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Abstract Several studies have demonstrated the existence of a link between action observation (AO) and language. However, the optimizing parameters for this link have not been explored until now. To answer this question, the present study proposed two experiments for assessing the role of motor repertory and attentional focus. Sixty participants performed a priming task in which they had to decide if a verb was or was not an action verb after they saw a point-light display (PLD) representing an action. Only one difference distinguished the experiments. In experiment one, the PLD was either in accordance or not with the gender kinematics of the observer, whereas in the second experiment, the PLD either focused on or was unfocused on the main limbs implied in the action. The results show that motor repertory affects the link between action observation and action verb processing, whereas attentional focus does not. Implications of these results are highlighted in the discussion, notably to better understand the mechanisms that explain the link between action observation and action verb processing.

Qualitative research has been strongly affected by the COVID-19 pandemic, highlighting the possibilities that Voice over Internet Protocol (VoIP) technologies such as Skype, WhatsApp, and Zoom offer to qualitative scholars. Based on the experience of using such technologies to collect qualitative data for our PhD studies, we present how we dealt with the challenges of this interview mode. Precisely, we discuss problems related to rapport, technology, digital exclusion, and ethics frequently pointed out in the methodological literature on online interviews. Thereby we put forward strategies and techniques that helped us to 1) build a rapport, 2) manage technical difficulties, 3) reflect on risks of digital exclusion, and 4) comply with the ethical standards of our institution. In doing so, we draw on our qualitative data to support the arguments. The aim of this paper is, thus, to deepen the methodological debate on online interviews in social sciences.

Abstract Sequence‐specific endonucleases have been key to the study of the mechanisms and control of DNA double‐strand break (DSB) repair and recombination, and the availability of CRISPR‐Cas nucleases over the last decade has driven rapid progress in the understanding and application of targeted recombination in many organisms, including plants. We present here an analysis of recombination at targeted chromosomal 5′ overhang DSB generated by the FnCas12a endonuclease in the plant, Arabidopsis thaliana. The much‐studied Cas9 nuclease cleaves DNA to generate blunt‐ended DSBs, but relatively less is known about the repair of other types of breaks, such as those with 5′‐overhanging ends. Sequencing the repaired breaks clearly shows that the majority of repaired DSB carry small deletions and are thus repaired locally by end‐joining recombination, confirmed by Nanopore sequencing of larger amplicons. Paired DSBs generate deletions at one or both cut‐sites, as well as deletions and reinsertions of the deleted segment between the two cuts, visible as inversions. While differences are seen in the details, overall the deletion patterns are similar between repair at single‐cut and double‐cut events, notwithstanding the fact that only the former involve cohesive DNA overhangs. A strikingly different repair pattern is however observed at breaks flanked by direct repeats. This change in sequence context results in the presence of a major alternative class of repair events, corresponding to highly efficient repair by single‐strand annealing recombination.

Extraintestinal pathogenic Escherichia coli and Streptococcus agalactiae are bacterial pathogens that commonly cause early-onset neonatal sepsis (EOS) in industrialized countries. EOS is confirmed by a blood or cerebrospinal fluid culture [...]

Abstract Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1 +AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1, RUNX1 and NPM1. Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1 +AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50–91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1 +AML, CML-BP, 2017 ELN intermediate (n = 643) and adverse-risk patients (n = 863) showed that patients with BCR::ABL1 +AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1 +AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.

Using whole-genome sequencing, we characterized Escherichia coli strains causing early-onset sepsis (EOS) in 32 neonatal cases from a 2019–2021 prospective multicenter study in France and compared them to E. coli strains collected from vaginal swab specimens from women in third-trimester gestation. We observed no major differences in phylogenetic groups or virulence profiles between the 2 collections. However, sequence type (ST) analysis showed the presence of 6/32 (19%) ST1193 strains causing EOS, the same frequency as in the highly virulent clonal group ST95. Three ST1193 strains caused meningitis, and 3 harbored extended-spectrum β-lactamase. No ST1193 strains were isolated from vaginal swab specimens. Emerging ST1193 appears to be highly prevalent, virulent, and antimicrobial resistant in neonates. However, the physiopathology of EOS caused by ST1193 has not yet been elucidated. Clinicians should be aware of the possible presence of E. coli ST1193 in prenatal and neonatal contexts and provide appropriate monitoring and treatment.

Background Engineered arenavirus vectors have recently been developed to leverage the body’s immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized.Methods To advance our understanding of the immunobiology of these two vectors, we analyzed and compared their individual properties in preclinical in vivo and in vitro systems. Immunogenicity and antitumor effect of intratumoral or intravenous administration of both vectors, as well as combination with NKG2A blockade, were evaluated in naïve or TC-1 mouse tumor models. Flow cytometry, Nanostring, and histology analysis were performed to characterize the tumor microenvironment (TME) and T-cell infiltrate following treatment.Results Despite being phylogenetically distant, both vectors shared many properties, including preferential infection and activation of professional antigen-presenting cells, and induction of potent tumor-specific CD8+ T-cell responses. Systemic as well as localized treatment induced a proinflammatory shift in the TME, promoting the infiltration of inducible T cell costimulator (ICOS)+CD8+ T cells capable of mediating tumor regression and prolonging survival in a TC-1 mouse tumor model. Still, there was evidence of immunosuppression built-up over time, and increased expression of H2-T23 (ligand for NKG2A T cell inhibitory receptor) following treatment was identified as a potential contributing factor. NKG2A blockade improved the antitumor efficacy of artARENA vectors, suggesting a promising new combination approach. This demonstrates how detailed characterization of arenavirus vector-induced immune responses and TME modulation can inform novel combination therapies.Conclusions The artARENA platform represents a strong therapeutic vaccine approach for the treatment of cancer. The induced antitumor immune response builds the backbone for novel combination therapies, which warrant further investigation.

Arenavirus-based vectors are being investigated as therapeutic vaccine candidates with the potential to elicit robust CD8 T-cell responses. We compared the immunogenicity of replicating (artPICV and artLCMV) and non-replicating (rPICV and rLCMV) arenavirus-based vectors expressing simian immunodeficiency virus (SIV) Gag and Envelope (Env) immunogens in treatment-naïve non-human primates. Heterologous regimens with non-replicating and replicating vectors elicited more robust SIV IFN-γ responses than a homologous regimen, and replicating vectors elicited significantly higher cellular immunogenicity than non-replicating vectors. The heterologous regimen elicited high anti-Env antibody titers when administered intravenously, with replicating vectors inducing significantly higher titers than non-replicating vectors. Intramuscular immunization resulted in more durable antibody responses than intravenous immunization for both vector platforms, with no difference between the replicating and non-replicating vectors. Overall, both replicating and non-replicating arenavirus vectors generated robust T- and B-cell-mediated immunity to SIV antigens in treatment-naïve non-human primates, supporting further evaluation of these vectors in a clinical setting for HIV therapy.

Abstract Background PTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples. We report a PHTS patient with no variant identified from blood sample. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral samples. Case presentation Our patient presented clinical Cowden syndrome at 56 years of age, with three major criteria (macrocephaly, Lhermitte Duclos disease, oral papillomatosis), and two minor criteria (structural thyroid lesions, esophageal glycogenic acanthosis). Deep sequencing of PTEN of blood leukocytes did not reveal any pathogenic variants. Exploration of tumoral (colonic ganglioneuroma, esophageal papilloma, diapneusia fibroids) and non-tumoral stomach tissues found the same PTEN pathogenic variant (NM_000314.4 c.389G > A; p.(Arg130Gln)), with an allelic frequency of 12 to 59%, confirming genomic mosaicism for Cowden syndrome. Conclusions This case report, and review of the literature, suggests that systematic tumor analysis is essential for patients presenting PTEN hamartoma syndrome in the absence of any causal variant identified in blood leukocytes, despite deep sequencing. In 65 to 70% of cases of clinical Cowden syndrome, no pathogenic variant in the PTEN is observed in blood samples: mosaicism may explain a significant number of these patients. Tumor analysis would improve our knowledge of the frequency of de novo variations in this syndrome. Finally, patients with mosaicism for PTEN may not have a mild phenotype; medical care identical to that of heterozygous carriers should be offered.

Abstract Background Group A streptococcus is found in 20–40% of cases of childhood pharyngitis; the remaining cases are viral. Streptococcal pharyngitis (“strep throat”) is usually treated with antibiotics, while these are not indicated in viral cases. Most guidelines recommend relying on a diagnostic test confirming the presence of group A streptococcus before prescribing antibiotics. Conventional first-line tests are rapid antigen detection tests based on throat swabs. Recently, rapid nucleic acid tests were developed; they allow the detection of elements of the genome of group A streptococcus. We hypothesize that these rapid nucleic acid tests are sensitive enough to be performed on saliva samples instead of throat swabs, which could be more convenient in practice. Methods This is a multicenter, prospective diagnostic accuracy study evaluating the performance of a rapid nucleic acid test for group A streptococcus (Abbott ID NOW STREP A2) in saliva, compared with a conventional pharyngeal rapid antigen detection test (EXACTO PRO STREPTATEST, lateral flow assay, comparator test), with a composite reference standard of throat culture and group A streptococcus PCR in children with pharyngitis in primary care (i.e., 27 primary care pediatricians or general practitioners). To ensure group A streptococcus is not missed, the salivary rapid nucleic acid test requires a minimally acceptable value of sensitivity (primary outcome) set at 80%. Assuming 35% of participants will have group A streptococcus, we will recruit 800 consecutive children with pharyngitis. Secondary outcomes will include difference in sensitivity between the pharyngeal rapid antigen detection test and the salivary rapid nucleic acid test; variability in sensitivity and specificity of the salivary rapid nucleic acid test with the level of McIsaac score; time to obtain the result of the salivary rapid nucleic acid test; patient, physician, and parents satisfaction; and barriers and facilitators to using rapid tests for group A streptococcus in primary care. Ethics and dissemination Approved by the Institutional Review Board “Comité de protection des personnes Ile de France I” (no. 2022-A00085-38). Results will be presented at international meetings and disseminated in peer-reviewed journals. Trial registration number ClinicalTrials.gov: NCT05521568.

Abstract Background Acute myeloid leukemia (AML) with myelodysplasia‐related characteristics is a heterogeneous subset of AML that has been challenged throughout the history of myeloid malignancies classifications, considered to have similar outcomes as intermediate‐ or adverse‐risk AML depending on the subgroup. However, little is known about the fate of these patients in refractory or relapsed situation (R/R) after first line therapy. Methods A large series of R/R AML patients, recorded in the French DATAML registry, have received either intensive chemotherapy (ICT), azacitidine (AZA) as single agent, or best supportive care (BSC). A cohort of 183 patients (median age 63‐year‐old) with what was called at the time AML‐MRC has been explored, and data are reported here. Results Patient status was refractory for 93, while 90 had relapsed. Respectively, 88, 34, and 61 were included in the three treatment arms. The median OS of the whole cohort was 4.2 months (95%CI: 3.1–5.6) with a mean 1‐year overall survival of 24% ± 3.2%. There was no significant survival difference between refractory and relapsed patients. The BSC group had overall a significantly worse outcome (p = 0.0001), and this remained true in both refractory (p = 0.01) and relapsed (p = 0.002) patients. Similar survivals were observed in both groups comparing ICT and AZA. Conclusions These data, reporting about an ill‐explored population, indicate the poor prognosis of this condition where both ICT and AZA can be proposed. The latter, which was demonstrated here to be a feasible option, should be added to new targeted therapies.

Several studies have shown that the acquisition of number meaning is related to finger motor representations. However, no study has tried to distinguish the respective roles of fingers representation and finger kinematics in this effect. Forty-three children (23 boys and 20 girls) enrolled in the middle class of kindergarten took part in the study. They were divided into two equivalent groups and compared on the acquisition of number meaning after a 2-week program designed to teach them a song about the numbers 1–9, scaffolded by visual supports. Each visual support included the symbolic representation of the number, the picture of an object mentioned in the song that rhymed with the number in French, and either a static image (static group) or an animated point-light display (animated group) of the finger representation. Results showed no difference between the two groups on the acquisition of numbers regarded as low (i.e., less than 5) but the animated group performed significantly better for numbers regarded as high (i.e., more than 5). Therefore, the present study shows the interest of using the observation of animated counting movement to teach number meaning in young children and suggests that finger kinematics may be more instrumental than static finger representation in the learning of number meaning. Future research is needed to confirm and specify this effect.

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

We report fatal meningitis in 2 neonates in France caused by Shiga toxin 1–producing Escherichia coli. Virulence factors capsular K1 antigen and salmochelin were present in both strains, potentially representing a new hybrid pathotype. Clinicians should remain aware of emerging pathotypes and design therapeutic strategies for neonatal E. coli infections.

The Mutehekau Shipu or Magpie is the third river in the world to become a legal entity under international law. It flows through Quebec's North Shore into the St. Lawrence River. Reacting to the fate of its "big sister", the nearby Romaine River, which has just been harnessed by four large hydroelectric dams, the Magpie's destiny had other plans: it has been protected as a legal person since 2021. On a regional and Quebec scale, this is a first that testifies to a synergy between natives (Innu) and non-natives, a strategy of environment and decolonization; on an international scale, it is a third that refers to a paradigm shift and an environmental genuine ontological turning point. This case study is illuminated by the fieldwork and stories collected.

The objective of this study was to assess the clinical impact and financial costs of next-generation sequencing (NGS) in 5 categories of pediatric and adult hematological cancers. NGS prescriptions were prospectively collected from 26 laboratories, with varied technical and reporting practice (all or only significant targets). Impact was defined by the identification of (1) an actionable mutation, (2) a mutation with prognostic and/or theranostic value, and/or (3) a mutation allowing nosological refinement, reported by local investigators. A microcosting study was undertaken in 4 laboratories, identifying the types and volumes of resources required for each procedural step. Individual index prescriptions for 3961 patients were available for impact analysis on the management of myeloid disorders (two thirds) and, mainly mature B, lymphoid disorders (one third). NGS results were considered to impact the management for 73.4% of prescriptions: useful for evaluation of prognostic risk in 34.9% and necessary for treatment adaptation (actionable) in 19.6%, but having no immediate individual therapeutic impact in 18.9%. The average overall cost per sample was 191 € for the restricted mature lymphoid amplicon panel. Capture panel costs varied from 369 € to 513 €. Unit costs varied from 0.5 € to 5.7 € per kb sequenced, from 3.6 € to 11.3 € per target gene/hot-spot sequenced and from 4.3 € to 73.8 € per target gene/hot-spot reported. Comparable costs for the Amplicon panels were 5–8 € per kb and 10.5–14.7 € per target gene/hot-spot sequenced and reported, demonstrating comparable costs with greater informativity/flexibility for capture strategies. Sustainable funding of precision medicine requires a transparent discussion of its impact on care pathways and its financial aspects.