•Incidental findings (IFs) are present in 61.5% of head and neck cancer patients.•Relevant IFs (21.6%) result in significant delay in treatment initiation.•The majority of relevant incidental ...findings were found in the thorax (53.9%).•The frequency of additional imaging and subsequent IFs increased over the years.•Another independent factor associated with delay was initial (chemo)radiation.
As a result of the increasing number of diagnostic scans, incidental findings (IFs) are more frequently encountered during oncological work-up in patients with head and neck squamous cell carcinomas (HNSCC). IFs are unintentional discoveries found on diagnostic imaging. Relevant IFs implicate clinical consequences, resulting in delay in oncologic treatment initiation, which is associated with unfavorable outcomes. This study is the first to investigate the incidence and nature of IFs over the years and establish the effect of relevant IFs on delay.
This retrospective study compared two time periods (2010–2011 and 2016–2017), described associations between relevant IFs and delay in carepathway interval (days between first visit and treatment initiation) and assessed the effect of relevant IFs on overall two-year survival.
In total, 592 patients were included. At least one IF was found in 61.5% of the patients, most frequently on chest-CT. In 128 patients (21.6%) a relevant IF was identified, resulting for the majority in radiologist recommendations (e.g. additional scanning). Presence of a relevant IF was an independent significant factor associated with delay in treatment initiation. The risk of dying was higher for patients with a relevant IF, although not significant in the multivariable model (HR: 1.46, p = 0.079).
In diagnostic work-up for HNSCC patients, relevant IFs are frequently encountered. As the frequency of additional imaging rises over the years, the number of IFs increased simultaneously. These relevant IFs yield clinical implications and this study described that relevant IFs result in significant delay in treatment initiation.
In natural environments, microorganisms are exposed to a wide variety of antibiotic compounds produced by competing organisms. Target organisms have evolved various mechanisms of natural resistance ...to these metabolites. In this study, the role of ATP-binding cassette (ABC) transporters in interactions between the plant-pathogenic fungus Botrytis cinerea and antibiotic-producing Pseudomonas bacteria was investigated in detail. We discovered that 2,4-diacetylphloroglucinol, phenazine-1-carboxylic acid and phenazine-1-carboxamide (PCN), broad-spectrum antibiotics produced by Pseudomonas spp., induced expression of several ABC transporter genes in B. cinerea. Phenazines strongly induced expression of BcatrB, and deltaBcatrB mutants were significantly more sensitive to these antibiotics than their parental strain. Treatment of B. cinerea germlings with PCN strongly affected the accumulation of 14Cfludioxonil, a phenylpyrrole fungicide known to be transported by BcatrB, indicating that phenazines also are transported by BcatrB. Pseudomonas strains producing phenazines displayed a stronger antagonistic activity in vitro toward ABcatrB mutants than to the parental B. cinerea strain. On tomato leaves, phenazine-producing Pseudomonas strains were significantly more effective in reducing gray mold symptoms incited by a ABcatrB mutant than by the parental strain. We conclude that the ABC transporter BcatrB provides protection to B. cinerea in phenazine-mediated interactions with Pseudomonas spp. Collectively, these results indicate that fungal ABC transporters can play an important role in antibiotic-mediated interactions between bacteria and fungi in plant-associated environments. The implications of these findings for the implementation and sustainability of crop protection by antagonistic microorganisms are discussed.
Objective
Head and neck squamous cell carcinomas (HNSCC) are rapidly developing tumours, and substantial delay in treatment initiation is associated with decreased overall survival. The effect of ...delay on health‐related quality of life (HRQOL) is unknown. The aim of this study was to assess the impact of delay on QOL and overall survival.
Methods
Patients with mucosal HNSCC were prospectively included. HRQOL and 2‐year overall survival were analysed using linear mixed‐model analyses and cox regression, respectively. Delay was defined as care pathway interval (CPI) of ≥30 days between first consultation and treatment initiation.
Results
Median CPI was 39 days for the 173 patients included. A trend towards higher HRQOL‐scores (indicating better HRQOL) during 2‐year follow‐up for patients with delay in treatment initiation was visible in the adjusted models (HRQOL summary score—β: 2.62, 95% CI: 0.57–4.67, p = 0.012). Factors associated with decreased overall survival were moderate comorbidities (HR: 5.10, 95% CI: 1.65–15.76, p = 0.005) and stage‐IV tumours (HR: 12.37, 95% CI: 2.81–54.39, p = 0.001). Delay was not associated with worse overall survival.
Conclusion
Timely treatment initiation is challenging, especially for patients with advanced tumours and initial radiotherapy treatment. Encountering delay in treatment initiation did not result in clinically relevant differences in HRQOL‐scores or decreased overall survival during 2‐year follow‐up.
Botrytis cinerea and Sclerotinia sclerotiorum secrete oxalic acid as a pathogenicity factor with a broad action. Consequently, it should be possible to interfere with the infection process by ...degrading oxalic acid during the interaction of these pathogens with their hosts. We have evaluated the potential of oxalate-degrading bacteria to protect plants against pathogenic fungi. Such bacteria were isolated from agricultural soil and selected on agar plates with Ca-oxalate as the sole carbon source. Four strains were retained with a medium-to-strong protective activity on Arabidopsis thaliana leaves against B. cinerea and S. sclerotiorum. They can provide 30 to 70% protection against fungal infection in different pathosystems, including B. cinerea on A. thaliana, cucumber, grapevine, and tomato. The oxalate-degrading bacteria induced only some marker genes for common plant signaling pathways for defenses, but protective effects were slightly reduced in A. thaliana mutants impaired in the ethylene and jasmonic acid signaling pathways. More detailed studies on the protective mechanism were performed in ox-strain B, identified as Cupriavidus campinensis, by analysis of transposon-tagged mutants that have a reduced ability to degrade oxalic acid.
Several geminal bis‐urea compounds were synthesised by means of an acid‐catalysed condensation of various benzaldehydes with different monoalkylureas. Many of these compounds form thermoreversible ...gels with a number of organic solvents at very low concentrations (<3 mM) and which are stable to temperatures higher than 100 °C. Electron microscopy revealed a three‐dimensional (3D) network of intertwined fibres, which are several tens of micrometers long and have a width ranging from approximately 30 to 300 nm. The possible aggregate forms and aggregate symmetries were evaluated by means of molecular mechanics calculations. 1H NMR, 2D NMR, 13C NMR and 13CCP/MAS NMR techniques were used to obtain information about the aggregation and possible aggregate symmetry of geminal bis‐ureas in solution, in the gel state, and in the solid state.
Survival of microorganisms in natural environments is favored by the capacity to produce compounds toxic to competing organisms and the ability to resist the effects of such toxic compounds. Both ...factors contribute to a competitive advantage of organisms in ecosystems. All organisms have evolved active transport mechanisms by which endogenous and exogenous toxicants can be secreted. Two major classes of transporter proteins are the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) transporters. Members of both classes can have broad and overlapping substrate specificities for natural toxic compounds and can be regarded as a “first-line defense barrier” in survival mechanisms. In plant pathogens, these transporters can play an essential role in protection against plant defense compounds during pathogenesis. Also, some transporters actively secrete host-specific and non-host-specific toxins. Remarkably, ABC and MFS transporters can also play a major role in fungicide sensitivity and resistance. Their role in multidrug resistance of Aspergillus nidulans, Candida albicans, and Saccharomyces cerevisiae to azoles and other fungitoxic compounds is well established. Knowledge of ABC and MFS transporters opens possibilities of developing novel strategies for controlling plant diseases, either by modulation of transporter activity or by transgenic expression of transporter genes in plants.
Disease resistance genes encoding nucleotide-binding and leucine-rich repeat (NLR) intracellular immune receptor proteins detect pathogens by the presence of pathogen effectors. Plant genomes ...typically contain hundreds of NLR-encoding genes. The availability of the hexaploid wheat (
) cultivar Chinese Spring reference genome allows a detailed study of its NLR complement. However, low
expression and high intrafamily sequence homology hinder their accurate annotation. Here, we developed NLR-Annotator, a software tool for in silico NLR identification independent of transcript support. Although developed for wheat, we demonstrate the universal applicability of NLR-Annotator across diverse plant taxa. We applied our tool to wheat and combined it with a transcript-validated subset of genes from the reference gene annotation to characterize the structure, phylogeny, and expression profile of the
gene family. We detected 3,400 full-length NLR loci, of which 1,560 were confirmed as expressed genes with intact open reading frames. NLRs with integrated domains mostly group in specific subclades. Members of another subclade predominantly locate in close physical proximity to NLRs carrying integrated domains, suggesting a paired helper function. Most
(88%) display low basal expression (in the lower 10 percentile of transcripts). In young leaves subjected to biotic stress, we found up-regulation of 266 of the
To illustrate the utility of our tool for the positional cloning of resistance genes, we estimated the number of
genes within the intervals of mapped rust resistance genes. Our study will support the identification of functional resistance genes in wheat to accelerate the breeding and engineering of disease-resistant varieties.
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