CHERIE: User-Centred Development of an XAI System for Chest Radiology through Co-Design

Modern medical imaging systems increasingly use AI for analysis and diagnosis, yet the "black-box" nature of current deep learning algorithms limits their practical use in radiology. Explainable AI (XAI) aims to address this by making AI decisions more transparent and interpretable. In medical imaging, XAI tools often highlight critical regions in images to explain AI decisions, but their complex visual explanations and poor UI design impede their clinical adoption. This study introduced CHERIE, an XAI prototype designed to enhance transparency in AI-assisted chest radiology. Using our pre-developed XAI diagnostic tool for chest radiology, we adopted a user-centered design (UCD) methodology to develop user interfaces for the AI-enabled diagnostic tool. In particular, we engaged medical practitioners, AI developers, and HCI experts in a multidisciplinary co-design workshop. This collaborative effort was crucial in identifying requirements from the user perspectives, aiming to boost understanding and trust in AI-driven diagnostics. Our findings emphasise the need for UCD for the adoption of XAI systems, proposing user requirements to seamlessly integrate these systems into clinical workflows and effectively address end-user needs

A Two-year Outcome of Various Techniques of Discectomy On Complications: A Multicentric Retrospective Study

Objective Various techniques of performing lumbar discectomy are prevalent, each having its rationale and claimed benefits. The authors ventured to assess the total complication rate of lumbar discectomy as well as the complication rates of individual complications, namely CSF leaks, superficial wound infections, deep wound infections, recurrence rates, re-operation rates, and wrong level surgery. Methods This was a retrospective study of patients operated using open discectomy (OD), microdiscectomy (MD), microendoscopic discectomy (MED), interlaminar endoscopic lumbar discectomy (IELD), transforaminal endoscopic lumbar discectomy (TELD), and Destandau techniques (DT) with a minimum follow-up of 2 years. The inclusion criteria were age>15 years, failed conservative treatment for 4-6 weeks, and the involvement of a single lumbar level. Results There is no statistically significant association between surgical technique and complications. The total complication rate was 12.89% in 946 operated cases. The most common complication was recurrence (5.81%), followed by re-operation (3.69%), CSF leak (1.90%), wrong level surgery (0.63%), superficial infection (0.52%) and deep infection (0.31%). There were minor differences in the incidence of complications between techniques. Conclusion This is the first study to compare the complication rates of all the prevalent discectomy techniques across the globe in 946 patients. Although there were minor differences in incidences of complications between individual techniques, there was no statistical significance. The various rates of individual complications provide a reference value for future studies related to complications following discectomy

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field