Assessment of Color Reproducibility and Mitigation of Color Variation in Whole Slide Image Scanners for Toxicologic Pathology.

Digital pathology workflows in toxicologic pathology rely on whole slide images (WSIs) from histopathology slides. Inconsistent color reproduction by WSI scanners of different models and from different manufacturers can result in different color representations and inter-scanner color variation in the WSIs. Although pathologists can accommodate a range of color variation during their evaluation of WSIs, color variability can degrade the performance of computational applications in digital pathology. In particular, color variability can compromise the generalization of artificial intelligence applications to large volumes of data from diverse sources. To address these challenges, we developed a process that includes two modules: (1) assessing the color reproducibility of our scanners and the color variation among them and (2) applying color correction to WSIs to minimize the color deviation and variation. Our process ensures consistent color reproduction across WSI scanners and enhances color homogeneity in WSIs, and its flexibility enables easy integration as a post-processing step following scanning by WSI scanners of different models and from different manufacturers.

Probiotics combination effectively improves constipation in pregnancy by modifying the gut microbiota composition.

Constipation during pregnancy can induce serious complications, including miscarriage and preterm labour, while the evidence of probiotics in improving constipation during pregnancy was little. In this study, 29 healthy pregnant women and 65 constipated pregnant women were enrolled to assess the effectiveness of probiotics on constipation during pregnancy. Our results showed that the probiotics were effective in improving the Constipation Severity Scale (CSS) and Bristol Stool Scale (BSS) scores, including increasing defecation frequency, decreasing defecation time, and improving fecal characteristics. 16S rRNA sequencing revealed that the probiotics effectively restored the diversity of intestinal microbiota. At the phylum level, Firmicutes (13.27% vs 57.20%) and Actinobacteria (3.77% vs 12.80%) were increased, while Bacteroidetes (77.82% vs 20.24%) was decreased. At the level of the genus, Faecalibacterium (2.03% vs 10.33%), Bifidobacterium (1.21% vs 8.56%), and Phascolarctobacterium (0.05% vs 2.88%), the beneficial bacteria were increased, while the Bacteroides (29.23% vs 12.28%) and Prevotella (24.32% vs 4.92%) were decreased. In conclusion, these results indicated that probiotics can effectively relieve the constipation symptoms by improving the diversity of intestinal microbiota, regulating the disturbance of microflorae, and restoring the balance of microflorae to exert a stronger moderating effect than diet and lifestyle modification. Our results provided clinical data and a theoretical basis for the exploitation of probiotics in treating constipation during pregnancy. Chinese Clinical Trial Registry: ChiCTR2100052069.

Revealing potential long non-coding RNA biomarkers in lung adenocarcinoma using long non-coding RNA-mediated competitive endogenous RNA network

In our study, we aimed to reveal potential long non-coding RNAs (lncRNA) biomarkers in lung adenocarcinoma (LAD) using lncRNA-mediated competing endogenous RNAs (ceRNAs) network (LMCN). Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis for the competing lncRNA-mRNA interactions was implemented, and relying on the weight value >0.8, a highly competitive LMCN was further constructed. Degree distribution, betweenness and closeness for LMCN were carried out to analyze the network structure. Functional analyses of mRNAs in LMCN were carried out to further explore the biological functions of lncRNAs. Biclique algorithm was utilized to extract competing modules from the LMCN. Finally, we verified our findings in an independent sample set using qRT-PCR. Based on degrees >60, we identified 4 hubs, including DLEU2, SNHG12, HCP5, and LINC00472. Furthermore, 2 competing modules were identified, and LINC00472 in module 1 functioned as a hub in both LMCN and module. Functional implications of lncRNAs demonstrated that lncRNAs were related to histone modification, negative regulation of cell cycle, neuroactive ligand-receptor interaction, and regulation of actin cytoskeleton. qRT-PCR results demonstrated that lncRNAs LINC00472, and HCP5 were down-regulated in LAD tissues, while the expression level of SNHG12 was up-regulated in LAD tissues. Our study sheds novel light on the roles of lncRNA-related ceRNA network in LAD and facilitates the detection of potential lncRNA biomarkers for LAD diagnosis and treatment. Remarkably, in our study, LINC00472, HCP5, and SNHG12 might be potential biomarkers for LAD management.

Single-nucleotide polymorphism analysis of GH, GHR, and IGF-1 genes in minipigs

Tibetan (TB) and Bama (BM) miniature pigs are two popular pig breeds that are used as experimental animals in China due to their small body size. Here, we analyzed single-nucleotide polymorphisms (SNPs) in gene fragments that are closely related to growth traits [growth hormone (GH), growth hormone receptor (GHR), and insulin-like growth factor (IGF)-1)] in these pig breeds and a large white (LW) control pig breed. On the basis of the analysis of 100 BMs, 108 TBs, and 50 LWs, the polymorphic distribution levels of GH, GHR, and IGF-1 were significantly different among these three pig breeds. According to correlation analyses between SNPs and five growth traits - body weight (BW), body length (BL), withers height (WH), chest circumference (CC), and abdomen circumference (AC) - three SNP loci in BMs and four SNP loci in TBs significantly affected growth traits. Three SNP sites in BMs and four SNP sites in TBs significantly affected growth traits. SNPs located in the GH gene fragment significantly affected BL and CC at locus 12 and BL at locus 45 in BMs, and also BW, WH, CC, and AC at locus 45 and WH and CC at locus 93 in TBs. One SNP at locus 85 in the BM GHR gene fragment significantly affected all growth traits. All indices were significantly reduced with a mixture of alleles at locus 85. These results provide more information regarding the genetic background of these minipig species and indicate useful selection markers for pig breeding programs.