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Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection “liquid biopsy” test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3–60.0%) sensitivity and a 98.5% (95% CI: 97.0–99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4–90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3–68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.

Opportunities for HIV testing could be enhanced by offering HIV self-testing (HIVST) in populations that fear stigma and discrimination when accessing conventional HIV counselling and testing in health care facilities. Field experience with HIVST has not yet been reported in French-speaking African countries.The practicability of HIVST was assessed using the prototype the Exacto® Test HIV (Biosynex, Strasbourg, France) self-test in 322 adults living in Kisangani and Bunia, Democratic Republic of the Congo, according to World Health Organization's recommendations. Simplified and easy-to-read leaflet was translated in French, Lingala and Swahili.Forty-nine percent of participants read the instructions for use in French, while 17.1% and 33.9% read the instructions in Lingala and Swahili, respectively. The instructions for use were correctly understood in 79.5% of cases. The majority (98.4%) correctly performed the HIV self-test; however, 20.8% asked for oral assistance. Most of the participants (95.3%) found that performing the self-test was easy, while 4.7% found it difficult. Overall, the results were correctly interpreted in 90.2% of cases. Among the positive, negative, and invalid self-tests, misinterpretation occurred in 6.5%, 11.2%, and 16.0% of cases, respectively (P

This study used a contingent choice method to determine the economic value of improving various ecosystem services (ESs) of the Blue Network of Greater Montreal (Quebec, Canada). Three real projects were used and the evaluation focused on six ESs that are related to freshwater aquatic ecosystems: biodiversity, water quality, carbon sequestration, recreational activities, landscape aesthetics and education services. We also estimated the value associated with the superficies of restored sites. We calculated the monetary value that a household would be willing to pay for each additional qualitative or quantitative unit of different ESs, and these marginal values range from $0.11 to $15.39 per household per unit. Thus, under certain assumptions, we determined the monetary values that all Quebec households would allocate to improve each ES in Greater Montreal by one unit. The most valued ES was water quality ($13.5 million), followed by education services ($10.7 million), recreational activities ($8.9 million), landscape aesthetics ($4.1 million), biodiversity ($1.2 million), and carbon sequestration ($0.1 million). Our results ascribe monetary values to improved (or degraded) aquatic ecosystems in the Blue Network of Greater Montreal, but can also enhance economic analyses of various aquatic ecosystem restoration and management projects.

Chemokines are chemotactic cytokines comprised of 70-100 amino acids. The chemokines CXCL12 and CCL5 are the endogenous ligands of the CXCR4 and CCR5 G protein-coupled receptors that are also HIV co-receptors. Biochemical, structural and functional studies of receptors are ligand-consuming and the cost of commercial chemokines hinders their use in such studies. Here, we describe methods for the expression, refolding, purification, and functional characterization of CXCL12 and CCL5 constructs incorporating C-terminal epitope tags. The model tags used were hexahistidines and Strep-Tag for affinity purification, and the double lanthanoid binding tag for fluorescence imaging and crystal structure resolution. The ability of modified and purified chemokines to bind and activate CXCR4 and CCR5 receptors was tested in Xenopus oocytes expressing the receptors, together with a Kir3 G-protein activated K(+) channel that served as a reporter of receptor activation. Results demonstrate that tags greatly influence the biochemical properties of the recombinant chemokines. Besides, despite the absence of any evidence for CXCL12 or CCL5 C-terminus involvement in receptor binding and activation, we demonstrated unpredictable effects of tag insertion on the ligand apparent affinity and efficacy or on the ligand dissociation. These tagged chemokines should constitute useful tools for the selective purification of properly-folded chemokines receptors and the study of their native quaternary structures.

Langerin is a C-type lectin specifically expressed in Langerhans cells. As recently shown for HIV, Langerin is thought to capture pathogens and mediate their internalisation into Birbeck Granules for elimination. However, the precise functions of Langerin remain elusive, mostly because of the lack of information on its binding properties and physiological ligands. Based on recent reports that Langerin binds to sulfated sugars, we conducted here a comparative analysis of Langerin interaction with mannose-rich HIV glycoprotein gp120 and glycosaminoglycan (GAGs), a family of sulfated polysaccharides expressed at the surface of most mammalian cells. Our results first revealed that Langerin bound to these different glycans through very distinct mechanisms and led to the identification of a novel, GAG-specific binding mode within Langerin. In contrast to the canonical lectin domain, this new binding site showed no Ca(2+)-dependency, and could only be detected in entire, trimeric extracellular domains of Langerin. Interestingly binding to GAGs, did not simply rely on a net charge effect, but rather on more discrete saccharide features, such as 6-O-sulfation, or iduronic acid content. Using molecular modelling simulations, we proposed a model of Langerin/heparin complex, which located the GAG binding site at the interface of two of the three Carbohydrate-recognition domains of the protein, at the edge of the a-helix coiled-coil. To our knowledge, the binding properties that we have highlighted here for Langerin, have never been reported for C-type lectins before. These findings provide new insights towards the understanding of Langerin biological functions.

Malaria and Aedes-borne diseases remain major causes of mortality, morbidity, and disability in most developing countries. Surveillance of transmission patterns associated with vector control remains strategic for combating these diseases. Due to the limitions of current surveillance tools used to assess human exposure to mosquito bites, human antibody (Ab) responses to salivary peptides from Anopheles (gSG6-P1) and Aedes (Nterm-34kDa) are increasingly being used to measure direct human-Anopheles or Aedes contact. This study reports on the assessment of Human IgG Ab responses to gSG6-P1 and Nterm-34-kDa salivary peptides as biomarkers to track exposure to Anopheles and Aedes bites, in rural localities of Cameroon. Blood samples were collected between October and November 2022 from 173 individuals residing in four villages: Njombe, Kekem, Belabo, and Ouami. Sociodemographic characteristics and information regarding Long Lasting Insecticide Net (LLIN) ownership, use, and net characteristics were recorded using a questionnaire. The measurement of human IgG levels to gSG6-P1 and Nterm-34kDa peptides was conducted in blood samples using ELISA. The levels of IgG responses to Anopheles gSG6-P1 and Aedes Nterm-34kDa salivary peptides varied significantly across villages (all p<0.05). IgG responses to Anopheles gSG6-P1 were higher in Njombe compared to Belabo and Ouami (all p<0.01), while IgG responses to Aedes Nterm-34kDa were higher in Kekem compared to the other villages (all p<0.0001). Aweak correlation was observed between IgG responses to Anopheles and Aedes salivary peptides (Spearman r = 0.2689, p = 0.0003). However, the median level of IgG to Anopheles gSG6-P1 was higher than IgG to Aedes Nterm-34kDa in Njombé, Belabo, and Ouami. Individuals not using their LLIN, those using damaged bed nets, and those who reported vegetation around their houses developed higher IgG responses to gSG6-P1 and Nterm-34 kDa compared to those who did not (all p<0.05). The immune-epidemiological biomarkers have shown promising potential as indicators for monitoring human exposure to various mosquito bites and their heterogeneity in the same site. However, additional research is needed to validate the efficacy of this technique for surveillance purposes and to assess the effectiveness of vector control interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ngangue-Siewe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Surveillance of HIV-1 pre-treatment drug resistance (PDR) is essential for ensuring the success of first-line antiretroviral therapy (ART). Beside population-based surveys, sentinel surveillance of PDR and circulating HIV-1 clades in specific populations such as blood donors could efficiently inform decision-making on ART program. We therefore sought to ascertain HIV-1 residual infection, the threshold of PDR and viral diversity among recently-diagnosed blood donors in Gabon., Methods: A sentinel surveillance was conducted among 381 consenting blood donors at the National Blood Transfusion Center (NBTC) in Gabon from August 3,2020 to August, 31, 2021. In order to determine the residual risk of HIV transmission, viral load and HIV-1 Sanger-sequencing were performed at the Chantal BIYA International Reference Center (CIRCB)-Cameroon on HIV samples previously tested seronegative with ELISA in Gabon. Phylogeny was performed using MEGA X, PDR threshold>10% was considered high and data were analysed using p≤0.05 for statistical significance., Results: Five HIV-negative blood donors had a detectable viral load indicating a high residual risk of HIV transmission. Among the samples successfully sequenced, four participants had major drug resistance mutations (DRMs), giving a threshold of PDR of 25% (4/16). By drug class, major DRMs targeting NNRTI (K103N, E138G), NRTIs (L210W) and PI/r (M46L). The most representative viral clades were CRF02&#95;AG and subtype A1. The genetic diversity of HIV-1 had no significant effect on the residual risk in blood transfusion (CRF02&#95;AG, P = 0.3 and Recombinants, P = 0.5)., Conclusion: This sentinel surveillance indicates a high residual risk of HIV-1 transfusion in Gabon, thereby underscoring the need for optimal screening strategy for blood safety. Moreover, HIV-1 transmission goes with high-risk of PDR, suggesting suboptimal efficacy of ART. Nonetheless, the genetic diversity has limited (if any effect) on the residual risk of infection and PDR in blood donors., Competing Interests: The authors have declared that there are no interests competitors., (Copyright: © 2024 Mangala et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with breast cancer (BC) exhibit circadian rhythm disruptions, mainly of rest-activity rhythm (RAR), of which sleep is an essential component, and cortisol rhythm. Sleep complaints such as insomnia and cognitive impairments are prevalent in BC. In general population, sleep is known to contribute greatly to cognition. Thus, improving RAR (and particularly sleep) could help limiting cognitive impairments in BC patients. It has recently been suggested that, in addition to its essential role in spatial memory, the vestibular system contributes to RAR synchronization. Its stimulation could therefore limit both sleep disturbances and spatial memory deficits in BC., Objectives: The main aim of the ICANSLEEP-2 study is to assess the effects of galvanic vestibular stimulation (GVS) on circadian rhythms. The secondary aim is to assess whether GVS improves sleep and spatial memory in BC patients., Methods: Two groups with insomnia complaints (Insomnia Severity Index > 7) will be included: a patients' group with BC (n = 50) and a healthy control group without history of cancer (n = 25). There will be two assessment sessions, before and after 2 weeks of GVS. Patients will be randomly assigned to either a GVS group or a sham group (noneffective stimulation). Controls will receive GVS. GVS effects will be quantified and compared between groups. Assessments will include actigraphy, salivary cortisol, polysomnography, a cognitive test battery (including a computer-based task for spatial memory) and validated questionnaires (for psychological functioning and sleep complaints)., Discussion: Current methods for improving sleep in BC have had controversial outcomes regarding sleep structure. We expect GVS to offer a new mean of directly targeting RAR disruptions in BC patients, with beneficial effects on sleep structure. Given the crucial impact of sleep on cognitive functioning, notably spatial memory, improving sleep of BC patients should enhance their cognitive functioning., Ethics and Dissemination: This study received ethical approval from the Ile de France IV institutional review board on 19 April 2022 (no. ID-RCB: 2022-A00437-36). The findings yielded by this protocol will be presented at various conferences and in peer-reviewed journals., Clinicaltrials.gov Registration Number: NCT05414357., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Galin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The quest for higher spatial and/or temporal resolution in functional MRI (fMRI) while preserving a sufficient temporal signal-to-noise ratio (tSNR) has generated a tremendous amount of methodological contributions in the last decade ranging from Cartesian vs. non-Cartesian readouts, 2D vs. 3D acquisition strategies, parallel imaging and/or compressed sensing (CS) accelerations and simultaneous multi-slice acquisitions to cite a few. In this paper, we investigate the use of a finely tuned version of 3D-SPARKLING. This is a non-Cartesian CS-based acquisition technique for high spatial resolution whole-brain fMRI. We compare it to state-of-the-art Cartesian 3D-EPI during both a retinotopic mapping paradigm and resting-state acquisitions at 1mm3 (isotropic spatial resolution). This study involves six healthy volunteers and both acquisition sequences were run on each individual in a randomly-balanced order across subjects. The performances of both acquisition techniques are compared to each other in regards to tSNR, sensitivity to the BOLD effect and spatial specificity. Our findings reveal that 3D-SPARKLING has a higher tSNR than 3D-EPI, an improved sensitivity to detect the BOLD contrast in the gray matter, and an improved spatial specificity. Compared to 3D-EPI, 3D-SPARKLING yields, on average, 7% more activated voxels in the gray matter relative to the total number of activated voxels., Competing Interests: Guillaume Daval-Frérot was employed by Siemens Healthineers at the time this work was performed. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist., (Copyright: © 2024 Amor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Shared spaces are urban areas without physical separation between motorised and non-motorised users. Previous research has suggested that it is difficult for users to appropriate these spaces and that the advent of self-driving cars could further complicate interactions. It is therefore important to study the perception of these spaces from the users' perspectives to determine which conditions may promote their acceptance of the vehicles. This study investigates the perceived collision risk of a self-driving car's passenger when pedestrians cross the vehicle's path. The experiment was conducted with a driving simulator. Seven factors were manipulated to vary the dynamics of the crossing situations in order to analyse their influence on the passenger's perception of collision risk. Two measures of perceived risk were obtained. A continuous subjective assessment, reflecting an explicit risk evaluation, was reported in real time by participants. On the other hand, their skin conductance responses, which reflects implicit information processing, were recorded. The relationship between the factors and the risk perception indicators was studied using Bayesian networks. The best Bayesian networks demonstrate that subjective collision risk assessments are primarily influenced by the factors that determine the relative positions of the vehicle and the pedestrian as well as the distance between them when they are in close proximity. The analysis further reveals that variations in skin conductance response indicators are more likely to be explained by variations in subjective assessments than by variations in the manipulated factors. These findings could benefit the development of self-driving navigation among pedestrians by improving understanding of the factors that influence passengers' feelings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Petit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aims to develop high-performing Machine Learning and Deep Learning models in predicting hospital length of stay (LOS) while enhancing interpretability. We compare performance and interpretability of models trained only on structured tabular data with models trained only on unstructured clinical text data, and on mixed data., Methods: The structured data was used to train fourteen classical Machine Learning models including advanced ensemble trees, neural networks and k-nearest neighbors. The unstructured data was used to fine-tune a pre-trained Bio Clinical BERT Transformer Deep Learning model. The structured and unstructured data were then merged into a tabular dataset after vectorization of the clinical text and a dimensional reduction through Latent Dirichlet Allocation. The study used the free and publicly available Medical Information Mart for Intensive Care (MIMIC) III database, on the open AutoML Library AutoGluon. Performance is evaluated with respect to two types of random classifiers, used as baselines., Results: The best model from structured data demonstrates high performance (ROC AUC = 0.944, PRC AUC = 0.655) with limited interpretability, where the most important predictors of prolonged LOS are the level of blood urea nitrogen and of platelets. The Transformer model displays a good but lower performance (ROC AUC = 0.842, PRC AUC = 0.375) with a richer array of interpretability by providing more specific in-hospital factors including procedures, conditions, and medical history. The best model trained on mixed data satisfies both a high level of performance (ROC AUC = 0.963, PRC AUC = 0.746) and a much larger scope in interpretability including pathologies of the intestine, the colon, and the blood; infectious diseases, respiratory problems, procedures involving sedation and intubation, and vascular surgery., Conclusions: Our results outperform most of the state-of-the-art models in LOS prediction both in terms of performance and of interpretability. Data fusion between structured and unstructured text data may significantly improve performance and interpretability., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jaotombo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The adverse impacts of alien birds are widespread and diverse, and associated with costs due to the damage caused and actions required to manage them. We synthesised global cost data to identify variation across regions, types of impact, and alien bird species. Costs amount to US$3.6 billion, but this is likely a vast underestimate. Costs are low compared to other taxonomic groups assessed using the same methods; despite underreporting, alien birds are likely to be less damaging and easier to manage than many other alien taxa. Research to understand why this is the case could inform measures to reduce costs associated with biological invasions. Costs are biassed towards high-income regions and damaging environmental impacts, particularly on islands. Most costs on islands result from actions to protect biodiversity and tend to be low and one-off (temporary). Most costs at mainland locations result from damage by a few, widespread species. Some of these costs are high and ongoing (permanent). Actions to restrict alien bird invasions at mainland locations might prevent high, ongoing costs. Reports increased sharply after 2010, but many are for local actions to manage expanding alien bird populations. However, the successful eradication of these increasingly widespread species will require a coordinated, international response., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Evans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long-lasting insecticidal bed nets (LLINs) are a key measure for preventing malaria and their evaluation is coordinated by the World Health Organization Pesticide Evaluation Scheme (WHOPES). LifeNet® was granted WHOPES time-limited interim recommendation in 2011 after successful Phase I and Phase II evaluations. Here, we evaluated the durability and community acceptance of LifeNet® in a Phase III trial from June 2014 to June 2017 in Benin rural area., Methods: A prospective longitudinal, cluster-randomized, controlled trial with households as the unit of observation was designed to assess the performance of LifeNet® over a three-year period, using a WHOPES fully recommended LLIN (PermaNet® 2.0) as a positive control. The primary outcomes were the bioassay performance using WHO cone assays and tunnel tests, the insecticide content and physical integrity., Results: At baseline, 100% of LLINs were within the tolerance limits of their target deltamethrin concentrations. By 36 months only 17.3% of LifeNet® and 8.5% of PermaNet® LLINs still were within their target deltamethrin concentrations. Despite these low rates, 100% of both LLINs meet WHO efficacy criteria (≥ 80% mortality or ≥ 95% knockdown or tunnel test criteria of ≥ 80% mortality or ≥ 90% blood-feeding inhibition) after 36 months using WHO cone bio-assays and tunnel tests. The proportion of LLINs in good physical condition was 33% for LifeNet® and 29% for PermaNet® after 36 months. After 36 M the survivorship was 21% and 26% for LifeNet® and PermaNet® respectively. Although both LLINs were well accepted by the population, complaints of side effects were significantly higher among LifeNet® users than PermaNet® ones., Conclusion: LifeNet® LLINs did meet WHO criteria for bio-efficacy throughout the study period and were well accepted by the population. This is an important step towards getting a full WHO recommendation for use in malaria endemic countries., Competing Interests: The authors declare that they have no competing interests, (Copyright: © 2023 Djènontin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Two well-established numerical representations of the coagulation cascade either initiated by the intrinsic system (Chatterjee et al., PLOS Computational Biology 2010) or the extrinsic system (Butenas et al., Journal of Biological Chemistry, 2004) were compared with thrombin generation assays under realistic pathological conditions. Biochemical modifications such as the omission of reactions not relevant to the case studied, the modification of reactions related to factor XI activation and auto-activation, the adaptation of initial conditions to the thrombin assay system, and the adjustment of some of the model parameters were necessary to align in vitro and in silico data. The modified models are able to reproduce thrombin generation for a range of factor XII, XI, and VIII deficiencies, with the coagulation cascade initiated either extrinsically or intrinsically. The results emphasize that when existing models are extrapolated to experimental parameters for which they have not been calibrated, careful adjustments are required., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ranc et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Soon after the beginning of the COVID-19 pandemic in early 2020, the Betacoronavirus SARS-CoV-2 infection of several mink farms breeding American minks (Neovison vison) for fur was detected in various European countries. The risk of a new reservoir being formed and of a reverse zoonosis from minks quickly became a major concern. The aim of this study was to investigate the four French mink farms to see whether SARS-CoV-2 was circulating there in late 2020. The investigations took place during the slaughtering period, thus facilitating different types of sampling (swabs and blood). On one of the four mink farms, 96.6% of serum samples were positive when tested with a SARS-CoV-2 ELISA coated with purified N protein recombinant antigen, and 54 out of 162 (33%) pharyngo-tracheal swabs were positive by RT-qPCR. The genetic variability among 12 SARS-CoV-2 genomes sequenced from this farm indicated the co-circulation of several lineages at the time of sampling. All the SARS-CoV-2 genomes detected were nested within the 20A clade (Nextclade), together with SARS-CoV-2 genomes from humans sampled during the same period. The percentage of SARS-CoV-2 seropositivity by ELISA varied between 0.3 and 1.1% on the other three farms. Interestingly, among these three farms, 11 pharyngo-tracheal swabs and 3 fecal pools from two farms were positive by end-point RT-PCR for an Alphacoronavirus very similar to a mink coronavirus sequence observed on Danish farms in 2015. In addition, a mink Caliciviridae was identified on one of the two farms positive for Alphacoronavirus. The clinical impact of these inapparent viral infections is not known. The co-infection of SARS-CoV-2 with other viruses on mink farms could help explain the diversity of clinical symptoms noted on different infected farms in Europe. In addition, the co-circulation of an Alphacoronavirus and SARS-CoV-2 on a mink farm would potentially increase the risk of viral recombination between alpha and betacoronaviruses as already suggested in wild and domestic animals, as well as in humans., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wasniewski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The use of complementary therapies within oncology is a clinical issue, and their evaluation a methodological challenge. This paper reports the findings of a qualitative study exploring the lived experience of a French program of complementary therapies combining structured physical activity and MBSR among women with breast cancer., Methods: This French exploratory qualitative study followed the five stages of the Inductive Process to analyze the Structure of lived Experience (IPSE) approach. Data was collected from February to April 2021 through semi structured interviews. Participants, purposively selected until data saturation. Inclusion criteria were: being an adult woman with breast cancer whatever the stage who had completed their treatment and were part of the program of complementary therapies., Results: 29 participants were included. Data analysis produced a structure of experience based on two central axes: 1) the experience these women hoped for, with two principal expectations, that is to take care of their bodies and themselves, and to become actors in their own care; and 2) an experience of discovery, first of themselves and also in their relationship with the exterior, whether with others, or in society, and in the relationships with health-care providers., Conclusions: Our results from this French study reinforce the data described in other western countries about the needs of women receiving care in oncology departments for breast cancer: they need to be informed of the existence of supportive care in cancer by the health-care professionals themselves, to be listened to, and to receive support care. A systematic work of reflexivity about this redundancy in our results and in the qualitative literature, led us to question what impeded the exploration of more complex aspects of the experience of this women-the inherently emotional and anxiety-inducing experience of cancer, especially anxiety about its recurrence and of death-and to suggest new research perspectives to overcome these methodological and theoretical obstacles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sibeoni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Optical microscopy is frequently used to visualize microrobotic agents (i.e., micro-agents) and physical surroundings with a relatively high spatio-temporal resolution. However, the limited penetration depth of optical microscopy techniques used in microrobotics (in the order of 100 μm) reduces the capability of visualizing micro-agents below biological tissue. Two-photon microscopy is a technique that exploits the principle of two-photon absorption, permitting live tissue imaging with sub-micron resolution and optical penetration depths (over 500 μm). The two-photon absorption principle has been widely applied to fabricate sub-millimeter scale components via direct laser writing (DLW). Yet, its use as an imaging tool for microrobotics remains unexplored in the state-of-the-art. This study introduces and reports on two-photon microscopy as an alternative technique for visualizing micro-agents below biological tissue. In order to validate two-photon image acquisition for microrobotics, two-type micro-agents are fabricated and employed: (1) electrospun fibers stained with an exogenous fluorophore and (2) bio-inspired structure printed with autofluorescent resin via DLW. The experiments are devised and conducted to obtain three-dimensional reconstructions of both micro-agents, perform a qualitative study of laser-tissue interaction, and visualize micro-agents along with tissue using second-harmonic generation. We experimentally demonstrate two-photon microscopy of micro-agents below formalin-fixed tissue with a maximum penetration depth of 800 μm and continuous imaging of magnetic electrospun fibers with one frame per second acquisition rate (in a field of view of 135 × 135 μm2). Our results show that two-photon microscopy can be an alternative imaging technique for microrobotics by enabling visualization of micro-agents under in vitro and ex ovo conditions. Furthermore, bridging the gap between two-photon microscopy and the microrobotics field has the potential to facilitate in vivo visualization of micro-agents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huaroto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Factors underlying clinical tolerance and hemodynamic consequences of monomorphic sustained ventricular tachycardia (VT) need to be clarified., Methods: Intra-arterial pressures (IAP) during VT were collected in patients admitted for VT ablation and correlated to clinical, ECG and baseline echocardiographical parameters., Results: 114 VTs from 58 patients were included (median 67 years old, 81% ischemic heart disease, median left ventricular ejection fraction 30%). 61 VTs were untolerated needing immediate termination (54%). VT tolerance was tightly linked to the evolution of IAPs. Faster VT rates (p<0.0001), presence of resynchronization therapy (p = 0.008), previous anterior myocardial infarction (p = 0.009) and more marginally larger baseline QRS duration (p = 0.1) were independently associated with VT tolerance. Only an inferior myocardial infarction was more often present in patients with only tolerated VTs vs patients with only untolerated VTs in multivariate analysis (OR 3.7, 95% CI 1.4-1000, p = 0.03). In patients with both well-tolerated and untolerated VTs, a higher VT rate was the only variable independently associated with untolerated VT (p = 0.02). Two different patterns of hemodynamic profiles during VT could be observed: a regular 1:1 relationship between electrical (QRS) and mechanical (IAP) events or some dissociation between both. VT with the second pattern were more often untolerated compared to the first pattern (78% vs 29%, p<0.0001)., Conclusion: This study helps to explain the large variability in clinical tolerance during VT, which is clearly related to IAP. VT tolerance may be linked to resynchronization therapy, VT rate, baseline QRS duration and location of myocardial infarction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Delasnerie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Several tools exist to measure tightness of the gastrocnemius muscles; however, few of them are reliable enough to be used routinely in the clinic. The primary objective of this study was to evaluate the intra- and inter-rater reliability of a new equinometer. The secondary objective was to determine the load to apply on the plantar surface of the metatarsal heads to achieve the highest reliability when measuring gastrocnemius tightness., Methods: The equinometer consisted of a goniometer and an electronic dynamometer, hooked up to a computer. Three raters carried out three trials of passive dorsiflexion by applying controlled pressure to the metatarsal heads of both ankles in 29 healthy subjects under two experimental conditions: knee extended (KE) and knee flexed at 30 degrees (KF). The equinometer continuously recorded the ankle dorsiflexion values (in °) corresponding to each 1 N interval of plantar pressure between 4 N and 20 N. The intra- and inter-rater reliability of the ankle dorsiflexion were evaluated through the intra-class correlation (ICC) coefficients in each of the pressure intervals., Results: The intra-rater ICC in KE and KF was between 0.84 and 0.98. The inter-rater ICC in KE and KF was between 0.59 and 0.92. The pressure interval between 14 N and 15 N had the highest intra-rater (ICC = 1) and inter-rater reliability (0.87≤ICC≤0.99). A more refined analysis of this interval found that a load of 14.5 N yielded the best reliability., Conclusions: This compact equinometer has excellent intra-rater reliability and moderate to good inter-rater reliability. Since this reliability is optimal in the 14-15 N range, this load should be used going forward in clinical practice, especially when aiming to define a pathological threshold for tightness of the gastrocnemius muscles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Martinez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The steep cornea in keratoconus can greatly impair eyesight. The etiology of keratoconus remains unclear but early injury that weakens the corneal stromal architecture has been implicated. To explore keratoconus mechanics, we conducted two numerical simulation studies., Methods: A finite-element model describing the five corneal layers and the heterogeneous mechanical behaviors of the ground substance and lamellar collagen-fiber architecture in the anterior and posterior stroma was developed using the Holzapfel-Gasser-Ogden constitutive model. The geometry was from a healthy subject. Its stroma was divided into anterior, middle, and posterior layers to assess the effect of changing regional mechanical parameters on corneal displacement and maximum principal stress under intraocular pressure. Specifically, the effect of softening an inferocentral corneal button, the collagen-based tissues throughout the whole cornea, or specific stromal layers in the button was examined. The effect of simply disorganizing the orthogonally-oriented posterior stromal fibers in the button was also assessed. The healthy cornea was also subjected to eye rubbing-like loading to identify the corneal layer(s) that experienced the most tensional stress., Results: Conical deformation and corneal thinning emerged when the corneal button or the mid-posterior stroma of the button underwent gradual softening or when the collagen fibers in the mid-posterior stroma of the button were dispersed. Softening the anterior layers of the button or the whole cornea did not evoke conical deformation. Button softening greatly increased and disrupted the stress on Bowman's membrane while mid-posterior stromal softening increased stress in the anterior layers. Eye rubbing profoundly stressed the deep posterior stroma while other layers were negligibly affected., Discussion: These observations suggest that keratoconus could be initiated, at least partly, by mechanical instability/damage in the mid-posterior stroma that then imposes stress on the anterior layers. This may explain why subclinical keratoconus is marked by posterior but not anterior elevation on videokeratoscopy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Falgayrettes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Counting and sizing blood cells in hematological analyzers is achieved using the Coulter principle. The cells flow in a micro-aperture in which a strong electrical field is imposed, so that an electrical perturbation, called pulse, is measured each time a cell crosses the orifice. The pulses are expected to contain information on the shape and deformability of Red Blood Cells (RBCs), since recent studies state that RBCs rotate and deform in the micro-orifice. By implementing a dedicated numerical model, the present study sheds light on a variety of cells dynamics, which leads to different associated pulse signatures. Furthermore, simulations provide new insights on how RBCs shapes and mechanical properties affect the measured signals. Those numerical observations are confirmed by experimental assays. Finally, specific features are introduced for assessing the most relevant characteristics from the various pulse signatures and shown to highlight RBCs alterations induced by drugs. In summary, this study paves the way to a characterization of RBC rheology by routine hematological instruments., Competing Interests: Pierre Taraconat, Jean-Philippe Gineys and Damien Isèbe are paid employees of HORIBA Medical. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Taraconat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) was associated with better clinical success and a lower rate of adverse events (AEs) than fluoroscopy-guided percutaneous transhepatic biliary drainage (PTBD) in recent single center studies with mainly retrospective design and small case numbers (< 50). The aim of this prospective European multicenter study is to compare both drainage procedures using ultrasound-guidance and primary metal stent implantation in patients with malignant distal bile duct obstruction (PUMa Trial)., Methods: The study is designed as a non-randomized, controlled, parallel group, non-inferiority trial. Each of the 16 study centers performs the procedure with the best local expertise (PTBD or EUS-BD). In PTBD, bile duct access is performed by ultrasound guidance. EUS-BD is performed as an endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS), EUS-guided choledochoduodenostomy (EUS-CDS) or EUS-guided antegrade stenting (EUS-AGS). Insertion of a metal stent is intended in both procedures in the first session. Primary end point is technical success. Secondary end points are clinical success, duration pf procedure, AEs graded by severity, length of hospital stay, re-intervention rate and survival within 6 months. The target case number is 212 patients (12 calculated dropouts included)., Discussion: This study might help to clarify whether PTBD is non-inferior to EUS-BD concerning technical success, and whether one of both interventions is superior in terms of efficacy and safety in one or more secondary endpoints. Randomization is not provided as both procedures are rarely used after failed endoscopic biliary drainage and study centers usually prefer one of both procedures that they can perform best., Trial Registration: ClinicalTrials.gov ID: NCT03546049 (22.05.2018)., Competing Interests: The authors have declared that no competing interests exist.

Introduction: This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia., Methods: This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death., Results: The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes., Conclusion: Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia., Trial Registration: (NCT0172946)., Competing Interests: The authors have declared that no competing interests exist.

High-throughput screening of available genomic data and identification of potential antigenic candidates have promoted the development of epitope-based vaccines and therapeutics. Several immunoinformatic tools are available to predict potential epitopes and other immunogenicity-related features, yet it is still challenging and time-consuming to compare and integrate results from different algorithms. We developed the R script SILVI (short for: from in silico to in vivo), to assist in the selection of the potentially most immunogenic T-cell epitopes from Human Leukocyte Antigen (HLA)-binding prediction data. SILVI merges and compares data from available HLA-binding prediction servers, and integrates additional relevant information of predicted epitopes, namely BLASTp alignments with host proteins and physical-chemical properties. The two default criteria applied by SILVI and additional filtering allow the fast selection of the most conserved, promiscuous, strong binding T-cell epitopes. Users may adapt the script at their discretion as it is written in open-source R language. To demonstrate the workflow and present selection options, SILVI was used to integrate HLA-binding prediction results of three example proteins, from viral, bacterial and parasitic microorganisms, containing validated epitopes included in the Immune Epitope Database (IEDB), plus the Human Papillomavirus (HPV) proteome. Applying different filters on predicted IC50, hydrophobicity and mismatches with host proteins allows to significantly reduce the epitope lists with favourable sensitivity and specificity to select immunogenic epitopes. We contemplate SILVI will assist T-cell epitope selections and can be continuously refined in a community-driven manner, helping the improvement and design of peptide-based vaccines or immunotherapies. SILVI development version is available at: github.com/JoanaPissarra/SILVI2020 and https://doi.org/10.5281/zenodo.6865909., Competing Interests: The authors declare no competing interests exist.

Plasmodium falciparum, a protozoan parasite and causative agent of human malaria, has one of the most A/T-biased genomes sequenced to date. This may give the genome and the transcriptome unusual structural features. Recent progress in sequencing techniques has made it possible to study the secondary structures of RNA molecules at the transcriptomic level. Thus, in this study we produced the in vivo RNA structurome of a protozoan parasite with a highly A/U-biased transcriptome. We showed that it is possible to probe the secondary structures of P. falciparum RNA molecules in vivo using two different chemical probes, and obtained structures for more than half of all transcripts in the transcriptome. These showed greater stability (lower free energy) than the same structures modelled in silico, and structural features appeared to influence translation efficiency and RNA decay. Finally, we compared the P. falciparum RNA structurome with the predicted RNA structurome of an A/U-balanced species, P. knowlesi, finding a bias towards lower overall transcript stability and more hairpins and multi-stem loops in P. falciparum. This unusual protozoan RNA structurome will provide a basis for similar studies in other protozoans and also in other unusual genomes., Competing Interests: The authors have declared that no competing interests exist.

The objective of the study was to perform a cost-effectiveness analysis of bundled devices (BDs) versus standard devices (SDs) for the prevention of unscheduled peripheral venous catheter (PVC) removal due to complication from a French investigator-initiated, open-label, single center, randomized-controlled, two-by-two factorial trial (CLEAN-3 study). A 14-day time non homogeneous semi-markovian model was performed to be fitted to longitudinal individual patient data from CLEAN-3 database. This model includes five health states and eight transitional events; a base case scenario, two scenario analyses and bootstrap sensitivity analyses were performed. The cost-effectiveness criterion was the cost per patient with unscheduled PVC removal avoided. 989 adult (age≥18 years) patients were analyzed to compare the BDs group (494 patients), and the SDs group (495 patients). The assessed intervention was a combination of closed integrated catheters, positive displacement needleless-connectors, disinfecting caps, and single-use prefilled flush syringes compared with the use of open catheters and three-way stopcocks for treatment administration. For the base case scenario, an unscheduled 1st PVC removal before discharge was significantly more frequent in the SDs group (235 patients (47.5%) in the SDs group and 172 patients (34.8%) in the BDs group, p = 0.00006). After adjustment for 1st catheter time, the number of patients with unscheduled PVC removal per day was of 16 (95%CI: 15; 18) patients (out of 100) in the BDs group and of 26 (95%CI: 24; 28) patients (out of 100) in the SDs group. The mean cost per patient (adjusted on catheter-time) was of €144 (95%CI: €135-€154) for patients in the SDs group versus €102 (95%CI: €95-€109) for patients in the BDs group; the mean saving per patient was of €42 (95%CI: €32-€54). As a consequence, the assessed BDs strategy was less costly and more effective than the SDs strategy. Trail registration: CLEAN-3 study is registered with ClinicalTrials.gov, NCT03757143., Competing Interests: OM & JG received personal fees from Becton Dickinson, funding for congress attendance, and research funding from Becton Dickinson. MB received personal fees from Becton Dickinson. All other investigators and authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs., Competing Interests: AF, KMK, JAT, LMM, JMR, PCF, GEH, FM, PN, CAR-P, DMF, TJ, RM-P, KW, ALM-W, DSG, AP, KM, SCH, KML, LH, JC, IC, and DWYT are employed by or affiliated with PetDx; and receive compensation from PetDx and/or hold vested or unvested equity in PetDx. Drs. Flesner and Leibman are members of the PetDx clinical advisory board and receive compensation and equity. Dr. Borgatti has ownership interest (including patents) in a patent entitled “Reduction of EGFR therapeutic toxicity” filed by the University of Minnesota Office of Technology Commercialization. Drs. Cahalane, Phillips, and Aiken are investors in PetDx. Drs. Jensen, van den Boom, Dharajiya, and Diaz are advisors for PetDx and hold vested or unvested equity in PetDx. Drs. Chorny, Kruglyak, Grosu, Marass, Ruiz-Perez and Tsui hold pending patent applications related to technology described in this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The lumbricid earthworms Eisenia andrei (Ea) and E. fetida (Ef) have been used as model organisms for studies on hybridization. Previously they have been identified by species specific sequences of the mitochondrial COI gene of maternal origin ('a' or 'f') and the nuclear 28S gene of maternal/paternal origin ('A' or 'F'). In experimental crosses, these hermaphroditic species produce progeny of genotypes Ea (aAA), Ef (fFF) and hybrids (aAF and fFA) originating by self-fertilization or cross-fertilization. To facilitate studies on new aspects of the breeding biology and hybridization of earthworms, polymorphic microsatellite markers were developed based on 12 Ea and 12 Ef specimens and validated on DNA samples extracted from 24 genotyped specimens (aAA, fFF, aAF and fFA) from three laboratory-raised families and 10 of them were applied in the present study. The results indicate that microsatellite markers are valuable tools for tracking interspecific gene flow between these species., Competing Interests: The authors have declared that no competing interests exist.

SARS-CoV-2 variants are emerging with potential increased transmissibility highlighting the great unmet medical need for new therapies. Niclosamide is a potent anti-SARS-CoV-2 agent that has advanced in clinical development. We validate the potent antiviral efficacy of niclosamide in a SARS-CoV-2 human airway model. Furthermore, niclosamide remains its potency against the D614G, Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants. Our data further support the potent anti-SARS-CoV-2 properties of niclosamide and highlights its great potential as a therapeutic agent for COVID-19., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MOAS and AW are shareholders or benefit from an employee incentive scheme in UNION therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Further, UNION had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All other authors have nothing to disclose.

Background: "Sleep Low-Train Low" is a training-nutrition strategy intended to purposefully reduce muscle glycogen availability around specific exercise sessions, potentially amplifying the training stimulus via augmented cell signalling. The aim of this study was to assess the feasibility of a 3-week home-based "sleep low-train low" programme and its effects on cycling performance in trained athletes., Methods: Fifty-five trained athletes (Functional Threshold Power [FTP]: 258 ± 52W) completed a home-based cycling training program consisting of evening high-intensity training (6 × 5 min at 105% FTP), followed by low-intensity training (1 hr at 75% FTP) the next morning, three times weekly for three consecutive weeks. Participant's daily carbohydrate (CHO) intake (6 g·kg-1·d-1) was matched but timed differently to manipulate CHO availability around exercise: no CHO consumption post- HIT until post-LIT sessions [Sleep Low (SL), n = 28] or CHO consumption evenly distributed throughout the day [Control (CON), n = 27]. Sessions were monitored remotely via power data uploaded to an online training platform, with performance tests conducted pre-, post-intervention., Results: LIT exercise intensity reduced by 3% across week 1, 3 and 2% in week 2 (P < 0.01) with elevated RPE in SL vs. CON (P < 0.01). SL enhanced FTP by +5.5% vs. +1.2% in CON (P < 0.01). Comparable increases in 5-min peak power output (PPO) were observed between groups (P < 0.01) with +2.3% and +2.7% in SL and CON, respectively (P = 0.77). SL 1-min PPO was unchanged (+0.8%) whilst CON improved by +3.9% (P = 0.0144)., Conclusion: Despite reduced relative training intensity, our data demonstrate short-term "sleep low-train low" intervention improves FTP compared with typically "normal" CHO availability during exercise. Importantly, training was completed unsupervised at home (during the COVID-19 pandemic), thus demonstrating the feasibility of completing a "sleep low-train low" protocol under non-laboratory conditions., Competing Interests: The authors have declared that no competing interests exist.

For functional MRI with a multi-channel receiver RF coil, images are often reconstructed channel by channel, resulting into multiple images per time frame. The final image to analyze usually is the result of the covariance Sum-of-Squares (covSoS) combination across these channels. Although this reconstruction is quasi-optimal in SNR, it is not necessarily the case in terms of temporal SNR (tSNR) of the time series, which is yet a more relevant metric for fMRI data quality. In this work, we investigated tSNR optimality through voxel-wise RF coil combination and its effects on BOLD sensitivity. An analytical solution for an optimal RF coil combination is described, which is somewhat tied to the extended Krueger-Glover model involving both thermal and physiological noise covariance matrices. Compared experimentally to covSOS on four volunteers at 7T, the method yielded great improvement of tSNR but, surprisingly, did not result into higher BOLD sensitivity. Solutions to improve the method such as for example the t-score for the mean recently proposed are also explored, but result into similar observations once the statistics are corrected properly. Overall, the work shows that data-driven RF coil combinations based on tSNR considerations alone should be avoided unless additional and unbiased assumptions can be made., Competing Interests: The authors have declared that no competing interests exist.

Helicopter landing on a ship is a visually regulated "rendezvous" task during which pilots must use fine control to land a powerful rotorcraft on the deck of a moving ship tossed by the sea while minimizing the energy at impact. Although augmented reality assistance can be hypothesized to improve pilots' performance and the safety of landing maneuvers by guiding action toward optimal behavior in complex and stressful situations, the question of the optimal information to be displayed to feed the pilots' natural information-movement coupling remains to be investigated. Novice participants were instructed to land a simplified helicopter on a ship in a virtual reality simulator while minimizing energy at impact and landing duration. The wave amplitude and related ship heave were manipulated. We compared the benefits of two types of visual augmentation whose design was based on either solving cockpit-induced visual occlusion problems or strengthening the online regulation of the deceleration by keeping the current [Formula: see text] variable around an ideal value of -0.5 to conduct smooth and efficient landing. Our results showed that the second augmentation, ecologically grounded, offers benefits at several levels of analysis. It decreases the landing duration, improves the control of the helicopter displacement, and sharpens the sensitivity to changes in [Formula: see text]. This underlines the importance for designers of augmented reality systems to collaborate with psychologists to identify the relevant perceptual-motor strategy that must be encouraged before designing an augmentation that will enhance it., Competing Interests: The authors have declared that no competing interests exist.

Background: Regional analgesia is worth performing in the multimodal postoperative management of hip fracture (HF) because it reduces hospital morbidity and mortality. The aim of this study is to compare the efficacy and side effects of the recently described "Pericapsular Nerve Group (PENG) Block" with those of the femoral block, which is considered the standard of care for postoperative pain control after femoral neck fracture., Materials and Methods: We conducted a comparative observational study at a university hospital (Saint Antoine Hospital, Sorbonne University, Paris, France), where the PENG block was introduced in August 2019. We include all patients from June to October 2019, who were coming for femoral neck fractures and who had an analgesic femoral block or PENG block before their surgery. The primary outcome was the comparison of cumulative postoperative morphine consumption 48 hours after surgery., Results: Demographics, medical charts, and perioperative data of 42 patients were reviewed: 21 patients before (Femoral group) and 21 patients after the introduction of PENG block (PENG group) in clinical practice. Thirteen total hip arthroplasties (THA) and eight hemi arthroplasties (HA) were included in each group. Demographics were also comparable. The median, postoperative, morphine equivalent consumption at 48 hours was 10 [0-20] mg and 20 [0-50] mg in Femoral and PENG groups respectively (p = 0.458). No statistically significant differences were found in postoperative pain intensity, time to ambulation, incidence of morphine-related side effects, or length of hospital stay. The postoperative muscle strength of the quadriceps was greater in the PENG group than in the Femoral group (5/5 vs. 2/5, p = 0.001)., Conclusion: In the management of hip fractures, PENG block is not associated in our study with a significant change in postoperative morphine consumption, compared to femoral block. However, it does significantly improve the immediate mobility of the operated limb, making it appropriate for inclusion in enhanced recovery programs after surgery., Competing Interests: The authors have declared that no competing interests exist.

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: HP reports personal fees from MSD, Janssen, and Biomerieux. ET reports research grants from Servier and Vaxeal; reports honorarium fees from BMS and Merck-MSD; reports honorarium fees for participation on advisory boards from BMS and Astra-Zeneca. PLT reports honorarium fees for participation on advisory boards for Retrophin Inc not related to this work. JBA reports consultancy/expert testimony and honoraria from Novartis and Pfizer. BC reports receiving consulting fees and honoraria for lectures at symposia from Edwards Life Sciences, Orion Pharma, Amomed, and Nordic Pharma. MZ reports research grants from the French Ministry of Health, Quantum Genomics, and the European Horizon 2020 program; reports grant support and nonfinancial support from ReCor Medical and Idorsia; and reports personal fees from CVRx. JSH reports grants from Bioserenity, Sanofi, Servier and Novo Nordisk. J.S.H; reports speaker, advisory board or consultancy fees from Amgen, Astra Zeneca, Bayer, Bristol-Myers Squibb, Novartis, Novo Nordisk. SC reports personal fees from Novonordisk, Lilly, Kabi, Janssen-Cilag, Servier, outside the submitted work; reports other from MyGoodLife. FP reported receiving grants from Bristol-Myers and Squibb and HalioDx outside the submitted work; participation in Scientific Advisory Boards & Meetings for Bristol-Myers Squibb, Roche, Janssen, Merck, and Gilead. DMS received consulting fees or travels expenses from Boehringer Ingelheim, Léo Pharma, Aspen and Carmat. None of them are related to the work described here. M-ADD reported having received speaker fees from BMS, Gilead and Roche outside the submitted work. The remaining authors declared no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: A year after the COVID-19 pandemic started, there are still few scientific reports on COVID-19 in Africa. This study explores the clinical profiles and factors associated with COVID-19 in Cameroon., Materials and Methods: In this prospective cohort study, we followed patients admitted for suspicion of COVID-19 at Djoungolo Hospital between 01st April and 31st July 2020. Patients were categorised by age groups and disease severity: mild (symptomatic without clinical signs of pneumonia), moderate (with clinical signs of pneumonia without respiratory distress) and severe cases (clinical signs of pneumonia and respiratory distress not requiring invasive ventilation). Demographic information and clinical features were summarised. Multivariable analysis was performed to predict risk., Findings: A total of 313 patients were admitted during the study period; 259 were confirmed cases of COVID-19 by Polymerase Chain Reaction (PCR). Among the confirmed cases, the male group aged 40 to 49 years (13.9%) was predominant. Disease severity ranged from mild (26.2%; n = 68) to moderate (59%; n = 153) to severe (14.7%; n = 38); the case fatality rate was 1% (n = 4). Dysgusia (46%; n = 119) and hyposmia/anosmia (37.8%; n = 98) were common features of COVID-19. Nearly one-third of patients had comorbidities (29%; n = 53), of which hypertension was the most common (18.9%; n = 49). Participation in mass gatherings (Odds Ratio (OR) = 2.37; P = 0.03) and dysgusia (OR = 2.09, P = 0.02) were predictive of diagnosis of COVID-19. Age groups 60 to 69 (OR = 7.41; P = 0.0001), 50 to 59 (OR = 4.09; P = 0.03), 40 to 49 (OR = 4.54; P = 0.01), male gender (OR = 2.53; P = 0.04), diabetes (OR = 4.05; P = 0.01), HIV infection (OR = 5.57; P = 0.03), lung disease (OR = 6.29; P = 0.01), dyspnoea (OR = 3.70; P = 0.008) and fatigue (OR = 3.35; P = 0.02) significantly predicted COVID-19 severity., Conclusions: Most COVID-19 cases in this study were benign with low fatality. Age (40-70), male gender, HIV infection, lung disease, dyspnoea and fatigue are associated with severe COVID-19. Such findings may guide public health decision-making., Competing Interests: The authors have declared that no competing interests exist.

A numerical approach is presented to efficiently simulate time-resolved 3D phase-contrast Magnetic resonance Imaging (or 4D Flow MRI) acquisitions under realistic flow conditions. The Navier-Stokes and Bloch equations are simultaneously solved with an Eulerian-Lagrangian formalism. A semi-analytic solution for the Bloch equations as well as a periodic particle seeding strategy are developed to reduce the computational cost. The velocity reconstruction pipeline is first validated by considering a Poiseuille flow configuration. The 4D Flow MRI simulation procedure is then applied to the flow within an in vitro flow phantom typical of the cardiovascular system. The simulated MR velocity images compare favorably to both the flow computed by solving the Navier-Stokes equations and experimental 4D Flow MRI measurements. A practical application is finally presented in which the MRI simulation framework is used to identify the origins of the MRI measurement errors., Competing Interests: This study was funded by ALARA Expertise (https://www.alara-expertise.fr/) and Spin Up (https://www.spin-up.fr/). Thomas Puiseux and Anou Sewonu are paid employees of Spin Up and Ramiro Moreno is paid employee of ALARA Expertise. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Odorant metabolizing enzymes (OMEs) are expressed in the olfactory epithelium (OE) where they play a significant role in the peripheral olfactory process by catalyzing the fast biotransformation of odorants leading either to their elimination or to the synthesis of new odorant stimuli. The large family of OMEs gathers different classes which interact with a myriad of odorants alike and complementary to olfactory receptors. Thus, it is necessary to increase our knowledge on OMEs to better understand their function in the physiological process of olfaction. This study focused on a major olfactory UDP-glucuronosyltransferase (UGT): UGT2A1. Immunohistochemistry and immunogold electronic microscopy allowed to localize its expression in the apical part of the sustentacular cells and originally at the plasma membrane of the olfactory cilia of the olfactory sensory neurons, both locations in close vicinity with olfactory receptors. Moreover, using electroolfactogram, we showed that a treatment of the OE with beta-glucuronidase, an enzyme which counterbalance the UGTs activity, increased the response to eugenol which is a strong odorant UGT substrate. Altogether, the results supported the function of the olfactory UGTs in the vertebrate olfactory perireceptor process., Competing Interests: The authors have declared that no competing interests exist.

Background: Self-administered massage interventions with a roller massager are commonly used as part of warm-ups and post-workout recovery routines. There is yet no clear consensus regarding the practical guidelines for efficient embedded interventions., Objectives: The present randomized crossover pilot trial aimed at examining the effects of a rolling intervention with a roller massager embedded within the rests periods of a resistance training protocol. The rolling intervention targeted quadriceps muscles., Setting: Participants (n = 14) performed two resistance training protocols expected to elicit momentary muscle failure. The protocol consisted in 10 sets of 10 rest-pause repetitions of back squats, with a poundage set up at 50% of the maximal one-repetition. Two min were allocated to recovery between sets. During the recovery periods, participants completed a rolling routine with a roller massager for 60 s (Roller-massager), or underwent passive recovery (Control). The total workload, concentric power, thigh circumference rate of perceived exertion (RPE) and delayed onset of muscle soreness (DOMS) from 24 h to 120 h after completion of the protocol were the dependent variables., Results: Roller-massager was associated with a reduction in total workload (-11.6%), concentric power (-5.1%) and an increase in perceived exertion compared to Control (p < 0.05). Roller-massager was also associated with reduced thigh circumference after the resistance training protocol, indicating reduced muscle swelling, and reduced DOMS 24 h to 120 h post-workout (p < 0.001)., Conclusion: These findings support that embedded rolling with a roller massager hinders performance and increases effort perception. Embedded interventions may not be suitable during conditioning periods designed to maximize training intensity., Competing Interests: The authors declare no conflict of interest. The commercial affiliation to CAPSIX Robotics does not alter authors’ adherence to all PLOS ONE policies on sharing data and materials. CAPSIX Robotics is not a company promoting self-myofascial release or conditioning products.

Background: The WHO African region frequently experiences outbreaks and epidemics of infectious diseases often exacerbated by weak health systems and infrastructure, late detection, and ineffective outbreak response. To address this, the WHO Regional Office for Africa developed and began implementing the Integrated Disease Surveillance and Response strategy in 1998., Objectives: This systematic review aims to document the identified successes and challenges surrounding the implementation of IDSR in the region available in published literature to highlight areas for prioritization, further research, and to inform further strengthening of IDSR implementation., Methods: A systematic review of peer-reviewed literature published in English and French from 1 July 2012 to 13 November 2019 was conducted using PubMed and Web of Science. Included articles focused on the WHO African region and discussed the use of IDSR strategies and implementation, assessment of IDSR strategies, or surveillance of diseases covered in the IDSR framework. Data were analyzed descriptively using Microsoft Excel and Tableau Desktop 2019., Results: The number of peer-reviewed articles discussing IDSR remained low, with 47 included articles focused on 17 countries and regional level systems. Most commonly discussed topics were data reporting (n = 39) and challenges with IDSR implementation (n = 38). Barriers to effective implementation were identified across all IDSR core and support functions assessed in this review: priority disease detection; data reporting, management, and analysis; information dissemination; laboratory functionality; and staff training. Successful implementation was noted where existing surveillance systems and infrastructure were utilized and streamlined with efforts to increase access to healthcare., Conclusions and Implications of Findings: These findings highlighted areas where IDSR is performing well and where implementation remains weak. While challenges related to IDSR implementation since the first edition of the technical guidelines were released are not novel, adequately addressing them requires sustained investments in stronger national public health capabilities, infrastructure, and surveillance processes., Competing Interests: The authors have declared that no competing interests exist.

This study assesses the cost-effectiveness of Technology Lipido-Colloid with Nano Oligo Saccharide Factor (TLC-NOSF) wound dressings versus neutral dressings in the management of diabetic foot ulcers (DFUs) from a French collective perspective. We used a Markov microsimulation cohort model to simulate the DFU monthly progression over the lifetime horizon. Our study employed a mixed method design with model inputs including data from interventional and observational studies, French databases and expert opinion. The demographic characteristics of the simulated population and clinical efficacy were based on the EXPLORER double-blind randomized controlled trial. Health-related quality of life, costs, and resource use inputs were taken from the literature relevant to the French context. The main outcomes included life-years without DFU (LYsw/DFU), quality-adjusted life-years (QALYs), amputations, and lifetime costs. To assess the robustness of the results, sensitivity and subgroup analyses based on the wound duration at treatment initiation were performed. Treatment with the TLC-NOSF dressing led to total cost savings per patient of EUR 35,489, associated with gains of 0.50 LYw/DFU and 0.16 QALY. TLC-NOSF dressings were established as the dominant strategy in the base case and all sensitivity analyses. Furthermore, the model revealed that, for every 100 patients treated with TLC-NOSF dressings, two amputations could be avoided. According to the subgroup analysis results, the sooner the TLC-NOSF treatment was initiated, the better were the outcomes, with the highest benefits for ulcers with a duration of two months or less (+0.65 LYw/DFU, +0.23 QALY, and cost savings of EUR 55,710). The results from the French perspective are consistent with the ones from the German and British perspectives. TLC-NOSF dressings are cost-saving compared to neutral dressings, leading to an increase in patients' health benefits and a decrease in the associated treatment costs. These results can thus be used to guide healthcare decisionmakers. The potential savings could represent EUR 3,345 per treated patient per year and even reach EUR 4,771 when TLC-NOSF dressings are used as first line treatment. The EXPLORER trial is registered with ClinicalTrials.gov, number NCT01717183., Competing Interests: This cost-effectiveness study was funded by Urgo Medical Company FM, https://www.urgo-group.fr/. The assessed dressings are devices marketed by Urgo Medical. The funder provided support in the form of salaries for authors AO, SF, LT, and SB. FM is the CEO of Statesia. A service agreement (commercial contract) was arranged between Urgo Medical and Statesia. Statesia had no other competing interests in the area of this publication relating to employment, consultancy, patents, products in development, or marketed products. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Purpose: To describe drug prescription for gastrointestinal symptoms during pregnancy., Methods: Using the French national health database, we identified pregnancies ending with a birth between April 2010 and December 2018, in France. We studied prescription of antacids, antispasmodics, antinauseants, laxatives and antidiarrheals during pregnancy, between two trimesters before and two trimesters after delivery. We also assessed hospitalization for gastrointestinal symptoms during pregnancy., Results: Among 6,365,471 pregnancies, 4,452,779 (74.0%) received at least one gastrointestinal drug during pregnancy; 2,228,275 (37.0%) received an antacid, 3,096,858 (51.5%) an antispasmodic, 1,861,731 (31.0%) an antinauseant, 919,116 (15.3%) a laxative and 617,808 (10.3%) an antidiarrheal. Prescription of proton pump inhibitors doubled from 12.2% in 2010 to 26.0% in 2018, while domperidone use decreased from 18.3% in 2010 to 2.2% in 2018. In addition, prescription of antacids increased from 7.0% during the trimester before pregnancy to 11.8% during the 1st trimester, 17.0% during the 2nd trimester and 23.4% during the 3rd trimester. Antispasmodic use was 10.6% during the trimester before pregnancy, 23.1% during the 1st trimester, 25.2% during the 2nd trimester and 24.0% during the 3rd trimester. Prescription of antinauseant drugs increased from 5.0% during the trimester before pregnancy to 25.7% during the 1st trimester, then decreased to 6.4% during the 2nd trimester and 3.2% during the 3rd trimester. Nausea/vomiting was the most common cause of hospitalization for gastrointestinal symptoms or diseases during pregnancy, although it accounted for only 1.0% of pregnancies., Conclusions: Approximately three-quarters of women use drugs for gastrointestinal symptoms during pregnancy in France. Prescription of gastrointestinal drugs during pregnancy should be the subject of more detailed risk-benefit assessment and recommendations., Competing Interests: Conflict of Interest: - Antoine Meyer: no conflict of interest. - Marion Fermaut: no conflict of interest. - Jérôme Drouin: no conflict of interest. - Franck Carbonnel: received honoraria from Amgen, BMS, Celltrion, Enterome, Ferring, Janssen, Medtronic, Pfizer, Pharmacosmos, Roche and Tillotts as well as lecture fees from Abbvie, Astra, BMS, Ferring, Janssen, MSD, Pfizer, Pileje, and Takeda. - Alain Weill: no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Five French oncology institutions had participated in a funded study aiming at implementing an Evidence-Based Practice tool (PAM-13), which allowed nurses to measure the level of activation of the patient to support his or her own empowerment in the cancer care pathway. The purpose of this ancillary study is to (i) describe the caregivers' perceptions of addictions and their management concurrently with cancer treatment, (ii) explore the role that Motivational Interviewing techniques can play., Methods: 15 individual semi-structured interviews of caregivers were performed, using the Theoretical Domains Framework for the interview guide. Qualitative data were analyzed inductively, in a thematic analysis. The COREQ guided the reporting of this qualitative study., Results: Views on addictions influence the way caregivers manage patients suffering from unresolved issues of addiction. Care is mainly focused on the pathology (cancer-centered) and strictly curative. When practiced, Motivational Interviewing is patient-centered, fostering the patient's empowerment on the cancer care pathway., Conclusions: The dissemination of Motivational Interviewing techniques in current practices in oncology, both in terms of doctors and nursing teams, would enable improvement to the management of addictions on the cancer care pathway, by deploying a patient-centered approach. This new paradigm of care would support the empowerment of patients enrolled in the cancer care pathway and promote better communication between caregivers and patients. Hence, a paradigm shift is essential. Motivational Interviewing techniques could provide a caring approach that promotes communication between the patient and the caregiver and also supports the former's empowerment. This research suggests the need to adapt the cancer care pathway in order to integrate the necessary care for patients who concomitantly suffer from unresolved addictive disorders., Trial Registration: NCT03706937., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The gold-standard for reconstruction of large mandibular defects is the use of free flaps of vascularized autologous bone with the fibula as the preferred donor site. The use of "custom cutting guides" for this indication is becoming increasingly prevalent. But cost of the procedure averages around 2,500 dollars per patient excluding treatment and entails selection criteria. We think it is possible to standardize mandibular reconstructions from an anatomical mean. The objective of this study was to perform a mandibular morphometric analysis in order to obtain a set of "mean" measurements, which can be used by all surgeons interested in mandibular reconstruction., Methods: We performed a morphometric analysis consisting of three-dimensional mandibular reconstructions of 30 men and 30 women. Several reference points were set and defined to evaluate specific lengths and angles of interest. We conducted an intra and inter-sexual descriptive analysis of measurements obtained., Results: We did not identify any major intra-sexual differences within each group. The gonial angle is more open in women and the measurements characterizing the basilar contour are more prominent in men. We did not identify any differences in alveolar region parameters., Conclusion: The results of this study constitute a morphological tool for surgeons, from bone graft to free flap. These results also confirm us that the use of «custom cutting guides» for mandibular reconstruction may be excessive. It is pertinent to examine the value of "custom made" mandibular reconstructions since the differences observed are of the order of millimeters., Competing Interests: The authors have declared that no competing interests exist.

Background: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor., Methods: We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry)., Results: We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively; P-value < 5×10-8) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84×10-8)., Conclusions: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk., Impact: Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: Leidos Biomedical Research Inc. and Information Management Services, Inc. provided salaries for authors J.M., E.K., C.L.D., L.B., K.J., M.M., K.W., and W.Z. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity., Competing Interests: The authors have declared that no competing interests exist. Micromem is not a commercial source, but the name of the project that is financed by the French National Agency for Research.

The success of tree recruitment in Mediterranean holm oak (Quercus ilex) forests is threatened by the increasing intensity, duration and frequency of drought periods. Seedling germination and growth are modulated by complex interactions between abiotic (microhabitat conditions) and biotic factors (mycorrhiza association) that may mitigate the impacts of climate change on tree recruitment. To better understand and anticipate these effects, we conducted a germination experiment in a long-term precipitation reduction (PR) field experiment where we monitored seedling establishment and survival, micro-habitat conditions and ectomycorrhizal (ECM) colonization by different mycelia exploration types during the first year of seedling growth. We hypothesized that (i) the PR treatment decreases seedling survival relative to the control with ambient conditions, (ii) microhabitat conditions of water and light availability are better predictors of seedling survival than the PR treatment, (iii) the PR treatment will favour the development of ECM exploration types with drought-resistance traits such as differentiated rhizomorphs. Contrary to our first hypothesis, seedling survival was lower in control plots with overall higher soil moisture. Micro-habitat light and soil moisture conditions were better predictors of seedling survival and growth than the plot-level PR treatment, confirming our second hypothesis. Furthermore, in line with our third hypothesis, we found that ECM with longer extramatrical mycelia were more abundant in the PR treatment plots and were positively correlated to survival, which suggests a potential role of this ECM exploration type in seedling survival and recruitment. Although summer drought was the main cause of seedling mortality, our study indicates that drier conditions in spring can increase seedling survival, presumably through a synergistic effect of drought adapted ECM species and less favourable conditions for root pathogens., Competing Interests: The authors have declared that no competing interests exist.

Objective: Aggressive antidiabetic therapy and rapid glycemic control are associated with diabetic neuropathy. Here we investigated if this is also the case for Charcot neuroarthropathy., Research Design and Methods: HbA1c levels and other relevant data were extracted from medical databases of 44 cases of acute Charcot neuroarthropathy., Results: HbA1c levels significantly declined from 8.25% (67mmol/mol) [7.1%-9.4%](54-79mmol/mol), at -6 months (M-6), to 7.40%(54mmol/mol) [6.70%-8.03%] (50-64 mmol/mol) during the six months preceding the diagnosis of Charcot neuroarthropathy (P <0.001)., Conclusions: HbA1c levels significantly declined during the six months preceding the onset of Charcot neuroarthropathy. This decline seems to be a associated factor with the appearance of an active phase of Charcot neuroarthropathy in poorly controlled patients with diabetic sensitive neuropathy., Competing Interests: The authors have declared that no competing interests exist.

[This corrects the article DOI: 10.1371/journal.pone.0229145.].

Introduction: Intestinal atresia is a rare congenital affliction that is often associated with severe bacterial infections despite adequate neonatal surgery. Previous studies have focused on enteric nervous system variations. We hypothesized that epithelial systems (ES) may also be involved in the pathophysiology of postnatal disorders., Materials and Methods: Global gene expression was measured by transcriptomic analysis in a rat model of induced intestinal atresia. The analyses then focused on genes involved in ES (enterocytes and goblet cells). Rat fetus small intestines at various stages of development (ED15, ED17, ED19, and ED21, n = 22), were used as non-operated controls and compared to the upper and lower segments of rat fetus small intestines with an induced atresia (n = 14; ligature at ED18). The pattern of gene expression was then confirmed by histochemistry, electron microscopy, and RT-qPCR., Results: From ED15 to ED21, the expression of several genes exhibited a physiological increase of ES markers, with a significant increase at the end of gestation. The operated embryos exhibited significantly higher variations of gene expression in the proximal segment than in the distal segment in terms of absorption and the epithelial barrier. An increase in goblet cells and markers was observed in the proximal segment compared to the controls., Conclusion: Fetal intestinal obstruction accelerates maturation in the proximal segment and disrupts the intestinal wall in the distal segment, with a decrease in the number of mucosal cells. Moreover, the epithelial cells underwent significant changes, supporting the notion that intestinal disorders involve more than the ENS., Competing Interests: The authors have declared that no competing interests exist.