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Background Stomach adenocarcinoma (STAD) is one of the common gastrointestinal cancers, characterized by late discovery and metastasis. However, research of gene methylation and expression in gastric cancer (GC) metastasis has been quite limited. This study aimed to investigate the altered gene expression patterns between metastasis and non-metastasis samples using high-throughput RNA and methylation profiles from a large number of patients. Another aim was to identify a specific potential metastasis biomarker, with the ability to predict the metastasis possibility and prognosis of patients with STAD. Methods In this study, we integrated The Cancer Genome Atlas (TCGA) program STAD datasets, analyzed the RNA expression and DNA methylation data between non-metastasis (M0) and distant metastasis (M1) samples, and evaluated the candidate biomarker in survival and prognosis of GC. Results Among all patients enrolled, 329 with M0 and M1 information were positive for RNA analysis, and 353 with M0 and M1 information were positive for methylation analysis. We found 29 upregulated and 200 downregulated genes in RNA level, and 5,046 hypermethylated and 8,563 hypomethylated probes in methylation level. Among these genes, we found high RNA expression level and low DNA methylation level of ALOX12B and PACSIN1 in GC metastasis samples. Patients with high expression of these 2 genes had poor overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS). Conclusions The expression levels of ALOX12B and PACSIN1 were higher in the metastasis than non-metastasis group, and participants with high expression of these 2 genes were found to have poor survival. The genes ALOX12B and PACSIN1 are potential biomarkers of metastasis and poor prognosis, especially in early stage GC, and provide additional information for subsequent comprehensive treatment of GC.

Gadolinium (Gd)-contrast MRI for reliable detection of blood–brain barrier (BBB) breakdown is widely used in neuromyelitis optica spectrum disorder (NMOSD) attack. Nonetheless, little is known about the predictive role of gadolinium-enhancing lesion in prognosis of NMOSD attack. The aim of this work is to investigate the predictive value of persistently Gd-enhanced lesions to medium-term outcome after attack. Data for this analysis came from an ongoing prospective cohort study (CLUE). NMOSD patients with acute attack were enrolled from January 2019 to March 2020. All patients underwent Gd-contrast MRI at baseline and 1 month, and disability was assessed by Expanded Disability Status Scale (EDSS). Primary outcome was EDSS improvement from baseline to month 6. Multiple logistic regression identified predictors for poor recovery of NMOSD attack. Forty-one participants were analyzed, of which 21 patients had persistently Gd-enhancing lesions. Patients in no enhancement (NE) group showed a significant shift in 6-month EDSS distributions compared with those in persistent enhancement (PE) group (p = 0.005). Poor recovery rate of the PE group was higher than that of the NE group at 6 months (p = 0.033). In patients with aquaporin-4-positive, first-attack, transverse myelitis or in a high-dose steroid treatment subgroup, the improvement of EDSS scores in the PE group was still less compared with that in the NE group (p

The application of design knowledge determines the innovativeness of a technical scheme obtained by trimming (a tool for problem analysis and solving in TRIZ). However, limitations in the knowledge, experience and expertise of designers constrain the range of design knowledge that they can apply, thus reducing the effectiveness of trimming. In this paper, biological strategies are introduced to the trimming process to compensate for limitations imposed by the insufficient professional knowledge of designers, thereby improving design innovation. Therefore, this paper proposes a new design method that combines the trimming method and bio-inspired design (BID). First, a trimming analysis of the target system is carried out. Taking the missing functions of the trimmed system as a potential breakthrough point, a keyword search mode based on “V(verb)O(object)P(property) + the effect/features of the associated function” is used to search for biological prototypes in the biological knowledge base. Second, a fuzzy comprehensive evaluation method is used to analyze the biological prototypes from three dimensions, namely, compatibility, completeness and feasibility, and the best-matching biological prototype is selected. Finally, the biological solution is transformed into an engineering design scheme through a resource derivation process based on structure–function–attribute analogies. The proposed method can expand the range of design solutions by adding biological strategies as a new resource to solve trimming problems. The feasibility and effectiveness of the method are verified by redesigning a steel tape armoring machine.

Objective Deep venous thrombosis (DVT) is a severe complication in longitudinally extensive transverse myelitis (LETM) patients. It may interfere with LETM treatment and delay the recovery of the spinal dysfunction. However, there is less data about the prevalence and risk factors of DVT in patients with LETM. We analyzed data retrospectively to ascertain the prevalence of DVT and the clinical risk factors for DVT. Methods Clinical data on 255 LETM patients were collected from medical records. All patients were performed color Doppler ultrasound(US) to screen DVT in both lower extremities when admitted. Clinical characteristics of LETM patients with DVT were compared with those without DVT using corresponding statistical methods. Multivariate logistic regression was performed to identify risk factors related to DVT. Results DVT were found in 11.8% patients with LETM. Univariate analysis showed that age, muscle force and elevated baseline D-dimer were risk factors for DVT. After multivariate logistic regression, age, dyslipidemia, segments of lesions, and elevated baseline D-dimer remained significant independent risk factors. Conclusions DVT is common in patients with LETM and related to patient’s age, dyslipidemia, segments of lesions, and elevated baseline D-dimer. Early recognition of DVT and thrombosis prophylaxis are appropriate in patients with LETM.

Reduction in CO2 emissions from fossil fuel-based electric power generation is a primary focus of both the public and private sector. Over 1,500 corporations, representing $11.4 trillion in revenue and 6.5 gigatonnes of carbon emissions, have formally announced their objective of meeting net-zero emissions by 2030. In this paper, we focus specifically on CO2 emissions from electricity consumption, and how corporations can reach net-zero goals with respect to these emissions. We focus on three points: (1) the mathematically and economically correct methodology (Marginal Emission Rate, or MER) for calculation of CO2 footprint in the power sector, (2) a detailed comparative analysis and critique of the generally-referenced alternative methodologies, (3) a detailed analysis of the economic benefits of using MER versus other methodologies to private sector corporations focused on net-zero emissions. This paper presents a mathematical framework for organizations to account for and plan their carbon footprint accurately and efficiently whether it is ex post carbon accounting using RTO published real time nodal MER data, or planning for renewable investment using forecasted MER under various future scenarios.

Objective: To evaluated the prognostic ability of several serum cytokines in clinically isolated syndrome (CIS) patients regarding second events and conversion to multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Methods: We enrolled 69 CIS patients whose serum samples were collected during the acute phase of the first onset before immunotherapy. Fifteen other non-inflammatory neurological disorder (OND) patients were also included. The serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21, IL-23, interferon-γ (IFN-γ), and transforming growth factor beta 1 (TGF-β1) were measured using the human cytokine multiplex assay or ELISA. Patients were seen every 3-6 months. Unscheduled visits occur in case of exacerbations. Clinical measures of disease progression were recorded. Results: Twenty CIS cases had second events during follow-up at a mean time of 15.3 ± 9.9 months. Serum IL-10 levels were significantly lower in CIS patients who relapsed compared to patients who did not. Low serum IL-10 levels were associated with higher risk and shorter times to second events. In clinical correlations, a significantly higher CSF white blood cells count, number of T2 lesions, and gadolinium-enhancing (Gd+) lesions in baseline MRI were found in the low serum IL-10 level group. Of the 20 relapsed cases, seven converted to MS, and eight converted to NMOSD. No significant differences were found in any cytokine levels between these patients at first onset. Conclusions: These findings support using serum IL-10 as a biomarker associated with the risk of relapse and the time to second events in patients with CIS. However, serum cytokine levels can not differentiate between the conversion from CIS to MS or NMOSD.

Background Despite inclusion in neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated diseases are increasingly recognized as an independent disease entity. In this study, we conducted a systematic review and meta-analysis to comprehensively update the rate of occurrence of MOG-Ab in Aquaporin4 (AQP4)-antibody seronegative NMOSD. Methods We searched PubMed, EMBASE, and Cochrane databases for studies reporting the rates of patients with MOG-Ab in NMOSD. Fixed or random-effects models were used to pool results across studies. Results Fourteen studies met the inclusion criteria. Overall, MOG-Abs positive patients comprised 9.3% of all NMO/NMOSD (95% confidence interval [CI] 7.9%–10.8%, I2 = 13.1%), 32.5% of all AQP4-Ab seronegative NMO/NMOSD (95% CI 25.7%–39.3%, I2 = 45.8%), and 41.6% of AQP4-Ab seronegative NMOSD cases diagnosed by IPND 2015 criteria (95% CI 35.1%–48.2%, I2 = 0.0%). The pooled prevalence of MOG-Ab was 31.0% among Asian AQP4-Ab seronegative NMO/NMOSD patients (95% CI 22.1%–39.9% I2=54.1%) and 34.3% in European seronegative NMO/NMOSD (95% CI 21.9%–46.7%, I2 = 51.9%). Conclusions This study shows that MOG-Abs represent a substantial proportion of AQP4-Ab seronegative NMOSD patients despite different underlying mechanisms, clinical manifestations, and treatment response, suggesting MOG-Ab screening in AQP4-Ab seronegative NMOSD patients can facilitate accurate diagnoses and treatments.

Background During acute attacks of neuromyelitis optica spectrum disorder (NMOSD), intravenous immunoglobulin (IVIG) maybe useful building on experience treating autoimmune disorders. Methods We conducted a retrospective study of several treatment modes for NMOSD attacks at Beijing Tiantan Hospital and Tianjin Medical University General Hospital. Clinical outcomes were defined as the short-term remission status. The good (GR), moderate (MR) or poor remission (PR) was respectively defined to triple-grade based on percentage change of initial and follow-up Expanded Disability Status Scale (EDSS) scores. Results A total of 243 attacks was analyzed in 198 patients from 2014 to 2019. Treatment groups included 153 attacks given high-dose intravenous steroids (HD-S), 14 given IVIG, 69 episodes of IVIG plus HD-S and 7 treated with plasma exchange. The proportion of patients with better outcomes were significantly lower in IVIG alone group than HD-S alone group (p = 0.004). However, sequential treatments for IVIG and HD-S yielded a higher likelihood of clinical improvement in severe attacks with EDSS ≥ 6.5 (OR = 5.85, p = 0.007). Conclusion These results did not support IVIG-alone therapy as a first-line option for acute NMOSD. However, adding HD-S to IVIG therapy was superior to HD-S alone for patients with high-onset EDSS.

We formulate an economic optimal control problem for transport of natural gas over a large-scale transmission pipeline network under transient flow conditions. The objective is to maximize economic welfare for users of the pipeline system, who provide time-dependent price and quantity bids to purchase or supply gas at metered locations on a system with time-varying injections, withdrawals, and control actions of compressors and regulators. Our formulation ensures that pipeline hydraulic limitations, compressor station constraints, operational factors, and pre-existing contracts for gas transport are satisfied. A pipeline is modeled as a metric graph with gas dynamics partial differential equations on edges and coupling conditions at the nodes. These dynamic constraints are reduced using lumped elements to a sparse nonlinear differential algebraic equation system. A highly efficient temporal discretization scheme for time-periodic formulations is introduced, which we extend to develop a rolling-horizon model-predictive control scheme. We apply the computational methodology to a pipeline system test network case study. In addition to the physical flow and compressor control solution, the optimization yields dual functions that we interpret as the time-dependent economic values of gas at each location in the network., Comment: To appear in Proc. 58th IEEE Conference on Decision and Control

In this paper., after obtaining the point cloud data of the failed parts by the 3D laser scanner, the 3D modeling and reverse design framework for failed casting parts based on CATIA is proposed. The paper combines the 3D design software CATIA V5 to reverse design the acquired data to obtain the digital model. The failed part was remanufactured without the digital model and was copied and restored by using sand type 3D printing technology. By using the framework given in this paper, the parts and part molds are reverse designed and remanufactured, and the production cost is reduced and the manufacturing efficiency is improved by using the sand type 3D printing technology.

This paper presents the method for comparative analysis of 3D bullet mark data and proposes the technology of realizing accurate comparative analysis by extracting multidimensional features of bullet data. In our approach, the first step is to denoise the data, and then extract multidimensional feature, finally we make the comparison of coarse level to fine level. The experimental results demonstrate the effectiveness of the method.

Astrocytic impairment is a pathologic feature of neuromyelitis optica spectrum disorder (NMOSD). S100B and glial fibrillary acidic protein (GFAP) are the two most commonly used astrocytic markers. The aim of this study was to evaluate whether CSF-S100B could serve as a marker of NMOSD. We enrolled 49 NMOSD patients [25 aquaporin-4 antibody (AQP4-Ab)–positive, 8 myelin-oligodendrocyte glycoprotein antibody (MOG-Ab)-positive, and 16 seronegative patients], 12 multiple sclerosis (MS) patients, and 15 other noninflammatory neurological diseases (OND) patients. The CSF levels of S100B and GFAP were measured by ELISA. Both CSF-S100B and GFAP levels significantly discriminated NMOSD from MS [area under curve (AUC) = 0.839 and 0.850, respectively] and OND (AUC = 0.839 and 0.850, respectively). The CSF-S100B levels differentiated AQP4-Ab–positive NMOSD from MOG-Ab–positive NMOSD with higher accuracy than the CSF-GFAP levels (AUC=0.865 and 0.772, respectively). The CSF-S100B levels also significantly discriminated MOG-Ab–positive patients from seronegative patients (AUC = 0.848). Both CSF-S100B and GFAP levels were correlated with the Expanded Disability Status Scale (EDSS) during remission. Only the CSF-S100B levels were correlated with the CSF WBC count and the EDSS during attack. The levels of CSF-S100B seemed to have a longer lasting time than the levels of CSF-GFAP, which may benefit patients who present late. As a result, CSF-S100B might be a potential candidate biomarker for NMOSD in discriminating, evaluating severity, and predicting disability.

Objective: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. Methods: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy. Fifteen patients with other noninflammatory neurological diseases (OND) were also included. The serum and CSF levels of interleukin (IL)-6, IL-10, IL-17, IL-21, IL-23, transforming growth factor (TGF)-β1 and the CSF levels of 3 biomarkers of axonal loss and astrocytic damage were measured using the human cytokine multiplex assay or ELISA. Results: Serum levels of IL-10 and TGF-β1 and CSF levels of IL-6, IL-10, and TGF-β1 were significantly increased in first-onset NMOSD compared to in OND patients. In a subgroup analysis, the CSF levels of IL-6, neurofilament light protein (NFL), S100B, and glial fibrillary acidic protein (GFAP) were significantly more elevated in the AQP4-IgG-positive patients than in the AQP4-IgG-negative NMOSD patients. Correlations were found between the CSF cytokines and tissue damage biomarkers and the clinical findings in NMOSD patients. Notably, the CSF IL-6 level had the strongest correlation with the tissue damage biomarkers and it also correlated with CSF white blood cell (WBC) count. Conclusions: IL-6 plays a role in the pathogenetic process of NMOSD, especially in the AQP4-IgG-positive subtype. Distinct pathogenesis exists between AQP4-IgG-positive and AQP4-IgG-negative NMOSD in the initial phase of the disease.

Thiopurines are effective drugs in treating neuromyelitis optica spectrum disorders and other diseases. Thiopurines' toxicity is mainly imputed to thiopurine S-methyltransferase activity. In Chinese population, the most common and important variation of thiopurine S-methyltransferase is TPMT*3C (rs1142345). This study aims to reveal the association between thiopurine S-methyltransferase activity and genetic polymorphisms of thiopurine S-methyltransferase in patients with neuromyelitis optica spectrum disorders in China.A liquid chromatography tandem mass/mass method was used to evaluate the thiopurine S-methyltransferase activity by using 6-mercapthioprine as the substrate in human erythrocyte haemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine. The amount of 6-methylmercaptopurine was adjusted by haematocrit and normalized to 8 × 10In 69 patients with neuromyelitis optica spectrum disorders, thiopurine S-methyltransferase activity was 80.29-154.53 (127.51 ± 16.83) pmol/h/8 × 10TPMT*3C affects TPMT activity in Chinese patients with neuromyelitis optica spectrum disorders. Further studies are warranted to confirm the results.TPRs = thiopurines; NMOSD = neuromyelitis optica spectrum disorders; TPMT = thiopurine S-methyltransferase; LC-MS/MS = liquid chromatography tandem mass/mass; 6-MMP = 6-methylmercaptopurine; IS = internal standard; SNP = single nucleotide polymorphism; MAF = minor allele frequency; HWE = Hardy-Weinberg equilibrium; BETA = regression coefficients; UTR-3 = untranslated region 3.

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating autoimmune diseases in the central nervous system (CNS) that are characterized by a high relapse rate and the presence of anti-aquaporin 4 antibodies (AQP4-IgG) in the serum. Azathioprine (AZA) is a first-line immunomodulatory drug that is widely used for the treatment of patients with NMOSD. However, the efficacy and safety of AZA vary in different individuals. Thirty-two patients with NMOSD who regularly took AZA were enrolled in the study at Beijing Tiantan Hospital, Capital Medical University. The efficacy of AZA was evaluated using the expanded disability status scale (EDSS) and the annual relapse rate (ARR). The erythrocyte concentrations of AZA metabolites were detected using an LC-MS/MS method. The erythrocyte concentrations of 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) were 202.03 ± 63.35 pmol/8*108 RBC and 1618.90 ± 1607.06 pmol/8*108 RBC, respectively. After the patients had received AZA therapy for more than one year, the EDSS score decreased from 5.21 ± 0.24 to 2.57 ± 0.33 (p

Objective: To extract the computed tomography (CT) imaging features of the primary lesions in patients with advanced esophageal squamous cell carcinoma (ESCC) and to study whether these imaging features can predict the short-term outcome after concurrent chemoradiotherapy (CCRT). Methods: From January 2014 to December 2015, a total of 49 patients with locally advanced ESCC who underwent CCRT were analyzed retrospectively. They were randomly categorized into the training and validation groups. Collection of CT imaging of patients before and intermediate stage undergoing radiotherapy. The correlations between imaging characteristics and short-term outcome were analyzed. The accuracy of cutoff value was verified by imaging characteristics of patients in validation group. Result: There were 38 patients in the training group and 11 patients in the validation group. 13 patients in the training group were classified as responders and 25 patients as nonresponders. According to the CT imaging before radiotherapy, there are no significant differences between responders and nonresponders. According to the CT imaging in the middle stage of radiotherapy, responders showed significantly higher Roundness than nonresponders ( P = .004, 95% confidence interval [CI] = 0.0419-0.212). The areas under the ROC curves for the ability to predict significantly tumor response were 0.768 for Roundness ( P = .001, 95% CI = 0.603-0.889). The cutoff value of Roundness is 0.3099. Roundness showed no significant associations with survival parameters. Conclusions: Computed tomography imaging in the middle stage of radiotherapy can predict the short-term outcome of concurrent chemoradiotherapy for patients with locally advanced ESCC but have no predictive effect on the total survival time.

Azathioprine is a first-line drug in treating neuromyelitis optica spectrum disorders (NMOSD). To exhibit its bioactivity, azathioprine needs to be converted to thiopurine nucleotides (TPNs) including 6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-MMPNs) that are affected by genetic polymorphisms. This study aims to develop an LC-MS/MS method for the analysis of erythrocyte concentrations of TPNs and to evaluate their associations with variants of various genes (MTHFR, TPMT, HLA, SLC29A1, SLC28A2, SLC28A3, ABCB1, and ABCC4) in patients with NMOSD.Erythrocyte 6-TGNs and 6-MMPNs were converted to their free bases 6-thioguanine and 6-methylmercaptopurine derivative by 1-hour acid hydrolysis at 95°C. An LC-MS/MS method was developed, validated, and used to study 32 patients with NMOSD to determine these free bases. Genetic variants were identified by MassARRAY (Sequenom) and multiple SNaPshot techniques. The associations between genetic variants and the concentrations of TPNs or the 6-MMPNs:6-TGNs ratio were evaluated by PLINK software using linear regression.Methanol and water were used for separation with a total run time of 6.5 minutes. The lowest limit of quantification was 0.1 μmol/L with an injection volume of 10 μL. rs10868138 (SLC28A3) was associated with a higher erythrocyte concentration of 6-TGNs (P = 0.031), whereas rs12378361 (SLC28A3) was associated with a lower erythrocyte concentration of 6-TGNs (P = 0.0067). rs507964 (SLC29A1) was significantly associated with a lower erythrocyte concentration of 6-MMPNs (P = 0.024) and a lower 6-MMPNs:6-TGNs ratio (P = 0.029).An LC-MS/MS method for the analysis of erythrocyte TPNs was developed, validated, and used to study 32 patients with NMOSD. SLC29A1 and SLC28A3 were associated with the erythrocyte concentrations of TPNs and 6-MMPNs:6-TGNs ratio. Further studies are needed to confirm these results.

Background Alexander disease (AxD) is a rare neurological disease, especially in adults. It shows variable clinical and radiological features. Case presentation We diagnosed a female with AxD presenting with paroxysmal numbness of the limbs at the onset age of 28-year-old, progressing gradually to spastic paraparesis at age 30. One year later, she had ataxia, bulbar paralysis, bowel and bladder urgency. Her mother had a similar neurological symptoms and died within 2 years after onset (at the age of 47), and her maternal aunt also had similar but mild symptoms at the onset age of 54-year-old. Her brain magnetic resonance imaging (MRI) showed abnormal signals in periventricular white matter with severe atrophy in the medulla oblongata and thoracic spinal cord, and mild atrophy in cervical spinal cord, which is unusual in the adult form of AxD. She and her daughter’s glial fibrillary acidic protein (GFAP) gene analysis revealed the same heterozygous missense mutation, c.1246C > T, p.R416W, despite of no neurological symptoms in her daughter. Conclusions Our case report enriches the understanding of the familial adult AxD. Genetic analysis is necessary when patients have the above mentioned symptoms and signs, MRI findings, especially with family history.

The study investigates the gender disparity in video face replacement perception. This is inspired by the prevalent face replacement techniques being utilised in the film making industry as well as the existence of gender disparity in various aspects of human life. A user study was conducted which contained quality rating task of face replacement videos. Results show that there is a significant difference in face replacement perception for females compared to males, with females demonstrating different patterns in viewing face replacement videos to males. These results have implication for face replacement in advertising, the film industry, and for extremely high compression rate video conferencing.

A novel broadband and multiwavelength stimulated-emission source that consists of a Kerr liquid-filled hollow-fiber system pumped with a monochromatic laser beam is described. The device operates by multiorder stimulated Raman scattering (SRS) and stimulated Kerr scattering (SKS) that result from the high local optical intensity and long gain length provided by the liquid-core hollow-fiber system. A number of transparent liquids have been investigated; CS(2) is identified as the medium that most efficiently generates SKS and SRS. The overall efficiency from the pump input to the coherent output of the system is measured as a function of the fiber parameters (internal diameter and length), inputcoupling focusing length, and pump conditions (pulse duration, spectral width, and wavelength). A number of other experimental results, such as optimized working conditions, output spectral structure, total spectral-covering range, pump-threshold requirements, and the maximum capacity for high pump operation are also presented and discussed.