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The structural virtuosity of carbohydrates forms the basis of a molecular recognition language that is ubiquitous in immunomodulatory processes. This diversity generates the complexity required to accommodate the bandwidth of information generated by immune interactions: it logically follows that this capacity underpins the evolutionary success of oligosaccharide permutations in this endeavour. Placing glycan function on a structural level is therefore a core research endeavour in understanding the non-covalent interactions that elicit an immune response and, by extension, leveraging these data to identify and validate new vaccine leads. Innovations to expedite the construction of well-defined, immuno-relevant carbohydrates has revolutionized the field, and focused attention on further structural refinements that are new to biology. Echoing the success of site-selective fluorination in pharmaceutical design, the precision introduction of C(sp3)-F bonds to tailor the physicochemical properties of key targets is an exciting new frontier in targeted immunology. In this short Perspective, the key milestones in the design and validation of carbohydrate-based vaccine leads are discussed through the lense of fluorination.

The Publisher regrets that this article is an accidental duplication of an article that has already been published in Endeavour 50 (2026) 101049, http://dx.doi.org/10.1016/j.endeavour.2026.101049. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.

Campylorrhinus lateralis ('wry nose') is a rare congenital maxillofacial deformity of foals resulting in compromise of the airway and severe class 4 malocclusion. Various surgical techniques to correct the deformity have been described, but contemporary data on single-stage transection and fixation, including use of a rib graft, and long-term functional and cosmetic outcomes remain underreported. To describe the transection-and-fixation technique and perioperative management used to correct wry nose in horses, and to report postoperative complications and long-term outcomes of horses undergoing this treatment. Retrospective case series. Wry nose of four horses was corrected by using a single-stage transection-and-fixation technique. Pre-operative assessment included physical, oral, and radiographic examinations, and when available, CT imaging. The surgical procedure involved temporary tracheostomy and laryngotomy, resection of the nasal septum, osteotomy and fixation of the nasal bones, and orthognathic transection and fixation of the premaxillae and maxillae, with bone grafting and alar fold resection performed when indicated. The outcome of horses with complete records and ≥12 months follow-up is reported using descriptive statistics. All four horses were presented with respiratory difficulty. The transected premaxillae were stabilised with pins and wires, and the transected nasal bones were stabilised with plates/screws; only one horse received a rib graft. All horses developed a plate-associated infection, and one horse developed an oronasal fistula. At the time of follow-up, all grazed and masticated normally, maintained good body condition, and owners were satisfied with the functional and cosmetic outcome. Small sample size, retrospective design. Correcting wry nose of four foals using a single-stage transection-and-fixation procedure achieved satisfactory long-term outcomes. Respiratory function of all horses improved, and all horses grazed and masticated normally. Three horses were able to perform their intended athletic endeavour. All owners reported satisfaction with the functional and cosmetic outcome.

Child development is cultural in nature, yet a divide persists between a (cross-)cultural developmental science niche alongside a seemingly a-cultural mainstream. In particular, childhood research relying on convenience sampling in often Western, post-industrial (i.e., WEIRD) societies rarely ventures into issues of culture and context, promoting excessive overgeneralization and false assumptions of what is considered 'typical' in child development. This article has two aims: First, it illustrates the cultural make-up of the communities traditionally overrepresented yet often unmarked in developmental science, while highlighting important variations within this cluster. Second, it demonstrates how this cultural make-up, in turn, is key to the methods employed, the findings produced and the theories postulated in developmental science. Regardless of where it is conducted, developmental science is a cultural endeavour and thus needs to grapple with its cultural foundations.

Mix networks play a vital role in enhancing security and privacy within the communication channel. Mix networks are anonymous communication channels that provide a practical solution to the traffic analysis problem. This manuscript presents an algorithm for a mix network consisting of five nodes. The algorithm employs the Elliptic Curve Integrated Encryption Scheme (ECIES) algorithm for both encryption and decryption processes while utilizing XOR shuffling to permute the messages. The algorithm effectively manages the data flow, encompassing encryption, decryption, and shuffling operations, while also calculating the load factors for each node. By conducting MATLAB simulations, we assess the flow of data within the mix network, considering the encryption, decryption, and XOR shuffling operations at each node. The integration of ECIES encryption and XOR shuffling within the algorithm exemplifies its effectiveness in ensuring secure and anonymous communication over untrusted networks. This research conducted a comparative analysis of load factor percentages across various key sizes, revealing nuanced efficiency differences among nodes. One of the outcomes of the research was that we were able to identify the optimal key among the five different keys supported by the ECIES algorithm. For all system tests, the 224 bits key demonstrated optimal security with reasonable performance. Our results show that the ECIES 224 bits key works well for building a scalable and efficient Mix Network. The research endeavour contributes significantly to the advancement of secure communication protocols, providing a fundamental framework for the implementation and analysis of mix networks.

The human microbiota comprises a diverse and extensive community of microorganisms that participate in intricate interactions with the host, several of which are increasingly acknowledged as key modulators of health and disease. Among these, Fusobacterium nucleatum (Fn), an oral commensal bacterium, has emerged as a significant oncobacterium implicated in tumour progression. The Fn genus comprises distinct subspecies, clades and strains, exhibiting marked phylogenetic and physiological heterogeneity. Consequently, pinpointing the true functional modulators within this complex community and elucidating their mechanisms in various physio-pathological states remains a critical yet challenging endeavour. Moreover, the complete mechanism underlying Fn's function across different spatial locations and physiological states remains to be fully elucidated. This review details the genetic and phenotypic heterogeneity among Fn subspecies, which underlies their differential characteristics and niche adaptation. We further delineate key effectors of Fn, such as adhesins, metabolites and exoproteins, which collectively facilitate host cell invasion, immune evasion and chemoresistance induction. We explore the translational potential of Fn, underscoring its utility as a diagnostic biomarker and a promising target for novel therapeutic strategies.

With alarming demographic and workforce developments in healthcare systems globally, digital health innovations are often heralded as solutions. Despite promises, empirical work points towards the complexity of such endeavours. Various sources of fragmentation complicate scaling up local initiatives and collaborations between different care institutions. In this paper we take fragmentation as ontological reality and conceptual starting point. Mobilizing literature on sociotechnical infrastructures and alignment work, we follow how a hospital-based innovations programme developed a digital care infrastructure in a major urbanized region. Combining these theoretical notions allows us to trace how digital infrastructure is 'done' in practice and continuously 'under construction'. Drawing on longitudinal ethnographic methods (observations, interviews and document analysis) conducted over an extensive period of time (17 months), we examine how various actors involved in a digital innovations programme try to build a digital infrastructure in a healthcare system characterised by fragmentation. We focus on how actors within the programme attempt to align social, technical, organisational and professional elements within the fragmented context. Our approach allowed us to identify five types of alignment work: narrative, internal, organisational, regional, and technical alignment work, and address emerging tensions and interactions between them. We argue that by using this more granular and comprehensive typology, and through conceptualizing infrastructures as moving targets, we can better appreciate the complexity and variety of alignment activities that support 'the' digital transformation in healthcare.

Developing a universal representation space for cells that encompasses the tremendous molecular diversity of cell types across species would be transformative for cell biology. Recent work using single-cell transcriptomic approaches to create molecular definitions of cell types in the form of cell atlases has provided the necessary data for such an endeavour1-3. Here we present the universal cell embedding (UCE) foundation model. UCE was trained on a large corpus of cell data using self-supervision, creating a unified biological latent space that can represent cells across diverse tissues and species. This latent space captures important biological variation despite the presence of experimental noise. UCE's universality means that new cells can be embedded with no data labelling, model training or fine-tuning. We used UCE to create the Integrated Mega-scale Atlas, embedding 36 million cells, with more than 1,000 uniquely named cell types, from hundreds of experiments, dozens of tissues and eight species. We gain insights into the organization of cell types and tissues within the space. UCE's embedding space exhibits emergent behaviour, identifying biology that it was never trained for, such as identifying developmental lineages and embedding data from species that were not included in the training set. Overall, by enabling a universal representation for every cell state and type, UCE is a valuable tool for analysis, annotation and hypothesis generation over single-cell data.

Child marriage remains a pressing social and public health issue globally, with significant implications for the rights, well-being and development of affected individuals. In Iran, legal frameworks that permit marriage from as young as 9 lunar years for girls-despite countervailing influences such as rising education levels and social reforms-have failed to curb the persistence of early marriage, which continues to be driven by entrenched cultural, socioeconomic and legal factors. Understanding the multifaceted nature of child marriage within this context is crucial for developing effective interventions and policies. Existing research predominantly focuses on quantitative assessments, leaving qualitative insights underexplored. The aim of this protocol is to address the existing gap by undertaking a scoping review and meta-synthesis of qualitative evidence concerning child marriage in Iran. This study seeks to provide an in-depth understanding of the underlying determinants, lived experiences and associated consequences of child marriage with the aim of informing future research endeavours and guiding policy development. This scoping review protocol will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and the methodological framework proposed by Arksey and O'Malley, incorporating recent methodological advancements. Selection criteria will be established through the Population, Concept and Context framework, targeting qualitative studies addressing child marriage within Iran. To ensure comprehensive coverage, an inclusive search will be conducted across diverse databases, including PubMed, Scopus, Web of Science, Scientific Information Database (SID), MagIran and the Barakat Knowledge Network System (BKNS), without any restriction on publication date, extending up to the search date. Both Persian and English language sources will be reviewed. Two independent reviewers will undertake the screening of titles, abstracts and full texts, resolving conflicting decisions through consensus or third-party arbitration. The methodological integrity of eligible studies will be assessed using the Joanna Briggs Institute critical appraisal checklist for qualitative research. Data will be synthesised through content analysis methods. Confidence in the integrated findings will be evaluated employing the GRADE-CERQual approach to enhance the trustworthiness and applicability of the review outcomes. The Research Ethics Committee of Tabriz University of edical Sciences approved this proposed scoping review and meta-synthesis, confrming ethical compliance absent patient involvement. Results from this investigation will be shared through peer-reviewed journal articles and presentations at relevant academic conferences locally and internationally. Furthermore, the synthesised insights into the phenomenon of child marriage in Iran are intended to inform scholars, policymakers and practitioners, supporting evidence-based strategies and policies to mitigate the issue and promote social change.

To date, the genus Isotopenola Potapov, Babenko, Fjellberg & Greenslade comprises only five known species. In the present paper, two new species, i.e., Isotopenolachownisp. nov. and Isotopenolahallasae sp. nov., are described from Endeavour Hills, Melbourne, Australia. Isotopenolachownisp. nov. has a markedly large and variable number of tergal sensilla. It is similar to Isotopenola loftyensis (Womersley), but can be distinguished from the latter mainly by having equal sized ocelli and less chaetae on Ant. I and tibiotarsi. Isotopenolahallasae sp. nov. has a moderate number of tergal sensilla. It is similar to I. perterrens Greenslade & Potapov, but can be distinguished from the latter mainly by having less chaetae on Ant. I, tibiotarsi, and dens. A key to all species of Isotopenola is provided.

To understand (1) how collaborative governance for creative health is being enacted in different health and social care systems across the UK and (2) why collaborative governance for creative health was needed in these systems and the factors that enable it to be effective. Qualitative interviews with creative health stakeholders within UK health and social care systems (n = 16) to develop realist-informed initial programme theories (IPTs) about the purpose and efficacy of creative health collaborative governance approaches. Collaborative governance describes arrangements where one or more public agencies and non-state stakeholders engage in collective decision-making through formal, consensus-oriented and deliberative processes. We identified eight IPTs in relation to collaborative governance for creative health. Two of these IPTs relate to why collaborative governance is needed and are associated with the need to secure buy-in from senior stakeholders within the health and social care system to secure access to the resources needed for creative health provision to be sustainable. The remaining six IPTs cover how participants in the creative governance initiatives suggest it could be effective. These include mechanisms such as building trust between key actors and institutions, providing opportunities to develop the creative health workforce, gathering and disseminating evidence about the efficacy of creative health, being responsive to lived experience perspectives, having clearly defined lines of accountability and ensuring alignment with and between key policies and strategies. Collaborative endeavours for creative health should focus on relationships, trust building and accountability mechanisms first and foremost. These will provide a platform for further collaborative activities with a focus on sustainability, workforce development, evidence, lived experience and alignment with key policies and strategies. Collaborative priorities should be based on an appreciation of local strengths and gaps and recognise that 'what works' in one area is not guaranteed to work in another. What factors support cross-sector collaborations in creative health?Creative health is a term used to describe creative approaches and activities which have benefits for health and wellbeing. We undertook qualitative research with people from different sectors and working in a range of roles related to creative health in the UK to understand what factors support effective cross-sector collaboration. Key factors included the need to secure buy-in from senior leaders; funding and financial resources; building trust and accountability; support for the creative workforce; evidence about the effectiveness of creative approaches; meaningfully involvement of creative participants; and having good alignment with key policies and strategies. However, it is important not to take a one-size-fits-all approach and make decisions based on what matters to people locally.

Emotions are of utmost relevance for everyday life and the development and maintenance of psychological disorders. Emotion theories mainly describe emotions as generalisable experiences, whereas differences in individual affective dynamics are less researched. Therefore, we endeavoured developing a tool to assess individual mental representations of emotions, aiming for a rich, yet replicable informational structure. We compared three methods: (1) A Multi-Arrangement Task (MAT), (2) Pairwise Comparisons (PC), and (3) Self-Assessment Manikin (SAM) rating scales. Using a within-subjects design (N = 103), emotional adjectives were arranged or rated on a computer monitor with subsequent calculation of a dissimilarity matrix of each item's emotional impact. These matrices showed good test-retest reliabilities for each method, while clear differences emerged in the exploratory analyses. Dimensionality analyses using multidimensional scaling showed two, respectively three, dimensions yielding an ideal solution to represent the data in the SAM, with some participants using up to five dimensions in the MAT. Quantifying the affective spaces as polygons revealed the highest correlation of surface areas in the MAT, indicating that MAT might be particularly useful when focusing on emotion differentiation. By developing an instrument measuring the individual affective space, we propose applying the personalised medicine approach to emotions and, eventually, transferring the results to psychiatry and psychotherapy for better treatments.

In the study of children's thinking, the research process includes not just the visible steps of study design, data collection, data analyses and write-up but also hidden yet crucial steps that have consequences throughout the workflow process. These steps include informal observations, pilot testing, decisions about inclusion and exclusion criteria and decisions about how to communicate the results. In this article, we critically evaluate the benefits and challenges of these often invisible steps, provide suggestions for determining how best to avoid potential pitfalls and encourage researchers to more transparently communicate decisions that often fall outside traditional method sections. Although we situate this discussion within the context of our specific field of inquiry, we believe that the lessons apply across a range of research endeavours. We end by suggesting that a critical look at this aspect of workflow may provide insights into some of the resistance to methodological reforms in the social sciences. This article is part of the theme issue 'Statistical workflow'.

Finding new therapeutic applications of known natural products remains a continuous endeavour in drug discovery. In this work, we report a strain of Streptomyces sp. PS-15, isolated from the soil of the Qinghai-Tibet Plateau. This strain produces berninamycin C as its main metabolite, which demonstrated potent antibacterial activity against Gram-positive bacteria, particularly Bacillus subtilis and Corynebacterium glutamicum, with an MIC <1.25&#x2009;&#xb5;M. Furthermore, both berninamycin C and D were found to significantly reduce the secretion of multiple inflammatory factors in RAW264.7 and A549 cells. Especially, berninamycin C and D at 25&#x2009;&#xb5;M showed 68.24% and 71.08% inhibition of inflammatory signalling in RAW264.7 cells. Both compounds exhibited low cytotoxicity in all tested cell lines, with IC50 more than 200&#x2009;&#xb5;M. These findings highlight the potential of berninamycins as promising candidates for the development of novel anti-inflammatory therapeutics.

The human body hosts an intricate array of microbial communities, outnumbering eukaryotic cells. Delving into the nuanced interplay between the microbiota and human cells is essential for comprehending health homeostasis and disease progression. Notably, the microbiota's influence commences even before birth, sculpting immune responses and delineating susceptibility to chronic diseases in later stages of life. Throughout the course of human life, variations in microbial composition have been observed to correlate with a wide range of pathologies, prompting the development of pioneering treatments aimed at reinstating a healthier microbial balance. Within this narrative review, we expound upon the fundamental role of the microbiota in the continuum of health and disease. Our endeavour is to contribute to a nuanced comprehension of diseases and the development of targeted interventions for their judicious management.

Despite the availability of various advanced treatments for inflammatory bowel disease (IBD), it has been impossible to predict which therapy would offer the best response to the patient. The aim of this systematic review is to explore current and novel biomarkers for predicting and assessing therapeutic response to advanced therapies presently in clinical use in IBD. A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO ID: CRD42024559652). A systematic literature search for all primary research looking at biomarkers in predicting response to advanced therapy in Crohn's disease (CD) or ulcerative colitis (UC) was conducted across MEDLINE, EMBASE and PubMed databases. Abstracts, case studies, commentary papers and review articles were excluded. Fifty-five studies were included in this review investigating baseline predictors of response to anti-tumour necrosis factor, ustekinumab, vedolizumab and ozanimod therapies in both CD and UC. The various biomarkers studied included blood, serum, faecal, histological, nutrient, genetic and pharmacokinetic markers. C-reactive protein and faecal calprotectin were among the most commonly studied biomarkers; however, there were inconsistencies with regard to optimum cutoff values used and hence their roles as baseline predictors of response to advanced therapies are yet unclear. None of the biomarker studies to date has yet transitioned to clinical use. Biomarker identification to predict therapeutic response persists to be an ongoing challenge. Further work through large well-designed prospective cohort studies is needed to further refine the clinical utility of these tools. The protocol was prospectively registered with the PROSPERO database (CRD42024559652). Current and future predictors of response to advanced medical therapy in inflammatory bowel disease Inflammatory Bowel Disease (IBD) is a long term disease that usually requires prolonged medical therapy. Currently, there are multiple classes of drugs available for use, many of which are expensive. However, it has not been possible to predict which patient would benefit from which drug. Biomarkers are tests which would help in this endeavour. Till date, the most commonly used biomarkers are tests such as CRP and stool calprotectin. However, this review goes onto describe the limitations in the evidence to their use. This article goes on to look at other novel tests which would help predict response to various advanced treatment in IBD such as anti-TNF, vedolizumab, ustekinumab or ozanimod. These include tests on blood, serum, stool and others. Some of the larger studies even looked at genetic predictors for this. However, none of these tests have yet been accepted in standard medical practice because of the lack of good quality evidence. Well designed studies would help answer this perennial question.

This study was an endeavour to investigate how self-regulated learning (SRL) and perfectionism play a part in predicting the levels of listening anxiety among foreign language learners. A sample of 350 English as a Foreign Language (EFL) students was chosen using cluster random sampling to fill out three well-established questionnaires related to the study topics (i.e., SRL, perfectionism, and listening anxiety). The data was analysed using a structural equation modelling (SEM) approach. Based on the findings, a significant linear relationship was found among variables and their components. The findings revealed that both SRL and perfectionism played a role in increasing listening anxiety, with perfectionism emerging as the more dominant factor. SRL followed closely behind in terms of predicting listening anxiety. In simpler terms, students who aim for perfection are more likely to experience heightened anxiety during listening tasks. Moreover, individuals who possess strong self-regulation skills typically encounter lower levels of anxiety during listening activities, in contrast to those who have difficulties in managing themselves, leading to heightened feelings of anxiety. This study suggests that developers of learning materials and EFL teachers should consider both emotional and cognitive factors when addressing listening anxiety among learners.