MobiCT: a UMI-based circulating tumor DNA analysis pipeline

International audienceMobiCT is a bioinformatics pipeline designed to detect ultra-low-frequency variants present in cell-free DNA samples using unique molecular identifier (UMI). The pipeline is composed of three main stages: (i) UMI deduplication, (ii) alignment to reference genome, and (iii) variant calling. It has been validated using a range of cancer patients and control samples, demonstrating sensitivity, precision, and F1-score around 90%. Implemented in Nextflow, following the nf-core guidelines, MobiCT ensures reliability and reproducibility, making it suitable for both research and clinical applications

Organic geochemical investigations of an MIS 5 fire in the Palaeolithic deposits of Ormesson (Seine-et-Marne, France): Anthropic or natural?

International audienceDespite the central role of fire in Pleistocene and Palaeolithic lifeways, the relationship among hominins, fire, and their environment remains unclear. Ancient combustion residues hold a wealth of molecular data that may help to resolve some of these questions, yet standardised guidelines for reconstructing past fire traces are notably lacking. In this study, we examine extensive combustion residues overlying Middle Palaeolithic deposits from the open-air site of Ormesson (France). To determine whether the combustion residues are of natural or human origin, multiproxy approaches including anthracology, lipid biomarker, and benzene polycarboxylic acid (BPCA) analyses are applied. These techniques are used to characterise organic matter and pyrogenic carbon compositions in the deposits, providing insights into surrounding vegetation, palaeoenvironmental shifts, and the production parameters involved in the formation of the char assemblage. Lipid biomarker evidence suggests that the pre-fire local environment featured abundant coniferous vegetation (e.g., Pinaceae taxa), which is supported by anthracological evidence for a predominance of Pinus cf. sylvestris/nigra complemented by Betula sp. taxa. The post-fire environment saw a contraction of coniferous vegetation, concurrent with an expansion of deciduous taxa, grasses and herbaceous material. The combustion event, which resulted in 67 % of the charcoal assemblage exhibiting vitrification, produced PyC contents of up to 362 g/kg OC in soil samples and 443 g/kg OC in charcoal samples, with aromatic condensation values of up to 34 %. BPCA-derived predictions of heat treatment temperatures yielded values of approximately 300–400 °C for charcoal samples and 400–550 °C for soil samples in the burned layer, constituting the first instance in which quantitative temperature estimations are obtained from BPCA results. Based on the integrated evidence, we accept the null hypothesis that the studied combustion residues are natural in origin. However, the similarity of archaeometric and geochemical signatures from natural and human-controlled fires underscores the need for interdisciplinary, multiproxy efforts to improve the identification of past fire regimes

Continuous Infusion of Aztreonam–Avibactam After High Loading Dose for an Infection Caused by an OXA-48- and NDM-1-Co-producing ST147 Klebsiella pneumoniae

International audienceIntroduction: Infections caused by metallo-β-lactamase-producing Enterobacterales offer limited therapeutic options. Aztreonam-avibactam (ATM-AVI) provides a promising alternative, but its approved intermittent regimen is complex and can lead to substantial drug waste.Methods: We describe a case of mastoiditis with a retrotympanic abscess due to OXA-48- and NDM-1-producing Klebsiella pneumoniae, managed with continuous infusion (CI) of ATM-AVI after a full-vial loading dose, supported by therapeutic drug monitoring (TDM) and whole-genome sequencing (EPISEQ CS V2.0, bioMérieux).Results: A 35-year-old man previously treated abroad for meningitis and brain abscesses presented with residual deep-seated infection caused by OXA-48- and NDM-1-producing K. pneumoniae. After initial treatment with ceftazidime-avibactam plus aztreonam, therapy was switched to ATM-AVI using a full-vial loading dose followed by CI. TDM demonstrated sustained plasma levels of both drugs, and the patient improved without adverse events.Conclusion: CI of ATM-AVI following a high loading dose was feasible, safe, and allowed optimized pharmacokinetic/pharmacodynamic (PK/PD) exposure while preventing drug wastage. Larger studies are warranted to determine the clinical utility of CI ATM-AVI across different MIC ranges

Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs

International audienceIn animals and fungi, bulk messenger RNA (mRNA) export to the cytoplasm is mediated by the Mex67/Mtr2 (NXF1/NXT1) heterodimer and driven by an ATP-dependent remodeling machinery on the cytoplasmic side of nuclear pore complexes, the exclusive gateways of nucleocytoplasmic transport. Uniquely, we show that trypanosomes have three distinct Mex67 paralogs (TbMex67, TbMex67b, and TbMex67L); each having a different non-redundant role in ribosomal RNA (rRNA) processing and mRNA export. Specifically, TbMex67 and TbMex67b retain canonical roles in mRNA export, albeit associating with specific mRNA cohorts and differing protein and mRNA interactomes in the vertebrate host and insect vector forms of the parasite. Further, TbMex67 and TbMex67b paralogs associate with the GTPase Ran export machinery, rather than ATP-dependent helicases, demonstrating significant departure in RNA export mechanisms in trypanosomes. In contrast, TbMex67L is not involved in mRNA export but primarily associates with ribosome biogenesis factors. Thus, in trypanosomes Mex67 paralogs have diverse functionalities with implications for evolutionary origins and diversity of the control of gene expression

Impact of Cardiac Resynchronization Therapy in Patients With Left Ventricular Assist Devices: A Systematic Review and Meta-analysis

International audienceBackground:Many patients with left ventricular assist devices (LVADs) have cardiac resynchronization therapy (CRT). However, the impact of CRT on their clinical and hemodynamic outcomes remains unclear.Methods:We conducted a systematic review and meta-analysis to evaluate CRT's impact on survival in LVAD patients. We searched PUBMED, EMBASE, and Cochrane databases from inception through April 30, 2025, for studies reporting outcomes in LVAD patients with CRT. The primary outcome was all-cause mortality in patients with versus without CRT. Secondary clinical outcomes included ventricular arrhythmias (VAs) and shocks delivered. Hemodynamic outcomes included heart rate, right atrial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, thermodilution cardiac output, pulmonary artery saturation, right ventricular stroke work index, and left ventricular end-diastolic diameter.Results:13 studies including 3,665 patients were analyzed. CRT did not demonstrate any significant survival benefit, whether comparing CRT-D versus ICD (OR 1.12 [0.85–1.48]), CRT on versus CRT off (OR 1.48 [0.87–2.53]), CRT versus no device (OR 0.99 [0.61–1.59]), or CRT versus no device or ICD (OR 1.00 [0.16–6.31]). Similarly, none of the tested comparisons showed significant differences in VAs incidence or shock rates. Biventricular pacing demonstrated no advantage for any hemodynamic outcomes, whether compared to right ventricular pacing or intrinsic rhythm.Conclusion:In this meta-analysis, CRT was not associated with overall survival benefit in LVAD recipients, nor with hemodynamic improvement. Future randomized trials may be warranted to definitively establish CRT's value in this population and refine patient selection criteria for optimal outcomes

Neoantigenic properties of TP53 variants influence cancer risk in individuals with Li-Fraumeni syndrome

International audienceBackground Li-Fraumeni Syndrome (LFS) is a heterogenous cancer predisposition condition caused by pathogenic TP53 variants, characterised by a lifelong high risk of a broad spectrum of cancers. Certain pathogenic TP53 variants have been shown be immunogenic in a somatic context. Whether neoantigenicity contributes to LFS heterogeneity is unknown. In this study we analysed the correlations between predicted neoantigenic properties of pathogenic TP53 missense variants and LFS phenotypes. MethodsMHC-I presentation scores were generated for the set of nonameric neo-peptides surrounding each TP53 missense variant against 145 different HLA-I using NetMHCpan 4.1 and the Allele Frequency Net Database. A predicted neoantigenic score (PNS) was calculated for each variant. Association study was performed between PNS, LFS presentation and individual HLA-I genotyping, in individuals carrying TP53 germline pathogenic variants using data from mutation databases and clinical registries. Genotype-phenotype data were leveraged from the public TP53 database (germline dataset, n = 3446; https://tp53.isb-cgc.org/) and two independent LFS clinical registries (n = 339). Individual correlations between HLA-I genotyping, TP53 missense variants and phenotypes were investigated in a group of 173 subjects with LFS. Findings Among individuals with frequent TP53 pathogenic variants, PNS was strongly correlated with median age at first cancer (range 18-43 years, R = 0.69, p = 0.0132). Compared to individuals with low PNS (<1) variants, those with high PNS (<1) variants showed delayed median age at first diagnosis (34 years vs. 25 years, p = 0.0009), fewer sarcomas (osteosarcoma [RR 0.29, p = 0.02]; soft-tissue [RR 0.41, p = 0.02]), and more cancer types typically not associated with LFS spectrum [RR 1.61, p = 0.02]. Interpretation MHC-I neoantigenic properties of TP53 variants are associated with differences in cancer risk and spectrum in individuals with pathogenic TP53 variants, suggesting that individual variant-specific immune response could contribute to the heterogenous presentation of LFS

Chemical inhibition of SUMOylation activates the FSHD locus

International audienceFacioscapulohumeral muscular dystrophy (FSHD) is a progressive and debilitating muscle disease for which no cure currently exists. In the majority of cases, FSHD is associated with the contraction of the D4Z4 macrosatellite repeat array at the 4q35 locus, leading to the inappropriate activation of DUX4 , normally expressed during early embryogenesis. In FSHD, the genetic contraction is accompanied by hypomethylation of the D4Z4 array. Although a connection between DNA hypomethylation and DUX4 expression has been suggested, the precise mechanisms that regulate DUX4 transcription remain incompletely defined. The post-translational modification by SUMO was shown previously to repress the expression of Dux , the DUX4 homolog, in mouse embryonic stem cells. Based on these findings, we explored here the contribution of SUMOylation in the regulation of DUX4 in human muscle cells. We demonstrate that TAK‑981 (subasumstat), a selective SUMOylation inhibitor, promotes transcriptional reprogramming of the 4q35 locus and induces DUX4 expression. Importantly, this activation occurs independently of changes in DNA methylation or SMCHD1 ATPase activity. Our findings identify SUMOylation inhibition as a novel regulatory process driving DUX4 expression. This work uncovers the importance of SUMOylation in the epigenetic control of the 4q35 locus and DUX4 transcription, providing a potential therapeutic strategy to modulate DUX4 expression in FSHD

Three- to 8-year old children do not favor male power when allocating resources

International audienceAbstract From an early age, children perceive power imbalances between genders, but their attitudes toward gendered power remain largely unexplored. We studied this issue using a resource allocation task with 653 French children aged 3–8 (50.15% girls) recruited between 2022 and 2023. Participants were exposed to a dyadic power interaction and had to distribute more resources to either the dominant or the subordinate character. We tested three hypotheses: H1 predicted a male dominance bias; H2 predicted own-gender favoritism; and H3 predicted sensitivity to hierarchical status only. Contrary to H1, no pro-male bias was found. Results supported H3: younger children favored dominant characters, while older children favored subordinates. H2 was partially supported, showing own-gender bias, stronger in girls, without overriding sensitivity to status

Regioselective C-alkylation in a series of functionalized 1,2,3-triazoles: An unexpected preference over O-alkylation

International audienceA series of novel 1,2,3-triazole derivatives were synthesized via Cu(I)-catalyzed click chemistry, introducing structural diversity at positions 1 and 4 of the triazole ring, to explore their reactivity toward alkylation. Attempts to perform O-alkylation on hydroxymethyl-substituted triazoles unexpectedly led to unreported regioselective C-alkylation at the methylene adjacent to the triazole ring. The C-alkylation was optimized using DBU and choline acetate in acetonitrile and subsequently examined across a range of alkyl and benzyl bromides to establish its scope and generality. The resulting racemic C-alkylated products were fully characterized, including confirmation of the regioselectivity by X-ray crystallography, and their enantiomers were separated by supercritical fluid chromatography. This work reveals a novel and synthetically valuable C-alkylation pathway for 1,2,3-triazoles, offering new opportunities for the development of structurally diverse and potentially bioactive triazole derivatives

Evaluating portable EEG: a comparison between two wireless systems (EPOC Flex and LiveAmp) and the wired BrainAmp system

International audienceBackground Recent advances in equipment miniaturization have led to low-cost, portable electroencephalography (EEG) systems that facilitate data collection in real-world settings and with larger samples. Although wireless EEG systems were originally developed for non-research applications, recent studies have provided valuable information to help researchers make informed choices, particularly about participant comfort, mobility during recordings, and data validity. This study aimed to assess the impact of portability by comparing the performance of portable consumer- and research-grade systems (EPOC Saline Flex, EM; LiveAmp, LA) with fixed research-grade systems (BrainAmp, BA). Method Continuous EEG was recorded with each system in healthy adults performing five benchmark tasks in fundamental and clinical cognitive neuroscience. Mental states (alpha power variations in open/closed eyes) and unconscious perception (steady-state visual evoked potential, SSVEP) were analyzed through time/frequency methods, while active (N200 and P300 components during active listening and N170 component during face recognition) and passive cognitive processes (Mismatch negativity, MMN component during passive listening) were examined using time/amplitude analyses (event-related potential, ERPs). Our analyses compared system efficiency at native and equalized sampling rates and examined 100%, 75%, and 50% of the datasets to determine the required trial number for satisfactory signal quality. Results Despite the smaller amount of signal retained for EM, all systems recorded the expected resting state alpha power decrease and SSVEP responses, with EM showing lower spectral effects ([EM < (LA≈BA)]). ERPs for active (N170, N200, P300) and passive (MMN) processes emerged across all systems, with EM and LA showing lower amplitudes only for N170 compared to BA. Furthermore, the dataset reduction resulted in a decreased N170 at P7 only for EM ([EM < LA < BA]). EM also exhibited shorter latencies for all ERPs except for MMN. Conclusion This study provides concrete guidance for designing EEG experiments in real-world settings, with significant potential for investigating children and vulnerable populations. The efficiency of the three EEG systems is more influenced by task duration than sampling rates. A wireless EEG device, such as the EM, can effectively support both time/frequency and time/amplitude analyses in cognitive science, provided that the number of trials is sufficient and latencies are controlled