ABSTRACT Haematopoietic cell transplantation (HCT) with HLA‐mismatched unrelated donors (MMUD) offers access to curative therapy for patients lacking well‐matched donors. Accumulating evidence suggests that functional matching among allele‐mismatched pairs can significantly influence patient outcomes. Therefore, real‐world data on mismatch frequencies in MMUD‐HCT could provide fundamental information for the assessment of patient risks and donor selection strategies. Here, we analysed HLA matching in 28,376 first unrelated transplants reported to the EBMT Registry with available 6‐locus high‐resolution typing. Mismatches at each locus were quantified and characterised at the allelic, antigenic and functional (antigen‐recognition domain, peptide‐binding motif) levels. 25% of the transplants were performed across one (9/10; n = 6053) or more (< 9/10; n = 1013) high‐resolution mismatches at the five main HLA loci, a proportion that was markedly higher (43.9%) among transplants performed with post‐transplantation cyclophosphamide (PTCy). Median time from diagnosis to transplant was longer for MMUD compared to 10/10 transplants, but this difference decreased over time (14.9 vs. 11.3 months pre‐2011, p = 0.003; 8.1 vs. 7.4 months 2021–2022, p = 0.016). Across transplant eras, single class I mismatches were three times more common than class II mismatches. Conversely, matching for HLA‐DPB1 increased from 15% pre‐2011 to 31% in 2021–2022. The landscapes of allelic mismatches differed markedly between HLA loci. For class II, skewed distributions dominated by frequent combinations result in significantly higher frequencies of functional matching compared to class I in both PTCy and non‐PTCy pairs. Our study constitutes the first large‐scale characterisation of real‐world HLA mismatch frequencies in contemporary unrelated HCT, bearing implications for future clinical outcome studies.
ABSTRACT Introduction To address placement capacity issues in the face of rising medical student numbers, there has been a move towards simulation and technology enhanced learning. However, observing and learning from real clinical practice remains valuable to students. Can we prioritise the finite resources of the clinical environment by identifying what works best for medical students when learning on clinical placements? Methods Q methodology is a qualiquantological approach that determines the diversity of viewpoints held within a population into groups (factors). A Q concourse, a compendium of all the thoughts that the participant population might have on clinical placements, was collected from published literature, grey literature, four interviews and three focus groups with final year medical students and undergraduate educational faculty members. Forty‐six statements were constructed from the concourse to be sorted by our foundation year one participants. Results Analysis of 25 participant Q‐sorts resulted in a three‐factor solution. Factor 1 saw value in nearly all learning opportunities. Factor 2 needed support to find learning opportunities, enjoyed teacher‐led activities such as simulation and were critical of activities where they were not directly engaged. Factor 3 strongly valued real patient interaction over simulation and preferred more independence with their timetable. All factors confirmed that students need preceptors to explore the reasons behind clinical decisions with them. Conclusion The replacement of real patient experience with simulation divides opinion. When allocating resources for students on clinical placement, there is educational potential in all clinical activities, but it varies with each factor.
ABSTRACT Background Teaching philosophy statements (TPS) are concise, reflective narratives that articulate an educator's beliefs, values and approaches to teaching and learning. In health professions education, TPS can serve as tools for promotion and tenure, teaching portfolios and professional identity formation. Despite their potential to enhance reflective practice and teaching effectiveness, the prevalence and application of TPS in health professions education remain unclear. Methods A scoping review was conducted in which six databases were searched for English‐language peer‐reviewed articles published from 2003 to 2024. Inclusion criteria required that articles address health professions education, include the concept of philosophy and reference an educational process. Data extraction included publication characteristics, educational and career contexts and described uses of TPS. Findings Fourteen articles met inclusion criteria, representing medicine, nursing, basic sciences, occupational therapy, medical sciences and interprofessional education. Thirteen journals were represented; eight articles were research‐focused, with the remainder descriptive, theoretical or narrative reviews. Most commonly, TPS were described as artefacts for teaching portfolios ( n = 8), reflective guides ( n = 7) or components of promotion packets ( n = 6). Few studies examined the impact of TPS on teaching effectiveness, learner outcomes or faculty development. Conclusion TPS appear infrequently in the health professions education literature and are often discussed superficially. While recognised for their reflective and professional development potential, empirical evidence of their direct impact is lacking. Future research should explore longitudinal effects of TPS adoption, their role in faculty identity development and strategies for integrating TPS meaningfully into faculty development programmes.
Abstract All of the world's spoken languages make consistent use of a relatively narrow set of contrastive speech sounds—phonemes. Here, we argue that phonemes constitute cognitive tools, supporting, guiding, and extending speaker cognitive capacities. We outline commonalities between phonemes and other cognitive tools, which include tendencies in their usage based on biological constraints, their extensive variation across cultural lineages, their criticality to the efficient transmission of information, and their importance in the scaffolding of various cognitive capacities. Studies of the commonalities of phonological systems reveal the physical and biological underpinnings upon which the tools of phonemes are necessarily predicated, and the constraints on their cross‐cultural refinement. Our view complements cognitive linguistic perspectives on other cognitive tools, and on human perception and consciousness more broadly, by emphasizing the sounds of speech themselves.
SUMMARY Plants actively monitor the state of their cell walls and adapt their structure and composition as needed. THESEUS1 (THE1), a receptor kinase from the Catharanthus roseus RECEPTOR‐LIKE KINASE 1‐LIKE ( Cr RLK1L) family, was the first receptor kinase described to be involved in this maintenance of cell wall integrity in Arabidopsis thaliana . It contributes to the regulation of cell wall stiffness, participates in lateral root development, and modulates production of the stress hormones abscisic acid and jasmonic acid. Besides, it is required for responses to cellulose biosynthesis inhibition, such as growth inhibition and ectopic lignification. The THE1 ligand, RAPID ALKALINIZATION FACTOR 34, and one intracellular interaction partner, GUANINE EXCHANGE FACTOR 4, have been identified. However, relatively little is known about other interaction partners and mechanisms by which THE1 influences downstream responses. Given that FERONIA, a related member of the Cr RLK1L family, has dozens of interaction partners, it is likely that there is a wealth of interactors waiting to be described for THE1. Here, we shed light on the evolutionary origin of THE1 and describe the many open questions surrounding THE1‐dependent signaling processes. We expect that many of these questions will be answered in the coming years and that these answers will provide more insight into the molecular mechanism of cell wall integrity maintenance mediated by THE1.
SUMMARY Pinosylvin and its derivatives are defense‐related stilbenoids that contribute to pathogen and decay resistance of Scots pine ( Pinus sylvestris L.) heartwood. While most enzymes in the pinosylvin biosynthesis pathway in Scots pine have been identified, the enzyme responsible for activating cinnamic acid to cinnamoyl‐CoA, an essential precursor for pinosylvin biosynthesis, has remained unknown. In this study, we explored Scots pine transcriptomic data to observe the expression profiles of the 4‐coumarate:CoA ligase (4CL) genes and produced the enzymes in Nicotiana benthamiana to assay their kinetic properties. We identified and characterized four 4CL isoforms, one of which (Ps4CL2) was both co‐expressed with pinosylvin biosynthesis genes under stilbene‐inducing conditions and exhibited an unusually high affinity for cinnamic acid surpassing that of previously characterized cinnamate‐activating 4CLs. Through site‐directed mutagenesis and domain‐swapping experiments with the closely related Ps4CL3, we showed that substrate preference in Ps4CL2 results from multiple interacting regions within the enzyme. Our findings establish Ps4CL2 as the prime candidate for cinnamate activation as the last missing enzyme for pinosylvin biosynthesis in Scots pine and provide insight into enzyme specialization within the 4CL family.
Abstract Background The implementation of metabolomics‐based quality assessment of stored red blood cells (RBCs) has been limited by logistical constraints and the need for sterile, scalable sampling strategies. Sampling RBC segments, routinely used for compatibility testing, offers a practical alternative to direct unit interrogation, but the biochemical equivalence of segments and transfusates has not been systematically evaluated. Study Design and Methods We performed semi‐targeted metabolomics on 51 paired segments and transfusates collected immediately after transfusion to determine concordance across sampling sources. Results and Discussion Of the 250 metabolites detected in both matrices, approximately 70% showed significant positive correlations, spanning glycolytic, redox, lipid, and nucleotide pathways previously implicated in the RBC storage lesion. The top correlated metabolites displayed strong linear relationships independent of storage duration, confirming that segments reliably capture unit‐level metabolic phenotypes. These results support the utility of segment‐based omics profiling as a scalable, minimally disruptive approach for next‐generation precision transfusion medicine.
Abstract In 2025, the Parasitology Subgroup of the International Society of Blood Transfusion (ISBT) Transfusion‐Transmitted Infectious Diseases (TTID) Working Party (WP) transitioned into the Emerging Pathogens and Parasitology (EPP) Subgroup (referred to here as the EPP). This followed recognition that the parasitology subgroup's relevance was limited in scope given the small number of transfusion‐transmissible parasites that still lacked effective mitigation. The EPP was proposed to address themes that are not adequately covered by existent subgroups of the TTID WP. In addition to maintaining a focus on transfusion‐transmissible parasitic infections, a major objective of the EPP is horizon scanning for emerging pathogens. Horizon scanning refers to a systematic and proactive approach of information gathering and evaluation to identify early—and often subtle—signals of possible threats, which in this case pertain to blood safety. The EPP will characterize those risks to guide decision making and preparedness, pertaining to the safety and sufficiency of the blood supply. We describe the scope, structure and functioning of the EPP, within the broader TTID WP. We include examples of projects that may be pursued and outputs from horizon scanning a contemporary emerging pathogen. This collectively highlights the strategic relevance and objectives of the EPP.