forty-five patients with BMPR2 variants and 11 patients with biallelic EIF2AK4 variants were recruited. PAH patients with BMPR2 or biallelic EIF2AK4 variants presented symptoms at the ages of 25.57 ± 10.17 years and 31.6 ± 9.38 years, respectively. The whole group of patients showed female dominance either with BMPR2 variants or biallelic EIF2AK4 variants. Specific radiological abnormalities are more prominent in EIF2AK4 variant carriers but can also be found in some patients with BMPR2 variants. Biallelic EIF2AK4 variant carriers had worse survival than BMPR2 variant carriers (p Conclusions Clinical pictures of PAH patients with BMPR2 and biallelic EIF2AK4 variants in the Chinese population differ from other populations by a younger age at diagnosis and demonstrate female dominance in the whole patient group. High-resolution chest CT can help assist in differentiating PAH with PVOD/PCH. BMPR2 variants and biallelic EIF2AK4 variants are associated with adverse outcomes, but the survival of patients with biallelic EIF2AK4 variants is dismal.

Aqueous solubility is an important physicochemical property of compounds in anti-cancer drug discovery. Artificial intelligence solubility prediction tools have scored impressive performances by employing regression, machine learning, and deep learning methods. The reported performances vary significantly partly because of the different datasets used. Solubility prediction on novel compounds needs to be improved, which may be achieved by going deeper with deep learning. We constructed deeper-net models of ~20-layer modified ResNet convolutional neural network architecture, which were trained and tested with 9,943 compounds encoded by molecular fingerprints. Retrospectively tested by 62 recently-published novel compounds, one deeper-net model outperformed four established tools, shallow-net models, and four human experts. Deeper-net models also outperformed others in predicting the solubility values of a series of novel compounds newly-synthesized for anti-cancer drug discovery. Solubility prediction may be improved by going deeper with deep learning. Our deeper-net models are accessible at http://www.npbdb.net/solubility/index.jsp.

Background Drug safety in children is a major concern; however, there is still a lack of methods for quantitatively measuring, let alone to improving, drug safety in children under different clinical conditions. To assess pediatric drug safety under different clinical conditions, a computational method based on Electronic Medical Record (EMR) datasets was proposed. Methods In this study, a computational method was designed to extract the significant drug-diagnosis associations (based on a Bonferroni-adjusted hypergeometric P-value Results The comparison between the children’s hospital and the general hospital showed unique features of pediatric drug use and identified the drug treatment gap between children and adults. In total, 591 drugs were used in the children’s hospital; 18 drug clusters that were associated with certain clinical conditions were generated based on our method; and the quantitative drug safety levels of each drug cluster (under different clinical conditions) were calculated, analyzed, and visualized. Conclusion With this method, quantitative drug safety levels under certain clinical conditions in pediatric patients can be evaluated and compared. If there are longitudinal data, improvements can also be measured. This method has the potential to be used in many population-level, health data-based drug safety studies.

The self-heterodyne detection Brillouin optical time domain reflectometer (BOTDR) system using broad-band laser is proposed to reduce coherent Rayleigh noise and improve the system performance. Compared with the system with narrow-band laser, the stimulated Brillouin scattering (SBS) threshold can be improved by about 3 dB. The experimental results of the narrow-band laser measurements for three times independently and the broad-band laser measurement for one time are compared. The root-mean-square (RMS) errors of Brillouin linewidth for two systems with narrow-band laser and broad-band laser are 6.9 MHz and 2.7 MHz, respectively, and the RMS errors of temperature for the heated fiber are about 1.3 °C and 0.7 °C. With the broad-band laser, signal-to-noise ratio (SNR) of the unheated fiber is approximately equivalent to that of the integrated three independent Brillouin signals for the narrowband laser, and the results are believed to be beneficial for performance improvement and measurement time reduction.

With current trends to progressively miniaturize optical systems, it is now essential to look for alternative methods to control light at extremely small dimensions. Metalenses are composed of subwavelength nanostructures and have an excellent ability to manipulate the polarization, phase, and amplitude of incident light. Although great progress of metalenses has been made, the compact metalens-integrated devices have not been researched adequately. In the study, we present compact imaging devices for near-infrared microscopy, in which a metalens is exploited. The indicators including resolution, magnification, and image quality are investigated via imaging several specimens of intestinal cells to verify the overall performance of the imaging system. The further compact devices, where the metalens is integrated directly on the CMOS imaging sensor, are also researched to detect biomedical issues. This study provides an approach to constructing compact imaging devices based on metalenses for near-infrared microscopy, micro-telecopy, etc., which can promote the miniaturization tending of futural optical systems.

Pose variations are still challenging problems in 3D face recognition because large pose variations will cause self-occlusion and result in missing data. In this paper, a new method for pose-invariant 3D face recognition is proposed to handle significant pose variations. For pose estimation and registration, a coarse-to-fine strategy is proposed to detect landmarks under large yaw variations. At the coarse search step, candidate landmarks are detected using HK curvature analysis and subdivided according to a facial geometrical structure-based classification strategy. At the fine search step, candidate landmarks are identified and labeled by comparing with a Facial Landmark Model. By using the half face matching, we perform the matching step with respect to frontal scans and side scans. Experiments carried out on the Bosphorus and UND/FRGC v2.0 databases show that our method has high accuracy and robustness to pose variations.

BackgroundBalloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients.MethodsFrom May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1–3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function.ResultsTwenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO2, oxygen uptake efficiency slope). Further analysis among ten CTEPH patients receiving multiple BPA sessions (2–4 sessions) indicated BPA resulted in lasting improvements in hemodynamics and cardiopulmonary function.ConclusionsBPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.

To explore the value of right ventricular (RV) parameters detected by three-dimensional echocardiography (3DE) in risk stratification in pulmonary arterial hypertension (PAH) patients. We prospectively recruited 130 pulmonary hypertension patients from National Center for Cardiovascular Diseases, Fuwai Hospital. Each participant was performed a transthoracic echocardiography and 3DE parameters were measured using an off-line software (4D RV Function 2.0, TomTec). Patients were classified into low, intermediate-high risk group based on 2015 ESC Guidelines. A total of 91 PAH patients (34 ± 12 years old, 25 males) were enrolled, among which, 42 were classified into low risk group, while 49 were intermediate-high risk group. Compared with low-risk patients, those with intermediate-high risk had significantly larger 3DE-RV volumes, worse ejection fraction (EF) and tricuspid annular plane systolic excursion, and decreased longitudinal strain (LS). Receive operating characteristic curves illustrated all the 3DE parameters were able to predict intermediate-high risk stratification, especially 3D-RVEF (area under curve, 0.82, 95% CI 0.73–0.91, P

We investigated and compared the correlations between two-dimensional speckle tracking echocardiography detected left ventricular peak early diastolic strain rates (global: left ventricular global peak early diastolic strain rate; septum: left ventricular peak early diastolic strain rate of septum; free wall: left ventricular peak early diastolic strain rate of free wall) and disease severity in pre-capillary pulmonary hypertension. Seventy-four pre-capillary pulmonary hypertension patients (23 males and 51 females, 35 ± 13 years) and thirty healthy controls were consecutively recruited for two-dimensional speckle tracking echocardiography analyses in our study. Medical records of pre-capillary pulmonary hypertension patients were reviewed to capture clinical data; risk assessments were performed based on the 2015 ESC Guidelines. Compared with healthy controls, left ventricular global peak early diastolic strain rate was lower in pre-capillary pulmonary hypertension patients (1.11 ± 0.60 s −1 versus 1.47 ± 0.45 s −1 , P = 0.001), especially that of the septum (1.13 ± 0.58 s −1 versus 1.68 ± 0.46 s −1 , P

To investigate and compare the value of right ventricular longitudinal strain detected by two-dimensional and three-dimensional speckle-tracking echocardiography in risk stratification evaluation in pre-capillary pulmonary hypertension. We consecutively screened 66 patients diagnosed with pre-capillary pulmonary hypertension in our center. According to the risk assessment recommended by 2015 European Society of Cardiology Guidelines, all participants were classified into low- and intermediate-high-risk group. Two-dimensional and three-dimensional strains were measured using off-line softwares (GE EchoPAC version 201 and TomTec, 4D RV Function 2.0). Fifty-seven pre-capillary pulmonary hypertension patients (average 35 years old, 18 males and 39 females) were finally enrolled in our study, 32 (56.1%) were classified in low-risk group, while 25 (43.9%) were in the intermediate-high-risk group. Clinical data associated with disease severity, such as N-terminal pro-brain natriuretic peptide ( r = 0.574, P

OBJECTIVES Our objectives were to identify the risk factors for postoperative complications after paediatric cardiac surgery, develop a tool for predicting postoperative complications and compare it with other risk adjustment tools of congenital heart disease. METHODS A total of 2308 paediatric patients who had undergone cardiac surgeries with cardiopulmonary bypass support in a single centre were included in this study. A univariate analysis was performed to determine the association between perioperative variables and postoperative complications. Statistically significant variables were integrated into a synthetic minority oversampling technique-based XGBoost model which is an implementation of gradient boosted decision trees designed for speed and performance. The 7 traditional risk assessment tools used to generate the logistic regression model as the benchmark in the evaluation included the Aristotle Basic score and category, Risk Adjustment for Congenital Heart Surgery (RACHS-1), Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery (STS-EACTS) mortality score and category and STS morbidity score and category. RESULTS Our XGBoost prediction model showed the best prediction performance (area under the receiver operating characteristic curve = 0.82) when compared with these risk adjustment models. However, all of these models exhibited a relatively lower sensitivity due to imbalanced classes. The sensitivity of our optimization approach (synthetic minority oversampling technique-based XGBoost) was 0.74, which was significantly higher than the average sensitivity of the traditional models of 0.26. Furthermore, the postoperative length of hospital stay, length of cardiac intensive care unit stay and length of mechanical ventilation duration were significantly increased for patients who experienced postoperative complications. CONCLUSIONS Postoperative complications of paediatric cardiac surgery can be predicted based on perioperative data using our synthetic minority oversampling technique-based XGBoost model before deleterious outcomes ensue.

C14orf166, a 28 kD protein regulating RNA transcription and translation, may serve a critical role in oncogenesis. The aim of the current study was to explore the association between C14orf166 expression and esophageal squamous cell carcinoma (ESCC) and to draw attention to the association between C14orf166 and the initiation, progression and prognosis of ESCC. C14orf166 expression in ESCC and paired normal tissues was detected by immunohistochemical staining, western blotting and reverse transcription-quantitative polymerase chain reaction, and the association between C14orf166 expression and clinicopathological characters of ESCC was analyzed. Survival analysis was used to assess the prognostic significance of C14orf166 and it was observed that C14orf166 expression was higher in the ESCC tissues when compared with adjacent non-cancerous tissues at protein (P

A usable velocity model in microseismic projects plays a crucial role in achieving statistically reliable microseismic event locations. Existing methods for velocity model optimization rely mainly on picking arrival times at individual receivers. However, for microseismic monitoring with surface stations, seismograms of perforation shots have such low signal-to-noise ratios (S/N) that they do not yield sufficiently reliable picks. In this study, we develop a framework for constructing a 1-D flat-layered a priori velocity model using a non-linear optimization technique based on amplitude stacking. The energy focusing of the perforation shot is improved thanks to very fast simulated annealing (VFSA), and the accuracies of shot relocations are used to evaluate whether the resultant velocity model can be used for microseismic event location. Our method also includes a conventional migration-based location technique that utilizes successive grid subdivisions to improve computational efficiency and source location accuracy. Because unreasonable a priori velocity model information and interference due to additive noise are the major contributors to inaccuracies in perforation shot locations, we use velocity model optimization as a compensation scheme. Using synthetic tests, we show that accurate locations of perforation shots can be recovered to within 2 m, even with pre-stack S/N ratios as low as 0.1 at individual receivers. By applying the technique to a coal-bed gas reservoir in Western China, we demonstrate that perforation shot location can be recovered to within the tolerance of the well tip location.

Objective To simulate the clinical reasoning of doctors, retrieve analogous patients of an index patient automatically and predict diagnoses by the similar/dissimilar patients. Methods We proposed a novel patient-similarity-based framework for diagnostic prediction, which is inspired by the structure-mapping theory about analogy reasoning in psychology. Patient similarity is defined as the similarity between two patients’ diagnoses sets rather than a dichotomous (absence/presence of just one disease). The multilabel classification problem is converted to a single-value regression problem by integrating the pairwise patients’ clinical features into a vector and taking the vector as the input and the patient similarity as the output. In contrast to the common k-NN method which only considering the nearest neighbors, we not only utilize similar patients (positive analogy) to generate diagnostic hypotheses, but also utilize dissimilar patients (negative analogy) are used to reject diagnostic hypotheses. Results The patient-similarity-based models perform better than the one-vs-all baseline and traditional k-NN methods. The f-1 score of positive-analogy-based prediction is 0.698, significantly higher than the scores of baselines ranging from 0.368 to 0.661. It increases to 0.703 when the negative analogy method is applied to modify the prediction results of positive analogy. The performance of this method is highly promising for larger datasets. Conclusion The patient-similarity-based model provides diagnostic decision support that is more accurate, generalizable, and interpretable than those of previous methods and is based on heterogeneous and incomplete data. The model also serves as a new application for the use of clinical big data through artificial intelligence technology.

Background Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder associated with high pulmonary artery pressure. Genetic testing enables early diagnosis and offers an opportunity for family screening. To identify genetic mutations and help make a precise diagnosis, we performed genetic testing in 191 probands with PAH and tried to analyze the genotype-phenotype correlation. Methods Initially, PAH samples (n = 119) were submitted to BMPR2 screening using Sanger sequencing. Later, we developed a PAH panel test to identify causal mutations in 13 genes related to PAH and tried to call BMPR2 copy number variations (CNVs) with the panel data. Multiplex ligation-dependent probe amplification (MLPA) was used to search for CNVs in BMPR2, ACVRL1 and ENG. Notably, EIF2AK4 gene was also involved in the panel, which allowed to distinguish pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) patients from idiopathic PAH (IPAH). Characteristics of patients were compared using t test for continuous variables. Results Pathogenic BMPR2 mutations were detected most frequently in 32 (17.9%) IPAH and 5 (41.7%) heritable PAH (HPAH) patients by sequencing, and 12 BMPR2 CNVs called from the panel data were all successfully confirmed by MLPA analysis. In addition, homozygous or compound heterozygous EIF2AK4 mutations were identified in 6 patients, who should be corrected to a diagnosis of PVOD/PCH. Genotype-phenotype correlation analysis revealed that PAH patients with BMPR2 mutations were younger at diagnosis (27.2y vs. 31.6y, p = 0.0003) and exhibited more severe pulmonary hemodynamic impairment and a worse cardiac index compared with those without BMPR2 mutations. Conclusions The panel assay represented a highly valuable tool in PAH genetic testing, not only for the detection of small sequence alterations, but also for an indication of BMPR2 CNVs, which had implications for the specific samples to perform further MLPA assay. Analyses of PAH causal genes have a great help to clinical diagnosis and deep implications in disease treatment. Electronic supplementary material The online version of this article (10.1186/s12931-018-0789-9) contains supplementary material, which is available to authorized users.

In order to obtain the full view image, proposing a fast method of generating full view images based on camera. the method based on multi-camera equipment and the spherical transform of the camera image acquisition using sphere transformation model. the improved SIFT algorithm is used to extract keypoints and match keypoints, and then calculating the transformation matrix based on the keypoints that filtered. finally, according to the projection matrix and transform matrix of each image, the images of subsequent cameras are spliced together. Using this method to generate full view images. the speed is fast and real-time.

Probiotics have been widely explored for health benefits, animal cares, and agricultural applications. Recent advances in microbiome, microbiota, and microbial dark matter research have fueled greater interests in and paved ways for the study of the mechanisms of probiotics and the discovery of new probiotics from uncharacterized microbial sources. A probiotics database named PROBIO was developed to facilitate these efforts and the need for the information on the known probiotics, which provides the comprehensive information about the probiotic functions of 448 marketed, 167 clinical trial/field trial, and 382 research probiotics for use or being studied for use in humans, animals, and plants. The potential applications of the probiotics data are illustrated by several literature-reported investigations, which have used the relevant information for probing the function and mechanism of the probiotics and for discovering new probiotics. PROBIO can be accessed free of charge at http://bidd2.nus.edu.sg/probio/homepage.htm .

Many factors have been reported to affect the long-term survival of gastric carcinoma patients after gastrectomy; the present study took the first attempt to find out the potential role of weekday carried out surgery in the postoperative prognosis of gastric cancer patients. 463 gastric cancer patients have been followed up successfully. Pearsonχ2test was used for univariate analyses. Survival curves were constructed by using Kaplan-Meier method and evaluated by using the log-rank test. The Cox proportional hazard regression model was used to find out the risk factors, and subgroup analysis was conducted to rule out confounding factors. We found that the patients who underwent gastrectomy on the later weekday (Wednesday–Friday) more easily suffered from a higher postoperative morbidity. Weekday of surgery was one of the independent indicators for the prognosis of patients after gastric cancer surgery. However, the role of weekday of surgery was significantly weakened in the complications group. In conclusion, surgery performed in the later weekday was more likely to lead to increased postoperative complications and an unfavorable role in prognosis of Chinese gastric cancer patients after curative gastrectomy.

The surface centralized control system of belt transmission of coal mine is the main channel coal transmission in coal mine, whether or not to normally operate directly affect the safety of coal production and economic benefits. With the expansion of coal production, the original capacity and safety of the belt transport cannot meet the development needs of the current. In response to the problems above, this system will the surface belt transmission of coal mine factory. Focus on control, to realize centralized control of the system. And perfect testing and protecting of the most vital part of the system.

Rescue work should be improved in terms of flexibility, safety and reliability. A system is designed with an ARM11 processor as the controller. WiFi Wireless Ad Hoc Networks is used in the rescue communication. The system is modular programmed and has integrated many rescue techniques. Part of the hardware circuit has been modified to improve the functionality. Experiment results show that the system is full-featured, highly efficient, and practicable. It can be used in the complicated environment of major accident scenes and is of high engineering value.

The structure and pressure-induced phase transitions for CdSe are investigated using first- principles calculations. The pressure-induced phase transition sequence WZ/ZB → Rs → Cmcm → CsCl for CdSe is drawn reasonably for the fist time, the corresponding transition pressures are 3.8, 29 and 107 GPa, respectively and the intermediate states between the Cmcm structure and the CsCl structure should exist.

A type of water dispenser remote wireless control system which concludes remote user terminal and household electrical appliances control terminal, connected by Internet, is designed and studied. The system can achieve message transmitting and remote controlling with using embedded technology, Internet and single chip microcomputer. According to the improved circuit, the control message of the remote terminal transmitted by infrared module is receipted and processed by ARM processor with energy saving as the remote wireless control for water dispensers is achieved.

Given the path situation of Xiyue substation 220kV four outlets project crossing Shunde waterway section,this article applies of Dao Heng tower full stress analysis software and the finite element analysis software ANSYS to two steel pipe combination of angle steel towers to carry on design research,contrast axial stress of two kinds of software,analyse the reasons of axial stress difference.

A dynamic model for helical planetary gear train (HPGT) is proposed. Based on the model, the free vibration characteristics, steady-state dynamic responses and effects of design parameters on system dynamics are investigated through numerical simulations. The free vibration of the HGPT is classified into 3 categories. The classified vibration modes are demonstrated as axial translational and torsional mode (AT mode), radial translational and rotational mode (RR mode) and planet mode (P mode) followed by the characteristics of each category. The simulation results agree well with those of previous discrete model when neglecting the component flexibilities, which validates the correctness of the present dynamic model. The steady-state dynamic responses indicate that the dynamic meshing forces fluctuate about the average static values and the time-varying meshing stiffness is one of the major excitations of the system. The parametric sensitivity analysis shows that the impact of the central component bearing stiffness on the dynamic characteristic of the HPGT system is significant.

Weld seam tracking is the key technology of industrial robot. It satisfies accuracy and real-time demand. This paper presents a robust recognition algorithm for weld seam images based on mathematical morphology. This algorithm used the morphological filtering for image enhancement at first, and then applied Otsu threshold segmentation in local. Besides, it implemented region filling and morphological thinning operation to get the segmented weld seam. Finally, the Hough transform was adopted to detect the straight lines from the weld image. The results prove that this method not only can detect the seam tracking in real-time, but also can identify weld seam automatically.

Pancreatic ductal adenocarcinoma has a high rate of neural invasion (80 to 100%) and can be associated with moderate to severe pain in pancreatic cancer. Treatment of pain with celiac plexus blockage (CPB) combined with the three-step ladder utilization of pharmaceutical analgesics following WHO guidelines is used, but the evidence in randomized controlled trials is inconsistent. This meta-analysis identified and compared seven randomized control trials of pain relief from pancreatic cancer, by treatment with medical management alone to celiac plexus blockade with medical management. While no evidence of potential publication bias was detected, group size and statistical power may account for some of the inconsistent conclusions. The combined CPB groups had a significantly lower pain score at 4 weeks, but significance was not maintained at 8 weeks. The combined CPB groups required significantly less drug use compared to the combined control groups treated with pharmaceutical analgesics.

Detailed geological profile and complementary prospecting histogram revealed a series of hard rocks in the Line 9 tunnel of the Guangzhou metro, greatly increasing the difficulty of shield construction. The geological and hydrological condition of the project was very complex and vertical shafts were used to remove the rocks in order to reduce the cost of the project. Reverse construction technology was applied to the construction of vertical shafts. The calculation of internal forces and relevant design of the vertical shaft wall are introduced herein. The vertical shafts and surrounding buildings were monitored and the monitored contents are also described in detail. At the same time, some emergency measures were applied to ensure the safety of the project. The rocks removal technologies before shield-driving in the line 9 of the Guangzhou metro are introduced herein and the results can be referenced to other similar projects.

To measure the similarity between two images, the local information around all the points were usually used for traditional image retrieval methods based on interest points. The accuracy would be influenced by the dissimilar interest points in the background region or in the uninterested regions. A new image retrieval method based on interest points was proposed in this paper. The most similar interest points were chosen firstly based on feature matching techniques, then the similarity was measured based on the local gray information around the preserved similar interest points. Experiments show that the proposed method is more accurate than traditional image retrieval method based on interest points.

Objectives: It was the aim of this study to investigate the effect of ZP123 on prolonged ventricular fibrillation (VF) in swine. Methods: VF was electrically induced in 20 pigs. The animals randomly received either ZP123 or saline control infusion before VF. After 8 min of untreated VF, cardiopulmonary resuscitation and biphasic defibrillation shocks were applied. VF mean frequency (VFmf) and mean amplitude (VFma), hemodynamics, outcome of defibrillation and the rate of return of spontaneous circulation (ROSC) were analyzed. Results: Compared with the control group, VFmf was higher but VFma lower during the 8 min of VF in the drug group (11.8 ± 2.1 vs. 10.4 ± 2.0 Hz and 0.24 ± 0.10 vs. 0.31 ± 0.16 mV, respectively; p < 0.05). Hemodynamic variables in the 2 groups were comparable (p > 0.05). The defibrillation threshold was lower and the rate of successful defibrillation was higher in the drug group compared with the control group (92.2 ± 26.4 vs. 133.3 ± 28.9 J and 90 vs. 30%, respectively; p < 0.05). The rate of ROSC was not different between the 2 groups (40 vs. 30%; p > 0.05). Conclusion: In prolonged VF, ZP123 could decrease the defibrillation threshold and improve the rate of successful defibrillation. However, it could not improve the rate of ROSC – which may be due to its side effect of decreasing VFma.

Workflow technologies are becoming pervasive in the area of space. They enable the execution of space business processes in distributed and ubiquitous computing environments. However, there are some problems such as cross-platform workflow which need to be solved urgently in space test and launch. Aiming at enhancing the efficiency of space test and launch, the distributed workflow engine model of the space test and launch based on JMX was designed. And the workflow engine routing control algorithm was proposed. At last, the performance of the workflow engine system was analyzed. The model was applied in a launch base successfully. The actual operation tests show that: the proposed design model was rational and effective. It enabled changing the engine process dynamically and enhancing the flexibility of the engine system. Furthermore, it enabled setting workflow engines according to the task and application of the test and launch departments. The performance and efficiency of the space test and launch system was improved greatly.