Finnish Red Cross

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.

A combination of biomedical imaging and photodynamictherapy (PDT)in a single nanomaterial would be a breakthrough in nanomedicine.However, devising a single photosensitizer capable of efficient PDTwithout requiring an external oxygen source under typically hypoxictumor conditions, combined with high photostability, biocompatibility,and renal clearance, remains a challenge. Atomically precise ultrasmall(<2 nm) gold nanoclusters (AuNCs) are emerging as potential multifunctionalbiomedicines, encompassing imaging, diagnosis, and therapy in a singlenanoplatform. Herein, we report bioderived cellulose nanocrystal-supportedgold nanoclusters (CNC-AuNCs) with selective mono or multiheteroatom(Ag, Pd, and Pt) substitution at the core of the nanoclusters. Thereplacement of one or more gold atoms significantly modulates theiremission wavelengths, photoluminescence quantum yields, as well asexcited-state relaxation kinetics. These materials can easily penetratethe cells, accumulating in the cytoplasm and emitting bright luminescence.While the nanocomposites are highly biocompatible, they can producereactive oxygen species (ROS) through the formation of free radicals(O2–· and ·OH) uponexposure of light. The synergistic effect of the light absorptionby the matrix and the diverse excited-state relaxation pathways ofthe nanoclusters results in the efficient generation of ROS in variableconcentrations, ultimately leading to the complete destruction oftargeted cancer cells via Type-I photodynamic effect. The optimalROS efficacy combined with minimal cytotoxicity suggests a universalstrategy for developing strong PDT-I agents, paving the way for versatilenanomaterials in theranostic applications.

Many blood establishments worldwide monitor serum ferritin alongside mandatory haemoglobin (Hb) screening to better protect donors from iron deficiency and anaemia. However, the relationship between ferritin and Hb, and the ferritin level that indicates iron deficiency, remains unclear. Whole blood donation results in significant iron loss, and repeated donations can deplete iron stores. This study analysed over 1 million whole-blood donations from four countries to explore the association between Hb change and ferritin levels. Hb change was defined relative to a donor's initial Hb level. A consistent two-phase relationship emerged: At low ferritin levels, Hb change is linearly associated with log ferritin; above a certain threshold, this association disappears as donors recover their reference Hb. The transition point and slope of this association differ by population. These results suggest that ferritin thresholds for identifying limited Hb recovery are not universal but population-specific, influenced by biological and procedural differences, including ferritin assay variability. While the overall pattern is consistent, the absence of standardized procedures and assays limits the ability to define global ferritin thresholds for donor care. This underscores the importance of localized approaches to ferritin-based donor management and the need for harmonized methodologies across blood services.

Infections of the dental pulp are common sequelae of microbial activity and host susceptibility, affecting >80% of adult population. We performed a genome-wide association study on endodontic infections utilizing Finnish health registry and genotype data from FinnGen. Cases [132,124 (27.2%)] had at least one ICD10-diagnosis code of pulpal or apical diseases, whereas 353,106 individuals without diagnoses served as controls. We investigated two clinical sub-phenotypes, Pulpitis and Necrosis of pulp or apical periodontitis. Our analysis resulted in significant associations in 12 chromosomes and 15 independent loci, such as those near HORMAD2 gene and those in the HLA region. The imputed HLA alleles, especially DRB1 * 04:01 and DQB1 * 03:01, were associated with endodontic infections. Bioinformatic analysis of the top variants indicated several potential regulatory variants which are involved in MHC class II protein complex, humoral immune responses, and antigen processing. Our study widens understanding on how immune dysregulation resulting from immunogenetic variation is involved in the pathogenesis of endodontic infections.

Surgical nerve injuries lead to persistent neuropathic pain (NP) in up to 30% of patients. Among many other factors, polymorphisms in the human leukocyte antigen (HLA) genes have been suggested to contribute to the development of neuropathic pain. We performed a genetic association analysis of HLA class I and class II alleles in women who had been operated on for breast cancer. Patients had a surgeon-confirmed perioperative nerve injury and were examined 4-9 years after their surgery. Patients with painful (cases, n = 27) and painless (controls, n = 30) intercostobrachial nerve resection were studied. Cases included patients with definite NP with worst pain intensity in the past week ≥ 4/10 on a numerical rating scale (NRS) and controls had the same nerve injury with no NP or other pains. Whole-genome single nucleotide polymorphism data were produced, and HLA class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQA1, -DQB1 and -DPB1) alleles were determined by imputation. HLA-DRB1*03:01, DQA1*05:01 and DQB1*02:01 alleles appeared to be associated with painful nerve injury after breast cancer surgery (nominal p = 0.007 for all, carriership OR = 12.0, 95% CI 1.38-104; FDR corrected p > 0.07). These alleles comprise the DR3-DQ2 haplotype, which is part of the ancestral haplotype AH8.1. Our results provide further support for the role of HLA genetic variation in the development of persistent post-surgical neuropathic pain, which indirectly implies a mechanism involving immunological memory in this process. We report a novel association between the HLA-DR3-DQ2 haplotype and the development of persistent neuropathic pain after breast cancer surgery. Our results provide further evidence for the role of HLA polymorphism in persistent neuropathic pain.

Orofacial granulomatosis (OFG) is a rare chronic inflammatory condition. It is under debate, whether it is a condition of its own or merely a subtype of Crohn’s disease (CD). We aimed to search for markers characteristic of patients with pediatric-onset OFG compared to patients with pediatric-onset CD. We recruited young patients with OFG (with or without CD, n = 29), CD (n = 24), and healthy controls (n = 20). All participants provided a fecal sample for microbiota and calprotectin analyses and saliva for DNA analysis of genes associated with OFG and kept a 3-day food diary. Oral disease activity was evaluated using The Oral Disease Activity Score by an otorhinolaryngologist and a dentist. We observed decreased relative abundance in class Clostridia and increased relative abundances of classes Actinobacteria and Bacilli in the feces of patients with OFG when compared to patients with CD and healthy controls. The relative abundances of Bifidobacterium adolescentis increased and Faecalibacterium prausnitzii decreased along with the increase in the Oral Disease Activity Score. We found the NOD2 gene rs8057341 allele A to be enriched in patients with OFG compared to patients with CD. These findings support the theory that OFG is a distinct disease phenotype.

Platelets are abundant in blood, where they maintain the integrity of the vasculature. Megakaryocytes, the cells responsible for platelet genesis, produce membrane protrusions from which as many as 5000 anucleate platelets can be released into the bloodstream. Platelets lack genomic DNA but contain different molecules, such as RNA, as well as organelles transmitted from the parent megakaryocyte. There is no consensus in the scientific community on whether platelets are cells or not: for example, they are sometimes called cells, small cells, anucleated cells, cell fragments, or megakaryocyte fragments. Extracellular vesicles are particles delimited by a lipid bilayer that are released from cells but cannot replicate on their own. Like platelets, extracellular vesicles lack a nucleus and carry components from their donor cell. Herein, we will explore various viewpoints suggesting that platelets may be cells, albeit not conventional cells, or may be a previously unrecognized type of extracellular vesicle. Beyond a mere debate over terminology, this perspective seeks to help properly define and classify platelets, aiming for better integration into the concept of either cells or extracellular vesicles. This will foster a clearer understanding and drive advances in platelet research.

BackgroundExtracellular vesicles (EVs) have procoagulative properties. As EVs are known to accumulate in stored blood products, we compared the EV content and coagulation capacity of leukoreduced cold‐stored whole blood (CSWB) with current prehospital and in‐hospital component therapies to understand the role of EVs in the haemostatic capacity of ageing CSWB.Materials and MethodsBlood was obtained from 12 O RhD‐positive male donors. CSWB was compared with in‐hospital component therapy of red blood cells (RBCs), OctaplasLG and buffy‐coat platelets and prehospital component therapy of RBC and lyophilized plasma. Samples were drawn on Days 1 and 14 of CSWB and RBC cold storage. Blood count, haemolysis markers, rotational thromboelastometry, sonorheometry and thrombin generation were analysed. EVs were analysed using nanoparticle tracking analysis and cellular origin was determined using imaging flow cytometry.ResultsThere was a trend towards increased production of both platelet and RBC‐derived EVs during CSWB storage. Particle count increased during storage, whereas thrombin generation slowed down and in viscoelastic assays, clotting times prolonged, clot formation became impaired, and stiffness of the resulting clot decreased.ConclusionBoth platelet and RBC‐derived EVs increased in number in CSWB during storage. This did not appear to compensate for the in vitro decreasing haemostatic capacity of ageing CSWB, suggesting EVs produced during storage may not have active procoagulative effects, but rather reflect the ageing of blood cells.