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BackgroudInterleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population.MethodsWe genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP).ResultsThere were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P = 0.041) and larger tumor size (P = 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p = 0.022) and higher tumor stage(p = 0.028) of breast cancer at the time of diagnosis compared with others.ConclusionsOur findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.

1049 Background: HER2 is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker. Methods: This was a single arm, open-label, multicenter, dose escalating Phase 1 first-in-human study of A166 as monotherapy in solid tumor patients. Dose escalation and MTD identification was directed using a Bayesian logistic regression model with overdose control. The following dose levels were evaluated in this study: 0.3, 1.2, 3.6, 4.8 mg/kg. (ClinicalTrials.gov NCT03602079) Results: As of November 1, 2019 35 pts have completed the DLT evaluation period across 4 dose levels. Overall, A166 had an acceptable toxicity profile with no unexpected toxicities related to the study drug. No adverse events recorded met the protocol specified definition of a dose limiting toxicity at any studied dose level. Most frequently (≥10%) occurring TEAEs include were Keratitis, Decreased appetite, Dry eye, Vision blurred etc. Overall incidence of ophthalmic toxicities in the 3.6 mg/kg cohort was 80% and in the 4.8 mg/kg cohort it was 83%. Among the 27 patients evaluable for efficacy, best response was progression of disease in 11 patients (41%), stable disease in 9 patients (33%) and partial response in 7 patients (26%), for the total disease control rate of 59%.Responses were seen only at the dose levels of 3.6 mg/kg and 4.8 mg/kg. Conclusions: A166 demonstrated clinically meaningful efficacy in heavily pretreated patients with relapsed or refractory advanced solid cancers. The achievement of an ORR of 36% at efficacious dose levels and up to 100% in HER2 positive patients regardless of histology (2 CRC, 1 BC and 1 NSCLC) at the highest studied dose level exceed Clinical trial information: NCT03602079 .

The Nectin cell adhesion molecule (Nectin) family members are Ca 2+ -independent immunoglobulin-like cellular adhesion molecules (including Nectins 1-4), involved in cell adhesion via homophilic/heterophilic interplay. In addition, the Nectin family plays a significant role in enhancing cellular viability and movement ability. In contrast to enrichment of Nectins 1-3 in normal tissues, Nectin-4 is particularly overexpressed in a number of tumor types, including breast, lung, urothelial, colorectal, pancreatic and ovarian cancer. Moreover, the upregulation of Nectin-4 is an independent biomarker for overall survival in numerous cancer types. A large number of studies have revealed that high expression of Nectin-4 is closely related to tumor occurrence and development in various cancer types, but the manner in which Nectin-4 protein contributes to the onset and development of these malignancies is yet unknown. The present review summarizes the molecular mechanisms and functions of Nectin-4 protein in the biological processes and current advances with regard to its expression and regulation in various cancer types. Contents 1. Introduction 2. Molecular structures of Nectin family members 3. Nectin-induced signaling during the formation of cell-cell junctions 4. Distribution and physiological function of Nectins 5. Biological role of Nectin-4 proteins in cancer 6. Nectin-4 serves as a prognostic or diagnostic marker for selected types of cancer 7. Enfortumab vedotin (EV) 8. Oncolytic virus 9. Conclusion

In recent years, there have been numerous cyber security issues that have caused considerable damage to the society. The development of efficient and reliable Intrusion Detection Systems (IDSs) is an effective countermeasure against the growing cyber threats. In modern high-bandwidth, large-scale network environments, traditional IDSs suffer from a high rate of missed and false alarms. Researchers have introduced machine learning techniques into intrusion detection with good results. However, due to the scarcity of attack data, such methods’ training sets are usually unbalanced, affecting the analysis performance. In this paper, we survey and analyze the design principles and shortcomings of existing oversampling methods. Based on the findings, we take the perspective of imbalance and high dimensionality of datasets in the field of intrusion detection and propose an oversampling technique based on Generative Adversarial Networks (GAN) and feature selection. Specifically, we model the complex high-dimensional distribution of attacks based on Gradient Penalty Wasserstein GAN (WGAN-GP) to generate additional attack samples. We then select a subset of features representing the entire dataset based on analysis of variance, ultimately generating a rebalanced low-dimensional dataset for machine learning training. To evaluate the effectiveness of our proposal, we conducted experiments based on the NSL-KDD, UNSW-NB15, and CICIDS-2017 datasets. The experimental results show that our method can effectively improve the detection performance of machine learning models and outperform the baselines.

Objective We investigated scoliosis incidence among junior high school students in Zhongshan city, Guangdong, China and the expression of miR-30e among those with scoliosis. Methods A total 41,258 students were included. From July 2015 to December 2017, all students underwent screening including routine observation of the standing and sitting posture, Adam's forward bend test, dorsal tilt angle measurement, and X-ray examination. Age, sex, height, weight, and body mass index (BMI) were recorded. Reverse transcription-quantitative polymerase chain reaction was used to assess miR-30e expression among students with scoliosis and 200 healthy students. Results Overall, 743 students were diagnosed with scoliosis, with an incidence rate of 1.80%. A total 646 (86.9%) students were diagnosed with idiopathic scoliosis, 38 (5.1%) with congenital scoliosis, and 59 (7.9%) with other scoliosis types. Compared with healthy students, height was significantly greater whereas weight and BMI were significantly lower among students with scoliosis, and expression of miR-30e was significantly lower. However, no significant difference was found in height, weight, BMI, and mean Cobb angle between high/low miR-30e groups. Conclusion The incidence rate for scoliosis was 1.80%, Compared with healthy students, those with scoliosis were taller, had lower weight and BMI, and miR-30e expression was significantly downregulated.

The plethora of complex Artificial Intelligence (AI) algorithms and available High-Performance Computing (HPC) power stimulates the expeditious development of AI components with heterogeneous designs. Consequently, the need for cross-stack performance benchmarking of AI-HPC systems has rapidly emerged. In particular, the de facto HPC benchmark, LINPACK, cannot reflect the AI computing power and input/output performance without a representative workload. Current popular AI benchmarks, such as MLPerf, have a fixed problem size and therefore limited scalability. To address these issues, we propose an end-to-end benchmark suite utilizing automated machine learning, which not only represents real AI scenarios, but also is auto-adaptively scalable to various scales of machines. We implement the algorithms in a highly parallel and flexible way to ensure the efficiency and optimization potential on diverse systems with customizable configurations. We utilize Operations Per Second (OPS), which is measured in an analytical and systematic approach, as a major metric to quantify the AI performance. We perform evaluations on various systems to ensure the benchmark's stability and scalability, from 4 nodes with 32 NVIDIA Tesla T4 (56.1 Tera-OPS measured) up to 512 nodes with 4096 Huawei Ascend 910 (194.53 Peta-OPS measured), and the results show near-linear weak scalability. With a flexible workload and single metric, AIPerf can easily scale on and rank AI-HPC, providing a powerful benchmark suite for the coming supercomputing era.

Purpose Nectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied. Methods The expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p. Results Nectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing. Conclusions Nectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.