Further assessment of the clinical relevance of anatomical structures through PubMed and other measures.

A previous paper has demonstrated a statistically significant moderate correlation between the number of citations obtained from PubMed and a Delphi study for 251 anatomical structures of the Head and Neck region, suggesting that clinical significance is a major driver of research involving anatomical structures. This raises the possibility that these ranks could be an objective measure of clinical relevance of individual anatomical structures. In the present study, we revisited the rankings of the PubMed results from the previous paper and compared it with a Delphi study for 450 musculoskeletal structures. PubMed ranks were derived using different search parameters; a PubMed search with quotations yielded a moderate, statistically significant correlation coefficient of 0.639 with the musculoskeletal dataset. Additionally, we developed a Python tool, PDF Term Search, to calculate the frequency of anatomical terms in four authoritative textbooks, and these frequencies exhibited moderate significant correlations ranging (0.549-0.646) with our PubMed-derived ranks. We further explored strategies to improve the accuracy of our PubMed results by addressing limitations identified in the previous paper. We refined the syntax of search queries for 500 anatomical structures, resulting in marked improvement in the correlation coefficients with the musculoskeletal dataset, demonstrating clear avenues for future iterations of PubMed-derived ranks. We also created a spreadsheet of 2181 anatomical structures ranked using PubMed, published Delphi studies, and authoritative texts, providing a resource for anatomical educators who are adjusting their curricula to better train future healthcare practitioners.

Krüppel-like Factor 5 Regulates Stemness, Lineage Specification, and Regeneration of Intestinal Epithelial Stem Cells.

BACKGROUND & AIMS: Self-renewal and multipotent differentiation are cardinal properties of intestinal stem cells (ISCs), mediated in part by WNT and NOTCH signaling. Although these pathways are well characterized, the molecular mechanisms that control the 'stemness' of ISCs are still not well defined. Here, we investigated the role of Krüppel-like factor 5 (KLF5) in regulating ISC functions. METHODS: We performed studies in adult Lgr5EGFP-IRES-creERT2;Rosa26LSLtdTomato (Lgr5Ctrl) and Lgr5EGFP-IRES-creERT2;Klf5fl/fl;Rosa26LSLtdTomato (Lgr5ΔKlf5) mice. Mice were injected with tamoxifen to activate Cre recombinase, which deletes Klf5 from the intestinal epithelium in Lgr5ΔKlf5 but not Lgr5Crtl mice. In experiments involving irradiation, mice were subjected to 12 Gy total body irradiation (TBI). Tissues were collected for immunofluorescence (IF) analysis and next generation sequencing. Oganoids were derived from fluoresecence activated cell sorted- (FACS-) single cells from tamoxifen-treated Lgr5ΔKlf5 or Lgr5Crtl mice and examined by immunofluorescence stain. RESULTS: Lgr5+ ISCs lacking KLF5 proliferate faster than control ISCs but fail to self-renew, resulting in a depleted ISC compartment. Transcriptome analysis revealed that Klf5-null Lgr5+ cells lose ISC identity and prematurely differentiate. Following irradiation injury, which depletes Lgr5+ ISCs, reserve Klf5-null progenitor cells fail to dedifferentiate and regenerate the epithelium. Absence of KLF5 inactivates numerous selected enhancer elements and direct transcriptional targets including canonical WNT- and NOTCH-responsive genes. Analysis of human intestinal tissues showed increased levels of KLF5 in the regenerating epithelium as compared to those of healthy controls. CONCLUSION: We conclude that ISC self-renewal, lineage specification, and precursor dedifferentiation require KLF5, by its ability to regulate epigenetic and transcriptional activities of ISC-specific gene sets. These findings have the potential for modulating ISC functions by targeting KLF5 in the intestinal epithelium.