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Participation in Organised Extracurricular Social Activities (OESA) can provide positive outcomes for children. This study investigated whether children aged 4 to 12 years diagnosed with autism differ in their OESA participation and experience compared to neurotypical peers. Parents of autistic children (n = 35) and those of neurotypical peers (n = 171) responded to questions that asked them to reflect on their child's participation and experiences in OESAs. Parents of autistic children reported significantly less OESA participation compared to parents of neurotypical children. Additionally, when evaluating factors that facilitated OESA participation, parents of autistic children rated their child's individual abilities and behaviour, the OESA's features, and the social environment less positively, compared to parents of neurotypical children. OESA participation and experiences differ for autistic and neurotypical children. This study identifies factors that can be adjusted to mitigate this difference.

Communication and interaction in neurotypical environments can be challenging for autistic individuals, potentially disrupting the parent-child relationship. In Relationship Development Intervention (RDI) that facilitates improved interactions between autistic children and their parents, RDI Consultants play key roles in enabling parents to develop skills that support the parent-child relationship. Parents follow the guidance of the Consultants to build their capacities to model reciprocal communications with their autistic children. Given the significant role played by the Consultant, their perspectives should be explored. Two research questions were explored: 1) What are the lived experiences of RDI Consultants in delivering RDI to autistic children and their families? 2) What are RDI Consultants' perspectives regarding the outcomes of engaging in RDI for autistic children and their families? Eleven RDI Consultants participated in semi-structured interviews to explore their experiences in using RDI. Interviews were conducted via Zoom. All interviews were transcribed verbatim and thematically analysed. Three main themes were produced: 1) RDI helps autistic children reach their potential; 2) Parents learn to embrace parenthood through RDI; and 3) Consultants form a team with parents. Overall, RDI was perceived to be beneficial in improving autistic children's social engagement, such as parent-child interactions, as well as enhancing parenting experiences. The results add to and extend the existing evidence of RDI, which may provide families of autistic children and those professionals who are working with these families more therapeutic choices to consider. Future research implications for parents and health professionals involved in therapies are discussed.

Abstract Background Oral sensory hypersensitivity has been linked with fussy eating predominantly in non-typically developing children. We hypothesized that child ‘Oral’ (touch, smell and taste in the mouth) and ‘Social-Emotional’ (response to social expectations) sensory processing are associated with child appetitive traits in typically developing preteen children. Additionally, we explored relationships between maternal sensory profiles and their offspring’s sensory profile. Methods This is secondary analysis of 130 mother-child dyads from the 9–11-year-old follow-up of the ROLO longitudinal birth cohort study. The Dunn Sensory Profile (Adolescent/Adult) and the Dunn Child Sensory Profile 2 were used to assess maternal and child sensory profiles, respectively. The Children’s Eating Behaviour Questionnaire was used to assess child appetitive traits. Multiple linear regression examined associations between ‘Oral’ and ‘Social-Emotional’ segments of the child sensory profile and child appetitive traits. Associations between maternal and child sensory profiles were examined using sensory profile quadrants (Dunn’s sensory processing framework). These refer to four distinct patterns of sensory processing that indicate how an individual responds to sensory input. Results In total, 130 mother-child dyads were included. In adjusted analysis child ‘Oral’ sensory processing was associated with higher mean scores in the appetitive traits ‘Desire to Drink’ (B = 0.044, 95% CI = 0.025,0.062) and ‘Food Fussiness’ (B = 0.080, 95% CI = 0.059,0.101) and with lower mean scores in ‘Enjoyment of Food’ (B=-0.038, 95% CI -0.055,-0.022). Child ‘Social-Emotional’ responses were associated with higher mean scores in ‘Desire to Drink’ and ‘Food Fussiness’. Higher scores in the maternal sensory profile quadrants of ‘Sensitivity’, ‘Avoiding’ and ‘Registration’ were positively associated with higher scores in the corresponding child sensory profile quadrants. Conclusion Our findings suggest that in typically developing children presenting with fussy eating, oral sensory hypersensitivity and higher scores in social-emotional responses to sensory processing may be an underlying determinant. The relationship observed between ‘Oral’ and ‘Social-Emotional’ sensory processing segments and ‘Desire to Drink’ requires further research to ascertain the type of drinks being consumed and how this impacts appetite. Further research is also required to explore the influence of maternal sensory profile on their offsprings response to sensory input.

Abstract Objective Invasive lobular breast cancer (ILC) is the most common special type of breast cancer and has unique clinicopathological and molecular hallmarks that differentiate it from the more common invasive carcinoma—no special type (NST). Despite these differences, ILC and NST are treated as a single entity and there is a lack of ILC-targeted therapies. To fill this gap, we sought to identify novel molecular alterations in ILC that could be exploited for targeted therapies. Methods Differential gene expression and Geneset Enrichment and Variation analyses were performed on RNA-seq data from three large public breast cancer databases—the Sweden Cancerome Analysis Network-Breast (SCAN-B; luminal A ILC N = 263, luminal A NST N = 1162), The Cancer Genome Atlas (TCGA; luminal A ILC N = 157, luminal A NST N = 307) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; luminal A ILC N = 65, luminal A NST N = 533). Pathways enriched in overlapping differentially expressed genes from these datasets were clustered using Jaccard similarity to identify pathways enriched in ILC. The cAMP/PKA/CREB signaling was studied in ILC, ILC-like and NST cell lines and patient-derived organoids (PDOs) using forskolin, an activator of the pathway. Results Clinicopathological features of patients with ILC and NST in SCAN-B were similar to prior population-based studies. There was a consistent pattern of up-regulation of cAMP/PKA/CREB related signaling in ILC compared to NST in SCAN-B, TCGA and METABRIC. Treatment with forskolin resulted in a greater increase in phospho-CREB in ILC cell lines and organoids than NST. CRISPR deletion of CDH1 in NST cell lines did not alter response of cells to forskolin as measured by phospho-CREB. Forskolin treatment caused growth inhibition in ILC and NST, with ILC cell lines being more sensitive to forskolin-mediated growth inhibition. Conclusion In three separate datasets, cAMP/PKA/CREB signaling was identified to be higher in ILC than NST. This in silico finding was validated in cell line and organoid models. Loss of CDH1 was not sufficient to mediate this phenotype. Future studies should investigate the mechanisms for differential cAMP/PKA/CREB signaling and the potential for therapeutic targeting in patients with ILC. Graphical abstract

Abstract Endometriosis is a chronic systemic disease, which results in endometrial-type tissue growing outside the uterus, and affects approximately 10% of reproductive-aged women worldwide. Its aetiology is poorly understood, and there is currently no long-term cure. Development and persistence of the disease depend on several coexisting factors including the vaginal microbiome. However, the role played by this important entity in endometriosis and its systemic involvement is not fully understood. Here, we investigated the vaginal microbiota, the serum and urine glycome, and antibody glycosylation in endometriosis patients. We reveal an endometriosis-specific vaginal microbiota in patients, being distinct from that present in a control group. Endometriosis patients were typified by a loss of the dominant Lactobacillus species, i.e. Lactobacillus iners, increased bacterial diversity and the presence of species such as Anaerococcus senegalensis, Prevotella jejuni, Porphyromonas bennonis and Anaerococcus octavius. The presence of trigalactosylated and triantennary serum glycans and urine core fucosylated mono-antennary glycans from IgG correlated with the vaginal presence of the bacterium A. senegalensis in endometriosis patients. Urine glycans did not differ in endometriosis, but urine IgG identified four novel sulfated glycans differing from serum IgG indicating functional relevance. Our findings contribute to understanding the relationships between the vaginal microbiota and the serum and urine glycome on the one hand, and endometriosis on the other. Further functional studies are warranted.

Abstract Mucopolysaccharidoses are inherited metabolic disorders caused by the deficiency in lysosomal enzymes required to break down glycosaminoglycans. Accumulation of glycosaminoglycans leads to progressive, systemic degenerative disease. The central nervous system is particularly affected, resulting in developmental delays, neurological regression, and early mortality. Current treatments fail to adequately address neurological defects. Here we explore the potential of human induced pluripotent stem cell (hiPSC)-derived microglia progenitors as a one-time, allogeneic off-the-shelf cell therapy for several mucopolysaccharidoses (MPS). We show that hiPSC-derived microglia progenitors, possessing normal levels of lysosomal enzymes, can deliver functional enzymes into four subtypes of MPS knockout cell lines through mannose-6-phosphate receptor-mediated endocytosis in vitro. Additionally, our findings indicate that a single administration of hiPSC-derived microglia progenitors can reduce toxic glycosaminoglycan accumulation and prevent behavioral deficits in two different animal models of MPS. Durable efficacy is observed for eight months after transplantation. These results suggest a potential avenue for treating MPS with hiPSC-derived microglia progenitors.

Abstract People often display ingroup bias in punishment, punishing outgroup members more harshly than ingroup members. However, the impact of group membership may be less pronounced when people are choosing whether to stop interacting with someone (i.e., partner rejection). In two studies (N = 1667), we investigate the impact of group membership on both response types. Participants were assigned to groups based on a “minimal” groups paradigm (Study 1) or their self-reported political positions (Study 2) and played an incentivized economic game with other players. In this game, participants (Responders) responded to other players (Deciders). In the Punishment condition, participants could decrease the Decider’s bonus pay. In the Partner Rejection condition, participants could reject future interactions with the Decider. Participants played once with an ingroup member and once with an outgroup member. To control for the effects of intent and outcome, scenarios also differed based on the Decider’s Intent (selfish versus fair) and the Outcome (equal versus unequal distribution of resources). Participants punished outgroup members more than ingroup members, however group membership did not influence decisions to reject partners. These results highlight partner rejection as a boundary condition for the impact of group on responses to transgressions.

Abstract Background Breastfeeding self-efficacy is a woman’s self-belief and confidence in her perceived ability to breastfeed. This modifiable determinant is strongly associated with breastfeeding initiation, exclusivity, and duration. It is unclear how important the timing of breastfeeding self-efficacy measurement and interventions are. The prenatal period appears underexplored in the literature and yet a prenatal focus provides increased opportunity for breastfeeding self-efficacy enhancement and further potential improvement in breastfeeding outcomes. This scoping review aims to synthesise the evidence on prenatal breastfeeding self-efficacy, describing for the first time the theoretical frameworks, measurement tools, and interventions used in the prenatal period. Methods 8 databases were searched using the PCC framework (Problem: breastfeeding, Concept: self-efficacy, Context: prenatal period). From 4,667 citations and 156 additional sources identified through grey literature and snowballing, data were extracted from 184 studies and 2 guidance documents. All were summarised descriptively and narratively. Results Just over half (57%) of included studies stated their theoretical underpinning, with Bandura’s Self-Efficacy Theory / Dennis’ Breastfeeding Self-Efficacy Framework predominant. Only half of intervention studies incorporated theory in their design. More intervention studies were undertaken in the past decade than previously, but the level of theoretical underpinning has not improved. Prenatal interventions incorporating theory-led design and using components addressing the breadth of theory, more frequently reported improving breastfeeding self-efficacy and breastfeeding outcomes than those not theory-led. Intervention components used less frequently were vicarious or kinaesthetic learning (52.5%) and involvement of social circle support (26%). The Breastfeeding Self-Efficacy Scales were the most common measurement tool, despite being designed for postpartum use. Overall, issues were identified with the late prenatal timing of breastfeeding self-efficacy investigation and the design, content and phraseology of measurements and interventions used in the prenatal period. Conclusion This review provides novel insights for consideration in the design and conduct of breastfeeding self-efficacy studies in the prenatal period. Future research should aim to be theory-led, commence earlier in pregnancy, and embed the breadth of self-efficacy theory into the design of interventions and measurement tools. This would provide more robust data on prenatal breastfeeding self-efficacy’s role in impacting breastfeeding outcomes.

Abstract Background Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated. Methods We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up. Results Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus Black women. We identified differences in ER and HER2 expression, tumor microenvironment composition, and copy number variations by SRR and outcome groups. Conclusions Our results suggest that different molecular mechanisms drive initiation and subsequent ipsilateral breast events in Black versus White women.

The transition to school is a sensitive developmental period for young children. Although children born very/extremely preterm have increased risk of health and developmental concerns, predictors of their school readiness and adjustment remain largely unexamined. Parents of very/extremely preterm-born children (aged 3-7 years; pre-transition n = 114, post-transition n = 112) completed an online survey assessing their perceptions of children's school readiness (pre-transition) or adjustment (post-transition), support needs, child behaviour, parent distress, and parent confidence. Poorer school readiness and adjustment and greater needs for support correlated with child health/developmental condition/s; hyperactivity, peer problems, conduct problems, emotional symptoms, and less prosocial behaviour; and lower parent confidence. Using hierarchical linear regression, parent confidence emerged as the strongest common predictor of school readiness (pre-transition) and school adjustment (post-transition), followed by low hyperactivity, high parent education (tertiary), and no diagnosed child health/developmental condition/s. Results will be used to identify families needing support and develop tailored support strategies.

Abstract Women represent 70% of the global health workforce but only occupy 25% of health and social care leadership positions. Gender-based stereotypes, discrimination, family responsibilities, and self-perceived deficiencies in efficacy and confidence inhibit the seniority and leadership of women. The leadership inequality is often compounded by the intersection of race and socio-economic identities. Resolving gender inequalities in healthcare leadership brings women’s expertise to healthcare decision making, which can lead to equity of healthcare access and improve healthcare services. With the aim of enhancing women’s advancement to leadership positions, a rapid realist review (RRR) was conducted to identify the leadership and career advancement interventions that work for women in healthcare, why these interventions are effective, for whom they are effective, and within which contexts these interventions work. A RRR ultimately articulates this knowledge through a theory describing an intervention’s generative causation. The Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) for conducting a realist synthesis guided the methodology. Preliminary theories on leadership and career advancement interventions for women in healthcare were constructed based on an appraisal of key reviews and consultation with an expert panel, which guided the systematic searching and initial theory refinement. Following the literature search, 22 studies met inclusion criteria and underwent data extraction. The review process and consultation with the expert panel yielded nine final programme theories. Theories on programmes which enhanced leadership outcomes among women in health services or professional associations centred on organisational and management involvement; mentorship of women; delivering leadership education; and development of key leadership skills. The success of these strategies was facilitated by accommodating programme environments, adequacy and relevance of support provided and programme accessibility. The relationship between underlying intervention entities, stakeholder responses, contexts and leadership outcomes, provides a basis for underpinning the design for leadership and career advancement interventions for women in healthcare.

Abstract This study addresses the effect of using animal excreta on the nutritional content of forages, focusing on macro- and micro-element concentrations (nitrogen; N, phosphorus; P, sulphur; S, copper; Cu, zinc; Zn, manganese; Mn, selenium; Se) from animal feed to excreta, soil, and plants. Data were collected from pot and field trials using separate applications of sheep or cattle urine and faeces. Key findings indicate that soil organic carbon (SOC) and the type of excreta significantly influences nutrient uptake by forages, with varied responses among the seven elements defined above. Although urine contributes fewer micronutrients compared to faeces (as applied at a natural volume/mass basis, respectively), it notably improves forage yield and micronutrient accumulation, thus potentially delivering positive consequences at the farm level regarding economic performance and soil fertility when swards upon clayey soil types receive said urine in temperate agro-climatic regions (i.e., South West England in the current context). In contrast, faeces application in isolation hinders Se and Mn uptake, once again potentially delivering unintended consequences such as micronutrient deficiencies in areas of high faeces deposition. As it is unlikely that (b)ovine grazing fields will receive either urine or faeces in isolation, we also explored combined applications of both excreta types which demonstrates synergistic effects on N, Cu, and Zn uptake, with either synergistic or dilution effects being observed for P and S, depending largely on SOC levels. Additionally, interactions between excreta types can result in dilution or antagonistic effects on Mn and Se uptake. Notably, high SOC combined with faeces reduces Mn and Se in forages, raising concerns for grazed ruminant systems under certain biotic situations, e.g., due to insufficient soil Se levels typically observed in UK pastures for livestock growth. These findings underscore the importance of considering SOC and excreta nutritional composition when designing forage management to optimize nutrient uptake. It should be noted that these findings have potential ramifications for broader studies of sustainable agriculture through system-scale analyses, as the granularity of results reported herein elucidate gaps in knowledge which could affect, both positively and negatively, the interpretation of model-based environmental impact assessments of cattle and sheep production (e.g., in the case of increased yields [beneficial] or the requirement of additional synthetic supplementation [detrimental]).

Abstract Immunological adaptions during pregnancy play a crucial role in healthy fetal development. Aberrant immune modifications however contribute to adverse pregnancy outcomes, which may be driven by maternal factors such as previous pregnancies and BMI. This secondary analysis of the MicrobeMom2 RCT investigates the changes to maternal inflammatory biomarkers derived from serum and stimulated peripheral blood mononuclear cells (PBMCs) during pregnancy, and the effects of previous pregnancies (parity) and BMI on maternal immune responses. Changes in immune and metabolic biomarkers from early (11–15 weeks’ gestation) to late (28–32 weeks’ gestation) pregnancy were compared using paired t-tests. Participants were then split by parity (nulliparous, parous) and BMI (BMI = 25), and the relationship between parity and BMI with immune biomarker levels was examined using independent t-tests, paired t-tests, ANCOVA, and linear regression. Equivalent non-parametric tests were used for skewed data. Recruited women (n = 72) were on average 31.17 (SD ± 4.53) years of age and 25.11 (SD ± 3.82) BMI (kg/m2). Of these, 51 (70.8%) had a previous term pregnancy. Throughout gestation, PBMC cytokines displayed contrasting trends to serum, with a dampening of immune responses noted in PBMCs, and enhanced production of cytokines observed in the serum. Significant decreases in PBMC derived TNF-α, IL-10 and IFN-γ were seen from early to late pregnancy. Serum C3, IL-17A, IL-6, TNF-α, CD163, GDF-15 and leptin increased throughout gestation. First pregnancy was associated with higher levels of leptin in late pregnancy, while parous women showed significant decreases in PBMC derived TNF-α, IL10, and IFN-γ with gestation. Differences in levels of C3, IL-17A, TNF-α, GDF-15 and leptin were observed across BMI groups. Overall, serum-derived cytokines exhibit contrasting levels to those derived from stimulated PBMCs. Maternal immune responses undergo significant changes from early to late pregnancy, which are influenced by parity and BMI. These differences aid our understanding as to why first-time mothers are at greater risk of placental disease such as pre-eclampsia and fetal growth restriction.

Abstract The demand for open data and open science is on the rise, fueled by expectations from the scientific community, calls to increase transparency and reproducibility in research findings, and developments such as the Final Data Management and Sharing Policy from the U.S. National Institutes of Health and a memorandum on increasing public access to federally funded research, issued by the U.S. Office of Science and Technology Policy. This paper explores the pivotal role of data repositories in biomedical research and open science, emphasizing their importance in managing, preserving, and sharing research data. Our objective is to familiarize readers with the functions of data repositories, set expectations for their services, and provide an overview of methods to evaluate their capabilities. The paper serves to introduce fundamental concepts and community-based guiding principles and aims to equip researchers, repository operators, funders, and policymakers with the knowledge to select appropriate repositories for their data management and sharing needs and foster a foundation for the open sharing and preservation of research data.

Background Primary cam morphology, an acquired bony prominence at the head-neck junction of the femur, is highly prevalent in athlete populations, and causally associated with femoroacetabular impingement syndrome and early hip osteoarthritis. Experts agreed on key elements for primary cam morphology and a prioritised research agenda for the field. This research agenda will require higher-quality research to achieve meaningful progress on the aetiology, prognosis and treatment of primary cam morphology in athletes. Aim To explore stakeholders’ perspectives of high-quality research in the research field of primary cam morphology and its natural history. Methods Grounded in interpretive description, we used semi-structured interviews to explore stakeholders’ perspectives of high-quality research in the primary cam morphology research field. The framework for INcreasing QUality In patient-orientated academic clinical REsearch (INQUIRE) informed the interview guide. Audio-recorded interviews were transcribed and analysed using thematic analysis. We recruited a heterogenous and purposive maximum variation sample, drawing from a network of research contacts. Results Fifteen individuals, several with multiple perspectives on research quality in the field, participated. Exploring stakeholders’ perspectives on research quality through an established research quality framework (INQUIRE) illuminated areas for immediate action for research communities in the field of primary cam morphology and its natural history. We crafted five action inviting themes: research communities should: partner with athletes/patients; champion equity, diversity and inclusion; collaborate with one another; pursue open science; and nurture young scholars. Conclusion The findings of this study could inform concrete actions by research communities to pursue higher quality research—more research value and less waste—in the field of primary cam morphology and its natural history. Although the five action-inviting themes reflect contemporary trends in research, and could therefore be transferable to other areas of research, their practical application remains context- and field-specific.

ABSTRACT The vaginal microbiome is a key player in the etiology of spontaneous preterm birth. This study aimed to illustrate maternal environmental factors associated with vaginal microbiota composition and function in pregnancy. Women in healthy pregnancy had vaginal microbial sampling from the posterior vaginal fornix performed at 16 weeks gestation. After shotgun metagenomic sequencing, heatmaps of relative abundance data were generated. Community state type (CST) was assigned, and alpha diversity was calculated. Demography, obstetric history, well-being, exercise, and diet using food frequency questionnaires were collected and compared against microbial parameters. A total of 119 pregnant participants had vaginal metagenomic sequencing performed. Factors with strongest association with beta diversity were dietary lysine (adj-R2 0.113, P = 0.002), valine (adj-R2 0.096, P = 0.004), leucine (adj-R2 0.086, P = 0.003), and phenylalanine (adj-R2 0.085, P = 0.005, Fig. 2D). Previous vaginal delivery and breastfeeding were associated with vaginal beta diversity (adj-R2 0.048, P = 0.003; adj-R2 0.045, P = 0.004), accounting for 8.5% of taxonomy variation on redundancy analysis. Dietary fat, starch, and maltose were positively correlated with alpha diversity (fat +0.002 SD/g, P = 0.025; starch +0.002 SD/g, P = 0.043; maltose +0.440 SD/g, P = 0.013), particularly in secretor-positive women. Functional signature was associated with CST, maternal smoking, and dietary phenylalanine, accounting for 8.9%–11% of the variation in vaginal microbiome functional signature. Dietary amino acids, previous vaginal delivery, and breastfeeding history were associated with vaginal beta diversity. Functional signature of the vaginal microbiome differed with community state type, smoking, dietary phenylalanine, and vitamin K. Increased alpha diversity correlated with dietary fat and starch. These data provide a novel snapshot into the associations between maternal environment, nutrition, and the vaginal microbiome.IMPORTANCEThis secondary analysis of the MicrobeMom randomized controlled trial reveals that dietary amino acids, macronutrients, previous vaginal birth, and breastfeeding have the strongest associations with vaginal taxonomy in early pregnancy. Function of the vaginal niche is associated mainly by species composition, but smoking, vitamin K, and phenylalanine also play a role. These associations provide an intriguing and novel insight into the association between host factors and diet on the vaginal microbiome in pregnancy and highlight the need for further investigation into the complex interactions between the diet, human gut, and vaginal microbiome.

Background Melanoma antigen gene (MAGE)-type antigens are promising targets for cancer immunotherapy as they are expressed in cancer cells but not in normal tissues, except for male germline cells. The mouse P1A antigen shares this MAGE-type expression pattern and has been used as a target antigen in preclinical tumor models aiming to induce antitumor CD8+ T-cell responses. However, so far only one MHC I-restricted P1A epitope has been identified. It is presented by H-2Ld in mice of the H-2d genetic background such as DBA/2 and BALB/c. Given the availability of multiple genetically altered strains of mice in the C57BL/6 background, it would be useful to define P1A T-cell epitopes presented by the H-2b haplotype, to facilitate more refined mechanistic studies.Methods We employed a heterologous prime-boost vaccination strategy based on a chimpanzee adenovirus (ChAdOx1) and a modified vaccinia Ankara (MVA) encoding P1A, to induce P1A-specific T-cell responses in C57BL/6 mice. Vaccine-induced responses were measured by intracellular cytokine staining and multiparameter flow cytometry. We mapped the immunogenic CD8 epitope and cloned the cognate T-cell receptor (TCR), which we used for adoptive cell therapy.Results ChAdOx1/MVA-P1A vaccination induces a strong P1A-specific CD8+ T-cell response in C57BL/6 mice. This response is directed against a single 9-amino acid peptide with sequence FAVVTTSFL, corresponding to P1A amino acids 43–51. It is presented by H-2Db. P1A vaccination, especially with ChAdOx1 administered intramuscularly and MVA delivered intravenously, protected mice against P1A-expressing EL4 (EL4.P1A) tumor cell challenge. We identified and cloned four TCRs that are specific for the H-2Db-restricted P1A43-51 peptide. T cells transduced with these TCRs recognized EL4.P1A but not MC38.P1A and B16F10.P1A tumor cells, likely due to differences in the proteasome subtypes present in these cells. Adoptive transfer of these T cells in mice bearing EL4.P1A tumors reduced tumor growth and increased survival.Conclusions We identified the first CD8+ T-cell epitope of the MAGE-type P1A tumor antigen presented in the H-2b background. This opens new perspectives for mechanistic studies dissecting MAGE-type specific antitumor immunity, making use of the wealth of genetically altered mouse strains available in the C57BL/6 background. This should facilitate the advancement of specific cancer immunotherapies.

Context: Providing high-quality care to older people living in long-term care homes requires consideration of their cultural backgrounds and spiritual beliefs. Objective: To ascertain the views of key informants from Australian culturally and linguistically diverse (CALD), Aboriginal and Torres Strait Islander (ATSI), and spiritual care organisations about providing high-quality cultural and spiritual care in long-term care homes. Method: Semi-structured interviews were undertaken with seven representatives of these Australian organisations. Interview transcripts were thematically analysed. Findings: The importance of cultural and spiritual care to older people living in long-term care was acknowledged. However, it was noted that this care for older people from diverse CALD, ATSI, and spiritual backgrounds was often absent due to staff ignorance, lack of awareness, and assumptions. Staff need further education to provide culturally and spiritually appropriate care; long-term care homes need to incorporate an organizational approach to providing culturally and spirituality appropriate care; and staff should be encouraged to consult experts in cultural and spiritual care when the care they provide is insufficient. Cultural and spiritual care champions may be an appropriate way of disseminating knowledge and establishing a culturally and spiritually aware workforce. Limitations: The small number of existing Australian cultural and spiritual care organisations, and the smaller number of representatives within these organisations who have experience with older people living in long-term care homes, limited the number of eligible participants. Implications for practice • Long-term care homes must invest in comprehensive education to better equip staff to provide high-quality cultural and spiritual care to older people. • Education should assist staff in identifying the range of life areas to which culture and spiritual care have relevance and how to apply appropriate knowledge. Staff should be aware of the available guidelines about culturally and spiritually informed care; and recognise when to consult experts. • Workplace champions can provide and encourage an ethos where culture and spirituality are considered in everyday care.

A Twinning Induced Plasticity (TWIP) steel with a nominal composition of Fe-16.4Mn-0.9C-0.5Si-0.05Nb-0.05V was deformed to an engineering strain of 6%. The strain around the deformation twins were mapped using the 4D-STEM technique. Strain mapping showed a large average elastic strain of approximately 6% in the directions parallel and perpendicular to the twinning direction. However, the large average strain comprised of several hot spots of even larger strains of up to 12%. These hot spots could be attributed to a high density of sessile Frank dislocations on the twin boundary and correspond to shear stresses of 1–1.5 GPa. The strain and therefore stress fields are significantly larger than other materials known to twin and are speculated to be responsible for the early thickness saturation of TWIP steel nanotwins. The ability to keep twins extremely thin helps improve grain fragmentation, i.e. the dynamic Hall–Petch effect, and underpins the large elongations and strain hardening rates in TWIP steels.