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Principals have an important function in schools' ability to create high-quality learning and teaching. As the expectations placed on principals are high, large resources are invested in school leadership training, thus necessitating research on the impact of such initiatives. In this article, we report on a longitudinal research study on the training programme for principals in Sweden. The aim was to examine the programme's impacts on the principals' leadership and school organisations. We did this by interviewing principals, teachers and students at four schools during the principals' participation in the programme. Giddens's theory of structuration was used to analyse the study. The results showed that leadership needs to be foregrounded throughout the training and that awareness of the function of principals in leading schools' structuration processes (i.e., their creation of meaning making) should be clarified.

Abstract Background Many post-myocardial infarction (MI) patients struggle with physical activity behavior change (BC) for life-long secondary prevention. There is limited knowledge about factors influencing long-term physical activity BC among post-MI patients. This qualitative study aimed to explore the beliefs and experiences related to post-MI patients’ physical activity BC process following a year’s participation in a supervised and self-monitored exercise program: the Norwegian Trial of Physical Exercise After MI (NorEx). Methods We conducted a qualitative study, performing in-depth semi-structured interviews with a randomly selected sample of NorEx participants when they were scheduled for cardiopulmonary exercise testing after one year of participation. Interviews were transcribed verbatim and the data was analyzed by applying reflexive thematic analysis. Results Seventeen participants (n = 4 female [24%]; median age, 61 years; median time since index MI, 4 years) were recruited and interviewed once. Analysis resulted in four main themes (nine sub-themes): (1) Personal responsibility to exercise (Exercise is safe, Health benefits, Habitual exercise); (2) Peer social support for a sense of safety and belonging (Social exercise, Supervision is preferred); (3) Research participation transformed exercise beliefs (High-intensity exercise is superior, Personal Activity Intelligence (PAI) promotes exercise adherence); and (4) Mind the intention-behavior gap (Initial anxiety, Lack of continued follow-up). Conclusions Several participants reported that they were able to maintain exercise BC during a year’s participation in NorEx. Nevertheless, a perceived lack of continued and individualized follow-up made some participants struggle with motivation and self-regulation, leading to an intention-behavior gap. Therefore, our findings suggest there is a need for individualized and continued social support and supervision from health and exercise professionals to maintain long-term exercise BC for secondary prevention among post-MI patients. Trial registration The NorEx study has been registered at ClinicalTrials.gov (NCT04617639, registration date 2020-10-21).

A 1D imaging soft X-ray spectrometer installed on the small quantum systems (SQS) scientific instrument of the European XFEL is described. It uses movable cylindrical constant-line-spacing gratings in the Rowland configuration for energy dispersion in the vertical plane, and Wolter optics for simultaneous 1D imaging of the source in the horizontal plane. The soft X-ray fluorescence spectro-imaging capability will be exploited in pump–probe measurements and in investigations of propagation effects and other nonlinear phenomena.

OBJECTIVES: Quick returns (

This study focuses on computer-based formative assessment for supporting problem solving and reasoning in mathematics. To be able to assist students who find themselves in difficulties, the software suggested descriptions - diagnoses - of the encountered difficulty the students could choose from. Thereafter, the software provided metacognitive and heuristic feedback as suitable. The findings provide insight into how formative assessment can be designed to support students during their problem solving and indicate that diagnosis and feedback could be helpful for promoting students' creative reasoning. In other words, the feedback guided students in justifying, monitoring, and controlling their solution method.

Background Healthy lifestyle behaviors in pregnancy are important for maternal and offspring health. Mobile health (mHealth) tools have potential to provide support for lifestyle behaviors at scale but such tools are commonly developed only in native languages, limiting reach in migrant populations. Objectives This qualitative study, in two of the largest migrant populations in Sweden (Arabic- and Somali-speaking women), aimed to explore (a) perceptions and needs of knowledge and support related to pregnancy and lifestyle behaviors and (b) needs of and attitudes towards a pregnancy app and how features and content in the app can be adapted to support healthier lifestyle behaviors in migrant women. Method Individual semi-structured interviews were conducted with Arabic ( n = 10) and Somali-speaking women ( n = 9). Data was analyzed using content analysis (inductive latent approach). Results Arabic- and Somali-speaking women described an increased need of knowledge regarding pregnancy and lifestyle behaviors. The social environment could both motivate behavior change and be a source of misinformation. Women expressed great trust in maternity healthcare but requested more information related to lifestyle behaviors. A pregnancy app was perceived as a helpful tool to support healthy lifestyle behaviors. Mere translations were suggested to be valuable, however, audio- and video-format to deliver content and inclusion of women's partners in the app were described as desirable adaptations. Conclusion Our findings can guide maternity healthcare on what support migrant women need and inform future development of mHealth tools for pregnant migrant populations. Future research should disentangle the degree of cultural adaptations required for mHealth lifestyle interventions provided by healthcare.

Introduction Poor sexual and reproductive health (SRH) is a global public health concern, particularly among adolescents. While school health services (SHS) play a crucial role in preventative care, professionals are inconsistent in addressing SRH issues. This study explored school health professionals’ (SHPs) experiences of an implementation of structured assessments of sexual health and experiences of violence among youth in Sweden using the SEXual health Identification Tool (SEXIT).Methods A qualitative sequential study was conducted from October 2023 to January 2024 to explore the experiences of 57 SHPs trained in the SEXIT method. Data collection included a questionnaire with open-ended questions, group discussions and individual interviews, analysed using qualitative content analysis.Results Addressing sexual risk taking and violence was considered a priority to help youths make informed SRH choices. SEXIT aided SHPs in acting as educators to promote SRH and freedom from violence, normalised conversations about sensitive topics, facilitated the identification of students needing support, and could be integrated as a routine part of preventive work within SHS. However, hindering factors for effective implementation included a lack of supportive leadership and a unified approach among involved organisations to clarify roles, responsibilities and referral pathways. Furthermore, it is essential to further adapt SEXIT and train SHPs to meet the specific needs of vulnerable youths and perpetrators, ensuring equitable support.Conclusions SEXIT offers unique opportunities for SHPs to discuss SRH and violence with school youths, a priority part of their preventive work; however, it is not routinely used, underscoring the need for supportive leadership and a unified approach among organisations.

With the objective of finding new classes of cognitive enhancers with potential for the treatment of neurodegenerative disorders, such as Alzheimer's disease, small molecule inhibitors of insulin-regulated aminopeptidase (IRAP) were designed and synthesized. IRAP is a member of the M1 family of zinc aminopeptidases and is abundantly expressed in areas of the brain associated with cognition, such as the amygdala, hippocampus and cerebral cortex. IRAP inhibitors were previously shown to enhance memory and learning in animal models. A comprehensive high throughput screening of 400,000 small molecules from the European Lead Factory library provided a series of 50 promising compounds in a qualified hit list (QHL). More than 30 IRAP inhibitors with an IC50 below 3.5 μM were identified. Herein, selected compounds from this QHL were assayed for solubility and permeability. Most of the selected compounds displayed good solubility, but further permeability studies on the best compounds revealed low blood brain barrier (BBB) permeability and high efflux in cells overexpressing P-gp pumps, rendering them less promising as starting points in drug discovery processes. Two compounds from the QHL were prioritized for further structural optimization; the pyridyl-substituted isoxazole 1a (QHL27) and the benzylhydroxamic acid derivative 1b (QHL1), both demonstrating fair BBB permeability and no indication of efflux. While our attempts to improve the isoxazole derivative 1a were not fruitful, a structural modification of 1b to provide the chloro-substituted benzylhydroxamic acid 14b resulted in a ten-fold improvement of the IRAP inhibition with an IC50 value of 60 nM. The binding modes of 1b and 14b were determined by free energy perturbation (FEP) analysis performed on candidate docking poses, determining a binding mode that accurately explained the experimental SAR. Further FEP studies of compound 14b suggested that it exhibits selectivity towards IRAP over Aminopeptidase N (APN), indicating its potential for targeted therapeutic applications.

Within precision agriculture, yield mapping is important in the evaluation of crop management and delineation of management zones. It can also be used to assess within-field yield potential, in order to guide different precision agriculture practices. However, some farmers do not have a yield monitoring system, and some who do may obtain incomplete or erroneous yield data. This study examined the accuracy with which winter wheat (Triticum aestivum L.) yield could be mapped in 18 fields in southern Sweden using a simple empirical relationship between Sentinel-2 (ESA, Paris, France) data, vegetation index (VI) maps and combined harvester data collected in nearby fields. The results showed that a decrease in map resolution to 40 m reduced the error in the yield maps obtained. Normalised difference water index (NDWI) was the most efficient VI, while a combination of satellite data from earlier and later plant development (booting and milk development stages) performed slightly better than data for other development stages and combinations. The best-performing model at a within-field scale (40-m resolution) had an average mean absolute error (MAE) of 0.40 tonnes ha−1 in a leave-one-field-out cross validation. When the prediction model at field-means scale was applied on 69 farms in a 1055 km2 area, MAE was 0.75 tonnes ha−1 when comparing predictions with mean yields reported by farmers in a phone survey. Therefore, if adequate combined harvester and/or mean yield data are available, a modelling framework that translates satellite imagery into yield maps on-the-fly could be made available for different stakeholders via decision support systems for precision agriculture.

Purpose Aortic stiffness, assessed as estimated aortic pulse wave velocity (aPWV), and carotid intima-media thickness (cIMT) are markers of vascular age, and carotid plaques are a marker of early atherosclerosis. In this cross-sectional study we aimed to investigate the association between aPWV, cIMT and plaques across different age groups and in women and men, in a middle-aged healthy population.Materials and methods Participants in the 6.5-year follow-up of the VIPVIZA trial who were aged 47, 57 and 67 underwent an oscillometric measurement which estimates aPWV between 2020 and 2023. Carotid ultrasound examinations were also performed. Linear and ordinal regression models were used to investigate how aPWV associates with cIMT and with carotid plaques, for the overall study group and stratified for age groups and sex.Results A total of 1046 subjects were included in the analyses. Linear associations between aPWV and cIMT (β = 0.018, 95% CI: 0.006–0.030, p = 0.003), and between aPWV and plaques (OR: 1.19, 95% CI: 1.03–1.38, p = 0.018), were seen in the 57-year-olds. In the 47-year-olds a significant association was seen between aPWV and plaques (OR: 2.98 95% CI: 1.44–6.14, p = 0.003). No significant associations were seen in the 67-year-olds. For women, a significant association between aPWV and cIMT (β = 0.011, 95% CI: 0.004–0.017, p = 0.002) was shown.Conclusion Estimated aPWV was positively associated with increasing cIMT and the presence of carotid plaques in younger middle-aged individuals, and with cIMT in women, suggesting that measurement of estimated aPWV may improve cardiovascular risk assessment in younger middle-aged individuals and women.Clinical Trial Registration date 8 May 2013: URL: www.clinicaltrials.gov. Unique identifier: NCT01849575.

Background: The COVID-19 pandemic contributed to increased pressure on healthcare systems. During periods when the demands exceed the capacity of healthcare organizations, adaptive strategies are used to meet these demands. During the COVID-19 pandemic, working hours for nursing staff were reorganized and extended. This has posed challenges for recovery, which may be a key factor for maintaining health and safety under such conditions. Objectives: The aim of the study was to bring insights into how nursing staff perceived their working hours and recovery during the COVID-19 pandemic, and if they experienced any changes in their sleep and well-being. Design: A qualitative descriptive design was chosen, as it is suitable for gaining insight into perceptions and experiences. Methods: Qualitative semi-structured interviews were conducted using an interview guide. The interviews were analyzed using thematic analysis. Sixteen registered nurses and six certified nursing assistants from four Swedish hospitals participated in the study. Results: The organization of working hours during the COVID-19 pandemic was considered suboptimal and resulted in more demanding working hours and poor recovery. Nursing staff experienced loss of control as they lost influence over working hours, working hours became more unpredictable and the boundaries between work and leisure became blurred. Nursing staff also experienced a decline in their health and well-being, including extreme fatigue, impaired sleep and physical/mental changes. Conclusion: The strategies used by healthcare organizations to meet increasing demands during the COVID-19 pandemic contributed to impaired recovery and well-being of nursing staff, which could generate negative feedback loops contributing to depletion of resources at the organizational level.

Abstract Introduction Digital technologies have enabled new possibilities to assess dietary intake and have shown promise in terms of decreased participant burden, improved accuracy and lower costs. However, their potential and validity in pregnant populations are scarcely explored. Objectives This study aimed to (a) validate energy intakes obtained from a web-based dietary recall method developed for national surveys (RiksmatenFlex) against total energy expenditure (TEE) by means of the doubly labelled water (DLW) method, and (b) to compare intakes of macronutrients, key unhealthy and healthy foods as well as adherence to food-based dietary guidelines between RiksmatenFlex and repeated 24 h telephone dietary recalls in healthy Swedish pregnant women. Methods This study was conducted as a nested validation within the HealthyMoms trial. Intakes of foods, macronutrients and energy were assessed during three days through RiksmatenFlex and 24 h telephone dietary recalls, and Swedish Healthy Eating Index (SHEI) scores were also calculated for both methods (n = 52). For 24 women, TEE was also assessed through the DLW method. Paired Samples T-tests and Wilcoxon Signed Ranks Tests were used to identify differences between means for foods, macronutrients, energy and SHEI scores. Pearson correlation coefficient or Spearman’s rho were performed to identify relationships between variables. To compare energy intake (RiksmatenFlex) with TEE (DLW method) and 24 h telephone dietary recalls, Bland and Altman plots were constructed. Results Average energy intake from RiksmatenFlex (10,015 [SD 2004] kJ) was not statistically different from TEE (10,252 [SD 1197] kJ) (p = 0.596) (mean difference: -237 kJ/24 h). Correspondingly, there were small mean differences between average intakes of key unhealthy and healthy foods and average SHEI scores between RiksmatenFlex and 24 h telephone dietary recalls. However, the Bland and Altman plots showed wide limits of agreement for all dietary variables (e.g., for energy intake using RiksmatenFlex versus TEE: ±4239 kJ/24 h). High correlations between the investigated dietary variables for the two dietary methods were observed (r = 0.751 to 0.931; all p

Abstract Background Virtual reality (VR) training can enhance health professionals’ learning. However, there are ambiguous findings on the effectiveness of VR as an educational tool in mental health. We therefore reviewed the existing literature on the effectiveness of VR training on health professionals’ knowledge, skills, and attitudes in assessing and treating patients with mental health disorders. Methods We searched MEDLINE, PsycINFO (via Ovid), the Cochrane Library, ERIC, CINAHL (on EBSCOhost), Web of Science Core Collection, and the Scopus database for studies published from January 1985 to July 2023. We included all studies evaluating the effect of VR training interventions on attitudes, knowledge, and skills pertinent to the assessment and treatment of mental health disorders and published in English or Scandinavian languages. The quality of the evidence in randomized controlled trials was assessed with the Cochrane Risk of Bias Tool 2.0. For non-randomized studies, we assessed the quality of the studies with the ROBINS-I tool. Results Of 4170 unique records identified, eight studies were eligible. The four randomized controlled trials were assessed as having some concern or a high risk of overall bias. The four non-randomized studies were assessed as having a moderate to serious overall risk of bias. Of the eight included studies, four used a virtual standardized patient design to simulate training situations, two studies used interactive patient scenario training designs, while two studies used a virtual patient game design. The results suggest that VR training interventions can promote knowledge and skills acquisition. Conclusions The findings indicate that VR interventions can effectively train health care personnel to acquire knowledge and skills in the assessment and treatment of mental health disorders. However, study heterogeneity, prevalence of small sample sizes, and many studies with a high or serious risk of bias suggest an uncertain evidence base. Future research on the effectiveness of VR training should include assessment of immersive VR training designs and a focus on more robust studies with larger sample sizes. Trial registration This review was pre-registered in the Open Science Framework register with the ID-number Z8EDK.

ABSTRACT Uropathogenic Escherichia coli (UPEC) requires an adaptable physiology to survive the wide range of environments experienced in the host, including gut and urinary tract surfaces. To identify UPEC genes required during intracellular infection, we developed a transposon-directed insertion-site sequencing approach for cellular infection models and searched for genes in a library of ~20,000 UTI89 transposon-insertion mutants that are specifically required at the distinct stages of infection of cultured bladder epithelial cells. Some of the bacterial functional requirements apparent in host bladder cell growth overlapped with those for M9-glycerol, notably nutrient utilization, polysaccharide and macromolecule precursor biosynthesis, and cell envelope stress tolerance. Two genes implicated in the intracellular bladder cell infection stage were confirmed through independent gene deletion studies: neuC (sialic acid capsule biosynthesis) and hisF (histidine biosynthesis). Distinct sets of UPEC genes were also implicated in bacterial dispersal, where UPEC erupts from bladder cells in highly filamentous or motile forms upon exposure to human urine, and during recovery from infection in a rich medium. We confirm that the dedD gene linked to septal peptidoglycan remodeling is required during UPEC dispersal from human bladder cells and may help stabilize cell division or the cell wall during envelope stress created by host cells. Our findings support a view that the host intracellular environment and infection cycle are multi-nutrient limited and create stress that demands an array of biosynthetic, cell envelope integrity, and biofilm-related functions of UPEC.IMPORTANCEUrinary tract infections (UTIs) are one of the most frequent infections worldwide. Uropathogenic Escherichia coli (UPEC), which accounts for ~80% of UTIs, must rapidly adapt to highly variable host environments, such as the gut, bladder sub-surface, and urine. In this study, we searched for UPEC genes required for bacterial growth and survival throughout the cellular infection cycle. Genes required for de novo synthesis of biomolecules and cell envelope integrity appeared to be important, and other genes were also implicated in bacterial dispersal and recovery from infection of cultured bladder cells. With further studies of individual gene function, their potential as therapeutic targets may be realized. This study expands knowledge of the UTI cycle and establishes an approach to genome-wide functional analyses of stage-resolved microbial infections.

The neutron-rich rare isotope 190W is discussed as a candidate for a prolate-oblate transitional nucleus with maximum γ-softness. The collectivity of this isotope is assessed for the first time by the measurement of the reduced E2 transition probability of its first 2+ state to the ground state. The experiment employed the FAst TIming Array (FATIMA), comprised of 36 LaBr3(Ce) scintillators, which was part of the DESPEC setup at GSI, Darmstadt. The 41+ and 21+ states of 190W were populated subsequently to the decay of its 127(12) μs isomeric Jπ=10− state. The mean lifetime of the 21+ state was determined to be τ=274(28) ps, which corresponds to a B(E2;21+→01+) value of 95(10) W.u. The results motivated a revision of previous calculations within an energy-density functional-based interacting boson model-2 approach, yielding E2 transition properties and spectroscopic quadrupole moments for tungsten isotopes. From comparison to theory, the new data suggest that 190W is at the transition from prolate to oblate structure along the W isotopic chain, which had previously been discussed as a nuclear shape-phase transition.

The temporal dynamics of the perception of within-word coarticulatory cues remain a subject of ongoing debate in speech perception research. This behavioral gating study sheds light on the unfolding predictive use of anticipatory coarticulation in onset fricatives. Word onset fricatives (/f/ and /s/) were split into four gates (15, 35, 75 and 135 milliseconds). Listeners made a forced choice about the word they were listening to, based on the stimulus gates. The results showed fast predictive use of coarticulatory lip rounding during /s/ word onsets, as early as 15 ms from word onset. For /f/ onsets, coarticulatory backness and height began to be used predictively after 75 ms. These findings indicate that onset times of the occurrence and use of coarticulatory cues can be extremely fast and have a time course that differs depending on fricative type.

The calcium isotopes are an ideal system to investigate the evolution of shell structure and magic numbers. Although the properties of surface nucleons in calcium have been well studied, probing the structure of deeply bound nucleons remains a challenge. Here, we report on the first measurement of unbound states in 53Ca and 55Ca, populated from 54,56Ca(p,pn) reactions at a beam energy of around 216 MeV/nucleon at the RIKEN Radioactive Isotopes Beam Factory. The resonance properties, partial cross sections, and momentum distributions of these unbound states were analyzed. Orbital angular momentum l assignments were extracted from momentum distributions based on calculations using the distorted wave impulse approximation (DWIA) reaction model. The resonances at excitation energies of 5516(41)keV in 53Ca and 6000(250)keV in 55Ca indicate a significant l =3 component, providing the first experimental evidence for the ν0f7/2 single-particle strength of unbound hole states in the neutron-rich Ca isotopes. The observed excitation energies and cross-sections point towards extremely localized and well separated strength distributions, with some fragmentation for the ν0f7/2 orbital in 55Ca. These results are in good agreement with predictions from shell-model calculations using the effective GXPF1Bs interaction and ab initio calculations and diverge markedly from the experimental distributions in the nickel isotones at Z=28.

The first ever liverwort and hornwort checklist is provided for the Maluku Islands (Moluccas/Spice Islands) of Indonesia. We report 355 accepted and 16 doubtful species and reject 22 species previously reported for Maluku Islands. The list is based on the specimens housed in the Herbarium Bogoriense (BO) and reports from over 500 literature references, including monographs, regional studies, and molecular investigations. The Maluku Islands are part of the Wallacea Biodiversity Hotspot with many unique species found only in Wallacea. Publications focusing on liverworts and hornworts of Maluku Islands are few and scattered. Considering regionally widespread species that have been recorded elsewhere, we predict that further fieldwork exploring the diversity of habitats coupled with collections unveiled from regional herbaria, a number of new records remain to be reported.

Research has shown that students’ learning gains in mathematics are greater when they work with problems rather than routine tasks. These learning gains from problem-solving activities may be enhanced by providing feedback that does not give away the solutions to the problems, but helps students construct their solution methods themselves and anchor their reasoning in intrinsic properties of the mathematical components involved in the reasoning. However, in order to use feedback, students would need to perceive it as useful, and not all students may find such feedback useful. In this study, we investigate how students’ ability and motivational beliefs affect how useful they perceive feedback aimed at supporting mathematical reasoning to be. In the study, students worked with mathematical problems and received metacognitive and heuristic feedback when they needed help. We used structural equation modeling (SEM) to analyze the effects. The results show that students’ mastery goals had a direct effect on the perceived usefulness of the feedback, but no such effects were found for students’ national test grades, self-efficacy beliefs, performance goals, or intrinsic or extrinsic forms of motivation. The proportion of successful use of feedback did not mediate the effects.

Abstract Microturbellarians are abundant and ubiquitous members of marine meiofaunal communities around the world. Because of their small body size, these microscopic animals are rarely considered as hosts for parasitic organisms. Indeed, many protists, both free-living and parasitic ones, equal or surpass meiofaunal animals in size. Despite several anecdotal records of “gregarines”, “sporozoans”, and “apicomplexans” parasitizing microturbellarians in the literature—some of them dating back to the nineteenth century—these single-celled parasites have never been identified and characterized. More recently, the sequencing of eukaryotic microbiomes in microscopic invertebrates have revealed a hidden diversity of protist parasites infecting microturbellarians and other meiofaunal animals. Here we show that apicomplexans isolated from twelve taxonomically diverse rhabdocoel taxa and one species of proseriate collected in four geographically distinct areas around the Pacific Ocean (Okinawa, Hokkaido, and British Columbia) and the Caribbean Sea (Curaçao) all belong to the apicomplexan genus Rhytidocystis. Based on comprehensive molecular phylogenies of Rhabdocoela and Proseriata inferred from both 18S and 28S rDNA sequences, as well as a molecular phylogeny of Marosporida inferred from 18S rDNA sequences, we determine the phylogenetic positions of the microturbellarian hosts and their parasites. Multiple lines of evidence, including morphological and molecular data, show that at least nine new species of Rhytidocystis infect the microturbellarian hosts collected in this study, more than doubling the number of previously recognized species of Rhytidocystis, all of which infect polychaete hosts. A cophylogenetic analysis examining patterns of phylosymbiosis between hosts and parasites suggests a complex picture of overall incongruence between host and parasite phylogenies, and varying degrees of geographic signals and taxon specificity.

Abstract Background In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. Results Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. Conclusion Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

Abstract Background Children with brain tumors are at high risk of neurocognitive decline after radiotherapy (RT). However, there is a lack of studies on how RT doses to organs at risk (OARs) impacts neurocognition. The aim of this study was to examine dose-risk relationships for mean RT dose to different brain structures important for neurocognitive networks. We explored previously established OARs and potentially new OARs. Methods A sample of 44 pediatric brain tumor survivors who had received proton and/or photon RT were included. Correlations between mean RT doses to OARs and IQ were analyzed. Previously established OARs were cochleae, optic chiasm, optic nerve, pituitary gland, hypothalamus, hippocampus and pons. Potential new OARs for RT-induced neurocognitive decline were cerebellum, vermis and thalamus. Results Mean RT dose to different OARs correlated with several IQ subtests. Higher mean RT dose to cochleae, optic nerve, cerebellum, vermis and pons was correlated with lower performance on particularly full-scale IQ (FIQ), Perceptual Reasoning (PRI), Working Memory (WMI) and Processing Speed Index (PSI). Higher mean RT dose to hippocampus correlated with lower performance on processing speed and working memory. For those receiving whole brain RT (WBRT), higher mean RT dose to the pituitary gland correlated with lower performance on working memory. Conclusion A high dose-risk correlation was found between IQ subtests and mean RT dose in established and potential new OARs. Thus, in the lack of validated dose constraints for vulnerable brain structures, a parsimonious approach in RT planning should be considered to preserve neurocognitive networks.