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They are conceived to optimize the meaningfulness of epidemiological and clinical studies, aligning them with the Aristotelian \u201cmesotes\u201d curve, namely, the principle of achieving balance and avoiding extremes to best reflect\n                    <jats:italic>the most truthful<\/jats:italic>\n                    approximation of reality. This commentary addresses situations where strict adherence to STROBE guidelines may be impossible or inappropriate, potentially distorting results, and shows how statistical tools can mitigate these issues. Specific challenges arise in real-life randomization scenarios, situations lacking placebo arms, and in correcting for multiple comparisons. We discuss these challenges, examine the role of Bonferroni and similar corrections, and propose alternative approaches such as false discovery rate (FDR) and Bayesian hierarchical models. We illustrate these points with examples from the literature and a simulation study evaluating p-value adjustments in multiple hypothesis testing. This work provides a framework for researchers to navigate STROBE guidelines thoughtfully, ensuring that observational studies are both rigorous and relevant.\n                  <\/jats:p>","DOI":"10.1007\/s42000-026-00758-3","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:15:37Z","timestamp":1777922137000},"page":"343-356","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The STROBE guidelines and the \u0391ristotelian mesotes curve"],"prefix":"10.1007","volume":"25","author":[{"given":"George P.","family":"Chrousos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nektaria","family":"Papadopoulou-Marketou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Tsiamyrtzis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"issue":"10","key":"758_CR1","doi-asserted-by":"publisher","first-page":"CD010856","DOI":"10.1002\/14651858.CD010856","volume":"10","author":"Z Iheozor-Ejiofor","year":"2015","unstructured":"Iheozor-Ejiofor Z, Worthington HV, Walsh T, O\u2019Malley L, Clarkson JE, Macey R et al (2015) Water fluoridation for the prevention of dental caries. 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