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Early-life stages play a key role in the dynamics of bipartite life cycle marine fish populations. Difficult to monitor, observations of these stages are often scattered in space and time. While Mediterranean coastlines have often been surveyed, no effort has been made to assemble historical observations. Here we build an exhaustive compilation of dispersal traits for coastal fish species, considering in situ observations and growth models (Di Stefano et al., 2023; https://doi.org/10.17882/91148). Our database contains over 110 000 entries collected from 1993 to 2021 in various subregions. All observations are harmonized to provide information on dates and geolocations of both spawning and settlement, along with pelagic larval durations. When applicable, missing data and associated confidence intervals are reconstructed from dynamic energy budget theory. Statistical analyses allow traits’ variability to be revisited and sampling biases to be revealed across taxa, space and time, hence providing recommendations for future studies and sampling. Comparison of observed and modelled entries provides suggestions to improve the feed of observations into models. Overall, this extensive database is a crucial step to investigate how marine fish populations respond to global changes across environmental gradients.

We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform.

Slow paced breathing via heart rate variability (HRV) biofeedback stimulates vagus-nerve pathways that counter noradrenergic stress and arousal pathways that can influence production and clearance of Alzheimer's disease (AD)-related proteins. Thus, we examined whether HRV biofeedback intervention affects plasma Αβ40, Αβ42, total tau (tTau), and phosphorylated tau-181 (pTau-181) levels. We randomized healthy adults (N = 108) to use slow-paced breathing with HRV biofeedback to increase heart rate oscillations (Osc+) or to use personalized strategies with HRV biofeedback to decrease heart rate oscillations (Osc-). They practiced 20-40 min daily. Four weeks of practicing the Osc+ and Osc- conditions produced large effect size differences in change in plasma Aβ40 and Aβ42 levels. The Osc+ condition decreased plasma Αβ while the Osc- condition increased Αβ. Decreases in Αβ were associated with decreases in gene transcription indicators of β-adrenergic signaling, linking effects to the noradrenergic system. There were also opposing effects of the Osc+ and Osc- interventions on tTau for younger adults and pTau-181 for older adults. These results provide novel data supporting a causal role of autonomic activity in modulating plasma AD-related biomarkers.Trial registration: NCT03458910 (ClinicalTrials.gov); first posted on 03/08/2018.

Abstract We recently reported the properties of RNA hairpins constrained by a dimethylene (DME) disulfide (S−S) linker incorporated between two adjacent nucleosides in the loop and showed that this linker locked the hairpin conformation thus disturbing the duplex/hairpin equilibrium. We have now investigated the influence of the length of the linker and synthesized oligoribonucleotides containing diethylene (DEE) and dipropylene (DPE) S−S bridges. This was achieved via the preparation of building blocks, namely 2′‐O‐acetylthioethyl (2′‐O‐AcSE) and 2′‐O‐acetylthiopropyl (2′‐O‐AcSP) uridine phosphoramidites, which were successfully incorporated into RNA sequences. Thermal denaturation analysis revealed that the DEE and DPE disulfide bridges destabilize RNA duplexes but do not disrupt the hairpin conformation. Furthermore, our investigation of the duplex/hairpin equilibrium indicated that sequences modified with DME and DEE S−S linkers predominantly lock the hairpin form, whereas the DPE S−S linker provides flexibility. These findings highlight the potential of S−S linkers to study RNA interactions.

Abstract The real‐life retrospective observational study CARMYN aimed at investigating the long‐term efficacy and safety of carfilzomib in combination with dexamethasone and lenalidomide (KRd, 159 patients). These patients (62% in first and 38% in second relapse, median age 62 yo) were treated between 02/2014 and 02/2017. Most had been pre‐exposed to bortezomib (98.2%) and to an IMID (75.4%). At the time of collection, 90% had permanently discontinued carfilzomib. Data collection was conducted from January to July 2021 in 27 participating sites, after a median of 39 months follow‐up. For patients treated with KRd, an overall response rate of 78.4% translated in a median progression free survival (PFS) of 24.0 months (95% CI 18.8–27.6) and a median overall survival (OS) of 51.1 months (95% CI 41.3–not reached). Results were poorer but difficult to interpret in the small cohort of Kd recipients. The study is one of the longest real‐life studies of carfilzomib treatment in patients in first or second relapse. CARMYN confirmed the real‐life long‐term efficacy of carfilzomib in combination with lenalidomide and dexamethasone with results similar to those of clinical trials. The KRd regimen is thus an option to consider for late relapses in the current context of MM management.

Background: The 2019 coronavirus disease (COVID-19) pandemic induced a major health crisis worldwide, notably among end-stage kidney disease (ESKD) patients. Vaccination against SARS-CoV-2, especially with messenger RNA (mRNA) vaccines, is highly effective and reduces hospitalization and mortality in both the general and ESKD populations. Age and previous COVID-19 infection have been identified as major determinants of the vaccine response in both the general population and ESKD patients. Methods: To determine the specific phenotype of ESKD patients in relation to their vaccine response, a clustering approach was used in a cohort of 117 fully vaccinated patients. Results: Clustering revealed three distinct clinical phenotypes among hemodialysis patients in terms of immunological response. Two clusters, consisting of either women with a long dialysis history or male subjects with diabetes with a moderate history of dialysis, exhibited low levels of IgG anti-spike antibodies. The third cluster consisted of non-diabetic middle-aged men with a moderate dialysis vintage and a very good serological response to vaccination. Conclusions: These vaccinal phenotypes of dialysis patients are easily identifiable in current practice, allowing for differential serological follow-up and tailored booster SARS-CoV-2 vaccination.

Abstract We present data from the Heart Rate Variability and Emotion Regulation (HRV-ER) randomized clinical trial testing effects of HRV biofeedback. Younger (N = 121) and older (N = 72) participants completed baseline magnetic resonance imaging (MRI) including T1-weighted, resting and emotion regulation task functional MRI (fMRI), pulsed continuous arterial spin labeling (PCASL), and proton magnetic resonance spectroscopy (1H MRS). During fMRI scans, physiological measures (blood pressure, pulse, respiration, and end-tidal CO2) were continuously acquired. Participants were randomized to either increase heart rate oscillations or decrease heart rate oscillations during daily sessions. After 5 weeks of HRV biofeedback, they repeated the baseline measurements in addition to new measures (ultimatum game fMRI, training mimicking during blood oxygen level dependent (BOLD) and PCASL fMRI). Participants also wore a wristband sensor to estimate sleep time. Psychological assessment comprised three cognitive tests and ten questionnaires related to emotional well-being. A subset (N = 104) provided plasma samples pre- and post-intervention that were assayed for amyloid and tau. Data is publicly available via the OpenNeuro data sharing platform.

Total avulsion of the scalp is a serious traumatic injury and an absolute surgical emergency. Despite well-stocked literature on its immediate care, there is insufficient literature regarding its long-term complications. Here, we describe the case of a patient who developed chronic pain 24 months after replantation. The patient underwent several needle rigotomy sessions associated with lipofilling to reconstruct a sliding plane between the scalp and periosteum, followed by nanofat sessions to improve skin elasticity. This autologous fat injection treatment was successful, and the patient is currently pain-free. Therefore, lipofilling followed by nanofat injection is an effective treatment for this complication.

O texto visa apresentar o debate ocorrido entre Jürgen Haberntas e John Rawls no âmbito do The Journal of Philosophy (Vol. XCll, n. 3. Março de 1995). Neste, Habermas publicou um artigo, intitulado “Reconciliação mediante o uso da razão pública: notas sobre o liberalismo político de John Rawls” , no qual efetuava uma crítica das principais posições de Rawts desde a publicação de Uma teoria d Justiça (1971) . Em primeiro lugar, questiona a validade da posição original como fundamentação do caráter deontológico da justiça. Em segundo lugar, afirma que Rawls confunde“ aceitação” com “aceitabilidade”, no que concerne ao “ overtaping consensus” ,. Em terceiro lugar, Rawls privitegiaria os direitos básicos liberais sobre o princípio democrático. Por faz uma avaliação do papel que cabe à Filosofia política no contexto atual “pós-metafísico”. Neste artigo, procuro responder a cada tinta dessas objeções, apoiando-me em escritos de Rawls, inclusive sua “Réplica a Habermas ” , publicada no mesmo Journal.

Objective This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients.Design Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry.Setting Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France.Participants This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020.Primary outcome measures Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave).Results The first medical contact procedure time was longer for elderly (p

IntroductionCombination molecular BRAF/MEK inhibitors targeted therapy has been shown to improve overall survival in patients with BRAF V600 mutated unresectable or metastatic melanoma. Most patients treated with BRAF/MEK inhibitors will experience adverse events but neurological adverse events (nAEs) remain rare.Case reportA 42-year-old woman diagnosed with metastatic melanoma presented with an intense pain in the left shoulder 7 days after the beginning of encorafenib/binimetinib after immune checkpoint inhibitors (ICI) combination. No other triggering factors were identified. Electromyogram performed one month after the pain onset revealed a left brachial plexopathy suggestive of a Parsonage-Turner syndrome. The weakness slowly improved with intensive rehabilitation and targeted therapies were continued.ConclusionWe report the first case of Parsonage-Turner syndrome in a melanoma patient treated with encorafenib/binimetinib following checkpoint inhibitors combination.We cannot rule out the implication of ICI in the development of this syndrome but the rapid onset of the symptoms after the beginning of targeted therapies makes their involvment more likely.Given the increased use of BRAF/MEK inhibitors in managing of stage III and IV melanoma, as well as the development in stage II, clinicians should be aware of this potential side effect.

Abstract Slow paced breathing via heart rate variability (HRV) biofeedback stimulates vagus-nerve pathways that counter noradrenergic stress and arousal pathways that can influence production and clearance of Alzheimer's disease (AD)-related proteins. Thus, we examined whether HRV biofeedback intervention affects plasma Αβ40, Αβ42, total tau (tTau), and phosphorylated tau-181 (pTau-181) levels. We randomized healthy adults (N = 108) to use slow-paced breathing with HRV biofeedback to increase heart rate oscillations (Osc+) or to use personalized strategies with HRV biofeedback to decrease heart rate oscillations (Osc−). They practiced 20–40 min daily. Four weeks of practicing the Osc+ and Osc− conditions produced large effect size differences in change in plasma Aβ40 and Aβ42 levels. The Osc+ condition decreased plasma Αβ while the Osc− condition increased Αβ. Decreases in Αβ were associated with decreases in gene transcription indicators of β-adrenergic signaling, linking effects to the noradrenergic system. There were also opposing effects of the Osc+ and Osc− interventions on tTau for younger adults and pTau-181 for older adults. These results provide novel data supporting a causal role of autonomic activity in modulating plasma AD-related biomarkers. Trial registration: NCT03458910 (ClinicalTrials.gov); first posted on 03/08/2018.

Abstract Background Epidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT). Methods Within a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences. Results Median age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045). Conclusion EGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis.

Bordetella pertussis is a highly contagious respiratory pathogen responsible for whooping-cough or pertussis. Despite high vaccination coverage worldwide, this gram-negative bacterium continues to spread among the population. B. pertussis is transmitted by aerosol droplets from an infected individual to a new host and will colonize its upper respiratory tract. Alveolar macrophages (AMs) are effector cells of the innate immune system that phagocytose B. pertussis and secrete both pro-inflammatory and antimicrobial mediators in the lungs. However, understanding their role in B. pertussis pathogenesis at the molecular level is hampered by the limited number of primary AMs that can be collected in vivo. In order to decipher the regulation of innate response induced by B. pertussis infection, we used for the first time self-renewing, non-transformed cells, called Max Planck Institute (MPI) cells, which are phenotypically and functionally very close to pulmonary AMs. Using optimized infection conditions, we characterized the entry and the clearance of B. pertussis within MPI macrophages. We showed that under these conditions, MPI cells exhibit a pro-inflammatory phenotype with the production of TNF, IL-1β, IL-6 and MIP-2α, similarly to primary AMs purified from broncho-alveolar fluids of mice. In addition, we explored the yet uncharacterized role of the signal transduction activator of transcription (STAT) proteins family in the innate immune response to B. pertussis infection and showed for the first time the parallel regulation of pro-inflammatory cytokines by STAT3 and STAT5 in MPI macrophages infected by B. pertussis. Altogether, this work highlights the interest of using MPI cells for experiments optimization and preliminary data acquisition to understand B. pertussis interaction with AMs, and thus significantly reduce the number of animals to be sacrificed.

Background Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM).Objectives To assess the significance of DH/BS in patients with IM.Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1.Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p

Abstract Background Benzamide-based radioligands targeting melanin were first developed for imaging melanoma and then for therapeutic purpose with targeted radionuclide therapy (TRT). [131I]ICF01012 presents a highly favorable pharmacokinetics profile in vivo for therapy. Tumour growth reduction and increase survival have been established in preclinical models of melanoma. According the these preclinical results, we initiate a first-in-human study aimed to determine the recommended dose of [131I]ICF01012 to administer for the treatment of patients with pigmented metastatic melanoma. Methods The MELRIV-1 trial is an open-label, multicentric, dose-escalation phase I trial. The study is divided in 2 steps, a selection part with an IV injection of low activity of [131I]ICF01012 (185 MBq at D0) to select patients who might benefit from [131I]ICF01012 TRT in therapeutic part, i.e. patient presenting at least one tumour lesion with [131I]ICF01012 uptake and an acceptable personalized dosimetry to critical organs (liver, kidney, lung and retina). According to dose escalation scheme driven by a Continual Reassessment Method (CRM) design, a single therapeutic injection of 800 MBq/m2, or 1600 MBq/m2, or 2700 MBq/m2 or 4000 MBq/m2 of [131I]ICF01012 will be administered at D11 (± 4 days). The primary endpoint is the recommended therapeutic dose of [131I]ICF01012, with DLT defined as any grade 3-4 NCI-CT toxicity during the 6 weeks following therapeutic dose. Safety, pharmacokinetic, biodistribution (using planar whole body and SPECT-CT acquisitions), sensitivity / specificity of [131I]ICF01012, and therapeutic efficacy will be assessed as secondary objectives. Patients who received therapeutic injection will be followed until 3 months after TRT. Since 6 to 18 patients are needed for the therapeutic part, up to 36 patients will be enrolled in the selection part. Discussion This study is a first-in-human trial evaluating the [131I]ICF01012 TRT in metastatic malignant melanomas with a diagnostic dose of the [131I]ICF01012 to select the patients who may benefit from a therapeutic dose of [131I]ICF01012, with at least one tumor lesion with [131I]ICF01012 uptake and an acceptable AD to healthy organ. Trial registration Clinicaltrials.gov : NCT03784625 . Registered on December 24, 2018. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2016-002444-17.

BackgroundConflict affected populations, in particular women in such settings, face an increased risk of developing mental health disorders as well as well as economic vulnerability and reduced productivity. However, the link between the two has rarely been studied.Data and methodsThe data in this paper come from a cross-sectional dataset (n = 1053) and a panel dataset of (n = 499) women suffering from post-traumatic stress disorder (PTSD) in eastern Democratic Republic of the Congo. This paper investigates the association between mental health disorders (PTSD, depression and/or anxiety) and employment for women in a conflict-affected setting.ResultsThe study finds that worsened local functioning is associated with reduced likelihood of working, earnings, and engagement in paid work. Reduction in probable depression and/or anxiety and PTSD are both associated with increased likelihood of engaging in paid work compared to unpaid work. Reduction in probable depression and/or anxiety is also associated with engaging in a secondary economic activity, as well as with higher productivity. However, when controlling for daily (local) functioning impairment, the primary pathway through which mental health may impact working, we detect a positive relationship between work or working hours and increased symptoms of PTSD and depression and/or anxiety. Working women with worse PTSD and depression and/or anxiety symptoms are also less likely to be self-employed, especially in an off-farm setting, and more likely to be engaged in farming.ConclusionA complex relationship between working and mental health emerges. Our findings also suggest that in this population farming, particularly farm-based wage work, is positively associated with worse mental health even after accounting for wealth and other relevant socio-demographic factors. These findings highlight the importance of paying close attention to the mental health of beneficiaries of livelihood support projects in post-conflict settings, where the relationship between mental health and employment is not straightforward.

Introduction The management of mid and low rectal cancer is based on neoadjuvant chemoradiotherapy (CRT) followed by standardised surgery. There is no biomarker in rectal cancer to aid clinicians in foreseeing treatment response. The determination of factors associated with treatment response might allow the identification of patients who require tailored strategies (eg, therapeutic de-escalation or intensification). Colibactin-producing Escherichia coli (CoPEC) has been associated with aggressive colorectal cancer and could be a poor prognostic factor. Currently, no study has evaluated the potential association between intestinal microbiota composition and tumour response to CRT in mid and low rectal cancer. The aim of this study is to assess the association between response to neoadjuvant CRT and faecal intestinal microbiota composition and/or CoPEC prevalence in patients with mid or low rectal cancer.Methods and analysis This is a non-randomised bicentric prospective clinical study with a recruitment capacity of 200 patients. Three stool samples will be collected from participants with histological-proven adenocarcinome of mid or low rectum who meet eligibility criteria of the study protocol: one before neoadjuvant treatment start, one in the period between CRT end and surgery and one the day before surgery. In each sample, CoPEC will be detected by culture in special media and molecular (PCR) approaches. The global microbiota composition will be also assessed by the bacterial 16S rRNA gene sequencing. Neoadjuvant CRT response and tumour regression grade will be described using the Dworak system at pathological examination. Clinical data and survival outcomes will also be collected and investigated.Ethics and dissemination MICARE was approved by the local ethics committee (Comité de Protection des Personnes Sud-Est II, 18 December 2019. Reference number 2019-A02493-54 and the institutional review board. Patients will be required to provide written informed consent. Results will be published in a peer reviewed journal.Trial registration number NCT04103567.

Excessive nutrient inputs are generally perceived to be responsible for the eutrophication of estuarine and coastal systems. Here, we show that the alteration of estuarine water circulation may be a very critical driver in the case of macrotidal systems. For this study, we intensively sampled the upstream part of the Ria Penfeld in June 2021, in a period of maximum irradiance and after a period of ~7 days of closure of the Kervallon dam gate. We observed that the physico-chemical structure of the Ria Penfeld reservoir (RPR), with very high biomass (chl-a values up to 120 µg L−1) and anoxic conditions in the bottom, was radically different from what is usually observed in the other estuaries of the region. The very high net primary production (~1700 mg C m−2 d−1) in the RPR was associated with an important removal of nutrients, especially phosphate, resulting in a strong nutritional imbalance (molar N:Si:P ratio of 2100:1500:1) for the water exported to the downstream estuary.

Background99mTc-NTP 15-5 is a SPECT radiotracer targeting proteoglycans (PG), components of the cartilaginous extracellular matrix. Imaging of PGs would be useful for the early detection of cartilage disorders (osteoarthritis, arthritis and chondrosarcoma, Aromatase Inhibitor associated arthralgia (AIA) in breast cancer), and the follow-up of patients under treatment. According to preclinical study results, 99mTc-NTP 15-5, is a good candidate for a specific functional molecular imaging of joints. We intend to initiate a first in-human study to confirm and quantify 99mTc-NTP 15-5 uptake in healthy joints.MethodsAs the clinical development of this radiotracer would be oriented toward the functional imaging of joint pathologies, we have chosen to include patients with healthy joints (unilateral osteoarthritis of the knee or breast cancer with indication of AI treatment). This phase I study will be an open-label, multicenter, dose-escalation trial of a radiopharmaceutical orientation to determine the recommended level of activity of 99mTc-NTP 15-5 to obtain the best joint tracer contrasts on images, without dose limiting toxicity (DLT). The secondary objectives will include the study of the pharmacology, biodistribution (using planar whole body and SPECT-CT acquisitions), toxicity, and dosimetry of this radiotracer. The dose escalation with 3 activity levels (5, 10, and 15 MBq/kg), will be conditioned by the absence at the previous level of DLT and of a visualized tracer accumulation on more than 80% of healthy joints as observed on scintigraphy performed at ≤ 2 h post-injection.DiscussionThis first in-human phase I trial will be proof-of-concept of the relevance of 99mTc-NTP 15-5 as a cartilage tracer, with the determination of the optimal methodology (dose and acquisition time) to obtain the best contrast to provide a functional image of joints with SPECT-CT.Trial registration numberClinicaltrials.gov: NCT04481230. Identifier in French National Agency for the Safety of Medicines and Health Products (ANSM): N°EudraCT 2020-000495-37.