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Abstract Recent years have seen an increased research interest in the determinants of public trust in science. While some argue that democracy should be the political regime most conducive to science, recent debates about salient scientific findings revealed considerable cracks in the public perception of science. We argue that existing cross-national work on trust in science is incomplete because it uses an aggregate concept of “science”. People in different political environments likely have different conceptions of what science is, which can have consequences for perceptions and trust. To remedy this shortcoming, we present results from a preregistered survey experiment in ten countries (N = 8441), which covers a broad spectrum of political regimes and tests how science and scientists’ characteristics influence public trust. We find that, against expectations, female scientists and scientists engaging in public activism are both perceived as more trustworthy. High-impact research is trusted more than low-impact research, and it does not matter whether a scientist is a co-national. Overall, our experiment reveals few differences across political regimes. Additional survey results show that respondents’ education and exposure to science have similar relationships with trust across autocratic and democratic countries. A striking difference we find is that while political orientation has little impact in autocratic countries, it is strongly related to trust across democracies as perceptions of science become increasingly politicized.

The paper at hand presents results of the online survey "Attitude(s) towards inclusion" which inquires the attitudes of the German population towards inclusion in various life contexts (i.e., recreation, work, residence) with regard to people with ‘intellectual disabilities’1. Extensive data were generated from a representative sample (n= 3695) which was analyzed using hierarchical cluster analysis and one-factorial analyses of variance. Here, we examine selected results that focus on the demographic parameters that influence people’s attitudes towards inclusion. Overall, we found a mostly positive and supportive attitude, especially among older demographic groups, female persons, persons with regular contact with people with ‘(intellectual) disabilities’, and voters of socially progressive parties2. Notably, a small but distinct demographic group was identified that was rather unsympathetic towards inclusion. Significant characteristics of this group included being male, being well-educated and favoring socially conservative politics. The ensuing discussion implies that perhaps the negative attitudes towards inclusion held by this group are intertwined with the issue of social privileges.

Abstract To cope with environmental stresses, organisms, including lactic acid bacteria such as O. oeni, produce stress proteins called HSPs. In wine, O. oeni is constantly confronted by stress affecting its membrane fluidity. To survive through in these deleterious conditions, O. oeni synthesizes Lo18, a unique, small HSP which acts as a molecular chaperone and a lipochaperone. The molecular mechanism underlying its lipochaperone activity, particularly regarding membrane lipid composition, remains poorly understood. In this context, Lo18 lipochaperone activity and the associated modification in protein structure were studied during interaction with different liposomes from O. oeni cultures representing unstressed, stressed and stressed-adapted physiological states. The results showed that the presence of the membrane (whatever its nature) induces a modification of Lo18’s structure. Also, the presence of oleic acid and/or phosphatidylglycerol is important to favor Lo18-membrane interaction, allowing lipochaperone activity. This research enhances understanding of sHSP-membrane interactions in bacterial systems.

Este editorial está siendo co-publicado por todas las revistas de la International Collaboration of Pharmacy Journal Editors

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Methane emissions from natural gas systems are increasingly scrutinized, and accurate reporting requires quantification of site- and source-level measurement. We evaluate the performance of 10 available state-of-the-art CH4 emission quantification approaches against a blind controlled-release experiment at an inerted natural gas compressor station in 2021. The experiment consisted of 17 blind 2 h releases at a single exhaust point or multiple simultaneous ones. The controlled releases covered a range of methane flow rates from 0.01 to 50 kg h−1. Measurement platforms included aircraft, drones, trucks, vans, ground-based stations, and handheld systems. Herewith, we compare their respective strengths, weaknesses, and potential complementarity depending on the emission rates and atmospheric conditions. Most systems were able to quantify the releases within an order of magnitude. The level of errors from the different systems was not significantly influenced by release rates larger than 0.1 kg h−1, with much poorer results for the 0.01 kg h−1 release. It was found that handheld optical gas imaging (OGI) cameras underestimated the emissions. In contrast, the “site-level” systems, relying on atmospheric dispersion, tended to overestimate the emission rates. We assess the dependence of emission quantification performance on key parameters such as wind speed, deployment constraints, and measurement duration. At the low wind speeds encountered (below 2 m s−1), the experiments did not reveal a significant dependence on wind speed. The ability to quantify individual sources degraded during multiple-source releases. Compliance with the Oil and Gas Methane Partnership's (OGMP 2.0) highest level of reporting may require a combination of the specific advantages of each measurement technique and will depend on reconciliation approaches. Self-reported uncertainties were either not available or were based on the standard deviation in a series of independent realizations or fixed values from expert judgment or theoretical considerations. For most systems, the overall relative errors estimated in this study are higher than self-reported uncertainties.

Abstract A method for methane emissions monitoring at industrial facility level was developed based on a high precision multi-open-path laser dispersion spectrometer combined with Bayesian analysis algorithms using Monte Carlo Markov Chain (MCMC) inference. From the methane path-averaged concentrations spatially distributed over the facility under study, together with the wind vector, the analysis allows detection, localization and quantification of fugitive methane emissions. This paper describes the very first long term (3 months), continuous (24 h/7 days) deployment of this monitoring system at an operational gas processing and distribution facility. The continuous monitoring system, made of the combination of the open-path high-precision (

A global effort towards improved quantitative understanding of greenhouse gas emissions is taking pace. This includes developing source identification, quantification, and apportionment in an attempt to understand global budget and trends, but also developing monitoring systems making emission reduction commitment verifiable. In this context, we demonstrate a novel approach to continuous methane emission monitoring at the spatial scale of an industrial facility. By combining multi-directional measurements of path-integrated methane concentrations with Bayesian state estimation, we show a realistic tomographic gas plume reconstruction, its evolution in time, and the associated estimation of the source map. The method is validated using measurements from controlled methane releases over a domain of area 120×40 m2. For the first demonstration, a two dimensional geometry has been used in the gas flow model; nevertheless, sources are located within 3–12 meters, and mass emission rates are estimated within

Abstract To cope with environmental stresses, bacteria have developed different strategies, including the production of small heat shock proteins (sHSP). All sHSPs are described for their role as molecular chaperones. Some of them, like the Lo18 protein synthesized by Oenococcus oeni, also have the particularity of acting as a lipochaperon to maintain membrane fluidity in its optimal state following cellular stresses. Lipochaperon activity is poorly characterized and very little information is available on the domains or amino-acids key to this activity. The aim in this paper is to investigate the importance at the protein structure and function level of four highly conserved residues in sHSP exhibiting lipochaperon activity. Thus, by combining in silico, in vitro and in vivo approaches the importance of three amino-acids present in the core of the protein was shown to maintain both the structure of Lo18 and its functions.

Abstract This paper presents an approach for achieving full optical photoacoustic imaging with enhanced resolution utilizing speckle pattern analysis. The proposed technique involves projecting patterns derived from binary masks corresponding to orthogonal functions onto the target to elicit a photoacoustic signal. The resulting signal is then recorded using a high-speed camera and analyzed using correlation analysis of the speckle motion. Our results demonstrate the feasibility of this optical approach to achieve imaging with enhanced resolution without the need for physical contact with the target, opening up new possibilities for non-invasive medical imaging and other applications.

The androgen receptor (AR) is an established orchestrator of cell metabolism in prostate cancer (PCa), notably by inducing an oxidative mitochondrial program. Intriguingly, AR regulates cytoplasmic isocitrate dehydrogenase 1 (IDH1), but not its mitochondrial counterparts IDH2 and IDH3. Here, we aimed to understand the functional role of IDH1 in PCa. Mouse models, in vitro human PCa cell lines, and human patient‐derived organoids (PDOs) were used to study the expression and activity of IDH enzymes in the normal prostate and PCa. Genetic and pharmacological inhibition of IDH1 was then combined with extracellular flux analyses and gas chromatography–mass spectrometry for metabolomic analyses and cancer cell proliferation in vitro and in vivo. In PCa cells, more than 90% of the total IDH activity is mediated through IDH1 rather than its mitochondrial counterparts. This profile seems to originate from the specialized prostate metabolic program, as observed using mouse prostate and PDOs. Pharmacological and genetic inhibition of IDH1 impaired mitochondrial respiration, suggesting that this cytoplasmic enzyme contributes to the mitochondrial tricarboxylic acid cycle (TCA) in PCa. Mass spectrometry‐based metabolomics confirmed this hypothesis, showing that inhibition of IDH1 impairs carbon flux into the TCA cycle. Consequently, inhibition of IDH1 decreased PCa cell proliferation in vitro and in vivo. These results demonstrate that PCa cells have a hybrid cytoplasmic–mitochondrial TCA cycle that depends on IDH1. This metabolic enzyme represents a metabolic vulnerability of PCa cells and a potential new therapeutic target.

The Total Carbon Column Observing Network (TCCON) and the Infrared Working Group of the Network for the Detection of Atmospheric Composition Change (NDACC-IRWG) are two ground-based networks that provide the retrieved concentrations of up to 30 atmospheric trace gases, using solar absorption spectrometry. Both networks provide reference measurements for the validation of satellites and models. TCCON concentrates on long-lived greenhouse gases (GHGs) for carbon cycle studies and validation. The number of sites is limited, and the geographical coverage is uneven, covering mainly Europe and the USA. A better distribution of stations is desired to improve the representativeness of the data for various atmospheric conditions and surface conditions and to cover a large latitudinal distribution. The two successive Fiducial Reference Measurements for Greenhouse Gases European Space Agency projects (FRM4GHG and FRM4GHG2) aim at the assessment of several low-cost portable instruments for precise measurements of GHGs to complement the existing ground-based sites. Several types of low spectral resolution Fourier transform infrared (FTIR) spectrometers manufactured by Bruker, namely an EM27/SUN, a Vertex70, a fiber-coupled IRCube, and a Laser Heterodyne spectro-Radiometer (LHR) developed by UK Rutherford Appleton Laboratory are the participating instruments to achieve the Fiducial Reference Measurements (FRMs) status. Intensive side-by-side measurements were performed using all four instruments next to the Bruker IFS 125HR high spectral resolution FTIR, performing measurements in the NIR (TCCON configuration) and MIR (NDACC configuration) spectral range. The remote sensing measurements were complemented by AirCore launches, which provided in situ vertical profiles of target gases traceable to the World Meteorological Organization (WMO) reference scale. The results of the intercomparisons are shown and discussed. Except for the EM27/SUN, all other instruments, including the reference TCCON spectrometer, needed modifications during the campaign period. The EM27/SUN and the Vertex70 provided stable and precise measurements of the target gases during the campaign with quantified small biases. As part of the FRM4GHG project, one EM27/SUN is now used as a travel standard for the verification of column-integrated GHG measurements. The extension of the Vertex70 to the MIR provides the opportunity to retrieve additional concentrations of N2O, CH4, HCHO, and OCS. These MIR data products are comparable to the retrieval results from the high-resolution IFS 125HR spectrometer as operated by the NDACC. Our studies show the potential for such types of spectrometers to be used as a travel standard for the MIR species. An enclosure system with a compact solar tracker and meteorological station has been developed to house the low spectral resolution portable FTIR systems for performing solar absorption measurements. This helps the spectrometers to be mobile and enables autonomous operation, which will help to complement the TCCON and NDACC networks by extending the observational capabilities at new sites for the observation of GHGs and additional air quality gases. The development of the retrieval software allows comparable processing of the Vertex70 type of spectra as the EM27/SUN ones, therefore bringing them under the umbrella of the COllaborative Carbon Column Observing Network (COCCON). A self-assessment following the CEOS-FRM Maturity Matrix shows that the COCCON is able to provide GHG data products of FRM quality and can be used for either short-term campaigns or long-term measurements to complement the high-resolution FTIR networks.

BackgroundThe routine use of donor-derived cell-free DNA (dd-cfDNA) assays to monitor graft damage in patients after kidney transplantation is being implemented in many transplant centers worldwide. The interpretation of the results can be complicated in the setting of multiple sequential kidney transplantations where accurate donor assignment of the detected dd-cfDNA can be methodologically challenging.MethodsWe investigated the ability of a new next-generation sequencing (NGS)-based dd-cfDNA assay to accurately identify the source of the detected dd-cfDNA in artificially generated samples as well as clinical samples from 31 patients who had undergone two sequential kidney transplantations.ResultsThe assay showed a high accuracy in quantifying and correctly assigning dd-cfDNA in our artificially generated chimeric sample experiments over a clinically meaningful quantitative range. In our clinical samples, we were able to detect dd-cfDNA from the first transplanted (nonfunctioning) graft in 20% of the analyzed patients. The amount of dd-cfDNA detected from the first graft was consistently in the range of 0.1%–0.6% and showed a fluctuation over time in patients where we analyzed sequential samples.ConclusionThis is the first report on the use of a dd-cfDNA assay to detect dd-cfDNA from multiple kidney transplants. Our data show that a clinically relevant fraction of the transplanted patients have detectable dd-cfDNA from the first donor graft and that the amount of detected dd-cfDNA is in a range where it could influence clinical decision-making.

Infectious pancreatic necrosis virus (IPNV) causes economic losses with a highly variable mortality rate worldwide, especially in rainbow trout. The virus has a double-stranded bi-partite RNA genome designated segment A and B. New complete genome sequences of nine rainbow trout isolates from Turkey were determined and subjected to phylogenetic analysis, identifying all as genotype 5 (serotype Sp). A time-dependent change in the extended pathogenicity motif of VP2 from P217T221A247 (PTA) to PTE P217T221E247 over a period of 10 years was identified. A wider analysis of 99 IPNV sequences from Turkey and Iran revealed the emergence of the motif PTE from 2007 to 2017, inducing significant morbidity in fry by 2013. In fact, displacement of the PTA motif, by the PTE motif in IPNV isolates appeared to be connected to a production peak of rainbow trout in 2013. An additional CAI analysis provided more evidence, indicating that rainbow trout culture in Turkey has an influence on the evolution of IPNV.

Abstract Introduction Mycolicibacter kumamotonensis is a slowly growing, non-chromogenic non-tuberculous mycobacteria (NTM) that was initially distinguished from the M. terrae complex in 2006. Since then it has been rarely reported as the cause of pulmonary and soft-tissue infections in both immunocompromised and immunocompetent patients. Case presentation We present a case of severe pulmonary disease due to Mycolicibacter kumamotonensis in a 57-year-old male who was immunocompetent at time of diagnosis, with a history of interstitial lung disease and a prior diagnosis of tuberculosis (TB). After initial treatment for TB in 2017, his condition stabilized until a recurrence in September 2021, leading to an evaluation for lung transplant in the setting of pulmonary fibrosis and emphysema which led to the identification of Mycolicibacter kumamotonensis. A lung transplant was completed, and the patient was successfully treated with a combination of Ethambutol, Azithromycin, and Rifabutin. Conclusions This represents the first case reported of M. kumamotonensis in a patient undergoing lung transplant, and the first case with rapid culture growth during identification of the organism (4 days). This report highlights the need for consideration of M. kumamotonensis as a pathogen in humans, with the potential for rapid growth in liquid media, and the importance of early identification to inform empiric therapy.

Routine microbial inactivation procedures used in microbiology laboratories must be verified. In this study, the efficacy of surface disinfection using 70% Isopropanol, 0.45% Presept, and 1% Virkon was tested against 24 bacterial strains commonly handled in aquaculture microbiology laboratories. Isopropanol was ineffective against Nocardia asteroides NCIMB 1290, while Virkon was not effective against Aeromonas eucrenophila NCIMB 74 or Pediococcus acidilacti R52037.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.

Due to its sensitivity to hormonal signaling, the mammary gland is often referred to as a sentinel organ for the study of endocrine-disrupting chemicals (EDCs), environmental pollutants that can interfere with the estrogen signaling pathway and induce mammary developmental defects. If and how EDCs impact mammary epithelial cell metabolism has not yet been documented. Herein, to study how estrogens and EDCs modulate mammary gland metabolism, we performed bioenergetic flux analyses using mouse mammary epithelial organoids compared to cells grown in monolayer culture. Several EDCs were tested, including bisphenol A (BPA), its close derivative BPS, a new BPA replacement copolyester called TritanTM, and the herbicide glyphosate. We report that estrogens reprogrammed mammary epithelial cell metabolism differently when grown in two- and three-dimensional models. Specific EDCs were also demonstrated to alter bioenergetic fluxes, thus identifying a new potential adverse effect of these molecules. Notably, organoids were more sensitive to low EDC concentrations, highlighting them as a key model for screening the impact of various environmental pollutants. Mechanistically, transcriptomic analyses revealed that EDCs interfered with the regulation of estrogen target genes and the expression of metabolic genes in organoids. Furthermore, co-treatment with the anti-estrogen fulvestrant blocked these metabolic impacts of EDCs, suggesting that, at least partially, they act through modulation of the estrogen receptor activity. Finally, we demonstrate that mammary organoids can be used for long-term studies on EDC exposure to study alterations in organogenesis/morphogenesis and that past pregnancies can modulate the sensitivity of mammary epithelial organoids to specific EDCs. Overall, this study demonstrates that estrogens and EDCs modulate mammary epithelial cell metabolism in monolayer and organoid cultures. A better understanding of the metabolic impacts of EDCs will allow a better appreciation of their adverse effects on mammary gland development and function.

Crimean–Congo hemorrhagic fever (CCHF), the most widespread tick-borne viral human infection, poses a threat to global health. In this study, clinical samples collected through national surveillance systems were screened for acute CCHF virus (CCHFV) infection using RT-PCR and for exposure using ELISA. For any CCHF-positive sample, livestock and tick samples were also collected in the neighborhood of the confirmed case and tested using ELISA and RT-PCR, respectively. Genome sequencing and phylogenetic analyses were also performed on samples with positive RT-PCR results. In Eastern Senegal, two human cases and one Hyalomma tick positive for CCHF were identified and a seroprevalence in livestock ranging from 9.33% to 45.26% was detected. Phylogenetic analyses revealed that the human strain belonged to genotype I based on the available L segment. However, the tick strain showed a reassortant profile, with the L and M segments belonging to genotype I and the S segment belonging to genotype III. Our data also showed that our strains clustered with strains isolated in different countries, including Mauritania. Therefore, our findings confirmed the high genetic variability inside the CCHF genotypes and their introduction to Senegal from other countries. They also indicate an increasing CCHF threat in Senegal and emphasize the need to reinforce surveillance using a one-health approach.

IntroductionIn the Northeast US, respiratory viruses such as influenza and respiratory syncytial virus (RSV), which were largely suppressed by COVID-19-related social distancing, made an unprecedented resurgence during 2022, leading to a substantial rise in viral co-infections. However, the relative rates of co-infection with seasonal respiratory viruses over this period have not been assessed.MethodsHere we reviewed multiplex respiratory viral PCR data (BioFire FilmArray™ Respiratory Panel v2.1 [RPP]) from patients with respiratory symptoms presenting to our medical center in New York City to assess co-infection rates of respiratory viruses, which were baselined to total rates of infection for each virus. We examined trends in monthly RPP data from adults and children during November 2021 through December 2022 to capture the full seasonal dynamics of respiratory viruses across periods of low and high prevalence.ResultsOf 50,022 RPPs performed for 34,610 patients, 44% were positive for at least one target, and 67% of these were from children. The overwhelming majority of co-infections (93%) were seen among children, for whom 21% of positive RPPs had two or more viruses detected, as compared to just 4% in adults. Relative to children for whom RPPs were ordered, children with co-infections were younger (3.0 vs 4.5 years) and more likely to be seen in the ED or outpatient settings than inpatient and ICU settings. In children, most viral co-infections were found at significantly reduced rates relative to that expected from the incidence of each virus, especially those involving SARS-CoV-2 and influenza. SARS-CoV-2 positive children had an 85%, 65% and 58% reduced rate of co-infection with influenza, RSV, and Rhino/enteroviruses, respectively, after compensating for the incidence of infection with each virus (p< 0.001).DiscussionOur results demonstrate that most respiratory viruses peaked in different months and present in co-infections less than would be expected based on overall rates of infection, suggesting a viral exclusionary effect between most seasonal respiratory viruses, including SARS-CoV-2, influenza and RSV. We also demonstrate the significant burden of respiratory viral co-infections among children. Further work is necessary to understand what predisposes certain patients for viral co-infection despite this exclusionary effect.

BackgroundCircumferential ablation around the ipsilateral pulmonary veins (PVs) is the standard strategy for atrial fibrillation ablation. The present study seeks to assess which regions of the standard ablation circumference are the main contributors to the venoatrial electrical connection.MethodsA total of 41 patients were included under a specific atrial fibrillation ablation protocol in which the anterior and posterior segments of the standard circumference, between the equatorial line of the superior and the inferior ipsilateral PVs, were ablated first. If PV isolation was not achieved, ablation was extended superiorly or inferiorly, on the basis of the earliest atrial activation recorded during pacing from inside the PV. Complete PV isolation and the length of the areas not requiring ablation (ANRA) at the time of electrical isolation were evaluated.ResultsAblation of the anterior and posterior segments of the standard circumference led to the isolation of 77% left-PV pairs and 51% right-PV pairs (p = 0,015). A superior extension was required in 23% left-PV pairs and in 46% right-PV pairs, while an inferior extension was required only in 10% left-PV pairs and in 11% right-PV pairs. PV isolation was achieved before completing the standard ablation circumference in 97% left-PV pairs and in 94% right-PV pairs, with a median ANRA of 36.9 (IQR: 30.9–42.1) mm in the left PVs [16.0 (IQR: 12.0–19.0) mm superior and 18.8 (IQR: 16.1–24.9) mm inferior, p

Arthropod-borne diseases currently constitute a source of major health concerns worldwide. They account for about 50% of global infectious diseases and cause nearly 700,000 deaths every year. Their rapid increase and spread constitute a huge challenge for public health, highlighting the need for early detection during epidemics, to curtail the virus spread, and to enhance outbreak management. Here, we compared a standard quantitative polymerase chain reaction (RT-qPCR) and a direct RT-qPCR assay for the detection of Zika (ZIKV), Chikungunya (CHIKV), and Rift Valley Fever (RVFV) viruses from experimentally infected-mosquitoes. The direct RT-qPCR could be completed within 1.5 h and required 1 µL of viral supernatant from homogenized mosquito body pools. Results showed that the direct RT-qPCR can detect 85.71%, 89%, and 100% of CHIKV, RVFV, and ZIKV samples by direct amplifications compared to the standard method. The use of 1:10 diluted supernatant is suggested for CHIKV and RVFV direct RT-qPCR. Despite a slight drop in sensitivity for direct PCR, our technique is more affordable, less time-consuming, and provides a better option for qualitative field diagnosis during outbreak management. It represents an alternative when extraction and purification steps are not possible because of insufficient sample volume or biosecurity issues.

IntroductionOutcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI).MethodsObservational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW

It is essential to discriminate between B. bruxellensis isolates at the strain level, because stress resistance capacities are strain dependent and also related to the genetic groups (GG). In this work, we investigated further the correlation between genetic groups and cell polymorphism by analysing optical microscopy images via deep learning. A Convolutional Neural Network (CNN) was trained to discriminate between 74 different B. bruxellensis isolates belonging to 4 of the 6 genetic groups described. Compared to the microsatellite analysis, the CNN enabled the prediction of the genetic groups of B. bruxellensis isolates with 96.6 % accuracy in a faster and cheaper way and with the same genetic group affiliations. Based on these very promising results, further research is needed to validate this technique for all genetic groups.

BackgroundProgressive atrial fibrotic remodeling has been reported to be associated with atrial cardiomyopathy (ACM) and the transition from paroxysmal to persistent atrial fibrillation (AF). We sought to identify the anatomical/structural and electrophysiological factors involved in atrial remodeling that promote AF persistency.MethodsConsecutive patients with paroxysmal (n = 134) or persistent (n = 136) AF who presented for their first AF ablation procedure were included. Patients underwent left atrial (LA) high-definition mapping (1,835 ± 421 sites/map) during sinus rhythm (SR) and were randomized to training and validation sets for model development and evaluation. A total of 62 parameters from both electro-anatomical mapping and non-invasive baseline data were extracted encompassing four main categories: (1) LA size, (2) extent of low-voltage-substrate (LVS), (3) LA voltages and (4) bi-atrial conduction time as identified by the duration of amplified P-wave (APWD) in a digital 12-lead-ECG. Least absolute shrinkage and selection operator (LASSO) and logistic regression were performed to identify the factors that are most relevant to AF persistency in each category alone and all categories combined. The performance of the developed models for diagnosis of AF persistency was validated regarding discrimination, calibration and clinical usefulness. In addition, HATCH score and C2HEST score were also evaluated for their performance in identification of AF persistency.ResultsIn training and validation sets, APWD (threshold 151 ms), LA volume (LAV, threshold 94 mL), bipolar LVS area < 1.0 mV (threshold 4.55 cm2) and LA global mean voltage (GMV, threshold 1.66 mV) were identified as best determinants for AF persistency in the respective category. Moreover, APWD (AUC 0.851 and 0.801) and LA volume (AUC 0.788 and 0.741) achieved better discrimination between AF types than LVS extent (AUC 0.783 and 0.682) and GMV (AUC 0.751 and 0.707). The integrated model (combining APWD and LAV) yielded the best discrimination performance between AF types (AUC 0.876 in training set and 0.830 in validation set). In contrast, HATCH score and C2HEST score only achieved AUC < 0.60 in identifying individuals with persistent AF in current study.ConclusionAmong 62 electro-anatomical parameters, we identified APWD, LA volume, LVS extent, and mean LA voltage as the four determinant electrophysiological and structural factors that are most relevant for AF persistency. Notably, the combination of APWD with LA volume enabled discrimination between paroxysmal and persistent AF with high accuracy, emphasizing their importance as underlying substrate of persistent AF.

Abstract Background Nurses are trained to establish a trusting relationship with patients to create an environment promoting patients’ quality of life. However, in tech-heavy care settings, such as haemodialysis units, dehumanising practices may emerge and take root for various reasons to the potential detriment of both patients and nurses. For patients, this may lead to a deterioration of quality of life and, ultimately, of health status. For nurses, it may cause a deterioration of the work environment and, in turn, of quality of working life. Based on Watson’s Theory of Human Caring, we developed a brief educational intervention for haemodialysis nurses to strengthen their humanistic practice in the aim of improving the nurse-patient relationship and nurse quality of working life.. The intervention was tested by way of an experimental design. Methods One hundred and one haemodialysis nurses, recruited in ten hospitals in French-speaking Switzerland, were randomised into an experimental group that received the intervention and a control group. The nurse-patient relationship was measured with the Caring Nurse-Patient Interaction Scale (EIIP-70) and nurse quality of life at work was measured with the Quality of Work Life Questionnaire at four time points: pre-intervention, intervention completion, and six-month and one-year follow-ups. Random intercept regression analysis was used to evaluate change over time in the two variables under study. Results The intervention appeared to reinforce nurse attitudes and behaviours geared to a more humanistic practice. The effect seemed to fade over time but, 1 year post-intervention, six dimensions of the nurse-patient relationship (hope, sensibility, helping relationship, expression of emotions, problem solving, teaching) scored above baseline. Nurse quality of working life, too, seemed positively impacted. The cultural dimension of nurse quality of working life, that is, the degree to which everyday work activities attune with personal and cultural values, seemed positively impacted, as well, with improvement stable throughout the year following the intervention. Conclusions Results support a positive effect of the intervention over both the short term and the medium-to-long term. A brief intervention of the sort may constitute an effective means to improve the nurse-patient relationship by preventing or reducing dehumanising practices. Trial registration NCT03283891 .

Abstract Background Regular outpatient rehabilitation is prescribed for many patients with chronic neurological disorders, such as Parkinson’s disease or multiple sclerosis, to constantly support patients and their proxies in disease management. Due to the coronavirus disease 2019 pandemic, federal institutions and governments worldwide have directed local or nationwide lockdowns. During these times, the provision of regular outpatient rehabilitation service is drastically limited, making it actually impossible for community-dwelling patients with neurological disorders to receive prescribed rehabilitation interventions. Case presentation A 67-year-old White Swiss man with two chronic neurological diseases, Parkinson’s disease and multiple sclerosis, underwent a 4-week inpatient rehabilitation in our hospital. The main rehabilitation goals were related to improvements of mobility and a decrease in the risk of falls. The patient gained significant functional improvements that he maintained over the following months, supported by the continuation of physiotherapy in the domestic environment. Due to a coronavirus disease 2019 pandemic-related interruption of the regular ambulatory rehabilitation for several weeks during the first coronavirus disease 2019 wave in Switzerland, the patient’s functional abilities decreased significantly. Thus, the patient was again referred to our hospital for intensive inpatient rehabilitation to regain his physical functioning and mobility capacity. At hospital discharge, the patient improved most of his physical functioning to a prepandemic level. Conclusions The interruption of a rehabilitation service due to a pandemic-related lockdown can significantly impact the functional abilities of patients with chronic neurological diseases. This case report supports the claim for continuous access to rehabilitation services for all people with rehabilitation needs.

Varios reportes comunicaron diferentes tipos de vasculitis en asociación temporal con una variedad de vacunas, y más recientemente con las vacunas para enfermedad por SARS-CoV-2 (COVID-19). Sin embargo, la escasez de estudios controlados y la heterogeneidad metodológica de los reportes no permiten una conclusión clara sobre su relación causal. Informamos el caso de un varón que desarrolló vasculitis leucocitoclástica, confirmada por biopsia de piel y sin compromiso sistémico, luego de la inmunización contra la COVID-19 con la vacuna de AstraZeneca.

BackgroundLong-term unemployed have poor nutritional and physical activity statuses, and, therefore, special health promotion needs. Particularly in rural areas, however, they often do not have access to health promotion service. Thus, new promising strategies to improve the health of long-term unemployed are needed. Hence, a digital health intervention to promote nutritional and physical health behaviors was conceived, and the effectiveness of the intervention in combination with face-to-face sessions will be evaluated in a randomized controlled trial. ObjectiveThe aim of this study is to elucidate the effectiveness of a mobile digital health intervention to promote the nutritional and physical activity behaviors of long-term unemployed in the rural areas of Germany. MethodsThe 9-week intervention aims to promote nutritional or physical activity behavior by improving drinking habits, increasing the consumption of fruits, vegetables, and whole grains, increasing daily step count, strengthening muscles, and improving endurance. The intervention design is based on the transtheoretical model and is implemented in a mobile app using the MobileCoach open-source platform. The effectiveness of the intervention will be elucidated by a 9-week, 2-armed, parallel-designed trial. Therefore, long-term unemployed will be recruited by employees of the German social sector institutions and randomized either to receive information brochures; the digital intervention in the form of a mobile app; and 3 face-to-face sessions regarding technical support, healthy eating, and physical activity (n=100) or to receive a control treatment consisting of solely the hand over of information brochures (n=100). The effectiveness of the intervention will be assessed using questionnaires at baseline, after 9 weeks in face-to-face appointments, and after a 3-month follow-up period by postal contact. The use of the mobile app will be monitored, and qualitative interviews or focus groups with the participants will be conducted. Incentives of €50 (US $49.7) will be paid to the participants and are tied to the completion of the questionnaires and not to the use of the mobile app or progress in the intervention. ResultsThe effectiveness of the intervention in promoting the nutritional and physical activity behaviors of long-term unemployed participants will be elucidated. The adherence of the participants to and the acceptance and usability of the mobile device app will be evaluated. Recruitment started in March 2022, and the final publication of the results is expected in the first half of 2023. ConclusionsPositive health-related changes made by the intervention would display the potency of digital health interventions to promote nutritional and physical activity behaviors among long-term unemployed in the rural areas of Germany, which would also contribute to an improved health status of the German population in general. Trial RegistrationGerman Clinical Trials Register DRKS00024805; https://www.drks.de/DRKS00024805 International Registered Report Identifier (IRRID)PRR1-10.2196/40321

BackgroundLow-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR.Materials and methodsThirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high—density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined.ResultsPFPs displayed low voltages both during AF (median 0.30 mV (Q1–Q3: 0.20–0.50 mV) and SR (median 0.35 mV (Q1–Q3: 0.20–0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1–Q3: 51–76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA < 0.5 mV was more extensive in AF (median: 25.2% of LA surface, Q1–Q3:16.6–50.5%) than in SR (median: 12.3%, Q1–Q3: 4.7–29.4%, p = 0.001). CFP in both rhythms occurred in 80% of PFP-SR and 59% of PFP-AF (p = 0.008). Notably, CFP was positively correlated to the extent of LVA in SR (p = 0.004), but not with LVA in AF (p = 0.226). Additionally, the extent of LVA < 0.5 mV in SR was the only significant predictor for CFP, with an optimal threshold of 16% predicting high (>80%) fractionation concordance in AF and SR.ConclusionSubstrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF.

Many asexual individuals are in long-term satisfying romantic relationships. However, the contributors to relational commitment among asexual individuals have received little attention. How do investment model characteristics and attachment orientations predict relationship commitment among asexual individuals? Our study looked at a sample of 485 self-identified asexual individuals currently in a romantic relationship (Mage = 25.61, SD = 6.24; MRelationshipLength = 4.42 years, SD = 4.74). Individuals reported on Investment Model characteristics (i.e., their relationship satisfaction, investment, alternatives, and commitment) and their attachment orientations. Satisfaction, investment, and fewer alternatives were associated with greater commitment. Attachment orientations only occasionally moderated the results: for people low in anxiety, satisfaction and investment were more strongly related to commitment compared to people high in anxiety. The current study provided an extension of the Investment Model to describe romantic relationships among asexual individuals.

Objective: The prostate is metabolically unique: it produces high levels of citrate for secretion via a truncated tricarboxylic acid (TCA) cycle to maintain male fertility. In prostate cancer (PCa), this phenotype is reprogrammed, making it an interesting therapeutic target. However, how the truncated prostate TCA cycle works is still not completely understood. Methods: We optimized targeted metabolomics in mouse and human organoid models in ex vivo primary culture. We then used stable isotope tracer analyses to identify the pathways that fuel citrate synthesis. Results: First, mouse and human organoids were shown to recapitulate the unique citrate-secretory program of the prostate, thus representing a novel model that reproduces this unusual metabolic profile. Using stable isotope tracer analysis, several key nutrients were shown to allow the completion of the prostate TCA cycle, revealing a much more complex metabolic profile than originally anticipated. Indeed, along with the known pathway of aspartate replenishing oxaloacetate, glutamine was shown to fuel citrate synthesis through both glutaminolysis and reductive carboxylation in a GLS1-dependent manner. In human organoids, aspartate entered the TCA cycle at the malate entry point, upstream of oxaloacetate. Our results demonstrate that the citrate-secretory phenotype of prostate organoids is supported by the known aspartate–oxaloacetate–citrate pathway, but also by at least three additional pathways: glutaminolysis, reductive carboxylation, and aspartate–malate conversion. Conclusions: Our results add a significant new dimension to the prostate citrate-secretory phenotype, with at least four distinct pathways being involved in citrate synthesis. Better understanding this distinctive citrate metabolic program will have applications in both male fertility as well as in the development of novel targeted anti-metabolic therapies for PCa.

Purpose: The present study aimed to examine the link between physical activity (PA) and life satisfaction in a large international study of adolescents. We also aimed to test whether overweight and underweight perceptions act as mediators and whether age and sex acted as moderators. Methods: For this purpose, we analyzed data from the Health Behavior in School-aged Children study, which comprises 727,865 observations from 44 nations at 4 measurement occasions. Results: Multilevel analyses revealed a positive link between PA and life satisfaction. In addition, underweight and overweight perceptions mediated the effect of PA on life satisfaction. We further found that age and sex acted as moderators. In older adolescents, stronger effects were found in the links between PA and life satisfaction, PA and overweight perception, and both weight perceptions and life satisfaction. In addition, in female adolescents, the link between overweight perception and life satisfaction was stronger. Conversely, the links between PA and both weight perceptions were stronger for boys. Conclusion: The results suggest that weight perception explains part of the relationship between PA and life satisfaction in adolescents and that these effects vary as a function of age and sex.

Autocratic governments routinely interfere in digital communication technology for political purposes. However, citizens can use different technologies to bypass government interference. This article examines how political protest influences the use of anonymity-preserving digital services in autocracies. Citizens should be more likely to use these tools during high political tension because they fear governmental surveillance or censorship. The analysis combining data on the Tor anonymization network with protest event data demonstrates noticeable increases in Tor usage after days with many protest events but not days with single protest events.

The Total Carbon Column Observing Network (TCCON) is the baseline ground-based network of instruments that record solar absorption spectra from which accurate and precise column-averaged dry-air mole fractions of CO2 (XCO2), CH4 (XCH4), CO (XCO), and other gases are retrieved. The TCCON data have been widely used for carbon cycle science and validation of satellites measuring greenhouse gas concentrations globally. The number of stations in the network (currently about 25) is limited and has a very uneven geographical coverage: the stations in the Northern Hemisphere are distributed mostly in North America, Europe, and Japan, and only 20 % of the stations are located in the Southern Hemisphere, leaving gaps in the global coverage. A denser distribution of ground-based solar absorption measurements is needed to improve the representativeness of the measurement data for various atmospheric conditions (humid, dry, polluted, presence of aerosol), various surface conditions such as high albedo (>0.4) and very low albedo, and a larger latitudinal distribution. More stations in the Southern Hemisphere are also needed, but a further expansion of the network is limited by its costs and logistical requirements. For this reason, several groups are investigating supplemental portable low-cost instruments. The European Space Agency (ESA) funded campaign Fiducial Reference Measurements for Ground-Based Infrared Greenhouse Gas Observations (FRM4GHG) at the Sodankylä TCCON site in northern Finland aims to characterise the assessment of several low-cost portable instruments for precise solar absorption measurements of XCO2, XCH4, and XCO. The test instruments under investigation are three Fourier transform spectrometers (FTSs): a Bruker EM27/SUN, a Bruker IRcube, and a Bruker Vertex70, as well as a laser heterodyne spectroradiometer (LHR) developed by the UK Rutherford Appleton Laboratory. All four remote sensing instruments performed measurements simultaneously next to the reference TCCON instrument, a Bruker IFS 125HR, for a full year in 2017. The TCCON FTS was operated in its normal high-resolution mode (TCCON data set) and in a special low-resolution mode (HR125LR data set), similar to the portable spectrometers. The remote sensing measurements are complemented by regular AirCore launches performed from the same site. They provide in situ vertical profiles of the target gas concentrations as auxiliary reference data for the column retrievals, which are traceable to the WMO SI standards. The reference measurements performed with the Bruker IFS 125HR were found to be affected by non-linearity of the indium gallium arsenide (InGaAs) detector. Therefore, a non-linearity correction of the 125HR data was performed for the whole campaign period and compared with the test instruments and AirCore. The non-linearity-corrected data (TCCONmod data set) show a better match with the test instruments and AirCore data compared to the non-corrected reference data. The time series, the bias relative to the reference instrument and its scatter, and the seasonal and the day-to-day variations of the target gases are shown and discussed. The comparisons with the HR125LR data set gave a useful analysis of the resolution-dependent effects on the target gas retrieval. The solar zenith angle dependence of the retrievals is shown and discussed. The intercomparison results show that the LHR data have a large scatter and biases with a strong diurnal variation relative to the TCCON and other FTS instruments. The LHR is a new instrument under development, and these biases are currently being investigated and addressed. The campaign helped to characterise and identify instrumental biases and possibly retrieval biases, which are currently under investigation. Further improvements of the instrument are ongoing. The EM27/SUN, the IRcube, the modified Vertex70, and the HR125LR provided stable and precise measurements of the target gases during the campaign with quantified small biases. The bias dependence on the humidity along the measurement line of sight has been investigated and no dependence was found. These three portable low-resolution FTS instruments are suitable to be used for campaign deployment or long-term measurements from any site and offer the ability to complement the TCCON and expand the global coverage of ground-based reference measurements of the target gases.

Abstract Aim Despite its importance in nursing, perceived quality of the nurse–patient relationship has seldom been researched. This study sought to examine and compare the quality of caring attitudes and behaviours as perceived by haemodialysis patients and their nurses. Design This comparative descriptive study involved 140 haemodialysis patients and 101 nurses caring for them in ten haemodialysis units in the French‐speaking part of Switzerland. Methods Participants completed a sociodemographic questionnaire and the Caring Nurse‐Patient Interaction Scale (CNPI‐70). Results Both nurses and patients reported a high frequency of caring attitudes and behaviours. Patients gave higher ratings than nurses did on all the caring dimensions, except spirituality. Implications are discussed.

An unprecedented use of high-throughput sequencing for routine monitoring of SARS-CoV-2 viruses in patient samples has created a dataset of over 6 million SARS-CoV-2 genomes. To monitor genomes, deposited in the GISAID database, and to track the continuous sequence evolution of molecular assay oligonucleotide target sequences. A simple pipeline tool for non-experts was developed to mine this database for nucleotide changes in oligonucleotides and tested with the long oligonucleotides of a Recombinase polymerase amplification (RPA) assay targeting the RNA-dependent RNA polymerase (RdRP) gene of the SARS-CoV-2. Results indicate the emergence of a single nucleotide change in the reverse oligonucleotide from 0.03 to 26.23% (January to May 2021) in Alpha variant genomes, which however reduced to 17.64% by September after which the Alpha variant was completely displaced by the Delta variant. For all other variants, no relevant nucleotide changes were observed. The oligonucleotide screening pipeline allows efficient screening of nucleotide changes in oligonucleotides of all sizes in minutes.

The prostate is a gland that contributes to men's fertility. It is highly responsive to androgens and is often the site of carcinogenesis, as prostate cancer is the most frequent cancer in men in over a hundred countries. To study the normal prostate, few in vitro models exist, and most of them do not express the androgen receptor (AR). To overcome this issue, prostate epithelial cells can be grown in primary culture ex vivo in 2- and 3-dimensional culture (organoids). However, methods to purify these cells often require flow cytometry, thus necessitating specialized instruments and expertise. Herein, we present a detailed protocol for the harvest, purification, and primary culture of mouse prostate epithelial cells to grow prostate organoids ex vivo. This protocol does not require flow cytometry approaches, facilitating its implementation in most research laboratories, and organoids grown with this protocol are highly responsive to androgens. In summary, we present a new simple method that can be used to grow prostate organoids that recapitulate the androgen response of this gland in vivo.

In Senegal, the burden of dengue is increasing and expanding. As case management and traditional diagnostic techniques can be difficult to implement, rapid diagnostic tests (RDTs) deployed at point of care are ideal for investigating active outbreaks. The aim of this study was to evaluate the diagnostic performance of the Dengue NS1 and Dengue IgM/IgG RDTs on the serum/plasma samples in a laboratory setting and in the field. During laboratory evaluation, performance of the NS1 RDT was assessed using NS1 ELISA as the gold standard. Sensitivity and specificity were 88% [75–95%] and 100% [97–100%], respectively. Performance of the IgM/IG RDT was assessed using the IgM Antibody Capture (MAC) ELISA, indirect IgG, and PRNT as gold standards. The IgM and IgG test lines respectively displayed sensitivities of 94% [83–99%] and 70% [59–79%] and specificities of 91% [84–95%] and 91% [79–98%]. In the field, the Dengue NS1 RDT sensitivity and specificity was 82% [60–95%] and 75% [53–90%], respectively. The IgM and IgG test lines displayed sensitivities of 86% [42–100%] and 78% [64–88%], specificities of 85% [76–92%] and 55% [36–73%], respectively. These results demonstrate that RDTs are ideal for use in a context of high prevalence or outbreak setting and can be implemented in the absence of a confirmatory test for acute and convalescent patients.

Objective To explore the patients’ experiences on initiation of treatment with antineoplastic medicines for colorectal cancer.Design A qualitative study using semistructured, face-to-face interviews based on the adapted patients’ lived experience with medicines conceptual model was conducted. Ethics approval was granted. Interviews took place while eligible patients were receiving their first cycle of antineoplastic medicines, audiorecorded and transcribed verbatim. Interpretative phenomenological analysis was used.Setting National oncology hospital in Malta.Participants Adult patients over 18 years, newly diagnosed with colorectal cancer and initiating treatment with 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin (XELOX) between October 2018 and September 2019 were recruited. Patients were included if fully aware of their diagnosis and the treatment being received. A purposive sample of 16 patients participated in the study.Results Five themes emerged from our analysis: (1) beliefs and knowledge on cancer and treatment; (2) healthcare system in relation to treatment; (3) medicine-taking practice; (4) medicine-related impact and (5) personal support structure. In addition, 16 subthemes were identified to describe the interplay of all aspects of the patients’ experiences on initiation of treatment with antineoplastic medicines.Conclusion This qualitative study illustrated that the patients find themselves in a complex situation on initiation of treatment with antineoplastic medicines. The patients’ knowledge on their specific treatment and active participation in making an informed decision need to be addressed. The healthcare system should develop tailored patient-centred services that specifically address the lack of patient empowerment and patient’s concern about treatment specific information.

Background: High-power short-duration (HPSD) recently emerged as a new approach to radiofrequency (RF) catheter ablation. However, basic and clinical data supporting its effectiveness and safety is still scarce.Objective: We aim to characterize HPSD with an advanced virtual model, able to assess lesion dimensions and complications in multiple conditions and compare it to standard protocols.Methods: We evaluate, on both atrium and ventricle, three HPSD protocols (70 W/8 s, 80 W/6 s, and 90 W/4 s) through a realistic 3D computational model of power-controlled RF ablation, varying catheter tip design (spherical/cylindrical), contact force (CF), blood flow, and saline irrigation. Lesions are defined by the 50°C isotherm contour. Ablations are deemed safe or complicated by pop (tissue temperature >97°C) or charring (blood temperature >80°C). We compared HPSD with standards protocols (30–40 W/30 s). We analyzed the effect of a second HPSD application.Results: We simulated 432 applications. Most (79%) associated a complication, especially in the atrium. The three HPSD protocols performed similarly in the atrium, while 90 W/4 s appeared the safest in the ventricle. Low irrigation rate led frequently to charring (72%). High-power short-duration lesions were 40–60% shallower and smaller in volume compared to standards, although featuring similar width. A second HPSD application increased lesions to a size comparable to standards.Conclusion: High-power short-duration lesions are smaller in volume and more superficial than standards but comparable in width, which can be advantageous in the atrium. A second application can produce lesions similar to standards in a shorter time. Despite its narrow safety margin, HPSD seems a valuable new clinical approach.

Glaciers in Switzerland are shrinking rapidly in response to ongoing climate change. Repeated glacier inventories are key to monitor such changes at the regional scale. Here we present the new Swiss Glacier Inventory 2016 (SGI2016) that has been acquired based on sub-meter resolution aerial imagery and digital elevation models, bringing together topographical and glaciological approaches and knowledge. We define the process, workflow and required glaciological adaptations to compile a highly detailed inventory based on the digital Swiss Topographic Landscape model. The SGI2016 provides glacier outlines (areas), supraglacial debris cover and ice divides for all Swiss glaciers referring to the years 2013–2018. The SGI2016 maps 1,400 individual glacier entities with a total surface area of 961 ± 22 km2, whereof 11% (104 km2) are debris-covered. It constitutes the so far most detailed cartographic representation of glacier extent in Switzerland. Interpretation in the context of topographic parameters indicates that glaciers with moderate inclination and low median elevation tend to have highest fractions of supraglacial debris. Glacier-specific area changes since 1973 show the largest relative changes for small and low-elevation glaciers. The analysis further indicates a tendency for glaciers with a high share of supraglacial debris to show larger relative area changes. Between 1973 and 2016, an area change rate of –0.6% a−1 is found. Based on operational data sets and the presented methodology, the Swiss Glacier Inventory will be updated in 6-yr time intervals, leading to a high consistency in future glacier change assessments.

Lymphocystis disease viruses (LCDVs) are viruses that infect bony fish which has been found in different locations across the globe. Four virus species have been classified by the International Committee on Taxonomy of Viruses (ICTV), despite remarkable discrepancies in genome size. Whole genome sequencing and phylogenetic analysis of LCDVs from wild fish from the North Sea and partial sequences from gilthead sea bream of an aquafarm located in the Aegean Sea in Turkey confirm that the LCDV1 genome at 100 kb is approximately half the size of the genomes of LCDV2-4. Since the fish species, of which LCDV1 was isolated, differ taxonomically at the order level, co-speciation can be excluded as the driver of the adaptation of the genome of this nucleocytoplasmic large DNA virus, but may represent an adaptation to the lifestyle of this demersal fish in the northeast Atlantic.

Few in vitro models are used to study mammary epithelial cells (MECs), and most of these do not express the estrogen receptor α (ERα). Primary MECs can be used to overcome this issue, but methods to purify these cells generally require flow cytometry and fluorescence-activated cell sorting (FACS), which require specialized instruments and expertise. Herein, we present in detail a FACS-free protocol for purification and primary culture of mouse MECs. These MECs remain differentiated for up to six days with >85% luminal epithelial cells in two-dimensional culture. When seeded in Matrigel, they form organoids that recapitulate the mammary gland’s morphology in vivo by developing lumens, contractile cells, and lobular structures. MECs express a functional ERα signaling pathway in both two- and three-dimensional cell culture, as shown at the mRNA and protein levels and by the phenotypic characterization. Extracellular metabolic flux analysis showed that estrogens induce a metabolic switch favoring aerobic glycolysis over mitochondrial respiration in MECs grown in two-dimensions, a phenomenon known as the Warburg effect. We also performed mass spectrometry (MS)-based metabolomics in organoids. Estrogens altered the levels of metabolites from various pathways, including aerobic glycolysis, citric acid cycle, urea cycle, and amino acid metabolism, demonstrating that ERα reprograms cell metabolism in mammary organoids. Overall, we have optimized mouse MEC isolation and purification for two- and three-dimensional cultures. This model represents a valuable tool to study how estrogens modulate mammary gland biology, and particularly how these hormones reprogram metabolism during lactation and breast carcinogenesis.

En el marco de las grandes transformaciones que se han desarrollado en el sector agropecuario en las últimas décadas, este trabajo analiza los impactos que a nivel estructura ha tenido la expansión del modelo de agronegocios sobre la agricultura familiar en Argentina y Uruguay. Se busca describir las particularidades y generalidades que ha tenido este fenómeno en la región baja análisis a partir de un estudio comparativo enfatizado las políticas públicas hacia el sector, tomando como unidades de análisis los casos de Argentina y Uruguay. Se utilizaron fuentes estadísticas de organismos nacionales oficiales, entidades intermedias y estudios sectoriales. Como variables de análisis se tomaron: la concentración económica, la composición de la estructura agraria, la intervención pública.

This study examines the influence of thickness change on bond strength of welded hybrid joints of physically surface-treated steel sheets and glass fiber reinforced polyamide 6. The quasi-static, discontinuous induction welding was used as joining method. The steel sheets were either treated by a parallel line shaped laser structuring, which is perpendicular to the load direction and has a line distance of 0.3 mm or 0.6 mm or by a compressed air blasting. Furthermore, the influence of joining temperature on bond strength was examined as a comparison. In both cases bond strength was determined using tensile shear tests according to DIN 1465. In addition, the void content in the laminate and in the joining zone was investigated by cross section images. A time-temperature-thickness change diagram was developed to gain insight into the processes during welding. Based on these findings, it can be stated that thickness change is suitable for process control and as a quality assurance feature in hybrid induction welding.

Background & Aims: The tumor-suppressor sterile α motif– and Src-homology 3–domain containing 1 (SASH1) has clinical relevance in colorectal carcinoma and is associated specifically with metachronous metastasis. We sought to identify the molecular mechanisms linking decreased SASH1 expression with distant metastasis formation. Methods: SASH1-deficient, SASH1-depleted, or SASH1-overexpressing HCT116 colon cancer cells were generated by the Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9-method, RNA interference, and transient plasmid transfection, respectively. Epithelial-mesenchymal transition (EMT) was analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblotting, immunofluorescence microscopy, migration/invasion assays, and 3-dimensional cell culture. Yeast 2-hybrid assays and co-immunoprecipitation/mass-spectrometry showed V-Crk avian sarcoma virus CT10 oncogene homolog-like (CRKL) as a novel interaction partner of SASH1, further confirmed by domain mapping, site-directed mutagenesis, co-immunoprecipitation, and dynamic mass redistribution assays. CRKL-deficient cells were generated in parental or SASH1-deficient cells. Metastatic capacity was analyzed with an orthotopic mouse model. Expression and significance of SASH1 and CRKL for survival and response to chemotherapy was assessed in patient samples from our department and The Cancer Genome Atlas data set. Results: SASH1 expression is down-regulated during cytokine-induced EMT in cell lines from colorectal, pancreatic, or hepatocellular cancer, mediated by the putative SASH1 promoter. Deficiency or knock-down of SASH1 induces EMT, leading to an aggressive, invasive phenotype with increased chemoresistance. SASH1 counteracts EMT through interaction with the oncoprotein CRKL, inhibiting CRKL-mediated activation of SRC kinase, which is crucially required for EMT. SASH1-deficient cells form significantly more metastases in vivo, depending entirely on CRKL. Patient tumor samples show significantly decreased SASH1 and increased CRKL expression, associated with significantly decreased overall survival. Patients with increased CRKL expression show significantly worse response to adjuvant chemotherapy. Conclusions: We propose SASH1 as an inhibitor of CRKL-mediated SRC signaling, introducing a potentially druggable mechanism counteracting chemoresistance and metastasis formation. Keywords: EMT, Tumor Suppressor, SRC-Kinase, Chemoresistance

In this study, the mechanical properties of purposefully synthesized vitrimer repairable epoxy composites were investigated and compared to conventional, commercial systems. The purpose was to assess the knockdown effect, or the relative property deterioration, from the use of the vitrimer in several testing configurations. Mechanical tests were performed using ILSS, low-velocity impact, and compression after impact configurations. At modeled structure level, the lap strap geometry that can simulate the stiffening of a composite panel was tested. Several non-destructive evaluation techniques were utilized simultaneously with the mechanical testing in order to evaluate (i) the production quality, (ii) the damage during or after mechanical testing, and (iii) the repair efficiency. Results indicated that the new repairable composites had the same mechanical properties as the conventional aerospace-grade RTM6 composites. The electrical resistance change method proved to be a valuable technique for monitoring deformations before the initiation of the debonding and the progress of the damage with consistency and high sensitivity in real time. In terms of repair efficiency, the values ranged from 70% to 100%.

Introduction: Awake craniotomy is widely used for surgery in eloquent brain in order to facilitate maximal safe resection of brain tumours. There has been huge progress in both surgical and anaesthetic techniques used during awake craniotomy. This study reports a single surgeon experience of awake craniotomy for tumour resection over a 14 year period focusing on the safety and feasibility of a simple technique. Methods: Patients who underwent awake craniotomy for tumour resection between 2006 and 2019 (inclusive) were identified retrospectively from theatre logbooks in an NHS neurosciences centre. Case note review was performed to collect data on demographics, histology, intra-operative mapping and complications. Results: Four hundred and sixty-nine patients were included with a mean age of 52.0 ± 14.3 years. Three hundred and seventy-seven (80.2%) of the tumours were primary tumours of which WHO grade IV were the most common (n = 204, 54.1%). Ninety-two (19.6%) of the tumours were metastases with breast (n = 23, 25.0%), skin (n = 22, 23.91%) and lung (n = 22, 23.9%) being the most common primary malignancies. The frontal lobe was the most common location (n = 221, 47.1%). The median length of stay was 1 day. One hundred and seven (22.8%) patients had complications with neurological deficits (n = 73, 15.6%), being the most common however only 8 patients (1.7%) had permanent neurological deficits. Discussion: This is the largest published UK series of awake craniotomy for tumour resection. It demonstrates the safety and feasibility of a simple and easily reproducible technique with a low incidence of permanent neurological deficits and short durations of hospital admission.