Université de Bretagne Occidentale

While modern technology is increasingly available to identify efficiently the molecular alterations responsible for variant phenotype, a subset of samples still escapes those analyses. In addition to the promoter region, two intronic regions containing GATA1 binding sites within the RHD gene locus were recently shown to modulate the transcriptional activity of the gene. We then thought to explore these regions in a subset of samples with unresolved genotypes. Thirty-three Thai donor samples (weak D, n = 10; D-negative, 23) were selected for molecular analysis by conventional Sanger sequencing. In parallel, a novel functional assay was designed for investigating the potential effect of variants within the RHD gene promoter. Three variants previously reported, that is, c.1-115A>C, c.1-110A>C, and c.1-83G>T, were tested by this approach. No variant was identified in the 33 samples, suggesting that the molecular basis of the respective phenotypes remains to be resolved. Interestingly, beyond the ~200 base pair (bp) promoter region commonly described, another ~300 bp region located upstream appears to contain elements that positively regulate the transcriptional activity of the RHD gene. Also, the deleterious effect of the c.1-110A>C variant was confirmed, conversely to the two other variants, which did not show any functional alteration. Regulation of RH gene expression is likely to involve other levels of complexity that remain to be identified. Future investigations are necessary to characterize those critical genomic regions that potentially carry rare variants responsible for weakening or abolishment of D antigen expression.

The absence of JK antigens carried by the erythroid urea transporter due to null alleles is well documented. To date, over 50 alleles have been identified and registered by the International Society of Blood transfusion (ISBT Blood Group Database). An elderly woman of European ancestry developed anti-JK1 (Jka) 3 days after the transfusion of two units of packed red blood cells (RBCs), one of which was from a JK:1 (or Jk(a+)) donor. The JK phenotype of the other unit was unknown. We report the identification of a novel JK*01 allele carrying the c.151+1G>C variant in the SLC14A1 gene that was shown to be responsible for the lack of JK1 (Jka) expression by functional analysis. Antibody identification was done using standard methods. The patient's plasma was tested with native or papain or trypsin-treated RBC. A direct antiglobulin test (DAT) was performed on the patient's RBC. Subsequently, the eluate using Gamma ELU-KIT II (Werfen, Norcross, USA) was tested in an indirect agglutination test (IAT) to identify a potential alloantibody. Genomic DNA was isolated from whole blood with NucleoMag (Macherey-Nagel, Hoerdt, France) according to the manufacturer's instructions. Genotyping was performed using the HEA BeadChip array (BioArray Solutions/Immucor-Werfen, Warren, New Jersey, USA) and Sanger sequencing (SLC14A1 coding exons 3 to 10 and flanking regions; 3500 Dx genetic analyzer, Thermo Fisher), as previously described.1 The effect of the variant was predicted in silico using SpliceAI2 and SPIP3 and reporter minigene splicing assay was performed to further investigate the effect of the variant in an in vitro model.4, 5 Anti-JK1 was identified in the patient's plasma by IAT. The DAT was 2+ with anti-C3d, and the eluate also contained anti-JK1, consistent with an allo-antibody due to a recent RBC transfusion. By the HEA Beadchip, the sample was found to be heterozygous (G/A) at position c.838 defining the JK1/JK2 antigen specificity, which is consistent with a JK*01/JK*02 genotype. According to the reference sequence NM_015865, Sanger sequencing of SLC14A1 confirmed c.838G/A in exon 8, and additionally detected the c.151+1G>C single nucleotide variant, which is located within the consensus donor splice site of intron 3, at the heterozygous state. This variant was predicted to disrupt splicing by in silico investigation (SpliceAI score: 0.71 [donor loss]; SPiP v2.1 score: 0.986 [Alter by SPiCE]). The deleterious effect was confirmed in vitro by the minigene splicing assay demonstrating the complete disruption of the constitutive donor splice site and the full skipping of SLC14A1 exon 3 (Figure 1, black arrowhead). Very importantly, this exon carries the methionine initiation codon. Therefore, it is thought that translation initiation cannot occur and no normal protein can be expressed from the novel allele carrying the c.151+1G>C variant. In this work, we describe the novel JK*01 N c.151 + 1 G>C null allele (Genbank accession number: PX849538) that disrupts the expression of the JK1 antigen in a patient of European descent who made anti-JK1 after being transfused with JK:1 RBC. This demonstrates, once again, that caution must be exercised when interpreting targeted genotyping results when antibodies are present. ISBT Blood Group Database (JK blood group system): blooddatabase.isbtweb.org/system/JK (accessed on January 12, 2026). Open access publication funding provided by COUPERIN CY26. The authors have nothing to report. The authors have disclosed no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Peripherally inserted central catheters (PICCs) are increasingly used in France for prolonged intravenous therapies such as chemotherapy, parenteral nutrition, or antibiotics. They are easier to place than traditional central venous catheters and carry fewer immediate risks, but remain associated with delayed complications, mainly infections, thromboembolic events, and mechanical issues. This literature review aimed to identify risk factors for PICC-related infections and thrombosis. The study used BIBOT, an artificial intelligence program for natural language processing, already validated in prior reviews and the IA language model LLaMA3. PubMed was searched for studies published between 2013 and 2023. Using the AI-based tool BIBOT, 1896 PubMed abstracts on PICCs were automatically screened. After filtering and AI-assisted content analysis, 343 original articles focusing on PICC complications were identified, enabling a targeted selection of 113 articles on infectious and 281 on thrombotic complications. In total, 20 infectious and 59 thrombotic risk factors were manually identified. Among these, the most frequently reported in the reviewed articles for infections were number of lumens, chemotherapy and catheter dwell time. For thrombosis, the most commonly cited factors included cancer or hematologic disease, chemotherapy, PICC diameter and number of lumens (>2). The study highlights the value of AI-based tools to accelerate article selection and data extraction in medical literature. However, human validation remains essential to avoid errors and misinterpretations, particularly with acronyms or heterogeneous definitions. Hybrid approaches combining AI with expert review save considerable time and are expected to improve further with multimodal models and multi-agent strategies.

Acoustic surveillance of oceans is of great interest for monitoring both wildlife and anthropogenic activities. In this paper, we focus on passive, non-communicating sonar systems that are suitable for efficiently monitoring the marine environment. With such a network, no live tracking is possible; instead, we aim to record activities in the most discreet manner for surveillance purposes. General guidelines can be established to assist in designing a network of underwater acoustic sensors. These guidelines serve as both objectives and constraints, such as sensor detection capabilities, deployment area alternatives, acoustic propagation properties, and potential noise source areas. The optimization of network design, in terms of the distribution and locations of sensors (or groups of sensors physically stacked on a mooring line, for example, and referred to as anchors ), involves trade-offs between network cost, coverage of the targeted marine area, network redundancy, and localization capabilities. In this paper, we propose several approaches to address these various constraints and optimization objectives. These approaches rely on numerical simulations of underwater acoustic propagation, which allow accounting for environmental characteristics such as bathymetry, sea floor properties, and sound speed profiles. A discretized model of the network design problem is presented. It relies on a grid representation of anchor locations, and a complete Integer Programming formulation of the problem is defined. The model is used to identify sets of solutions that represent trade-offs among the different optimization criteria. Both exact and heuristic multi-objective approaches are proposed to exploit the model. The former are applicable to smaller sets of instances and optimization objectives than the latter. However, the exact approaches enable the derivation of precise bounds on the optimized criteria, as well as initial solutions that can enhance heuristic multi-objective methods based on evolutionary multi-objective optimization frameworks. This supports the designer’s choice of the final network configuration. Numerical experiments conducted on a set of sixteen semi-synthetic test cases, as well as on an actual network deployed at sea, demonstrate that an exact -constraint method is applicable to industrial-scale instances involving up to 2000 monitoring points. It provides the complete Pareto set for the coverage vs. cost problem in a few minutes. One of the proposed heuristic methods yields, in less than a second, sets of solutions with a loss of quality below 1% for the same design problem. When the triangulation capabilities of the network are optimized as a complementary objective for noise source localization, hybrid heuristic approaches are able to improve the results of the basic algorithm by up to 156% on average. • a modelling of the design of UWASN as a Multi Objective optimization problem. • 4 different optimization criteria, 2 exact methods, 2 ad-hoc heuristics and 2 meta-heuristics for solving the problem. • 4 experiments to compare exact and reference methods to approximate approaches. • 16 testcases used and a mixed approach for efficiently extending an existing real-life network.

Abstract Since 1995, European fisheries of Pecten maximus have faced the presence of Pseudo-nitzschia species, which are able to produce the neurotoxin domoic acid responsible for Amnesic Shellfish Poisoning (ASP). As filter-feeders, scallops can accumulate and retain domoic acid much longer than most other bivalves, from months to years. When concentrations exceed the regulatory threshold, fisheries are closed leading to economic concern. Inter-individual variability increases the difficulty to predict the depuration dynamics. Quantifying the correlations between domoic acid depuration in P. maximus and individual physiological traits, particularly body size, could improve the understanding of contamination and depuration. We analysed toxin dynamics in organs and assessed the effects of body size and growth. This analysis was based on two datasets from an experimental and an in situ depuration monitoring of P. maximus exposed to a natural bloom of toxic P. australis . Results showed that the distribution of domoic acid shifted among organs between contamination and two months of depuration. Toxin concentrations correlated negatively with body size during contamination and after two months of depuration, but shifted to a positive correlation after 7 months of depuration. This suggested that smaller scallops both accumulate more domoic acid and depurate it more rapidly. Dilution by growth appeared to explain the inversion of the correlation between domoic acid and body size throughout depuration. These results yield useful information for modelling these mechanisms, thus providing valuable tools for scallop fishery management facing ASP. Graphical Abstract Highlights Experimental and in situ datasets allowed to quantify DA proportion dynamics in organs in P. maximus DA concentration and body size are negatively correlated during contamination phase, but positively after a 7-month depuration Considering dilution by growth is important for young scallops to assess DA depuration dynamics Both depuration rate and dilution by growth need to be considered to model DA depuration over the whole scallop size range

The COVID-19 pandemic has left many survivors with persistent respiratory symptoms such as dyspnea, chronic cough, and reduced exercise capacity. Fibrosis-like abnormalities on high-resolution CT are frequently reported in theses patient. This study aimed to describe the morphological pulmonary abnormalities identified on V/Q SPECT/CT after COVID-19 infection and to evaluate their functional consequences on regional ventilation and perfusion. We also sought to identify clinical predictors of abnormal V/Q SPECT/CT findings. This retrospective multicenter study was based on a national registry of patients referred for V/Q SPECT/CT because of persistent respiratory symptoms after COVID-19 infection. CT abnormalities were characterized using standard radiological criteria. Ventilation and perfusion were visually graded using a five-point scale. Clinical, demographic, and acute COVID-19 characteristics were analyzed to identify predictors of abnormal imaging. Among the 217 included patients (mean age 58 ± 15 years), 122 (56%) presented pulmonary abnormalities on V/Q SPECT or CT. The most frequent parenchymal abnormalities were reticulations, consolidations, atelectasis, emphysema, and ground-glass opacities. Emphysema, consolidations, and fibrosis were associated with the most severe impairments of both ventilation and perfusion. Age and pre-existing chronic lung disease were the strongest predictors of abnormal imaging, while a mild acute COVID-19 course without oxygen therapy was protective. V/Q SPECT/CT provides a comprehensive structural and functional assessment of long COVID pulmonary sequelae. It allows the differentiation between reversible inflammatory lesions and persistent structural abnormalities with lasting functional consequences.

In the absence of telomerase, telomere shortening triggers replicative senescence, a tumor suppressor mechanism that is also associated with oncogenic genomic instability. Yet, the precise mechanism that connects these seemingly opposing forces remains poorly understood. To directly study the complex interplay between senescence, telomere dynamics, and genomic instability, we develop a system in Saccharomyces cerevisiae to generate and track telomeres of precise length in the absence of telomerase. Using single-telomere and single-cell analyses combined with mathematical modeling, we identify a threshold length at which telomeres switch into dysfunction. A single shortest telomere below the threshold length is necessary and sufficient to trigger the onset of replicative senescence in a majority of cells. At population level, fluctuation assays establish that rare genomic instability arises predominantly in cis to the shortest telomere as Pol32-dependent non-reciprocal translocations that result in re-elongation of the shortest telomere and likely transient escape from senescence. The switch of the shortest telomere into dysfunction and subsequent processing in telomerase-negative cells thus serves as the mechanistic link between replicative senescence onset, genomic instability and the initiation of post-senescence survival.

The closure of the Sea Level Budget (SLB) is a key challenge for modern physical oceanography. First, it is essential that we ensure the proper identification and quantification of each significant contributor to sea level change through this closure. Second, it provides an efficient means to closely monitor and cross-validate the performance of intricate global observation systems, such as the satellite altimetry constellation, satellite gravimetry missions (GRACE/GRACE-FO), and the Argo in-situ network. Third, this closure reveals to be a beneficial approach for assessing how well the observed climate variables, such as sea level, barystatic sea level, temperature and salinity, land ice melt, and changes in land water storage, comply with conservation laws, in particular those related to mass and energy.In this presentation, we will discuss the state of knowledge of global mean and regional sea level budget with up-to-date observations, encompassing 1) an up-to-date assessment of the budget components and residuals, along with their corresponding uncertainties, spanning from 1993 to 2023 in global mean and throughout the GRACE and Argo era for spatial variations; 2) the identification of the periods and areas where the budget is not closed, i.e. where the residuals are significant; 3) advancements in the analysis and understanding of the spatial patterns of the budget residuals. To investigate the sea level budget (SLB) misclosure, we developed an objective solution that closes the SLB globally. This approach is based on an inverse method that optimally combines the contributions to sea level, weighted by their estimated instrumental uncertainties, and draws from publications such as those by Rodell et al. (2015) and L’Ecuyer et al. (2015).This objective method allows us to precisely identify the dates when the SLB misclosure falls outside the uncertainty estimates, as well as the contributor most likely responsible for the discrepancy. The results of this analysis will be detailed during the presentation.A focus will be made on the North Atlantic Ocean where the residuals are significantly high. We investigate the potential errors causing non-closure in each of the components (e.g., in situ data sampling for the thermosteric component, geocenter correction in the gravimetric data processing) as well as potential inconsistencies in their processing that may impact large-scale patterns (e.g., centre of reference and atmosphere corrections). This work is performed within the framework of the Sea Level Budget Closure Climate Change Initiative (SLBC_cci+) programme of the European Space Agency (https://climate.esa.int/en/projects/sea-level-budget-closure/). This project was initiated by the International Space Science Institute Workshop on Integrative Study of Sea Level Budget (https://www.issibern.ch/workshops/sealevelbudget/).

Zenith Total Delay (ZTD) estimates derived from GNSS observations are essential for atmospheric and geodetic applications. When processed using Precise Point Positioning (PPP), ZTD time series exhibit enhanced stability compared to network-based approaches. However, occasional outliers - ranging from a few centimetres to several meters - still occur, potentially degrading product quality and impacting downstream applications. The mechanisms driving these anomalies remain poorly understood, and their characterisation is critical for improving PPP-based ZTD products. This study examines the nature, origins, and possible mitigation strategies for such outliers in order to enhance the reliability of GNSS-derived tropospheric parameters.We perform sensitivity tests using the CNES’s GINS software in PPP mode with integer ambiguity resolution, complemented by simplified PPP-like simulations, to identify the mechanisms underlying ZTD outliers. Particular attention is given to pre-processing procedures, which are critical for detecting and handling problematic observations and significantly impact ZTD accuracy. Building on this diagnostic phase, we explore parameter regularisation strategies aimed at mitigating the occurrence of ZTD outliers while preserving high processing quality. These analyses provide insights into both the origin of anomalies and practical approaches for improving the robustness of PPP-based tropospheric products.In addition, we investigate complementary post-processing screening methods based either on purely statistical approaches or on the comparison with independent atmospheric reanalysis ZTD data. Combined with the strategies described above, these methods aim to reduce ZTD outliers while preserving geophysical variability. This integrated approach enhances GNSS positioning performance and improves the reliability of long-term GNSS-derived tropospheric time series, supporting climate monitoring and other atmospheric applications.