Queen Mary University of London

Hearing our own voice is commonly assumed to be an unpleasant experience. In contrast, some studies of voice perception have reported that we actually find our own voice to be more attractive than other voices. It remains however unclear whether previously observed enhancements of self-voice attractiveness were mediated by the recognition of the self-voice during the task, because recognition was never explicitly and rigorously examined in previous studies. We therefore conducted a voice attractiveness rating task under conditions that limited the likelihood of self-voice recognition, in order to directly compare the perceived attractiveness of one's own voice when recognised versus when not. We found that both participants who did (N=59) and did not (N=80) recognise their own voice rated their own voice differently from other voices. However, crucially, the direction of this difference depended on whether the self-voice was recognised during the task or not: listeners who spontaneously recognised their voice rated it as more attractive than other voices, whereas listeners who did not recognise their voice rated it as less attractive. The findings help to explain one source of contradictory perspectives in the voice perception literature and beyond, highlighting a possible interplay between self-perception and voice identity recognition.

Trained immunity is the ability of the innate immune system to mount a heightened response to an environmental stimulus after a previous encounter with a noxious trigger. This effect is mediated by metabolic rewiring and epigenetic reprogramming in innate immune cells. In the context of neuroinflammation, trained immunity may represent a major contributor to the pathogenesis of neurological diseases, exerting both detrimental and potentially beneficial effects. While the general mechanisms and systemic implications of trained immunity are widely discussed, evidence in central nervous system (CNS) diseases remains fragmented and largely confined to individual pathological conditions. As a result, a comprehensive framework integrating these findings and identifying shared mechanisms across neurological disorders is still lacking. In this review, we explore the concept of trained immunity with a focus on neuroinflammatory and neurodegenerative diseases, synthetizing evidence from multiple CNS pathologies, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, and cerebrovascular disorders. We first critically examine preclinical and experimental studies addressing innate immune memory in the CNS and subsequently integrate these findings with emerging clinical evidence, aiming to identify convergent mechanisms and disease-relevant immune memory signatures. Finally, we discuss potential therapeutic targets identified in preclinical settings and outline key unresolved issues, including the nature of triggering stimuli, thresholds, and temporal dynamics shaping innate immune memory in the CNS. By highlighting current limitations and defining critical questions for future research, this review presents a unifying perspective on trained immunity in neurological diseases and underscores the translational potential to modulate neuroinflammation and to influence disease progression.

Follow-up of radiologically suspicious lung nodules from screening programs remains complex and unstandardized. This study analyses distribution and characteristics of solid and part-solid non-calcified nodules ≥100mm3 and non-solid nodules ≥8mm detected at baseline in the UK Lung cancer Screening (UKLS) trial, with insights into their relationship to screen-detected lung cancers. UKLS participants with baseline indeterminate and positive lung nodules were included. Nodule location was categorized by lobe and by attachment: intraparenchymal, juxta pleural or pleural-based. Solid and part-solid were classified based on semi-automated volume: 100-300mm3 and ≥300mm3, and non-solid nodules based on diameter ≥8mm. This measurement approach aligns with UKLS protocol and the British Thoracic Society (BTS) guideline. Their relationship to screen-detected lung cancer was based on histological outcomes after a 2-year follow-up period. 279 UKLS participants with 373 solid or part-solid lung nodules ≥100mm3 and 57 participants with 62 nonsolid nodules ≥8mm were included. Among solid and part-solid nodules, 233 were 100-300mm3, with 39.5% in upper lobes and 72.5% intraparenchymal; 140 nodules were ≥300mm3, with 51.4% in upper lobes and 53.6% intraparenchymal. Nodules ≥300mm3 group were more likely to be in the upper lobes (OR 1.97 [95% CI 1.12-3.48]). Within 2years, 34 solid or part-solid nodules were diagnosed as lung cancer, yielding a 2-year cancer probability of 9.1% (95% CI 6.6-12.5). The 2-year lung cancer probability was higher in nodules ≥300mm3 (RR 18.1, 95% CI 5.6-58.4; p<0.001) and in upper lobe nodules (RR 2.7, 95% CI 1.3-5.5; p=0.009). Solid and part-solid nodules with volume ≥300mm3 were more often found in the upper lobes and were associated with a higher probability of lung cancer within a two-year follow-up period.

The CALYPSO study demonstrated activity of savolitinib and durvalumab in MET-driven papillary renal cancer (PRC). We report final efficacy outcomes and exploratory circulating tumor DNA (ctDNA) biomarker analysis. This single-arm phase II study evaluated savolitinib and durvalumab in treatment-naïve or pretreated PRC. End points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). FoundationOne CDx assessed DNA alterations and MET/PD-L1 or MET/tumor mutational burden (TMB) copositivity. ctDNA collected at baseline and on treatment was correlated with outcomes. At 41-months median follow-up, ORR was 34% (95% CI, 20.0 to 51.0) in the intention-to-treat (ITT) population (N = 41) and 53% (95% CI, 28.0 to 77.0) in MET-driven patients (n = 17). Median PFS was 6.5 (95% CI, 2.7 to 12.0) versus 13.9 months (95% CI, 2.9 to 23.8), and OS was 18.3 (95% CI, 7.3 to 30.7) versus 27.4 months (95% CI, 9.3 to 37.4), in the ITT population and the MET-driven population, respectively. PD-L1 (66% positive) and TMB (median 2.5 mut/Mb) status did not correlate with response. Baseline ctDNA positivity (10/21) correlated with shorter OS (median 7.3 v 33.3 months), while ctDNA clearance and mean variant allele frequency reduction correlated with improved OS (median 31.3 v 7.2 and 31.3 v 15.5 months, respectively). Savolitinib plus durvalumab shows OS in MET-driven PRC, supporting the ongoing SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.

Blood transfusion is one of the most common interventions in hospitals. Blood tests that support this widespread practice are considered routine, such as 'group and save' (also known as 'type and screen'), yet there has been very limited evaluation of the needs for these tests and the associated costs. The aim of this systematic review is to synthesise international evidence on the costs of group and save and crossmatch tests and their component processes. Seventy-two studies published between 2012 and 2023 were identified and data were extracted. Most cost estimates were derived from local institutional sources with few using national reference data, and reporting methods varied widely. Median unit costs for group and save tests were £19.8 (interquartile range [IQR] £11.8-£52.5) overall, £13.8 in the United Kingdom and £57.4 in the United States. Crossmatch costs were £9.6 (IQR £5.9-£37.3). Understanding costs for group and save testing will inform hospital teams making decisions about sample requirements for procedures with a low likelihood of transfusion. It also provides benchmarking to assess the impact of implementing electronic systems to improve safety and efficiency of transfusion practice.

Smokers quitting successfully with the help of e-cigarettes often continue vaping. It is not known whether this promotes or prevents relapse back to smoking. This study aimed to determine whether use of e-cigarettes after successful smoking cessation affects the probability of relapse later on. Secondary analysis of a randomised controlled trial where participants received combination nicotine replacement therapy (NRT) or e-cigarettes to compare relapse rates in the two study arms and in abstainers who did and did not use e-cigarettes. Four stop-smoking services in the United Kingdom. 886 smokers (median age 41, smoking on average 15 cigarettes per day, 48% female) seeking help with stopping smoking. Main outcome was relapse to smoking by 12 months in participants who were abstinent at 4 weeks or at 6months. Relapse was defined as abstinence at 4weeks but not at one year or abstinence at 6months but not at one year. Abstinence from smoking was defined as no smoking over the past 7days. E-cigarette use was defined as using e-cigarettes at the time of abstinence on at least one day per week. Abstainers in the e-cigarette arm were less likely to relapse than abstainers in the NRT arm [relative risk (RR) =0.78, 95% confidence interval (CI) = 0.64-0.96 for relapse between 4weeks and 1year; RR =0.71, 95% CI = 0.55-0.93 for relapse between 6months and 1year). Relapse rates over both time periods were also lower in abstainers who used e-cigarettes compared with abstainers who did not use e-cigarettes (RR =0.79, 95% CI = 0.65-0.97 and RR =0.75, 95% CI = 0.57-0.98, respectively). Use of e-cigarettes after stopping smoking is associated with a reduced risk of relapse.