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Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: ‘NSCLC-Radiomics’ and ‘NSCLC-Radiomics-Interobserver1’ (‘Interobserver’). For ‘NSCLC-Radiomics’, we created an additional set of manual contours for 92 patients, and for ‘Interobserver’, there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 (‘NSCLC-Radiomics’) to 0.85 (‘Interobserver’—semi-automated). The median ICC for the ‘NSCLC-Radiomics’, ‘Interobserver’ (manual) and ‘Interobserver’ (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the ‘NSCLC-Radiomics’ dataset compared to the ‘Interobserver’ dataset. Survival analysis showed similar separation of curves for three of four RF apart from ‘original_shape_Compactness2’, a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features’ prognostic capability.

Sleep-wake state discrepancy, the discrepancy between self-reported and objective sleep measures, is commonly experienced in poor sleep and insomnia. While perfectionism is implicated in insomnia, its relationship to sleep-wake state discrepancy has not been investigated. This study aimed to assess the association between sleep-wake state discrepancy and perfectionism and explore whether dysfunctional sleep beliefs and pre-sleep arousal mediate that relationship. Sixty adult participants from community and clinical populations were conveniently sampled (85% females, mean age 30.28 ± 11.13 years, 38% with insomnia symptoms). Sleep-wake state discrepancy measures were calculated using data from actigraphy and sleep diary collected over 14 days. The Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS), Dysfunctional Beliefs about Sleep (DBAS), and Pre-sleep Arousal Scale (PSAS) were also collected. High perfectionism levels were associated with high levels of sleep-wake state discrepancy. Concern over Mistakes and Doubts about Actions correlated with sleep onset latency discrepancy with small effects ( = 0.26 and 0.29, respectively). Doubts about Actions was associated with sleep onset latency discrepancy. Furthermore, pre-sleep arousal and cognitive pre-sleep arousal mediated relationships between sleep onset latency discrepancy and Concern over Mistakes and Doubts about Actions. Concern over Mistakes and Doubts about Actions relate to a poorer perception of sleep relative to objective sleep measures. During sleep onset, cognitive pre-sleep arousal appears to mediate relationships between perfectionism and sleep-wake state discrepancy. Therefore, perfectionism may be an important cognitive-emotional factor to consider when assessing and treating sleep-wake state discrepancy that commonly accompanies insomnia.

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite Plasmodium falciparum shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the P. falciparum orthologs of two core NMD components: Pf UPF1 (PF3D7_1005500) and Pf UPF2 (PF3D7_0925800). We localize both Pf UPF1 and Pf UPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in P. falciparum , they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in P. falciparum has no functional role and that NMD is not required for parasite growth ex vivo . In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.

Internationally, the designation of a patient as an increased viral risk organ donor has been associated with lower utilisation rates. The actual prevalence of blood borne viruses in Australian potential organ donors, and the predictive performance of questionnaires administered to stratify this risk, remains unknown. We conducted a retrospective review of all patients who commenced workup for donation on the national database between 2014–2020. The prevalence of HIV, Active HBV and Active HCV in 3650 potential organ donors was 0.16%, 0.9%, and 2.2%, respectively. The behavioural risk profile was assessed in a subset of 3633 patients. Next-of-kin reported increased risk behaviours were associated with an increased prevalence of HCV but not of HIV or HBV (OR 13.8, p < 0.01, OR 0.3. p = 0.42, OR 1.5, p = 0.14). Furthermore, the majority of HIV and HBV infections occurred in potential donors without a disclosed history of increased risk behaviours. In this series, donors had a higher prevalence of HCV, and similar rates of HBV and HIV to the broader community. Behavioural transmission risks were poorly predictive of HIV and HBV. Rather than pre-transplantation behavioural risk screening, routine post-transplant recipient screening may provide a more powerful tool in mitigating the consequences of unexpected viral transmission.

Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction 1 – 3 . The properties of these materials evolve dynamically and heterogeneously 4 with applied voltage through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation 5 . The catalytic state is thus inherently far from equilibrium, which complicates its direct observation. Here, using a suite of correlative operando scanning probe and X-ray microscopy techniques, we establish a link between the oxygen evolution activity and the local operational chemical, physical and electronic nanoscale structure of single-crystalline β-Co(OH) 2 platelet particles. At pre-catalytic voltages, the particles swell to form an α-CoO 2 H 1.5· 0.5H 2 O-like structure—produced through hydroxide intercalation—in which the oxidation state of cobalt is +2.5. Upon increasing the voltage to drive oxygen evolution, interlayer water and protons de-intercalate to form contracted β-CoOOH particles that contain Co 3+ species. Although these transformations manifest heterogeneously through the bulk of the particles, the electrochemical current is primarily restricted to their edge facets. The observed Tafel behaviour is correlated with the local concentration of Co 3+ at these reactive edge sites, demonstrating the link between bulk ion-insertion and surface catalytic activity. Mapping the operational chemical, physical and electronic structure of an oxygen evolution electrocatalyst at the nanoscale links the properties of the material with the observed oxygen evolution activity.

Bacteria in the class Alphaproteobacteria have a wide variety of lifestyles and physiologies. They include pathogens of humans and livestock, agriculturally valuable strains, and several highly abundant marine groups. The ancestor of mitochondria also originated in this clade. Despite significant effort to investigate the phylogeny of the Alphaproteobacteria with a variety of methods, there remains considerable disparity in the placement of several groups. Recent emphasis on phylogenies derived from multiple protein-coding genes remains contentious due to disagreement over appropriate gene selection and the potential influences of systematic error. We revisited previous investigations in this area using concatenated alignments of the small and large subunit (SSU and LSU) rRNA genes, as we show here that these loci have much lower GC bias than whole genomes. This approach has allowed us to update the canonical 16S rRNA gene tree of the Alphaproteobacteria with additional important taxa that were not previously included, and with added resolution provided by concatenating the SSU and LSU genes. We investigated the topological stability of the Alphaproteobacteria by varying alignment methods, rate models, taxon selection and RY-recoding to circumvent GC content bias. We also introduce RYMK-recoding and show that it avoids some of the information loss in RY-recoding. We demonstrate that the topology of the Alphaproteobacteria is sensitive to inclusion of several groups of taxa, but it is less affected by the choice of alignment and rate methods. The majority of topologies and comparative results from Approximately Unbiased tests provide support for positioning the Rickettsiales and the mitochondrial branch within a clade. This composite clade is a sister group to the abundant marine SAR11 clade (Pelagibacterales). Furthermore, we add support for taxonomic assignment of several recently sequenced taxa. Accordingly, we propose three subclasses within the Alphaproteobacteria: the Caulobacteridae, the Rickettsidae, and the Magnetococcidae.

Singlet fission is a process whereby two triplet excitons can be produced from one photon, potentially increasing the efficiency of photovoltaic devices. Endothermic singlet fission is desired for a maximum energy-conversion efficiency, and such systems have been considered to form an excimer-like state with multiexcitonic character prior to the appearance of triplets. However, the role of the excimer as an intermediate has, until now, been unclear. Here we show, using 5,12-bis((triisopropylsilyl)ethynyl)tetracene in solution as a prototypical example, that, rather than acting as an intermediate, the excimer serves to trap excited states to the detriment of singlet-fission yield. We clearly demonstrate that singlet fission and its conjugate process, triplet-triplet annihilation, occur at a longer intermolecular distance than an excimer intermediate would impute. These results establish that an endothermic singlet-fission material must be designed to avoid excimer formation, thus allowing singlet fission to reach its full potential in enhancing photovoltaic energy conversion.

Background The diagnosis of periprosthetic joint infection (PJI) remains a serious clinical challenge. There is a pressing need for improved diagnostic testing methods; biomarkers offer one potentially promising approach. Questions/purposes We evaluated the diagnostic characteristics of 16 promising synovial fluid biomarkers for the diagnosis of PJI. Methods Synovial fluid was collected from 95 patients meeting the inclusion criteria of this prospective diagnostic study. All patients were being evaluated for a revision hip or knee arthroplasty, including patients with systemic inflammatory disease and those already receiving antibiotic treatment. The Musculoskeletal Infection Society (MSIS) definition was used to classify 29 PJIs and 66 aseptic joints. Synovial fluid samples were tested by immunoassay for 16 biomarkers optimized for use in synovial fluid. Sensitivity, specificity, and receiver operating characteristic curve analysis were performed to assess for diagnostic performance. Results Five biomarkers, including human α-defensin 1-3, neutrophil elastase 2, bactericidal/permeability-increasing protein, neutrophil gelatinase-associated lipocalin, and lactoferrin, correctly predicted the MSIS classification of all patients in this study, with 100% sensitivity and specificity for the diagnosis of PJI. An additional eight biomarkers demonstrated excellent diagnostic strength, with an area under the curve of greater than 0.9. Conclusions Synovial fluid biomarkers exhibit a high accuracy in diagnosing PJI, even when including patients with systemic inflammatory disease and those receiving antibiotic treatment. Considering that these biomarkers match the results of the more complex MSIS definition of PJI, we believe that synovial fluid biomarkers can be a valuable addition to the methods utilized for the diagnosis of infection. Level of Evidence Level II, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Mineralocorticoid receptor antagonists can prevent cardiovascular events in patients with heart failure and non-severe chronic kidney disease, but their effects in patients with kidney failure requiring dialysis are uncertain. We aimed to assess the efficacy and safety of mineralocorticoid receptor antagonists in this patient population. In this systematic review and meta-analysis, we updated our previous systematic review by searching MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature for randomised controlled trials published between database inception and March 18, 2025. Trials comparing a mineralocorticoid receptor antagonist with placebo or standard of care in adults (aged ≥18 years) receiving maintenance dialysis were eligible. Studies that did not report an outcome of interest (cardiovascular mortality, heart failure hospitalisation, all-cause mortality, all-cause hospitalisation, hyperkalaemia, gynaecomastia or breast pain, or hypotension) were excluded. Two reviewers independently identified studies, extracted data, and assessed the risk of bias using the Cochrane risk-of-bias tool. The main outcome was cardiovascular mortality assessed using the empirical Bayes random-effects models, stratified by risk-of-bias. The protocol is registered with PROSPERO (CRD420251008119). 19 trials of steroidal mineralocorticoid receptor antagonists including 4675 participants met eligibility criteria. Effect estimates differed trials with low and high risk of bias. In four trials with a low risk of bias (n=3562), 264 cardiovascular deaths occurred in 1785 patients in the mineralocorticoid receptor antagonist group compared with 276 of 1777 patients in the control group (odds ratio 0·98 [95% CI 0·80–1·20]; I2=0·0%; τ2=0·0; moderate certainty) resulting in an absolute risk reduction of 1 fewer event per 1000 patients per year (95% CI 14 fewer to 11 more). Our findings suggest that steroidal mineralocorticoid receptor antagonists have little to no effect on cardiovascular mortality in patients requiring dialysis. There is insufficient information on the effects of steroidal mineralocorticoid receptor antagonists in subgroups of patients requiring dialysis and no information on non-steroidal mineralocorticoid receptor antagonists. Future trials would need to consider the likelihood of only smaller effects or effects limited to patients or events with pathophysiology that is more clearly driven by aldosterone in their design. None.

Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied. Herein, we investigated the membrane insertion of RW16 into zwitterionic membranes, a versatile CPP that also presents antibacterial and antitumor activities. Using complementary approaches, including NMR spectroscopy, fluorescence spectroscopy, circular dichroism, and molecular dynamic simulations, we determined the high-resolution structure of RW16 and measured its membrane insertion and orientation properties into zwitterionic membranes. Altogether, these results contribute to explaining the versatile properties of this peptide toward zwitterionic lipids.