DRNet: Double Recalibration Network for Few-Shot Semantic Segmentation.

Few-shot segmentation aims at learning to segment query images guided by only a few annotated images from the support set. Previous methods rely on mining the feature embedding similarity across the query and the support images to achieve successful segmentation. However, these models tend to perform badly in cases where the query instances have a large variance from the support ones. To enhance model robustness against such intra-class variance, we propose a Double Recalibration Network (DRNet) with two recalibration modules, i.e., the Self-adapted Recalibration (SR) module and the Cross-attended Recalibration (CR) module. In particular, beyond learning robust feature embedding for pixel-wise comparison between support and query as in conventional methods, the DRNet further exploits semantic-aware knowledge embedded in the query image to help segment itself, which we call 'self-adapted recalibration'. More specifically, DRNet first employs guidance from the support set to roughly predict an incomplete but correct initial object region for the query image, and then reversely uses the feature embedding extracted from the incomplete object region to segment the query image. Also, we devise a CR module to refine the feature representation of the query image by propagating the underlying knowledge embedded in the support image's foreground to the query. Instead of foreground global pooling, we refine the response at each pixel in the query feature map by attending to all foreground pixels in the support feature map and taking the weighted average by their similarity; meanwhile, feature maps of the query image are also added back to weighted feature maps as a residual connection. Our DRNet can effectively address the intra-class variance under the few-shot setting with such two recalibration modules, and mine more accurate target regions for query images. We conduct extensive experiments on the popular benchmarks PASCAL- 5i and COCO- 20i . The DRNet with the best configuration achieves the mIoU of 63.6% and 64.9% on PASCAL- 5i and 44.7% and 49.6% on COCO- 20i for 1-shot and 5-shot settings respectively, significantly outperforming the state-of-the-arts without any bells and whistles. Code is available at: https://github.com/fangzy97/drnet.

Association of Blood Biochemical Indexes and Antibiotic Exposure With Severe Immune-related Adverse Events in Patients With Advanced Cancers Receiving PD-1 Inhibitors.

Some patients with cancer treated with programmed death 1 (PD-1) inhibitors experience immune-related severe adverse events (ir-SAEs), however, predictors are limited. The objective was to identify clinicopathologic features that may be associated with a higher ir-SAE risk. This was a nested case-control study. After screening a total of 832 PD-1 inhibitor-treated patients, we identified 42 ir-SAE cases. According to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, ir-SAEs were defined as grade ≥3 toxic effects associated with immunotherapy. A total of 126 controls were matched. The crude and adjusted risks of ir-SAEs were estimated by odds ratio (ORs) and 95% CIs using multivariate logistic regression models. Baseline neutrophil-to-lymphocyte ratio (NLR) [per SD increment-adjusted (aOR): 1.16], lactate dehydrogenase (LDH) ≥245 U/L (aOR: 2.39), and antibiotic exposure (aOR: 4.39) were associated with a higher risk of ir-SAEs. When NLR was categorized in 3 groups, significantly higher risks of ir-SAEs (aOR: 4.95) were found in participants in group 3 (>6) than in those in group 1 (<3). Furthermore, NLR (per SD increment-adjusted hazard ratio:1.08) were also significantly associated with shorter overall survival (OS). Baseline LDH ≥245 U/L and antibiotic exposure were no significant association with OS. In conclusion, ir-SAEs were associated between baseline NLR, LDH ≥245 U/L and antibiotic exposure. Lower NLR was correlated with longer OS for cancer.

A review of gene-gene interaction studies in rheumatoid arthritis / 中华疾病控制杂志

To date, multiple genetic susceptible genes/loci associated with rheumatoid arthritis (RA) have been identified and confirmed through large-scale genetic association studies and genome-wide association study (GWAS). However, the heritability of RA could be not fully explained by these genetic factors, and gene-gene interaction might account for part of the missing heritability. Indeed, genetic interaction study is a critical research direction in the field of genetic epidemiology of RA, and these studies have provided novel insights into the genetic basis and pathogenesis of RA. Additionally, these studies have also provided scientific reference for risk prediction and prevention of RA. This review is aimed to present a summary of recent progress in genetic interaction study of RA, thus implicate further research in this field.

Effects of stocking density on antioxidant status, metabolism and immune response in juvenile turbot (Scophthalmus maximus).

This study was designed to evaluate the physiological and immune responses of juvenile turbot to stocking density. Turbot (average weight 185.4g) were reared for 120days in a land based recirculating aquaculture system (RAS) under three stocking densities: low density (LD, ~9.3-26.1kg/m2, initial to final density), medium density (MD, ~13.6-38.2kg/m2) and high density (HD, ~19.1-52.3kg/m2). Fish were sampled at days 0, 40, 80 and 120 to obtain growth parameters and liver tissues. No significant difference was detected in growth, biochemical parameters and gene expression among the three densities until at the final sampling (day 120). At the end of this trial, fish reared in HD group showed lower specific growth rate (SGR) and mean weight than those reared in LD and MD groups. Similarly, oxidative stress and metabolism analyses represented that antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH)) and metabolic enzymes (glycerol-3-phosphate dehydrogenase (G3PDH) and glucose-6-phosphate dehydrogenase (G6PDH)) clearly reduced in the liver of turbot reared in HD group. The gene expression data showed that glutathione S-transferase (GST), cytochrome P450 1A (CYP1A), heat shock protein 70 (HSP 70) and metallothionein (MT) mRNA levels were significantly up-regulated, and lysozyme (LYS) and hepcidin (HAMP) mRNA levels were significantly down-regulated in HD group on day 120. Overall, our results indicate that overly high stocking density might block the activities of metabolic and antioxidant enzymes, and cause physiological stress and immunosuppression in turbot.

Stress and immune responses in skin of turbot (Scophthalmus maximus) under different stocking densities.

Fish skin and its mucus provide the first line of defense against chemical, physical and biological stressors, but little is known about the role of skin and its mucus in immune response to crowding stress. In the present study, we investigated the stress and immune responses in skin of turbot (Scophthalmus maximus) under different stocking densities. Turbot (average weight 185.4 g) were reared for 120 days under three densities: low density (LD), medium density (MD), and high density (HD). After 120 days, fish were weighed and sampled to obtain blood, mucus and skin tissues which were used for analyses of biochemical parameters and genes expression. The results showed HD treatment significantly suppressed growth and enhanced plasma cortisol and glucose levels (P < 0.05). In mucus, the activities of lysozyme (LZM), alkaline phosphatase (ALP) and esterase in HD treatment were lower than LD and MD treatments (P < 0.05) In skin, HD treatment resulted in up-regulation in malondialdehyde (MDA) formation and heat shock protein 70 (HSP 70) mRNA level, and down-regulation in activity of superoxide dismutase (SOD) and the transcriptions of glutathione-s-transferase (GST), interleukin-1ß (IL-1ß), tumor necrosis factor -α (TNF-α), insulin-like growth factor- (IGF-) and LZM (P < 0.05). Overall, the data suggested that overly high stocking density was a stressor which caused an immunosuppression in skin of turbot. Moreover, this information would help to understand the skin immunity and their relation with stress and disease in fish.

The physiological performance and immune response of juvenile turbot (Scophthalmus maximus) to nitrite exposure.

Nitrite (NO(2-)) is the most common toxic nitrogenous compound in aquatic environment. The aim of the present study was to investigate the effects of nitrite physiological performance and immune response of turbot. Fish were exposed to 0, 0.02, 0.08, 0.4 and 0.8 mM nitrite for 96 h. After 0, 24, 48 and 96 h of exposure, blood were collected to measure the levels of glutamate pyruvate transaminase (GPT), glutamate oxalate transaminase (GOT), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), complement C3 (C3), complement C4 (C4), immunoglobulin M (IgM) and lysozyme (LYS); gill samples were taken to analyze mRNA levels of LYS, heat shock protein 70 (HSP 70), heat shock protein 90 (HSP 90), metallothionein (MT), toll-like receptor 3 (TLR-3), tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and insulin-like growth factor I (IGF-I). The results showed that nitrite (0.4 and/or 0.8mM) significantly increased the levels of GPT, GOT, ALP, C3 and C4, reduced the levels of IgM and LYS, up-regulated the gene expressions of HSP 70, HSP 90, MT, TLR-3, TNF-α and IL-1ß, and down-regulated the gene expressions of LYS and IGF-1 after 48 and 96 h of exposure. Based on the results, it can be concluded that high level nitrite exposure results in dysfunction of the blood physiology and immunity in turbot. Further, this study will be helpful to understand the mechanism of aquatic toxicology induced by nitrite in marine fish.

Effects of nitrite exposure on haematological parameters, oxidative stress and apoptosis in juvenile turbot (Scophthalmus maximus).

Nitrite (NO2(-)) is commonly present as contaminant in aquatic environment and toxic to aquatic organisms. In the present study, we investigated the effects of nitrite exposure on haematological parameters, oxidative stress and apoptosis in juvenile turbot (Scophthalmus maximus). Fish were exposed to various concentrations of nitrite (0, 0.02, 0.08, 0.4 and 0.8mM) for 96 h. Fish blood and gills were collected to assay haematological parameters, oxidative stress and expression of genes after 0, 24, 48 and 96 h of exposure. In blood, the data showed that the levels of methemoglobin (MetHb), triglyceride (TG), potassium (K(+)), cortisol, heat shock protein 70 (HSP70) and glucose significantly increased in treatments with higher concentrations of nitrite (0.4 and/or 0.8mM) after 48 and 96 h, while the levels of haemoglobin (Hb) and sodium (Na(+)) significantly decreased in these treatments. In gills, nitrite (0.4 and/or 0.8mM) apparently reduced the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH), increased the formation of malondialdehyde (MDA), up-regulated the mRNA levels of c-jun amino-terminal kinase (JUK1), p53, caspase-3, caspase-7 and caspase-9 after 48 and 96 h of exposure. The results suggested caspase-dependent and JUK signaling pathways played important roles in nitrite-induced apoptosis in fish. Further, this study provides new insights into how nitrite affects the physiological responses and apoptosis in a marine fish.