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Background: Monomicrobial Enterobacterales necrotizing fasciitis is associated with exceedingly high mortality rates. Although effective antimicrobial therapy is an important part of treatment, the traditional microbiological diagnostic methods are not fast enough to meaningfully influence early therapeutic decisions. Methods: Here, we report the application of the BioMérieux Biofire Filmarray Joint Infection Panel (BFJIP) for the rapid detection of the causative agent and susceptibility prediction in such a case. Aside from the BFJIP-based rapid diagnostic approach and culturing, the whole genome sequencing (WGS) of the causative agent was performed using Illumina MiSeq and Oxford Nanopore MinION platforms. Results: The BFJIP indicated the presence of K. pneumoniae, without KPC, VIM, IMP, NDM, OXA-48 carbapenemase genes, and CTX-M-type extended-spectrum beta-lactamases. Based on the WGS data, the isolate belonged to the K1-capsule-type ST23, harboured a pNTUH-2044-like plasmid, and was positive for all the virulence factors associated with this lineage. The conventional susceptibility results were also in accordance with the BFJIP results; the isolate lacked any of these acquired resistance mechanisms. Conclusions: Despite this being the first case of the successful identification of pathogenic bacteria in necrotising fasciitis using this assay, the BFJIP may become a useful tool for rapid identification of pathogens in necrotising fasciitis cases and guiding antimicrobial therapy for better clinical outcomes. [ABSTRACT FROM AUTHOR]

This research study investigated the production and properties of zinc oxide (ZnO) nanoparticles derived from corn husks and their priming effects on wheat plant proliferation and antioxidant mechanisms compared to the nutri-priming technique under regular irrigation and drought-stressed conditions. Transmission and scanning electron microscopy (TEM and SEM), energy-dispersive X-ray spectroscopy (EDAX), and X-ray diffraction confirmed the nanoparticles' hexagonal morphology and typical dimensions of 51 nm. The size and stability of these nanoparticles were assessed through the size distribution and zeta potential analysis, indicating reasonable stability. Fourier-transform infrared spectroscopy (FTIR) detected the newly formed functional groups. This study emphasized the role of reactive oxygen species (ROS) and phenolic compounds in plant responses to nanoparticle treatment, particularly in detoxifying harmful radicals. The research also examined the activity of antioxidant enzymes, including peroxidase (POX), catalase (CAT), and glutathione reductase (GR), in alleviating stress caused by oxidation while subjected to various treatments, including micronutrient seed priming with DR GREEN fertilizer. Some biochemical compounds, such as total phenolics (TPCs), total flavonoids (TFCs), and total hydrolysable sugars, were estimated as well to show the effect of the different treatments on the wheat plants. The findings suggested that ZnO nanoparticles can enhance antioxidant enzyme activity under certain conditions while posing phytotoxic risks, underscoring the complexity of plant–nanoparticle interactions and the potential for improving crop resilience through targeted micronutrient applications. [ABSTRACT FROM AUTHOR]

The study investigated the application of humic acids (HAs) and a combination of humic acids and amino acids (HA+AA) in maize under field conditions. Based on preliminary data in the literature, the aim was to investigate the effects of the two plant conditioning compounds on plant physiological parameters. In addition to measuring plant physiological parameters in the field, a complete transcriptome analysis was performed to determine exactly which genes were expressed after the treatments and in which physiological processes they play a role. Maize plants showed significant positive yield changes after two priming treatments. Genome-wide transcriptomic analysis revealed the activation of photosynthetic and cellular respiration processes, as well as protein synthesis pathways, which explains the increased yield even under extreme precipitation conditions. The results show that the HA treatment helped in water management and increased the chlorophyll content, while the HA+AA treatment led to higher protein and dry matter contents. The post-harvest tests also show that the HA+AA treatment resulted in the highest yield parameters. Functional annotation of the maize super transcriptome revealed genes related to translation processes, photosynthesis, and cellular respiration. The combined pathway analysis showed that the HA and combined treatments activated genes related to photosynthesis, carbon fixation, and cellular respiration, providing valuable in-depth insight into the usefulness of the HA and HA+AA treatments in priming. Based on the studies, we believe that the use of natural-based humic acid plant conditioners may provide a beneficial opportunity to promote renewable, regenerative agriculture. [ABSTRACT FROM AUTHOR]

Biochar, a carbon-rich by-product of organic matter pyrolysis, has a variety of physiochemical properties beside a variety of applications. This review highlights some physical and chemical characteristics of herbaceous, woody, and sewage waste biochar under different pyrolysis conditions, as well as soil and foliar applications of biochar. The controlling role of pyrolysis temperature was the reason for selecting the discussed biochar types in the study. This review concludes that increasing pyrolysis temperature mainly raised the values of some chemical properties of the biochar, such as pH, electrical conductivity (EC), ash content, total phosphorus (TP), and a few values of physical properties like porosity and specific surface area (SSA). On the other hand, yield and total nitrogen (TN) decreased with rising pyrolysis temperature. Among biochar application methods to soil, mixing biochar with soil before planting is one of the best methods of application, and in most cases, biochar reapplication improved soil properties, while foliar application of biochar has positive effects on plant growth and yield parameters, ranging from low rates to the highest ones. [ABSTRACT FROM AUTHOR]

Objectives: Rezafungin is the first new drug approved to treat candidaemia and invasive candidiasis in more than 10 years. However, data are scant on the in vivo efficacy of rezafungin and the other three approved echinocandins against different Candida auris clades. Methods: This study involved 10 isolates representing 4 C. auris clades: South Asian (n = 2), East Asian (n = 2), South African (n = 2), and South American (n = 4, including 2 environmental isolates). In the lethality experiment and fungal tissue burden experiment (kidney, heart, and brain), cyclophosphamide-treated BALB/c male mice were intravenously infected (107 and 8 × 106 colony-forming units [CFU]/mouse, respectively). A 20 mg/kg dose of rezafungin was administered on days 1, 3, and 6. Alternatively, beginning 24 h post-infection, mice received 3 mg/kg of caspofungin, 5 mg/kg of micafungin, or 5 mg/kg of anidulafungin once daily for 6 days. Results: Regardless of isolate and clade, all echinocandin regimens improved survival after 21 days (p = 0.0041 to p < 0.0001). All echinocandins frequently produced >3-log mean CFU/g decreases in the fungal kidney and heart burdens, although some of these decreases were not statistically significant. Rezafungin, regardless of clade, produced 3–5 and 2–4 log CFU/g decreases in the kidney and heart burdens, respectively. Echinocandins did not inhibit fungal growth in the brain. Histopathological examination performed on day 7 showed no fungal cells in the heart and kidneys of rezafungin-treated mice and to a lesser extent, caspofungin-treated mice, regardless of the clinical isolate. All echinocandin-treated mice showed medium and/or large foci of fungal cells in their cerebrum or cerebellum. Conclusions: Regardless of the C. auris clade, rezafungin activity in vivo was comparable to or improved over that of the three previously approved echinocandins. [ABSTRACT FROM AUTHOR]

Bilophila wadsworthia is a Gram-negative anaerobic bacterium. In current study, it was identified in the bloodstream of a 69-year-old man admitted to the Neurology Clinic at the University of Debrecen, Clinical Centre, Hungary, for internal carotid artery stent implantation. Bacteraemia caused by B. wadsworthia is extremely rare, with very few cases reported worldwide. This case is notable because it is the first instance in which whole-genome sequencing of B. wadsworthia derived from blood was performed. Moreover, the sequence data have been deposited in a public database. [ABSTRACT FROM AUTHOR]

High salinity reduces agriculture production and quality, negatively affecting the global economy. Zinc oxide nanoparticles (ZnO-NPs) enhance plant metabolism and abiotic stress tolerance. This study investigated the effects of 2 g/L foliar Zinc oxide NPs on Zea mays L. plants to ameliorate 150 mM NaCl-induced salt stress. After precipitation, ZnO-NPs were examined by UV–visible spectroscopy, transmission electron microscopy, scanning transmission electron microscopy, energy dispersive X-ray, and particle size distribution. This study examined plant height, stem diameter (width), area of leaves, chlorophyll levels, hydrolyzable sugars, free amino acids, protein, proline, hydrogen peroxide, and malondialdehyde. Gas chromatographic analysis quantified long-chain fatty acids, and following harvest, leaves, stalks, cobs, seeds, and seeds per row were weighed. The leaves' acid and neutral detergent fibers were measured along with the seeds' starch, fat, and protein. Plant growth and chlorophyll concentration decreased under salt stress. All treatments showed significant changes in maize plant growth and development after applying zinc oxide NPs. ZnO-NPs increased chlorophyll and lowered stress. ZnO-NPs enhanced the ability of maize plants to withstand the adverse conditions of saline soils or low-quality irrigation water. This field study investigated the effect of zinc oxide nanoparticles on maize plant leaves when saline water is utilized for growth season water. This study also examined how this foliar treatment affected plant biochemistry, morphology, fatty acid synthesis, and crop production when NaCl is present and when it is not. [ABSTRACT FROM AUTHOR]

Plants endure the repercussions of environmental stress. As the advancement of global climate change continues, it is increasingly crucial to protect against abiotic and biotic stress effects. Some naturally occurring plant compounds can be used effectively to protect the plants. By externally applying priming compounds, plants can be prompted to trigger their defensive mechanisms, resulting in improved immune system effectiveness. This review article examines the possibilities of utilizing exogenous alpha-, beta-, and gamma-aminobutyric acid (AABA, BABA, and GABA), which are non-protein amino acids (NPAAs) that are produced naturally in plants during instances of stress. The article additionally presents a concise overview of the studies' discoveries on this topic, assesses the particular fields in which they might be implemented, and proposes new avenues for future investigation. [ABSTRACT FROM AUTHOR]

Salinity reduces crop yields and quality, causing global economic losses. Zinc oxide nanoparticles (ZnO-NPs) improve plant physiological and metabolic processes and abiotic stress resistance. This study examined the effects of foliar ZnO-NPs at 75 and 150 mg/L on tomato Kecskeméti 549 plants to alleviate salt stress caused by 150 mM NaCl. The precipitation procedure produced ZnO-NPs that were characterized using UV-VIS, TEM, STEM, DLS, EDAX, Zeta potential, and FTIR. The study assessed TPCs, TFCs, total hydrolyzable sugars, total free amino acids, protein, proline, H2O2, and MDA along with plant height, stem width, leaf area, and SPAD values. The polyphenolic burden was also measured by HPLC. With salt stress, plant growth and chlorophyll content decreased significantly. The growth and development of tomato plants changed by applying the ZnO-NPs. Dosages of ZnO-NPs had a significant effect across treatments. ZnO-NPs also increased chlorophyll, reduced stress markers, and released phenolic chemicals and proteins in the leaves of tomatoes. ZnO-NPs reduce salt stress by promoting the uptake of minerals. ZnO-NPs had beneficial effects on tomato plants when subjected to salt stress, making them an alternate technique to boost resilience in saline soils or low-quality irrigation water. This study examined how foliar application of chemically synthesized ZnO-NPs to the leaves affected biochemistry, morphology, and phenolic compound synthesis with and without NaCl. [ABSTRACT FROM AUTHOR]

One of the most significant environmental challenges to crop growth and yield worldwide is soil salinization. Salinity lowers soil solution water potential, causes ionic disequilibrium and specific ion effects, and increases reactive oxygen species (ROS) buildup, causing several physiological and biochemical issues in plants. Plants have developed biological and molecular methods to combat salt stress. Salt-signaling mechanisms regulated by phytohormones may provide additional defense in salty conditions. That discovery helped identify the molecular pathways that underlie zinc-oxide nanoparticle (ZnO-NP)-based salt tolerance in certain plants. It emphasized the need to study processes like transcriptional regulation that govern plants' many physiological responses to such harsh conditions. ZnO-NPs have shown the capability to reduce salinity stress by working with transcription factors (TFs) like AP2/EREBP, WRKYs, NACs, and bZIPs that are released or triggered to stimulate plant cell osmotic pressure-regulating hormones and chemicals. In addition, ZnO-NPs have been shown to reduce the expression of stress markers such as malondialdehyde (MDA) and hydrogen peroxide (H2O2) while also affecting transcriptional factors. Those systems helped maintain protein integrity, selective permeability, photosynthesis, and other physiological processes in salt-stressed plants. This review examined how salt stress affects crop yield and suggested that ZnO-NPs could reduce plant salinity stress instead of osmolytes and plant hormones. [ABSTRACT FROM AUTHOR]

Using native species for urban green space is rather important nowadays. Plant cover on soil is necessary for agronomical and architectural investments as well as conservational programs, which all need minimal maintenance and have to be cost efficient. Commercially available seed mixtures for grasslands and lawns include species that partly originated from other mesoclimatic zones, and thus they may not be able to survive in the long-term, nor will they be adventive to the local ecosystem. With a focus on climate change, the most arid part of the Pannon geographical region was selected (near Törökszentmiklós in Nagykunság, Hungarian Great Plain). The local flora has adapted effectively to the environment; therefore, many species growing there were candidates for this study. Annuals and herbaceous perennials were investigated with respect to harvestability, reproducibility, decorativity, seed production, seed morphological characters (size, mass) and germination features. The selected 20 taxa were inoculated with INOQ Agri mycorrhiza (Rhizophagus irregularis) to increase the drought tolerance and biomass of the plants. Mycorrhizal frequency was significantly different among the taxa, reflecting various responses to the symbiotic interaction and possibly various mycorrhizal dependence of the plant species examined. We did not observe significantly higher colonization rate in most cases of the samples with artificial inoculation treatment. We conclude that the degraded mowed lawn soil that we used could contain propagules of AM fungi in a sufficient amount, so in the artificial grassland restorations, the additional AM inoculation treatment is not necessary to achieve a higher AM colonization rate. [ABSTRACT FROM AUTHOR]

Bacterial spot disease on peppers is caused by four species of the genus Xanthomonas. This disease causes black spot lesions not only on the leaves but also on the fruit, leading to yield and quality loss. Xanthomonas species cause major disease outbreaks in tropical, subtropical and humid continental regions worldwide. Bacterial blight caused by xanthomonads occurs on both greenhouse- and field-grown peppers and is particularly important in areas characterized by hot and humid environmental conditions. As pesticides are currently not sufficiently effective in the control of bacterial spot, the development of pepper varieties resistant to Xanthomonas species, including X. hortorum pv. gardneri, is of primary importance for sustainable production. In our research, 119 lines of Capsicum baccatum from the USDA ARS gene bank (Griffin, GA) and MATE (Hungarian University of Agriculture and Life Sciences) were tested against strains of X. hortorum pv. gardneri under greenhouse conditions. Four accessions of the wild pepper species C. baccatum appeared to be resistant to seven strains of X. hortorum pv. gardneri in greenhouse trials. The resistant genotypes of X. hortorum pv. gardneri identified in this study can be used for the resistance gene pyramidation against different bacterial spotted Xanthomonas species in pepper. [ABSTRACT FROM AUTHOR]

Azadirachta indica has several medicinal uses, especially its leaves. Over 4000 years ago, Ayurvedic medicine used it for its therapeutic benefits. This study examined the biological activity of Neem crude extracts and green-chemically produced Ag-NPs. TPCs and TFCs were measured for polyphenolic burden in consecutive extracts. DPPH, ABTS, and FRAP experiments measured antioxidant and antimicrobial activity against seven strains of food-borne pathogenic bacteria and eight mycotoxigenic fungi. At 1000 μg/mL, ethanolic and aqueous extracts of Neem leaves had 80.10% and 69.41% in DPPH and 71.42% and 74.61% in ABTS assays for the antioxidant activity, compared to 93.58% for BHT. At 800 μg/mL, both extracts showed antioxidant activity with 57.52 and 57.87 μM in the FRAP assay, compared to 139.97 μM for Ascorbic acid. Both extracts demonstrated antimicrobial activity with 0.02 to 0.35 mg/mL as antibacterials, 0.03 to 2.17 mg/mL as antifungals, and 0.04 to 0.42 mg/mL as antibacterials. Compared to Neem crude extract, Neem Ag-NPs had the lowest MIC values as antibacterials and antifungals at 0.05 to 0.07 mg/mL and 0.07 to 0.20 mg/mL, respectively. Neem Ag-NPs and crude extract boost antioxidant and antibacterial properties. [ABSTRACT FROM AUTHOR]

Gene function analysis, molecular breeding, and the introduction of new traits in crop plants all require the development of a high-performance genetic transformation system. In numerous crops, including tomatoes, Agrobacterium-mediated genetic transformation is the preferred method. As one of our ongoing research efforts, we are in the process of mapping a broad-spectrum nematode resistance gene (Me1) in pepper. We work to transform tomato plants with candidate genes to confer resistance to nematodes in Solanaceae members. The transformation technology development is designed to produce a reproducible, rapid, and highly effective Agrobacterium-mediated genetic transformation system of Micro-Tom. In our system, a transformation efficiency of over 90% was achieved. The entire procedure, starting from the germination of seeds to the establishment of transformed plants in soil, was completed in 53 days. We confirmed the presence of the NeoR/KanR and DsRed genes in the transformed roots by polymerase chain reaction. The hairy root plants were infected with nematodes, and after 3 months, the presence of DsRed and NeoR/KanR genes was detected in the transformant roots to confirm the long-term effectiveness of the method. The presented study may facilitate root-related research and exploration of root–pathogen interactions. [ABSTRACT FROM AUTHOR]

Candida auris is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against C. auris is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four C. auris clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the FKS1 gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of FKS1 but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of FKS1, but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of FKS1. The simultaneous inhibition of β-1,3 glucan and chitin synthases in wild-type C. auris isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible C. auris isolates. [ABSTRACT FROM AUTHOR]

Research on the use of different parts of the Moringa oleifera plant as a nutritional and pharmaceutical resource for human and animals has increased in recent years. This study aimed to investigate the chemical composition and the TPCs and TFCs of Moringa leaves, the antimicrobial activities of Moringa successive ethanolic, aqueous, crude aqueous extracts, and green-chemically synthesized characterized Ag-NPs. The results indicated that the ethanolic extract recorded the highest activity against E. coli. On the other side, the aqueous extract showed higher activity, and its effects ranged from 0.03 to 0.33 mg/mL against different strains. The MIC values of Moringa Ag-NPs against different pathogenic bacteria ranged from 0.05 mg/mL to 0.13 mg/mL, and the activity of the crude aqueous extract ranged from 0.15 to 0.83 mg/mL. For the antifungal activity, the ethanolic extract recorded the highest activity at 0.04 mg/mL, and the lowest activity was recorded at 0.42 mg/mL. However, the aqueous extract showed effects ranging from 0.42 to 1.17 mg/mL. Moringa Ag-NPs showed higher activity against the different fungal strains than the crude aqueous extract, and they ranged from 0.25 to 0.83 mg/mL. The MIC values of the Moringa crude aqueous extract ranged from 0.74 to 3.33 mg/mL. Moringa Ag-NPs and their crude aqueous extract may be utilized to boost antimicrobial attributes. [ABSTRACT FROM AUTHOR]

A major abiotic barrier to crop yield and profitability is salt stress, which is most prevalent in arid and semi-arid locations worldwide. Salinity tolerance is complicated and multifaceted, including a variety of mechanisms, and to adapt to salt stress, plants have constructed a network of biological and molecular processes. An expanding field of agricultural research that combines physiological measures with molecular techniques has sought to better understand how plants deploy tolerance to salinity at various levels. As the first line of defense against oxidative damage brought on by salt stress, host plants synthesize and accumulate several osmoprotectants. They (osmoprotectants) and other phytohormones were shown to serve a variety of protective roles for salt stress tolerance. Intrinsic root growth inhibition, which could be a protection mechanism under salty conditions, may be dependent on phytohormone-mediated salt signaling pathways. This article may also make it easier for scientists to determine the precise molecular processes underlying the ZnO-NPs-based salinity tolerance response for some plants. ZnO-NPs are considered to improve plant growth and photosynthetic rates while also positively regulating salt tolerance. When plants are under osmotic stress, their administration to zinc nanoparticles may also affect the activity of antioxidant enzymes. So, ZnO-NPs could be a promising method, side by side with the released osmoprotectants and phytohormones, to relieve salt stress in plants. [ABSTRACT FROM AUTHOR]

Increasing prevalence of A. baumannii was found in the faecal samples of inpatients without infection caused by A. baumannii (0.15%; 55/7806). The aim of the study was to determine whether there is a relationship between the clinical strains and the increased faecal occurrence. Characteristics of faecal and clinical isolates were compared between 2017 and 2019, and the direction of causality was assessed by Granger causality tests. In the case of the antibiotic resistance, faecal carriage of carbapenem-resistant Acinetobacter baumannii (CRAb) was Granger-caused by prevalence of CRAb in inpatients (F = 15.84, p < 0.001), but inpatient prevalence was not Granger-caused by CRAb faecal carriage (F = 0.03, p = 0.855). Whole genomes of 16 faecal isolates were sequenced by Illumina MiSeq; cgMLST types were determined. In faecal isolates, the occurrence of carbapenem resistance was lower than among the clinical isolates from the same period; only blaOXA-72 harbouring ST636 and ST492 were detected, and the blaOXA-23 harbouring ST2 and ST49 strains previously dominant in clinical isolates were absent. Carriage of blaOXA-72 was linked to pMAL-1-like and pA105-2-like plasmids in ST636 and ST492 isolates, respectively, both in clinical and faecal isolates. The new ST636 and ST492 strains may colonise the gut microbiota of the patients, which thus may play a role as a reservoir. [ABSTRACT FROM AUTHOR]

Philadelphus coronarius is a versatile plant and its use in folk medicine has a long tradition; however, scientifically, the medical utilization of the herb is a less explored research field. The aim of our study was to identify and determine the quantity of the bioactive compounds of both the leaf and the flower and prepare a lyophilized product of them, from which medical ointments were formulated, since the topical application of P. coronarius has also not been studied. In vitro drug release, texture analysis and biocompatibility experiments were carried out, as well as the investigation of microbiological, antioxidant and anti-inflammatory properties. According to our results the composition and the selected excipients of the ointments have a great impact on the drug release, texture and bioavailability of the preparation. During the microbiological testing, the P. coronarius leaf was effective against Escherichia coli and Staphylococcus aureus, but it did not significantly decrease IL-4 production when it was tested on HaCaT cells. P. coronarius is a promising herb, and its topical application in antimicrobial therapy can be a useful addition to modern medical therapy. [ABSTRACT FROM AUTHOR]

The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data. [ABSTRACT FROM AUTHOR]

The use of yeast-containing probiotics is on the rise; however, these products occasionally cause fungal infections and possibly even fungemia among susceptible probiotic-treated patients. The incidence of such cases is probably underestimated, which is why it is important to delve deeper into the pathomechanism and the adaptive features of S. 'boulardii'. Here in this study, the potential role of the gene heme oxygenase-1 (HMX1) in probiotic yeast bloodstream-derived infections was studied by generating marker-free HMX1 deletion mutants with CRISPR/Cas9 technology from both commercial and clinical S. 'boulardii' isolates. The six commercial and clinical yeasts used here represented closely related but different genetic backgrounds as revealed by comparative genomic analysis. We compared the wild-type isolates against deletion mutants for their tolerance of iron starvation, hemolytic activity, as well as kidney burden in immunosuppressed BALB/c mice after lateral tail vein injection. Our results reveal that the lack of HMX1 in S. 'boulardii' significantly (p < 0.0001) increases the kidney burden of the mice in most genetic backgrounds, while at the same time causes decreased growth in iron-deprived media in vitro. These findings indicate that even a single-gene loss-of-function mutation can, surprisingly, cause elevated fitness in the host during an opportunistic systemic infection. Our findings indicate that the safety assessment of S. 'boulardii' strains should not only take strain-to-strain variation into account, but also avoid extrapolating in vitro results to in vivo virulence factor determination. [ABSTRACT FROM AUTHOR]

Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system. [ABSTRACT FROM AUTHOR]

Rezafungin is a next-generation echinocandin that has favorable pharmacokinetic properties. We compared the occurrence of paradoxical growth (PG) and trailing effect (TE) characteristics to echinocadins with rezafungin, caspofungin, micafungin and anidulafungin using 365 clinical Candida isolates belonging to 13 species. MICs were determined by BMD method according to CLSI (M27 Ed4). Disconnected growth (PG plus TE) was most frequent with caspofungin (49.6%), followed by anidulafungin (33.7%), micafungin (25.7%), while it was least frequent with rezafungin (16.9%). PG was relatively common in the case of caspofungin (30.1%) but was rare in the case of rezafungin (3.0%). C. tropicalis, C. albicans, C. orthopsilosis and C. inconspicua exhibited PG most frequently with caspofungin, micafungin or anidulafungin. PG never occurred in the case of C. krusei isolates. Against C. tropicalis and C. albicans, echinocandins frequently showed PG after 24 h followed by TE after 48 h. All four echinocandins exhibited TE for the majority of C. auris and C. dubliniensis isolates. Disconnected growth was common among Candida species and was echinocandin- and species-dependent. In contrast to earlier echinocandins, PG was infrequently found with rezafungin. [ABSTRACT FROM AUTHOR]

To ensure an adequate level of protection in the European Union (EU), the European Commission (EC) adopted the Soil Thematic Strategy in 2006, including a proposal for a Soil Framework Directive (the Directive). However, a minority of Member States (United Kingdom, Germany, France, Austria, and The Netherlands) could not agree on the text of the proposed Directive. Consequently, the EC decided to withdraw the proposal in 2014. In the more than 10 years that have passed since the initial proposal, a great number of new evidences on soil degradation and its negative consequences, have proved the necessity of a common European soil protection Directive. This study is aimed at specifying the possible obstacles, differences, and gaps in legislature and administration in the countries that formed the blocking minority, which resulted in the refusal of the Directive. The individual legislations of the opposing countries on the matter, were summarized and compared with the goals set by the Directive, in three highlighted aspects: (1) soil-dependent threats, (2) contamination, and (3) sealing. We designed a simple schematic evaluation system to show the basic levels of differences and similarities. We found that the legislative regulations concerning soil-dependent degradation and contamination issues in the above countries were generally well defined, complementary, and thorough. A common European legislation can be based on harmonised approaches between them, focusing on technical implementations. In the aspect of sealing we found recommendations, principles, and good practices rather than binding regulations in the scrutinised countries. Soil sealing is an issue where the proposed Directive’s measures, could have exceeded those of the Member States. [ABSTRACT FROM AUTHOR]

The effect of two types of organic amendment (manure and straw incorporation) and various doses (0–200 kg N*ha−1) of mineral N fertilization on microbial biomass C (MBC), aggregate stability (AS), soil organic C (SOC) and grain yield were investigated in an IOSDV long-term fertilization experiment (Keszthely, Hungary). This study was conducted during years 2015–2016 in a sandy loam Ramann-type brown forest soil (Eutric Cambisol according to WRB). Organic amendments had a significant effect on AS, MBC and SOC, increased their values compared to the unamended control. The organic amendments showed different effects on AS and MBC. AS was increased the most by straw incorporation and MBC by manure application. The magnitude of temporal variability of AS and MBC differed. Presumably, the different effects of organic amendments and the different degrees of temporal variability explain why there was only a weak (0.173) correlation between AS and MBC. AS did not correlate with SOC or grain yield. MBC correlated (0.339) with SOC but not with the grain yield. The N fertilizer dose did not have a significant effect on AS and MBC, but had a significant effect on SOC and grain yield. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections. [ABSTRACT FROM AUTHOR]

Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades. [ABSTRACT FROM AUTHOR]

Bug prediction aims at finding source code elements in a software system that are likely to contain defects. Being aware of the most error-prone parts of the program, one can efficiently allocate the limited amount of testing and code review resources. Therefore, bug prediction can support software maintenance and evolution to a great extent. In this paper, we propose a function level JavaScript bug prediction model based on static source code metrics with the addition of a hybrid (static and dynamic) code analysis based metric of the number of incoming and outgoing function calls (HNII and HNOI). Our motivation for this is that JavaScript is a highly dynamic scripting language for which static code analysis might be very imprecise; therefore, using a purely static source code features for bug prediction might not be enough. Based on a study where we extracted 824 buggy and 1943 non-buggy functions from the publicly available BugsJS dataset for the ESLint JavaScript project, we can confirm the positive impact of hybrid code metrics on the prediction performance of the ML models. Depending on the ML algorithm, applied hyper-parameters, and target measures we consider, hybrid invocation metrics bring a 2–10% increase in model performances (i.e., precision, recall, F-measure). Interestingly, replacing static NOI and NII metrics with their hybrid counterparts HNOI and HNII in itself improves model performances; however, using them all together yields the best results. [ABSTRACT FROM AUTHOR]

Background: The spread of herbicide-resistance Ambrosia artemisiifolia threatens not only the production of agricultural crops, but also the composition of weed communities. The reduction of their spread would positively affect the biodiversity and beneficial weed communities in the arable habitats. Detection of resistant populations would help to reduce herbicide exposure which may contribute to the development of sustainable agroecosystems. Methods: This study focuses on the application of target-site resistance (TSR) diagnostic of A. artemisiifolia caused by different herbicides. We used targeted amplicon sequencing (TAS) on Illumina Miseq platform to detect amino acid changes in herbicide target enzymes of resistant and wild-type plants. Results: 16 mutation points of four enzymes targeted by four herbicide groups, such as Photosystem II (PSII), Acetohydroxyacid synthase (AHAS), 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) and protoporphyrinogen IX oxidase (PPO) inhibitors have been identified in common ragweed populations, so far. All the 16 mutation points were analyzed and identified. Out of these, two mutations were detected in resistant biotypes. Conclusions: The applied next-generation sequencing-targeted amplicon sequencing (NGS-TAS) method on A. artemisiifolia resistant and wild-type populations enable TSR detection of large sample numbers in a single reaction. The NGS-TAS provides information about the evolved herbicide resistance that supports the integrated weed control through the reduction of herbicide exposure which may preserve ecological properties in agroecosystems. [ABSTRACT FROM AUTHOR]

The dominant carbapenem resistant Acinetobacter baumannii harboring blaOXA-23-like carbapenemase was replaced by blaOXA-40-like carriers in a Hungarian tertiary-care center with high meropenem but relatively low imipenem use. We hypothesized that alterations in antibiotic consumption may have contributed to this switch. Our workgroup previous study examined the relation between resistance spiral and the antibiotic consumption, and the results suggest that the antibiotic usage provoked the increasing resistance in case of A. baumannii. We aimed at measuring the activity of imipenem and meropenem to compare the selection pressure exerted by the different carbapenems in time-kill assays. Strain replacement was confirmed by whole genome sequencing, core-genome multilocus sequence typing (cgMLST), and resistome analysis. Based on results of the time-kill assays, we found a significant difference between two different sequence-types (STs) in case of meropenem, but not in case of imipenem susceptibility. The newly emerged ST636 and ST492 had increased resistance level against meropenem compared to the previously dominant ST2 and ST49. On the other hand, the imipenem and colistin resistance profiles were similar. These results suggest, that the uniform meropenem usage may have contributed to A. baumannii strain replacement in our setting. [ABSTRACT FROM AUTHOR]

Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312–0.5, 0.155–0.5, 0.037–0.375, 0.064–0.375, and 0.064–0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 μM2%, 2.16 μM2%, 33.31 μM2%, 10.72 μM2%, and 111.19 μM2% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat C. auris biofilms. [ABSTRACT FROM AUTHOR]

Vineyard floor management has been widely discussed for many decades, but it is still unclear how its intensity levels change the fungal community structure of grape rhizosphere. Our objective was to examine the density and rate of the habitats of fungi in three vineyards that differ only in the methods of tillage procedure applied, namely intensive, extensive and none (abandoned). The hypothesis was that in the cases of lower intensity or no soil tillage, there would be a higher level of fungal diversity with a lower ratio of pathogen strains in grape rhizosphere. In the course of this research, it has been determined that the level of fungal colonization of roots is the highest in the extensively managed vineyard, unrelated to season (spring and summer). Four of the five fungal genera detectable in all of the three sampled vineyards are registered as opportunist grape pathogens, however the fifth one, Trichoderma, is commonly used in biological plant protection. The diversity of fungal communities in grape rhizosphere, in accordance with the expectations, was the lowest in the intensively cultivated and highest in the abandoned vineyard, and it was not affected by seasons. The proportion of opportunist plant pathogen groups was higher in the intensive variant than in the other two (less-intensive variants); therefore, it is possible to conclude that soil under similar conditions but disturbed by intensive tillage methods tends to exhibit lower suppressivity. [ABSTRACT FROM AUTHOR]

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens. [ABSTRACT FROM AUTHOR]