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The Src family of protein tyrosine kinases (SFKs) plays key roles in regulating signal transduction by a diverse set of cell surface receptors in the context of a variety of cellular environments. SFKs have evolved many ingenious molecular strategies to couple receptors with the cytoplasmic signaling machinery. The contributions to this issue of ONCOGENE describe how this machinery regulates fundamental cellular processes, including cell growth, differentiation, cell shape, migration and survival, and specialized cell signals. The pleotropic functions of Src and Src family members underscore the importance of these kinases and explain why many of the members of this family have been identified as cellular oncogenes. In this volume, we have attempted to provide the reader with an overview of the current understanding of the function of Src family kinases in the regulation of selected cellular signaling pathways.

Background While each young person has the right to participate in shared decision-making about their care and support, autistic young people often report poor experiences of mental health services and are frequently excluded from, or misunderstood within, care planning conversations. Given that shared decision-making requires practitioners and service users to discuss options together, the differences in communication profiles across autistic and non-autistic populations raises questions as to how mutual understanding can be maximised within care planning conversations. This study sought to explore how shared decision-making took place with autistic young people within a specialist NHS autism community mental health service in England, and to elucidate the features of practice that enabled the effective participation of autistic young people in decision-making discussions. Methods A qualitative case study was undertaken within an NHS Autism and Learning Disability Keyworker Programme in England involving 13 participants (4 autistic young people, 3 parent/carers, and 6 service keyworkers). Data were collected through regular service observations, interviews and focus groups across six months. Results Four themes were generated to explain how shared decision-making was enacted within and across the service: (1) navigating organisational tensions, (2) bridging different communication styles, (3) enabling autistic thinking patterns and (4) creating conditions for reciprocity and dialogue. Eight subcategories were developed to illustrate distinctive features of practice which enabled autistic young people’s participation in decision-making conversations. Conclusion The findings demonstrate that specialist keyworkers were central to facilitating shared decision-making with autistic young people. Their strong understanding of autism enabled them to bridge communication differences across multiple stakeholders and by adapting communication approaches to suit an autistic profile, their practice encouraged meaningful dialogue. The study offers depth and clarity on strategies used by the keyworkers to enable shared decision-making conversations to take place effectively with autistic young people and has wider applicability across healthcare services.

Targeting of Toxoplasma gondii by autophagy is an effective mechanism by which host cells kill the protozoan. Thus, the parasite must avoid autophagic targeting to survive. Here we show that the mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion of host cells. Activated FAK appears to accompany the formation of the moving junction (as assessed by expression the parasite protein RON4). FAK activation was inhibited by approaches that impaired β1 and β3 integrin signaling. FAK caused activation of Src that in turn mediated Epidermal Growth Factor Receptor (EGFR) phosphorylation at the unique Y845 residue. Expression of Src-resistant Y845F EGFR mutant markedly inhibited ROP16-independent activation of STAT3 in host cells. Activation of FAK, Y845 EGFR or STAT3 prevented activation of PKR and eIF2α, key stimulators of autophagy. Genetic or pharmacologic inhibition of FAK, Src, EGFR phosphorylation at Y845, or STAT3 caused accumulation of the autophagy protein LC3 and LAMP-1 around the parasite and parasite killing dependent on autophagy proteins (ULK1 and Beclin 1) and lysosomal enzymes. Parasite killing was inhibited by expression of dominant negative PKR. Thus, T. gondii activates a FAK→Src→Y845-EGFR→STAT3 signaling axis within mammalian cells, thereby enabling the parasite to survive by avoiding autophagic targeting through a mechanism likely dependent on preventing activation of PKR and eIF2α.

‘I am’ Digital Stories are short, 3-5 minute videos that are co-constructed with autistic children and families to provide a more holistic, strengths-based representation of them in support of transitions within or between schools. These Stories provide counter-narratives to the often deficit-focused accounts that accompany children through their school life and are intended to help to introduce who the child really is beyond paper-based descriptions of their needs and difficulties. Inspired by Lambert’s digital storytelling tradition, the ‘I am’ Digital Stories methodology has been developed to support the diversity of voices of autistic people to be heard including those who may be ‘unvoiced and differently voiced’. As an arts-based method within a participatory research approach, the ‘I am’ Digital Stories take a strengths-based stance towards supporting understanding and awareness of children beyond the labels of difference that are attached to them. While there has been more research in health-oriented spheres that uses digital storytelling methods, there has been less within education and specifically in co-construction with autistic children and young people. A recent review of the digital storytelling literature published in this journal concluded that there is a lack of detail and description of the theories, frameworks and models that underpin research applying this method, and a lack of consideration of ethical issues. Our paper seeks to provide detail on these aspects with the aim of contributing to the strengthening of the evidence base in this area. Specifically, we frame ‘I am’ Digital Stories as a praxeological methodology that includes consideration of power redistribution, reflection and action with others, values and ethics, non-orthodox methods, and pathway to impact. We conclude that the ‘I am’ Digital Stories methodology is powerful for sharing autistic ways of knowing about the world that actively tackle marginalisation.

Exotic plants are common in urban landscapes and are often planted by landscape managers in an effort to reduce herbivory damage and improve landscape aesthetics. However, exotic plants may be less palatable to many native insects and reduce herbivore biomass that may fuel higher trophic levels. Furthermore, a loss of herbivores in exotic ornamental landscapes may reduce top-down control by natural enemies. In this study, we compare herbivory in native and exotic congener ornamental landscapes. We also explore if caterpillar abundance, natural enemy abundance, diversity, community composition, spider biomass, and egg predation differ between the two landscape types. We predicted that herbivory, as well as natural enemy abundance and predation would be greater in native landscapes. Although we found that leaf area lost to herbivory was greater in native plots in one of the collection years, this relationship was weak. Natural enemy diversity differed between landscape types, but depended on plant genus. The relationship between plant origin and natural enemy diversity was also weak. Caterpillar abundance, natural enemy community composition, spider biomass, and predation services did not differ between treatments. Overall, our results suggest that ornamental landscapes planted in native plants may not differ from landscapes planted in exotic congeners in the pest management and conservation services they provide, particularly with regard to invertebrate natural enemies. However, our findings cannot be used to make more general claims about plant origin, especially with regard to native plants and non-congeners, as we only compared ornamental landscapes with native plants and their exotic congeners in this study. We conclude that for optimizing natural enemy diversity and biomass on city landscapes, plant choice and other plant traits may be as important as plant origin to consider. Our work demonstrates that both native and exotic congener ornamental landscapes provide valuable ecosystem services and will help guide landscape design that serves both the people and wildlife that use them.

It is important for allocation of resources to predict those COVID patients at high risk of dying or organ failure. Early signals to initiate cellular events of host immunity can be derived from essential fatty acid metabolites preceding the cascade of proinflammatory signals. Much research has focused on understanding later proinflammatory responses. We assessed if remodelling of plasma phospholipid content of essential fatty acids by the COVID-19 virus provides early markers for potential death and disease severity. Here we show that, at hospital admission, COVID-19 infected subjects who survive exhibit higher proportions of C20:4n-6 in plasma phospholipids concurrent with marked proinflammatory cytokine elevation in plasma compared to healthy subjects. In contrast, more than half of subjects who die of this virus exhibit very low C18:2n-6 and C20:4n-6 content in plasma phospholipids on hospital admission compared with healthy control subjects. Moreover, in these subjects who die, the low level of primary inflammatory signals indicates limited or aberrant stimulation of host immunity. We conclude that COVID-19 infection results in early fundamental remodelling of essential fatty acid metabolism. In subjects with high mortality, it appears that plasma n-6 fatty acid content is too low to stimulate cellular events of host immunity.

Background & aims There is increasing recognition of the importance of challenging deficit-focused, medical model approaches to supporting autistic people in daily life, however there is a lack of inclusion of autistic perspectives to inform approaches that may empower autistic people in conversations. Methods This multiple case study used a participatory approach to explore the conversation experiences and exchange in dyads of five autistic and five non-autistic adults over four to 12 months. The study was grounded in the perspectives of autistic people through a series of semi-structured interviews, observations, reflective conversations, and diary records. Results The findings focus on autistic participants’ existing knowledge of conversations that they reported could be useful to them, including the communication environment, and type and structure of talk. The study also helped participants to identify and use previously unrecognised metacognitive abilities (what they already knew about conversations) within naturalistic interactive contexts. Conclusions These findings provide novel insights as to how the ‘interactional expertise’ of non-autistic people could be strengthened to enable the effective contribution of the voices of autistic people in everyday conversations. Implications The identification and use of successful conversation strategies identified by autistic adults gave them a greater sense of empowerment within the conversation based on their accounts of their experiences. Understanding these strategies has valuable implications for staff training, for working with families and for learning by autistic adults.

How children and young people understand and exercise their autonomy, engagement and decision-making is fundamental to learning how to become active and engaged citizens, and to be socially included. Digital technologies are increasingly an integral part of children’s everyday lives and, therefore, valuable tools for supporting social inclusion. This paper discusses how digital technologies might positively support autonomy, engagement and decision-making through the lens of informed consent practices within social research. Current research practices are dominated by paper-based methods for obtaining informed consent which could be exclusionary for children and young people generally, and children with additional learning and support needs in particular. Digital technologies (laptops, PCs, tablet devices, smartphones) offer the potential to support accessibility and understanding of ideas and activities, as well as engagement with and autonomy in decision-making and participation. This paper explores this potential as well as the challenges that researchers may face in this context.

Background: Neonatal intensive care units (NICU) are associate with a high level of antibiotic consumption. Appropriate antibiotic use is crucial to minimize the emergence of resistance and unintended consequences to the patient. Our antimicrobial stewardship program (ASP) performed a baseline review of NICU antibiotic prescribing, which revealed excessive meropenem use and inconsistent empiric antibiotic prescribing practices within the unit. Third generation cephalosporins were vastly underutilized due to concerns of increased Candida infections resulting in the unwarranted excessive use of meropenem.1 Methods: In 2023, the ASP created an institution specific empiric NICU sepsis guideline to align empiric prescribing practices with current guidelines and reduce the unwarranted use of carbapenems. After education and guideline implementation, a retrospective review, pre (April 16, 2021 to April 16, 2023) and post (April 17, 2023 to April 17, 2024) implementation was conducted. The primary objectives were to evaluate the effect of the guideline implementation on antibiotic days of therapy (DOT) per 1000 patient-days, overall meropenem and third generation cephalosporin utilization, differences in the incidence of Candida infections, and variations in antimicrobial sensitivity. Microbiologic data from sterile site cultures were obtained April 2021 to March 2023 and post-implementation (April 2023 to March 2024) to evaluate cephalosporin and meropenem resistance for each period. Results: Meropenem DOT/1000 patient-days declined from 3.9 to 2.0 (51.3%), and an associated rise in third-generation cephalosporin DOT/1000 patient-days from 15.7 to 22.9 (69.7%) occurred post-guideline implementation. There were no observed differences in the incidence of Candida infections, cephalosporin resistance in Gram-negative bacilli, or the organisms isolated over the observation period. Conclusions: Guideline implementation safely and successfully reduced the use of carbapenems by providing alternative antibiotic regimens encouraging the use of third generation cephalosporins and reduced antibiotic pressure in our NICU. There were no differences in the incidence of Candida infections, organisms, or resistance patterns. Implementation of this guideline resulted in safe decreases in antibiotic use in the NICU. Cotton CM, McDonald S, Stoll B, et al. The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics. 2006;118(2):717-22.

BackgroundSudden cardiac death (SCD) is a major global health problem, accounting for up to 20% of deaths in Western societies. Clinical quality registries have been shown in a range of disease conditions to improve clinical management, reduce variation in care and improve outcomes.AimTo identify existing cardiac arrest (CA) and SCD registries, characterising global coverage and methods of data capture and validation.MethodsBiomedical and public search engines were searched with the terms ‘registry cardio*’; ‘sudden cardiac death registry’ and ‘cardiac arrest registry’. Registries were categorised as either CA, SCD registries or ‘other’ according to prespecified criteria. SCD registry coordinators were contacted for contemporaneous data regarding registry details.ResultsOur search strategy identified 49 CA registries, 15 SCD registries and 9 other registries (ie, epistries). Population coverage of contemporary CA and SCD registries is highly variable with registries densely concentrated in North America and Western Europe. Existing SCD registries (n=15) cover a variety of age ranges and subpopulations, with some enrolling surviving patients (n=8) and family members (n=5). Genetic data are collected by nine registries, with the majority of these (n=7) offering indefinite storage in a biorepository.ConclusionsMany CA registries exist globally, although with inequitable population coverage. Comprehensive multisource surveillance SCD registries are fewer in number and more challenging to design and maintain. Challenges identified include maximising case identification and case verification.Trial registration numberCRD42019118910.