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Background Acute exacerbations of fibrosing interstitial lung diseases (ILDs) are associated with high mortality. We used prospective data from the INBUILD trial to investigate risk factors for acute exacerbations and the impact of these events in patients with progressive pulmonary fibrosis. Methods Patients with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) were randomised to receive nintedanib or placebo. Associations between baseline characteristics and time to first acute exacerbation were assessed using pooled data from both treatment groups using Cox proportional hazard models, firstly univariable models and then a multivariable model using forward stepwise selection. The risk of death was estimated based on the Kaplan−Meier method. Results Over a median follow-up of approximately 19 months, acute exacerbations were reported in 58 (8.7%) of 663 patients. In the risk factor analysis, the final model included diffusing capacity of the lung for carbon monoxide (DLCO) % predicted, treatment and age. Lower DLCO % predicted was associated with an increased risk of acute exacerbation with a hazard ratio (HR) of 1.56 (95% CI 1.21–2.02) per 10 units lower (p

Social science research on severe burns has brought to light the challenges people with skin injuries face regarding visibility in the public space. When affected individuals face the issues that come with self-exposure, they attempt to control their public appearance or how the public perceives burns. Drawing on semi-structured interviews and the study of a corpus of audiovisual content and social media, we highlight different modalities of public exposure to severe burns. Accentuated by the Internet, the plurality of exposure modes allows us to identify a typology of engaged postures (epistemic, recognition, appreciation) as well as pragmatic and normative tensions emerging between them. Due to the increased weight of digital technology, the posture of appreciation prevails over the other two, to the detriment of the public learning that is central to the quest for visibility of severe burn victims.

Summary: We report the characterization of a novel tri-segmented RNA virus infecting Mercurialis annua, a common crop weed and model species in plant science. The virus, named “Mercurialis latent virus” (MeLaV) was first identified in a mixed infection with the recently described Mercurialis orthotospovirus 1 (MerV1) on symptomatic plants grown in glasshouses in Lausanne (Switzerland). Both viruses were found to be transmitted by Thrips tabaci, which presumably help the inoculation of infected pollen in the case of MeLaV. Complete genome sequencing of the latter revealed a typical ilarviral architecture and close phylogenetic relationship with members of the Ilarvirus subgroup 1. Surprisingly, a short portion of MeLaV replicase was found to be identical to the partial sequence of grapevine angular mosaic virus (GAMV) reported in Greece in the early 1990s. However, we have compiled data that challenge the involvement of GAMV in angular mosaic of grapevine, and we propose alternative causal agents for this disorder. In parallel, three highly-conserved MeLaV isolates were identified in symptomatic leaf samples in The Netherlands, including a herbarium sample collected in 1991. The virus was also traced in diverse RNA sequencing datasets from 2013 to 2020, corresponding to transcriptomic analyses of M. annua and other plant species from five European countries, as well as metaviromics analyses of bees in Belgium. Additional hosts are thus expected for MeLaV, yet we argue that infected pollen grains have likely contaminated several sequencing datasets and may have caused the initial characterization of MeLaV as GAMV.

Abstract Background During the COVID-19 pandemic, most countries introduced temporary visiting restrictions on the relatives of acute care hospital patients, whether or not they were infected with SARS-CoV-2. This affected relatives’ psychological and emotional states and how closely they could be involved in their loved one’s hospitalization. Study aims Investigate relatives’ experiences of visiting restrictions during the COVID-19 pandemic’s first wave and the support offered by Valais Hospital’s healthcare staff. Methods Relatives and patients who had been discharged between February 28 and May 13, 2020, were asked to complete a patient-reported experience measures (PREMs) questionnaire, whether or not they had been infected by SARS-CoV-2. Relatives were asked about how visiting restrictions had affected them, their perceptions of the severity of the COVID-19 pandemic, the quality of communication concerning their loved ones’ health status during their hospitalization, and the information received from healthcare staff. Descriptive and inferential statistics were computed. Results Of 866 PREMs questionnaires returned, 818 were analyzable, and 543 relatives had experienced visiting restrictions to their loved ones: 92 relatives (87%) of COVID-19 patients and 451 relatives (66%) of non-infected patients, with heterogenous effects on their psychological and affective status. Overall, whether or not relatives were subjected to visiting restrictions, they perceived themselves to be well treated, well informed, and that communication with hospital healthcare staff was satisfactory. However, relatives subjected to visiting restrictions reported significantly lower scores on the quality of communication than other relatives. The relatives of patients in gynecology/obstetrics and internal medicine wards were significantly more affected by visiting restrictions than were the relatives of patients in other wards. Numerous relatives subjected to visiting restrictions reported regular communication with their loved ones or with healthcare staff, at least once a day (n = 179), either via videoconferences using FaceTime®, WhatsApp®, Zoom®, or Skype® or via mobile phone text messages. Conclusion Visiting restrictions affected relatives differently depending on the wards their loved ones were hospitalized. Healthcare institutions should investigate the utility of visiting restrictions on patients, how they affect relatives, and how to improve personalized patient–relative communications. Future research should attempt to develop reliable, validated measurement instruments of relatives’ experiences of acute-care visiting restrictions during pandemics.

Introduction Disposable electronic cigarettes (DEC) appeared in Switzerland in 2020. The aim of this study is to determine the prevalence of DEC use among youth (14–25 year olds) living in French-speaking Switzerland and their characteristics.Methods Data were obtained from a web‐based survey conducted in August 2022. Participants were divided into four DEC user groups according to and were compared on sociodemographic data, substance use, family substance use and advertising viewing. Additional questions such as purchase methods and motivations were asked to the user groups.Results Among the 1362 participants, 41.2% had never used a DEC (NEVER), 14.4% once (ONCE), 15.1% several times but not in the last 30 days (PAST) and 29.2% several times in the last 30 days (CURRENT). At the multivariate level, compared with the NEVER group, participants in the CURRENT group were more likely to have used cigarettes and cannabis in the last 30 days, to report family electronic cigarettes use and to have seen online advertising for DEC. Among DEC users, compared with the ONCE group, those in the CURRENT group were less likely to be cisgender males, to have acquired their last DEC through peers or family and to use DEC out of curiosity.Conclusions Although most youth do not consume DEC regularly, these results raise concerns about growing exposure of young people to highly addictive products. They underline the importance of monitoring products availability, marketing and prevalence. They also confirm the necessity to inform the public, denormalise use and strengthen regulations.

How can inaccessible cultural heritage be made available to immobile or distant audiences, to meet their cultural needs? Information and communication technologies offer instrumental responses to this new challenge. This type of resource promotes informational mobility as a substitute for real mobility.After introducing the concept of informational mobility and quickly reviewing existing solutions, the body of the article considers digital devices that do more than simply transpose a situation marked by physical inaccessibility. This is the case for the survival of certain heritages, notably immaterial, confronted with the impossibility of physical encounter due to the disappearance or death of their witnesses.The second part of the article addresses historical testimony, and illustrates it using the example of a holographic device implemented in the United States for witnesses to the Shoah. The same device was used to record and share the testimony of mine survivors in the framework of the ANR MémoMines, the subject of the third part of the article. This latter context allowed an experimental study with the public. Beyond providing a simple technical answer to the initial question, this exploratory study provides clues as to how the experience of temporal informational mobility is experienced/appreciated by the public.

Abstract Cancer cells reprogram their metabolism to support growth and invasion. While previous work has highlighted how single altered reactions and pathways can drive tumorigenesis, it remains unclear how individual changes propagate at the network level and eventually determine global metabolic activity. To characterize the metabolic lifestyle of cancer cells across pathways and genotypes, we profiled the intracellular metabolome of 180 pan‐cancer cell lines grown in identical conditions. For each cell line, we estimated activity for 49 pathways spanning the entirety of the metabolic network. Upon clustering, we discovered a convergence into only two major metabolic types. These were functionally confirmed by 13C‐flux analysis, lipidomics, and analysis of sensitivity to perturbations. They revealed that the major differences in cancers are associated with lipid, TCA cycle, and carbohydrate metabolism. Thorough integration of these types with multiomics highlighted little association with genetic alterations but a strong association with markers of epithelial–mesenchymal transition. Our analysis indicates that in absence of variations imposed by the microenvironment, cancer cells adopt distinct metabolic programs which serve as vulnerabilities for therapy.

Purpose: Flavobacterium lindanitolerans is an environmental Gram-negative, non-spore-forming rod which is usually not considered to be a human pathogen. Isolation from human clinical samples has been described only once. We report the first case of meningoencephalitis and bacteraemia with Flavobacterium lindanitolerans. Case description: A 76-year-old female presented with fever, headache, alteration of mental status, marked meningism and dysarthria. A lumbar puncture demonstrated cerebrospinal fluid findings consistent with bacterial meningitis, and a broad-spectrum antibiotic therapy was initiated. Blood and cerebrospinal fluid cultures revealed a growth of Flavobacterium lindanitolerans. Based on antimicrobial susceptibilities testing, antibiotic treatment was changed to levofloxacin, resulting in a remission of the clinical symptoms after 21 days of treatment. Conclusion: Flavobacterium species are extremely rare human pathogens. However, some of them have been reported to cause opportunistic infections. We describe the first case of meningoencephalitis and bacteraemia caused by Flavobacterium lindanitolerans which was effectively treated with levofloxacin for 21 days.

With the ongoing energy transition, power grids are evolving fast. They operate more and more often close to their technical limit, under more and more volatile conditions. Fast, essentially real-time computational approaches to evaluate their operational safety, stability and reliability are therefore highly desirable. Machine Learning methods have been advocated to solve this challenge, however they are heavy consumers of training and testing data, while historical operational data for real-world power grids are hard if not impossible to access. This manuscript presents a large synthetic dataset of power injections in an electric transmission grid model of continental Europe, and describes the algorithm developed for its generation. The method allows one to generate arbitrarily large time series from the knowledge of the grid – the admittance of its lines as well as the location, type and capacity of its power generators – and aggregated power consumption data, such as the national load data given by ENTSO-E. The obtained datasets are statistically validated against real-world data. [ABSTRACT FROM AUTHOR]

The skin hydration level is a key factor that influences the physical and mechanical properties of the skin. The stratum corneum (SC), the outermost layer of the epidermis, is responsible for the skin's barrier function. In this study, we investigated the role of a unique composition of Viola yedoensis extract for its ability to activate CD44, a cell-surface receptor of hyaluronic acid, and aquaporin-3, a water-transporting protein, in human keratinocytes (HaCaT). An ELISA assay evaluating the protein expression levels of CD44, aquaporin-3 (AQP3), filaggrin, and keratin-10 revealed that V. yedoensis extract upregulated the levels of CD44 and AQP3 by 15% and 78%, respectively. Additionally, V. yedoensis extract demonstrated a comparative effect on water vapor flux in TEWL and lipid perturbation in DSC versus the reference, glycerin. In light of this new biological efficacy, a detailed phytochemical characterization was undertaken using an integrated LC-HRMS/MS-based metabolomics approach, which provided further insights on the chemistry of V. yedoensis. This led to the identification of 29 secondary metabolites, 14 of which are reported here for the first time, including esculetin, aesculin, apigenin and kaempferol C-glycosides, megastigmane glycosides, roseoside, platanionoside B, and an eriojaposide B isomer, along with the rare, calenduloside F and esculetin diglucoside, which are reported for the first time from the genus, Viola. Notably, two active components identified in the V. yedoensis extract, namely, aesculin and schaftoside, showed an upregulation of the protein expression of CD44 in HaCaT cells by 123% and 193% within 24 h of treatment, respectively, while aesculin increased AQP3 levels by 46%. Aesculin and schaftoside also significantly upregulated the expression of K-10 levels by 299% and 116%, which was considerably higher than sodium hyaluronate, the positive control. The rationale used to characterize the new structures is outlined along with the related biosynthetic pathways envisioned to generate roseoside and Eriojaposide B. These findings provide new molecular insights to deepen the understanding of how V. yedoensis extract, along with the biomarkers aesculin and schaftoside, restores the skin barrier and skin hydration benefits. [ABSTRACT FROM AUTHOR]

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by three enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

Abstract Background Colistin is used against multi-drug resistant pathogens, yet resistance emerges through dissemination of plasmid-mediated genes (mcr) or chromosomal mutation of genes involved in lipopolysaccharide synthesis (i.e. mgrB, phoPQ, pmrCAB). Phenotypic susceptibility testing is challenging due to poor diffusion of colistin in agar media, leading to an underestimation of resistance. Performance of five phenotypic approaches was compared in the context of different molecular mechanisms of resistance. We evaluated Vitek 2® (bioMérieux, AST N242), Colistin MIC Test Strip (Liofilchem Diagnostici), UMIC (Biocentric), and Rapid Polymyxin™ NP test (ELITechGroup) against the standard broth microdilution (BMD) method. We used whole genome sequencing (WGS) to infer molecular resistance mechanisms. We analysed 97 Enterobacterales and non-fermenting bacterial isolates, largely clinical isolates collected up to 2018. Data was analysed by comparing susceptibility categories (susceptible or resistant) and minimal inhibitory concentrations (MIC). Susceptibility category concordance is the percentage of test results sharing the same category to BMD. MIC concordance was calculated similarly but considering ±1 MIC titre error range. We determined genomic diversity by core genome multi locus sequencing typing (cgMLST) and identified putative antimicrobial resistance genes using NCBI and CARD databases, and manual annotation. Results Of 97 isolates, 54 (56%) were resistant with standard BMD. Highest susceptibility category concordance was achieved by Rapid Polymyxin™ NP (98.8%) followed by UMIC (97.9%), Colistin E-test MIC strip (96.9%) and Vitek 2® (95.6%). Highest MIC concordance was achieved by UMIC (80.4%), followed by Vitek 2® (72.5%) and Colistin E-test MIC strip (62.9%). Among resistant isolates, 23/54 (43%) were intrinsically resistant to colistin, whereas 31/54 (57%) isolates had acquired colistin resistance. Of these, mcr-1 was detected in four isolates and mcr-2 in one isolate. Non-synonymous mutations in mgrB, phoQ, pmrA, pmrB, and pmrC genes were encountered in Klebsiella pneumoniae, Escherichia coli, and Acinetobacter bereziniae resistant isolates. Mutations found in mgrB and pmrB were only identified in isolates exhibiting MICs of ≥16 mg/L. Conclusions The Rapid Polymyxin™ NP test showed highest categorical concordance and the UMIC test provided MIC values with high concordance to BMD. We found colistin resistance in diverse species occurred predominantly through spontaneous chromosomal mutation rather than plasmid-mediated resistance.

Abstract Background Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. Methods We conducted a case-control study of 304 TGCT cases, aged 18–45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants’ mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son’s birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80–2.01) or herbicides (OR = 1.15, CI = 0.67–2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04–2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26–4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06–5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12–3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. Conclusions Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

Endovascular management of aortic complications in patients with Marfan syndrome (MFS) is uncommon. We treated a patient with MFS with a diagnosis of a 75-mm aortic arch aneurysm and uncomplicated aortic type B dissection using single-stage hybrid surgery combining total arch replacement with elephant trunk and the STABILISE (stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair) technique for complete aortic remodeling. The repair was successful, and the aortic true lumen was completely expanded. At 6 months after surgery, clinical evaluation confirmed the early success of the intervention. This type of surgery must be studied further before it can become routine treatment for patients with MFS but it proved safe and feasible.

Abstract Magnetic Weyl semimetals with spontaneously broken time-reversal symmetry exhibit a large intrinsic anomalous Hall effect originating from the Berry curvature. To employ this large Hall current for room temperature topo-spintronics applications, it is necessary to fabricate these materials as thin or ultrathin films. Here, we experimentally demonstrate that Weyl semimetal Co2MnGa thin films (20–50 nm) show a large anomalous Hall angle ~11.4% at low temperature and ~9.7% at room temperature, which can be ascribed to the non-trivial topology of the band structure with large intrinsic Berry curvature. However, the anomalous Hall angle decreases significantly with thicknesses below 20 nm, which band structure calculations confirm is due to the reduction of the majority spin contribution to the Berry curvature. Our results suggest that Co2MnGa is an excellent material to realize room temperature topo-spintronics applications; however, the significant thickness dependence of the Berry curvature has important implications for thin-film device design.

Abstract An a posteriori error estimate is derived for the approximation of the transport equation with a time dependent transport velocity. Continuous, piecewise linear, anisotropic finite elements are used for space discretization, the Crank-Nicolson scheme scheme is proposed for time discretization. This paper is a generalization of Dubuis S, Picasso M (J Sci Comput 75(1):350–375, 2018) where the transport velocity was not depending on time. The a posteriori error estimate (upper bound) is shown to be sharp for anisotropic meshes, the involved constant being independent of the mesh aspect ratio. A quadratic reconstruction of the numerical solution is introduced in order to obtain an estimate that is order two in time. Error indicators corresponding to space and time are proposed, their accuracy is checked with non-adapted meshes and constant time steps. Then, an adaptive algorithm is introduced, allowing to adapt the meshes and time steps. Numerical experiments are presented when the exact solution has strong variations in space and time, illustrating the efficiency of the method. They indicate that the effectivity index is close to one and does not depend on the solution, mesh size, aspect ratio, and time step.

Ever-growing concerns and governmental restrictions related to the use of pesticides in modern agriculture has driven the need for more adept decision-making tools to minimize unnecessary treatments whilst still efficiently preventing a spread of infection. To this effect, a network of cost-effective, laser-based holographic detectors were developed and placed in vineyards in Switzerland and France with the objective of detecting and identifying airborne spores of downy and powdery mildew before they have the potential to infect crops. The data collected are remotely sent to a server where image processing techniques and artificial intelligence classify the spores and determine the quantitative intervention thresholds. Knowledge on the quantitative development of fungal diseases has been successfully used to temporally and spatially identify the primary infection of downy mildew which was confirmed by a visual evaluation of symptoms within the parcel. This data coupled with the current risk prediction models provide farmers with a powerful decision-making tool to optimise strategies in the management of grapevine diseases.