We argue that making accept/reject decisions on scientific hypotheses, including a recent call for changing the canonical alpha level from p = 0.05 to p = 0.005, is deleterious for the finding of new discoveries and the progress of science. Given that blanket and variable alpha levels both are problematic, it is sensible to dispense with significance testing altogether. There are alternatives that address study design and sample size much more directly than significance testing does; but none of the statistical tools should be taken as the new magic method giving clear-cut mechanical answers. Inference should not be based on single studies at all, but on cumulative evidence from multiple independent studies. When evaluating the strength of the evidence, we should consider, for example, auxiliary assumptions, the strength of the experimental design, and implications for applications. To boil all this down to a binary decision based on a p-value threshold of 0.05, 0.01, 0.005, or anything else, is not acceptable.

Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group. Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs. Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05). Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.

The Wnt/β-Catenin pathway alterations present in colorectal cancer (CRC) are of special interest in the development of new therapeutic strategies to impact carcinogenesis and the progression of CRC. In this context, different polyphenols present in natural products have been reported to have modulatory effects against the Wnt pathway in CRC. In this study, we evaluate the effect of two polyphenol-rich coffee extracts and chlorogenic acid (CGA) against SW480 and HT-29 CRC cells. This involved the use of MTT and SRB techniques for cell viability; wound healing and invasion assay for the evaluation of the migration and invasion process; T cell factor (TCF) reporter plasmid for the evaluation of transciption factor (TCF) transcriptional activity; polymerase chain reaction (PCR) of target genes and confocal fluorescence microscopy for β-Catenin and E-Cadherin protein fluorescence levels; and subcellular localization. Our results showed a potential modulatory effect of the Wnt pathway on CRC cells, and we observed a reduction in the transcriptional activity of β-catenin. All the results were prominent in SW480 cells, where the Wnt pathway deregulation has more relevance and implies a constitutive activation of the signaling pathway. These results establish a starting point for the discovery of a mechanism of action associated with these effects and corroborate the anticancer potential of polyphenols present in coffee, which could be explored as chemopreventive molecules or as adjunctive therapy in CRC.

Chest pain diagnosis in emergency care is hindered by overlapping cardiac and non-cardiac symptoms, causing diagnostic uncertainty. Artificial Intelligence, such as RAPIDx AI, aims to enhance accuracy through clinical and biochemical data integration, but its adoption relies on addressing usability, explainability, and seamless workflow integration without disrupting care. Evaluate RAPIDx AI's integration into clinical workflows, address usability barriers, and optimise its adoption in emergencies. The PROLIFERATE_AI framework was implemented across 12 EDs (July 2022-January 2024) with 39 participants: 15 experts co-designed a survey via Expert Knowledge Elicitation (EKE), applied to 24 ED clinicians to assess RAPIDx AI usability and adoption. Bayesian inference, using priors, estimated comprehension, emotional engagement, usage, and preference, while Monte Carlo simulations quantified uncertainty and variability, generating posterior means and 95% bootstrapped confidence intervals. Qualitative thematic analysis identified barriers and optimisation needs, with data triangulated through the PROLIFERATE_AI scoring system to rate RAPIDx AI's performance by user roles and demographics. Registrars exhibited the highest comprehension (median: 0.466, 95 % CI: 0.41-0.51) and preference (median: 0.458, 95 % CI: 0.41-0.48), while residents/interns scored the lowest in comprehension (median: 0.198, 95 % CI: 0.17-0.26) and emotional engagement (median: 0.112, 95 % CI: 0.09-0.14). Registered nurses showed strong emotional engagement (median: 0.379, 95 % CI: 0.35-0.45). Novice users faced usability and workflow integration barriers, while experienced clinicians suggested automation and streamlined workflows. RAPIDx AI scored "Good Impact," excelling with trained users but requiring targeted refinements for novices. RAPIDx AI enhances diagnostic accuracy and efficiency for experienced users, but usability challenges for novices highlight the need for targeted training and interface refinements. The PROLIFERATE_AI framework offers a robust methodology for evaluating and scaling AI solutions, addressing the evolving needs of sociotechnical systems.