NIR Imaging of the Integrin-Rich Head and Neck Squamous Cell Carcinoma Using Ternary Copper Indium Selenide/Zinc Sulfide-Based Quantum Dots

The efficient intraoperative identification of cancers requires the development of the bright, minimally-toxic, tumor-specific near-infrared (NIR) probes as contrast agents. Luminescent semiconductor quantum dots (QDs) offer several unique advantages for in vivo cellular imaging by providing bright and photostable fluorescent probes. Here, we present the synthesis of ZnCuInSe/ZnS core/shell QDs emitting in NIR (~750 nm) conjugated to NAVPNLRGDLQVLAQKVART (A20FMDV2) peptide for targeting αvβ6 integrin-rich head and neck squamous cell carcinoma (HNSCC). Integrin αvβ6 is usually not detectable in nonpathological tissues, but is highly upregulated in HNSCC. QD-A20 showed αvβ6 integrin-specific binding in two-dimension (2D) monolayer and three-dimension (3D) spheroid in vitro HNSCC models. QD-A20 exhibit limited penetration (ca. 50 µm) in stroma-rich 3D spheroids. Finally, we demonstrated the potential of these QDs by time-gated fluorescence imaging of stroma-rich 3D spheroids placed onto mm-thick tissue slices to mimic imaging conditions in tissues. Overall, QD-A20 could be considered as highly promising nanoprobes for NIR bioimaging and imaging-guided surgery

Sperm cryostorage in a dry tank: An accurate alternative

International audienceThis prospective study aimed to determine the effects of dry nitrogen cryostorage on human sperm characteristics in comparison with liquid nitrogen cryostorage. For this purpose, 42 men undergoing routine semen analysis (21 normozoospermia and 21 with altered semen parameters) were analyzed. After slow freezing, half of the straws of each sample were randomly stored in liquid and dry tanks, at the top and bottom levels of the latter. After 6 months storage, thawed samples were treated by density gradient centrifugation and sperm characteristics were compared. There was no difference in sperm progressive motility (15.1% ± 14.2% vs. 15.1% ± 12.7%; p = 0.76), sperm vitality (25.5% ± 17.7% vs. 26.2% ± 19%; p = 0.71), percentages of acrosome-reacted spermatozoa (38% ± 8.5% vs. 38.5% ± 7.4%; p = 0.53) and DNA fragmentation spermatozoa (27.3% ± 12.4% vs. 28.5% ± 12.9%, p = 0.47) after cryostorage in the dry or the liquid nitrogen tank. Moreover, we did not observe differences between either cryostorage system for normal and altered sperm samples. This lack of difference was also observed whatever the floor level of cryostorage in the dry tank. The temperature measurement of the dry tank showed a stable temperature at −194 °C throughout storage whatever the storage floor level, guaranteeing the stability of the low temperatures suitable for human sperm storage. Because of its greater safety, dry storage without contact with the liquid phase should be preferred and can be a useful alternative for the cryostorage of human sperm samples

Performance of 11 host biomarkers alone or in combination in the diagnosis of late-onset sepsis in hospitalized neonates: the prospective EMERAUDE study

International audienceAbstract Background : Despite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units (NICUs), a reliable diagnosis remains difficult. The time needed to obtain laboratory results of biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) and blood culture explains why an unjustified antibiotic use is observed in numerous hospitalized neonates. This results in an increased frequency of antibiotic resistance, microbiota modification, and neonatal complications. The objective of EMERAUDE study was to identify biomarkers (alone or in combination) to early exclude the diagnosis of LOS in neonates with suggestive clinical signs. Methods : A prospective, multicenter cohort study (EMERAUDE)was conducted in 2 French NICUs. The participants were hospitalized neonates at ≥7 days of life with signs of suspected LOS enrolled from November 2017 to November 2020. Serum samples were collected during the venipuncture prescribed for blood culture. Eleven biomarkers were measured using customized multiplexed assays in the ELLA Automated Immunoassay System (ProteinSimple, San Jose, CA, USA) for PCT, IP-10, IL-6, IL-10, NGAL, PTX3, presepsin and LBP, and using conventional ELISA for calprotectin (R&D Systems, Minneapolis, MN, USA), gelsolin(Elabsciences, Houston, TX, USA) and IL-27(R&D Systems, Minneapolis, MN, USA). An independent adjudication committee, blind to biomarkers, assigned each patient to either infected, not infected or unclassified groups. Performances of biomarkers were assessed considering a sensitivity of at least 0.898. Results : A total of 230 patients were analyzed. They were mainly preterm (80%) with a median gestational age of 27 weeks and a median birth weight of 940 grams. The adjudication committee classified 22% of patients (51/230) as infected and all of these received antibiotics. Among patients of the not infected group, 27% (42/153) also received antibiotics. The best biomarkers alone were IL-6, IL-10 and NGAL; the area under the curve [95%CI] was, respectively, 0.864 [0.798-0.929], 0.845 [0.777-0.914], and 0.829 [0.760-0.898]. Combinations of up to 4 biomarkers were analyzed and the best were PCT/IL-10, PTX3/NGAL, and PTX3/NGAL/gelsolin. The best models of biomarkers could avoid up to 64% of unjustified antibiotics. Conclusions : At the onset of clinical suspicion of LOS, the dosing of additional biomarkers could help the clinician in identifying not infected patients. Trial registration : ClinicalTrials.gov ID: NCT03299751. Registered 3 October 2017

Delivering adapted physical activity by videoconference to patients with fatigue under immune checkpoint inhibitors: Lessons learned from the PACTIMe-FEAS feasibility study

INTRODUCTION: Fatigue is one of the most frequent symptoms in anti-cancer immune therapy. Physical activity has been proven effective in reducing fatigue, but unmet needs remain regarding the provision and access to adapted programmes, which efficiently addresses the main barriers to PA. METHODS: The PACTIMe-FEAS study primarily aimed at primarily to evaluate the feasibility and the acceptability of a videoconference-based 6-month programme promoting physical activity, and secondarily to assess its potential post-immediate and short-term effectiveness in reducing fatigue in cancer patients under immune therapy. Numeric self-reported questionnaires (Visual Analogue Scale-fatigue, Multidimensional Fatigue Inventory, International Physical Activity Questionnaire, Échelle de Motivation envers l'Activité Physique en contexte de Santé, Medical Outcomes Study 36-Item Short Form Health Survey, Hospital Anxiety and Depression Scale and Insomnia Severity Index) were completed by participants through an online secure platform at three time points: just before (T1), and after (T2) the programme, and 3 months later (T3). RESULTS: Sixteen participants (50% male, 50% female, mean age 54 years, 69% melanoma, 31% overweight), with moderate-to-severe fatigue, entered the internet-delivered intervention; 14 completed it, with an average completion rate of physical activity supervised sessions of 75%. Satisfaction was high, confirming a demand for group format, personalised approach, professional guidance and home-based device, to support the practice of regular physical activity. A decrease in fatigue was observed at the end of the programme. DISCUSSION: The recruitment process did prove to be challenging, with a relatively small eligible population, and will need to be reconsidered to envision a larger scale trial. But here and now, this feasibility study provides the first promising foundations to develop further research on the effectiveness of an original remote programme

Therapie

Les Ateliers de Giens avaient consacré en 2018 une table ronde à l’intelligence artificielle (IA) et conduit ses experts à confirmer l’apport potentiel et le bénéfice théorique que représente l’IA en recherche clinique et en matière d’amélioration de l’efficience de soins. La table ronde de 2022 s’inscrit dans la continuité de cette réflexion sur l’IA et l’automatisation intelligente (AI) en la ciblant sur son apport en pharmacovigilance et les applications et tâches qu’elles pourraient optimiser afin de préserver et de renforcer l’expertise médicale et pharmacologique en pharmacovigilance. En effet, l’évolution du travail en pharmacovigilance est caractérisée par de nombreuses tâches à faible valeur ajoutée, une volumétrie croissante des déclarations de pharmacovigilance, la rareté des personnels médicaux ayant une expertise en pharmacologique clinique et en pharmacovigilance et des ressources humaines qui ne sont pas et ne seront pas en adéquation avec l’évolution constatée. Tous ces paramètres concourent à une embolisation du système de pharmacovigilance avec le risque de passer à côté de sa mission première qui est d’identifier et de caractériser un risque, voire une alerte sanitaire, sur un médicament. Les participants de la table ronde (représentants des centres régionaux de pharmacovigilance (CRPV), de l’Agence nationale de sécurité du médicament et des produits de santé (ANSM), des patients, de l’industrie du médicament ou encore de start-ups travaillant dans le développement de l’IA dans le domaine du médicament) ont partagé leurs expériences, leurs projets pilotes et leurs attentes sur les potentialités attendues, théoriques ou avérées, de l’IA et l’AI. Ce travail a permis de dégager les besoins et les enjeux réels que représentent, ou pas, l’IA ou l’AI dans les modes d’organisation actuelles ou futures de la pharmacovigilance. Cette démarche a permis l’élaboration d’une matrice SWOT (forces, faiblesses, opportunités, menaces), socle de réflexion pour identifier des points critiques et envisager quatre principales recommandations : (1) préserver et développer l’expertise métier en pharmacovigilance (incluant la partie recherche et développement en méthodes) avec l’intégration de nouvelles technologies ; (2) améliorer la qualité des déclarations en pharmacovigilance ; (3) adapter les moyens techniques et réglementaires ; (4) implémenter une stratégie de développements des outils AI et IA au service de l’expertise

Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study

International audienceDespite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units, a reliable diagnosis remains difficult. This prospective, multicenter cohort study aimed to identify biomarkers early to rule out the diagnosis of LOS in 230 neonates ≥7 days of life with signs of suspected LOS. Blood levels of eleven protein biomarkers (PCT, IL-10, IL-6, NGAL, IP-10, PTX3, CD14, LBP, IL-27, gelsolin, and calprotectin) were measured. Patients received standard of care blinded to biomarker results, and an independent adjudication committee blinded to biomarker results assigned each patient to either infected, not infected, or unclassified groups. Performances of biomarkers were assessed considering a sensitivity of at least 0.898. The adjudication committee classified 22% of patients as infected and all of these received antibiotics. A total of 27% of the not infected group also received antibiotics. The best biomarkers alone were IL-6, IL-10, and NGAL with an area under the curve (95% confidence interval) of 0.864 (0.798–0.929), 0.845 (0.777–0.914), and 0.829 (0.760–0.898), respectively. The best combinations of up to four biomarkers were PCT/IL-10, PTX3/NGAL, and PTX3/NGAL/gelsolin. The best models of biomarkers could have identified not infected patients early on and avoided up to 64% of unjustified antibiotics. At the onset of clinical suspicion of LOS, additional biomarkers could help the clinician in identifying non-infected patients

P2Y13 Receptor is Critical for Reverse Cholesterol Transport

A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote "reverse cholesterol transport" (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y(13) (purinergic receptor P2Y, G protein coupled, 13) activation is essential for HDL uptake but the potential of P2Y(13) as a target to promote RCT has not been documented. Here, we show that P2Y(13)-deficient mice exhibited a decrease in hepatic HDL cholesterol uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL and other lipid levels were normal. These changes translated into a substantial decrease in the rate of macrophage-to-feces RCT. Therefore, hallmark features of RCT are impaired in P2Y(13)-deficient mice. Furthermore, cangrelor, a partial agonist of P2Y(13), stimulated hepatic HDL uptake and biliary lipid secretions in normal mice and in mice with a targeted deletion of scavenger receptor class B type I (SR-BI) in liver (hypomSR-BI- knockout(liver)) but had no effect in P2Y(13) knockout mice, which indicate that P2Y(13)-mediated HDL uptake pathway is independent of SR-BI mediated HDL selective cholesteryl ester uptake. Conclusion: These results establish P2Y(13) as an attractive novel target for modulating RCT and support the emerging view that steady-state plasma HDL levels do not necessarily reflect the capacity of HDL to promote RCT. (HEPATOLOGY 2010;52:1477-1483

Evaluation des effets d'une contamination chimique complexe d'origine industrielle d'un petit cours d'eau forestier (Vosges, France) : une approche interdisciplinaire

International audienceLa contamination observée depuis plusieurs années dans la rivière Cleurie (Vosges, France) constitue un cadre de travail idéal pour étudier la contamination des écosystèmes aquatiques par des pesticides. En raison d’activités industrielles (textiles), ce petit cours d’eau vosgien de tête de bassin versant forestier présente des concentrations élevées de pesticides (dont le glyphosate et son principal produit de dégradation, l’acide aminométhylphosphonique – AMPA) mais inférieures aux normes environnementales. De fortes concentrations d’azurants optiques et de colorants sont également fréquemment observées, induisant un changement de coloration de l’eau spectaculaire. Les données disponibles, basées sur les indicateurs classiques (diatomées, invertébrés), indiquent pourtant une relativement bonne qualité de l’eau le long du linéaire. Du fait que les rejets soient localisés au niveau d’une zone naturelle d'intérêt écologique (site Natura 2000), que la Cleurie est une rivière très pêchée et que ces entreprises constituent une source essentielle d’emplois dans la vallée, ce site représente un cas d’étude sensible du point de vue socio-économique. Dans ce contexte, un projet interdisciplinaire est mené afin d’identifier des indicateurs/marqueurs globaux permettant de caractériser (1) la pression toxique in situ ainsi que (2) ses effets sur un compartiment clé du milieu aquatique (biofilms) mais également (3) la circulation des savoirs scientifiques produits entre les différents acteurs (scientifiques, pouvoirs publics, citoyens…) impliqués dans une controverse locale mais qui s’inscrit dans celle plus générale et ancienne sur la toxicité des pesticides

Integrated nowcasting of flash floods and related socio-economic impacts: The French ANR PICS project

International audienc

Integrated nowcasting of flash floods and related socio-economic impacts: The French ANR PICS project

International audienc