Improving Ki67 assessment concordance by the use of an artificial intelligence-empowered microscope: a multi-institutional ring study.

AIMS: The nuclear proliferation biomarker Ki67 plays potential prognostic and predictive roles in breast cancer treatment. However, the lack of interpathologist consistency in Ki67 assessment limits the clinical use of Ki67. The aim of this article was to report a solution utilising an artificial intelligence (AI)-empowered microscope to improve Ki67 scoring concordance. METHODS AND RESULTS: We developed an AI-empowered microscope in which the conventional microscope was equipped with AI algorithms, and AI results were provided to pathologists in real time through augmented reality. We recruited 30 pathologists with various experience levels from five institutes to assess the Ki67 labelling index on 100 Ki67-stained slides from invasive breast cancer patients. In the first round, pathologists conducted visual assessment on a conventional microscope; in the second round, they were assisted with reference cards; and in the third round, they were assisted with an AI-empowered microscope. Experienced pathologists had better reproducibility and accuracy [intraclass correlation coefficient (ICC) = 0.864, mean error = 8.25%] than inexperienced pathologists (ICC = 0.807, mean error = 11.0%) in visual assessment. Moreover, with reference cards, inexperienced pathologists (ICC = 0.836, mean error = 10.7%) and experienced pathologists (ICC = 0.875, mean error = 7.56%) improved their reproducibility and accuracy. Finally, both experienced pathologists (ICC = 0.937, mean error = 4.36%) and inexperienced pathologists (ICC = 0.923, mean error = 4.71%) improved the reproducibility and accuracy significantly with the AI-empowered microscope. CONCLUSION: The AI-empowered microscope allows seamless integration of the AI solution into the clinical workflow, and helps pathologists to obtain higher consistency and accuracy for Ki67 assessment.

Ozonation of diclofenac in the aqueous solution: Mechanism, kinetics and ecotoxicity assessment.

The pharmaceutical and personal care products (PPCPs) in aquatic environment have aroused more interest recently. Many of them are hard to degrade by the typical biological treatments. Diclofenac (DCF), as a significant anti-inflammatory drug, is a typical PPCP and widely existed in water environment. It is reported that DCF has adverse effects on aquatic organisms. This work aims to investigate the mechanism, kinetics and ecotoxicity assessment of DCF transformation initiated by O3 in aqueous solution, and provide a solution to the degradation of DCF. The O3-initiated oxidative degradations of DCF were performed by quantum chemical calculations, including thirteen primary reaction pathways and subsequent reactions of the Criegee intermediates with H2O, NO and O3. Based on the thermodynamic data, the kinetic parameters were calculated by the transition state theory (TST). The total reaction rate constant of DCF initiated by O3 is 2.57 × 103 M-1 s-1 at 298 K and 1 atm. The results show that the reaction rate constants have a good correlation with temperature. The acute and chronic toxicities of DCF and its degradation products were evaluated at three different trophic levels by the ECOSAR program. Most products are converted into less toxic or harmless products. Oxalaldehyde (P3) and N-(2,6-dichlorophenyl)-2-oxoacetamide (P6) are still harmful to the three aquatic organisms, which should be paid more attention in the future.

Theoretical study on the mechanisms, kinetics and ecotoxicity assessment of OH-initiated reactions of guaiacol in atmosphere and wastewater.

The OH-initiated transformation mechanisms, kinetics and ecotoxicity assessment of guaiacol (2-methoxyphenol) in the presence of O2/NOx were investigated both in atmosphere and wastewater. The solvent effect lowers the energy barriers of initial OH-addition reactions more than H-abstraction reactions, leading to much higher addition branching ratio (Γadd) of 0.92 in aqueous solution than that of 0.42 in gas-phase. At 298 K, the overall rate constants of the title reactions in atmosphere and wastewater are 5.56 × 10-12 and 1.41 × 10-11 cm3 molecule-1 s-1 with corresponding half-lives of 34.6 h and 0.82 s, respectively. In atmosphere, all the proposed favorable products including nitroguaiacols, methoxybenzoquinone, 2-hydroxyphenyl formate, 2-methoxybenzene-1, 3-diol and dialdehyde could contribute to secondary organic aerosols (SOAs). In wastewater, NO2 addition reactions lead to higher toxicity of products (nitroguaiacols and 2-methoxybenzene-1, 4-diol) than that of parental guaiacol. However, O2/NO addition pathways may generate less harmful products except for methoxybenzoquinone (P3) which is with higher toxicity than guaiacol. Therefore, more attention should be focused on the products formed from OH-initiated reactions of guaiacol both in atmosphere and wastewater.