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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 The duplicate article has therefore been withdrawn.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.

We have seen more progress in computational biology for macromolecules in the last five years than we experienced in the five preceding decades. Thus, it is very challenging to forecast future progress. It is possible that we have reached a plateau, and we will be stuck with similar problems as we have today. Still, it is also possible that the field will continue its rapid progress and completely transform other fields, such as biochemistry, molecular and cell biology, and medicine. It is also possible that general AI will take over, and all scientific endeavours will be conducted without human input. To be honest, we do not know what will happen, but we will highlight a few of the challenges and the most critical research questions that we face today. Hopefully, these will be resolved within the following decades, or hopefully much earlier. Looking back over the last decade, we can see that machine learning and deep learning have become significantly more popular (T-test residual > 2) among the papers published within our section of PlosCB. We do believe that this trend will continue; therefore, we focus on the challenges that must be overcome for it to make significant and notable contributions. The future of computational biology for macromolecules in 20 years is likely to be characterised by transformative advances in accuracy, automation, integration, and explainability, with AI playing a role in one form or another.

Family members play an important role in supporting their loved ones with first episode psychosis (FEP), but few have access to interventions demonstrated to support them in this endeavour. Psychosis REACH (Recovery by Enabling Adult Carers at Home; p-REACH) is a family intervention for psychosis (FIp), delivered directly to families by clinicians and peers, that provides both psychoeducation and Cognitive Behavioural Therapy for psychosis (CBT-p) informed skills to family carers. This study aimed to qualitatively explore family participants' experiences of receiving the p-REACH intervention and assess its feasibility and acceptability within an early psychosis service. Following the p-REACH intervention, all participants were invited to partake in qualitative interviews and analysed using a Reflexive Thematic Analysis approach. Family carers reported positive experiences with the intervention. Key themes indicated that it helped build (1) internal resources, as participants valued increasing their knowledge and understanding of psychosis and learning skills to support themselves and their loved ones-leading to greater confidence and (2) external resources, as the group-based, peer-supported format enhanced their sense of connection with their loved ones and with other families. This study demonstrates that the intervention was both feasible and acceptable to participants in an early psychosis setting. It contributes to the growing body of evidence supporting the positive impact of family interventions in psychosis, specifically the teaching of CBTp skills to caregivers of those with early psychosis.

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.

We aim to explore the support needs of individuals living with type 2 diabetes and disordered eating behaviours. We conducted semistructured interviews with adult participants living with type 2 diabetes and self-identified disordered eating behaviours recruited from an Australian allied health service. Data were analysed through reflective thematic analysis. Ten adults with type 2 diabetes (seven female, three male; mean age 66.3 ± 8.97, range: 52-80) were interviewed. Four themes are presented related to participants' support needs: (1) the need for increased information about the interactions between food, eating behaviours and diabetes and self-management; (2) a desire for increased time with knowledgeable health professionals who provide tailored person-centred diabetes care and support; (3) mental health services integrated into diabetes care are desired due to relationships between mental health, disordered eating behaviours and diabetes management; and (4) family, peers and community can offer invaluable support, but stigma can be a barrier to support seeking. Individuals living with T2DM and disordered eating behaviours report diverse support needs including tailored informational support and emotional support from health professionals, family and peers. Although further research is required to develop and evaluate the implementation of specific interventions and care pathways, health professionals should endeavour to provide adequate time and resources for personalised education, and to promote and facilitate appropriate mental health and peer supports.

Historically, young people with genetic heart diseases were discouraged from active sport due to concerns about the increased risk of sudden cardiac death during competitive or intensive exercise. The shock resulting from the sudden death of a young athlete, an event often highly publicised, tends to generate concern in the general population, and fear of litigation in a low-evidence area: both influence decision-making by the medical profession when discussing 'restrictions', especially in patients with genetic heart diseases, who by definition, are at increased risk of sudden cardiac death. In recent years, however, we have moved to a point where many athletes with certain genetic heart diseases can, with optimal medical therapy, be considered for involvement in various sporting and athletic pursuits. We are cautiously moving away from the assumption that exercise is contraindicated; we are factoring in the wishes of the patient-athlete (shared decision-making), and we are encouraging optimal protection for these athletes during their sporting endeavours (easily available automated external defibrillators [AEDs], and club personnel trained in basic life support [BLS]), while ensuring regular medical assessment to identify alterations in risk status. With dedicated follow-up of all such patient-athletes, we can refine our understanding of how best to advise (and protect) them in terms of exercise for enhanced quality of life.

Motor learning underlies our ability to acquire and perfect movements across all domains of human behaviour. Its study encompasses two distinct but related endeavours: basic research on how we learn movement skills and applied research on how to enhance skill acquisition in real-world contexts. Despite their natural complementarity, these approaches developed historically in two largely independent communities with different disciplinary roots. One is closely associated with computational neuroscience and focuses predominantly on basic research. The other comes from experimental psychology and movement sciences with a stronger focus on applied research. The division between these communities is reflected in the experimental tasks they use, the theoretical frameworks they develop and the cultural norms that shape their training and communication. In this Perspective, we scrutinize this divide, review emerging efforts towards better integration and identify future opportunities. We contend that bridging these gaps can build a more comprehensive science of motor learning.

This qualitative inquiry aimed to explore the lived experiences of pregnant women with self-management of type 1 diabetes (T1D) using closed-loop insulin delivery in the CIRCUIT trial9 to provide a qualitative overview of its impacts and improve the understanding of T1D experiences in pregnancy. We used semi-structured, individual interviews with 18 CIRCUIT randomized trial participants. Two team members analysed verbatim transcripts using inductive thematic analysis. Four major themes emerged: 1. Independence and isolation; 2. Support is key; 3. Closed-loop impacts; and 4. Control and autonomy. Diabetes management during pregnancy was an emotionally overwhelming experience that was managed largely independently. Closed-loop was noted as a gamechanger for diabetes management during and after pregnancy. Participants felt the transition to and use of this technology would not have been possible without their healthcare team's support. Permeating all themes was the importance of control to achieve the best possible glycaemic outcomes for the health of their babies and autonomy over personal treatment decisions. The perceptions of loss of personal autonomy were associated with high anxiety. Managing T1D while pregnant is an independent and isolating endeavour, due to the 'invisible labour' involved and the lack of knowledge about T1D management in personal networks. Support from partners and care providers alleviated stress. Experiences with intrapartum care providers who had limited T1D understanding were perceived as a challenge by some for maintaining autonomy. The closed-loop system was seen as a 'gamechanger' in T1D pregnancy management, with unanimous perception of positive impacts that far outweigh any challenges. Use of this closed-loop system has potential to vastly improve pregnancy experiences among those with T1D.

Cross-disciplinary endeavours are well recognized to be incubators and propellors for frontier advancements. Established scientific fields often emerge out of commonality of research interests, and the need to consolidate knowledge through interactive exchanges within a commonly identified arena. Counter-intuitively, there is a rapid paradigm shift for mining new knowledge through the willingness of crossing established fields. Paradoxically, when seemingly irrelevant chemistry fields are knitted together through their commonality in bond-forming chemical phenomena, fresh new ideas to tackle long-standing challenges emerge along the boundary lines. In this perspective dedicated to the Advanced Science 2025 Young Innovator Award, I will narrate my research group and my personal exciting journey in the discovery of knowledge at the intersection of numerous fields of catalysis, carbohydrate chemistry, and supramolecular chemistry/non-covalent interactions. By sharing our laboratory's story in the discovery of the σ-hole based catalytic glycosylation strategy, we hope this rewarding experience will provide the sparks for younger researchers to innovate beyond field-specific paradigms. As researchers return to curiosity, inquisitiveness, and the pure enjoyment for chemistry, I believe that the assimilation of an interdisciplinary research paradigm into catalytic carbohydrate synthesis will serve as an impetus for the discovery of novel chemical phenomena throughout the chemical sciences.

Conference of the Parties 30, the 2025 annual United Nations Framework Convention on Climate Change conference, took place in Belém, Brazil, located right on the edge of the Amazon forest. It was championed by Brazilian authorities as a symbolic centring of the Global South. Nonetheless, as previous studies in this series have shown, long-haul air travel often dominates total emissions, and this was the case for COP30. However, Belém presented a new logistical challenge. Both its location and general lack of adequate accommodation prompted the authorities to charter two large cruise ships to house thousands of delegates over the two weeks of the conference. The expected operational emission from such ships makes them several times more carbon-intensive than standard hotels. Yet the challenge was compounded by the affordability problem for delegates from the Global South, while the complete lack of affordable and accessible accommodation for civil society organisations directly contradicted the symbolic inclusion echoed by the organisers. This paper reports on travel emissions to Belém, highlights the paradox of housing delegates on carbon-intensive cruise ships, as well as the contradictions of not catering to civil society organisations in a supposedly inclusive COP. This paper concludes with a recommendation that subsequent conferences should endeavour to also account for accommodation emissions from participants.

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.

In October 2024, an Expert Meeting hosted by the United States National Academies of Sciences, Engineering, and Medicine (NASEM) took place in Washington, D.C. (USA). The participating experts discussed ideas for advancing the integration of functioning in rehabilitation practice and research by focusing on International Classification of Functioning, Disability and Health (ICF)-based data collection tools with particular emphasis on the International Society of Physical and Rehabilitation Medicine's universal clinical functioning information tool (ClinFIT). This paper shares key insights revealed in these discussions: Implementing practical, patient-centric data collection tools strengthens rehabilitation; scientifically robust research is essential to provide evidence on the utility of ICF-based tools in clinical practice and the implementation of ClinFIT in clinical routine; and concrete solutions are needed to enable clinicians to adopt new assessment tools in practice are needed. To support this endeavour, this paper calls on physical and rehabilitation medicine (PRM) physicians worldwide to explore ClinFIT and integrate it in clinical practice and research.

Across practice and policy, assistive technologies (ATs) are positioned as a pathway to economic inclusion for graduates with sensory disabilities in South Africa. Still, systemic barriers persist. Developing workable interventions requires in-depth attention to the lived experiences of graduates, which include knowledge on the way devices, systems and attitudes interact in everyday employment seeking and enterprise activities. The study endeavoured to examine how unemployed tertiary-level graduates with sensory disabilities in Gauteng use AT in seeking employment and practising entrepreneurship. Specific enablers and challenges were identified to provide an explanation of variation in economic participation. Interpretive methods guided the study within a qualitative design. Sixteen participants took part in semi-structured interviews: 10 unemployed graduates (with visual or hearing impairments), three human resources professionals and three helping professionals. Coding and analytic development followed Braun and Clarke's six-phase thematic approach. Overall patterns were organised into six themes: (1) discrimination and stigma, (2) accessibility, (3) use and effectiveness of AT, (4) training and support, (5) institutional and government support, and (6) self-initiated strategies and adaptation. Device access proved insufficient. Most constraints operated at the system level, consistent with the social model of disability, as stigma, accessibility failures, limited training and weak enforcement shaped outcomes. Sustained change had to address stigma, accessibility, training and support and accountable policy implementation through coordinated multi-stakeholder action. By centring graduate voices, this article contributed evidence on adaptability and multi-stakeholder lenses relevant to inclusive policy and practice in resource-constrained settings.

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.

Crystallography has facilitated the development of inhibitors in modern drug discovery. Complex structures are traditionally obtained by co-crystallization or soaking methods, but they are not always successful; co-crystallization may lead to selective crystallization of the apoprotein, and compounds cannot necessarily be soaked into preformed crystals. Successful endeavours in this field include human tankyrases TNKS1 and TNKS2, which are promising drug targets controlling a wide range of signalling events. In the case of TNKS2, apo crystals have a closed conformation in the donor loop, delineating the NAD+-binding active site, and compound soaking requires a large conformational change, which often damages the crystals and deteriorates the diffraction quality. This work describes a crystal form of TNKS2 that can be used efficiently in replacement soaking (also known as cross-soaking) when TNKS2 is co-crystallized with a low-affinity inhibitor. Replacement soaking is demonstrated with recently described nanomolar inhibitors as well as a nonhydrolysable analogue of NAD+, which all occupy the substrate-binding site. The obtained complex structures offer new insight into the binding modes of the inhibitors and the substrate NAD+, and comparison to previously published complex structures of closely related PARP proteins with NAD+ analogues reveals key characteristics of the NAD+-binding site of TNKS2. In cases where traditional methods fail to yield complex structures, the replacement soaking method provides an alternative method, which was demonstrated here to be necessary for elucidating the complex structures.

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.