Sanquin

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To meet the long-term demand for blood products while preserving donor health in the long run, blood establishments must recruit a sufficient number of new donors annually. To determine what will suffice, it is essential to be able to forecast future blood donation volumes as a function of new donors using estimates based on historical donation activity. Donor (n = 11,629,873) and donation data (n = 64,510,294) extracted from operational information systems of seven blood establishments were transformed into anonymous donation activity data (grouped by blood establishment, sex and blood group) in the form of time series of mean number of donations per donor, indexed by years since first donation. Linear models were fitted to the time series using ordinary least squares. Out of the various estimated models, the best fit (mean R2 over blood establishments 99.95%) for past mean donation activity was achieved when regressing the logarithm of cumulative donation activity on the logarithm of years since first donation and an indicator variable for the year of first donation. In addition to the predictions, comparison of the estimated parameters revealed that there are significant differences between blood establishments, translating to differences in the expected number of donations accumulated over the lifetime of a donor. Average donation activity can be modelled using a few variables and simple models, with high precision. The estimates can be used to create forecasts of future donation volumes, which in turn can be useful in long-term blood donation management.

RNA-binding proteins (RBPs) are key regulators of T cell function by controlling (m)RNA fate and fine-tuning protein expression dynamics. Dysregulated RBPs can drive immune diseases and malignancies, highlighting their potential as therapeutic targets. To achieve this, a systematic analysis of the dynamic RBP-RNA interactions is required. Here, we mapped the RNA-binding proteome in human T cells and measured its alterations upon T cell activation using orthogonal organic phase separation (OOPS), analysed with PROMOGEB, a Bayesian linear regression model. This approach uncovered the intricate RNA-binding dynamics of the RBProteome. Gene-editing of such dynamic RNA binders revealed that TUT1 (Star-PAP) maintains the integrity of the T cell differentiation program, and that mutating SF3A1 enhanced the cytotoxic molecule expression and thus target cell killing. Our work provides the most comprehensive analysis of the effector T cell RBProteome to date and shows the potential of identifying RBPs and their binding dynamics as therapeutic agents.

Restrictive red blood cell transfusion strategies are widely recommended for acute anemia but may not adequately address the needs of chronically anemic patients with transfusion-dependent myelodysplastic syndromes or myeloproliferative neoplasms. For these patients with chronic anemia, alleviating symptoms and improving quality of life are key objectives. This study evaluates the impact of additional red blood cell (RBC) transfusions administered alongside standard-of-care transfusions on heart rate, physical activity, quality of life, and cognitive function. This interim analysis of a randomized, multicenter, within-subject, cross-over trial evaluated 12 transfusion-dependent patients receiving three transfusion regimens: standard-of-care, standard-of-care + 1 additional unit, and standard-of-care + 2 additional units. The primary outcome was heart rate, and secondary outcomes were physical activity, quality of life, and cognitive performance. Heart rate and activity were continuously monitored, while questionnaires and cognitive tasks assessed outcomes at predefined visits. Greater hemoglobin augmentation was associated with significant reductions in heart rate, with the largest decrease in patients receiving the standard-of-care + 2 regimen. Quality of life and fatigue measures showed transient improvements with more red blood cells transfused, though these changes were not statistically significant. Cognitive performance trends suggested possible benefits, but findings were inconsistent. Physical activity, as measured by daily step count, was unaffected by transfusions. This interim analysis suggests that higher post-transfusion hemoglobin is associated with lower heart rate, reflecting enhanced oxygen delivery. Wearable monitoring was sensitive to these changes. Nonsignificant, hypothesis-generating trends toward improved QoL, fatigue, and cognition were observed.

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Capillary blood microsampling enables the sampling of small blood volumes, making it suitable for vulnerable populations, remote collection, and repeated sampling. Owing to its minimal invasiveness, blood microsampling has emerged as an alternative to venipuncture in many fields. However, as capillary blood differs from venous blood in composition and analytes vary in their distribution between the blood cell and plasma fractions, plasma and capillary blood concentrations may differ. Because plasma is often the standard matrix for routine analyses, this discrepancy can compromise the clinicians' interpretation of capillary blood results. Hence, to ensure comparability with results obtained through plasma-based assays and reference ranges, accurate conversion to plasma concentrations may be required, which may improve the reliability and validity of microsampling-based outcomes. Despite its relevance, guidance on whether conversion is appropriate or desired and on how to translate and validate the translation of capillary blood microsampling results to plasma concentrations is lacking. To address this gap, members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) expert committees have prepared this guideline to discuss the "what, when, and how" of converting capillary to plasma concentrations and provide guidance on the decision of fit-for-purpose conversion. In addition, guidance to assess capillary blood results when the reference matrix is whole blood and to assess liquid capillary plasma results is provided. The included topics, as well as considerations and recommendations presented in this guideline, were based on a previously published dried blood spot-based IATDMCT guideline, literature review and expert opinions of the authors. Key points include the importance of conducting a comprehensive clinical validation study to fully understand capillary blood microsampling results. In addition, the performance of the conversion method should be evaluated case by case, as it depends on both the microsampling-based method and analyte of interest. Furthermore, an independent set of paired capillary and venous samples should be used to validate an established conversion formula. Finally, a key point for future studies is to focus on the clinical impact of (converted) capillary blood concentrations in comparison with decisions based on results in the reference matrix to guarantee any microsampling-based outcome.