12 research outputs found
Influence of physiciansâ risk perception on switching treatments between high- efficacy and nonâhigh-efficacy diseaseâmodifying therapies in multiple sclerosis
Background: The decision of initiating treatment for multiple sclerosis (MS) with a high-efficacy DMT (HE DMT) or nonâhigh-efficacy DMT (non-HE DMT) is influenced by several factors, including risk perception of patients and physicians. Objective: Investigate the influence of physiciansâ risk perception on decision-making when switching treatments for MS and the reasons for switching. Methods: Data were drawn from the Adelphi Real-World MS Disease-Specific Program (a retrospective survey) and analysis included people with RMS identified between 2017â 2021. Results: Of 4129 patients with reasons for switch available, 3538 switched from non-HE DMT and 591 from HE DMT. Overall, 4.7% of patients were switched treatment by their physicians due to the risk of malignancies and infections including PML risk. The proportion of switches that were made due to the risk of PML were 23.9% in the HE DMT and 0.5% in the non-HE DMT groups. The top reasons for switching were relapse frequency (non-HE DMT vs HE-DMT: 26.8% vs 15.2%), lack of efficacy (20.9 vs 11.7) and increased number of MRI lesions (20.3% vs 12.4%). Conclusions: Physiciansâ risk perception of malignancies and infection excluding PML was not a leading factor when switching treatment. The risk of PML was a key factor, especially for switching patients from HE DMTs. In both groups, lack of efficacy was the key contributing factor for switching. Initiating the treatment with HE DMTs may potentially reduce the number of switches due to sub-optimal efficacy. These findings might help physicians to engage more in discussions with patients about the benefit/risk profile of DMTs
The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B5
Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops
The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B5.
Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops
Strongly Coupled Plasmonic Modes on Macroscopic Areas via Template-Assisted Colloidal Self-Assembly
We
present ensembles of surface-ordered nanoparticle arrangements, which
are formed by template-assisted self-assembly of monodisperse, protein-coated
gold nanoparticles in wrinkle templates. Centimeter-squared areas
of highly regular, linear assemblies with tunable line width are fabricated
and their extinction cross sections can be characterized by conventional
UV/vis/NIR spectroscopy. Modeling based on electrodynamic simulations
shows a clear signature of strong plasmonic coupling with an interparticle
spacing of 1â2 nm. We find evidence for well-defined plasmonic
modes of quasi-infinite chains, such as resonance splitting and multiple
radiant modes. Beyond elementary simulations on the individual chain
level, we introduce an advanced model, which considers the chain length
distribution as well as disorder. The step toward macroscopic sample
areas not only opens perspectives for a range of applications in sensing,
plasmonic light harvesting, surface enhanced spectroscopy, and information
technology but also eases the investigation of hybridization and metamaterial
effects fundamentally