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Background Globocan data for 2020 rank lung cancer as the third most common malignancy (12.1%) and the deadliest cancer (18.3%) in Bulgaria. The current study aims to analyze lung cancer patient pathways and time to treatment from diagnosis based on real-world data. Methods We conducted an observational database study based on the secondary use of data collected for other purposes for 3 years (2020–2022). The main outcomes of interest were time from diagnosis to therapy measured in days on national and regional levels, stratified by therapy type and year and number of newly diagnosed patients with lung cancer in each of the years for the observed period. Data were analyzed through descriptive statistics. Results Throughout the observed period, 8,585 patients were newly diagnosed with lung cancer, averaging approximately 2,861 diagnoses per year. Most patients’ records reported non-small cell lung cancer (4536, 64%), Furthermore, most patients were diagnosed with advanced stages of cancer, with 61% (4297) being diagnosed with Stage IV. Time from Diagnosis to First Treatment (median) outcome showed variance by regions and type, from 7 to 40 days in the case of surgical treatment and 26 to 85 days in the case of combination therapy. The time from Diagnosis to First Systemic Treatment indicator shows a median delay between diagnosis to treatment of 42 days. Conclusions The study confirms that dynamic patient registers are crucial for performing real-world studies of treatment patterns and identifying gaps and inequities on a national level. There is a significant need to address the lack of screening programs for lung cancer in Bulgaria and ensure more equitable distribution of oncology centers.

Diversifying cropping systems by increasing the number of cash and cover crops in crop rotation plays an important role in improving resource use efficiency and in promoting synergy between ecosystem processes. The objective of this study was to understand how the combination of crop diversification practices influences the performance of arable crop sequences in terms of crop grain yield, crop and weed biomass, and nitrogen acquisition in a temperate climate. Two field experiments were carried out. The first was a 3-year crop sequence with cereal or grain legume as the first crops, with and without undersown forage legumes and forage legume-grass crops, followed by a cereal crop. The second experiment was a 2-year crop sequence with cereal or legume as the first crops, a legume cover crop, and a subsequent cereal crop. For the first time, crop diversification practices were combined to identify plant-plant interactions in spatial and temporal scales. The results partly confirm the positive effect of diversifying cereal-based cropping systems by including grain legumes and cover crops in the crop sequence. Legume cover crops had a positive effect on subsequent cereal grain yield in one of the experiments. Using faba beans as the first crop in the crop sequence had both a positive and no effect on crop biomass and N acquisition of the subsequent cereal. In cover crops composed of a forage legume-grass mixture, the grass biomass and N acquisition were consistently increased after the grain legume, compared to the cereal-preceding crop. However, differences in the proportion of legume to grass in mixture did not influence crop yield or N acquisition in the subsequent cereal. In conclusion, these results support that increased crop diversity across spatial and temporal scales can contribute to resource-efficient production and enhance the delivery of services, contributing to more sustainable cropping systems.

The perennial forage grass Thinopyrum intermedium (Host) Barkworth & Dewey, commonly known as intermediate wheatgrass (IWG) or by the commercial name Kernza™, is being developed as a perennial grain crop, i.e. being bred for its improved agronomic performance and food qualities. Intercropping legumes and grasses is a strategy for improving resource use and sustainability in cropping systems. Here, we show for the first time the agronomic performance of IWG as a perennial cereal grown as a monocrop and as an intercrop (alternate row, 0.5:0.5) with Medicago sativa L. (alfalfa/lucerne) in southern Sweden. The seeds of cycle 3 IWG were accessed from The Land Institute (TLI) of Salinas, Kansas, USA, and used to establish a local seed production plot (in 2014) for the establishment of the perennial systems (in 2016) utilised in this study. Both the monocrop and intercrop were sown with 25 cm row spacing with alternate rows of IWG and alfalfa in the intercrop (i.e. replacement design) with unknown sowing density. Intercropping provided sustained IWG grain production under the dry conditions of 2018, but also in the following year. This was evidently associated with a higher nitrogen accumulation in intercropped practice. Thus, intercropping seems to have stabilised the IWG grain production in the dry conditions of 2018, when the grain production in the intercrop was similar to that of the monocrop in the same year. This result was further supported by the lower discrimination against 13 C (as an indicator of water use efficiency) in the intercrop components compared to the sole crop in 2018. The lower discrimination indicates high water use efficiency in the intercropped IWG in comparison to the IWG in monoculture, and we conclude that intercropping perennial cereal grain crops with legumes provides better growing conditions in terms of nitrogen acquisition, and water status, to cope with more extreme drought spells expected from climate change.

Diversification of cropping and farming systems is a central agroecological principle, which may improve resource use efficiency, reduce pests and diseases, diversify income sources, and enhance the resilience of the production. The main objective of this study was to identify challenges related to the sustainability of organic cropping systems that were diversified according to one or several of the following practices: diverse crop rotation, integration of cover crops, and intercropping. The sustainability assessments were made using a multi-criteria decision aid method (MCDA) and a framework based on the FAO Sustainability Assessment of Food and Agricultural Systems (SAFA) guidelines. Social, economic and environmental aspects were integrated in the sustainability assessments and combined with semi-structured interviews to identify and discuss farmer's perceptions of barriers to crop diversification and sustainability transition. The results showed that diversified organic cropping systems could achieve high overall sustainability, especially in the environmental dimension thanks to non-inputs of pesticides or mineral fertilizers and efficient use of resources. On the other hand, social and economic dimensions were more variable, with challenges of lower sustainability in profitability and management complexity for several of the diversified cropping systems. Limited access to knowledge, technology and markets for minor crops, and concerns about the consistency of policies were highlighted by farmers as barriers for crop diversification. We discuss how the identified challenges can be overcome and argue that fostering collaboration among stakeholders may increase investment capacity and improve access to new or alternative markets, thereby stimulating transitions toward more diversified and sustainable cropping systems.

ObjectivesTo compare costs associated with different models of outpatient parenteral antimicrobial therapy (OPAT) delivery with costs of inpatient (IP) care across key infection groups managed via OPAT in the UK.DesignA cost-minimisation design was used due to evidence of similarities in patient and treatment outcomes between OPAT and IP care. A bottom-up approach was undertaken for the evaluation of OPAT associated costs. The British Society of Antimicrobial Chemotherapy National Outcomes Registry System was used to determine key infection diagnoses, mean duration of treatment and most frequent antibiotics used.SettingSeveral OPAT delivery settings were considered and compared with IP care.InterventionsOPAT models considered were OP clinic model, nurse home visits, self (or carer)-administration by a bolus intravenous, self-administration by a commercially prefilled elastomeric device, continuous intravenous infusion of piperacillin with tazobactam or flucloxacillin with elastomeric device as OP once daily and, specifically for bone and joint and diabetic foot infections, complex outpatient oral antibiotic therapies.ResultsBase case and a range of scenario results showed all evaluated OPAT service delivery models to be less costly than IP stay of equivalent duration. The extent of savings varied by OPAT healthcare delivery models. Estimated OPAT costs as a proportion of IP costs were estimated at 0.23–0.53 (skin and soft-tissue infections), 0.34–0.46 (complex urinary tract infections), 0.23–0.51 (orthopaedic infections), 0.24–0.42 (diabetic foot infections) 0.40–0.56 (exacerbations of bronchiectasis) and 0.25–0.42 (intra-abdominal infections). Partial or full complex oral antibiotic therapies in orthopaedic or diabetic foot infections costs were estimated to be 0.13–0.26 of IP costs. Main OPAT costs were associated with staff time and antimicrobial medications.ConclusionsOPAT is a cost-effective use of National Health Service resources for the treatment of a range of infections in the UK in patients who can be safely managed in a non-IP setting.

Background Seed endophytes have a significant impact on plant health and fitness. They can be inherited and passed on to the next plant generation. However, the impact of breeding on their composition in seeds is less understood. Here, we studied the indigenous seed microbiome of a recently domesticated perennial grain crop (Intermediate wheatgrass, Thinopyrum intermedium L.) that promises great potential for harnessing microorganisms to enhance crop performance by a multiphasic approach, including amplicon and strain libraries, as well as molecular and physiological assays. Results Intermediate wheatgrass seeds harvested from four field sites in Europe over three consecutive years were dominated by Proteobacteria (88%), followed by Firmicutes (10%). Pantoea was the most abundant genus and Pantoea agglomerans was identified as the only core taxon present in all samples. While bacterial diversity and species richness were similar across all accessions, the relative abundance varied especially in terms of low abundant and rare taxa. Seeds from four different breeding cycles (TLI C3, C5, C704, C801) showed significant differences in bacterial community composition and abundance. We found a decrease in the relative abundance of the functional genes nirK and nifH as well as a drop in bacterial diversity and richness. This was associated with a loss of amplicon sequence variants (ASVs) in Actinobacteria , Alphaproteobacteria , and Bacilli , which could be partially compensated in offspring seeds, which have been cultivated at a new site. Interestingly, only a subset assigned to potentially beneficial bacteria, e.g. Pantoea, Kosakonia , and Pseudomonas , was transmitted to the next plant generation or shared with offspring seeds. Conclusion Overall, this study advances our understanding of the assembly and transmission of endophytic seed microorganisms in perennial intermediate wheatgrass and highlights the importance of considering the plant microbiome in future breeding programs.

The coal industry is the largest global emitter of carbon dioxide (CO2). However, recent data suggests that coal mine methane (CH4) emissions worldwide are higher than those of the oil and gas industry. Furthermore, the coal industry is less active in reducing methane emissions than the oil and gas sectors due to lower profitability. Although uncertainties remain in quantifying methane emissions from mines, the use of satellite observations is revolutionizing the process of monitoring and improving the accuracy of emission accounting. The methodology presented here allows us to determine background CH4 concentrations and improve our ability to detect emission events using Sentinel-5P data. Knowing the background concentrations for the area of interest provides us the opportunity to track seasonal and annual variations and trends, as well as quickly detect periodic or accidental emissions from unregulated sources, etc. The methodology and systematic research applied in this paper for the period of May 2018 to the end of 2022 enables us to detect hundreds of large-scale emissions of CH4, NO2, and CO from the coal mines in the Kuznetsk Basin (the Kemerovo region), the largest coal mining area in Russia. We estimated that the amount of these emissions is significantly higher than the emissions reported by various authors for other coal mining regions such as Poland and Australia. We found that in cases of high methane quantity there is a positive correlation between NO2 and CO emissions in time and location. The source of emissions in the study area is homogeneous, which allows it to be used as a benchmark for building models to estimate and track emissions in heterogeneous areas.

Mammalian target‐of‐rapamycin (mTOR) triggers S6 kinase (S6K) activation to phosphorylate targets linked to translation in response to energy, nutrients, and hormones. Pathways of TOR activation in plants remain unknown. Here, we uncover the role of the phytohormone auxin in TOR signalling activation and reinitiation after upstream open reading frame (uORF) translation, which in plants is dependent on translation initiation factor eIF3h. We show that auxin triggers TOR activation followed by S6K1 phosphorylation at T449 and efficient loading of uORF‐mRNAs onto polysomes in a manner sensitive to the TOR inhibitor Torin‐1. Torin‐1 mediates recruitment of inactive S6K1 to polysomes, while auxin triggers S6K1 dissociation and recruitment of activated TOR instead. A putative target of TOR/S6K1—eIF3h—is phosphorylated and detected in polysomes in response to auxin. In TOR‐deficient plants, polysomes were prebound by inactive S6K1, and loading of uORF‐mRNAs and eIF3h was impaired. Transient expression of eIF3h‐S178D in plant protoplasts specifically upregulates uORF‐mRNA translation. We propose that TOR functions in polysomes to maintain the active S6K1 (and thus eIF3h) phosphorylation status that is critical for translation reinitiation. The phytohormone Auxin activates the TOR pathway to dissociate inactive S6K1 from polysomes and to stimulate phosphorylation of the translation initiation factor eIF3h, resulting in the enhanced translation of uORF‐containing mRNAs.

The intensification of agriculture has led to environmental degradation, including the loss of biodiversity. This has prompted interest in perennial grain cropping systems to address and mitigate some of these negative impacts. In order to determine if perennial grain cultivation promotes a higher microbial diversity, we assessed the endophytic microbiota of a perennial grain crop (intermediate wheatgrass, Thinopyrum intermedium L.) in comparison to its annual counterpart, wheat (Triticum aestivum L.). The study covered three sampling sites in a pan-European gradient (Sweden, Belgium, and France), two plant genotypes, three plant compartments (roots, stems, and leaves), and two sampling time points. We observed that the host genotype effect was mainly evident in the belowground compartment, and only to a lesser extent in the aboveground tissues, with a similar pattern at all three sampling sites. Moreover, intermediate wheatgrass roots harbored a different bacterial community composition and higher diversity and richness compared to their annual counterparts. The root bacterial diversity was influenced by not only several soil chemical parameters, such as the carbon:nitrogen ratio, but also soil microbial parameters, such as soil respiration and dehydrogenase activity. Consistent findings across time and space suggest stable mechanisms in microbiota assembly associated with perennial grain cropping, underscoring their potential role in supporting biodiversity within sustainable agricultural systems.