Hemodialysis or Peritoneal Dialysis, Which Is Better for Patients with Delayed Graft Function?

Background/Aims: Hemodialysis (HD) or peritoneal dialysis (PD) is an important renal replacement method in patients with delayed graft function (DGF) after kidney transplantation; however, it is not clear which dialysis modality is superior. This study determined the impact of different dialysis modalities on patients with DGF. Methods: It was a single-center, retrospective and descriptive study. We performed 673 kidney transplants from donors after cardiac death (DCD) between January 2010 and December 2016 at our center and 138 (20.5%) recipients developed DGF after transplantation. We classified the recipients into two groups according to post-transplant dialysis: DGF-HD (n=96) and DGF-PD (n=42). We analyzed the outcomes of the different dialysis modalities 30 days and 1 year post-transplantation. Results: There were no differences in baseline factors between patients with post-transplant HD (n = 96) or PD (n = 42). There were 10 patients with conversion from PD to HD during DGF. The DGF-PD patients had a higher rate of treatment failure than the DGF-HD patients (23.8% vs. 0%, p < 0.001), peritonitis (7.1% vs. 0%, p = 0.027), and longer duration of dialysis dependence (10.5 vs. 9 days, p = 0.003). There was no statistically significant difference between both groups with respect to acute rejection, hemorrhage, and patient and graft survival at 1 year. Conclusion: In renal transplant recipients with DGF, post-transplant PD led to increased treatment failure. PD did not result in rapid recovery of transplanted renal function, and had a high probability of peritonitis

A Web Cache Replacement Strategy for Safety-Critical Systems

A Safety-Critical System (SCS), such as a spacecraft, is usually a complex system. It produces a large amount of test data during a comprehensive testing process. The large amount of data is often managed by a comprehensive test data query system. The primary factor affecting the management experience of a comprehensive test data query system is the performance of querying the test data. It is a big challenge to manage and maintain the huge and complex testing data.To address this challenge, a web cache replacement algorithm which can effectively improve the query performance and reduce the network latency is needed. However, a general-purpose web cache replacement algorithm usually cannot be directly applied to this type of system due to the low hit rate and low byte hit rate. In order to improve the hit rate and byte hit rate, a data stream mining technology is introduced, and a new web cache algorithm GDSF-DST (Greedy Dual-Size Frequency with Data Stream Technology) for the Safety-Critical System (SCS) is proposed based on the original GDSF algorithm. The experimental results show that compared with state of the art traditional algorithms, GDSF-DST achieves competitive performance and improves the hit rate and byte hit rate by about 20%

Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice.

DVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study

Elevated Serum IL-21 Levels Are Associated With Stable Immune Status in Kidney Transplant Recipients and a Mouse Model of Kidney Transplantation

Allograft rejection after renal transplantation remains a challenge to overcome. Interleukin (IL)-21, a cytokine with pleiotropic effects, maintains immune homeostasis post-transplantation. Here, we report higher levels of IL-21 in kidney transplant recipients with non-rejection (NR) than in recipients with T cell-mediated rejection (TCMR, P \u3c 0.001) and antibody-mediated rejection (ABMR, P = 0.005). We observed a negative correlation between IL-21 and creatinine (Cr) levels (P = 0.016). The receiving operating characteristic (ROC) curve showed a promising diagnostic value of IL-21 to identify acute rejection with an area under the curve (AUC) of 0.822 (P \u3c 0.001). In contrast, exogenous administration of IL-21 accelerated acute rejection in a comparative translational kidney transplant (KT) mouse model. Reduced IL-21 levels in the peripheral blood were observed in KT mice after IL-21 injection. Further analysis revealed that increased IL-21 levels in the spleen induced proliferation of CD4+ T cells and CD19+ B cells after IL-21 treatment. Our findings suggest a critical function of IL-21 in kidney transplantation and the potential involvement of the IL-21/IL-21R pathway in acute rejection management

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Time-Frequency Analysis and Target Recognition of HRRP Based on CN-LSGAN, STFT, and CNN

Aiming at the problem of radar target recognition of High-Resolution Range Profile (HRRP) under low signal-to-noise ratio conditions, a recognition method based on the Constrained Naive Least-Squares Generative Adversarial Network (CN-LSGAN), Short-time Fourier Transform (STFT), and Convolutional Neural Network (CNN) is proposed. Combining the Least-Squares Generative Adversarial Network (LSGAN) with the Wasserstein Generative Adversarial Network with Gradient Penalty (WGAN-GP), the CN-LSGAN is presented and applied to the HRRP denoise. The frequency domain and phase features of HRRP are gained by STFT in order to facilitate feature learning and also match the input data format of the CNN. These experimental results show that the CN-LSGAN has better data augmentation performance and can effectively avoid the model collapse compared to the generative adversarial network (GAN) and LSGAN. Also, the method has better recognition performance than the one-dimensional CNN method and the Long Short-Term Memory (LSTM) network method

DAEOM: A Deep Attentional Embedding Approach for Biomedical Ontology Matching

Ontology Matching (OM) is performed to find semantic correspondences between the entity elements of different ontologies to enable semantic integration, reuse, and interoperability. Representation learning techniques have been introduced to the field of OM with the development of deep learning. However, there still exist two limitations. Firstly, these methods only focus on the terminological-based features to learn word vectors for discovering mappings, ignoring the network structure of ontology. Secondly, the final alignment threshold is usually determined manually within these methods. It is difficult for an expert to adjust the threshold value and even more so for a non-expert user. To address these issues, we propose an alternative ontology matching framework called Deep Attentional Embedded Ontology Matching (DAEOM), which models the matching process by embedding techniques with jointly encoding ontology terminological description and network structure. We propose a novel inter-intra negative sampling skill tailored for the structural relations asserted in ontologies, and further improve our iterative final alignment method by introducing an automatic adjustment of the final alignment threshold. The preliminary result on real-world biomedical ontologies indicates that DAEOM is competitive with several OAEI top-ranked systems in terms of F-measure

Efficacy and safety of SGLT2 inhibitors in nondiabetic patients with CKD: a review of recent evidence

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed as glucose-lowering agents in patients with type-2 diabetes. However, available data from clinical trials and meta-analyses suggest that SGLT2i have pleiotropic benefits in reducing mortality and delaying the progression of chronic kidney disease (CKD) in both diabetic and nondiabetic patients. Thus, we herein review the current evidence regarding the efficacy and safety of SGLT2i in patients with nondiabetic CKD, and appraise the recently reported clinical trials that might facilitate the management of CKD in routine clinical practice. Summary: The benefits of SGLT2i on nondiabetic CKD are multifactorial and is mediated by a combination of mechanisms. The landmark DAPA-CKD trial revealed that dapagliflozin administered with renin-angiotensin system blockade drugs reduced the risk of a sustained decline (at least 50%) in the estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), or death from cardio-renal causes. The recent EMPA-KIDNEY trial showed that empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes. These benefits were consistent in patients with and without diabetes. Moreover, a meta-analysis of DAPA-HF and EMPEROR-Reduced trials confirmed reductions in the combined risk of cardiovascular death or worsening heart failure including composite renal endpoint. Key Messages: Considering the robust data available from DAPA-CKD, EMPA-KIDNEY and other trials such as EMPEROR-Preserved, DIAMOND that included nondiabetic patients, it may be necessary to update current guidelines to include SGLT2i as a first-line therapy for CKD and re-evaluate current CKD therapeutic approaches

Combinatorial pathway enzyme engineering and host engineering overcomes pyruvate overflow and enhances overproduction of N-acetylglucosamine in Bacillus subtilis

Abstract Background Glucosamine-6-phosphate N-acetyltransferase (GNA1) is the key enzyme that causes overproduction of N-acetylglucosamine in Bacillus subtilis. Previously, we increased GlcNAc production by promoting the expression of GNA1 from Caenorhabditis elegans (CeGNA1) in an engineered B. subtilis strain BSGN12. In this strain overflow metabolism to by-products acetoin and acetate had been blocked by mutations, however pyruvate accumulated as an overflow metabolite. Although overexpression of CeGNA1 drove carbon flux from pyruvate to the GlcNAc synthesis pathway and decreased pyruvate accumulation, the residual pyruvate reduced the intracellular pH, resulting in inhibited CeGNA1 activity and limited GlcNAc production. Results In this study, we attempted to further overcome pyruvate overflow by enzyme engineering and host engineering for enhanced GlcNAc production. To this end, the key enzyme CeGNA1 was evolved through error-prone PCR under pyruvate stress to enhance its catalytic activity. Then, the urease from Bacillus paralicheniformis was expressed intracellularly to neutralize the intracellular pH, making it more robust in growth and more efficient in GlcNAc production. It was found that the activity of mutant CeGNA1 increased by 11.5% at pH 6.5–7.5, with the catalytic efficiency increasing by 27.5% to 1.25 s−1 µM−1. Modulated expression of urease increased the intracellular pH from 6.0 to 6.8. The final engineered strain BSGN13 overcame pyruvate overflow, produced 25.6 g/L GlcNAc with a yield of 0.43 g GlcNAc/g glucose in a shake flask fermentation and produced 82.5 g/L GlcNAc with a yield of 0.39 g GlcNAc/g glucose by fed-batch fermentation, which was 1.7- and 1.2-times, respectively, of the yield achieved previously. Conclusions This study highlights a strategy that combines pathway enzyme engineering and host engineering to resolve overflow metabolism in B. subtilis for the overproduction of GlcNAc. By means of modulated expression of urease reduced pyruvate burden, conferred bacterial survival fitness, and enhanced GlcNAc production, all of which improved our understanding of co-regulation of cell growth and metabolism to construct more efficient B. subtilis cell factories