Bulk and single-cell RNA-sequencing analyses along with abundant machine learning methods identify a novel monocyte signature in SKCM.

Background: Global patterns of immune cell communications in the immune microenvironment of skin cutaneous melanoma (SKCM) haven't been well understood. Here we recognized signaling roles of immune cell populations and main contributive signals. We explored how multiple immune cells and signal paths coordinate with each other and established a prognosis signature based on the key specific biomarkers with cellular communication. Methods: The single-cell RNA sequencing (scRNA-seq) dataset was downloaded from the Gene Expression Omnibus (GEO) database, in which various immune cells were extracted and re-annotated according to cell markers defined in the original study to identify their specific signs. We computed immune-cell communication networks by calculating the linking number or summarizing the communication probability to visualize the cross-talk tendency in different immune cells. Combining abundant analyses of communication networks and identifications of communication modes, all networks were quantitatively characterized and compared. Based on the bulk RNA sequencing data, we trained specific markers of hub communication cells through integration programs of machine learning to develop new immune-related prognostic combinations. Results: An eight-gene monocyte-related signature (MRS) has been built, confirmed as an independent risk factor for disease-specific survival (DSS). MRS has great predictive values in progression free survival (PFS) and possesses better accuracy than traditional clinical variables and molecular features. The low-risk group has better immune functions, infiltrated with more lymphocytes and M1 macrophages, with higher expressions of HLA, immune checkpoints, chemokines and costimulatory molecules. The pathway analysis based on seven databases confirms the biological uniqueness of the two risk groups. Additionally, the regulon activity profiles of 18 transcription factors highlight possible differential regulatory patterns between the two risk groups, suggesting epigenetic event-driven transcriptional networks may be an important distinction. MRS has been identified as a powerful tool to benefit SKCM patients. Moreover, the IFITM3 gene has been identified as the key gene, validated to express highly at the protein level via the immunohistochemical assay in SKCM. Conclusion: MRS is accurate and specific in evaluating SKCM patients' clinical outcomes. IFITM3 is a potential biomarker. Moreover, they are promising to improve the prognosis of SKCM patients.

New algorithms based on autophagy-related lncRNAs pairs to predict the prognosis of skin cutaneous melanoma patients.

Skin cutaneous melanoma (SKCM) is the most malignant skin tumor for it is enormously easy to develop invasion and metastasis. Autophagy is a process by which cellular material is degraded by lysosomes or vacuoles and recycled. Autophagy-related long non-coding RNAs (lncRNAs) have been thought to correlate with SKCM. This study aims to explore the prognostic significance of autophagy-related lncRNAs and establish a prognostic model of autophagy-related lncRNA pairs in SKCM. Firstly, the RNA-seq data and related clinical information were downloaded from the TCGA database. 446 qualified samples were enrolled. 222 autophagy-related genes were obtained from the HADb database. Pearson correlation analysis was conducted to identify autophagy-related lncRNAs (ARLs). After that, we obtained prognosis-related ARLs and autophagy-related lncRNA pairs (ARLPs). Using Lasso-Cox regression analysis, an autophagy-related lncRNA-pair prognostic signature was established. The accuracy of the signature were confirmed through a series of validations in terms of mutation profiles, immunity infiltration, and cellular pathways. And we used the random forest method to find USP30-AS1 as a key mediating factor in SKCM.

Identification of Novel Molecular Therapeutic Targets and Their Potential Prognostic Biomarkers Based on Cytolytic Activity in Skin Cutaneous Melanoma.

Skin cutaneous melanoma (SKCM) attracts attention worldwide for its extremely high malignancy. A novel term cytolytic activity (CYT) has been introduced as a potential immunotherapy biomarker associated with counter-regulatory immune responses and enhanced prognosis in tumors. In this study, we extracted all datasets of SKCM patients, namely, RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database, conducted differential expression analysis to yield 864 differentially expressed genes (DEGs) characteristic of CYT and used non-negative matrix factorization (NMF) method to classify molecular subtypes of SKCM patients. Among all genes, 14 hub genes closely related to prognosis for SKCM were finally screen out. Based on these genes, we constructed a 14-gene prognostic risk model and its robustness and strong predictive performance were further validated. Subsequently, the underlying mechanisms in tumor pathogenesis and prognosis have been defined from a number of perspectives, namely, tumor mutation burden (TMB), copy number variation (CNV), tumor microenvironment (TME), infiltrating immune cells, gene set enrichment analysis (GSEA) and immune checkpoint inhibitors (ICIs). Furthermore, combined with GTEx database and HPA database, the expression of genes in the model was verified at the transcriptional level and protein level, and the relative importance of genes in the model was described by random forest algorithm. In addition, the model was used to predict the difference in sensitivity of SKCM patients to chemotherapy and immunotherapy. Finally, a nomogram was constructed to better aid clinical diagnosis.

Gaussian fitting algorithm with multi-geometric parameters for rotated elliptical beam profiling using pixel ion chamber.

PURPOSE: A high-precision rotated elliptical beam profiling method based on pixel ion chamber is proposed in this paper. This method aims to improve the accuracy by modeling the transverse profile of rotated beam as an ellipse with additional correlation coefficient and eliminating the fitting error due to the volume averaging effect of pixel ion chamber. METHODS: In pencil beam scanning (PBS) proton therapy systems, the transverse beam profile model is generally represented as a standard Gaussian distribution. Considering the elliptical spots, two-dimensional (2D) joint Gaussian distribution characterized with the correlation coefficient ρ is adopted in this study. Gaussian-type particle distribution with white noise was generated and processed in MATLAB to simulate the secondary particle collection in the pixel ion chamber. The simulated pixel ion chamber is a commercially available ion chamber which consists of 12 × 12 small square pixels (3.75 × 3.75 mm2 ) with a 0.05 mm interval. The simulated signals were preprocessed by filtering with the noise threshold and extracting the maximum simply connected domain (MSCD) of the signal. Then, five geometric parameters that identify the transverse beam profiles were fitted under different signal-to-noise ratio (SNR) conditions: the center of the beam (x0 , y0 ), the spot size (σmajor , σminor ), and the rotation angle θ formed between the major axes of elliptical spot and the x axes of the ion chamber. First, the simulated signals were preprocessed by filtering with the noise threshold and extracting the MSCD of the signal. Second, a rectification curve of systematic error in fitted spot size versus the prescribed spot size was used to predict the systematic error due to the volume averaging effect. Finally, the effects of fitting errors on therapeutic dose were evaluated in terms of gamma index and relative dose difference. RESULTS: When the SNR is not less than 20 dB, the relative fitting error of spot size and the absolute fitting error of angle θ are less than 1% and 6.1°, respectively. The fitting error of beam center increases with spot size and will not exceed 0.22 mm when spot size reaches up to 12 mm. At a SNR equal to 20 dB, neither cold nor hot spots were presented in dose distribution calculated with the fitted spot parameters. CONCLUSION: The improved Gaussian fitting algorithm performs well when SNR is not less than 20 dB. This method can effectively distinguish the nominal beam and rotated elliptical beam. An ideal systematic error curve can be predicted and used to correct the fitted spot size, thus eliminating the systematic error due to the volume averaging effect of the pixel ion chamber. The fitting error of spot size cannot be fully corrected, but it is negligible and shows little effect on the overall therapeutic dose.

CNN-Based Volume Flow Rate Prediction of Oil-Gas-Water Three-Phase Intermittent Flow from Multiple Sensors.

In this paper, we propose a deep-learning-based method using a convolutional neural network (CNN) to predict the volume flow rates of individual phases in the oil-gas-water three-phase intermittent flow simultaneously by analyzing the measurement data from multiple sensors, including a temperature sensor, a pressure sensor, a Venturi tube and a microwave sensor. To build datasets, a series of experiments for the oil-gas-water three-phase intermittent flow in a horizontal pipe, in which gas volume fraction and water-in-liquid ratio ranges are 23.77-94.45% and 14.95-86.97%, respectively, and gas flow superficial velocity and liquid flow superficial velocity ranges are 0.66-5.23 and 0.27-2.14 m/s, respectively, have been carried out on a test loop pipeline. The preliminary results indicate that the model can provide relative prediction errors on the testing-1 dataset for the volume flow rates of oil-phase, gas-phase and water-phase within ±10% with 94.49%, 92.56% and 95.71% confidence levels, respectively. Additionally, the prediction results on the testing-2 dataset also demonstrate the generalization ability of the model. The consuming time of a prediction with one sample is 0.43 s on an Intel Xeon CPU E5-2678 v3, and 0.01 s on an NVIDIA GeForce GTX 1080 Ti GPU. Hence, the proposed CNN-based prediction model, which can fulfill the real-time application requirements in the petroleum industry, reveals the potential of using deep learning to obtain accurate results in the multiphase flow measurement field.

HIF-1α Enhances Vascular Endothelial Cell Permeability Through Degradation and Translocation of Vascular Endothelial Cadherin and Claudin-5 in Rats With Burn Injury.

The mechanism underlying burn injury-induced enhanced vascular endothelial permeability and consequent body fluid extravasation is unclear. Here, the rat aortic endothelial cells (RAECs) were treated with the serum derived from rats with burn injury to elucidate the mechanism. Sprague-Dawley (SD) rats were grouped as follows (10 rats/group): control, 2, 4, 8, 12, and 24 hours postburn groups. The heart, liver, kidney, lung, jejunum, and ileum of rats injected with 2% Evans blue (EB) through the tail vein were excised to detect the EB level in each organ. The serum levels of hypoxia-inducible factor-1α (HIF-1α) and endothelin-1 (ET-1) were examined using enzyme-linked immunosorbent assay (ELISA). The effect of serum from 12-hour postburn group on the membrane permeability of RAEC monolayer, as well as on the mRNA and protein levels of ET-1, endothelin receptor A (ETA), ETB, and zonula occludens (ZO-1), was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The membrane permeability of GV230/HIF-1α-transfected or shRNA-HIF-1α-transfected RAECs, as well as the expression levels of HIF-1α, ET-1, ETA, ETB, vascular endothelial (VE)-cadherin, and claudin-5, was analyzed using qRT-PCR and western blotting, whereas the localization of VE-cadherin and claudin-5 was examined using immunofluorescence. The serum HIF-1α and ET-1 levels in the burn groups, which peaked at 12 hours postburn, were significantly upregulated (P < .01) when compared with those in the control group. Additionally, the serum HIF-1α levels were positively correlated with vascular permeability. Compared with the shRNA-negative control-transfected RAECs, the shRNA-II/HIF-1α-transfected RAECs exhibited downregulated expression of HIF-1α, ET-1, ETA, and ETB (P < .01), and upregulated expression of ZO-1, claudin-5, and VE-cadherin (P < .05). Compared with the GV230-transfected RAECs, the GV230/HIF-1α-transfected RAECs exhibited upregulated expression of HIF-1α, ET-1, ETA, and ETB (P < .01), and downregulated expression of ZO-1, claudin-5, and VE-cadherin (P < .05). The GV230/HIF-1α-transfected RAECs exhibited degradation and translocation of VE-cadherin and claudin-5. In addition to degradation of VE-cadherin and claudin-5, HIF-1α mediated enhanced endothelial cell permeability through upregulation of ET-1, ETA, and ETB, and downregulation of ZO-1 and VE-cadherin in rats with burn injury.

Lower trapezius myocutaneous flap repairs adjacent deep electrical burn wounds.

BACKGROUND: Local tissue damage caused by electrical burns is often deep and severe. High-voltage electrical burns are common in the head, neck and torso areas. These are mostly caused by direct contact with the power supply and are often accompanied by deep injuries of the nerve, blood vessel, muscle, tendon, and bone. We must pay great attention to the clinical treatment of these parts injured by electrical burn. CASE PRESENTATION: The first case involved a migrant worker who touched a 6-kV high-tension wire when welding steel; this electric shock caused burns in many places. Deep electrical burn wounds were mainly located on the left shoulder and back, characterized by widespread skin and soft tissue defect and bone necrosis. We utilized a lower trapezius myocutaneous flap to repair these wounds in the neck and back caused by deep electrical burns. The flap survived completely and the wound was effectively repaired. The function and shape of the shoulder and back after the restoration were satisfactory. The second case involved a 29-year-old who accidentally touched a high-voltage wire while working and was burned by a 30,000-V electric shock. His wounds were mainly located on the left head, neck, back and left upper limbs. We designed a 30 cm × 12 cm right trapezius myocutaneous flap which completely covered the wound surface; the electrical burn wounds on the neck and back were effectively repaired. After the electrical burn wound was repaired, the neck function returned to normal with a satisfactory shape. CONCLUSION: The authors report two cases of patients who were burned by high voltage. We used lower trapezius myocutaneous flaps to repair their wounds, which achieved satisfactory clinical results. This study has provided a reliable surgical method for the clinical treatment of deep electrical burn wounds in the neck, shoulders and back.

Flow Adversarial Networks: Flowrate Prediction for Gas-Liquid Multiphase Flows Across Different Domains.

The solution of how to accurately and timely predict the flowrate of gas-liquid mixtures is the key to help petroleum and other related industries to reduce costs, improve efficiency, and optimize management. Although numerous studies have been carried out over the past decades, the problem is still significantly challenging due to the complexity of multiphase flows. This paper attempts to seek new possibilities for multiphase flow measurement and novel application scenarios for state-of-the-art machine learning (ML) techniques. Convolutional neural networks (CNNs) are applied to predict the flowrate of multiphase flows for the first time and can achieve promising performance. In addition, considering the difference between data distributions of training and testing samples and its negative impact on prediction accuracy of the CNN models on testing samples, we propose flow adversarial networks (FANs) that can distill both domain-invariant and flowrate-discriminative features from the raw input. The method is evaluated on dynamic experimental data of different multiphase flows on different flow conditions and operating environments. The experimental results demonstrate that FANs can effectively prevent the accuracy degradation caused by the gap between training and testing samples and have better performance than state-of-the-art approaches in the flowrate prediction field.

Ilioinguinal Flap Combined With Tensor Fascia Lata Muscle Flap to Repair Deep Electrical Burns in the Lower Abdomen: A Report of Two Cases.

INTRODUCTION: Electrical burns are caused by the conversion of electrical energy flowing through the body into heat energy, which can cause coagulative necrosis of the skin and deep tissues. Deep tissue damage is often more serious than skin damage. Electrical burns have the characteristics of destructive and progressive damage and present the common symptoms of severe local tissue damage accompanied by a wide range of deep tissue necrosis, resulting in injury of nerves, blood vessels, bones, and internal organs. Autologous skin grafting alone cannot effectively cover deep tissues or repair electrical burn wounds. CASE REPORT: This article describes 2 patients with deep electrical burns in the lower abdomen that showed extensive skin and soft tissue damage, partial necrosis of abdominal muscle tissue, and weak abdominal wall. As a single tissue flap was too small to effectively cover the defect wound, ilioinguinal flap and tensor fascia lata muscle flap were utilized in both cases with good outcomes. These flaps survived completely, and the wounds were effectively repaired. After repair, the shape was satisfactory, and the function of the lower abdomen was normal. CONCLUSIONS: Transfer of flaps from a site near the wound for repairing electrical burns is convenient for transfer with minimal surgical trauma and a simpler operating procedure than the free flap.

Analysis of MnS Inclusions Formation in Resulphurised Steel via Modeling and Experiments.

Controlling the formation of MnS inclusions during solidification influences the mechanical properties and machinability of the resulfurized steel. A coupled segregation-nucleation-growth model was developed by the finite-difference method involving solute redistribution, heterogeneous nucleation and growth kinetics. Laboratory solidification experiments were performed under various cooling rates in resulphurised 49MnVS steel. In this work, the influence of cooling rate on solute redistribution and growth size of MnS inclusions were simulated using the current coupled model, and the calculated results can provide a valuable reference for MnS formation. Increasing of the cooling rate led to early precipitation and refinement of formed MnS inclusions. Based on the simulation results and experimental data, mathematical relationships between the growing size of MnS with the cooling rate in the low ductility temperature region and in the whole solidification were obtained.

[Study on the mechanism of hypertonic salt solution alleviates lung injury of rats at the early stage of severe scald].

OBJECTIVE: To explore the mechanism of hypertonic salt solution (HS) alleviates lung injury of rats at the early stage of severe scald. METHODS: Thirty-two female Sprague-Dawley (SD) rats were randomly assigned to sham group, lactated Ringer solution (LR) group, HS200 group (200 mmol/L HS group, 1 L 200 mmol/L HS contained 955 mL LR and 45 mL 10% NaCl) and HS400 group (400 mmol/L HS group, 1 L 400 mmol/L HS contained 846 mL LR and 154 mL 10% NaCl), with 8 rats in each group. A 30% total body surface area (TBSA) III degree scalded model was reproduced by scalded on the back with 98 centigrade boiling water for 12 seconds, whereas those in the sham group were exposed to 37 centigrade water without liquid resuscitation. Rats in the three drug intervention groups were resuscitated with LR, 200 mmol/L HS and 400 mmol/L HS by caudal vein according to the Parkland formula, respectively. All rats were sacrificed at 8 hours after scald injury to harvest abdominal aorta blood and lung tissues. Interleukins (IL-6, IL-10 and IL-17) in serum were determined by enzyme-linked immunosorbent assay (ELISA). Samples from the lung tissue were used to measure malondialdehyde (MDA) and superoxide dismutase (SOD) levels by ultraviolet spectrophotometer. Expressions of p38 mitogen-activated protein kinase (p38MAPK) and extracellular regulated protein kinase 1/2 (ERK1/2) in the lung were determined by Western Blot. The lung tissue was stained with hematoxylin and eosin (HE), and the pathological changes were observed with a light microscope. RESULTS: Compared with the sham group, the lung tissues in the LR group were damage obviously, which accompanied with more inflammatory cell infiltration, cell edema and pulmonary septum thickening, and the levels of IL-6, IL-10, IL-17 in serum and MDA content, the phosphorylation of p38MAPK and ERK1/2 in lung tissues were increased whereas the activity of SOD was decreased. Compared with the LR group, the lung injury was significantly alleviated, the levels of IL-6, IL-17 in serum and MDA content and the phosphorylation of p38MAPK and ERK1/2 were decreased, and the levels of IL-10 and SOD were increased in both HS groups with a dose-dependent manner. There were significant difference in above parameters between HS400 group and LR group [serum IL-6 (ng/L): 3.76±0.12 vs. 6.72±0.90, serum IL-10 (ng/L): 33.76±3.71 vs. 16.77±3.19, serum IL-17 (ng/L): 103.52±2.78 vs. 124.96±4.96, lung MDA (nmol/mg): 5.59±0.24 vs. 7.09±0.39, lung SOD (U/mg): 226.7±3.9 vs. 172.7±3.4, lung phosphorylation of p38MAPK (p-p38MAPK)/p38MAPK: 0.15±0.09 vs. 0.35±0.19, lung phosphorylation of ERK1/2 (p-ERK1/2)/ERK1/2: 0.27±0.01 vs. 0.70±0.01, all P < 0.01]. CONCLUSIONS: HS protected against lung injury induced by severe burns in rats with a dose-dependent manner, and it was better than LR, and its possible mechanism was related with reducing the expression of p38MAPK and ERK1/2 pathway in lung tissue, increasing the level of anti-inflammatory cytokines and decreasing the release of pro-inflammatory cytokines, thus inhibiting excessive inflammation and oxidative stress injury in lung.

[Meek technique skin graft for treating exceptionally large area burns].

OBJECTIVE: To investigate the clinical effect of Meek technique skin graft in treating exceptionally large area burns. METHODS: The clinical data were retrospectively analysed from 10 cases of exceptionally large area burns treated with Meek technique skin graft from April 2009 to February 2010 (Meek group), and were compared with those from 10 cases of exceptionally large area burns treated with the particle skin with large sheet of skin allograft transplantation from January 2002 to December 2006 (particle skin group). In Meek group, there were 8 males and 2 females with an average age of 34.5 years (range, 5-55 years), including 6 cases of flame burns, 2 cases of hot liquid burns, 1 case of electrical burn, and 1 case of high-temperature dust burn. The burn area was 82.6% +/- 3.1% of total body surface area (TBSA). The most were deep II degree to III degree burns. The time from burn to hospitalization was (3.5 +/- 1.3) hours. In particle skin group, there were 8 males and 2 females with an average age of 36.8 years (range, 18-62 years), including 5 cases of flame burns, 2 cases of hot liquid burns, and 3 cases of gunpowder explosion injury. The burn area was 84.1% +/- 7.4% of TBSA. The most were deep II degree to III degree burns. The time from burn to hospitalization was (4.9 +/- 2.2) hours. There was no significant difference in general data between 2 groups (P > 0.05). RESULTS: The skin graft survival rate, the time of skin fusion, the systemic wound healing time, and the treatment cost of 1% of burn area were 91.23% +/- 5.61%, (11.14 +/- 2.12) days, (38.89 +/- 10.36) days, and (5113.28 +/- 552.44) yuan in Meek group, respectively; and were 78.65% +/- 12.29%, (18.37 +/- 4.63) days, (48.73 +/- 16.92) days, and (7386.36 +/- 867.64) yuan in particle skin group; showing significant differences between 2 groups (P < 0.05). CONCLUSION: Meek technique skin graft has good effect in treating exceptionally large area burns with the advantages of high survival rate of skin graft, short time of skin fusion, and low treatment cost of 1% of burn area.