Showing papers by "University of Bordeaux published in 2022"

Third dose of anti-SARS-CoV-2 vaccine for patients with cancer: Should humoral responses be monitored? A position article

Abstract: Taking into account higher risk of severe coronavirus disease 2019 or death among patients with cancer, as well as impaired immunogenicity after anti-SARS-CoV-2 vaccines, in addition to waning immunity, booster dosing appears mandatory in this patient population. This review sought to provide reasonable evidence so as to assist oncologists in their daily practice, helping them decide when an anti-SARS-Cov2 antibody (Ab) dosage should be scheduled after a full two-dose vaccination and, if necessary, propose an early third dose (D3). Such D3 could apply to non-responder patients with anti-Spike (S) Abs titres <40 binding Ab unit (BAU)/mL. For lowresponder patients with anti-S Ab titres between 40 BAU/mL and 100/260 BAU/mL (suggested area of uncertainty), an early D3 may similarly be proposed. Nevertheless, this D3 could be administered in a less urgent manner, taking into account associated comorbidities and regional epidemic incidence rates. This latter strategy may comprise a monthly dosage of anti-S titres so as to better assess the kinetics of waning immunity. For responder patients with anti-S titres above 260 BAU/mL, we suggest to follow the recommendations outlined for the general population. Given this context, patients with anti-S titres above 1000 BAU/mL should be given the possibility to undergo anti-S titre control after three months, designed to assess rapid humoral waning immunity. We strongly recommend that patients with cancer be included into observational serological monitoring studies or clinical trials that are dedicated to severe immunocompromised patients without any humoral seroconversion after D3.

An Asymmetric Sodium Extraction/Insertion Mechanism for the Fe/V-Mixed NASICON Na₄FeV(PO₄)₃

Abstract: Vanadium multi redox reactions of V4+/3+ and V5+/4+ can contribute to significant capacity gain in positive electrodes for Na-Ion batteries, but the activation of the V5+/4+ redox couple is often accompanied by asymmetric and irreversible electrochemical reactions that are very important to understand for developing high capacity materials while maintaining the structural stability. Here, the asymmetric Na+ extraction/insertion process in Fe/V-mixed NASICON Na4FeV(PO4)3 electrode material is thoroughly investigated from both local and bulk perspectives. X-ray diffraction analysis demonstrates that the Na(1) site is depopulated at the third charge domain when the V5+/4+ redox couple is activated. Local environments of Fe and V were investigated through Mössbauer and X-ray absorption spectroscopies. The results point toward the existence of a distorted VO6 octahedral environment, including a short V–O bond, when the V5+/4+ redox couple is activated at high voltage. This study presents valuable aspects of the asymmetric behavior during multielectron reactions that are commonly observed in V-based NASICON materials.

mTOR Inhibitors Prevent CMV Infection through the Restoration of Functional αβ and γδ T cells in Kidney Transplantation

Abstract: The reported association of mTOR-inhibitor (mTORi) treatment with a lower incidence of cytomegalovirus (CMV) infection in kidney transplant recipients (KTR) who are CMV seropositive (R+) remains unexplained.The incidence of CMV infection and T-cell profile was compared between KTRs treated with mTORis and mycophenolic acid (MPA), and in vitro mTORi effects on T-cell phenotype and functions were analyzed.In KTRs who were R+ and treated with MPA, both αβ and γδ T cells displayed a more dysfunctional phenotype (PD-1+, CD85j+) at day 0 of transplantation in the 16 KTRs with severe CMV infection, as compared with the 17 KTRs without or with spontaneously resolving CMV infection. In patients treated with mTORis (n=27), the proportion of PD-1+ and CD85j+ αβ and γδ T cells decreased, when compared with patients treated with MPA (n=44), as did the frequency and severity of CMV infections. mTORi treatment also led to higher proportions of late-differentiated and cytotoxic γδ T cells and IFNγ-producing and cytotoxic αβ T cells. In vitro, mTORis increased proliferation, viability, and CMV-induced IFNγ production of T cells and decreased PD-1 and CD85j expression in T cells, which shifted the T cells to a more efficient EOMESlow Hobithigh profile. In γδ T cells, the mTORi effect was related to increased TCR signaling.Severe CMV replication is associated with a dysfunctional T-cell profile and mTORis improve T-cell fitness along with better control of CMV. A dysfunctional T-cell phenotype could serve as a new biomarker to predict post-transplantation infection and to stratify patients who should benefit from mTORi treatment.Proportion of CMV Seropositive Kidney Transplant Recipients Who Will Develop a CMV Infection When Treated With an Immunosuppressive Regimen Including Everolimus and Reduced Dose of Cyclosporine Versus an Immunosuppressive Regimen With Mycophenolic Acid and Standard Dose of Cyclosporine A (EVERCMV), NCT02328963.

Efficacy and tolerance of osilodrostat in patients with Cushing’s syndrome due to adrenocortical carcinomas

Abstract: no abstract needed

The visual appearances of disordered optical metasurfaces

Abstract: Nanostructured materials have recently emerged as a promising approach for material appearance design. Research has mainly focused on creating structural colours by wave interference, leaving aside other important aspects that constitute the visual appearance of an object, such as the respective weight of specular and diffuse reflectances, object macroscopic shape, illumination and viewing conditions. Here we report the potential of disordered optical metasurfaces to harness visual appearance. We develop a multiscale modelling platform for the predictive rendering of macroscopic objects covered by metasurfaces in realistic settings, and show how nanoscale resonances and mesoscale interferences can be used to spectrally and angularly shape reflected light and thus create unusual visual effects at the macroscale. We validate this property with realistic synthetic images of macroscopic objects and centimetre-scale samples observable with the naked eye. This framework opens new perspectives in many branches of fine and applied visual arts.

Identification of constitutive equations at very high strain rates using shock wave produced by laser

Abstract: A method coupling experiments and simulations, is developed to characterize the yield stress and strain hardening of several metals loaded at 1 0 6 s − 1 and 25 ns, typically involved during Laser Shock Peening . It was applied to four materials: pure aluminum, 2024-T3 and 7175-T7351 aluminum alloys and Ti6Al4V-ELI titanium alloy . Thin foils have been irradiated with high-power laser to induce high-pressure shock wave. Plastic deformation is activated through the thickness up to the rear free-surface of the foils. These experiments have been simulated using three material constitutive equations: Elastic–Perfectly Plastic model considering static yield stress, Johnson–Cook model without strain hardening and Johnson–Cook model with strain hardening. The material parameters of Johnson–Cook law were identified by comparison of the experimental and calculated velocity profiles of the rear-free surface. Results are shown and discussed.

An Item Response Theory analysis of the Unified Multiple System Atrophy Rating Scale

Abstract: The Unified Multiple System Atrophy Rating Scale (UMSARS) has four subscales that have been specifically designed for the clinical assessment of MSA patients. UMSARS I (activities of daily living) and II (motor examination) subscales are regularly used as primary endpoints in treatment trials. The main objective of this study was to identify UMSARS I and II subscale items that best describe progression over time.All MSA patients seen at the French Reference Centre for MSA from 2007 to 2020 were included in a prospective cohort with an annual follow-up assessment including UMSARS. The repeated measures of the 26 UMSARS I and II items were analyzed using a longitudinal Item Response Theory model to identify the most informative items for each of the five UMSARS IV disease stages. Sample size estimates were further calculated for the most informative items as a group.A total of 557 MSA patients were included with a mean follow-up of 2.3 years. The majority of items progressed with disease duration or across the different UMSARS IV disability stages, with the exception of those related to dysautonomia. Roughly 70% of the scale information was carried by only 11/26 items, many reflecting the patient perspective. These yielded similar sample size estimates than UMSARS I + II items.This study provides important information about the progression of UMSARS I and II subscale items. Improvements seem particularly necessary regarding those assessing dysautonomia. A shortened scale may be useful as outcome for future clinical trials.

Rectal cancer radiotherapy

Abstract: We present the updated recommendations of the French society of oncological radiotherapy for rectal cancer radiotherapy. The standard treatment for locally advanced rectal cancer consists in chemoradiotherapy followed by radical surgery with total mesorectal resection and adjuvant chemotherapy according to nodal status. Although this strategy efficiently reduced local recurrences rates below 5% in expert centres, functional sequelae could not be avoided resulting in 20 to 30% morbidity rates. The early introduction of neoadjuvant chemotherapy has proven beneficial in recent trials, in terms of recurrence free and metastasis free survivals. Complete pathological responses were obtained in 15% of tumours treated by chemoradiation, even reaching up to 30% of tumours when neoadjuvant chemotherapy is associated to chemoradiotherapy. These good results question the relevance of systematic radical surgery in good responders. Personalized therapeutic strategies are now possible by improved imaging modalities with circumferential margin assessed by magnetic resonance imaging, by intensity modulated radiotherapy and by refining surgical techniques, and contribute to morbidity reduction. Keeping the same objectives, ongoing trials are now evaluating therapeutic de-escalation strategies, in particular rectal preservation for good responders after neoadjuvant treatment, or radiotherapy omission in selected cases (Greccar 12, Opera, Norad).

N-3 PUFA deficiency disrupts oligodendrocyte maturation and myelin integrity during brain development.

Abstract: Westernization of dietary habits has led to a progressive reduction in dietary intake of n-3 polyunsaturated fatty acids (n-3 PUFAs). Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental disorders, conditions in which myelination processes are abnormal, leading to defects in brain functional connectivity. Only little is known about the role of n-3 PUFAs in oligodendrocyte physiology and white matter development. Here, we show that lifelong n-3 PUFA deficiency disrupts oligodendrocytes maturation and myelination processes during the postnatal period in mice. This has long-term deleterious consequences on white matter organization and hippocampus-prefrontal functional connectivity in adults, associated with cognitive and emotional disorders. Promoting developmental myelination with clemastine, a first-generation histamine antagonist and enhancer of oligodendrocyte precursor cell differentiation, rescues memory deficits in n-3 PUFA deficient animals. Our findings identify a novel mechanism through which n-3 PUFA deficiency alters brain functions by disrupting oligodendrocyte maturation and brain myelination during the neurodevelopmental period.

Linkage of impact pathways to cultural perspectives to account for multiple aspects of mineral resource use in life cycle assessment

Abstract: Important advances have been made to define the multiple impact pathways relating mineral resource use to the area of protection (AoP) natural resources in life cycle assessment (LCA). Yet, the link between stakeholders’ interests and the aspects relevant to resource use as addressed by existing impact assessment methods has so far only marginally been explored. This article proposes to go beyond the case-specific determination of stakeholders’ interests (and the associated selection of impact assessment method) by defining multiple groups of different values based on cultural perspectives, in order to determine the corresponding relevant impact pathways and assessment methods. Relying on the Cultural Theory and related potential development scenarios, we identify socio-economic objectives and resource management strategies that fit the egalitarian, individualist and hierarchist perspectives. Our analysis reveals that different aspects of resource use may be most relevant to assess for each perspective since they pursue different socio-economic objectives. Egalitarians are expected to prioritize the long-term availability of geological stocks for future generations by keeping extraction flows to a minimum to reach global sufficiency, and individualists, to safeguard their short-term accessibility to resources by managing their supply risk. Hierarchists are likely to aim to maximize the value obtained from resources globally, and could thus focus on addressing dissipative flows. Building on this analysis, we provide a proposal for a more holistic assessment of the impact pathways linked to mineral resource use using existing LCIA methods, and identify ways forward for method developments to come.

Multi-scale deterministic optimisation of blended composite structures: case study of a box-wing

Abstract: This work presents a multi-scale design methodology for the deterministic optimisation of thin-walled composite structures integrating a global–local approach for the assessment of the buckling strength and a dedicated strategy to recover blended stacking sequences. The methodology is based on the multi-scale two-level optimisation strategy for anisotropic materials and structures. In the first step, focused on the macroscopic scale, several design requirements are included in the problem formulation: lightness, feasibility, manufacturing, blending, buckling failure, static failure and stiffness. The second step, which focuses on the laminate mesoscopic scale, deals with the recovery of blended stacking sequences, for the structure at hand, matching the optimal geometric and elastic properties determined in the first step. As a case study, the unconventional PrandtlPlane box-wing system is used to show the effectiveness of the proposed design methodology.

Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward

Abstract: Psychostimulant exposure alters the activity of ventral pallidum (VP) projection neurons. However, the molecular underpinnings of these circuit dysfunctions are unclear. We used RNA-sequencing to reveal alterations in the transcriptional landscape of the VP that are induced by cocaine self-administration in mice. We then probed gene expression in select VP neuronal subpopulations to isolate a circuit associated with cocaine intake. Finally, we used both overexpression and CRISPR-mediated knockdown to test the role of a gene target on cocaine-mediated behaviors as well as dendritic spine density. Our results showed that a large proportion (55%) of genes associated with structural plasticity were changed 24 h following cocaine intake. Among them, the transcription factor Nr4a1 (Nuclear receptor subfamily 4, group A, member 1, or Nur77) showed high expression levels. We found that the VP to mediodorsal thalamus (VP → MDT) projection neurons specifically were recapitulating this increase in Nr4a1 expression. Overexpressing Nr4a1 in VP → MDT neurons enhanced drug-seeking and drug-induced reinstatement, while Nr4a1 knockdown prevented self-administration acquisition and subsequent cocaine-mediated behaviors. Moreover, we showed that Nr4a1 negatively regulated spine dynamics in this specific cell subpopulation. Together, our study identifies for the first time the transcriptional mechanisms occurring in VP in drug exposure. Our study provides further understanding on the role of Nr4a1 in cocaine-related behaviors and identifies the crucial role of the VP → MDT circuit in drug intake and relapse-like behaviors.