Hôpital Saint-François d'Assise

Reference materials are essential for the validation, verification, and implementation of clinical assays. Seracare has developed the Seraseq line-commercial reference standards for non-invasive prenatal testing (NIPT)-which are designed to simulate maternal plasma containing cell-free DNA (cfDNA). This study aims to evaluate the performance of Seraseq reference materials compared to natural maternal plasma, particularly assessing their quality and reliability as reference standards in NIPT workflows, both with and without size selection to enrich fetal fraction. We analyzed six replicates from eight different Seraseq genotypes. cfDNA was extracted, prepared into sequencing libraries, and sequenced following the same protocols used for natural plasma samples. Size-selection was also applied to enrich shorter cfDNA fragments. The key performance metrics included cfDNA yield and integrity, library preparation efficiency, sequencing quality, fetal fraction estimation, and detection of aneuploidies and sex chromosome abnormalities. cfDNA quantity and quality from Seraseq materials were comparable to natural plasma. The materials yielded consistent library concentrations. Sequencing showed reliable detection of all targeted aneuploidies except the microdeletion del22q11, even with elevated fetal fraction. Size-selection increased fetal fraction and improved Z-scores for aneuploidy detection across all genotypes. Fragment size profiles exhibited slight but consistent deviations from natural plasma, notably after size selection. Seraseq reference materials closely mimic the cfDNA characteristics of maternal plasma and perform reliably across multiple testing dimensions. While they may present slight differences in fragment size periodicity, these did not affect analytical performance. These materials are therefore suitable for validating and monitoring NIPT workflows.

Abstract In this work, the electrical properties of a semi-industrial dielectric barrier discharge (DBD) system, characterized by a single thin dielectric, were investigated over a one-hour operation period. The discharge, generated in nitrogen, operated in the classical filamentary regime. While the discharge operated over an hour, measurements at low applied voltage, i.e. without discharge, have been introduced. The applied voltage and the charge were recorded during the non-discharge period. These measurements, analyzed using Lissajous figures and an equivalent circuit model of the setup, allowed extraction of several electrical parameters. Using basic PSIM simulations, it is first shown that the parasitic resistance (Rp) and capacitance (Cp) induce changes in the area and slope of the Lissajous figures, respectively. Those are usually used to estimate the power (Poff) and the cell capacitance (Ccell). The results demonstrated that both Poff and Ccell are increasing over one hour. Such trends are seen to be occurring whatever the electrical conditions chosen for the discharge operation. Simultaneous time resolved temperature measurements on the polymer present the same evolution than Poff and Ccell. From the strongest variation, Cp is estimated to increase from 5 pF to 64 pF, while Rp is decreasing from 14 MΩ to 3 MΩ. Such modifications are not trivial. No change in power was observed during the one-hour discharge operation. Therefore, several hypotheses are proposed to explain the observed phenomena, particularly regarding the relationship between temperature and the charge storage properties of PTFE, as discussed in recent literature.

ABSTRACTCell‐free DNA (cfDNA) screening for fetal aneuploidy is typically offered from 10 weeks of gestational age (GA) onward. Fetal fraction (FF) enrichment may enable screening before 10 weeks with a low failure rate. This study aimed to assess the feasibility of cfDNA screening with in vitro enrichment before 10 weeks of gestation. 435 pregnant women were recruited between 7w0d and 9w6d of GA (EARLY samples) and scheduled for a second cfDNA sample after 11 weeks of GA (12w+ samples). 371 women provided both an EARLY and a 12w+ sample, and we compared cfDNA results between EARLY and 12w+ samples and sex at birth. For sex determination using cfDNA, EARLY, and 12w+ samples were 100% concordant with clinical sex at birth. In 170 male pregnancies, EARLY samples 5.9% had FF < 4% after enrichment. Seven aneuploidies were observed early, but eight at 12+ weeks (one false positive after invasive diagnostic testing). We observed 4.4% spontaneous abortions between the EARLY and 12w+ sampling. Our findings suggest that in vitro fetal enrichment provides sufficient cfDNA for reliable prenatal cfDNA screening results as early as 8 weeks, but one limitation lies in the high proportion of spontaneous abortions before 12w0d.

Polyethylene terephthalate (PET) is widely used in packaging due to its high clarity and transparency. However, some applications require anti-fog surfaces, which untreated PET cannot provide. In this study, PET films were treated using two plasma systems: an atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge (DBD), both operating with nitrogen as the working gas and aiming to develop anti-fog properties. The effect of treatment time on wettability and anti-fog properties was investigated. An increase in wettability was observed after all plasma treatments. The stability of the surface modification was also evaluated after 7 days. Treatments with the APPJ exhibited significant hydrophobic recovery after aging, while those with the DBD maintained stable hydrophilicity. Anti-fog properties were assessed in samples treated with the DBD system, revealing that the anti-fog area persisted after aging, with a reduction of 20%–30%, depending on the treatment time. These findings demonstrate the potential of atmospheric pressure plasma as an effective method for modifying PET surfaces to achieve anti-fog functionality.

Background/Objectives: Chemoresistance of breast cancers (BCs) is a major impediment to current chemotherapeutics that urges the development of new drugs and new therapeutic approaches. To that end, phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) were recently prepared to fulfill some of the unmet needs with classic chemotherapeutics. PAIB-SOs are prodrugs bioactivated into potent antimitotics by the cytochrome P450 1A1 (CYP1A1), which is a frequent enzyme in resistant BC cells, but mostly missing in normal cells. Our screening program studies of PAIB-SO chemolibraries selected three prototypical PAIB-SOs as antimitotic prodrugs amenable for studies using BC animal models. Methods: Healthy female CD1® IGS mice were treated with three prototypical PAIB-SOs, namely CEU-835, -934, and -938, for the determination of their toxicity and half-lives. Moreover, MCF7 tumor-bearing CD1-Foxn1nu Nude female mice were treated with the three prototypical PAIB-SOs for the determination of their antitumor activity. Results: Herein, we show that multi-intravenous administrations of CEU-835, -934, and -938 at their maximal solubilities are well tolerated in healthy female CD1® IGS mice, as depicted by the evaluation of distress behaviors, organ necropsy, total blood cell count, and histology. Moreover, the half-life of CEU-835, -934, and -938 administered intravenously in healthy CD1® IGS female mice were 8.1, 23.2, and 21.5 h, respectively. Finally, their intravenous administrations of CEU-934 and -938 decreased MCF7 tumor growth as efficiently as paclitaxel in MCF7 tumor-bearing CD1-Foxn1nu Nude mouse model. Conclusions: overall, our study demonstrated for the first time that pentyl-bearing PAIB-SOs are new CYP1A1-dependent prodrugs efficiently decrease breast cancer tumor growth, and show no side effects at their pharmacological concentration in mouse models.

Abstract The negative impact of Coronavirus SARS CoV-2 related Disease (COVID-19) in patients with chronic liver disease (CLD) has been described in several cohorts. We report here the results from the largest French cohort in “real-life”. The primary outcome was 30-days mortality. Patients with CLD regardless of etiology, who developed COVID-19 confirmed by a positive PCR and/or an evocative chest CT scan were included. The prognostic influence of clinical and biological features was assessed and multivariate analyses were made. Between 08/05/2020 and 31/12/2021, 1219 patients were included, mostly men (62%), median age 61 years, with advanced liver fibrosis in 46%, alcohol-related in 21% of the cases, complicated by liver failure (CHILD-PUGH B/C) in 170 of patients with cirrhosis (40%). Moreover 366 patients (30%) were immunocompromised, including 271 organ transplant recipients. Hospitalization in intensive care unit was required in 11% of the patients and 159 patients (13%) died, 70% of them from extra-hepatic causes. Overall, the independent risk factors for death were age &gt; 61 years, diabetes, advanced liver fibrosis, and alcoholic etiology of the liver disease. Immunosuppression was not a prognostic factor in multivariate analysis. The results of this cohort confirm a significant vulnerability of COVID-19 patients with CLD. On the other hand, they confirm the absence of excess mortality related to immunosuppression, particularly in liver transplant recipients.

Biomaterial surface engineering and the integration of cell-adhesive ligands are crucial in biological research and biotechnological applications. The interplay between cells and their microenvironment, influenced by chemical and physical cues, impacts cellular behavior. Surface modification of biomaterials profoundly affects cellular responses, especially at the cell-surface interface. This work focuses on enhancing cellular activities through material manipulation, emphasizing silanization for further functionalization with bioactive molecules such as RGD peptides to improve cell adhesion. The grafting of three distinct silanes onto silicon wafers using both spin coating and immersion methods was investigated. This study sheds light on the effects of different alkyl chain lengths and protecting groups on cellular behavior, providing valuable insights into optimizing silane-based self-assembled monolayers (SAMs) before peptide or protein grafting for the first time. Specifically, it challenges the common use of APTES molecules in this context. These findings advance our understanding of surface modification strategies, paving the way for tailoring biomaterial surfaces to modulate the cellular behavior for diverse biotechnological applications.

Wood has a lower carbon footprint compared to many other materials used in construction. However, its hygroscopic nature poses significant challenges, including dimensional fluctuations in response to humidity shifts. Here we investigate a new treatment method mitigating swelling and shrinkage using dairy by-product named whey ultrafiltration permeate (mainly composed of lactose) and citric acid. Trembling aspen and black spruce samples were impregnated with ultrafiltration permeate and citric acid. Infrared and Raman spectroscopy were used to evaluate the esterification reaction and the location of the impregnates. We found increased ester bonds in the cell walls and the middle lamella (leaving the lumens empty), explaining the improved wood stability. Trembling aspen was more receptive to the treatment than black spruce, as shown by a higher weight gain (39 % vs. 13 %) and anti-swelling efficiency (54 % vs. 37 %). No leaching was observed during characterization of the treated wood. The modulus of elasticity and rupture, and the Brinell hardness were only slightly affected for both wood species. Upon combustion, esterified wood samples degraded at a lower temperature, but the stability of the residues was increased. This study highlights a promising use of ultrafiltration permeate in wood esterification.