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Due to the huge capacities of computing and storage resources, wide-area distributed computing environment has become important infrastructures supporting computing power and data interconnection.In wide-area distributed computing environment, matching of tasks and resources is important to improve system performance.However, the diversity of tasks and resources and the geographical dispersion of resources increase the complexity of matching problems.To solve the problems of high response delay and low matching efficiency, a dynamic bidirectional matching method of tasks and resources oriented to wide-area distributed computing environments is proposed.The matching process is simplified and the response delay is mitigated by building a unified task requirement model and resource capability model.Moreover, the task-oriented and resource-oriented matching degrees are defined to express the preference of task-perspective and resource-perspective; the two-side comprehensive matching degree of tasks and resources is defined by the trade-off of the task-oriented and resource-oriented matching degree.The two-side comprehensive matching degrees are dynamically calculated for each task group and the resources to improve the matching quality.The experimental results show that the proposed method can effectively promoting the matching quality and significantly reduce the response delay compared with the existing methods.

In the existing large-scale distributed environments, there is still much room for improvement in the performance and computational efficiency of big data applications.However, performance analysis and optimization in large-scale environments requires a large number of human resources from domain experts.This paper proposes a general lowperformance query statement detection and optimization process for performance optimization in big data applications, summarizes four types of low-performance behaviors that significantly affect the performance of big data applications, and proposes specific optimization strategies for each type of low-performance behavior.Finally, through experimental evaluation, the effectiveness of the optimization scheme in actual large-scale cluster is verified.

Abstract Background In the treatment of advanced pancreatic cancer, chemotherapy plays a pivotal role. Despite its effectiveness, this regimen is often marred by side effects such as anemia, neuropathy, fatigue, nausea, and malnutrition, which significantly affect patients’ tolerance to the treatment. Some studies have shown that vitamin C could potentially augment chemotherapy’s tolerability, notably by boosting iron absorption, ameliorating anemia, and relieving pain and numbness in hands and feet. Nevertheless, the integration of vitamin C with chemotherapy to mitigate toxic side effects and enhance the quality of life for advanced pancreatic cancer patients has not been examined in any randomized controlled trials to date. Methods A prospective, single-center, open-label, randomized controlled trial will be conducted at Fudan University Shanghai Cancer Center from September 2023 to September 2026. A total of at least 100 patients with advanced pancreatic adenocarcinoma exhibiting distant metastases will be recruited and randomly assigned to the chemotherapy group or the chemotherapy plus vitamin C group. The primary endpoint is the rate of anemia. Secondary endpoints include the rate of grade 3 neuropathy, change of numeric rating scale, quality of life, and overall survival. Discussion This study aims to assess the impact of low-dose vitamin C on enhancing the quality of life for patients with metastatic pancreatic cancer undergoing gemcitabine and nab-paclitaxel chemotherapy. Trial registration The trial was registered with the ClinicalTrials.gov (NCT06018883) on August 31, 2023.

This study aimed to explore the specific AT-rich sequence-binding protein 2 (SATB2) regulated Warburg effect of laryngeal squamous cell carcinoma (LSCC) and its possible mechanism of action.Bioinformatic and single-cell analyses revealed that SATB2 expression was suppressed in patients with LSCC. In an in vitro model, SATB2 suppressed LSCC cells proliferation and migration. Si-SATB2 promotes LSCC cells proliferation and migration. Additionally, sh-SATB2 promotes LSCC proliferation in a mouse model. SATB2 suppresses Wnt expression in an in vitro model and si-SATB2 induces Wnt expression in an in vitro model. Additionally, sh-SATB2 suppresses Wnt expression in a mouse model. Wnt inhibitors reduce the effects of si-SATB2 or sh-SATB2 on the Warburg effect and cell proliferation in a mouse or in vitro model of LSCC. SATB2 interacts with Wnt proteins to reduce Wnt protein ubiquitination. Methyltransferase-like 3 (METTL3)-mediated m6A modification decreases SATB2 stability in a YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) −dependent manner in an LSCC model.The interaction between the active constituents of SATB2 and Wnt1 results in the inhibition of Wnt/β-catenin, thereby affecting the Wnt/β-catenin-mediated Warburg effect. This study demonstrated that METTL3-mediated m6A modification reduces SATB2 stability in a YTHDF1-dependent manner in an LSCC model, with remarkable efficacy in inducing the Warburg effect in an LSCC model.

Cache plays a crucial role in improving system response time, alleviating server pressure, and achieving load balancing in various aspects of modern information systems. The data prefetch and cache replacement algorithms are significant factors influencing caching performance. Due to the inability to learn user interests and preferences accurately, existing rule-based and data mining caching algorithms fail to capture the unique features of the user access behavior sequence, resulting in low cache hit rates. In this article, we introduce BERT4Cache, an end-to-end bidirectional Transformer model with attention for data prefetch in cache. BERT4Cache enhances cache hit rates and ultimately improves cache performance by predicting the user’s imminent future requested objects and prefetching them into the cache. In our thorough experiments, we show that BERT4Cache achieves superior results in hit rates and other metrics compared to generic reactive and advanced proactive caching strategies.

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Deep brain stimulation (DBS) is an effective treatment for neurological disorders, and accurately reconstructing the DBS lead trajectories is crucial for MRI compatibility assessment and surgical planning. This paper presents a novel fully automated framework for reconstructing DBS lead trajectories from postoperative CT images. The leads were first segmented by thresholding, but would be fused together somewhere. Mean curvature analysis of multi-layer CT number isosurfaces was introduced to effectively address lead fusion, due to the different topological characteristics of the isosurfaces in and out of the fusion regions. The position of electrode contacts was determined through morphological analysis to get the starting point and the initial direction for trajectory tracking. The next trajectory point was derived by calculating the weighted average coordinates of the candidate points, using the distance from the current estimated trajectory and the CT number as weights. This method has demonstrated high accuracy and efficiency, successfully and automatically reconstructing complex bilateral trajectories for 13 patient cases in less than 10 minutes with errors less than 1 mm. This work overcomes the limitations of existing semi-automatic techniques that require extensive manual intervention. It paves the way for optimizing DBS lead trajectory to reduce tissue heating and image artifacts, which will contribute to neuroimaging studies and improve clinical outcomes. Code for our proposed algorithm is publicly available on Github.

Abstract Recent advances in neoantigen research have accelerated the development of tumor immunotherapies, including adoptive cell therapies (ACTs), cancer vaccines and antibody-based therapies, particularly for solid tumors. With the development of next-generation sequencing and bioinformatics technology, the rapid identification and prediction of tumor-specific antigens (TSAs) has become possible. Compared with tumor-associated antigens (TAAs), highly immunogenic TSAs provide new targets for personalized tumor immunotherapy and can be used as prospective indicators for predicting tumor patient survival, prognosis, and immune checkpoint blockade response. Here, the identification and characterization of neoantigens and the clinical application of neoantigen-based TCR-T immunotherapy strategies are summarized, and the current status, inherent challenges, and clinical translational potential of these strategies are discussed.

The integration of diverse devices has made the establishment of multi-class classification models for multi-source data a primary concern for data mining in cloud–edge system. Developing rule-based classifiers is essential because they present results that express the reasons for classification. However, existing rule learning methods are not compatible with multi-source tabular data containing mixed features, imbalanced labels and missing values, making it difficult to build cross-data source and cross-device data mining models. We developed a heuristic multi-class rule learning method that can handle complex tabular datasets without relying too much on cumbersome preprocessing techniques. We abstract the training process of the classifier into a multi-objective optimization problem and design a novel hybrid evolutionary algorithm to obtain Pareto-optimal solutions as rule-based classifier. Compared with the existing explainable classification methods, this method has obvious advantages in the classification performance of tabular data.

Abstract Background Carbohydrate antigen 19–9 (CA19-9) is the most widely used biomarker for pancreatic cancer. Since CA19-9 closely correlates with patient outcome and tumor stage in pancreatic cancer, the deciphering of CA19-9 biosynthesis provides a potential clue for treatment. Methods Concentration of amino acids was detected by ultrahigh-performance liquid chromatography tandem mass spectrometry. Metabolic flux of glutamine was examined by isotope tracing untargeted metabolomics. Label-free quantitative n-glycosylation proteomics was used to examine n-glycosylation alterations. Results Among all amino acids, glutamine was higher in CA19-9-high pancreatic cancers (> 37 U/mL, 66 cases) than in CA19-9-normal clinical specimens (≤ 37 U/mL, 37 cases). The glutamine concentration in clinical specimens was positively correlated with liver metastasis or lymphovascular invasion. Glutamine blockade using diazooxonorleucine suppressed pancreatic cancer growth and intraperitoneal and lymphatic metastasis. Glutamine promotes O-GlcNAcylation, protein glycosylation, and CA19-9 biosynthesis through the hexosamine biosynthetic pathway. UDP-n-acetylglucosamine (UDP-GlcNAc) levels correlated with the glutamine influx through hexosamine biosynthetic pathway and supported CA19-9 biosynthesis. Conclusions Glutamine is a substrate for CA19-9 biosynthesis in pancreatic cancer. Glutamine blockade may be a potential therapeutic strategy for pancreatic cancer.

Aiming at the limited degree of revealing vegetation growth pattern by simple topographic factors, it is essential to find an index that can explain the vegetation cover mechanism to a greater extent. By introducing a certainty factor into vegetation cover evaluation, LSW, LS, topographic wetness index, and aspect were also chosen to carry out control group experiments. The grid digital elevation model of 10 disaster-stricken counties (cities) in Sichuan Province was used as the basis to obtain LSW, while vegetation susceptibility levels were categorized using the natural breaks classification. The results of the multi-factor analysis demonstrated that the certainty factor corresponding to LSW climbed linearly from negative to positive values as the susceptibility level rose, indicating that it was highly correlated with vegetation cover and had an obvious advantage in revealing the vegetation growth potential. Statistically, the vegetation occurrence rate increased regularly with the improvement of the susceptibility level, in which the high and very high susceptibility zones corresponded to 83.66% and 89.95% of vegetation coverage respectively, suggesting a good consistency between the delineated high susceptibility areas and the actual vegetation cover. The findings proved that LSW has a substantial advantage in evaluating vegetation cover, with an evaluation model accuracy of 72.9%. It has been established that LSW will serve as a promising new model for assessing vegetation restoration and planning.

Abstract Distant metastasis remains the major cause for treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, it is necessary to investigate the underlying regulation mechanisms and potential biomarkers for NPC metastasis. Nogo-B (neurite outgrowth inhibitor B), encoded by reticulon-4, has been shown to be associated with the progression and advanced stage of several cancer types. However, the relationship between Nogo-B and NPC remains unknown. In this study, we found that higher expression of Nogo-B was detected in NPC cells and tissues. Higher expression of Nogo-B was statistically relevant to N stage, M stage, and poor prognosis in NPC patients. Further functional investigations indicated that Nogo-B overexpression could increase the migration, invasion, and metastasis ability of NPC cells in vitro and in vivo. Mechanistically, Nogo-B promoted epithelial-mesenchymal transition (EMT) and enhanced the invasive potency by interacting directly with its receptor NgR3 in NPC. Additionally, overexpression of Nogo-B could upregulate the protein levels of p-RhoA, SRF, and MRTFA. A positive relationship was found between the expression of Nogo-B and the p-RhoA in NPC patients as well as in mouse lung xenografts. Nogo-Bhigh p-RhoAhigh expression was significantly associated with N stage, M stage, and poor prognosis in NPC patients. Notably, CCG-1423, an inhibitor of the RhoA-SRF-MRTFA pathway, could reverse the invasive potency of Nogo-B and NgR3 in NPC cell lines, and decrease the expression of N-Cadherin, indicating that CCG-1423 may be a potential target drug of NPC. Taken together, our findings reveal that Nogo-B enhances the migration and invasion potency of NPC cells via EMT by binding to its receptor NgR3 to regulate the RhoA-SRF-MRTFA pathway. These findings could provide a novel insight into understanding the metastasis mechanism and targeted therapy of advanced NPC.

Background. Matrix metalloproteinase-7 (MMP7) is markedly expressed in patients with chronic kidney disease; its expression in dialysate and role in patients undergoing peritoneal dialysis (PD) have not been well established. Methods. Participants undergoing PD from June 1st, 2015, to June 30th, 2020, were involved and were followed up every 3 months for the first year and every 6 months thereafter until death, PD withdrawal, or the end of the study. Data at each follow-up point were collected and analyzed for the association with congestive heart failure (CHF), PD withdrawal, and combined endpoint. Results. A total of 283 participants were included in this study. During a median follow-up of 21 months, 20 (7%) participants died, 93 (33%) withdrew from PD, and 105 (37%) developed CHF. A significantly increased level of serum and dialysate MMP7 was observed at baseline. Dialysate MMP7 presented a good linearity with serum MMP7. Baseline serum and dialysate MMP7 levels were associated with CHF in multivariable Cox proportional hazards regression models. After categorization, participants with high baseline MMP7 levels had a higher incidence of CHF (42%), and the hazard ratios (95% confidence intervals) were 1.595 (1.023-2.488). Interestingly, participants with higher serum MMP7 levels were trended to use dialysate with higher glucose concentration. However, the ultrafiltration volumes were not significantly increased. Higher MMP7 levels were also positively associated with PD withdrawal and combined endpoint. Conclusions. The expression of MMP7 in serum and dialysate was markedly increased and was tightly associated with the risk of CHF in PD patients. This finding suggests that the measurement of MMP7 may inform strategies for managing CHF at an earlier stage.

In the process of zinc smelting, when the chloride ion concentration exceeds 100 mg/L, it continuously corrodes the electrode plate and affects the stability of the electrodeposition process. Therefore, the chloride concentration must be reduced below 100 mg/L. Compared with other methods used to control the reactions of Cu(II), the use of the copper slag produced in zinc smelting without other additives does not cause reverse dissolution; to reduce the cost, turn the waste into treasure, and protect the environment, research was carried out on chloride removal by the copper slag via a synergistic valence control process. In this study, the influencing factors, such as the amount of copper slag, the reaction time, and reaction temperature, were systematically investigated. The results showed that the optimum dechlorination conditions were as follows: the copper: copper(II): chloride molar ratio was 6:5:1, the reaction time was 60 min, and the reaction temperature was 20 °C. The chloride ion concentration was decreased from 1.6 g/L to 0.05 g/L, the dechlorination efficiency was 96.875%, and the residual chloride ion concentration was less than 100 mg/L, which provides a basis for industrial use.

Summary: Background: Previously, we uncovered a patient subgroup with highly malignant pancreatic cancer with serum markers CEA+/CA125+/CA19-9 ≥ 1000 U/mL (triple-positive, TP). However, the underlying immunosuppressive mechanism in the tumor immune microenvironment (TIME) of this subgroup is still unknown. Methods: Human tissues were analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Mouse pancreatic ILC2s were expanded in vivo and used for RNA sequencing, chromatin immunoprecipitation (ChIP), and chemotaxis assays. Findings: Through microarray data, we identified the accumulation of the hypoxia-induced factor-1α (HIF-1α) pathway in these TP patients. Via flow and mass cytometry, we discovered that a special subset of ILC2s were highly infiltrated in TP patients. Under the hypoxia microenvironment, ILC2s were found undergo a transition to a IL10+ regulatory phenotype, we named ILCregs which was correlated with pancreatic ductal adenocarcinoma (PDAC) progression. Further, neoadjuvant chemotherapy could ameliorate hypoxic tumor microenvironments so that significantly reverse the regulatory phenotype of ILCregs. Moreover, most tumor ILC2 were CD103−, which indicated its circulatory origin. The expression of Ccr2 was significantly upregulated on mouse ILCregs, and these cells selectively migrated to CCL2. Interpretation: Our results indicate that the hypoxia microenvironment creates an immunosuppressive TIME by inducing ILCregs from a population of circulating group 2 ILCs in TP PDAC patients. Funding: This study was jointly supported by the National Natural Science Foundation of China (U21A20374, 82173091, and 81701630)

Background and AimsWheat gluten is a critical trigger for celiac disease, often causing inflammatory lesions and oxidative stress damage in the intestines of patients. In daily life, it is difficult for celiac disease patients to strictly avoid the dietary intake of gluten, which makes complementary preventive therapy particularly urgent. As such, we investigated the alleviating effects of resveratrol in vivo and in vitro models of celiac disease.MethodsWe established in vivo and in vitro models of gluten protein-induced celiac disease. The intervention effect of resveratrol was defined well based on relevant indicators of inflammation, immunity and oxidative stress, and its possible involvement in signaling pathways and genes were also identified.ResultsResveratrol was effective in reducing intestinal oxidative stress and inflammatory damage induced by wheat gluten in both cell and mouse models for celiac disease. We identified correlations between the genes (Fgf15, Nr0b2, Aire and Ubd) and signaling pathways (PPAR, AMPK and FoxO) in which resveratrol performed critical roles.ConclusionsResveratrol contributed to regulate development of autoimmunity through up-regulation of Aire and Ubd genes and promote nutrient absorption in intestine through down-regulation of Fgf15 and Nr0b2 genes, as well as played a role in regulating complex response system of oxidative stress, inflammatory response and immune response in intestine by activating PPAR, AMPK and FoxO signaling pathways, thus effectively alleviating the intestinal symptoms of celiac disease.

Background: Serum phosphorus (SP) level is closely associated with overall mortality and cardiovascular events, while the role of SP controlled duration is not fully recognized. Here, we conducted a retrospective cohort study in our department to identify the relationship of SP controlled duration with clinical outcomes in patients undergoing peritoneal dialysis (PD). Methods: PD patients in our center from January 1, 2009, to June 30, 2019, were followed up at 2-month (the first year) or 5-month (the next follow-up period) intervals, and until death, until PD withdrawal, or until June 30, 2019. Data at each follow-up point were collected from their medical records. SP levels, changed degree of SP over baseline, and SP controlled duration were analyzed with overall mortality, PD withdrawal (including death, transferred to hemodialysis, and received renal transplantation), and combined endpoint (including death, acute heart failure, cardiovascular event, and stroke). Results: A total of 530 patients entered the analysis. Of them, 456 (86.0%) had hyperphosphatemia before dialysis, and the SP levels decreased soon after dialysis. The degree of SP change over baseline was the maximum at the 3rd month after dialysis (−31.0%), and lower degree was associated with higher overall mortality (hazard ratio [HR], 1.012; 95% CI, 1.004–1.020; p = 0.003). The median SP controlled duration was 13 (5–28) months, and longer duration was significantly associated with lower overall mortality (HR, 0.968; 95% CI, 0.956–0.981; p < 0.001). After categorization, duration more than 12 months greatly improved overall mortality with a HR of 0.197 (0.082–0.458; p < 0.001 vs. SP never controlled group) and 0.329 (0.150–0.724; p = 0.006 vs. duration

Objective. Head and neck squamous cell carcinoma (HNSCC) is a highly heterotopic malignant tumor. Alternative splicing (AS) and RNA modification have been reported to be involved in tumorigenesis. Therefore, we constructed RNA modification-associated AS (RMA-AS) signature model to predict the prognosis of HNSCC. Methods. AS events and RNA-modified gene expression information were downloaded from TCGA-HNSCC database. Univariate Cox regression analysis was employed for analyzing prognosis-related AS events. RMA-AS events were obtained by constructing a coexpression network between RNA modification-associated genes and AS events using WGCNA package. The prognostic signatures were analyzed by LASSO, univariate Cox, and multivariate Cox regression. Kaplan-Meier survival analysis, proportional hazard model, and ROC curve were performed to verify the prognostic value. “ESTIMATE” R package, ssGSEA algorithm, and CIBERSORT method were used to detect immune microenvironment in HNSCC. Cytoscape was utilized to build a regulatory network of splicing factor-regulated RMA-AS. Results. There were 16,574 prognostic AS events and 4 differentially expressed RNA modification-associated genes in HNSCC. Based on RMA-AS events, we obtained a risk model consisting of 14 AS events, named RMA-AS_Score. The samples were divided into RMA-AS_Score high- and RMA-AS_Score low-risk groups, according to the risk score. The RMA-AS_Score high group was related to poor prognosis. Moreover, the RMA-AS_Score signature was an independent prognostic predictor and was related to tumor grade. Meanwhile, the AUC value of RMA-AS_Score was 0.652, which is better than other clinical characteristics. Besides, a nomogram prediction model of quantitative prognosis has also been developed, which has robust effectiveness in predicting prognosis. In addition, the prognostic signature was observably related to immune microenvironment and immune checkpoint. Finally, 14 splicing factors were identified and constructed into a network of splicing factor-regulated RMA-AS. Conclusion. We identified the RMA-AS signature of HNSCC. This signature could be treated as an independent prognostic predictor.

The journal Buildings was launched in 2011 and is dedicated to promoting advancements in building science, building engineering and architecture. Motivated by its 10th anniversary in 2021, this study aims to develop a bibliometric analysis of the publications of the journal between April 2011 and October 2021. This work analyzes bibliometric performance indicators, such as publication and citation structures, the most cited articles and the leading authors, institutions and countries/regions. Science mappings based on indicators such as the most commonly used keywords, citation and co-citation, and collaboration are also developed for further analysis. In doing so, the work uses the Scopus database to collect data and Bibliometrix to conduct the research. The results show the strong growth of Buildings over time and that researchers from all over the world are attracted by the journal.

The discovery of antibiotics has long helped humans in the battle against bacteria. However, the misuse of antibiotics in industries and medical systems has unintentionally provided an ideal environment for bacteria to develop resistance mechanisms through mutations and gene transfer, resulting in the emergence of antimicrobial-resistant bacteria. This has proven to be an urgent and pressing issue in the global healthcare system, resulting in increased mortality. Therefore, increasing resources are invested to study their different resistance mechanisms and develop corresponding novel drugs and treatment methods. This review briefly introduces several key resistance mechanisms with examples from both Gram-negative and Gram-positive bacteria, the current and novel methods for treating multiple drug-resistant bacteria as well as the potential actions that could be done to improve the situation. [ABSTRACT FROM AUTHOR]