Relevance of the College of American Pathologists guideline for validating whole slide imaging for diagnostic purposes to cytopathology

Whole slide imaging (WSI) allows pathologists to view virtual versions of slides on computer monitors. With increasing adoption of digital pathology, laboratories have begun to validate their WSI systems for diagnostic purposes according to reference guidelines. Among these the College of American Pathologists (CAP) guideline includes three strong recommendations (SRs) and nine good practice statements (GPSs). To date, the application of WSI to cytopathology has been beyond the scope of the CAP guideline due to limited evidence. Herein we systematically reviewed the published literature on WSI validation studies in cytology. A systematic search was carried out in PubMed-MEDLINE and Embase databases up to November 2021 to identify all publications regarding validation of WSI in cytology. Each article was reviewed to determine if SRs and/or GPSs recommended by the CAP guideline were adequately satisfied. Of 3963 retrieved articles, 25 were included. Only 4/25 studies (16%) satisfied all three SRs, with only one publication (1/25, 4%) fulfilling all three SRs and nine GPSs. Lack of a suitable validation dataset was the main missing SR (16/25, 64%) and less than a third of the studies reported intra-observer variability data (7/25, 28%). Whilst the CAP guideline for WSI validation in clinical practice helped the widespread adoption of digital pathology, more evidence is required to routinely employ WSI for diagnostic purposes in cytopathology practice. More dedicated validation studies satisfying all SRs and/or GPSs recommended by the CAP are needed to help expedite the use of WSI for primary diagnosis in cytopathology.     

Catabolite repression 1985

The present status of catabolite repression is summarized with respect to the involvement of cyclic AMP and other mediators. A model is presented which may account for the relationship between positive control of gene expression exerted by cAMP and its receptor, CAP, and negative control of catabolite repression mediated by specific metabolites.     

Mutagenic DNA repair in Escherichia coli. VII. Constitutive and inducible manifestations.

Incubation of E. coli WP2 in the presence of chloramphenicol (CAP) for 90 min before and 60 min after γ-irradiation had no effect on the induction of Trp⁺ mutations. Bacteria that had been treated with CAP for 90 min prior to UV irradiation showed normal or near normal yields of induced mutations to streptomycin or colicin E2 resistance. Most of these mutations lost their photoreversibility (indicating “fixation”) during continued incubation with CAP for a further 60 min after irradiation, during which time neither protein nor DNA synthesis was detectable. It is suggested that CAP-sensitive protein synthesis is not required for mutagenic (error-prone) repair of lesions in pre-existing DNA, arguing against an inducible component in this repair.In contrast the frequency of UV-induced mutations to Trp⁺ (largely at suppressor loci) was drastically reduced by CAP pretreatment, confirming the need for an active replication fork for UV-mutagenesis at these loci. It is known from the work of others that CAP given after UV abolishes mutagenesis at these loci. We conclude that CAP-sensitive protein synthesis (consistent with a requirement for an inducible function) is necessary for mutagenic repair only in newly-replicated DNA (presumably at daughter strand gaps) and not in pre-existing DNA. The data are consistent with but do not prove the hypothesis that CAP-sensitive and insensitive modes of mutagenesis reflect minor differences in the operation of a single basic mutagenic repair system.     

The cornerstone of integrating circulating tumor DNA into cancer management

Recent circulating tumor DNA (ctDNA) research has demonstrated its potential as a non-invasive biomarker for cancer. However, the deployment of ctDNA assays in routine clinical practice remains challenging owing to variability in analytical approaches and the assessment of clinical significance. A well-developed, analytically valid ctDNA assay is a prerequisite for integrating ctDNA into cancer management, and an appropriate analytical technology is crucial for the development of a ctDNA assay. Other determinants including pre-analytical procedures, test validation, internal quality control (IQC), and continual proficiency testing (PT) are also important for the accuracy of ctDNA assays. In the present review, we will focus on the most widely used ctDNA detection technologies and the key quality management measures used to assure the accuracy of ctDNA assays. The aim of this review is to provide useful information for technology selection during ctDNA assay development and assure a reliable test result in clinical practice.