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Morphological subphenotypes of acute pancreatitis-related acute respiratory distress syndrome
No full textInternational audienceNo abstract availabl
Deciphering pro‐arrhythmogenic mechanisms of EPAC in human atrial cardiomyocytes
No full textInternational audienceExchange protein directly activated by cAMP (EPAC) 1 and EPAC2 are involved in electrophysiological modulation in ventricular cardiomyocytes. Their putative contribution in supra‐ventricular arrhythmogenic processes has been suggested in animal models. However, nothing is known about the electrophysiological remodelling and the underlying signalling pathway regulated by EPACs in human atrial cardiomyocyte. Action potentials (AP) and K + currents ( I K ) were recorded with the patch‐clamp technique in enzymatically freshly isolated human atrial cardiomyocytes. Acute EPAC activation with the EPAC agonist 8‐(4‐chlorophenylthio)‐2′‐ O ‐methyl‐cAMP acetoxymethyl ester (8‐CPTAM; 10 µmol/l) lengthened APs by inhibition of the repolarizing K + currents in myocytes obtained from sinus rhythm (SR) patients. The selective EPAC1 pharmacological blocker AM‐001 (20 µmol/l) or the EPAC2 inhibitor ESI‐05 (25 µmol/l) prevented the effect of 8‐CPTAM on APs and I K , indicating that both EPAC isoforms participate in this electrophysiological regulation. Mechanistically, the effects of EPAC1 and EPAC2 proteins on the inhibition of three major components of K + currents, I to , I KDR, and I KUR , were Ca 2+ ‐independent but involved Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) and the AMP‐activated protein kinase (AMPK)–nitric oxide synthase (NOS)–protein kinase G (PKG) axis. Interestingly, immunoblot analysis showed that EPAC1 but not EPAC2 was overexpressed in the atria of atrial fibrillation (AF) patients. Finally, the application of AM‐001 consecutively to the 8‐CPTAM treatment significantly corrected the EPAC‐dependent downregulation of I K in AF cardiomyocytes. Our results uncover that EPAC activation influences I K by CaMKII and the AMPK–NOS–PKG signalling pathways in human atrial cardiomyocytes. Moreover, our findings suggest that EPAC1 over‐activation in AF cardiomyocytes promotes the electrophysiological remodelling underlying the initiation of AF. image Key points Activation of exchange proteins directly activated by cAMP (EPAC) lengthens action potentials (AP) in human atrial cardiac myocytes. This AP duration increase is mediated by an inhibition of the repolarizing K + current. Using EPAC1 and EPAC2 pharmacological inhibitors (AM‐001 and ESI‐05, respectively), we show that both EPAC1 and EPAC2 isoforms are involved in these electrophysiological effects. Mechanistically, EPAC‐induced K + current inhibition signalling involves both CaMKII and AMPK–NOS–PKG pathways. EPAC1 but not EPAC2 is overexpressed in atrial samples of patients with atrial fibrillation (AF). A selective pharmacological inhibitor of EPAC1, AM‐001 prevents the downregulation of K + current in cardiomyocytes from AF patients. Our results suggest that over‐activation of EPAC1 and its signalling represent a cellular mechanism for atrial arrythmia and might be a potential target for the treatment of AF
7-year trend of timely hepatitis B birth dose vaccination coverage in The Gambia: a retrospective, population-based analysis
No full textInternational audienceBackgroundAccording to WHO and UNICEF, Africa has the lowest coverage (18%) of timely (within the first 24 h) hepatitis B birth dose (HepB-BD) vaccination worldwide. To eliminate hepatitis B by 2030, 90% vaccination coverage is required. Experiences from The Gambia, the first African country to adopt HepB-BD vaccination in 1990, could guide HepB-BD implementation and scale-up in Africa. We aimed to assess the trend of, and barriers to, timely HepB-BD vaccination coverage over a 7-year period in The Gambia.MethodsIn this retrospective analysis, 2015–21 data were extracted from population-based Health and Demographic Surveillance Systems in three rural areas (Basse, Bansang, and Farafenni) in The Gambia. Fluctuation tests and Bayesian analysis using Markov chain Monte Carlo methods assessed the rate of timely (within days 0–1 of birth) and delayed HepB-BD vaccination coverage, change points (abrupt variation between two stable periods) in the average coverage of timely HepB-BD vaccination, and the factors associated with delayed HepB-BD vaccination during the first 7 years following the WHO recommendations on hepatitis B elimination.FindingsBetween Jan 1, 2015, and Dec 31, 2021, 4560 of 71 088 livebirths (6·4%, 95% CI 6·2–6·6) received a timely HepB-BD. Timely HepB-BD vaccination coverage increased from 1·7% (95% CI 1·3–2·0) in the first half of 2015 (ie, January to June) to 22·4% (21·3–23·6) in the second half of 2021 (ie, July to December; p<0·0001). Delayed HepB-BD administration was associated with being born on Friday (odds ratio [OR] 3·51 [95% CI 3·03–4·08]; p<0·0001) or Saturday (5·93 [4·96–7·13]; p<0·0001) compared with Tuesday; being born in Basse (2·03 [95% CI 1·83–2·25]; p<0·0001) or Farafenni (1·84 [1·63–2·08]; p<0·0001); and being born during the rainy season (1·16 [1·08–1·25]; p<0·0001). Average timely HepB-BD vaccination coverage significantly decreased from 10·1% (95% CI 9·5–10·6) pre-COVID-19 pandemic to 5·4% (4·5–6·3) during the first COVID-19 wave (p<0·0001). After adjusting for all other factors, being born during the first COVID-19 wave was associated with delayed HepB-BD vaccination (OR 1·41 [1·22–1·64]; p<0·0001).Interpretation30 years after the adoption of HepB-BD in The Gambia, the rate of vaccination coverage remains low and was significantly affected by the COVID-19 pandemic, highlighting the challenges for its implementation
Revisiting the time to positivity in blood cultures as a prediagnostic tool: an in vitro experiment and retrospective study
No full textInternational audienceBackground: Sepsis is an acute response to infection; rapid detection of pathogens is essential. In this work, the time to positivity (TTP) of blood culture (BC), a key factor for species diagnosis, was studied. Methods: In the experimental phase, six bacterial reference strains were tested under varying conditions, and three years of clinical blood culture data were reviewed. A total of 4,924 first positive BC bottles from 3864 patients hospitalized from 2019 to 2021 were analysed. Results: Experimental results revealed that reducing the inoculum by a factor of 10 increased the TTP by an average of 1.5 hours. A blood sample volume between 1 and 3 mL per vial significantly improved bacterial detection. Each hour of delay before incubation reduced the TTP by 21 minutes; however, the overall TTP was still prolonged. Bacterial growth and viability were preserved at room temperature for up to 24 h. TTP could be exploited as a first diagnostic tool, as it significantly varied between species. Staphylococcus aureus can be differentiated from coagulase-negative staphylococci when the TTP is <12 hours (Specificity (Sp) = 0.95, positive predictive value (PPV) = 62 %, negative predictive value (NPV) = 76 %), and Enterobacteriaceae can be differentiated from Pseudomonas aeruginosa under the same threshold (Sensibility (Se) = 0.70, Sp = 0.93, PPV = 99 %). A TTP >15 hours exclude clinically relevant pathogens such as S. pneumoniae, S. agalactiae, and S. pyogenes. Conclusion: This work shows how preanalytical factors play a major role in the time required for diagnosis, and highlights the potential of the TTP as a prediagnostic tool to improve sepsis management
Assessing radiofrequency safety of active implants by measuring induced radiofrequency currents using MRI
No full textInternational audiencePurpose: During MRI in the presence of active wire-like implants, such as deep brain stimulation leads, there is a risk of thermal lesions in tissues adjacent to implant contacts due to radiofrequency currents induced in the wire. Currently, there is no established method to evaluate the radiofrequency (RF) safety of an implant in situ, due to complex interactions between the implant and the electric field inside the patient during MRI. This article presents a method to quantify the RF current in an implant using MRI acquisitions at very low SAR.Theory and Methods: To measure RF current in situ, a modified B1-mapping sequence is proposed to image the associated perturbation of the B + 1 field. A forward signal model links the RF current intensity to the MRI signal and is used to fit the RF current from acquired data. Electromagnetic simulations and experiments on a homogeneous phantom are presented for simplified and real implant wires to validate the method.Results: The presented model can correctly reconstruct RF current amplitudes from field maps obtained with detailed electromagnetic simulations, with a normalized RMS error of 4.7%. Phantom experiments show a good linearity between the square of the current measured by MRI and temperature increase (R 2 > 0.91), demonstrating that the RF current measurements quantitatively represent the effective heating.Conclusion: A method has been developed to quantify the RF current in situ from MRI signals. This method enables to predict the individual heating risk for other MRI sequences performed in the same scanning session
Rotiferometer: An automated system for quantification of rotifer cultures
No full textInternational audienceThe accurate quantification and continuous monitoring of Brachionus plicatilis. rotifer cultures are essential for aquaculture and aquatic animal research laboratories. Manual counting methods are labor-intensive, error-prone, and inefficient for large-scale operations, necessitating automated solutions. This study presents the Rotiferometer, an automated and cost-effective system that integrates mechanical design, deep learning, and automation for precise rotifer detection, classification and counting. Using a YOLOv8 model, the system achieves a mean average precision ([email protected]) of 94.7 % in distinguishing gravid and non-gravid rotifers. It proceeds by scanning a 1 mL Sedgewick Rafter slide under 3 min, ensuring rapid and accurate enumeration. A strong correlation was observed between manual and Rotiferometer counts, (with R2 values of 0.9729 and 0.9868 for gravid (egg-bearing) and non-gravid (non-egg-bearing) rotifers, respectively), confirming the system’s accuracy. Additionally, the analysis of operator variability using the Rotiferometer delivered consistent results regardless of the user, minimizing the need for specialized expertise. Finally, a 45-day monitoring experiment with the Rotiferometer effectively tracked rotifer population changes, identifying key phases of growth, decline, and recovery. These results highlight the device’s potential to enhance rotifer culture management by providing real-time, reliable, and automated monitoring, thereby optimizing aquaculture productivity and research efficiency
Attitudes des Français vis-à-vis des facteurs de risque de cancer liés au milieu professionnel : résultats du Baromètre Cancer 2021
No full textNational audienceIntroduction. - Cancer is a major public health issue, with a rising incidence in France and a persistent underreporting of occupational cancers. In this study, we describe the French population's awareness of occupational cancer risk factors and their attitudes toward these factors in 2021, with a view to improving preventive actions. Methods. - This study is based on data from the 2021 Cancer Barometer, a national telephone survey conducted with a structured questionnaire. The survey targeted adults residing in mainland France with no history of cancer and at least one experience in the workplace. The questionnaire collected sociodemographic data, information about attitudes toward occupational risk factors, the degree to which participants considered themselves informed and the sources of information the participants considered reliable. Results. - The sample included 3,974 respondents with a mean age of 49.7 years (SD = 16.8 years), 42.0% of whom reported having been exposed to occupational risk factors, principally chemical agents (69.5%). Exposures to physical (6.5%) and biological (1.8%) agents were much less frequently identified. More than one third of the respondents (33.4%) considered night work to be a risk factor for cancer. Over half the participants (51.5%) reported feeling \"rather poorly\" or \"very poorly\" informed about these risks. Healthcare professionals (24.3%) and television (23.6%) were cited as the most reliable sources of information. Conclusions. - These findings highlight the need to improve public awareness of occupational cancer risk factors in France, particularly for lesser-known agents and night work. Targeted communication campaigns involving all primary prevention stakeholders appear essential to strengthen such campaigns.IntroductionLe cancer est un enjeu majeur de santé publique, avec une incidence en augmentation en France, et une sous-déclaration persistante des cancers d’origine professionnelle. Cette étude vise à décrire, en 2021, les attitudes et le niveau d’information de la population française concernant les facteurs de risque professionnels de cancer, afin de mieux orienter les actions de prévention.MéthodeL’étude repose sur les données du Baromètre Cancer 2021, une enquête nationale téléphonique réalisée à l’aide d’un questionnaire, auprès d’adultes résidant en France hexagonale, sans antécédent de cancer et ayant eu au moins une expérience professionnelle. Les items ont permis de recueillir des informations sociodémographiques, les attitudes vis-à-vis des facteurs de risque professionnels, le sentiment d’être informé et les sources d’information jugées fiables.RésultatsL’échantillon comprend 3974 répondants d’âge moyen 49,7 ans (ET = 16,8). Parmi eux, 42,0 % déclarent avoir été exposés à des facteurs de risque en milieu professionnel, principalement à des agents chimiques (69,5 %). Les agents physiques (6,5 %) et biologiques (1,8 %) sont beaucoup moins fréquemment identifiés. Par ailleurs, plus d’un tiers des répondants (33,4 %) considère le travail de nuit comme un facteur de risque de cancer. Plus de la moitié (51,5 %) se déclare « plutôt mal » ou « très mal » informée sur ces risques. Les professionnels de santé (24,3 %) et la télévision (23,6 %) sont les sources d’information jugées les plus fiables.ConclusionsCes résultats mettent en évidence un besoin de renforcer la sensibilisation de la population française aux facteurs de risque de cancer en milieu professionnel, notamment les agents moins connus et le travail de nuit. Des campagnes de communication ciblées, mobilisant l’ensemble des acteurs de la prévention primaire, apparaissent essentielles pour la renforcer
Evaluating portable EEG: a comparison between two wireless systems (EPOC Flex and LiveAmp) and the wired BrainAmp system
No full textInternational audienceBackground Recent advances in equipment miniaturization have led to low-cost, portable electroencephalography (EEG) systems that facilitate data collection in real-world settings and with larger samples. Although wireless EEG systems were originally developed for non-research applications, recent studies have provided valuable information to help researchers make informed choices, particularly about participant comfort, mobility during recordings, and data validity. This study aimed to assess the impact of portability by comparing the performance of portable consumer- and research-grade systems (EPOC Saline Flex, EM; LiveAmp, LA) with fixed research-grade systems (BrainAmp, BA). Method Continuous EEG was recorded with each system in healthy adults performing five benchmark tasks in fundamental and clinical cognitive neuroscience. Mental states (alpha power variations in open/closed eyes) and unconscious perception (steady-state visual evoked potential, SSVEP) were analyzed through time/frequency methods, while active (N200 and P300 components during active listening and N170 component during face recognition) and passive cognitive processes (Mismatch negativity, MMN component during passive listening) were examined using time/amplitude analyses (event-related potential, ERPs). Our analyses compared system efficiency at native and equalized sampling rates and examined 100%, 75%, and 50% of the datasets to determine the required trial number for satisfactory signal quality. Results Despite the smaller amount of signal retained for EM, all systems recorded the expected resting state alpha power decrease and SSVEP responses, with EM showing lower spectral effects ([EM < (LA≈BA)]). ERPs for active (N170, N200, P300) and passive (MMN) processes emerged across all systems, with EM and LA showing lower amplitudes only for N170 compared to BA. Furthermore, the dataset reduction resulted in a decreased N170 at P7 only for EM ([EM < LA < BA]). EM also exhibited shorter latencies for all ERPs except for MMN. Conclusion This study provides concrete guidance for designing EEG experiments in real-world settings, with significant potential for investigating children and vulnerable populations. The efficiency of the three EEG systems is more influenced by task duration than sampling rates. A wireless EEG device, such as the EM, can effectively support both time/frequency and time/amplitude analyses in cognitive science, provided that the number of trials is sufficient and latencies are controlled
MQAD-net: multi-modal quantum-attentive deep learning framework for early mental health detection and personalized therapy recommendation
No full textInternational audienceMental health issues are a major global concern that not only affect millions of people but also create significant societal and economic costs. Traditional ways of diagnosing mental health problems are usually based on the opinions of experts, thus prolonging the process of getting a diagnosis, causing inconsistencies, and even sometimes leading to the wrong conclusion. The already available computational models are not fully equipped to cope with the problem of redundancy of features, complicated through capturing interdependencies between various types of data, and the issue of having to really scale them for actual use cases of the world. The paper introduces the MQAD-Net (Multi-Modal Quantum-Attentive Deep Learning Network), an advanced framework for mental health prediction and personalized therapy recommendation, as a solution. The suggested method uses GAT for temporal-spatial EEG feature extraction and transformer-based embeddings for behavioral text analysis to combine various kinds of data such as EEG signals, voice patterns, and behavioral text responses through Graph Attention Networks (GAT). Feature selection is being optimized through Quantum Greylag Multi-Criteria Decision-Making Feature Selection (QGMFS) which is a combination of Quantum-Based Particle Swarm Optimization (QPSO), Grey Wolf Optimization (GWO), and Multi-Criteria Decision Making (MCDM) that assists in choosing the most informative and non-redundant features. Dense-DualLSTMNet (DDL-Net) classification is conducted, which innovatively integrates three methodologies, namely, DenseNet, DPN-68, and BiLSTM, for better multi-modal feature learning and sequential modeling. The outcome of the experimental evaluation shows that MQAD-Net significantly exceeds the traditional deep learning models, achieving an accuracy of 95%, a precision of 94%, a recall of 93%, and an F1-score of 94%, which also allows it to recommend personalized therapy. These results highlight the potential of the framework to enhance the early diagnosis of mental health conditions, to facilitate the treatment planning for each individual, and to provide support for clinical decision-making in healthcare settings that are real-world
Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A
No full textInternational audienceFilamin A (FLNA) is an actin binding protein that organizes the cytoskeleton and controls many fundamental biological processes, such as cell migration and adhesion. The interaction between FLNA and the Myocardin-related transcription factor A (MRTF-A) promotes the activity of serum response factor (SRF) and cell migration. MRTF-A and SRF play an important role for tumor growth and senescence of hepatocellular carcinoma (HCC). Here, we identified a novel interaction between FLNA and the tumor suppressor Deleted in Liver Cancer 1 (DLC1) in vitro and in vivo in organoids and mapped the regions of interaction between DLC1 and FLNA. Association with FLNA enhanced DLC1 RhoGAP function, impaired SRF transcriptional activity, and induced cellular senescence. We found a novel molecular switch between the DLC1-FLNA and the MRTF-A-FLNA complexes that is mediated by FLNA phosphorylation at serine 2152. We generated DLC1 binding peptides that dissociate the MRTF-A-FLNA complex and favor the novel DLC1-FLNA complex by preventing actin polymerization and FLNA phosphorylation at serine 2152. Since FLNA phosphorylation at serine 2152 was increased in mouse xenografts, reinforcing the DLC1-FLNA complex by targeting FLNA phosphorylation at serine 2152 represents a promising therapeutic approach for HCC treatment