A comprehensive AI model development framework for consistent Gleason grading.

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

Effective treatment of levofloxacin wastewater by an electro-Fenton process with hydrothermal-activated graphite felt as cathode.

The performance of the cathode significantly affects the ability of the electro-Fenton (EF) process to degrade chemicals. In this study, a simple method to modify the graphite felt (GF) cathode was proposed, i.e. oxidizing GF by hydrothermal treatment in nitric acid. The surface physical and electrochemical properties of modified graphite felt were characterized by several techniques: scanning electron microscope (SEM), water contact angle, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and linear scanning voltammetry (LSV). Compared with an unmodified GF (GF-0), the oxygen reduction reaction (ORR) activity of a modified GF was significantly improved due to the introduction of more oxygen-containing functional groups (OGs). Furthermore, the results showed that GF was optimally modified after 9 h (GF-9) of treatment. As an example, the H2O2 generation by GF-9 was 2.26 times higher than that of GF-0. After optimizing the process parameters, which include the initial Fe2+ concentration and current density, the apparent degradation rate constant of levofloxacin (LEV) could reach as high as 0.40 min-1. Moreover, the total organic carbon (TOC) removal rate and mineralization current efficiency (MCE) of the modified cathode were much higher than that of the GF-0. Conclusively, GF-9 is a promising cathode for the future development in organic pollutant removal via EF.

Aberrant Methylation-Mediated Silencing of lncRNA MEG3 Functions as a ceRNA in Esophageal Cancer.

Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), has tumor-suppressor properties and its expression is lost in several human tumors. However, its biological role in esophageal squamous cell carcinoma (ESCC) tumorigenesis is poorly defined. The present study determined the role and methylation status of MEG3 in esophageal cancer cells and ESCC clinical specimens, and further observed the competing endogenous RNA (ceRNA) activity of MEG3 in the pathogenesis and development of ESCC. Significant downregulation of MEG3 was detected in esophageal cancer cells and ESCC tissues and the expression level of MEG3 was significantly increased in cancer cells after treated with the DNA methyltransferase inhibitor 5-Aza-dC. Upregulation of MEG3 led to the inhibition of proliferation and invasiveness of the cancer cells. The aberrant promoter hypermethylation of MEG3 indicates silencing of its expression. Furthermore, MEG3 acts as a ceRNA to regulate the expression of E-cadherin and FOXO1 by binding hsa-miR-9. Upregulation of miR-9 was detected in esophageal cancer cell lines and ESCC tissues, and miR-9 promoted esophageal cancer cell proliferation and invasion. Finally, downregulation and hypermethylation of MEG3 was associated with ESCC patients' survival.Implications: MEG3 functions as a tumor-suppressive lncRNA and aberrant promoter hypermethylation is critical for MEG3 gene silencing in ESCC. In addition, MEG3 acts as a ceRNA to regulate expression of E-cadherin and FOXO1 by competitively binding miR-9 and may be used as a potential biomarker in predicting ESCC patients' progression and prognosis. Mol Cancer Res; 15(7); 800-10. ©2017 AACR.

Aberrant methylation-mediated downregulation of long noncoding RNA LOC100130476 correlates with malignant progression of esophageal squamous cell carcinoma.

BACKGROUND: Dysregulated long non-coding RNAs (lncRNAs) are involved in many complicated human diseases including cancer. AIMS: To determine the role and methylation status of a new lncRNA LOC100130476 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and twenty three ESCC patients with tumor tissues and corresponding adjacent normal tissues were enrolled. The expression level and methylation status of LOC100130476 in esophageal cancer cell lines and primary ESCC samples were respectively detected. RESULTS: Significant downregulation of LOC100130476 was detected in esophageal cancer cell lines and primary ESCC tumor tissues. Up-regulation of LOC100130476 led to the inhibition of proliferation and invasiveness of the cancer cells. Aberrant hypermethylation of the CpG sites in exon 1 closing to the transcription start site was found to be more tumor-specific and to be more critical for gene silencing. Hypermethylation of these CpG sites was associated with TNM stage and pathological differentiation. ESCC patients in stage III and IV, with low expression or hypermethylation of the CpG sites in exon 1 demonstrated poor patient survival. CONCLUSIONS: LOC100130476 is down-regulated in ESCC at least partly by hypermethylation of CpG sites in exon 1 and its hypermethylation may have prognostic implications for ESCC patients.

Methylation-mediated downregulation of long noncoding RNA LOC100130476 in gastric cardia adenocarcinoma.

Accumulating evidences indicate that long non-coding RNAs (lncRNAs) play important roles in several biological processes and dysregulated lncRNAs are involved in different kinds of cancer and are associated with carcinogenesis, metastasis, and prognosis of cancer. The role of a new lncRNA LOC100130476 in gastric cardia adenocarcinoma (GCA) has remained unknown. The present study investigated the role and methylation status of LOC100130476 in the pathogenesis of GCA, and further evaluated the potential prognostic role of LOC100130476 in GCA. Significant downregulation of LOC100130476 was detected in SGC-7901 and BGC-823 cell lines and primary GCA tissues. Methylation frequency of LOC100130476 was gradually increased from exon 1 to exon 2 both in tumor tissues and corresponding normal tissues; however, methylation status of region 1 closing to the transcription start site was more tumor-specific among the three regions examined. The findings of the association between LOC100130476 expression, methylation and TNM stage, pathological differentiation, and GCA patients' survival further identified the role of LOC100130476 as a tumor suppressor gene. Furthermore, the hypermethylation of LOC100130476 was also detected in peripheral white blood cells of GCA cases. Thus, LOC100130476 may be act as a tumor suppressor gene in GCA carcinogenesis and aberrant methylation at the CpG sites near the transcription start site within exon 1 may be critical for gene silencing. In addition, aberrant methylation of LOC100130476 in peripheral white blood cells and GCA tissues may be used as a potential valuable biomarker in GCA diagnosis and prognosis.

Crystal structure of tetra-aquabis(1,3-dimethyl-2,6-dioxo-3,7-di-hydro-1H-purin-9-ido)magnesium.

The title complex, [Mg(C7H7N4O2)2(H2O)4], lies across an inversion centre and the Mg(II) atom is coordinated in a slightly distorted octa-hedral environment by four aqua ligands in the equatorial sites and two 1,3-dimethyl-2,6-dioxo-3,7-di-hydro-1H-purin-9-ide ligands, through imidazole ring N atoms, in the axial sites. An intra-molecular O-H⋯O hydrogen bond forms an S(7) graph-set motif. In the crystal, O-H⋯O and O-H⋯N hydrogen bonds link complex mol-ecules forming a three-dimensional network incorporating R 4 (2)(8) and R 2 (2)(18) graph-set motifs.

5-Nitro-1-benzofuran-2(3H)-one.

In the crystal structure of the title compound, C(8)H(5)NO(4), essentially planar mol-ecules [largest deviation from the least-squares plane = 0.030 (2) Å] form stacks along the a-axis direction. Intercentroid separations between overlapping benzene rings within the stack are 3.6594 (12) Šand 3.8131 (12) Å. Mol-ecules from neighboring stacks are linked by weak C-H⋯O hydrogen bonds into inversion dimers.

Ethyl 2-[1,3-dioxo-6-(piperidin-1-yl)-2,3-dihydro-1H-benz[de]isoquinolin-2-yl]acetate.

In the title compound, C(21)H(22)N(2)O(4), the naphthalimide unit is almost planar (r.m.s. deviation = 0.081Å). The carboximide N atom and the five C atoms of the eth-oxy-carbonyl-methyl substituent also lie close to a common plane (r.m.s. deviation = 0.119Å), which subtends an angle of 71.06 (8)° to the naphthalamide plane. The piperidine ring adopts a chair conformation. In the crystal, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into zigzag chains along the a axis.

2-Methyl-4-(2-methyl-benzamido)-benzoic acid.

In the crystal structure of the title compound, C(16)H(15)NO(3), inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains parallel to the b axis and pairs of inter-molecular O-H⋯O hydrogen bonds between inversion-related carb-oxy-lic acid groups link the mol-ecules into dimers. The dihedral angle between the two benzene rings is 82.4 (2)°.

Methyl 4-(3-chloro-prop-oxy)benzoate.

In the crystal structure of the title compound, C(11)H(13)ClO(3), inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into zigzag chains along the c axis.

Ethyl 2-(2-hy-droxy-5-nitro-phen-yl)acetate.

In the crystal structure of the title compound, C(10)H(11)NO(5), inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains along the b-axis direction. Weak C-H.·O hydrogen bonds also occur.

Methyl 5-chloro-2-(4-methyl-benzene-sulfonamido)-benzoate.

In the title compound, C(15)H(14)ClNO(4)S, the benzene rings are oriented at a dihedral angle of 85.42 (1)°. An intra-molecular N-H⋯O hydrogen bond results in the formation of a five-membered ring and an intramolecular C-H⋯O inter-action also occurs.

Methyl 5-chloro-2-[N-(3-eth-oxy-carbonyl-prop-yl)-4-methyl-benzene-sulfonamido]-benzoate.

In the title compound, C(21)H(24)ClNO(6)S, the benzene rings are oriented at a dihedral angles of 41.6 (2)°. In the crystal structure, weak inter-molecular C-H⋯O inter-actions link the mol-ecules.

2,2,2-Trifluoro-ethyl 4-methyl-benzene-sulfonate.

In the crystal structure of the title compound, C(9)H(9)F(3)O(3)S, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules along the c-axis direction. Also present are slipped π-π stacking inter-actions between phenyl-ene rings, with perpendicular inter-planar distances of 3.55 (2) Šand centroid-centroid distances of 3.851 (2) Å.

Methyl 2-amino-5-chloro-benzoate.

The title compound, C(8)H(8)ClNO(2), is almost planar, with an r.m.s. deviation of 0.0410 Šfrom the plane through the non-hydrogen atoms. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into chains along the b axis. An intra-molecular N-H⋯O hydrogen bond results in the formation of a six-membered ring.