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BACKGROUND: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination. METHODS: A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. RESULTS: Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2-5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7-2.8), which is the main finding. CONCLUSION: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8). Based on the upper limits of the pooled estimate we can rule out with 95% certainty that the number of excess GBS cases after influenza A(H1N1)pdm09 vaccination would be more than 3 per million vaccinated.

Abstract Aromatic belts, ultrashort carbon nanotubes, and related structures, are emerging molecular entities in the fields of organic electronics and supramolecular chemistry owing to their structural rigidity, fully fused π-conjugation, and well-defined cavity. Synthesis of aromatic belts with embedded thiophene structures, which manifest significant optoelectronic and conductive properties, has not yet been achieved. Herein, we report the synthesis of thiophene-fused aromatic belts (thiophene belts) via one-step sulfur cross-linking reaction of partially fluorinated cycloparaphenylenes. Their structural features, including unidirectional columnar stacking with high dipole moment in crystals, two-dimensional layer assembly on metal surfaces, and photophysical properties, such as long-lifetime phosphorescence, are uncovered. These distinctive features of the thiophene belts should inspire a range of applications such as optoelectronic devices and polar materials.

Abstract Multi-environmental trials (MET) with temporal and spatial variance are crucial for understanding genotype-environment-management (GxExM) interactions in crops. Here, we present a MET dataset for winter wheat in Germany. The dataset encompasses MET spanning six years (2015–2020), six locations and nine crop management scenarios (consisting of combinations for three treatments, unbalanced in each location and year) comparing 228 cultivars released between 1963 and 2016, amounting to a total of 526,751 data points covering 24 traits. Beside grain yield, ten agronomic traits, four baking quality traits, plant height, heading date, maturity date and six fungal disease infection indices are included. Additionally, we provide management records, including fertilizer use, plant protection measures, irrigation, and weather data. We demonstrate how this dataset can address four agronomic questions related to GxExM interactions. Further potential applications of the dataset include empirical analyses, genomic and enviromic analyses for breeding targets, or development of decision-supporting models for agricultural management and policy decisions.

Abstract Background Root growth is most commonly determined with the destructive soil core method, which is very labor-intensive and destroys the plants at the sampling spots. The alternative minirhizotron technique allows for root growth observation throughout the growing season at the same spot but necessitates a high-throughput image analysis for being labor- and cost-efficient. In this study, wheat root development in agronomically varied situations was monitored with minirhizotrons over the growing period in two years, paralleled by destructive samplings at two dates. The aims of this study were to (i) adapt an existing CNN-based segmentation method for wheat minirhizotron images, (ii) verify the results of minirhizotron measurements with root growth data obtained by the destructive soil core method, and (iii) investigate the effect of the presence of the minirhizotron tubes on root growth. Results The previously existing CNN could successfully be adapted for wheat root images. The minirhizotron technique seems to be more suitable for root growth observation in the subsoil, where a good agreement with destructively gathered data was found, while root length results in the topsoil were dissatisfactory in comparison to the soil core method in both years. The tube presence was found to affect root growth only if not installed with a good soil-tube contact which can be achieved by slurrying, i.e. filling gaps with a soil/water suspension. Conclusions Overall, the minirhizotron technique in combination with high-throughput image analysis seems to be an alternative and valuable technique for suitable research questions in root research targeting the subsoil.

Targeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis, and enabling easy surface modifications for targeting. However, the ability of the formulation to incorporate DNA is limited, which restricts the number of DNA molecules that can be incorporated into the particle, thereby reducing gene expression. Here we use polymerase chain reaction (PCR)-generated linear DNA molecules to augment the coding sequences of gene-carrying nanoparticles, thereby maximizing nucleic acid loading and minimizing the size of these nanocarriers. This approach results in a remarkable 16-fold increase in protein expression six days post-transfection in cells transfected with particles carrying the linear DNA compared with particles bearing circular plasmid DNA. The study also showed that the use of linear DNA entrapped in DNA@SiO2 resulted in a much more efficient level of gene expression compared to standard transfection reagents. The system developed in this study features simplicity, scalability, and increased transfection efficiency and gene expression over existing approaches, enabled by improved embedment capabilities for linear DNA, compared to conventional methods such as lipids or polymers, which generally show greater transfection efficiency with plasmid DNA. Therefore, this novel methodology can find applications not only in gene therapy but also in research settings for high-throughput gene expression screenings.

Abstract BackgroundThe Charité Alarm Fatigue Questionnaire (CAFQa) is a 9-item questionnaire that aims to standardize how alarm fatigue in nurses and physicians is measured. We previously hypothesized that it has 2 correlated scales, one on the psychosomatic effects of alarm fatigue and the other on staff’s coping strategies in working with alarms. ObjectiveWe aimed to validate the hypothesized structure of the CAFQa and thus underpin the instrument’s construct validity. MethodsWe conducted 2 independent studies with nurses and physicians from intensive care units in Germany (study 1: n=265; study 2: n=1212). Responses to the questionnaire were analyzed using confirmatory factor analysis with the unweighted least-squares algorithm based on polychoric covariances. Convergent validity was assessed by participants’ estimation of their own alarm fatigue and exposure to false alarms as a percentage. ResultsIn both studies, the χ2χ226Pχ226Prrrr ConclusionsThe questionnaire measures the construct of alarm fatigue as proposed in our previous study. Researchers and clinicians can rely on the CAFQa to measure the alarm fatigue of nurses and physicians.

The extreme persistence and environmental mobility of per- and polyfluoroalkyl substances (PFAS) make their presence ubiquitous in the marine environment. Target analysis of 20 most common PFAS revealed the presence of nine perfluoroalkyl acids at low levels in surface sediments from five Norwegian marine areas covering the vast region from the eastern North Sea in the south to the Arctic Ocean north of Svalbard in the north. After correcting for sediment characteristics, no substantial difference in the sum of the nine PFAS (Σ9PFAS) between the five areas was found. Among separate compounds, PFOS, PFOA and PFNA dominate sample composition. Only two compounds, PFOS and PFUnDA, showed a statistically significant difference for one of the areas, the levels of these compounds being somewhat higher in the southernmost area than in the other areas. This may be due to local inputs in the fjords in this area. Open-sea and coastal sediments of the North-east Atlantic outside of locations with significant local sources seem to share a common, anthropogenic “PFAS background”, which may be part of a larger, global pattern.

Biological materials found in nacre or glass sponges reveal specific layered organic and inorganic structures known for their fracture toughness caused by crack deflection and bridging. This work aims to bio-mimic the brick-and-mortar (BnM) structure from nacre and the layer-by-layer (LbL) structure from the glass sponge filaments to incorporate these effects into the contact zone of carbon fiber-reinforced concrete (CFRC) in order to prevent brittle composite failure. To build up BnM- and LbL-structure materials such as nanoclays, sodium water glass, and polymer dispersions were selected since they are well-established low-cost materials in building. Nanoclays were analyzed regarding their size, dispersibility and exfoliation. Montmorillonite (MMT) was used to be mixed with polymers to produce self-assembled BnM-structured films and coatings. Also, LbL-structures were formed by alternating layers of sodium water glass and polymer. Scanning electron microscopy and energy-dispersive X-ray spectroscopy were used to verify the morphology. The MMT-containing coatings demonstrated enhanced nucleation potential when exposed to cementitious eluate. Micromechanical pull-out tests on single carbon fibers with BnM- and LbL-coatings embedded in concrete demonstrate the potential to increase composite toughness. The successful implementation of the bio-inspired structures using affordable materials lays the groundwork for their scalability and integration into composite structures for building.

Background: Conspiracy theory belief – explaining the ultimate causes of social and political events with claims of secret conspiracies – is assumed to arise from a desire to make sense of uncertainty, especially in times of crisis. However, there is no compelling evidence that conspiracy theory belief actually fulfils this function, particularly in terms of evaluating one's life as meaningful. We posit that the adoption of conspiracy theory belief can be explained as a fluid compensation when a more proximal source of meaning, a sense of belonging to society, is threatened. Thus, a positive association between conspiracy theory belief and meaningfulness should emerge when people feel alienated from society. We therefore tested the hypotheses that alienation from society correlates negatively with meaningfulness (H1), and that it moderates the relationship between conspiracy theory belief and meaningfulness (H2). Method: Conspiracy theory belief related to the COVID-19 pandemic, meaningfulness (Meaning and Purpose Scales, MAPS), and perceived alienation from society were assessed in a representative sample of N = 974 German residents. Results: As expected, alienation from society was inversely related to meaningfulness and moderated the relationship between conspiracy theory belief and meaningfulness. According to the interaction, a positive association between belief in conspiracy theory and meaningfulness emerged when individuals experienced themselves as alienated from society. Conclusion: The results suggest that conspiracy theory belief might alleviate a lack of meaningfulness caused by experienced alienation from society. Individuals who felt discriminated against, treated unequally, or having their rights restricted were more likely to hold conspiracy theory belief, which was associated with a greater sense of meaning in their lives.

Abstract The lack of physiological parity between 2D cell culture and in vivo culture has led to the development of more organotypic models, such as organoids. Organoid models have been developed for a number of tissues, including the liver. Current organoid protocols are characterized by a reliance on extracellular matrices (ECMs), patterning in 2D culture, costly growth factors and a lack of cellular diversity, structure, and organization. Current hepatic organoid models are generally simplistic and composed of hepatocytes or cholangiocytes, rendering them less physiologically relevant compared to native tissue. We have developed an approach that does not require 2D patterning, is ECM independent, and employs small molecules to mimic embryonic liver development that produces large quantities of liver-like organoids. Using single-cell RNA sequencing and immunofluorescence, we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, and a population of resident macrophages: Kupffer cells. The organoids exhibit key liver functions, including drug metabolism, serum protein production, urea synthesis and coagulation factor production, with preserved post-translational modifications such as N-glycosylation and functionality. The organoids can be transplanted and maintained long term in mice producing human albumin. The organoids exhibit a complex cellular repertoire reflective of the organ and have de novo vascularization and liver-like function. These characteristics are a prerequisite for many applications from cellular therapy, tissue engineering, drug toxicity assessment, and disease modeling to basic developmental biology.

IntroductionChronic inflammation is a hallmark of chronic wounds and inflammatory skin diseases. Due to a hyperactive and prolonged inflammation triggered by proinflammatory immune cells, transitioning to the repair and healing phase is halted. T cells may exacerbate the proinflammatory milieu by secreting proinflammatory cytokines. Chamomilla recutita L. (chamomile) has been suggested for use in several inflammatory diseases, implying a capability to modulate T cells. Here, we have characterized and compared the effects of differently prepared chamomile extracts and characteristic pure compounds on the T cell redox milieu as well as on the migration, activation, proliferation, and cytokine production of primary human T cells.MethodsPhytochemical analysis of the extracts was carried out by LC-MS/MS. Primary human T cells from peripheral blood (PBTs) were pretreated with aqueous or hydroethanolic chamomile extracts or pure compounds. Subsequently, the effects on intracellular ROS levels, SDF-1α induced T cell migration, T cell activation, proliferation, and cytokine production after TCR/CD3 and CD28 costimulation were determined. Gene expression profiling was performed using nCounter analysis, followed by ingenuity pathway analysis, and validation at protein levels.ResultsThe tested chamomile extracts and pure compounds differentially affected intracellular ROS levels, migration, and activation of T cells. Three out of five differently prepared extracts and two out of three pure compounds diminished T cell proliferation. In line with these findings, LC-MS/MS analysis revealed high heterogeneity of phytochemicals among the different extracts. nCounter based gene expression profiling identified several genes related to T cell functions associated with activation and differentiation to be downregulated. Most prominently, apigenin significantly reduced granzyme B induction and cytotoxic T cell activity.ConclusionOur results demonstrate an anti-inflammatory effect of chamomile- derived products on primary human T cells. These findings provide molecular explanations for the observed anti-inflammatory action of chamomile and imply a broader use of chamomile extracts in T cell driven chronic inflammatory diseases such as chronic wounds and inflammatory skin diseases. Importantly, the mode of extract preparation needs to be considered as the resulting different phytochemicals can result in differential effects on T cells.

In the last decades, the slow-spreading Red Sea rift has been the objective of several geophysical investigations to study the extension of the oceanic crust, the thickness of the sedimentary cover, and the formation of transform faults. However, local seismology datasets are still lacking despite their potential to contribute to the understanding of the tectonic evolution of the Red Sea. The Zabargad Fracture Zone is located in the Northern Red Sea and significantly offsets the rift axis to the East. Thus, it is considered a key tectonic element to understand better the formation of the Red Sea rift. To fill the gap in the dataset availability, we deployed the first passive seismic network in the Red Sea, within the Zabargad Fracture Zone. This network included 12 Lobster OBSs from the DEPAS pool, 2 OBS developed and deployed by Fugro, and 4 portable seismic land stations deployed on islands and onshore on the Saudi Arabian coast. Our data-quality analysis confirms that the head-buoy cable free to strum, as well as other additional elements of the DEPAS OBSs, generate seismic noise at frequencies $>$ 10 Hz. However, the Fugro OBSs show high-frequency disturbances even if they lack vibrating elements. Comparison between land and OBS stations reveals that noise between 1 and 10 Hz is due to ocean-generated seismic noise, and not due to resonance of the OBS elements. We also found that waveforms of teleseismic earthquakes recorded by the Fugro OBSs, islands, and onshore stations have comparable signal-to-noise ratios. Instead, differences in signal-to-noise ratio for local earthquakes are affected more by site and path effects than instrument settings.

Abstract When exposed to hundreds of medical device alarms per day, intensive care unit (ICU) staff can develop “alarm fatigue” (i.e., desensitisation to alarms). However, no standardised way of quantifying alarm fatigue exists. We aimed to develop a brief questionnaire for measuring alarm fatigue in nurses and physicians. After developing a list of initial items based on a literature review, we conducted 15 cognitive interviews with the target group (13 nurses and two physicians) to ensure that the items are face valid and comprehensible. We then asked 32 experts on alarm fatigue to judge whether the items are suited for measuring alarm fatigue. The resulting 27 items were sent to nurses and physicians from 15 ICUs of a large German hospital. We used exploratory factor analysis to further reduce the number of items and to identify scales. A total of 585 submissions from 707 participants could be analysed (of which 14% were physicians and 64% were nurses). The simple structure of a two-factor model was achieved within three rounds. The final questionnaire (called Charité Alarm Fatigue Questionnaire; CAFQa) consists of nine items along two scales (i.e., the “alarm stress scale” and the “alarm coping scale”). The CAFQa is a brief questionnaire that allows clinical alarm researchers to quantify the alarm fatigue of nurses and physicians. It should not take more than five minutes to administer.

Significant greenhouse gas emissions during substrate cultivation reduces the potential environmental benefits of biogas production. This study investigates the productivity of different cropping systems and their environmental impact in terms of nitrous oxide (N2O) emissions under the environmental conditions of the coastal marsh regions (Northern Germany) with heavy clay soils, in a 2-year field trial (April 2009-March 2011). Treatments included four cropping systems (perennial ryegrass (Lolium perenne, PR) ley, continuous maize (Zea mays), a rotation (CR1) of spring wheat (Triticum aestivum), Italian ryegrass (Lolium multiflorum, IR) and maize, and a rotation (CR2) of maize, winter wheat and IR; two sources of N (nitrogen) fertilizers (calcium ammonium nitrate, and biogas residue (BR)), and three levels of N fertilizer applications (control, moderate, high). Nitrous oxide emissions were determined for the unfertilized and highly fertilized cropping systems comprising PR ley, CR1 and CR2. Cumulative annual N2O emissions varied across the treatments, ranging from 0.82 to 3.4 kg N2O-N ha−1 year−1. Under high N fertilizer applications, PR ley incurred higher N2O-N losses compared to other tested cropping systems, and IR cover crop caused relatively high N2O-N emissions in a short vegetation period. The study observed wide range of yield-scaled emissions (0.00–5.60 kg N2O-N (Mg DM)−1) for different crops, emphasizing the variability in N2O emissions linked to cropping systems. The N2O-N emission factors for the three cropping systems were found to be low to moderate for all treatments, ranging from 0.03% to 0.53% compared to IPCC default Tier 1 N2O-N EFs. The lower emissions in the study were associated with prolonged high soil moisture conditions (water filled pore space >70%.), indicated by its negative correlation with N2O-N fluxes. Low dry matter and N yield of PR and of the wheat-IR sequence after BR application compared to other crops indicated a low N use efficiency. The estimation of N2O-N emissions based on N surplus was not promising specifically for the coastal study site where high groundwater level and organic matter in the soils were the predominant drivers for N2O-N emissions.

Abstract X-ray free-electron laser sources enable time-resolved X-ray studies with unmatched temporal resolution. To fully exploit ultrashort X-ray pulses, timing tools are essential. However, new high repetition rate X-ray facilities present challenges for currently used timing tool schemes. Here we address this issue by demonstrating a sensitive timing tool scheme to enhance experimental time resolution in pump-probe experiments at very high pulse repetition rates. Our method employs a self-referenced detection scheme using a time-sheared chirped optical pulse traversing an X-ray stimulated diamond plate. By formulating an effective medium theory, we confirm subtle refractive index changes, induced by sub-milli-Joule intense X-ray pulses, that are measured in our experiment. The system utilizes a Common-Path-Interferometer to detect X-ray-induced phase shifts of the optical probe pulse transmitted through the diamond sample. Owing to the thermal stability of diamond, our approach is well-suited for MHz pulse repetition rates in superconducting linear accelerator-based free-electron lasers.

Abstract Wild boar is increasingly establishing populations in the outskirts of European cities, with the largest German urban population occurring in Berlin. Related soil disturbance in grasslands is common and often considered as damage to biodiversity. However, it is unknown how animal and plant species in urban grasslands respond to wild boar activity - an important limitation for conservation management. We sampled plants, grasshoppers and sand lizards in 22 dry grasslands and measured wild boar activity. We show that plant diversity decreased with rooting intensity, but not species richness, endangered or specialist species. Relationships with animals were mostly positive. Grasshopper diversity, total richness and richness of endangered and specialist species were positively related to rooting, as was sand lizard abundance. These relationships contrast to mostly negative effects in the wild boar’s non-native range. This first multi-taxa study in a large city suggests that soil disturbance by wild boars is not necessarily a threat to biodiversity. An implication for conservation is to consider the context-dependence of biodiversity responses to wild boar activity. For dry grasslands, disturbed patches should be accepted in management plans rather than re-vegetated by seeding.

The functional role of airway basal cells has not been comprehensively studied in idiopathic pulmonary fibrosis (IPF). Here, the authors show that airway basal cells of IPF patients display a distinct phenotype, are profibrotic if transplanted to mice and that fibrosis can be ameliorated by Src iinhibitors.

Summary: Background: Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious—and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia. Methods: We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5–20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2–4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority. Findings: We identified 22 randomised studies with 1350 patients reporting on serious—and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01–2.43, 17 studies, I2 = 47%). Three studies reported little or no influence on pubertal development following 2–4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations. Interpretation: Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

Summary: Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5–20 years with idiopathic chronic insomnia. Methods: A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5–20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96–41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI −26.61 to −9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25–9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Interpretation: Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. Funding: The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.

Summary: Background: Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2–20 years, with chronic insomnia due to disorders beyond indication. Methods: We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2–20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2–4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2–4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3–6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I2 statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42–6.34, 9 studies, I2 = 60%) and increased total sleep time by 18.97 min (95% CI 0.37–37.57, 10 studies, I2 = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low. Interpretation: Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential. Funding: The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.

BackgroundMaintaining good mental health is important during a crisis. However, little attention has been given to how people achieve this, or how they evaluate emotions associated with stressors, such as the COVID-19 pandemic. This study aims to (1) investigate whether emotion regulation, in particular cognitive reappraisal and suppression, moderates the relationship between COVID-19 stress and general mental distress and (2) examine gender differences in the interrelations between COVID-19 stress, emotion regulation, and mental distress.MethodsData from a population in Norway (n = 1.225) were collected using a cross-sectional survey during the early months of the COVID-19 pandemic. Emotion regulation was measured using the Emotion Regulation Questionnaire Scale (ERQ), COVID-19 stress with the COVID-19 Stress Scale, and mental distress with the Patient Health Questionnaire 4 (PHQ-4). Moderation analyses were conducted using the PROCESS macro for SPSS.ResultsThere was a strong association between COVID-19 stress and general mental distress (r = 0.61). The moderation analyses showed substantial moderation effects of cognitive reappraisal and suppression on the relationship between COVID-19 stress and mental distress. Cognitive reappraisal served as a buffer (p = 0.001) and suppression (p = 0.002) exacerbated the relation between COVID-19 stress and mental distress. Men had higher scores of suppression (p

Background: Trauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury. Methods: A retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury. Results: In all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6–93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8–214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge. Conclusions: Pancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.

The present research aims at giving an approach to the issue of surface water contamination due to micropollutants in rural areas. The catchment of the Sûre river was selected as a reference case for the Greater Region, characterized mainly by settlements with low population density, small water bodies and small- to medium-sized wastewater treatment plants (WWTPs). For these WWTPs, conventional technical solutions for micropollutant elimination are not suitable; therefore, an adapted mitigation strategy is needed to prevent the impact of micropollutants, especially during the dry season. As a suitable alternative to more intensive technologies, Constructed Wetlands (CW) in Vertical Flow (VF) configuration have been successfully tested over a 1-year period and the elimination rate of 27 micropollutants was quantified. Emission reduction by VF was then considered in a static mass balance model that calculates the longitudinal concentration profile for the entire river catchment. The EmiSûre approach, which focuses on river quality (concentrations of pollutants) instead of emitted loads, effectively allowed simulation of adopted measures a priori and resulted in efficient support for decision-makers with WWTP upgrade scenarios. HIGHLIGHTS A novel approach is applied to assess mitigation measures for micropollutants elimination in rural areas.; Constructed wetlands are promising for micropollutants elimination.; Emission reductions by Constructed Wetlands are considered in a static mass balance model.; The selection of the WWTPs resulted in a significant load reduction.; The EmiSûre model successfully serves as a valuable tool for decision-makers.;

The low nitrogen (N)-use efficiency of intensive winter oilseed rape (WOSR) cropping systems may cause negative environmental impacts, especially due to N leaching and gaseous losses. The aim of this study was to use data from field experiments (five sites across Germany representing typical WOSR regions) for parametrization of a nitrous oxide (N2O) emission component for implementation into a process-based dynamic plant-soil-atmosphere model (PSAM). After calibration and evaluation with three years of field data from five different N fertilizer treatments, a long-term simulation with 25-year historical weather data was conducted to derive functional relations and emission factors (EFs). The model performed best at higher aggregation levels (cumulative emissions over the entire cropping period, R2 of 0.48/0.77 for calibration/evaluation), but also reasonably simulated short-term dynamics (e.g., fertilizer applications, extreme weather events). Site-specific and year-specific N2O emissions varied within the range of medians from 0.56–4.93 kg N2O-N ha−1. Mineral fertilizer-induced EFs at economic optimal N inputs ranged from 0.16–0.65%, which was markedly below the aggregated IPCC standard value of 1% for direct N2O emissions. Generally, the simulated emissions were consistently higher with finer soil textures and increasing N inputs. The process-based approach, moreover, allowed the identification of the major source of N2O, which mainly originated from nitrification processes.

Abstract Background Reactions to the COVID-19 pandemic are diverse, and both mental distress and existential crises can arise. The identification of protective and exacerbating factors and their progress over time is therefore highly relevant. The current study examined longitudinal protective effects of meaningfulness and exacerbating effects of crisis of meaning on general mental distress. Methods N = 431 participants from Germany and Austria (mean age: 42 years) completed an online survey in both April/May (T1) and July/August 2020 (T2). After determining temporal stability or changes in meaningfulness, crisis of meaning, and general mental distress (PHQ-4), we examined whether (i) meaningfulness and (ii) crisis of meaning, measured at T1, incrementally predicted PHQ-4 at T2, beyond baseline levels of PHQ-4. We further tested (iii) a within-subject mediation of temporal changes in PHQ-4 by changes in crisis of meaning. Results Meaningfulness prospectively predicted lower PHQ-4, and crisis of meaning predicted higher PHQ-4. From the first wave of the pandemic until a slowdown three months later, meaningfulness was stable, and crisis of meaning and PHQ-4 decreased. Changes in crisis of meaning mediated the changes in PHQ-4. Conclusions Meaningfulness appears to have a protective, and crisis of meaning an exacerbating effect on psychological distress, as shown here for the time of the first pandemic wave until three months later. Attention to existential experiences of meaningfulness and loss of meaning thus proves relevant to the clinical and public health context. Measures that support meaningfulness will help coping with crises of meaning, which in turn supports overcoming general mental distress.

Jakob Emanuel Lange (1864–1941), Danish mushroom taxonomist and illustrator, was an agricultural educator and economic philosopher. A follower and translator of the American Henry George, Lange was Headmaster of a “Small-holders High-School,” which served as a model for American folk-schools. Lange visited North America on three occasions. The first, in 1927, relied on his professional expertise; the second, in 1931, was purely mycological; and the third, 1939, was a combination of the two. All of this was lived against two World Wars and the Great Depression. This paper summarises the circumstances of Lange’s life against a background of the American mycologists of the day, the ominous events over his adult lifetime and his magnum opus, “Flora Agaricina Danica”, of five volumes illustrating ca. 1200 species on 200 coloured plates.

Nitrogen (N) loss by leaching is a major concern in common crop rotations in Central Europe due to high post-harvest soil mineral N, low N uptake in autumn/winter, and percolation. This can lead to eutrophication of water bodies and indirect greenhouse gas emissions. One potential solution is to control microbial immobilization through the incorporation of organic matter. To examine the effectiveness of this approach, we compared the incorporation of crop residues from winter oilseed rape, faba beans, and winter wheat with the application of sawdust in a field-scale experiment. Field observations of the impact on autumn/winter N-dynamics were supplemented with model-derived parameters. Our results showed that the incorporation of crop residues significantly reduced autumn net mineralization in topsoil, with the largest reduction seen with cereal straw. However, the temporal dynamics of the effect did not meet the desired time frame, and the impact on N leaching was low. Field data, modeling processes, and a theoretical amendment assessment suggested that resistant organic matter accumulated under the given environmental conditions, probably resulting in a long-term effect on nutrient dynamics. In conclusion, incorporating crop residues from the preceding crop is the best option to date for mitigating post-harvest N losses and improving soil health with minimal crop management effort. However, controlling microbial immobilization through organic matter incorporation can be a useful measure whose effectiveness depends on the amendment used and field conditions.

PurposeThe purpose of this study is to investigate the impact of Bergen Epileptiform Morphology Score (BEMS) and interictal epileptiform discharge (IED) candidate count in EEG classification.MethodsWe included 400 consecutive patients from a clinical SCORE EEG database during 2013–2017 who had focal sharp discharges in their EEG, but no previous diagnosis of epilepsy. Three blinded EEG readers marked all IED candidates. BEMS and IED candidate counts were combined to classify EEGs as epileptiform or non-epileptiform. Diagnostic performance was assessed and then validated in an external dataset.ResultsInterictal epileptiform discharge (IED) candidate count and BEMS were moderately correlated. The optimal criteria to classify an EEG as epileptiform were either one spike at BEMS > = 58, two at > = 47, or seven at > = 36. These criteria had almost perfect inter-rater reliability (Gwet’s AC1 0.96), reasonable sensitivity of 56–64%, and high specificity of 98–99%. The sensitivity was 27–37%, and the specificity was 93–97% for a follow-up diagnosis of epilepsy. In the external dataset, the sensitivity for an epileptiform EEG was 60–70%, and the specificity was 90–93%.ConclusionQuantified EEG spike morphology (BEMS) and IED candidate count can be combined to classify an EEG as epileptiform with high reliability but with lower sensitivity than regular visual EEG review.

Use of chimeric antigen receptor (CAR) T cells to treat B cell lymphoma and leukemia has been remarkably successful. Unfortunately, the therapeutic efficacy of CAR T cells against solid tumors is very limited, with immunosuppression by the pro-oxidative tumor microenvironment (TME) a major contributing factor. High levels of reactive oxygen species are well-tolerated by tumor cells due to their elevated expression of antioxidant proteins; however, this is not the case for T cells, which consequently become hypo-responsive. The aim of this study was to improve CAR T cell efficacy in solid tumors by empowering the antioxidant capacity of CAR T cells against the pro-oxidative TME. To this end, HER2-specific human CAR T cells stably expressing two antioxidant systems: thioredoxin-1 (TRX1), and glutaredoxin-1 (GRX1) were generated and characterized. Thereafter, antitumor functions of CAR T cells were evaluated under control or pro-oxidative conditions. To provide insights into the role of antioxidant systems, gene expression profiles as well as global protein oxidation were analyzed. Our results highlight that TRX1 is pivotal for T cell redox homeostasis. TRX1 expression allows CAR T cells to retain their cytolytic immune synapse formation, cytokine release, proliferation, and tumor cell-killing properties under pro-oxidative conditions. Evaluation of differentially expressed genes and the first comprehensive redoxosome analysis of T cells by mass spectrometry further clarified the underlying mechanisms. Taken together, enhancement of the key antioxidant TRX1 in human T cells opens possibilities to increase the efficacy of CAR T cell treatment against solid tumors.

Hyperspectral imaging (HSI) is a non-invasive technology that provides information on biochemical tissue properties, including skin oxygenation and perfusion quality. Microcirculatory alterations are associated with organ dysfunction in septic COVID-19 patients. This prospective observational study investigated associations between skin HSI and organ dysfunction severity in critically ill COVID-19 patients. During the first seven days in the ICU, palmar HSI measurements were carried out with the TIVITA® tissue system. We report data from 52 critically ill COVID-19 patients, of whom 40 required extracorporeal membrane oxygenation (ECMO). HSI parameters for superficial tissue oxygenation (StO2) and oxygenation and perfusion quality (NPI) were persistently decreased. Hemoglobin tissue content (THI) increased, and tissue water content (TWI) was persistently elevated. Regression analysis showed strong indications for an association of NPI and weaker indications for associations of StO2, THI, and TWI with sequential organ failure assessment (SOFA) scoring. StO2 and NPI demonstrated negative associations with vasopressor support and lactate levels as well as positive associations with arterial oxygen saturation. These results suggest that skin HSI provides clinically relevant information, opening new perspectives for microcirculatory monitoring in critical care.

Due to the demand for decarbonization of the construction sector, research on alkali-activated binders and material-minimized carbon-reinforced structures has gained momentum in recent years. Most of the research into alkali-activated binders is focused on developing market-ready alternatives, mainly using a trial-and-error approach. In this study, an attempt is made to identify and quantify the factors influencing compressive strength development. Due to their worldwide availability, investigations are being carried out into binders based on calcined clays and natural pozzolans. The goal is to develop a method to produce tailor-made AAB for continuous manufacturing methods to combine carbon reinforcement and alkali-activated materials. For this purpose, an experimental matrix with 20 variation parameters was set up, in which the activator solution and the precursor composition varied. The design of the experiments was used to minimize the number of experiments. It was shown that no single factor is responsible for the development of compressive strength but instead involves several interacting factors. It was possible to find empirical formulas for predicting the compressive strength after 2, 7, and 28 days.

Abstract Background An internal locus of control (LoC I) refers to the belief that the outcome of events in one’s life is contingent upon one’s actions, whereas an external locus of control (LoC E) describes the belief that chance and powerful others control one’s life. This study investigated whether LoC I and LoC E moderated the relationship between COVID-19 stress and general mental distress in the general population during the early months of the COVID-19 pandemic. Methods This cross-sectional survey study analysed data from a Norwegian (n = 1225) and a German-speaking sample (n = 1527). We measured LoC with the Locus of Control-4 Scale (IE-4), COVID-19 stress with a scale developed for this purpose, and mental distress with the Patient Health Questionnaire 4 (PHQ-4). Moderation analyses were conducted using the PROCESS macro for SPSS. Results The association between COVID-19 stress and general mental distress was strong (r = .61 and r = .55 for the Norwegian and the German-speaking sample, respectively). In both samples, LoC showed substantial moderation effects. LoC I served as a buffer (p

We considered discrete and continuous representations of a thermodynamic process in which a random walker (e.g., a molecular motor on a molecular track) uses periodically pumped energy (work) to pass N sites and move energetically downhill while dissipating heat. Interestingly, we found that, starting from a discrete model, the limit in which the motion becomes continuous in space and time (N→∞) is not unique and depends on what physical observables are assumed to be unchanged in the process. In particular, one may (as usually done) choose to keep the speed and diffusion coefficient fixed during this limiting process, in which case, the entropy production is affected. In addition, we also studied processes in which the entropy production is kept constant as N→∞ at the cost of a modified speed or diffusion coefficient. Furthermore, we also combined this dynamics with work against an opposing force, which made it possible to study the effect of discretization of the process on the thermodynamic efficiency of transferring the power input to the power output. Interestingly, we found that the efficiency was increased in the limit of N→∞. Finally, we investigated the same process when transitions between sites can only happen at finite time intervals and studied the impact of this time discretization on the thermodynamic variables as the continuous limit is approached.

This is the first study exclusively dedicated to the study of Hebeloma in Greenland. It is based on almost 400 collections, the great majority of which were collected by three of the co-authors over a period of 40 years and were lodged in the fungarium of the Natural History Museum in Copenhagen. The material was identified using molecular and morphological methods. In total, 28 species were recognized, 27 belonging to three sections, H. sects Hebeloma, Denudata and Velutipes. One species sampled was new to science and is here described as H. arcticum. For all species, a description, a distribution map within Greenland and macro and microphotographs are presented. A key is provided for the 28 species. The distribution of species within Greenland is discussed. The findings are placed in the context of studies of arctic and alpine Hebeloma from other parts of the world where comparable data exist. Notably, H. grandisporum, H. louiseae and H. islandicum, previously only known from Romania, Svalbard, Iceland or Norway, respectively, have been found in Greenland. The latter is also the only species encountered that does not belong to any of the above sections. Hebeloma excedens and H. colvinii – for the latter we here publish the first modern description – are to date only known from continental North America and now Greenland.

IntroductionA higher 30-day mortality has been observed in patients with first-presentation ST elevation myocardial infarction (STEMI) who have no standard modifiable cardiovascular risk factors (SMuRFs), i. e., diabetes, hypertension, hyperlipidemia, and current smoker. In this study, we evaluate the clinical outcomes and CMR imaging characteristics of patients with and without SMuRFs who presented with first-presentation STEMI.MethodsPatients from the Third DANish Study of Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction (DANAMI-3) with first-presentation STEMI were classified into those with no SMuRFs vs. those with at least one SMuRF.ResultsWe identified 2,046 patients; 283 (14%) SMuRFless and 1,763 (86%) had >0 SMuRF. SMuRFless patients were older (66 vs. 61 years, p < 0.001) with more males (84 vs. 74%, p < 0.001), more likely to have left anterior descending artery (LAD) as the culprit artery (50 vs. 42%, p = 0.009), and poor pre-PCI (percutaneous coronary intervention) TIMI (thrombolysis in myocardial infarction) flow ≤1 (78 vs. 64%; p < 0.001). There was no difference in all-cause mortality, non-fatal reinfarction, or hospitalization for heart failure at 30 days or at long-term follow-up. CMR imaging was performed on 726 patients. SMuRFless patients had larger acute infarct size (17 vs. 13%, p = 0.04) and a smaller myocardial salvage index (42 vs. 50%, p = 0.02). These differences were attenuated when the higher LAD predominance and/or TIMI 0-1 flow were included in the model.ConclusionDespite no difference in 30-day mortality, SMuRFless patients had a larger infarct size and a smaller myocardial salvage index following first-presentation STEMI. This association was mediated by a larger proportion of LAD culprits and poor TIMI flow pre-PCI.Clinical trial registrationclinicaltrials.gov, unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER) and NCT01960933 (DANAMI 3-PRIMULTI).

While the relationship between loneliness and psychological distress is well documented, the mechanisms underlying this relationship are less clear. One factor known to be related to loneliness as well as psychological distress, is social support, with some studies suggesting that support–both received and provided–can serve as a mechanism to reduce the distress associated with loneliness. In this paper we examine the mediating role of both aspects of support in the relationship between loneliness and psychological distress in the COVID-19 context. We used a multi-country dataset collected at two timepoints during the pandemic; the first during the early stages (N = 6,842, 11 countries) and the second collected for a subset of countries (N = 1,299, 3 countries) 3 months later. Across all eleven countries, results revealed significant positive associations between loneliness and distress. Furthermore, using longitudinal data, we investigated the directionality of this relationship and found that increased loneliness over time was associated with increased psychological distress. The data also showed that both feeling unsupported and feeling unable to provide support to others mediated this relationship. These findings point to the need to facilitate people's ability to draw effective social support and help others–particularly at times when social connectedness is threatened–as a way of alleviating the psychological distress that commonly presents with loneliness.

Background: Every medical decision is based on balancing medical knowledge, ethical considerations, and patient preferences. Previous surveys have mainly covered the ethical knowledge of medical staff. The aim of this study is to evaluate the feasibility of an innovative concept regarding how ethical criteria are applied to clinical decision-making during critical illness. Methods: An online survey including a short case vignette was carried out at a university hospital among physicians specialising in intensive care medicine in Germany. After free text responses regarding further required case information, the participants were asked to rank decision criteria during the course of the case vignette. A qualitative evaluation was performed by two independent investigators, based on a transcription into categories. This was followed by a quantitative analysis of ranked criteria. Results: Our analysis has shown that doctors are initially inclined to consider medical information when making treatment decisions. When complications occur, ethical values are more often included in the decision-making. The qualitative evaluation reveiled that the patient's will was consistently regarded as the leading criterion for decision-making. In the quantitative evaluation, patient's well-being, quality of life, and patient autonomy were rated as the most important decision criteria. Economic factors were ranked least important. Conclusion: A mixed methods approach is able to reflect the complexity of ethical reasoning within the medical decision-making process, suggesting the feasibility of this concept. Clinical trial registration: The study was registered under DRKS-ID: DKRS00011905 (April 2017).

Abstract Background This prospective, cross-sectional, observational study examined associations between sense of coherence (SOC), mental well-being, and perceived preoperative hospital and surgery related stress of surgical patients with malignant, benign, and no neoplasms. The objective was to assess a putative association between SOC and preoperative stress, and to test for a statistical mediation by mental well-being. Method The sample consisted of 4918 patients from diverse surgical fields, of which 945 had malignant neoplasms, 333 benign neoplasms, and 3640 no neoplasms. For each subsample, we conducted simple mediation analyses to test an indirect effect of SOC on preoperative stress mediated by mental well-being. The models were adjusted for age, gender, and essential medical factors. Results Patient groups did not differ significantly regarding degrees of SOC and mental well-being (SOC, M [SD]: 12.31 [2.59], 12.02 [2.62], 12.18 [2.57]; mental well-being M [SD]: 59.26 [24.05], 56.89 [22.67], 57.31 [22.87], in patients with malignant, benign, and without neoplasms, respectively). Patients without neoplasms reported significantly lower stress (4.19 [2.86], M [SD]) than those with benign (5.02 [3.03], M [SD]) and malignant neoplasms (4.99 [2.93], M [SD]). In all three mediation models, SOC had significant direct effects on stress, with higher SOC being associated with lower stress (− 0.3170 [0.0407], − 0.3484 [0.0752], − 0.2919 [0.0206]; c’ [SE], p

Background. Household air pollution (HAP) is one of the most important environmental risk factors worldwide associated with chronic respiratory diseases. Objectives. The present study focused on respiratory health in a population with high wood smoke exposure in Nicaragua. Methods. We employed a cross-sectional study with 213 participants. Data on the prevalence of chronic bronchitis (chronic bronchitis), chronic obstructive pulmonary disease (COPD) and asthma, including respiratory scores and pulmonary function tests, were documented. The role of risk factors for chronic bronchitis was analyzed. Results. We found a high prevalence of chronic airway diseases in the population exposed to wood smoke. A higher prevalence of chronic bronchitis was found in persons serving as primary cooks in households. Further confounding factors for chronic bronchitis included age, a prior diagnosis of asthma, inhalational allergies and lower socioeconomic status. Respiratory scores were elevated in individuals with chronic bronchitis. Conclusions. This is one of the first studies in a wood smoke-exposed population in Nicaragua showing a high prevalence of chronic bronchitis and COPD with an emphasis on the analysis of personal and environmental risk factors. Further studies are needed to address which combination of interventions is most efficient for ameliorating respiratory health hazards. Participant Consent. Obtained Ethics Approval. The study protocol was approved by the Ethics Committee of the University of Luebeck, Germany (reference number 12-214), and by the Ethics Committee of the Department of Medical Sciences at National Autonomous University of Nicaragua, Managua, Nicaragua. Competing Interests. The authors declare no competing financial interests.

The first taxonomic treatment of the smut fungi in Greenland is provided. A total of 43 species in 11 genera are treated and illustrated by photographs of sori, microphotographs of spores in LM and SEM, and distribution maps. Two species, Anthracoidea pseudofoetidae and Urocystis tothii, are recorded as new from North America. Thirteen species, Anthracoidea altera, A. capillaris, A. limosa, A. liroi, A. pseudofoetidae, A. scirpoideae, A. turfosa, Microbotryum lagerheimii, M. stellariae, Schizonella elynae, Stegocintractia luzulae, Urocystis fischeri, and U. tothii, are reported for the first time from Greenland. Three new fungus-host combinations, Anthracoidea capillaris on Carex boecheriana, Anthracoidea pseudofoetidae on Carex maritima, and Urocystis tothii on Juncus biglumis, are given. Five plant species are reported as new hosts of smut fungi in Greenland, namely, Carex nigra for Anthracoidea heterospora, C. canescens for Anthracoidea karii, C. fuliginosa subsp. misandra for Anthracoidea misandrae, C. maritima for Orphanomyces arcticus, and C. fuliginosa subsp. misandra for Schizonella melanogramma. Three species, Microbotryum violaceum s. str. (recorded as ‘Ustilago violacea’), Urocystis anemones, and U. junci, which were previously reported from Greenland, are considered wrongly identified. Additional distribution records are given for 12 species from Greenland: Anthracoidea bigelowii, A. caricis, A. elynae, A. lindebergiae, A. misandrae, A. nardinae, A. rupestris, A. scirpi, Schizonella melanogramma, Stegocintractia hyperborea, Urocystis agropyri, and U. sorosporioides. The most numerous distribution groups are the following: circumpolar–alpine and Arctic–alpine species – 14; circumboreal–polar species – 10; and circumpolar and Arctic species – 6. The most widely distributed smut fungi in Greenland were Anthracoidea bigelowii, A. elynae, Microbotryum bistortarum, and M. vinosum. Most species were found in the High Arctic zone (29 species), while from the Low Arctic zone and the Subarctic zone, 26 and 19 species were known, respectively. Ten species, Anthracoidea bigelowii, A. capillaris, A. elynae, Microbotryum bistortarum, M. koenigiae, M. pustulatum, M. silenes-acaulis, M. vinosum, Schizonella elynae, and Urocystis sorosporioides, were recorded from all three zones. Only plants belonging to six families, Cyperaceae, Poaceae, Juncaceae, Ranunculaceae, Caryophyllaceae, and Polygonaceae, out of a total of 55 in the flora of Greenland, hosted smut fungi. Cyperaceae was the plant family with most host species (23). Carex was the genus with the highest number of host species (22). The total number of the host plants (45 species) was 8.5 % out of a total of 532 vascular plants in the flora of Greenland. A new combination in Carex, C. macroprophylla subsp. subfilifolia, is proposed for Kobresia filifolia subsp. subfilifolia.

BackgroundDigital health technologies such as continuous remote monitoring and artificial intelligence–driven clinical decision support systems could improve clinical outcomes in intensive care medicine. However, comprehensive evidence and guidelines for the successful implementation of digital health technologies into specific clinical settings such as the intensive care unit (ICU) are scarce. We evaluated the implementation of a remote patient monitoring platform and derived a framework proposal for the implementation of digital health technology in an ICU. ObjectiveThis study aims to investigate barriers and facilitators to the implementation of a remote patient monitoring technology and to develop a proposal for an implementation framework for digital health technology in the ICU. MethodsThis study was conducted from May 2018 to March 2020 during the implementation of a tablet computer–based remote patient monitoring system. The system was installed in the ICU of a large German university hospital as a supplementary monitoring device. Following a hybrid qualitative approach with inductive and deductive elements, we used the Consolidated Framework for Implementation Research and the Expert Recommendations for Implementing Change to analyze the transcripts of 7 semistructured interviews with clinical ICU stakeholders and descriptive questionnaire data. The results of the qualitative analysis, together with the findings from informal meetings, field observations, and previous explorations, provided the basis for the derivation of the proposed framework. ResultsThis study revealed an insufficient implementation process due to lack of staff engagement and few perceived benefits from the novel solution. Further implementation barriers were the high staff presence and monitoring coverage in the ICU. The implementation framework includes strategies to be applied before and during implementation, targeting the implementation setting by involving all ICU stakeholders, assessing the intervention’s adaptability, facilitating the implementation process, and maintaining a vital feedback culture. Setting up a unit responsible for implementation, considering the guidance of an implementation advisor, and building on existing institutional capacities could improve the institutional context of implementation projects in the ICU. ConclusionsImplementation of digital health in the ICU should involve a thorough preimplementation assessment of the ICU’s need for innovation and its readiness to change, as well as an ongoing evaluation of the implementation conditions. Involvement of all stakeholders, transparent communication, and continuous feedback in an equal atmosphere are essential, but leadership roles must be clearly defined and competently filled. Our proposed framework may guide health care providers with concrete, evidence-based, and step-by-step recommendations for implementation practice, facilitating the introduction of digital health in intensive care. Trial RegistrationClinicalTrials.gov NCT03514173; https://clinicaltrials.gov/ct2/show/NCT03514173

Abstract We read with great interest the recent review, entitled “Current status and recent advances in resection cavity irradiation of brain metastases”. It is a comprehensive summary of currently available techniques for treatment of post-resection cavity in patients with this diagnosis. We would like to complement this manuscript by including intraoperative techniques as other viable approaches in the management of these patients.

Background: As today’s organizations are becoming increasingly globalized and adding the impetus to a more remote form of working due to the present COVID-19 pandemic, new ways of collaboration—like virtual teams—have gained importance. In the present study, we aim to investigate how virtual team outcomes are linked to perceived diversity and subgroup formation and attempt to gain some initial insight into the role of the social identity approach to leadership in virtual teams.Method: In the present cross-sectional study, a total of 102 virtual team members participated in an online survey measuring perceived diversity, identity leadership, subgroup formation, perceived performance, and team satisfaction, to examine the factors moderating the relationship between perceived diversity and subgroup formation as well as between perceived diversity and team performance and satisfaction.Results: Moderation analysis revealed that perceived diversity had a negative influence on performance ratings when subgroups were highly perceived to be present, but not if subgroup formation was rated as low. The relationship between perceived diversity and team satisfaction was not moderated by perceived subgroup formation. Furthermore, identity leadership was found to be positively related to team satisfaction and perceived performance, while subjective diversity was negatively associated with both team outcomes. Identity leadership moderated the relationship between perceived diversity and subgroup formation, in that high levels of identity leadership weakened the positive relationship.Conclusion: This study provides first evidence to the importance of the team leader’s role as a manager of a shared social identity in virtual teams where perceived differences can lead to subgroup splits, as identity leaders may hinder the emergence of subgroups in virtual teams.

Background The optimal timing of invasive examination and treatment of high‐risk patients with non–ST‐segment–elevation acute coronary syndrome has not been established. We investigated the efficacy of early invasive coronary angiography compared with standard‐care invasive coronary angiography on the risk of all‐cause mortality according to the GRACE (Global Registry of Acute Coronary Events) risk score in a predefined subgroup analysis of the VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) trial. Methods and Results Patients with clinical suspicion of non–ST‐segment–elevation acute coronary syndrome with ECG changes indicating new ischemia and/or elevated troponin, in whom invasive coronary angiography was clinically indicated and deemed logistically feasible within 12 hours, were eligible for inclusion. Patients were randomized 1:1 to an early (≤12 hours) or standard (48–72 hours) invasive strategy. The primary outcome of the present study was all‐cause mortality. Of 2147 patients randomized in the VERDICT trial, 2092 patients had an available GRACE risk score. Of these, 1021 (48.8%) patients had a GRACE score >140. During a median follow‐up of 4.1 years, 192 (18.8%) and 54 (5.0%) patients died in the high and low GRACE score groups, respectively. The risk of death with the early invasive strategy was increased in patients with a GRACE score ≤140 (hazard ratio [HR], 2.04 [95% CI, 1.16–3.59]), whereas there was a trend toward a decreased risk of death with the early invasive strategy in patients with a GRACE score >140 (HR, 0.83 [95% CI, 0.63–1.10]) (Pinteraction=0.006). Conclusions In patients with non–ST‐segment–elevation acute coronary syndrome, we found a significant interaction between timing of invasive coronary angiography and GRACE score on the risk of death. Randomized clinical trials are warranted to establish the efficacy and safety among high‐risk and low‐risk patients with non–ST‐segment–elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02061891.

Abstract Objective Studies of postoperative cognitive dysfunction (POCD) rely on repeat neuropsychological testing. The stability of the applied instruments, which are affected by natural variability in performance and measurement imprecision, is often unclear. We determined the stability of a neuropsychological test battery using a sample of older adults from the general population. Forty-five participants aged 65 to 89 years performed six computerized and non-computerized neuropsychological tests at baseline and again at 7 day and 3 months follow-up sessions. Mean scores on each test were compared across time points using repeated measures analyses of variance (ANOVA) with pairwise comparison. Two-way mixed effects, absolute agreement analyses of variance intra-class correlation coefficients (ICC) determined test–retest reliability. Results All tests had moderate to excellent test–retest reliability during 7-day (ICC range 0.63 to 0.94; all p

Abstract Bacterial cells have long been thought to be simple cells with little spatial organization, but recent research has shown that they exhibit a remarkable degree of subcellular differentiation. Indeed, bacteria even have organelles such as magnetosomes for sensing magnetic fields or gas vesicles controlling cell buoyancy. A functionally diverse group of bacterial organelles are the bacterial microcompartments (BMCs) that fulfill specialized metabolic needs. Modification and reengineering of these BMCs enable innovative approaches for metabolic engineering and nanomedicine.

The actin-remodelling protein L-plastin promotes tumour migration and invasion. Here, the authors show that L-plastin is regulated spatially by ROS-induced thiol oxidation which inhibits its actin-bundling function and cell spreading and filopodial extension formation in tumor cells.

Summary: Aiming at clinical translation, robust directed differentiation of human pluripotent stem cells (hPSCs), preferentially in chemically defined conditions, is a key requirement. Here, feasibility of suspension culture based hPSC-cardiomyocyte (hPSC-CM) production in low-cost, xeno-free media compatible with good manufacturing practice standards is shown. Applying stirred tank bioreactor systems at increasing dimensions, our advanced protocol enables routine production of about 1 million hPSC-CMs/mL, yielding ∼1.3 × 108 CM in 150 mL and ∼4.0 × 108 CMs in 350–500 mL process scale at >90% lineage purity. Process robustness and efficiency is ensured by uninterrupted chemical WNT pathway control at early stages of differentiation and results in the formation of almost exclusively ventricular-like CMs. Modulated WNT pathway regulation also revealed the previously unappreciated role of ROR1/CD13 as superior surrogate markers for predicting cardiac differentiation efficiency as soon as 72 h of differentiation. This monitoring strategy facilitates process upscaling and controlled mass production of hPSC derivatives. : Directed differentiation of human pluripotent stem cell cardiomyocytes (CMs) is required for clinical translation. Here, xeno-free suspension culture production in stirred bioreactors is shown to enable routine generation of ∼1.3 × 108 CMs/150 mL and ∼4.0 × 108 CMs/500 mL scale at >90% purity. Uninterrupted chemical WNT pathway control and the previously unappreciated role of ROR1/CD13 as predictive differentiation markers facilitate large-scale production of ventricular-like CMs. Keywords: human pluripotent stem cells, chemically defined process, cardiac differentiation, cardiomyocyte, suspension culture, stirred tank bioreactor, ROR1, WNT, process development, upscaling