Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

A comprehensive investigation was undertaken at Vytautas Magnus University Experimental Station, located at 54°52’50” N latitude and 23°49’41” E longitude on soil (Epieutric Endocalcaric Planosol – PLe-gln-w) since 1999, to understand the impacts of different agrotechnical measures on soil health and crop yield. Two primary factors were assessed. Factor A incorporated practices of straw removal versus straw chopping and spreading, while Factor B evaluated a spectrum of tillage techniques: conventional deep ploughing, shallow ploughing, ploughless tillage, single seedbed discing, and two no-tillage practices, one of which involved cover crops. Findings from this long-term study highlight the significant potential of specific farming systems in enhancing soil organic carbon. It has a positive effect on the release of CO2 emissions from the soil, thus promoting soil resilience and increasing plant productivity. These insights are paramount in devising sustainable agricultural strategies to counter the challenges of climate change on agroecosystems. This research showcases the profound effects of combining residue management and tillage practices, setting a novel standard for sustainable soil management of climatic uncertainties.

:Peat substrate is made from peat from drained peatlands, which is a limited resource. A realistic estimate is that 50% of the world’s wetlands have been lost. Peat is used in horticulture, especially for the cultivation of vegetables in greenhouses. The consequences of peatland exploitation are an in-crease in the greenhouse effect and a decrease in carbon stocks. Wood fiber can be used as an al-ternative to peat. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the growing container. This study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) variety “Dirigent H” developed in the Netherlands, were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) con-ventional fertilization (CF); (2) N13; (3) N23; (4) N30. The experiment was carried out in three repli-cations. As the amount of wood fiber increased, the humidity and pH of the growing medium in-creased. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in 50/50 and 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat sub-strate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

Soil tillage intensity influences the distribution of nutrients, and soil’s physical and me-chanical properties, as well as gas flows. The impact of reduced tillage on these indices in spring barley cultivation is still insufficient and requires more analysis on a global scale. This study was carried out at Vytautas Magnus University, Agriculture Academy (Lithu-ania) in 2022–2023. The aim of the investigation was to determine the effect of the tillage systems on the soil temperature, moisture content, CO2 respiration and concentration in spring barley cultivation limited by the semi-humid subarctic climate. Based on a long-term tillage experiment, five tillage systems were tested: deep and shallow mold-board ploughing, deep cultivation-chiselling, shallow cultivation-chiselling, and no-tillage. Shallow ploughing technology was found to be better at conserving soil moisture and maintaining a higher temperature. Deep cultivation had a lower moisture content and lower soil temperature. Shallow cultivation fields in most cases increased CO2 emissions and CO2 concentration. The results show that in direct sowing fields, most cases had a positive effect on crop density. Direct sowing fields resulted in significantly lower grain yields of spring barley in the years studied.

To date, the patent foramen ovale (PFO) does not get the deserved medical attention. The PFO poses a serious threat to health and even life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to do harm. Yet at the same time by the sheer number, it discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting at the same time mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for prevention of paradoxical embolism not infrequently betters or cures migraine or exercise dyspnea, thereby improving quality of life as a collateral benefit.

Dry periods and drought are inherent natural occurrences. However, due to the increasing pressures of global warming and climate change, these events become more frequent and severe on a global scale. These phenomena can be traced with various indicators and related indices proposed by various scholars. In general, drought risk assessment is done by modelling these indicators and determining the drought occurrence probabilities. The proposed adaptation introduces the "Kaplan-Meier Estimator," a non-parametric statistic traditionally used in medical contexts to estimate survival functions from lifetime data. The study aims to repurpose this methodology to assess drought risk by treating past droughts as "events" and evaluating the Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) and map these results for a better understanding of the drought risks within larger spatial scales such as a river basin. The adapted method provides the probability of non-occurrence, with inverted results indicating the likelihood of drought occurrence. As a case study, the method is applied to SPI and SPEI values at different time steps (3, 6, and 12 months) across 27 meteorological stations in the Gediz River Basin, located in Western Turkey—a region anticipated to be profoundly affected by global climate change. The results are represented as the generated drought risk maps and curves, which indicate that (i) drought risks increase as the considered period extends, (ii) drought risks decrease as the utilized indicator timescales increase, (iii) locally plotted drought curves indicate higher drought risks as their initial slope get steeper. The method used enables the generation of historical evidence based spatially distributed drought risk maps which expose more vulnerable areas within the river basin.

In the second half of the 19th century a wave of modernisation, industrialisation and urbanisation swept the Nordic countries, catapulting what had until then been lagging and primarily rural countries into modernity. These major upheavals, however, also plunged the Nordic countries into a profound social and cultural crisis resulting from their consciousness of their own backwardness vis-a-vis the countries on the European continent, as well as the recognition that a nostalgic nationalism recalling a mythical past had become obsolete in the industrial age. In response to this crisis, a life reform movement emerged that was based on Arts and Crafts movements as well as various artistic and literary reform movements and—equally absorbing rural traditions and progressive social ideas—tried to establish a new national everyday culture. In this article, the two key terms coined by Ellen Key, “Festive Customs” (‘festvanor’) and “Everyday Beauty” (‘vardagsskönhet’)—the programmatic core of the Nordic life reform movement—are analysed and illustrated in various typical manifestations. It also examines to what extent the Nordic life reform movement with these two key concepts as its core agenda found expression in arts and crafts, in painting as well as in the architecture of the late nineteenth and early twentieth century and contributed to the progress of social and cultural renewal.

Plant biomass could become a new world-class "currency" because almost everything can be made of it: fuels, foods, feeds, constructing materials, furniture, etc. Currently, growing biomass for energy needs is particularly relevant in so complicated socioeconomical situation. There are important its productivity and the lowest possible ecological footprint. Can increasing crop biodiversity address these challenges? A field experiment was started at the Vytautas Magnus University Agricultural Academy in 2020-2022. Maize, hemp and faba bean were grown as single, binary and ternary crops to determine its effect on soil properties. Studies have shown that most intercrops failed to stabilize soil aggregate composition, NPK levels and pH, and enzyme urease activity. Binary maize-hemp and the ternary crops reduced the amount of the main macroelements in the soil the most because of the highest yields, which were removed from the fields. Regardless of the ecological services provided by faba beans, biomass removal leads to degradation of most soil properties and making the soil vulnerable to erosion. In the future, the cultivation of such multicrops should be investigated under conditions of more abundant fertilization or the effect of green manure should be used by increasing the number of fast- and short-growing interior plant species in the cultivation.

Multicropping can solve the energy and GHG balance problems, but the emergence, development and productivity of such mixed crops are at risk due to uneven distribution of precipitation. For this reason, investigations were performed at the Experimental Station of Vytautas Magnus University, Lithuania. Single maize crop was compared with Crimson/red clover, Persian clover, and alfalfa intercropped maize cultivations. Results showed that under arid conditions, the intercrops biomass was about 4 times less than under humid. Humid conditions were less suitable for maize and when growing with intercrops they produced about 3-5 t ha-1 less dried biomass, and when growing sole - about 6 t ha-1 less biomass than in arid conditions. Due to the higher yield of maize biomass in arid season, better energy indicators of the crop were obtained in arid conditions than in humid. The difference between net energy was about 122-123 MJ ha-1 in all treatments, except for the maize crop with intercropped alfalfa, where the difference was 62 MJ ha-1. All tested technologies were environmentally friendly, CO2 equivalent varied between treatments from 804 to 884 kg ha-1. Uneven distribution of precipitation during vegetative season makes us think about the improvement of intercropping technologies. Sowing intercrops at the same time with maize could improve its germination but increase the problem of weed spread.

In the second half of the 19th century new methods for quarrying and processing natural stone are developed. In the Nordic countries Sweden, Norway and Finland this technological pro­gress goes hand in hand with a systematic geological mapping and large-scale exploitation of natural stone deposits. As a result, new constructions are developed—changing the building practice in these countries. With the end of historicism a new architecture arises that particularly in Norway and Finland acquires a national-romantic character. This paper examines the interaction between geological exploration, commercial development, technical inventions and the development of a national-romantic architecture.

With the breakthrough of modernism, various efforts are undertaken to rationalize architecture and building processes using industrial principles. Few architects explore these as intensively as Walter Gropius, the founder of the Bauhaus. Even before World War One, and increasingly in the interwar years, Gropius and a number of colleagues undertake various experiments which manifest in a series of projects, essays, model houses and Siedlungen. These aim at conceptually different goals, i.e. they follow two different categories of industrial logic: first, a flexible construction kit and, second, an assembly line serial production. This article traces the genesis of these two concepts and analyses their characteristics using these early manifestations. Compared to existing literature, this article takes into account hitherto neglected primary sources as well as technological and construction history aspects—allowing for a distinction based not only on theoretical, but also technological and structural characteristics. This article shows that Gropius succeeds in formulating and exploring the two principles in theory and practice as well as drawing conclusions by the end of the 1920s. With them, he contributed significantly to the rationalization of architecture, and his principles have been picked up and developed further by numerous architects since then.

Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are safe and effective in pregnancy. There are no Mexican surveys in physicians on knowledge, beliefs, and practices towards influenza and influenza immunization during pregnancy. A 32 questions cross-sectional and descriptive survey was conducted addressing general knowledge of influenza, as well as beliefs and practices regarding influenza vaccination during pregnancy among Mexican physicians responsible for prenatal care, traditionally Obstetricians (OBGYNs), and Family Physicians (FPs). A total of 206 surveys were available, 98 (47.6%) from OBGYNs, and 108 (52.4%) from FPs representing an estimated 2,472 daily pregnancy consultations. 54 from 206 (26.2%) weren´t aware that influenza is more severe during pregnancy, 106 from 206 (51.5%) ignored the potential side effects of influenza infection on the fetus, and 56.8% did not know when to vaccinate pregnant women. Pregnancy as a risk factor for developing influenza complications was known only by 99 from 206(48.1%), and 6.1 % believed that vaccination does not confer protection to the fetus. Current beliefs of Mexican OBGYNs and FPs for both influenza morbidity and mortality, and the importance of influenza vaccination during pregnancy, is suboptimal. Understanding drivers for beliefs should be assessed to improve influenza vaccination recommendations, as knowledge alone is not sufficient.

Multi-cropping can solve the energy and GHG balance problems, but the emergence, development and productivity of such mixed crops are at risk due to increasing drought periods. For this reason, single maize crops with inter-row mellowing and weed-mulching practices were compared with faba bean, crimson and Persian clover, and alfalfa intercropped maize cultivations. Tests were performed at the Experimental Station of Vytautas Magnus University, Lithuania. Results showed that by the 30% higher energy inputs were calculated in technologies with intercropped crimson, Persian clover, and alfalfa than in monocropped maize. Single maize crops produced by the 23-40% higher biomass yields compare to clover and alfalfa intercropped maize because, due to the drought periods, intercrops weakly sprouted and developed. Lower harvests reduced the energy output by up to 38%, energy efficiency ratio - by up to 2.5 times and net energy - by up to 42%. All tested technologies were environmentally friendly and similar according to the CO2 equivalent. Long-term drought periods during vegetative season due to climate change make us think about the improvement of intercropping technologies. Sowing intercrops at the same time with maize could solve the problem of its germination but highlight the problem of abundant weed spread. Therefore, this takes us to another sphere of agrotechnologies - the effective non-chemical weed control.

In the early decades of the 19th century, the deaf population in the eastern US and Canada was distributed across a vast area. After the 1817 founding of the American School for the Deaf (ASD) in Hartford, CT and the subsequent establishment of schools for the deaf in New York City (NYSD), Philadelphia, and many other US states, hundreds of deaf students called these schools home for several years. After leaving school, the early American Deaf community faced a challenge: How would the community maintain its social and linguistic ties across a vast geographical area once community members had dispersed to their hometowns? In this paper we analyze the attendance registries of two large gatherings of deaf individuals in Hartford in the years 1850 and 1854. These were among the largest and earliest known gatherings of deaf adults. The demographic data included in these registries open a window onto the evolving American Deaf community of the mid-19th century. Our analyses of the attendees’ school affiliations, ages, and marital status show that the signing community that had taken root among students at schools in Hartford and New York persisted among the adult graduates of those schools in towns across the northeastern US. We compare the places of residence of ASD and NYSD alumni in 1850 and 1854 to their hometowns when they first enrolled at school. Our comparisons suggest the mid-19th-century signing community had become more urban; it was centered to a greater extent in populous cities such as New York, Boston, and Hartford than had been true when the attendees had enrolled in school. We consider how the geography of deafness in the 19th century might inform our understanding of the sources of regional variation in ASL. We also consider how early cross-regional interactions may have inhibited such regional variation.

Architecture is more than just buildings. Its associated production and reception pro­cesses take place through a variety of different media. Among those media, the model is of special significance: because architecture, like almost every science or art, works with models as representa­tionally or theoretically simplified images mediating between the abstract and the reality. The properties that characterise models give them a special significance in archi­tecture—both in the abstract, as well as in the concrete. The following article sketches out the history of the architectural model as a medium in a short tour d’horizon. A special focus is placed on showing the versatility of the model—for design and presentation and as an artefact, teaching resource and research medium. It transmits a specific form of knowledge which can be replaced by no other medium.

There were warnings before; nevertheless the current CoVID-19 pandemic took the world by surprise: within just four month, it conquered the globe and claimed over 200'000 lives. Unprecedented governmental actions put about half of the population under curfew or lock-down. The resulting economic meltdown is expected to eliminate globally 9’000’000’000’000 (9 trillion) USD in 2020 and 2021 alone, a value roughly the size of the yearly GDP of the world’s 150 smallest economies. The resulting crises might cause mass-unemployment and a hunger pandemic later this year. This Essay analyses current statistical data of the CoVID-19 pandemic to develop a guideline for a path through the crisis, minimizing both loss of lives and economic costs. Part 1 details the current situation; part 2 develops a small set of measures, allowing a near normal life until a future vaccination campaign has reached sufficient numbers of people; and part 3 provides some important lessons for the future beyond SARS-CoV-2. The Essay leads to the following key-messages: 1) The CoVID-19 pandemic will stay for at least two more years. This is the minimum time required for a vaccination campaign to reach sufficient numbers of people. 2) The crucial element to control the pandemic is keeping case numbers under the threshold required for a functional tracing, testing & isolation (TTI) strategy. That threshold differs from country to country and strongly depends on culture and the applied tracing technology as well as available testing capacities. 3) The economic burden of a TTI strategy is moderate while fatalities are also reduced. Hence, such an approach is strongly recommended. Its implementation requires a set of simple and cost-effective measures (see figure below), which in combination seem to be sufficient to keep CoVID-2’s reproductive rate at or below 1. 4) Implementing international coordination of actions will be necessary for effective infection-chain tracing5) If case numbers are above the TTI threshold, shutdown measures remain the only option until tracing of infection chains becomes feasible again.6) In the future, neglected pandemic-related research requires a funding boost. Just 1% of the bill of the current crisis could support the research of 45’000 scientist for 20 years.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

Abstract: Field studies with large-stemmed plants Artemisia dubia (wormwood) have been carried out at Vėžaičiai Branch LAMMC since 2018. According to three years of experimental results, annual dry matter (DM) yield varied from 7.94 to 10.14 t ha-1. Growing conditions, nitrogen ap-plication level and harvesting time had significant impacts on Artemisia dubia productivity. This article presents the results of research on preparation and use of Artemisia dubia biomass for en-ergy conversion and evaluation of technological-technical and environmental parameters of these plants utilization for solid biofuel. For experiments were used 6 variants of Artemisia dubia samples, which were grown in 2021: plants were cut three times and two fertilization options were used: (1) no fertilization and (2) fertilization with 180 kg ha-1 of nitrogen fertilizer. These harvested plants were chopped, milled and were pressed into the pellets. The physi-cal-mechanical characteristics (mоisture content, density and strength) of Artemisia dubia pellets were investigated. During this study, it was found that the density in dry mass (DM) of pellets ranged from 1119.86 to 1192.44 kg m-3. The pellet moisture content ranged from 8.80 to 10.49%. After testing of pellet strength, it was found that the pellets which were made from plant bio-mass PK-1-1, were the most resistant to compression, they withstood 560.36 N of pressure. Dry fuel lower heating value (LHV) of pellets was sufficiently high and was very close to pine saw-dust pellets, it varied from 17.46±0.25 MJ kg-1 to 18.14±0.28 MJ kg-1. The ash content of burned pellets ranged from 3.62±0.02% to 6.47±0.09%. Emissions of harmful pollutants – CO2, CO, NOx and unburnt hydrocarbons (CxHy) did not exceed the maximum permissible levels. Summariz-ing the results of investigated properties, cоmbustion and emissiоns of Artemisia dubia pellets, it can be concluded that this biofuel can be used for production of pressed biofuel and it is charac-terized by sufficient high quality, efficient combustion and permissible emissions to the envi-ronment.

The design of curved surface sliders (CSS) based on the elastic response spectrum is done by iteration to find the combination of friction coefficient and displacement capacity which satisfies the condition that the maximum horizontal CSS force is equal to the horizontal force of the structure. Although this CSS design is valid it does not necessarily minimize structural acceleration. This paper therefore describes the optimum CSS design for minimum structural acceleration. All valid CSS designs and the optimum CSS design are represented by their associated trajectory in the elastic response spectrum plane which visualizes the optimization problem. The results demonstrate that the optimum CSS design is not obtained at maximum tolerated effective damping ratio. The subsequent sensitivity analysis describes how much the structural acceleration increases if the actual friction coefficient of the real CSS deviates from its optimum design value. The analysis points out that the increase in structural acceleration is approximately one order of magnitude smaller than the deviation in friction. The sensitivity data may be used by structural engineer to determine tolerable deviations in friction coefficient which still results in acceptable structural accelerations.

Multi-cropping is becoming an increasingly popular approach in agriculture to tackle major and complex agroecosystem problems such as biodiversity and soil fertility losses, erosion and degradation, increased greenhouse gas emissions, etc. Comprehensive assessment of the impact of multi-cropping intensity on the agroecosystem is a new and still under-researched approach that provides a better understanding of the impact of the individual indicators studied on the overall functioning of the biodiversed agroecosystems. Data from a stationary field experiment with multi-cropping at the Vytautas Magnus University, Experimental Station between 2020 and 2022 were used to achieve this objective. The study included maize, hemp and faba bean as single, binary, and ternary crops. A complex assessment approach (CEI value) was used to determine the impact of these diversified crops on the agroecosystem, the interrelationships between the main indicators and the strength of their effects. It was found that the most positive effect on agroecosystem had ternary maize-hemp-faba bean crop. The effectiveness of other crops was from 2 to 35% less. The lowest one was calculated for the maize-faba bean crop.

Lactococcus lactis is a potential bacterial cell factory to develop delivery systems for vaccines and therapeutic proteins. Large progress has been made in applications using engineered L. lactis against, e.g., inflammatory bowel disease and cervical cancer, but improvement of secretion and cell anchoring efficacy is still desirable. A double-labelling method based on biarsenical hairpin binding and nickel-polyhistidine affinity was used for visualization of protein trafficking and quantification of targeted proteins on the cell surface and in the cytoplasm. To investigate the importance of mature domain targeting signals (MTSs), we generated truncated constructs encoding 126, 66, and 26 amino acid residues from the N-terminus of the basic membrane protein A (BmpA) and fused those with the gene for the human papillomavirus serotype 16 (HPV16) E7 oncoprotein. Overexpression of fusion proteins was observed to come at a cost of cell proliferation. L. lactis cells produced and displayed the shortest fusion protein only with difficulty, suggesting that the entire absence of a homologous sequence containing MTSs significantly impedes export and surface anchoring of fusion proteins. With 40 amino acids following the signal peptide and containing one MTS, effective translocation was possible. Mutations of MTSs towards increased hydrophobicity resulted in an increase of secreted and surface-displayed fusion protein, suggesting the potential to design rationally improved constructs.

In the evolving landscape of pharmaceutical manufacturing, a comprehensive continuous production process is being crafted for small-scale active pharmaceutical ingredient production. This study focuses on continuous crystallization with separate nucleation and crystal growth units, as well as continuous downstream processing, encompassing filtration, washing, and drying until the formation of free-flowing particles. We introduce a novel continuous nucleator designed based on solubility data and produced via 3D printing, enabling a fast and precise small-scale manufacturing of a nucleator meeting the requirements for nucleation and for the further growth processes. The nucleator was evaluated with regard to its suitability for continuous long-term operation across various coupled crystallizers. As a practical application example it is connected to a slug flow crystallizer to enable high-quality continuous crystallization. Additionally, the full integration of downstream processes using the continuous vacuum screw filter to achieve free-flowing product particles is realized. Even under non-optimized process conditions, with the help of in-situ generation of nuclei free-flowing product particles were successfully obtained. This is particularly useful during drug development when no material is available for seed addition and quickly obtain product for further characterization.

Many academics are critical of the current publishing system, but it is difficult to create a better alternative. This review relates to the Sciences and Social Sciences, and discusses the primary purpose of academic journals as providing a seal of approval for perceived quality, impact, significance, and importance. The key issues considered include the role of anonymous refereeing, continuous rather than discrete frequency of publications, avoidance of time wasting, and seeking adventure. Here we give recommendations about the organization of journal articles, the roles of associate editors and referees, measuring the time frame for refereeing submitted articles in days and weeks rather than months and years, encouraging open access internet publishing, emphasizing the continuity of publishing online, academic publishing as a continuous dynamic process, and how to improve research after publication. Citations and functions thereof, such as the journal impact factor and h-index, are the benchmark for evaluating the importance and impact of academic journals and published articles. Even in the very top journals, a high proportion of published articles are never cited, not even by the authors themselves. Top journal publications do not guarantee that published articles will make significant contributions, or that they will ever be highly cited. The COVID-19 world should encourage academics worldwide not only to rethink academic teaching, but also to re-evaluate key issues associated with academic journal publishing in the future.

Transparent electrodes (TEs) made of metallic nanowires, such as Ag, Au, Cu, and Ni, have attracted rising attention for several reasons: 1) they can act as a substitute for tin oxide-based TEs such as indium-tin oxide (ITO) and fluorine-doped tin oxide (FTO); 2) various methods exist for fabricating such TEs such as filtration, spraying and meyer bar coating; 3) greater compatibility with different substrates can be achieved due to the variety of fabrication methods; and 4) extra functions in addition to serving as electrodes, such as catalytic abilities, can be obtained due to the metals that compose the TEs. There are a large number of applications for TEs, ranging from electronics and sensors to biomedical devices. This short review is a summary of recent progress, mainly during the past five years, on silver nanowire-based TEs. The focus of the review will be on theory development, mechanical, chemical and thermal stability and optical properties. The many applications of TEs are outside the scope of this review.

With increased participation in telework expected to continue, to support emerging hybrid work models in the aftermath of the Covid-19, it is important to consider the long-term impact this practice could have on sustainability outcomes. This paper describes a systematic review of 113 academic journal articles and identifies associations between telework and sustainability, explored by previous researchers. Those associations were categorized and discussed, based on their contributions to different United Nations Social Development Goals. Most of research was found to focus on countries classified as having a very high human development index status, and regions with a low, medium or high human development index, largely ignored. The SWOT matrix technique was used to illustrate the strengths and weaknesses identified in the current literature as well as threats and opportunities for future work. This can help to ensure policy coherence and that strategies to promote one outcome, such as economic productivity improvements, does not undermine another, such as improved health. Practical implications and potential research opportunities were identified across a range of SDG impact areas, including good health and well-being, gender equality, reduced inequality, climate mitigation, sustainable cities and resilient communities. On the whole, our impression is that increased rates of telework present an important opportunity to improve sustainability outcomes, however, it will be important that integrated and holistic policy is developed that mitigates key risks.

Measurement-Device-Independent Quantum Key Distribution (MDI-QKD) is a two-photon protocol devised to eliminate eavesdropping attacks that interrogate or control the detector in realized quantum key distribution systems. In MDI-QKD, the measurements are carried out by an untrusted third party, and the measurement results are announced openly. Knowledge or control of the measurement results gives the third party no information about the secret key. Error-free implementation of the MDI-QKD protocol requires the crypto-communicating parties, Alice and Bob, to independently prepare and transmit single photons that are physically indistinguishable, with the possible exception of their polarization states. In this paper, we apply the formalism of quantum optics and Monte Carlo simulations to quantify the impact of small errors in wavelength, bandwidth, polarization and timing between Alice's photons and Bob's photons on the MDI-QKD quantum bit error rate (QBER). Using published single-photon source characteristics from two-photon interference experiments as a test case, our simulations predict that the finite tolerances of these sources contribute (4.04+/-20/N_sifted) to the QBER in an MDI-QKD implementation generating an N_sifted-bit sifted key.

We propose a model for medium-term hydropower scheduling (MTHS) with variable head and uncertainty in inflow, reserve capacity, and energy price. With an increase of intermittent energy sources in the generation mix, it is expected that a flexible hydropower producer can obtain added profits by participating in other markets than just the energy market. To capture this added potential the hydropower system should be modeled with a higher level of details. In this context, we apply an algorithm based on stochastic dual dynamic programming (SDDP) to solve the nonconvex MTHS problem, and show that the use of Strengthened Benders (SB) cuts to represent the expected future profit (EFP) function provide accurate scheduling results for slightly nonconvex problems. A method to visualize the EFP function in a dynamic programming setting is provided, serving as a useful tool for a priori inspection of the EFP shape and its nonconvexity.

Stable half-sandwich iron(II) dihalido complexes of the type [Fe(5-Cp’)X2] are extremely scarce, being limited to congeners containing the bulky C5H2-1,2,4-tBu3 ligand. We have extended this to homologues [Fe(5-Cp*)X2] (X = Cl – I) containing the particularly popular C5Me5 (Cp*) ligand. Corresponding ionic compounds ER4[Fe(5-Cp*)X2] are easily accessible from FeX2, MCp* (M = Li, K) and a suitable halide source R4EX (E = N, P) in THF. The new compounds NnPr4[Fe(5-Cp*)X2] (X = Cl, Br), NnPr4[Fe(5-Cp*)BrCl] and PPh4[Fe(5-Cp*)X2] (X = Cl, Br, I) have been structurally characterised by single-crystal X-ray diffraction. NnPr4[Fe(5-Cp*)Cl2] reacts readily with CO to afford [Fe(5-Cp*)Cl(CO)2], indicating the synthetic potential of ER4[Fe(5-Cp*)X2] in FeCp* half-sandwich chemistry.

A modification to the conventional spark plasma sintering (SPS) process was undertaken to allow edge-free deformation of grains longitudinally to the loading axis in a process termed spark plasma texturing (SPT). The resulting Al7075 SPT compact was compared to SPSed Al7075 in terms of densification behaviour, microstructural evolution, and mechanical properties. The result reported herein highlights the unique benefits of the SPT technique and potential application in the manufacturing of advanced materials.

This paper presents a comparison of two methods to represent variable blade inertia in two codes for aero-servo-elastic simulations of wind turbines: the nonlinear aeroelastic multi-body model HAWC2 and the nonlinear geometrically exact beam model BeamDyn for OpenFAST. The main goal is to enable these tools to simulate the dynamic behavior of a wind turbine with variable blade inertia. However, in order to simulate the structural response of wind turbines with variable blade inertias, the source code of load simulation tools need to be modified. This is due to the fact that, currently, state-of-the-art load simulation tools for wind turbines are unable to simulate variable rotor blade inertias. The validity of the modified codes is proven based on a simple beam model. The validation shows very good agreement between the modified codes of HAWC2, BeamDyn and an analytical calculation. The add-on of variable blade inertias is applied to reduce the mechanical loads of a 5 megawatt reference wind turbine with an integrated hydraulic-pneumatic flywheel in its rotor blades.

Plasmodium vivax causes the second highest number of malaria morbidity and mortality cases in humans. Several biological traits of this parasite species, including the formation of dormant stages (hypnozoites) that persist inside the liver for prolonged periods of time, present an obstacle for intervention measures and create a barrier for the elimination of malaria. Research into the biology of hypnozoites requires efficient systems for parasite transmission, liver stage cultivation and genetic modification. However, P. vivax research is hampered by the lack of an in vitro blood stage culture system, rendering it reliant on in vivo derived, mainly patient material, for transmission and liver stage culture. This has also resulted in a limited capability for genetic modification, creating a bottleneck in investigations into the mechanisms underlying the persistence of the parasite inside the liver. This bottleneck can be overcome through optimal use of the closely related and experimentally more amenable nonhuman primate (NHP) parasite Plasmodium cynomolgi as model system. In this review we discuss the genetic modification tools and liver stage cultivation platforms available for studying P. vivax persistent stages and highlight how their combined use may advance our understanding of hypnozoite biology.

Bistable rhodopsins have two stable forms which can be interconverted by light. Due to their ability to act as photoswitches, these proteins are considered as ideal candidates for applica-tions such as optogenetics. In this work we analyze a recently crystalized bistable rhodopsin, namely the jumping spider rhodopsin-1 (JSR1). This rhodopsin exhibits identical absorption maxima for the parent and the photoproduct form, which impedes its broad application. We have performed hybrid QM/MM simulations to study three isomers of the retinal chromo-phore: the 9-cis, 11-cis and all-trans configurations. The main aim was to gain insight into the specific interactions of each isomer and their impact on the absorption maximum in JSR1. The absorption spectra were computed using sampled snapshots from a QM/MM molecular dy-namics trajectory and compared to experimental counterparts. The chromophore-protein in-teractions were analyzed by visualizing the electrostatic potential of the protein and projecting it onto chromophore. It was found that the distance between a nearby tyrosine (Y126) residue plays a larger role in the predicted absorption maximum than the primary counterion (E194). Geometric differences between the isomers were also noted including a structural change in the polyene chain of the chromophore as well as changes in the nearby hydrogen bond network.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay demonstrated that variant c.449+5G>A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

Cesiumtrifluoroacetate (CsTFA) is a key chemical for RNA-based stable isotope analyses to link the structure and function of microbial communities. We report a protocol to easily synthesize CsTFA from Cesiumcarbonate (Cs₂CO₃₎ and Trifluoroacetate (TFA) and show that self-synthesized CsTFA behaves similar to commercial CsTFA in the separation of isotopically labelled and unlabelled E. coli RNA.

The question of building sustainable in a geographical locality is inexorably linked to cost. In 2011, one of the authors built a sustainable house that was (at the time) the highest certified sustainable home based on the National Association of Home Builder’s standards for sustainable construction. This Texas house has been used for residential and research purposes for the past decade. In this case study, the authors evaluate components of the construction and their effectiveness as well as unseen secondary and tertiary effects. Some of the specific components discussed are home site placement; rainwater harvesting (100% of residential requirements); aerobic septic system; grid-tied solar array power; electric car charging; geothermal heating and cooling; reclaimed wood framing; spray foam installation; selection of windows, fixtures, and appliances; on-demand electric water heaters for guest areas; generator backups; and use of local items. Electric bills and water system improvements are discussed in detail, as improvements were made as part of residential and research requirements. This case study suggests that the financial outlay is worth the extra up-front costs if residents in this geographical area and climate will occupy the residence 7 years.

Background: As the opioid epidemic continues, understanding the geospatial, temporal and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement. Based on GIS analysis, the opioid epidemic is likely to spread or diffuse through the country, and interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: prevention, treatment, and enforcement.

A number of experimental and numerical studies point out that incorporating a rotating cylinder can superiorly enhance the aerofoil performance, especially for higher velocity ratios. Yet, there have been less or no studies exploring the effects of lower velocity ratio at a higher Reynolds number. In the present study, we investigated the effects of Moving Surface Boundary-layer Control (MSBC) at lower velocity ratios (i.e. cylinder tangential velocity to free stream velocity) and higher Reynolds number on a symmetric aerofoil (e.g. NACA 0021) and an asymmetric aerofoil (e.g. NACA 23018). In particular, the aerodynamic performance with and without rotating cylinder at the leading edge of the NACA 0021 and NACA 23018 aerofoil was studied on the wind tunnel installed at Aerodynamics Laboratory. The aerofoil section was tested in the low subsonic wind tunnel, and the lift coefficient and the drag coefficient were studied for different angles of attack. The experiments were conducted for two Reynolds numbers: 200000 and 250000 corresponding to two free stream velocities: 20 m/s and 25 m/s, respectively, for six different angle of attacks (-5°, 0°, 5°, 10°, 15° and 20°). This study demonstrates that the incorporation of a leading edge rotating cylinder results in an increase of lift coefficient at lower angle of attacks (maximum around 33%) and delay in stall angle (from 10° to 15°) relative to the aerofoil without rotating cylinder.

(1) Background: Targeted (TT) and immune checkpoint inhibitor (ICI) therapies have become available in the routine care of metastatic melanoma in recent years. (2) Objective: We compared mortality in patients with metastatic melanoma and different systemic therapies. (3) Methods: A retrospective cohort study, based on pseudonymized health insurance data of about 2 million individuals from Saxony, Germany, was conducted for the years 2010 to 2020. Only patients with an advanced stage, i.e. distant metastases were considered for the main analysis. Relative survival since metastasis and predicted survivor curves derived from a Cox model were used to assess potential differences in mortality. (4) Results: Relative survival was highest in the subgroup with sequential use of ICI and TT. All treatments except interferon had significant hazard ratios (HR) in the Cox model with time-dependent effects indicating a protective effect after treatment initiation (HR 0.01-0.146) but decreasing over time (HR 1.351-2.310). The predicted survivor curves revealed best survival under ICI-TT treatment and worst survival under TT treatment alone. (5) Conclusions: We found real-world evidence for survival benefits of patients with metastatic melanoma who received sequential ICI and TT treatment. It is conceivable that the observed high survival differences were overestimated due to bias, such as confounding by indication.

The following study reports on the first thraustochytrid isolates identified from Iceland. They were collected from three different locations off the northern coast of the country (Location A, Skagaströnd; Location B, Hveravík; and Location C, Eyjafjörður). Using 18S rDNA sequence analysis, isolates from Locations A and B were identified within the Thraustochytrium kinnei species while other isolates within the Sicyoidochytrium minutum species when compared to other known strains. Cells isolated from Locations A (2.10 ± 0.70 g/L) and B (1.54 ± 0.17 g/L) produced more biomass than the ones isolated from Location C (0.43 ± 0.02 g/L). This study offers the first-time examination of the utility of byproducts from fisheries as a nitrogen source in media formulation for thraustochytrids. Experiments showed that isolates produced more biomass (per unit of substrate) when cultured on nitrogen of marine (2.55 ± 0.74 g/L) as compared to of commercial origin (1.06 ± 0.57 g/L). Glycerol (2.43 ± 0.56 g/L) was a better carbon source than glucose (1.84 ± 0.57 g/L) in growth studies. Fatty acid (FA) profiles showed that the isolates from Location C (S. minutum) had low ratios of monounsaturated (4.21 ± 2.96%) and omega-6 (0.68 ± 0.59%) FAs. However, the isolates also had high ratios of docosahexaenoic acid (DHA; 35.65 ± 1.73%) and total omega-3 FAs (40.39 ± 2.39%), indicating that they could serve as a source of marine oils for human consumption and in aquaculture feeds. The T. kinnei isolates from Location A could be used in biodiesel production due to their high ratios of monounsaturated (18.38 ± 6.27%) long chain (57.43 ± 8.27%) FAs.

This article discusses the outcomes of a quantitative analysis of the competitiveness of grain and its recycling in the countries-members of the Eurasian Economic Union (EEU) through econometric panel data models. The analysis is based on the data of public authorities’ statistics of the countries-members of the EEU, as well as the United Nations Comtrade Database which is a repository of official international trade statistics. The results of the analysis allow to assess the level of competitiveness of produced agro-food products in the countries-members of the EEU and determine the extent to which various factors affect it. The research conclusions can be used to develop and adjust the agreed with the agro-food policy in the EEU.

Studies in animal models have suggested that the ketogenic diet may be effective in the treatment of cancer. However, human cohort studies on the ketogenic diet have, thus far, failed to show benefits in cancer survival or in any other hard clinical endpoints of the disease. This paper presents a case report of a patient with glioblastoma multiforme. The patient had initially been treated with standard oncotherapy including surgery, radiotherapy and chemotherapy. Despite standard treatment, the patient experienced a recurrence of the glioblastoma seven months later. Subsequently, the patient refused radiotherapy and chemotherapy and opted to use the paleolithic ketogenic diet (PKD) as a stand-alone therapy. Following the adoption of the PKD, progression of the disease has been completely halted. At the time of writing, the patient has remained in remission for 48 months, is without side-effects and experiences an excellent quality of life without the use of any drugs.

The study findings revealed significant variability in various wood properties among different genetic families, although the static modulus of elasticity did not exhibit significant differences between the chosen genetic families. All measured wood properties decreased from the bottom to the top of the model trees. Wood hardness displayed a moderately negative correlation with wood density and weak correlations with MOE and MOR. Given the weak correlations between wood hardness and other wood mechanical properties, it is suggested that the MOEdyn would be a more suitable trait for genetic studies.

Using digital media has become the most popular leisure activity for children and adolescents. The effects of digital media use on the developing brain and cognitive processes of children are subject to debate. Here, we examine the effect of digital media use on attention subdomains in children aged 6 to 10 years. In total, 77 children participated in the study. Selective and divided attention as well as switching between attentional demands were quantified by the SwAD task. Parents were asked to assess the screen time of their children (TV, smartphone, laptop/PC, game console, tablet). Results show no main or interaction effects of screen time on any of the attention conditions investigated. Based on the present findings, as well as previous studies, we suggest a possible non-linear relationship between the amount of screen time and attention function. Furthermore, we emphasize the relevance of considering the socio-economic background of children and a need for longitudinal studies.

Over 250 million people are infected chronically with hepatitis B virus (HBV), the leading cause of liver cancer worldwide. HBV persists due in part to its compact, stable minichromosome, the covalently-closed, circular DNA (cccDNA), which resides in the hepatocytes’ nuclei. Current therapies target downstream replication products, however, a true virological cure will require targeting the cccDNA. Finding targets on such a small, compact genome is challenging. For HBV, to remain replication-competent, it needs to maintain nucleotide fidelity in key regions, such as the promoter regions, to ensure that it can continue to utilize the necessary host proteins. HBVdb (HBV database) is a repository of HBV sequences spanning all genotypes (A-H) amplified from clinical samples, and hence implying an extensive collection of replication-competent viruses. Here, we analyzed the HBV sequences from HBVdb using bioinformatics tools to comprehensively assess the HBV core and X promoter regions amongst the nearly 70,000 HBV sequences for highly-conserved nucleotides and variant frequencies. Notably, there is a high degree of nucleotide conservation within specific segments of these promoter regions highlighting their importance in potential host protein-viral interactions and thus the virus’ viability. Such findings may have key implications for designing antivirals to target these areas.

Several design methods and principles have been presented so far, in order to guide the design of autonomous operations. Putting the required efforts into learning and using the methods for designing autonomous operations is a daunting task. Experiences so far have shown that the use of methods meant to the help the design process are often ignored. One reason could be that the design guidelines are too complex and contain much information often not relevant for the project at hand, and therefore there is no easy way to distinguish what is important from what is not. This is an issue that needs to be solved with our approach. In this article, the Autonomous Job Analysis (AJA) method is presented. The proposed methodology is created in order to guide the design of autonomous operations in maritime systems by breaking them down in to sub-operations in order to reveal challenges, needs and limitations regarding autonomous behavior. The canvas contains the categories of the AJA method on a single page format -the canvas- and each category is supported with questions to be asked during the design procedure, as well as example answers. We will describe the AJA method and the AJA canvas in detail, and present a use case scenario of an autonomous operation in order to show how they can be applied. The particular use-case is the design of an autonomous operation for the detection, inspection and tracking of a waste water plume.

Micronutrient deficiencies are a major public health problem. Beans are an important plant-based source of iron, zinc and copper, but their absorption is reduced in the presence of anti-nutrients such as phytates, polyphenols and tannins. Soaking and discarding the soaking water before cooking is unanimously recommended, but this can result in mineral loss. Data on the consequences for mineral bioaccessibility is still limited. This study aimed to evaluate iron, zinc and copper bioaccessibility in black beans cooked (regular pan, pressure cooker) with and without the soaking water. Minerals were quantified by ICP-MS, myo-inositol phosphates (InsP₅, InsP₆) by HPLC ion-pair chromatography, total polyphenols using Folin-Denis reagent and condensed tannins using Vanillin assay. Mineral bioaccessibility was determined by in vitro digestion and dialysis. All treatments resulted in a statistically significant reduction of total polyphenols (30%) and condensed tannins (20%). Only when discarding the soaking water a loss of iron (6%) and copper (30%) was observed, and InsP₆ was slightly decreased (7%) in one treatment. Bioaccessibility of iron and zinc were low (about 0.2% iron and 35% zinc), but copper presented high bioaccessibility (about 70%). Cooking beans under pressure without discarding the soaking water resulted in the highest bioaccessibility levels among all household procedures. Discarding the soaking water before cooking did not improve the nutritional quality of the beans.

Nitric acid is a key component in the production of nitrate fertilisers and is industrially produced using the Ostwald process. The Ostwald process can be further intensified by oxidising nitric oxide to nitrogen dioxide using heterogeneous catalysts. We have explored various monometallic and bimetallic catalysts for NO to NO2 oxidation and found ruthenium supported on ceria, containing 10 wt.% manganese to be a promising catalyst for oxidising NO to NO2 at low temperatures at industrially relevant conditions. For a feed comprising 10% NO, 6% O2, 15% H2O and rest Ar, and 8% NO, 2% NO2 5% O2, 15% H2O and rest Ar, the ruthenium-manganese catalysts attained NO-NO2 equilibrium below 400∘C. For the 5wt.% ruthenium and 10 wt.% manganese on ceria catalyst, an apparent activation energy of 39.4 kJ/mol and 85.4 kJ/mol were observed in the absence and presence of NO2, respectively. These findings demonstrate the potential of supported bimetallic ruthenium-manganese catalysts for efficient oxidation of NO to NO2 at low temperatures which can lead to significant process intensification of nitric acid plants.

The impact of organizational accreditation and professional certification and the evidence-based measurable impact of those for both academic programs and affiliates is one of specific interest to universities and individuals in the healthcare management field [1]. The authors’ analysis examined the impact of hiring graduates from higher education programs that held external accreditation from the Commission on Accreditation of Healthcare Management Education (CAHME). Graduates’ affiliation with the American College of Healthcare Executives (ACHE) professional healthcare leadership organization was also assessed as an independent variable. Study outcomes focused on these graduates’ respective healthcare organization’s performance measures (cost, quality, and access) to assess the researchers’ inquiry into the perceived value of a CAHME-accredited graduate degree in healthcare administration and a professional ACHE affiliation [2]. The results from this study found no effect of CAHME accreditation or ACHE affiliation on healthcare organization performance outcomes. The study findings support the need for future research surrounding healthcare administration professional graduate degree program characteristics and leader development affiliations, as perceived by various industry stakeholders.

Interdisciplinary research into the underlying neural processes of music therapy (MT) and subjective experiences of patients and therapists are largely lacking. The aim of the current study was to assess the feasibility of newly developed procedures (including EEG/ECG hyperscanning, synchronous audio-video monitoring, and qualitative interviews) to study the personal experiences and neuronal dynamics of moments of interest during MT with stroke survivors. The feasibility of our mobile set-up and procedures as well as their clinical implementation in a rehabilitation centre and an acute hospital ward were tested with four phase C patients. Protocols and interviews were used for the documentation and analysis of the feasibility. Recruiting patients for MT sessions was feasible, although data collection on three consecutive weeks was not always possible due to organisational constraints, especially in the hospital with acute ward routines. Research procedures were successfully implemented, and according to interviews, none of the patients reported any burden, tiredness or increased stress due to the research procedures, which lasted approx. 3 hours (ranging from 135min to 209min) for each patient. Implementing the research procedures in a rehabilitation unit with stroke patients was feasible and only small adaptations were made for further research.

Abstract: (1) Background: Post-COVID syndrome is defined as symptoms that occur simultane-ously with or after COVID-19 infection, last for 12 weeks, and are not due to another diagnosis. Limited data are available on people’s long-term quality of life (QoL) following COVID-19 infection. The aim of this cross-sectional study was to investigate long-term QoL after COVID-19 among employees of the St. Josef Hospital in Paderborn, Germany, and to identify risk factors. (2) Methods: A monocentric, cross-sectional study was conducted using the validated and digitized WHOQOL-BREF questionnaire via Netigate® between 10/2022 and 02/2023. Data on QoL and global health status were collected in the following four domains: physical health, mental health, social relationships, and environment. (3) Results: The response rate was 73.84% (923/1250). Furthermore, 63.45% of hospital staff respondents reported at least one persistent symptom after COVID-19 infection, leading to significant differences in QoL. Pre-existing conditions, persistent symptoms, and disability after COVID-19 infection, as well as high BMI, no partnership, and low educational level were found to significantly contribute to long-term low QoL. (4) Conclusions: Obesity, lack of partnership, and a low level of education were independent risk factors for lower QoL post-COVID-19 infection in this cohort of hospital staff. Further multicenter studies are re-quired to validate the incidence and their suitability as independent risk factors for post-COVID syndrome.

Adenine nucleotide (AN) 2^nd messengers such as 3’,5’-cyclic adenosine monophosphate (cAMP) are central elements of intracellular signaling, but many details of underlying processes remain still elusive. Like all nucleotides, cyclic nucleotide monophosphates (cNMPs) are net-negatively charged at physiologic pH which limits their applicability in cell-based settings. Thus, many cellular assays rely on sophisticated techniques like microinjection or electroporation. This setup is not feasible for medium- to high-throughput formats, and the mechanic stress that cells are exposed to raises the probability of interfering artefacts or false-positives. Here, we present a short and flexible chemical route yielding membrane-permeable, bio-reversibly masked cNMPs for which we employed the octanoyloxybenzyl (OB) group. We further show hydrolysis studies on chemical stability and enzymatic activation, and present results of real-time assays, where we used cAMP and Ca²⁺ live cell imaging to demonstrate high permeability and prompt intracellular conversion of some selected masked cNMPs. Consequently, our novel OB-masked cNMPs constitute valuable precursor-tools for non-invasive studies on intracellular signaling.

Knowledge about laminar-turbulent transition on operating multi-megawatt wind turbine blades needs sophisticated equipment like hot-films or microphone arrays. Contrarily thermographic pictures can easily be taken from the ground and temperature differences indicate different states of the boundary layer. The accuracy however, still is an open question, so that an aerodynamic glove known from experimental research on aero-planes was used to classify the boundary-layer state of a 2 megawatt wind turbine blade operating in the orthern part of Schleswig-Holstein, Germany. State-of-the-art equipment for measurering static surface pressure was used for monitoring the lift distribution. To distinguish laminar and turbulent parts of the boundary layer (suction side only) 48 microphones were applied together with ground-based thermographic cameras from two teams. Additionally, an optical camera mounted on the hub was used to survey vibrations. During start-up (from 0 to 9 rpm) extended, but irregularly shaped regions of a laminar boundary layer were observed which had the same extension measured both with microphones and Thermography. When an approximately constant rotor rotation (9 rpm corresponding to approximately 6 m/s wind-speed) was achieved, a flow transition was visible at the expected position of 40 % chord length on the rotor blade, which was fouled with dense turbulent wedges and an almost complete turbulent state on the glove was detected. In all observations, quantitative determination of the flow transition positions from thermography and microphones agree well within their accuracy.

Lactic acid bacteria (LAB) have an extracellular proteolytic system that includes a multi-domain, cell envelope protease (CEP) with a subtilisin homologous protease domain. These CEPs have different proteolytic activities despite having similar protein sequences. Structural characterization has previously been limited to CEP homologs of dairy and human derived LAB strains, excluding CEPs of plant derived LAB strains. CEP structures are a challenge to determine experimentally due to their large size and attachment to the cell envelope. This study aims to clarify the prevalence and structural diversity of CEPs by using the structure prediction software AlphaFold 2. Domain boundaries are clarified based on a comparative analysis of 21 three-dimensional structures, revealing novel domain architectures of CEP homologs that are not necessarily restricted to specific LAB species or ecological niches. The C-terminal flanking region of the protease domain is divided into fibronectin type-III-like domains with various structural traits. The analysis also emphasizes the existence of two distinct domains for cell envelope attachment that are preceded by an intrinsically disordered cell wall spanning domain. The domain variants and their combinations provide CEPs with different stability, proteolytic activity and potentially adhesive properties, making CEPs targets for steering proteolytic activity with relevance for both food development and human health.

Driver drowsiness is one of the leading causes of traffic accidents. This paper proposes a new method for classifying driver drowsiness using deep convolution neural networks trained by wavelet scalogram images of electrocardiogram (ECG) signals. Three different classes were de-fined for drowsiness based on video observation of driving tests performed in a simulator for manual and automated modes. The Bayesian optimization method is employed to optimize the hyperparameters of the designed neural networks, such as the learning rate and the number of neurons in every layer. To assess the results of the deep network method, Heart Rate Variability (HRV) data is derived from the ECG signals, some features are extracted from this data, and finally, random forest and k-nearest neighbors (KNN) classifiers are used as two traditional methods to classify the drowsiness levels. Results show that the trained deep network achieves balanced accuracies of about 77% and 79% in the manual and automated modes, respectively. However, the best obtained balanced accuracies using traditional methods are about 62% and 64%. We conclude that designed deep networks working with wavelet scalogram images of ECG signals significantly outperform KNN and random forest classifiers which are trained on HRV-based features.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

The cultivation of berry crops by the type of "intensive plantings" is an economic and scientific approach in modern horticulture. The principles of forming a red currant assortment adapted to mechanized harvesting are considered. The bush should be compact for mechanized harvesting and have a straight-growing or slightly spreading shape. The morphological structure of the bush is a feature determined by the genotype. The ripening period of berries and the mechanical parameters of berries assess the effectiveness of the berry harvesting process. With the help of agrotechnical techniques, the mechanical parameters of berries cannot be improved and are de-termined by weather, soil, water, and climatic factors. The present study was conducted in the 2021-2022 season using 14 red currant genotypes of different geographical and genetic origins to assess cultivars' suitability for machine harvesting. In most of the studied cultivars, berry quality indicators, the parameters of separation force (Fs) and crushing force (Fc) decreased by the time of biological maturity of the genotype. Several cultivars have shown a non-simultaneous decrease in Fs and Fc. A minor limiting feature determines the duration of harvesting. The high correlation of Fs and Fc (R=0.75-0.85) allows us to predict the most significant period for the high-quality operation of a mechanized harvester. There was no dependence of the strength of the attachment of berries to the peduncle on the thickness of the skin of the berries. Jonkheer Van Tets, Red Lake, Rovada, Rolan, Vika, Asya, and Niva can be attributed to technological cultivars as sources of compact and erect bush habit, Jonkheer Van Tets, Rovada, Rolan, Vika, and Asya are recommended for mechanized harvesting.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

Virtual tours with 360 photos present a quick, easy and accessible way to create immersive experiences. The visualization in diverse devices, provide a user experience that can be different. A virtual tour with 360 photos of the Chapel of Dolores (Tenerife), has been created. Whose access is limited to specific days, so the creation of a virtual tour allows you to visit it at any time, in addition, a pilot test has been carried out with students of the degree of restoration and conservation of cultural heritage in order to measure the user experience of the virtual tour depending on the device used. The participants took a virtual tour of the Dolores Chapel, first with a cell phone and then with the virtual reality headset, and then completed a user experience questionnaire. The results obtained comparing both visualization technologies are detailed, highlighting that when using the virtual reality headset no better results are obtained in the immersion subscale, in addition, the visualization on a Smartphone is more comfortable and obtains better results in consequences such as dizziness and vertigo. Therefore, it may be an interesting strategy to have simple versions that work quickly on the cell phones.

The agricultural industry relies on physical fences to manage livestock. However, physical fences present some practical, financial, and ecological problems, that partly may be solved by virtual fencing. However, it is necessary for the livestock to be adapted to virtual fencing. This study aims to identify if adaptation to virtual fence can be improved through social facilitation between experienced cattle and the remaining herd. Moreover, which of the two different learning processes, a gradual or instant introduction to virtual fence is the most effective in associating warnings with impulses. Three pastures containing Angus (Bos taurus) will be used to examine these investigations; A, B and C. All investigations are conducted on the Danish Island of Fanø. Three methods of learning process were used, one gradual and two instant introductions to the virtual fence. The investigations had varying amounts of experienced cattle. Impulses and warnings were recorded during a learning period and the following observation period. To quantify if the cattle adapt to the warnings, impulses per warning are used. There was no evidence of improvement with the presence of experienced cattle for any pastures, indicating no social facilitation. Gradual introduction was found to be more beneficial than instant introduction. More standardized tests are necessary to discover the full effect of experienced cattle.

Osteoarthritis (OA) is a common joint disorder found mostly in elderly people. The role of mechanical behavior in the progression of OA is complex and remains unclear. The stress-relaxation behavior of human articular cartilage in clinically defined osteoarthritic stages may have importance in diagnosis and prognosis of OA. In this study we investigated differences in the biomechanical responses among human cartilage of ICRS grades I, II and III using polymer dynamics theory. We collected 24 explants of human articular cartilage (eight each of ICRS grade I, II and III) and acquired stress-relaxation data applying a continuous load on the articular surface of each cartilage explant for 1180 s. We observed a significant decrease in Young’s modulus, stress-relaxation time, and stretching exponent in advanced stages of OA (ICRS grade III). The stretch exponential model indicated that significant loss in hyaluronic acid polymer might be the reason for the loss of proteoglycan in advanced OA. This work encourages further biomechanical modelling of osteoarthritic cartilage utilizing these data as input parameters to enhance the fidelity of computational models aimed at revealing how mechanical behaviors play a role in pathogenesis of OA.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.

The food system represents a key industry for Europe and particularly Germany. However, it is also the single most significant contributor to climate and environmental change. A food system transformation is necessary to overcome the system's major and constantly increasing challenges in the upcoming decades. One possible facilitator for this transformation are radical and disrup-tive innovations that start-ups develop. There are many challenges for start-ups in general and food start-ups in particular. Various support opportunities and resources are crucial to ensure the success of food start-ups. One aim of this study is to identify how the success of start-ups in the food system can be supported and further strengthened by players in the innovation ecosystem in Germany. There is still room for improvement and collaboration toward a thriving innovation ecosystem. A successful innovation ecosystem is characterised by a well-organised, collaborative, and supportive environment with a vivid exchange between the members in the ecosystem. The interviewees confirmed this, and although the different actors are already cooperating, there is still room for improvement. The most common recommendation for improving cooperation is learning from other countries and bringing the best to Germany.

Energy system models have become indispensable to shape future energy systems by providing insights into different trajectories. However, sustainable systems with high shares of renewable energy are characterized by growing cross-sectoral interdependencies and decentralized structures. To capture important properties of increasingly complex energy systems, sophisticated and flexible modelling tools are needed. At the same time open science becomes increasingly important in energy system modelling. This paper presents the Open Energy Modelling Framework (oemof) as a novel approach in energy system modelling, representation and analysis. The framework forms a toolbox to construct comprehensive energy system models and has been published open source under a free license. With a collaborative development based on open processes the framework seeks for a maximum level of participation and transparency to facilitate open science principles in energy system modelling. Based on a generic graph based description of energy systems it is well suited to flexibly model complex cross-sectoral systems and incorporate various modelling approaches. This makes the framework a multi-purpose modelling environment for modelling and analyzing different systems ranging from an urban to a transnational scale.

The detection of antibiotic-resistant facultative pathogenic bacteria in surface waters is common in the present day. However, there is limited understanding of the factors that influence the spread and stabilization of resistance in this habitat, particularly regarding the role of biofilms. Despite the perceived differences between sediments, biofilms, and open water, their potential contribution to the long-term maintenance of resistances remains unclear. In this study, we investigated Escherichia coli isolates obtained from the Mur and Drava rivers in Austria. Samples were collected from both the water column and sediment at two locations per river: upstream and downstream of an urban area, including a sewage treatment plant. The iso-lates were subjected to antimicrobial susceptibility testing against 21 antibiotics belonging to seven distinct classes. Additionally, any isolates exhibiting an extended-spectrum beta-lactamase (ESBL) or carbapenemase phenotype were further analyzed for the presence of specific antimi-crobial resistance genes. E. coli isolates obtained from the two rivers exhibited resistance to at least one of the tested anti-biotics, with rates of 25.83% and 23.66% respectively. The most prevalent antimicrobial re-sistances observed were towards ampicillin, amoxicillin-clavulanic acid, tetracycline, and na-lidixic acid. Surprisingly, there was a similar proportion of resistant bacteria observed in both open water and sediment samples, contrary to expectations. The difference in resistance levels between samples collected upstream and downstream of the cities was minimal. Out of the total isolates, 13 E. coli were found to carry ESBL genes with one isolate carrying the gene for KPC-2 carbapenemase. There were no significant differences between the biofilm (sediment) and open water samples in the occurrence of antimicrobial resistance. Even the difference between the samples upstream and downstream of the cities and their wastewater treatment plants was minor. There seems to be no evidence of a large adaptive effect in this analysed biofilm population of E. coli. The un-typical phenotype of the KPC-producing and some of the ESBL-producing E. coli from this study could, however, be an indication that such adaptation effects generally exist in water.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten time to antibiotic administration in the Emergency Department. We retrospectively evaluated all patients above 18 years of age that were diagnosed with sepsis or severe infection in our Emergency Department between 2018 and 2020. We recorded the suspected diagnosis at time of presentation, type of referring healthcare provider and time until initiation of antibiotic treatment. Differences between groups were calculated using Kruskal-Wallis rank sum test. Of the 277 patients that were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well described outcome benefits to early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce time to antibiotic administration and improve patient outcomes.

In this study we present gas-phase fluorination as a method to create a thin LiF layer on Li6.5La3Zr1.5Ta0.5O12 (LLZTO). We compare these fluorinated films with LiF films produced by RF-magnetron sputtering, where we investigated the interface between the LLZTO and the deposited LiF showing no formation of a reaction layer. Furthermore, we investigate the ability of this LiF layer as a protection layer against Li2CO3 formation in ambient air. By this we show that Li2CO3 formation is absent at the LLZTO surface after 24 h in ambient air supporting the protective character of the formed LiF films and hence could enhance the handling of LLZTO in air for battery production. With respect to the use within hybrid electrolytes consisting of LLZTO and a mixture of polyethylene oxide (PEO) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) we also investigated the interface between the formed LiF films and a mixture of PEO LiTFSI by X-ray photoelectron spectroscopy (XPS) showing decomposition of the LiTFSI at the interface.

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.

The most important predictors for outcomes after ischemic stroke, that is, for health deterioration and death, are chronological age and stroke severity; gender, genetics and lifestyle / environmental factors also play a role. Of all these, only the latter can be influenced after the event, even though recurrent stroke may be prevented by antiaggregant/anticoagulant therapy, angioplasty of high-grade stenoses, and treatment of cardiovascular risk factors. Moreover, blood cell composition and protein biomarkers such as C-reactive protein or interleukins in serum are frequently considered as biomarkers of outcome. We surveyed protein biomarkers that were reported to be predictive for outcome after ischemic stroke, specifically considering biomarkers that predict long-term outcome (≥3 months) and that are measured over the first days following the event. We classified the protein biomarkers as immune‑inflammatory, coagulation-related, and adhesion-related biomarkers. Some of these biomarkers are closely related to cellular senescence and, in particular, to the inflammatory processes that can be triggered by senescent cells. Moreover, the processes that underlie inflammation, hypercoagulation and cellular senescence connect stroke to cancer, and biomarkers of cancer-associated thromboembolism, as well as of sarcopenia, overlap strongly with the biomarkers discussed here. Finally, we demonstrate that most of the outcome-predicting protein biomarkers form a close-meshed functional interaction network, suggesting that the outcome after stroke is partially determined by an interplay of molecular processes relating to inflammation, coagulation, cell adhesion and cellular senescence.

The purpose of this research is to determine if the tradeoffs that Kissick proposed among cost containment, quality, and access remain as rigidly interconnected as originally conceived in the contemporary health care context. Although many have relied on the Kissick model to advocate for health policy decisions, to our knowledge, the model has never been empirically tested. Some have called for policy makers to come to terms with the premise of the Kissick model tradeoffs, others have questioned the model given the proliferation of quality enhancing initiatives, automation, and information technology in the health care industry. One wonders whether these evolutionary changes alter or disrupt the originality of the Kissick paradigms themselves. Methods: Structural Equation Modeling (SEM) was used to evaluate the Kissick hypothetical relationships among the unobserved constructs of cost, quality, and access in hospitals for the year 2018. Hospital data were obtained from Definitive Healthcare a subscription site which contains Medicare data as well as non-Medicare data for networks, hospitals, and clinics (final n= 2,766). Results: Reporting significant net effects as defined by our chosen study variables, we find that as quality increases costs increase, as access increases quality increases, and as access increases, costs increase. Policy and Practice Implications: Our findings lend continued relevance to a balanced approach to health care policy reform efforts. Simultaneously bending the health care cost curve, increasing access to care, and advancing quality of care is as challenging now as it was when the Kissick model was originally conceived.

G protein-coupled receptors (GPCRs) are amongst the most pharmaceutically relevant and well-studied protein targets, yet unanswered questions in the field leave significant gaps in our understanding of their nuanced structure and function. 3D pharmacophore models are powerful computational tools in silico drug discovery, presenting myriad opportunities for the integration of GPCR structural biology and cheminformatics. This review highlights success stories in the application of 3D pharmacophore modeling to de novo drug design, discovery of biased and allosteric ligands, scaffold hopping, QSAR analysis, hit-to-lead optimization, GPCR de-orphanization, mechanistic understanding of GPCR pharmacology and elucidation of ligand-receptor interactions. Furthermore, advances in the incorporation of dynamics and machine learning will be highlighted. The review will analyze challenges in the field of GPCR drug discovery, detailing how 3D pharmacophore modeling can be used to address them. Finally, we will present opportunities afforded by 3D pharmacophore modeling in the advancement of our understanding and targeting of GPCRs.

Ferroelectric materials are crucial for today’s technological society, and nanostructured ferroelectric materials are important for downscaling of devices. Controlled and reproducible synthesis of these materials are therefore of immense importance. Hydrothermal synthesis is a well-established synthesis route, with a large parameter space for optimization, but a better understanding of nucleation and growth mechanisms is needed for full utilization and control. Here we use in situ X-ray diffraction to follow the nucleation and growth of BaTiO₃ formed by hydrothermal synthesis using two different titanium precursors, an amorphous titania precipitate slurry and a Ti-citric acid complex solution. Sequential Rietveld refinement was used to extract the time dependency of lattice parameters, crystallite size, strain and atomic displacement parameters. Phase pure BaTiO₃ nanoparticles 10 - 15 nm in size were successfully synthesized at different temperatures (100, 125, and 150 °C) from both precursors after reaction times ranging from a few seconds, to several hours. The two precursors resulted in phase pure BaTiO₃ with similar final crystallite size. Finally, two different growth mechanisms were revealed, where the effect of surfactants present during hydrothermal synthesis is discussed as one of the key parameters.

Among extensive studies on click chemistry the inverse electron-demand Diels-Alder reaction between 1,2,4,5-tetrazine (Tz) and trans-cyclooct-2-en (TCO) has gained increasing attraction due to its exceptionally fast reaction kinetics and high selectivity for in vivo pretargeting applications including PET imaging. The facile two-step approach utilizing TCO-modified antibodies as targeting structures has not made it into clinic though as the increase in blood volume from mice to human seems to be the major limitation. This study aimed to show if the design of multimeric Tz-ligands by chelator scaffolding can improve the binding capacity and may lead to enhanced PET imaging with gallium-68. For this purpose we utilized the macrocyclic siderophore Fusarinine C (FSC) which allows to conjugate up to three Tz-residues due to three primary amines available for site specific modification. The resulting mono- di- and trimeric conjugates were radiolabelled with gallium-68 and characterized in vitro (logD, protein binding, stability, binding towards TCO modified rituximab (RTX)) and in vivo (biodistribution- and imaging studies in normal BALB/c mice using a simplified RTX-TCO tumour surrogate). The 68Ga-labelled FSC-based Tz-ligands showed suitable hydrophilicity, high stability, high targeting specificity and the binding capacity to RTX-TCO was increased by the grade of multimerization. Corresponding in vivo studies showed a multimerization typical profile but generally suitable pharmacokinetics with low accumulation in non-targeted tissue. Imaging studies in RTX-TCO tumour surrogate bearing BALB/c mice confirmed this trend and revealed improved targeting by multimerization as increased accumulation in RTX-TCO positive tissue was observed.

There has been an increased focus on new technologies to monitor habitat use and behaviour of cattle, to develop a more sustainable livestock grazing system, without compromising animal welfare. The currently most used method for monitoring cattle behaviour is tri-axial accelerometer data from systems such as virtual fencing technology or bespoke monitoring technology. This method requires high frequency data, and as such, quickly drains contemporary systems of power making it unsuitable for long-term monitoring. In this paper, we explore the possibility of determining habitat preference and habitat utilisation patterns in cattle, using low frequency activity and location data. We do this by (1) calculating habitat selection ratios, (2) determining daily activity patterns and based on those, (3) inferring grazing and resting sites in a group of cattle wearing virtual fencing collars in a coastal setting with grey, wooded and decalcified dunes, humid dune slacks and salt meadows. We found that GPS data, and a measure of activity, combined with accurate mapping of habitats can be an effective tool in assessing habitat preference. The animals preferred salt meadows over the other habitats, with wooded dunes and humid dune slacks being the least preferred. We were able to identify daily patterns in activity. By comparing general trends in activity levels to existing literature, it was possible to somewhat infer resting and grazing behaviour in the different habitats. According to our inference of behaviour the herd predominantly used the salt meadows for resting and ruminating. The approach used in this study allowed us to use GPS location data for measuring the activity and combine it with accurate habitat mapping in a cheap and effective way, which can be an important tool for guiding management decisions.

We introduce a series of twisted donor-acceptor (D-A) carbazole-benzophenone based electroactive bipolar derivatives that were synthesized through the reaction of 4-fluorobenzophenone with various partially alkylated 3,3’-bicarbazoles. The comprehensive structural characterization of these compounds is provided. These amorphous materials exhibit suitable glass transition temperatures ranging from 57 to 102 °C and demonstrate high thermal stability, with decomposition temperatures reaching 400 °C. Moreover, the developed materials exhibit elevated photoluminescence quantum yields (PLQY) of up to 75.5% and favorable HOMO-LUMO levels, along with suitable triplet-singlet state energy values. Due to their good solubility and suitable film-forming properties, all the compounds were evaluated as blue emitters dispersed in 4,4’-bis(N-carbazolyl)-1,10-biphenyl (CBP) host for the fabrication of organic light-emitting diodes (OLEDs) in concentration dependent experiments. Among these experiments, the device containing 15 wt% of the guest 4-(9’-{2-ethylhexyl}-[3,3’]-bicarbazol-9-yl)benzophenone demonstrated the best characteristics, achieving maximum brightness of 3581 cd/m2, current efficiency of 5.7 cd/A, power efficiency of 4.1 lm/W and external quantum efficiency of 2.7%.

An inorganic solid electrolyte is the most favorable candidate for replacing flammable liquid electrolytes in lithium batteries. Lithium Lanthanum Zirconium Oxide (LLZO) is considered as a promising solid electrolyte due to its safe operating potential window (0-5V) combined with its good electrochemical stability. In this work, 250 g batches of pre-sintered Tadoped (Li7La3Zr1.6Ta0.4O12, TaLLZO) were synthesized for bulk production of dense LLZO electrolyte. A simple two-step thermal treatment process was developed. The first thermal step at 950 °C initiates nucleation of LLZO carefully controlling process parameters such as heating atmosphere, temperature and dopant concentration. In the second thermal step at 1150 °C, sintered discs were obtained as solid electrolytes, with relative densities of 96%. X-ray diffraction analysis confirmed the phase purity of the sintered TaLLZO disc, and refined data was used to calculate the lattice parameter (12.944 Å). Furthermore, the presence of the Ta dopant in the disc was confirmed through X-ray photoelectron spectroscopy (XPS) analysis. The ionic and electronic conductivity values of TaLLZO disc were 104 S cm-1 and 10-10 S cm-1, respectively. These values confirm that the prepared (Ta-LLZO) discs exhibit ionic conductivity while being electronically insulating, being suitable for use as solid electrolytes with the requisite electrical properties.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of >95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

Background/Objectives: We defined the value of a machine learning algorithm to distinguish between the EEG response to no light or any light stimulation, and between red or green light stimulation in awake volunteers with closed eyelids. This new method of EEG analysis is visionary in the understanding of visual signal processing and will facilitate anaesthetic depth research. Methods: X-gradient boosting models were used to classify the cortical response to VEP stimulation (no light vs. any light stimulation; red vs. green light stimulation). For each of the two classifications, three scenarios were tested: training and prediction in all participants (all), training and prediction in one participant (individual), training across all but one participant with prediction in the participant left out (one out). Results: Ninety-four Caucasian adults were included. The machine learning algorithm had a very high predictive value and accuracy in differentiating between no light and any light stimulation (AUCROCall: 0.96; accuracyall: 0.94; AUCROCindividual: 0.96±0.05, accuracyindividual: 0.94±0.05; AUCROConeout: 0.98±0.04; accuracyo-neout:0.96±0.04). The machine learning algorithm was highly predictive and accurate in distinguishing between green and red colour stimulation (AUCROCall: 0.97; accuracyall: 0.91; AUCROCin-dividual: 0.98±0.04, accuracyindividual: 0.96±0.04; AUCROConeout: 0.96±0.05; accuracyoneout: 0.93±0.06). The predictive value and accuracy of both classification tasks was comparable between males and females. Conclusions: Machine learning algorithms could almost continuously and reliably differentiate between the cortical EEG responses to no light or any light stimulation and between green or red colour stimulation using VEPs in awake female and male volunteers with eyes closed. Our findings may open new possibilities for using VEPs in the intraoperative setting.

This paper reviews research on community efforts to reduce greenhouse gas emissions. We conducted a systematic search of relevant literature and supplemented our findings with an analysis of review papers previously published on the topic. Results indicate that there have been no peer-reviewed experimental evaluations of community-wide interventions to reduce greenhouse gases involving electricity, refrigeration, or food. The lack of findings limits the conclusions which can be made about the efficacy of these efforts. As a result, we are not accumulating effective interventions and some communities may be implementing strategies that are not effective. We advocate the funding of experimental evaluations of multi-sector community interventions to reduce greenhouse gas emissions. Such interventions would attempt to engage every sector of the community in identifying and implementing policies and practices to reduce emissions. Comprehensive multi-sector interventions are likely to have synergistic effects, such that the total impact is greater than the sum of impact of individual components. We describe the value of interrupted time-series designs as an alternative to randomized trials because these designs confer particular advantages for evaluating strategies in entire communities.

This paper presents technical solutions to increase Industry 4.0 maturity. Within the “5G-Enabled Manufacturing” project, a 5G network has been deployed at the shop floor to enable fast and scalable connectivity. This network was used to connect a grinding machine to a private cloud to enable visibility and transparency of the production data, which is the basis for Industry 4.0 and smart manufacturing. Results indicate a present lack of commercially available product independent solutions for interconnection and data transfer despite the availability of open standards and well-documented demonstrator projects. The solution is described and discussed regarding technical interoperability, focusing on the system layout, communication standards, and open systems. From the discussion, it is derived that manufacturing end-users are in need to expand and further internalize knowledge on future information and communication technologies to reduce their dependency on equipment and technology providers.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Adverse Outcome Pathways (AOP) provide structured frameworks for systematic organization of research data and knowledge. The AOP framework follows a set of key principles that allow for broad application across diverse disciplines related to human health, including toxicology, pharmacology, virology and medical research. The COVID-19 pandemic engages a great number of scientists world-wide and data is increasing with exponential speed. Diligent data management strategies are employed but approaches for systematically organizing the data-derived information and knowledge are lacking. We believe AOPs can play an important role in improving interpretation and efficient application of scientific understanding of COVID-19. Here, we outline a newly initiated effort to streamline collaboration between scientists across the world towards development of AOPs for COVID-19, and describe the overarching aims of the effort, as well as the expected outcomes and research support that they will provide.

The COVID-19 pandemic has become a public health emergency of international concern, which may affect lifestyle habits and mental health. Based on national health profile assessments, this study investigates perceived changes of lifestyle habits in response to the COVID-19 pandemic and associations between perceived lifestyle changes and mental health in Swedish working adults. Among 5,599 individuals (50% women, 46.3 years), the majority reported no change (sitting 77%, daily physical activity 71%, exercise 69%, diet 87%, alcohol 90%, and smoking 97%) due to the pandemic. Changes were more pronounced during the first wave (April-June) compared to the second (October-December). Women, individuals <60 years, having a university degree, being white-collar workers and having unhealthy lifestyle habits at baseline had higher odds of changing lifestyle habits compared to their counterparts. Negative changes in lifestyle habits as well as more time in mentally passive sitting at home was associated with higher odds of mental ill-health (including health anxiety regarding one’s own and relatives’ health, generalized anxiety and depression symptoms, and concerns regarding employment and economy). The results em-phasize the need to support healthy lifestyle habits to strengthen the resilience in vulnerable groups of individuals to future viral pandemics, and prevent health inequalities in society.

Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, leaving a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequent frequent variants and associated mechanisms. Variants of unknown significance (VUS) in these genes are discovered at a rate that outpaces current ability to classify them using databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns, and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

The process of modelling energy systems is accompanied by challenges inherently connected with mathematical modelling. However, due to modern realities in the 21st century, existing challenges are gaining in magnitude and are supplemented with new ones. Modellers are confronted with a rising complexity of energy systems and high uncertainties on different levels. In addition, interdisciplinary modelling is necessary for getting insight in mechanisms of an integrated world. At the same time models need to meet scientific standards as public acceptance becomes increasingly important. In this intricate environment model application as well as result communication and interpretation is also getting more difficult. In this paper we present the open energy modelling framework (oemof) as a novel approach for energy system modelling and derive its contribution to existing challenges. Therefore, based on literature review, we outline challenges for energy system modelling as well as existing and emerging approaches. Based on a description of the philosophy and elementary structural elements of oemof, a qualitative analysis of the framework with regard to the challenges is undertaken. Inherent features of oemof such as the open source, open data, non-proprietary and collaborative modelling approach are preconditions to meet modern realities of energy modelling. Additionally, a generic basis with an object-oriented implementation allows to tackle challenges related to complexity of highly integrated future energy systems and sets the foundation to address uncertainty in the future. Experiences from the collaborative modelling approach can enrich interdisciplinary modelling activities. Our analysis concludes that there are remaining challenges that can neither be tackled by a model nor a modelling framework. Among these are problems connected to result communication and interpretation.

Background / Objective: Historically, fasting has not only been practiced for medical but also for religious reasons. Bahá’ís follow an annual religious fast of 19 days. We assessed motivation behind and subjective health impacts of Bahá’í fasting. Methods: A convergent parallel mixed methods design was embedded in a clinical single arm observational study. Semi-structured interviews were conducted with six fasters before, during and after fasting. Three months after the fasting period, two focus group interviews were conducted. 146 Bahá’í volunteers answered an online survey at five time points before, during and after fasting. Results: Interviews: Fasting was found to play a central role for the religiosity of interviewees, implying changes in daily structures, spending time alone, engaging in religious practices, and experiencing social belonging. Results show an increase in mindfulness and well-being, accompanied by behavioural changes and experiences of self-efficacy and inner freedom. Survey: Scores point to an increase in mindfulness and well-being during fasting, while stress, anxiety and fatigue decreased. Mindfulness remained elevated even three months after the fast. Conclusion: Bahá'í intermittent dry fast seems to enhance participants’ mindfulness and well-being, lowering stress levels and reducing fatigue. Some of these effects lasted more than three months after fasting.

Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing the composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium (Tropaeolum majus) is known for its antimicrobial activity and is used for the treatment against infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question whether 14 d nasturtium intervention (3 g daily, N=30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak, but significant antibacterial effect against Escherichia coli. A significant increase in human beta defensin 1 as parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did circulating serum metabolome. On an individual level, partly large changes were observed between sampling points, though. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species.

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

The interest in virtual fencing, as opposed to traditional physical barriers, has increased since it makes it easier to move the boundaries of animal enclosures for agricultural and rewilding purposes. Despite this, the implementation of virtual fence systems, such as the Nofence© system, requires large financial investments. The necessity of individual collars also makes it more difficult to implement this system on a larger scale. If a herd of cattle tend to maintain cohesive social groups around dominant individuals, it might be possible to use fewer collars thereby making the system more cost efficient. This study investigates the pattern in spatial distribution in a herd of 17 Angus cows on Fanø in Denmark with GPS locations, using a Nofence© system. The aim of this paper is to determine how individuals position themselves in a herd, spatially, and identify a pattern in ranks. The method used in this study examines the distances between an individual to the rest of the herd mates using nearest neighbour and distribution plots. Contrary to the expectations, this study did not show a distinct pattern in herd distribution. While some tendencies in spatial distribution patterns were observed, only a low concordance could be found (W=0.15,p=3.02e−16). Therefore, interactions among individuals should be considered in future studies, rather than only investigating the herd as one unit. A cumulative curves of the ranks estimated over the entire periods allowed however a rough estimation of the hierarchy and allowed the identification of the highest ranked cows. Therefore it might be possible to use fewer collars if the high ranked cows are discovered, but the estimation of the hierarchy will require a period of observation overall several days as the hierarchical positions are fluctuating too much from days to days. Therefore the cumulative rank curves seems to be a valid solution.

Although extracorporeal membrane ventilation offers the possibility for low frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low frequency ventilation on ventilator free days (VFDs) in patients suffering from ARDS treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to control group (conventional ventilation) or treatment group (low fre-quency ventilation during first 72 hours on ECMO: respiratory rate 4-5/min; PEEP 14-16cm H2O; plateau pressure 23-25 cm H2O, tidal volume: < 4mL/kg). The primary endpoint was VFDs at day 28 of ECMO start. The major secondary endpoint was ICU mortality, 28-day and 90-day mortality. Results Twenty-three (52%) patients could be successfully weaned from ECMO and were discharged from intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 after ECMO. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (P = 0.117). Until day 28 after ECMO initiation, patients in the treatment group could be more often successfully weaned from ventilator (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036-0.758; P = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; P = 0.227). Conclusions: Low frequency ventilation is comparable to conventional protec-tive ventilation in patients with ARDS treated with ECMO. However, low frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS treated with ECMO therapy.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Previous studies suggested that trauma-focused cognitive behavior therapy (TF-CBT) is effective in reducing symptoms of post-traumatic stress disorder (PTSD) and depression in children and adolescents. However, the effects of app-assisted TF-CBT-based interventions in psychiatric clinics compared to treatment-as-usual (TAU) are under-explored. The purpose of this study was to reveal the added value of the app-assisted TF-CBT-based intervention as an add-on to TAU. The digitalized measures of the Child and Adolescent Trauma Screen (CATS), The Adolescent Dissociative Experience Scale (A-DES), Short Moods and Feelings Questionnaire (SMFQ), PTSD Checklist (PCL-5), and Children's Post-Traumatic Cognitions Inventory (CPTCI) were applied at baseline and post-treatment. The app-assisted TF-CBT-based group participants started with higher levels of negative alterations in cognition and mood compared to TAU participants but at post-treatment, no significant differences were observed between the app-assisted TF-CBT and TAU groups. Within the app-assisted TF-CBT group, post-treatment scores were significantly lower in post-traumatic stress symptoms, intrusion symptoms, alterations in arousal and reactivity, overall post-traumatic cognitions, and belief in being "a fragile person in a scary world”. Within the TAU group, post-treatment scores were notably lower just in dissociation and intrusion symptoms. The study suggests that app-assisted TF-CBT-based intervention can be effective in addressing specific trauma-related symptoms. The findings imply the necessity for screening for traumatic experiences, incorporating trauma-informed care, implementation of TF-CBT into treatment protocols, utilization of app-assisted interventions, tailoring interventions to individual needs, and comprehensive assessment and monitoring of treatment progress.

Idiopathic lung fibrosis (IPF) is a progressive and fatal degenerative lung disease of unknown etiology. Although in its final stages it implicates in a reactive manner all lung cell types, the initial damage involves the alveolar epithelial compartment, in particular the alveolar epithelial type 2 cells (AEC2s). AEC2s serve dual progenitor and surfactant secreting functions, both of which are deeply impacted in IPF. Thus, we hypothesize that the size of the surfactant processing compartment, as measured by Lysotracker incorporation, allows the identification of different epithelial states in the IPF lung. Flow cytometry analysis of epithelial Lysotracker incorporation delineates two populations (Lysohigh and Lysolow) of AEC2s which behave in a compensatory manner during bleomycin injury and in the donor/IPF lung. Employing flow cytometry and transcriptomic analysis of cells isolated from donor and IPF lungs, we demonstrate that the Lysohigh population expresses all classical AEC2 markers and is drastically diminished in IPF. The Lysolow population, which is increased in proportion in IPF, co-expresses AEC2s and basal cell markers resembling the phenotype of the previously identified intermediate AEC2 population in the IPF lung. In that regard, we provide an in-depth flow-cytometry characterization of Lysotracker uptake, HTII-280, proSP-C, mature SP-B, NGFR, KRT5 and CD24 expression in human lung epithelial cells. Combining functional analysis with extra- and intra- cellular marker expression and transcriptomic analysis, we advance the current understanding of epithelial cell behavior and fate in lung fibrosis.

The night has historically been neglected in both disciplinary and interdisciplinary research. To some extent, this is not surprising, given the diurnal bias of human researchers, and the difficulty of performing work at night. The night is, however, a critical element of biological, chemical, physical, and social systems on Earth. Moreover, research into social issues such as inequality, demographic changes, and the transition to a sustainable economy will be compromised if night is not considered. Recent years, however, have seen a surge in research into the night. We argue that “night studies” is on the cusp of coming into its own as an interdisciplinary field, and when it does, the field will consider questions that disciplinary researchers haven’t yet thought to ask.

Biometric fingerprint identification hinges on the reliability of its sensors, however, calibrating and standardizing these sensors poses significant challenges, particularly in regard to repeatability and data diversity. To tackle these issues, we propose methodologies for fabricating synthetic 3D fingerprint targets, or phantoms, that closely emulate real human fingerprints. These phantoms enable the precise evaluation and validation of fingerprint sensors under controlled and repeatable conditions. Our research employs laser engraving, 3D printing, and CNC machining techniques, utilizing different materials. We assess the phantoms' fidelity to synthetic fingerprint patterns, intra-class variability, and interoperability across different manufacturing methods. The findings demonstrate that a combination of laser engraving or CNC machining with silicone casting produces finger-like shaped phantoms with high accuracy and consistency for rolled fingerprint recordings. For slap recordings, direct laser engraving of flat silicone targets excels and in the contactless fingerprint sensor setting, 3D printing and silicone filling provides the most favorable attributes. Our work enables a comprehensive, method-independent comparison of various fabrication methodologies, offering a unique perspective on the strengths and weaknesses of each approach. This facilitates a broader understanding of fingerprint recognition system validation and performance assessment.

Background: Manoka Health District (MHD), an enclaved archipelago district in Cameroon, is home to about 1,732 under-2 children. Over 90% of these children have not received a single dose of any vaccine. In this paper, we explored the reasons for the high proportion of zero-dose children in this district so as to generate information that policymakers can use to develop context-specific interventions to boast coverage for routine immunization (RI) in this remote fishing island Methodology: We collected qualitative data via key informant interviews (KII) and focused group discussions (FGD) and analyzed it using thematic analysis. Participants for KII were selected using purposive sampling, and a snowballing approach helped to recruit an intermixed population of locals and immigrants for FGDs. Results: MHD is a hard-to-reach zone with a lone health facility that lack a functional cold chain equipment to cover the 47 islets of the district. Diurnal floods, long distance, sea turbulence, infrastructural and resource constraints, and immigrant population without residence permits hinders optimal childhood vaccination. Insufficient community health workers and lack of proper community engagement with feedback loops hamper effective communication and vaccine uptake during campaigns and outreaches. The reasons for vaccination hesitancy included hospital-based vaccination preference over home-based vaccination, fear of post-vaccination fever, rumors, repeated postponement of the vaccination schedules, and refusal by some ethnic group leaders. Conclusion: This study revealed context-specific reasons for zero-dose childhood vaccination status in MHD. These findings should be leveraged to design tailored interventions to raise RI in MHD and similar under-vaccinated communities. Keywords: zero-dose, childhood vaccination, missed communities, Cameroon

Operational weather and also flood forecasting has been performed successfully for decades and is of great socioeconomic importance. Up to now, forecast products focus on atmospheric variables, such as precipitation, air temperature and, in hydrology, on river discharge. Considering the full terrestrial system from groundwater across the land surface into the atmosphere, a number of important hydrologic variables are missing especially with regard to the shallow and deeper subsurface (e.g. groundwater), which are gaining considerable attention in the context of global change. In this study, we propose a terrestrial monitoring/forecasting system using the Terrestrial Systems Modeling Platform (TSMP) that predicts all essential states and fluxes of the terrestrial hydrologic and energy cycles from groundwater into the atmosphere. Closure of the terrestrial cycles provides a physically consistent picture of the terrestrial system in TSMP. TSMP has been implemented over a regional domain over North Rhine-Westphalia and a continental domain over European in a real-time forecast/monitoring workflow. Applying a real-time forecasting/monitoring workflow over both domains, experimental forecasts are being produced with different lead times since the beginning of 2016. Real-time forecast/monitoring products encompass all compartments of the terrestrial system including additional hydrologic variables, such as plant available soil water, groundwater table depth, and groundwater recharge and storage.

A roadmap is proposed that defines a systematic approach for craft preservation and its evaluation. The proposed roadmap aims at deepening craft understanding, so blueprints of appropriate tools that support craft documentation, education, and training can be designed while achieving preservation through the stimulation and diversification of practitioner income. A roadmap is required because understanding making activities that include “care, judgement, and dexterity” [1] call for interdisciplinary contributions from Anthropology, Cognitive Science, Art History, as well as Physical and Computational Sciences, to cover the multifaceted expression of crafts as living and developing heritage, as a source of income, and as the expression of the mind through “imagery, technology, and sedimented knowledge” [2]. In addition to this roadmap, an evaluation strategy is proposed to validate the efficacy of the developed results and provide a benchmark for the efficacy of craft preservation approaches. The proposed contribution aims at the catalysation of craft education and training with digital aids, widening access and engagement to crafts, economising learning, increasing exercisability, and relaxing remoteness constraints in craft learning.

In this work commercial 18650 lithium-ion cells with LiMn₂O₄, LiFePO₄ and Li(Ni_0.33Mn_0.33Co_0.33)O₂ cathodes were exposed to external heating in an Accelerating Rate Calorimeter (es-ARC, THT Company) to investigate the thermal behavior under abuse conditions. New procedures for measuring external and internal pressure change of cells were developed. The external pressure was measured utilizing a gas-tight cylinder inside the calorimeter chamber in order to detect venting of the cells. For internal pressure measurements, a pressure line connected to a pressure transducer was directly inserted into the cell. During the thermal runaway experiments, three stages (low rate, medium rate and high rate reaction) have been observed. Both pressure and temperature change indicated different stages of exothermic reactions, which produced gases or/and heat. The onset temperature of thermal runaway was estimated according to temperature and pressure changes. Moreover, the different activation energies for the exothermic reactions could be derived from Arrhenius plots.